Science.gov

Sample records for botulinum c2 toxin

  1. The actin-ADP-ribosylating Clostridium botulinum C2 toxin.

    PubMed

    Aktories, Klaus; Barth, Holger

    2004-04-01

    Clostridium botulinum C2 toxin is the prototype of actin-ADP-ribosylating toxins. The toxin consists of the enzyme component C2I and the separated binding/translocation component C2II. C2II is proteolytically activated to form heptamers, which bind the enzyme component. After endocytosis of the receptor-toxin complex, the enzyme component enters the cytosol from an acidic endosomal compartment to modify G-actin at arginine177. Recent data indicate that chaperons are involved in the translocation process of the toxin.

  2. Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin.

    PubMed

    Prisilla, A; Prathiviraj, R; Chellapandi, P

    2017-04-05

    Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure-function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure-function link, not only of a molecule but also of the pathogenesis.

  3. Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol

    PubMed Central

    Pavlik, Benjamin J.; Hruska, Elizabeth J.; Van Cott, Kevin E.; Blum, Paul H.

    2016-01-01

    Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. Using toxins with naturally unlinked components as a starting point is advantageous because it allows for the development of payloads separately from the binding/translocation components. Here the Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This fusion protein was used to deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery was quantified by flow cytometry and found to be dependent on artificial enrichment of cells with the polysialoganglioside receptor GT1b. Visualization by confocal microscopy showed a dissociation of payloads from the early endosome indicating translocation of the chimeric toxin. The natural Clostridium botulinum C2 toxin was then delivered to human glioblastoma A172 and synchronized HeLa cells. In the presence of the fusion protein, native cytosolic enzymatic activity of the enzyme was observed and found to be GT1b-dependent. This retargeted toxin may enable delivery of therapeutics to peripheral neurons and be of use in addressing experimental questions about neural physiology. PMID:27025362

  4. Retargeting the Clostridium botulinum C2 toxin to the neuronal cytosol.

    PubMed

    Pavlik, Benjamin J; Hruska, Elizabeth J; Van Cott, Kevin E; Blum, Paul H

    2016-03-30

    Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. Using toxins with naturally unlinked components as a starting point is advantageous because it allows for the development of payloads separately from the binding/translocation components. Here the Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This fusion protein was used to deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery was quantified by flow cytometry and found to be dependent on artificial enrichment of cells with the polysialoganglioside receptor GT1b. Visualization by confocal microscopy showed a dissociation of payloads from the early endosome indicating translocation of the chimeric toxin. The natural Clostridium botulinum C2 toxin was then delivered to human glioblastoma A172 and synchronized HeLa cells. In the presence of the fusion protein, native cytosolic enzymatic activity of the enzyme was observed and found to be GT1b-dependent. This retargeted toxin may enable delivery of therapeutics to peripheral neurons and be of use in addressing experimental questions about neural physiology.

  5. EGA Protects Mammalian Cells from Clostridium difficile CDT, Clostridium perfringens Iota Toxin and Clostridium botulinum C2 Toxin.

    PubMed

    Schnell, Leonie; Mittler, Ann-Katrin; Sadi, Mirko; Popoff, Michel R; Schwan, Carsten; Aktories, Klaus; Mattarei, Andrea; Azarnia Tehran, Domenico; Montecucco, Cesare; Barth, Holger

    2016-04-01

    The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins.

  6. Structure, Function and Evolution of Clostridium botulinum C2 and C3 Toxins: Insight to Poultry and Veterinary Vaccines.

    PubMed

    Chellapandi, P; Prisilla, A

    2016-12-01

    Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced from this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines. C2 toxin is a binary toxin that consists of a catalytic subunit (C2I) and a translocation subunit (C2II). C2I component is structurally and functionally similar to the VIP2 and iota A toxin whereas C2II component shows a significant homology with the protective antigen from anthrax toxin and iota B. Unlike C2 toxin, C3 toxin is devoid of translocation/binding subunit. Extensive studies on their sequence-structure-function link spawn additional efforts to understand the catalytic mechanisms and target recognition. Structural and functional relationships of them are often determined by using evolutionary constraints as valuable biological measures. Enzyme-deficient mutants derived from these toxins have been used as drug/protein delivery systems to eukaryotic cells. Thus, current knowledge on their molecular diversity is a well-known perspective to design immunotoxin or subunit vaccine for C. botulinum infection.

  7. The susceptibility of the mallard duck (Anas platyrhynchos) to Clostridium botulinum C2 toxin

    USGS Publications Warehouse

    Jensen, W.I.; Duncan, R.M.

    1980-01-01

    Most strains of Clostridium botulinum type C, after having lost their capacity to produce their dominant toxin (C1) as a result of being "cured" of their prophages, continue to produce C2, a trypsin-activable toxin reported by other investigators. While of relatively low toxicity when administered perorally to the adult mallard duck (Anas platyrhynchos), it was highly toxic when given parenterally. By the intravenous route, for example, it was more than 1,000 times as toxic as C1 toxin by the same route, when compared on the basis of mouse intraperitoneal toxicity. The cause of death in every instance was massive pulmonary edema and hemorrhage rather than the respiratory paralysis that occurs in C1 intoxication.

  8. Clostridium botulinum C2 toxin--new insights into the cellular up-take of the actin-ADP-ribosylating toxin.

    PubMed

    Aktories, Klaus; Barth, Holger

    2004-04-01

    Clostridium botulinum C2 toxin is a member of the family of binary actin-ADP-ribosylating toxins. It consists of the enzyme component C2I, and the separated binding/translocation component C2II. Proteolytically activated C2II forms heptamers and binds to a carbohydrate cell surface receptor. After attachment of C2I, the toxin complex is endocytosed to reach early endosomes. At low pH of endosomes, C2II-heptamers insert into the membrane, form pores and deliver C2I into the cytosol. Here, C2I ADP-ribosylates actin at Arg177 to block actin polymerization and to induce depolymerization of actin filaments. The mini-review describes main properties of C2 toxin and discusses new findings on the involvement of chaperones in the up-take process of the toxin.

  9. Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.

    PubMed

    Kreidler, Anna-Maria; Benz, Roland; Barth, Holger

    2017-03-01

    The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B7) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B7 components of C2 toxin and LT, C2IIa and PA63, respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.

  10. [Intoxication of botulinum toxin].

    PubMed

    Chudzicka, Aleksandra

    2015-09-01

    Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon.

  11. Botulinum toxin injection - larynx

    MedlinePlus

    Injection laryngoplasty; Botox-larynx: spasmodic dysphonia-BTX; Essential voice tremor (EVT)-btx; Glottic insufficiency; Percutaneous electromyography-guided botulinum toxin treatment; Percutaneous indirect laryngoscopy- ...

  12. Botulinum Toxin

    DTIC Science & Technology

    2009-01-01

    resulting from antibiotic treatment (Cherington, 1998). Foodbome and inhalational have noninfectious etiologies and are the result of ingesting or...infants Self- Antibiotic -treated All exposed All exposed individuals Patients treated with local toxin injections (2 to 4 months of age) prior to...typically take place except under circumstances where the normal flora has been altered by antibiotic treatment (Cherington, 1998). Botulism results

  13. Diffusion of Botulinum Toxins

    PubMed Central

    Brodsky, Matthew A.; Swope, David M.; Grimes, David

    2012-01-01

    Background It is generally agreed that diffusion of botulinum toxin occurs, but the extent of the spread and its clinical importance are disputed. Many factors have been suggested to play a role but which have the most clinical relevance is a subject of much discussion. Methods This review discusses the variables affecting diffusion, including protein composition and molecular size as well as injection factors (e.g., volume, dose, injection method). It also discusses data on diffusion from comparative studies in animal models and human clinical trials that illustrate differences between the available botulinum toxin products (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB). Results Neither molecular weight nor the presence of complexing proteins appears to affect diffusion; however, injection volume, concentration, and dose all play roles and are modifiable. Both animal and human studies show that botulinum toxin products are not interchangeable, and that some products are associated with greater diffusion and higher rates of diffusion-related adverse events than others. Discussion Each of the botulinum toxins is a unique pharmacologic entity. A working knowledge of the different serotypes is essential to avoid unwanted diffusion-related adverse events. In addition, clinicians should be aware that the factors influencing diffusion may range from properties intrinsic to the drug to accurate muscle selection as well as dilution, volume, and dose injected. PMID:23440162

  14. Botulinum toxin, Quo Vadis?

    PubMed

    Lim, Erle C H; Seet, Raymond C S

    2007-01-01

    Botulinum toxin (BTX), derived from the exotoxin of Clostridium botulinum, cleaves Soluble N-ethylmaleimide-sensitive factor-Attachment protein REceptor (SNARE) proteins, causing chemodenervation of cholinergic neurons. BTX also inhibits exocytosis of vesicles containing norepinephrine, glutamate, substance P and calcitonin gene-related peptide (CGRP) and inhibits expression of the vanilloid receptor. Clinical applications of BTX, which include the treatment of overactive skeletal and smooth muscles, hypersecretory and painful disorders, have increased exponentially since it was first used clinically to treat strabismus more than two decades ago. In this editorial, we discuss reports of new therapeutic indications of BTX, and propose new areas for research.

  15. Botulinum toxin: bioweapon & magic drug.

    PubMed

    Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

    2010-11-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

  16. Botulinum toxin: Bioweapon & magic drug

    PubMed Central

    Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

    2010-01-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility. It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin. PMID:21149997

  17. Botulinum toxin in clinical practice

    PubMed Central

    Jankovic, J

    2004-01-01

    Botulinum toxin, the most potent biological toxin, has become a powerful therapeutic tool for a growing number of clinical applications. This review draws attention to new findings about the mechanism of action of botulinum toxin and briefly reviews some of its most frequent uses, focusing on evidence based data. Double blind, placebo controlled studies, as well as open label clinical trials, provide evidence that, when appropriate targets and doses are selected, botulinum toxin temporarily ameliorates disorders associated with excessive muscle contraction or autonomic dysfunction. When injected not more often than every three months, the risk of blocking antibodies is slight. Long term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for an increasing number of off-label indications. PMID:15201348

  18. Botulinum Toxin in Migraine Treatment

    PubMed Central

    ILGAZ AYDINLAR, Elif; YALINAY DİKMEN, Pınar; SAĞDUYU KOCAMAN, Ayşe

    2013-01-01

    Since botulinum toxin might have a therapeutic effect on pain, many studies investigating the efficiency of botulinum toxin in headache treatment have been done. The most satisfying results were achieved by botulinum toxin type A (BoNT/A) in the treatment of chronic migraine. In this paper, we reviewed the clinical effectiveness of BoNT/A in migraine and included our clinical experience. In our ongoing pilot study, where we have repeated BoNT/A injections every 12 weeks, The difference in the Migraine Disability Assessment (MIDAS) scores between the first and the second injections was 61.1%; and between the first and the 3rd injections was found to be 65.72%.

  19. Botulinum toxin: The Midas touch

    PubMed Central

    Shilpa, P. S.; Kaul, Rachna; Sultana, Nishat; Bhat, Suraksha

    2014-01-01

    Botulinum Toxin (BT) is a natural molecule produced during growth and autolysis of bacterium called Clostridium botulinum. Use of BT for cosmetic purposes has gained popularity over past two decades, and recently, other therapeutic uses of BT has been extensively studied. BT is considered as a minimally invasive agent that can be used in the treatment of various orofacial disorders and improving the quality of life in such patients. The objective of this article is to review the nature, mechanism of action of BT, and its application in various head and neck diseases. PMID:24678189

  20. Botulinum toxin to minimize facial scarring.

    PubMed

    Sherris, David A; Gassner, Holger G

    2002-02-01

    Botulinum toxin injection has been used for a variety of indications in humans, including blepharospasm and hyperfunctional facial lines. This article describes a novel formulation of botulinum toxin, which supplies immediate feedback to the injecting physician. Additionally, recent findings are described that indicate the immediate injection of botulinum toxin into the muscles underlying a wound can improve the cosmetic outcome of the facial cutaneous scar. Future applications of these findings are discussed.

  1. Botulinum Toxin and Gastrointestinal Tract Disorders

    PubMed Central

    Weiser, Kirsten; Kennedy, Abigail

    2008-01-01

    The history of botulinum toxin is fascinating. First recognized as the cause of botulism nearly 200 years ago, it was originally feared as a deadly poison. Over the last 30 years, however, botulinum toxin has been transformed into a readily available medication used to treat a variety of medical disorders. Interest in the use of botulinum toxin has been particularly strong for patients with spastic smooth muscle disorders of the gastrointestinal tract. Patients with achalasia, diffuse esophageal spasm, gastroparesis, sphincter of Oddi dysfunction, and anal fissures have all been treated with botulinum toxin injections, often with impressive results. However, not all patients respond to botulinum toxin therapy, and large randomized controlled trials are lacking for many conditions commonly treated with botulinum toxin. This paper reviews the history, microbiology, and pharmacology of botulinum toxin, discusses its mechanism of action, and then presents recent evidence from the literature regarding the use of botulinum toxin for the treatment of a variety of gastrointestinal tract disorders. PMID:21960915

  2. Botulinum toxin for the treatment of bruxism.

    PubMed

    Tinastepe, Neslihan; Küçük, Burcu Bal; Oral, Koray

    2014-08-14

    Aims: Botulinum toxin, the most potent biological toxin, has been shown to be effective for a variety of disorders in several medical conditions, when used both therapeutically and cosmetically. In recent years, there has been a rising trend in the use of this pharmacological agent to control bruxing activity, despite its reported adverse effects. The aim of this review was to provide a brief overview to clarify the underlying essential ideas for the use of botulinum toxin in bruxism based on available scientific papers. Methodology: An electronic literature search was performed to identify publications related to botulinum toxin and its use for bruxism in PubMed. Hand searching of relevant articles was also made to identify additional studies. Results: Of the eleven identified studies, only two were randomized controlled trials, compared with the effectiveness of botulinum toxins on the reduction in the frequency of bruxism events and myofascial pain after injection. The authors of these studies concluded that botulinum toxin could be used as an effective treatment for reducing nocturnal bruxism and myofascial pain in patients with bruxism. Conclusion: Evidence-based research was limited on this topic. More randomized controlled studies are needed to confirm that botulinum toxin is safe and reliable for routine clinical use in bruxism.

  3. [Botulinum toxin in disabling dermatological diseases].

    PubMed

    Messikh, R; Atallah, L; Aubin, F; Humbert, P

    2009-05-01

    Botulinum toxin could represent nowadays a new treatment modality especially for cutaneous conditions in course of which conventional treatments remain unsuccessful. Besides palmar and plantar hyperhidrosis, botulinum toxin has demonstrated efficacy in different conditions associated with hyperhidrosis, such as dyshidrosis, multiple eccrine hidrocystomas, hidradenitis suppurativa, Frey syndrome, but also in different conditions worsened by hyperhidrosis such as Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenital. Moreover, different cutaneous conditions associated with sensitive disorders and/or neurological involvements could benefit from botulinum toxin, for example anal fissures, leg ulcers, lichen simplex, notalgia paresthetica, vestibulitis. Endly, a case of cutis laxa was described where the patient was improved by cutaneous injections of botulinum toxin.

  4. [Potential antinociceptive mechanisms of botulinum toxin].

    PubMed

    Aoki, K R; Francis, J; Jost, W H

    2006-09-01

    Botulinum toxin has been used in pain therapy for several years. Its application in migraine and headaches is particularly interesting. Clinical results have not yet been definitely conclusive, and a uniform model of the mode of action has not been established either. Apart from a purely muscular effect, a direct antinociceptive effect of botulinum toxin has been found in patients, in the preclinical model, and in a clinical pain model. This is contradicted by negative observations in the clinical model of pain, which might be related to methodological deficits. Further basics need to be worked out before arriving at any final result. Clinical studies with patients and pain models should then follow. Studying botulinum toxin within the context of pain will also provide many new insights into pain therapy in general. In which pain model botulinum toxin may play a role in the future, has to be awaited.

  5. [Botulinum toxin as a biological weapon].

    PubMed

    Rossow, Heidi; Kinnunen, Paula M; Nikkari, Simo

    2012-01-01

    Botulism is caused by botulinum neurotoxin produced by the bacterium Clostridium botulinum. It is a flaccid paralysis in which consciousness and nociception are preserved. Natural botulism typically results from ingestion of inadequately heated or unheated vacuum-packed foods. In addition, botulinum toxin is one of the most feared biological weapons. In the diagnosis and treatment of botulism early suspicion is essential. Several coinciding or local clusters without a typical connecting source, or an uncommon type of toxin may indicate an intentionally caused epidemic.

  6. Botulinum Toxin Injections: A Treatment for Muscle Spasms

    MedlinePlus

    ... Procedures & Devices Botulinum Toxin Injections: A Treatment for Muscle Spasms Botulinum Toxin Injections: A Treatment for Muscle Spasms Drugs, Procedures & DevicesProcedures & DevicesYour Health Resources Share ...

  7. [Botulinum toxin therapy for spasticity].

    PubMed

    Masakado, Yoshihisa

    2014-09-01

    Botulinum toxin (BTX) administered as an adjunct to other interventions for spasticity can act as a useful and effective therapeutic tool for treating patients disabled by spasticity. Presence of other non-reflex motor disorders (muscle stiffness, shortness, and contracture) can complicate the clinical course and disturb rehabilitative process of patients with spasticity. Treatment of spasticity using BTX can improve paralysis by correcting muscular imbalance that follows these diseases. In patients with chronic severe spasticity, we also have to address unique and difficult-to-treat clinical conditions such as abnormal posture and movement disorders. The effectiveness of BTX in treating some of these conditions is discussed. Because patients with neurological disabilities can show complex dysfunctions, specific functional limitations, goals, and expected outcomes of treatment should be evaluated and discussed with the patient, family members, and caregivers, prior to initiating BTX therapy. BTX therapy might improve not only care, passive function, but also motor functions in these patients by supplementing intensive rehabilitation with repetitive transcranial magnetic stimulation, transcranial direct-current stimulation, peripheral electrical stimulation, muscle stretching, and other rehabilitation strategies.

  8. Botulinum toxin: mechanisms of action.

    PubMed

    Dressler, Dirk; Adib Saberi, Fereshte

    2005-01-01

    Botulinum toxin (BT) has been perceived as a lethal threat for many centuries. In the early 1980s, this perception completely changed when BT's therapeutic potential suddenly became apparent. We wish to give an overview over BT's mechanisms of action relevant for understanding its therapeutic use. BT's molecular mode of action includes extracellular binding to glycoprotein structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated by blockade of substance P, glutamate and calcitonin gene-related peptide.

  9. Use of botulinum toxin in Meige's disease.

    PubMed

    Maurri, S; Brogelli, S; Alfieri, G; Barontini, F

    1988-01-01

    Four patients with severe Meige's disease (blepharospasm-oromandibular dystonia) have been treated, after having given an informed consent, by local injections of purified botulinum toxin type "A". Previous systemic therapy with anticholinergics, dopamine antagonists and other drugs had been unsuccessful in all these subjects. Each patient was treated by saline solution injected with the same method as botulinum toxin, just once. The self-evaluation of patients and the clinical evaluation that some of us- unaware of the kind of therapy which had been performed- gave to the symptoms on the basis of videotapes, for each session of injection, showed that the injections of botulinum toxin are effective in the treatment of such disorder. The duration of the beneficial effect was slightly shorter in these patients than in patients with blepharospasm treated by the same method.

  10. Use of botulinum toxin in dentistry.

    PubMed

    Hoque, Afreen; McAndrew, Maureen

    2009-11-01

    A growing number of dentists are providing botulinum toxin to patients. The research presented here outlines potential uses of Botox related to oral health and facial problems as compared to traditional treatment methods. The administration of Botox (historically done by dermatologists and neurologists) may fall under dentists' jurisdiction, as their training and knowledge encompasses the entire head and neck. A review is made of the literature, based on Ovid and PubMed searches, selecting articles describing the injection of botulinum toxin A in areas related to the oral cavity and the face, excluding cosmetic purposes.

  11. Thermal sensitivity of Clostridium botulinum type C toxin.

    PubMed Central

    Hubálek, Z.; Halouzka, J.

    1988-01-01

    A sterile suspension containing 950 mouse LD50 per ml of type C botulinum toxin was exposed for various periods to different temperatures. The time required for the 99% (hundred-fold) reduction of toxicity was more than 5 years at -70 degrees C or -20 degrees C, 6 months at +5 degrees C, 3 weeks at +20 degrees C, 2 weeks at +28 degrees C, 2 days at +37 degrees C, 9 h at +42 degrees C, less than 30 min at +56 degrees C, less than 20 min at +60 degrees C, and below 5 min at +80 degrees C. The results suggest that Clostridium botulinum type C toxin, if produced in an ecosystem of the mild climatic zone, might persist there over the winter season and cause the intoxication of vertebrates next early spring in the absence of further microbial toxigenesis. PMID:2972554

  12. Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States.

    PubMed

    Patil, Shilpadevi; Willett, Olga; Thompkins, Terin; Hermann, Robert; Ramanathan, Sathish; Cornett, Elyse M; Fox, Charles J; Kaye, Alan David

    2016-03-01

    Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients.

  13. Botulinum toxin to minimize facial scarring.

    PubMed

    Jablonka, Eric M; Sherris, David A; Gassner, Holger G

    2012-10-01

    Chemoimmobilization with botulinum toxin A is an ideal biochemical agent that allows near-total elimination of muscle pull on the healing facial wound. The goal of chemoimmobilization of facial cutaneous wounds is to eliminate dynamic tension on the healing tissues to improve wound healing and minimize scarring for optimal aesthetic results.

  14. Mechanisms of Toxin Production of Food Bacteria (Clostridium botulinum)

    DTIC Science & Technology

    1983-12-01

    l~ V- 9;-iC -’.1,- r, 4. •, . . . . . MECHANISMS OF TOXIN PRODUCTION OF FOOD BACTERIA ( CLOSTRIDIUM BOTULINUM) FINAL REPORT DR. H. U. EKLUND F. T...Mechanisms of Toxin Production of Food Bacteria Clostridium botulinum Final Y,’v/ ’ "D30 • ’q• 6, PERFORM G ORG. REPORT NUMBER 7. AUTHOR(.) S...WORDS (Continue on reverse aide If necessary and Identify by block number) Clostridium botulinum Bacteriophages Plasmids Food Poisoning Toxins

  15. Clostridial Binary Toxins: Iota and C2 Family Portraits

    PubMed Central

    Stiles, Bradley G.; Wigelsworth, Darran J.; Popoff, Michel R.; Barth, Holger

    2011-01-01

    There are many pathogenic Clostridium species with diverse virulence factors that include protein toxins. Some of these bacteria, such as C. botulinum, C. difficile, C. perfringens, and C. spiroforme, cause enteric problems in animals as well as humans. These often fatal diseases can partly be attributed to binary protein toxins that follow a classic AB paradigm. Within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-ADP-ribosylation of globular actin by the A component. However, much less is known about B component binding to cell-surface receptors. These toxins share sequence homology amongst themselves and with those produced by another Gram-positive, spore-forming bacterium also commonly associated with soil and disease: Bacillus anthracis. This review focuses upon the iota and C2 families of clostridial binary toxins and includes: (1) basics of the bacterial source; (2) toxin biochemistry; (3) sophisticated cellular uptake machinery; and (4) host–cell responses following toxin-mediated disruption of the cytoskeleton. In summary, these protein toxins aid diverse enteric species within the genus Clostridium. PMID:22919577

  16. Botulinum toxin therapy for abductor spasmodic dysphonia.

    PubMed

    Woodson, Gayle; Hochstetler, Heidi; Murry, Thomas

    2006-03-01

    Botulinum toxin has been widely accepted as an effective therapy for controlling the symptoms of adductor spasmodic dysphonia (ADSD). Reported experience with botulinum treatment for abductor spasmodic dysphonia (ABSD) has been less impressive. Factors that may impair outcomes for ABSD include differences in the pathophysiology of ADSD and ABSD and limitation of maximal dose from airway restriction with posterior cricoarytenoid muscle (PCA) weakness. We report our experience with botulinum injection of the PCA with an asymmetric dose escalation protocol, based on clinical observations that in ABSD, abductor spasms are often stronger on one side, usually the left. The nondominant side was injected with 1.25 units. Dominant side dose began at 5 units, with step-wise increments of 5 units per week until one of three endpoints was reached: Elimination of breathy voice breaks, complete abductor paralysis of the dominant side, or airway compromise. Fourteen of 17 patients achieved good or fair voice, with dominant-side doses ranging from 10 to 25 units. Exercise intolerance limited PCA dose in two patients. One patient had persisting breathiness that improved with medialization thyroplasty. Asymmetric botulinum toxin injection into PCA muscles can suppress abductor spasm in patients with ABSD, but breathiness may persist, because of inadequate glottal closure.

  17. Use of botulinum toxin in musculoskeletal pain

    PubMed Central

    Singh, Jasvinder A

    2013-01-01

    Chronic musculoskeletal pain is a common cause of chronic pain, which is associated with a total cost of $635 billion per year in the U.S. Emerging evidence suggests an anti-nociceptive action of botulinum toxin, independent of its muscle paralyzing action. This review provides a summary of data from both non-randomized and randomized clinical studies of botulinum toxin in back pain and various osteoarticular conditions, including osteoarthritis, tennis elbow, low back pain and hand pain. Three randomized controlled trials (RCTs) of small sizes provide evidence of short-term efficacy of a single intra-articular injection of 100 units of botulinum toxin A (BoNT/A) for the relief of pain and the improvement of both function and quality of life in patients with chronic joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis elbow with one showing a significant improvement in pain relief compared with placebo, another one showing no difference from placebo, and the third finding that pain and function improvement with BoNT/A injection were similar to those obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain found improvement in pain and function compared to placebo. Single RCTs using local injections of BoNT in patients with either temporomandibular joint (TMJ) pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found improvement in pain in both BoNT/B and placebo groups, but no significant difference between groups. Most evidence is based on small studies, but the use of BoNT is supported by a single, and sometimes up to three, RCTs for several chronic musculoskeletal pain conditions. This indicates that botulinum toxin may be a promising potential new treatment for chronic refractory musculoskeletal pain. Well-designed large clinical trials are needed. PMID:24715952

  18. Botulinum toxin for meralgia paresthetica in type 2 diabetes.

    PubMed

    Dhull, Pawan; Tewari, A K; Upreti, Vimal; Prakash, M S; Hari Kumar, K V S

    2013-01-01

    Botulinum toxin has been used for a variety of neuropathic conditions in diabetes mellitus. Meralgia paresthetica is a mononeuropathy of femoral nerve seen in diabetes and obesity with an unclear etiopathogenesis. We studied the role of botulinum toxin in resistant cases of meralgia paresthetica in type 2 diabetes.

  19. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    PubMed

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter.

  20. Botulinum toxin type B micromechanosensor

    PubMed Central

    Liu, W.; Montana, Vedrana; Chapman, Edwin R.; Mohideen, U.; Parpura, Vladimir

    2003-01-01

    Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to humans; early and rapid detection is essential for adequate medical treatment. Presently available tests for detection of BoNTs, although sensitive, require hours to days. We report a BoNT-B sensor whose properties allow detection of BoNT-B within minutes. The technique relies on the detection of an agarose bead detachment from the tip of a micromachined cantilever resulting from BoNT-B action on its substratum, the synaptic protein synaptobrevin 2, attached to the beads. The mechanical resonance frequency of the cantilever is monitored for the detection. To suspend the bead off the cantilever we use synaptobrevin's molecular interaction with another synaptic protein, syntaxin 1A, that was deposited onto the cantilever tip. Additionally, this bead detachment technique is general and can be used in any displacement reaction, such as in receptor-ligand pairs, where the introduction of one chemical leads to the displacement of another. The technique is of broad interest and will find uses outside toxicology. PMID:14573702

  1. Botulinum Toxin: Poisoning the Spastic Bladder and Urethra

    PubMed Central

    Smith, Christopher P; Somogyi, George T; Chancellor, Michael B

    2002-01-01

    Botulinum toxin has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. Urologists are now finding clinical success with urethral and bladder injection of this fascinating toxin for detrusor sphincter dyssynergia, conditions of pelvic floor spasticity, and overactive bladder. One cannot deny the ingenuity of man in transforming the lethal toxin of Clostridium botulinum into a modern day therapeutic medicine. PMID:16985657

  2. Treatment of Gastrointestinal Sphincters Spasms with Botulinum Toxin A

    PubMed Central

    Brisinda, Giuseppe; Sivestrini, Nicola; Bianco, Giuseppe; Maria, Giorgio

    2015-01-01

    Botulinum toxin A inhibits neuromuscular transmission. It has become a drug with many indications. The range of clinical applications has grown to encompass several neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum toxin A provides benefit in diseases of the gastrointestinal tract. Although toxin blocks cholinergic nerve endings in the autonomic nervous system, it has also been shown that it does not block non-adrenergic non-cholinergic responses mediated by nitric oxide. This has promoted further interest in using botulinum toxin A as a treatment for overactive smooth muscles and sphincters. The introduction of this therapy has made the treatment of several clinical conditions easier, in the outpatient setting, at a lower cost and without permanent complications. This review presents current data on the use of botulinum toxin A in the treatment of pathological conditions of the gastrointestinal tract. PMID:26035487

  3. Treatment of gastrointestinal sphincters spasms with botulinum toxin A.

    PubMed

    Brisinda, Giuseppe; Sivestrini, Nicola; Bianco, Giuseppe; Maria, Giorgio

    2015-05-29

    Botulinum toxin A inhibits neuromuscular transmission. It has become a drug with many indications. The range of clinical applications has grown to encompass several neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum toxin A provides benefit in diseases of the gastrointestinal tract. Although toxin blocks cholinergic nerve endings in the autonomic nervous system, it has also been shown that it does not block non-adrenergic non-cholinergic responses mediated by nitric oxide. This has promoted further interest in using botulinum toxin A as a treatment for overactive smooth muscles and sphincters. The introduction of this therapy has made the treatment of several clinical conditions easier, in the outpatient setting, at a lower cost and without permanent complications. This review presents current data on the use of botulinum toxin A in the treatment of pathological conditions of the gastrointestinal tract.

  4. Botulinum toxin physiology in focal hand and cranial dystonia.

    PubMed

    Karp, Barbara Illowsky

    2012-11-20

    The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features, such as task specificity in focal hand dystonia which is not a common feature of cranial dystonia. The physiologic effects of botulinum toxin in these 2 disorders also show both similarities and differences. This paper compares and contrasts the physiology of focal hand and cranial dystonias and of botulinum toxin in the management of these disorders.

  5. Ten Mistakes To Avoid When Injecting Botulinum Toxin.

    PubMed

    Ruiz-Rodriguez, R; Martin-Gorgojo, A

    2015-01-01

    Injection of botulinum toxin is currently the most common cosmetic procedure in the United States, and in recent years it has become-together with dermal fillers-the mainstay of therapy for the prevention and treatment of facial aging. However, in some cases the treatment may lead to a somewhat unnatural appearance, usually caused by loss of facial expression or other telltale signs. In the present article, we review the 10 mistakes that should be avoided when injecting botulinum toxin. We also reflect on how treatment with botulinum toxin influences us through our facial expressions, both in terms of how we feel and what others perceive.

  6. Characterization of Botulinum Progenitor Toxins by Mass Spectrometry†

    PubMed Central

    Hines, Harry B.; Lebeda, Frank; Hale, Martha; Brueggemann, Ernst E.

    2005-01-01

    Botulinum toxin analysis has renewed importance. This study included the use of nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to characterize the protein composition of botulinum progenitor toxins and to assign botulinum progenitor toxins to their proper serotype and strain by using currently available sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with trypsin, and identified by matching the processed product ion spectra of the tryptic peptides to proteins in accessible databases. All proteins known to be present in progenitor toxins from each serotype were identified. Additional proteins, including flagellins, ORF-X1, and neurotoxin binding protein, not previously reported to be associated with progenitor toxins, were present also in samples from several serotypes. Protein identification was used to assign toxins to a serotype and strain. Serotype assignments were accurate, and strain assignments were best when either sufficient nucleotide or amino acid sequence data were available. Minor difficulties were encountered using neurotoxin-associated protein identification for assigning serotype and strain. This study found that combined nanoscale chromatographic and mass spectrometric techniques can characterize C. botulinum progenitor toxin protein composition and that serotype/strain assignments based upon these proteins can provide accurate serotype and, in most instances, strain assignments using currently available information. Assignment accuracy will continue to improve as more nucleotide/amino acid sequence information becomes available for different botulinum strains. PMID:16085839

  7. Characterization of botulinum progenitor toxins by mass spectrometry.

    PubMed

    Hines, Harry B; Lebeda, Frank; Hale, Martha; Brueggemann, Ernst E

    2005-08-01

    Botulinum toxin analysis has renewed importance. This study included the use of nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to characterize the protein composition of botulinum progenitor toxins and to assign botulinum progenitor toxins to their proper serotype and strain by using currently available sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with trypsin, and identified by matching the processed product ion spectra of the tryptic peptides to proteins in accessible databases. All proteins known to be present in progenitor toxins from each serotype were identified. Additional proteins, including flagellins, ORF-X1, and neurotoxin binding protein, not previously reported to be associated with progenitor toxins, were present also in samples from several serotypes. Protein identification was used to assign toxins to a serotype and strain. Serotype assignments were accurate, and strain assignments were best when either sufficient nucleotide or amino acid sequence data were available. Minor difficulties were encountered using neurotoxin-associated protein identification for assigning serotype and strain. This study found that combined nanoscale chromatographic and mass spectrometric techniques can characterize C. botulinum progenitor toxin protein composition and that serotype/strain assignments based upon these proteins can provide accurate serotype and, in most instances, strain assignments using currently available information. Assignment accuracy will continue to improve as more nucleotide/amino acid sequence information becomes available for different botulinum strains.

  8. The history of Botulinum toxin: from poison to beauty.

    PubMed

    França, Katlein; Kumar, Anagha; Fioranelli, Massimo; Lotti, Torello; Tirant, Michael; Roccia, Maria Grazia

    2017-03-15

    Botulinum toxin, also called the "miracle toxin," is a neurotoxin produced by the bacteria Clostridium botulinum. It is known to block nerve signals that contract muscles resulting in a temporary paralysis of the muscles. Toxins type A and B have been extensively studied and utilized in the realm of beauty and cosmetology. Initially, the toxin gained popularity as a disease-causing "poison". It was only later that it found its way to becoming a must have in modern aesthetic practice. Today, this wonder toxin has proven to be an apt and convenient option in the field of anti-aging medicine.

  9. [Spasticity and botulinum toxin in 2003. An update].

    PubMed

    Fève, A

    2003-05-01

    After the spastic foot in cerebral palsy, there are now wider indications for botulinum toxin injections in spasticity. Post stroke upper limb spasticity has been usefully treated by botulinum toxin in several studies, including double blind placebo-controlled studies. Two serotypes and one serotype B are marketed, with various properties. Botulinum toxin has been studied in multiple etiologies of spasticity. In multiple sclerosis, few studies revealed an efficacy in angulations and comfort. In spinal cord injuries, gait and sphincter disorders can be improved. In post stroke spasticity, lower limb angulations are improved, but gait remained difficult to evaluate. In upper limb spasticity, angulation, function and quality of life were improved in double blind, placebo controlled studies. Comparisons of costs and efficacy are made between botulinum toxin and the other antispastic methods.

  10. Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke

    PubMed Central

    Hou, Saiyun; Ivanhoe, Cindy; Li, Sheng

    2015-01-01

    Abstract Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases. This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance. During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization. The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia. PMID:26266368

  11. Mechanisms of Toxin Production of Food Bacteria (Clostridium botulinum)

    DTIC Science & Technology

    1980-03-25

    food bacteria such as ’Clostridium botulinum. and closely related > organisms. Results from these studies show that C. botulinum types C and D cease...S to produce their dominant toxins when -they are cured o’ftheir prophages.’. These i nontoxigenic derivatives then become sensitive to bacteriophages...of other. culture C.) which induce the production of different toxins . One cured-strain of type C was shown to be sensitive to bacteriophages from C

  12. Treatment of a painful keloid with botulinum toxin type A.

    PubMed

    Uyesugi, Betty; Lippincott, Benjamin; Dave, Shashank

    2010-02-01

    Keloids are associated with small-fiber neuropathy and typically present with itching, pain, and allodynia. The following is a case presentation in which painful neuropathic symptoms from a keloid were treated successfully with botulinum toxin type A. To our knowledge, this is the first such case report in the literature. Further research in the use of botulinum toxin to treat keloidal pain is warranted.

  13. Botulinum toxin drugs: brief history and outlook.

    PubMed

    Dressler, D

    2016-03-01

    The global botulinum toxin (BT) market is currently undergoing rapid changes: this may be the time to review the history and the future of BT drug development. Since the early 1990s Botox(®) and Dysport(®) dominated the international BT market. Later, Myobloc(®)/NeuroBloc(®), a liquid BT type B drug, came out, but failed. Xeomin(®) is the latest major BT drug. It features removal of complexing proteins and improved neurotoxin purity. Several new BT drugs are coming out of Korea, China and Russia. Scientific challenges for BT drug development include modification of BT's duration of action, its transdermal transport and the design of BT hybrid drugs for specific target tissues. The increased competition will change the global BT market fundamentally and a re-organisation according to large indication groups, such as therapeutic and cosmetic applications, might occur.

  14. [Use of botulinum toxin for pain therapy].

    PubMed

    Nodera, Hiroyuki

    2008-05-01

    Preventive measures are necessary against contraction of botulism through food intake or due to other factors because the botulinum neurotoxin (BoNT) is one of the strongest toxins. Despite this, given its therapeutic utility in the controll of neuromuscular transmission, BoNT has been utilized to treat diseases related to muscular hyperactivity, such as dystonia and spasticity. Furthermore, it has been recognized that BoNT is also useful in controlling the neurotransmitter release of sensory and autonomic nerve terminals as well. This paper reviews the recent progress in the therapeutic use of BoNT in pain management, for example, in condition such as migraine, myofascial pain syndrome, pelvic pain, and interstitial cystitis.

  15. Botulinum toxin A for the Treatment of Overactive Bladder.

    PubMed

    Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

    2016-02-29

    The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

  16. Botulinum toxin A for the Treatment of Overactive Bladder

    PubMed Central

    Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

    2016-01-01

    The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder. PMID:26938559

  17. Toxin yet not toxic: Botulinum toxin in dentistry.

    PubMed

    Archana, M S

    2016-04-01

    Paracelsus contrasted poisons from nonpoisons, stating that "All things are poisons, and there is nothing that is harmless; the dose alone decides that something is a poison". Living organisms, such as plants, animals, and microorganisms, constitute a huge source of pharmaceutically useful medicines and toxins. Depending on their source, toxins can be categorized as phytotoxins, mycotoxins, or zootoxins, which include venoms and bacterial toxins. Any toxin can be harmful or beneficial. Within the last 100 years, the perception of botulinum neurotoxin (BTX) has evolved from that of a poison to a versatile clinical agent with various uses. BTX plays a key role in the management of many orofacial and dental disorders. Its indications are rapidly expanding, with ongoing trials for further applications. However, despite its clinical use, what BTX specifically does in each condition is still not clear. The main aim of this review is to describe some of the unclear aspects of this potentially useful agent, with a focus on the current research in dentistry.

  18. Effectiveness of Botulinum Toxin Administered to Abolish Acquired Nystagmus

    NASA Technical Reports Server (NTRS)

    Leigh, R. John; Tomsak, Robert L.; Grant, Michael P.; Remler, Bernd F.; Yaniglos, Stacy S.; Lystad, Lisa; Dell'Osso, Louis F.

    1992-01-01

    We injected botulinum toxin into the horizontal rectus muscles of the right eyes of two patients who had acquired pendular nystagmus with horizontal, vertical, and torsional components. This treatment successfully abolished the horizontal component of the nystagmus in the injected eye in both patients for approximately 2 months. Both patients showed a small but measurable improvement of vision in the injected eye that may have been limited by coexistent disease of the visual pathways. The vertical and torsional components of the nystagmus persisted in both patients. In one patient, the horizontal component of nystagmus in the noninjected eye increased; we ascribe this finding to plastic-adaptive changes in response to paresis caused by the botulinum toxin. Such plastic-adaptive changes and direct side effects of the injections - such as diplopia and ptosis - may limit the effectiveness of botulinum toxin in the treatment of acquired nystagmus. Neither patient elected to repeat the botulinum treatment.

  19. Botulinum Toxin A for Controlling Obesity

    PubMed Central

    Pero, Raffaela; Coretti, Lorena; Lembo, Francesca

    2016-01-01

    Rapid growth of the overweight population and the number of obese individuals in recent decades suggests that current strategies based on diet, exercise, and pharmacological knowledge are not sufficient to address this epidemic. Obesity is the result of a high caloric intake and energy storage, not counterbalanced by an equally important energy expense. Botulinum toxin type A (BoNT-A) use is rapidly expanding to include treatment of a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, painful, and cosmetic disorders. Many studies evaluating the effect of BoNT-A in gastric antrum e/o fundus for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BoNT-A in laparatomized rats induced a significant reduction of food intake and body weight. These studies have been published yielding debated results. Differences in the selection of patients, the doses of BoNT-A, the method of administration of the toxin, and the instruments of evaluation of some parameters among these studies may be the cause. In this review, it will study the state-of-the-art use of BoNT-A in obesity basic science models and review the clinical evidence on the therapeutic applications of BoNT-A for obesity. PMID:27681739

  20. FDA Approves First Botulism Antitoxin for Use in Neutralizing All Seven Known Botulinum Nerve Toxin Serotypes

    MedlinePlus

    ... approves first Botulism Antitoxin for use in neutralizing all seven known botulinum nerve toxin serotypes Product to ... contains a mixture of antibody fragments that neutralize all of the seven botulinum nerve toxin serotypes known ...

  1. An aptamer beacon responsive to botulinum toxins.

    PubMed

    Bruno, John G; Richarte, Alicia M; Carrillo, Maria P; Edge, Allison

    2012-01-15

    Sixty candidate DNA aptamers were developed against botulinum neurotoxin (BoNT) type A light chain (LC) from ten rounds of selection, resulting in several identical sequences. Secondary structures of the identical aptamers were compared to structures of previously reported BoNT A DNA aptamers. A series of ten candidate loop structures were selected from this comparison as potential binding pockets and aptamer beacons. These candidate beacons were synthesized with 5'-TYE 665 and 3'-Iowa Black quencher labels for comparison of fluorescence levels as a function of BoNT A LC concentration. Only three of the ten candidates exhibited any fluorescence response to increasing levels of BoNT A LC. However, of the two most responsive candidates, one represented a subset loop of the larger more intensely fluorescent double-looped structure, designated Beacon 10. This beacon yielded a lower limit of detection of 1 ng/mL in buffer using a spectrofluorometer and a portable handheld fluorometer, but also responded substantially to BoNT A, B, E holotoxins and heavy or light chain components even in a dilute soil suspension, but not in 50% human serum. Beacon 10 did not respond strongly to a variety of other divergent peptides, suggesting that it is relatively specific to the level of botulinum toxins and is only useful for environmental testing. Beacon 10 also shared short sequence segments with other published BoNT aptamer DNA sequences, suggesting that these may be points of physical contact between the aptamers and BoNTs.

  2. The use of botulinum toxin A in perioral rejuvenation.

    PubMed

    Kaplan, Seth E; Sherris, David A; Gassner, Holger G; Friedman, Oren

    2007-11-01

    Botulinum toxin A is an effective and safe treatment for perioral rejuvenation. This article explores the application of this toxin for cosmetic use in the perioral region, facial asymmetry, and improved facial wound healing. This article also describes how the use of botulinum toxin A, which has traditionally been used on the upper one third of the face, has expanded to the lower two thirds with the advent of a new formulation that consists of botulinum toxin combined with an anesthetic agent and a vasoconstrictor. The new formula provides the injecting physician with immediate feedback on the eventual treatment effect and reduces local diffusion of the simultaneously injected agents, potentially limiting systemic absorption and diffusion to neighboring muscle groups and adding to an already remarkable safety profile.

  3. Botulinum toxin the poison that heals: A brief review

    PubMed Central

    Dutta, Shubha Ranjan; Passi, Deepak; Singh, Mahinder; Singh, Purnima; Sharma, Sarang; Sharma, Abhimanyu

    2016-01-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram-positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. This paper aims at discussing botulinum neurotoxin, its structure, mechanism of action, pharmacology, its serotypes and the reasons for wide use of type A, the various indications and contraindications of the use of botulinum neurotoxin and finally the precautions taken when botulinum neurotoxin is used as a treatment approach. We have searched relevant articles on this subject in various medical databases including Google Scholar, PubMed Central, ScienceDirect, Wiley Online Library, Scopus, and Copernicus. The search resulted in more than 2669 articles, out of which a total of 187 were reviewed. However, the review has been further constricted into only 54 articles as has been presented in this manuscript keeping in mind the page limitation and the limitation to the number of references. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin (BT) is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle-associated proteins responsible for acetylcholine release into the neuromuscular junction. A fascinating aspect of BT research in recent years has been the development of the most potent toxin into a molecule of significant therapeutic utility. It is the first biological toxin which is licensed for the treatment of human diseases. The present review focuses on both warfare potential as well as medical uses of botulinum neurotoxin. PMID:28163472

  4. Botulinum toxin the poison that heals: A brief review.

    PubMed

    Dutta, Shubha Ranjan; Passi, Deepak; Singh, Mahinder; Singh, Purnima; Sharma, Sarang; Sharma, Abhimanyu

    2016-01-01

    Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram-positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. This paper aims at discussing botulinum neurotoxin, its structure, mechanism of action, pharmacology, its serotypes and the reasons for wide use of type A, the various indications and contraindications of the use of botulinum neurotoxin and finally the precautions taken when botulinum neurotoxin is used as a treatment approach. We have searched relevant articles on this subject in various medical databases including Google Scholar, PubMed Central, ScienceDirect, Wiley Online Library, Scopus, and Copernicus. The search resulted in more than 2669 articles, out of which a total of 187 were reviewed. However, the review has been further constricted into only 54 articles as has been presented in this manuscript keeping in mind the page limitation and the limitation to the number of references. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin (BT) is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle-associated proteins responsible for acetylcholine release into the neuromuscular junction. A fascinating aspect of BT research in recent years has been the development of the most potent toxin into a molecule of significant therapeutic utility. It is the first biological toxin which is licensed for the treatment of human diseases. The present review focuses on both warfare potential as well as medical uses of botulinum neurotoxin.

  5. Development of a quail embryo model for the detection of botulinum toxin type A activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clostridium botulinum is a ubiquitous microorganism which under certain anaerobic conditions can produce botulinum toxins. Due to concerns in regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or...

  6. Emerging treatments for overactive bladder: clinical potential of botulinum toxins.

    PubMed

    Tincello, Douglas G; Rashid, Tina; Revicky, Vladimir

    2014-01-01

    Overactive bladder (OAB) is a symptom syndrome including urgency, frequency, and nocturia - with or without incontinence. It is a common manifestation of detrusor overactivity (DO). DO is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. OAB is, therefore, both a motor and sensory disorder. Botulinum toxin is a purified form of the neurotoxin from Clostridium botulinum and has been used in medicine for many years. Over the last 10 years, it has been used for the treatment of DO and OAB when standard treatments, such as bladder training and oral anticholinergic medication, have failed to provide symptom relief. Botulinum toxin acts by irreversibly preventing neurotransmitter release from the neurons in the motor end plate and also at sensory synapses, although the clinical effect is not permanent due to the growth of new connections within treated tissues. It is known that botulinum toxin modulates vanillioid, purinergic, capsaicin, and muscarinic receptor expression within the lamina propria, returning them to levels seen in normal bladders. Clinically, the effect of botulinum toxin on symptoms of OAB and DO is profound, with large effects upon the symptom of urgency, and also large effects on frequency, nocturia, leakage episodes, and continence rates. These effects have been seen consistently within eight randomized trials and numerous case series. Botulinum toxin appears safe, with the only common side effect being that of voiding difficulty, occurring in up to 10% of treated patients. Dosing regimens are variable, depending on which preparation is used, but it is clear that dose recommendations have fallen over the last 5 years. There is limited evidence about the efficacy of repeat treatments. Botulinum toxin is an effective and safe second-line treatment for patients with OAB and DO.

  7. Methods for detection of Clostridium botulinum toxin in foods.

    PubMed

    Sharma, Shashi K; Whiting, Richard C

    2005-06-01

    Botulism is a deadly disease caused by ingestion of the preformed neurotoxin produced from the anaerobic spore-forming bacteria Clostridium botulinum. Botulinum neurotoxins are the most poisonous toxins known and have been a concern in the food industry for a long time. Therefore, rapid identification of botulinum neurotoxin using molecular and biochemical techniques is an essential component in the establishment of coordinated laboratory response systems and is the focus of current research and development. Because of the extreme toxicity of botulinum neurotoxin, some confirmatory testing with the mouse bioassay is still necessary, but rapid methods capable of screening large numbers of samples are also needed. This review is focused on the development of several detection methods for botulinum neurotoxins in foods.

  8. Botulinum toxin A, brain and pain.

    PubMed

    Matak, Ivica; Lacković, Zdravko

    2014-01-01

    Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a potential biological threat. At the same time, it is among the most widely used therapeutic proteins used yearly by millions of people, especially for cosmetic purposes. Currently, its clinical use in certain types of pain is increasing, and its long-term duration of effects represents a special clinical value. Efficacy of BoNT/A in different types of pain has been found in numerous clinical trials and case reports, as well as in animal pain models. However, sites and mechanisms of BoNT/A actions involved in nociception are a matter of controversy. In analogy with well known neuroparalytic effects in peripheral cholinergic synapses, presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On the other hand, growing number of behavioral and immunohistochemical studies demonstrated the requirement of axonal transport for BoNT/A's antinociceptive action. In addition, toxin's enzymatic activity in central sensory regions was clearly identified after its peripheral application. Apart from general pharmacology, this review summarizes the clinical and experimental evidence for BoNT/A antinociceptive activity and compares the data in favor of peripheral vs. central site and mechanism of action. Based on literature review and published results from our laboratory we propose that the hypothesis of peripheral site of BoNT/A action is not sufficient to explain the experimental data collected up to now.

  9. Treatment of camptocormia with botulinum toxin.

    PubMed

    Bertram, Kelly L; Stirpe, Paola; Colosimo, Carlo

    2015-12-01

    Camptocormia is defined as an involuntary axial postural distortion of >45° flexion which occurs in the upright position, increases whilst walking and resolves when supine (Ashour and Jankovic, 2006). Unlike orthopaedic or age related kyphosis it is not a fixed structural deformity and produces kyphosis at predominantly lumbar and thoracic rather than cervical regions. Camptocormia has been reported due to a wide range of neurologic, psychiatric, muscular and orthopaedic conditions as well as rare reports of its emergence following the initiation of a number of medications (Finsterer and Strobl, 2010). Parkinson's disease (PD) includes prominent motor features of bradykinesia, rigidity and reduced postural balance responses in all those affected with this disease, but can also cause a range of other motor and non-motor features. Camptocormia is reported in a minority of patients with PD, and it is usually associated with longer disease duration and greater disease burden (Tiple et al., 2009). The aetiology of camptocormia in PD is debated, and responses to treatment have been generally poor and variable between studies. Recent studies have suggested the use of botulinum toxin may improve posture in some affected individuals.

  10. [Botulinum toxin: from drug to poison].

    PubMed

    Dressler, D; Saberi, F A

    2009-08-01

    For most of its time, the history of botulinum toxin (BT) has been the history of botulism, i. e. of an intoxication with BT. By the end of the 1960's a paradigm shift took place which in this radicalness had never occurred before in the history of mankind. At that time BT was first used therapeutically to treat strabismus. From ophthalmology BT rapidly spread into numerous medical specialties. For most of its indications BT is the therapy of choice, for some it has revolutionized their treatment altogether. The widespread therapeutic use of BT allowed detailed clinical and technical investigations of BT's action upon the human body. Applying this knowledge we diagnosed for the first time chronic botulism in adults living on a farm with chronic bovine botulism. This constitutes another radical paradigm shift. The history of BT is the history of a dual paradigm shift each time induced by a complete reversal of the viewing perspective. Knowledge gain can be a linear process. It can, however, also be a circular one. Changes of the viewing perspective are crucial. Changing the viewing perspective may facilitate knowledge gain. This might be used to develop an instrument to facilitate knowledge gain.

  11. Treatment of displaced mandibular condylar fracture with botulinum toxin A.

    PubMed

    Akbay, Ercan; Cevik, Cengiz; Damlar, Ibrahim; Altan, Ahmet

    2014-04-01

    The aim of this case report is to discuss the effect on condylar reduction of botulinum toxin A treatment used in a child with displaced fracture at condylar neck of mandible. A 3-years old boy was admitted to our clinic for incomplete fracture of mandibular symphysis and displaced condylar fracture at the left side. An asymmetrical occlusal splint with intermaxillary fixation was used instead of open reduction and internal fixation because of incomplete fracture of symphysis and possible complications of condyle surgery. However, it was observed that condylar angulation persisted despite this procedure. Thus, botulinum toxin A was administered to masseter, temporalis and pterygoideus medialis muscles. At the end of first month, it was seen that mandibular condyle was almost completely recovered and that fusion was achieved. In conclusion, Botulinum A toxin injection aiming the suppression of masticatory muscle strength facilitates the reduction in the conservative management of displaced condyle in pediatric patients.

  12. Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes.

    PubMed

    Hill, Karen K; Smith, Theresa J

    2013-01-01

    Clostridium botulinum is a species of spore-forming anaerobic bacteria defined by the expression of any one or two of seven serologically distinct botulinum neurotoxins (BoNTs) designated BoNT/A-G. This Gram-positive bacterium was first identified in 1897 and since then the paralyzing and lethal effects of its toxin have resulted in the recognition of different forms of the intoxication known as food-borne, infant, or wound botulism. Early microbiological and biochemical characterization of C. botulinum isolates revealed that the bacteria within the species had different characteristics and expressed different toxin types. To organize the variable bacterial traits within the species, Group I-IV designations were created. Interestingly, it was observed that isolates within different Groups could express the same toxin type and conversely a single Group could express different toxin types. This discordant phylogeny between the toxin and the host bacteria indicated that horizontal gene transfer of the toxin was responsible for the variation observed within the species. The recent availability of multiple C. botulinum genomic sequences has offered the ability to bioinformatically analyze the locations of the bont genes, the composition of their toxin gene clusters, and the genes flanking these regions to understand their variation. Comparison of the genomic sequences representing multiple serotypes indicates that the bont genes are not in random locations. Instead the analyses revealed specific regions where the toxin genes occur within the genomes representing serotype A, B, C, E, and F C. botulinum strains and C. butyricum type E strains. The genomic analyses have provided evidence of horizontal gene transfer, site-specific insertion, and recombination events. These events have contributed to the variation observed among the neurotoxins, the toxin gene clusters and the bacteria that contain them, and has supported the historical microbiological, and biochemical

  13. Regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani.

    PubMed

    Connan, Chloé; Denève, Cécile; Mazuet, Christelle; Popoff, Michel R

    2013-12-01

    Botulinum and tetanus neurotoxins are structurally and functionally related proteins that are potent inhibitors of neuroexocytosis. Botulinum neurotoxin (BoNT) associates with non-toxic proteins (ANTPs) to form complexes of various sizes, whereas tetanus toxin (TeNT) does not form any complex. The BoNT and ANTP genes are clustered in a DNA segment called the botulinum locus, which has different genomic localization (chromosome, plasmid, phage) in the various Clostridium botulinum types and subtypes. The botulinum locus genes are organized in two polycistronic operons (ntnh-bont and ha/orfX operons) transcribed in opposite orientations. A gene called botR lying between the two operons in C. botulinum type A encodes an alternative sigma factor which regulates positively the synthesis of BoNT and ANTPs at the late exponential growth phase and beginning of the stationary phase. In Clostridium tetani, the gene located immediately upstream of tent encodes a positive regulatory protein, TetR, which is related to BotR. C. botulinum and C. tetani genomes contain several two-component systems and predicted regulatory orphan genes. In C. botulinum type A, four two-component systems have been found that positively or negatively regulate the synthesis of BoNT and ANTPs independently of BotR/A. The synthesis of neurotoxin in Clostridia seems to be under the control of complex network of regulation.

  14. Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins.

    PubMed

    Dolly, Oliver

    2003-01-01

    Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.

  15. Receptor Binding and Membrane Transport of Botulinum Toxins.

    DTIC Science & Technology

    1988-03-01

    their mechanism of action most important. The history of the study of botulinum toxins ( botox ) reveals the difficulties brought about by i) the...dangers of working with such a poison, ii) the number of different serotypes of botox which can confuse the field of study, iii) the lack of precedence...from other systems of protein toxins to produce working models that can be tested and applied to experiments on botox , and iv) the deficiency of suitable

  16. Receptor Binding and Membrane Transport of Botulinum Toxins

    DTIC Science & Technology

    1987-03-31

    Prevous eoatos are cosoiee ,-,,j - -C,:.;S3,CATCI OF ;J T AG-’E Introduction The study of the mechanism of action of botulinum toxin ( botox ) would be...define a model system of study for botox . It has become apparent that different toxin molecules, such as diphtheria or bacteriocins, contain some...similar structure exists between these molecules from diverse sources. Recent reports on the ability of the botox molecule in supported planar bilayer

  17. Pharmacotherapy in Pediatric Neurogenic Bladder Intravesical Botulinum Toxin Type A

    PubMed Central

    Sager, Cristian; Burek, Carol; Durán, Victor; Corbetta, Juan Pablo; Weller, Santiago; Juan, Bortagaray; López, Juan Carlos

    2012-01-01

    When the neurogenic bladder is refractory to anticholinergics, botulinum toxin type A is used as an alternative. The neurotoxin type A reduces bladder pressure and increases its capacity and wall compliance. Additionally, it contributes to improving urinary continence and quality of life. This novel therapy is ambulatory with a low incidence of adverse effects. Due to its transitory effect, it is necessary to repeat the injections in order to sustain its therapeutic effect. In these review article we talk about Mechanism of Action, Indications, effects, administration and presentations of the Botulinum Neurotoxin Type A in pediatric patients. Also, we make references to controversial issues surrounding its use. A bibliographic search was done selecting articles and revisions from Pubmed. The key words used were botulinum toxin A, neurogenic bladder, and children. The search was limited to patients younger than 18 years of age and reports written in English in the past ten years. PMID:22720170

  18. Longitudinal Phonatory Characteristics after Botulinum Toxin Type A Injection.

    ERIC Educational Resources Information Center

    Fisher, Kimberly V.; And Others

    1996-01-01

    A study investigated the long-term effects of a Botulinum Toxin Type A injection on the glottal competency of a man with adductor spasmodic dysphonia. Results suggest that change in degree of glottal adduction over time can be observed even when vocal instability is present within each recording session. (CR)

  19. History of Botulinum Toxin Treatment in Movement Disorders

    PubMed Central

    Jabbari, Bahman

    2016-01-01

    Background The frontiers of clinical medicine constantly expand as a result of the innovative efforts of visionary researchers and keen observations of seasoned clinicians. In medicine, rarely has a therapeutic agent been found efficacious in the management of so many symptoms and in such a relatively short time as botulinum toxin. One of the most notable contributions of botulinum toxin therapy in clinical medicine is in the field of movement disorders. Methods The English literature was searched using the Yale search engine including but not limited to PubMed and Ovid. The search includes articles from January 1 1980 to March 1 2016. Results A total of 2055 articles were identified. Of these, 132 met the criteria for this review. Discussion This historical review highlights early and seminal contributions that have introduced the application of botulinum toxins in the field of movement disorders and provides evidence-based contributions that have established botulinum toxin as an effective treatment for abnormal movements. PMID:27917308

  20. Botulinum toxin in the management of acquired motor fusion deficiency

    PubMed Central

    Murthy, Ramesh; Kesarwani, Siddharth

    2009-01-01

    Acquired disruption of motor fusion is a rare condition characterized by intractable diplopia. Management of these patients is extremely difficult. Prisms in any combination or even surgery may not help relieve their symptoms. We describe a longstanding case of acquired motor fusion disruption which was managed successfully with botulinum toxin injection. PMID:19861751

  1. Centrifugal microfluidic platform for ultrasensitive detection of Botulinum Toxin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Botulinum neurotoxin – a global public health threat and category A bioterrorism agent - is the most toxic substance known and one of the most challenging toxins to detect due to its lethality at extremely low concentrations. Hence the live-mouse bioassay because of its superior sensitivity, remains...

  2. From poison to remedy: the chequered history of botulinum toxin.

    PubMed

    Erbguth, F J

    2008-01-01

    Botulinum toxin poisoning has afflicted mankind through the mists of time. However, the first incident of food-borne botulism was documented as late as the 18th century, when the consumption of meat and blood sausages gave rise to many deaths throughout the kingdom of Württemberg in South Western Germany. The district medical officer Justinus Kerner (1786--1862), who was also a well-known German poet, published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822 and attributed the intoxication to a biological poison. Kerner also postulated that the toxin might be used for treatment purposes. In 1895, an outbreak of botulism in the small Belgian village of Ellezelles led to the discovery of the pathogen "Clostridium botulinum" by Emile Pierre van Ermengem. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz in the early 1970s, when the type-A serotype was used in medicine to correct strabismus. Other preparations of the type-A toxin were developed and manufactured in the United Kingdom, Germany, and China, whereas a therapeutic type-B toxin was prepared in the United States. To date, the toxin has been used to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain.

  3. Effect of Botulinum Toxin and Surgery among Spasmodic Dysphonia Patients.

    PubMed

    van Esch, Babette F; Wegner, Inge; Stegeman, Inge; Grolman, Wilko

    2017-02-01

    Objective The effect of botulinum toxin among patients with adductor spasmodic dysphonia (AdSD) is temporary. To optimize long-term treatment outcome, other therapy options should be evaluated. Alternative treatment options for AdSD comprise several surgical treatments, such as thyroarytenoid myotomy, thyroplasty, selective laryngeal adductor denervation-reinnervation, laryngeal nerve crush, and recurrent laryngeal nerve resection. Here, we present the first systematic review comparing the effect of botulinum toxin with surgical treatment among patients diagnosed with AdSD. Data Sources MEDLINE (PubMed), EMBASE, and the Cochrane Library. Methods Articles were reviewed by 2 independent authors, and data were compiled in tables for analysis of the objective outcome (voice expert evaluation after voice recording), the subjective outcome (patient self-assessment scores), and voice-related quality of life (Voice Health Index scores). Results No clinical trials comparing both treatment modalities were identified. Single-armed studies evaluated either the effect of botulinum toxin or surgical treatment. Thirteen studies reported outcomes after botulinum toxin treatment (n = 419), and 9 studies reported outcomes after surgical treatment (n = 585 patients). A positive effect of bilateral botulinum toxin injections was found for the objective voice outcome, subjective voice outcome, and quality of life. The duration of the beneficial effect ranged from 15 to 18 weeks. Surgical treatment had an overall positive effect on objective voice improvement, subjective voice improvement, and quality of live. Conclusion No preference for one treatment could be demonstrated. Prospective clinical trials comparing treatment modalities are recommended to delineate the optimal outcomes by direct comparison.

  4. Botulinum Toxin for the Treatment of Tremor and Tics.

    PubMed

    Lotia, Mitesh; Jankovic, Joseph

    2016-02-01

    The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the U.S. Food and Drug Administration for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and nonneurologic disorders. Despite a paucity of randomized controlled trials, BoNT has been found to be beneficial in treating a variety of tremors and tics when used by clinicians skilled in the administration of the drug for these hyperkinetic movement disorders. Botulinum toxin injections can provide meaningful improvement in patients with localized tremors and tics; in some cases, they may be an alternative to other treatments with more undesirable adverse effects.

  5. Botulinum toxins: mechanisms of action, antinociception and clinical applications.

    PubMed

    Wheeler, Anthony; Smith, Howard S

    2013-04-05

    Botulinum toxin (BoNT) is a potent neurotoxin that is produced by the gram-positive, spore-forming, anaerobic bacterium, Clostridum botulinum. There are 7 known immunologically distinct serotypes of BoNT: types A, B, C1, D, E, F, and G. Clostridum neurotoxins are produced as a single inactive polypeptide chain of 150kDa, which is cleaved by tissue proteinases into an active di-chain molecule: a heavy chain (H) of ∼100 kDa and a light chain (L) of ∼50 kDa held together by a single disulfide bond. Each serotype demonstrates its own varied mechanisms of action and duration of effect. The heavy chain of each BoNT serotype binds to its specific neuronal ecto-acceptor, whereby, membrane translocation and endocytosis by intracellular synaptic vesicles occurs. The light chain acts to cleave SNAP-25, which inhibits synaptic exocytosis, and therefore, disables neural transmission. The action of BoNT to block the release of acetylcholine botulinum toxin at the neuromuscular junction is best understood, however, most experts acknowledge that this effect alone appears inadequate to explain the entirety of the neurotoxin's apparent analgesic activity. Consequently, scientific and clinical evidence has emerged that suggests multiple antinociceptive mechanisms for botulinum toxins in a variety of painful disorders, including: chronic musculoskeletal, neurological, pelvic, perineal, osteoarticular, and some headache conditions.

  6. Botulinum toxin type A in the treatment of patients with cervical dystonia

    PubMed Central

    Brashear, Allison

    2009-01-01

    Dystonia is an involuntary movement involving twisting and turning of agonist and antagonist muscles. Cervical dystonia is isolated to neck musculature. Botulinum toxin type A is a safe and effective treatment of this disabling and often painful syndrome. Three forms of botulinum toxin type A are available worldwide to treat patients with cervical dystonia. This is a review of the studies of botulinum toxin type A to treat cervical dystonia. PMID:19707390

  7. Botulinum toxin in the treatment of lingual dystonia induced by speaking.

    PubMed

    Budak, F; Aydın, E; Koçkaya, A; Ilbay, G

    2013-01-01

    Primary lingual dystonia is a rare condition, especially when it is only induced by speaking. Trihexyphenidyl failed to improve the symptoms. Several case series have demonstrated the effectiveness of botulinum toxin injection for the management of focal lingual movement disorders. Only 1 case of botulinum toxin injection for primary lingual dystonia induced by speaking has been reported, but this treatment has limited effectiveness. Our patient was treated with botulinum toxin using a superficial approach for injection into the tongue with continuing excellent results. Lingual botulinum toxin injection is a fairly simple, safe and viable treatment option for lingual dystonia induced by speaking.

  8. Temporomandibular Myofacial Pain Treated with Botulinum Toxin Injection

    PubMed Central

    Mor, Niv; Tang, Christropher; Blitzer, Andrew

    2015-01-01

    This article reviews the diagnoses and treatment of temporomandibular disorders (TMD) and outlines of the role of botulinum toxin (BoNT) in the treatment of myofacial TMD. This manuscript includes a brief history of the use of BoNT in the treatment of pain, the mechanism of action of BoNT, and the techniques for injections, adverse effects and contraindications when using BoNT to treat mayofacial pain caused by TMD. PMID:26213970

  9. Characterization of Botulinum Progenitor Toxins by Mass Spectrometry

    DTIC Science & Technology

    2005-08-01

    strains Hall, Okra , Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with...sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra , Stockholm, MDPH, Alaska, Langeland, and 89 representing...from sero- types A (strain 62A), B (strain Okra ), C (003-9), D (CB-16), E (no designation; equivalent to NCTC 11219 by analysis), and F (Langeland) that

  10. Botulinum toxin testing in animals: the questions remain unanswered.

    PubMed

    Balls, Michael

    2003-12-01

    Questions are raised concerning the testing of botulinum toxin in animals, and the British Government's answers to Parliamentary Questions on this issue are reviewed, with an emphasis on the potential for reducing, refining and replacing the animal tests, which can involve substantial severity, and on the responsibility of the Home Office so see that the Three Rs approach is fully applied in this specific case.

  11. A Beautician's Dystonia: Long-Lasting Effect of Botulinum Toxin

    PubMed Central

    Di Martino, Siria; Dalise, Stefania; Lamola, Giuseppe; Venturi, Martina; Rossi, Bruno; Chisari, Carmelo

    2014-01-01

    Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders). Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin) into the extensor digitorum communis (35 U), flexor carpi radialis (35 U), and flexor digitorum superficialis (30 U) muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment). In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients' ability to work and quality of life. PMID:25143844

  12. Evidence for antinociceptive activity of botulinum toxin type A in pain management.

    PubMed

    Aoki, K Roger

    2003-01-01

    The neurotoxin, botulinum toxin type A, has been used successfully, in some patients, as an analgesic for myofascial pain syndromes, migraine, and other headache types. The toxin inhibits the release of the neurotransmitter, acetylcholine, at the neuromuscular junction thereby inhibiting striated muscle contractions. In the majority of pain syndromes where botulinum toxin type A is effective, inhibiting muscle spasms is an important component of its activity. Even so, the reduction of pain often occurs before the decrease in muscle contractions suggesting that botulinum toxin type A has a more complex mechanism of action than initially hypothesized. Current data points to an antinociceptive effect of botulinum toxin type A that is separate from its neuromuscular activity. The common biochemical mechanism, however, remains the same between botulinum toxin type A's effect on the motor nerve or the sensory nerve: enzymatic blockade of neurotransmitter release. The antinociceptive effect of the toxin was reported to block substance P release using in vitro culture systems. The current investigation evaluated the in vivo mechanism of action for the antinociceptive action of botulinum toxin type A. In these studies, botulinum toxin type A was found to block the release of glutamate. Furthermore, Fos, a product of the immediate early gene, c-fos, expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin. These findings suggest that botulinum toxin type A blocks peripheral sensitization and, indirectly, reduces central sensitization. The recent hypothesis that migraine involves both peripheral and central sensitization may help explain how botulinum toxin type A inhibits migraine pain by acting on these two pathways. Further research is needed to determine whether the antinociceptive mechanism mediated by botulinum toxin type A affects the neuronal signaling pathways that are activated during migraine.

  13. Chloroquine Analog Interaction with C2- and Iota-Toxin in Vitro and in Living Cells

    PubMed Central

    Kronhardt, Angelika; Beitzinger, Christoph; Barth, Holger; Benz, Roland

    2016-01-01

    C2-toxin from Clostridium botulinum and Iota-toxin from Clostridium perfringens belong both to the binary A-B-type of toxins consisting of two separately secreted components, an enzymatic subunit A and a binding component B that facilitates the entry of the corresponding enzymatic subunit into the target cells. The enzymatic subunits are in both cases actin ADP-ribosyltransferases that modify R177 of globular actin finally leading to cell death. Following their binding to host cells’ receptors and internalization, the two binding components form heptameric channels in endosomal membranes which mediate the translocation of the enzymatic components Iota a and C2I from endosomes into the cytosol of the target cells. The binding components form ion-permeable channels in artificial and biological membranes. Chloroquine and related 4-aminoquinolines were able to block channel formation in vitro and intoxication of living cells. In this study, we extended our previous work to the use of different chloroquine analogs and demonstrate that positively charged aminoquinolinium salts are able to block channels formed in lipid bilayer membranes by the binding components of C2- and Iota-toxin. Similarly, these molecules protect cultured mammalian cells from intoxication with C2- and Iota-toxin. The aminoquinolinium salts did presumably not interfere with actin ADP-ribosylation or receptor binding but blocked the pores formed by C2IIa and Iota b in living cells and in vitro. The blocking efficiency of pores formed by Iota b and C2IIa by the chloroquine analogs showed interesting differences indicating structural variations between the types of protein-conducting nanochannels formed by Iota b and C2IIa. PMID:27517960

  14. Does vitamin B alter the efficacy of botulinum toxin?

    PubMed

    Tatlidede, Soner; Baslo, M Baris; Özkaya, Özay; Soydan, Tufan; Orhan, Elif Kocasoy; Yeşilada, Ayşin Karasoy

    2012-06-01

    Botulinum toxin prevents acetylcholine release at motor nerve terminals. Group B vitamins (B-vit) are essential for proper nerve function. The present study addresses the question of whether B-vit accelerate recovery in rat skeletal muscle after botulinum toxin A (Btx-A) injection. Forty-four adult male Wistar albino rats were used in this experimental study. Rats were divided into three groups: group 1 rats were given Btx-A injection only, group 2 rats were given B-vit supplementation before Btx-A injection, and group 3 rats were given Btx-A and B-vit injections together. During the experiment, compound muscle action potential (CMAP) of the gastrocnemius muscle was recorded before Btx-A injection and sequentially ten times after toxin injection. The statistical significance of the CMAP amplitude change among the groups was analyzed. All groups showed similar amplitude change between consecutive measurement points. In conclusion, combining Btx-A injection with B-vit supplement does not decrease the efficacy of the toxin.

  15. Centrifugal Microfluidic Platform for Ultrasensitive Detection of Botulinum Toxin

    PubMed Central

    2015-01-01

    We present an innovative centrifugal microfluidic immunoassay platform (SpinDx) to address the urgent biodefense and public health need for ultrasensitive point-of-care/incident detection of botulinum toxin. The simple, sample-to-answer centrifugal microfluidic immunoassay approach is based on binding of toxins to antibody-laden capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk and quantification by laser-induced fluorescence. A blind, head-to-head comparison study of SpinDx versus the gold-standard mouse bioassay demonstrates 100-fold improvement in sensitivity (limit of detection = 0.09 pg/mL), while achieving total sample-to-answer time of <30 min with 2-μL required volume of the unprocessed sample. We further demonstrate quantification of botulinum toxin in both exogeneous (human blood and serum spiked with toxins) and endogeneous (serum from mice intoxicated via oral, intranasal, and intravenous routes) samples. SpinDx can analyze, without any sample preparation, multiple sample types including whole blood, serum, and food. It is readily expandable to additional analytes as the assay reagents (i.e., the capture beads and detection antibodies) are disconnected from the disk architecture and the reader, facilitating rapid development of new assays. SpinDx can also serve as a general-purpose immunoassay platform applicable to diagnosis of other conditions and diseases. PMID:25521812

  16. Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin.

    PubMed

    Koh, Chung-Yan; Schaff, Ulrich Y; Piccini, Matthew E; Stanker, Larry H; Cheng, Luisa W; Ravichandran, Easwaran; Singh, Bal-Ram; Sommer, Greg J; Singh, Anup K

    2015-01-20

    We present an innovative centrifugal microfluidic immunoassay platform (SpinDx) to address the urgent biodefense and public health need for ultrasensitive point-of-care/incident detection of botulinum toxin. The simple, sample-to-answer centrifugal microfluidic immunoassay approach is based on binding of toxins to antibody-laden capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk and quantification by laser-induced fluorescence. A blind, head-to-head comparison study of SpinDx versus the gold-standard mouse bioassay demonstrates 100-fold improvement in sensitivity (limit of detection = 0.09 pg/mL), while achieving total sample-to-answer time of <30 min with 2-μL required volume of the unprocessed sample. We further demonstrate quantification of botulinum toxin in both exogeneous (human blood and serum spiked with toxins) and endogeneous (serum from mice intoxicated via oral, intranasal, and intravenous routes) samples. SpinDx can analyze, without any sample preparation, multiple sample types including whole blood, serum, and food. It is readily expandable to additional analytes as the assay reagents (i.e., the capture beads and detection antibodies) are disconnected from the disk architecture and the reader, facilitating rapid development of new assays. SpinDx can also serve as a general-purpose immunoassay platform applicable to diagnosis of other conditions and diseases.

  17. Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin

    SciTech Connect

    Koh, Chung -Yan; Schaff, Ulrich Y.; Piccini, Matthew E.; Stanker, Larry H.; Cheng, Luisa W.; Ravichandran, Easwaran; Singh, Bal -Ram; Sommer, Greg J.; Singh, Anup K.

    2014-12-18

    In this study, we present an innovative centrifugal microfluidic immunoassay platform (SpinDx) to address the urgent biodefense and public health need for ultrasensitive point-of-care/incident detection of botulinum toxin. The simple, sample-to-answer centrifugal microfluidic immunoassay approach is based on binding of toxins to antibody-laden capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk and quantification by laser-induced fluorescence. A blind, head-to-head comparison study of SpinDx versus the gold-standard mouse bioassay demonstrates 100-fold improvement in sensitivity (limit of detection = 0.09 pg/mL), while achieving total sample-to-answer time of <30 min with 2-μL required volume of the unprocessed sample. We further demonstrate quantification of botulinum toxin in both exogeneous (human blood and serum spiked with toxins) and endogeneous (serum from mice intoxicated via oral, intranasal, and intravenous routes) samples. SpinDx can analyze, without any sample preparation, multiple sample types including whole blood, serum, and food. It is readily expandable to additional analytes as the assay reagents (i.e., the capture beads and detection antibodies) are disconnected from the disk architecture and the reader, facilitating rapid development of new assays. SpinDx can also serve as a general-purpose immunoassay platform applicable to diagnosis of other conditions and diseases.

  18. Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin

    DOE PAGES

    Koh, Chung -Yan; Schaff, Ulrich Y.; Sandstone Diagnostics, Livermore, CA; ...

    2014-12-18

    In this study, we present an innovative centrifugal microfluidic immunoassay platform (SpinDx) to address the urgent biodefense and public health need for ultrasensitive point-of-care/incident detection of botulinum toxin. The simple, sample-to-answer centrifugal microfluidic immunoassay approach is based on binding of toxins to antibody-laden capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk and quantification by laser-induced fluorescence. A blind, head-to-head comparison study of SpinDx versus the gold-standard mouse bioassay demonstrates 100-fold improvement in sensitivity (limit of detection = 0.09 pg/mL), while achieving total sample-to-answer time of <30 min with 2-μL required volume of themore » unprocessed sample. We further demonstrate quantification of botulinum toxin in both exogeneous (human blood and serum spiked with toxins) and endogeneous (serum from mice intoxicated via oral, intranasal, and intravenous routes) samples. SpinDx can analyze, without any sample preparation, multiple sample types including whole blood, serum, and food. It is readily expandable to additional analytes as the assay reagents (i.e., the capture beads and detection antibodies) are disconnected from the disk architecture and the reader, facilitating rapid development of new assays. SpinDx can also serve as a general-purpose immunoassay platform applicable to diagnosis of other conditions and diseases.« less

  19. Utilization of quail and chicken embryos for the detection of botulinum toxin type A activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clostridium botulinum is a ubiquitous microorganism which can produce botulinum toxins and the ability to assess toxin activity in a food sample is critical. As an alternative to the mouse assay incubating quail (Coturnix coturnix japonica) and chicken (Gallus gallus domestics) embryos were evaluat...

  20. Prevention of arterial graft spasm by botulinum toxin: an in-vitro experiment.

    PubMed

    Murakami, Eiji; Iwata, Hisashi; Imaizumi, Matsuhisa; Takemura, Hirohumi

    2009-09-01

    In coronary artery bypass surgery, arterial grafts result in improved patency rates. However, these grafts frequently fail due to spasm. Papaverine has been used to prevent graft spasm, but its effect is short-lived. Botulinum toxin inhibits muscle contraction for about three months. We investigated the usefulness of botulinum toxin in preventing arterial grafts spasm in vitro. Samples of abdominal aorta from male Wistar rats were cut into 2 mm rings and treated with various doses of botulinum toxin or papaverine for 30 min. All rings were stimulated with KCl and noradrenaline. Tension was recorded using myography. We compared constriction caused by noradrenaline or KCl in rings treated with botulinum toxin, or papaverine, or physiological salt solution (PSS) (control). In the presence of KCl and noradrenaline, almost all concentrations of botulinum toxin completely inhibited arterial contraction when compared with controls. Spasm prevention was lost after 60 min in rings with papaverine but persisted for 120 min in rings with botulinum toxin. In the histological examination, arterial wall structure was not destroyed by botulinum toxin. Botulinum toxin prevented arterial graft spasm in vitro and had a longer lasting effect than papaverine, with no toxic effect on the artery.

  1. Nonspecific toxicites in the mouse assay test for botulinum toxin.

    PubMed

    Segner, W P; Schmidt, C F

    1968-08-01

    In inoculated pack experiments on Clostridium botulinum type E, unirradiated and 0.1-Mrad irradiated haddock fillets often gave nonspecific toxicities by the mouse assay test for botulinum toxin. Samples given 0.2-Mrad radiation failed to produce nonspecific reactions. Nonspecific deaths sometimes occurred within 24 hr after injection, although deaths between 24 and 48 hr were more common. The symptoms and the pattern of these deaths suggested a septicemia. Heart-blood cultured from mice showing nonspecific symptoms indicated an infectious process. Among 23 isolates from the blood, eight were identified as Proteus vulgaris, two P. morganii, one P. rettgeri, one Providence subgroup B, two Aerobacter aerogenes, one Actinobacillus, three enterococci, one Alcaligenes marshalli, and four Erysipelothrix insidiosa. The E. insidiosa, Aerobacter, Providence group, and most of the Proteus isolates were infectious for mice when injected by the intraperitoneal route. But the enterococci, Alcaligenes, and Actinobacillus isolates were not infectious and probably represent secondary invaders. The cultural characteristics of the E. insidiosa isolates conform to those described in the literature, with the exception that the four strains grew in the temperature range 50 F (10 C) to 40 F (4.4 C). Nonspecific toxicities were avoided in assays for botulinum toxin by the protection of mice with chloramphenicol and oxytetracycline.

  2. In Vitro Acetylcholinesterase Inhibition by Type A Botulinum Toxin

    PubMed Central

    Marshall, R.; Quinn, L. Y.

    1967-01-01

    Type A botulinum toxin was studied for its ability to inhibit the action of acetyl-cholinesterase. The chromogenic substrate, indophenyl acetate, was used for assay of enzyme activity. Inhibition of enzyme function was detected through use of both 6.6 × 10−6 mg (20 ld50) and 6.6 × 10−10 mg (2 × 10−3ld50) of type A botulinal toxin. Control assays were performed by use of both homologous antitoxin and heterologous antitoxins (types B and E). Enzyme inhibition was effectively prevented by use of homologous antitoxin only. The inhibition noted was specific and reproducible for given substrate, enzyme, and toxin concentrations. PMID:4860916

  3. The medicinal chemistry of botulinum, ricin and anthrax toxins.

    PubMed

    Hicks, Rickey P; Hartell, Mark G; Nichols, Daniel A; Bhattacharjee, Apurba K; van Hamont, John E; Skillman, Donald R

    2005-01-01

    The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population from the medical consequences of these weapons. In addition there are major health concerns associated with a pre-exposure mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria Bacillus anthracis. Anthrax will be addressed because of its similarity in both structure and mechanism of catalytic activity with botulinum toxin. The common feature of these three agents is that they exhibit their biological activity via toxin enzymatic hydrolysis of a specific bond in their respective substrate molecules. A brief introduction to the history of each of the biological warfare agents is presented followed by a discussion on the mechanisms of action of each at the molecular level, and a review of current potential inhibitors under investigation.

  4. Advances in Assays and Analytical Approaches for Botulinum Toxin Detection

    SciTech Connect

    Grate, Jay W.; Ozanich, Richard M.; Warner, Marvin G.; Bruckner-Lea, Cindy J.; Marks, James D.

    2010-08-04

    Methods to detect botulinum toxin, the most poisonous substance known, are reviewed. Current assays are being developed with two main objectives in mind: 1) to obtain sufficiently low detection limits to replace the mouse bioassay with an in vitro assay, and 2) to develop rapid assays for screening purposes that are as sensitive as possible while requiring an hour or less to process the sample an obtain the result. This review emphasizes the diverse analytical approaches and devices that have been developed over the last decade, while also briefly reviewing representative older immunoassays to provide background and context.

  5. Botulinum toxin: a novel treatment for pediatric cyclic esotropia.

    PubMed

    Jones, Alistair; Jain, Saurabh

    2014-12-01

    Cyclic esotropia is a rare entity in which an esotropia presents in a regular 48-96 hour cycle, typically described as a 24-hour period of orthotropia followed by a 24-hour period of esotropia. The underlying mechanism of this phenomenon is unknown. Treatment usually involves surgical correction of the manifest strabismus. We report the case of a 3-year-old girl whose cyclic esotropia was broken following injection of botulinum toxin to both medial rectus muscles. She has remained constantly esophoric for 1 year.

  6. A new treatment for frostbite sequelae; Botulinum toxin

    PubMed Central

    Norheim, Arne Johan; Mercer, James; Musial, Frauke; de Weerd, Louis

    2017-01-01

    ABSTRACT Frostbite sequelae are a relevant occupational injury outcome for soldiers in arctic environments. A Caucasian male soldier suffered frostbite to both hands during a military winter exercise. He developed sensory-motor disturbances and cold hypersensitivity. Angiography and thermography revealed impaired blood flow while Quantitative Sensory Testing indicated impaired somato-sensory nerve function. Two years after the initial event, he received an off label treatment with Botulinum toxin distributed around the neurovascular bundles of each finger. After treatment, cold sensitivity was reduced while blood flow and somato-sensory nerve function improved. The successful treatment enabled the soldier to successfully pursue his career in the army.

  7. In Silico Analysis for the Study of Botulinum Toxin Structure

    NASA Astrophysics Data System (ADS)

    Suzuki, Tomonori; Miyazaki, Satoru

    2010-01-01

    Protein-protein interactions play many important roles in biological function. Knowledge of protein-protein complex structure is required for understanding the function. The determination of protein-protein complex structure by experimental studies remains difficult, therefore computational prediction of protein structures by structure modeling and docking studies is valuable method. In addition, MD simulation is also one of the most popular methods for protein structure modeling and characteristics. Here, we attempt to predict protein-protein complex structure and property using some of bioinformatic methods, and we focus botulinum toxin complex as target structure.

  8. Tonsils--place of botulinum toxin production: results of routine laboratory diagnosis in farm animals.

    PubMed

    Böhnel, H; Wagner, C; Gessler, F

    2008-08-25

    Since a case of a veterinarian was reported, who was likely to be infected/intoxicated by Clostridium botulinum during the handling of a diseased animal, tonsils in animals were tested for botulinum neurotoxin and bacterial forms of neurotoxic Clostridium botulinum during routine botulism laboratory examinations including standard samples (intestinal tract and liver) from 48 cattle, 11 horses, and 14 goats. Ten out of 60 samples from tonsils contained free botulinum toxin, and 12 out of 59 were positive for live toxin producing bacteria. In 32 out of 162 intestinal samples toxin was detected. Toxin producing bacteria were found in 37 samples. Eight of 56 liver samples contained free toxin, and 15 out of 43 toxigenic bacteria. Samples from 10 slaughter pigs were all negative, whereas from slaughter cattle tonsils had a high incidence of toxin (7 of 10) or toxigenic bacteria (2 of 8). The results are discussed in the context of effects on animal health and botulism as zoonosis.

  9. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin.

    PubMed

    Erbguth, Frank J

    2004-03-01

    Food-borne botulism probably has accompanied mankind since its beginning. However, we have only few historical sources and documents on food poisoning before the 19th century. Some ancient dietary laws and taboos may reflect some knowledge about the life-threatening consumption of poisoned food. One example of such a dietary taboo is the 10th century edict of Emperor Leo VI of Byzantium in which manufacturing of blood sausages was forbidden. Some ancient case reports on intoxications with Atropa belladonna probably described patients with food-borne botulism, because the combination of dilated pupils and fatal muscle paralysis cannot be attributed to an atropine intoxication. At the end of the 18th century, some well-documented outbreaks of "sausage poisoning" in Southern Germany, especially in Württemberg, prompted early systematic botulinum toxin research. The German poet and district medical officer Justinus Kerner (1786-1862) published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822. Kerner did not succeed in defining the suspected "biological poison" which he called "sausage poison" or "fatty poison." However, he developed the idea of a possible therapeutic use of the toxin. Eighty years after Kerner's work, in 1895, a botulism outbreak after a funeral dinner with smoked ham in the small Belgian village of Ellezelles led to the discovery of the pathogen Clostridium botulinum by Emile Pierre van Ermengem, Professor of bacteriology at the University of Ghent. The bacterium was so called because of its pathological association with the sausages (Latin word for sausage = "botulus") and not-as it was suggested-because of its shape. Modern botulinum toxin treatment was pioneered by Alan B. Scott and Edward J. Schantz.

  10. Type C botulinum toxin causes degeneration of motoneurons in vivo.

    PubMed

    Zhao, Li-Chun; Yang, Bo; Wang, Rengang; Lipton, Stuart A; Zhang, Dongxian

    2010-01-06

    All botulinum toxins (BoNTs, types A-G) inhibit synaptic transmitter release from motoneurons, and thus result in respiratory arrest and death. Rapid treatment with anti-BoNT antibodies can prevent progression, but recovery still requires weeks on a ventilator. Even after recovery, there is a potential for persistent fatigue in some cases of botulism even years after the insult, possibly because of motoneuron dropout for previously unknown reasons. Unique among BoNTs, the C-type (BoNT/C) cleaves two proteins involved in neurotransmitter release, syntaxin and SNAP-25, and induces apoptotic cell death in cultured cerebellar neurons. It is not clear, however, whether BoNT/C also affects neurons that encounter toxin in vivo, namely motoneurons. Here, we provide experimental evidence that BoNT/C causes a slow degeneration of motoneurons both in vitro and in vivo. This novel form of BoNT/C-induced cell death may require new treatment strategies.

  11. Efficacy of botulinum toxins on bruxism: an evidence-based review.

    PubMed

    Long, Hu; Liao, Zhengyu; Wang, Yan; Liao, Lina; Lai, Wenli

    2012-02-01

    The objective of this study was to assess the efficacy of botulinum toxins on bruxism. Electronic databases (PubMed, Embase and Science Citation Index), websites (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) and the literature database of SIGLE (System for Information on Grey Literature in Europe) were searched from January 1990 to April 2011 for randomised controlled trials or nonrandomised studies assessing the efficacy of botulinum toxins on bruxism. There was no language restriction. Through a predefined search strategy, we retrieved 28 studies from PubMed, 94 from Embase, 60 from the Science Citation Index, two ongoing clinical trials and two from the Cochrane Central Register of Controlled Trials. Of these, only four studies met our inclusion criteria and were finally included. Of the four included studies, two were randomised controlled trials and two were controlled before-and-after studies. These studies showed that botulinum toxin injections can reduce the frequency of bruxism events, decrease bruxism-induced pain levels and satisfy patients' self-assessment with regard to the effectiveness of botulinum toxins on bruxism. In comparison with oral splint, botulinum toxins are equally effective on bruxism. Furthermore, botulinum toxin injections at a dosage of <100 U are safe for otherwise healthy patients. Botulinum toxin injections are effective on bruxism and are safe to use. Therefore, they can be used clinically for otherwise healthy patients with bruxism.

  12. Dual toxin-producing strain of Clostridium botulinum type Bf isolated from a California patient with infant botulism.

    PubMed

    Barash, Jason R; Arnon, Stephen S

    2004-04-01

    A retrospective study of Clostridium botulinum strains isolated from patients from California with infant botulism identified the fourth known C. botulinum strain that produces both type B and type F botulinum toxins. This unique strain represented 0.12% of the California infant botulism case isolates from 1976 to 2003. The relative concentrations of type B and F toxins produced were temperature dependent.

  13. Beneficial effects of botulinum toxin type a for patients with painful tic convulsif.

    PubMed

    Micheli, Federico; Scorticati, María Clara; Raina, Gabriela

    2002-01-01

    Botulinum toxin is a well-known therapy for patients with diverse movement disorders. Its application has been extended to other disorders. Here, we document the case of a 70-year-old man with hemifacial spasm associated to trigeminal neuralgia secondary to an ectatic basilar artery. He was treated with botulinum toxin type A, 2.5 mouse units over five sites at the orbicularis oculi and one over the buccinator muscle. After botulinum toxin injections, relief was gained not only from twitching but also from pain. When the effects of the toxin vanished, spasms and pain recurred. Further infiltrations were given every 12 weeks following the same response pattern. This observation further validates the increasing role of botulinum toxin in pain management.

  14. Severe compensatory hyperhidrosis following thoracic sympathectomy successfully treated with low doses of botulinum toxin A.

    PubMed

    Santana-Rodríguez, Norberto; Clavo, Bernardino; Calatayud-Gastardi, Joaquín; García-Castellano, José Manuel; Ponce-González, Miguel A; Olmo-Quintana, Vicente; Llontop, Pedro; Alvarez-Prats, Alejandro; Yordi, Nagib Atallah; Ruíz-Caballero, José Antonio

    2012-12-01

    Compensatory hyperhidrosis is an adverse effect of thoracic sympathectomy that can be debilitating, which is why an efficient treatment is demanded. Botulinum toxin is an emerging treatment, not well known yet. We report two cases of compensatory hyperhidrosis following thoracic sympathectomy which were both treated with low doses of botulinum toxin A. The patients, a male and a female, noted a high level of satisfaction with the abolishment of sweating that was maintained up to 10 months. We consider that low doses of botulinum toxin A is a well tolerated, safe and effective treatment for compensatory hyperhidrosis and should be offered as an alternative treatment.

  15. A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Botulism is a serious foodborne neuroparalyic disease caused by botulinum neurotoxin (BoNT) produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We repo...

  16. Ranula successfully treated by botulinum toxin type A: report of 3 cases.

    PubMed

    Chow, Tam-Lin; Chan, Sharon W W; Lam, Siu-Ho

    2008-01-01

    The conventional treatment of ranula is surgical procedure. We report an innovative method for ranula by using botulinum toxin type A on 3 patients. All 3 cases of ranula resolved after this minimally invasive therapy. The treatment complication was minimal.

  17. Frontal Alopecia after Repeated Botulinum Toxin Type A Injections for Forehead Wrinkles: An Underestimated Entity?

    PubMed Central

    Di Pietro, Antonino; Piraccini, Bianca Maria

    2016-01-01

    Background Injections of botulinum toxin type A in the forehead have never been reported to cause hair side effects. Objective The aim of this paper is to report a new type of alopecia, which we have seen in women undergoing periodic injections of botulinum toxin type A for forehead wrinkles, and to differentiate it from other types of hair loss. Methods We conducted an observational study on 5 females recruited from a private and an institutional practice who complained of progressive recession of the hairline after periodic injections of botulinum toxin type A in the forehead. Results Alopecia of the frontal hairline was evident in all 5 patients, with absence of skin atrophy or scarring and progressive hair miniaturization at trichoscopy. Conclusion Dermatologists should be aware of the possible occurrence of frontal alopecia after repeated injections of botulinum toxin type A for forehead wrinkles. PMID:27843928

  18. Botulinum toxin type a in the treatment of children with congenital muscular torticollis.

    PubMed

    Oleszek, Joyce L; Chang, Nicki; Apkon, Susan D; Wilson, Pamela E

    2005-10-01

    This is a retrospective case series describing the use of botulinum toxin type A in the treatment of children with congenital muscular torticollis who fail to progress with conservative management. A total of 27 children with congenital muscular torticollis, 6-18 mos of age, received 30 botulinum toxin type A injections into their sternocleidomastoid or upper trapezius muscle, or both, at a pediatric tertiary care center between 1995 and 2001. Three children received repeat injections. Twenty of 27 children (74%) had improved cervical rotation or head tilt after the injections, and 2 of 27 (7%) experienced transient adverse events, specifically, mild dysphagia and neck weakness. This series suggests that botulinum toxin type A may be a safe and effective treatment option for children with congenital muscular torticollis who are unresponsive to a traditional regimen of physical therapy and a home program. A prospective, randomized controlled trial is necessary to definitively assess the role of botulinum toxin type A in this population.

  19. Botulinum toxin type A in the healing of chronic lesion following bilateral spasticity of gluteus muscle.

    PubMed

    Cigna, Emanuele; Maruccia, Michele; Fanelli, Benedetta; Scuderi, Nicolò

    2014-08-01

    Use of botulinum toxin is expanding as the clinical studies demonstrate new potential therapeutic applications. In rehabilitation, botulinum toxin is above all used as adjunct therapy for the treatment of spasticity, but it may prove useful for other atypical clinical situations. A 17-year-old man had a sub-arachnoid haemorrhage following the rupture of cerebral aneurism. The patient presented gluteus maximus and medius bilaterally spasticity that produced a chronic lesion in the intergluteal cleft, a flexed wrist and a flexed elbow. As treatment for this spasticity, a total of 100 U botulinum toxin type A were injected into the glutei muscles. This treatment allowed for application of topical medication and subsequently, chronic lesion healing. Botulinum toxin A may be an important therapeutic aid for clinicians faced with treating persistent pathological conditions caused by spasticity.

  20. Botulinum Toxin Injection for Spastic Scapular Dyskinesia After Stroke: Case Series.

    PubMed

    Hou, Saiyun; Ivanhoe, Cindy; Li, Sheng

    2015-08-01

    Spastic scapular dyskinesia after stroke is rare, which causes impaired shoulder active range of motion (ROM). To date, there has been no report about botulinum toxin injection to spastic periscapular muscles. This study presents botulinum toxin A injection for management of spastic periscapular muscles after stroke in 2 cases.This is a retrospective study of 2 cases of spastic scapular dyskinesia after stroke. Spasticity of periscapular muscles including rhomboid and lower trapezius was diagnosed by physical examination and needle electromyographic study. Botulinum toxin was injected into the spastic periscapular muscles under ultrasound imaging guidance.During the 3-week follow-up visit after injection, both patients showed increased shoulder active ROM, without any sign of scapular destabilization.The results suggest that botulinum toxin injection to spastic periscapular muscles can increase shoulder active ROM without causing scapular destabilization in patients with poststroke spastic scapular dyskinesia.

  1. Use of botulinum toxin in cheiloplasty: A new method to decrease tension

    PubMed Central

    Galárraga, Iván Marcelo Cueva

    2009-01-01

    OBJECTIVE: To determine if the use of botulinum toxin during cheiloplasty could help in the management of tension at the surgical wound level. INTERVENTIONS: Five children younger than six months of age, who were born with complete cleft lip and palate, were treated with a dose of 10 units of botulinum toxin injected into the upper lip during surgery. Before the surgery, an electromyographic study was carried out on the patients’ upper lips. A Millard-type cheiloplasty was performed and 10 days later, a second electromyographic study was performed on the upper lips of all the patients. RESULTS: There was a significant change (P<0.039) in the electromyographic tracing obtained after the application of botulinum toxin, especially during rest. CONCLUSION: As confirmed by electromyography, botulinum toxin effectively inhibits the action of the orbicularis oris muscle, especially when at rest; consequently, the tension is decreased at the level of the surgical wound. PMID:20808741

  2. Presence of Clostridium botulinum and botulinum toxin in milk and udder tissue of dairy cows with suspected botulism.

    PubMed

    Böhnel, H; Gessler, F

    2013-04-13

    Clostridium botulinum is an anaerobic spore-forming bacterium prevalent in the environment, and causes botulism in man and animals via toxins. Dairy cattle may be contaminated or infected by feed, water or other environmental factors. Milk may also carry the pathogen. Hence, milk and udder samples need to be tested. The number of clinical cases of bovine botulism in Germany has been increasing since the mid-1990s. Besides routine samples, additional 99 milk samples from 37 farms, and 51 udder samples from 51 farms from sick animals presumably affected by botulism were tested microbiologically by the mouse bioassay. Milk from three farms (8.1 per cent) contained botulinum toxin, and from two (5.4 per cent) bacterial states of C botulinum. Ten udder samples (19.6 per cent) contained toxin, and 7 (13.7 per cent) bacterial forms, including one case where both toxin and bacteria were found. The findings are discussed. Positive milk samples containing botulinum toxin or bacteria raise concern of food safety for the human consumer. Pathological udder samples may show either infection prior to, or contamination after death.

  3. Bruxism secondary to brain injury treated with Botulinum toxin-A: a case report

    PubMed Central

    El Maaytah, Mohammed; Jerjes, Waseem; Upile, Tahwinder; Swinson, Brian; Hopper, Colin; Ayliffe, Peter

    2006-01-01

    We report a successful treatment of bruxism in a patient with anoxic brain injury using botulinum toxin-A (BTX-A). On examination the mouth opening was 0 mm, no feeding was possible through the mouth. Botulinum toxin was injected into the masseter and temporalis; great improvement in trismus and bruxism was noted after 3 weeks. One further treatment improved the mouth opening on the following week and the patient was discharged from our care to be reviewed when required. PMID:17123443

  4. Objective tinnitus from palatal myoclonus. Use of botulinum toxin: a case report.

    PubMed

    Conill Tobías, Noemi; de Paula Vernetta, Carlos; García Callejo, Francisco Javier; Marco Algarra, Jaime

    2012-01-01

    Objective tinnitus can have many different etiologies, palatal myoclonus being one of the less frequent. This type of tinnitus is generated by involuntary rhythmic contraction of the soft palate, which generates an audible click for the patient and for the explorer. Botulinum toxin achieves temporary muscle paralysis through presynaptic inhibition of the acetylcholine level at the neuromuscular union. We present a patient with long-term objective tinnitus, along with this patient's response to botulinum toxin injection.

  5. Botulinum Toxin Treatment for Limb Spasticity in Childhood Cerebral Palsy

    PubMed Central

    Pavone, Vito; Testa, Gianluca; Restivo, Domenico A.; Cannavò, Luca; Condorelli, Giuseppe; Portinaro, Nicola M.; Sessa, Giuseppe

    2016-01-01

    CP is the most common cause of chronic disability in childhood occurring in 2–2.5/1000 births. It is a severe disorder and a significant number of patients present cognitive delay and difficulty in walking. The use of botulinum toxin (BTX) has become a popular treatment for CP especially for spastic and dystonic muscles while avoiding deformity and pain. Moreover, the combination of physiotherapy, casting, orthotics and injection of BTX may delay or decrease the need for surgical intervention while reserving single-event, multi-level surgery for fixed musculotendinous contractures and bony deformities in older children. This report highlights the utility of BTX in the treatment of cerebral palsy in children. We include techniques for administration, side effects, and possible resistance as well as specific use in the upper and lower limbs muscles. PMID:26924985

  6. Applications of botulinum toxin in dentistry: A comprehensive review

    PubMed Central

    Srivastava, Sanjeev; Kharbanda, Smriti; Pal, U. S.; Shah, Vinit

    2015-01-01

    The horizons of treatment options in dentistry are broadening rapidly. In this scenario, applications of unconventional treatment options like use of botulinum toxin (BT) are gaining momentum. The use of BT has been popularly accepted in esthetic procedures like management of facial wrinkles; however, it has been documented to be successful in a variety of conditions. Of particular interest to this paper are applications of BT in the maxillofacial region, concerned to dentistry. BT offers a transient, reversible, relatively safe treatment option to many conditions of interest to a dental practitioner. Dental surgeons by their virtue of being extensively aware of the anatomy of faciomaxillary region are a potential pool of operators who can use BT in their armamentarium with minor skill enhancement and thus widen the perspective of alternative, minimally invasive options to refractory conditions or invasive protocols. PMID:27390488

  7. Bilateral Lower Sternocleidomastoid Botulinum Toxin Injections to Address Refractory Anterocollis.

    PubMed

    Peng-Chen, Zhongxing; Thompson, Amanda; Rodriguez, Ramon L

    2016-03-01

    Anterocollis is a type of cervical dystonia characterized by simultaneous and repetitive antagonist muscles contractions, resulting in abnormal neck flexion. It was described with a frequency of 6.8% from 399 patients with diagnosis of cervical dystonia and usually coexists with torticollis and/or laterocollis, as mixed cervical dystonia patterns. Botulinum toxin is usually a practical and effective treatment for cervical dystonia. The target muscles to inject in anterocollis are usually sternocleidomastoid and scalene muscles. There is also a case report suggesting longus collis involvement. Nevertheless, the dosage of the medication in anterocollis is limited by frequent side effects of dysphagia. We described 2 cases of refractory anterocollis. They did not benefit from conventional bilateral upper portion of sternocleidomastoid muscle injections with OnabotulinumtoxinA, but notably improved their symptoms and clinical global impression after switching to injections into bilateral lower portion of sternocleidomastoid muscles, without significant side effects.

  8. Botulinum Toxin in Secondarily Nonresponsive Patients with Spasmodic Dysphonia.

    PubMed

    Mor, Niv; Tang, Christopher; Blitzer, Andrew

    2016-09-01

    Chemodenervation with botulinum toxin (BoNT) has been effective and well tolerated for all types of dystonia for >30 years. We reviewed outcomes of our patients treated with BoNT serotype A (BoNT-A) for spasmodic dysphonia (SD) who became secondarily nonresponsive. We found that 8 of 1400 patients became nonresponsive to BoNT-A (0.57%), which is lower than the secondary nonresponse rate in other dystonias. After a cessation period, 4 of our patients resumed BoNT-A injections, and recurrence of immunoresistance was not seen in any of them. When compared with patients with other dystonias, patients with SD receive extremely low doses of BoNT. Small antigen challenge may explain the lower rate of immunoresistance and long-lasting efficacy after BoNT-A is restarted among secondary nonresponsive patients with SD.

  9. Dataset of botulinum toxin A influence on interleukins under neuropathy.

    PubMed

    Zychowska, Magdalena; Rojewska, Ewelina; Makuch, Wioletta; Luvisetto, Siro; Pavone, Flaminia; Marinelli, Sara; Przewlocka, Barbara; Mika, Joanna

    2016-12-01

    Our data show that botulinum toxin A (BoNT/A) didn't influence motor functions in naïve and CCI-exposed rats, but diminished the neuropathic pain-related behavior. The results indicate that BoNT/A administration diminished the spinal Iba-1 positive cells activation and, in parallel, downregulated IL-1beta. Moreover, we observed that in DRG the protein level of pronociceptive factors (IL-1beta and IL-18) decreased and antinociceptive (IL-10 and IL-1RA) factors increased. Additionally, our behavioral analysis shows that chronic minocycline treatment together with a single BoNT/A injection in CCI-exposed rats has beneficial analgesic effects (M. Zychowska, E. Rojewska, W. Makuch, S. Luvisetto, F. Pavone, S. Marinelli, B. Przewlocka, J. Mika, 2016) [1].

  10. Local injection of botulinum toxin A: an alternative therapy for axillary osmidrosis.

    PubMed

    Xie, Aiguo; Nie, Lanjun; Tan, Qian

    2014-02-01

    The objective of this study was to investigate the efficacy of local injection of botulinum toxin A for treating axillary osmidrosis. One hundred and fifty patients with axillary osmidrosis were randomly divided to receive botulinum toxin A injection treatment (50 U of botulinum toxin A was injected intracutaneously into 6-20 different sites within each axilla, n = 74) or surgical excision of the apocrine glands (n = 76). The patients were followed up for 1-3 months to analyze the therapeutic effect and complications of the two methods. The curative effect in patients with mild and moderate axillary osmidrosis was not significantly different between the botulinum toxin A injection group and operation group. However, for patients with severe axillary osmidrosis, surgery treatment seemed to be superior to botulinum toxin A treatment (P = 0.005). There was also no significant difference in the modified Dermatology Life Quality Index between the two treatments. Two cases showed complications related to hemorrhage and incision infection in the operation group. In conclusion, local injection of botulinum toxin A is a safe, fast and effective treatment for mild and moderate axillary osmidrosis, but the long-term effect remains to be further investigated.

  11. Clinical resistance to three types of botulinum toxin type A in aesthetic medicine.

    PubMed

    Stephan, Farid; Habre, Maya; Tomb, Roland

    2014-12-01

    Botulinum toxin injections have become the most frequent noninvasive cosmetic procedure carried out worldwide. Botulinum toxin has also multiple other indications in different medical fields. However, with the repetition of injections, a new concern has emerged: clinical resistance and loss of effectiveness of the treatment. After reporting a case of primary nonresponsiveness to three types of botulinum toxin type A injections, we conducted a review about all factors leading to the primary or secondary nonresponsiveness, as well as the factors affecting the immunogenicity of this neurotoxin. Most of the reports and studies focused on secondary resistance to botulinum toxin (BT) and the neurotoxin immunogenicity; primary nonresponsiveness was rarely reported. Factors leading to primary or secondary resistance to BT injections were numerous. In the majority of the studies, development of neutralizing antibodies to botulinum toxin was considered responsible of the induced clinical resistance. Patients should be aware of this rising concern as well as clinicians who should learn how to minimize the risk of resistance development, sparing the patients more invasive treatment modalities. Further studies related to botulinum toxin resistance are needed.

  12. Patient considerations in the treatment of cervical dystonia: focus on botulinum toxin type A

    PubMed Central

    Mills, Reversa R; Pagan, Fernando L

    2015-01-01

    Cervical dystonia is the most common form of focal dystonia characterized by involuntary muscle contractions causing abnormal movements and posturing of the head and neck and is associated with significant pain. Botulinum toxin is considered first-line therapy in the treatment of pain and abnormal head posturing associated with cervical dystonia. There are currently three botulinum toxin type A neurotoxins and one botulinum type B neurotoxin commercially available and US Food and Drug Administration (FDA) labeled for the treatment of cervical dystonia. This review will focus on the efficacy, safety, and therapeutic use of botulinum type A neurotoxins in the treatment of cervical dystonia. We conclude with a discussion of factors influencing toxin selection including therapeutic effect, duration of effect, side effect profile, cost, and physician preference. PMID:26082621

  13. Effects of botulinum toxin type D on secretion of tumor necrosis factor from human monocytes

    SciTech Connect

    Imamura, K.; Spriggs, D.; Ohno, T.; Kufe, D.

    1989-05-01

    Botulinum toxins are potent neurotoxins which block the release of neurotransmitters. The effects of these toxins on hematopoietic cells, however, are unknown. Monocytes secrete a variety of polypeptide growth factors, including tumor necrosis factor (TNF). In the study reported here, the effects of botulinum toxin type D on the secretion of TNF from human monocytes were examined. The results demonstrate that biotulinum toxin type D inhibits the release of TNF from monocytes activated by lipopolysaccharide (LPS) but not by 12-O-tetradecanoylphorbol-13-acetate. Botulinum toxin type D had no detectable effect on intracellular TNF levels in LPS-treated monocytes, indicating that the effects of this toxin involve the secretory process. This inhibitory effect of botulinum toxin type D on TNF secretion from LPS-treated monocytes was partially reversed by treatment with 12-O-tetradecanoylphorbol-13-acetate or introduction of guanosine 5'-(/gamma/-thio)t-riphosphate into these cells. The results demonstrate that TNF secretion is regulated by at least two distinct guanine nucleotide-binding proteins, one responsible for the activation of phospholiphase C and another which acts as a substrate for botulinum toxin type D. ADP-ribosylation of monocyte membranes by botulinum toxin type D demonstrated the presence of three substrates with M/sub r/s of 45,000, 21,000, and 17,000. While the role of these substrates in exocytosis is unknown, the results suggest that the M/sub r/ 21,000 substrate is involved in a process other than TNF secretion.

  14. The Case of Botulinum Toxin in Milk: Experimental Data▿ †

    PubMed Central

    Weingart, Oliver G.; Schreiber, Tanja; Mascher, Conny; Pauly, Diana; Dorner, Martin B.; Berger, Thomas F. H.; Egger, Charlotte; Gessler, Frank; Loessner, Martin J.; Avondet, Marc-Andre; Dorner, Brigitte G.

    2010-01-01

    Botulinum neurotoxin (BoNT) is the most toxic substance known to man and the causative agent of botulism. Due to its high toxicity and the availability of the producing organism Clostridium botulinum, BoNT is regarded as a potential biological warfare agent. Because of the mild pasteurization process, as well as rapid product distribution and consumption, the milk supply chain has long been considered a potential target of a bioterrorist attack. Since, to our knowledge, no empirical data on the inactivation of BoNT in milk during pasteurization are available at this time, we investigated the activities of BoNT type A (BoNT/A) and BoNT/B, as well as their respective complexes, during a laboratory-scale pasteurization process. When we monitored milk alkaline phosphatase activity, which is an industry-accepted parameter of successfully completed pasteurization, our method proved comparable to the industrial process. After heating raw milk spiked with a set amount of BoNT/A or BoNT/B or one of their respective complexes, the structural integrity of the toxin was determined by enzyme-linked immunosorbent assay (ELISA) and its functional activity by mouse bioassay. We demonstrated that standard pasteurization at 72°C for 15 s inactivates at least 99.99% of BoNT/A and BoNT/B and at least 99.5% of their respective complexes. Our results suggest that if BoNTs or their complexes were deliberately released into the milk supply chain, standard pasteurization conditions would reduce their activity much more dramatically than originally anticipated and thus lower the threat level of the widely discussed “BoNT in milk” scenario. PMID:20363798

  15. Evaluation of a quail embryo model for the detection of botulinum toxin type A activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The quail embryo was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving 20 ng of BoNT or higher had m...

  16. Rapid Detection and Quantitative Estimation of Type A Botulinum Toxin by Electroimmunodiffusion

    PubMed Central

    Miller, Carol A.; Anderson, Arthur W.

    1971-01-01

    An experimental system is described for the detection and quantitative estimation of type A botulinum toxin by electroimmunodiffusion. The method is shown to be rapid, specific, and quantitative. As little as 14 mouse LD50 per 0.1 ml of type A toxin was detected within 2 hr. When applied to experimentally contaminated foods such as canned tuna, pumpkin, spinach, green beans, and sausage, the technique detected botulinum toxin rapidly and identified it as to type and quantity. A specific rabbit type A antitoxin was produced for this in vitro system since the equine antitoxin (Center for Disease Control) tested in this experiment was found to be unsuitable. Images PMID:5005291

  17. Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation

    NASA Astrophysics Data System (ADS)

    Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra

    1984-02-01

    Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

  18. [Treated patients in survey: High satisfaction with botulinum toxin in palmar hyperhidrosis].

    PubMed

    Deebaj, Richard; Emtestam, Lennart; Lundeberg, Lena; Brandin Samuelsson, Karin; Girnita, Ada

    2015-01-27

    When debilitating, hyperhidrosis can be seen as a disease and not just as a symptom. It is most often a primary condition but can be secondary to other diseases. Aluminum chloride products are the initial treatment modality for palmar hyperhidrosis followed by anticholinergics, iontophoresis and botulinum toxin. The Dermatology Department of the Karolinska University Hospital in Stockholm, Sweden treated 151 patients at 289 visits with botulinum toxin for palmar hyperhidrosis during a two year period (2012-2013). It was found that botulinum toxin had good effect, which lasted between two and five months in 72% of cases. Muscle weakness (pincer grip) was reported at 41% of return visits and was present for less than one to four weeks in 62% of cases. At 56% of return visits, no side effects of botulinum toxin were reported. 90% of patients surveyed thought that botulinum toxin worked well or very well for their condition and 99% valued the treatment they received at the clinic as good to excellent.

  19. Histological and immunohistochemical findings of the action of botulinum toxin in salivary gland: systematic review.

    PubMed

    Oliveira, J B; Evêncio-Neto, J; Baratella-Evêncio, L

    2016-09-05

    The treatment of sialorrhea is necessary for the constant risks posed by hypersalivation. A new therapeutic option comes up with the application of botulinum toxin in salivary glands. However, little is known about its mechanism of action in glandular tissue. Based on the above, this work had the objective to systematically review the literature about the action of botulinum toxin on submandibular and parotid salivary glands tissues. Electronic search was performed in databases of great relevance for this study (PubMed, SciELO, HighWire, Crossref, Scopus, Science Direct, MEDLINE, OLDMEDLINE, Serials Database, NLM Catalog, LILACS and IBECS). Inclusion and exclusion criteria for articles were established, and a total number of 14 articles were selected and used. There are few publications that clarify how the salivary gland acini behave with application of botulinum toxin. Although, the immunohistochemical findings were consistent among authors, showing weak immunoreactivity in glands treated with botulinum toxin. Histometric data are divergent, requiring more detailed studies to answer the questions about the efficacy and safety of botulinum toxin in salivary glands.

  20. Safety and efficacy of botulinum toxin injection therapy for esophageal achalasia in Japan.

    PubMed

    Yamaguchi, Daisuke; Tsuruoka, Nanae; Sakata, Yasuhisa; Shimoda, Ryo; Fujimoto, Kazuma; Iwakiri, Ryuichi

    2015-11-01

    Botulinum toxin injection is an accepted treatment modality for esophageal achalasia in western countries. This pilot study aimed to clarify the effectiveness of botulinum toxin injection for esophageal achalasia in Japanese patients. We enrolled 10 patients diagnosed with esophageal achalasia between 2008 and 2014. A total of 100 U botulinum toxin A was divided into eight aliquots and injected around the esophagogastric junction. We compared the lower esophageal sphincter pressure before and 1 week after treatment. Scores of subjective symptoms for esophageal achalasia were assessed using a visual analog scale (VAS) before and after 1 week of follow-up of treatment. Barium passage was improved in barium esophagography and passage of contrast agent was also improved. Mean Eckardt score was reduced from 5.5 to 1.6 after treatment (p<0.001). By esophageal manometric study, mean lower esophageal sphincter pressure was reduced from 46.9 to 29.1 mmHg after treatment (p = 0.002). One week after treatment, mean VAS score was reduced from 10 to 3.9 (p<0.001). There were no side effects in any cases. Botulinum toxin injection for esophageal achalasia was safe and effective with few complications. Therefore, botulinum toxin could be used as minimally invasive therapy for esophageal achalasia in Japan.

  1. In situ detection of the Clostridium botulinum type C1 toxin gene in wetland sediments with a nested PCR assay

    USGS Publications Warehouse

    Williamson, J.L.; Rocke, T.E.; Aiken, Judd M.

    1999-01-01

    A nested PCR was developed for detection of the Clostridium botulinum type C1 toxin gene in sediments collected from wetlands where avian botulism outbreaks had or had not occurred. The C1 toxin gene was detected in 16 of 18 sites, demonstrating both the ubiquitous distribution of C. botulinum type C in wetland sediments and the sensitivity of the detection assay.

  2. Iatrogenic botulism after the therapeutic use of botulinum toxin-A: a case report and review of the literature.

    PubMed

    Ghasemi, Majid; Norouzi, Rasul; Salari, Mehri; Asadi, Bahador

    2012-01-01

    Local injection of botulinum toxin-A is an accepted treatment for hyperhidrosis. We report 2 cases of primary hyperhidrosis who developed iatrogenic botulism after the therapeutic dose of onabotulinumtoxinA (Botox). This case report highlights the necessity of clinicians having sufficient information of potentially adverse effects, optimal dose, and correct preparation and injection of botulinum toxin-A.

  3. Pain Relief in Cervical Dystonia with Botulinum Toxin Treatment

    PubMed Central

    Camargo, Carlos Henrique Ferreira; Cattai, Lígia; Teive, Hélio Afonso Ghizoni

    2015-01-01

    Dystonia is a neurological disorder characterized by intermittent or sustained muscle contractions that cause abnormal, usually repetitive, movements and postures. Dystonic movements can be tremulous and twisting and often follow a pattern. They are frequently associated with overflow muscle activation and may be triggered or worsened by voluntary action. Most voluntary muscles can be affected and, in the case of the neck muscles, the condition is referred to as cervical dystonia (CD), the most common form of dystonia. The high incidence of pain distinguishes CD from other focal dystonias and contributes significantly to patient disability and low quality of life. Different degrees of pain in the cervical region are reported by more than 60% of patients, and pain intensity is directly related to disease severity. Botulinum toxin (BoNT) is currently considered the treatment of choice for CD and can lead to an improvement in pain and dystonic symptoms in up to 90% of patients. The results for BoNT/A and BoNT/B are similar. The complex relationship between pain and dystonia has resulted in a large number of studies and more comprehensive assessments of dystonic patients. When planning the application of BoNT, pain should be a key factor in the choice of muscles and doses. In conclusion, BoNT is highly effective in controlling pain, and its analgesic effect is sustained for a long time in most CD patients. PMID:26110508

  4. Botulinum toxin A injections for the treatment of hand tremors.

    PubMed

    Trosch, R M; Pullman, S L

    1994-11-01

    We conducted an open-label study to determine the utility of treating severe hand tremors with intramuscular injections of botulinum toxin (BTX) in forearm and arm muscles in 26 patients, 12 with Parkinson's disease (PD) and 14 with essential tremor (ET). The effect after 6 weeks for each patient was evaluated using two clinical rating scales, subjective evaluations of functional improvement and global disability, measures of weakness, and computer-assisted quantitative assessments of tremor. Although none of the clinical scores averaged > 3/4 point change, statistical significance was found on comparison of pre- and postinjection scores in the Webster Tremor and Global Disability Scales in the ET patients. Similarly, although average tremor amplitudes decreased by no more than 25% by quantitative analysis, amplitude decrease significantly correlated with patient subjective assessment in ET. In only two of 12 PD (17%) and three of 14 ET patients (21%) were major quantitative changes in tremor amplitude (> 50% reduction) found after BTX injections. Nevertheless, 10 patients (38%; five PD and five ET) reported moderate to marked subjective improvement in functional benefit after BTX. These findings suggest that although there were no major changes in clinical ratings or objective measurements, BTX injections may subjectively improve tremor in some patients, particularly those with ET.

  5. Botulinum toxin injections for treating neurogenic detrusor overactivity

    PubMed Central

    Bayrak, Ömer; Sadioğlu, Erkan; Onur, Rahmi

    2015-01-01

    Neurogenic detrusor overactivity (NDO) is a disorder that can cause high intravesical pressure, decreased capacity, decreased bladder compliance, and upper urinary system damage. The current treatment options for NDO are established on the basis of agents that block parasympathetic innervation of the detrusor and inhibit involuntary bladder contractions. Several side effects, such as dryness of mouth, constipation, dyspepsia, changes in visual accommodation, somnolence, and being unable to obtain consistently favorable results, caused by anticholinergic agents, which are frequently used for this purpose, decrease the patient’s compliance to treatment. Procedures such as neuromodulation, auto-augmentation, and enterocystoplasty are surgical options, and they could be used as the last alternative. Thus, botulinum toxin (BTX) injections to the detrusor have been commonly performed in recent years and lead to satisfactory results. The mechanism of action of BTX in NDO is based on the principal of smooth muscle relaxation in the bladder by the transient inhibition of neuromuscular nerve signals. The aim is to decrease acetylcholine secretion by blocking presynaptic vesicles in the neuromuscular junction. When studies were evaluated, it was observed that BTX injections to the detrusor muscle are a necessary and effective option in patients with incontinence caused by NDO. This treatment option could be indicated in situations where anticholinergic agents are not effective or could not be tolerated, and it could be a valuable alternative to major surgical treatments. In this review, we evaluated the effectiveness and reliability of BTX in patients with NDO. PMID:26623152

  6. Hemagglutinin gene shuffling among Clostridium botulinum serotypes C and D yields distinct sugar recognition of the botulinum toxin complex.

    PubMed

    Miyata, Keita; Suzuki, Tomonori; Hayashi, Shintaro; Miyashita, Shin-Ichiro; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro; Sagane, Yoshimasa

    2015-10-01

    Clostridium botulinum strains produce a large-sized toxin complex (TC) that is composed of botulinum neurotoxin (BoNT), non-toxic non-hemagglutinin and three different hemagglutinins (HA-70, HA-33 and HA-17). HA components enhance toxin delivery across the intestinal cell wall in a sugar chain-dependent manner. Here we characterized the sugar recognition of serotype D strain 1873 (D-1873) botulinum L-TC. Most L-TCs produced by serotype C and D strains bind to cells via interactions between HA-33 and cell surface sialo-oligosaccharides. However, like the previously reported L-TC produced by serotype C strain Yoichi (C-Yoichi), D-1873 L-TC binds only to cells that have been treated with neuraminidase, indicating that they recognize asialo-oligosaccharides. The D-1873 HA-33 amino acid sequence is similar to that of C-Yoichi, but had lower similarity to the majority of serotype C and D HA-33s. A comparison of TC component primary structures for 12 serotype C and D strains suggested that at least three types of HA-33 genes exist, and these are shuffled among the serotype C and D strains independently of BoNT serotype. This shuffling produces the distinct sugar recognition of serotype C and D botulinum TCs.

  7. [Botulism: structure and function of botulinum toxin and its clinical application].

    PubMed

    Oguma, Keiji; Yamamoto, Yumiko; Suzuki, Tomonori; Fatmawati, Ni Nengah Dwi; Fujita, Kumiko

    2012-08-01

    Clostridium botulinum produces seven immunological distinct poisonous neurotoxins, A to G, with molecular masses of approximately 150kDa. In acidic foods and culture fluid, the neurotoxins associate with non-toxic components, and form large complexes designated progenitor toxins. The progenitor toxins are found in three forms named LL, L, and M. These neurotoxins and progenitor toxins were purified, and whole nucleotide sequences of their structure genes were determined. In this manuscript, the structure and function of these toxins, and the application of these toxins to clinical usage have been described.

  8. Failure to Inhibit In Vitro or In Vivo Acetycholinesterase with Botulinum Toxin Type A

    PubMed Central

    Simpson, Lance L.; Morimoto, Hiromi

    1969-01-01

    An attempt has been made to replicate an earlier finding that type A botulinum toxin can inhibit the in vitro activity of acetylcholinesterase. Two methods of enzyme assay were employed, but with neither technique were we able to reproduce the finding of in vitro enzyme inhibition. In fact, an examination of the data from the previous report leads us to question the possibility of the observations that were given. Furthermore, an investigation was carried out to determine if botulinum toxin can exert an inhibiting effect on acetylcholinesterase that is situated in the biological tissue. The answer again is negative. The experimental observations, coupled with several mathematical computations, do not support the notion that botulinum toxin is an acetylcholinesterase inhibitor. PMID:5773011

  9. Improvement of chronic facial pain and facial dyskinesia with the help of botulinum toxin application

    PubMed Central

    Junghans, Katharina; Rohrbach, Saskia; Ellies, Maik; Laskawi, Rainer

    2007-01-01

    Background Facial pain syndromes can be very heterogeneous and need individual diagnosis and treatment. This report describes an interesting case of facial pain associated with eczema and an isolated dyskinesia of the lower facial muscles following dental surgery. Different aspects of the pain, spasms and the eczema will be discussed. Case presentation In this patient, persistent intense pain arose in the lower part of her face following a dental operation. The patient also exhibited dyskinesia of her caudal mimic musculature that was triggered by specific movements. Several attempts at therapy had been unsuccessful. We performed local injections of botulinum toxin type A (BTX-A) into the affected region of the patient's face. Pain relief was immediate following each set of botulinum toxin injections. The follow up time amounts 62 weeks. Conclusion Botulinum toxin type A (BTX-A) can be a safe and effective therapy for certain forms of facial pain syndromes. PMID:17714591

  10. Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value.

    PubMed

    Zoons, E; Dijkgraaf, M G W; Dijk, J M; van Schaik, I N; Tijssen, M A

    2012-12-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the pharmaco-therapeutic and pharmaco-economic value of botulinum toxin as treatment for focal dystonia, which yielded the following results. Botulinum toxin is the most effective treatment for reducing dystonic symptoms measured with dystonia-specific and general questionnaires, and pain in patients with focal dystonia. Seventy-one percent of patients with cervical dystonia had a reduction in neck pain compared to 12 % in placebo groups. Adverse events occur in 58 % of patients during treatment with botulinum toxin compared to 46 % treated with placebo. Especially dry mouth, neck weakness, dysphagia, and voice changes are common. Adverse events are usually mild and self-limiting. Health-related quality of life, measured with the SF-36 is 20-50 points lower in patients with focal dystonia compared to controls and the effect of botulinum toxin on health-related quality of life is unclear. Botulinum toxin treatment is expensive because the drug itself is expensive. Yearly costs for treating a patient with focal dystonia with botulinum toxin range from EUR 347 to EUR 3,633 and the gain in QALYs with BTX treatment is small. Focal dystonia impairs the productivity and the ability to work. At start of botulinum toxin treatment only 47-50 % was working. Botulinum toxin partly improves this. Overall, we conclude that botulinum toxin is an expensive drug with good effects. From a societal perspective, the costs may well weigh up to the regained quality of life. However, the available literature concerning costs, health-related quality of life and labor participation is very limited. An extensive cost-effectiveness study should be performed incorporating all these aspects.

  11. Arrangement of the Clostridium baratii F7 Toxin Gene Cluster with Identification of a σ Factor That Recognizes the Botulinum Toxin Gene Cluster Promoters

    SciTech Connect

    Dover, Nir; Barash, Jason R.; Burke, Julianne N.; Hill, Karen K.; Detter, John C.; Arnon, Stephen S.

    2014-05-22

    Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bont gene that is part of a toxin gene cluster that includes several accessory genes. In this paper, we sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. Finally, this TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.

  12. Arrangement of the Clostridium baratii F7 toxin gene cluster with identification of a σ factor that recognizes the botulinum toxin gene cluster promoters.

    PubMed

    Dover, Nir; Barash, Jason R; Burke, Julianne N; Hill, Karen K; Detter, John C; Arnon, Stephen S

    2014-01-01

    Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bont gene that is part of a toxin gene cluster that includes several accessory genes. We sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. This TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.

  13. How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

    PubMed Central

    Baron, Maximilien; Grise, Philippe; Cornu, Jean-Nicolas

    2016-01-01

    Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefits of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral reflux, hydronephrosis, renal function based on a comprehensive literature review. PMID:26981445

  14. Safety and efficacy of botulinum toxin in primary orthostatic tremor.

    PubMed

    Bertram, Kelly; Sirisena, Dharshana; Cowey, Max; Hill, Aron; Williams, David R

    2013-11-01

    Primary orthostatic tremor (POT) is a rapid 13-18 Hertz tremor that produces a subjective feeling of unsteadiness when standing, and is absent when seated or supine. It predominantly affects the legs during isometric contraction though a similar tremor can be seen in the arms and jaw. When present in the jaw this rapid tremor has been successfully treated with botulinum toxin. We sought to test whether symptoms of POT improved following injection of abobotulinumtoxinA to muscles in the legs. This randomised, double blind, placebo controlled cross-over design study enrolled eight patients with electrophysiologically confirmed POT. Each patient received injections of either 200 mU abobotulinumtoxinA or 0.9% saline in the tibialis anterior bilaterally, with cross-over after 20 weeks. Electrophysiological and clinical assessments were performed before and 6 weeks after each injection. Seven patients completed the study. No significant differences were seen in the primary outcome measures of time from standing to unsteadiness or symptom diary scores. Electrophysiological characteristics of POT remained remarkably constant throughout the study in all patients with variability of less than 1 Hertz in the frequency recorded. Falls were common, with one patient experiencing a fall with upper limb fracture whilst on the placebo. The frequency of falls correlated with both the severity of the self-rated symptoms and a shorter time to feeling unsteady with eyes closed. In conclusion, treatment with 200 mU of abobotulinumtoxinA in the tibialis anterior does not alter subjective experience of unsteadiness in POT. Postural instability and falls are common.

  15. Therapeutic use of botulinum toxin in migraine: mechanisms of action

    PubMed Central

    Ramachandran, Roshni; Yaksh, Tony L

    2014-01-01

    Migraine pain represents sensations arising from the activation of trigeminal afferents, which innervate the meningeal vasculature and project to the trigeminal nucleus caudalis (TNC). Pain secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the TNC. Such viscerosomatic convergence accounts for referral of migraine pain arising from meningeal afferents to particular extracranial dermatomes. Botulinum toxins (BoNTs) delivered into extracranial dermatomes are effective in and approved for treating chronic migraine pain. Aside from their well-described effect upon motor endplates, BoNTs are also taken up in local afferent nerve terminals where they cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, and prevent local terminal release. However, a local extracranial effect of BoNT cannot account for allthe effects of BoNT upon migraine. We now know that peripherally delivered BoNTs are taken up in sensory afferents and transported to cleave SNARE proteins in the ganglion and TNC, prevent evoked afferent release and downstream activation. Such effects upon somatic input (as from the face) likewise would not alone account for block of input from converging meningeal afferents. This current work suggests that BoNTs may undergo transcytosis to cleave SNAREs in second-order neurons or in adjacent afferent terminals. Finally, while SNAREs mediate exocytotic release, they are also involved in transport of channels and receptors involved in facilitated pain states. The role of such post-synaptic effects of BoNT action in migraine remains to be determined. PMID:24819339

  16. "Off" painful dystonia in Parkinson's disease treated with botulinum toxin.

    PubMed

    Pacchetti, C; Albani, G; Martignoni, E; Godi, L; Alfonsi, E; Nappi, G

    1995-05-01

    The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in

  17. Short communication: Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows.

    PubMed

    Moeller, R B; Puschner, B; Walker, R L; Rocke, T E; Smith, S R; Cullor, J S; Ardans, A A

    2009-06-01

    Three adult lactating Holstein cows were injected in the subcutaneous abdominal vein with 175 ng/kg of body weight of Clostridium botulinum type C toxin (451 cow median toxic doses) to determine if this botulinum toxin crosses the blood-milk barrier. Whole blood (in sodium heparin) and clotted blood serum samples were taken at 0 min, 10 min, and 3, 6, 9, and 12 h postinoculation. Milk samples were taken at 0 min and at 3, 6, 9 and 12 h postinoculation. All samples were tested for the presence of the toxin using the mouse bioassay and immunostick ELISA test. The immunostick ELISA identified the toxin in whole blood and the mouse bioassay identified the toxin in serum at all times examined in all 3 animals. Toxin was not identified by either detection method in milk samples collected from the 3 animals. From these results, it appears that Clostridium botulinum type C toxin does not cross from the blood to the milk in detectable concentrations.

  18. Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows

    USGS Publications Warehouse

    Moeller, R.B.; Puschner, B.; Walker, R.L.; Rocke, T.E.; Smith, S.R.; Cullor, J.S.; Ardans, A.A.

    2009-01-01

    Three adult lactating Holstein cows were injected in the subcutaneous abdominal vein with 175 ng/kg of body weight of Clostridium botulinum type C toxin (451 cow median toxic doses) to determine if this botulinum toxin crosses the blood-milk barrier. Whole blood (in sodium heparin) and clotted blood serum samples were taken at 0 min, 10 min, and 3, 6, 9, and 12 h postinoculation. Milk samples were taken at 0 min and at 3, 6, 9 and 12 h postinoculation. All samples were tested for the presence of the toxin using the mouse bioassay and immunostick ELISA test. The immunostick ELISA identified the toxin in whole blood and the mouse bioassay identified the toxin in serum at all times examined in all 3 animals. Toxin was not identified by either detection method in milk samples collected from the 3 animals. From these results, it appears that Clostridium botulinum type C toxin does not cross from the blood to the milk in detectable concentrations. ?? American Dairy Science Association, 2009.

  19. Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

    PubMed Central

    Hassel, Bjørnar

    2013-01-01

    Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection. PMID:23299659

  20. Employment of higher doses of botulinum toxin type A to reduce spasticity after stroke.

    PubMed

    Santamato, Andrea; Micello, Maria Francesca; Ranieri, Maurizio; Valeno, Giovanni; Albano, Antonio; Baricich, Alessio; Cisari, Carlo; Intiso, Domenico; Pilotto, Alberto; Logroscino, Giancarlo; Panza, Francesco

    2015-03-15

    Spasticity is a common disabling symptom for several neurological conditions. Botulinum toxin type A injection represents the gold standard treatment for focal spasticity with efficacy, reversibility, and low prevalence of complications. Current guidelines suggest a dose up to 600 units (U) of onabotulinumtoxinA/incobotulinumtoxinA or up to 1,500 U of abobotulinumtoxinA to treat post-stroke spasticity to avoid important adverse effects. However, recently, higher doses of botulinum toxin type A were employed, especially in case of upper and lower limb severe spasticity. With searches of US National Library of Medicine databases, we identified all studies published from December 1989 to July 2014 concerning the use of higher doses of this neurotoxin for spasticity treatment with at least a dose of 600 U of onabotulinumtoxinA and incobotulinumtoxinA or 1,800 U of abobotulinumtoxinA. The cumulative body of evidence coming from the eight studies selected suggested that higher doses of botulinum toxin type A appeared to be efficacious in reducing spasticity of the upper and lower limbs after stroke, with adverse effects generally mild. However, further investigations are needed to determine the safety and reproducibility in larger case series or randomized clinical trials of higher doses of botulinum toxin type A also after repeated injections.

  1. Distribution of Botulinum Toxin-Producing Clostridia in Soils of Argentina

    PubMed Central

    Lúquez, Carolina; Bianco, María I.; de Jong, Laura I. T.; Sagua, María D.; Arenas, Graciela N.; Ciccarelli, Alberto S.; Fernández, Rafael A.

    2005-01-01

    We studied the presence of botulinum toxin-producing clostridia in 2,009 soil samples from five geographical regions of Argentina. The prevalence was 23.5%, and the distribution was not homogeneous among the regions. We observed a great multiplicity of serological types and a higher prevalence in nonvirgin soils than in virgin soils. PMID:16000834

  2. Distribution of botulinum toxin-producing clostridia in soils of Argentina.

    PubMed

    Lúquez, Carolina; Bianco, María I; de Jong, Laura I T; Sagua, María D; Arenas, Graciela N; Ciccarelli, Alberto S; Fernández, Rafael A

    2005-07-01

    We studied the presence of botulinum toxin-producing clostridia in 2,009 soil samples from five geographical regions of Argentina. The prevalence was 23.5%, and the distribution was not homogeneous among the regions. We observed a great multiplicity of serological types and a higher prevalence in nonvirgin soils than in virgin soils.

  3. Elevation of the Corner of the Mouth Using Botulinum Toxin Type A

    PubMed Central

    Goldman, Alberto; Wollina, Uwe

    2010-01-01

    Indications for botulinum toxin type A have been constantly evolving, and it can currently be used in virtually any area of the face and neck. The authors present their experience with this neurotoxin in treating the platysmal bands and depressor anguli oris muscle with the purpose of cosmetically improving the anterior neck and lifting the oral commissure. PMID:21430826

  4. Thickened Saliva after Effective Management of Drooling with Botulinum Toxin A

    ERIC Educational Resources Information Center

    Erasmus, Corrie E.; van Hulst, Karen; van den Hoogen, Frank J. A.; van Limbeek, Jacques; Roeleveld, Nel; Veerman, Enno C. I.; Rotteveel, Jan J.; Jongerius, Peter H.

    2010-01-01

    Aim: The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. Method: We enrolled 15 children (11 males and six females; age range 3-17y, mean age 9y 10mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function…

  5. Botulinum toxin A as a treatment for delayed gastric emptying in a dog

    PubMed Central

    Rinaldi, Max L.; Fransson, Boel A.; Barry, Sabrina L.

    2014-01-01

    A toy Australian shepherd dog was referred for bile peritonitis following excision of a biliary mucocele. Subsequent delayed gastric emptying was refractory to prokinetic therapy but responded to injection of botulinum toxin A into the muscularis layer of the pylorus; a novel therapy for delayed gastric emptying in dogs. PMID:24982520

  6. Botulinum Toxin A Injection in the Bladder Neck: A Promising Treatment for Urinary Retention

    PubMed Central

    Alam, Marianne; Zgheib, Joseph; El Khoury, Fouad

    2016-01-01

    Secondary to failure of optimal medical therapy and the high morbidity that accompanies surgical techniques in high risk patients, the use of de novo treatments including botulinum toxin A is emerging in the treatment of benign prostatic hyperplasia (BPH). However, the treatment of urinary retention secondary to BPH via injecting botulinum toxin into the bladder neck is not well established in the literature. This case report describes the case of a 75-year-old male patient with a chronic history of obstructive lower urinary tract symptoms (LUTS) and multiple comorbidities who was admitted to the hospital for management of recurrent urinary retention. The patient was not a surgical candidate for transurethral incision of the prostate (TUIP) or transurethral resection of the prostate (TURP). Botulinum toxin injection into the bladder neck was performed with very satisfying results. Botulinum toxin injection in the bladder neck presents a promising minimally invasive, tolerated, and cost-effective approach for the treatment of urinary retention in patients with benign prostatic obstruction who are not candidates for surgery or in whom medical treatment has failed. More research is needed to identify the efficacy of this novel approach. PMID:27088032

  7. Detection of botulinum toxin types A, B, E, and F activity using the quail embryo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We recently demonstrated an effective new model for the detection of botulinum toxin type A using quail embryos in place of the mouse model. These experiments demonstrated that the Japanese quail embryo at 15 days of incubation was an effective vertebrate animal model to detect the activity of botu...

  8. Botulinum toxin A as a treatment for delayed gastric emptying in a dog.

    PubMed

    Rinaldi, Max L; Fransson, Boel A; Barry, Sabrina L

    2014-07-01

    A toy Australian shepherd dog was referred for bile peritonitis following excision of a biliary mucocele. Subsequent delayed gastric emptying was refractory to prokinetic therapy but responded to injection of botulinum toxin A into the muscularis layer of the pylorus; a novel therapy for delayed gastric emptying in dogs.

  9. Botulinum Toxin A Injection into the Subscapularis Muscle to Treat Intractable Hemiplegic Shoulder Pain

    PubMed Central

    2016-01-01

    Objective To evaluate the beneficial effect of botulinum toxin A (Botox) injection into the subscapularis muscle on intractable hemiplegic shoulder pain. Methods Six stroke patients with intractable hemiplegic shoulder pain were included. Botulinum toxin A was injected into the subscapularis muscle. Intractable hemiplegic shoulder pain was evaluated using an 11-point numerical rating scale. Pain-free range of motion was assessed for shoulder abduction and external rotation. The spasticity of the shoulder internal rotator was measured using the modified Ashworth scale. Assessments were carried out at baseline and at 1, 2, 4, and, if possible, 8 weeks. Results Intractable hemiplegic shoulder pain was improved (p=0.004) after botulinum toxin injection into the subscapularis muscle. Restricted shoulder abduction (p=0.003), external rotation (p=0.005), and spasticity of the shoulder internal rotator (p=0.005) were also improved. Improved hemiplegic shoulder pain was correlated with improved shoulder abduction (r=–1.0, p<0.001), external rotation (r=–1.0, p<0.001), and spasticity of the internal rotator (r=1.0, p<0.001). Conclusion Botulinum toxin A injection into the subscapularis muscle appears to be valuable in the management of intractable hemiplegic shoulder pain. PMID:27606265

  10. Stensen's duct injuries: the role of sialendoscopy and adjuvant botulinum toxin injection

    PubMed Central

    Wierzbicka, Małgorzata; Szyfter, Witold

    2013-01-01

    Introduction Stensen's duct injuries are uncommon but troublesome sequelae of facial surgery or other external traumas. Aim To investigate the feasibility of sialendoscopic control of Stensen's duct in iatrogenic injuries and the efficiency of botulinum toxin adjuvant therapy. Material and methods In 2008 and 2010, 5 patients with parotid sialoceles or fistulas, infrequent complications after plastic surgery or trauma, were treated in a single institution, Poznan University of Medical Sciences ENT Department. The group consisted of 5 patients with diagnosed Stensen's duct injuries, which were post-surgery and post-traumatic sequelae. All were treated by means of open surgery. Botulinum toxin injection was administered during the procedure to decrease the saliva secretion and to improve the healing process. A sialendoscopy was performed to control the lumen of the junction after the duct injury was repaired. Results Complete healing of the fistulas and sialoceles after the reparative surgery followed by a single botulinum toxin application was observed in all patients within 10-14 days. No side effects were noticed. Conclusions Our findings suggest that sialendoscopy is a valuable tool and an important step of control in the surgery of parotid duct injuries and the injection of botulinum toxin is an effective and safe second-line treatment. PMID:23837095

  11. Treatment of cerebral palsy with botulinum toxin A: functional benefit and reduction of disability. Three case reports.

    PubMed

    Mall, V; Heinen, F; Linder, M; Philipsen, A; Korinthenberg, R

    1997-01-01

    Three patients with cerebral palsy are described suffering, respectively, of pes equinus, spasm of the m. teres major and flexion spasm of the hand, who were treated with botulinum toxin A. These patients demonstrate not only the local reduction of the muscular hyperactivity following treatment with botulinum toxin A but also the potential functional benefit resulting from such a treatment. Thus, local intramuscular injection of botulinum toxin A in children with cerebral palsy should be considered as part of a multidisciplinary treatment concept, since reduction of the disability and the functional improvements could have high impact on daily living activities.

  12. Properties and use of botulinum toxin and other microbial neurotoxins in medicine.

    PubMed Central

    Schantz, E J; Johnson, E A

    1992-01-01

    Crystalline botulinum toxin type A was licensed in December 1989 by the Food and Drug Administration for treatment of certain spasmodic muscle disorders following 10 or more years of experimental treatment on human volunteers. Botulinum toxin exerts its action on a muscle indirectly by blocking the release of the neurotransmitter acetylcholine at the nerve ending, resulting in reduced muscle activity or paralysis. The injection of only nanogram quantities (1 ng = 30 mouse 50% lethal doses [U]) of the toxin into a spastic muscle is required to bring about the desired muscle control. The type A toxin produced in anaerobic culture and purified in crystalline form has a specific toxicity in mice of 3 x 10(7) U/mg. The crystalline toxin is a high-molecular-weight protein of 900,000 Mr and is composed of two molecules of neurotoxin (ca. 150,000 Mr) noncovalently bound to nontoxic proteins that play an important role in the stability of the toxic unit and its effective toxicity. Because the toxin is administered by injection directly into neuromuscular tissue, the methods of culturing and purification are vital. Its chemical, physical, and biological properties as applied to its use in medicine are described. Dilution and drying of the toxin for dispensing causes some detoxification, and the mouse assay is the only means of evaluation for human treatment. Other microbial neurotoxins may have uses in medicine; these include serotypes of botulinum toxins and tetanus toxin. Certain neurotoxins produced by dinoflagellates, including saxitoxin and tetrodotoxin, cause muscle paralysis through their effect on the action potential at the voltage-gated sodium channel. Saxitoxin used with anaesthetics lengthens the effect of the anaesthetic and may enhance the effectiveness of other medical drugs. Combining toxins with drugs could increase their effectiveness in treatment of human disease. PMID:1579114

  13. Channels Formed by Botulinum, Tetanus, and Diphtheria Toxins in Planar Lipid Bilayers: Relevance to Translocation of Proteins across Membranes

    NASA Astrophysics Data System (ADS)

    Hoch, David H.; Romero-Mira, Miryam; Ehrlich, Barbara E.; Finkelstein, Alan; Dasgupta, Bibhuti R.; Simpson, Lance L.

    1985-03-01

    The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as ``tunnel proteins'' for translocation of active peptide fragments. These findings support the hypothesis that the active fragments of botulinum neurotoxin and tetanus toxin, like that of diphtheria toxin, are translocated across the membranes of acidic vesicles.

  14. Botulinum toxin for the prevention and healing of wound scars: A systematic review of the literature

    PubMed Central

    Prodromidou, Anastasia; Frountzas, Maximos; Vlachos, Dimitrios-Efthymios G; Vlachos, Georgios D; Bakoyiannis, Ioannis; Perrea, Despina; Pergialiotis, Vasilios

    2015-01-01

    BACKGROUND: Botulinum toxin injections have been investigated for the treatment or prevention of hypertrophic scars in several clinical studies. However, its clinical effectiveness has not yet been established. OBJECTIVE: To examine all available evidence that support the use of botulinum toxin injections for the treatment or prevention of hypertrophic scars in current clinical practice. METHODS: A systematic review searching the MEDLINE (1966 to 2014), Scopus (2004 to 2014), Popline (1974 to 2014), ClinicalTrials.gov (2008 to 2014) and Cochrane Central Register of Controlled Trials (CENTRAL) (1999 to 2014) databases together with reference lists from included studies was conducted. RESULTS: Ten studies (255 patients) were included. Of these, 123 patients were injected with botulinum toxin type A, nine patients were offered botulinum toxin type B and the remaining 123 patients represented the control groups. Significantly improved cosmetic outcomes were observed among certain studies using the visual analogue scale (experimental group: median score 8.25 [range 6 to 10]) versus control group: median score 6.38 [range 2 to 9]; P<0.001) and the Stony Brook Scar Evaluation Scale (experimental group score: 6.7 versus control group score: 4.17; P<0.001) assessments. However, the methodological heterogeneity of the included studies, the lack of control group in the majority of them, the use of subjective scales of measurement and the frequent use of patient self-assessment precluded unbiased results. CONCLUSIONS: Current evidence does not support the usage of botulinum toxin. Future randomized controlled trials are needed in the field to reach firm conclusions regarding its place in current clinical practice. PMID:26665143

  15. “Non-Toxic” Proteins of the Botulinum Toxin Complex Exert In-vivo Toxicity

    PubMed Central

    Miyashita, Shin-Ichiro; Sagane, Yoshimasa; Suzuki, Tomonori; Matsumoto, Takashi; Niwa, Koichi; Watanabe, Toshihiro

    2016-01-01

    The botulinum neurotoxin (BoNT) causes muscle paralysis and is the most potent toxin in nature. BoNT is associated with a complex of auxiliary “Non-Toxic” proteins, which constitute a large-sized toxin complex (L-TC). However, here we report that the “Non-Toxic” complex of serotype D botulinum L-TC, when administered to rats, exerts in-vivo toxicity on small-intestinal villi. Moreover, Serotype C and D of the “Non-Toxic” complex, but not BoNT, induced vacuole-formation in a rat intestinal epithelial cell line (IEC-6), resulting in cell death. Our results suggest that the vacuole was formed in a manner distinct from the mechanism by which Helicobacter pylori vacuolating toxin (VacA) and Vibrio cholerae haemolysin induce vacuolation. We therefore hypothesise that the serotype C and D botulinum toxin complex is a functional hybrid of the neurotoxin and vacuolating toxin (VT) which arose from horizontal gene transfer from an ancestral BoNT-producing bacterium to a hypothetical VT-producing bacterium. PMID:27507612

  16. Kinetic and Reaction Pathway Analysis in the Application of Botulinum Toxin A for Wound Healing

    PubMed Central

    Lebeda, Frank J.; Dembek, Zygmunt F.; Adler, Michael

    2012-01-01

    A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical), surgical (incision) wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data. From several case reports, we developed a qualitative model of how botulinum toxin disrupts the vicious cycle of muscle spasm, pain, inflammation, decreased blood flow, and ischemia. We transformed this model into a minimal kinetic scheme for healing chronic wounds. The model helped us to estimate the rate of decline of this toxin's therapeutic effect by calculating the rate of recurrence of clinical symptoms after a wound-healing treatment with this neurotoxin. PMID:22174710

  17. Botulinum toxin detection using AlGaN /GaN high electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Lin; Chu, B. H.; Chen, K. H.; Chang, C. Y.; Lele, T. P.; Tseng, Y.; Pearton, S. J.; Ramage, J.; Hooten, D.; Dabiran, A.; Chow, P. P.; Ren, F.

    2008-12-01

    Antibody-functionalized, Au-gated AlGaN /GaN high electron mobility transistors (HEMTs) were used to detect botulinum toxin. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN /GaN HEMT drain-source current showed a rapid response of less than 5s when the target toxin in a buffer was added to the antibody-immobilized surface. We could detect a range of concentrations from 1to10ng/ml. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN /GaN HEMTs for botulinum toxin detection.

  18. Study on Potential Clostridium Botulinum Growth and Toxin Production in Parma Ham

    PubMed Central

    Ramini, Mattia; Parolari, Giovanni; Barbuti, Silvana; Frustoli, Maria Angela; Taddei, Roberta; Pongolini, Stefano; Ardigò, Paolo; Cozzolino, Paolo

    2016-01-01

    The objective of this study was to investigate Clostridium botulinum growth and toxin production in the industrially manufactured Italian Parma ham. The study focuses on the Parma ham production phase identified as maximum risk to C. botulinum proliferation, i.e. the transition from cold phase (salting and resting) to a phase carried out at temperature between 15 and 23°C (drying). A preliminary in vitro test was carried out in order to verify the capability of 6 C. botulinum strains (1 type A, 4 type B, and 1 type E strains) to grow in conditions of temperature, pH and NaCl concentration comparable to those of the beginning stage of ham drying. Five C. botulinum strains grew at 20°C and pH 6, four strains produced toxin when inoculated at a concentration equal to 103 cfu/mL at NaCl concentration of 4%, while when the inoculum concentration was 10 cfu/mL, NaCl concentration of 3% resulted the toxin-genesis limiting factor. An experimental contamination with a mixture of the 5 C. botulinum strains selected by the preliminary in vitro test was performed on 9 thighs inoculated at the end of the resting phase. The study was designed to evaluate the potential growth and toxin production in extremely favourable conditions for the bacterium. Type B proteolytic C. botulinum toxin was produced after 14 days of incubation at 20°C in 2 thighs characterised by high weight, low number of days of resting and anomalous physiochemical characteristics [one for very low NaCl concentration (1.59%), the other for elevated pH (6.27) and both for high water activity values (>0.970)]. The results of this research confirm that the cold resting step is a critical phase in the production process of Parma ham for the investigated hazard. Based on the present study, the long resting phase adopted in the manufacturing of Parma ham is proven effective to prevent the growth of C. botulinum, an event which could not otherwise be excluded if the hams were processed under less stringent

  19. Botulinum toxin injection for hypercontractile or spastic esophageal motility disorders: may high-resolution manometry help to select cases?

    PubMed

    Marjoux, S; Brochard, C; Roman, S; Gincul, R; Pagenault, M; Ponchon, T; Ropert, A; Mion, F

    2015-01-01

    Endoscopic injections of botulinum toxin in the cardia or distal esophagus have been advocated to treat achalasia and spastic esophageal motility disorders. We conducted a retrospective study to evaluate whether manometric diagnosis using the Chicago classification in high-resolution manometry (HRM) would be predictive of the clinical response. Charts of patients with spastic and hypertensive motility disorders diagnosed with HRM and treated with botulinum toxin were retrospectively reviewed at two centers. HRM recordings were systematically reanalyzed, and a patient's phone survey was conducted. Forty-five patients treated between 2008 and 2013 were included. Most patients had achalasia type 3 (22 cases). Other diagnoses were jackhammer esophagus (8 cases), distal esophageal spasm (7 cases), esophagogastric junction outflow obstruction (5 cases), nutcracker esophagus (1 case), and 2 unclassified cases. Botulinum toxin injections were performed into the cardia only in 9 cases, into the wall of the distal esophagus in 19 cases, and in both locations (cardia and distal esophagus) in 17 cases. No complication occurred in 31 cases. Chest pain was noticed for less than 7 days in 13 cases. One death related to mediastinitis occurred 3 weeks after botulinum toxin injection. Efficacy was assessed in 42 patients: 71% were significantly improved 2 months after botulinum toxin, and 57% remained satisfied for more than 6 months. No clear difference was observed in terms of response according to manometric diagnosis; however, type 3 achalasia previously dilated and with normal integrated relaxation pressure (4s-integrated relaxation pressure < 15 mmHg) had the worst outcome: none of these patients responded to the endoscopic injection of botulinum toxin. Endoscopic injections of botulinum toxin may be effective in some patients with spastic or hypercontractile esophageal motility disorders. The manometric Chicago classification diagnosis does not seem to predict the results

  20. No clinical or neurophysiological evidence of botulinum toxin diffusion to non-injected muscles in patients with hemifacial spasm.

    PubMed

    Lorenzano, C; Bagnato, S; Gilio, F; Fabbrini, G; Berardelli, A

    2006-04-01

    Botulinum toxin injected into a muscle may diffuse to nearby muscles thus producing unwanted effects. In patients with hemifacial spasm, we evaluated clinically and neurophysiologically, whether botulinum toxin type A (BoNT-A) diffuses from the injection site (orbicularis oculi) to untreated muscles (orbicularis oris from the affected side and orbicularis oculi and oris from the unaffected side). We studied 38 patients with idiopathic hemifacial spasm. Botulinum toxin was injected into the affected orbicularis oculi muscle alone (at 3 standardized sites) at a clinically effective dose. Patients were studied before (T0) and 3-4 weeks after treatment (T1). We evaluated the clinical effects of botulinum toxin and muscle strength in the affected and unaffected muscles. We also assessed the peak-to-peak amplitude compound muscle action potential (CMAP) recorded from the orbicularis oculi and orbicularis oris muscles on both sides after supramaximal electrical stimulation of the facial nerve at the stylomastoid foramen. In all patients, botulinum toxin treatment reduced muscle spasms in the injected orbicularis oculi muscle and induced no muscle weakness in the other facial muscles. The CMAP amplitude significantly decreased in the injected orbicularis oculi muscle, but remained unchanged in the other facial muscles (orbicularis oris muscle on the affected side and contra-lateral unaffected muscles). In conclusion, in patients with hemifacial spasm, botulinum toxin, at a clinically effective dose, induces no clinical signs of diffusion and does not reduce the CMAP size in the nearby untreated orbicularis oris or contralateral facial muscles.

  1. Potential therapeutic effect of intravesical botulinum toxin type A on bladder pain syndrome/interstitial cystitis.

    PubMed

    Jhang, Jia-Fong; Jiang, Yuan-Hong; Kuo, Hann-Chorng

    2014-04-01

    Bladder pain syndrome/interstitial cystitis is characterized by bladder pain associated with urgency, frequency, nocturia, dysuria and sterile urine. Recent studies have shown that these bladder dysfunctions could originate from chronic inflammation or urothelial insult and proceed to a cascade of tissue reactions, which finally ascends to the central nervous system. Pilot studies of intravesical injection of botulinum toxin type A for bladder pain syndrome/interstitial cystitis had been introduced since 2005 with a promising result. Recent evidence suggests that botulinum toxin type A could significantly improve symptoms such as daytime frequency, nocturia, pain, quality of life and bladder capacity in bladder pain syndrome/interstitial cystitis patients. Single injection of botulinum toxin could not achieve long-term successful therapeutic result, and repeat injections could provide a better long-term success rate. However, patients with ulcer type bladder pain syndrome/interstitial cystitis might not gain a benefit from botulinum toxin type A injection. Laboratory evidence showed that botulinum toxin type A for bladder pain syndrome/interstitial cystitis injection could induce peripheral desensitization, reduces bladder chronic inflammation and decreases apoptotic signal molecules in the urothelium. The present article reviewed the recent advances of botulinum toxin type A on bladder pain syndrome/interstitial cystitis.

  2. Production of toxin by Clostridium botulinum type A strains cured by plasmids.

    PubMed Central

    Weickert, M J; Chambliss, G H; Sugiyama, H

    1986-01-01

    Twelve strains of Clostridium botulinum type A and seven strains of Clostridium sporogenes were screened for plasmids by agarose gel electrophoresis of cleared lysates of cells from 5 ml of mid-log-phase culture. Nine type A strains had one or more plasmids of 4.3, 6.8, or 36 megadaltons (MDa); several strains showed a large plasmid of 61 MDa, but it was not consistently recovered. Four C. sporogenes strains had one or more plasmids of 4.3, 5.6 or 36 MDa. Isolates obtained from cultures of plasmid-containing C. botulinum type A strains grown in ionic detergent broth and from spontaneously arising variants were screened both for toxin production and for plasmid content. Toxigenicity of C. botulinum could not be correlated with the presence of any one plasmid. Images PMID:3082278

  3. Analyzing a bioterror attack on the food supply: the case of botulinum toxin in milk.

    PubMed

    Wein, Lawrence M; Liu, Yifan

    2005-07-12

    We developed a mathematical model of a cows-to-consumers supply chain associated with a single milk-processing facility that is the victim of a deliberate release of botulinum toxin. Because centralized storage and processing lead to substantial dilution of the toxin, a minimum amount of toxin is required for the release to do damage. Irreducible uncertainties regarding the dose-response curve prevent us from quantifying the minimum effective release. However, if terrorists can obtain enough toxin, and this may well be possible, then rapid distribution and consumption result in several hundred thousand poisoned individuals if detection from early symptomatics is not timely. Timely and specific in-process testing has the potential to eliminate the threat of this scenario at a cost of <1 cent per gallon and should be pursued aggressively. Investigation of improving the toxin inactivation rate of heat pasteurization without sacrificing taste or nutrition is warranted.

  4. A Monoclonal Antibody Based Capture ELISA for Botulinum Neurotoxin Serotype B: Toxin Detection in Food

    PubMed Central

    Stanker, Larry H.; Scotcher, Miles C.; Cheng, Luisa; Ching, Kathryn; McGarvey, Jeffery; Hodge, David; Hnasko, Robert

    2013-01-01

    Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A – H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD’s) for individual antibodies ranging from 10 to 48 × 10−11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested. PMID:24253240

  5. Use of Clostridium botulinum toxin in gastrointestinal motility disorders in children

    PubMed Central

    Arbizu, Ricardo A; Rodriguez, Leonel

    2015-01-01

    More than a century has elapsed since the identification of Clostridia neurotoxins as the cause of paralytic diseases. Clostridium botulinum is a heterogeneous group of Gram-positive, rod-shaped, spore-forming, obligate anaerobic bacteria that produce a potent neurotoxin. Eight different Clostridium botulinum neurotoxins have been described (A-H) and 5 of those cause disease in humans. These toxins cause paralysis by blocking the presynaptic release of acetylcholine at the neuromuscular junction. Advantage can be taken of this blockade to alleviate muscle spams due to excessive neural activity of central origin or to weaken a muscle for treatment purposes. In therapeutic applications, minute quantities of botulinum neurotoxin type A are injected directly into selected muscles. The Food and Drug Administration first approved botulinum toxin (BT) type A in 1989 for the treatment of strabismus and blepharospasm associated with dystonia in patients 12 years of age or older. Ever since, therapeutic applications of BT have expanded to other systems, including the gastrointestinal tract. Although only a single fatality has been reported to our knowledge with use of BT for gastroenterological conditions, there are significant complications ranging from minor pain, rash and allergic reactions to pneumothorax, bowel perforation and significant paralysis of tissues surrounding the injection (including vocal cord paralysis and dysphagia). This editorial describes the clinical experience and evidence for the use BT in gastrointestinal motility disorders in children. PMID:25992183

  6. Management of gummy smile with Botulinum Toxin Type-A: A case report

    PubMed Central

    Dinker, Sudeeptha; Anitha, A; Sorake, Abhinay; Kumar, Kishore

    2014-01-01

    A 23 year old female patient presented with the chief complaint of gummy smile after previously undergoing Orthodontic treatment. Patient had a straight profile with competent lips and during posed and unposed smile the patient exhibited excessive gingival display. Since the patient was unwilling to undergo Orthodontic treatment and apprehensive about surgical procedures, this problem was addressed by injecting Botulinum toxin type-A as an alternative treatment approach. Two weeks post treatment; on follow up examination, improved results were seen without any side effects. As a result, an attractive and confident smile was perceived by the patient. How to cite the article: Dinker S, Anitha A, Sorake A, Kumar K. Management of gummy smile with Botulinum Toxin Type-A: A case report. J Int Oral Health 2014;6(1):111-5. PMID:24653614

  7. Application of botulinum toxin to treat sialorrhea in amyotrophic lateral sclerosis patients: a literature review

    PubMed Central

    de Oliveira, Ademar Francisco; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier

    2016-01-01

    ABSTRACT Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. PMID:27759834

  8. Clostridium botulinum type A progenitor toxin binds to Intestine-407 cells via N-acetyllactosamine moiety.

    PubMed

    Kojima, Shoudou; Eguchi, Hironobu; Ookawara, Tomomi; Fujiwara, Noriko; Yasuda, Jun; Nakagawa, Kazuhiko; Yamamura, Takehira; Suzuki, Keiichiro

    2005-06-03

    Botulism is a highly fatal disease caused by the botulinum progenitor toxin. In this study, the role of oligosaccharides for the binding of botulinum type A progenitor toxin (type A PTX) to human intestinal cells was investigated. The binding of type A PTX to Intestine-407 cells was inhibited by the addition of N-acetyllactosamine, lactose, and galactose. Treatment of Intestine-407 cells with neuraminidase led to a significant increase in the binding of type A PTX, while further digestion of cell surface oligosaccharides by beta-galactosidase and beta-N-acetylhexosaminidase decreased the binding. These results indicate that the N-acetyllactosamine moiety is responsible for the binding of type A PTX. These findings were further confirmed by a binding assay using synthesized oligosaccharides. Interestingly, sialylation or fucosylation of oligosaccharides inhibited the binding of type A PTX. These data suggest that the type A PTX binds to intestinal cells via cell surface N-acetyllactosamine moiety.

  9. Autologous blood injection and botulinum toxin for resistant plantar fasciitis accompanied by spasticity.

    PubMed

    Logan, Lynne Romeiser; Klamar, Karl; Leon, Jerry; Fedoriw, Wladislaw

    2006-08-01

    An originally ambulatory 18-yr-old woman with spastic left hemiplegic cerebral palsy developed left plantar fasciitis with a gradual loss of function requiring use of a wheelchair. Her symptoms were resistant to physical therapy. Two hundred units of botulinum toxin A was diluted in 4 mL of saline and injected into the gastrocnemius. Three milliliters of autologous blood was injected into the plantar fascia. She reported decreased pain at 3 days postinjection. At 10 days, she had no pain on walking. Dorsiflexion increased and Ashworth and Tardieu improved. A stretching program was taught and a better-fitting night splint was obtained. At 21 days, she exhibited no pain and increased dorsiflexion. Autologous blood injection combined with botulinum toxin A may be an alternative treatment for resistant plantar fasciitis accompanied by spasticity. Our hypothesis is that chronic plantar fasciitis is a degenerative condition and thus is relieved when a mild inflammatory process is created that leads to healing.

  10. Analysis of the mechanisms that underlie absorption of botulinum toxin by the inhalation route.

    PubMed

    Al-Saleem, Fetweh H; Ancharski, Denise M; Joshi, Suresh G; Elias, M; Singh, Ajay; Nasser, Zidoon; Simpson, Lance L

    2012-12-01

    Botulinum toxin is a highly potent oral and inhalation poison, which means that the toxin must have an efficient mechanism for penetration of epithelial barriers. To date, three models for toxin passage across epithelial barriers have been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an auxiliary protein, HA35, transports toxin from the apical to the basal side of epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of epithelial cells to disrupt tight junctions, and this permits paracellular flux of toxin. These models were evaluated by studying toxin absorption following inhalation exposure in mice. Three types of experiments were conducted. In the first, the potency of pure neurotoxin was compared with that of progenitor toxin complex, which contains HA35. The results showed that the rate and extent of toxin absorption, as well as the potency of absorbed toxin, did not depend upon, nor were they enhanced by, the presence of HA35. In the second type of experiment, the potencies of pure neurotoxin and progenitor toxin complex were compared in the absence or presence of antibodies on the apical side of epithelial cells. Antibodies directed against the neurotoxin protected against challenge, but antibodies against HA35 did not. In the final type of experiment, the potency of pure neurotoxin and toxin complex was compared in animals pretreated to deliver antibodies to the basal side of epithelial cells. Once again, antibodies directed against the neurotoxin provided resistance to challenge, but antibodies directed against HA35 did not. Taken collectively, the data indicate that the toxin by itself is capable of crossing epithelial barriers. The data do not support any hypothesis in which HA35 is essential for toxin penetration of epithelial barriers.

  11. Arrangement of the Clostridium baratii F7 Toxin Gene Cluster with Identification of a σ Factor That Recognizes the Botulinum Toxin Gene Cluster Promoters

    DOE PAGES

    Dover, Nir; Barash, Jason R.; Burke, Julianne N.; ...

    2014-05-22

    Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bontmore » gene that is part of a toxin gene cluster that includes several accessory genes. In this paper, we sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. Finally, this TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.« less

  12. Botulinum Toxin Treatment of Autonomic Disorders: Focal Hyperhidrosis and Sialorrhea.

    PubMed

    Hosp, Christine; Naumann, Markus K; Hamm, Henning

    2016-02-01

    Primary focal hyperhidrosis is a common autonomic disorder that significantly impacts quality of life. It is characterized by excessive sweating confined to circumscribed areas, such as the axillae, palms, soles, and face. Less frequent types of focal hyperhidrosis secondary to underlying causes include gustatory sweating in Frey's syndrome and compensatory sweating in Ross' syndrome and after sympathectomy. Approval of onabotulinumtoxinA for severe primary axillary hyperhidrosis in 2004 has revolutionized the treatment of this indication. Meanwhile further type A botulinum neurotoxins like abobotulinumtoxinA and incobotulinumtoxinA, as well as the type B botulinum neurotoxin rimabotulinumtoxinB are successfully used off-label for axillary and various other types of focal hyperhidrosis. For unexplained reasons, the duration of effect differs considerably at different sites. Beside hyperhidrosis, botulinum neurotoxin is also highly valued for the treatment of sialorrhea affecting patients with Parkinson's disease, cerebral palsy, amyotrophic lateral sclerosis, motor neuron disease, and other neurologic conditions. With correct dosing and application, side effects are manageable and transient.

  13. Botulinum Toxin Treatment of Blepharospasm, Orofacial/Oromandibular Dystonia, and Hemifacial Spasm.

    PubMed

    Karp, Barbara Illowsky; Alter, Katharine

    2016-02-01

    Blepharospasm is a focal dystonia characterized by involuntary, repetitive eye closure. Orofacial and oromandibular dystonia describe involuntary dystonic movements of orofacial and oromandibular musculature. Hemifacial spasm is characterized by repetitive synchronous contraction of facial nerve innervated muscles on one side of the face. In this article, the clinical presentation, epidemiology, and approaches to treatment are reviewed. Technical aspects of using botulinum toxin for treatment and reported outcomes are discussed.

  14. Botulinum Toxin: Non-cosmetic Indications and Possible Mechanisms of Action

    PubMed Central

    Wollina, Uwe

    2008-01-01

    Botulinum toxin (BTX) has gained a great interest in cosmetic dermatology for its effects on hyperkinetic facial lines. Understanding the basic research and analysis of effects of this potent drug can lead to other possible indications of interest for dermatologists. The use of BTX in focal hyperhidrosis is well established, but BTX has also effects on pain perception, itch and inflammation as discussed in this review. PMID:20300330

  15. Aesthetic Applications of Botulinum Toxin A in Asians: An International, Multidisciplinary, Pan-Asian Consensus

    PubMed Central

    Sundaram, Hema; Huang, Po-Han; Hsu, Nai-Jen; Huh, Chang Hun; Wu, Woffles T.L.; Wu, Yan; Cassuto, Daniel; Kerscher, Martina J.

    2016-01-01

    Background: Botulinum toxin type A remains the most popular nonsurgical aesthetic treatment worldwide. Previous consensus statements have focused on Caucasians and on Koreans as generally representative of Asians. However, indications and dosages vary among different ethnic groups. This publication reports the results of a multidisciplinary, pan-Asian consensus focusing on incobotulinumtoxinA. Methods: A consensus group of plastic surgeons and dermatologists from Asia, Europe, and the United States convened for a live meeting in Asia, followed by a questionnaire-based Delphi procedure. Treatment of Asians in both their native countries and countries of migration was discussed. Results: For most items, the group achieved a majority consensus. A number of treatment indications, strategies, and dosages were identified in Asians, which are distinct to those previously described for Caucasians due to differences in facial morphotypes, anatomy, and cultural expectations. The group also formulated position statements for intradermal botulinum toxin type A (“mesotoxin”), body shaping with the calves as a paradigm, and reduction of parotid glands. While Asians have previously been considered a homogeneous group for the purposes of aesthetic treatment, this publication considers regional variations. A new classification of Asian facial morphotypes is proposed to aid treatment planning and implementation. Conclusions: This is the first pan-Asian consensus for aesthetic use of botulinum toxin type A. Its unique objective is to optimize treatment safety and efficacy for patients of complete or part-Asian ancestry in all regions. The recommendations for incobotulinumtoxinA may be extended with care to other botulinum toxin formulations. PMID:28293488

  16. Clinical and image improvement of Raynaud's phenomenon after botulinum toxin type A treatment.

    PubMed

    Zhao, HongMei; Lian, YaJun

    2015-08-01

    Raynaud's phenomenon is often accompanied by pain, digital ulceration and compromised daily activities. Pharmacological therapy or sympathectomies have been administered to diminish these symptoms but existing treatments are not invariably efficacious. A recent case series has described the use of botulinum toxin type A in the treatment of Raynaud's phenomenon. We report two patients with severe or mild Raynaud's phenomenon who were injected with BTX-A; both of whom experienced clinical and image improvement after treatment.

  17. Botulinum toxin injection to facilitate rehabilitation of muscle imbalance syndromes in sports medicine.

    PubMed

    Cullen, D M; Boyle, J J W; Silbert, P L; Singer, B J; Singer, K P

    2007-12-15

    Intramuscular injection of Botulinum toxin to produce reduction of focal muscle overactivity, and localized muscle spasm, has been utilized therapeutically for almost two decades. Muscle overactivity in neurologically normal muscle, where an imbalance exists between a relatively overactive muscle and its less active synergist or antagonist, can inhibit control of the antagonist producing a functional muscle imbalance. This brief review provides an overview of the role of muscle imbalance in sports-related pain and dysfunction, and outlines the potential for intramuscular injection of Botulinum toxin to be used as an adjunct to specific muscle re-education and functional rehabilitation in this patient group. A comprehensive understanding of normal movement and the requirements of the sporting activity are essential to allow accurate diagnosis of abnormal motor patterns and to re-educate more appropriate movement strategies. Therapeutic management of co-impairments may include stretching of tight soft tissues, specific re-education aimed at isolation of the non-dominant weak muscles and improvement in their activation, 'unlearning' of faulty motor patterns, and eventual progression onto functional exercises to anticipate gradual return to sporting activity. Intramuscular injection of Botulinum toxin, in carefully selected cases, provides short term reduction of focal muscle overactivity, and may facilitate activation of relatively 'inhibited' muscles and assist the restoration of more appropriate motor patterns.

  18. Botulinum toxin injection for bruxism associated with brain injury: case report.

    PubMed

    Kesikburun, Serdar; Alaca, Rıdvan; Aras, Berke; Tuğcu, Ilknur; Tan, Arif Kenan

    2014-01-01

    Bruxism is involuntary grinding of the teeth and can occur as a complication of brain injury. If untreated, bruxism can lead to severe occlusal trauma. Herein, we present a patient with traumatic brain injury and nocturnal bruxism that was treated with botulinum toxin injection. A 21 yr old male patient with traumatic brain injury from a car accident was admitted to our inpatient rehabilitation unit. He had a history of coma for 2 wk in the intensive care unit. The initial cranial computed tomography scan indicated a superior thalamic hemorrhage. On admission to our department 3 mo postinjury, his mental status was good and he was able to walk without assistance, but he had mild ataxia. He complained about severe teeth grinding at night, which began 2 mo postinjury. Botulinum toxin-A was injected into the masseter muscles (20 U in each muscle) and temporalis muscles (15 U in each muscle) bilaterally. A decrease in bruxism was reported within 3 d. Clinical improvement persisted at assessment 4 mo posttreatment. Botulinum toxin injection can be used as an effective treatment for bruxism associated with brain injury.

  19. Intravesical Botulinum Toxin for Persistent Autonomic Dysreflexia in a Pediatric Patient

    PubMed Central

    Durkee, Charles; Groth, Travis

    2016-01-01

    Introduction. We present a novel case of persistent autonomic dysreflexia in a pediatric spinal cord injury patient treated successfully with intravesical botulinum toxin. Study Design. A retrospective chart review of one patient seen at the Children's Hospital of Wisconsin from 2006 to 2012 was performed. Results. A pediatric spinal cord injury patient with known neurogenic bladder presented with severe hypertension consistent with autonomic dysreflexia. His symptoms and hypertension did not improve with conservative measures, and he necessitated ICU admission and antihypertensive drips. He was taken to the operating room for intravesical botulinum toxin for refractory bladder spasms. Following this, his symptoms abated, and he was weaned off IV antihypertensives and returned to his baseline state. His symptoms were improved for greater than six months. Conclusions. There are few treatment options for the management of refractory autonomic dysreflexia. Intravesical botulinum toxin has never been reported for this use. Dedicated research is warranted to assess its efficacy, as it was used successfully to abort autonomic dysreflexia in this patient. PMID:27006855

  20. The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain

    PubMed Central

    Singer, Barbara J.; Silbert, Benjamin I.; Silbert, Peter L.; Singer, Kevin P.

    2015-01-01

    Anterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional “denervation” which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief. PMID:26308056

  1. Characterization of six type A strains of Clostridium botulinum that contain type B toxin gene sequences.

    PubMed

    Kirma, Nameer; Ferreira, Joseph L; Baumstark, Barbara R

    2004-02-16

    Six Clostridium botulinum isolates exhibiting type A toxicity as measured by the mouse bioassay were found to contain both type A and type B neurotoxin DNA sequences. The six strains were divided into three groups based on the DNA sequence of the type B neurotoxin gene. Members of each group exhibited 100% sequence identity over the 3876 bp type B toxin open reading frame. The type B toxin sequence of all groups differed at more than 60 positions when compared to the BGB control strain.

  2. Effect of Botulinum Toxin on Disabling Neuropathic Pain: A Case Presentation Suggesting a New Therapeutic Strategy.

    PubMed

    Buonocore, Michelangelo; Demartini, Laura; Mandrini, Silvia; Dall'Angelo, Anna; Dalla Toffola, Elena

    2017-02-01

    This case presentation describes a 47-year-old woman who developed complex regional pain syndrome type II with severe neuropathic pain following iatrogenic transection of the tibial nerve at the ankle. The pain and disability progressively worsened over time, markedly impaired ambulation, and were not relieved despite various analgesic treatments. After injection of botulinum toxin (abobotulinumtoxinA, BoNT-A) in the leg muscles the tendons of which pass through the tarsal tunnel (together with the tibial nerve), her pain decreased and her walking capacity improved. This case suggests a new therapeutic role for botulin toxin in treating peripheral neuropathic pain caused by movement-evoked ectopic potentials.

  3. Association of toxin-producing Clostridium botulinum with the macroalga Cladophora in the Great Lakes.

    PubMed

    Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N; Whitman, Richard L; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Peller, Julie; Sadowsky, Michael J

    2013-03-19

    Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism

  4. Association of toxin-producing Clostridium botulinum with the macroalga Cladophora in the Great Lakes

    USGS Publications Warehouse

    Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Tepp, William H.; Lin, Guangyun; Johnson, Eric A.; Peller, Julie; Sadowsky, Michael J.

    2013-01-01

    Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15 000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism

  5. Electron Microscopy of the Toxin and Hemagglutinin of Type A Clostridium botulinum

    PubMed Central

    Boroff, Daniel A.; Nyberg, Sverker; Höglund, Stefan

    1972-01-01

    Electron micrographs of the toxin and the hemagglutinin of type A Clostridium botulinum showed the toxin to be either round or disclike particles of 4 to 4.5 nm. These particles could also be seen as arranged in long strands or tubules of 9 nm in width. The hemagglutinin appeared as a crystalloid monolayer of stacked particles of 9 nm forming regularly arranged structures of 20 nm. Seen in cross section, these structures appeared as tubules with a lumen of 9 nm. The regularity of the angle of 83° to the long axis of the structure in which the individual particles were arranged suggested that the hemagglutinins formed a helix with sufficient space within its coil to admit the strands of the toxins. A model of the possible arrangement of the toxin and the hemagglutinin in the native state is proposed. Images PMID:4565051

  6. Construction of "Toxin Complex" in a Mutant Serotype C Strain of Clostridium botulinum Harboring a Defective Neurotoxin Gene.

    PubMed

    Suzuki, Tomonori; Nagano, Thomas; Niwa, Koichi; Uchino, Masataka; Tomizawa, Motohiro; Sagane, Yoshimasa; Watanabe, Toshihiro

    2017-01-01

    A non-toxigenic mutant of the toxigenic serotype C Clostridium botulinum strain Stockholm (C-St), C-N71, does not produce the botulinum neurotoxin (BoNT). However, the original strain C-St produces botulinum toxin complex, in which BoNT is associated with non-toxic non-hemagglutinin (NTNHA) and three hemagglutinin proteins (HA-70, HA-33, and HA-17). Therefore, in this study, we aimed to elucidate the effects of bont gene knockout on the formation of the "toxin complex." Nucleotide sequence analysis revealed that a premature stop codon was introduced in the bont gene, whereas other genes were not affected by this mutation. Moreover, we successfully purified the "toxin complex" produced by C-N71. The "toxin complex" was identified as a mixture of NTNHA/HA-70/HA-17/HA-33 complexes with intact NTNHA or C-terminally truncated NTNHA, without BoNT. These results indicated that knockout of the bont gene does not affect the formation of the "toxin complex." Since the botulinum toxin complex has been shown to play an important role in oral toxin transport in the human and animal body, a non-neurotoxic "toxin complex" of C-N71 may be valuable for the development of an oral drug delivery system.

  7. Sensing the Deadliest Toxin: Technologies for Botulinum Neurotoxin Detection

    PubMed Central

    Čapek, Petr; Dickerson, Tobin J.

    2010-01-01

    Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently developed alternative in vitro detection methods and assess their ability to supplement or replace the mouse bioassay in the analysis of complex matrix samples. PMID:22069545

  8. Sensing the deadliest toxin: technologies for botulinum neurotoxin detection.

    PubMed

    Capek, Petr; Dickerson, Tobin J

    2010-01-01

    Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently developed alternative in vitro detection methods and assess their ability to supplement or replace the mouse bioassay in the analysis of complex matrix samples.

  9. Botulinum Toxin A for Bladder Pain Syndrome/Interstitial Cystitis

    PubMed Central

    Chiu, Bin; Tai, Huai-Ching; Chung, Shiu-Dong; Birder, Lori A.

    2016-01-01

    Botulinum neurotoxin A (BoNT-A), derived from Clostridium botulinum, has been used clinically for several diseases or syndrome including chronic migraine, spasticity, focal dystonia and other neuropathic pain. Chronic pelvic or bladder pain is the one of the core symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC). However, in the field of urology, chronic bladder or pelvic pain is often difficult to eradicate by oral medications or bladder instillation therapy. We are looking for new treatment modality to improve bladder pain or associated urinary symptoms such as frequency and urgency for patients with BPS/IC. Recent studies investigating the mechanism of the antinociceptive effects of BoNT A suggest that it can inhibit the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. In this review, we will examine the evidence supporting the use of BoNTs in bladder pain from basic science models and review the clinical studies on therapeutic applications of BoNT for BPS/IC. PMID:27376330

  10. Botulinum Toxin for Neuropathic Pain: A Review of the Literature

    PubMed Central

    Oh, Hyun-Mi; Chung, Myung Eun

    2015-01-01

    Botulinum neurotoxin (BoNT), derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that it inhibits the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. There is some evidence showing the axonal transport of BoNT, but it remains controversial. The aim of this review is to summarize the experimental and clinical evidence of the antinociceptive effects, mechanisms, and therapeutic applications of BoNT for neuropathic pain conditions, including postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia. The PubMed and OvidSP databases were searched from 1966 to May 2015. We assessed levels of evidence according to the American Academy of Neurology guidelines. Recent studies have suggested that BoNT injection is an effective treatment for postherpetic neuralgia and is likely efficient for trigeminal neuralgia and post-traumatic neuralgia. BoNT could also be effective as a treatment for diabetic neuropathy. It has not been proven to be an effective treatment for occipital neuralgia or complex regional pain syndrome. PMID:26287242

  11. The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells.

    PubMed

    Nishikawa, Atsushi; Uotsu, Nobuo; Arimitsu, Hideyuki; Lee, Jae-Chul; Miura, Yutaka; Fujinaga, Yukako; Nakada, Hiroshi; Watanabe, Toshihiro; Ohyama, Tohru; Sakano, Yoshiyuki; Oguma, Keiji

    2004-06-25

    Orally ingested botulinum toxin enters the circulatory system and eventually reaches the peripheral nerves, where it elicits a response of neurological dysfunction. In this study, we report the important findings concerning the mechanism of Clostridium botulinum type C progenitor toxin (C16S) endocytic mechanism. C16S toxin bound to high molecular weight proteins on the surface of human colon carcinoma HT-29 cells and was internalized, but not if the cells were pretreated with neuraminidase. Benzyl-GalNAc which inhibited O-glycosylation of glycoproteins also interfered in the toxin's ability to bind the cell surface. On the other hand, the toxin was internalized in spite of pretreatment of the cells with PPMP, an inhibitor of ganglioside synthesis. These results suggest that the glycoproteins, like mucin, fulfill the important roles of receptor and transporter of C16S toxin.

  12. Botulinum Toxin for the Treatment of Myofascial Pain Syndromes Involving the Neck and Back: A Review from a Clinical Perspective

    PubMed Central

    Climent, José M.; Fenollosa, Pedro; Martin-del-Rosario, Francisco

    2013-01-01

    Introduction. Botulinum toxin inhibits acetylcholine (ACh) release and probably blocks some nociceptive neurotransmitters. It has been suggested that the development of myofascial trigger points (MTrP) is related to an excess release of ACh to increase the number of sensitized nociceptors. Although the use of botulinum toxin to treat myofascial pain syndrome (MPS) has been investigated in many clinical trials, the results are contradictory. The objective of this paper is to identify sources of variability that could explain these differences in the results. Material and Methods. We performed a content analysis of the clinical trials and systematic reviews of MPS. Results and Discussion. Sources of differences in studies were found in the diagnostic and selection criteria, the muscles injected, the injection technique, the number of trigger points injected, the dosage of botulinum toxin used, treatments for control group, outcome measures, and duration of followup. The contradictory results regarding the efficacy of botulinum toxin A in MPS associated with neck and back pain do not allow this treatment to be recommended or rejected. There is evidence that botulinum toxin could be useful in specific myofascial regions such as piriformis syndrome. It could also be useful in patients with refractory MPS that has not responded to other myofascial injection therapies. PMID:23533477

  13. Treatment of chronic pain associated with nocturnal bruxism with botulinum toxin. A prospective and randomized clinical study

    PubMed Central

    Al-Wayli, Hessa

    2017-01-01

    Background To evaluate the role of botulinum toxin type A (BTX-A) in the treatment of pain associated with nocturnal bruxism. Material and Methods Fifty subjects reporting nocturnal bruxism were recruited for a randomized clinical trial. Twenty five bruxers were injected with botulinum toxin in both masseters, and twenty five were treated with traditional methods of treating bruxism. Patients were evaluated at 3rd week, 2nd and 6th month and one year after injection and then used to calculate bruxism events. Bruxism symptoms were investigated using questionnaires. Results Mean pain score due to Bruxism events in the masseter muscle decreased significantly in the botulinum toxin injection group A (P =0.000, highly significant). However, in the conventional treatment group, mean pain score does not show improvement with time (p>0.05). Conclusions Our results suggest that botulinum toxin injection reduced the mean pain score and number of bruxism events, most likely by decreasing the muscle activity of masseter rather than affecting the central nervous system. Key words:Temporomandibular pain, nocturnal bruxism, botulinum toxin. PMID:28149474

  14. Treatment of inferior lateral pterygoid muscle dystonia with zolpidem tartrate, botulinum toxin injections, and physical self-regulation procedures: a case report.

    PubMed

    Vazquez-Delgado, Eduardo; Okeson, Jeffrey P

    2004-10-01

    The following case report depicts the management of a patient suffering with a jaw opening oromandibular dystonia using a combination of botulinum toxin injections, zolpidem, and relaxation procedures. Eventually the botulinum toxin injections were eliminated, and the patient was maintained with only zolpidem and relaxation procedures.

  15. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin

    PubMed Central

    Contarino, Maria Fiorella; Van Den Dool, Joost; Balash, Yacov; Bhatia, Kailash; Giladi, Nir; Koelman, Johannes H.; Lokkegaard, Annemette; Marti, Maria J.; Postma, Miranda; Relja, Maja; Skorvanek, Matej; Speelman, Johannes D.; Zoons, Evelien; Ferreira, Joaquim J.; Vidailhet, Marie; Albanese, Alberto; Tijssen, Marina A. J.

    2017-01-01

    Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored. PMID:28286494

  16. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin.

    PubMed

    Contarino, Maria Fiorella; Van Den Dool, Joost; Balash, Yacov; Bhatia, Kailash; Giladi, Nir; Koelman, Johannes H; Lokkegaard, Annemette; Marti, Maria J; Postma, Miranda; Relja, Maja; Skorvanek, Matej; Speelman, Johannes D; Zoons, Evelien; Ferreira, Joaquim J; Vidailhet, Marie; Albanese, Alberto; Tijssen, Marina A J

    2017-01-01

    Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored.

  17. Bone and cartilage changes in rabbit mandibular condyles after a single injection of botulinum toxin

    PubMed Central

    Matthys, Tori; Ho Dang, Hong An; Rafferty, Katherine L.; Herring, Susan W.

    2015-01-01

    Introduction Temporary paralysis of the masseter muscle using botulinum toxin is a common treatment for temporomandibular disorders, bruxism, and muscle hypertrophy. Loss of masseter force is associated with decreased mandibular mineral density. Our objectives were (1) to establish whether bone loss at the mandibular condyle is regionally specific, and (2) to ascertain whether the treatment affects the condylar cartilage. Methods Young adult female rabbits received a unilateral masseter injection of botulinum neurotoxin serotype A (BoNT/A, n=31), saline (n=19) or no injection (n=3) and were also injected with bromodeoxyuridine (BrdU), a replication marker. Termination occurred 4 or 12 weeks following treatment. Condyles were processed by paraffin histology. Cortical thickness, cartilage thickness and trabecular bone areal density were measured, and replicating cells were counted after BrdU reaction. Results BoNT/A rabbits exhibited a high frequency of defects in the condylar bone surface, occurring equally on injected and uninjected sides. Bone loss was seen only on the side of the BoNT/A injection. Cortical as well as trabecular bone was severely affected. The midcondylar region lost the most bone. Recovery at 12 weeks was insignificant. Condylar cartilage thickness showed no treatment effect but did increase with time. Numbers of proliferating cells were similar in treatment groups, but BoNT/A animals showed more side asymmetry in association with the condylar defects. Conclusion Bone loss may be a risk factor for the use of botulinum toxin in jaw muscles. PMID:26672706

  18. Botulinum Toxin Treatment of Spasticity in Adults and Children.

    PubMed

    Moeini-Naghani, Iman; Hashemi-Zonouz, Taraneh; Jabbari, Bahman

    2016-02-01

    Spasticity is a frequent symptom in stroke, multiple sclerosis, cerebral or spinal trauma, and cerebral palsy that affects and disables a large number of adults and children. In this review, we discuss the pathophysiology and nonpharmacologic and pharmacologic treatments of spasticity with emphasis on the role of botulinum neurotoxins (BoNTs). The world literature is reviewed on double-blind and placebo-controlled clinical trials reporting safety and efficacy of BoNT treatment in adult spasticity and spasticity of children with cerebral palsy. The evidence for efficacy is presented from recommendations of the Assessment and Therapeutics subcommittee of the American Academy of Neurology. A technical section describes the techniques and recommended doses of BoNTs in spasticity.

  19. Effect of fermentation conditions on toxin production by Clostridium botulinum type B.

    PubMed

    Siegel, L S; Metzger, J F

    1980-12-01

    To obtain high yields of toxin for the preparation of purified neurotoxoids, we examined the time of appearance and the quantity of toxin produced by the Bean strain of Clostridium botulinum type B under various conditions by using a fermentor system. The medium employed consisted of 2.0% casein hydrolylsate and 1.5% yeast extract plus an appropriate concentration of glucose. The maximum toxin concentration (4 x 10(5) to 5 x 10(5) mouse median lethal doses per ml) was attained within 48 h under the following fermentation conditions: an initial glucose concentration of 0.5 or 1.0%, a temperature of 35 degrees C, a nitrogen overlay at a rate of 5 liters/min, and an agitation rate of 50 rpm.

  20. An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production

    PubMed Central

    Walshaw, John; Peck, Michael W.; Barker, Gary C.

    2016-01-01

    Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics. PMID:27855161

  1. An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production.

    PubMed

    Ihekwaba, Adaoha E C; Mura, Ivan; Walshaw, John; Peck, Michael W; Barker, Gary C

    2016-11-01

    Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics.

  2. The management of oromandibular motor disorders and facial spasms with injections of botulinum toxin.

    PubMed

    Clark, Glenn T

    2003-11-01

    Although much work is yet to be done in this area, nine general conclusions can be derived: 1. Local site-of-injection side effects from botulinum toxin injections are rare, assuming proper technique is used. 2. The two most common medication-related side effects from botulinum toxin orofacial injections are alterations in salivary consistency and inadvertent weakness of the swallowing, speech, and facial muscles. These complications are injection site-specific (eg, more common with lateral pterygoid injections and palatal and tongue muscle injections) and dose-dependent problems. These problems are bothersome but are not contraindications for the therapy if it is needed. 3. The data presented in this article are mostly case series-based and open trial-based information that is promising, but randomized, blinded, controlled trials are needed to establish the true efficacy of this method for the orofacial motor and pain disorders. 4. The novice should begin with injection of muscles he or she can inject with low risk of incorrect placement. The hard-to-find muscles should be avoided when starting out. The novice clinician should inject and dissect a few cadavers to improve injection technique. 5. The general latency for botulinum toxin type A is 1 week, its duration is 2 to 3 months, and it is recommended that injection be done no more than once every 12 weeks to avoid development of antibodies against the toxin. 6. Depending on the target muscle, injection dose is 10 to 50 U of Botox type A per site with a total dose of 200 U in the masticatory system. More than this can be used (400 U maximum) if other sites in the head and neck are included in the injection protocol. 7. Regarding injecting painful muscles that do not exhibit palpable muscle hardness or EMG-determined spasticity or observable involuntary movements but have chronic myofascial trigger points or the patient localizes them as the site of their chronic daily headache pain, botulinum toxin injections

  3. Efficacy of DNA vaccines expressing the type F botulinum toxin Hc fragment using different promoters.

    PubMed

    Jathoul, Amit P; Holley, Jane L; Garmory, Helen S

    2004-09-28

    DNA vaccines which expressed the Hc fragment of the Clostridium botulinum type F neurotoxin (BoNT/F Hc) fused to a signal peptide downstream of four different eukaryotic promoters were prepared. Subsequently, the immunogenicity of the DNA vaccines and protection afforded in mice against challenge with 10(4) MLD of type F botulinum toxin was evaluated. The DNA vaccine containing the human ubiquitin gene (UbC) promoter induced the highest BoNT/F Hc-specific antibody concentration following two intramuscular immunisations and afforded 90% protection against challenge. The results from this study indicate that the selection of promoter used in DNA vaccination studies may be of importance in designing optimised vaccines.

  4. Botulinum toxin A does not alter capsaicin-induced pain perception in human skin.

    PubMed

    Schulte-Mattler, Wilhelm J; Opatz, Oliver; Blersch, Wendelin; May, Arne; Bigalke, Hans; Wohlfahrt, Kai

    2007-09-15

    A genuine peripheral antinociceptive and anti-inflammatory effect of Botulinum neurotoxin type A (BoNT/A) has been proposed but could not be demonstrated in humans so far. Therefore, 100 mouse units of Botulinum toxin A (Dysport) and placebo were injected in a double blind paradigm in defined skin areas of 50 subjects. At baseline and after 4 and 8 weeks allodynia was induced in the skin areas with capsaicin ointment. Heat and cold pain threshold temperatures were measured with quantitative sensory testing, and threshold intensities upon electrical stimulation with a pain specific surface electrode were determined. No BoNT/A related differences in pain perception were found at any quality. There is neither a direct peripheral antinociceptive effect nor a significant effect against neurogenic inflammation of BoNT/A in humans.

  5. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

    PubMed

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

    2016-12-01

    Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P < 0.01). These data demonstrate that botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures.

  6. The Action of Botulinum Toxin at the Neuromuscular Junction

    DTIC Science & Technology

    1980-12-22

    6. PERFORMING ORG. REPORT NUMBER AUTHOR(&) 8. CONTRACT OR GRANT NUMBER(&) SELLIN,/Lawrence C,’c ISM PERFORMING ORGANIZATION NAME AND ADDRESS 10...one quantum. however, end-plate potentials remained subthreshold and did not produce a muscle contraction upon nerve stimulation. Low frequency (0.5 Hz...muscle fibers -"_re not significantly affected by the toxin. It is interesting to note that, although fast- twitch and slow-twitch mucles were

  7. Bruxism after brain injury: successful treatment with botulinum toxin-A.

    PubMed

    Ivanhoe, C B; Lai, J M; Francisco, G E

    1997-11-01

    Bruxism, the rhythmic grinding of teeth--usually during sleep--is not an infrequent complication of traumatic brain injury. Its prevalence in the general population is 21%, but its incidence after brain injury is unknown. Untreated, bruxism causes masseter hypertrophy, headache, temporomandibular joint destruction, and total dental wear. We report a case of complete resolution of postanoxic bruxism after treatment with botulinum toxin-A (BTX-A). The patient was a 28-year-old man with no history of bruxism who sustained an anoxic brain injury secondary to cardiac arrest of unknown etiology. On admission to our rehabilitation unit 2 months after the injury, the patient presented with severe bruxism and heavy dental wear. The patient was injected with a total of 200 units of BTX-A to each masseter and temporalis. There was total resolution of bruxism 2 days after injection, with no complications. On follow-up 3 months after injection, the patient remained free of bruxism. We propose that botulinum toxin be considered as a treatment for bruxism secondary to anoxic brain injury. Further studies regarding muscle selection and medication dosage are warranted to elucidate the toxin's efficacy in this condition.

  8. Drug Insight: biological effects of botulinum toxin A in the lower urinary tract.

    PubMed

    Chancellor, Michael B; Fowler, Clare J; Apostolidis, Apostolos; de Groat, William C; Smith, Christopher P; Somogyi, George T; Aoki, K Roger

    2008-06-01

    Botulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

  9. Botulinum Toxin in the Treatment of Pediatric Upper Limb Spasticity

    PubMed Central

    Schwabe, Aloysia L.

    2016-01-01

    Botulinum neurotoxin (BoNT) is one of the mainstays in the treatment of pediatric spasticity and dystonia. When considering initiation of BoNT treatment for spasticity, treatment goals and responses to prior conservative measures such as passive range of motion exercises, splinting, and other medication trials should be reviewed. As a general rule, children should be engaged in therapy services around the time of the injections and have a robust home program in place. When managing spasticity in children with BoNT injections, the practitioner should be well versed in functional anatomy with specialized training in injection techniques. Localization techniques in addition to anatomical landmarks are recommended for improved efficacy and include limited electromyography, electrical stimulation, and/or ultrasound guidance. A follow-up visit for the purpose of reassessment during the peak effect of the drug is advised. It is known that BoNT is effective at reducing spasticity and improving range of motion, but it remains to be determined to what degree this translates into improved function, activity, and participation. PMID:26869860

  10. Botulinum toxin in the treatment of OAB, BPH, and IC.

    PubMed

    Smith, Christopher P

    2009-10-01

    Botulinum neurotoxins (BoNTs) are well known for their ability to potently and selectively disrupt and modulate neurotransmission. BoNT is currently undergoing regulatory evaluation for urological disorders in the United States and the European Union and is not FDA approved for urologic use. Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are common urologic conditions characterized by urinary frequency, urgency, nocturia, urge incontinence and, in the case of BPH, decreased urine flow that are currently being evaluated in clinical trials with BoNT-A. Interstitial cystitis (IC) is a chronic condition in which patients describe urinary frequency, urgency and associated bladder/pelvic pain. In the two former conditions, BoNT-A is currently being evaluated in Phase II or Phase III clinical trials as a therapeutic agent. Evidence for BoNT in the treatment of IC is limited to small case series. The purpose of this article is to provide up to date clinical evidence regarding the use of BoNT to treat these three urologic problems. For the sake of clarity, BoNT-A describes the use of Botox unless otherwise specified. In addition, when describing OAB, two sub-populations exist: those with OAB of neurogenic origin (NDO) and those with OAB of unknown (idiopathic) origin (IDO).

  11. Clostridium botulinum Toxin Production in Relation to Spoilage of Atlantic Salmon (Salmo salar) Packaged in Films of Varying Oxygen Permeabilities and with Different Atmospheres.

    PubMed

    Erickson, Marilyn C; Ma, Li M; Doyle, Michael P

    2015-11-01

    Shelf life of fish packaged under modified atmosphere (MA) is extended, but within the United States, commercial application of MA with impermeable packaging films is restricted due to concerns that botulinum toxin production would precede spoilage when contaminated fish are held at abusive storage temperatures. Use of semipermeable packaging films has been advocated; however, previous studies are inconclusive in determining the oxygen transmission rate (OTR) of a film that is needed to achieve an acceptable margin of safety (i.e., toxin production occurs only after spoilage). This study was conducted to determine the influence of OTR (target OTRs of 3 to 15,000) on the development of spoilage volatiles and toxin in salmon inoculated with type E Clostridium botulinum and subjected to air, vacuum, or 75:25 CO2:N2 MA and storage temperatures of 4, 8, 12, or 16°C. The most dominant headspace volatile peak that was produced during spoilage of samples at 4, 8 or 12°C was a peak, having a Kovats retention index (KI) of 753, and at which external standards of 2- or 3-methyl 1-butanol also eluted. Under anaerobic conditions, both the aerobic microbial populations and the size of the KI 753 spoilage peak were less in inoculated samples compared with uninoculated samples. C. botulinum-inoculated samples that were stored at 12 or 16°C under conditions favorable for anaerobic growth were also characterized by a KI 688 peak. Using a previously developed model that related the percentage of elderly consumers who would prepare a sample having the KI 753 spoilage peak of a specific size, it was determined that for salmon packaged with 3 or 3,000 OTR films under any atmosphere and stored at 12 or 16°C, 2 to 61% of the consumers could potentially prepare toxin-contaminated samples. Hence, when abusive storage conditions are suspected, the fish should not be consumed.

  12. Comparison of pneumatic dilation with pneumatic dilation plus botulinum toxin for treatment of achalasia.

    PubMed

    Bakhshipour, Alireza; Rabbani, Romina; Shirani, Shapoor; Soleimani, Hosein A S L; Mikaeli, Javad

    2010-01-01

    Among the therapeutic options for achalasia are pneumatic dilatation (PD), an appropriate long-term therapy, and botulinum toxin injection (BT) that is a relatively short-term therapy. This study aimed to compare therapeutic effect of repetitive pneumatic dilation with a combined method (botulinum toxin injection and pneumatic dilation) in a group of achalasia patients who are low responder to two initial pneumatic dilations. Thirty-four patients with documented primary achalasia that had low response to two times PD (<50% decrease in symptom score and barium height at 5 minute in timed esophagogram after 3 month of late PD) were randomized to receive pneumatic dilation (n=18) or botulinum toxin injection and pneumatic dilation by four weeks interval (n=16), PD and BT+PD groups respectively. Symptom scores were evaluated before and at 1, 6 and 12 months after treatment. Clinical remission was defined as a decrease in symptom score > or = 50% of baseline. There were no significant differences between the two groups in gender, age and achalasia type. Remission rate of patients in BT-PD group in comparison with PD group were 87.5% vs. 67.1% (P = 0.7), 87.5% vs. 61.1% (P = 0.59) and 87.5% vs. 55.5% (P = 0.53) at 1, 6 and 12 months respectively .There were no major complications in either group. The mean symptom score decreased by 62.71% in the BT-PD group (P < 0.002) and 50.77% in the PD group (P < 0.01) at the end of the first year. Despite a better response rate in BT+PD group, a difference was not statistically significant. A difference may be meaningful if a large numbers of patients are included in the study.

  13. Evaluating the role of botulinum toxin in the management of focal hypertonia in adults

    PubMed Central

    Richardson, D.; Sheean, G.; Werring, D.; Desai, M.; Edwards, S.; Greenwood, R.; Thompson, A.

    2000-01-01

    OBJECTIVES—To investigate the effects of EMG guided botulinum toxin (BTX-A) on impairment and focal disability in adults presenting with focal hypertonia.
METHODS—A prospective, randomised, double blind, placebo controlled, parallel group trial was carried out with standardised assessment before and at 3 week intervals until 12 weeks after injection, in patients with focal hypertonia affecting upper or lower limbs. Botulinum toxin or placebo was injected with EMG guidance after multidisciplinary assessment. The modified Ashworth scale of spasticity, percentage passive range of joint motion, subjective rating of problem severity, the Rivermead motor assessment scale, a timed 10 metre walk (lower limb patients), nine hole peg test (upper limb patients), and a modified goal attainment scale were used as outcome measures. The patients were 52 adults; 34 male, 18female; mean age 40.31, range 16-79 years; mean duration of symptoms 35 months (range 3 months to 22 years). Diagnoses included cerebrovascular accidents (23), head injury (12), incomplete spinal cord injury (six), tumour (five), cerebral palsy (three), and anoxic episodes (three).
RESULTS—For each variable an overall score for the treatment period was computed by summing the scores from the 3, 6, 9, and 12 week assessments. These overall scores were significantly better in the treated group for the Ashworth scale, percentage passive range of movement, Rivermead lower limb, and subjective rating of problem severity. The significant treatment effect on the Ashworth scale was seen on analysis of variance (ANOVA) at 3 weeks and the subjective rating of problem severity at 3 and 6 weeks. The goal attainment scale score in both groups was similar at 12weeks.
CONCLUSION—Selective use of botulinum toxin to weaken muscles can lead to a reduction in resistance to passive movement about a distal limb joint. This allows for improvements in passive range of movement and focal disability, particularly in

  14. Adult cases of congenital muscular torticollis successfully treated with botulinum toxin.

    PubMed

    Bouchard, Manon; Chouinard, Sylvain; Suchowersky, Oksana

    2010-10-30

    Congenital muscular torticollis (CMT) is the most common cause of torticollis in childhood. This condition is usually recognized and successfully treated in infancy, but may persist in adulthood, particularly if not treated. In adult patients, CMT can be differentiated from idiopathic cervical dystonia by the frequent association with facial asymmetry, presence of a cord-like sternocleiodmastoid muscle (SCM), absence of head tremor, lack of sensory trick, and head tilt since infancy. We describe 3 patients with persistent CMT, who were successfully treated with botulinum toxin injections with long lasting benefit.

  15. Combined treatment with botulinum toxin and hyaluronic acid to correct unsightly lateral-chin depression*

    PubMed Central

    Braz, André Vieira; Louvain, Dailana; Mukamal, Luana Vieira

    2013-01-01

    With aging, anatomical changes are observed in the face. In the lower third, these changes are expressed as ptosis of the angle of the mouth, lip enhancement groove mentalis; decrease in concavity between the jaw and neck and very noticeable platysmal banding. The repeated contraction of muscles of the lateral-chin together with the band platysmal side form what are called a marionette groove. Treating the whole lateral-chin area can result in a more harmonious aspect of the face when compared with treatment of a marionette groove in isolation. In this paper we describe combined treatment of the lateral chin area using botulinum toxin and fillers. PMID:23539022

  16. Recurrent TMJ Dislocation Managed with Botulinum Toxin Type A Injections in a Pediatric Patient.

    PubMed

    Stark, Thomas R; Perez, Cristina V; Okeson, Jeffrey P

    2015-01-01

    Chronic recurrent temporomandibular joint (TMJ) dislocation is an uncommon condition that is painful and distressing to patients and uniquely challenging for clinicians. Sustained TMJ dislocation is not amenable to manual reduction alone when the etiology is muscular in nature. The purpose of this report was to describe the case of a child presenting with recurring temporomandibular joint dislocation secondary to muscle hyperactivity of unknown etiology that was managed with injections of botulinum toxin type A into the inferior lateral pterygoid muscles. The use of this peripheral antispasmoic neurotoxin is a reasonable, safe, and conservative, palliative treatment option for pediatric patients suffering from chronic recurring TMJ dislocation.

  17. Role of medical thermography in treatment of Frey's syndrome with botulinum toxin A.

    PubMed

    Green, Richard James; Endersby, Simon; Allen, John; Adams, James

    2014-01-01

    Frey syndrome classically causes gustatory sweating and facial flushing. We describe 2 cases in which medical thermography was used to investigate the symptoms. Images were taken after patients chewed a sialagogue and 2 weeks later they were given injections of botulinum toxin A. Images taken 4 weeks after treatment showed a considerable reduction in sweating and facial flushing, which was supported by the results of quality of life questionnaires completed before and after treatment. Medical thermography is much cleaner than the Minor's starch iodine test. It identifies areas of gustatory sweating, changes in temperature, and vascular changes, which potentially enable treatment to be targeted accurately.

  18. The Prediction of Botulinum Toxin Structure Based on in Silico and in Vitro Analysis

    NASA Astrophysics Data System (ADS)

    Suzuki, Tomonori; Miyazaki, Satoru

    2011-01-01

    Many of biological system mediated through protein-protein interactions. Knowledge of protein-protein complex structure is required for understanding the function. The determination of huge size and flexible protein-protein complex structure by experimental studies remains difficult, costly and five-consuming, therefore computational prediction of protein structures by homolog modeling and docking studies is valuable method. In addition, MD simulation is also one of the most powerful methods allowing to see the real dynamics of proteins. Here, we predict protein-protein complex structure of botulinum toxin to analyze its property. These bioinformatics methods are useful to report the relation between the flexibility of backbone structure and the activity.

  19. Spotlight on botulinum toxin and its potential in the treatment of stroke-related spasticity

    PubMed Central

    Kaku, Michelle; Simpson, David M

    2016-01-01

    Poststroke spasticity affects up to one-half of stroke patients and has debilitating effects, contributing to diminished activities of daily living, quality of life, pain, and functional impairments. Botulinum toxin (BoNT) is proven to be safe and effective in the treatment of focal poststroke spasticity. The aim of this review is to highlight BoNT and its potential in the treatment of upper and lower limb poststroke spasticity. We review evidence for the efficacy of BoNT type A and B formulations and address considerations of optimal injection technique, patient and caregiver satisfaction, and potential adverse effects of BoNT. PMID:27022247

  20. Prevalence of toxin-producing Clostridium botulinum associated with the macroalga Cladophora in three Great Lakes: growth and management

    USGS Publications Warehouse

    Chun, Chan Lan; Kahn, Chase I.; Borchert, Andrew J.; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Peller, Julie R.; Pier, Christina; Lin, Guangyun; Johnson, Eric A.; Sadowsky, Michael J.

    2015-01-01

    The reemergence of avian botulism caused by Clostridium botulinum type E has been observed across the Great Lakes in recent years. Evidence suggests an association between the nuisance algae, Cladophoraspp., and C. botulinum in nearshore areas of the Great Lakes. However, the nature of the association between Cladophora and C. botulinum is not fully understood due, in part, to the complex food web interactions in this disease etiology. In this study, we extensively evaluated their association by quantitatively examining population size and serotypes of C. botulinum in algal mats collected from wide geographic areas in lakes Michigan, Ontario, and Erie in 2011–2012 and comparing them with frequencies in other matrices such as sand and water. A high prevalence (96%) of C. botulinum type E was observed inCladophora mats collected from shorelines of the Great Lakes in 2012. Among the algae samples containing detectable C. botulinum, the population size of C. Botulinum type E was 100–104 MPN/g dried algae, which was much greater (up to 103 fold) than that found in sand or the water column, indicating thatCladophora mats are sources of this pathogen. Mouse toxinantitoxin bioassays confirmed that the putativeC. botulinum belonged to the type E serotype. Steam treatment was effective in reducing or eliminating C. botulinum type E viable cells in Cladophora mats, thereby breaking the potential transmission route of toxin up to the food chain. Consequently, our data suggest that steam treatment incorporated with a beach cleaning machine may be an effective treatment of Cladophora-borne C. botulinum and may reduce bird mortality and human health risks.

  1. Prevalence of toxin-producing Clostridium botulinum associated with the macroalga Cladophora in three Great Lakes: growth and management.

    PubMed

    Lan Chun, Chan; Kahn, Chase I; Borchert, Andrew J; Byappanahalli, Muruleedhara N; Whitman, Richard L; Peller, Julie; Pier, Christina; Lin, Guangyun; Johnson, Eric A; Sadowsky, Michael J

    2015-04-01

    The reemergence of avian botulism caused by Clostridium botulinum type E has been observed across the Great Lakes in recent years. Evidence suggests an association between the nuisance algae, Cladophora spp., and C. botulinum in nearshore areas of the Great Lakes. However, the nature of the association between Cladophora and C. botulinum is not fully understood due, in part, to the complex food web interactions in this disease etiology. In this study, we extensively evaluated their association by quantitatively examining population size and serotypes of C. botulinum in algal mats collected from wide geographic areas in lakes Michigan, Ontario, and Erie in 2011-2012 and comparing them with frequencies in other matrices such as sand and water. A high prevalence (96%) of C. botulinum type E was observed in Cladophora mats collected from shorelines of the Great Lakes in 2012. Among the algae samples containing detectable C. botulinum, the population size of C. Botulinum type E was 10(0)-10(4) MPN/g dried algae, which was much greater (up to 10(3) fold) than that found in sand or the water column, indicating that Cladophora mats are sources of this pathogen. Mouse toxinantitoxin bioassays confirmed that the putative C. botulinum belonged to the type E serotype. Steam treatment was effective in reducing or eliminating C. botulinum type E viable cells in Cladophora mats, thereby breaking the potential transmission route of toxin up to the food chain. Consequently, our data suggest that steam treatment incorporated with a beach cleaning machine may be an effective treatment of Cladophora-borne C. botulinum and may reduce bird mortality and human health risks.

  2. Involvement of a Botulinum Toxin-Sensitive 22-kDa G Protein in Stimulated Exocytosis of Human Neutrophils

    DTIC Science & Technology

    1994-01-01

    FUNDING NUMBERS ]involvement -of -a Botulinun toxin -sesftUv&2_2At6-d -- Protein in stinulated exocytosis of humnan neutrophi1s. WICD I. AUTHOR(S) Nath...Botulinum Toxin -Sensitive 22-kDa G Protein in Stimulated Exocytosis of Human Neutrophils jaymaree Nath,’ Annette Powledge, and Daniel G. Wright2...observed. Although both peslussis toxin and ST-O Inhibited excocytosis In FlMvLP-stimvulated PMNs, the inhibitory effects o( the two toxins were found to be

  3. Botulinum toxin type A in motor nervous system: unexplained observations and new challenges.

    PubMed

    Matak, I; Lacković, Z; Relja, M

    2016-12-01

    In the motor system, botulinum toxin type A (BoNT/A) actions were classically attributed to its well-known peripheral anticholinergic actions in neuromuscular junctions. However, the enzymatic activity of BoNT/A, assessed by the detection of cleaved synaptosomal-associated protein 25 (SNAP-25), was recently detected in motor and sensory regions of the brainstem and spinal cord after toxin peripheral injection in rodents. In sensory regions, the function of BoNT/A activity is associated with its antinociceptive effects, while in motor regions we only know that BoNT/A activity is present. Is it possible that BoNT/A presence in central motor nuclei is without any function? In this brief review, we analyze this question. Limited data available in the literature warrant further investigations of BoNT/A actions in motor nervous system.

  4. Determination of Injection Site in Flexor Digitorum Longus for Effective and Safe Botulinum Toxin Injection

    PubMed Central

    Kim, Hong Geum; Chung, Myung Eun; Song, Dae Heon; Kim, Ju Yong; Sul, Bo Mi; Oh, Chang Hoon

    2015-01-01

    Objective To determine the optimal injection site in the flexor digitorum longus (FDL) muscle for effective botulinum toxin injection. Methods Fourteen specimens from eight adult Korean cadavers were used in this study. The most proximal medial point of the tibia plateau was defined as the proximal reference point; the most distal tip of the medial malleolus was defined as the distal reference point. The distance of a line connecting the proximal and distal reference points was defined as the reference length. The X-coordinate was the distance from the proximal reference point to the intramuscular motor endpoint (IME), or motor entry point (MEP) on the reference line, and the Y-coordinate was the distance from the nearest point from MEP on the medial border of the tibia to the MEP. IME and MEP distances from the proximal reference point were evaluated using the raw value and the X-coordinate to reference length ratio was determined as a percentage. Results The majority of IMEs were located within 30%-60% of the reference length from the proximal reference point. The majority of the MEPs were located within 40%-60% of the reference length from the proximal reference point. Conclusion We recommend the anatomical site for a botulinum toxin injection in the FDL to be within a region 30%-60% of the reference length from the proximal reference point. PMID:25750869

  5. Effect of botulinum toxin concentration on reduction in sweating: a randomized, double-blind study.

    PubMed

    Rystedt, Alma; Karlqvist, Mattias; Bertilsson, Maria; Naver, Hans; Swartling, Carl

    2013-11-01

    Dose-response studies of botulinum toxin for reduction of sweating are sparse in the literature. The aim of this study was to determine the most appropriate concentrations of Botox®, Dysport®, Xeomin® and NeuroBloc®, respectively, in order to achieve the greatest reduction in sweating, thus reducing the costs and increasing the safety of treatment. Four concentrations of each product were investigated. Intradermal injections of all products and concentrations were applied to the backs of 20 consenting subjects, in a randomized, double-blind manner. Areas of anhidrotic and hypohidrotic skin were measured with an iodine-starch test after 4, 8 and 12 weeks, respectively. Optimal concentrations were found to be 25 U/ml for Botox and Xeomin, approximately 100 U/ml for Dysport, and 50 U/ml for NeuroBloc. When comparing the mean anhidrotic area per unit for 100 U/ml of each product, the calculated dose conversion ratios were 1:1.6:1.2:1.3 (Botox:Dysport:Xeomin:NeuroBloc). If, instead, the optimal concentration for each product was compared, the dose conversion ratios were 1:4.8:1.3:2.2. Thus, it is crucial to consider botulinum toxin concentration in a treatment regimen.

  6. Botulinum Toxin as an Alternative to Treat the Spasm of the Near Reflex.

    PubMed

    Laria, Carlos; Merino-Suárez, María L; Piñero, David P; Gómez-Hurtado, Arantxa; Pérez-Cambrodí, Rafael J

    2015-01-01

    We describe the case of an eight-year-old girl with complaints of headaches and blurred vision (uncorrected visual acuity: 0.1 decimal) that showed on examination miotic pupils, pseudomyopia, no ocular motility restrictions, and no associated neurological disease. After initial treatment with cyclopentolate for two months, pseudomyopia persisted with an intermittent and variable esotropia. Spectacles of +1 both eyes and atropine 1% one drop daily were then prescribed. The situation improved and remained stable for several weeks, with pseudomyopia and esotropia reappearing later. Finally, botulinum toxin (2.5 iu Botox) was injected in the medial rectus muscle on two occasions and a visual therapy program based on the stimulation of fusional divergence, diplopia, and stereopsis consciousness was recommended. This prescription was combined with the use of atropine during the first few weeks. Orthotropia and corrected distance visual acuity of 1.0 were found three months after treatment. The evolution and clinical results of this case report suggest that botulinum toxin in combination with other therapeutic alternatives may be useful in the treatment of spasm of the near reflex.

  7. Botulinum Toxin A for the Treatment of a Child with SUNCT Syndrome

    PubMed Central

    Zhang, Yi; Zhang, Haifeng; Lian, Ya-Jun; Ma, Yun-Qing; Xie, Nan-Chang; Cheng, Xuan; Zhang, Lu

    2016-01-01

    Background. Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome is an unusual cause of headache, mainly described in older adults, and is rare in children. Pain attacks may be severe, frequent, and prolonged. The therapeutic benefits of many drugs are disappointing. Patient and Methods. A 12-year-old boy suffered severe headache and toothache for 20 days. As treatment with nonsteroidal anti-inflammatory drugs, anticonvulsants, and steroids proved ineffective, he was treated with ipsilateral multisite subcutaneous injections of botulinum toxin A 70 U around the orbit, the temporal area, and the upper gum. Results. The pain had reduced in frequency and severity by the fourth day after treatment and had completely disappeared after 7 days. There were no side effects or recurrence during a subsequent 17-month follow-up period. Conclusion. Botulinum toxin A can be used to treat the first episode of SUNCT in children over the age of 12 years. PMID:27445629

  8. Characterization of toxin complex produced by a unique strain of Clostridium botulinum serotype D 4947.

    PubMed

    Hasegawa, Kimiko; Watanabe, Toshihiro; Sato, Hiroaki; Sagane, Yoshimasa; Mutoh, Shingo; Suzuki, Tomonori; Yamano, Akihito; Kouguchi, Hirokazu; Takeshi, Kouichi; Kamaguchi, Arihide; Fujinaga, Yukako; Oguma, Keiji; Ohyama, Tohru

    2004-08-01

    A unique strain of Clostridium botulinum, serotype D 4947 (D-4947), produces a considerable amount of a 650 kDa toxin complex (L-TC) and a small amount of a 280 kDa M-TC, a 540 kDa TC, and a 610 kDa TC. The complexes are composed of only un-nicked components, including neurotoxin (NT), nontoxic nonhemagglutinin (NTNHA) and hemagglutinin subcomponents (HA-70, HA-33 and HA-17). Unlike other NTs from all serotype strains, separation of D-4947 NT from L-TC, except for M-TC, during chromatography required highly alkaline conditions around pH 8.8. The separated NT and NTNHA/HAs complex can be reconstituted to L-TC that is indistinguishable from the parent L-TC with respect to toxicity, hemagglutination activity and gel filtration profile. The isoelectric points of NT and NTNHA/HAs were close together depending on the number of HA-33/17 molecules. We have established a new method to separate the unique D-4947 NT from the complex, which will yield valuable information on structure of botulinum toxin.

  9. Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis

    PubMed Central

    Kober, Johanna; Schmid, Melanie; Buchberger, Elisabeth; Kamolz, Lars-Peter; Keck, Maike

    2016-01-01

    Background: Botulinum (neuro)toxin A (BoNT) is widely used in the field of plastic and reconstructive surgery. Among treatment of pain, hyperhidrosis, or aesthetic purposes, it is also used to enhance wound healing and prevent excessive scar formation. Some clinical data already exist, but only little is known on a cellular level. The aim of this study was to evaluate the effect of BoNT on cells essential for wound healing in vitro. Therefore, primary human keratinocytes and endothelial cells were treated with different concentrations of BoNT and tested on proliferation, migration, and angiogenic behavior. Methods: BoNT was exposed to human keratinocytes and endothelial cells in a low (1 IU/mL), medium (10 IU/mL), and high (20 IU/mL) concentrations in cell culture. Proliferation and migration of the 2 cell types were observed and also the angiogenic potential of endothelial cells in vitro. Results: BoNT 20 IU/mL negatively influenced proliferation and migration of keratinocytes but not those of endothelial cells. Angiogenesis in vitro was less effective with the highest BoNT concentrations tested. Low concentrations of BoNT supported sprouting of endothelial cells. Conclusions: High concentrations of botulinum toxin interfered with wound closure as keratinocytes’ proliferation and migration were deteriorated. Furthermore, BoNT concentrations of 20 IU/mL constrain in vitro vessel formation but do not influence proliferation or migration of endothelial cells. PMID:27622105

  10. Rapid, Sensitive Detection of Botulinum Toxin on a Flexible Microfluidics Platform

    SciTech Connect

    Warner, Marvin G.; Dockendorff, Brian P.; Feldhaus, Michael J.; Anheier, Norman C.; Marks, James D.; Grate, Jay W.; Bruckner-Lea, Cindy J.

    2004-10-30

    In this paper we will describe how high affinity reagents and a sensor configuration enabling rapid mass transport can be combined for rapid, sensitive biodetection. The system that we have developed includes a renewable surface immunoassay, which involves on-column detection of a fluorescently labeled secondary antibody in a sandwich immunoassay. Yeast display and directed molecular evolution were used to create high affinity antibodies to the botulinum toxin heavy chain receptor binding domain, AR1 and 3D12. A rotating rod renewable surface microcolumn was used to form a microliter-sized column containing beads functionalized with the capture antibody (AR1). The column was perfused with sample, wash solutions, and a fluorescently labeled secondary antibody (3D12) while the on-column fluorescence was monitored. Detection was accomplished in less than 5 minutes, with a total processing time of about 10 minutes. On-column detection of botulinum toxin was more sensitive and much faster than flow cytometry analysis on microbeads using the same reagents.

  11. Purification and characterization of neurotoxin complex from a dual toxin gene containing Clostridium Botulinum Strain PS-5.

    PubMed

    Singh, Ajay K; Sachdeva, Amita; Degrasse, Jeffrey A; Croley, Timothy R; Stanker, Larry H; Hodge, David; Sharma, Shashi K

    2013-04-01

    Botulinum neurotoxins are produced as a toxin complex (TC) which consists of neurotoxin (NT) and neurotoxin associated proteins. The characterization of NT in its native state is an essential step for developing diagnostics and therapeutic countermeasures against botulism. The presence of NT genes was validated by PCR amplification of toxin specific fragments from genomic DNA of Clostridium botulinum strain PS-5 which indicated the presence of both serotype A and B genes on PS-5 genome. Further, TC was purified and characterized by Western blotting, Digoxin-enzyme linked immunosorbent assay, endopeptidase activity assay, and Liquid chromatography-Mass spectrometry. The data showed the presence of serotype A specific neurotoxin. Based on the analysis of neurotoxin genes and characterization of TC, PS-5 strain appears as a serotype A (B) strain of C. botulinum which produces only serotype A specific TC in the cell culture medium.

  12. Use of immunofluorescence and animal tests to detect growth and toxin production by Clostridum botulinum type E in food.

    PubMed

    Midura, T; Taclindo, C; Nygaard, G S; Bodily, H L; Wood, R M

    1968-01-01

    The appearance of Clostridium botulinum type E organisms and of toxin in experimentally inoculated packages of turkey roll was followed to study the time relationship between the presence of vegetative cells and the demonstration of toxin. The presence of vegetative cells was determined by immunofluorescence, and animal tests were used to assay toxin production. Growth initiated from detoxified spores of C. botulinum type E resulted in toxin formation within 24 hr. Presence of fluorescing vegetative cells and of toxin coincided from 1 to 14 days of incubation. Beginning with the next testing date, day 21, differences were observed. Toxin could be detected for a longer time than vegetative cells. Neither toxin nor organisms could be found after 56 days of incubation. The mouse lethal dose tests (MLD per gram of turkey roll) showed fluctuations in the amount of toxin present throughout the period of testing. Maximal amounts of toxin were present during the period when fluorescing organisms were also more numerous. The applications of immunofluorescence in the study and in the diagnosis of botulism is discussed.

  13. A comparative assessment of three formulations of botulinum toxin A for facial rhytides: a systematic review and meta-analyses

    PubMed Central

    2013-01-01

    Background Botulinum toxin A is a commonly used biological medication in the field of facial plastic surgery. Currently, there are three distinct formulations of botulinum toxin A, each with their purported benefits and advantages. However, there is considerable confusion as to the relative efficacy and side-effects associated with each formulation. Therefore, the purpose of this paper is to systematically assess published studies and perform a meta-analysis to determine if there is a significant advantage of any of the individual formulations. Methods/design A systematic literature search was performed for all relevant English language randomized controlled trials using Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register, Cochrane Library databases of clinical trials, and ClinicalTrials.gov. Inclusion criteria included any randomized controlled trial (RCT) that assessed the use of botulinum toxin for cosmetic purposes. The included articles were also analyzed for bias using the Cochrane Collaboration’s tool for assessing the risk of bias in RCTs. Discussion The results of this review will provide clinicians with an unbiased, high level of evidence of the comparative efficacy of individual preparations of botulinum toxin A. Trial registration PROSPERO: CRD4201200337 PMID:23763852

  14. Quality of life in cervical dystonia after treatment with botulinum toxin A: a 24-week prospective study

    PubMed Central

    Kongsaengdao, Subsai; Maneeton, Benchalak; Maneeton, Narong

    2017-01-01

    Objective This study aimed to identify possible improvements in disease-specific health-related quality of life (HRQoL) after multiple injections of botulinum toxin A over 24 weeks in Thai cervical dystonia (CD) patients. Materials and methods A 24-week prospective study comparing HRQoL of Thai CD patients before and after multiple injections of botulinum toxin A at 3-month intervals was performed. Disease-specific HRQoL was assessed by using the Cervical Dystonia Impact Profile-58 questionnaire (CDIP-58) and the Craniocervical Dystonia Questionnaire-24 (CDQ-24). General HRQoL was assessed by using the Medical Outcomes’ 36-Item Short Form Health Survey (SF-36) and the EuroQoL 5-dimension questionnaire (EQ-5D). All the assessments were performed before and after the 24-week treatment period. Results A total of 20 CD patients were enrolled in this study from April to December 2011. CDIP-58 and CDQ-24 scores, which assess disease-specific HRQoL, showed a significant improvement after 24 weeks of treatment by botulinum toxin A (P<0.001). However, EQ-5D and SF-36 scores, which assess general HRQoL, showed no significant improvement after the treatment (P>0.05). Conclusion CD patients’ disease-specific HRQoL improved after being treated with multiple botulinum toxin A injections. However, general HRQoL was not improved. PMID:28138245

  15. Purification and characterization of neurotoxin complex from a dual toxin gene containing Clostridium botulinum strain PS-5

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Botulinum neurotoxins (BoNTs) are produced as a toxin complex (TC) which consists of neurotoxin (NT) and neurotoxin associated proteins (NAPs). The characterization of NT in its native state is an essential step for developing diagnostics and therapeutic countermeasures against botulism. The presenc...

  16. The Use of Botulinum Toxin for the Treatment of Muscle Spasticity in the First 2 Years of Life

    ERIC Educational Resources Information Center

    Bakheit, Abdel Magid

    2010-01-01

    Although there are sound theoretical reasons for the use of botulinum toxin (Btx) as early as possible in the management of severe childhood muscle spasticity, the experience with its safety in children younger than 2 years of age is limited and information about its possible effects on the development and maturation of the human motor system…

  17. Food safety objective approach for controlling Clostridium botulinum growth and toxin production in commercially sterile foods.

    PubMed

    Anderson, N M; Larkin, J W; Cole, M B; Skinner, G E; Whiting, R C; Gorris, L G M; Rodriguez, A; Buchanan, R; Stewart, C M; Hanlin, J H; Keener, L; Hall, P A

    2011-11-01

    As existing technologies are refined and novel microbial inactivation technologies are developed, there is a growing need for a metric that can be used to judge equivalent levels of hazard control stringency to ensure food safety of commercially sterile foods. A food safety objective (FSO) is an output-oriented metric that designates the maximum level of a hazard (e.g., the pathogenic microorganism or toxin) tolerated in a food at the end of the food supply chain at the moment of consumption without specifying by which measures the hazard level is controlled. Using a risk-based approach, when the total outcome of controlling initial levels (H(0)), reducing levels (ΣR), and preventing an increase in levels (ΣI) is less than or equal to the target FSO, the product is considered safe. A cross-disciplinary international consortium of specialists from industry, academia, and government was organized with the objective of developing a document to illustrate the FSO approach for controlling Clostridium botulinum toxin in commercially sterile foods. This article outlines the general principles of an FSO risk management framework for controlling C. botulinum growth and toxin production in commercially sterile foods. Topics include historical approaches to establishing commercial sterility; a perspective on the establishment of an appropriate target FSO; a discussion of control of initial levels, reduction of levels, and prevention of an increase in levels of the hazard; and deterministic and stochastic examples that illustrate the impact that various control measure combinations have on the safety of well-established commercially sterile products and the ways in which variability all levels of control can heavily influence estimates in the FSO risk management framework. This risk-based framework should encourage development of innovative technologies that result in microbial safety levels equivalent to those achieved with traditional processing methods.

  18. Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

    PubMed

    Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

    2010-01-01

    The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations.

  19. A mixed treatment comparison to compare the efficacy and safety of botulinum toxin treatments for cervical dystonia.

    PubMed

    Han, Yi; Stevens, Andrea L; Dashtipour, Khashayar; Hauser, Robert A; Mari, Zoltan

    2016-04-01

    A systematic pair-wise comparison of all available botulinum toxin serotype A and B treatments for cervical dystonia (CD) was conducted, as direct head-to-head clinical trial comparisons are lacking. Five botulinum toxin products: Dysport(®) (abobotulinumtoxinA), Botox(®) (onabotulinumtoxinA), Xeomin(®) (incobotulinumtoxinA), Prosigne(®) (Chinese botulinum toxin serotype A) and Myobloc(®) (rimabotulinumtoxinB) have demonstrated efficacy for managing CD. A pair-wise efficacy and safety comparison was performed for all toxins based on literature-reported clinical outcomes. Multi-armed randomized controlled trials (RCTs) were identified for inclusion using a systematic literature review, and assessed for comparability based on patient population and efficacy outcome measures. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was selected as the efficacy outcome measurement for assessment. A mixed treatment comparison (MTC) was conducted using a Bayesian hierarchical model allowing indirect comparison of the interventions. Due to the limitation of available clinical data, this study only investigated the main effect of toxin treatments without explicitly considering potential confounding factors such as gender and formulation differences. There was reasonable agreement between the number of unconstrained data points, residual deviance and pair-wise results. This research suggests that all botulinum toxin serotype A and serotype B treatments were effective compared to placebo in treating CD, with the exception of Prosigne. Based on this MTC analysis, there is no significant efficacy difference between Dysport, Botox, Xeomin and Myobloc at week four post injection. Of the adverse events measured, neither dysphagia nor injection site pain was significantly greater in the treatment or placebo groups.

  20. Vaccination against type F botulinum toxin using attenuated Salmonella enterica var Typhimurium strains expressing the BoNT/F H(C) fragment.

    PubMed

    Foynes, Susan; Holley, Jane L; Garmory, Helen S; Titball, Richard W; Fairweather, Neil F

    2003-03-07

    The utility of the htrA, pagC and nirB promoters to direct the expression of the carboxy-terminal (H(C)) fragment of botulinum toxin F (FH(C)) in Salmonella enterica var Typhimurium has been evaluated. Only low levels of serum antibody were induced after immunisation, and some protection against botulinum toxin type F was demonstrated after oral immunisation of mice with two doses of any of these recombinant Salmonella. Immunisation with two doses of recombinant Salmonella expressing FH(C) from the htrA promoter gave the greatest protection, against up to 10,000 mouse lethal doses of botulinum toxin type F. These results demonstrate the feasibility of an orally delivered vaccine against botulinum toxin type F.

  1. Botulinum toxin type A products are not interchangeable: a review of the evidence

    PubMed Central

    Brin, Mitchell F; James, Charmaine; Maltman, John

    2014-01-01

    Botulinum toxin type A (BoNTA) products are injectable biologic medications derived from Clostridium botulinum bacteria. Several different BoNTA products are marketed in various countries, and they are not interchangeable. Differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. These differences result in a specific set of interactions between each BoNTA product and the tissue injected. Consequently, the products show differences in their in vivo profiles, including preclinical dose response curves and clinical dosing, efficacy, duration, and safety/adverse events. Most, but not all, published studies document these differences, suggesting that individual BoNTA products act differently depending on experimental and clinical conditions, and these differences may not always be predictable. Differentiation through regulatory approvals provides a measure of confidence in safety and efficacy at the specified doses for each approved indication. Moreover, the products differ in the amount of study to which they have been subjected, as evidenced by the number of publications in the peer-reviewed literature and the quantity and quality of clinical studies. Given that BoNTAs are potent biological products that meet important clinical needs, it is critical to recognize that their dosing and product performance are not interchangeable and each product should be used according to manufacturer guidelines. PMID:25336912

  2. Beneficial effect of botulinum A toxin in blepharospasm: 16 months' experience with 16 cases.

    PubMed

    Maurri, S; Brogelli, S; Alfieri, G; Barontini, F

    1988-08-01

    After introducing the problem of blepharospasm, we report our experience on treatment with purified botulinum A toxin in 16 cases of blepharospasm, symptomatic in two and essential in 14, than had not responded to drugs. The changes in intensity and frequency of spasm after treatment were evaluated on a clinical scale and by review of videotapes. The beneficial effect appeared within a week in most patients, lasting from 6 to 28 weeks (mean 13), and reached the maximum at the third-seventh week. Mild spasms and female patients responded better. Repeated injections were followed by better response to the drug. Complications, exclusively local, were represented by transient corneal exposure, ptosis, lacrimation or diplopia.

  3. Critical analysis of the use of onabotulinumtoxinA (botulinum toxin type A) in migraine

    PubMed Central

    Robertson, Carrie E; Garza, Ivan

    2012-01-01

    OnabotulinumtoxinA, a neurotoxin, has been studied in numerous trials as a novel preventive therapy for migraine headache. The data would support that it may be effective at reducing headache days in patients suffering from chronic migraine (≥15 headache days/month, with eight or more of those migraine headache days). The mechanism by which onabotulinumtoxinA exerts its effects on migraine is not yet understood. It is known to inhibit acetylcholine release at the neuromuscular junction, but this probably does not explain the observed antinociceptive properties noted in preclinical and clinical trials. This review will discuss the known mechanisms of action of botulinum toxin type A, and will review the available randomized, placebo-controlled trials that have looked at its efficacy as a migraine preventative. We also describe the onabotulinumtoxinA injection sites used at our institution. PMID:22275844

  4. Somatosensory temporal discrimination tested in patients receiving botulinum toxin injection for cervical dystonia.

    PubMed

    Scontrini, Alessandra; Conte, Antonella; Fabbrini, Giovanni; Colosimo, Carlo; Di Stasio, Flavio; Ferrazzano, Gina; Berardelli, Alfredo

    2011-03-01

    We designed this study to find out more about the relationship between the sensory effects of Botulinum toxin type A (BTX) and the clinical benefits of BTX therapy in patients with cervical dystonia (CD). In 24 patients with CD, we tested sensory temporal discrimination (STD) in the affected and two unaffected body regions (neck, hand, and eye) before and 1 month after BTX injection. In 8 out of the 24 patients with CD, STDT values were tested bilaterally in the three body regions before, 1 and 2 months after BTX injection. As expected, STD testing disclosed altered STD threshold values in all three body regions tested (affected and unaffected by dystonic spasms) in patients with CD. STD threshold values remained unchanged at all time points of the follow-up in all CD patients. The lack of BTX-induced effects on STD thresholds suggests that STD recruits neural structures uninvolved in muscle spindle afferent activation.

  5. Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception.

    PubMed

    Kim, Dong-Wan; Lee, Sun-Kyung; Ahnn, Joohong

    2015-06-30

    Botulinum neurotoxins (BoNTs) have been widely used to treat a variety of clinical ailments associated with pain. The inhibitory action of BoNTs on synaptic vesicle fusion blocks the releases of various pain-modulating neurotransmitters, including glutamate, substance P (SP), and calcitonin gene-related peptide (CGRP), as well as the addition of pain-sensing transmembrane receptors such as transient receptor potential (TRP) to neuronal plasma membrane. In addition, growing evidence suggests that the analgesic and anti-inflammatory effects of BoNTs are mediated through various molecular pathways. Recent studies have revealed that the detailed structural bases of BoNTs interact with their cellular receptors and SNAREs. In this review, we discuss the molecular and cellular mechanisms related to the efficacy of BoNTs in alleviating human pain and insights on engineering the toxins to extend therapeutic interventions related to nociception.

  6. Botulinum toxin type-A in the management of spastic equinovarus deformity after stroke

    PubMed Central

    Otom, Ali H.; Al-Khawaja, Imad M.; Al-Quliti, Khalid W.

    2014-01-01

    Objective: To retrospectively compare 2 injection techniques in the management of spastic equinovarus deformity after stroke. Methods: Patients with stroke were seen at King Hussein Medical Center, Amman, Jordan between January and December 2009. The study design involved an open label retrospective analysis of medical records of 2 groups of comparable age and onset of first stroke. Botulinum toxin was injected into the calf muscles at 2 sites in group I (12 patients) and 4 sites in group II (14 patients). Functional gain was evaluated by the time to walk 10 meters at month one, 3, and 6 compared with baseline. Results: There was significant improvement in walking time in each study group. However, there was no significant difference between the 2 groups as measured by the 10-meter walking time. Conclusion: Fewer injection sites would minimize patient discomfort and possibly the production of antibodies, yielding similar therapeutic effects. PMID:24983281

  7. New techniques in the treatment of common perianal diseases: stapled hemorrhoidopexy, botulinum toxin, and fibrin sealant.

    PubMed

    Singer, Marc; Cintron, Jose

    2006-08-01

    There have been several recent advances in the treatment of common perianal diseases. Stapled hemorrhoidopexy is a procedure of hemorrhoidal fixation, combining the benefits of rubber band ligation into an operative technique. The treatment of anal fissure has typically relied upon internal sphincterotomy; however, it carries a risk of incontinence. The injection of botulinum toxin represents a new form of sphincter relaxation, without division of any sphincter muscle; morbidity is minimal and results are promising. For the treatment of fistula in a fistulotomy remains the gold standard, however, it carries significant risk of incontinence. Use of fibrin sealant to treat fistulae has been met with variable success. It offers sealing of the tract, and then provides scaffolding for native tissue ingrowth.

  8. Treatment of focal dystonias of the hand with botulinum toxin injections.

    PubMed Central

    Cohen, L G; Hallett, M; Geller, B D; Hochberg, F

    1989-01-01

    The effects of botulinum toxin injections have been studied on 19 patients with hand dystonia. The dystonic muscles were identified by clinical examination and EMG findings of localised bursts of muscle activation with fine wire electrodes during the tasks that precipitated the dystonia. Injections into the most active muscles were given to each patient every 2 weeks in increasing doses (up to 20 U the first week, up to 40 U the second week, and up to 80 U the third week) until performance improvement was achieved. Subjective improvement of cramping, pain and/or tension was associated with temporary weakness in injected muscles. Benefit was seen in 16 patients, lasted between 1 and 6 months, and was reproducible. PMID:2926421

  9. Botulinum toxin injections into salivary glands to decrease oral secretions in CHARGE syndrome: prospective case study.

    PubMed

    Blake, Kim D; MacCuspie, Jillian; Corsten, Gerard

    2012-04-01

    CHARGE syndrome is a genetic disorder caused by a mutation in the CHD7 gene on chromosome 8. Major clinical diagnostic criteria for this heterogeneous disorder include ocular coloboma, choanal atresia/stenosis, characteristic external and internal ear abnormalities, and cranial nerve abnormalities. Patients with CHARGE syndrome often have dysphagia and are at high risk for aspiration of both upper and lower gastrointestinal secretions. The following case-report describes the use of Botulinum toxin A (Botox) to reduce excess salivary secretions in a ventilator dependant infant who would have required a tracheotomy. Thereafter, Botox was used regularly (4-5 months) to decrease the salivary secretions. This case-report is unique in that it describes the intermittent and prospective use of Botox to reduce excess salivary secretions and prevent the resulting aspiration-related complications in an infant with CHARGE syndrome.

  10. Efficacy of botulinum toxin in pachyonychia congenita type 1: report of two new cases.

    PubMed

    González-Ramos, Jéssica; Sendagorta-Cudós, Elena; González-López, Guillermo; Mayor-Ibarguren, Ander; Feltes-Ochoa, Rosa; Herranz-Pinto, Pedro

    2016-01-01

    Pachyonychia congenita (PC) is a rare genodermatosis caused by a mutation in keratin genes, which can lead to hypertrophic nail dystrophy and focal palmoplantar keratoderma (predominantly plantar), amongst other manifestations. Painful blisters and callosities, sometimes exacerbated by hyperhidrosis, are major issues that can have a significant impact on patient quality of life. Many alternative treatments for this condition have been applied with variable and partial clinical response, but a definitive cure for this disease has yet to be discovered. After obtaining informed consent, two patients with genetically confirmed PC type 1 were treated with plantar injections of botulinum toxin type A. Both patients showed a marked improvement in pain and blistering with an average response time of one week, a six-month mean duration of effectiveness, and a lack of any side effects or tachyphylaxis.

  11. Medium- to long-term outcomes of botulinum toxin A for idiopathic overactive bladder

    PubMed Central

    Eldred-Evans, David; Sahai, Arun

    2016-01-01

    Botulinum toxin A (BoNT-A) has become an important therapeutic tool in the management of refractory overactive bladder (OAB). Over the last decade, there have been growing numbers of patients receiving repeat injections and these outcomes have begun to be reported in large, high-quality cohorts. This article reviews the current evidence for the medium- to long-term use of BoNT-A in adults with idiopathic detrusor overactivity (IDO) receiving repeat injections. We find that medium-term outcomes are encouraging but long-term outcomes are not as extensively reported. There is high-quality evidence that efficacy following the first injection persists across multiple treatment cycles. There are no additional safety concerns from repeat injections up to six treatment cycles. However, there is a need for further data to confirm the efficacy and safety of BoNT-A beyond the follow-up period in the current literature. PMID:28042308

  12. Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception

    PubMed Central

    Kim, Dong-Wan; Lee, Sun-Kyung; Ahnn, Joohong

    2015-01-01

    Botulinum neurotoxins (BoNTs) have been widely used to treat a variety of clinical ailments associated with pain. The inhibitory action of BoNTs on synaptic vesicle fusion blocks the releases of various pain-modulating neurotransmitters, including glutamate, substance P (SP), and calcitonin gene-related peptide (CGRP), as well as the addition of pain-sensing transmembrane receptors such as transient receptor potential (TRP) to neuronal plasma membrane. In addition, growing evidence suggests that the analgesic and anti-inflammatory effects of BoNTs are mediated through various molecular pathways. Recent studies have revealed that the detailed structural bases of BoNTs interact with their cellular receptors and SNAREs. In this review, we discuss the molecular and cellular mechanisms related to the efficacy of BoNTs in alleviating human pain and insights on engineering the toxins to extend therapeutic interventions related to nociception. PMID:26134255

  13. Botulinum toxin: An effective treatment for prosthesis-related hyperhidrosis in patients with traumatic amputations

    PubMed Central

    Lezanski-Gujda, Amanda; Bingham, Jonathan L.; Logemann, Nicholas F.

    2015-01-01

    Hyperhidrosis-related to prosthesis use in patients who have suffered a traumatic limb amputation presents itself as a barrier to comfort, prosthesis use and overall quality of life. This review intends to encourage dermatologists to consider the use of botulinum toxin A or B for the treatment of hyperhidrosis in the residual limb and may serve as a stimulus for a modern, in-depth, and more comprehensive study. A review of the literature was conducted using the PubMed database, focusing on hyperhidrosis treatment after traumatic limb amputation. Articles discussing hyperhidrosis treatment for amputations secondary to chronic medical conditions were excluded. Seven case studies published over the last 12 years have demonstrated positive outcomes of this treatment strategy. Overall, there is little data examining this topic and current publications focus primarily on small case series. A larger, double-blind, placebo-controlled study would likely benefit veterans, service members, and civilians. PMID:25657907

  14. Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

    PubMed Central

    Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

    2015-01-01

    Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A. PMID:26404377

  15. Antagonism of botulinum toxin-induced muscle weakness by aminopyridines in rat phrenic nerve-hemidiaphragm preparations

    SciTech Connect

    Adler, M.; Scovill, J.; Deshpande, S.S.

    1993-05-13

    The effects of the potassium channel inhibitor and putative botulinum toxin antagonists 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the contractile and electrophysiological properties of rat diaphragm muscle. In the presence of 300 pM botulinum toxin A (BoTx A), twitches elicited by supramaximal nerve stimulation (0. 1 Hz) were reduced by over 80% in 3 hr. The time to block decreased with increases in temperature, toxin concentration and stimulation frequency. Addition of 4-AP or 3,4-DAP led to a prompt reversal of the BoTx A-induced depression of twitch tension. This reversal was concentration-dependent such that, in the presence of 1 mM 4-AP, reversal of the BoTx A-induced blockade was complete in 6.7 min. The beneficial effect of the APs were well maintained and persisted for up to 6 hr after addition. Application of 1 microns M neostigmine 1 hr after 3,4-DAP produced a further potentiation of twitch tensions, but this action lasted for < 5 min and led to the appearance of tetanic fade during repetitive stimulation. It is concluded that the APs are of benefit in antagonizing the muscle paralysis following exposure to botulinum toxin. Co-application of neostigmine, however, appears to confer no additional benefit.

  16. Functional end-plate recovery in long-term botulinum toxin therapy of hemifacial spasm: a nerve conduction study.

    PubMed

    Butera, C; Guerriero, R; Amadio, S; Ungaro, D; Tesfaghebriel, H; Bianchi, F; Comi, G; Del Carro, U

    2013-02-01

    Botulinum toxin type-A is currently thought to be effective and safe for hemifacial spasm (HFS). The pre-synaptic block of acetylcholine release at the neuromuscular junction induces depression of orbicularis oculi muscle compound motor action potential (CMAP). The aim of our study was to evaluate at what extent end-plate functional recovery is possible even in botulinum toxin treatments lasting up to 15 years. We examined 81 outpatients with primary HFS (mean treatment duration = 7.2 ± 4.2 years) who underwent neurophysiologic study, once clinical effect of the previous treatment had vanished. The mean CMAP amplitude, mean rectified amplitude of response 1 (R1) of the blink reflex and area of response 2 (R2) of treated orbicularis oculi muscle were measured in comparison to the controlateral side. Mean amplitude of the above mentioned parameters was slightly lower (about 20%; p < 0.001) in the treated side at the end of the follow-up period (4.7 ± 1.7 months). The CMAP amplitude reduction weakly correlated with the interval from last treatment, while other neurophysiologic parameters did not change due to treatment duration or total toxin amount. Our study demonstrates that botulinum toxin affects compound motor action potential and blink-reflex responses for at least 4-5 months in HFS patients. The residual block is slight and does not increase with repeated injections after several years of treatment. Our study, beside confirming the long-term efficacy of botulinum toxin treatment for HFS, provides neurophysiologic evidence that therapeutic effect may be obtained without hindering the regenerative potential of the nerve-muscle complex.

  17. Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

    PubMed

    Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

    2014-11-01

    The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method.

  18. Combined effect of botulinum toxin and splinting on motor components and function of people suffering a stroke

    PubMed Central

    Amini, Malek; Shamili, Aryan; Frough, Bijan; Pashmdarfard, Marzieh; Fallahzadeh Abarghouei, AbolGhasem

    2016-01-01

    Background: Spasticity is one of the problems after a stroke. Due to this increase in muscle tone, patients are confronted with problems in motor control and difficulties in activities of daily living and complications such as shortness and contracture. The aim of this study was to examine the effects of the simultaneous use of both splint and botulinum toxin-A (BTX-A) injection on spasticity, range of motion and upper extremity function in a 3-month period. Methods: In this study a comparison was done between three groups of interventions, conducted in rehabilitation clinics in Tehran. Sixty people with chronic stroke were recruited. Based on the inclusion criteria, a total of 39 stroke patients after completing the consent forms were entered to intervention groups; splint or botulinum toxin injection or combined splint/botulinum toxin injection. They were followed up about three months and the evaluations were done monthly. Goniometry was the method to measure the range of motion, and Modified Ashworth Scale was used to examine the spasticity and the upper extremity function was scored based on Fugl- Meyer Assessment. Statistical analysis was done using SPSS 17. And ANOVAs was used for comparison between groups and times. Significance was set at 0.05. Results: All outcome measures were improved within each group but the differences between splint group and BTX-A group and the BTX-A-splint group was not significant in most outcomes during the 3 periods (first evaluation until end of the first month, the end of first month until the end of second month, the end of second month until the end of the third month) (p>0.05). The results also showed that the changes in elbow`s spasticity (p=0.05) and wrist`s spasticity (p=0.007) and upper extremity function (p=0.04) were obvious between the three groups over the 3-months and the difference in the group of combined use of botulinum toxin, and the splint was more than other groups. Conclusion: In this study, the effects of

  19. Crystallization and preliminary X-ray analysis of the HA3 component of Clostridium botulinum type C progenitor toxin

    SciTech Connect

    Nakamura, Toshio; Tonozuka, Takashi; Kotani, Mao; Obata, Kanae; Oguma, Keiji; Nishikawa, Atsushi

    2007-12-01

    HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type C 16S progenitor toxin. In this report, recombinant HA3 protein was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.6 Å resolution and the crystal belonged to the hexagonal space group P6{sub 3}. Matthews coefficient and self-rotation function calculations indicate that there is probably one molecule of HA3 in the asymmetric unit. A search for heavy-atom derivatives has been undertaken.

  20. The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment: ROSETTA Trial^, ^^

    PubMed Central

    Amundsen, Cindy L.; Richter, Holly E.; Menefee, Shawn; Vasavada, Sandip; Rahn, David D.; Kenton, Kim; Harvie, Heidi S.; Wallace, Dennis; Meikle, Susie

    2014-01-01

    We present the rationale for and design of a randomized, open-label, active-control trial comparing the effectiveness of 200 units of onabotulinum toxin A (Botox A®) versus sacral neuromodulation (InterStim®) therapy for refractory urgency urinary incontinence (UUI). The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment (ROSETTA) trial compares changes in urgency urinary incontinence episodes over 6 months, as well as other lower urinary tract symptoms, adverse events and cost effectiveness in women receiving these two therapies. Eligible participants had previously attempted treatment with at least 2 medications and behavioral therapy. We discuss the importance of evaluating two very different interventions, the challenges related to recruitment, ethical considerations for two treatments with significantly different costs, follow up assessments and cost effectiveness. The ROSETTA trial will provide information to healthcare providers regarding the technical attributes of these interventions as well as the efficacy and safety of these two interventions on other lower urinary tract and pelvic floor symptoms. Enrollment began in March, 2012 with anticipated end to recruitment in mid 2014. PMID:24486637

  1. Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation.

    PubMed

    Bach-Rojecky, Lidija; Dominis, Mara; Lacković, Zdravko

    2008-10-01

    Botulinum toxin type A (BTX-A) has a long-lasting antinociceptive activity and less clear effect on inflammation. It was proposed that these two effects share the same mechanism--the inhibition of neurotransmitter exocytosis from peripheral nerve endings. However, till now possible anti-inflammatory action of BTX-A did not evoke much attention. In the present paper, we investigate possible anti-inflammatory action of the toxin in carrageenan and capsaicin models of inflammation in rats. BTX-A (5 and 10 U/kg) was injected into the plantar surface of the rat right hind-paw pad 5 days before the injection of the carrageenan (1%) or capsaicin (0.1%) at the same site. Carrageenan-induced paw oedema and capsaicin-induced protein extravasation were measured. Control, inflamed and BTX-A pretreated inflamed paws were photographed and histopathological analysis (haematoxylin & eosin) was performed. Pretreatment with BTX-A had no effect on the size of carrageenan-induced paw oedema, measured as paw volume and weight or capsaicin-induced plasma extravasations, measured by Evans blue as a marker of protein leakage. Neither macroscopic nor microscopic analysis showed a significant difference between BTX-A pretreated and control inflamed tissue. Results show dissociation between the effect of BTX-A on pain and inflammation thus questioning the validity of the suggested assumption about the common peripheral mechanism of action.

  2. Safety of Botulinum Toxin A in Children and Adolescents with Cerebral Palsy in a Pragmatic Setting

    PubMed Central

    Papavasiliou, Antigone S.; Nikaina, Irene; Foska, Katerina; Bouros, Panagiotis; Mitsou, George; Filiopoulos, Constantine

    2013-01-01

    This retrospective study aimed to examine the safety of botulinum toxin A (BoNT-A) treatment in a paediatric multidisciplinary cerebral palsy clinic. In a sample of 454 patients who had 1515 BoNT-A sessions, data on adverse events were available in 356 patients and 1382 sessions; 51 non-fatal adverse events were reported (3.3% of the total injections number, 8.7% of the patients). On five occasions, the adverse reactions observed in GMFCS V children were attributed to the sedation used (rectal midazolam plus pethidine; buccal midazolam) and resulted in prolongation of hospitalization. Of the reactions attributed to the toxin, 23 involved an excessive reduction of the muscle tone either of the injected limb(s) or generalized; others included local pain, restlessness, lethargy with pallor, disturbance in swallowing and speech production, seizures, strabismus, excessive sweating, constipation, vomiting, a flu-like syndrome and emerging hypertonus in adjacent muscles. Their incidence was associated with GMFCS level and with the presence of epilepsy (Odds ratio (OR) = 2.74 − p = 0.016 and OR = 2.35 − p = 0.046, respectively) but not with BoNT-A dose (either total or per kilogram). In conclusion, treatment with BoNT-A was safe; adverse reactions were mostly mild even for severely affected patients. Their appearance did not necessitate major changes in our practice. PMID:23482250

  3. Anticholinergic Versus Botulinum Toxin A Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC Trial

    PubMed Central

    Visco, Anthony G.; Brubaker, Linda; Richter, Holly E.; Nygaard, Ingrid; Paraiso, Marie Fidela; Menefee, Shawn A.; Schaffer, Joseph; Wei, John; Chai, Toby; Janz, Nancy; Spino, Cathie; Meikle, Susan

    2011-01-01

    This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 unit of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC Trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost-effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intradetrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug naïve women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intradetrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intradetrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. PMID:22008247

  4. The use of botulinum toxin injections to manage drooling in amyotrophic lateral sclerosis/motor neurone disease: a systematic review.

    PubMed

    Squires, Nina; Humberstone, Miles; Wills, Adrian; Arthur, Antony

    2014-08-01

    Difficulty in managing oral secretions is commonly experienced by patients with amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) and associated bulbar weakness including dysphagia. There are no definitive evidence-based treatment guidelines to manage the distressing symptom of drooling. We reviewed the evidence for the effectiveness of botulinum toxin injections to reduce saliva in ALS/MND. The search strategy was conducted in four stages: (1) electronic search of relevant databases, (2) hand searches of all international ALS/MND symposium journals, (3) email request to MND care centres in the UK and Ireland, and (4) hand searching of reference lists. All studies were critically appraised and relevant data extracted. Botulinum toxin type A and type B were analysed separately. Due to heterogeneity, it was not possible to calculate a pooled estimate of effect. Twelve studies met the inclusion criteria (9 for type A and 3 for type B). Only two randomised controlled trials were identified. Study sample sizes were small with a mean of 12.5 subjects. The most frequently reported outcomes were weight of cotton rolls and number of tissues used. All studies claimed the intervention tested was effective, but only seven studies (4 for type A and 3 for type B) reported statistically significant differences. Although there is evidence to suggest that botulinum toxin B can reduce drooling, the evidence base is limited by a lack of randomized controlled trials. Evidence to support the use of botulinum toxin A is weaker. Larger trials will help remove the uncertainty practitioners face in treating this disabling symptom.

  5. Botulinum Toxin Type a Injection, Followed by Home-Based Functional Training for Upper Limb Hemiparesis after Stroke

    ERIC Educational Resources Information Center

    Takekawa, Toru; Kakuda, Wataru; Taguchi, Kensuke; Ishikawa, Atsushi; Sase, Yousuke; Abo, Masahiro

    2012-01-01

    Botulinum toxin type A (BoNT-A) has been reported to be an effective treatment for limb spasticity after stroke. However, the reduction in the spasticity after BoNT-A injection alone does not ensure an improvement in the active motor function of the affected limb. The aim of this study was to clarify the clinical effects of a BoNT-A injection,…

  6. A Randomized Controlled Trial Comparing Botulinum Toxin A Dosage in the Upper Extremity of Children with Spasticity

    ERIC Educational Resources Information Center

    Kawamura, Anne; Campbell, Kent; Lam-Damji, Sophie; Fehlings, Darcy

    2007-01-01

    This study compared the effects of low and high doses of botulinum toxin A (BTX-A) to improve upper extremity function. Thirty-nine children (22 males, 17 females) with a mean age of 6 years 2 months (SD 2y 9mo) diagnosed with spastic hemiplegia or triplegia were enrolled into this double-blind, randomized controlled trial. The high-dose group…

  7. Botulinum toxin type A and B improve quality of life in patients with axillary and palmar hyperhidrosis.

    PubMed

    Rosell, Karolina; Hymnelius, Kristina; Swartling, Carl

    2013-05-01

    Hyperhidrosis is a common disorder that may have a severe impact on quality of life. The aim of this study was to investigate the clinical effect of two novel botulinum toxins, Xeomin®, a type A botulinum toxin, and Neuro-bloc®, a type B botulinum toxin, in the treatment of axillary and palmar hyperhidrosis. A total of 84 patients, 58 with axillary and 26 with palmar hyperhidrosis, were included in this open study. Axillae were injected with 107 ± 22 U Xeomin® and palms were injected with 213 ± 19 U Xeomin® and 264 ± 60 U Neurobloc® over the thenar eminences to avoid muscle weakness. At follow-up 3 weeks post-treatment, all patients treated for axillary hyperhidrosis reported satisfaction in self-ranking, evaporation decreased > 40%, and Dermatology Life Quality Index (DLQI) score improved from 12.0 to 1.7 (p < 0.05). In the palmar group 95% were satisfied, evaporation decreased > 50% and DLQI score improved from 10.3 to 1.2 (p < 0.05). Only one patient in the palmar group experienced muscle weakness. In conclusion, Xeomin® has an excellent effect on axillary hyperhidrosis and in combination with Neurobloc® on palmar hyperhidrosis. Neurobloc® may be an option for use in the treatment of palmar hyperhidrosis in order to minimize muscular side-effects.

  8. Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization

    PubMed Central

    1981-01-01

    Taking advantage of the fact that nerve terminal mitochondria swell and sequester calcium during repetitive nerve stimulation, we here confirm that this change is caused by calcium influx into the nerve and use this fact to show that botulinum toxin abolishes such calcium influx. The optimal paradigm for producing the mitochondrial changes in normal nerves worked out to be 5 min of stimulation at 25 Hz in frog Ringer's solution containing five time more calcium than normal. Applying this same stimulation paradigm to botulinum-intoxicated nerves produced no mitochondrial changes at all. Only when intoxicated nerves were stimulated in 4-aminopyridine (which grossly exaggerates calcium currents in normal nerves) or when they were soaked in black widow spider venom (which is a nerve-specific calcium ionophore) could nerve mitochondria be induced to swell and accumulate calcium. These results indicate that nerve mitochondria are not damaged directly by the toxin and point instead to a primary inhibition of the normal depolarization- evoked calcium currents that accompany nerve activity. Because these currents normally provide the calcium that triggers transmitter secretion from the nerve, this demonstration of their inhibition helps to explain how botulinum toxin paralyzes. PMID:6259176

  9. Botulinum Toxin to Improve Results in Cleft Lip Repair: A Double-Blinded, Randomized, Vehicle-Controlled Clinical Trial

    PubMed Central

    Chang, Chun-Shin; Wallace, Christopher Glenn; Hsiao, Yen-Chang; Chang, Chee-Jen; Chen, Philip Kuo-Ting

    2014-01-01

    Background Most patients with facial scarring would value even a slight improvement in scar quality. Botulinum toxin A is widely used to alleviate facial dynamic rhytides but is also believed to improve scar quality by reducing wound tension during healing. The main objective was to assess the effect of Botulinum toxin on scars resultant from standardized upper lip wounds. Methods In this double-blinded, randomized, vehicle-controlled, prospective clinical trial, 60 consecutive consenting adults undergoing cleft lip scar revision (CLSR) surgery between July 2010 and March 2012 were randomized to receive botulinum toxin A (n = 30) or vehicle (normal saline; n = 30) injections into the subjacent orbicularis oris muscle immediately after wound closure. Scars were independently assessed at 6-months follow-up in blinded fashion using: Vancouver Scar Scale (VSS), Visual Analogue Scale (VAS) and photographic plus ultrasound measurements of scar widths. Results 58 patients completed the trial. All scar assessment modalities revealed statistically significantly better scars in the experimental than the vehicle-control group. Conclusion Quality of surgical upper lip scars, which are oriented perpendicular to the direction of pull of the underlying orbicularis oris muscle, is significantly improved by its temporary paralysis during wound healing. Trial Registration ClinicalTrials.gov NCT01429402 PMID:25541942

  10. A prospective study of the use of botulinum toxin injections in the treatment of Raynaud's syndrome associated with scleroderma.

    PubMed

    Uppal, L; Dhaliwal, K; Butler, P E

    2014-10-01

    Raynaud's syndrome contributes to the pain, paraesthesia, ulceration, and gangrene of scleroderma. Botulinum toxin has been shown to improve digital perfusion in patients with Raynaud's. This is the first study to objectively assess hand function following this treatment in patients with scleroderma. Twenty patients were treated with 100 units of botulinum toxin injected into the hand. An assessment of hand function and symptoms was performed prior to injection and then 8-12 weeks later. The outcomes assessed were change in pain, appearance, cold intolerance, pinch and power grip, ranges of movement, and Disabilities of the Arm, Shoulder and Hand (DASH) score. In total, 80% of patients reported an overall improvement in their symptoms, reduction in pain, and improved DASH score and 65% reported improvement in cold intolerance. Overall, 90% showed an improvement in pinch grip and 65% an improvement in power grip. Objective parameters were statistically significantly improved; however, subjective outcomes only showed a trend. We have found botulinum toxin to be an effective treatment for Raynaud's syndrome secondary to scleroderma.

  11. Myofascial pain of the jaw muscles: comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique.

    PubMed

    Guarda-Nardini, Luca; Stecco, Antonio; Stecco, Carla; Masiero, Stefano; Manfredini, Daniele

    2012-04-01

    A randomized controlled trial was performed to compare the short-term effectiveness of botulinum toxin injections and physiatric treatment provided by means of Fascial Manipulation techniques in the management of myofascial pain of jaw muscles. Thirty patients with a Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) diagnosis of myofascial pain were randomized to receive either single-session botulinum toxin injections (Group A) or multiple-session Fascial Manipulation (Group B). Maximum pain levels (VAS ratings) and jaw range of motion in millimeters (maximum mouth opening, protrusion, right and left laterotrusion) were assessed at baseline, at the end of treatment, and at a three-month follow-up. Both treatment protocols provided significant improvement over time for pain symptoms. The two treatments seem to be almost equally effective, Fascial Manipulation being slightly superior to reduce subjective pain perception, and botulinum toxin injections being slightly superior to increase jaw range of motion. Differences between the two treatment protocols as to changes in the outcome parameters at the three-months follow-up were not relevant clinically. Findings from the present investigation are in line with literature data supporting the effectiveness of a wide spectrum of conservative treatment approaches to myofascial pain of the jaw muscles. Future studies on larger samples over a longer follow-up span are needed on the way to identify tailored treatment strategies.

  12. Placebo controlled, randomised, double blind study of the effects of botulinum A toxin on detrusor sphincter dyssynergia in multiple sclerosis patients

    PubMed Central

    Gallien, P; Reymann, J; Amarenco, G; Nicolas, B; de Seze, M; Bellissant, E

    2005-01-01

    Objective: The purpose of the study was to evaluate the efficacy and safety of botulinum A toxin in the treatment of detrusor sphincter dyssynergia in multiple sclerosis patients. Methods: This was a multicentre, placebo controlled, randomised, double blind study. Patients with chronic urinary retention were included if they had post-voiding residual urine volume between 100 and 500 ml. They received a single transperineal injection of either botulinum A toxin (100 U Allergan) or placebo in the sphincter and also 5 mg slow release alfuzosin bid over 4 months. Main endpoint was post-voiding residual urine volume assessed 1 month after injection. Follow up duration was 4 months. Statistical analysis was performed using a sequential method, the triangular test. Results: The study was stopped after the fourth analysis (86 patients had been included: placebo: 41, botulinum A toxin: 45). At inclusion, there was no significant difference between groups whichever variable was considered. Mean (standard deviation) post-voiding residual urine volume was 217 (96) and 220 (99) ml in placebo and botulinum A toxin groups, respectively. One month later, post-voiding residual urine volume was 206 (145) and 186 (158) ml (p = 0.45) in placebo and botulinum A toxin groups, respectively. However, compared to placebo, botulinum A toxin significantly increased voiding volume (+54%, p = 0.02) and reduced pre-micturition (–29%, p = 0.02) and maximal (–21%, p = 0.02) detrusor pressures. Other secondary urodynamic endpoints and tolerance were similar in the two groups. Conclusions: In multiple sclerosis patients with detrusor sphincter dyssynergia, a single injection of botulinum A toxin (100 U Allergan) does not decrease post-voiding residual urine volume. PMID:16291892

  13. High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex

    PubMed Central

    Lee, Kwangkook; Lam, Kwok-Ho; Kruel, Anna Magdalena; Perry, Kay; Rummel, Andreas; Jin, Rongsheng

    2014-01-01

    Botulinum neurotoxins (BoNTs) are produced as progenitor toxin complexes (PTCs) by Clostridium botulinum. The PTCs are composed of BoNT and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver BoNT through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich PTC on the intestinal lumen preceding its transport across the epithelial barriers. Here, we report the crystal structure of HA33 of type B PTC (HA33/B) in complex with lactose at 1.46 Å resolution. The structural comparisons among HA33 of serotypes A–D reveal two different HA33–glycan interaction modes. The glycan-binding pockets on HA33/A and B are more suitable to recognize galactose-containing glycans in comparison to the equivalent sites on HA33/C and D. On the contrary, HA33/C and D could potentially recognize Neu5Ac as an independent receptor, whereas HA33/A and B do not. These findings indicate that the different oral toxicity and host susceptibility observed among different BoNT serotypes could be partly determined by the serotype-specific interaction between HA33 and host carbohydrate receptors. Furthermore, we have identified a key structural water molecule that mediates the HA33/B–lactose interactions. It provides the structural basis for development of new receptor-mimicking compounds, which have enhanced binding affinity with HA33 through their water-displacing moiety. PMID:24631690

  14. The structure of the neurotoxin-associated protein HA33/A from Clostridium botulinum suggests a reoccurring beta-trefoil fold in the progenitor toxin complex.

    PubMed

    Arndt, Joseph W; Gu, Jenny; Jaroszewski, Lukasz; Schwarzenbacher, Robert; Hanson, Michael A; Lebeda, Frank J; Stevens, Raymond C

    2005-03-04

    The hemagglutinating protein HA33 from Clostridium botulinum is associated with the large botulinum neurotoxin secreted complexes and is critical in toxin protection, internalization, and possibly activation. We report the crystal structure of serotype A HA33 (HA33/A) at 1.5 A resolution that contains a unique domain organization and a carbohydrate recognition site. In addition, sequence alignments of the other toxin complex components, including the neurotoxin BoNT/A, hemagglutinating protein HA17/A, and non-toxic non-hemagglutinating protein NTNHA/A, suggests that most of the toxin complex consists of a reoccurring beta-trefoil fold.

  15. Factors affecting growth and toxin production by Clostridium botulinum type E on irradiated (0. 3 Mrad) chicken skins

    SciTech Connect

    Firstenberg-Eden, R.; Rowley, D.B.; Shattuck, G.E.

    1982-05-01

    A model system (chicken skins with chicken exudate) was used to determine if Clostridium botulinum type E (Beluga) spores, stressed by low dose irradiation, would develop and produce toxin at abuse temperatures of 10 and 30/sup 0/C in the absence of characteristic spoilage. Unstressed spores germinated, multiplied, and produced toxin on vacuum-packed chicken skins, stored at either 30 or 10/sup 0/C. Cell numbers increased faster and toxin was evident sooner at 30/sup 0/C than at 10/sup 0/C. At 30/sup 0/C, growth occurred and toxin was produced more slowly when samples were incubated aerobically than anaerobically. When samples were incubated aerobically at 10/sup 0/C, no toxin was detected within a test period of 14 days. An irradiation dose of 0.3 Mrad at 5/sup 0/C reduced a spore population on vacuum-sealed chicken skins by about 90%. The surviving population produced toxin at 30/sup 0/C under either aerobic or anaerobic conditions, at 10/sup 0/C no toxin was detected even on skins incubated anaerobically. Under the worst conditions (30/sup 0/C, vacuum packed) toxin was not detected prior to characteristic spoilage caused by the natural flora surviving 0.3 Mrad.

  16. The changes of serum proteome and tissular pathology in mouse induced by botulinum toxin E injection.

    PubMed

    Wang, J F; Mao, X Y; Zhao, C

    2014-01-01

    The experiment were performed to investigate the poisoning-related proteins and main pathological changes after mouse suffered from injection of botulinum toxin serotype E. Dose of 0.75 LD50 botulinum toxin serotype E per mice were administrated by intraperitoneal injection. Survival mouse were picked as experimental group. The blood were collected from orbital blood and serum sample was separated by centrifugation. The heart, liver, spleen, lung, kidney were fixed in 10 % neutral buffered formalin and then developed paraffin sections. Serum protein components were analyzed by SDS-PAGE gel electrophoresis coupled with 2-DE SDS-PAGE gel electrophoresis. Differentially expressed proteins were analyzed by PDQUest8.0 software and subjected to ion trap mass spectrometry equipped with a high performance liquid chromatography system. The observation of pathological section showed that heart, liver, spleen, lung, kidney exhibited pathological changes in different degree, especially in heart, liver and lung tissues. Heart muscle tissue display serious inflammatory response, heart muscle fiber compulsively expanded and filled with erythrocyte and inflammatory exudates, some heart muscle fiber ruptured, even necrosis; hepatic cell in edge of liver occur apoptosis and some hepatic cell have disintegrated, and even died; pulmonary alveoli broken and partial vein filled with blood. Serum proteins component present a significant changes between control serum and botulism in 24 h by SDS-PAGE gel electrophoresis and 2-DE-SDS-PAGE gel electrophoresis. Twenty differentially expressed protein spots were observed in 2-DE profiles, in which 14 protein spots were undetectable in serum proteome under botulism, 3 protein spots exclusively expressed in state of botulism, 3 protein spots were low-expressed in serum proteome under botulism. Fourteen proteins have been identified among 20 spots elected on two-dimensional electrophoresis gels. Crystal proteins family exclusively expressed in

  17. Botulinum Toxin Infiltration for Pain Control After Mastectomy and Expander Reconstruction

    PubMed Central

    Layeeque, Rakhshanda; Hochberg, Julio; Siegel, Eric; Kunkel, Kelly; Kepple, Julie; Henry-Tillman, Ronda S.; Dunlap, Melinda; Seibert, John; Klimberg, V Suzanne

    2004-01-01

    Introduction: We hypothesized botulinum toxin (BT) infiltration of the chest wall musculature after mastectomy would create a prolonged inhibition of muscle spasm and postoperative pain, facilitating tissue expander reconstruction. Methods: An Institutional Review Board (IRB)-approved prospective study was conducted of all patients undergoing mastectomy with tissue expander placement during a 2-year period. Study patients versus controls had 100 units of diluted BT injected into the pectoralis major, serratus anterior, and rectus abdominis insertion. Pain was scored using a visual analog scale of 0 to 10. Wilcoxon rank sum test was used for continuous variables and the χ2 test for nominal level data to test for significance. Results: Forty-eight patients were entered into the study; 22 (46%) with and 26 (54%) without BT infiltration. Groups were comparable in terms of age (55 ± 11 years versus 52 ± 10 years; P = 0.46), bilateral procedure (59% versus 61%; P = 0.86), tumor size (2 ± 2 cm versus 2 ± 3 cm; P = 0.4), expander size and volume (429 ± 119 mL versus 510 ± 138 mL; P = 0.5). The BT group did significantly better with pain postoperatively (score of 3 ± 1 versus 7 ± 2; P < 0.0001), during initial (score of 2 ± 2 versus 6 ± 3; P = 1.6 × 10−6), and final expansion (1 ± 1 versus 3 ± 2; P = 0.009). Volume of expansion per session was greater thus expansion sessions required less in the BT group (5 ± 1 versus 7 ± 3; P = 0.025). There was a significant increase in narcotic use in control patients in the first 24 hours (17 ± 10 mg versus 3 ± 3 mg; P < 0.0001), initial as well as final expansion periods (P = 0.0123 and 0.0367, respectively). One expander in the BT group versus 5 in the control group required removal (P = 0.13). There were no BT-related complications. Conclusion: Muscular infiltration of botulinum toxin for mastectomy and tissue expander placement significantly reduced postoperative pain and discomfort without complications. PMID

  18. Application of botulinum toxin to treat sialorrhea in amyotrophic lateral sclerosis patients: a literature review.

    PubMed

    Oliveira, Ademar Francisco de; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier

    2016-01-01

    Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. RESUMO Esclerose lateral amiotrófica é uma doença neurodegenerativa progressiva e fatal, caracterizada pela degeneração dos neurônios motores, as células do sistema nervoso central que controlam os movimentos voluntários dos músculos. A salivação excessiva (sialorreia) está presente em cerca de 50% dos casos de esclerose lateral amiotrófica. Dessa forma, surgem medidas terapêuticas alternativas como drogas anticolinérgicas e cirurgia, e recentemente, o uso da toxina botulínica, aplicada em um ponto central das glândulas salivares, muitas vezes guiado por ultrassonografia, demostrou resultados positivos. Objetivou-se revisar a literatura no intuito de demonstrar um método alternativo aos tratamentos de sialorreia em pacientes com esclerose lateral amiotrófica. Em estudos recentes, a eficácia do tratamento com toxina botulínica foi confirmada e, mesmo requerendo novas aplicações, os efeitos colaterais são ínfimos. Ela surge então como alternativa não só ao

  19. Severity and impact of xerostomia in patients treated with botulinum toxin type b for cervical dystonia: Observations on the quality of life of patients with xerostomia

    PubMed Central

    Hogan, Patrick; Charles, P.David; Wooten Watts, Maureen; Massey, Janice M.; Miller, Tamara; Mackowiack, John

    2004-01-01

    Background: Although dry mouth (xerostomia) has been reported with botulinum toxin type B used as treatment for cervical dystonia, the impact of this adverse effect (AE) on patients' activities of daily living (ADLs) has not been assessed. tObjective: The aim of this study was to examine the severity, duration, and impact of xerostomia in patients with cervical dystonia who reported this AE in routine clinical practice following treatment with botulinum toxin type B. Methods: In this uncontrolled study, investigators at 5 study centers across the United States retrospectively identified patients who were diagnosed with cervical dystonia and had received ≥ 1 treatment with botulinum toxin type B injection and who had reported xerostomia, based on patients' charts. These patients were mailed a survey that included questions about their treatment history, disease severity, and xerostomia (severity, onset, duration, change with subsequent injections, and effects on dental and oral health), as well as an 8-item Patient Benefit Questionnaire (PBQ), which was designed to assess the impact of xerostomia symptoms on patients' ADLs. Results: A total of 45 patients received a mean of 2.91 injections with botulinum toxin type B (mean dose per injection, 11,958 U), with a total of 131 injections. The mean severity of patient-rated xerostomia following the first injection of botulinum toxin type B was 3.88 on a scale of 1 (mild) to 5 (severe), and this rating did not change for patients who received subsequent injections (mean, 3.76). Following atypical injection of botulinum toxin type B, xerostomia began a mean (SD) of 4.82 (3.32) days later and persisted for a mean (SD) duration of 5.56 (3.57) weeks. The overall mean score on the 10-point PBQ prior to botulinum toxin treatment was 8.89, which decreased to 5.42 following botulinum toxin type B injection (lower scores indicate more severe xerostomia). Conclusions: This study of patients with cervical dystonia suggests that

  20. The Efficacy of Botulinum Toxin Treatment for Children with a Persistent Esotropia Following Bilateral Medial Rectus Recessions and Lateral Rectus Resections

    PubMed Central

    Lambert, Scott R.; Shainberg, Marla J.

    2015-01-01

    Background and Purpose To report on the outcomes of treating children with a persistent esotropia with an injection of botulinum toxin in a medial rectus muscle. Patients and Methods The medical records of all children at one institution with a persistent esotropia after bilateral medial rectus recessions and bilateral lateral rectus resections who were then treated with a botulinum toxin injection were reviewed. Results Five patients with a mean preoperative esotropia of 37 PD (range, 25-50 PD) underwent bilateral medial rectus recessions and then bilateral lateral rectus resections. Their residual esotropia (mean, 25 PD; range, 18-35) was then treated with a single injection of 3- 5 units of botulinum toxin into one medial rectus muscle. The patients were then followed for a mean of 34 months (range, 14 to 79 months). At last follow-up, 2 patients had an esotropia <10 PD. The other 3 patients had no long-term improvement in their ocular alignment. Two of these patients then underwent additional strabismus surgery. In both cases, they then developed a consecutive exotropia. Conclusion Treatment with a single injection of botulinum toxin was beneficial in 2 of 5 children. Botulinum toxin treatment alone did not result in a consecutive exotropia in any patients treated. PMID:24260804

  1. Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

    PubMed

    Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

    2016-02-01

    This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P < .001). These findings suggest that the combined use of botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A.

  2. Botulinum toxin type A with oral baclofen versus oral tizanidine: a nonrandomized pilot comparison in patients with cerebral palsy and spastic equinus foot deformity.

    PubMed

    Dai, Alper I; Wasay, Mohammad; Awan, Safia

    2008-12-01

    The objective of this study was to compare the effectiveness of baclofen versus tizanidine as adjuvant treatment of botulinum toxin type A botulinum toxin type A in the management of children with spasticity. Thirty children with gastrocnemius spasticity were retrospectively reviewed at Gaziantep University Hospital, Gaziantep, Turkey. All patients were treated with localized botulinum toxin injections and baclofen or tizanidine for spasticity and were followed at 2- to 4-week intervals and evaluated for a total of 12 weeks; 17 children (57%) received baclofen and 13 (43%) received tizanidine. The mean score of Gross Motor Functional Measurement (76.63 +/- 5.88 vs 68.17 +/- 1.99; P < .001) and caregiver questionnaire scores (70.23 +/- 4.76 vs 66.59 +/- 3.53; P = .03) for the tizanidine group were significantly higher as compared with the baclofen group. This study suggests that combination of botulinum toxin type A with oral tizanidine is more effective with fewer side effects than combination of botulinum toxin type A and oral baclofen for spastic cerebral palsy.

  3. Spatial, Temporal, and Matrix Variability of Clostridium botulinum Type E Toxin Gene Distribution at Great Lakes Beaches.

    PubMed

    Wijesinghe, Rasanthi U; Oster, Ryan J; Haack, Sheridan K; Fogarty, Lisa R; Tucker, Taaja R; Riley, Stephen C

    2015-07-01

    Clostridium botulinum type E toxin is responsible for extensive mortality of birds and fish in the Great Lakes. The C. botulinum bontE gene that produces the type E toxin was amplified with quantitative PCR from 150 sloughed algal samples (primarily Cladophora species) collected during summer 2012 from 10 Great Lakes beaches in five states; concurrently, 74 sediment and 37 water samples from four sites were also analyzed. The bontE gene concentration in algae was significantly higher than in water and sediment (P < 0.05), suggesting that algal mats provide a better microenvironment for C. botulinum. The bontE gene was detected most frequently in algae at Jeorse Park and Portage Lake Front beaches (Lake Michigan) and Bay City State Recreation Area beach on Saginaw Bay (Lake Huron), where 77, 100, and 83% of these algal samples contained the bontE gene, respectively. The highest concentration of bontE was detected at Bay City (1.98 × 10(5) gene copies/ml of algae or 5.21 × 10(6) g [dry weight]). This study revealed that the bontE gene is abundant in the Great Lakes but that it has spatial, temporal, and matrix variability. Further, embayed beaches, low wave height, low wind velocity, and greater average water temperature enhance the bontE occurrence.

  4. Spatial, Temporal, and Matrix Variability of Clostridium botulinum Type E Toxin Gene Distribution at Great Lakes Beaches

    PubMed Central

    Oster, Ryan J.; Haack, Sheridan K.; Fogarty, Lisa R.; Tucker, Taaja R.; Riley, Stephen C.

    2015-01-01

    Clostridium botulinum type E toxin is responsible for extensive mortality of birds and fish in the Great Lakes. The C. botulinum bontE gene that produces the type E toxin was amplified with quantitative PCR from 150 sloughed algal samples (primarily Cladophora species) collected during summer 2012 from 10 Great Lakes beaches in five states; concurrently, 74 sediment and 37 water samples from four sites were also analyzed. The bontE gene concentration in algae was significantly higher than in water and sediment (P < 0.05), suggesting that algal mats provide a better microenvironment for C. botulinum. The bontE gene was detected most frequently in algae at Jeorse Park and Portage Lake Front beaches (Lake Michigan) and Bay City State Recreation Area beach on Saginaw Bay (Lake Huron), where 77, 100, and 83% of these algal samples contained the bontE gene, respectively. The highest concentration of bontE was detected at Bay City (1.98 × 105 gene copies/ml of algae or 5.21 × 106 g [dry weight]). This study revealed that the bontE gene is abundant in the Great Lakes but that it has spatial, temporal, and matrix variability. Further, embayed beaches, low wave height, low wind velocity, and greater average water temperature enhance the bontE occurrence. PMID:25888178

  5. Pocketed microneedles for rapid delivery of a liquid-state botulinum toxin A formulation into human skin

    PubMed Central

    Torrisi, B.M.; Zarnitsyn, V.; Prausnitz, M.R.; Anstey, A.; Gateley, C.; Birchall, J.C.; Coulman, S.A

    2012-01-01

    Botulinum toxin A (BT) is used therapeutically for the treatment of primary focal hyperhidrosis, a chronic debilitating condition characterised by over-activity of the eccrine sweat glands. Systemic toxicity concerns require BT to be administered by local injection, which in the case of hyperhidrosis means multiple painful intradermal injections by a skilled clinician at 6-monthly intervals. This study investigates the potential of a liquid-loaded pocketed microneedle device to deliver botulinum toxin A into the human dermis with the aim of reducing patient pain, improving therapeutic targeting and simplifying the administration procedure. Initially, β-galactosidase was employed as a detectable model for BT to (i) visualise liquid loading of the microneedles, (ii) determine residence time of a liquid formulation on the device and (iii) quantify loaded doses. An array of five stainless steel pocketed microneedles was shown to possess sufficient capacity to deliver therapeutic doses of the potent BT protein. Microneedle-mediated intradermal delivery of β-galactosidase and formaldehyde-inactivated botulinum toxoid revealed effective deposition and subsequent diffusion within the dermis. This study is the first to characterise pocketed microneedle delivery of a liquid formulation into human skin and illustrates the potential of such systems for the cutaneous administration of potent proteins such as BT. A clinically appropriate microneedle delivery system for BT could have a significant impact in both the medical and cosmetic industries. PMID:23178949

  6. Botulinum toxin inhibits quantal acetylcholine release and energy metabolism in the Torpedo electric organ.

    PubMed Central

    Dunant, Y; Esquerda, J E; Loctin, F; Marsal, J; Muller, D

    1987-01-01

    1. Type A Botulinum toxin (BoTX) blocked nerve-electroplaque transmission in small fragments of Torpedo marmorata electric organ incubated in vitro. The effect was observed either with the crystalline toxin complex (associated with haemagglutinin) or with the purified neurotoxin (molecular weight approximately 150,000). 2. The quantal content of the evoked post-synaptic response was reduced by BoTX but the quantum size remained unchanged till complete blockade of the evoked response. 3. Spontaneous electroplaque potentials were composed of two populations: one with a bell-shaped amplitude distribution (miniature potentials or quanta) and a population of small events with a skewed distribution (subminiatures). In BoTX-poisoned tissue, the bell-distributed miniatures progressively disappeared, but the subminiatures kept on occurring. Occasionally, larger spontaneous potentials with a slow time course were recorded; they were also BoTX resistant. 4. A biochemical assay showed that evoked acetylcholine (ACh) release was impaired by BoTX. During the period when evoked transmission was blocked, spontaneous ACh release transiently increased. 5. At the time of transmission blockade, there was no significant change of ACh content, of ACh turnover, of ACh repartition in the vesicle-bound and free compartments, or of the number of synaptic vesicles. 6. The amount of ATP was reduced to 50% by BoTX, and that of creatine phosphate (CrP) to less than 20%. The ATP-CrP-converting enzyme, creatine kinase, was inhibited in BoTX-poisoned tissue. 7. Thus, the electrophysiological effects of BoTX are very similar at the nerve-electroplaque and the neuromuscular junctions. The present work suggests in addition that suppression of quantal release by BoTX is related to marked alterations of the energy metabolism in the tissue. Images Plate 1 PMID:3656169

  7. Use of botulinum toxin type A in symptomatic accessory soleus muscle: first five cases.

    PubMed

    Isner-Horobeti, M-E; Muff, G; Lonsdorfer-Wolf, E; Deffinis, C; Masat, J; Favret, F; Dufour, S P; Lecocq, J

    2016-11-01

    Symptomatic accessory soleus muscle (ASM) can cause exercise-induced leg pain due to local nerve/vascular compression, muscle spasm, or local compartment syndrome. As intramuscular injections of botulinum toxin type A (BTX-A) can reduce muscle tone and mass, we investigated whether local BTX-A injections relieve the pain associated with symptomatic ASM. We describe five patients presenting peri/retromalleolar exertional pain and a contractile muscle mass in the painful region. Com-pression neuropathy was ruled out by electromyo-graphic analysis of the lower limb muscles. Doppler ultrasonography was normal, excluding a local vascular compression. ASM was confirmed by magnetic resonance imaging. After a treadmill stress test, abnormal intramuscular pressure values in the ASM, confirmed the diagnosis of compartment syndrome only in one patient. All five patients received BTX-A injections in two points of the ASM. The treatment efficacy was evaluated based on the disappearance of exercise-induced pain and the resumption of normal physical and sports activities. After BTX-A injection, exertional pain disappeared and all five patients resumed their normal level of physical and sports performances. Neither side effects nor motor deficits were observed. BTX-A is well tolerated in patients with ASM and could be used as a new conservative therapeutic strategy for the treatment of symptomatic ASM before surgery.

  8. Long-term efficacy and safety of botulinum toxin injections in dystonia.

    PubMed

    Ramirez-Castaneda, Juan; Jankovic, Joseph

    2013-02-04

    Local chemodenervation with botulinum toxin (BoNT) injections to relax abnormally contracting muscles has been shown to be an effective and well-tolerated treatment in a variety of movement disorders and other neurological and non-neurological disorders. Despite almost 30 years of therapeutic use, there are only few studies of patients treated with BoNT injections over long period of time. These published data clearly support the conclusion that BoNT not only provides safe and effective symptomatic relief of dystonia but also long-term benefit and possibly even favorably modifying the natural history of this disease. The adverse events associated with chronic, periodic exposure to BoNT injections are generally minor and self-limiting. With the chronic use of BoNT and an expanding list of therapeutic indications, there is a need to carefully examine the existing data on the long-term efficacy and safety of BoNT. In this review we will highlight some of the aspects of long-term effects of BoNT, including efficacy, safety, and immunogenicity.

  9. Botulinum toxin A for palmar hyperhidrosis: assessment with sympathetic skin responses evoked by train of stimuli.

    PubMed

    Al-Hashel, J Y; Youssry, D; Rashaed, H M; Shamov, T; Rousseff, R T

    2016-07-01

    Objective assessment of the effect of botulinum toxin A (BT) treatment in primary palmar hyperhidrosis (PH) is attempted by different methods. We decided to use for this purpose sympathetic skin responses evoked by train of stimuli (TSSR). Twenty patients with severe PH (five female, median age 24, range 18-36) were examined regularly over 3 months after receiving 50 UI BT in each palm. TSSR were recorded from the palms after sensory stimulation by a train of three supramaximal electric pulses 3 millisecond apart. Results were compared to longitudinally studied TSSR of 20 healthy sex- and age-matched control subjects. All hyperhidrosis patients reported excellent improvement. TSSR amplitudes decreased at week 1 (mean 54% range 48%-67%) and over the following months in a clinically significant trend (slope R=-.82, P<.0001). TSSR in controls changed insignificantly (±13% from the baseline). The difference between patients and controls was highly significant at any time point (P<.001). This study suggests that TSSR may help in assessment of treatments in PH. It confirms objectively the efficacy of BT in PH.

  10. Ultrasound-guided injection of botulinum toxin A in the treatment of iliopsoas spasticity

    PubMed Central

    Sconfienza, L.M.; Perrone, N.; Lacelli, F.; Lentino, C.; Serafini, G.

    2008-01-01

    Purpose Intramuscular injection of botulinum toxin A (BTX-A) is a common treatment for iliopsoas muscle spasticity, but it is not easy to position the needle in this muscle without guidance. In this paper we describe an ultrasound-guided technique for the intramuscular injection of BTX-A to treat spasticity of the iliopsoas muscle. Its effectiveness was assessed in 10 patients. Method and materials The ultrasound-guided technique for BTX-A injection was used on 10 patients. The needle was inserted into the muscle belly at an angle of 45° along the longitudinal axis of the muscle when allowed by patient's condition. Results In all cases, the iliopsoas muscle was easily identified and both the iliac and psoas components were assessed. Introduction of the needle and drug injection were entirely carried out under ultrasonographic guidance. The procedure was successful in all patients, even in those with a high-grade spasticity, and general anesthesia was not required. Conclusions This ultrasound-guided technique allows accurate guidance for the injection of BTX-A, and it can be considered as an alternate supportive therapy in patients with spasticity and dystonia. PMID:23396653

  11. Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury.

    PubMed

    Uchiyama, Akihiko; Yamada, Kazuya; Perera, Buddhini; Ogino, Sachiko; Yokoyama, Yoko; Takeuchi, Yuko; Ishikawa, Osamu; Motegi, Sei-Ichiro

    2015-03-13

    Botulinum toxin A (BTX-A) blocks the release of acetylcholine vesicles into the synaptic space, and has been clinically used for aesthetic indications, neuromuscular disorders and hyperhidrosis. Several studies have demonstrated that BTX-A enhanced the blood flow and improved ischemia in animal models. Our objective was to assess the effects of BTX-A on cutaneous ischemia-reperfusion (I/R) injuries, mimicking decubitus ulcers. The administration of BTX-A in I/R areas significantly inhibited the formation of decubitus-like ulcer in cutaneous I/R injury mouse model. The number of CD31(+) vessels and αSMA(+) pericytes or myofibroblasts in wounds were significantly increased in the I/R mice treated with BTX-A. The hypoxic area and the number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R sites were reduced by BTX-A administration. In an in vitro assay, BTX-A significantly prevented the oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in vascular endothelial cells. Furthermore, the administration of BTX-A completely suppressed the ulcer formation in an intermittent short-time cutaneous I/R injury model. These results suggest that BTX-A might have protective effects against ulcer formation after cutaneous I/R injury by enhancing angiogenesis and inhibiting hypoxia-induced cellular damage. Exogenous application of BTX-A might have therapeutic potential for cutaneous I/R injuries.

  12. The use of Botulinum toxin-a injection for facial wrinkles: a histological and immunohistochemical evaluation.

    PubMed

    El-Domyati, Moetaz; Attia, Sameh K; El-Sawy, Ashraf E; Moftah, Noha H; Nasif, Ghada A; Medhat, Walid; Marwan, Belkais

    2015-06-01

    Botulinum toxin (BTX)-A has been used for years in the reduction of facial wrinkles; however, histological and immunohistochemical changes after its use were not previously investigated. To evaluate histological and immunohistochemical changes after BTX-A injection for facial wrinkles, sixteen volunteers, with wrinkles on the upper third of the face, were subjected to single injection of BTX-A. Skin biopsy specimens were obtained from peri-orbital wrinkle site (crow's feet area) before and after 3 months of BTX-A injection. Using histological and immunohistochemical evaluation coupled with computerized morphometric analysis, measurement of epidermal thickness, wrinkle depth and width as well as quantitative evaluation of collagen types I and III and elastin was performed for skin biopsies. After BTX-A injections, there were significant increase in wrinkle width and granular layer thickness (P < 0.001), while the other histometrical measures as well as the immunohistochemical expression of collagen types I and III and elastin showed no significant difference (P > 0.05). However, collagen fibers showed better organization and orientation after BTX-A injection. The histological changes observed after BTX-A injection for facial wrinkles may help in better understanding of its mechanism of action.

  13. A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor

    PubMed Central

    Saifee, Tabish A.; Teodoro, Tiago; Erro, Roberto; Edwards, Mark J.; Cordivari, Carla

    2016-01-01

    Background We aimed to investigate the efficacy and safety of botulinum toxin (BT) injections for jerky action tremor of the upper limb. Methods We performed an uncontrolled, prospective study of electromyography (EMG)-guided BT injections for jerky, position-specific, upper limb action tremor. The primary outcome was clinical global impression at 3–6 weeks after baseline. Results Eight patients with jerky, position-specific action tremor involving the upper limb were consecutively recruited. After a median follow-up of 4.4 weeks (interquartile range [IQR] 3.6–6 weeks), four of them rated themselves as “improved” and two as “much improved.” Five of these six subjects reported improvements in specific activities of daily living (bringing liquids to mouth, feeding, shaving, and dressing). Upper limb subscore of the Fahn–Tolosa–Marin Tremor Rating Scale (FTM) significantly decreased from 4.5 (4–6) to 3 (2–5) (p = 0.01). Discussion This pilot, prospective cohort study suggests that EMG-guided BT injections may improve jerky, position-specific, upper limb action tremor. Placebo-controlled studies evaluating larger samples of patients are warranted to confirm these findings. PMID:27818844

  14. Tonic pupil after botulinum toxin-A injection for treatment of esotropia in children

    PubMed Central

    2016-01-01

    A total of 27 children with esotropia (mean age, 3.9 years; range, 9 months to 13.8 years) were enrolled in a 9-month observational study following botulinum toxin A (BTX-A) injection of one (n = 7) or both (n = 20) medial rectus muscles. BTX-A dosage ranged from 3.0 to 6.0 units per muscle. Three participants developed tonic pupil, noted at the first follow-up visit, occurring 12-19 days after injection. All 3 cases occurred in the left eye of participants who underwent bilateral BTX-A injection by the same surgeon. Anisocoria diminished from a maximum of 4 mm at the 2-week visit to 1–2 mm in all patients over the 9-month postinjection data collection period. No adverse visual outcomes were noted. Tonic pupil is an infrequently reported complication of BTX-A injection for strabismus. The experience of our investigator group suggests the need for careful injection technique and thorough preinjection counseling. PMID:26917081

  15. Microfluidic tectonics platform: A colorimetric, disposable botulinum toxin enzyme-linked immunosorbent assay system.

    PubMed

    Moorthy, Jaisree; Mensing, Glennys A; Kim, Dongshin; Mohanty, Swomitra; Eddington, David T; Tepp, William H; Johnson, Eric A; Beebe, David J

    2004-06-01

    A fabrication platform for realizing integrated microfluidic devices is discussed. The platform allows for creating specific microsystems for multistep assays in an ad hoc manner as the components that perform the assay steps can be created at any location inside the device via in situ fabrication. The platform was utilized to create a prototype microsystem for detecting botulinum neurotoxin directly from whole blood. Process steps such as sample preparation by filtration, mixing and incubation with reagents was carried out on the device. Various microfluidic components such as channel network, valves and porous filter were fabricated from prepolymer mixture consisting of monomer, cross-linker and a photoinitiator. For detection of the toxoid, biotinylated antibodies were immobilized on streptavidin-functionalized agarose gel beads. The gel beads were introduced into the device and were used as readouts. Enzymatic reaction between alkaline phosphatase (on secondary antibody) and substrate produced an insoluble, colored precipitate that coated the beads thus making the readout visible to the naked eye. Clinically relevant amounts of the toxin can be detected from whole blood using the portable enzyme-linked immunosorbent assay (ELISA) system. Multiple layers can be realized for effective space utilization and creating a three-dimensional (3-D) chaotic mixer. In addition, external materials such as membranes can be incorporated into the device as components. Individual components that were necessary to perform these steps were characterized, and their mutual compatibility is also discussed.

  16. Alterations in gene expression precede sarcopenia and osteopenia in botulinum toxin immobilized mice

    PubMed Central

    Vegger, J.B.; Brüel, A.; Dahlgaard, A.F.; Thomsen, J.S.

    2016-01-01

    Objectives: To investigate alteration of bone and muscle gene expression at different time points during 3 weeks of botulinum toxin (BTX) induced immobilization and how this correlate with conventional analysis of bone and muscle. Methods: Thirty-five 16-week-old female C57BL/6-mice were investigated; 15 were injected with BTX, 15 served as age-matched controls, and 5 as baseline. 5 BTX-injected and 5 control mice were euthanized after 1, 2, and 3 weeks. Analysis included RT-qPCR, dynamic bone histomorphometry, DEXA, µCT, mechanical testing, and muscle cell cross-sectional-area (CSA). Results: Genes related to osteoblasts were expressed at a lower level after 1 week, but not after 2 and 3 weeks of disuse. Moreover, genes related to osteoclasts were expressed at a higher level after 1 and 2 weeks of disuse, whereafter they approached the level of the controls. Genes related to muscle atrophy were upregulated 1 and 2 weeks after the BTX-injection, but not after 3 weeks. In contrast, deterioration of bone microstructure and strength, and reduction in muscle cell CSA were most evident after 3 weeks of disuse. Conclusions: Gene expression should be investigated during the first two weeks of immobilization, whereas changes in bone microstructure and muscle cell CSA are most prominent after 3 weeks of immobilization. PMID:27973388

  17. The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain

    PubMed Central

    Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

    2016-01-01

    The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo. PMID:27443638

  18. A self-pumping lab-on-a-chip for rapid detection of botulinum toxin.

    PubMed

    Lillehoj, Peter B; Wei, Fang; Ho, Chih-Ming

    2010-09-07

    A robust poly(dimethylsiloxane) (PDMS) surface treatment was utilized for the development of a self-pumping lab-on-a-chip (LOC) to rapidly detect minute quantities of toxic substances. One such toxin, botulinum neurotoxin (BoNT), is an extremely lethal substance, which has the potential to cause hundreds of thousands of fatalities if as little as a few grams are released into the environment. To prevent such an outcome, a quick (<45 min) and sensitive detection format is needed. We have developed a self-pumping LOC that can sense down to 1 pg of BoNT type A (in a 1 microL sample) within 15 min in an autonomous manner. The key technologies enabling for such a device are a sensitive electrochemical sensor, an optimized fluidic network and a robust hydrophilic PDMS coating, thereby facilitating autonomous delivery of liquid samples for rapid detection. The stability, simplicity and portability of this device make possible for a storable and distributable system for monitoring bioterrorist attacks.

  19. Molecular mechanisms of treadmill therapy on neuromuscular atrophy induced via botulinum toxin A.

    PubMed

    Tsai, Sen-Wei; Chen, Hsiao-Ling; Chang, Yi-Chun; Chen, Chuan-Mu

    2013-01-01

    Botulinum toxin A (BoNT-A) is a bacterial zinc-dependent endopeptidase that acts specifically on neuromuscular junctions. BoNT-A blocks the release of acetylcholine, thereby decreasing the ability of a spastic muscle to generate forceful contraction, which results in a temporal local weakness and the atrophy of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy, and cervical dystonia. However, the combined effect of treadmill exercise and BoNT-A treatment is not well understood. We previously demonstrated that for rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running improved the recovery of the sciatic functional index (SFI), muscle contraction strength, and compound muscle action potential (CMAP) amplitude and area. Treadmill training had no influence on gastrocnemius mass that received BoNT-A injection, but it improved the maximal contraction force of the gastrocnemius, and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine receptor (AChR) subunits α and β was found following treadmill training. Taken together, these results suggest that the upregulation of genes associated with neurite and AChR regeneration following treadmill training may contribute to enhanced gastrocnemius strength recovery following BoNT-A injection.

  20. SYSTEMS ANALYSIS OF TRANSCRIPTIONAL DATA PROVIDES INSIGHTS INTO MUSCLE’S BIOLOGICAL RESPONSE TO BOTULINUM TOXIN

    PubMed Central

    MUKUND, KAVITHA; MATHEWSON, MARGIE; MINAMOTO, VIVIANE; WARD, SAMUEL R.; SUBRAMANIAM, SHANKAR; LIEBER, RICHARD L.

    2014-01-01

    Introduction In this study we provide global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)–treated muscle over a 1-year period. Methods Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n =4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks. Results Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoforms, activation of genes in competing pathways of repair and atrophy, impaired mitochondrial biogenesis, and increased metal ion imbalance. Adaptations of the basal lamina and fibrillar extracellular matrix (ECM) occurred by 4 weeks. The muscle transcriptome returned to its unperturbed state 12 weeks after injection. Conclusion Acute transcriptional adaptations resemble denervated muscle with some subtle differences, but resolved more quickly compared with denervation. Overall, gene expression, across time, correlates with the generally accepted BoNT-A time course and suggests that the direct action of BoNT-A in skeletal muscle is relatively rapid. PMID:24536034

  1. Antinociceptive effect of botulinum toxin type A on experimental abdominal pain.

    PubMed

    Drinovac, Višnja; Bach-Rojecky, Lidija; Babić, Ana; Lacković, Zdravko

    2014-12-15

    Visceral pain, especially in the abdominal region, represents one of the most common types of pain. Its chronic form is usually very hard to treat by conventional analgesic agents and adjuvants. We investigated the antinociceptive effect of botulinum toxin type A (BTX-A) in male Wistar rats in two models of visceral pain: peritonitis induced by intraperitoneal injection of 1% acetic acid and colitis induced by intracolonic instillation of 0.1% capsaicin. Pain was measured as the number of abdominal writhes. Additionally, referred mechanical sensitivity in the ventral abdominal area was evaluated by von Frey test and the extent of spinal c-Fos expression was immunohistochemically examined. BTX-A significantly reduced the number of abdominal writhes in both models of visceral pain after intrathecal application in a dose of 2 U/kg. In the experimental colitis model, BTX-A (2 U/kg) reduced both referred mechanical allodynia and c-Fos expression in the dorsal horn of the spinal cord (S2/S3 segments). In contrast to intrathecal administration, BTX-A (2 U/kg) administered into the cisterna magna had no effect on pain suggesting that the primary site of its action is a spinal cord.

  2. Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms.

    PubMed

    Cruz, Francisco; Dinis, Paulo

    2007-10-01

    Resiniferatoxin (RTX) and botulinum toxin subtype A (BTX-A) are increasingly viewed as potential treatments for lower urinary tract symptoms (LUTS) refractory to conventional therapy. RTX, a capsaicin analogue devoid of severe pungent properties, acts by desensitizing the transient receptor potential vanilloid type 1 (TRPV1) receptor and inactivating C-fibers. BTX-A cleaves soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in afferent and efferent nerve endings, therefore impeding the fusion of synaptic vesicles with the neuronal membrane necessary for the release of neurotransmitters. In patients with neurogenic and idiopathic detrusor overactivity, RTX and BTX-A have been shown to increase the volume to first detrusor contraction, increase bladder capacity, and improve urinary incontinence and quality of life. Recent data also suggest a role for these neurotoxins in treating urgency, the primary symptom in overactive bladder (OAB) syndrome. Furthermore, experimental data strongly support the use of both neurotoxins in the treatment of pain and frequency in patients with interstitial cystitis/painful bladder syndrome (IC/PBS), although the results from available clinical trials for this use are still inconclusive. In spite of promising results overall, it should be made clear that the administration of these neurotoxins is still considered an experimental procedure and that more clinical studies are necessary before a license for their use will be issued by health authorities.

  3. Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin.

    PubMed

    Esposito, Marcello; Dubbioso, R; Apisa, P; Allocca, R; Santoro, L; Cesari, U

    2015-09-01

    Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-to-noise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time.

  4. Tridimensional assessment of adductor spasmodic dysphonia pre- and post-treatment with Botulinum toxin.

    PubMed

    Dejonckere, P H; Neumann, K J; Moerman, M B J; Martens, J P; Giordano, A; Manfredi, C

    2012-04-01

    Spasmodic dysphonia voices form, in the same way as substitution voices, a particular category of dysphonia that seems not suited for a standardized basic multidimensional assessment protocol, like the one proposed by the European Laryngological Society. Thirty-three exhaustive analyses were performed on voices of 19 patients diagnosed with adductor spasmodic dysphonia (SD), before and after treatment with Botulinum toxin. The speech material consisted of 40 short sentences phonetically selected for constant voicing. Seven perceptual parameters (traditional and dedicated) were blindly rated by a panel of experienced clinicians. Nine acoustic measures (mainly based on voicing evidence and periodicity) were achieved by a special analysis program suited for strongly irregular signals and validated with synthesized deviant voices. Patients also filled in a VHI-questionnaire. Significant improvement is shown by all three approaches. The traditional GRB perceptual parameters appear to be adequate for these patients. Conversely, the special acoustic analysis program is successful in objectivating the improved regularity of vocal fold vibration: the basic jitter remains the most valuable parameter, when reliably quantified. The VHI is well suited for the voice-related quality of life. Nevertheless, when considering pre-therapy and post-therapy changes, the current study illustrates a complete lack of correlation between the perceptual, acoustic, and self-assessment dimensions. Assessment of SD-voices needs to be tridimensional.

  5. Botulinum toxin therapy for temporomandibular joint disorders: a systematic review of randomized controlled trials.

    PubMed

    Chen, Y-W; Chiu, Y-W; Chen, C-Y; Chuang, S-K

    2015-08-01

    The objective of this study was to undertake a systematic review to assess the efficacy of botulinum toxin therapy (BTX) for temporomandibular joint disorders (TMDs). A comprehensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to locate all relevant articles published from inception to October 2014. Eligible studies were selected based on inclusion criteria and included English language, peer-reviewed publications of randomized controlled trials comparing BTX versus any alternative intervention or placebo. Quality assessment and data extraction were done according to the Cochrane risk of bias tool and recommendations. The entire systematic search and selection process was done independently by two reviewers. Five relevant study trials were identified, involving 117 participants. Two trials revealed a significant between-group difference in myofascial pain reduction, another trial that compared BTX with fascial manipulation showed equal efficacy of pain relief on TMDs, while the remaining two trials showed no significant difference between the BTX and placebo groups. Because of considerable variations in study methods and evaluation of results, a meta-analysis could not be performed. Based on this review, no consensus could be reached on the therapeutic benefits of BTX on TMDs. A more rigorous design of trials should be carried out in future studies.

  6. Evaluation of voice quality in adductor spasmodic dysphonia before and after botulinum toxin treatment.

    PubMed

    Langeveld, T P; van Rossum, M; Houtman, E H; Zwinderman, A H; Briaire, J J; Baatenburg de Jong, R J

    2001-07-01

    In this prospective study, the efficacy of botulinum toxin (Botox) injections in patients with adductor spasmodic dysphonia (AdSD) was assessed by 3 different modalities: perceptual and acoustic analyses and subjective self-assessment. This was done by comparing AdSD patients' pretreatment and posttreatment values and comparing these values with those of normal control speakers. In contrast to most other studies, the posttreatment status was defined as the optimal voice quality as judged by the patient. The aim of the study was to assess to what extent Botox injections actually improve voice quality and function. The AdSD subjects rated a significantly improved voice quality and function after Botox treatment. However, the results were never within normal limits. Perceptually, the characteristic and severely impaired AdSD voice improved, but another "type" of pathological voice was detected after Botox treatment. Acoustic analyses demonstrated a significant improvement, as well. Nevertheless, the "optimally" treated AdSD voice still remained significantly deviant as compared to normal voice production. Currently, Botox injection is the therapy of first choice for AdSD. Although significant improvement could be measured in our study perceptually, acoustically, and subjectively, the optimal voice that was achieved never fully matched normal voice quality or function.

  7. Botulinum Toxin Complex Increases Paracellular Permeability in Intestinal Epithelial Cells via Activation of p38 Mitogen-Activated Protein Kinase

    PubMed Central

    MIYASHITA, Shin-ichiro; SAGANE, Yoshimasa; INUI, Ken; HAYASHI, Shintaro; MIYATA, Keita; SUZUKI, Tomonori; OHYAMA, Tohru; WATANABE, Toshihiro; NIWA, Koichi

    2013-01-01

    ABSTRACT Clostridium botulinum produces a large toxin complex (L-TC) that increases paracellular permeability in intestinal epithelial cells by a mechanism that remains unclear. Here, we show that mitogen-activated protein kinases (MAPKs) are involved in this permeability increase. Paracellular permeability was measured by FITC-dextran flux through a monolayer of rat intestinal epithelial IEC-6 cells, and MAPK activation was estimated from western blots. L-TC of C. botulinum serotype D strain 4947 increased paracellular dextran flux and activated extracellular signal-regulated kinase (ERK), p38, but not c-Jun N-terminal kinase (JNK) in IEC-6 cells. The permeability increase induced by L-TC was abrogated by the p38 inhibitor SB203580. These results indicate that L-TC increases paracellular permeability by activating p38, but not JNK and ERK. PMID:23884081

  8. Development of human-like scFv-Fc antibodies neutralizing Botulinum toxin serotype B

    PubMed Central

    Rasetti-Escargueil, Christine; Avril, Arnaud; Chahboun, Siham; Tierney, Rob; Bak, Nicola; Miethe, Sebastian; Mazuet, Christelle; Popoff, Michel R; Thullier, Philippe; Hust, Michael; Pelat, Thibaut; Sesardic, Dorothea

    2015-01-01

    Botulinum neurotoxins (BoNTs) are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. BoNTs have been classified as category A agents by the Centers for Disease Control and Prevention. To date, 7 subtypes of BoNT/B were identified showing that subtypes B1 (16 strains) and B2 (32 strains) constitute the vast majority of BoNT/B strains. Neutralizing antibodies are required for the development of anti-botulism drugs to deal with the potential risk. In this study, macaques (Macaca fascicularis) were immunized with recombinant light chain (LC) or heavy chain (HC) of BoNT/B2, followed by the construction of 2 hyper-immune phage display libraries. The best single-chain variable fragments (scFvs) isolated from each library were selected according to their affinities and cross reactivity with BoNT/B1 toxin subtype. These scFvs against LC and HC were further analyzed by assessing the inhibition of in vitro endopeptidase activity of BoNT/B1 and B2 and neutralization of BoNT/B1 and B2 toxin-induced paralysis in the mouse ex vivo phrenic nerve assay. The antibodies B2–7 (against HC) and BLC3 (against LC) were produced as scFv-Fc, and, when tested individually, neutralized BoNT/B1 and BoNT/B2 in a mouse ex vivo phrenic nerve assay. Whereas only scFv-Fc BLC3 alone protected mice against BoNT/B2-induced paralysis in vivo, when B2–7 and BLC3 were combined they exhibited potent synergistic protection. The present study provided an opportunity to assess the extent of antibody-mediated neutralization of BoNT/B1 and BoNT/B2 subtypes in ex vivo and in vitro assays, and to confirm the benefit of the synergistic effect of antibodies targeting the 2 distinct functional domains of the toxin in vivo. Notably, the framework regions of the most promising antibodies (B2–7 and BLC3) are close to the human germline sequences

  9. Quantitative effects of carbohydrates and aromatic amino acids on Clostridium botulinum toxin gene expression using a rapid competitive RT/PCR assay.

    PubMed

    Sharkey, Freddie H; Dooley, James S; Haylock, Richard W

    2005-01-01

    A rapid competitive RT/PCR assay was developed to determine the effects of nutrients on Clostridium botulinum type E toxin gene expression. The type E strain (EVH) was grown in a nutrient-rich broth containing 1% glucose (base medium). Toxin gene expression was quantified at both mid and late exponential phases of growth. It was found that toxin encoding mRNA levels were highly growth phase dependent with elevated levels found in late exponential phase compared to mid exponential phase. Changing the carbohydrate source had a smaller effect on toxin encoding mRNA levels but as earlier results have suggested, toxin encoding mRNA levels show a strong correlation with type E growth rate. The results have important implications for the food industry whereby risk of type E botulism could be correlated to the nutrient composition of the contaminated food or assessed from C. botulinum growth rates in challenged foodstuffs.

  10. Global Aesthetics Consensus: Botulinum Toxin Type A—Evidence-Based Review, Emerging Concepts, and Consensus Recommendations for Aesthetic Use, Including Updates on Complications

    PubMed Central

    Signorini, Massimo; Liew, Steven; Trindade de Almeida, Ada R.; Wu, Yan; Vieira Braz, André; Fagien, Steven; Goodman, Greg J.; Monheit, Gary; Raspaldo, Hervé

    2016-01-01

    Background: Botulinum toxin type A injection remains the leading nonsurgical cosmetic procedure worldwide, with a high rate of efficacy and patient satisfaction. Methods: A multinational, multidisciplinary group of plastic surgeons and dermatologists convened the Global Aesthetics Consensus Group to develop updated consensus recommendations with a worldwide perspective for botulinum toxin and hyaluronic acid fillers. This publication on botulinum toxin type A considers advances in facial analysis, injection techniques, and avoidance and management of complications. Results: Use of botulinum toxin has evolved from the upper face to also encompass the lower face, neck, and midface. The Global Aesthetics Consensus Group emphasizes an integrative, diagnostic approach. Injection dosage and placement are based on analysis of target muscles in the context of adjacent ones and associated soft and hard tissues. The indication for selection of botulinum toxin as a primary intervention is that excessive muscular contraction is the primary etiology of the facial disharmony to be addressed. Global Aesthetics Consensus Group recommendations demonstrate a paradigm shift toward neuromodulation rather than paralysis, including lower dosing of the upper face, more frequent combination treatment with hyaluronic acid fillers, and intracutaneous injection where indicated to limit depth and degree of action. Conclusions: The accumulation of clinical evidence and experience with botulinum toxin has led to refinements in treatment planning and implementation. The Global Aesthetics Consensus Group advocates an etiology-driven, patient-tailored approach, to enable achievement of optimal efficacy and safety in patient populations that are rapidly diversifying with respect to ethnicity, gender, and age. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID:26910696

  11. Botulinum toxin type A reconstituted in lidocaine with epinephrine for facial rejuvenation: results of a participant satisfaction survey.

    PubMed

    Kim, Alex; Jung, Jeong; Pak, Alexis

    2013-07-01

    To assess the feasibility, safety, and lack of inferiority of reconstituting botulinum toxin type A (BTX-A) in 1% lidocaine hydrochloride with epinephrine 1:100,000, 181 participants were asked to complete a satisfaction survey 3 to 6 months after treatment with the reconstituted formulation for facial rejuvenation. The addition of lidocaine was believed to achieve an immediate paralyzing effect on the injected muscles, and the addition of epinephrine was hypothesized to minimize diffusion to adjacent muscles. Participants were treated in the areas of the forehead and glabella, as well as the orbicularis oculi, orbicularis oris, and procerus muscles, in varying doses (10-60 U). Fifty-eight percent (91/157) of participants reported being more satisfied with BTX-A reconstituted in 1% lidocaine with epinephrine 1:100,000, with 85.7% (78/91) of these participants reporting that the immediate results made the formulation superior; 35.7% (56/157) were indifferent and 6.4% (10/157) reported that the modified formulation did not work better. The injection of BTX-A reconstituted in 1% lidocaine with epinephrine 1:100,000 presented no increased adverse effects (AEs), no decrease in pharmacologic potency, immediate feedback to the clinician, and higher satisfaction for the participants who previously had been treated with BTX-A reconstituted in unpreserved saline. Botulinum toxin type A reconstituted in 1% lidocaine with epinephrine 1:100,000 may increase the duration and efficacy of this widely used toxin.

  12. Prevention of unfavourable effects of cigarette smoke on flap viability using botulinum toxin in random pattern flaps: An experimental study

    PubMed Central

    Karayel, Hikmet; Kaya, Burak; Caydere, Muzaffer; Terzioğlu, Ahmet; Aslan, Gürcan

    2015-01-01

    BACKGROUND: There are numerous clinical and experimental studies reporting unfavourable effects of cigarette smoke on skin flaps. OBJECTIVE: To investigate whether unfavourable effects of cigarette smoke on flap survival could be reduced by botulinum toxin type A. METHODS: Twenty-eight male Wistar albino rats (15 months of age, mean weight 210 g [range 180 g to 230 g]) were included. They were divided into four groups of seven animals each. The control group underwent the surgical procedure alone. Surgical procedure was performed after administration of botulinum toxin type A in the botulinum toxin (BTX) group, after exposure to cigarette smoke in the cigarette smoke (CS) group, and after BTX type A administration and exposure to CS in the CS+BTX (CS+BTX) group. Random pattern cutaneous flaps (3 cm × 9 cm) were elevated from the dorsum of all rats. Necrosis area was calculated in percentages (%) using Image J computer software. Tissue samples were examined histopathologically. RESULTS: The mean necrotic area in the control group (26%) and in the BTX group (21%) were similar (P=0.497), whereas administration of BTX type A significantly decreased flap necrosis area in the rats exposed to CS (the mean necrosis areas were 41.5% in the CS group, and 26% in the CS+BTX group; P<0.001). Histopathological examination findings corroborated the unfavourable effects of CS and preventive effects of BTX type A. CONCLUSION: Preoperative administration of BTX significantly enhanced flap viability in the rats exposed to CS. Further human studies are warranted to verify whether BTX type A could be used as an agent to reduce the risk of flap necrosis in patients who smoke. PMID:26361625

  13. Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction.

    PubMed

    Janicki, Joseph J; Chancellor, Michael B; Kaufman, Jonathan; Gruber, Michele A; Chancellor, David D

    2016-03-18

    Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction.

  14. Botulinum toxin induces muscle paralysis and inhibits bone regeneration in zebrafish.

    PubMed

    Recidoro, Anthony M; Roof, Amanda C; Schmitt, Michael; Worton, Leah E; Petrie, Timothy; Strand, Nicholas; Ausk, Brandon J; Srinivasan, Sundar; Moon, Randall T; Gardiner, Edith M; Kaminsky, Werner; Bain, Steven D; Allan, Christopher H; Gross, Ted S; Kwon, Ronald Y

    2014-11-01

    Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (eg, development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model that bridges in vitro and more complex in vivo model systems), in this study, we developed a model of BTx-induced muscle paralysis in adult zebrafish, and we examined its effects on intramembranous ossification during tail fin regeneration. BTx administration induced rapid muscle paralysis in adult zebrafish in a manner that was dose-dependent, transient, and focal, mirroring the paralytic phenotype observed in animal and human studies. During fin regeneration, BTx impaired continued bone ray outgrowth, morphology, and patterning, indicating defects in early osteogenesis. Further, BTx significantly decreased mineralizing activity and crystalline mineral accumulation, suggesting delayed late-stage osteoblast differentiation and/or altered secondary bone apposition. Bone ray transection proximal to the amputation site focally inhibited bone outgrowth in the affected ray, implicating intra- and/or inter-ray nerves in this process. Taken together, these studies demonstrate the potential to interrogate pathological features of BTx-induced osteoanabolic dysfunction in the regenerating zebrafish fin, define the technological toolbox for detecting bone growth and mineralization deficits in this process, and suggest that pathways mediating neuromuscular regulation of osteogenesis may be conserved beyond established mammalian models of bone anabolic disorders.

  15. Intramuscular nerve distribution patterns of anterior forearm muscles in children: a guide for botulinum toxin injection.

    PubMed

    Yang, Fangjiu; Zhang, Xiaoming; Xie, Xiadan; Yang, Shengbo; Xu, Yan; Xie, Peng

    2016-01-01

    Botulinum toxin (BoNT) can relieve muscle spasticity by blocking axon terminals acetylcholine release at the motor endplate (MEP) and is the safest and most effective agent for the treatment of muscle spasticity in children with cerebral palsy. In order to achieve maximum effect with minimum effective dose of BoNT, one needs to choose an injection site as near to the MEP zone as possible. This requires a detailed understanding about the nerve terminal distributions within the muscles targeted for BoNT injection. This study focuses on BoNT treatment in children with muscle spasms caused by cerebral palsy. Considering the differences between children and adults in anatomy, we used child cadavers and measured both the nerve entry points and nerve terminal sense zones in three deep muscles of the anterior forearm: flexor digitorum profundus (FDP), flexor pollicis longus (FPL), and pronator quadratus (PQ). We measured the nerve entry points by using the forearm midline as a reference and demonstrated intramuscular nerve terminal dense zones by using a modified Sihler's nerve staining technique. The locations of the nerve entry points and that of the nerve terminal dense zones in the muscles were compared. We found that all nerve entry points are away from the corresponding intramuscular nerve terminal dense zones. Simply selecting nerve entry points as the sites for BoNT injection may not be an optimal choice for best effects in blocking muscle spasm. We propose that the location of the nerve terminal dense zones in each individual muscle should be used as the optimal target sites for BoNT injection when treating muscle spasms in children with cerebral palsy.

  16. Intramuscular nerve distribution patterns of anterior forearm muscles in children: a guide for botulinum toxin injection

    PubMed Central

    Yang, Fangjiu; Zhang, Xiaoming; Xie, Xiadan; Yang, Shengbo; Xu, Yan; Xie, Peng

    2016-01-01

    Botulinum toxin (BoNT) can relieve muscle spasticity by blocking axon terminals acetylcholine release at the motor endplate (MEP) and is the safest and most effective agent for the treatment of muscle spasticity in children with cerebral palsy. In order to achieve maximum effect with minimum effective dose of BoNT, one needs to choose an injection site as near to the MEP zone as possible. This requires a detailed understanding about the nerve terminal distributions within the muscles targeted for BoNT injection. This study focuses on BoNT treatment in children with muscle spasms caused by cerebral palsy. Considering the differences between children and adults in anatomy, we used child cadavers and measured both the nerve entry points and nerve terminal sense zones in three deep muscles of the anterior forearm: flexor digitorum profundus (FDP), flexor pollicis longus (FPL), and pronator quadratus (PQ). We measured the nerve entry points by using the forearm midline as a reference and demonstrated intramuscular nerve terminal dense zones by using a modified Sihler’s nerve staining technique. The locations of the nerve entry points and that of the nerve terminal dense zones in the muscles were compared. We found that all nerve entry points are away from the corresponding intramuscular nerve terminal dense zones. Simply selecting nerve entry points as the sites for BoNT injection may not be an optimal choice for best effects in blocking muscle spasm. We propose that the location of the nerve terminal dense zones in each individual muscle should be used as the optimal target sites for BoNT injection when treating muscle spasms in children with cerebral palsy. PMID:28078019

  17. Occurrence of Dysphagia Following Botulinum Toxin Injection in Parkinsonism-related Cervical Dystonia: A Retrospective Study

    PubMed Central

    Patterson, Addie; Almeida, Leonardo; Hess, Christopher W.; Martinez-Ramirez, Daniel; Okun, Michael S.; Rodriguez, Ramon L.; Rundle-Gonzalez, Valerie; Shukla, Aparna Wagle; Malaty, Irene A.

    2016-01-01

    Background The aim was to compare the occurrence of post-injection dysphagia in parkinsonism-related cervical dystonia (PRCD) versus cervical dystonia (CD) of other etiologies (non-PRCD). A secondary objective was to explore potential clinical differences between PRCD and non-PRCD and their respective responses to botulinum toxin (BoNT). Methods A cross-sectional chart review was carried out of patients treated for CD with Onabotulinumtoxin A at the University of Florida. We collected demographic information, dose of BoNT injected, patient-reported presence of dysphagia as a side effect, patient-perceived duration of benefit and efficacy according to the Clinical Global Impression Scale (CGIS). Results Of the 144 patients included, 24 patients were diagnosed with PRCD and 120 were diagnosed as non-PRCD. Data analysis showed no significant differences in number of weeks of benefit from BoNT (PRCD 9.1±3.7 versus non-PRCD 9.4±3.7 weeks, p = 0.830), BoNT dosage (PRCD 235.0±95.6 versus non-PRCD 263.7±101.3 units, p = 0.181), median CGIS score (median = 2 or “much improved” for both groups, p = 0.88), or the presence of dysphagia after BoNT (PRCD 17% versus non-PRCD 19 %, p = 0.753, n = 132). In a subgroup analysis of the non-PRCD group, patients who experienced dysphagia were older than those who did not (63.9±8.9 years versus 58.1±14.4 years, p = 0.02). Discussion Despite an increased baseline risk of dysphagia in patients with PRCD, BoNT appears to be equally safe and equally beneficial in PRCD and non-PRCD patients. PMID:27830106

  18. Cellular and Matrix Response of the Mandibular Condylar Cartilage to Botulinum Toxin

    PubMed Central

    Dutra, Eliane H.; O’ Brien, Mara H.; Lima, Alexandro; Kalajzic, Zana; Tadinada, Aditya; Nanda, Ravindra; Yadav, Sumit

    2016-01-01

    Objectives To evaluate the cellular and matrix effects of botulinum toxin type A (Botox) on mandibular condylar cartilage (MCC) and subchondral bone. Materials and Methods Botox (0.3 unit) was injected into the right masseter of 5-week-old transgenic mice (Col10a1-RFPcherry) at day 1. Left side masseter was used as intra-animal control. The following bone labels were intraperitoneally injected: calcein at day 7, alizarin red at day 14 and calcein at day 21. In addition, EdU was injected 48 and 24 hours before sacrifice. Mice were sacrificed 30 days after Botox injection. Experimental and control side mandibles were dissected and examined by x-ray imaging and micro-CT. Subsequently, MCC along with the subchondral bone was sectioned and stained with tartrate resistant acid phosphatase (TRAP), EdU, TUNEL, alkaline phosphatase, toluidine blue and safranin O. In addition, we performed immunohistochemistry for pSMAD and VEGF. Results Bone volume fraction, tissue density and trabecular thickness were significantly decreased on the right side of the subchondral bone and mineralized cartilage (Botox was injected) when compared to the left side. There was no significant difference in the mandibular length and condylar head length; however, the condylar width was significantly decreased after Botox injection. Our histology showed decreased numbers of Col10a1 expressing cells, decreased cell proliferation and increased cell apoptosis in the subchondral bone and mandibular condylar cartilage, decreased TRAP activity and mineralization of Botox injected side cartilage and subchondral bone. Furthermore, we observed reduced proteoglycan and glycosaminoglycan distribution and decreased expression of pSMAD 1/5/8 and VEGF in the MCC of the Botox injected side in comparison to control side. Conclusion Injection of Botox in masseter muscle leads to decreased mineralization and matrix deposition, reduced chondrocyte proliferation and differentiation and increased cell apoptosis in the

  19. Injection of botulinum toxin for the treatment of post-laryngectomy pharyngoesophageal spasm-related disorders

    PubMed Central

    Lightbody, KA; Wilkie, MD; Kinshuck, AJ; Gilmartin, E; Lewis-Jones, H; Jones, TM; Lancaster, J

    2015-01-01

    Introduction Pharyngoesophageal spasm (PES) can cause dysphagia, central valve leak (CVL), and dypshonia in post-laryngectomy patients. Botulinum toxin has been used effectively for the treatment of PES, but data regarding patient-reported outcomes and efficacy for CVL are limited. We evaluated the results of botox injection for PES spasm using subjective and objective measures. Methods Data were collected prospectively (February 2010 to August 2013) on 13 patients undergoing botox injection for PES as identified by video fluoroscopy. We collected digital voice recordings, air-pressure measurements (APMs) for speech, and quality of life (QoL) data before and after the procedure: University of Washington QoL questionnaire (UW-QoL), MD Anderson Swallowing Inventory (MDADI) and the Voice Handicap Index (VHI-30). Results APMs for a sustained vowel decreased by 18% after botox injection, whereas maximum phonatory times increased by 63% (mean increase, 8 to 13 seconds). Sustained vowel amplitude decreased (mean, 87db to 83db) with an associated reduction in sustained vowel frequency (117Hz to 77Hz). MDADI scores improved by 10.2% overall, and UW-QoL scores showed an improvement in score of 7.6%. Mean scores for VHI-30 deteriorated by 2% overall but, when considering only those patients experiencing dysphonia, an improvement of 9.4% was seen. There was an overall net reduction for the CVL cohort of 12 speech valves in the year after injection. Conclusions Our series confirm the safety and objective efficacy of botox injection for PES. QoL measurements were less convincing, and this disparity between subjective and objective measurements must be considered when treating such patients. PMID:26414361

  20. Neuro-exocytosis: botulinum toxins as inhibitory probes and versatile therapeutics.

    PubMed

    Dolly, J Oliver; Lawrence, Gary W; Meng, Jianghui; Wang, Jiafu; Ovsepian, Saak V

    2009-06-01

    For the fundamental process of quantal neurotransmitter release, a consensus is being reached on the recycling pathways for transmitter-containing, small synaptic vesicles (SSVs), and major inroads have been made into deciphering the multiple steps of regulated exocytosis. These advances arose from the identification of approximately 80 proteins in SSVs, elucidation of the structures of pertinent macromolecular complexes, utilisation of different serotypes (A-G) of botulinum neurotoxin (BoNT) together with transgenic mice lacking key genes. Hence, converging evidence continues to emerge for the sequential formation of complexes between the three SNAREs (SNAP-25, syntaxin and VAMP) and their regulatory proteins (complexins, Munc18), as well as for the Ca2+ triggering of membrane fusion/exocytosis via its sensor, synaptotagmin. Moreover, molecular data gained on BoNTs have been translated into Clinical Medicine with type A now being applied worldwide for effectively treating >100 human conditions due to overactivity of nerves supplying various muscles or glands. A recent advance is the successful engineering of a chimera from two BoNTs to acquire the capability of re-targeting a more active moiety to sensory neurons, with resultant inhibition of the release of a pain mediator. Encouragingly, this novel recombinant protein blocks the exocytotic response triggered by a stimulant (capsaicin) of nociceptive C fibres that activates their vanilloid receptors, a feat not possible for either parental toxin. Reaching this landmark has generated optimism for designing further variants of such a versatile therapeutic for normalising the hyper-activity of particular cell types, especially those underlying the many cases of chronic pain that do not respond to existing drugs.

  1. Botulinum toxin in Migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents

    PubMed Central

    Roshni, Ramachandran; Carmen, Lam; Yaksh Tony, L

    2015-01-01

    Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi) -SO capsaicin (2.5 μg/30 μl) or meningeal capsaicin (4 μl of 1mg/ml). Pre-treatment with ipsi-SO BONT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent. PMID:25958249

  2. Does botulinum toxin improve the function of the patient with spasticity after stroke?

    PubMed

    Cardoso, Eduardo; Pedreira, Glícia; Prazeres, Antônio; Ribeiro, Nildo; Melo, Ailton

    2007-09-01

    Post-stroke spasticity is an important cause of disability in adults, due to muscle hyperactivity, which results in limb stiffness and muscle spasm. The prognosis for these patients depends on several features such as early management and adequate physical therapy to avoid muscle shortening, pain, and their consequences. Although several papers have shown that intramuscular injections of botulinum toxin type A (BT-A) decreases spasticity in post-stroke patients, few authors have demonstrated functional improvement after this therapy. In order to assess if individualized BT-A injections improves upper limb function in post-stroke spastic patients, we prospectively followed 20 consecutive patients of 18 years of age or more with spastic hemiparesis secondary to stroke. Fulg-Meyer scale modified for upper limbs, measure of functional independence (MFI), Ashworth modified scale, and goniometry were applied in the beginning of the investigation and in the 16th and 32nd weeks. BT-A was applied at baseline and in the 16th week. All subjects were submitted to rehabilitation therapy. All patients showed improvement according to Ashworth modified scale and increase in the range of motion, which were sustained until the 32nd week (p<0.05). The assessment of the first three parameters of the Fulg-Meyer scale and the evaluations of the motor part of the Functional Independence Measure showed statistically improvement until the end of the study. We conclude that proper choice of muscles and individualized doses of BT-A can improve function in selected post-stroke patients.

  3. Single event multilevel botulinum toxin type A treatment and surgery: similarities and differences.

    PubMed

    Molenaers, G; Desloovere, K; De Cat, J; Jonkers, I; De Borre, L; Pauwels, P; Nijs, J; Fabry, G; De Cock, P

    2001-11-01

    The present study attempts to provide objective evidence of two treatment options for children with cerebral palsy (CP): multilevel botulinum toxin type A (BTX-A) injections and multilevel surgery. The purpose of the study was to clarify the differences and the similarities, and common treatment principles of both treatment strategies. Objective three dimensional gait analysis data were studied retrospectively in two patient groups pre- and post-treatment (randomly selected from a group of children that were treated between 1998 and 1999). In the first group, 29 children with CP were managed with BTX-A injections according to an integrated multilevel approach (Molenaers et al., 1999a). A second group of 23 children with CP were managed by a more traditional single event multilevel surgery, also according to an integrated approach. Our aim was to evaluate the differences as well as the similarities between both patient groups, using a set of 56 parameters selected from three-dimensional gait analysis. The unifying concept between management with BTX-A injections and orthopaedic surgery was the adoption of a multilevel approach at one session. The groups demonstrated considerable differences with respect to age, pretreatment condition and amount and level of improvement after treatment. The children who received BTX-A were typically younger, and showed primary gait problems in the distal joints, whereas the children who underwent surgery demonstrated a higher frequency of gait deviations in the transverse plane and had more complications. Although the benefit of both treatments was confirmed by the present study, a difference in the amount and level of improvement was also demonstrated. In conclusion, these treatment modalities should be regarded as complementary rather than mutually exclusive treatments, with both calling for an integrated approach.

  4. Repetitive transcranial magnetic stimulation versus botulinum toxin injection in chronic migraine prophylaxis: a pilot randomized trial

    PubMed Central

    Shehata, Hatem S; Esmail, Eman H; Abdelalim, Ahmad; El-Jaafary, Shaimaa; Elmazny, Alaa; Sabbah, Asmaa; Shalaby, Nevin M

    2016-01-01

    Background Chronic migraine is a prevalent disabling disease, with major health-related burden and poor quality of life. Long-term use of preventive medications carries risk of side effects. Objectives The aim of this study was to compare repetitive transcranial magnetic stimulation (rTMS) to botulinum toxin-A (BTX-A) injection as preventive therapies for chronic migraine. Methods A pilot, randomized study was conducted on a small-scale sample of 29 Egyptian patients with chronic migraine, recruited from Kasr Al-Aini teaching hospital outpatient clinic and diagnosed according to ICHD-III (beta version). Patients were randomly assigned into two groups; 15 patients received BTX-A injection following the Phase III Research Evaluating Migraine Prophylaxis Therapy injection paradigm and 14 patients were subjected to 12 rTMS sessions delivered at high frequency (10 Hz) over the left motor cortex (MC, M1). All the patients were requested to have their 1-month headache calendar, and they were subjected to a baseline 25-item (beta version) Henry Ford Hospital Headache Disability Inventory (HDI), Headache Impact Test (HIT-6), and visual analogue scale assessment of headache intensity. The primary efficacy measures were headache frequency and severity; secondary measures were 25-item HDI, HIT-6, and number of acute medications. Follow-up visits were scheduled at weeks 4, 6, 8, 10, and 12 after baseline visit. Results A reduction in all outcome measures was achieved in both the groups. However, this improvement was more sustained in the BTX-A group, and both the therapies were well tolerated. Conclusion BTX-A injection and rTMS have favorable efficacy and safety profiles in chronic migraineurs. rTMS is of comparable efficacy to BTX-A injection in chronic migraine therapy, but with less sustained effect. PMID:27785091

  5. Botulinum toxin B in the sensory afferent: transmitter release, spinal activation, and pain behavior.

    PubMed

    Marino, Marc J; Terashima, Tetsuji; Steinauer, Joanne J; Eddinger, Kelly A; Yaksh, Tony L; Xu, Qinghao

    2014-04-01

    We addressed the hypothesis that intraplantar botulinum toxin B (rimabotulinumtoxin B: BoNT-B) has an early local effect upon peripheral afferent terminal releasing function and, over time, will be transported to the central terminals of the primary afferent. Once in the terminals it will cleave synaptic protein, block spinal afferent transmitter release, and thereby prevent spinal nociceptive excitation and behavior. In mice, C57Bl/6 males, intraplantar BoNT-B (1 U) given unilaterally into the hind paw had no effect upon survival or motor function, but ipsilaterally decreased: (1) intraplantar formalin-evoked flinching; (2) intraplantar capsaicin-evoked plasma extravasation in the hind paw measured by Evans blue in the paw; (3) intraplantar formalin-evoked dorsal horn substance P (SP) release (neurokinin 1 [NK1] receptor internalization); (4) intraplantar formalin-evoked dorsal horn neuronal activation (c-fos); (5) ipsilateral dorsal root ganglion (DRG) vesicle-associated membrane protein (VAMP); (6) ipsilateral SP release otherwise evoked bilaterally by intrathecal capsaicin; (7) ipsilateral activation of c-fos otherwise evoked bilaterally by intrathecal SP. These results indicate that BoNT-B, after unilateral intraplantar delivery, is taken up by the peripheral terminal, is locally active (blocking plasma extravasation), is transported to the ipsilateral DRG to cleave VAMP, and is acting presynaptically to block release from the spinal peptidergic terminal. The observations following intrathecal SP offer evidence for a possible transsynaptic effect of intraplantar BoNT. These results provide robust evidence that peripheral BoNT-B can alter peripheral and central terminal release from a nociceptor and attenuate downstream nociceptive processing via a presynaptic effect, with further evidence suggesting a possible postsynaptic effect.

  6. Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain.

    PubMed

    Drinovac Vlah, V; Bach-Rojecky, L; Lacković, Z

    2016-12-01

    "Mirror pain" or mirror-image pain (MP) is pain opposite to the side of injury. Mechanism and frequency in humans are not known. There is no consent on therapy. Here we report that unilaterally injected botulinum toxin type A (BT-A) has bilateral effect in experimental MP, thus deserves to be investigated as therapy for this condition. We examined the localization of BT-A's bilateral antinociceptive action in MP induced by 3 % carrageenan intramuscular injection in Wistar rats. BT-A was applied peripherally (5 U/kg), into ipsilateral or contralateral hind paw pad (i.pl.) and centrally (1 U/kg), at spinal (intrathecally, i.t.) or supraspinal (intracisternally, i.c.) level. Additionally, we examined the involvement of central opioid and GABAergic systems, as well as the contribution of peripheral capsaicin-sensitive neurons to BT-A's bilateral antinociceptive effect. Ipsilateral i.pl. and i.t. BT-A reduced the bilateral mechanical sensitivity to von Frey filaments, while contralateral i.pl. and i.c. treatments had no effect on either tested side. Bilateral antinociceptive effect of ipsilateral i.pl. BT-A was prevented by μ-opioid antagonist naloxonazine (1.5 μg/10 μl) and GABAA antagonist bicuculline (1 μg/10 μl) if applied at the spinal level, in contrast to supraspinal application of the same doses. Local treatment of sciatic nerve with 2 % capsaicin 5 days following BT-A i.pl. injection caused desensitization of sciatic capsaicin-sensitive fibers, but did not affect bilateral antinociceptive effect of BT-A and the presence of cleaved SNAP-25 at the spinal cord slices. Present experiments suggest segmental actions of peripheral BT-A at spinal level, which are probably not solely dependent on capsaicin-sensitive neurons.

  7. Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin.

    PubMed

    Tugnoli, Valeria; Capone, Jay Guido; Eleopra, Roberto; Quatrale, Rocco; Sensi, Mariachiara; Gastaldo, Ernesto; Tola, Maria Rosaria; Geppetti, Pierangelo

    2007-07-01

    The effect of Botulinum Toxin type A (BoNT/A) on pain and neurogenic vasodilatation induced by application to the human skin of thermal stimuli and capsaicin was evaluated in a double blind study. A capsaicin cream (0.5 ml of a 0.075%) was applied to the skin of both forearms of eighteen subjects randomly pretreated with either BoNT/A (Botox) or 0.9% saline (NS). Capsaicin was applied to a skin area either inside (protocol A) or adjacent to the BoNT/A treated area (protocol B). Pre-treatment with BoNT/A did not affect thermal-specific and thermal-pain thresholds (by quantitative sensory testing). However, capsaicin-induced pain sensation (by a visual analogue scale), flare area (by acetate sheet) and changes in cutaneous blood flow (CBF, by laser Doppler flowmetry) were reduced when capsaicin was administered inside (protocol A) the BoNT/A treated area. In Protocol B, capsaicin-induced pain was unchanged, and capsaicin-induced flare/increase in CBF were reduced only in the area treated with BoNT/A, but not in the BoNT/A untreated area. Results indicate that (i) BoNT/A reduces capsaicin-induced pain and neurogenic vasodilatation without affecting the transmission of thermal and thermal-pain modalities; (ii) reduction in capsaicin-induced pain occurs only if capsaicin is administered into the BoNT/A pretreated area; (iii) reduction in neurogenic vasodilatation by BoNT/A does not contribute to its analgesic action. BoNT/A could be tested for the treatment of conditions characterised by neurogenic inflammation and inflammatory pain.

  8. Botulinum toxin in migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents.

    PubMed

    Ramachandran, Roshni; Lam, Carmen; Yaksh, Tony L

    2015-07-01

    Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi)-SO capsaicin (20 μl of 0.5mM solution) or meningeal capsaicin (4 μl of 0.35 μM). Pre-treatment with ipsi-SO BoNT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; and vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent.

  9. Dissociation between nerve-muscle transmission and nerve trophic effects on rat diaphragm using type D botulinum toxin.

    PubMed Central

    Bray, J J; Harris, A J

    1975-01-01

    Small doses of botulinum toxin can produce partial blockage of transmitter release at the nerve--muscle junction. 2. Subthreshold e.p.p.s, 3--10 days after poisoning, show a distribution of amplitudes that is fitted by Poisson statistics. Successive e.p.p.s. in a short train show a marked facilitation. 3. Two weeks or more after poisoning with a dose of toxin that paralyses the whole muscle, when nerve--muscle transmission is in course of recovery, subthreshold e.p.p.s have an amplitude distribution that is fitted by binomial statistics. This property of transmission is similar to those described in newly formed nerve--muscle junctions, during embryogenesis or regeneration. 4. Muscle fibres with subthreshold transmission in the 5--10 day group of muscles were all supersensitive to ACh, as were a number of fibres in which nerve stimulation still produced an action potential. 5. Two weeks or more after poisoning, muscle fibres with subthreshold transmission had lost their extrajunctional ACh-sensitivity, as had many fibres with m.e.p.p.s of roughly normal frequency but no response to nerve stimulation. 6. In diaphragm muscles poisoned with botulinum toxin between 1 and 4 days previously, the rate of fast axonal transport of radioactively labelled proteins down the phrenic nerve is not greatly affected, but the amount of materials carried is reduced to about one quarter of normal. These labelled proteins accumulate in the intramuscular portion of the phrenic nerve, in or near the nerve terminals, to a much greater extent than in controls, showing that the normal release of some of these materials has been prevented by the toxin. 7. It is concluded that the blockage of the trophic effects of nerves by botulinum toxin is due to a blockage of release of trophic factors other than ACh. 8. The muscle nerve cannot maintain a muscle in its normal state simply by activation of contraction, and a regenerating nerve terminal can restore a muscle towards its normal state before

  10. How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats.

    PubMed

    Shen, Jian; Ma, Jianjun; Lee, Cassandra; Smith, Beth P; Smith, Thomas L; Tan, Kim H; Koman, L Andrew

    2006-05-01

    Botulinum toxin A (BoNT-A) is a potent biological toxin widely used for the management of skeletal muscle spasticity or dynamic joint contracture. Intramuscular injection of BoNT-A causes muscle denervation, paresis, and atrophy. This clinical effect of botulinum toxin A lasts 3 to 6 months, and injected muscle eventually regains muscle mass and recovers muscle function. The goal of the present study was to characterize the molecular and cellular mechanisms leading to neuromuscular junction (NMJ) regeneration and skeletal muscle functional recovery after BoNT-A injection. Fifty-six 1-month-old Sprague-Dawley rats were used. Botulinum toxin A was injected into the left gastrocnemius muscle at a dosage of 6 units/kg body weight. An equivalent volume of saline was injected into the right gastrocnemius muscle to serve as control. The gastrocnemius muscle samples were harvested from both hind limbs at 3 days, 7 days, 15 days, 30 days, 60 days, 90 days, 180 days, and 360 days after administration of toxin. In addition, the gastrocnemius muscles from 1-month-old rats with no injections were harvested to serve as uninjected control group. Muscle samples were processed and mRNA was extracted. Real-time polymerase chain reaction (PCR) and gene microarray technology were used to identify key molecules involved in NMJ stabilization and muscle functional recovery. More than 28,000 rat genes were analyzed and approximately 9000 genes are expressed in the rat gastrocnemius muscle. Seven days following BoNT-A injection, 105 genes were upregulated and 59 genes were downregulated. Key molecules involved in neuromuscular junction (NMJ) stabilization and muscle functional recovery were identified and their time course of gene expression following BoNT-A injection were characterized. This animal study demonstrates that following intramuscular injection of BoNT-A, there is a sequence of cellular events that eventually leads to NMJ stabilization, remodeling, and myogenesis and muscle

  11. Eradication of keloids: Surgical excision followed by a single injection of intralesional 5-fluorouracil and botulinum toxin

    PubMed Central

    Wilson, Adel Michel

    2013-01-01

    BACKGROUND: Keloids may complicate wound healing secondary to trauma, inflammation or surgical incision. Although various treatment modalities have been used with variable degrees of success, overall recurrence rates have remained unacceptably high. METHODS: The present study involved 80 patients with keloids of at least one-years’ duration. Following total surgical excision of the keloid, a single dose of 5-fluorouracil was injected into the edges of the healing wound on postoperative day 9 together with botulinum toxin. The concentration of 5-fluorouracil used was 50 mg/mL and approximately 0.4 mL was infiltrated per cm of wound tissue, with the total dose <500 mg. The concentration of botulinum toxin was 50 IU/mL with the total dose <140 IU. RESULTS: Patients were followed-up for 17 to 24 months and a recurrence rate of 3.75% was found, which was significantly lower than in previously reported studies using other therapeutic modalities. CONCLUSION: The author recommends that this treatment be routinely applied to all keloids because it is significantly more effective than those described by other authors. PMID:24431948

  12. The use of botulinum toxin in the treatment of the consequences of bruxism on cervical spine musculature.

    PubMed

    Finiels, P J; Batifol, D

    2014-03-01

    Hypertonia and hyperactivity of masticatory muscles are involved in pain and contractions of the cervical spine musculature, but their pathophysiology remains nonetheless unknown and its treatment far to be codified. In this study, 8 patients, showing disabling posterior neck muscle contractures linked with bruxism were prospectively treated and followed for an average 15 months period, after having received Injections of botulinum toxin A essentially in masticatory muscles. Injections were made every 3 months, varying from 10 to 100 U Botox* by muscles, without administrating more than 300 U Botox* in the same patient. The angle of cervical lordosis were calculated on lateral sitting radiographs in neutral position, good results being considered to be achieved in the case of a 2 point diminution of VAS score as well as at least a 5° positive gain in the curve. 7 patients out of 8 showed a real improvement in their symptoms after an average of 3 injections, showing a decrease of 4.5 points on the VAS score and an average increment of 15° in cervical lordosis. Although the follow-up period of patients was relatively short and the sample quite small, the general impression, confirmed by the patients' experience, seems to suggest a potential place for the use of botulinum toxin amongst the array of treatments which can be offered in certain selected cases which associate bruxism and posterior cervical contractions.

  13. Renewable surface fluorescence sandwich immunoassay biosensor for rapid sensitive botulinum toxin detection in an automated fluidic format.

    PubMed

    Grate, Jay W; Warner, Marvin G; Ozanich, Richard M; Miller, Keith D; Colburn, Heather A; Dockendorff, Brian; Antolick, Kathryn C; Anheier, Norman C; Lind, Michael A; Lou, Jianlong; Marks, James D; Bruckner-Lea, Cynthia J

    2009-05-01

    A renewable surface biosensor for rapid detection of botulinum neurotoxin serotype A is described based on fluidic automation of a fluorescence sandwich immunoassay, using a recombinant protein fragment of the toxin heavy chain ( approximately 50 kDa) as a structurally valid simulant. Monoclonal antibodies AR4 and RAZ1 bind to separate non-overlapping epitopes of the full botulinum holotoxin ( approximately 150 kDa). Both of the targeted epitopes are located on the recombinant fragment. The AR4 antibody was covalently bound to Sepharose beads and used as the capture antibody. A rotating rod flow cell was used to capture these beads delivered as a suspension by a sequential injection flow system, creating a 3.6 microL column. After perfusing the bead column with sample and washing away the matrix, the column was perfused with Alexa 647 dye-labeled RAZ1 antibody as the reporter. Optical fibers coupled to the rotating rod flow cell at a 90 degrees angle to one another delivered excitation light from a HeNe laser (633 nm) using one fiber and collected fluorescent emission light for detection with the other. After each measurement, the used Sepharose beads are released and replaced with fresh beads. In a rapid screening approach to sample analysis, the toxin simulant was detected to concentrations of 10 pM in less than 20 minutes using this system.

  14. [Treatment of spastic paraparesis with botulinum toxin with reference to beneficial effects, disease severity and long-term treatment].

    PubMed

    Takenaga, S; Kawahigashi, Y; Sonoda, Y; Horikiri, T; Hirata, K; Arimura, K; Osame, M

    1995-03-01

    We administered local botulinum toxin injections on the leg adductors of 12 patients with spastic paraparesis (9 patients with HAM, 2 patients with spinal spastic paraparesis, 1 patient with an identified degenerative disease). Two of them were wheelchair-bound and the other patients could walk with or without help. The patients were assessed by the time to walk 10 m and the spasticity score which was derived from the degree of muscle tone and spasm frequency of leg adductors. After the initial injection, 7 of the 12 patients improved spasticity scores and 8 of the 10 patients could walk 10 m within a shorter time. The time to walk 10 m was markedly shortened in moderate cases. However, one patient complained of leg weakness and the time to walk 10 m was prolonged. Five of the 12 patients received injections 3 to 7 times, and were followed up for a mean of 16.2 months. In 4 of the 5 patients, repeated injections could maintain the improvement of spasticity score and time to walk 10 m. However, injection was discontinued in one patient because of leg weakness. The other side effects were pain and swelling at the injected site and dysarthria. However, these side effects were slight and transient and did not require treatment. No other systemic side effects were observed. In conclusion, the beneficial effects of botulinum injections to spastic paraparesis were (1) improvement of objective symptoms in mild cases, (2) improvement of ADL in moderate cases, and (3) improvement of objective symptoms and ease of nursing care in severe cases. Furthermore, we confirmed the long-term efficacy and safety of botulinum toxin.

  15. Alterations in CNS Activity Induced by Botulinum Toxin Treatment in Spasmodic Dysphonia: An H[subscript 2][superscript 15]O PET Study

    ERIC Educational Resources Information Center

    Ali, S. Omar; Thomassen, Michael; Schulz, Geralyn M.; Hosey, Lara A.; Varga, Mary; Ludlow, Christy L.; Braun, Allen R.

    2006-01-01

    Speech-related changes in regional cerebral blood flow (rCBF) were measured using H[subscript 2][superscript 15]O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest…

  16. High-throughput enzyme-linked immunoabsorbant assay (ELISA) electrochemiluminescent detection of botulinum toxins in foods for food safety and defence purposes.

    PubMed

    Phillips, R W; Abbott, D

    2008-09-01

    Clostridum species produce seven serotypes (A-G) of botulinum toxin, four of which (A, B, E, and F) are normally associated with human illness. To date, the most reliable test for botulinum toxin is the mouse bioassay. The authors' laboratory has been exploring the use of an antibody-based assay similar to an enzyme-linked immunoabsorbant assay (ELISA) but utilizing electrochemiluminescent technology (BioVerify assay) as an alternative to the mouse bioassay for testing food samples. The detection limit of this assay is as low as 10 ng g(-1) depending on the food matrix and the serotype detected. Detection of botulinum toxin between 10 and 200 ng g(-1) is a linear curve allowing for the possibility of performing quantitative as well as qualitative testing of samples. The ease of the assay, limited sample preparation, and low detection limit make the BioVerify assay and instrument an excellent, high-throughput option for detecting botulinum toxins in food matrices.

  17. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: A review of the science, the clinical data, and patient satisfaction

    PubMed Central

    De Boulle, Koenraad; Fagien, Steven; Sommer, Boris; Glogau, Richard

    2010-01-01

    Botulinum toxin type A treatment is the foundation of minimally invasive aesthetic facial procedures. Clinicians and their patients recognize the important role, both negative and positive, that facial expression, particularly the glabellar frown lines, plays in self-perception, emotional well-being, and perception by others. This article provides up-to-date information on fundamental properties and mechanisms of action of the major approved formulations of botulinum toxin type A, summarizes recent changes in naming conventions (nonproprietary names) mandated by the United States Food and Drug Administration, and describes the reasons for these changes. The request for these changes provides recognition that formulations of botulinum toxins (eg, onabotulinumtoxinA and abobotulinumtoxinA) are not interchangeable and that dosing recommendations cannot be based on any one single conversion ratio. The extensive safety, tolerability, and efficacy data are summarized in detail, including the patient-reported outcomes that contribute to overall patient satisfaction and probability treatment continuation. Based on this in-depth review, the authors conclude that botulinum toxin type A treatment remains a cornerstone of facial aesthetic treatments, and clinicians must realize that techniques and dosing from one formulation cannot be applied to others, that each patient should undergo a full aesthetic evaluation, and that products and procedures must be selected in the context of individual needs and goals. PMID:20458348

  18. Feasibility of a Day-Camp Model of Modified Constraint-Induced Movement Therapy with and without Botulinum Toxin A Injection for Children with Hemiplegia

    ERIC Educational Resources Information Center

    Eliasson, Ann-Christin; Shaw, Karin; Ponten, Eva; Boyd, Roslyn; Krumlinde-Sundholm, Lena

    2009-01-01

    The objective of the study was to investigate the feasibility of modified constraint-induced (CI) therapy provided in a 2-week day-camp model with and without intramuscular botulinum toxin type A (BoNT-A) injections for children with congenital cerebral palsy. Sixteen children with congenital hemiplegia, Manual Ability Classification System (MACS)…

  19. The Profile of Patients and Current Practice of Treatment of Upper Limb Muscle Spasticity with Botulinum Toxin Type A: An International Survey

    ERIC Educational Resources Information Center

    Bakheit, Abdel Magid

    2010-01-01

    To document the current practice in relation with the treatment of patients with upper limb spasticity with botulinum toxin type A to inform future research in this area. We designed an international, cross-sectional, noninterventional survey of current practice. Nine hundred and seventy-four patients from 122 investigational centres in 31…

  20. Efficacy and safety of botulinum toxin in treatment of anismus: A systematic review

    PubMed Central

    Emile, Sameh Hany; Elfeki, Hossam Ayman; Elbanna, Hosam Ghazy; Youssef, Mohamed; Thabet, Waleed; Abd El-Hamed, Tito M; Said, Basem; Lotfy, Ahmed

    2016-01-01

    AIM: To evaluate the efficacy and safety of botulinum toxin type A (BTX-A) in the management of patients with anismus. METHODS: An organized search of published literature was conducted using electronic databases including: PubMed/MEDLINE, and Cochrane Central Register of Controlled Trials, also an internet-based search using “Google Scholar” service was conducted. Both comparative and observational studies were included. We excluded irrelevant articles, editorials, case reports, reviews, and meta-analyses. The studies that followed the patients less than 6 mo were excluded. Variables collected were demographic data of the patients, technique of BTX-A injection and number of sessions, short-term and long-term clinical improvement, post-injection changes in electromyography (EMG), defecography, manometry, and balloon expulsion test, and complications recorded after BTX-A injection. RESULTS: Seven studies comprising 189 patients were included in the review. The median age of the patients was 41.2 years and female-to-male ratio was 1.3:1. The median dose of BTX-A injected per procedure was 100 IU (range, 20-100 IU). Lateral injection was done in five trails and combined lateral and posterior injections in two trials. Three studies used endorectal ultrasonography-guided technique, one study used EMG-guided technique, whereas the remaining three studies used manual palpation with the index finger. The median percentage of patients who reported initial improvement of symptoms was 77.4% (range 37.5%-86.7%), this percentage declined to a median of 46% (range 25%-100%) at 4 mo after injection of BTX-A. Rates of improvement evaluated by balloon expulsion test, EMG, and defecography ranged between (37.5%-80%), (54%-86.7%), and (25%-86.6%), respectively. Fourteen (7.4%) patients developed complications after injection of BTX-A. Complication rates across the studies ranged from 0% to 22.6%. CONCLUSION: Initial satisfactory improvement of symptoms after BTX-A injection

  1. Combined treatment of achalasia - botulinum toxin injection followed by pneumatic dilatation: long-term results.

    PubMed

    Kroupa, R; Hep, A; Dolina, J; Valek, V; Matyasova, Z; Prokesova, J; Mrazova, J; Sedmik, J; Novotny, I

    2010-02-01

    Injection of botulinum toxin (BT) and pneumatic dilatation are available methods in nonsurgical treatment of achalasia. Authors anticipate beneficial effect of prior BT injection on the success of pneumatic dilatation and duration of its effect. There are no long-term data available to assess efficacy of combined treatment. From 1998 to 2007, 51 consecutive patients (20 men and 31 women, age 24-83) with achalasia were included and prospectively followed up. Each patient received injection of 200 IU of BT into the lower esophageal sphincter (LES) during endoscopy and 8 days later pneumatic dilatation (PD) under X-ray control was performed. The follow-up was established every 3 months first year and then annually. The efficacy was evaluated by a questionnaire concerning patient's symptoms and manometry. Results were compared with 40 historical controls (16 men and 24 women, age 26-80) treated by PD alone using the same method and follow-up. Fifty-one patients underwent combined treatment. Four patients failed in follow-up and were not included for analysis. The mean duration of follow-up was 48 months with range 12-96 months. Thirty-four of forty-seven (72%) patients were satisfied with results with none or very rare and mild troubles at the time of the last visit. Forty-one patients were followed up more than 2 years. Effect of therapy lasted in 75% (31/41) of them. In 17 patients, more than 5 years after treatment, effect lasted in 12 (70%). Mean tonus of LES before therapy was 29 mm Hg (10-80), 3 months after therapy decreased to 14 mmHg (5-26). The cumulative 5 years remission rate (+/-95% CI) in combined treated patients 69% +/- 8% was higher than in controls 50% +/- 9%; however it, was not statistically significant (P= 0.07). In control group 1, case of perforation (2.5%) occurred. Eight patients (17%) with relapse of dysphagia were referred to laparoscopic Heller myotomy with no surgical complication. The main adverse effect was heartburn that appeared in 17

  2. Effect of Botulinum Toxin Type A on a Rat Surgical Wound Model

    PubMed Central

    Lee, Byung-Joo; Jeong, Jae-Hwi; Wang, Soo-Geun; Lee, Jin-Choon; Kim, Hwal-Woong

    2009-01-01

    Objectives The tension on a wound is one of the important factors that determine the degree of fibrosis and scar formation. We hypothesized that local botulinum toxin type A (Botox) induced paralysis of the musculature subjacent to a surgical wound with a skin defect would minimize the repetitive tensile forces on the surgical wound's edges, and this will result in a decreased fibroplastic response and fibrosis of the wound. Methods This is a prospective randomized experimental study. Two distinct surgical wounds were made to the dorsum of 15 adult rats, respectively. One of the 2 wounds was injected with Botox, and the other wound was used as a control, and this was done for all the rats' wounds. We evaluated the wound size, the degree of fibrosis and inflammation, the blood vessel proliferation, the thickness of the wound and the expression of transforming growth factor (TGF)-β1 in the wounds. Results There were significant differences of wound size at the 3rd and 4th week between the Botox and control groups (P<0.05). The Botox group showed less infiltration of inflammatory cells than the control group at the 2nd week (P<0.05). The Botox group showed a smaller number of fibroblasts and less fibrosis than the control group at the 4th week (P<0.05). The Botox group showed much strong collagen density than the control group at the 8th week (P<0.05). For the immunohistochemical staining, there was a lower transforming growth factor (TGF)-β1 expression in the Botox group than that of the control group at the 4th week (P<0.05). Conclusion The wounds of the Botox-treated group showed a larger wound size, less infiltration of inflammatory cells and less fibrosis, a much greater amount of collagen and a lower expression of TGF-β1 than did the control group. Botox might be used to decrease the fibrosis of a surgical wound without damaging the epithelial growth in situations for which decreased fibrosis is necessary, such as for treating laryngeal, tracheal and nasal

  3. Anatomy of the sweat glands, pharmacology of botulinum toxin, and distinctive syndromes associated with hyperhidrosis.

    PubMed

    Kreyden, Oliver P; Scheidegger, E Paul

    2004-01-01

    For a long period the therapeutic modalities to treat focal hyperhidrosis (HH) were very limited. Due to this the problem of focal HH was delt with stepmotherly. Nowadays we can consider BTX as the therapy of choice for axillary HH after topical treatment with aluminium salts have failed. The amount of successful reports on botulinum toxin (BTX) in the treatment of focal HH brought a change and the interest for this specific disorder grew. This article gives details on anatomy and physiology of sweating and mechanism of BTX. Further distinctive syndromes associated with HH, which all can be treated with BTX like localized unilateral hyperhidrosis (LUH), Ross' Syndrome and Frey' Syndrome are presented. A diagnosis of primary HH is usually based on the patients's history, typical younger age and visible signs of excessive sweating. Before treatment it is important to objectify focal HH with performing sweat tests such like Minor starch test and/or gravimetry. The total number of sweat glands is somewhere between 2 and 4 million and only about 5% are active at the same time, indicating the enormous potential for sweat production. The eccrine sweat gland is a long-branched tubular structure with highly coiled secretory portion and a straight ductular portion. Sweat is produced by clear and dark cells and is a clear hypotonic, odorless fluid. In response to nerve impulses, Acetylcholine (ACh) is released from the presynaptic nerve endings and then binds to postsynaptic cholinergic receptors presumably present in the basolateral membrane of the clear cells. This activates a complex in- and efflux of electrolytes creating the hypotonic sweat. Injection of BTX leads to temporary chemodenervation with the loss or reduction of activity of the target organ. BTX is consisted of a heavy and a light chain. The structural architecture of BTX comprises three domains-L, H(N) and H(C)-each with a specific function in the mechanism of cell intoxication. The heavy chain is responsible

  4. Effect of botulinum toxin type-A in patients with focal spasticity

    PubMed Central

    Selimoglu, Esra; Turgut, Selin Turan; Akpinar, Pinar; Yumusakhuylu, Yasemin; Haliloglu, Sema; Baklacioglu, Hatice Sule; Icagasioglu, Afitap

    2015-01-01

    OBJECTIVE: To investigate the effect of botulinum toxin type-A (BTX-A) on spasticity and function in patients with focal spasticity. METHODS: Patients attended to the outpatient clinic of physical medicine and rehabilitation department with a diagnosis of focal spasticity and had BTX-A injections because of spasticty were evaluated for the study. Demographic data, exercise status, orthoses, drugs used for spasticity, functional status, stages of spasticity of muscles before and after 1st and 3rd months of BTX-A injection according to Modified Ashworth Scale (MAS) were evaluated retrospectively. MedCalc 11.6 statistical program was used for statistical analyses. Statistical significance was defined as p<0.05. RESULTS: Forty-nine patients with focal spasticity were recruited for the study (35 men, 14 women). Mean age of the patients was 21.59±20.09 years. The patients had cerebral palsy (CP, n=28), 19 had hemiplegia (n=19) and paraplegia (n=2). Forty-three patients were using orthoses and exercising regularly. Mean Pediatric Functional Independence Measurement (WeeFIM) scores of the patients with CP was 54.82±28.91 and according to the Gross Motor Function Classification System (GMFCS) the patients were in stages 2 (14%), 3 (46%), 4 (11%) and 5 (29%). Mean Functional Independence Measure (FIM) of hemiplegic and paraplegic patients was 80.80±20.88. Brunnstrom staging scores for upper extremity (3.52±0.96), hands (2.68±0.82), lower extremity (4.57±1.01) were calculated. MAS muscles demonstrated statistically significant decrease in spasticity at the end of first and third months (p<0.05). CONCLUSION: We saw a significant decrease in the spasticity of upper and lower extremities in patients with focal spasiticity who received BTX-A injections. We suggest that if BTX-A injections are supported with orthoses and exercise programs, then functional status of the patients would be better. PMID:28058322

  5. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    PubMed Central

    Intiso, Domenico; Basciani, Mario; Santamato, Andrea; Intiso, Marta; Di Rienzo, Filomena

    2015-01-01

    Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX) as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders including post

  6. Botulinum toxin in hemifacial spasm: the challenge to assess the effect of treatment.

    PubMed

    Wabbels, Bettina; Roggenkämper, Peter

    2012-08-01

    Hemifacial spasm is characterized by intermittent tonic or clonic contractions of the muscles supplied by the facial nerve. Although vision is less impaired than in patients with blepharospasm, the disease can impose significant psychosocial burden on patient's life. Botulinum toxin (BoNT) is the well-established pharmacotherapy of choice, but evidence from controlled clinical trials is sparse. There is a broad variety of rating scales used in clinical studies with BoNT and obviously no consensus has been reached how to assess treatment outcome in hemifacial spasm. Clinical rating scales focusing on objective function were used in a couple of controlled studies with BoNT and were appropriate to discriminate between BoNTA and placebo. But it has not been shown that they would be sensitive enough to detect minor differences between several BoNT formulations. Although most of the clinical scales consist of a five-point rating, the descriptors for the ordinal numbers are not necessarily the same so that the results of different clinical studies are not comparable to each other. The main disadvantage of clinical scales is that they do not take into account patient's perspective of disability and impact on daily life. For this reason some clinical studies applied health-related quality of life (HRQoL) questionnaires to assess efficacy, and one research group worked on the development of disease-specific tools. Although these HRQoL questionnaires have been validated and a good correlation to disease severity could be demonstrated, they are far from having become an established variable for efficacy assessment in hemifacial spasm trials. The challenge remains to establish tools which are appropriate to rate BoNT treatment effects in hemifacial spasm. Currently, it is virtually impossible to identify one rating scale which can cover all relevant aspects of the disorder. In consequence we recommend the implementation of a combination of different rating scales which address

  7. Efficacy of a potential trivalent vaccine based on Hc fragments of botulinum toxins A, B, and E produced in a cell-free expression system.

    PubMed

    Zichel, R; Mimran, A; Keren, A; Barnea, A; Steinberger-Levy, I; Marcus, D; Turgeman, A; Reuveny, S

    2010-05-01

    Botulinum toxins produced by the anaerobic bacterium Clostridium botulinum are the most potent biological toxins in nature. Traditionally, people at risk are immunized with a formaldehyde-inactivated toxin complex. Second generation vaccines are based on the recombinant carboxy-terminal heavy-chain (Hc) fragment of the neurotoxin. However, the materialization of this approach is challenging, mainly due to the high AT content of clostridial genes. Herein, we present an alternative strategy in which the native genes encoding Hc proteins of botulinum toxins A, B, and E were used to express the recombinant Hc fragments in a cell-free expression system. We used the unique property of this open system to introduce different combinations of chaperone systems, protein disulfide isomerase (PDI), and reducing/oxidizing environments directly to the expression reaction. Optimized expression conditions led to increased production of soluble Hc protein, which was successfully scaled up using a continuous exchange (CE) cell-free system. Hc proteins were produced at a concentration of more than 1 mg/ml and purified by one-step Ni(+) affinity chromatography. Mice immunized with three injections containing 5 microg of any of the in vitro-expressed, alum-absorbed, Hc vaccines generated a serum enzyme-linked immunosorbent assay (ELISA) titer of 10(5) against the native toxin complex, which enabled protection against a high-dose toxin challenge (10(3) to 10(6) mouse 50% lethal dose [MsLD(50)]). Finally, immunization with a trivalent HcA, HcB, and HcE vaccine protected mice against the corresponding trivalent 10(5) MsLD(50) toxin challenge. Our results together with the latest developments in scalability of the in vitro protein expression systems offer alternative routes for the preparation of botulinum vaccine.

  8. Action of brown widow spider venom and botulinum toxin on the frog neuromuscular junction examined with the freeze-fracture technique.

    PubMed Central

    Pumplin, D W; Reese, T S

    1977-01-01

    1. Structural changes which normally accompany transmitter release at frog neuromuscular junctions are visualized with the freeze-fracture technique. The effects of brown widow spider venom and botulinum toxin were evaluated in terms of their ability to block or produce these structural changes. Changes produced by these neuropoisons were correlated with their known effects on neurotransmitter release. 3. Fusion of synaptic vesicles with the presynaptic plasmalemma, normally evoked by electrical stimulation, was abolished at neuromuscular junctions from frogs treated with botulinum toxin. 3. The concentration of large intramembranous particles in the presynaptic plasmalemma, an indication of the excess of synaptic vesicle fusion over recovery of synaptic vesicle membrane, was increased by treatment with brown widow spider venom, even in the presence of botulinum toxin. 4. When external calcium was present, sites of vesicle fusion induced by brown widow spider venom, as well as by electrical stimulation, were located mainly in the active zone. In the absence of external calcium, many plasmalemmal deformations, also though to be sites of vesicle fusion, were more evenly dispersed over the presynaptic surface of nerve terminals. 5. Botulinum toxin decreased the number of vesicle fusion sites in the active zone induced by spider venom in the presence of external calcium but had little effect on the number of fusion sites induced by spider venom in the absence of external calcium. 6. Nerve terminals soaked in a sodium-free Ringer solution were partially depleted of vesicles. Addition of spider venom to this Ringer did not cause additional depletion of vesicles. 7. Formation of cation-permeable channels in the presynaptic membrane could account for these effects of spider venom on the frog neuromuscular junction. Botulinum toxin blocks vesicle fusion by some means which is not yet understood. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:202700

  9. A case report of the beneficial effects of botulinum toxin type A on Raynaud phenomenon in a patient with lung cancer

    PubMed Central

    Wang, Lu; Lei, Qi-song; Liu, Yu-ying; Song, Guan-jie; Song, Chun-ling

    2016-01-01

    Abstract Objective: Raynaud phenomenon is a vasospastic disorder affecting the hands and feet, and the efficacies of traditional treatments, such as pharmacological therapies and sympathectomy, are not uniform. Patients with paraneoplastic Raynaud phenomenon do not benefit from the traditional treatments. The use of botulinum toxin type A (BTX-A) for Raynaud phenomenon has been reported for several years; however, there are few reports regarding botulinum toxin type A in the treatment of paraneoplastic Raynaud phenomenon. We describe a case report of the beneficial effects of botulinum toxin type A on Raynaud phenomenon in a patient with lung cancer. Methods: A 63-year-old male complained of pain and discoloration of his fingers and indicated that oral nifedipine and low-dose aspirin were not effective. After approximately 8 months, he was diagnosed with lung cancer. Chemotherapy partially reduced the pain and discoloration of his fingers; however, no significant changes occurred in his fingers after the fourth cycle. We used BTX-A to treat this patient with paraneoplastic RP. A visual analogue scale (VAS) was used to assess the clinical response. Results: After approximately 2 months, the patient reported relief from pain, stiffness, numbness, and cold sensation. Furthermore, no local or general adverse effects were exhibited by the patient. Conclusion: This study used botulinum toxin type A for a patient with paraneoplastic Raynaud phenomenon. Botulinum toxin type A significantly improved the patient's clinical symptoms without significant complications. These findings suggest that BTX-A may represent a good option for the treatment of paraneoplastic RP. PMID:27749585

  10. Effects of modified atmosphere packaging on toxin production by Clostridium botulinum in raw aquacultured summer flounder fillets (Paralichthys dentatus).

    PubMed

    Arritt, Fletcher M; Eifert, Joseph D; Jahncke, Michael L; Pierson, Merle D; Williams, Robert C

    2007-05-01

    Packaging fishery products under vacuum atmosphere packaging (VAC) and modified atmosphere packaging (MAP) conditions can significantly extend the shelf life of raw, refrigerated fish products. There is considerable commercial interest in marketing VAC and MAP refrigerated (never frozen) raw fish fillets. The objective of this study was to determine if Clostridium botulinum toxin development precedes microbiological spoilage in raw, refrigerated flounder fillets. Aquacultured flounder (Paralichthys dentatus) individual fish fillets either were packed with a film having an oxygen transmission rate (OTR) of 3000 cm3 m(-2) 24 h(-1) at 22.8 degrees C or were vacuum packaged or packaged under 100% CO2 with a film having an OTR of 7.8 cm3 m(-2) 24 h(-1) at 21.1 degrees C and were stored at 4 and 10 degrees C. Samples were analyzed by aerobic plate count (APC) for spoilage and qualitatively for botulinum toxin with a mouse bioassay. The results demonstrate that flounder fillets (4 degrees C) packaged with a film having an OTR of 3,000 were microbiologically spoiled (APC, > 10(7) CFU/g) on day 15, but there was no toxin formation, even after 35 days of storage. However, at 10 degrees C, toxin production occurred (day 8), but it was after microbial spoilage and absolute sensory rejection (day 5). Vacuum-packaged fillets and 100% CO2 fillets (4 degrees C) packaged with a film having an OTR of 7.8 were toxic on days 20 and 25, respectively, with microbial spoilage (APC, >10(7) CFU/g) not occurring during the tested storage period (i.e., >35 days). At 10 degrees C, in vacuum-packaged flounder, toxin formation coincided with microbiological spoilage (days 8 to 9). In the 100% CO2-packaged fillets, toxin formation occurred on day 9, with microbial spoilage occurring on day 15. This study indicates that films with an OTR of 3,000 can be used for refrigerated fish fillets and still maintain the safety of the product.

  11. Quantification of toxin-encoding mRNA from Clostridium botulinum type E in media containing sorbic acid or sodium nitrite by competitive RT-PCR.

    PubMed

    Sharkey, Freddie H; Markos, Spiros I; Haylock, Richard W

    2004-03-19

    Competitive reverse transcription polymerase chain reaction (cRT-PCR) was used to quantify the toxin-encoding mRNA production of a Clostridium botulinum type E strain in media containing either sorbic acid or sodium nitrite. A 10-fold reduction in toxin mRNA production and a 25-fold reduction in the proportion of toxin mRNA to total RNA, was estimated when either 1 mg ml(-1) sorbic acid or 100 microg ml(-1) sodium nitrite were added to the medium at pH 7.0.

  12. Effect of Fill Temperature on Clostridium botulinum Type A Toxin Activity during the Hot Filling of Juice Bottles.

    PubMed

    Skinner, Guy E; Fleischman, Gregory J; Balster, Fran; Reineke, Karl; Reddy, N Rukma; Larkin, John W

    2015-08-01

    The potential threat of terrorist attacks against the United States food supply using neurotoxin produced by Clostridium botulinum (BoNT) has resulted in the need for studying the effect of various food process operations on the bioavailability of this toxin. The objective of this study was to evaluate C. botulinum type A neurotoxin bioavailability after a simulated hot fill juice bottling operation. C. botulinum type A acid mud toxin (∼10(6) mouse lethal dose [MLD50]/ml) was deposited into juice bottles at an experimentally determined fastest cooling spot. Bottles (12 or 20 oz [355 and 592 ml]) were filled with either apple juice or an orange drink, at 80 or 85°C, in either upright or inverted orientations. Toxicity of the juice was evaluated as a function of holding time (1 to 2 min) by the mouse bioassay. The fastest cooling point in the upright orientation was determined to be at a bottle's bottom rim. In the inverted orientation, the fastest cooling point was in the bottle cap region. With respect to these two points, the upright bottle cooled faster than the inverted bottle, which was reflected in a higher inactivation of BoNT in the latter. For the orange drink (pH 2.9) toxicity was reduced by 0.5 × 10(6) MLD50/ml to a nondetectable level after 1 min in all bottle sizes, orientations, and temperatures as measured by the mouse bioassay. This indicates that there was at least a 0.5 × 10(6) MLD50/ml reduction in activity. Inactivation in apple juice (pH 4.0), to the same degree as in the orange drink, was found only for the inverted orientation at 85°C. Complete inactivation in apple juice for all conditions was found at a lower added toxin level of 0.25 × 10(5) MLD50/ml. In general, bottle inversion and filling at 85°C provided complete inactivation of BoNT to the 0.5 × 10(6) MLD50/ml level. All experiments resulted in the inactivation of 2.5 × 10(4) MLD50/ml of BoNT regardless of juice type, fill temperature, or bottle orientation and size.

  13. Renewable Surface Fluorescence Sandwich Immunoassay Biosensor for Rapid Sensitive Botulinum Toxin Detection in an Automated Fluidic Format

    SciTech Connect

    Grate, Jay W.; Warner, Marvin G.; Ozanich, Richard M.; Miller, Keith D.; Colburn, Heather A.; Dockendorff, Brian P.; Antolick, Kathryn C.; Anheier, Norman C.; Lind, Michael A.; Lou, Jianlong; Marks, James D.; Bruckner-Lea, Cindy J.

    2009-03-05

    A renewable surface biosensor for rapid detection of botulinum toxin is described based on fluidic automation of a fluorescence sandwich immunoassay, using a recombinant fragment of the toxin heavy chain as a structurally valid simulant. Monoclonal antibodies AR4 and RAZ1 bind to separate epitopes of both this fragment and the holotoxin. The AR4 antibody was covalently bound to Sepharose beads and used as the capture antibody. A rotating rod flow cell was used to capture these beads delivered as a suspension by the sequential injection flow system, creating a 3.6 microliter column. After perfusing the bead column with sample and washing away the matrix, the column was perfused with Alexa 647 dye-labeled RAZ1 antibody as the reporter. Optical fibers coupled to the rotating rod flow cell at a 90 degree angle to one another delivered excitation light from a HeNe laser and collected fluorescent emission light for detection. After each measurement, the used sepharose beads are released and replaced with fresh beads. In a rapid screening approach to sample analysis, the toxin simulant was detected to concentrations of 10 pM in less than 20 minutes.

  14. The therapeutic usage of botulinum toxin (Botox) in non-cosmetic head and neck conditions - An evidence based review.

    PubMed

    Awan, Kamran Habib

    2017-01-01

    Botulinum toxin (Botox) is an exotoxin produced from Clostridium botulinum. It blocks the release of acetylcholine from the cholinergic nerve end plates resulting in inactivity of the muscles or glands innervated. The efficacy of Botox in facial aesthetics is well established; however, recent literature has highlighted its utilization in multiple non-cosmetic medical and surgical conditions. The present article reviews the current evidence pertaining to Botox use in the non-cosmetic head and neck conditions. A literature search was conducted using MEDLINE, EMBASE, ISI Web of Science and the Cochrane databases limited to English Language articles published from January 1980 to December 2014. The findings showed that there is level 1 evidence supporting the efficacy of Botox in the treatment of laryngeal dystonia, headache, cervical dystonia, masticatory myalgia, sialorrhoea, temporomandibular joint disorders, bruxism, blepharospasm, hemifacial spasm and rhinitis. For chronic neck pain there is level 1 evidence to show that Botox is ineffective. Level 2 evidence exists for vocal tics and trigeminal. For stuttering, facial nerve paresis, Frey's syndrome and oromandibular dystonia the evidence is level 4. Thus, there is compelling evidence in the published literature to demonstrate the beneficial role of Botox in a wide range of non-cosmetic conditions pertaining to the head and neck (mainly level 1 evidence). With more and more research, the range of clinical applications and number of individuals getting Botox will doubtlessly increase. Botox appears to justify its title as 'the poison that heals'.

  15. Paroxysmal Autonomic Instability With Dystonia Managed Using Chemodenervation Including Alcohol Neurolysis and Botulinum Toxin Type A Injection: A Case Report

    PubMed Central

    Lee, Hye-Sun; Oh, Hyun-Seung

    2015-01-01

    Paroxysmal autonomic instability with dystonia (PAID) is a rare complication of brain injury. Symptoms of PAID include diaphoresis, hyperthermia, hypertension, tachycardia, and tachypnea accompanied by hypertonic movement. Herein, we present the case of a 44-year-old female patient, who was diagnosed with paraneoplastic limbic encephalopathy caused by thyroid papillary cancer. The patient exhibited all the symptoms of PAID. On the basis that the symptoms were unresponsive to antispastic medication and her liver function test was elevated, we performed alcohol neurolysis of the musculocutaneous nerve followed by botulinum toxin type A (BNT-A) injection into the biceps brachii and brachialis. Unstable vital signs and hypertonia were relieved after chemodenervation. Accordingly, alcohol neurolysis and BNT-A injection are proposed as a treatment option for intractable PAID. PMID:25932429

  16. [The efficacy of botulinum toxin therapy in patients with upper limb spasticity due to traumatic brain injury].

    PubMed

    Akulov, M A; Khat'kova, S E; Mokienko, O A; Orlova, O R; Usachev, D Yu; Zakharov, V O; Orlova, A S; Tomsky, A A

    Spasticity is a type of muscle hyperactivity that occurs in patients after focal lesions of the Central nervous system due to various diseases: stroke, traumatic brain injury or spinal cord injury, neurosurgical intervention, as well as multiple sclerosis and other diseases of the Central nervous system and is the most disability manifestation of the syndrome of upper motor neuron (UMNS). Focal spasticity of the upper limb requires a complex treatment. Botulinum toxin therapy is an effective treatment for focal/multifocal spasticity in reducing muscle tone and improving function with the highest level of evidence according to the latest American and European guidelines for treatment of spasticity. There are many publications devoted to BTA use in post-stroke patients. This article provides a review of the BTA use in patients with the upper limb spasticity due to severe traumatic brain injury. Some local data on the BTA efficacy in the cohort of patients with traumatic brain injury are also presented.

  17. An in vivo analysis of facial muscle change treated with botulinum toxin type A using digital image speckle correlation

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Palmaccio, Samantha Palmaccio; Bui, Duc; Dagum, Alexander; Rafailovich, Miriam

    Been famous for clinical use from early 1980s, the neuromuscular blocking agent Botulinum toxin type A (BTX-A), has been used to reduce wrinkles for a long time. Only little research has been done to quantify the change of muscle contraction before and after injection and most research paper depend on subjective evaluation from both patients and surgeons. In our research, Digital Image Speckle Correlation (DISC) was employed to study the mechanical properties of skin, contraction mode of muscles (injected) and reaction of neighbor muscle group (un-injected).At the same time, displacement patterns (vector maps)generated by DISC can predict injection locus for surgeons who normally handle it depending only on visual observation.

  18. Botulinum toxin in severe upper extremity spasticity among patients with traumatic brain injury: an open-labeled trial.

    PubMed

    Yablon, S A; Agana, B T; Ivanhoe, C B; Boake, C

    1996-10-01

    We studied the effect of botulinum toxin A (BTXA) among patients with traumatic brain injury (TBI) and severe spasticity unresponsive to conservative management. Twenty-one consecutive adult patients with severe spasticity involving the wrist and finger flexor musculature were treated with BTXA injection (20 to 40 units per muscle) under EMG guidance. After injection, patients received passive range of motion (ROM) exercise, with modalities and casting as clinically indicated. Outcome measures, including wrist ROM and the modified Ashworth Scale (MAS), were assessed 2 to 4 weeks after injection. Among the respective acute and chronic groups, mean ROM improved 42.9 (p = 0.001) and 36.2 degrees (p < 0.001). Mean MAS rating improved 1.5 (p = 0.01) and 1.47 (p = 0.002) points. There were no significant adverse effects. BTXA, in conjunction with conventional modalities, significantly improves spasticity and ROM in the distal upper extremity musculature of patients with TBI.

  19. Technique for iliopsoas ultrasound-guided active electromyography-directed botulinum a toxin injection in cerebral palsy.

    PubMed

    Willenborg, Michael J; Shilt, Jeffrey S; Smith, Beth Paterson; Estrada, Roquel L; Castle, Jason A; Koman, L Andrew

    2002-01-01

    Symptomatic hip flexion deformity secondary to iliopsoas spasticity may interfere with gait, impair sitting balance, or contribute to hip subluxation or dislocation. A nonsurgical, minimally invasive technique to ameliorate iliopsoas spasticity is presented. The technique uses intramuscular injections of botulinum A toxin to provide selective neuromuscular blockade of the iliacus or psoas muscles or both. Because of the anatomic location of the target muscles, this technique uses ultrasound guidance for needle placement. Active electromyographic stimulation is used to verify the needle position adjacent to active myoneural interfaces. The authors' experience to date includes the treatment of 28 patients (53 hips). Use of this technique has resulted in improved hip range of motion. No intraoperative or postoperative adverse events or complications have been observed.

  20. Application of motion analysis in the study of the effect of botulinum toxin to rat vocal folds

    NASA Astrophysics Data System (ADS)

    Saadah, Abdul K.; Galatsanos, Nikolas P.; Inagi, K.; Bless, D.

    1997-05-01

    In the past we have proposed a system that measures the deformations of the vocal folds from videostroboscopic images of the larynx, in that system: (1) we extract the boundaries of the vocal folds, (2) we register elastically the vocal fold boundaries in successive frames. This yields the displacement vector field (DVF) between adjacent frames, and (3) we fit using a least-squares approach an affine transformation model to succinctly describe the deformations between adjacent frames. In this paper, we present as an example of the capabilities of this system, an initial study of the deformation changes in rat vocal folds pre and post injection with Botulinum toxin. For this application the generated DVF was segmented into right DVF and left DVF and the deformation of each segment is studied separately.

  1. Effects of Botulinum Toxin on Jaw Motor Events during Sleep in Sleep Bruxism Patients: A Polysomnographic Evaluation

    PubMed Central

    Shim, Young Joo; Lee, Moon Kyu; Kato, Takafumi; Park, Hyung Uk; Heo, Kyoung; Kim, Seong Taek

    2014-01-01

    Study Objectives: To investigate the effects of botulinum toxin type A (BoNT-A) injection on jaw motor episodes during sleep in patients with or without orofacial pain who did not respond to oral splint treatment. Methods: Twenty subjects with a clinical diagnosis of SB completed this study. Ten subjects received bilateral BoNT-A injections (25 U per muscle) into the masseter muscles only (group A), and the other 10 received the injections into both the masseter and temporalis muscles (group B). Video-polysomnographic (vPSG) recordings were made before and at 4 weeks after injection. Rhythmic masticatory muscle activity (RMMA) and orofacial activity (OFA) were scored and analyzed for several parameters (e.g., frequency of episodes, bursts per episode, episode duration). The peak amplitude of electromyographic (EMG) activity in the two muscles was also measured. Results: BoNT-A injection did not reduce the frequency, number of bursts, or duration for RMMA episodes in the two groups. The injection decreased the peak amplitude of EMG burst of RMMA episodes in the injected muscles (p < 0.001, repeated measure ANOVA) in both groups. At 4 weeks after injection, 9 subjects self-reported reduction of tooth grinding and 18 subjects self-reported reduction of morning jaw stiffness. Conclusions: A single BoNT-A injection is an effective strategy for controlling SB for at least a month. It reduces the intensity rather than the generation of the contraction in jaw-closing muscles. Future investigations on the efficacy and safety in larger samples over a longer follow-up period are needed before establishing management strategies for SB with BoNT-A. Citation: Shim YJ; Lee MK; Kato T; Park HU; Heo K; Kim ST. Effects of botulinum toxin on jaw motor events during sleep in sleep bruxism patients: a polysomnographic evaluation. J Clin Sleep Med 2014;10(3):291-298. PMID:24634627

  2. Botulinum Toxin Type A Injections for Cervical and Shoulder Girdle Myofascial Pain Using an Enriched Protocol Design

    PubMed Central

    Nicol, Andrea L.; Wu, Irene I.; Ferrante, F. Michael

    2014-01-01

    Background Myofascial pain syndrome is a regional condition of muscle pain and stiffness and is classically characterized by the presence of trigger points in affected musculature. Botulinum toxin type A (BoNT-A) has been shown to have antinociceptive properties and elicit sustained muscle relaxation, thereby possibly affording even greater relief than traditional strategies. Our goal in this study was to determine whether direct injection of BoNT-A into painful muscle groups is effective for cervical and shoulder girdle myofascial pain. Methods An enriched protocol design was used wherein 114 patients with cervical and shoulder girdle myofascial pain underwent injection of BoNT-A to determine their response to the drug. Fifty-four responders were then enrolled in a twelve-week, randomized, double-blind, placebo-controlled trial. Pain scales and quality of life measures were assessed at baseline and at routine follow-up visits until completion of the study after 26 weeks. Results Injection of BoNT-A into painful muscle groups improved average visual numerical pain scores in subjects who received a second dose of BoNT-A compared to placebo (p = 0.019 (0.26, 2.78)). Subjects who received a second dose of BoNT-A had a reduced number of headaches per week (p = 0.04 (0.07, 4.55)). Brief Pain Inventory interference scores for general activity and sleep were improved (p = 0.046 (0.038, 3.7) and 0.02 (0.37, 4.33), respectively) in those who received a second dose of BoNT-A. Conclusion Botulinum toxin type A injected directly into painful muscle groups improves average pain scores and certain aspects of quality of life in patients suffering from severe cervical and shoulder girdle myofascial pain. PMID:24842179

  3. Use of anatomic measurement to guide injection of botulinum toxin for the management of chronic lateral epicondylitis: a randomized controlled trial

    PubMed Central

    Espandar, Ramin; Heidari, Pedram; Rasouli, Mohammad Reza; Saadat, Soheil; Farzan, Mahmood; Rostami, Mohsen; Yazdanian, Shideh; Mortazavi, S.M. Javad

    2010-01-01

    Background When using botulinum toxin for the management of lateral epicondylitis, injection at a fixed distance from an anatomic landmark could result in inadequate paralysis of the intended muscle. We assessed the effectiveness of injection of botulinum toxin using precise anatomic measurement in individual patients. Methods In this randomized placebo-controlled trial, 48 patients with chronic refractory lateral epicondylitis were randomly assigned to receive a single injection of either botulinum toxin (60 units) or placebo (normal saline). The site of injection was chosen as a distance one-third the length of the forearm from the tip of the lateral epicondyle on the course of the posterior interosseus nerve. The primary outcome measure was intensity of pain at rest, measured with the use of a 100-mm visual analogue scale, at baseline and at 4, 8 and 16 weeks after injection. Results Compared with the placebo group, the group given botulinum toxin had significant reductions in pain at rest during follow-up (decrease at 4 weeks 14.1 mm, 95% confidence interval [CI] 5.8–22.3; at 8 weeks 11.5 mm, 95% CI 2.0–21.0; at 16 weeks 12.6 mm, 95% CI 7.7–17.8; p = 0.01). As for the secondary outcomes, the intensity of pain during maximum pinch decreased in the botulinum toxin group; there was no difference in pain during maximum grip or in grip strength between the two groups. All but one of the patients in the intervention group experienced weakness in the extension of the third and fourth fingers at week 4 that resolved by week 16. No serious adverse events were reported. Interpretation The use of precise anatomic measurement to guide injection of botulinum toxin significantly reduced pain at rest in patients with chronic refractory lateral epicondylitis. However, the transient extensor lag makes this method inappropriate for patients whose job requires finger extension. (ClinicalTrials.gov trial register no. NCT00497913.) PMID:20421357

  4. Use of enzyme-linked immunoassays for antibody to types C and D botulinum toxins for investigations of botulism in cattle.

    PubMed

    Gregory, A R; Ellis, T M; Jubb, T F; Nickels, R J; Cousins, D V

    1996-02-01

    The development of specific enzyme-linked immunosorbent assays (ELISA) for antibody to types C and D Clostridium botulinum toxins for investigation of botulism in cattle is described. Partially purified type C and D toxins were used as antigens to develop these ELISAs. Specificity of the ELISAs was evaluated on sera from 333 adult beef and dairy cattle from areas with no history or evidence of botulism in animals or water birds. The test was also evaluated on sera from 41 herds that included herds vaccinated against botulism, confirmed botulism cases and herds from areas where the disease is considered endemic. The ELISAs detected the presence of antibody to botulinum toxins in samples from vaccinated cattle and both convalescent and clinically normal animals from unvaccinated herds with outbreaks of botulism. Antibody was also found in unvaccinated animals from herds in which there had been no diagnosed botulism cases in areas where botulism was considered endemic. Sera from some unvaccinated cattle with high ELISA reactivity was shown to be protective for mice in botulinum toxin neutralisation tests. The use of these tests in investigations of botulism in cattle is discussed.

  5. Growth and toxin production by Clostridium botulinum in steamed rice aseptically packed under modified atmosphere.

    PubMed

    Kasai, Yoshiaki; Kimura, Bon; Kawasaki, Susumu; Fukaya, Tetsuya; Sakuma, Kinya; Fujii, Tateo

    2005-05-01

    Sales and consumption of ready-to-eat aseptic steamed rice products have increased manyfold in Japan over the past 10 years. To determine the safety of steamed rice (water content 60%, pH 6.5) aseptically packaged under modified atmosphere, challenge studies were performed using a mixture of Clostridium botulinum proteolytic strains (five strains of type A and five strains of type B). Atmospheric conditions of 0 and 15% oxygen (with 5% CO2 and 5% N2 as the balance) were used. No neurotoxins were detected, and organoleptically acceptable conditions persisted for 24 weeks at 15% oxygen conditions. However, botulinum neurotoxin was found in one of three samples at 12 weeks and in one of two samples at 24 weeks at 0% oxygen and 30 degrees C. When samples were inoculated with C. botulinum with amylase (0% oxygen), neurotoxin and sample spoilage was detected after only 1 week of storage. Challenge studies using proteolytic strains of C. botulinum mixed with Bacillus subtilis (amylase formers) also were performed with atmosphere conditions of oxygen at 0, 5, 10, and 15% (with 5% CO2 and 5% N2 as the balance). Under 10 and 15% oxygen conditions, neurotoxin was not detected after 1 week of storage, but sample spoilage was detected after the same period. Under 0% oxygen conditions, neurotoxin was detected at 1 week, but the sample remained organoleptically acceptable even after 2 weeks of storage. Both neurotoxin and sample spoilage were detected at 1 week of storage under 5% oxygen conditions. Based on these results, cocontamination of amylase-producing Bacillus with C. botulinum would increase the risk of foodborne botulism when aseptic rice samples are packed under low-oxygen conditions (<5%). Therefore, to ensure the safety of these products, packing under atmospheric containing more than 10% oxygen is recommended.

  6. Expression, purification and development of neutralizing antibodies from synthetic BoNT/B LC and its application in detection of botulinum toxin serotype B.

    PubMed

    Ponmariappan, S; Jain, Swati; Sijoria, Richa; Tomar, Arvind; Kumar, Om

    2012-03-01

    Botulism is a neuroparalytic disease caused by Clostridium botulinum, which produces seven (A-G) neurotoxins (BoNTs). The mouse bioassay is the gold standard for the detection of botulinum neurotoxins, however it requires at least 3-4 days for completion. Most of the studies were carried out in botulinum toxin A and less on type B. Attempts have been made to develop an ELISA based detection system, which is potentially an easier and more rapid method of botulinum neurotoxin detection. In the present study, the synthetic BoNT/B LC gene was constructed using PCR overlapping primers, cloned in a pET28a+ vector and expressed in E. coli BL21DE3. The maximum yield of recombinant proteins was optimized after 16 hrs of post induction at 21°C and purified the recombinant protein in soluble form. Antibodies were raised in Mice and Rabbit. The IgG antibody titer in the case of Mice was 1: 1,024,000 and Rabbit was 1: 512,000 with alum as adjuvant via intramascular route. The biological activity of the recombinant protein was confirmed by in-vitro studies using PC12 cells by the synaptobrevin cleavage, the rBoNT/B LC protein showed the maximum blockage of acetylcholine release at a concentration of 150nM rBoNT/B LC in comparison to the control cells. When the cells were incubated with rBoNT/B LC neutralized by the antisera raised against it, the acetylcholine release was equivalent to the control. IgG specific to rBoNT/B LC was purified from raised antibodies. The results showed that the developed antibody against rBoNT/B LC protein were able to detect botulinum toxin type B approximately up to 1 ng/ml. These developed high titer antibodies may prove useful for the detection of botulinum neurotoxins in food and clinical samples.

  7. Molecular characterization of binding subcomponents of Clostridium botulinum type C progenitor toxin for intestinal epithelial cells and erythrocytes.

    PubMed

    Fujinaga, Yukako; Inoue, Kaoru; Watarai, Shinobu; Sakaguchi, Yoshihiko; Arimitsu, Hideyuki; Lee, Jae-Chul; Jin, Yingji; Matsumura, Takuhiro; Kabumoto, Yuko; Watanabe, Toshihiro; Ohyama, Tohru; Nishikawa, Atsushi; Oguma, Keiji

    2004-05-01

    Clostridium botulinum type C 16S progenitor toxin consists of a neurotoxin (NTX), a non-toxic non-HA (NTNH), and a haemagglutinin (HA). The HA acts as an adhesin, allowing the 16S toxin to bind to intestinal epithelial cells and erythrocytes. In type C, these bindings are dependent on sialic acid. The HA consists of four distinct subcomponents designated HA1, HA2, HA3a and HA3b. To identify the binding subcomponent(s) of HA of type C 16S toxin, all of the HA-subcomponents and some of their precursor forms were produced as recombinant proteins fused to glutathione S-transferase (GST). These proteins were evaluated for their capacity to adhere to intestinal epithelial cells of guinea pig and human erythrocytes. GST-HA1, GST-HA3b and GST-HA3 (a precursor form of HA3a and HA3b) bound intestinal epithelial cells and erythrocytes, whereas GST alone, GST-HA2 and GST-HA3a did not. GST-HA3b and GST-HA3 showed neuraminidase-sensitive binding to the intestinal epithelial cells and erythrocytes, whereas GST-HA1 showed neuraminidase-insensitive binding. TLC binding assay revealed that GST-HA3b and GST-HA3 recognized sialosylparagloboside (SPG) and GM3 in the ganglioside fraction of the erythrocytes, like native type C 16S toxin [Inoue, K. et al. (1999). Microbiology 145, 2533-2542]. On the other hand, GST-HA1 recognized paragloboside (PG; an asialo- derivative of SPG) in addition to SPG and GM3. Deletion mutant analyses of GST-HA3b showed that the C-terminal region of HA3b is important for its binding activity. Based on these data, it is concluded that the HA component contains two distinct carbohydrate-binding subcomponents, HA1 and HA3b, which recognize carbohydrates in different specificities.

  8. Bacteria associated with processed crawfish and potential toxin production by Clostridium botulinum type E in vacuum-packaged and aerobically packaged crawfish tails.

    PubMed

    Lyon, W J; Reddmann, C S

    2000-12-01

    Refrigerated vacuum-packaged storage has been shown to increase significantly the shelf life of fresh fish and seafood products, but the effect, if any, on the outgrowth and toxin production of Clostridium botulinum type E on cooked crawfish is unknown. Microflora associated with live crawfish reflect the microbial populations of the harvest water and sediments in which they are living. The presence or absence of specific pathogens in either vacuum-packaged or air-permeable bags of cooked crawfish have not been thoroughly evaluated. This study evaluates the potential survival and outgrowth of biological hazards in both vacuum-packaged and air-permeable-packaged cooked crawfish held at 4 and 10 degrees C for 30 days. During shelf-life studies of vacuum-packaged and air-permeable-bagged cooked crawfish, a total of 31 bacterial species were isolated and identified from crawfish samples using both selective and nonselective media. The only pathogens isolated from both vacuum-packed and air-permeable bags of processed crawfish samples during shelf-life studies were strains of Aeromonas hydrophila and Staphylococcus aureus. C. botulinum type E and Clostridium perfringens species were not isolated from any of the uninoculated crawfish samples. Cooked crawfish were inoculated with 10(3) C. botulinum type E spores per g of crawfish tail meat to determine whether cooked crawfish tails would support the growth of C. botulinum type E strains and produce toxin at refrigerated temperatures. Spore-inoculated crawfish tails were vacuum packaged in both a high barrier film and an air-permeable bag and stored at 4 degrees C and 10 degrees C for 30 days. C. botulinum toxin E was not detected in any of the spore-inoculated packages throughout the shelf-life study until day 30. Microbiological data from this study should be useful in the development and implementation of the hazard analysis and critical control point plans for processed crawfish tails.

  9. Crystal Structure of Botulinum Neurotoxin Type a in Complex With the Cell Surface Co-Receptor GT1b-Insight Into the Toxin-Neuron Interaction

    SciTech Connect

    Stenmark, P.; Dupuy, J.; Inamura, A.; Kiso, M.; Stevens, R.C.

    2009-05-26

    Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.

  10. The Design and Synthesis of Orally Active Inhibitors of Botulinum Toxin Metalloproteases

    DTIC Science & Technology

    1997-06-01

    succeeded in demonstrating the feasibility of our approach to the design of botulinum inhibitors based on using the weak activity of captopril as a lead...compound. We report the first prototype compounds that exceed our captopril lead compound by at least an order of magnitude in inhibitory properties...Develop solution chemical methods for synthesizing analogs of captopril in a combinatorial chemical approach 4. Extend the solution methods developed in

  11. Nanopore sensing of botulinum toxin type B by discriminating an enzymatically cleaved Peptide from a synaptic protein synaptobrevin 2 derivative.

    PubMed

    Wang, Yong; Montana, Vedrana; Grubišić, Vladimir; Stout, Randy F; Parpura, Vladimir; Gu, Li-Qun

    2015-01-14

    Botulinum neurotoxins (BoNTs) are the most lethal toxin known to human. Biodefense requires early and rapid detection of BoNTs. Traditionally, BoNTs can be detected by looking for signs of botulism in mice that receive an injection of human material, serum or stool. While the living animal assay remains the most sensitive approach, it is costly, slow and associated with legal and ethical constrains. Various biochemical, optical and mechanical methods have been developed for BoNTs detection with improved speed, but with lesser sensitivity. Here, we report a novel nanopore-based BoNT type B (BoNT-B) sensor that monitors the toxin's enzymatic activity on its substrate, a recombinant synaptic protein synaptobrevin 2 derivative. By analyzing the modulation of the pore current caused by the specific BoNT-B-digested peptide as a marker, the presence of BoNT-B at a subnanomolar concentration was identified within minutes. The nanopore detector would fill the niche for a much needed rapid and highly sensitive detection of neurotoxins, and provide an excellent system to explore biophysical mechanisms for biopolymer transportation.

  12. Botulinum toxin type A targets RhoB to inhibit lysophosphatidic acid-stimulated actin reorganization and acetylcholine release in nerve growth factor-treated PC12 cells.

    PubMed

    Ishida, Hiroshi; Zhang, Xieping; Erickson, Kelly; Ray, Prabhati

    2004-09-01

    Botulinum toxin type A (BoNT/A) produced by Clostridium botulinum inhibits Ca2+-dependent acetylcholine (ACh) release (neuroexocytosis) at peripheral neuromuscular junctions, sometimes causing neuromuscular paralysis. This inhibitory effect is attributed to its metalloprotease activity to cleave the 25-kDa synaptosomal-associated protein, which is essential for the exocytotic machinery. However, deletion of this protein does not result in a complete block of neuroexocytosis, suggesting that botulinum-mediated inhibition may occur via another mechanism. Rho GTPases, a class of small GTP-binding proteins (G proteins), control actin cytoskeletal organization, thereby regulating a variety of cellular functions in various cells, including neuronal cells. We have shown that the G protein activator lysophosphatidic acid (LPA) triggered actin reorganization followed by Ca2+-dependent ACh release in nerve growth factor-treated PC12 cells and that BoNT/A blocked both events through degradation of RhoB by the proteasome. Overexpression of wild-type RhoB caused actin reorganization and enhanced the release of ACh by LPA to overcome toxin's inhibitory effect on actin reorganization/exocytosis stimulated by LPA, whereas overexpression of a dominant negative RhoB inhibited ACh release, regardless of LPA and/or toxin treatment. Finally, a knockdown of the RhoB gene via sequence-specific, post-transcriptional gene silencing reduced RhoB expression in PC12 cells, resulting in total inhibition of both actin reorganization and ACh release induced by LPA. We conclude that the RhoB signaling pathway regulates ACh release via actin cytoskeletal reorganization and that botulinum toxin inhibits neuroexocytosis by targeting RhoB pathway.

  13. Strategy for treating motor neuron diseases using a fusion protein of botulinum toxin binding domain and streptavidin for viral vector access: work in progress.

    PubMed

    Drachman, Daniel B; Adams, Robert N; Balasubramanian, Uma; Lu, Yang

    2010-12-01

    Although advances in understanding of the pathogenesis of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) have suggested attractive treatment strategies, delivery of agents to motor neurons embedded within the spinal cord is problematic. We have designed a strategy based on the specificity of botulinum toxin, to direct entry of viral vectors carrying candidate therapeutic genes into motor neurons. We have engineered and expressed fusion proteins consisting of the binding domain of botulinum toxin type A fused to streptavidin (SAv). This fusion protein will direct biotinylated viral vectors carrying therapeutic genes into motor nerve terminals where they can enter the acidified endosomal compartments, be released and undergo retrograde transport, to deliver the genes to motor neurons. Both ends of the fusion proteins are shown to be functionally intact. The binding domain end binds to mammalian nerve terminals at neuromuscular junctions, ganglioside GT1b (a target of botulinum toxin), and a variety of neuronal cells including primary chick embryo motor neurons, N2A neuroblastoma cells, NG108-15 cells, but not to NG CR72 cells, which lack complex gangliosides. The streptavidin end binds to biotin, and to a biotinylated Alexa 488 fluorescent tag. Further studies are in progress to evaluate the delivery of genes to motor neurons in vivo, by the use of biotinylated viral vectors.

  14. Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

    PubMed

    Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

    2013-01-01

    Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

  15. Biological activity of two botulinum toxin type A complexes (Dysport and Botox) in volunteers: a double-blind, randomized, dose-ranging study.

    PubMed

    Wohlfarth, K; Schwandt, I; Wegner, F; Jürgens, T; Gelbrich, G; Wagner, A; Bogdahn, U; Schulte-Mattler, W

    2008-12-01

    Despite extensive clinical experience and published data regarding botulinum toxin, questions remain about the clinical substitution of one botulinum toxin formulation for another. In the case of Dysport and Botox, dose-equivalence ratios ranging from 1:1 to 6:1 (Dysport:Botox) have been advocated. This dose-ranging, electroneurographic study investigated the dose equivalence, diffusion characteristics (spread) and safety of these two type-A toxins in 79 volunteers. Dysport and Botox caused significant and similar reductions in compound muscle action potential (CMAP) amplitude in the target muscle (extensor digitorum brevis, EDB) 2 weeks after injection, with effects persisting to the 12-week timepoint. For both products, the reduction in amplitude was increased with increasing doses and with increasing concentration. The effects of toxin on neighbouring muscles were much smaller and of a shorter duration than those on the target muscle, implying a modest spread of toxin. Unlike the target muscle, the effects were greater with the higher volume, suggesting this volume led to greater diffusion from the EDB. No adverse events were reported. Statistical modelling with CMAP amplitude data from the target muscle gave a bioequivalence of 1.57 units of Dysport:1 unit of Botox (95 % CI: 0.77-3.20 units). The data indicate that a dose-equivalence ratio of 3:1 was within the statistical error limits, but ratios over 3:1 are too high.

  16. GaAs laser treatment of bilateral eyelid ptosis due to complication of botulinum toxin type A injection.

    PubMed

    Majlesi, Gholamreza

    2008-10-01

    The widespread use of botulinum toxin type A (BTX-A) for aesthetic procedures in recent years has brought about some unwanted side effects that, though they are self-limited, cause inconvenience for patients. Injection of this paralytic toxin inactivates target muscle(s) for many months and unwanted facial movements will thus be prevented. Spreading of the toxin beyond the target muscles sometimes involves muscles necessary for other facial movements, such as the levator palpebrae, inactivation of which causes upper eyelid ptosis. Mild cases resolve after 2-3 wk, but in severe cases the complication may last as long as the cosmetic results persist (3-4 mo), and until now there has been no medical intervention to accelerate healing. In an effort to achieve more rapid recovery from eyelid ptosis due to overdose of BTX-A in the glabella, laser therapy was used in a 46-year-old woman with bilateral eyelid ptosis (partial on the right side and complete on the left) 12 d after injection. A GaAs laser was used and the protocol consisted of irradiation of three points on the upper lid just above the levator, and one point on the corrugator muscle on each side in contact mode, with three sessions per week (wavelength 890 nm, peak power 94 W, output power 28 mW, pulse duration 200 ns, spot size 3 mm, pulse repetition rate 3000 Hz, duration of irradiation 40 sec per point, energy per point 1.1 J, total energy per session 8.8 J, dose 16 J/cm2). The result was complete recovery from ptosis after 10 sessions, but the cosmetic results persisted for several months. It appears that if this procedure has similar results in other case series, it will be an effective therapeutic option to treat this complication.

  17. Botulinum toxin type A selectivity for certain types of pain is associated with capsaicin-sensitive neurons.

    PubMed

    Matak, Ivica; Rossetto, Ornella; Lacković, Zdravko

    2014-08-01

    Unlike most classical analgesics, botulinum toxin type A (BoNT/A) does not alter acute nociceptive thresholds, and shows selectivity primarily for allodynic and hyperalgesic responses in certain pain conditions. We hypothesized that this phenomenon might be explained by characterizing the sensory neurons targeted by BoNT/A in the central nervous system after its axonal transport. BoNT/A's central antinociceptive activity following its application into the rat whisker pad was examined in trigeminal nucleus caudalis (TNC) and higher-level nociceptive brain areas using BoNT/A-cleaved synaptosomal-associated protein 25 (SNAP-25) and c-Fos immunohistochemistry. Occurrence of cleaved SNAP-25 in TNC was examined after nonselective ganglion ablation with formalin or selective denervation of capsaicin-sensitive (vanilloid receptor-1 or TRPV1-expressing) neurons, and in relation to different cellular and neuronal markers. Regional c-Fos activation and effect of TRPV1-expressing afferent denervation on toxin's antinociceptive action were studied in formalin-induced orofacial pain. BoNT/A-cleaved SNAP-25 was observed in TNC, but not in higher-level nociceptive nuclei. Cleaved SNAP-25 in TNC disappeared after formalin-induced trigeminal ganglion ablation or capsaicin-induced sensory denervation. Occurrence of cleaved SNAP-25 in TNC and BoNT/A antinociceptive activity in formalin-induced orofacial pain were prevented by denervation with capsaicin. Cleaved SNAP-25 localization demonstrated toxin's presynaptic activity in TRPV1-expressing neurons. BoNT/A reduced the c-Fos activation in TNC, locus coeruleus, and periaqueductal gray. Present experiments suggest that BoNT/A alters the nociceptive transmission at the central synapse of primary afferents. Targeting of TRPV1-expressing neurons might be associated with observed selectivity of BoNT/A action only in certain types of pain.

  18. Botulinum toxin in the management of chronic migraine: clinical evidence and experience

    PubMed Central

    Escher, Claus M; Paracka, Lejla; Dressler, Dirk; Kollewe, Katja

    2016-01-01

    Chronic migraine (CM) is a severely disabling neurological condition characterized by episodes of pulsating unilateral or bilateral headache. The United States Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox®) for the prophylactic treatment of CM in 2010. It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM. Treatment is well tolerated by the patients. This review reports on the history of botulinum neurotoxin (BoNT) in CM and presents the current clinical evidence for the use of onabotulinumtoxinA in the treatment of CM. PMID:28382110

  19. Global Aesthetics Consensus: Hyaluronic Acid Fillers and Botulinum Toxin Type A—Recommendations for Combined Treatment and Optimizing Outcomes in Diverse Patient Populations

    PubMed Central

    Liew, Steven; Signorini, Massimo; Vieira Braz, André; Fagien, Steven; Swift, Arthur; De Boulle, Koenraad L.; Raspaldo, Hervé; Trindade de Almeida, Ada R.; Monheit, Gary

    2016-01-01

    Background: Combination of fillers and botulinum toxin for aesthetic applications is increasingly popular. Patient demographics continue to diversify, and include an expanding population receiving maintenance treatments over decades. Methods: A multinational panel of plastic surgeons and dermatologists convened the Global Aesthetics Consensus Group to develop updated guidelines with a worldwide perspective for hyaluronic acid fillers and botulinum toxin. This publication considers strategies for combined treatments, and how patient diversity influences treatment planning and outcomes. Results: Global Aesthetics Consensus Group recommendations reflect increased use of combined treatments in the lower and upper face, and some midface regions. A fully patient-tailored approach considers physiologic and chronologic age, ethnically associated facial morphotypes, and aesthetic ideals based on sex and culture. Lower toxin dosing, to modulate rather than paralyze muscles, is indicated where volume deficits influence muscular activity. Combination of toxin with fillers is appropriate for several indications addressed previously with toxin alone. New scientific data regarding hyaluronic acid fillers foster an evidence-based approach to selection of products and injection techniques. Focus on aesthetic units, rather than isolated rhytides, optimizes results from toxin and fillers. It also informs longitudinal treatment planning, and analysis of toxin nonresponders. Conclusions: The emerging objective of injectable treatment is facial harmonization rather than rejuvenation. Combined treatment is now a standard of care. Its use will increase further as we refine the concept that aspects of aging are intimately related, and that successful treatment entails identifying and addressing the primary causes of each. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID:27119917

  20. Persistence of Clostridium botulinum type C toxin in blow fly (Calliphoridae) larvae as a possible cause of avian botulism in spring.

    PubMed

    Hubálek, Z; Halouzka, J

    1991-01-01

    Diverse samples were examined at a site of water-bird mortality, caused by Clostridium botulinum type C toxin in southern Moravia (Czechoslovakia). The toxin was detected in high concentrations in mute swan (Cygnus olor) carcasses (less than or equal to 1 x 10(6) LD50/g) as well as in necrophagous larvae and pupae of the blow flies Lucilia sericata and Calliphora vomitoria (less than or equal to 1 x 10(5) LD50/g) collected from them. It was detected in lower concentrations (less than or equal to 1 x 10(3) LD50/g) in other invertebrates (ptychopterid fly larvae, leeches, sow-bugs) associated with these carcasses, and occasionally in water samples (8 LD50/ml) close to the carrion. The toxin was not detected in the samples of water, mud or invertebrates collected at a distance greater than or equal to 5 m from the carcasses. The toxin-bearing larvae of L. sericata and C. vomitoria, containing 80,000 LD50/g of type C toxin, were exposed in the mud at the study site for 131 days from November to March. Although the toxin activity decreased 25-fold and 40-fold in the two samples of maggots exposed during this period, it remained very high (less than or equal to 3,200 LD50/g). Birds ingesting a relatively low number of these toxic larvae (or pupae) in the spring could receive a lethal dose of the toxin.

  1. Effectiveness of botulinum toxin type A treatment of neck pain related to nocturnal bruxism: a case report

    PubMed Central

    Santamato, Andrea; Panza, Francesco; Di Venere, Daniela; Solfrizzi, Vincenzo; Frisardi, Vincenza; Ranieri, Maurizio; Fiore, Pietro

    2010-01-01

    Objective This case report describes a patient with nocturnal bruxism and related neck pain treated with botulinum toxin type A (BTX-A). Clinical Features The patient was a 27-year-old man with nocturnal bruxism and difficulty in active mouth opening and chewing and neck pain at rest. His numeric pain score was 7 of 10. Surface electromyography of the temporalis and masseter muscles showed typical signs of hyperactivity, characterized by compound muscle action potential amplitude alterations. Intervention and Outcome After clinical evaluation, he was treated with BTX-A to reduce masseter and temporalis muscle hyperactivity. After 3 days of treatment with BTX-A, with each masseter muscle injected with a dose of about 40 mouse units with a dilution of 1 mL and with temporal muscle bilaterally injected with 25 mouse units with the same dilution, a decrease in bruxism symptoms was reported. Neck pain also decreased after the first treatment (visual analog scale of 2/10) and then resolved completely. After 4 weeks, electromyography showed the reduction of muscle hyperactivity with a decrease in the amplitude of the motor action potential. The same reduction in signs and symptoms was still present at assessment 3 months posttreatment. Conclusion These findings suggest that BTX-A may be a therapeutic option for the treatment of bruxism and related disorders. PMID:22027036

  2. Comparing the Effect of Botulinum Toxin Type B Injection at Different Dosages for Patient with Drooling due to Brain Lesion

    PubMed Central

    Park, Hee Dong; Park, Sang Jun; Choi, Yong Min

    2012-01-01

    Objective To investigate Botulinum toxin type B (BNT-B) injection's effect and duration depending on dose for patients with brain lesion. Method Twenty one patients with brain lesion and severe drooling were included and divided into three groups. All patients received conventional dysphagia therapy. Group A patients (n=7) received an injection of 1,500 units and group B patients (n=7) received an injection of 2,500 units of BNT-B in submandibular gland under ultrasound guidance. Group C patients (n=7) received conventional dysphagia therapy. Saliva secretion was assessed quantitatively at baseline and at weeks 1, 2, 4, 8, and 12. The severity and frequency of drooling was assessed using the Drooling Quotient (DQ) by patients and/or caregivers. Results Group A and B reported a distinct improvement of the symptoms within 2 weeks after BNT-B injection. Compared to the baseline, the mean amount of saliva decreased significantly throughout the study. However, there was no meaningful difference between the two groups. The greatest reductions were achieved at 2 weeks and lasted up to 8 weeks after BNT-B injection. Group C did not show any differences. Conclusion Local injection of 1,500 units of BNT-B into salivary glands under ultrasonic guidance proved to be a safe and effective dose for drooling in patient with brain lesion, as did 2,500 units. PMID:23342318

  3. Sleep bruxism possibly triggered by multiple sclerosis attacks and treated successfully with botulinum toxin: Report of three cases.

    PubMed

    Sevim, Serhan; Kaleağası, Hakan; Fidancı, Halit

    2015-09-01

    Sleep bruxism refers to a nocturnal parafunctional activity including the clenching, grinding or gnashing of teeth. While most of the nocturnal bruxism cases seen in the general population are apparently idiopathic, it has been reported to be associated with a range of neurological diseases such as Huntington's disease, cranio-cervical dystonia and post-anoxic brain damage, but not multiple sclerosis (MS). We describe three cases of MS patients who have had moderate to severe complaints of bruxism in the two weeks following their relevant MS attacks. None of the three patients had a diagnosis of bruxism prior to her attack. The diagnosis was confirmed in one out of three by a polysomnography. One patient did not have any complaints related to bruxism previous to her attack, whereas two had mild and infrequent complaints. The symptoms of the relevant attacks were left hemihypesthesia in all and hemiparesis in two. None of the patients had spasticity that could result in severe teeth clenching. All three patients presented with morning headaches and jaw pain or tightness and were treated successfully with botulinum toxin (Btx) injections applied to their masseter and temporalis muscles. The cause of bruxism is controversial but lesions of the cortico-basalganglia-thalamo-cotrical loops are thought to be most likely. However, acute or chronic lesions in those pathways were not demonstrated in the 3 patients. It is feasible that they had normal appearing white matter interruptions in their cortico-basalganglia-thalamocortical loops along with their relevant attack.

  4. Nanopore Sensing of Botulinum Toxin Type B by Discriminating an Enzymatically Cleaved Peptide from a Synaptic Protein Synaptobrevin 2 Derivative

    PubMed Central

    2015-01-01

    Botulinum neurotoxins (BoNTs) are the most lethal toxin known to human. Biodefense requires early and rapid detection of BoNTs. Traditionally, BoNTs can be detected by looking for signs of botulism in mice that receive an injection of human material, serum or stool. While the living animal assay remains the most sensitive approach, it is costly, slow and associated with legal and ethical constrains. Various biochemical, optical and mechanical methods have been developed for BoNTs detection with improved speed, but with lesser sensitivity. Here, we report a novel nanopore-based BoNT type B (BoNT-B) sensor that monitors the toxin’s enzymatic activity on its substrate, a recombinant synaptic protein synaptobrevin 2 derivative. By analyzing the modulation of the pore current caused by the specific BoNT-B-digested peptide as a marker, the presence of BoNT-B at a subnanomolar concentration was identified within minutes. The nanopore detector would fill the niche for a much needed rapid and highly sensitive detection of neurotoxins, and provide an excellent system to explore biophysical mechanisms for biopolymer transportation. PMID:25511125

  5. Polyclonal neural cell adhesion molecule antibody prolongs the effective duration time of botulinum toxin in decreasing muscle strength.

    PubMed

    Guo, Yan; Pan, Lizhen; Liu, Wuchao; Pan, Yougui; Nie, Zhiyu; Jin, Lingjing

    2015-11-01

    This study aimed to investigate if the effective duration time of botulinum toxin A (Btx-A) could be prolonged by polyclonal neural cell adhesion molecule antibody (P-NCAM-Ab). 175 male SD rats were randomly divided into three major groups: control group (n = 25), Btx-A group (n = 25), and P-NCAM-Ab groups. P-NCAM-Ab groups were composed of five sub-groups, with 25 rats each in the dose-response study. Muscle strength of rat lower limbs was determined using a survey system. The expressions of muscle-specific receptor tyrosine kinase (MuSK) and neural cell adhesion molecule (NCAM) were determined by real-time polymerase chain reactions (RT-PCR) and western blotting (WB). The muscle strength was significantly decreased by Btx-A in Btx-A/P-NCAM-Ab groups compared with normal control group. Besides, the muscle strength of P-NCAM-Ab group was significantly decreased compared with the Btx-A group. The recovery time of muscle strength in P-NCAM-Ab group was significantly longer compared with Btx-A group. RT-PCR and WB assay showed that PNCAM-Ab delayed the increase of MuSK and NCAM after Btx-A injection. P-NCAM-Ab prolongs the effective duration time of Btx-A in decreasing muscle strength, which could provide a novel enhancement in clinical application.

  6. [Early pharmacologic treatment with botulinum toxin A in post-stroke spasticity: consensus evidence-based recommendations].

    PubMed

    Lopez de Munain, L; Juan-Garcia, F J; Duarte, E; Martin-Mourelle, R; Rodriguez, S; Moraleda-Perez, S

    2016-10-16

    Spasticity is a common complication that occurs in those patients that have suffered a stroke. To identify those patients at high risk of having post-stroke spasticity and to start treatment at early stages would probably benefit the patient. The key aspects in the early management of post-stroke spasticity were review and the clinical implications and strength of evidences were also considered. The document drafted by the study coordinators was subsequently reviewed and then a validated document was developed. The experts recommend defining early treatment of spasticity as one that begins before the first three months after stroke. The panel considers very important to identify the risk factors associated with the onset of spasticity, since this might reduce its impact. Additionally, the most common conditions subsidiaries of early treatment of both upper and lower limb are defined. The panel recommends that the treatment with botulinum toxin A must only be given by specialists with experience in diagnosis and management of spasticity. In conclusion, the treatment of focal spasticity in the first three months after stroke is indicated in certain situations. These recommendations help to standardize the early management of post-stroke spasticity, with the consequent support to clinicians and patients.

  7. A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients.

    PubMed Central

    Burbaud, P; Wiart, L; Dubos, J L; Gaujard, E; Debelleix, X; Joseph, P A; Mazaux, J M; Bioulac, B; Barat, M; Lagueny, A

    1996-01-01

    OBJECTIVE: To confirm the apparent effectiveness of botulinum toxin (BTX) in hemiparetic patients with ankle plantar flexors and foot invertor spasticity. METHODS: Twenty three hemiparetic patients with spasticity of the ankle plantar flexors and foot invertors were included in a randomised double blind, placebo controlled study with BTX. Patients were examined on days 0, 30, 90, and 120 and received one injection of BTX and one of placebo in a random order at day 0 and day 90. RESULTS: Patients reported a clear subjective improvement in foot spasticity after BTX (P = 0.0014) but not after placebo. Significant changes were noted in Ashworth scale values for ankle extensors (P < 0.0001) and invertors (P = 0.0002), and for active ankle dorsiflexion (P = 0.0001). Gait velocity was slightly but not significantly (P = 0.0731) improved after BTX injections. The severity of spasticity did not modify treatment efficacy, but BTX was less effective in patients with longer duration of spasticity (P = 0.0081). CONCLUSION: The efficacy of BTX injections in the treatment of spastic foot suggests that BTX may be particularly useful during the first year after a stroke. PMID:8795597

  8. An Experimental Study on Botulinum Toxin Type A for the Treatment of Excessive Secretion after Submandibular Gland Transplantation in Rabbits

    PubMed Central

    Lin, Bo; Wang, Kan

    2016-01-01

    Objectives. To investigate whether botulinum toxin type A (BTXA) could control excessive secretion after submandibular gland (SMG) transplantation in rabbits and its possible mechanisms. Methods. A new SMG transplantation model was established in rabbit. 30 successfully constructed models were randomly assigned to five groups including control group and four experimental groups. Secretion outputs were used to analyze the effect of BTXA injection on excessive secretion. Hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), Western blot, and immunofluorescence were performed to analyze its possible mechanisms. Results. After BTXA injection, a significant decrease of excessive secretion after SMG transplantation was found in 2 and 4 weeks groups, but no significant effect on 12 and 24 weeks groups. HE and TEM results showed that BTXA led to morphological and ultrastructural changes of acinar cells of transplanted SMG. Western blot results suggested that BTXA decreased the aquaporin-5 (AQP5) protein expression after BTXA injection for 2 and 4 weeks. Immunofluorescence results showed that AQP5 protein was mainly expressed in the cytoplasm after BTXA injection for 2 and 4 weeks, which might indicate that BTXA promoted AQP5 expression from the cell membrane to cytoplasm. Conclusion. BTXA could effectively control excessive secretion after SMG transplantation in rabbits. PMID:27840738

  9. Efficacy and safety of botulinum toxin type A for treatment of Frey's syndrome: evidence from 22 published articles.

    PubMed

    Xie, Shang; Wang, Kan; Xu, Tao; Guo, Xue-Sheng; Shan, Xiao-Feng; Cai, Zhi-Gang

    2015-11-01

    Frey's syndrome (FS) is an unavoidable sequela following the surgery of the parotid gland. Although several treatment methods are available, their efficacy is short term or accompanied by unacceptable complications. In the past two decades, botulinum toxin type A (BTXA) has been widely used to treat FS. Although several systematic reviews have been reported recently, they were conflicting and with obvious deficiencies. Thus, we performed an objectively systematic review to determine whether BTXA is an effective and safe treatment for FS. A literature retrieval covering PubMed, Web of Science, Ovid, Embase and Cochrane library was performed on 16 January, 2015. Proportion meta-analysis and corresponding 95% confidence interval (CI) were performed to evaluate the efficacy and safety of BXTA in treatment of FS. A total of 499 records were retrieved and 22 articles with 23 studies were included after scrutiny by two independent authors. Statistical analyses regarding the effective rate, incidence of complications were used to estimate the efficacy and safety of BTXA. Our results suggested that the effective rate of BTXA for treatment of FS is 98.5% (95% CI = 0.971-0.994) and the incidence of complication is 3.6% (95% CI = 0.017-0.061). In conclusion, our study supports that BTXA produces meaningful benefits on the treatment of patients with FS. However, owing to lack of strong evidence, future studies with well-designed inclusion criteria and multicenter randomized controlled trials are needed to give more credible evidence, if possible.

  10. Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects.

    PubMed

    Rath, Judith J G; Tavy, Dénes L J; Wertenbroek, Agnes A A C M; van Woerkom, Theodoor C A M; de Bruijn, Sebastiaan F T M

    2010-08-01

    To determine the short-term and long-term treatment-effects of botulinum toxin type A in simple motor tics, we analyzed 15 consecutive patients (18 tics) with simple motor tics that were treated every 3 months with injections of BTX-A. Efficacy (rated on a 4-level scale) and duration of effect of the first 2 and last 2 (if treated 5 times or more) treatments were recorded, as well as latency of response, changes of premonitory urges (PMUs) and possible side effects. Total number of treatments for each tic varied from 2 to 50 (mean 11, median 6). In 16 of 18 tics (89%) short-term efficacy was reported successful (good or moderate). Long-term efficacy was reported in 12 tics of which 11 showed similar or even increased beneficial effects. Premonitory urge (PMU) was reported in 8 patients (53%). PMU, if present, lessened or disappeared after treatment with BTX-A. A permanent remission of the treated tic was seen in 3 patients with a maximum follow-up of 10 years. BTX-A appears a safe and effective treatment for simple motor tics and retains its efficacy after long-term treatment. BTX may also induce permanent remission of the treated tics and effects of BTX are not restricted to merely motor behaviour.

  11. Inhibitory effect of botulinum toxin type A on the NANC system in rat respiratory models of neurogenic inflammation.

    PubMed

    Chien, Chiang-Ting; Lee, Hsin-Min; Wu, Chia-Ching Josh; Li, Ping-Chia

    2012-08-15

    This study investigated whether botulinum toxin type A (BTX-A) inhibits respiratory neurogenic inflammation in the non-adrenergic, non-cholinergic (NANC) transmitter system in rats. Neurogenic inflammation models were induced in Sprague Dawley (SD) rats through bilateral cerebral artery occlusion (BCAO) for different times (0, 30 and 60 min) or by stimulation with capsaicin at different doses (5 or 15 g/kg). Pre-Bötzinger Complex-Spikes and the expression of substance P, synaptosomal-associated protein-25 (SNAP-25), and reactive oxygen species (ROS) were detected with or without pretreatment of rats with BTX-A (15 or 30 U/kg). BCAO reduced pre-Bot C spike activity (spike/s) and increased the breath rate (breaths/s) in an unstable pattern in comparison to controls, while pretreatment with BTX-A slightly reduced this phenomenon. Pretreatment with BTX-A inhibited BCAO- or capsaicin-induced increases in expression of SNAP-25, substance P, and ROS in a dose-dependent manner in brainstem and lung tissue. BTX-A exerts a suppressive effect on neurogenic inflammation via non-adrenergic, non-cholinergic transmitters. These results add to the body of evidence elucidating the non-cholinergic effects of BTX-A in the context of neurogenic inflammation.

  12. Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin.

    PubMed

    Ayyar, B Vijayalakshmi; Tajhya, Rajeev B; Beeton, Christine; Atassi, M Zouhair

    2015-10-28

    Botulinum neurotoxins (BoNTs) are the most toxic substances known. BoNT intoxicates cells in a highly programmed fashion initiated by binding to the cell surface, internalization and enzymatic cleavage of substrate, thus, inhibiting synaptic exocytosis. Over the past two decades, immunological significance of BoNT/A C-terminal heavy chain (HC) and light chain (LC) domains were investigated extensively leading to important findings. In the current work, we explored the significance of BoNT/A heavy chain N-terminal (HN) region as a vaccine candidate. Mice were immunized with recombinant HN519-845 generating antibodies (Abs) that were found to be protective against lethal dose of BoNT/A. Immuno-dominant regions of HN519-845 were identified and individually investigated for antibody response along with synthetic peptides within those regions, using in vivo protection assays against BoNT/A. Results were confirmed by patch-clamp analysis where anti-HN antibodies were studied for the ability to block toxin-induced channel formation. This data strongly indicated that HN519-593 is an important region in generating protective antibodies and should be valuable in a vaccine design. These results are the first to describe and dissect the protective activity of the BoNT/A HN domain.

  13. Physical Therapy for an Adult with Chronic Stroke after Botulinum Toxin Injection for Spasticity: A Case Report

    PubMed Central

    Phadke, Chetan P.; Ismail, Farooq; Boulias, Chris

    2015-01-01

    ABSTRACT Purpose: In this case report, we describe the type and duration of a physical therapy and botulinum toxin type A (BoNTA) intervention directed at lower limb spasticity and the gait and balance improvement in a patient post-stroke. Treatment of focal spasticity with BoNTA intramuscular injections combined with physical therapy is recommended by rehabilitation experts. However, the optimal type and duration of physical therapy intervention to optimize any functional gains that follow chemodenervation induced by BoNTA has not been established. Method: One individual with chronic stroke who received BoNTA injections for upper and lower extremity spasticity was included. Physical therapy intervention consisted of 45- to 60-min sessions twice weekly for 12 weeks, based on the Bobath–neurodevelopmental therapy approach, and an activity-based home program. Results: After BoNTA injections and physical therapy, the patient made clinically significant improvements in balance and gait speed and became more independent with his ambulation. Conclusions: This case report demonstrates that physical therapy after BoNTA injections can result in significant functional improvements for individuals with spasticity after chronic stroke that may not be possible with BoNTA injections alone. PMID:25931655

  14. Treatment of atlantoaxial rotatory fixation with botulinum toxin muscle block and manipulation.

    PubMed

    Lin, Chia-Hung; Chen, Chun-Jung; Chen, Chuan-Mu; Liao, Su-Lan; Raung, Shue-Ling; Tsai, Sen-Wei

    2010-04-01

    Slippage after reduction of atlantoaxial rotatory fixation (AARF) is usually treated with repeated cervical traction and brace immobilization. To date, no data have been published on the management of muscle spasm during treatment. Here, we describe the case of a 7-year-old girl with AARF for 1 month who visited our hospital for treatment. During physical examination, spasm of the sternocleidomastoid muscle was noted. The patient was treated with manipulative reduction, and slippage after reduction was managed with botulinum spasticity block of the sternocleidomastoid and splenius capitis muscles, and repeated manipulation. Cervical orthosis immobilization with a rehabilitation program of isometric contract-relax exercise for the neck was conducted for 3 months. The subject had full recovery from AARF at 1-year follow-up. This report demonstrates that, in selected cases of slippage after reduction from AARF, conservative management with manipulation under anesthesia is a good method, and the muscle components may play a crucial role in AARF.

  15. The Role of Botulinum Toxin A in the Treatment of Raynaud Phenomenon.

    PubMed

    Segreto, Francesco; Marangi, Giovanni Francesco; Cerbone, Vincenzo; Persichetti, Paolo

    2016-09-01

    Raynaud phenomenon (RP) is a transient digital ischemia that occurs after exposure to cold temperature or emotional distress. It presents with a triphasic course: the initial white phase is followed by cyanotic discoloration and, subsequently, erythema. The attacks may be associated with pain, paresthesia, and complicate with nonhealing ulceration often leading to amputation. To date, there are no clear-cut therapeutic guidelines and many medications are used off-label. Encouraging results were reported with the use of botulinum neurotoxin-A (BoNT-A). However, there is still ongoing debate regarding indications, contraindications, best injection technique, and mechanism of action. The aim of this study was to address these issues by providing an up-to-date and detailed overview of the use of BoNT-A in RP.A PubMed database search was conducted. The available studies and techniques were evaluated and compared.The search yielded a total of 29 studies. Ten papers, published between 2004 and 2014, were considered relevant. A total of 128 patients underwent BoNT-A injections. Seventy-five percent to 100 % of the patients reported pain reduction after treatment. Healing of ulcers was reported in 75% to 100% of the affected patients. The most common complication was temporary hand weakness, with an average incidence of 14.1%. Injections targeting the neurovascular bundle at or slightly proximal to the A1 pulley were the most commonly performed.Botulinum neurotoxin-A injection proved to be a valid approach in both primary and secondary RP. The available evidence shows the achievement of both symptomatic and functional improvements in this debilitating condition. However, the patient should be adequately informed about the risk of transient hand weakness.

  16. The story of Clostridium botulinum: from food poisoning to Botox.

    PubMed

    Ting, Patricia T; Freiman, Anatoli

    2004-01-01

    In the last fifty years, Clostridium botulinum has become notorious for its ability to produce the deadly botulinum neurotoxins. While botulinum toxin A, better known as Botox, is universally recognised by the public as a cosmetic enhancement tool, the botulinum neurotoxins are commonly used off-label for many medical conditions in ophthalmology, neurology and dermatology. The versatility of these botulinum toxins has made Clostridium botulinum one of the most widely known bacterial pathogens in medical history. This article outlines the discovery of botulinum toxins through to their present day applications in medicine.

  17. Rapidly Progressive Muscle Paralysis and Acute Respiratory Failure Following Endoscopic Botulinum Toxin Injection

    PubMed Central

    Khan, Ahmed; Shor, Julia; Forester, Gary P.

    2016-01-01

    Botulism toxin injection (BTI) is a well-known and relatively safe endoscopic treatment for achalasia. We report a case of a 90-year-old female diagnosed with achalasia who subsequently underwent BTI with symptomatic relief. The therapy was complicated by systemic botulism, however, leading to progressive muscle paralysis with diaphragmatic involvement requiring mechanical ventilation support. This is the first reported case of BTI for achalasia causing systemic botulism. PMID:27921065

  18. Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction

    PubMed Central

    Duregotti, Elisa; Zanetti, Giulia; Scorzeto, Michele; Megighian, Aram; Montecucco, Cesare; Pirazzini, Marco; Rigoni, Michela

    2015-01-01

    Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body. PMID:26670253

  19. Do botulinum toxins have a role in the management of neuropathic pain?: a focused review.

    PubMed

    Francisco, Gerard E; Tan, Huaiyu; Green, Michael

    2012-10-01

    Botulinum neurotoxin (BoNT) is usually used in physiatric practice in the treatment of spasticity and dystonia. Research involving both animal and human subjects has emerged suggesting potential benefits in painful neuropathic conditions. The animal data strongly support the use of BoNT in the treatment of sensitized pain states. BoNT is probably effective at treating postherpetic neuralgia, probably or possibly effective at treating postoperative/posttraumatic neuropathic pain, and probably effective at treating painful diabetic neuropathy. BoNT's proposed mechanism of action is described as decreasing sensitized nociception in four ways by (1) inhibiting glutamate release in peripheral tissues, (2) decreasing calcitonin gene-related peptide release in peripheral tissue, (3) decreasing transient receptor potential cation channel subfamily V member 1 trafficking to peripheral neuron cell membrane, and (4) decreasing substance P release in peripheral tissue. This review discusses pertinent cellular/animal basic science research in conjunction with clinical research with regard to the role of BoNT in treating neuropathic pain.

  20. Efficacy of two injection-site localisation techniques for botulinum toxin injections: a single-blind, crossover, randomised trial protocol among adults with hemiplegia due to stroke

    PubMed Central

    Morel, Claire; Hauret, Isabelle; Andant, Nicolas; Bonnin, Armand; Pereira, Bruno; Coudeyre, Emmanuel

    2016-01-01

    Introduction Botulinum toxin injections are an effective treatment for limb spasticity following stroke. Different tracking techniques are used for this purpose: palpation, electrostimulation, electromyography and ultrasound. Yet very few studies have compared these different techniques, and none has successfully proved the superior efficacy of ultrasound-guided injections compared to another tracking method. The primary objective of our study was therefore to compare the efficacy of botulinum toxin injections depending on the tracking technique used: ultrasound versus electrostimulation. Methods and analysis This is a clinical, single-centre, prospective, interventional, single-blind, crossover, randomised trial. In total, 30 patients aged between 18 and 80 years presenting with triceps surae spasticity (evaluated >1 on the modified Ashworth scale) associated with hemiplegia sequelae due to stroke will be included. The patients will be selected among those who attend for consultation the Physical Medicine and Rehabilitation Department of the Clermont-Ferrand University Hospital. One group will receive the abobotulinumtoxinA (BoNT-A) injection guided by electrostimulation then ultrasound, and the second group's botulinum toxin injections will be guided by ultrasound then electrostimulation. For each patient, the duration of study participation is 5 months. The primary end point is variation in passive ankle dorsiflexion range of motion at slow and high speeds (Tardieu scale) with the knee straight. Ethics and dissemination This study received ethics approval form the CPP of Rhônes-Alpes region. Results will be published in a peer-reviewed journal. Trial registration number NCT01935544; pre-results. PMID:27852706

  1. Botulinum toxin type a injections to salivary glands: combination with single event multilevel chemoneurolysis in 2 children with severe spastic quadriplegic cerebral palsy.

    PubMed

    Kim, Heakyung; Lee, Yung; Weiner, Daniel; Kaye, Robin; Cahill, Anne Marie; Yudkoff, Marc

    2006-01-01

    We describe 2 children with severe spastic quadriplegic cerebral palsy (CP) who have significant drooling and frequent aspiration pneumonia. They underwent simultaneous botulinum toxin type A (BTX-A) injections to salivary glands for drooling and prevention of aspiration pneumonia along with single-event multilevel chemoneurolysis (SEMLC) with BTX-A and 5% phenol for severe diffuse spasticity. There was significant improvement in drooling, frequency of aspiration pneumonia, and spasticity without adverse effect. BTX-A injections into the salivary glands, in addition to SEMLC, for these 2 children with medically complicated severe spastic quadriplegic CP, were safe and highly successful procedures, which improved their health-related quality of life.

  2. Characterizing the Lateral Border of the Frontalis for Safe and Effective Injection of Botulinum Toxin

    PubMed Central

    Choi, You-Jin; Won, Sung-Yoon; Lee, Jae-Gi; Hu, Kyung-Seok; Kim, Sung-Taek; Tansatit, Tanvaa; Kim, Hee-Jin

    2016-01-01

    Background The forehead is a common site for injection of botulinum neurotoxin type A (BoNT-A) to treat hyperactive facial muscles. Unexpected side effects of BoNT-A injection may occur because the anatomy of the forehead musculature is not fully characterized. Objectives The authors described the lateral border of the frontalis in terms of facial landmarks and reference lines to determine the safest and most effective forehead injection sites for BoNT-A. Methods The hemifaces of 49 embalmed adult Korean cadavers were dissected in a morphometric analysis of the frontalis. L2 was defined in terms of FT (the most protruding point of the frontotemporal region), L0 (the line connecting the infraorbital margin with the tragus), and L1 (the line parallel to L0 and passing through FT) such that L2 was positioned 45° from L1 and passed through FT. Results The distance from FT to the superior margin of the orbicularis oculi was 12.3 ± 3.3 mm. The frontalis extended more than 5 cm along L2 in 49 of 49 cases (100%), more than 6 cm in 47 cases (95.9%), more than 7 cm in 34 cases (69.4%), more than 8 cm in 11 cases (22.4%), and more than 9 cm in 3 cases (6.1%). The lateral border of the frontalis ran parallel to and within 1 cm of the medial side of L2. Conclusions Surface anatomy mapping can assist with predicting the lateral border of the frontalis to minimize the side effects and maximize the efficiency of BoNT-A injections into the forehead. PMID:26507959

  3. Patient-Identified Factors That Influence Spasticity in People with Stroke and Multiple Sclerosis Receiving Botulinum Toxin Injection Treatments

    PubMed Central

    Cheung, Janice; Rancourt, Amanda; Di Poce, Stephanie; Levine, Amy; Hoang, Jessica; Ismail, Farooq; Boulias, Chris

    2015-01-01

    ABSTRACT Purpose: To describe the nature, extent, and impact of spasticity; determine factors that are perceived to influence its severity; and examine the relationship between time since diagnosis and impact of spasticity on daily activities in people with stroke and multiple sclerosis (MS) who are receiving botulinum toxin injection treatments. Methods: After a cross-sectional telephone survey, descriptive statistics and correlations were analyzed separately for the stroke and MS groups. Results: A total of 29 people with stroke and 10 with MS were surveyed. Both groups perceived increased spasticity with outdoor cold (69% stroke, 60% MS), muscle fatigue (59% stroke, 80% MS), and mental stress (59% stroke, 90% MS). No statistically significant correlations were found between time since diagnosis and perceived impact of spasticity on function in the stroke (r=0.07, p=0.37) or MS (r=0.16, p=0.33) groups. The MS group experienced bilateral and more severe perception of spasticity in the legs than the stroke group and identified more factors as worsening their spasticity (p<0.05). Severity of leg (but not arm) spasticity was significantly correlated with severity of impact of the following factors in the MS group only: lying on the back (r=0.70, p<0.05), outdoor heat (r=0.61, p<0.05), and morning (r=0.59, p<0.05). Conclusion: Intrinsic and extrinsic triggers can influence the perception of spasticity differently depending on individual factors, severity, location (arm vs. leg), and distribution of spasticity (unilateral vs. bilateral). Clinicians can use the findings to better understand, educate, and treat people with stroke and MS. PMID:25931667

  4. Accuracy of Ultrasound-Guided and Non-ultrasound-Guided Botulinum Toxin Injection Into Cadaver Salivary Glands

    PubMed Central

    2017-01-01

    Objective To compare the accuracy of ultrasound (US)-guided and non-US-guided botulinum toxin (BTX) injection into the salivary glands (parotid and submandibular glands) of cadavers. Methods Two rehabilitation physician injected dye into three sites in the salivary glands (two sites in the parotid gland and one site in the submandibular gland) on one side of each cadaver (one was injected on the right side, while the other was injected on the left side), using either a non-US-guided injection procedure based on superficial landmarks or a US-guided procedure. Orange dye was used for the US-guided procedure, and green dye was used for the blind procedure. Two physicians uninvolved with the injection procedures and who were blinded to the method of injection dissected the cadavers to identify whether the dye was accurately injected into each target site. Results The accuracies of the blind and US-guided injections into the parotid gland were 79.17% and 95.83%, respectively. In the submandibular gland, the accuracies of the blind and US-guided injections were 50.00% and 91.67%, respectively. The difference in accuracy between the two procedures was statistically significant only in the submandibular gland (p=0.025). There were no significant differences in the accuracy of US-guided and non-US-guided injections between the two physicians for the two sites in the parotid gland (p=0.278 and p=0.146, respectively). Conclusion US-guided BTX injection into the submandibular gland offers significantly greater accuracy over blind injection. For the treatment of drooling by injecting BTX into the submandibular gland, clinicians should consider using US guidance for improved accuracy. PMID:28289635

  5. Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

    PubMed

    Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

    2012-04-01

    Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction.

  6. An Evaluation of Use of Botulinum Toxin Type A in the Management of Dynamic Forehead Wrinkles - A Clinical Study

    PubMed Central

    Susmita, Avvaru; Kolli, Naga Neelima Devi; Meka, Sridhar; Chakravarthi, Srinivas Pandi; Lingamaneni, Krishna Prasad; Shaik, Latheef Saheb

    2016-01-01

    Introduction The pursuit of youth and beauty has undergone a resurgence of interest which is evidenced by increasing cosmetic procedures. Botulinum Toxin Type A (Botox) is one among the many procedures invented for facial rejuvenation which denervates certain muscles of facial expression responsible for facial wrinkles. It has been applied in the forehead, glabella, lateral canthal area and neck. In maxillofacial area hyperactive forehead wrinkles show sagging. Aim This study was aimed to clinically evaluate the efficacy of Botox injection in the elimination of hyperdynamic forehead wrinkles and the objectives were to compare pre-operative and post-operative improvement in the number of wrinkles, photographic grading and patient satisfaction responses after 1st week, 4th week and 16th week. Materials and Methods A total of 10 patients were randomly included in the present study who were cooperative, motivated and aesthetically conscious with moderate to severe forehead wrinkles. Assessment was performed clinically, photographically (using standardized photographs) and patient satisfaction responses were recorded at 1st week, 4th week and 16th week. Results The study showed a significant difference in the elimination of wrinkles at rest and in action when assessed at 1st week and 4th week and it was consistent at 16th week. The patient showed positive satisfaction response without ptosis of the upper eyelid. Conclusion Treatment with Botox is simple, safe and an effective modality for reduction of forehead wrinkles. It offers an alternative management in a cost-effective way when compared to surgical procedures. PMID:27891474

  7. The Effect of Botulinum Toxin Type A on Expression Profiling of Long Noncoding RNAs in Human Dermal Fibroblasts

    PubMed Central

    Miao, Ying-ying; Liu, Juan; Zhu, Jie; Tao, Yan-ling; Zhang, Jia-an

    2017-01-01

    Objective. This study was aimed at analyzing the expressions of long noncoding RNAs (lncRNAs) in Botulinum Toxin Type A (BoNTA) treated human dermal fibroblasts (HDFs) in vitro. Methods. We used RNA sequencing to characterize the lncRNAs and mRNAs transcriptome in the control and BoNTA treated group, in conjunction with application of GO (gene ontology) analysis and KEGG (kyoto encyclopedia of genes and genomes) analysis to delineate the alterations in gene expression. We also obtained quantitative real time polymerase chain reaction (qRT-PCR) to confirm some differentially expressed genes. Results. Numerous differentially expressed genes were observed by microarrays between the two groups. qRT-PCR confirmed the changes of six lncRNAs (RP11-517C16.2-001, FR271872, LOC283352, RP11-401E9.3, FGFR3P, and XXbac-BPG16N22.5) and nine mRNAs (NOS2, C13orf15, FOS, FCN2, SPINT1, PLAC8, BIRC5, NOS2, and COL19A1). Farther studies indicated that the downregulating effect of BoNTA on the expression of FGFR3P was time-related and the dosage of BoNTA at a range from 2.5 U/106 cells to 7.5 U/106 cells increased the expression of FGFR3P and COL19A1 in HDFs as well. Conclusion. The expression profiling of lncRNAs was visibly changed in BoNTA treated HDFs. Further studies should focus on several lncRNAs to investigate their functions in BoNTA treated HDFs and the underlying mechanisms. PMID:28265570

  8. Activity of botulinum toxin type A in cranial dura: implications for treatment of migraine and other headaches

    PubMed Central

    Filipović, Boris; Matak, Ivica; Helyes, Zsuzsanna

    2016-01-01

    Background and Purpose Although botulinum toxin type A (BoNT/A) is approved for chronic migraine treatment, its mechanism of action is still unknown. Dural neurogenic inflammation (DNI) commonly used to investigate migraine pathophysiology can be evoked by trigeminal pain. Here, we investigated the reactivity of cranial dura to trigeminal pain and the mechanism of BoNT/A action on DNI. Experimental Approach Because temporomandibular disorders are highly comorbid with migraine, we employed a rat model of inflammation induced by complete Freund's adjuvant, followed by treatment with BoNT/A injections or sumatriptan p.o. DNI was assessed by Evans blue‐plasma protein extravasation, cell histology and RIA for CGRP. BoNT/A enzymatic activity in dura was assessed by immunohistochemistry for cleaved synaptosomal‐associated protein 25 (SNAP‐25). Key Results BoNT/A and sumatriptan reduced the mechanical allodynia and DNI, evoked by complete Freund's adjuvant. BoNT/A prevented inflammatory cell infiltration and inhibited the increase of CGRP levels in dura. After peripheral application, BoNT/A‐cleaved SNAP‐25 colocalized with CGRP in intracranial dural nerve endings. Injection of the axonal transport blocker colchicine into the trigeminal ganglion prevented the formation of cleaved SNAP‐25 in dura. Conclusions and Implications Pericranially injected BoNT/A was taken up by local sensory nerve endings, axonally transported to the trigeminal ganglion and transcytosed to dural afferents. Colocalization of cleaved SNAP‐25 and the migraine mediator CGRP in dura suggests that BoNT/A may prevent DNI by suppressing transmission by CGRP. This might explain the effects of BoNT/A in temporomandibular joint inflammation and in migraine and some other headaches. PMID:26493010

  9. Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.

    PubMed

    Barbero, Pierangelo; Busso, Marco; Tinivella, Marco; Artusi, Carlo Alberto; De Mercanti, Stefania; Cucci, Angele; Veltri, Andrea; Avagnina, Paolo; Calvo, Andrea; Chio', Adriano; Durelli, Luca; Clerico, Marinella

    2015-12-01

    Literature provides reports only of a limited follow-up single injection of botulinum toxin-A (BoNT-A) in patients with sialorrhea. The aim of our study is to evaluate the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for severe sialorrhea secondary to neurological dysphagia. We enrolled 38 severe adult sialorrhea patients referred consecutively to the neurology unit and performed bilateral parotid and submandibular gland BoNT-A injections under ultrasound guidance. The outcomes of the study were reduction of sialorrhea, duration of therapeutic effect, and subjective patient- and caregiver-reported satisfaction. A total of 113 BoNT-A administrations were given during the study period with a mean duration of follow-up of 20.2 ± 4.4 months. We observed a significant decrease from baseline in mean number of daily aspirations and a significant improvement in patient- and caregiver-reported outcomes following ultrasound-guided BoNT-A injections (p < 0.001 vs baseline for all comparisons) and the mean duration of the efficacy was 5.6 ± 1 months. No major treatment-related adverse events occurred and a low incidence of minor adverse events was reported. This study confirms the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for sialorrhea, regardless of the causative neurological disorder. These results should encourage the use of BoNT-A in the treatment of severe sialorrhea and highlight the role of ultrasound guidance to obtain optimal results in terms of safety and reproducible outcomes.

  10. Botulinum toxin in masticatory muscles: short- and long-term effects on muscle, bone, and craniofacial function in adult rabbits.

    PubMed

    Rafferty, Katherine L; Liu, Zi Jun; Ye, Wenmin; Navarrete, Alfonso L; Nguyen, Thao Tuong; Salamati, Atriya; Herring, Susan W

    2012-03-01

    Paralysis of the masticatory muscles using botulinum toxin (BTX) is a common treatment for cosmetic reduction of the masseters as well as for conditions involving muscle spasm and pain. The effects of this treatment on mastication have not been evaluated, and claims that the treatment unloads the jaw joint and mandible have not been validated. If BTX treatment does decrease mandibular loading, osteopenia might ensue as an adverse result. Rabbits received a single dose of BTX or saline into one randomly chosen masseter muscle and were followed for 4 or 12 weeks. Masticatory muscle activity was assessed weekly, and incisor bite force elicited by stimulation of each masseter was measured periodically. At the endpoint, strain gages were installed on the neck of the mandibular condyle and on the molar area of the mandible for in vivo bone strain recording during mastication and muscle stimulation. After termination, muscles were weighed and mandibular segments were scanned with micro CT. BTX paralysis of one masseter did not alter chewing side or rate, in part because of compensation by the medial pterygoid muscle. Masseter-induced bite force was dramatically decreased. Analysis of bone strain data suggested that at 4 weeks, the mandibular condyle of the BTX-injected side was underloaded, as were both sides of the molar area. Bone quantity and quality were severely decreased specifically at these underloaded locations, especially the injection-side condylar head. At 12 weeks, most functional parameters were near their pre-injection levels, but the injected masseter still exhibited atrophy and percent bone area was still low in the condylar head. In conclusion, although the performance of mastication was only minimally harmed by BTX paralysis of the masseter, the resulting underloading was sufficient to cause notable and persistent bone loss, particularly at the temporomandibular joint.

  11. Beneficial effect of botulinum toxin A on Raynaud's phenomenon in Japanese patients with systemic sclerosis: A prospective, case series study.

    PubMed

    Motegi, Sei-ichiro; Yamada, Kazuya; Toki, Sayaka; Uchiyama, Akihiko; Kubota, Yuka; Nakamura, Tetsuya; Ishikawa, Osamu

    2016-01-01

    Currently, there is no satisfactory treatment for Raynaud's phenomenon (RP) in systemic sclerosis (SSc). Recently, it has been reported that botulinum toxin A (BTX-A) injection was effective for the treatment of RP in SSc patients. The objective was to assess the efficacy and safety of BTX-A on RP in Japanese SSc patients. In the prospective, case series study, 10 Japanese SSc patients with RP received 10 U of BTX-A injections into the hand. The change in severity of RP, including the frequency of attacks/pain, color changes, duration time of RP and the severity of pain, was assessed by Raynaud's score and pain visual analog scale (VAS) at each visit during 16 weeks. The recovery of skin temperature 20 min after cold water stimulation was examined by thermography at baseline and 4 weeks after injection. The number of digital ulcers (DU) and adverse effects were assessed at each visit. BTX-A injection decreased Raynaud's score and pain VAS from 2 weeks after injection, and the suppressive effect was continued until 16 weeks after injection. Skin temperature recovery after cold water stimulation at 4 weeks after injection was significantly enhanced compared with that before injection. All DU in five patients were healed within 12 weeks after injection. Neither systemic nor local adverse effects were observed in all cases. We conclude that BTX-A injection significantly improved the activity of RP in SSc patients without any adverse events, suggesting that BTX-A may have possible long-term preventive and therapeutic potentials for RP in Japanese SSc patients.

  12. Identification of the factors that govern the ability of therapeutic antibodies to provide postchallenge protection against botulinum toxin: a model for assessing postchallenge efficacy of medical countermeasures against agents of bioterrorism and biological warfare.

    PubMed

    Al-Saleem, Fetweh H; Nasser, Zidoon; Olson, Rebecca M; Cao, Linsen; Simpson, Lance L

    2011-08-01

    Therapeutic antibodies are one of the major classes of medical countermeasures that can provide protection against potential bioweapons such as botulinum toxin. Although a broad array of antibodies are being evaluated for their ability to neutralize the toxin, there is little information that defines the circumstances under which these antibodies can be used. In the present study, an effort was made to quantify the temporal factors that govern therapeutic antibody use in a postchallenge scenario. Experiments were done involving inhalation administration of toxin to mice, intravenous administration to mice, and direct application to murine phrenic nerve-hemidiaphragm preparations. As part of this study, several pharmacokinetic characteristics of botulinum toxin and neutralizing antibodies were measured. The core observation that emerged from the work was that the window of opportunity within which postchallenge administration of antibodies exerted a beneficial effect increased as the challenge dose of toxin decreased. The critical factor in establishing the window of opportunity was the amount of time needed for fractional redistribution of a neuroparalytic quantum of toxin from the extraneuronal space to the intraneuronal space. This redistribution event was a dose-dependent phenomenon. It is likely that the approach used to identify the factors that govern postchallenge efficacy of antibodies against botulinum toxin can be used to assess the factors that govern postchallenge efficacy of medical countermeasures against any agent of bioterrorism or biological warfare.

  13. Striving for more good days: patient perspectives on botulinum toxin for the treatment of cervical dystonia

    PubMed Central

    Poliziani, Michele; Koch, Marco; Liu, Xierong

    2016-01-01

    Background The recommended reinjection interval for botulinum neurotoxin (BoNT) formulations in the treatment of cervical dystonia (CD) is generally ≥12 weeks, though intervals ≥10 weeks are approved for incobotulinumtoxinA in Europe. However, recurring symptoms can occur before the end of this period. Using qualitative research, we sought a greater understanding of disease burden, unmet patient needs, and barriers to treatment. Methods We conducted online semistructured, focus-group discussions, and online forum follow-up discussions among patients with CD, focusing on disease burden, patient needs, injection cycle preferences, and relationships with health care professionals. A subset of patients was also questioned in telephone interviews about individual experiences of CD and BoNT treatment. All participants were UK residents who had received onabotulinumtoxinA or abobotulinumtoxinA for CD for ≥1 year. Results Thirty-one patients (81% female; mean duration of CD 16.4 [range 4–31] years; mean BoNT injection cycle length 12.8 weeks) participated in the online focus-group and forum follow-up discussions. Of these, seven patients participated in telephone interviews. All had recurring symptoms between treatments, which substantially impacted on their work, family, and social life. Symptom severity fluctuated throughout an injection cycle and differed between patients and across injection cycles. Participants’ relationships with health care professionals and treatment satisfaction varied greatly. Many participants wanted longer-lasting and/or more stable symptom relief with shorter and/or more flexible injection intervals, according to individual needs. Lack of health care resources, long journeys to treatment centers, and immunogenicity/side-effect concerns were perceived as the main barriers to more flexible treatment. Conclusion The high burden of recurring primary and secondary symptoms of CD considerably affects patients’ quality of life. Patient

  14. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

    PubMed

    Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

    2015-01-01

    The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

  15. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle

    PubMed Central

    Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

    2015-01-01

    The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity. PMID:26485650

  16. Characterization of the interaction between subunits of the botulinum toxin complex produced by serotype D through tryptic susceptibility of the isolated components and complex forms.

    PubMed

    Suzuki, Tomonori; Watanabe, Toshihiro; Mutoh, Shingo; Hasegawa, Kimiko; Kouguchi, Hirokazu; Sagane, Yoshimasa; Fujinaga, Yukako; Oguma, Keiji; Ohyama, Tohru

    2005-05-01

    The 650 kDa large toxin complex (L-TC) produced by Clostridium botulinum serotype D strain 4947 (D-4947) has a subunit structure composed of unnicked components, i.e. neurotoxin (NT), non-toxic non-haemagglutinin (NTNHA) and three haemagglutinin subcomponents (HA-70, HA-33 and HA-17). In this study, subunit interactions were investigated through the susceptibilities of the toxin components to limited trypsin proteolysis. Additionally, complex forms were reconstituted in vitro by various combinations of individual components. Trypsin treatment of intact D-4947 L-TC led to the formation of mature L-TC with nicks at specific sites of each component, which is usually observed in other strains of serotype D. NT, NTNHA and HA-17 were cleaved at their specific sites in either the single or complex forms, but HA-33 showed no sign of proteolysis. Unlike the other components, HA-70 was digested into random fragments as a single form, but it was cleaved into two fragments in the complex form. Based on the relative position of exposed or hidden regions of the individual components in the complex derived from their tryptic susceptibilities, an assembly model is proposed for the arrangement of individual subunits in the botulinum L-TC.

  17. Three-dimensional CT might be a potential evaluation modality in correction of asymmetrical masseter muscle hypertrophy by botulinum toxin injection.

    PubMed

    No, Yeon A; Ahn, Byeong Heon; Kim, Beom Joon; Kim, Myeung Nam; Hong, Chang Kwon

    2016-01-01

    For correction of this asymmetrical hypertrophy, botulinum toxin type A (BTxA) injection is one of convenient treatment modalities. Unfortunately, physical examination of masseter muscle is not enough to estimate the exact volume of muscle hypertrophy difference. Two Koreans, male and female, of bilateral masseter hypertrophy with asymmetricity were evaluated. BTxA (NABOTA(®), Daewoong, Co. Ltd., Seoul, Korea) was injected at master muscle site with total 50 U (25 U at each side) and volume change was evaluated with three-dimensional (3D) CT image analysis. Maximum reduction of masseter hypertrophy was recognized at 2-month follow-up and reduced muscle size started to restore after 3 months. Mean reduction of masseter muscle volume was 36% compared with baseline. More hypertrophied side of masseter muscle presented 42% of volume reduction at 2-month follow-up but less hypertrophied side of masseter muscle showed 30% of volume shrinkage. In conclusion, 3D CT image analysis might be the exact evaluation tool for correction of asymmetrical masseter hypertrophy by botulinum toxin injection.

  18. The effects of botulinum toxin type A on improvement and dynamic spastic equinus correction in children with cerebral palsy – preliminary results

    PubMed Central

    Dimitrijevic, Lidija; Stankovic, Ivona; Nikolic, Dejan; Radovic-Janosevic, Dragana; Zivanovic, Dragoljub

    2014-01-01

    Introduction We evaluated the effects of botulinum toxin type A (BTA) with physical therapy on dynamic foot equinus correction and higher motor functional outcome in children with spastic type of cerebral palsy (CP). Material and methods Ankle joint active and passive movement, gastrocnemial muscle spasticity levels (Modified Ashworth Scale (MAS)), and higher motor functional status (Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM) (GMFM-D – standing and GMFM-E – walking) were assessed before treatment and 3, 8, 16 weeks and 6 months after BTA administration in 12 children. Results There was a significant improvement of active (initial – (–)13.07 ±5.78; 6 months – (–)10.64 ±4.77; p < 0.001) and passive (initial – 4.21 ±2.29; 6 months – 4.71 ±2.16; p < 0.05) ankle joint foot dorsiflexion. GMFM-D and GMFM-E were significantly higher after 3, 8, 16 weeks (p < 0.001) and GMFM-D after 6 months (p < 0.001). Conclusions Botulinum toxin type A administration and physical therapy in patients with spastic CP improves the motion range of dynamic foot equinus after 3 weeks and higher motor functional outcome (standing and walking). PMID:25395950

  19. The Effect of Total Cumulative Dose, Number of Treatment Cycles, Interval between Injections, and Length of Treatment on the Frequency of Occurrence of Antibodies to Botulinum Toxin Type A in the Treatment of Muscle Spasticity

    ERIC Educational Resources Information Center

    Bakheit, Abdel Magid O.; Liptrot, Anthea; Newton, Rachel; Pickett, Andrew M.

    2012-01-01

    A large cumulative dose of botulinum toxin type A (BoNT-A), frequent injections, a short interval between treatment cycles, and a long duration of treatment have all been suggested, but not confirmed, to be associated with a high incidence of neutralizing antibodies to the neurotoxin. The aim of this study was to investigate whether these…

  20. Botulinum toxin in spinal cord injury patients with neurogenic detrusor overactivity

    PubMed Central

    Cho, Young Sam; Kim, Khae Hawn

    2016-01-01

    Evidence for the efficacy and safety of intravesical onabotulinum toxin A (onabotA) injections has led to them being licensed in many countries, including Korea, for the treatment of patients with urinary incontinence due to neurogenic detrusor overactivity (NDO) resulting from spinal cord injury or multiple sclerosis who are refractory or intolerant to anticholinergic medications. OnabotA injections have an inhibitory effect on acetylcholine release for up to 10 months, with a recommended dose of 200 U. OnabotA treatment has a beneficial effect not only on urinary symptoms, but also on quality of life. Several clinical studies have shown onabotA to have better effects than placebo in achieving continence, reducing incontinence episodes, improving urodynamic parameters, and improving health-related quality of life. Urinary tract infections and postvoid residual volume are the most prevalent side effects. In patients with residual volume, clean intermittent catheterization may be necessary. In patients with spinal cord injury or multiple sclerosis, it is recommended to evaluate physical and cognitive function before intravesical onabotA injection to ensure that the patient and caregiver are able to perform catheterization if necessary. Further controlled trials should assess the optimal dose, injection technique, long-term safety of repeated injections, and optimal timing of onabotA treatment in the treatment of NDO. PMID:28119887

  1. Conversion of a Mouse Fab into a Whole Humanized IgG Antibody for Detecting Botulinum Toxin

    DTIC Science & Technology

    2006-04-01

    pentavalent toxoid; Fab, antibody fragment; HRP, horseradish peroxidase; LCκ, kappa light chain ; scFv, single- chain antibody fragments; VL, variable light ...The variable regions from an anti-botulinum Fab were cloned into human IgG heavy and light chain vectors and produced in myeloma cells. Purified...from an anti-botulinum Fab were cloned into human IgG heavy and light chain vectors and produced in myeloma cells. Purified humanized IgG demonstrated

  2. Botulinum toxin effects on gasatrocnemius strength and plantar pressure in diabetics with peripheral neuropathy and forefoot ulceration

    PubMed Central

    Hastings, Mary K.; Mueller, Michael J.; Sinacore, David R.; Strube, Michael J.; Crowner, Beth; Johnson, Jeffrey E.; Racette, Brad A.

    2013-01-01

    Background High forefoot plantar pressure is associated with plantar ulcers in people with diabetes and peripheral neuropathy. The purpose of this pilot study is to determine safety and efficacy of botulinum toxin A injected into the gastrocnemius-soleus muscles to reduce muscle strength and plantar pressure. Materials and Methods This double blind, randomized clinical trial studied 17 people with diabetes mellitus, peripheral neuropathy and forefoot plantar ulcer. Subjects were randomized into one of three groups receiving gastrocnemius-soleus muscle injections on the involved side with; 1) Saline (n=5, weight = 99 ± 21 kg), 2) 200 units of Botox® (n=7, weight = 101 ± 5 kg), or 3) 300 units of Botox® (n=5, weight=129 ± 22 kg). Botox® dose was converted to units/kg, the majority received between 1.9 and 2.4 units/kg (n=11) and one 3.2 units/kg. Plantarflexor peak torque and forefoot peak plantar pressure were quantified prior and two weeks post injection. Results There were no complications from the injections. Plantarflexor peak torque on the involved side increased in the placebo and 300 groups (3 ± 4 Nm and 6 ± 10 Nm respectively) and decreased −8 ± 11 Nm in the 200 group. There was no relationship between units/kg of Botox® for each subject and change in plantarflexor peak torque. Forefoot peak plantar pressure did not change in the placebo and 300 groups (0 ± 11 and 0 ± 5 N/cm2 respectively) and decreased −4 ± 16 N/cm2 (4%) for the 200 group. Conclusions There were no adverse events associated with the Botox® injections. This study was unable to determine the dose to consistently reduce plantarflexor strength and forefoot plantar pressure. Additional research is needed to investigate diabetes mellitus specific physiological changes and their impact of BoNT-A effectiveness in order to guide appropriate dosing. PMID:22735277

  3. Botulinum toxin therapy of cervical dystonia: comparing onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin (®)).

    PubMed

    Dressler, Dirk; Tacik, Pawel; Adib Saberi, Fereshte

    2014-01-01

    Several botulinum toxin (BT) drugs are licensed for the treatment of cervical dystonia (CD). We wanted to compare the efficacy and the potency labelling of incobotulinumtoxinA (Xeomin(®)) and onabotulinumtoxinA (Botox(®)) by analysing the duration of their therapeutic effect in a cross-over study. For this we studied 40 CD patients (26 females, 14 males, age at therapy onset 52.6 ± 12.0 years, duration of dystonia at therapy onset 10.0 ± 9.2 years, Tsui score 9.1 ± 3.9) who first received Botox(®) and then Xeomin(®) for at least 4 injection series each. BT doses were exchanged based on a 1:1 conversion ratio. Altogether 1,101 treatment cycles were evaluated. For each patient 27.5 ± 13.1 treatment cycles were recorded. Patients received 18.4 ± 12.4 treatment cycles with Botox(®) and 9.2 ± 4.5 with Xeomin(®). The treatment duration (TD) throughout the treatment course was 11.3 ± 1.0 weeks (Botox(®) 11.2 ± 1.1 weeks, Xeomin(®) 11.4 ± 1.3 weeks). The interinjection interval (II) throughout the treatment course was 14.8 ± 1.9 weeks (Botox(®) 14.7 ± 1.6 weeks, Xeomin(®) 15.0 ± 2.2 weeks). The mean difference between Botox(®) and Xeomin(®) was 0.3 weeks for TD (two-sided 95 % confidence interval [-0.3; 0.9]) and 0.5 weeks for II (two-sided 95 % confidence intervals [-0.4; 1.4]). The confidence intervals of both parameters were within the predefined therapeutic equivalence range set to ±1.5 weeks, thus indicating similar efficacy of both BT drugs. Having based the exchange of Botox(®) and Xeomin(®) on a conversion factor of 1:1 our data confirm previous findings of an identical potency labelling of both products, thus allowing comparisons of efficacy, adverse effects and costs.

  4. Subcutaneous Botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin.

    PubMed

    Gazerani, Parisa; Pedersen, Natalia Spicina; Staahl, Camilla; Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars

    2009-01-01

    The present human study aimed at investigating the effect of subcutaneous administration of Botulinum toxin type A (BoNT/A) on capsaicin-induced trigeminal pain, neurogenic inflammation and experimentally induced cutaneous pain modalities. Fourteen healthy males (26.3+/-2.6 years) were included in this double-blind and placebo-controlled trial. The subjects received subcutaneous BoNT/A (22.5U) and isotonic saline in the mirror sides of their forehead. Pain and neurogenic inflammation was induced by four intradermal injections of capsaicin (100mug/muL) (before, and days 1, 3 and 7 after treatments). The capsaicin-induced pain intensity, pain area, the area of secondary hyperalgesia, the area of visible flare and vasomotor reactions were recorded together with cutaneous heat, electrical and pressure pain thresholds. BoNT/A reduced the capsaicin-induced trigeminal pain intensity compared to saline (F=37.9, P<0.001). The perceived pain area was smaller for the BoNT/A-treated side compared to saline (F=7.8, P<0.05). BoNT/A reduced the capsaicin-induced secondary hyperalgesia (F=5.3, P<0.05) and flare area (F=10.3, P<0.01) compared to saline. BoNT/A reduced blood flow (F(1,26)=109.5, P<0.001) and skin temperature (F(1,26)=63.1, P<0.001) at the capsaicin injection sites compared to saline and its suppressive effect was maximal at days 3 and 7 (P<0.05, post hoc test). BoNT/A elevated cutaneous heat pain thresholds (F=17.1, P<0.001) compared to saline; however, no alteration was recorded for electrical or pressure pain thresholds (P>0.05). Findings from the present study suggest that BoNT/A appears to preferentially target Cfibers and probably TRPV1-receptors, block neurotransmitter release and subsequently reduce pain, neurogenic inflammation and cutaneous heat pain threshold.

  5. A Single-blind, Split-face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging

    PubMed Central

    Sapra, Priya; Sapra, Sheetal; Khanna, Julie; Mraud, Kelli; Bonadonna, Jennifer

    2017-01-01

    Objective: To examine the effectiveness of intradermal botulinum toxin type A injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods. Design: A 16-week, single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal botulinum toxin type A injections at Week 0 and intramuscular botulinum toxin type A injections at Week 2. Participants: Ten women aged 35 to 65 years who exhibited static rhytids in the glabellar and periorbital area. Measurements: The primary endpoint was efficacy of split-face treatment of intradermal and intramuscular onabotulinumtoxinA and abobotulinumtoxinA as assessed by a blinded evaluator using baseline and post-treatment photographs. The secondary endpoints included safety as assessed by adverse events and patient satisfaction measured by questionnaires completed at baseline and post-treatment. Results: Intradermal injection of botulinum toxin type A led to a statistically significant improvement in skin texture (p=0.004) while also resulting in mild midface lift (p=0.024), but did not provide a significant reduction of pore size and sebum production. There was no statistically significant difference between onabotulinumtoxinA and abobotulinumtoxinA when injected intradermally or intramuscularly. Conclusion: Intradermal injection of botulinum toxin type A appears to be a safe and effective therapy that provides an improvement in facial skin texture and midface lift. Registry: clinicaltrials.gov (ID#: NCT02907268). PMID:28367260

  6. GRIN: “GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial”: study protocol

    PubMed Central

    2014-01-01

    Background Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. Methods/Design An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child’s occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. Discussion This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised

  7. On Botulinum Neurotoxin Variability

    PubMed Central

    2015-01-01

    ABSTRACT  The rapidly growing number of botulinum neurotoxin sequences poses the problem of the possible evolutionary significance of the variability of these superpotent neurotoxins for toxin-producing Clostridium species. To progress in the understanding of this remarkable phenomenon, we suggest that researchers should (i) abandon an anthropocentric view of these neurotoxins as human botulism-causing agents or as human therapeutics, (ii) begin to investigate in depth the role of botulinum neurotoxins in animal botulism in the wilderness, and (iii) devote large efforts to next-generation sequencing of soil samples to identify novel botulinum neurotoxins. In order to compare the fitness of the different toxins, we suggest that assays of all the steps from toxin production to animal death should be performed. PMID:25564463

  8. Application of real-time PCR for quantitative detection of Clostridium botulinum type A toxin gene in food.

    PubMed

    Yoon, So-Yeon; Chung, Gyung Tae; Kang, Do-Hyun; Ryu, Chunsun; Yoo, Cheon-Kwon; Seong, Won-Keun

    2005-01-01

    The TaqMan real-time PCR method for the quantitative detection of C. botulinum type A was developed based on sequence-specific hybridization probes. The validity of this assay was verified by using 10 genera of 20 strains, including reference strains of C. botulinum types A, B, C, D, E and F. The detection limit of this assay was evaluated on C. botulinum type A, using a 10-fold dilution series of DNA and spores . The DNA and spores were detected up to level of 0.1 ng/ml and 10(2)spores/ml, respectively. Spore spiked food sample preparation prior to the real-time PCR was performed by two methods, heat treatment and GuSCN. The detection limits after heat treatment showed 10(2) spores/ml for spiked sausage slurry, and 10(3) spores/ml for spiked canned corn slurry, while detection limits after GuSCN precipitation showed 10(2) spores/ml in both sausage and canned corn. Therefore the real-time PCR assay after GuSCN precipitation is useful for the quantification of C. botulinum type A because it showed identical CT values in both pure spore solutions and food slurries. We suggest that quantitative analysis of C. botulinum type A by TaqMan real-time PCR can be a rapid and accurate assessment method for botulinal risk in food samples.

  9. Botulinum Toxin Type A Induces Changes in the Chemical Coding of Substance P-Immunoreactive Dorsal Root Ganglia Sensory Neurons Supplying the Porcine Urinary Bladder

    PubMed Central

    Bossowska, Agnieszka; Lepiarczyk, Ewa; Mazur, Urszula; Janikiewicz, Paweł; Markiewicz, Włodzimierz

    2015-01-01

    Botulinum toxin (BTX) is a potent neurotoxin which blocks acetylcholine release from nerve terminals, and therefore leads to cessation of somatic motor and/or parasympathetic transmission. Recently it has been found that BTX also interferes with sensory transmission, thus, the present study was aimed at investigating the neurochemical characterization of substance P-immunoreactive (SP-IR) bladder-projecting sensory neurons (BPSN) after the toxin treatment. Investigated neurons were visualized with retrograde tracing method and their chemical profile was disclosed with double-labelling immunohistochemistry using antibodies against SP, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP), neuronal nitric oxide synthase (nNOS), galanin (GAL), calbindin (CB), and somatostatin (SOM). In the control group (n = 6), 45% of the total population of BPSN were SP-IR. Nearly half of these neurons co-expressed PACAP or CGRP (45% and 35%, respectively), while co-localization of SP with GAL, nNOS, SOM or CB was found less frequently (3.7%, 1.8%, 1.2%, and 0.7%, respectively). In BTX-treated pigs (n = 6), toxin-injections caused a decrease in the number of SP-IR cells containing CGRP, SOM or CB (16.2%, 0.5%, and 0%, respectively) and a distinct increase in these nerve cells immunopositive to GAL (27.2%). The present study demonstrates that BTX significantly modifies the chemical phenotypes of SP-IR BPSN. PMID:26580655

  10. Usefulness of Magnetic Resonance Neurography for Diagnosis of Piriformis Muscle Syndrome and Verification of the Effect After Botulinum Toxin Type A Injection

    PubMed Central

    Yang, Hea Eun; Park, Jung Hyun; Kim, Sungjun

    2015-01-01

    Abstract Piriformis muscle syndrome (PMS) is a controversial neuromuscular disorder that is presumed to involve compression neuropathy of the sciatic nerve at the level of the piriformis muscle. Botulinum toxin A (BTX-A) injection into the piriformis muscle is widely used as a treatment aimed at relieving sciatic nerve compression. In 2 patients with PMS, magnetic resonance neurography (MRN) was taken before and after BTX-A injection. The first MRN was performed as a diagnostic tool, and the second to identify the effect of the treatment. Signal change of the sciatic nerve under the hypertrophied piriformis muscle was confirmed by MRN. In follow-up MRN performed after BTX-A injection into the piriformis muscle, changes of the sciatic nerve and piriformis muscle were noticed as well as improvement of clinical symptoms. MRN is a useful tool to add certainty of diagnosis and verify the effect of treatment in PMS. PMID:26402805

  11. Usefulness of Magnetic Resonance Neurography for Diagnosis of Piriformis Muscle Syndrome and Verification of the Effect After Botulinum Toxin Type A Injection: Two Cases.

    PubMed

    Yang, Hea Eun; Park, Jung Hyun; Kim, Sungjun

    2015-09-01

    Piriformis muscle syndrome (PMS) is a controversial neuromuscular disorder that is presumed to involve compression neuropathy of the sciatic nerve at the level of the piriformis muscle. Botulinum toxin A (BTX-A) injection into the piriformis muscle is widely used as a treatment aimed at relieving sciatic nerve compression. In 2 patients with PMS, magnetic resonance neurography (MRN) was taken before and after BTX-A injection. The first MRN was performed as a diagnostic tool, and the second to identify the effect of the treatment. Signal change of the sciatic nerve under the hypertrophied piriformis muscle was confirmed by MRN. In follow-up MRN performed after BTX-A injection into the piriformis muscle, changes of the sciatic nerve and piriformis muscle were noticed as well as improvement of clinical symptoms. MRN is a useful tool to add certainty of diagnosis and verify the effect of treatment in PMS.

  12. The profile of patients and current practice of treatment of upper limb muscle spasticity with botulinum toxin type A: an international survey.

    PubMed

    Bakheit, Abdel Magid; Zakine, Benjamin; Maisonobe, Pascal; Aymard, Claire; Fhedoroff, Klemens; Hefter, Harold; Jacinto, Jorge; Jost, Wolfgang H; Molteni, Franco; Stam, Henk; Turner-Stokes, Lynne; Wissel, Jorg

    2010-09-01

    To document the current practice in relation with the treatment of patients with upper limb spasticity with botulinum toxin type A to inform future research in this area. We designed an international, cross-sectional, noninterventional survey of current practice. Nine hundred and seventy-four patients from 122 investigational centres in 31 countries were studied. Most patients were over 40 years old and had a stroke. Improvement of active function was the most frequent treatment goal in the first 3 months after the onset of upper limb spasticity, but was less common than passive function in the chronic stage. Pain relief was a common goal in both the stages. As a rule, clinicians intended to assess the effectiveness of treatment with impairment level scales. Functional outcome measures seem to be rarely used in clinical practice. The use of these measures should be encouraged to assess whether the reduction in muscle tone translates into functional benefit to patients and their caregivers.

  13. Screening for variations in anterior digastric musculature prior to correction of post-traumatic anterior open bite by injection of botulinum toxin type A: a technical note.

    PubMed

    Zdilla, Matthew J

    2015-06-01

    It has recently been reported that long-standing post-traumatic open bite can be successfully corrected with botulinum toxin type A (BTX-A) injection into the anterior belly of the digastric muscle (ABDM). The report documented an individual with bilaterally symmetrical and otherwise unremarkable anterior digastric musculature. However, the existence of variant anterior digastric musculature is common and may complicate the management of anterior open bite with BTX-A injection. Screening for variant ABDM can be accomplished via ultrasound, computed tomography, and magnetic resonance imaging. Screening for variant ABDM should be performed prior to BTX-A injection in order to account for musculature that may exert undesired forces, such as inferolateral deviation, on the anterior mandible in patients with anterior open bite.

  14. Therapeutic synergism in the treatment of post-stroke arm paresis utilizing botulinum toxin, robotic therapy, and constraint-induced movement therapy.

    PubMed

    Takebayashi, Takashi; Amano, Satoru; Hanada, Keisuke; Umeji, Atsushi; Takahashi, Kayoko; Koyama, Tetsuo; Domen, Kazuhisa

    2014-11-01

    Botulinum toxin type A (BtxA) injection, constraint-induced movement therapy (CIMT), and robotic therapy (RT) each represent promising approaches to enhance arm motor recovery after stroke. To provide more effective treatment for a 50-year-old man with severe left spastic hemiparesis, we attempted to facilitate CIMT with adaptive approaches to extend the wrist and fingers using RT for 10 consecutive weeks after BtxA injection. This combined treatment resulted in substantial improvements in arm function and the amount of arm use in activities of daily living, and may be effective for stroke patients with severe arm paresis. However, we were unable to sufficiently prove the efficacy of combined treatment based only on a single case. To fully elucidate the efficacy of the combined approach for patients with severe hemiparesis after stroke, future studies of a larger number of patients are needed.

  15. SBOTE study: extracorporeal shock wave therapy versus electrical stimulation after botulinum toxin type a injection for post-stroke spasticity-a prospective randomized trial.

    PubMed

    Santamato, Andrea; Notarnicola, Angela; Panza, Francesco; Ranieri, Maurizio; Micello, Maria Francesca; Manganotti, Paolo; Moretti, Biagio; Fortunato, Francesca; Filoni, Serena; Fiore, Pietro

    2013-02-01

    Research is on-going to identify new methods of biostimulation to increase the effect of botulinum toxin type A (BTX-A) in the treatment of spasticity. The Spasticity treated by Botulinum Toxin and ESWT (SBOTE) study is a prospective, randomized controlled trial assessing the effectiveness of extracorporeal shock wave therapy (ESWT) given immediately after BTX-A injections compared with electrical stimulation (ES) given immediately after BTX-A therapy for the management of focal upper limb spasticity in stroke patients. ES was given for 30 min twice a day for 5 days starting at 5 Hz; ESWT was given once a day for 5 days. At study follow-up, patients treated with BTX-A injections and ESWT showed a statistically greater significance and continuous decrease of spasticity measure (modified Ashworth scale [MAS]: 1.37, 1.75 and 1.58 at 15, 30 and 90 days post-treatment, respectively), of spasms (spasm frequency scale [SFS]: 0.8 and 0.25 at 30 and 90 days post-treatment, respectively) and of pain (visual analogue scale [VAS]: 1.94 and 1.87 at 30 and 90 days, respectively) compared with patients treated with BTX-A injections and ES (MAS: 2.37, 2.18 and 2.18, respectively) (p < 0.05) (SFS: 1.5 and 1.06, respectively) (p < 0.05) (VAS: 2.44 and 2.69 respectively) (p < 0.05). ESWT enhances the effect of BTX-A to a greater extent than ES, probably by modulating rheology of the muscle and neurotransmission at the neuromuscular junction.

  16. A preliminary study of painless and effective transdermal botulinum toxin A delivery by jet nebulization for treatment of primary hyperhidrosis

    PubMed Central

    Iannitti, Tommaso; Palmieri, Beniamino; Aspiro, Anna; Di Cerbo, Alessandro

    2014-01-01

    Background Hyperhidrosis is a chronic disease characterized by increased sweat production. Local injections of botulinum toxin A (BTX-A) have been extensively used for treatment of primary hyperhidrosis (idiopathic). The current treatment for this condition involves several intradermal injections, resulting in poor patient compliance due to injection-related pain. Therefore, new protocols, including an improved anesthetic regimen, are required. Aim We designed the present study to determine whether JetPeel™-3, a medical device used for transdermal delivery of drugs by jet nebulization, could be used to deliver lidocaine prior to the standard multiple BTX-A injections or deliver lidocaine together with BTX-A in order to determine the protocol giving better results in terms of procedure-related pain, sweating, and patient satisfaction in subjects affected by primary axillary, palmar or plantar hyperhidrosis. Materials and methods Twenty patients with a visual analog scale (VAS) sweating score ≥ 8 cm were randomized to receive lidocaine 2% (5 mL) delivered by JetPeel™-3 followed by multiple injections of BTX-A (100 units) or lidocaine 2% (5 mL) and BTX-A (50 units) delivered together by JetPeel™-3. Effect of treatment on sweating was measured by VAS (0= minimum sweating; 10= maximum sweating) at 3-month follow-up. Pain induced by the procedure was assessed by VAS (0= minimum pain; 10= maximum pain) immediately after the procedure. Patient satisfaction was assessed at 3-month follow-up using a 5-point scale (1= not at all satisfied; 2= not satisfied; 3= partially satisfied; 4= satisfied; 5= highly satisfied). Results Both treatment modalities reduced sweating at 3-month follow-up, if compared with baseline (all P<0.001). Delivery of lidocaine and BTX-A by JetPeel™-3 resulted in lower procedure-related pain and reduced sweating, if compared with lidocaine delivered by JetPeel™-3 followed by multiple BTX-A injections (all P<0.001). Patient satisfaction with

  17. Botulinum Toxin Therapy

    MedlinePlus

    ... 2017 American Academy of Dermatology. All rights reserved. Reproduction or republication strictly prohibited without prior written permission. ... 2017 American Academy of Dermatology. All rights reserved. Reproduction or republication strictly prohibited without prior written permission.

  18. Production of anti-neurotoxin antibody is enhanced by two subcomponents, HA1 and HA3b, of Clostridium botulinum type B 16S toxin-haemagglutinin.

    PubMed

    Lee, Jae-Chul; Yokota, Kenji; Arimitsu, Hideyuki; Hwang, Hyun-Jung; Sakaguchi, Yoshihiko; Cui, Jinhua; Takeshi, Kouichi; Watanabe, Toshihiro; Ohyama, Tohru; Oguma, Keiji

    2005-11-01

    Clostridium botulinum type B strain produces two forms of progenitor toxin, 16S and 12S. The 12S toxin is formed by association of a neurotoxin (NTX) and a non-toxic non-haemagglutinin (NTNH), and the 16S toxin is formed by conjugation of the 12S toxin with a haemagglutinin (HA). HA consists of four subcomponents designated HA1, HA2, HA3a and HA3b. When mice were immunized with formalin-detoxified NTX, 12S or 16S, a significantly greater amount of anti-NTX antibody (Ab) was produced in the mice injected with 16S than in NTX- or 12S-injected mice. Immunization with NTX mixed with HA1 and/or HA3b also increased the anti-NTX Ab production, whereas NTX mixed with HA2 did not, indicating that HA1 and HA3b have adjuvant activity. This was further confirmed by immunizing mice with human albumin (Alb) alone or Alb mixed with either HA1 or HA3b. When mouse-spleen cells were stimulated with NTX, 16S or different HA subcomponents, 16S, HA1, HA3b and the mixture of HA1 and HA3 significantly increased interleukin 6 (IL6) production compared with NTX alone. Transcription of IL6 mRNA was low after stimulation with NTX alone, but increased to 16S-stimulation levels when NTX was mixed with HA1 or HA3b. In flow cytometry using labelled Abs against CD3 and CD19, the percentage of CD19 cells was higher following stimulation with 16S or NTX mixed with HA1 or HA3b compared with stimulation with NTX. The percentage of CD3 cells remained unchanged. These results suggest strongly that HA1 and HA3b demonstrate adjuvant activity via increasing IL6 production.

  19. Persistence of the synaptosomal-associated protein-25 cleavage product after intradetrusor botulinum toxin A injections in patients with myelomeningocele showing an inadequate response to treatment.

    PubMed

    Schulte-Baukloh, Heinrich; Zurawski, Tomas H; Knispel, Helmut H; Miller, Kurt; Haferkamp, Axel; Dolly, J Oliver

    2007-11-01

    OBJECTIVE To monitor the presence and cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) by botulinum toxin type A (botox-A), in human detrusor muscle, as the effects of botox-A in the urinary bladder last significantly longer than when applied for disorders of striated muscles. PATIENTS AND METHODS Tissue samples were obtained from eight patients with end-stage neurogenic bladder at different times after injection with botox-A. The resected bladder domes were examined using biochemical and immunohistological techniques. RESULTS The presence of intact SNAP-25 in human bladder was detected, for the first time, in all samples by both Western blotting and immunofluorescence. By contrast, detection of a band potentially representing toxin-cleaved SNAP-25(A) required its enrichment by precipitation with a specific antibody. This putative product was present in four of six patients treated with botox-A 5 weeks to 11 months previously, but could not be detected in one patient 30 months after botox injection, and in an untreated control. Fluorescence microscopy showed no obvious effects of the toxin treatment on the presence and pattern of SNAP-25-positive neurones. CONCLUSIONS A limited amount of SNAP-25 appears to be cleaved in nerves that innervate the smooth detrusor muscle in most patients who had been injected with botox-A; its absolute identification was precluded by the sensitivity of the detection. This protein was detectable much longer after toxin treatment than published for rodent striated muscle, and thus could contribute to the clinically reported longer duration of the effectiveness of botox-A.

  20. Genomics of Clostridium botulinum group III strains.

    PubMed

    Sakaguchi, Yoshihiko; Suzuki, Tomonori; Yamamoto, Yumiko; Nishikawa, Atsushi; Oguma, Keiji

    2015-05-01

    In Clostridium botulinum, the characteristics of type C and D strains are quite different from other types, and they are classified as group III. They produce C2 binary toxin and C3 exoenzyme in addition to type C and D neurotoxins. Two different phages and many plasmids are identified in the organisms. The genes of neurotoxin and C3 exoenzyme are converted from toxigenic strains to non-toxigenic strains by the specific bacteriophages (phages), whereas, the C2 toxin gene is carried by large or small plasmids. Classification of type C and D strains has been in confusion because 1) antigenicity of type C and D neurotoxins is complex, 2) the cells produce two types of toxins, neurotoxin and C2 toxin, and 3) some non-toxigenic strains can be converted to produce C or D neurotoxin by the infection with phages. Until now, entire nucleotide sequences of cell chromosomes, phages, and plasmids have been determined. Since both genetic and protein-chemical analyses have been clarifying the above confusions, these data are reviewed historically.

  1. Two Novel Toxin Variants Revealed by Whole-Genome Sequencing of 175 Clostridium botulinum Type E Strains

    PubMed Central

    Weedmark, K. A.; Lambert, D. L.; Mabon, P.; Hayden, K. L.; Urfano, C. J.; Leclair, D.; Van Domselaar, G.; Austin, J. W.

    2014-01-01

    We sequenced 175 Clostridium botulinum type E strains isolated from food, clinical, and environmental sources from northern Canada and analyzed their botulinum neurotoxin (bont) coding sequences (CDSs). In addition to bont/E1 and bont/E3 variant types, neurotoxin sequence analysis identified two novel BoNT type E variants termed E10 and E11. Strains producing type E10 were found along the eastern coastlines of Hudson Bay and the shores of Ungava Bay, while strains producing type E11 were only found in the Koksoak River region of Nunavik. Strains producing BoNT/E3 were widespread throughout northern Canada, with the exception of the coast of eastern Hudson Bay. PMID:25107978

  2. Regional diffusion of botulinum toxin in facial muscles: a randomised double-blind study and a consideration for clinical studies with split-face design.

    PubMed

    Punga, Anna Rostedt; Eriksson, Annika; Alimohammadi, Mohammad

    2015-11-01

    Despite the extensive use of botulinum toxin A (BoNTA) in medical and cosmetic treatments, the potential spreading of BoNTA to surrounding tissues remains unknown. A patient with hemifacial paralysis upon blepharospasm treatment with low dose of BoNTA, prompted us to investigate the spreading effect. A randomised, double-blind study was conducted in which 5 healthy women (33-52 years) were treated with different doses of onabotulinum toxin unilaterally in the corrugator muscle. Parameters of efficacy and diffusion (CMAP; EMG and jitter analysis) in both glabellar and frontalis muscles were assessed at baseline, 2 and 4 weeks following BoNTA injection. CMAP of the treated glabellar muscles was reduced to approximately 40% in all dose groups. Additionally, contralateral CMAP reduction was observed in 3 of 5 subjects. These data confirm regional diffusion of BoNTA in facial muscle application, which raises question on the reliability of split-face models in BoNTA studies.

  3. Monitoring of laying capacity, immunoglobulin Y concentration, and antibody titer development in chickens immunized with ricin and botulinum toxins over a two-year period.

    PubMed

    Pauly, D; Dorner, M; Zhang, X; Hlinak, A; Dorner, B; Schade, R

    2009-02-01

    One of the key benefits in using chickens for immunization is the high yield of antibodies obtainable. It is known that egg production decreases over time, while animal maintenance costs remain stable. It would, however, be desirable to keep hens as long as possible to obtain maximal amounts of antibodies. To identify a suitable length of time that animals can be kept and to optimize the cost:yield ratio, we monitored the number of eggs laid, the total amount of chicken IgY, and the specific antibody titer from individually prepared eggs over a 2-yr period. The plant toxin ricin and the Clostridium botulinum neurotoxins type A and B were used to immunize 4 chickens. The number of eggs laid in 2 yr was approximately 600 per hen (about 80% of the maximum egg number), yielding about 20 to 40 g of total IgY per hen. A stable antibody titer of 1:100,000 to 1:1,000,000, as measured by ELISA, was obtained following up to 11 injections of 10 to 20 microg of immobilized native toxin. Laying capacities were found to decrease, on average, from 7 eggs/wk at the point of first immunization to 2 eggs/wk after more than 2 yr. In parallel, the yield of total and specific IgY increased over time, so that the antibody recovery remained high, even after prolonged immunization times. Using purified IgY preparations, classical immunological assays such as ELISA and Western blotting were performed. Furthermore, the IgY showed neutralizing capacity when used to block the functional activity of the toxins both in vitro and in vivo. Analysis of the total IgY content over time demonstrated a complex biological oscillation (and the antigen-specific titer), with a shorter time period of around 7 d (circaseptan rhythm). In summary, we successfully immunized chickens with ricin and botulinum neurotoxins and monitored laying capacity, IgY concentration, and specific antibody titer over an extended period of 2 yr.

  4. Four molecules of the 33 kDa haemagglutinin component of the Clostridium botulinum serotype C and D toxin complexes are required to aggregate erythrocytes.

    PubMed

    Mutoh, Shingo; Suzuki, Tomonori; Hasegawa, Kimiko; Nakazawa, Yozo; Kouguchi, Hirokazu; Sagane, Yoshimasa; Niwa, Koichi; Watanabe, Toshihiro; Ohyama, Tohru

    2005-12-01

    Normally, large-sized botulinum toxin complexes (L-TC) of serotype C and D are composed of a single neurotoxin, a single non-toxic non-haemagglutinin, two HA-70 molecules, four HA-33 molecules and four HA-17 molecules that assemble to form a 650 kDa L-TC. The 540 and 610 kDa TC species (designated here as L-TC2 and L-TC3, respectively) were purified in addition to the 650 kDa L-TC from the culture supernatants of serotype D strains (D-4947 and D-CB16) and serotype C strains (C-6814 and C-Yoichi). The 650 kDa L-TC from D-4947, D-CB16 and C-6814 showed haemagglutination and erythrocyte-binding activity, but their L-TC2 and L-TC3 species had only binding activity. In contrast, every TC species from C-Yoichi having the C-terminally truncated variant of HA-33 exhibited neither haemagglutination activity nor erythrocyte-binding activity. Four strain-specific HA-33/HA-17 complexes were isolated from the 650 kDa L-TC of each strain. The 650 kDa HA-hybrid L-TCs were reconstituted by various combinations of isolated HA-33/HA-17 complexes and haemagglutination-negative L-TC2 or L-TC3 from each strain. HA-hybrid 650 kDa L-TC, including at least one HA-33/HA-17 complex derived from C-Yoichi, lost haemagglutination activity, leading to the conclusion that the binding of four HA-33 molecules is required for haemagglutination activity of botulinum L-TC. The results of the modelling approach indicated that the structure of a variant C-Yoichi HA-33 molecule reveals clear deformation of the beta-trefoil domain responsible for the carbohydrate recognition site.

  5. A dileucine in the protease of botulinum toxin A underlies its long-lived neuroparalysis: transfer of longevity to a novel potential therapeutic.

    PubMed

    Wang, Jiafu; Zurawski, Tomas H; Meng, Jianghui; Lawrence, Gary; Olango, Weredeselam M; Finn, David P; Wheeler, Larry; Dolly, J Oliver

    2011-02-25

    Blockade of neurotransmitter release by botulinum neurotoxin type A (BoNT(A)) underlies the severe neuroparalytic symptoms of human botulism, which can last a few years. The structural basis for this remarkable persistence remains unclear. Herein, recombinant BoNT(A) was found to match the neurotoxicity of that from Clostridium botulinum, producing persistent cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) and neuromuscular paralysis. When two leucines near the C terminus of the protease light chain of A (LC(A)) were mutated, its inhibition of exocytosis was followed by fast recovery of intact SNAP-25 in cerebellar neurons and neuromuscular transmission in vivo. Deletion of 6-7 N terminus residues diminished BoNT(A) activity but did not alter the longevity of its SNAP-25 cleavage and neuromuscular paralysis. Furthermore, genetically fusing LC(E) to a BoNT(A) enzymically inactive mutant (BoTIM(A)) yielded a novel LC(E)-BoTIM(A) protein that targets neurons, and the BoTIM(A) moiety also delivers and stabilizes the inhibitory LC(E), giving a potent and persistent cleavage of SNAP-25 with associated neuromuscular paralysis. Moreover, its neurotropism was extended to sensory neurons normally insensitive to BoNT(E). LC(E-)BoTIM(A)(AA) with the above-identified dileucine mutated gave transient neuromuscular paralysis similar to BoNT(E), reaffirming that these residues are critical for the persistent action of LC(E)-BoTIM(A) as well as BoNT(A). LC(E)-BoTIM(A) inhibited release of calcitonin gene-related peptide from sensory neurons mediated by transient receptor potential vanilloid type 1 and attenuated capsaicin-evoked nociceptive behavior in rats, following intraplantar injection. Thus, a long acting, versatile composite toxin has been developed with therapeutic potential for pain and conditions caused by overactive cholinergic nerves.

  6. Molecular diversity of Clostridium botulinum and phenotypically similar strains.

    PubMed

    Grenda, T; Kukier, E; Sieradzki, Z; Goldsztejn, M; Kwiatek, K

    2016-12-01

    This study was undertaken to examine phenotypic and genetic features of strains preliminary classified as Clostridium botulinum species. The phenotypic characteristics were assessed with different culture media and biochemical tests. The genetic characterization included detection of botulinum toxin genes by PCR and macrorestriction analysis with SmaI, XhoI and SacII by PFGE (Pulsed-field Gel Electrophoresis). Despite similar biochemical properties of all analysed strains, only 47% of them contained genes determining toxicity specific to C. botulinum species. The most valuable differentiation of C. botulinum and C. botulinum-like strains was obtained after SmaI digestion. The highest affinity was observed among C. botulinum type B profiles which was even up to 100%. It was found 100% of affinity between C. botulinum and C. botulinum-like strains, however, the similarity among C. botulinum and C. botulinum-like was generally lower than 80%.

  7. Efficacy of botulinum toxin type B for the treatment of primary palmar hyperhidrosis: a prospective, open, single-blind, multi-centre study.

    PubMed

    Basciani, Mario; Di Rienzo, Filomena; Bizzarrini, Massimo; Zanchi, Malvina; Copetti, Massimiliano; Intiso, Domenico

    2014-07-01

    Primary palmar hyperhidrosis is a distressing and disabling condition that can produce social, psychological and occupational problems. Although the use of botulinum toxin type A (BoNT-A) has been reported as an efficacious and safe intervention to improve palmar hyperhidrosis, only one study concerned botulinum toxin type B (BoNT-B) in this disorder. The aim of study was to evaluate the efficacy and safety of BoNT-B in treating primary palmar hyperhidrosis. Participants were injected with 5,000 IU of BoNT-B in each palm. Visual analogue test (VAS) to evaluate the intensity of decrease in sweat production, Minor's iodine starch test and measurement of paper towels' weight were used to ascertain palmar sweating at baseline, 4, 12 and 24 weeks after BoNT-B injections by a blind examiner. Thirty-two subjects (12 males, 20 females, mean age 31 ± 11) were enrolled. Significant reduction of palmar sweating was detected after BoNT-B injection: 2.9 ± 1.4, 0.3 ± 0.4, 0.9 ± 0.8, and 2.1 ± 1.5 g (p < 0.001) of paper towels' weight for the right palm at baseline, 4, 12 and 24 weeks; and 2.8 ± 1.7, 0.5 ± 0.6, 0.8 ± 0.7, and 1.8 ± 1.25 g (p < 0.001) at same time, respectively for the left palm. Significant reduction of mean VAS values were also detected after BoNT-B injections: 8.6 ± 1.1, 0.6 ± 0.8, 3.5 ± 2.5, and 7.1 ± 2.4 (p < 0.0001) at baseline, 4, 12 and 24 weeks, respectively. Mild side effects consisting in local pain and hand weakness were observed in 4 (12.5%) subjects. The findings indicated that the use of 5,000 IU BoNT-B injection in each palm was safe and significantly improved the severity of palmar hyperhidrosis.

  8. Expression of an anti-botulinum toxin A neutralizing single-chain Fv recombinant antibody in transgenic tobacco.

    PubMed

    Almquist, Kurt C; McLean, Michael D; Niu, Yongqing; Byrne, Greg; Olea-Popelka, Fernando C; Murrant, Coral; Barclay, Jack; Hall, J Christopher

    2006-03-15

    Botulinum neurotoxins (BoNTs) are the most poisonous substances known and are thus classified as high-risk threats for use as bioterror agents. To examine the potential of transgenic plants as bioreactors for the production of BoNT antidotes, we transformed tobacco with an optimized, synthetic gene encoding a botulinum neurotoxin A (BoNT/A) neutralizing single-chain Fv (scFv) recombinant antibody fragment. In vitro mouse muscle twitch assays demonstrated the functional utility of this scFv extracted from tobacco for neutralizing the paralytic effects of BoNT/A at neuromuscular junctions. Based on the efficiency of the scFv capture process and the dose required to antidote a human being, 1-2 ha of this tobacco could yield up to 4 kg of scFv, which would be enough to contribute to the manufacture of 1,000,000 therapeutic doses of a monoclonal antibody (mAb) cocktail capable of neutralizing the effects of BoNT poisoning. Transgenic plants could provide an inexpensive production platform for expression of multiple mAbs toward the creation of polyclonal therapies (i.e. pooled mAbs) as the next improvement in recombinant antibody therapy.

  9. Preparation of specifically activatable endopeptidase derivatives of Clostridium botulinum toxins type A, B, and C and their applications.

    PubMed

    Sutton, J Mark; Wayne, Jonathan; Scott-Tucker, Anthony; O'Brien, Susan M; Marks, Philip M H; Alexander, Frances C G; Shone, Clifford C; Chaddock, John A

    2005-03-01

    Clostridium botulinum neurotoxins are potently toxic proteins of 150 kDa with specific endopeptidase activity for SNARE proteins involved in vesicle docking and release. Following treatment with trypsin, a fragment of botulinum neurotoxin serotype A that lacks the C-terminal domain responsible for neuronal cell binding, but retains full catalytic activity, can be obtained. Known as the LH(N) fragment, we report the development of a recombinant expression and purification scheme for the isolation of comparable fragments of neurotoxin serotypes B and C. Expressed as maltose-binding protein fusions, both have specific proteolytic sites present between the fusion tag and the light chain to facilitate removal of the fusion, and between the light chain endopeptidase and the H(N) translocation domains to facilitate activation of the single polypeptide. We have also used this approach to prepare a new variant of LH(N)/A with a specific activation site that avoids the need to use trypsin. All three LH(N)s are enzymatically active and are of low toxicity. The production of specifically activatable LH(N)/A, LH(N)/B, and LH(N)/C extends the opportunities for exploitation of neurotoxin fragments. The potential utility of these fragments is discussed.

  10. Clostridium botulinum type D intoxication in a dairy herd in Ontario.

    PubMed

    Martin, Sarah

    2003-06-01

    Thirty-four Holstein cows died after exposure to Clostridium botulinum type D toxin, presumably from contaminated haylage. The presence of type D toxin in ruminal contents was confirmed by mouse inoculation. This is the first confirmation by direct toxin isolation of C. botulinum type D toxin in cattle in North America.

  11. Adeno-associated virus transfer of a gene encoding SNAP-25 resistant to botulinum toxin A attenuates neuromuscular paralysis associated with botulism.

    PubMed

    Raghunath, Arvind; Perez-Branguli, Francesc; Smith, Leonard; Dolly, J Oliver

    2008-04-02

    Advances in viral gene therapy have opened new possibilities for treating a range of motor neuron diseases, but these have not yet been translated into clinically applicable therapies because of difficulties in delivery to susceptible/damaged neurons, ambiguities in the identity of gene(s) implicated, and a paucity of means to quantify any physiological improvement. Most of these hurdles can be overcome by using the neuromuscular paralysis induced by botulinum neurotoxin type A (BoNT/A) as a prototype disease. Furthermore, because human botulism, occasionally fatal, causes prolonged muscle disablement as a result of the intraneuronal persistence of the toxin's SNAP-25 (S25)-cleaving protease, development of a genetic approach could lead to a potential treatment for this debilitating disease. Adeno-associated viral delivery of a cleavage-resistant S25 gene (S25-R198T) to chromaffin cells in vitro yielded exocytotically active S25-R198T that diminished subsequent blockade by BoNT/A of evoked catecholamine release. Evaluation in vivo, by administering this virus into rat spinal cord before injecting BoNT/A, showed a decreased inhibition of acetylcholine release as reflected in elevated retention of neuromuscular transmission. A similar, although smaller, protection of synaptic transmission from the toxin was seen after peripherally injecting the therapeutic virus. Such therapy also curtailed nerve sprouting normally induced by BoNT/A. This first demonstration of the utility of a DNA-based therapy for botulism paves the way for further advances in its treatment and for application to genetic disorders of motor neurons.

  12. Botulinum toxin type A-induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder.

    PubMed

    Bossowska, A; Majewski, M

    2012-01-01

    Botulinum toxin type A (BTX) is a potent neurotoxin, which in recent years has been effectively applied in experimental treatments of many neurogenic disorders of the urinary bladder. BTX is a selective, presynaptically-acting blocking agent of acetylcholine release from nerve terminals what, in turn, leads to the cessation of somatic motor and/or parasympathetic transmission. However, application of this toxin in urological practice is still in the developmental stages and the full mechanism of its action remain elusive. Thus, the present study was aimed at investigating the neurochemical characterization of dorsal root ganglion (DRG) neurons supplying the porcine urinary bladder after BTX treatment. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall in six juvenile female pigs and three weeks later, intramural bladder injections of BTX (100 IU per animal) were carried out in all the animals. After a week, DRG from L1 to Cql were harvested from the pigs and neurochemical characterization of FB+ neurons was performed using double- labeling immunofluorescence technique on 10-microm-thick cryostat sections. BTX injections led to a significant decrease in the number of FB+ neurons containing substance P (SP), calcitonin gene-related peptide (CGRP), calbindin (CB), somatostatin (SOM) and neuronal nitric oxide synthase (nNOS) when compared with that found in the healthy animals (19% vs. 45%, 18% vs. 36%, 0.6% vs. 3%, 0.4 vs. 4% and 0.1% vs. 6%, respectively) These data demonstrated that BTX changed the chemical coding of bladder sensory neurons, and therefore this drug should be taken into consideration when it planning experimental therapy of selected neurogenic bladder disorders.

  13. Botulinum Toxin Type A Injection for Spastic Equinovarus Foot in Children with Spastic Cerebral Palsy: Effects on Gait and Foot Pressure Distribution

    PubMed Central

    Choi, Ja Young; Jung, Soojin; Rha, Dong-wook

    2016-01-01

    Purpose To investigate the effect of intramuscular Botulinum toxin type A (BoNT-A) injection on gait and dynamic foot pressure distribution in children with spastic cerebral palsy (CP) with dynamic equinovarus foot. Materials and Methods Twenty-five legs of 25 children with CP were investigated in this study. BoNT-A was injected into the gastrocnemius (GCM) and tibialis posterior (TP) muscles under the guidance of ultrasonography. The effects of the toxin were clinically assessed using the modified Ashworth scale (MAS) and modified Tardieu scale (MTS), and a computerized gait analysis and dynamic foot pressure measurements using the F-scan system were also performed before injection and at 1 and 4 months after injection. Results Spasticity of the ankle plantar-flexor in both the MAS and MTS was significantly reduced at both 1 and 4 months after injection. On dynamic foot pressure measurements, the center of pressure index and coronal index, which represent the asymmetrical weight-bearing of the medial and lateral columns of the foot, significantly improved at both 1 and 4 months after injection. The dynamic foot pressure index, total contact area, contact length and hind foot contact width all increased at 1 month after injection, suggesting better heel contact. Ankle kinematic data were significantly improved at both 1 and 4 months after injection, and ankle power generation was significantly increased at 4 months after injection compared to baseline data. Conclusion Using a computerized gait analysis and foot scan, this study revealed significant benefits of BoNT-A injection into the GCM and TP muscles for dynamic equinovarus foot in children with spastic CP. PMID:26847306

  14. Quality of life and social isolation in Greek adolescents with primary focal hyperhidrosis treated with botulinum toxin type A: a case series.

    PubMed

    Kouris, Anargyros; Armyra, Kalliopi; Stefanaki, Christina; Christodoulou, Christos; Karimali, Polixeni; Kontochristopoulos, George

    2015-01-01

    Primary hyperhidrosis, although extensively documented in adults, typically has onset that dates back to early childhood. It is an unpleasant and socially disabling problem for the affected child, but little attention has been paid to the disease in adolescents. The objective of the current study was to evaluate the effectiveness of botulinum toxin type A (BTXA) in adolescents with primary palmar and axillary hyperhidrosis and to determine its effect on quality of life and social isolation. Thirty-five individuals (17 girls, 18 boys) with moderate to severe palmar and axillary hyperhidrosis were treated with BTXA (onabotulinum). Patients were examined at baseline and 6 months after treatment. The Hyperhidrosis Disease Severity Scale (HDSS) was used to evaluate disease severity and the Children's Dermatology Life Quality Index (CDLQI) was used to assess quality of life. The University of California at Los Angeles loneliness scale (UCLA version 3) was used to assess personal perception of loneliness and social isolation. The median age of the participants was 14 years, and 48.6% were female. Twenty-one had palmar hyperhidrosis, and 14 had axillary hyperhidrosis. Total CDLQI and social isolation scores decreased significantly after treatment with BTXA (both p < 0.001). There was a significant difference between pre- and post-treatment levels of severity of hyperhidrosis. No statistically significant difference was documented for CDLQI and UCLA scores between boys and girls. Treatment of hyperhidrosis with BTXA resulted in improvement in quality of life, social skills, and activities.

  15. Safety and efficacy of botulinum toxin A for the treatment of spasticity in amyotrophic lateral sclerosis: results of a pilot study.

    PubMed

    Vázquez-Costa, Juan F; Máñez, Inmaculada; Alabajos, Ana; Guevara Salazar, Maricruz; Roda, Cristina; Sevilla, Teresa

    2016-10-01

    Spasticity can be a very disabling problem in some amyotrophic lateral sclerosis (ALS) phenotypes, such as upper motor neuron-dominant ALS (UMN-D ALS) and primary lateral sclerosis (PLS). Our aim is to describe the safety and efficacy of botulinum toxin A (BoTox-A) for improving gait in those ALS phenotypes. UMN-D ALS and PLS outpatients experiencing gait disturbances, secondary to moderate-to-severe spasticity despite optimized oral medication, were offered BoTox-A treatment. Stretching exercises were indicated to complement BoTox-A effect, and ankle-foot orthotics were prescribed when appropriate. Tolerance (muscle strength, disease progression rate) and efficacy (10-m walk test) were measured at baseline and after treatment. Eight out of 122 ALS outpatients were offered BoTox-A treatment. One declined and the other seven were administered BoTox-A in the lower limbs, every 5-8 months. All of them experienced improvement in the clinical outcome and all but one referred subjective improvement. Moreover, after a median follow-up of 16 months and three injections, BoTox-A effect was maintained with no adverse events. This study provides class IV evidence that BoTox-A is safe , and could be beneficial in the short term and long term in a subset of ALS patients with moderate-to-severe spasticity.

  16. Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

    PubMed

    Young, Simon N

    2013-03-01

    Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

  17. Ultrasound-Guided Injection of Botulinum Toxin Type A for Piriformis Muscle Syndrome: A Case Report and Review of the Literature.

    PubMed

    Santamato, Andrea; Micello, Maria Francesca; Valeno, Giovanni; Beatrice, Raffaele; Cinone, Nicoletta; Baricich, Alessio; Picelli, Alessandro; Panza, Francesco; Logroscino, Giancarlo; Fiore, Pietro; Ranieri, Maurizio

    2015-08-10

    Piriformis muscle syndrome (PMS) is caused by prolonged or excessive contraction of the piriformis muscle associated with pain in the buttocks, hips, and lower limbs because of the close proximity to the sciatic nerve. Botulinum toxin type A (BoNT-A) reduces muscle hypertonia as well as muscle contracture and pain inhibiting substance P release and other inflammatory factors. BoNT-A injection technique is important considering the difficult access of the needle for deep location, the small size of the muscle, and the proximity to neurovascular structures. Ultrasound guidance is easy to use and painless and several studies describe its use during BoNT-A administration in PMS. In the present review article, we briefly updated current knowledge regarding the BoNT therapy of PMS, describing also a case report in which this syndrome was treated with an ultrasound-guided injection of incobotulinumtoxin A. Pain reduction with an increase of hip articular range of motion in this patient with PMS confirmed the effectiveness of BoNT-A injection for the management of this syndrome.

  18. Clinical Assessment of the Safety and Effectiveness of Nonablative Fractional Laser Combined with Transdermal Delivery of Botulinum Toxin A in Treating Periocular Wrinkles

    PubMed Central

    Yin, Yue; Wang, Shiping; Li, Tong; Xue, Ping; Yang, Qing; Ma, Qiaoxin

    2016-01-01

    Summary: The upper and lower eyelids are traditionally contraindicated for subcutaneous botulinum toxin A (BTX) injection because of possible complications. We assessed the clinical safety and effectiveness of nonablative fractional laser (NAFL) combined with transdermal delivery of BTX in the treatment of periocular wrinkles. Thirty patients who had periocular wrinkles were treated with 1,565-nm NAFL in combination in the left periocular area and normal saline in the corresponding area of the right eye. VISIA skin detector was used to photograph and compare the changes induced by treatment. We also recorded the comfort level of the patients. All 28 patients could tolerate the pain caused by the laser treatment and showed no apparent discomfort during percutaneous drug delivery. No chromatosis or ptosis of upper eyelids occurred after the treatment. We used VISIA to detect changes at 1 week, 1 month, 3 months, and 6 months, respectively, after the treatment. The periocular wrinkles decreased, and the flabbiness of eyelids was significantly reduced. The upper and lower eyelids are traditionally contraindicated for subcutaneous BTX injection, as it may cause complications. The treatment combining 1,565-nm NAFL and transdermal delivery of BTX can decrease periocular wrinkles and flabbiness while avoiding complications to the greatest extent. None of the 28 patients who had completed the treatment suffered from complications or adverse effects; all were satisfied with the treatment outcome. PMID:27622085

  19. Treatment of painful bladder syndrome/interstitial cystitis with botulinum toxin A: why isn’t it effective in all patients?

    PubMed Central

    Bjorling, Dale E.

    2015-01-01

    Botulinum toxin A (BTA) is currently used to treat a variety of painful disorders, including painful bladder syndrome/interstitial cystitis (PBS/IC). However, BTA is not consistently effective in all patients. This may be due to the disparity of causes of pain, but this may also relate to the processes by which BTA exerts anti-nociceptive effects. This review discusses mechanisms by which BTA may inhibit pain and studies of the use of BTA in PSB/IC patients. It is doubtful that any single treatment will effectively control pain in PBS/IC patients, and it is highly probable that multiple strategies will be required, both within individual patients and across the population of PBS/IC patients. The purpose of this review is to discuss those mechanisms by which BTA acts, with the intent that alternative strategies exploiting these mechanism, or work through alternative pathways, can be identified to more effectively treat pain in PBS/IC patients in the future. PMID:26816853

  20. Botulinum toxin, physical and occupational therapy, and neuromuscular electrical stimulation to treat spastic upper limb of children with cerebral palsy: a pilot study.

    PubMed

    Rodríguez-Reyes, Gerardo; Alessi-Montero, Aldo; Díaz-Martínez, Leticia; Miranda-Duarte, Antonio; Pérez-Sanpablo, Alberto Isaac

    2010-03-01

    Spasticity has been successfully managed with different treatment modalities or combinations. No information is available on the effectiveness or individual contribution of botulinum toxin type A (BTA) combined with physical and occupational therapy and neuromuscular electrical stimulation to treat spastic upper limb. The purpose of this study was to assess the effects of such treatment and to inform sample-size calculations for a randomized controlled trial. BTA was injected into spastic upper limb muscles of 10 children. They received 10 sessions of physical and occupational therapy followed by 10 sessions of neuromuscular electrical stimulation on the wrist extensors (antagonist muscles). Degree of spasticity using the Modified Ashworth scale, active range of motion, and manual function with the Jebsen hand test, were assessed. Meaningful improvement was observed in hand function posttreatment (P = 0.03). Median spasticity showed a reduction trend and median amplitude of wrist range of motion registered an increase; however, neither of these were significant (P > 0.05). There is evidence of a beneficial effect of the combined treatment. Adequate information has been obtained on main outcome-measurement variability for calculating sample size for a subsequent study to quantify the treatment effect precisely.

  1. Survey of practices employed by neurologists for the definition and management of secondary non-response to botulinum toxin in cervical dystonia.

    PubMed

    Ferreira, Joaquim J; Bhidayasiri, Roongroj; Colosimo, Carlo; Marti, Maria Jose; Zakine, Benjamin; Maisonobe, Pascal

    2012-01-01

    Secondary non-response (SNR) to botulinum toxin (BoNT) in cervical dystonia (CD) lacks a universal definition. We conducted a retrospective survey to develop a definition based on clinicians' practice. Fifty-seven neurologists completed a 17-item questionnaire. In defining SNR, insufficiently improved posture was considered to be more relevant (98% of physicians) than insufficiently improved pain (86%). The most frequently used diagnostic test for SNR was the frontalis test (68%); antibody testing was performed by only 13% of physicians. Three consecutive unsuccessful injection cycles were considered the most appropriate indicator of SNR (55% of physicians). Physicians reported that 5.9% (median) of patients treated in 2008 became secondary non-responders to BoNT-A. The most common strategy for SNR was optimization of physiotherapy, considered by 98% of the physicians. On the basis of our findings, SNR can be defined as insufficiently improved posture after ≥3 unsuccessful injection cycles in CD patients previously achieving satisfactory results.

  2. The Efficacy and Safety of Fractional CO2 Laser Combined with Topical Type A Botulinum Toxin for Facial Rejuvenation: A Randomized Controlled Split-Face Study

    PubMed Central

    Zhu, Jie; Ji, Xi; Li, Min; Chen, Xiao-e; Liu, Juan; Zhang, Jia-an; Luo, Dan; Zhou, Bing-rong

    2016-01-01

    Objective. We evaluated synergistic efficacy and safety of combined topical application of Botulinum Toxin Type A (BTX-A) with fractional CO2 laser for facial rejuvenation. Methods. Twenty female subjects were included for this split-face comparative study. One side of each subject's cheek was treated with fractional CO2 plus saline solution, and the other side was treated with fractional CO2 laser plus topical application of BTX-A. Patients received one session of treatment and evaluations were done at baseline, one, four, and twelve weeks after treatment. The outcome assessments included subjective satisfaction scale; blinded clinical assessment; and the biophysical parameters of roughness, elasticity, skin hydration, transepidermal water loss (TEWL), and the erythema and melanin index. Results. BTX-A combined with fractional CO2 laser sides showed higher physician's global assessment score, subject satisfaction score, roughness, skin hydration, and skin elasticity compared to that of fractional CO2 plus saline solution side at 12 weeks after treatment. TEWL and erythema and melanin index showed no significant differences between two sides at baseline, one, four, and twelve weeks after treatment. Conclusion. Topical application of BTX-A could enhance the rejuvenation effect of fractional CO2 laser. PMID:26998485

  3. Correction of post-traumatic anterior open bite by injection of botulinum toxin type A into the anterior belly of the digastric muscle: case report

    PubMed Central

    Park, Yong-Tae; Kim, Seong-Gon; Park, Young-Wook

    2013-01-01

    Post-traumatic anterior open bite can occur as a result of broken balance among the masticatory muscles. The superior hyoid muscle group retracts the mandible downward and contributes to the anterior open bite. Denervation of the digastric muscle by injection of botulinum toxin type A (BTX-A) can reduce the power of the digastric muscle and help to resolve the post-traumatic anterior open bite. A patient with a bilateral angle fracture had an anterior open bite even after undergoing three operations under general anesthesia and rubber traction. Although the open bite showed some improvement by the repeated operation, the occlusion was still unstable six weeks after the initial treatment. To eliminate the residual anterior open bite, BTX-A was injected into the anterior belly of the digastric muscle. Following injection of BTX-A, the anterior open bite showed immediate improvement. Complication and relapse were not observed during follow-up. Long-standing post-traumatic open bite could be successfully corrected by injection of BTX-A into the anterior belly of the digastric muscle without complication. PMID:24471041

  4. Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects☆☆☆

    PubMed Central

    Tedesco, Ana Paula; Martins, Juliana Saccol; Nicolini-Panisson, Renata D’Agostini

    2014-01-01

    Objective To report on the experience of injections of botulinum toxin A (BTA) in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS) level V. Methods This was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations), in which the basic aim was to look for adverse effects. Results The mean number of application sessions per patient was three, and the mean age at the time of each injection was 4 + 6 years (range: 1.6–13 years). The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month. Conclusion The absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia. PMID:26229827

  5. Ultrasound-Guided Injection of Botulinum Toxin Type A for Piriformis Muscle Syndrome: A Case Report and Review of the Literature

    PubMed Central

    Santamato, Andrea; Micello, Maria Francesca; Valeno, Giovanni; Beatrice, Raffaele; Cinone, Nicoletta; Baricich, Alessio; Picelli, Alessandro; Panza, Francesco; Logroscino, Giancarlo; Fiore, Pietro; Ranieri, Maurizio

    2015-01-01

    Piriformis muscle syndrome (PMS) is caused by prolonged or excessive contraction of the piriformis muscle associated with pain in the buttocks, hips, and lower limbs because of the close proximity to the sciatic nerve. Botulinum toxin type A (BoNT-A) reduces muscle hypertonia as well as muscle contracture and pain inhibiting substance P release and other inflammatory factors. BoNT-A injection technique is important considering the difficult access of the needle for deep location, the small size of the muscle, and the proximity to neurovascular structures. Ultrasound guidance is easy to use and painless and several studies describe its use during BoNT-A administration in PMS. In the present review article, we briefly updated current knowledge regarding the BoNT therapy of PMS, describing also a case report in which this syndrome was treated with an ultrasound-guided injection of incobotulinumtoxin A. Pain reduction with an increase of hip articular range of motion in this patient with PMS confirmed the effectiveness of BoNT-A injection for the management of this syndrome. PMID:26266421

  6. Development of a quail embryo model for the detection of botulinum neurotoxin activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clostridium botulinum is a ubiquitous microorganism that under anaerobic conditions produces botulinum neurotoxins. In regards to both food-borne illness and the potential use of botulinum toxin as a biological weapon, the capability to assess the amount of toxin in a food or environmental sample e...

  7. Use of Botulinum Toxin A in the Treatment of Lower Urinary Tract Disorders: A Review of the Literature

    PubMed Central

    Moore, David C.; Cohn, Joshua A.; Dmochowski, Roger R.

    2016-01-01

    Botulinum neurotoxin (BoNT) is used to treat a variety of ailments, and its therapeutic application in lower urinary tract disorders (LUTDs) is well studied. Robust evidence supporting the efficacy and tolerability of BoNT in the treatment of neurogenic detrusor overactivity (NDO) and non-neurogenic overactive bladder (OAB) has led to regulatory approval for these conditions. Use of BoNT in the treatment of interstitial cystitis/bladder pain syndrome, chronic pelvic pain, and detrusor sphincter dyssynergia has demonstrated some promise, but is still evolving and off-label for these indications. Trials to date do not support the use of BoNT for benign prostatic hyperplasia. This comprehensive review outlines the mechanisms of BoNT in the treatment of LUTDs in adults and presents background and updated data examining the efficacy and adverse events associated with the use of BoNT in common urologic applications. PMID:27023601

  8. Evaluation of quail and chicken embryos for the detection of botulinum toxin serotypes A, B, E and F activity.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Comparison of quail (Coturnix japonica) and chicken (Gallus domesticus) embryos for the detection of BoNT/A activity was conducted using equal dosages of toxin/g of embryo (quail at 7 g and chickens at 48 g). Quail embryos were injected at 0, 0.5 to 50 ng adn chicken embryos at 0, 3.4 to 342 ng and...

  9. Detection of Protein Toxins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have focused on ricin, shiga-like toxin, botulinum neurotoxin (BoNT), and staphylococcal enterotoxin A (SEA), developing sensitive test methods for toxins and marker compounds in food matrices. Although animal models provide the best means for risk assessment, especially for crude toxins in compl...

  10. Historical and current perspectives on Clostridium botulinum diversity.

    PubMed

    Smith, Theresa J; Hill, Karen K; Raphael, Brian H

    2015-05-01

    For nearly one hundred years, researchers have attempted to categorize botulinum neurotoxin-producing clostridia and the toxins that they produce according to biochemical characterizations, serological comparisons, and genetic analyses. Throughout this period the bacteria and their toxins have defied such attempts at categorization. Below is a description of both historic and current Clostridium botulinum strain and neurotoxin information that illustrates how each new finding has significantly added to the knowledge of the botulinum neurotoxin-containing clostridia and their diversity.

  11. Mechanism of botulinum toxin a neurotoxicity: Channel formation and protein phosphorylation. Final report, 30 April 1993-31 January 1997

    SciTech Connect

    Montal, M.

    1997-03-01

    A unique contribution of this program is the discovery of potentiation of botulinum neurotoxin (BoTx) A protease activity by tyrosine phosphorylation. This key finding underscores the requirement to screen for potential blockers using the pharmacologically relevant target, namely tyrosine phosphorylated neurotoxin, presumably the biologically active form within the cells. A most exciting outcome is the ability to design peptides that selectively block neurotransmitter release. The proteolytic products of the BoTx activity have proved to be instrumental in providing clues about the secretory vesicle fusion process. These peptides are suitable mimics of the neurotoxin itself, displaying effective inhibitory activity on transmitter release by inhibiting vesicle docking and thereby disabling the fusion machinery. Peptides designed along these principles may find clinical application as BoTx substitutes in the treatment or management of disorders associated with involuntary muscle spasms. A major finding is the identification of an ion channel-forming motif in BoTxA heavy chain. The ion channel activity of BoTx may be abrogated by identifying effective open channel blockers, lending credence to the concept that open channel blockers may be a single class of drugs effective against all BoTxs isoforms. The potency of such agents may, in principle, be augmented by combining active compounds against both the protease and channel activities of the neurotoxin which are considered necessary for its neurotoxicity.

  12. Development and Partial Characterization of High-affinity Monoclonal Antibodies for Botulinum Toxin Type A and their use in Analysis of Milk by Sandwich ELISA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Botulinum neurotoxins (BoNT), produced by the anaerobic bacterium Clostridium botulinum, cause severe neuroparalytic disease and are considered the most toxic biological agents known. While botulism is rare in the US, it often is fatal if not treated quickly, and recovery is long, requiring intensiv...

  13. Pore-forming activity of clostridial binary toxins.

    PubMed

    Knapp, O; Benz, R; Popoff, M R

    2016-03-01

    Clostridial binary toxins (Clostridium perfringens Iota toxin, Clostridium difficile transferase, Clostridium spiroforme toxin, Clostridium botulinum C2 toxin) as Bacillus binary toxins, including Bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. Clostridial binary toxins induce actin cytoskeleton disorganization through mono-ADP-ribosylation of globular actin and are responsible for enteric diseases. Clostridial and Bacillus binary toxins share structurally and functionally related binding components which recognize specific cell receptors, oligomerize, form pores in endocytic vesicle membrane, and mediate the transport of the enzymatic component into the cytosol. Binding components retain the global structure of pore-forming toxins (PFTs) from the cholesterol-dependent cytotoxin family such as perfringolysin. However, their pore-forming activity notably that of clostridial binding components is more related to that of heptameric PFT family including aerolysin and C. perfringens epsilon toxin. This review focuses upon pore-forming activity of clostridial binary toxins compared to other related PFTs. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.

  14. Clinical Characteristics and Response to Long-Term Botulinum Toxin Type A Therapy in Patients with Cervical Dystonia at a Neurology Clinic

    PubMed Central

    ŞEN, Aysu; SOYSAL, Aysun; ARPACI, Baki

    2014-01-01

    Introduction To determine the demographic and clinical characteristics and response to botulinum toxin type A (BoNT-A) therapy in patients with cervical dystonia (CD). Method A retrospective analysis of the detailed medical records of the patients with CD, followed up at our Botulinum Toxin Outpatient Clinic from 1998 to 2012, was performed. The treatment data were compared between the patients with primary CD and those with secondary CD; between patients receiving BoNT-A treatment for more than 5 years and less than five years, and between first applications and last applications. Results Fifty-seven patients (56.15% women) with CD were included in this study. The mean age was 41.01±13.42 years, the mean age at symptom onset was 32.93±15.45 years, and the mean dystonia duration was 8.10±8.5 years. The interval between onset of symptom and first BoNT-A treatment was 5.94±9.06 years, the duration of BoNT-A treatment was 36.13±29.17 months, and the number of applications was 8.48±6.23 in 45 patients with CD who were under treatment with BoNT-A for more than 1 year and had received at least three injections before. There was no difference between the patients with primary and secondary CD in terms of treatment results. The injection interval of the patients receiving BoNT-A treatment for more than 5 years and less than 5 years was 18.37±5.10 and 14.43±2.36 weeks, respectively (p=.001). There were no differences in the other treatment values. The mean doses were 559.00±147.60 vs. 681.66±188.09 units (p=.0001), the durations of improvement were 11.82±2.71 vs. 13.00±4.00 weeks (p=.014), the response scores were 2.71±.3 vs. 3.02±.5 (p=.002), the response ratings were 64.66%±16.18 vs. 71.22%±17.29 (p=.001), and the numbers of muscles applied were 3.15±1.16 vs. 3.51±0.99 (p=.012) in the first and last applications, respectively. Conclusion There were no differences between the response of the patients with primary and secondary CD. Our results showed a

  15. Consensus panel's assessment and recommendations on the use of 3 botulinum toxin type A products in facial aesthetics.

    PubMed

    Lorenc, Z Paul; Kenkel, Jeffrey M; Fagien, Steven; Hirmand, Haideh; Nestor, Mark S; Sclafani, Anthony P; Sykes, Jonathan M; Waldorf, Heidi A

    2013-03-01

    In this summary article, the authors discuss the characteristics of abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA. With 3 neuromodulators available in the US market, comparisons between and among products will invariably be made, so arguments for the most effective facial aesthetic uses of each neuromodulator are presented. Topics addressed in this article include patient expectations, toxin reconstitution and preparation, patient positioning, differences among products, the role of complexing proteins, and dosing and injection strategies. Recommendations are also provided by treatment area.

  16. Pentavalent replicon vaccines against botulinum neurotoxins and tetanus toxin using DNA-based Semliki Forest virus replicon vectors

    PubMed Central

    Yu, YunZhou; Liu, Si; Ma, Yao; Gong, Zheng-Wei; Wang, Shuang; Sun, Zhi-Wei

    2014-01-01

    The clostridial neurotoxin (CNT) family includes botulinum neurotoxin (BoNT), serotypes A, B, E, and F of which can cause human botulism, and tetanus neurotoxin (TeNT), which is the causative agent of tetanus. This suggests that the greatest need is for a multivalent or multiagent vaccine that provides protection against all 5 agents. In this study, we investigated the feasibility of generating several pentavalent replicon vaccines that protected mice against BoNTs and TeNT. First, we evaluated the potency of individual replicon DNA or particle vaccine against TeNT, which induced strong antibody and protective responses in BALB/c mice following 2 or 3 immunizations. Then, the individual replicon TeNT vaccines were combined with tetravalent BoNTs vaccines to prepare 4 types of pentavalent replicon vaccines. These replicon DNA or particle pentavalent vaccines could simultaneously and effectively induce antibody responses and protect effects against the 5 agents. Finally, a solid-phase assay showed that the sera of pentavalent replicon formulations-immunized mice inhibited the binding of THc to the ganglioside GT1b as the sera of individual replicon DNA or particle-immunized mice. These results indicated these pentavalent replicon vaccines could protect against the 4 BoNT serotypes and effectively neutralize and protect the TeNT. Therefore, our studies demonstrate the utility of combining replicon DNA or particle vaccines into multi-agent formulations as potent pentavalent vaccines for eliciting protective responses against BoNTs and TeNT. PMID:25424795

  17. Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential.

    PubMed

    Meng, Jianghui; Wang, Jiafu; Lawrence, Gary; Dolly, J Oliver

    2007-08-15

    Calcitonin-gene-related peptide (CGRP), a potent vasodilator that mediates inflammatory pain, is elevated in migraine; nevertheless, little is known about its release from sensory neurons. In this study, CGRP was found to occur in the majority of neurons from rat trigeminal ganglia, together with the three exocytotic SNAREs [SNAP25, syntaxin 1 and the synaptobrevin (Sbr, also known as VAMP) isoforms] and synaptotagmin. Ca(2+)-dependent CGRP release was evoked with K(+)-depolarisation and, to lower levels, by capsaicin or bradykinin from neurons that contain the vanilloid receptor 1 and/or bradykinin receptor 2. Botulinum neurotoxin (BoNT) type A cleaved SNAP25 and inhibited release triggered by K(+) > bradykinin > capsaicin. Unlike BoNT type D, BoNT type B did not affect exocytosis, even though the neurons possess its receptor and Sbr II and Sbr III got proteolysed (I is resistant in rat) but, in mouse neurons, it additionally cleaved Sbr I and blocked transmitter release. Sbr I and II were found in CGRP-containing vesicles, and each was shown to separately form a SNARE complex. These new findings, together with punctate staining of Sbr I and CGRP in neurites, implicate isoform Sbr I in exocytosis from large dense-core vesicles together with SNAP25 (also, probably, syntaxin 1 because BoNT type C1 caused partial cleavage and inhibition); this differs from Sbr-II-dependent release of transmitters from small synaptic vesicles. Such use of particular Sbr isoform(s) by different neurons raises the functional implications for other cells previously unrecognised.

  18. Protocol for a prospective observational study of cortical lower urinary tract control changes following intradetrusor injection of botulinum toxin-A in patients with multiple sclerosis

    PubMed Central

    Elizondo, Rodolfo A; Karmonik, Christof; Boone, Timothy B; Khavari, Rose

    2017-01-01

    Introduction Multiple sclerosis (MS) is a severe debilitating disease that affects patients' quality of life. Up to 90% of patients with MS will develop lower urinary tract dysfunction within the first 18 years of the disease. If oral pharmacotherapy with anticholinergics, behavioural modifications and pelvic floor physical therapy are unsuccessful, intradetrusor injection of botulinum toxin-A (OnaBotA; Botox Allergan, Dublin, Ireland) is a highly effective option for these patients. The local effects of OnaBotA are well understood, but not much is known of its afferent/sensory effects while treating the end organ. Our study will use functional MRI (fMRI) and task-related blood oxygen level-dependent signals to evaluate patients with MS and neurogenic detrusor overactivity (NDO) prior to, and after, intradetrusor injection of OnaBotA with simultaneous urodynamic evaluation. Urinary concentration of brain-derived neurotrophic factor and nerve growth factor will also be collected since it has been shown that patients with an overactive bladder have higher concentrations of these neuropeptides. Methods and analysis Female patients with MS and lower urinary tract symptoms who previously have undergone urodynamic screening and are refractory to conservative and oral pharmacotherapy management for NDO and are interested in OnaBotA intradetrusor injection will be invited to participate in the study. An fMRI will be performed preintradetrusor injection and postintradetrusor injection of OnaBotA with simultaneous MRI compatible with material urodynamics. Images will be collected and analysed accordingly. Ethics and dissemination All of the patients are properly consented before enrolling in this study that has been previously approved by the Institutional Review Board. Results of neural connectivity activation will be presented at national and international meetings and published in scholarly journals. PMID:28159850

  19. Botulinum Toxin Type A and the Prevention of Hypertrophic Scars on the Maxillofacial Area and Neck: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Xiao, Wen-lin; Xu, Yao-xiang

    2016-01-01

    Background The purpose of the meta-analysis was to evaluate the efficiency of therapeutic botulinum toxin type A (BTX-A) in the prevention of maxillofacial and neck scars. Methods and Findings Information came from the following electronic databases: Medline, PubMed, Cochrane Library, and EMBASE (time was ended by August 31, 2015) to retrieve RCTs evaluating the effect of the BTX-A for hypertrophic scar on the maxillofacial or neck. All languages were included as long as they met the inclusion criteria. Here the effects of BTX-A were evaluated by comparing the width of the scar, patient satisfaction, and the visual analysis scores (VAS), respectively. Pooled weighted mean differences (WMDs), pooled odds ratios (ORs), and 95% confidence intervals (CI) were calculated. Nine RCTs covering a total of 539 patients were included. A statistically significant difference in scar width was identified between the BTX-A group and control group (non-BTX-A used) (WMD = -0.41, 95% CI = -0.68 to -0.14, P = 0.003). A statistically significant difference in patient satisfaction was observed between the BTX-A group and control group (OR = 25.76, 95% CI = 2.58 to 256.67, P = 0.006). And in patients regarding visual analysis scores (VAS), a statistically significant difference was also observed between the BTX-A group and control group (WMD = 1.30, 95% CI = 1.00 to 1.60, P < 0.00001). Conclusions This meta-analysis evaluates the efficacy of the BTX-A and confirms that BTX-A is a suitable potential therapy for the prevention of hypertrophic scars in patients in the maxillofacial and neck areas. PMID:26985661