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Sample records for botulinum c2 toxin

  1. BOTULINUM TOXIN

    PubMed Central

    Nigam, P K; Nigam, Anjana

    2010-01-01

    Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C1, C2, D, E, F and G). All serotypes interfere with neural transmission by blocking the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, causing muscle paralysis. The weakness induced by injection with botulinum toxin A usually lasts about three months. Botulinum toxins now play a very significant role in the management of a wide variety of medical conditions, especially strabismus and focal dystonias, hemifacial spasm, and various spastic movement disorders, headaches, hypersalivation, hyperhidrosis, and some chronic conditions that respond only partially to medical treatment. The list of possible new indications is rapidly expanding. The cosmetological applications include correction of lines, creases and wrinkling all over the face, chin, neck, and chest to dermatological applications such as hyperhidrosis. Injections with botulinum toxin are generally well tolerated and side effects are few. A precise knowledge and understanding of the functional anatomy of the mimetic muscles is absolutely necessary to correctly use botulinum toxins in clinical practice. PMID:20418969

  2. 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

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

    PubMed

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

    2016-01-01

    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. Adenosine diphosphate-ribosylation of G-actin by botulinum C2 toxin increases endothelial permeability in vitro.

    PubMed Central

    Suttorp, N; Polley, M; Seybold, J; Schnittler, H; Seeger, W; Grimminger, F; Aktories, K

    1991-01-01

    The endothelial cytoskeleton is believed to play an important role in the regulation of endothelial permeability. We used botulinum C2 toxin to perturb cellular actin and determined its effect on the permeability of endothelial cell monolayers derived from porcine pulmonary arteries. The substrate for botulinum C2 toxin is nonmuscle monomeric actin which becomes ADP-ribosylated. This modified actin cannot participate in actin polymerization and, in addition, acts as a capping protein. Exposure of endothelial cell monolayers to botulinum C2 toxin resulted in a dose- (3-100 ng/ml) and time-dependent (30-120 min) increase in the hydraulic conductivity and decrease in the selectivity of the cell monolayers. The effects of C2 toxin were accompanied by a time- and dose-dependent increase in ADP-ribosylatin of G-actin. G-Actin content increased and F-actin content decreased time- and dose-dependently in C2 toxin-treated endothelial cells. Phalloidin which stabilizes filamentous actin prevented the effects of botulinum C2 toxin on endothelial permeability. Botulinum C2 toxin induced interendothelial gaps. The effects occurred in the absence of overt cell damage and were not reversible within 2 h. The data suggest that the endothelial microfilament system is important for the regulation of endothelial permeability. Images PMID:2022729

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

    PubMed Central

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

    2016-01-01

    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. PMID:27043629

  6. 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; Tehran, Domenico Azarnia; Montecucco, Cesare; Barth, Holger

    2016-01-01

    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. PMID:27043629

  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. 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-guided botulinum toxin Treatment; ...

  9. Botox (Botulinum Toxin)

    MedlinePlus

    ... people when there are many effective and safe cosmetic procedures that can temporarily reduce a very prominent ... form of botulinum toxin is Type A (Botox® Cosmetic, Allergan, Inc). Botulinum toxin, what we will now ...

  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. PMID:26449577

  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. Functional Characterization of an Extended Binding Component of the Actin-ADP-Ribosylating C2 Toxin Detected in Clostridium botulinum Strain (C) 2300 ▿

    PubMed Central

    Sterthoff, Charlott; Lang, Alexander E.; Schwan, Carsten; Tauch, Andreas; Aktories, Klaus

    2010-01-01

    Clostridium botulinum C2 toxin consists of the binding component C2II and the enzyme component C2I, which ADP-ribosylates G-actin of eukaryotic cells. Trypsin-activated C2II (C2IIa) forms heptamers that mediate cell binding and translocation of C2I from acidic endosomes into the cytosol of target cells. By genome sequencing of C. botulinum strain (C) 2300, we found that C2II from this strain carries a C-terminal extension of 129 amino acids, unlike its homologous counterparts from strains (C) 203U28, (C) 468, and (D) 1873. This extension shows a high similarity to the C-terminal receptor-binding domain of C2II and is presumably the result of a duplication of this domain. The C2II extension facilitates the binding to cell surface receptors, which leads to an increased intoxication efficiency compared to that of C2II proteins from other C. botulinum strains. PMID:20145093

  13. 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

  14. Effect of disruption of actin filaments by Clostridium botulinum C2 toxin on insulin secretion in HIT-T15 cells and pancreatic islets.

    PubMed Central

    Li, G; Rungger-Brändle, E; Just, I; Jonas, J C; Aktories, K; Wollheim, C B

    1994-01-01

    To examine their role in insulin secretion, actin filaments (AFs) were disrupted by Clostridium botulinum C2 toxin that ADP-ribosylates G-actin. Ribosylation also prevents polymerization of G-actin to F-actin and inhibits AF assembly by capping the fast-growing end of F-actin. Pretreatment of HIT-T15 cells with the toxin inhibited stimulated insulin secretion in a time- and dose-dependent manner. The toxin did not affect cellular insulin content or nonstimulated secretion. In static incubation, toxin treatment caused 45-50% inhibition of secretion induced by nutrients alone (10 mM glucose + 5 mM glutamine + 5 mM leucine) or combined with bombesin (phospholipase C-activator) and 20% reduction of that potentiated by forskolin (stimulator of adenylyl cyclase). In perifusion, the stimulated secretion during the first phase was marginally diminished, whereas the second phase was inhibited by approximately 80%. Pretreatment of HIT cells with wartmannin, a myosin light chain kinase inhibitor, caused a similar pattern of inhibition of the biphasic insulin release as C2 toxin. Nutrient metabolism and bombesin-evoked rise in cytosolic free Ca2+ were not affected by C2 toxin, indicating that nutrient recognition and the coupling between receptor activation and second messenger generation was not changed. In the toxin-treated cells, the AF web beneath the plasma membrane and the diffuse cytoplasmic F-actin fibers disappeared, as shown both by staining with an antibody against G- and F-actin and by staining F-actin with fluorescent phallacidin. C2 toxin dose-dependently reduced cellular F-actin content. Stimulation of insulin secretion was not associated with changes in F-actin content and organization. Treatment of cells with cytochalasin E and B, which shorten AFs, inhibited the stimulated insulin release by 30-50% although differing in their effects on F-actin content. In contrast to HIT-T15 cells, insulin secretion was potentiated in isolated rat islets after disruption of

  15. Botulinum toxin for pain.

    PubMed

    Casale, Roberto; Tugnoli, Valeria

    2008-01-01

    Botulinum toxin (BTX) injection is being increasingly used 'off label' in the management of chronic pain. Data support the hypothesis of a direct analgesic effect of BTX, different to that exerted on muscle. Although the pain-reducing effect of BTX is mainly due to its ability to block acetylcholine release at the synapse, other effects on the nervous system are also thought to be involved. BTX affects cholinergic transmission in both the somatic and the autonomic nervous systems. Proposed mechanisms of action of BTX for pain relief of trigger points, muscular spasms, fibromyalgia and myofascial pain include direct action on muscle and indirect effects via action at the neuromuscular junction. Invitro and invivo data have shown that BTX has specific antinociceptive activity relating to its effects on inflammation, axonal transport, ganglion inhibition, and spinal and suprasegmental level inhibition. Our review of the mechanisms of action, efficacy, administration techniques and therapeutic dosage of BTX for the management of chronic pain in a variety of conditions shows that although muscular tone and movement disorders remain the most important therapeutic applications for BTX, research suggests that BTX can also provide benefits related to effects on cholinergic control of the vascular system, autonomic function, and cholinergic control of nociceptive and antinociceptive systems. Furthermore, it appears that BTX may influence the peripheral and central nervous systems. The therapeutic potential of BTX depends mainly on the ability to deliver the toxin to the target structures, cholinergic or otherwise. Evidence suggests that BTX can be administered at standard dosages in pain disorders, where the objective is alteration of muscle tone. For conditions requiring an analgesic effect, the optimal therapeutic dosage of BTX remains to be defined. PMID:18095750

  16. Botulinum Toxin in Pediatric Neurology

    PubMed Central

    Abdallah, Enas Abdallah Ali

    2015-01-01

    Botulinum neurotoxins are natural molecules produced by anaerobic spore-forming bacteria called Clostradium boltulinum. The toxin has a peculiar mechanism of action by preventing the release of acetylcholine from the presynaptic membrane. Consequently, it has been used in the treatment of various neurological conditions related to muscle hyperactivity and/or spasticity. Also, it has an impact on the autonomic nervous system by acting on smooth muscle, leading to its use in the management of pain syndromes. The use of botulinum toxin in children separate from adults has received very little attention in the literature. This review presents the current data on the use of botulinum neurotoxin to treat various neurological disorders in children. PMID:27335961

  17. 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

  18. Botulinum toxin: The Midas touch.

    PubMed

    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

  19. [Use of botulinum toxin in strabismus].

    PubMed

    Wabbels, B

    2016-07-01

    Botulinum toxin can be a useful tool for treating acute sixth nerve palsy and excessive eye deviations due to unstable Graves' disease, when surgery is not yet possible. The diagnostic injection for estimation of possible postoperative double vision also makes sense. In convergence spasms, periocular botulinum toxin injections can be a therapeutic option. Botulinum toxin is not a first line option in infantile esotropia without binocularity or in adult horizontal strabismus. Side effects include ptosis and vertical deviations. PMID:27369733

  20. [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. PMID:19576479

  1. [Treatment of wrinkles with botulinum toxin].

    PubMed

    Lanzl, I; Merté, R-L

    2007-09-01

    The use of botulinum toxin A for the treatment of wrinkles is increasing. Botulinum toxin A inhibits exocytosis of acetylcholine from 3 to 12 months, depending on the target tissue. Low-dose botulinum toxin A is used to smooth hyperkinetic facial lines. This is especially successful in the upper facial parts, since the target muscles (procerus, corrugator supracilii, frontalis, orbicularis oculi) all directly overlie the osseous structures of the face. This is not the case for the lower facial parts, and more side effects are encountered when treating, for example, wrinkles around the mouth. Contraindications to the use of botulinum toxin A are diseases affecting neuromuscular signal transduction, allergic reactions to components of the solution, therapy with aminoglycosides or acetylsalicylic acid prior to treatment, infections in the planned treatment area, and pregnancy and lactation. Alternative and complementary treatments include erbium-YAG or CO2 laser, as well as augmentation and surgical plastic procedures. PMID:17823803

  2. Botulinum toxin. From poison to medicine.

    PubMed Central

    Davis, L E

    1993-01-01

    Although thousands of people in the world each year continue to be poisoned with botulinum toxin-food-borne, infantile, or wound botulism-the neurotoxin is now sufficiently understood to allow it to be used as a medicinal agent to paralyze specific muscles, giving temporary symptomatic relief from a variety of dystonic neurologic disorders. I review some of the epidemiologic, clinical, and pathophysiologic aspects of botulinum toxin and how the neurotoxin may act as a poison or a medicine. Images PMID:8470380

  3. 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. PMID:3247565

  4. 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. PMID:26879873

  5. Botulinum toxin (botox) chemodenervation for facial rejuvenation.

    PubMed

    Carruthers, J; Carruthers, A

    2001-05-01

    A positive attitude toward life at any age is now seen to be consistent with inclusion in all societal activities. A mere increase in years is no longer enough reason for "ageism." Botulinum Toxin (Botox) aesthetic treatments, because of their outstanding effectiveness and safety, can continue to play a positive role in the rebuttal of "ageism." PMID:11457686

  6. Botulinum Toxin in Neurogenic Detrusor Overactivity

    PubMed Central

    Ferreira, Rúiter Silva; Rassi, Mauricio Carneiro

    2012-01-01

    Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks) and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life. PMID:23094220

  7. [Treatment of spasticity with botulinum toxin].

    PubMed

    Mémin, B; Pollak, P; Hommel, M; Perret, J

    1992-01-01

    Spasticity following upper motor neuron lesion can be alleviated by few treatments such as physiotherapy, drugs and neurosurgery. However, they all have side effects, limitations or lack of selectivity. We tentatively used the paralyzing effects of botulinum toxin. Since the late 1970's the use of this toxin has increased and it has been extended to numerous muscles and diseases of various causes. In this pilot and open study we use botulinum toxin in spasticity. Eight patients (7 stroke, 1 head injury) with longstanding severe spasticity (minimum: 12 months, maximum: 15 years) were included. Spasticity greatly interfered with their activity in daily life and was resistant to oral antispastic medications. Six patients suffered from pain and 4 had cutaneous lesions especially maceration of the palm of the hand. A-botulinum toxin was injected with a 30-gauged needle. The sites chosen for injection were the following muscles: biceps brachii, brachioradialis, flexor digitorum, flexor carpi, tibialis anterior, flexor digitorum longus. Altogether 41 injections were performed. There were no side effects. Spasticity was improved in all patients. Five patients reported significant pain relief on a visual analogical scale. Most of them reported a benefit in their limb tone and referred to subjective improvement in the activity of daily life and nursing. The beneficial effects of one injection lasted more than 5 months. Seven patients received a second course of treatment. A double-blind study of botulinum toxin in spasticity is to be undertaken to assess its effectiveness and safety when prescribed in the required dose to treat this condition. PMID:1604136

  8. 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

  9. 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. PMID:26780946

  10. Overview of Botulinum Toxins for Aesthetic Uses.

    PubMed

    Gart, Michael S; Gutowski, Karol A

    2016-07-01

    Botulinum toxin type A (BTA) can be used for facial aesthetics. The 3 currently available BTA types include onabotulinumtoxinA (Botox; Botox Cosmetic, Allergan, Irvine, CA), abobotulinumtoxinA (Dysport; Ipsen, Ltd, Berkshire, UK), and incobotulinumtoxinA (Xeomin; Merz Pharmaceuticals, Frankfurt, Germany). The mechanism of action and clinical uses for treatment of dynamic lines of the forehead, brow, glabella, lateral orbit, nose, and lips are presented, as well as treatment of masseter hypertrophy, platysmal bands, and improvements of the perioral region. Specific BTA injection sites and suggested doses are presented. PMID:27363760

  11. 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

  12. 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

  13. 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. PMID:25956528

  14. Botulinum toxin type A for the management of glabellar rhytids

    PubMed Central

    Tremaine, Anne Marie; McCullough, Jerry L

    2010-01-01

    There is an increasing demand for minimally-invasive cosmetic procedures to arrest the aging process. Botulinum toxin type A injections are the most commonly used nonsurgical cosmetic procedures in the United States. There has been research spanning over two decades dedicated to safety, efficacy, dosing, and complications of botulinum toxin type A. There are now two Food and Drug Administration (FDA) approved botulinum toxin type A options in the United States: Botox® and Dysport™, with new advances being made in the field. PMID:21437056

  15. Treatment of Nystagmus in Brainstem Cavernous Malformation with Botulinum Toxin

    PubMed Central

    Fredrick, Douglas; Steinberg, Gary K; Liao, Yaping J

    2016-01-01

    We report a long-term eye movement study of a 68-year-old female with pontomedullary junction cavernous malformation whose dysconjugate nystagmus was treated with retrobulbar botulinum toxin A injections. Sequential, bilateral retrobulbar injections of botulinum toxin A were performed. Injections immediately decreased oscillopsia and nystagmus, and improved visual acuities. One to three months following injection, three-dimensional infrared oculography measured a significant 39-100% (P = 0.001) decrease in nystagmus amplitudes at multiple dimensions. This improvement diminished by six months in the right eye but sustained for about one year in the left eye. Over two years, botulinum toxin A injections were performed twice in the left eye and five times in the right eye. Our study supported the safe and effective use of repetitive retrobulbar botulinum toxin A injections in symptomatic nystagmus that failed medical therapy. PMID:27182467

  16. 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

  17. The setting of a botulinum toxin treatment service.

    PubMed

    Cavallini, Maurizio

    2014-05-01

    The administration of botulinum toxin is an activity performed mostly by a specialist service for the management of a wide range of neurological conditions. For therapeutic purposes botulinum toxin type A is used, although in selected patients who develop antibodies specific for the serotype A botulinum toxin B can be used for the treatment. Hereby, we describe the organizational arrangements for the botulinum toxin treatment service at the Department of Neurology of Hospital Cardinal Massaia based in Asti. The diseases most frequently treated are movement disorders (primary and secondary focal dystonia, blepharospasm, facial emispasmo) spasticity and, more recently, chronic migraine. In particular, the latter application is one of the most promising expansions of the use of this drug in the few past years, although a larger number of patients are required to determine its efficacy and the related tolerability profile. PMID:24867836

  18. [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. PMID:18516972

  19. 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. PMID:26559824

  20. 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

  1. 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. PMID:27486290

  2. 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.

  3. 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 ...

  4. An alternative treatment approach in tetanus: Botulinum toxin.

    PubMed

    Demir, Nazlim Aktug; Sumer, Sua; Ural, Onur; Ozturk, Serefnur; Celik, Jale Bengi

    2015-01-01

    Tetanus is a preventable infectious disease caused by tetanus toxin (tetanospasmin) produced by Clostridium tetani. Tetanus is still an important health problem in low- and middle-income countries (LMICs). Botulinum toxin administration is a treatment approach that has been used in recent years to reduce rigidity and spasms in tetanus patients. This case report focuses on its efficacy. PMID:25234426

  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. [Treatment of blepharospasm with botulinum toxin].

    PubMed

    Pikielny, R T; Micheli, F E; Fernández Pardal, M M; Casas Parera, I; Giannaula, R J; Gatto, M

    1990-01-01

    Blepharospasm is a relatively frequent cranial dystonia which may be seen either alone or related to orofacial-mandibular dystonia (Meige's syndrome). In its maximum degree it can cause functional blindness.Twelve patients with blepharospasm (4 essential and 8 Meige's syndrome) who had been previously treated unsuccessfully with drugs (trihexyphenidyl, biperiden, carbamazepine, lithium, baclofen, lisuride, imipramine, clonazepam and butyrophenones) were treated for 12 months with periocular injections of botulinum toxin (BOTOX). A "low" dose of 12,5 U per eye was employed. With this dose, eleven out of twelve patients experienced significant improvement which lasted from five to fifteen weeks. The only nonresponder obtained complete relief upon duplicating the dose. The only side effect was uni or bilateral ptosis in six patients which improved completely in seven to twenty one days. One patient developed a peripheral facial palsy with complete remission in nineteen days. No systemic side effects were noted. There was only one desertion from this study due to depression enhanced by prolonged (21 days) ptosis. All patients (including the deserter) agreed that treatment with BOTOX provided more relief than any other previous therapeutic method. Our results confirm those obtained by others but a more prolonged study is needed to better evaluate long term effects. PMID:2101846

  7. Therapeutic Use of Botulinum Toxin in Neurorehabilitation

    PubMed Central

    Intiso, Domenico

    2012-01-01

    The botulinum toxins (BTX), type A and type B by blocking vesicle acetylcholine release at neuro-muscular and neuro-secretory junctions can result efficacious therapeutic agents for the treatment of numerous disorders in patients requiring neuro-rehabilitative intervention. Its use for the reduction of focal spasticity following stroke, brain injury, and cerebral palsy is provided. Although the reduction of spasticity is widely demonstrated with BTX type A injection, its impact on the improvement of dexterity and functional outcome remains controversial. The use of BTX for the rehabilitation of children with obstetrical brachial plexus palsy and in treating sialorrhea which can complicate the course of some severe neurological diseases such as amyotrophic lateral sclerosis and Parkinson's disease is also addressed. Adverse events and neutralizing antibodies formation after repeated BTX injections can occur. Since impaired neurological persons can have complex disabling feature, BTX treatment should be viewed as adjunct measure to other rehabilitative strategies that are based on the individual's residual ability and competence and targeted to achieve the best functional recovery. BTX therapy has high cost and transient effect, but its benefits outweigh these disadvantages. Future studies must clarify if this agent alone or adjunctive to other rehabilitative procedures works best on functional outcome. PMID:21941544

  8. Treatment of ptosis as a complication of botulinum toxin injection.

    PubMed

    Omoigui, Sota; Irene, Sunday

    2005-01-01

    In this case report, we present one of the complications of botulinum toxin injection. Botulinum toxin injection could be used in the treatment of migraine headaches and this use could be complicated by ptosis. Botulinum toxin type A was injected into the frontalis, orbicularis oculi, corrugator supercillis, and temporalis muscles bilateral, as well as into the procerus muscle, in a patient with chronic migraine headache. Three days later the patient developed ptosis, conjunctival injection and pain initially in one eye, later involving both eyes. This complication was successfully treated after 9 days of instilling apraclonidine 0.5% ophthalmic solution and dexamethasone 0.1%/tobramycin 0.3% ophthalmic suspension into both eyes. PMID:15773880

  9. 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. PMID:24156980

  10. 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. PMID:23769754

  11. [Pittsburgh experience with botulinum toxin A injection].

    PubMed

    de Miguel, F; Chancellor, M B

    2006-03-01

    We report one institution's six-year experience using botulinum toxin A (BONT-A) in the bladder and urethra in 110 patients for a variety of lower urinary tract dysfunction. 110 patients (age 19-82) were injected with BONT-A into the bladder (n=42) or urethra (n=68), 35 M, 75 F. Voiding dysfunction included: neurogenic detrusor overactivity and/or detrusor sphincter dyssynergia, overactive bladder (OAB), benign prostatic hyperplasia (BPH), bladder neck obstruction (BNO) and interstitial cystitis (IC). Currently, 27 patients have undergone further injections (up to 6) at intervals > 6 months. All the patients with bladder BONT-A injection had preoperative evidence of involuntary detrusor contractions during urodynamic testing. Analysis of the 110 patients indicates that 67.3% reported a decrease or absence of incontinence. Diaries indicate a decrease in both day and night voiding symptoms. Efficacy occurred within 7 days and lasted for at least 6 months. Condition specific QOL symptom scores also demonstrated improvement. There have been no long-term complications. Two MS women with mild baseline stress urinary incontinence reported increased leakage with stress after BONT-A external sphincter injection. One MS woman who had a bladder injection had an increased residual urine from 78 to 155 ml. She did not have to perform intermittent catheterization. BONT-A injection is a safe and promising treatment modality for a variety of lower urinary tract dysfunctions for both skeletal and smooth muscle dysfunction. In our series, BONT-A is equally effective in women as it is in men. Bladder injections with BONT-A are effective for not only neurogenic detrusor overactivity but also overactive bladder. BONT-A can even be considered for IC. PMID:16749589

  12. 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)

  13. 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...

  14. Intraoral administration of botulinum toxin for trigeminal neuropathic pain.

    PubMed

    Herrero Babiloni, Alberto; Kapos, Flavia P; Nixdorf, Donald R

    2016-06-01

    This article presents 2 cases of different neuropathic trigeminal pain conditions treated with intraoral botulinum toxin injections. There is a growing body of evidence to support the use of this substance when administered subcutaneously in the treatment of neuropathic pain, such as in extraoral injections for trigeminal neuralgia. However, reports of intraoral submucosal administration are still lacking. In the 2 cases presented here, neuropathic pain was refractory to treatment with an important intraoral peripheral component, so onabotulinum toxin A was introduced as an adjuvant therapy. The technique, doses, and dilution are discussed. The patients reported significant reductions in pain frequency and intensity, with minimal side effects of temporary mucosal dryness and smile droopiness. The analgesic benefits of botulinum toxin may be utilized to address intraoral neuropathic pain. Further studies are needed to confirm safety and effectiveness in larger samples. PMID:27181448

  15. 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. PMID:26866497

  16. Brain Metabolic Changes of Cervical Dystonia with Spinocerebellar Ataxia Type 1 after Botulinum Toxin Therapy.

    PubMed

    Kikuchi, Akio; Takeda, Atsushi; Sugeno, Naoto; Miura, Emiko; Kato, Kazuhiro; Hasegawa, Takafumi; Baba, Toru; Konno, Masatoshi; Oshima, Ryuji; Watanuki, Shoichi; Hiraoka, Kotaro; Tashiro, Manabu; Aoki, Masashi

    2016-01-01

    We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions. PMID:27432104

  17. 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

  18. Botulinum toxin for neuropathic pain and spasticity: an overview.

    PubMed

    Brown, E Alexandra; Schütz, Sonja G; Simpson, David M

    2014-03-01

    In recent years, a large body of data has surfaced reporting the therapeutic benefit of botulinum toxin injection in multiple conditions. The aim of this review is: to summarize the highest quality literature pertaining to clinical application of botulinum toxin in neuropathic pain conditions including postherpetic neuralgia, trigeminal neuralgia, diabetic polyneuropathy, post-traumatic neuralgia, carpal tunnel syndrome, complex regional pain syndrome, phantom limb and stump pain, and occipital neuralgia; to provide an overview of the clinical trials using botulinum toxin in adult spasticity; and to assign levels of evidence according to the American Academy of Neurology guidelines. In summary, there is level A evidence for established efficacy in postherpetic neuralgia and adult spasticity; level B evidence for probable efficacy in trigeminal neuralgia and post-traumatic neuralgia; level B evidence for probable lack of efficacy in carpal tunnel syndrome; level C evidence for possible efficacy in diabetic polyneuropathy; and level U (insufficient) evidence in complex regional pain syndrome, phantom limb and stump pain, and occipital neuralgia. PMID:24641437

  19. Purification of Clostridium botulinum type G progenitor toxin.

    PubMed

    Nukina, M; Mochida, Y; Sakaguchi, S; Sakaguchi, G

    1988-04-01

    Clostridium botulinum type G cultured for 6 days at 30 degrees C in proteose peptone-yeast extract-glucose medium produced toxin of 1.3 x 10(4) LD50/ml. The toxin was precipitated at pH 4.0, extracted with 0.2 M phosphate buffer, pH 6.0, and activated with trypsin. Sonic treatment and trypsinization of the residual precipitate released additional toxin, the toxicity of which corresponded to that detected in whole culture. Activated toxin obtained from the first extract and that from the residual precipitate were combined and purified by salting out, acid precipitation, gel filtration on Sephadex G-200, chromatography on SP-Sephadex, and a second gel filtration on Sephadex G-200. The yield of purified toxin from 10 liters of culture was 22.9 mg an 1.1 X 10(8) mouse ip LD50 with a specific toxicity of 3.0 X 10(7) mouse ip LD50/mg nitrogen. The molecular weight of the toxin was about 500,000, corresponding to that of L toxin of the other types. No M nor LL toxin was detected. PMID:3293334

  20. Structure-function discrepancy in Clostridium botulinum C3 toxin for its rational prioritization as a subunit vaccine.

    PubMed

    Prathiviraj, R; Prisilla, A; Chellapandi, P

    2016-06-01

    Clostridium botulinum is anaerobic pathogenic bacterium causing food-born botulism in human and animals by producing botulinum neurotoxins A-H, C2, and C3 cytotoxins. Physiological group III strains (type C and D) of this bacterium are capable of producing C2 and C3 toxins in cattle and avian. Herein, we have revealed the structure-function disparity of C3 toxins from two different C. botulinum type C phage (CboC) and type D phage (CboD) to design avirulent toxins rationally. Structure-function discrepancy of the both toxins was computationally evaluated from their homology models based on the conservation in sequence-structure-function relationships upon covariation and point mutations. It has shown that 8 avirulent mutants were generated from CboC of 34 mutants while 27 avirulent mutants resulted from CboD mutants. No major changes were found in tertiary structure of these toxins; however, some structural variations appeared in the coiled and loop regions. Correlated mutation on the first residue would disorder or revolutionize the hydrogen bonding pattern of the coevolved pairs. It suggested that the residues coupling in the local structural environments were compensated with coevolved pairs so as to preserve a pseudocatalytic function in the avirulent mutants. Avirulent mutants of C3 toxins have shown a stable structure with a common blue print of folding process and also attained a near-native backrub ensemble. Thus, we concluded that selecting the site-directed mutagenesis sites are very important criteria for designing avirulent toxins, in development of rational subunit vaccines, to cattle and avian, but the vaccine specificity can be determined by the C3 toxins of C. botulinum harboring phages. PMID:26239365

  1. Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin

    DOE PAGESBeta

    Koh, Chung -Yan; Schaff, Ulrich Y.; Sandstone Diagnostics, Livermore, CA; Piccini, Matthew E.; Cepheid, Sunnyvale, CA; Stanker, Larry H.; Cheng, Luisa W.; Ravichandran, Easwaran; Singh, Bal -Ram; Sommer, Greg J.; et al

    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

  2. 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

  3. 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.

  4. 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...

  5. Botulinum Toxin Treatment of Neuropathic Pain.

    PubMed

    Mittal, Shivam Om; Safarpour, Delaram; Jabbari, Bahman

    2016-02-01

    Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medications. In this review the authors discuss the pathophysiology and conventional treatment of neuropathic pain and provide evidenced-based statements on the efficacy of botulinum neurotoxins (BoNTs) in this form of pain. The level of efficacy for BoNT treatment in each category of NP is defined according to the published guidelines of the American Academy of Neurology. The data indicate that BoNT treatment (most of the literature is with onabotulinumtoxinA) is effective (level A evidence) in postherpetic neuralgia and trigeminal neuralgia. It is probably effective (level B) in posttraumatic neuralgia and painful diabetic neuropathy. The data on complex regional pain syndrome, carpal tunnel syndrome, occipital neuralgia, and phantom limb pain are preliminary and await conduction of randomized, blinded clinical trials. Much remains to be learned about the most-effective dosage and technique of injection, optimum dilutions, and differences among BoNTs in the treatment of neuropathic pain. PMID:26866499

  6. Botulinum toxin a treatment of cricopharyngeal dysphagia after subarachnoid hemorrhage.

    PubMed

    Krause, Eike; Schirra, Jörg; Gürkov, Robert

    2008-12-01

    Elevated muscular tone associated with spastic syndromes can cause excessive contractility at the upper esophageal sphincter and impede swallowing. A 47-year-old male patient with spasticity predominantly of the lower extremities after a subarachnoid hemorrhage suffered from severe dysphagia and chronic salivary aspiration. He was dependent on a cuffed tracheostomy tube and a percutaneous enterogastric feeding tube. Barium swallow and esophageal manometry revealed cricopharyngeal spasm, while laryngeal elevation and pharyngeal contractility were well preserved. We endoscopically injected 180 MU botulinum toxin A into the cricopharyngeus muscle. Two days post injection, swallowing function had improved and oral nutrition was possible. This improvement lasted for six weeks. After another injection 8 weeks later, an undesired diffusion into the hypopharynx occurred and manometry showed diminished contractility without amelioration of dysphagia. Botulinum toxin therapy of cricopharyngeal spasm improves swallowing function in a subgroup of patients with spastic syndromes. The therapeutic effect is of limited duration. Toxin diffusion into the pharynx should be avoided. Manometry is useful in planning and monitoring the therapy. PMID:18437465

  7. 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. PMID:15790305

  8. Botulinum toxin: An emerging therapy in female bladder outlet obstruction

    PubMed Central

    Pradhan, Aditya A.

    2009-01-01

    Introduction: We evaluated the utility of botulinum toxin in functional female bladder outlet obstruction. Materials and Methods: A total of 7 consecutive female patients with bladder outlet obstruction were included. Patients with neurogenic bladder were excluded. All were previously treated with periodic dilations. Diagnosis was based on symptomatology, cystometry, and micturating cystograms. A total of 2 patients had been in chronic retention with residual volumes more than 400 ml. All were managed with an injection of botulinum toxin, 100 units in 2 ml of saline injected with a flexible cystoscopic needle. The site of the injection was deep submucosally, 0.5 ml in each quadrant at the level of the most prominent narrowing seen endoscopically. All the procedures were done as day care procedures under local anaesthesia. After the procedure, no catheter was placed. Patients were followed up for changes in IPSS scores and post void residual urine measurements. In all cases, multiple injections were used. Results: The follow-up period ranged from 48–52 weeks. The IPSS reduced by an average of 12 points. Post void residual urine reduced by 62%. Improvements commenced 4.85 days (average) after the procedure and lasted for an average of 16.8 weeks (range: 10.8–28 weeks). Discussion: There is a gradual improvement in symptoms over time and the maximal effect occurred at 10–14 days. The duration of improvement was approximately 16.8 weeks. All patients were satisfied by the degree of improvement felt. Conclusions: Botulinum toxin proved successful in improving the voiding characteristics. It possibly acts at the zone of hypertonicity at the bladder neck or midurethra. The only disadvantage is the high cost of the drug. PMID:19881122

  9. Mycobacterial Infection after Cosmetic Procedure with Botulinum Toxin A

    PubMed Central

    Saeb-Lima, Marcela; Solis-Arreola, Gerardo-Victor

    2015-01-01

    We report a case of mycobacterial infection at the sites of previous injections of botulinum toxin A in a 45-year-old woman. She presented with erythematous, swollen, warm, and tender plaques and nodules at the points of injection from which a biopsy was taken, demonstrating a deep dermal and hypodermal abscessified epithelioid granulomatous inflammatory infiltrate in which some acid-fast bacilli were identified with Ziehl-Neelsen and Fite-Faraco stains. The lesion was first treated with clarithromycin plus azithromycin, to which rifampicin was later added. A good therapeutic response was obtained. PMID:26023629

  10. [Botulinum toxin A for the treatment of familial benign pemphigus].

    PubMed

    López-Ferrer, A; Alomar, A

    2012-01-01

    Familial benign pemphigus or Hailey-Hailey disease is a rare bullous disease that presents clinically with recurrent flares of erosions and vesicles that mainly affect the skinfolds. Many topical and systemic therapies have been proposed. Hyperhidrosis is one of the factors that can trigger or aggravate a flare-up, and its treatment is therefore important for controlling the disease and preventing further episodes. We report 3 patients with axillary and/or inguinal benign familial pemphigus that responded favorably to treatment with subcutaneous botulinum toxin. PMID:21872830

  11. 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.

  12. Botulinum toxin: examining duration of effect in facial aesthetic applications.

    PubMed

    Flynn, Timothy Corcoran

    2010-01-01

    Patient satisfaction with botulinum toxin treatment is a key success factor in aesthetic procedures and is governed by the interaction of numerous variables. Duration of effect is important because it influences retreatment intervals as well as affecting cost and convenience to the patient. In order to review the evidence on the duration of benefit associated with various commercial formulations of botulinum toxin, MEDLINE was searched using the following terms: 'botulinum' and 'duration'/'retreatment' (limits: 'clinical trials,' 'meta-analyses,' 'English'). I also searched my existing reference files, reference lists of identified articles, and meeting/conference abstracts to ensure completeness. The focus was on clinical medicine and aesthetic trials. To be eligible for the analysis, studies had to include efficacy assessments at multiple timepoints. To estimate duration of benefit, the following outcomes were examined and summarized: responder rates, mean wrinkle severity scores at various timepoints (with or without changes from baseline), and relapse rates. Duration at both repose and maximum attempted muscle contraction was considered when provided. Where possible, duration was assessed by formulation and dose. The initial search yielded 164 articles. Of these, 35 included an adequate measure of duration in aesthetic indications. The majority of these (22) were on the glabellar area. Study designs and endpoints were highly heterogeneous, and duration of effect varied between studies. Several studies with the BOTOX Cosmetic (onabotulinumtoxinA; Allergan, Inc., Irvine, CA, USA) formulation of botulinum toxin type A (BoNTA) included relapse rates, defined conservatively as return to baseline levels of line severity for two consecutive visits approximately 30 days apart (at repose and maximum contraction). In these studies, duration of effect ranged from 3 to 5 months in female patients and from 4 to 6 months in male patients. Individual patients had longer

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

    PubMed

    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. 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

  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. Botulinum toxin type A (Botox) and idiopathic overactive bladder. For some severely affected patients.

    PubMed

    2016-03-01

    In two clinical trials, botulinum toxin injected during cystoscopy transiently prevented urinary incontinence in 1 in 5 patients but sometimes provoked urine retention and urinary tract infections. PMID:27152397

  17. 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

  18. [Botulinum toxin type A in headache treatment : Established and experimental indications].

    PubMed

    Gaul, C; Holle-Lee, D; Straube, A

    2016-08-01

    In recent years botulinum toxin type A has been used increasingly more in the treatment of specific headache disorders. Especially regarding chronic migraine with and without combined medication overuse, convincing randomized studies have proven the efficacy of this treatment option and have led to approval for this indication. Regarding other headache entities, such as episodic migraine, tension-type headache, trigeminal autonomic cephalalgia (TAC), neuralgic, neuropathic and myofascial pain, currently available scientific data on the efficacy of botulinum toxin type A are scarce and often ambiguous. The exact underlying mechanisms of the influence of botulinum toxin type A on the pathophysiology of headache are not completely clear but an influence on the release of calcitonin gene-related peptide (CGRP) seems to play a crucial role. This article summarizes the most important studies as well as experiences of treatment with botulinum toxin type A regarding different headache entities. PMID:27300190

  19. 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. PMID:26266368

  20. 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. PMID:23078619

  1. Growth and toxin production by Clostridium botulinum on inoculated fresh-cut packaged vegetables.

    PubMed

    Austin, J W; Dodds, K L; Blanchfield, B; Farber, J M

    1998-03-01

    To determine the safety of fresh-cut vegetables packaged in modified atmosphere, challenge studies using both nonproteolytic and proteolytic strains of Clostridium botulinum were performed with a variety of fresh-cut packaged salads and vegetables stored at different temperatures. When vegetables were inoculated with spores of C. botulinum and incubated in low-O2 atmospheres, spore germination and growth and toxin production were observed. Botulinum toxin was produced by proteolytic types A and B on onion, butternut squash, rutabaga, salad, and stir-fry vegetables. Nonproteolytic C. botulinum produced toxin on butternut squash and salad. Nonproteolytic C. botulinum was capable of producing neurotoxin at temperatures as low as 5 degree C whereas proteolytic strains produced neurotoxin at 15 degrees C and higher. Although most samples were visibly spoiled before detection of botulinum toxin, samples of butternut squash and onion remained acceptable after detection of toxin. The strict maintenance of low temperatures (< 5 degrees C) is recommended in order to control the potential growth of C. botulinum on fresh-cut vegetables packaged in a modified atmosphere. PMID:9708304

  2. Botulinum Toxin Suppression of CNS Network Activity In Vitro

    PubMed Central

    Pancrazio, Joseph J.; Gopal, Kamakshi; Keefer, Edward W.; Gross, Guenter W.

    2014-01-01

    The botulinum toxins are potent agents which disrupt synaptic transmission. While the standard method for BoNT detection and quantification is based on the mouse lethality assay, we have examined whether alterations in cultured neuronal network activity can be used to detect the functional effects of BoNT. Murine spinal cord and frontal cortex networks cultured on substrate integrated microelectrode arrays allowed monitoring of spontaneous spike and burst activity with exposure to BoNT serotype A (BoNT-A). Exposure to BoNT-A inhibited spike activity in cultured neuronal networks where, after a delay due to toxin internalization, the rate of activity loss depended on toxin concentration. Over a 30 hr exposure to BoNT-A, the minimum concentration detected was 2 ng/mL, a level consistent with mouse lethality studies. A small proportion of spinal cord networks, but not frontal cortex networks, showed a transient increase in spike and burst activity with exposure to BoNT-A, an effect likely due to preferential inhibition of inhibitory synapses expressed in this tissue. Lastly, prior exposure to human-derived antisera containing neutralizing antibodies prevented BoNT-A induced inhibition of network spike activity. These observations suggest that the extracellular recording from cultured neuronal networks can be used to detect and quantify functional BoNT effects. PMID:24688538

  3. Botulinum toxin suppression of CNS network activity in vitro.

    PubMed

    Pancrazio, Joseph J; Gopal, Kamakshi; Keefer, Edward W; Gross, Guenter W

    2014-01-01

    The botulinum toxins are potent agents which disrupt synaptic transmission. While the standard method for BoNT detection and quantification is based on the mouse lethality assay, we have examined whether alterations in cultured neuronal network activity can be used to detect the functional effects of BoNT. Murine spinal cord and frontal cortex networks cultured on substrate integrated microelectrode arrays allowed monitoring of spontaneous spike and burst activity with exposure to BoNT serotype A (BoNT-A). Exposure to BoNT-A inhibited spike activity in cultured neuronal networks where, after a delay due to toxin internalization, the rate of activity loss depended on toxin concentration. Over a 30 hr exposure to BoNT-A, the minimum concentration detected was 2 ng/mL, a level consistent with mouse lethality studies. A small proportion of spinal cord networks, but not frontal cortex networks, showed a transient increase in spike and burst activity with exposure to BoNT-A, an effect likely due to preferential inhibition of inhibitory synapses expressed in this tissue. Lastly, prior exposure to human-derived antisera containing neutralizing antibodies prevented BoNT-A induced inhibition of network spike activity. These observations suggest that the extracellular recording from cultured neuronal networks can be used to detect and quantify functional BoNT effects. PMID:24688538

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

    PubMed

    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

  5. Botulinum toxin injections to reduce adiposity: possibility, or fat chance?

    PubMed

    Lim, Erle C H; Seet, Raymond C S

    2006-01-01

    Obese individuals often suffer from negative self-image. Many, even those with a normal body mass index, resort to pharmacotherapy (lipase inhibitors or appetite suppressants), mesotherapy and surgery (gastric volume reduction, liposuction or apronectomy) in a bid to remove excess adipose tissue. These treatments are associated with inherent morbidity and even mortality, and hence should not be undertaken lightly. The observation that denervation of adipose tissue results in lipoatrophy leads us to postulate that chemodenervation using botulinum toxin may achieve the same result, i.e. fat loss, and we explore the methods by which selective fat loss may be achieved. We concede that removal of subcutaneous fat does not, however, reduce the risks associated with the metabolic syndrome, as visceral (intra-abdominal) fat is not reduced by the removal of subcutaneous fat. PMID:16716533

  6. 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. PMID:27143711

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

    PubMed

    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

  8. 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

  9. 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

  10. Jaundice following intravesical botulinum toxin – a previously unreported complication

    PubMed Central

    Marri, R R; Bromage, S J; Darmalingum, A; Calvert, C; Banait, G; Jones, D A; Islam, S

    2010-01-01

    A 59-year-old woman presented 5 days after her third instillation of intravesical botulinum toxin with right upper quadrant pain and jaundice. Blood tests demonstrated deranged liver function tests. An abdominal ultrasound, radiograph, magnetic resonance cholangiopancreatography, serum hepatitis screen, immunoglobulins and autoantibody testing were normal. An ultrasound-guided liver biopsy was performed. The histological appearances were those of chronic active/lobular hepatitis. Following treatment with steroids, her jaundice improved over a period of about 3 weeks. Her serum liver function tests returned to normal in 3 months. The steroids were discontinued once her liver function tests normalised. The patient had no further recurrence of jaundice and serum liver function tests have been within normal limits after 6 months follow-up. PMID:22791724

  11. Botulinum toxin in the treatment of strabismus. A review of its use and effects.

    PubMed

    Kowal, Lionel; Wong, Elaine; Yahalom, Claudia

    2007-12-15

    Botulinum Toxin as a medical therapy was introduced by Dr Alan Scott more than 20 years ago. The first clinical applications of Botulinum Toxin type A (BT-A) were for the treatment of strabismus and for periocular spasms. Botulinum Toxin type A is often effective in small to moderate angle convergent strabismus (esotropia) of any cause, and may be an alternative to surgery in these cases. Botulinum Toxin type A may have a role in acute or chronic fourth and sixth nerve palsy, childhood strabismus and thyroid eye disease. The use of BT-A for strabismus varies enormously in different cities and countries for no apparent reason. Botulinum Toxin type A may be particularly useful in situations where strabismus surgery is undesirable. This may be in elderly patients unfit for general anaesthesia, when the clinical condition is evolving or unstable, or if surgery has not been successful. Botulinum Toxin type A can give temporary symptomatic relief in many instances of bothersome diplopia irrespective of the cause. Ptosis and acquired vertical deviations are the commonest complications encountered. Vision-threatening complications are rare. Repeated use of BT-A is safe. PMID:18033607

  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. The role of botulinum toxin A in treating neurogenic bladder.

    PubMed

    Weckx, Filip; Tutolo, Manuela; De Ridder, Dirk; Van der Aa, Frank

    2016-02-01

    Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life-expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox(®), Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport(®), Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future. PMID:26904413

  14. The role of botulinum toxin A in treating neurogenic bladder

    PubMed Central

    Weckx, Filip; Tutolo, Manuela; De Ridder, Dirk

    2016-01-01

    Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life-expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox®, Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport®, Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future. PMID:26904413

  15. Reconstituting botulinum toxin drugs: shaking, stirring or what?

    PubMed

    Dressler, Dirk; Bigalke, Hans

    2016-05-01

    Most botulinum toxin (BT) drugs are stored as powders which need to be reconstituted with normal saline before clinical use. As botulinum neurotoxin (BNT), the therapeutically active ingredient, is a large double-stranded protein the process of reconstitution should be performed with special attention to mechanical stress applied. We wanted to test the mechanical stability of BNT during the reconstitution process. For this, 100 MU onabotulinumtoxinA (Botox(®), Irvine, CA, USA) was reconstituted with 2.0 ml of NaCl/H2O. Gentle reconstitution (GR) was performed with a 5 ml syringe, a 0.90 × 70 mm injection needle, one cycle of injection-aspiration-injection and two gentle shakes of the vial. Aggressive reconstitution (AR) was performed with a 5 ml syringe, a 0.40 × 40 mm injection needle, ten injection-aspiration-injection cycles and 30 s of continuous shaking of the vial. AR increased the time to paralysis in the mouse hemidiaphragm assay (HDA) from 72.0 ± 4.6 to 106.0 ± 16.0 min (*p = 0.002, two-tailed t test after Kolmogorov-Smirnova test with Lilliefors correction for normal distribution). Construction of a calibration curve revealed that the increase in the time to paralysis was correlated with a loss of potency of from 100 to 58 MU (-42 %). BT users should use large diameter injection needles for reconstitution, apply two or three injection-aspiration-injection cycles and, maybe, shake the vials a few times to rinse the entire glass wall. Aggressive reconstitution with small diameter needles, prolonged injection-aspiration-injection and violent shaking should be avoided. PMID:27100914

  16. 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.

  17. 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...

  18. 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.

  19. Quantification of Clostridium botulinum toxin gene expression by competitive reverse transcription-PCR.

    PubMed

    McGrath, S; Dooley, J S; Haylock, R W

    2000-04-01

    Clostridium botulinum produces a characteristic botulinum neurotoxin which can cause an often fatal neuroparalytic condition known as botulism. Although food-borne botulism is rare, critical screening by food companies is necessary to ensure that food products are safe. At present, the food industry assesses the risks of botulinum neurotoxin production by challenge testing to check any new food products and to check the efficacy of new storage regimes. Challenge testing involves artificial introduction of defined strains of microorganisms into food, and microbial growth and possible toxin production are then monitored. Botulinum toxin is normally analyzed by using the mouse bioassay. However, the mouse bioassay is expensive, slow, and politically sensitive because of animal rights issues. In this paper we describe adaptation of a new assay, competitive reverse transcription-PCR (RT-PCR), to monitor botulinum neurotoxin production. This method accurately measures the level of toxin-encoding mRNA in C. botulinum cells. Measurement of mRNA should provide a good indication of gene expression as mRNA is turned over rapidly in bacterial cells. In addition, the method is rapid, specific, and sensitive. The competitive RT-PCR method was developed to examine C. botulinum E VH toxin gene expression and was used to investigate the level of toxin production by C. botulinum E VH when the organism was grown in two different types of broth. The results which we obtained with the competitive RT-PCR method demonstrated that this method is more rapid and more sensitive than the mouse bioassay. PMID:10742222

  20. Clostridium botulinum spores and toxin in mascarpone cheese and other milk products.

    PubMed

    Franciosa, G; Pourshaban, M; Gianfranceschi, M; Gattuso, A; Fenicia, L; Ferrini, A M; Mannoni, V; De Luca, G; Aureli, P

    1999-08-01

    A total of 1,017 mascarpone cheese samples, collected at retail, were analyzed for Clostridium botulinum spores and toxin, aerobic mesophilic spore counts, as well as pH, a(w) (water activity), and Eh (oxidation-reduction potential). In addition 260 samples from other dairy products were also analyzed for spores and botulinum toxin. Experiments were carried out on naturally and artificially contaminated mascarpone to investigate the influence of different temperature conditions on toxin production by C. botulinum. Three hundred and thirty-one samples (32.5%) of mascarpone were positive for botulinal spores, and 7 (0.8%) of the 878 samples produced at the plant involved in an outbreak of foodborne botulism also contained toxin type A. The chemical-physical parameters (pH, a(w), Eh) of all samples were compatible with C. botulinum growth and toxinogenesis. Of the other milk products, 2.7% were positive for C. botulinum spores. Growth and toxin formation occurred in naturally and experimentally contaminated mascarpone samples after 3 and 4 days of incubation at 28 degrees C, respectively. PMID:10456738

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

    PubMed Central

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

    2015-01-01

    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. PMID:26566311

  2. 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.

  3. Botulinum toxin A inhibits salivary secretion of rabbit submandibular gland.

    PubMed

    Shan, Xiao-Feng; Xu, Hui; Cai, Zhi-Gang; Wu, Li-Ling; Yu, Guang-Yan

    2013-12-01

    Botulinum toxin A (BTXA) has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor (M3 receptor) and aquaporin-5 (AQP5) mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular glands. PMID:24158141

  4. 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

  5. Efficacy of Laryngeal Botulinum Toxin Injection: Comparison of Two Techniques

    PubMed Central

    Fulmer, Susan L.; Merati, Albert L.; Blumin, Joel H.

    2011-01-01

    Objectives It is hypothesized that there is no difference in the effectiveness of botulinum toxin(BTX) injection between electromyography (EMG) guided and non-EMG guided ‘point-touch’ techniques in treatment of adductor spasmodic dysphonia (AdSD). Study Design Retrospective chart review. Methods Patients selected for evaluation underwent sequential treatment by one or both of the senior authors utilizing two different injection techniques with similar BTX dilution & preparation. Data gathered included dose injected, injection effect, presence and duration of breathiness and dysphagia after injection. Statistical analysis was performed used a generalized estimating equations model. Results Four hundred seventeen injections in sixty-four patients were analyzed. There was no difference in the rate of successful injections between the EMG guidance group and the non-EMG guidance group (94.4% and 93.2%, respectively; p = 0.7). Conclusions This unique study demonstrates that efficacy of BTX does not necessarily depend on the method of injection utilized. In experienced hands, excellent clinical results can be achieved with either EMG or non-EMG guided injection techniques. PMID:22024846

  6. 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

  7. Treatment of chronic limb spasticity with botulinum toxin A.

    PubMed Central

    Dunne, J W; Heye, N; Dunne, S L

    1995-01-01

    The purpose of this open study was to find out whether botulinum toxin A (BTX-A) relieves the signs and symptoms of chronic limb spasticity. The study comprised 40 patients, aged 12-82 years, with moderate to severe spasticity of the upper (13) or lower limbs (27) refractory to conventional physical and medical treatments. Outcome measures were clinical and blinded videotape assessments of spasticity and motor function. Electromyography guided BTX-A injections were given in one or two sessions at total doses averaging 175 U in the upper limb (range 70-270 U) and 221 U in the lower limb (range 100-500 U). Thirty four patients (85%) derived worthwhile benefit, with improved limb posture and increased range of passive motion in 31, pain reduction in 28 of 31 with pain, and improved function in 16. Side effects were limited to local and usually mild discomfort from the injections (19), symptomatic local weakness (one), and local infection (one). Preliminary experience indicates that BTX-A is a promising adjunctive treatment for selected patients with spasticity. PMID:7876859

  8. Botulinum Toxin A Treatment of Consecutive Esotropia in Children

    PubMed Central

    Couser, Natario L.; Lambert, Scott R.

    2013-01-01

    Objective To assess the outcome of Botulinum A toxin (BTXA) to treat surgically overcorrected intermittent exotropia in children. Methods A retrospective analysis was performed on a series of children with consecutive esotropia treated with BTXA. Results Six children with a mean consecutive esotropia of 21 PD were treated with BTXA at a mean of 19.8 months following strabismus surgery. Two patients underwent a single injection, 3 patients 2 injections, and 1 patient 3 injections. Complications included transient ptosis and a vertical deviation. Mean follow-up from last BTXA injection was 16 months. At last follow-up, 4 of the 6 patients were orthotropic and stereopsis was present in 4 of 5 patients old enough to cooperate with testing. One patient was treated with strabismus surgery following a single BTXA injection. Conclusions BTXA is an efficacious treatment for consecutive esotropia in children. However, in our series, two-thirds of patients required multiple injections to achieve the desired outcome and one ultimately had an additional strabismus surgery. PMID:23211140

  9. 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. PMID:26223883

  10. Oromandibular dystonia in yemeni patients with khat chewing: a response to botulinum toxin treatment.

    PubMed

    Shehata, Hatem S; El-Tamawy, Mohamed S; Mohieldin, Nevin; Edrees, Mohammed; Bohlega, Saeed

    2014-04-22

    Khat-(Catha edulis)related oromandibular dystonia is a difficult-to-treat subset of movement disorders that involve masticatory muscles with diverse and incapacitating manifestations. The aim of this study was to evaluate the efficacy of Botulinum toxin-type A therapy in khat chewer Yemeni patients with oromandibular dystonia. This prospective study included 18 khat-chewers Yemeni patients with refractory oromandibular dystonia, who were subjected to Botulinum toxin-A injection and followed up for 3 months thereafter. Primary efficacy outcome was the global impression scale, and secondary outcome measure was the Unified Dystonia Rating Scale. Patients showed improvement of both efficacy measures, maximum satisfactory responses were detected at the forth week after injection. No major adverse events were detected. Botulinum toxin-A is considered an effective and safe treatment option for refractory oromandibular dystonia in khat-chewers. PMID:24987506

  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 Central

    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. PMID:24853378

  13. Botulinum toxin A relieved neuropathic pain in a case of post-herpetic neuralgia.

    PubMed

    Liu, Hsu-Tang; Tsai, Shen-Kou; Kao, Ming-Chang; Hu, Jenkin S

    2006-01-01

    Botulinum toxin type A (BTX-A) has been widely used in many clinical disorders including migraine, cervical dystonia, etc. The use of BTX-A in neuropathic pain, however, is uncommon, and the application of the anti-nociceptive effect of botulinum toxin is emerging. Here we report a case of an 80-year-old man who suffered from severe pain of post-herpetic neuralgia which was refractory to the usual therapies. However, this neuropathic pain was dramatically relieved by multiple BTX-A injection and the pain relief lasted 52 days. PMID:16533208

  14. Long-Term Blood Pressure Control Effect of Celiac Plexus Block with Botulinum Toxin

    PubMed Central

    Lee, Sung Hyun; Lim, Dae Hwan; Lee, Ju Ho; Chang, Kiyuk; Koo, Jung Min; Park, Hue Jung

    2016-01-01

    Celiac plexus block (CPB) is one of the main treatment options for patients resistant to conventional antihypertensive drugs. We present a case of resistant hypertension (RHTN) that was treated with CPB using botulinum toxin. An 18-year-old male patient with RHTN, who suffered from persistent hypertension even after combination therapy and a renal denervation procedure, was referred to our pain center for CPB. CPB using botulinum toxin following the use of only local anesthetics resulted in control of systolic blood pressure (BP) at ~150 mmHg for at least three months. PMID:26907344

  15. 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

  16. The use of botulinum toxin in the treatment of adductor spasmodic dysphonia.

    PubMed Central

    Whurr, R; Lorch, M; Fontana, H; Brookes, G; Lees, A; Marsden, C D

    1993-01-01

    Botulinum toxin injections have been used to treat 31 patients with adductor spasmodic dysphonia. Injections of 3.00-3.75 units of botulinum toxin were performed bilaterally into the thyroarytenoid muscle. This treatment significantly decreased the standard deviation of the fundamental frequency of the speech sample, indicating a reduction in the variability of pitch amongst patients. A total of 96% of patients' subjective diary reports showed an improvement with a median of 7 days to peak effect and a 5 week duration of peak effect. Images PMID:8505645

  17. Botulinum Toxin Type A (BOTOX) for Refractory Myofascial Pelvic Pain

    PubMed Central

    ADELOWO, Amos; HACKER, Michele R.; SHAPIRO, Alex; Modest, Anna Merport; ELKADRY, Eman

    2013-01-01

    Objective To assess intralevator Botulinum toxin type A (Botox) injections for refractory myofascial pelvic pain with short tight pelvic floor. Methods Retrospective cohort study of all women with intralevator Botox injection (100-300 Units) from 2005 through 2010 for refractory myofascial pelvic pain. Primary outcomes were self-reported pain on palpation and symptom improvement. Secondary outcomes included post-injection complications and repeat injection. Pain was assessed during digital palpation of the pelvic floor muscles using a scale of 0-10, with 10 being the worst possible pain. Follow-up occurred at <6 weeks post-injection and again at ≥ 6 weeks. Data are presented as median (interquartile range) or proportion. Results Thirty-one patients met eligibility criteria; 2 were lost to follow up and excluded. Median age was 55.0 years (38.0-62.0). Before Botox injection, median pain score was 9.5 (8.0-10.0). Twenty-nine patients (93.5%) returned for the first follow-up visit; 79.3% reported improvement in pain, while 20.7% reported no improvement. Median pain with levator palpation was significantly lower than before injection (P<0.0001). Eighteen women (58.0%) had a second follow-up visit with a median pain score that remained lower than before injection (P<0.0001). Fifteen (51.7%) women elected to have repeat Botox injection; the median time to repeat injection was 4.0 (3.0-7.0) months. Three (10.3%) women developed de-novo urinary retention, 2 (6.9%) reported fecal incontinence and 3 (10.3%) reported constipation and/or rectal pain; all side effects resolved spontaneously. Conclusions Intralevator injection of Botox demonstrates effectiveness in women with refractory myofascial pelvic pain with few, self-limiting adverse effects. PMID:23982578

  18. 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

  19. [Botulinum toxin for the treatment of pain syndromes].

    PubMed

    Ferreira, Joaquim J; Couto, Marina; Costa, João; Coelho, Miguel; Rosa, Mário M; Sampaio, Cristina

    2006-01-01

    Although botulinum toxin (BoNT) is being used for therapeutic purposes for more than 20 years, the list of potential new indications continues to increase and includes various pain syndromes. The pain relief experienced by patients with dystonia and spasticity from intramuscular BoNT injections suggested that other chronic skeletal-muscles pain conditions may also benefit. BoNT inhibits the release of acetylcholine at the neuromuscular junction thereby reducing striatal muscle contractions and the proposed analgesic property was initially attributed to muscular relaxation. A specific analgesic BoNT effect is difficult to conclude from studies where pain is conditioned by other associated symptoms like dystonia, muscle contraction or spasticity. One alternative is to critically appraise clinical trials where BoNT was studied as the active intervention and pain evaluated as an outcome. From this analysis there is convincing evidence for the effectiveness of BoNT in the treatment of pain associated with cervical dystonia. For all other pain syndromes there have been relatively few, small sized, placebo-controlled studies (myofascial pain syndrome, chronic neck and low back pain, piriformis syndrome and fibromyalgia) and the results of these studies have been contradictory or non conclusive. To establish the analgesic properties of BoNT there is a need for appropriately designed, exploratory randomized controlled studies in well accepted human models of nociceptive or neuropathic pain. This does not exclude the subsequent need to conduct pragmatic trials to evaluate the effectiveness of BoNT in conditions where the improvement of pain or any associated clinical sign or symptom may be of clinical relevance. PMID:17058384

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

    USGS Publications Warehouse

    Moeller, R.B., Jr.; 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.

  1. Tetanus: pathophysiology, treatment, and the possibility of using botulinum toxin against tetanus-induced rigidity and spasms.

    PubMed

    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

  2. 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

  3. 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...

  4. 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

  5. Botulinum toxin A in the treatment of Raynaud's phenomenon: a systematic review

    PubMed Central

    Puszczewicz, Mariusz J.

    2015-01-01

    Introduction The management of Raynaud's phenomenon in its most severe form is challenging, and current medical and surgical treatment methods frequently do not lead to optimal symptom control and prevention of ischemic complications. The aim of the study was to critically evaluate all existing evidence on the use of botulinum toxin A in the management of Raynaud's phenomenon. Material and methods We adopted the PRISMA methodology and searched Cochrane Library, MEDLINE, SCOPUS, EULAR and ACR congresses abstract archives for Raynaud* AND botulinum toxin OR onabotulinum. All studies that contained reports of botulinum toxin A use and its outcome in Raynaud's phenomenon were included in the review. Results Eleven studies met our inclusion criteria and involved a total of 125 patients. Two reviewers extracted data from the studies under review and achieved a consensus in their selection. The main outcomes measured were pain reduction and healing of digital ulcers. The level of evidence across studies was very low to moderate. Conclusions There is insufficient evidence to assess the efficacy of botulinum toxin A in Raynaud's phenomenon. Despite many promising reports, further research in the form of randomized controlled trials is warranted in order to investigate this new treatment method for Raynaud's phenomenon. PMID:27478469

  6. 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…

  7. The botulinum toxin LD50 potency assay - another chapter, another mystery.

    PubMed

    Pickett, Andy

    2012-09-01

    Observers of the potency assay used for botulinum toxin were greeted last year with the news that one company had an alternative, non-animal alternative in place. But all was not as it seemed from the press release, and over a year later, information is still lacking. PMID:23067303

  8. 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

  9. Successful botulinum toxin (onabotulinumtoxinA) treatment of Hailey-Hailey disease.

    PubMed

    Ho, Derek; Jagdeo, Jared

    2015-01-01

    Hailey-Hailey disease is a genetic disorder that affects flexural skin with scale, blisters, and maceration. Botulinum toxins have been previously used to treat Hailey-Hailey disease. Here, we present a patient who underwent one treatment of onabotulinumtoxinA and achieved excellent improvement that was sustained for three months post initial treatment. PMID:25607910

  10. Botulinum toxin type A treatment to the upper face: retrospective analysis of daily practice

    PubMed Central

    Prager, Welf; Huber-Vorländer, Jürgen; Taufig, A Ziah; Imhof, Matthias; Kühne, Ulrich; Weissberg, Ruth; Kuhr, Lars-Peter; Rippmann, Volker; Philipp-Dormston, Wolfgang G; Proebstle, Thomas M; Roth, Claudia; Kerscher, Martina; Ulmann, Claudius; Pavicic, Tatjana

    2012-01-01

    Background Botulinum toxin type A treatment has been used for over 20 years to enhance the appearance of the face. There are several commercially available botulinum toxin type A products used in aesthetic clinical practice. The aim of this retrospective analysis was to compare the clinical efficacy of the most commonly used botulinum toxin type A preparations in daily practice. Methods Physicians from 21 centers in Germany completed questionnaires based on an inspection of subject files for subjects 18 years of age or over who had received at least two, but not more than three, consecutive treatments with incobotulinumtoxinA, onabotulinumtoxinA, or abobotulinumtoxinA within a 12-month period in the previous 2 years. Data on subject and physician satisfaction, treatment intervals, dosages, and safety were collected from 1256 subjects. Results There were no statistically significant differences between incobotulinumtoxinA and onabotulinumtoxinA with respect to physician and subject satisfaction, dosages, and adverse effects experienced. Both botulinum toxin type A preparations were well tolerated and effective in the treatment of upper facial lines. Due to low treatment numbers, abobotulinumtoxinA was not included in the statistical analysis. Conclusion The results of this retrospective analysis confirm the results of prospective clinical trials by demonstrating that, in daily practice, incobotulinumtoxinA and onabotulinumtoxinA are used at a 1:1 dose ratio and display comparable efficacy and safety. PMID:22791996

  11. Vocal aging and adductor spasmodic dysphonia: Response to botulinum toxin injection

    PubMed Central

    Cannito, Michael P; Kahane, Joel C; Chorna, Lesya

    2008-01-01

    Aging of the larynx is characterized by involutional changes which alter its biomechanical and neural properties and create a biological environment that is different from younger counterparts. Illustrative anatomical examples are presented. This natural, non-disease process appears to set conditions which may influence the effectiveness of botulinum toxin injection and our expectations for its success. Adductor spasmodic dysphonia, a type of laryngeal dystonia, is typically treated using botulinum toxin injections of the vocal folds in order to suppress adductory muscle spasms which are disruptive to production of speech and voice. A few studies have suggested diminished response to treatment in older patients with adductor spasmodic dysphonia. This retrospective study provides a reanalysis of existing pre-to-post treatment data as function of age. Perceptual judgments of speech produced by 42 patients with ADSD were made by two panels of professional listeners with expertise in voice or fluency of speech. Results demonstrate a markedly reduced positive response to botulinum toxin treatment in the older patients. Perceptual findings are further elucidated by means of acoustic spectrography. Literature on vocal aging is reviewed to provide a specific set of biological mechanisms that best account for the observed interaction of botulinum toxin treatment with advancing age. PMID:18488884

  12. 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

  13. 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

  14. Comparison of Effects of Botulinum Toxin Injection Between Subacute and Chronic Stroke Patients

    PubMed Central

    Lim, Young-Ho; Choi, Eun-Hi; Lim, Jong Youb

    2016-01-01

    Abstract The aim of this study was to compare the effects of botulinum toxin injection between subacute and chronic stroke patients. Eighteen stroke patients (9 subacute and 9 chronic) with spasticity of 1+ or higher in the hemiplegic elbow or wrist joint, based on the modified Ashworth scale were recruited. Modified Ashworth scale, modified Tardieu scale, manual muscle testing, passive range of motion, Brunnstrom stage, modified Barthel index, and Fugl-Meyer scale evaluations of the hemiplegic upper extremity were performed just before the injection and 4 weeks later. A total dose of 200 U of botulinum toxin type A was injected into each patient. One or more of the elbow flexor muscles and one or more of the wrist flexor or finger flexor muscles were included. Modified Ashworth scale, manual muscle testing, passive range of motion, and modified Barthel index results were improved in subacute patients only. However, modified Tardieu scale for the elbow and Fugl-Meyer scale results were improved in both groups, and the improvement was comparable. In conclusion, botulinum toxin injection in subacute patients was more helpful for spasticity, contracture, and function than in chronic patients. However, beneficial effects of botulinum toxin injection on spasticity and function in chronic patients were found in the assessments of the modified Tardieu scale and Fugl-Meyer scale. PMID:26886649

  15. 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

  16. 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.

  17. Long-term outcomes of balloon dilation versus botulinum toxin injection in patients with primary achalasia

    PubMed Central

    Jung, Ho Eun; Lee, Tae Hee; Kim, Jin Nyoung; Hong, Su Jin; Kim, Jin Oh; Kim, Hyeon Geon; Jeon, Seong Ran; Cho, Joo Young

    2014-01-01

    Background/Aims We compared the long-term outcomes of balloon dilation versus botulinum toxin injection in Korean patients with primary achalasia and identified factors predicting remission. Methods We included 73 patients with achalasia newly diagnosed between January 1988 and January 2011. We ultimately enrolled 37 of 55 patients with primary achalasia through telephone interviews, who were observed for over 1 year. Short-term outcomes were evaluated from the medical records based on symptom relief after 1 month of treatment. Long-term outcomes were evaluated in a telephone interview using a questionnaire. Results Twenty-five patients were administered a botulinum toxin injection and 12 underwent balloon dilation. One month after the botulinum toxin injection, improvements were seen in chest pain (14 [56.0%] to 4 patients [16.0%]), regurgitation (16 [64.0%] to 4 [16.0%]), and dysphagia (25 [100.0%] to 5 [20.0%]). In the balloon dilation group, chest pain (8 [66.7%] to 1 [8.3%]), regurgitation (11 [91.7%] to 1 [8.3%]), and dysphagia (12 [100.0%] to 1 [8.3%]) had improved. A significant difference was observed in the mean remission duration between the botulinum toxin injection and balloon dilation groups (13 months [range, 1 to 70] vs. 29 months [range, 6 to 72], respectively; p = 0.036). Independent factors predicting long-term remission included treatment type (odds ratio [OR], 6.982; p = 0.036) and the difference in the lower esophageal sphincter pressure (OR, 7.198; p = 0.012). Conclusions Balloon dilation may be more efficacious than botulinum toxin for providing long-term remission in Korean patients with achalasia. Follow-up manometry may predict the long-term outcome. PMID:25378972

  18. Primary hyperhidrosis: Implications on symptoms, daily life, health and alcohol consumption when treated with botulinum toxin.

    PubMed

    Shayesteh, Alexander; Boman, Jens; Janlert, Urban; Brulin, Christine; Nylander, Elisabet

    2016-08-01

    Primary hyperhidrosis affects approximately 3% of the population and reduces quality of life in affected persons. Few studies have investigated the symptoms of anxiety, depression and hazardous alcohol consumption among those with hyperhidrosis and the effect of treatment with botulinum toxin. The first aim of this study was to investigate the effect of primary hyperhidrosis on mental and physical health, and alcohol consumption. Our second aim was to study whether and how treatment with botulinum toxin changed these effects. One hundred and fourteen patients answered questionnaires regarding hyperhidrosis and symptoms, including hyperhidrosis disease severity scale (HDSS), visual analog scale (VAS) 10-point scale for hyperhidrosis symptoms, hospital anxiety and depression scale (HADS), alcohol use disorder identification test (AUDIT) and short-form health survey (SF-36) before treatment with botulinum toxin and 2 weeks after. The age of onset of hyperhidrosis was on average 13.4 years and 48% described heredity for hyperhidrosis. Significant improvements were noted in patients with axillary and palmar hyperhidrosis regarding mean HDSS, VAS 10-point scale, HADS, SF-36 and sweat-related health problems 2 weeks after treatment with botulinum toxin. Changes in mean AUDIT for all participants were not significant. Primary hyperhidrosis mainly impairs mental rather than physical aspects of life and also interferes with specific daily activities of the affected individuals. Despite this, our patients did not show signs of anxiety, depression or hazardous alcohol consumption. Treatment with botulinum toxin reduced sweat-related problems and led to significant improvements in HDSS, VAS, HADS and SF-36 in our patients. PMID:26875781

  19. Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency

    PubMed Central

    Saunte, Jon Peiter; Holmes, Jonathan M.

    2015-01-01

    Introduction We evaluated the use of botulinum toxin A in adults with convergence insufficiency in whom prior treatment had failed. Methods We studied 8 patients (median age 36 years, range 17 to 77 years) with reading symptoms due to convergence insufficiency defined as an exodeviation greater at near, not exceeding 10 PD in the distance measured by prism and alternate cover test, and either convergence near point >6 cm or reduced fusional amplitudes. All patients were still symptomatic after prior treatment by convergence exercises (n = 8), base-in prism glasses (n = 5) or strabismus surgery (n = 2). Five patients received injection of 5 IU botulinum toxin in 0.1 ml saline to one lateral rectus muscle, two received 2.5 IU, and one received 2.5 IU to both lateral rectus muscles. Results At 1 month post injection, all patients had an initial reduction of exodeviation from baseline (median 9 PD, p = 0.008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p = 0.3) at near. Reading symptoms improved in 7 of 8 patients at 1-month post injection, and in all patients at 6 months. Two patients had health-related quality of life assessed with the Adult Strabismus 20 Questionnaire, showing improved Reading Function scores at 6 months. Interestingly, 3 patients reported improved reading despite returning to the baseline angle at 6 months, and 2 of 4 with 12-month follow-up still reported improvement. Conclusions In adult convergence insufficiency, botulinum toxin injection to a lateral rectus muscle improves reading symptoms beyond the duration of the pure pharmacological effect. Botulinum toxin injection may be useful in management of adult convergence insufficiency, although repeat injections may be needed. PMID:24786379

  20. “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

  1. "Non-Toxic" Proteins of the Botulinum Toxin Complex Exert In-vivo Toxicity.

    PubMed

    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

  2. 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

  3. 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

  4. 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. PMID:24807497

  5. Internalization and proteolytic action of botulinum toxins in CNS neurons and astrocytes.

    PubMed

    Verderio, C; Coco, S; Rossetto, O; Montecucco, C; Matteoli, M

    1999-07-01

    Tetanus and botulinum toxins bind and are internalized at the neuromuscular junction. Botulinum neurotoxins (BoNTs) enter the cytosol at the motor nerve terminal; tetanus neurotoxin (TeNT) proceeds retroaxonally inside the motor axon to reach the spinal cord inhibitory interneurons. Although the major target of BoNTs is the peripheral cholinergic terminals, CNS neurons are susceptible to intoxication as well. We investigated the route of entry and the proteolytic activity of BoNT/B and BoNT/F in cultured hippocampal neurons and astrocytes. We show that, differently from TeNT, which enters hippocampal neurons via the process of synaptic vesicle (SV) recycling, BoNTs are internalized and cleave the substrate synaptobrevin/VAMP2 via a process independent of synaptic activity. Labeling of living neurons with Texas Red-conjugated BoNTs and fluoresceinated dextran revealed that these toxins enter hippocampal neurons via endocytic processes not mediated by SV recycling. Botulinum toxins also exploit endocytosis to enter cultured astrocytes, where they partially cleave cellubrevin, a ubiquitous synaptobrevin/VAMP isoform. These results indicate that, in spite of their closely related protein structure, TeNT and BoNTs use different routes to penetrate hippocampal neurons. These findings bear important implications for the identification of the protein receptors of clostridial toxins. PMID:10386990

  6. 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

  7. 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

  8. Use of botulinum toxin type A in the management of patients with neurological disorders: a national survey

    PubMed Central

    Smania, Nicola; Colosimo, Carlo; Bentivoglio, Anna Rita; Sandrini, Giorgio; Picelli, Alessandro

    2013-01-01

    Summary The aim of this survey was to provide an overview of important issues relating to therapeutic strategies based on botulinum toxin type A injection for the treatment of patients with neurological disorders. Two hundred and ten physicians from neurology and neurorehabilitation units in Italian hospitals answered a questionnaire exploring some clinical aspects of the use of botulinum toxin type A in patients with spasticity/dystonia. 66% of the physicians treated patients with dystonia, 80% treated adults with spasticity, and 35% treated children with cerebral palsy. Palpation with no instrumental guidance was the injection technique most commonly used for treating patients with dystonia, spasticity and cerebral palsy; 57% of the physicians evaluated patients instrumentally before toxin injection, while 45% assessed post-injection improvements by instrumental means; 78% of the physicians prescribed (when appropriate) rehabilitation procedures after toxin injection. Our results seem to show that the routine use of botulinum toxin in clinics is far from standardized. PMID:24598392

  9. The use of botulinum toxin in head and face medicine: An interdisciplinary field

    PubMed Central

    Laskawi, Rainer

    2008-01-01

    Background In this review article different interdisciplinary relevant applications of botulinum toxin type A (BTA) in the head and face region are demonstrated. Patients with head and face disorders of different etiology often suffer from disorders concerning their musculature (example: synkinesis in mimic muscles) or gland-secretion. This leads to many problems and reduces their quality of life. The application of BTA can improve movement disorders like blepharospasm, hemifacial spasm, synkinesis following defective healing of the facial nerve, palatal tremor, severe bruxism, oromandibular dystonias hypertrophy of the masseter muscle and disorders of the autonomous nerve system like hypersalivation, hyperlacrimation, pathological sweating and intrinsic rhinitis. Conclusion The application of botulinum toxin type A is a helpful and minimally invasive treatment option to improve the quality of life in patients with head and face disorders of different quality and etiology. Side effects are rare. PMID:18331633

  10. Cranial dystonia, blepharospasm and hemifacial spasm: clinical features and treatment, including the use of botulinum toxin.

    PubMed Central

    Kraft, S P; Lang, A E

    1988-01-01

    Blepharospasm, the most frequent feature of cranial dystonia, and hemifacial spasm are two involuntary movement disorders that affect facial muscles. The cause of blepharospasm and other forms of cranial dystonia is not known. Hemifacial spasm is usually due to compression of the seventh cranial nerve at its exit from the brain stem. Cranial dystonia may result in severe disability. Hemifacial spasm tends to be much less disabling but may cause considerable distress and embarrassment. Patients affected with these disorders are often mistakenly considered to have psychiatric problems. Although the two disorders are quite distinct pathophysiologically, therapy with botulinum toxin has proven very effective in both. We review the clinical features, proposed pathophysiologic features, differential diagnosis and treatment, including the use of botulinum toxin, of cranial dystonia and hemifacial spasm. Images Fig. 2 Fig. 3 PMID:3052771

  11. Combined Treatment with Botulinum Toxin and 595-nm Pulsed Dye Laser for Traumatic Scarring.

    PubMed

    Lee, Sang Ju; Jeong, Se Yeong; No, Yeon A; Park, Kui Young; Kim, Beom Joo

    2015-12-01

    Traumatic scars on skin covering areas of high movement, especially areas on the face, can be stressful for patients. We report two cases of traumatic scars that occurred on the chin, and that were successfully treated with a combined therapy of 595-nm pulsed dye laser (PDL) and intramuscular injection of botulinum toxin. After the treatment, good cosmetic results were achieved in both patients. The only adverse effect during and after the treatments was mild pain, which resolved within several days without any additional treatment. In conclusion, the combination of 595-nm PDL and intramuscular botulinum toxin injection was shown to be a safe and effective treatment for traumatic scars on the mobile chin area in Korean patients. PMID:26719648

  12. Monoclonal antibody-based immunoassay for type A Clostridium botulinum toxin is comparable to the mouse bioassay.

    PubMed Central

    Shone, C; Wilton-Smith, P; Appleton, N; Hambleton, P; Modi, N; Gatley, S; Melling, J

    1985-01-01

    A monoclonal antibody (BA11) has been produced against Clostridium botulinum type A neurotoxin by the fusion of myeloma cells (P3 NS1/1-Ag4-1) with spleen cells from BALB/c mice immunized with botulinum type A neurotoxoid. The antibody bound specifically to botulinum type A neurotoxin, showing no cross-reactivity with types B and E botulinum toxins or with any of several other bacterial toxins tested. The monoclonal antibody did not bind to botulinum type A neurotoxin which had been denatured with sodium dodecyl sulfate and bound only weakly to each of the separated heavy and light subunits of the neurotoxin, suggesting a conformational requirement for the antigenic determinant of the antibody. A sensitive immunoassay for C. botulinum type A toxin with monoclonal antibody BA11 in conjunction with an enzyme amplication system has been developed which allows detection of 5 to 10 mouse 50% lethal doses ml-1 of purified neurotoxin. The assay was equally sensitive when applied to the detection of crude toxin in food stuffs; the average value for the minimum level of detectable toxin in extracts of tinned salmon or corned beef was 9 +/- 3.1 mouse 50% lethal doses ml-1. PMID:3927840

  13. Botulinum toxin for the treatment of hyperfunctional lines of the forehead

    PubMed Central

    Sunil, Sathigrama Malegowda; Babu, B. Ganesh; Deepthi, Soma; Veerabhadrappa, Anusha Channabasappa; Vadavadagi, Suneel V.; Punde, Prashant

    2015-01-01

    Background: In the 21st century, we live longer and a more active life. However, while our adult longevity continues to extend, society does not welcome a tired and aged appearance. We wish to continue to look as young as possible. Most facial rejuvenation techniques such as surgery and injection of collagen, silicone, or autogenous fat do not address the fact that these lines are functional, i.e. they do not target the cause of hyperfunctional lines: the underlying facial mimetic musculature. Aim: To find the efficacy of Botulinum toxin for the treatment of hyperfunctional lines of the forehead. Materials and Methods: The present study consisted of 25 subjects in the age group of 25–65 years with forehead wrinkles, who visited the Department of Oral and Maxillofacial Surgery, CIDS, Virajpet. The materials used for Botulinum toxin treatment were Botulinum toxin A, a standard freezer, sterile saline solution, alcohol swabs, and insulin syringes with 30 gauge needles. Results: Of the 25 patients, 21 patients showed satisfactory improvement of their hyperfunctional facial lines within 72 h. Maximum improvement was noted in the age group of 25–40 years, while the older age group of 50–65 years showed less improvement. Maximum improvement was seen in type 5 skin, followed by type 4 and type 3 skin. Type 2 skin showed the least improvement. Conclusion: We conclude that Botulinum toxin A is a safe and efficacious method of nonsurgically eliminating hyperfunctional facial lines of the forehead in the aesthetic patient for a period of 4–6 months. PMID:26312226

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

    DOE PAGESBeta

    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 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

  15. 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

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

    PubMed

    Lockwood, Gina; 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

  17. 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

  18. 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

  19. Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection

    PubMed Central

    Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P.; Ismail, Farooq

    2016-01-01

    Objective To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. Methods As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. Results International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%–30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. Conclusion In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients. PMID:27152278

  20. Studies on the irradiation of toxins of Clostridium botulinum and Staphylococcus aureus.

    PubMed

    Rose, S A; Modi, N K; Tranter, H S; Bailey, N E; Stringer, M F; Hambleton, P

    1988-09-01

    The effects of irradiation of Clostridium botulinum neurotoxin type A (BNTA) and staphylococcal enterotoxin A (SEA) in gelatin phosphate buffer and cooked mince beef slurries were investigated. Estimation of toxins by immunoassays showed that in buffer, toxins were destroyed by irradiation at 8.0 kGy; in mince slurries however, 45% of BTNA and 27-34% of SEA remained after this level of irradiation. At 23.7 kGy, over twice the dose of irradiation proposed for legal acceptance in the UK, 15% of BNTA and 16-26% of SEA still remained. Increasing concentrations of mince conferred increased protection against the effect of irradiation on both toxins. The biological activity of BNTA was more sensitive to irradiation than the immunological activity. Staphylococcal enterotoxin was more resistant to irradiation than BNTA. Irradiation should therefore only be used in conjunction with good manufacturing practices to prevent microbial proliferation and toxin production prior to irradiation. PMID:3230088

  1. 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

  2. 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

  3. 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

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

    PubMed

    Oh, Hyun-Mi; Chung, Myung Eun

    2015-08-01

    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

  5. 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

  6. Botulinum toxin for the treatment of myofascial pain syndromes involving the neck and back: a review from a clinical perspective.

    PubMed

    Climent, José M; Kuan, Ta-Shen; 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

  7. The response of motor neurones to intramuscular injection of botulinum toxin

    PubMed Central

    Watson, W. E.

    1969-01-01

    1. The dry mass and nucleic acid content of both nerve cell bodies and their nucleoli were measured by interference microscopy and ultra-violet absorption microspectrography respectively: succinoxidase and acetylcholine hydrolase activities were also determined. Autoradiography was used to follow synthesis of deoxyribonucleic acid (DNA) by glial cells, and to follow nucleic acid and protein metabolism in muscle fibres. 2. After injection of botulinum toxin the synthesis of ribosomal RNA by the neurone followed closely the pattern found after axotomy. 3. After injection of toxin neuronal dry mass increased before the rate of ribosomal RNA synthesis was raised. This early increase, which was not due to increased protein synthesis, probably represents a `damming back' of proteins within the nerve cell body. 4. After injection of toxin no local accumulation of microglial cells synthesizing DNA was found around the affected neurones: it is suggested that this reflects the intact system for intra-axonal transport under these conditions. 5. The affected muscles show increased nucleic acid and protein synthesis. 6. It is suggested that the results obtained indicate that membrane expansion or synthesis which occurs both in muscle and in neurone under these circumstances is the factor responsible for inducing directly or indirectly the changes found in nucleic acid metabolism after injection of botulinum toxin and after axotomy. ImagesFig. 1Fig. 2 PMID:4892690

  8. 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. PMID:26866498

  9. Comparative evaluation of botulinum toxin versus iontophoresis with topical aluminium chloride hexahydrate in treatment of palmar hyperhidrosis

    PubMed Central

    Rajagopal, R.; Mallya, Nikhitha B.

    2014-01-01

    Background Hyperhidrosis is generalised or focal excessive sweating and carries a substantial psychological and social burden. This study compares botulinum toxin versus iontophoresis with topical aluminium chloride hexahydrate in palmar hyperhidrosis. Methods The study included 60 cases of palmar hyperhidrosis randomly allocated to 2 groups. One group was given botulinum toxin type A 100 units per palm and the other group subjected to digital iontophoresis with topical application of aluminium chloride hexahydrate lotion for 4 weeks. They were assessed 4 weeks later and those without improvement were crossed over to the other arm for another 4 weeks. Those with improvement were followed up in the same arm for 6 months. Results Botulinum therapy showed significant improvement in the initial (80%) as well as cross over cases (75%) as compared to iontophoresis and aluminium chloride (47%) for initial cases and (17%) for cross over cases. Conclusion Better improvements were seen with botulinum therapy than with iontophoresis and topical therapy. Residual effects of relief lasted on an average for 4 months for botulinum toxin whereas it was one month with iontophoresis and topical therapy. Advantage with iontophoresis and topical therapy was that it was non invasive and did not require regional anaesthesia as with botulinum therapy. PMID:25378778

  10. Botulinum toxin injection techniques for the management of adult spasticity.

    PubMed

    Walker, Heather W; Lee, Michael Y; Bahroo, Laxman B; Hedera, Peter; Charles, David

    2015-04-01

    Spasticity is often experienced by individuals with injury or illness of the central nervous system from etiologies such as stroke, spinal cord injury, brain injury, multiple sclerosis, or other neurologic conditions. Although spasticity may provide benefits in some patients, it more often leads to complications negatively impacting the patient. Nonpharmacologic treatment options often do not provide long-term reduction of spasticity, and systemic interventions, such as oral medications, can have intolerable side effects. The use of botulinum neurotoxin injections is one option for management of focal spasticity. Several localization techniques are available to physicians that allow for identification of the selected target muscles. These methods include anatomic localization in isolation or in conjunction with electromyography guidance, electrical stimulation guidance, or ultrasound guidance. This article will focus on further description of each of these techniques in relation to the treatment of adult spasticity and will discuss the advantages and disadvantages of each technique, as well as review the literature comparing the techniques. PMID:25305369

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

    PubMed Central

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

    2011-01-01

    SUMMARY 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. PMID:18461049

  12. The Use of Botulinum Toxin in the Management of Headache Disorders.

    PubMed

    Silberstein, Stephen D

    2016-02-01

    Headache disorders can be further classified as episodic (< 15 headache days per month) or chronic (≥15 headache days per month for more than 3 months). Chronic migraine (CM) requires that headaches occur on 15 or more days a month for more than 3 months. These headaches must be migraines on at least 8 days per month. There are seven botulinum toxin (BoNT) serotypes (A1, A2, A3, B, C1, D, E, F, and G). All serotypes inhibit acetylcholine release, although their intracellular target proteins, physiochemical characteristics, and potencies are different. Its mechanism of action in pain is being investigated. Botulinum toxin type A (BoNT-A) has been the most widely studied serotype for therapeutic purposes. A major clinical advantage of type A toxin arises from its prolonged duration of action due to the longevity of its protease (90 days in rats and probably much longer in human neurons). Clinical studies suggest that BoNT is a safe treatment and is efficacious for the prevention of some forms of migraine, such as CM, and perhaps high-frequency episodic migraine. PMID:26866501

  13. The use of botulinum toxin in the treatment of sialorrhea in parkinsonian disorders.

    PubMed

    Gómez-Caravaca, María T; Cáceres-Redondo, María T; Huertas-Fernández, Ismael; Vargas-González, Laura; Carrillo, Fátima; Carballo, Manuel; Mir, Pablo

    2015-02-01

    Drooling is a common symptom in parkinsonian disorders. Our aim was to assess the safety and effect of botulinum toxin when applied to parotid glands without ultrasound guidance for sialorrhea in parkinsonian disorders in a retrospective study with a long-term follow-up. We evaluated 53 patients (64.2% male and 35.8% female) with a mean age of 70.18 ± 9.25 years who were treated in our centre between 2007 and 2013. We analysed the mean dose, latency, effect duration, response and adverse effects of treating sialorrhea by injecting botulinum toxin type A (Botox) into the parotid glands without ultrasound guidance. A total of 41 patients with Parkinson's disease, 6 with progressive supranuclear palsy, 4 with multiple system atrophy and 2 with corticobasal degeneration were included. The mean duration of the disease at onset was 10.51 ± 6.81 years and the mean sialorrhea duration was 1.99 ± 1.55 years. The initial dose used for each parotid gland was 14.53 ± 3.95 units of Botox, with a mean dose of 22.17 ± 8.76 units. There was an improvement after treatment in 65.22% of patients with an average score of 6.85 ± 1.58 points on a scale from 0 to 10. The duration of the treatment effect was 4.38 ± 2.11 months, with a latency period of 10.06 ± 9.63 days. Adverse effects were mild and infrequent. Botulinum toxin is a safe and effective therapy for the treatment of sialorrhea in parkinsonian disorders and there is no requirement for ultrasound guidance. It has a rapid onset and lasting effect without requiring a high dosage. PMID:25238916

  14. Botulinum toxin a injection to facial and cervical paraspinal muscles in a patient with stiff person syndrome: a case report.

    PubMed

    Pakeerappa, Praveen N; Birthi, Pravardhan; Salles, Sara

    2015-03-01

    Stiff person syndrome (SPS) is a rare neurologic disorder of unknown etiology characterized by increased resting muscle tone, progressive rigidity, and stiffness of the axial musculature. We present a case of a 48-year-old male patient with SPS who experienced facial and neck muscle spasms that were uncontrolled with oral medications and the use of an intrathecal baclofen pump. Botulinum toxin A injections into the bilateral masseter and neck paraspinal muscles provided pain relief and spasm control, illustrating the use of botulinum toxin A injections in the small muscles of face and neck in patients with SPS. PMID:25459656

  15. 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

  16. Role of Botulinum Toxin Type-A (BTX-A) in the Management of Trigeminal Neuralgia

    PubMed Central

    2013-01-01

    Trigeminal neuralgia (TN) is a clinical condition characterized by paroxysmal attacks of severe and electric shock-like pain along the distribution of one or more branches of the trigeminal nerve. Various medicinal or surgical modalities have been employed in the past with variable success. Newer methods were tried in search of permanent cure or long-lasting pain relief. The purpose of this paper is to present the review of the literature regarding the use of botulinum toxin type-A (BTX-A) in the management of trigeminal neuralgia. PMID:24194982

  17. Focal hyperhidrosis secondary to eccrine naevus successfully treated with botulinum toxin type A.

    PubMed

    Lera, M; España, A; Idoate, M Á

    2015-08-01

    Eccrine naevus (EN) is a rare skin hamartoma included in the organoid group of epidermal naevi, histologically defined as focal hyperplasia and/or hypertrophy of eccrine glands. Clinically, EN usually presents as hyperhidrotic patches with no visible skin changes, frequently located on the forearms. The decision to treat EN or not usually depends on the grade of hyperhidrosis, but there is no therapeutic consensus because of the rarity of this condition. We present a case diagnosed as EN in an adult patient with severe localized hyperhidrosis, which was successfully treated with botulinum toxin. PMID:25816711

  18. An update on the use of botulinum toxin therapy in Parkinson's disease.

    PubMed

    Mills, Reversa; Bahroo, Laxman; Pagan, Fernando

    2015-01-01

    Botulinum toxin (BoNT) has gained widespread use in a variety of neurological conditions. Parkinson's disease is a complex neurodegenerative disorder manifested by motor and non-motor symptoms that can cause significant disability. BoNT has been used to effectively treat a variety of symptoms related to Parkinson's disease. This review will examine the current therapeutic indications of BoNT use in the following disorders related to Parkinson's disease: cervical dystonia, blepharospasm and lid apraxia, focal hand dystonia, foot dystonia, laryngeal dystonia, oromandibular dystonia, camptocormia, hand and jaw tremor, sialorrhea, hyperhidrosis, dysphagia, constipation, and overactive bladder. PMID:25407133

  19. 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. PMID:26555524

  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. PMID:25577739

  2. Interaction of botulinum and tetanus toxins with the lipid bilayer surface.

    PubMed Central

    Montecucco, C; Schiavo, G; Gao, Z; Bauerlein, E; Boquet, P; DasGupta, B R

    1988-01-01

    The interaction of botulinum neurotoxins serotypes A, B and E (from Clostridium botulinum) and of tetanus neurotoxin (from Clostridium tetani) with the surface of liposomes made of different lipid compositions was studied by photolabelling with a radioiodinated photoactive phosphatidylethanolamine analogue [125I-dipalmitoyl (3,4-azidosalicylamido)phosphatidylethanolamine]. When the vesicles were made of negatively charged lipids (asolectin), each of these neurotoxic proteins was radioiodinated, thus providing evidence for their attachment to the membrane surface. The presence of gangliosides on liposome membranes enhanced fixation of the neurotoxic proteins to the lipid vesicle surface. Both the heavy and light chains of the clostridial neurotoxins were involved in the attachment to the lipid bilayer surface. Each of the toxins tested here attached poorly to liposomes made of zwitterionic lipids (egg phosphatidylcholine), even when polysialogangliosides were present. The data suggest that the binding of botulinum and tetanus neurotoxins to their target neuronal cells involves negatively charged lipids and polysialogangliosides on the cell membrane. Images Fig. 2. PMID:3401212

  3. An Alternative In Vivo Method to Refine the Mouse Bioassay for Botulinum Toxin Detection

    PubMed Central

    Wilder-Kofie, Temeri D; Lúquez, Carolina; Adler, Michael; Dykes, Janet K; Coleman, JoAnn D; Maslanka, Susan E

    2011-01-01

    Botulism is a rare, life-threatening paralytic disease of both humans and animals that is caused by botulinum neurotoxins (BoNT). Botulism is confirmed in the laboratory by the detection of BoNT in clinical specimens, contaminated foods, and cultures. Despite efforts to develop an in vitro method for botulinum toxin detection, the mouse bioassay remains the standard test for laboratory confirmation of this disease. In this study, we evaluated the use of a nonlethal mouse toe-spread reflex model to detect BoNT spiked into buffer, serum, and milk samples. Samples spiked with toxin serotype A and nontoxin control samples were injected into the left and right extensor digitorum longus muscles, respectively. Digital photographs at 0, 8, and 24 h were used to obtain objective measurements through effective paralysis scores, which were determined by comparing the width-to-length ratio between right and left feet. Both objective measurements and clinical observation could accurately identify over 80% of animals injected with 1 LD50 (4.3 pg) BoNT type A within 24 h. Half of animals injected with 0.5 LD50 BoNT type A and none injected with 0.25 LD50 demonstrated localized paralysis. Preincubating the toxin with antitoxin prevented the development of positive effective paralysis scores, demonstrating that (1) the effect was specific for BoNT and (2) identification of toxin serotype could be achieved by using this method. These results suggest that the mouse toe-spread reflex model may be a more humane alternative to the current mouse bioassay for laboratory investigations of botulism. PMID:21819693

  4. Identification of the interaction region between hemagglutinin components of the botulinum toxin complex.

    PubMed

    Suzuki, Tomonori; Miyashita, Shin-Ichiro; Hayashi, Shintaro; Miyata, Keita; Inui, Ken; Kondo, Yosuke; Miyazaki, Satoru; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro; Sagane, Yoshimasa

    2014-04-01

    The large toxin complex (L-TC) produced by Clostridium botulinum is formed from the M-TC (BoNT/NTNHA complex) by conjugation of M-TC with HA-33/HA-17 trimer consists of two HA-33 proteins and a single HA-17 protein. This association is mediated by HA-70, which interacts with HA-17. The current study aims to identify the regions of the HA-70 molecule that adhere to the HA-33/HA-17 complex. Products from limited proteolysis of HA-70 were resolved by SDS-PAGE and transferred onto PVDF membranes, where they were probed with HA-33/HA-17 in a far-western blot. Among the HA-70 fragments, HA-33/HA-17 bound to those containing at least the C-terminal half of the HA-70 molecule, but not those carrying the N-terminal half. Additional docking simulation analysis indicated that the HA-70 region Gln420-Tyr575 is responsible for binding to HA-17, which is consistent with the far-western blot data. The findings here reveal additional details concerning the three-dimensional structure of the functional HA sub-complex in the botulinum toxin complex. PMID:24472509

  5. 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.

  6. 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.

  7. Attomolar Detection of Botulinum Toxin Type A in Complex Biological Matrices

    PubMed Central

    Bagramyan, Karine; Barash, Jason R.; Arnon, Stephen S.; Kalkum, Markus

    2008-01-01

    Background A highly sensitive, rapid and cost efficient method that can detect active botulinum neurotoxin (BoNT) in complex biological samples such as foods or serum is desired in order to 1) counter the potential bioterrorist threat 2) enhance food safety 3) enable future pharmacokinetic studies in medical applications that utilize BoNTs. Methodology/Principal Findings Here we describe a botulinum neurotoxin serotype A assay with a large immuno-sorbent surface area (BoNT/A ALISSA) that captures a low number of toxin molecules and measures their intrinsic metalloprotease activity with a fluorogenic substrate. In direct comparison with the “gold standard” mouse bioassay, the ALISSA is four to five orders of magnitudes more sensitive and considerably faster. Our method reaches attomolar sensitivities in serum, milk, carrot juice, and in the diluent fluid used in the mouse assay. ALISSA has high specificity for the targeted type A toxin when tested against alternative proteases including other BoNT serotypes and trypsin, and it detects the holotoxin as well as the multi-protein complex form of BoNT/A. The assay was optimized for temperature, substrate concentration, size and volume proportions of the immuno-sorbent matrix, enrichment and reaction times. Finally, a kinetic model is presented that is consistent with the observed improvement in sensitivity. Conclusions/Significance The sensitivity, specificity, speed and simplicity of the BoNT ALISSA should make this method attractive for diagnostic, biodefense and pharmacological applications. PMID:18446228

  8. 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

  9. Anatomic considerations in botulinum toxin type A therapy for spasmodic dysphonia.

    PubMed

    Castellanos, P F; Gates, G A; Esselman, G; Song, F; Vannier, M W; Kuo, M

    1994-06-01

    Chemodenervation by injection of botulinum toxin type A into the vocal fold(s) has become the preferred treatment for patients with adductor spasmodic dysphonia. Injection may be done either perorally or transcutaneously; each method has its advocates and advantages. The authors have used the transcutaneous transcricothyroid membrane route exclusively with satisfactory results in more than 50 patients. Temporary breathliness and aspiration are common. The preferred injection site should be as close as possible to the motor end plates of the affected muscle. The thyroarytenoid muscle end plates are distributed throughout the muscle, whereas in the lateral cricoarytenoid muscle they are located in band in the center of the muscle. The transcutaneous injection site is below and posterior to the midpoint of the vibrating vocal fold as visualized by indirect laryngoscopy. The proximity of this site to the lateral cricoarytenoid muscle suggests that postinjection breathiness and aspiration may be related to spread of botulinum toxin type A to the lateral cricoarytenoid muscle. However, it is likely that thyroarytenoid muscle paresis is mainly responsible for this side effect and that the rapid clearing of the breathy dysphonia in the face of prolonged relief of spasmodic dysphonia symptoms suggests the action of an adaptive neural response, such as axonal sprouting. Further research of this subject is warranted. PMID:8196438

  10. 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…

  11. 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...

  12. 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. PMID:26914922

  13. Therapeutic efficacy and safety of botulinum toxin type A in trigeminal neuralgia: a systematic review

    PubMed Central

    2013-01-01

    Trigeminal neuralgia is a common disorder caused mainly by compression of the trigeminal nerve root by an overlying blood vessel. Pharmacotherapy and surgery are ineffective or unsuitable in many patients. Therefore, other therapeutic modalities have been tried, including injection of botulinum toxin type A (BTX-A). This study aims to systematically review the therapeutic efficacy and safety of BTX-A in trigeminal neuralgia. PubMed, EMBASE, Cochrane Library Clinical Trials and Web of Science from January 1966 to March 2013 were searched with the terms of “botulinum toxin” AND “trigeminal neuralgia”, and references of related articles were traced. Data on the efficacy and safety of BTX-A in this disorder were extracted and analyzed by at least 2 reviewers. Data for individual studies were reported, and pooled data were analyzed if appropriate. Five prospective studies and one double-blind, randomized, placebo-controlled study were identified. Response was achieved in approximately 70-100% of patients, and the mean pain intensity and frequency were reduced by approximately 60-100% at 4 weeks after treatment in most studies. Major adverse events were not reported. Available studies show BTX-A may be effective in treatment of trigeminal neuralgia. However, well-designed randomized, controlled, double-blinded trial is still lacking. Future BTX-A treatment studies on optimal dose, duration of the therapeutic efficacy, common AEs, and the time and indications for repeat injection would be promising. PMID:23964790

  14. Ultrasensitive detection of protease activity of anthrax and botulinum toxins by a new PCR-based assay.

    PubMed

    Kolesnikov, Alexander V; Kozyr, Arina V; Ryabko, Alyona K; Shemyakin, Igor G

    2016-02-01

    Anthrax and botulism are dangerous infectious diseases that can be fatal unless detected and treated quickly. Fatalities from these diseases are primarily due to endopeptidase toxins secreted by the pathogens. Rapid and sensitive detection of the presence of active toxins is the key element for protection from natural outbreaks of anthrax and botulism, as well as from the threat of bioterrorism. We describe an ultrasensitive polymerase chain reaction (PCR)-based assay for detecting proteolytic activity of anthrax and botulinum toxins using composite probes consisting of covalent peptide-DNA conjugate for the detection of anthrax, and noncovalent protein-aptamer assembly to assay botulinum toxin activity. Probes immobilized on the solid-phase support are cleaved by toxins to release DNA, which is detected by real-time PCR. Both assays can detect subpicogram quantities of active toxins isolated from composite matrices. Special procedures were developed to isolate intact toxins from the matrices under mild conditions. The assay is rapid, uses proven technologies, and can be modified to detect other proteolytic and biopolymer-degrading enzymes. PMID:26620058

  15. 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. PMID:3220708

  16. 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. PMID:26445325

  17. 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

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

    PubMed

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

    2015-07-01

    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

  19. Botulinum toxin in the treatment of muscle specific Oro-facial pain: a literature review.

    PubMed

    Sunil Dutt, C; Ramnani, Pooja; Thakur, Deepak; Pandit, Manish

    2015-06-01

    Facial pain associated with temporomandibular joint (TMJ) and surrounding structures has been a challenge to clinicians as far as diagnosis and management is concerned. Complexity of anatomical structures within a small area, function of teeth and surrounding periodontal ligament, action of muscles, pathologies, lack of diagnostic investigations, all these complicate specific diagnosis of TMJ disorders. Various classifications have been designed and studied to help diagnose and treat TMJ related disorders, of which the simplest one is pain from TMJ proper and surrounding muscles. Many treatment modalities to treat pain arising from muscles around TMJ like splints, mouth restriction exercises, injection of sclerosing agents etc. have been used with various degrees of success. Botulinum toxin has been shown to be effective in the treatment of oro-facial pain due to muscular disorders and the same is discussed in detail in this review literature. PMID:26028831

  20. 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. PMID:16905418

  1. [Tetanus and botulinum toxins are zinc metallopeptidases: molecular mechanisms and inhibition of their neurotoxicity].

    PubMed

    Cornille, F; Roques, B P

    1999-01-01

    The very high toxicity of tetanus neurotoxin (TeNT) and botulinum neurotoxin (BoNT) are related to their nature of zinc metallopeptidases able to selectively cleave small proteins involved in neurotransmitters exocytosis. At this time, there is no efficient and selective therapy towards tetanos and tobulism as well as protection against a possible spreading of the toxins. We have therefore investigated the minimum sequences of TeNT and BoNT substrates allowing an efficient and simple fluorescent dosage of the enzymatic activity to be developed. Using synaptobrevin (93 amino acids) as substrate of TeNT and several fragments synthesised by solid phase method, we have shown that the clostridial neurotoxins behave as allosteric-type enzymes. This is the first example in zinc metallopeptidases. Based on these results a strategy, including the use of combinatorial chemistry, was carried out issuing in the design of the first potent inhibitors of TeNT and BoNT. PMID:10783709

  2. Botulinum toxin-A treatment reduces human mechanical pain sensitivity and mechanotransduction.

    PubMed

    Paterson, Kathryn; Lolignier, Stéphane; Wood, John N; McMahon, Stephen B; Bennett, David L H

    2014-04-01

    The mechanisms underlying the analgesic effects of botulinum toxin serotype A (BoNT-A) are not well understood. We have tested the hypothesis that BoNT-A can block nociceptor transduction. Intradermal administration of BoNT-A to healthy volunteers produced a marked and specific decrease in noxious mechanical pain sensitivity, whereas sensitivity to low-threshold mechanical and thermal stimuli was unchanged. BoNT-A did not affect cutaneous innervation. In cultured rodent primary sensory neurons, BoNT-A decreased the proportion of neurons expressing slowly adapting mechanically gated currents linked to mechanical pain transduction. Inhibition of mechanotransduction provides a novel locus of action of BoNT-A, further understanding of which may extend its use as an analgesic agent. PMID:24550077

  3. Osteopenic consequences of botulinum toxin injections in the masticatory muscles: a pilot study.

    PubMed

    Raphael, K G; Tadinada, A; Bradshaw, J M; Janal, M N; Sirois, D A; Chan, K C; Lurie, A G

    2014-08-01

    Patients with temporomandibular muscle and joint disorder (TMJD) increasingly seek and receive treatment for their pain with botulinum toxin (BoNTA; botulinum toxin A). Used intramuscularly in therapeutic doses, it produces localised paresis. Such paresis creates risk of reduced bone mineral density, or 'disuse osteopenia'. Animal studies have frequently used BoNTA as a model of paralysis to induce bone changes within short periods. Osteopenic effects can be enduring in animals but have yet to be studied in humans. This is the first study in humans to examine bone-related consequences of BoNTA injections in the masticatory muscles, comparing oral and maxillofacial radiologists' ratings of trabecular bone patterns in the condyles of patients with TMJD exposed to multiple masticatory muscle injection sessions with BoNTA to a sample of patients with TMJD unexposed to masticatory muscle injections with BoNTA. Cone-beam computed tomography (CBCT)-derived images of bilateral condyles were evaluated in seven patients with TMJD receiving 2+ recent BoNTA treatment sessions for facial pain and nine demographically matched patients with TMJD not receiving BoNTA treatment. Two oral and maxillofacial radiologists evaluated CBCT images for evidence of trabecular changes consistent with osteopenia. Both evaluators noted decreased density in all participants exposed to BoNTA and in none of the unexposed participants (P < 0.001). No other abnormalities associated with reduced loading were detected. These findings need replication in a larger sample and over a longer time period, to ensure safety of patients with TMJD receiving multiple BoNTA injections for their pain. PMID:24836732

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

    PubMed

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

    2015-09-01

    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

  5. 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

  6. Botulinum Toxin Injection for Treatment of Acute Traumatic Superior Oblique Muscle Palsy

    PubMed Central

    Talebnejad, Mohammad Reza; Tahamtan, Maryam; Nowroozzadeh, M. Hossein

    2015-01-01

    Purpose: To evaluate the outcomes of botulinum toxin injection into the inferior oblique (IO) muscle for management of unilateral acute traumatic superior oblique (SO) palsy. Methods: In this prospective case series, 10-20 units of botulinum toxin A (Dysport, Ipsen, Biopharm Ltd., Wrexham, UK) was injected into the ipsilateral IO muscle of 13 consecutive patients with unilateral acute traumatic SO palsy. All patients received injections within four weeks of the incident. Results: Mean age was 29 ± 15 years and 12 (92%) subjects were male. Mean amount of hypertropia (in primary position) was decreased from 10.0 ± 3.9Δ at baseline to 4.6 ± 8.9Δ, one month after the injection, and to 1.5 ± 2.7Δ at final follow-up (P = 0.001). IO overaction improved from 2.7 ± 0.6 to 1.0 ± 1.2 and 0.6 ± 0.9 (P ≤ 0.001), and subjective torsion from 5.3 ± 3.9 to 3.2 ± 3.4 and 1.6 ± 2.5 degrees (P ≤ 0.001), at the same time intervals respectively. One month after the injection as well as at final follow-up, 10 (77%) patients were diplopia-free in primary and reading positions. Subgroup analysis showed that patients who recovered had less baseline hypertropia as compared to those who failed (8.3Δ vs. 15.7Δ, respectively; P = 0.01). All patients with a favorable outcome had baseline hypertropia of 10Δ or less. Conclusion: A single injection of BTA into the IO muscle can rapidly and safely resolve symptomatic diplopia in patients with acute traumatic SO palsy, while waiting for spontaneous recovery. PMID:26730311

  7. Esophageal perforation, inflammatory mediastinitis and pseudoaneurysm of the thoracic aorta as potential complications of botulinum toxin injection for achalasia.

    PubMed

    Chao, Che Yung; Raj, Ashok; Saad, Nivene; Hourigan, Luke; Holtmann, Gerald

    2015-07-01

    Primary achalasia is a motility disorder of the esophagus involving impaired relaxation of the esophageal sphincter and, in later stages, dilatation and aperistalsis of the tubular esophagus. Endoscopic botulinum toxin injection to the lower esophageal sphincter is an effective and safe option in the treatment algorithm of achalasia, particularly in high-surgical-risk patients. In the present case report, we describe a rare complication of esophageal perforation following botulinum injection, resulting in associated inflammatory mediastinitis and formation of a pseudoaneurysm in the descending aorta. To the authors' knowledge, this is the first report in the literature of this rare complication of endoscopic botulinum injection. A contributing factor might have been the use of an injecting device with a significantly longer adjustable needle. Endoscopists should remain clinically vigilant to the potential complications associated with this common procedure. PMID:25329507

  8. 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.

  9. Interneuronal Transfer and Distal Action of Tetanus Toxin and Botulinum Neurotoxins A and D in Central Neurons.

    PubMed

    Bomba-Warczak, Ewa; Vevea, Jason D; Brittain, Joel M; Figueroa-Bernier, Annette; Tepp, William H; Johnson, Eric A; Yeh, Felix L; Chapman, Edwin R

    2016-08-16

    Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. Here, we investigate the potential distal effects of BoNT/A, BoNT/D, and tetanus toxin (TeNT), using central neurons grown in microfluidic devices. Toxins acted upon the neurons that mediated initial entry, but all three toxins were also taken up, via an alternative pathway, into non-acidified organelles that mediated retrograde transport to the somato-dendritic compartment. Toxins were then released into the media, where they entered and exerted their effects upon upstream neurons. These findings directly demonstrate that these agents undergo transcytosis and interneuronal transfer in an active form, resulting in long-distance effects. PMID:27498860

  10. Antagonism of the paralysis produced by botulinum toxin in the rat. The effects of tetraethylammonium, guanidine and 4-aminopyridine.

    PubMed

    Lundh, H; Leander, S; Thesleff, S

    1977-05-01

    The injection of botulinum toxin type A into the hind-leg of adult rats causes complete paralysis of the leg lasting for several weeks. In the extensor digitorum longus (EDL) muscle transmitter release is reduced to a level of less than 1% of normal. Tetraethylammonium (TEA) and guanidine in concentrations of about 3 mM restore, in EDL muslces in vitro, neuromuscular transmission to about the normal level, provided that the external calcium concentration is 4 mM or higher. 4-Aminopyridine (4-AP) has similar restorative effect but is about 20-30 times more potent. Unlike TEA and guanidine, 4-AP is effective when the ambient calcium concentration is 2 mM; this drug is therefore also active in vivo. The intravenous injection of 4-AP (5 mg/kg body weight) restores neuromuscular transmission from complete paralysis by botulinum toxin to a normal level as shown by the recording of almost normal twitch and tetanic tensions in the EDL muscle. In rats paralysed by a lethal dose of botulinum toxin, the intraperitoneal administration of 4-AP restores general motor activity, the effect lasting 1-2 hours. A study of the effects of these drugs on spontaneous and evoked transmitter release suggests that all three compounds increase the level of free calcium inside the nerve terminals. In botulinum poisoning the transmitter release mechanism appears to be intact, but a reduced sensitivity to calcium has been shown (Cull-Candy et al. 1976), and this could explain why the drugs restore evoked transmitter release in botulinum poisoning. PMID:194021

  11. 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

  12. Botulinum toxin type-A injection to treat patients with intractable anismus unresponsive to simple biofeedback training

    PubMed Central

    Zhang, Yong; Wang, Zhen-Ning; He, Lei; Gao, Ge; Zhai, Qing; Yin, Zhi-Tao; Zeng, Xian-Dong

    2014-01-01

    AIM: To evaluate the efficacy of botulinum toxin type A injection to the puborectalis and external sphincter muscle in the treatment of patients with anismus unresponsive to simple biofeedback training. METHODS: This retrospective study included 31 patients suffering from anismus who were unresponsive to simple biofeedback training. Diagnosis was made by anorectal manometry, balloon expulsion test, surface electromyography of the pelvic floor muscle, and defecography. Patients were given botulinum toxin type A (BTX-A) injection and pelvic floor biofeedback training. Follow-up was conducted before the paper was written. Improvement was evaluated using the chronic constipation scoring system. RESULTS: BTX-A injection combined with pelvic floor biofeedback training achieved success in 24 patients, with 23 maintaining persistent satisfaction during a mean period of 8.4 mo. CONCLUSION: BTX-A injection combined with pelvic floor biofeedback training seems to be successful for intractable anismus. PMID:25253964

  13. 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.

  14. Sialorrhea: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins.

    PubMed

    Lakraj, Amanda Amrita; Moghimi, Narges; Jabbari, Bahman

    2013-05-01

    Sialorrhea or excessive drooling is a major issue in children with cerebral palsy and adults with neurodegenerative disorders. In this review, we describe the clinical features, anatomy and physiology of sialorrhea, as well as a review of the world literature on medical treatment using Yale University's search engine; including but not limited to Medline and Erasmus. Level of drug efficacy is defined according to the guidelines of American Academy of Neurology. Current medical management is unsatisfactory. Topical agents (scopolamine and tropicamide) and oral agents (glyccopyrolate) combined render a level B evidence (probably effective); however, this treatment is associated with troublesome side effects. Double-blind and placebo-controlled studies of botulinum toxin (BoNT) provide a level A evidence for type B (two class I studies; effective and established) and both overall and individual B level of evidence for OnabotulinumtoxinA (A/Ona) and AbobotulinumtoxinA (A/Abo); these are probably effective. For IncobotulinumtoxinA (A/Inco), the level of evidence is U (insufficient) due to lack of blinded studies. Side effects are uncommon; transient and comparable between the two types of toxin. A clinical note at the end of this review comments on fine clinical points. Administration of BoNTs into salivary glands is currently the most effective way of treating sialorrhea. PMID:23698357

  15. 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

  16. 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,…

  17. 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

  18. [INJECTION OF BOTULINUM TOXIN TYPE A IN THE BLADDER DETRUSOR AND SUBMUCOSA IN PATIENTS WITH OVERACTIVE BLADDER WITHOUT DETRUSOR OVERACTIVITY].

    PubMed

    Krivoborodov, G G; Tur, E I; Efremov, N S

    2015-01-01

    The objective of the study was to compare the efficacy and safety of injections of botulinum toxin type A in the submucosal layer of the bladder and in detrusor in patients who were refractory to anticholinergic therapy of overactive bladder without detrusor overactivity. 100 U botulinum toxin type A was diluted in 10 ml of 0.9% saline and injected with 0.5 ml (5 units) of this solution in 20 points of the bladder (the back and side walls except Letto triangle). In twenty-two patients (the first group) botulinum toxin was injected into the submucosal layer of the bladder, while in 34 patients (second group) - into the detrusor. In the first group after 1 and 3 months 3 (14%) patients and after 6 months 2 (9%) patients had positive treatment outcomes (improvement of symptoms in more than 50%). In 22 (65%) of the 34 patients of the second group positive results were observed at 1 and 3 months and in 17 (50%) - at 6 months. After 9 months, all patients had a relapse of urgent and frequent urination. Difficulties in emptying the bladder were observed in three (9%) of the second group patients who had to resort to periodic self-catheterization for 2-20 weeks. The obtained results allow us to state that the injections of 100 U of botulinum toxin type A in the submucosal layer of the bladder are ineffective in patients with overactive bladder without detrusor overactivity, whereas injections in the detrusor lead to a statistically significant improvement in symptoms of urgent and frequent urination for 6 months. PMID:26237802

  19. Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial.

    PubMed

    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

    2012-01-01

    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 U 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 intra-detrusor 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 intra-detrusor 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 intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. PMID:22008247

  20. 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…

  1. Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series

    PubMed Central

    Bhave, Anil; Zywiel, Michael G; Ulrich, Slif D; McGrath, Mike S; Seyler, Thorsten M; Marker, David R; Delanois, Ronald E; Mont, Michael A

    2009-01-01

    Background Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty. Methods Ten patients (14 hips) who had hip adductor, abductor, and/or flexor muscle contractures following total arthroplasty and had been refractory to physical therapeutic efforts were treated with injection of botulinum toxin A. Eight limbs received injections into the adductor muscle, 8 limbs received injections into the tensor fascia lata muscle, and 2 limbs received injection into the rectus femoris muscle, followed by intensive physical therapy for 6 weeks. Results At a mean final follow-up of 20 months, all 14 hips had increased range in the affected arc of motion, with a mean improvement of 23 degrees (range, 10 to 45 degrees). Additionally all hips had an improvement in hip scores, with a significant increase in mean score from 74 points (range, 57 to 91 points) prior to injection to a mean of 96 points (range, 93 to 98) at final follow-up. There were no serious treatment-related adverse events. Conclusion Botulinum toxin A injections combined with intensive physical therapy may be considered as a potential treatment modality, especially in difficult cases of muscle tightness that are refractory to standard therapy. PMID:19709429

  2. [Advantages of combined therapies in cosmetic medicine for the treatment of face aging: botulinum toxin, fillers and mesotherapy].

    PubMed

    Braccini, F; Dohan Ehrenfest, D M

    2010-01-01

    Non surgical cosmetic medicine procedures for the face are developing considerably, as they deliver good results using simple, non invasive, atraumatic and reproducible techniques. Aesthetic mesotherapy, also known as anti-aging mesotherapy, uses intra-dermal injections of a nutritive and moisturizing solution to improve brightness, skin hydration and tonus, and also smooth out superficial wrinkles. Subcutaneous filler injections enable to fill wrinkles and folds; by using high density products it is also able to provide genuine facial volumetric reconstruction. Finally, botulinum toxin acts by reducing certain muscle contractions to smooth out expression lines and folds induced by facial dynamics. In this article, we explore the concept of combined therapy and describe our experience associating anti-aging mesotherapy (NCTF-135HA, Filorga, Paris, France), hyaluronic acid based fillers (X-HA3 and X-HA-Volume, Filorga, Paris, France) and botulinum toxin (Vistabel, Allergan, Irvine CA, USA). A therapy combining anti-aging mesotherapy, botulinum toxin and filler injections, offers full treatment of the 3 biological levels of the covering tissues. This non-invasive therapeutic strategy brings patient satisfaction through a global approach to facial aging. PMID:21284223

  3. A comparative study of the efficacy and safety of radiofrequency ablation and botulinum toxin A in treating masseteric hypertrophy

    PubMed Central

    HUANG, JIN-LONG; CHEN, GANG; CHEN, XIAO-DONG; ZHOU, BING-RONG; LUO, DAN

    2014-01-01

    The aim of the present study was to evaluate the effects of two treatments for masseteric hypertrophy. In total, 24 patients with masseteric hypertrophy were enrolled in this study. Patients were randomly divided into two groups: 12 individuals were treated with radiofrequency (RF) ablation and 12 patients received an injection of botulinum toxin A. The thickness of the masseter muscle under tension was measured using ultrasound and clinical photographs were captured prior to treatment and at 6 and 12 months following treatment. Complications were observed during 12-month follow-up. In the group injected with botulinum toxin A, masseteric muscle thickness decreased to the lowest point 6 months after the injections but increased until 12 months after injection. However, in the group treated with RF ablation, muscle thickness decreased steadily over the 12 months following surgery. Therefore, the results of the present study indicated that the effect of RF ablation on the thickness of the masseter muscle may be much larger than that obtained following injection with botulinum toxin A. PMID:24940412

  4. Does Botulinum Toxin A Treatment Enhance the Walking Pattern in Idiopathic Toe-Walking?

    PubMed

    Sätilä, Heli; Beilmann, Anneli; Olsén, Päivi; Helander, Heli; Eskelinen, Mari; Huhtala, Heini

    2016-06-01

    Objective We conducted a randomized controlled trial to evaluate whether a combination of repeated botulinum toxin A (BTX-A) and conservative treatment is more effective in decreasing toe-walking than conservative treatment alone at 24 months follow-up. Patients and Methods Children between 2 and 9 years of age were randomized either into the conservative (CO) or botulinum treatment (BTX) group. The treatment in the CO group consisted of firm shoes, night splints, a home stretching program and physiotherapy. The BTX arm had all the same conservative treatments added with calf muscle BTX-A injections repeated in 6 months intervals if needed. Change in toe-walking pattern, ankle range of movement (ROM), and overall function were assessed at baseline and 6, 12, 18, and 24 months posttreatment. Results A total of 30 toe-walkers participated: 14 in CO and 16 in BTX group. At 24 months, all children in the BTX group and 85% in the CO group evaluated by the blinded physiotherapist (p = 0.065), 75% in the BTX group and 70% in the CO group graded by the research physiotherapist (p = 0.730), and 50% in the BTX group and 54% in the CO group reported by the parents ceased toe-walking (p = 0.837). The most prominent change was noted during the 1st year. The BTX group seemed to reach the goal earlier. No significant differences between the treatment groups in function or in ankle ROM ensued. Conclusion Adding BTX injections did not significantly enhance the goal to walk either flat foot or with heel strike at 24 months posttreatment. PMID:27089542

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

    PubMed

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

    2014-04-01

    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 1.46Å 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

  6. Repeated stimuli for axonal growth causes motoneuron death in adult rats: the effect of botulinum toxin followed by partial denervation.

    PubMed

    White, C M; Greensmith, L; Vrbová, G

    2000-01-01

    Axons of motoneurons to tibialis anterior and extensor digitorum longus muscles of adult rats were induced to sprout by injecting botulinum toxin into them, by partial denervation or by a combination of the two procedures. Ten weeks later, the number of motoneurons innervating the control and operated tibialis anterior and extensor digitorum longus muscles was established by retrograde labelling with horseradish peroxidase. In the same preparations, the motoneurons were also stained with a Nissl stain (gallocyanin) to reveal motoneurons in the sciatic pool. Examination of the spinal cords from animals treated with botulinum toxin showed that the number of retrogradely labelled cells and those stained with gallocyanin in the ventral horn on the treated compared to the control side was unchanged. In rats that had their L4 spinal nerve sectioned on one side, the number of retrogradely labelled cells on the operated side was 48+/-3% (n = 5) of that present in the control unoperated ventral horn. Thus, just over half the innervation was removed by cutting the L4 spinal nerve. Counts made from gallocyanin-stained sections showed that 94+/-4% (n = 5) of motoneurons were present in the ventral horn on the operated side. Thus, section of the L4 spinal nerve did not lead to any death of motoneurons. In rats that had their muscles injected with botulinum toxin three weeks prior to partial denervation, the number of retrogradely labelled cells was reduced from 48+/-3% (n = 5) to 35+/-4% (n = 5). Moreover, only 67+/-5% (n = 5) of motoneurons stained with gallocyanin, suggesting that a proportion of motoneurons died after this combined procedure. This result was supported by experiments in which motor unit numbers in extensor digitorum longus muscles were determined by measurements of stepwise increments of force in response to stimulation of the motor nerve with increasing stimulus intensity. In partially denervated extensor digitorum longus muscles, 16.6+/-0.7 (n = 5) motor

  7. An update on botulinum toxin A injections of trigger points for myofascial pain.

    PubMed

    Zhou, Jon Y; Wang, Dajie

    2014-01-01

    Myofascial pain syndrome (MPS) is a common chronic pain condition that is characterized by distinct "trigger points." Despite current treatments with physical therapy, analgesics, anti-depressants and trigger-point injections, myofascial pain remains a challenging chronic pain condition in clinical practice. Botulinum toxin A (BTX-A) can cause prolonged muscle relaxation through inhibition of acetylcholine release. It may offer some advantages over the current treatments for MPS by providing a longer sustained period of pain relief. Despite numerous clinical trials, the efficacy of BTX-A in alleviating MPS is not well-established due to mixed results from recent clinical trials. Active trigger points are associated with referred pain and greatly impact many aspects of activities of daily living, mood, and health status. This review is designed to analyze the clinical trials regarding the efficacy of BTX-A injection of active trigger points as a treatment for MPS. The literature referenced was obtained via a computer search with Google Scholar, Pubmed, Medline and EMbase. Our search terms included "Botulinum toxin," "myofascial pain," "trigger points," "myofascial trigger points," "chronic pain." Additional references were retrieved from the reference list of the reports found via this search. Studies were considered eligible for inclusion if they were double-blinded, randomized, controlled trials evaluating the efficacy of BTX-A injections into trigger points for pain reduction, and if the trigger point selection in the trial included referred pain and/or local twitch response. Open-label studies, case reports, and other non-randomized studies were excluded. Eight trials were found according to the above criteria and are summarized in Table 1. There are well-designed clinical trials to support the efficacy of trigger-point injections with BTX-A for MPS. However, further clinical trials with considerations of minimizing placebo effect, repeated dosing, adequate

  8. Ultrasound-guided botulinum toxin injection technique for the iliopsoas muscle.

    PubMed

    Westhoff, Bettina; Seller, Konrad; Wild, Alexander; Jaeger, Marcus; Krauspe, Ruediger

    2003-12-01

    Intramuscular botulinum toxin A injections are beneficial for the treatment of functional shortening of the iliopsoas muscle, but it is difficult to achieve precise needle positioning and injection. As a solution to this we present an ultrasound-guided injection technique for the iliopsoas muscle using an anterior approach from the groin. The procedure was performed 26 times in 13 patients (seven males, six females; mean age 11 years, SD 9 years 8 months; age range 4 to 31 years), 10 times bilaterally. Indications were functional iliopsoas shortening due to cerebral palsy (17 hips), hereditary spastic paraplegia (four hips), and Perthes disease (five hips). In all cases the iliopsoas muscle was identified easily by ultrasound; the placement of the injection needle and injection into the site of interest were observed during real time. No complications were encountered. Botulinum toxin A (BTX-A) injections have become established as a standard procedure for the treatment of functional shortening of different muscles in persons with spasticity or dystonia (Kessler et al. 1999, Bakheit et al. 2001, Kirschner et al. 2001). Optimal needle placement is essential to avoid severe side effects and to assess lack of response to the drug or incorrect region of injection. While injection into superficial, very palpable muscles is quite easy, the approach to other muscles such as the iliopsoas muscle may be more difficult and the placement of the needle for an optimal injection site is harder to control. As a solution to this, we present an ultrasound-guided injection technique. The main indications for BTX-A injections in the iliopsoas muscle are dynamic hip flexion deformities mostly due to spastic conditions which may compromise walking (increased anterior pelvic tilt during the whole gait cycle, decreased hip extension at terminal stance, increased peak hip flexion during swing; Molenaers et al. 1999. Another indication might be decentration of the femoral head (as part of

  9. 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

  10. 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.

  11. 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

  12. The effect of laser and botulinum toxin in the treatment of myofascial pain and mouth opening: A randomized clinical trial.

    PubMed

    De Carli, Bethânia Molin Giaretta; Magro, Alessandra Kuhn Dall; Souza-Silva, Bianca Núbia; Matos, Felipe de Souza; De Carli, João Paulo; Paranhos, Luiz Renato; Magro, Eduardo Dall

    2016-06-01

    This study conducted a randomized clinical trial in 15 patients, who sought care at the Dental Clinic of the University of Passo Fundo, in order to compare the use of low-level laser and botulinum toxin in the treatment of myofascial pain and whether they alter the mouth opening of patients with temporomandibular disorder. The patients were divided into two groups: the Laser group received low-level GaAlAs laser, 100mW of power at a wavelength of 830nm in continuous light emission; and the Toxin group received 30U of botulinum toxin type A (BTX-A) in the first session, and 15U after fifteen days. The assessments were performed by measuring pain with Visual Analogue Scale (VAS), and mouth opening with a digital caliper. Data were submitted to Student's t test at 5% significance level. Regarding pain symptoms, the results indicate that groups treated with laser and toxin registered 7U in VAS, at day 5 the scores were 4.75 and 4.86U, respectively. The laser worked faster (day 12) at 2.75U, and the group treated with BTX-A registered 2.86U at day 30. Both therapies investigated were effective in reducing pain, but the effect of low-level laser was faster than the use of BTX-A. Both treatments showed no statistically significant improvement in mouth opening. PMID:27045280

  13. 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

  14. 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

  15. Mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle.

    PubMed

    Caron, Guillaume; Rouzi, Talifujiang; Grelot, Laurent; Magalon, Guy; Marqueste, Tanguy; Decherchi, Patrick

    2014-07-01

    This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A-injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed. PMID:24615939

  16. Efficacy and Safety of a New Botulinum Toxin Type A Free of Complexing Proteins.

    PubMed

    Oh, Hyun-Mi; Park, Joo Hyun; Song, Dae Heon; Chung, Myung Eun

    2016-01-01

    MT10107 is botulinum neurotoxin type A derived drug which utilizes the 150 kDa portion without complexing proteins and human serum albumin contents. To evaluate the efficacy and the safety of MT10107, it was compared with onabotulinumtoxinA in this double-blind, randomized controlled trial. Twenty-five healthy males received a randomly selected dose of MT10107 into the extensor digitorum brevis (EDB) muscle of one foot, and an equivalent dose of onabotulinumtoxinA (BOTOX) was injected into the contralateral EDB muscle. While efficacy of the administered substance was determined by measuring paretic effects on the EDB, the local spread of toxin effects was evaluated by the paretic effects on the nearby abductor hallucis (AH) and abductor digiti quinti (ADQ) muscles. Paretic effects were defined as the percentage of reduction of the compound muscle action potential (CMAP) amplitudes, measured at 14, 30, 90 days after the injection, compared to the baseline value. Intergroup (MT10107 and onabotulinumtoxinA) differences were not significant in the percentage reduction of the amplitudes in the EDB muscles. In this study, there was no significant difference in efficacy and safety between the two test drugs. MT10107 may be effective and safe as much as onabotulinumtoxinA to produce the desired paretic effect. PMID:26712786

  17. [Botulinum toxin--the dose controls the poison. A historical sketch].

    PubMed

    Homann, C N; Wenzel, K; Kriechbaum, N; Suppan, K; Crevenna, R; Ivanic, G; Dressler, D

    2002-06-01

    Botulism, a potentially lethal form of paralytic food poisoning, was described as early as 1793. Basic research, especially in the late nineteenth and early twentieth centuries, revealed that botulism is caused by exotoxins. Further biochemical work around and after the Second World War gave insight into the molecular structure of seven different serotypes of botulinum toxin (BT/A-G) as well as into its acetylcholine blocking mode of action. In 1977, Scott treated patients with strabism by injecting minute amounts of purified BT/A. In short sequence, BT proved effective in blepharospasm, cervical dystonia, and various off-label indications. In the near future, registration of these new indications, marketing of new serotypes (BT/B), and availability of more practical antibody tests can be expected. The first applications of BT were performed by Roggenkaemper, Dressler, and Benecke in Germany and by Poewe and Auff in Austria. According to a worldwide trend, a rapid expansion regarding BT users and indications followed. Formation of BT competence centers in both countries aims at maintaining high standards in BT research and education. PMID:12242998

  18. Lumbar Sympathetic Block with Botulinum Toxin Type B for Complex Regional Pain Syndrome: A Case Study.

    PubMed

    Choi, Eunjoo; Cho, Chan Woo; Kim, Hye Young; Lee, Pyung Bok; Nahm, Francis Sahngun

    2015-01-01

    Lumbar sympathetic block (LSB) is an effective method for relief of sympathetically mediated pain in the lower extremities. To prolong the sympathetic blockade, sympathetic destruction with alcohol or radiofrequency has been used. The pre-ganglionic sympathetic nerves are cholinergic, and botulinum toxin (BTX) has been found to inhibit the release of acetylcholine at the cholinergic nerve terminals. Moreover, BTX type B (BTX-B) is more convenient to use than BTX type A. Based on these findings, we performed LSB on the 2 patients with complex regional pain syndrome (CRPS) in the lower extremity. Levobupivacaine 0.25% 5 mL mixed with BTX-B 5,000 IU was given under fluoroscopic guidance. Two months after LSB with BTX-B, pain intensity and the Leeds assessment of neuropathic symptoms and signs (LANSS) score were significantly reduced. Allodynia and coldness disappeared and skin color came back to normal. In conclusion, BTX-B can produce an efficacious and durable sympathetic blocking effect on patients with CRPS. PMID:26431145

  19. The Efficacy of Botulinum Toxin in Patients with Cervicogenic Headache: a Placebo-Controlled Clinical Trial

    PubMed Central

    Karadaş, Ömer; Öztürk, Bilgin; Ulaş, Ümit Hıdır; Kütükçü, Yaşar; Odabaşı, Zeki

    2012-01-01

    Objective: Botulinum toxin type-A (BoNTA) has been considered a treatment option for CH. The aim of this study was to assess the effectiveness of BoNTA treatment in patients with medically resistant CH. Materials and Methods: Forty patients with CH were included in the study. Patients in the BoNTA group (n=20) were administered 10 U of BoNTA bilaterally to the frontal muscles, 20 U to the temporal muscles, 15 U to the semispinalis capitis, 15 U to the splenius capitis, and 15 U to the trapezius muscles (total: 150 U). Patients in the placebo group (n=20) received 0.2 mL of saline administrated to the same sites. All participations were evaluated 6 and 12 weeks after treatment; side effects, the number of painful days, severity (by visual analogue scale, VAS) and frequency of pain were evaluated. Results: In the BoNTA group, the severity and frequency of pain 6 and 12 weeks post treatment were significantly lower than pre-treatment levels (p<0.05). At 12 weeks post treatment, the severity and frequency of pain in the BoNTA group were lower than in the placebo group (p<0.05). Conclusion: The findings suggest that BoNTA was an effective treatment for CH. PMID:25206992

  20. None detectable retrograde transport of Chinese botulinum toxin type A in mice by single intramuscular injection

    PubMed Central

    Hong, Bin; Yao, Lin-Lin; Hu, Xing-Yue

    2015-01-01

    Botulinum toxin type A (BoNT/A) can specifically cleave synaptosomal associated protein of 25 kDa (SNAP-25) into cleaved SNAP-25 (cl.SNAP-25), thus blocking the synaptic transmission in motor end plate and resulting in paralysis. It has been widely applied in clinical for treatment of various conditions characterized by muscle hyperactivity, such as dystonia and spasticity. BoNT/A is used locally, with little diffusion. Its paralyzing role is considered to be restricted to the nerve muscle junction, or close to the injection site. Recently, more and more studies, however, have suggested that BoNT/A also has central effects. In addition, some investigators have demonstrated that BoNT/A enters into central nervous system via retrograde transport after local intramuscular administration. The retrograde axonal transport of Chinese BoNT/A (CBoNT/A) was studied in this paper, which was rare in report. And the results showed that cl.SNAP-25 appeared not only at the injection site but also in contralateral muscle. Retrograde transport, however, was non-existent or too little to be detected in our study. PMID:26629081

  1. Use of botulinum toxin for genitourinary conditions: What is the evidence?

    PubMed

    da Silva, Carlos Martins; Chancellor, Michael B; Smith, Christopher Patrick; Cruz, Francisco

    2015-12-01

    Botulinum toxin A is licensed for the treatment of urinary incontinence due to neurogenic detrusor overactivity (NDO) and overactive bladder (OAB). Only onabotulinumtoxinA has at this moment such approval, in NDO at a dose of 200 U and in OAB at a dose of 100 U. Regulatory phase 3 trials have been carried out in both conditions. In NDO it was shown to decrease urinary incontinence, to improve urodynamic parameters and to increase quality of life in multiple sclerosis and spinal cord injured patients. Adverse events included urinary tract infections and necessity of de novo clean intermittent catheterization, which occurred mainly in patients with multiple sclerosis. In OAB patients with urge incontinence, onabotulinumtoxinA decreased urinary incontinence and micturition frequency while improving quality of life. Again, main adverse events were urinary tract infections and transient urinary retentions. Long-term studies in both NDO and OAB demonstrate the efficacy and safety of the treatment. Available phase 3 trials of onabotulinumtoxinA in benign prostatic hyperplasia did not show any relevant efficacy in improving lower urinary tract symptoms. PMID:26235907

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

    PubMed

    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

  3. Efficacy and Safety of a New Botulinum Toxin Type A Free of Complexing Proteins

    PubMed Central

    Oh, Hyun-Mi; Park, Joo Hyun; Song, Dae Heon; Chung, Myung Eun

    2015-01-01

    MT10107 is botulinum neurotoxin type A derived drug which utilizes the 150 kDa portion without complexing proteins and human serum albumin contents. To evaluate the efficacy and the safety of MT10107, it was compared with onabotulinumtoxinA in this double-blind, randomized controlled trial. Twenty-five healthy males received a randomly selected dose of MT10107 into the extensor digitorum brevis (EDB) muscle of one foot, and an equivalent dose of onabotulinumtoxinA (BOTOX) was injected into the contralateral EDB muscle. While efficacy of the administered substance was determined by measuring paretic effects on the EDB, the local spread of toxin effects was evaluated by the paretic effects on the nearby abductor hallucis (AH) and abductor digiti quinti (ADQ) muscles. Paretic effects were defined as the percentage of reduction of the compound muscle action potential (CMAP) amplitudes, measured at 14, 30, 90 days after the injection, compared to the baseline value. Intergroup (MT10107 and onabotulinumtoxinA) differences were not significant in the percentage reduction of the amplitudes in the EDB muscles. In this study, there was no significant difference in efficacy and safety between the two test drugs. MT10107 may be effective and safe as much as onabotulinumtoxinA to produce the desired paretic effect. PMID:26712786

  4. Extended effect after a single dose of type A botulinum toxin for asymmetric masseter muscle hypertrophy

    PubMed Central

    Bhattacharjee, Kasturi; Singh, Manpreet; Bhattacharjee, Harsha

    2015-01-01

    Facial asymmetry can either be physiological or pathological and is a common cosmetic concern. A 35-year-old Indian male presented with broad appearing lower face and prominent left jaw since adolescence. Parotid enlargement and other local disorders were ruled out. Ultrasonographic thickness of right masseter muscle was 13 mm while that of left was 14.9 mm, in unclenched state. Type-A botulinum toxin (T-ABT) was injected, evenly at five points, in both muscles within the “safe zone”. Using a 29 gauge needle, 15 and 25 international units were delivered to right and left masseters, respectively. Six months post — injection, a reduction of 2.9 mm and 4.4 mm was observed along with a reduced external facial asymmetry. At 24 months, patient maintains a satisfactory facial contour with no significant early or late post-injection complications. Intra-massteric injection of T-ABT can be used effectively as a primary or adjunct procedure for holistic oculo-facial sculpting. PMID:26424987

  5. Botulinum Toxin in the Treatment of Drooling in Tetraplegic Patients With Brain Injury

    PubMed Central

    Ko, Sung Hwa; Min, Ji Hong; Shin, Myung Jun; Chang, Jae Hyeok; Shin, Yong-Il; Ko, Hyun-Yoon

    2013-01-01

    Objective To investigate the effect of botulinum toxin type A (BTA) injection into the salivary gland and to evaluate the changes of drooling in varied postures in tetraplegic patients with brain injury. Methods Eight tetraplegic patients with brain injury were enrolled. BTA was injected into each parotid and submandibular gland of both sides under ultrasonographic guidance. Drooling was measured by a questionnaire-based scoring system for drooling severity and frequency, and the sialorrhea was measured by a modified Schirmer test for the patients before the injection, 3 weeks and 3 months after the injection. Drooling was evaluated in each posture, such as supine, sitting, and tilt table standing, and during involuntary mastication, before and after the injection. Results The severity and frequency of drooling and the modified Schirmer test improved significantly at 3 weeks and 3 months after the injection (p<0.05). Drooling was more severe and frequent in tilt table standing than in the sitting position and in sitting versus supine position (p<0.05). The severity of drooling was significantly increased in the patients with involuntary mastication (p<0.05). Conclusion Salivary gland injection of BTA in patients with tetraplegia resulting from brain injury who had drooling and sialorrhea could improve the symptoms for 3 months without complications. The severity and frequency of drooling were dependent on posture and involuntary mastication. Proper posture and involuntary mastication of the patients should be taken into account in planning drooling treatment. PMID:24466514

  6. 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

  7. 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. PMID:25966878

  8. Inhibitory Effects of Botulinum Toxin Type A on Pyloric Cholinergic Muscle Contractility of Rat.

    PubMed

    Zhao, Peng; Sun, Hong-Xu; Chu, Min; Hou, Yi-Ping

    2016-08-31

    Botulinum toxin type A (BTX-A) selectively cleaves synaptosomal-associated protein of 25 kDa (SNAP-25) and results in inhibition of the fusion of synaptic vesicles containing neurotransmitters with the presynaptic membrane to undergo exocytosis and release. The aim of this study was to investigate whether BTX-A inhibited the pyloric smooth muscle contractility induced by acetylcholine (ACh) after BTX-A-mediated cleavage of SNAP-25 antagonized by toosendanin (TSN). Three groups of rat pyloric muscle strips were studied in vitro. All strips were allowed to equilibrate for 52 min under a basal loading tension of 1 g in Krebs solution and spontaneous contractile waves were recorded as their own controls before adding each drug. According to experimental protocols, 100 μM ACh, 1 μM atropine, 29.6 μM TSN and 10 U/ml BTX-A was added, respectively. BTX-A directly inhibited pyloric spontaneous contraction and ACh-induced contractile response. Addition of 10 U/ml BTX-A still inhibited pyloric smooth muscle contractility following incubation of TSN, while subsequent administration of 100 μM ACh had no effect. BTX-A inhibits pyloric smooth muscle contractility in our study suggesting BTX-A inhibits not only ACh release from cholinergic nerves but also muscarinic cholinergic muscular transmission. PMID:27426259

  9. Ultrasound-Guided Nerve Block with Botulinum Toxin Type A for Intractable Neuropathic Pain

    PubMed Central

    Moon, Young Eun; Choi, Jung Hyun; Park, Hue Jung; Park, Ji Hye; Kim, Ji Hyun

    2016-01-01

    Neuropathic pain includes postherpetic neuralgia (PHN), painful diabetic neuropathy (PDN), and trigeminal neuralgia, and so on. Although various drugs have been tried to treat neuropathic pain, the effectiveness of the drugs sometimes may be limited for chronic intractable neuropathic pain, especially when they cannot be used at an adequate dose, due to undesirable severe side effects and the underlying disease itself. Botulinum toxin type A (BoNT-A) has been known for its analgesic effect in various pain conditions. Nevertheless, there are no data of nerve block in PHN and PDN. Here, we report two patients successfully treated with ultrasound-guided peripheral nerve block using BoNT-A for intractable PHN and PDN. One patient had PHN on the left upper extremity and the other patient had PDN on a lower extremity. Due to side effects of drugs, escalation of the drug dose could not be made. We injected 50 Botox units (BOTOX®, Allergan Inc., Irvine, CA, USA) into brachial plexus and lumbar plexus, respectively, under ultrasound. Their pain was significantly decreased for about 4–5 months. Ultrasound-guided nerve block with BoNT-A may be an effective analgesic modality in a chronic intractable neuropathic pain especially when conventional treatment failed to achieve adequate pain relief. PMID:26761032

  10. 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