Search results for "botulinum"
showing 10 items of 84 documents
Differences in the temperature dependencies of uptake of botulinum and tetanus toxins in Aplysia neurons
1992
The respective neuroselective actions of botulinum type A (BoNT) and tetanus (TeTx) neurotoxins on cholinergic and non-cholinergic synapses of Aplysia are mainly due to differences in their extracellular neuronal targetting. Further information was gained on this neuroselectivity by examining the temperature dependencies of binding, internalization and intracellular action of both toxins. After reduction of temperature from 22 degrees C to 10 degrees C, the binding of neither BoNT nor TeTx was significantly altered whereas the neuronal uptake of BoNT, but not of TeTx, was prevented. Although TeTx internalization could be detected at the low temperature, its intracellular activity was greatl…
A role for Rho in receptor- and G protein-stimulated phospholipase C Reduction in phosphatidylinositol 4,5-bisphosphate by Clostridium difficile toxi…
1996
Receptors coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins) activate phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-hydrolyzing phospholipase C (PLC) enzymes by activated alpha of free beta gamma subunits of the relevant G proteins. To study whether low molecular weight G proteins of the Rho family are involved in receptor signaling to PLC, we examined the effect of Clostridium difficile toxin B, which glucosylates and thereby inactivates Rho proteins, on the regulation of PLC activity in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor (mAChR) subtype. Toxin B treatment of HEK cells did not affect basal PLC activi…
Inhibition of Receptor Signaling to Phospholipase D by Clostridium difficile Toxin B
1996
Rho proteins have been reported to activate phospholipase D (PLD) in in vitro preparations. To examine the role of Rho proteins in receptor signaling to PLD, we studied the effect of Clostridium difficile toxin B, which glucosylates Rho proteins, on the regulation of PLD activity in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor (mAChR). Toxin B treatment of HEK cells potently and efficiently blocked mAChR-stimulated PLD. In contrast, basal and phorbol ester-stimulated PLD activities were not or only slightly reduced. Cytochalasin B and Clostridium botulinum C2 toxin, mimicking the effect of toxin B on the actin cytoskeleton but without involvi…
Botulinum A and the light chain of tetanus toxins inhibit distinct stages of Mg.ATP-dependent catecholamine exocytosis from permeabilised chromaffin …
1994
Susceptibilities of Mg.ATP-independent and Mg.ATP-requiring components of catecholamine secretion from digitonin-permeabilised chromaffin cells to inhibition by Clostridial botulinum type A and tetanus toxins were investigated. These toxins are Zn(2+)-dependent proteases which specifically cleave the 25-kDa synaptosomal-associated protein (SNAP-25) and vesicle-associated membrane protein (VAMP) II, respectively. When applied to permeabilised chromaffin cells they rapidly inhibited secretion in the presence of Mg.ATP but the catecholamine released in the absence of Mg.ATP, thought to represent fusion of primed granules, was not perturbed. The toxins can exert their effects per se in the abse…
Processing of tetanus and botulinum A neurotoxins in isolated chromaffin cells.
1995
Tetanus and botulinum A neurotoxins were introduced into the cytosol of chromaffin cells by means of an electric field in which the plasma membrane is forced to form pores of approximately 1 micron at the sites facing the electrodes. As demonstrated by electron microscopy, both [125I] and gold-labelled tetanus toxin (TeTx) diffuse through these transient openings. Dichain-TeTx, with its light chain linked to the heavy chain by means of a disulfide bond, causes the block of exocytosis to develop more slowly than does the purified light chain. The disulfide bonds, which in both toxins hold the subunits together, were cleaved by the intrinsic thioredoxin-reductase system. Single chain TeTx, in…
Inhibition in vivo of the activity of botulinum neurotoxin A by small molecules selected by virtual screening
2012
To search for small molecular size inhibitors of botulinum neurotoxin A (BoNT/A) endopeptidase activity, we have screened the NCI library containing about 1 million structures against the substrate binding pocket of BoNT/A. Virtual screening (VS) was performed with the software Glide (Grid-based ligand docking energetics) and the findings were confirmed by AutoDock. Ten compounds were found that had favorable energetic and glide criteria and 5 of these compounds were selected for their ability to protect mice in vivo against a lethal dose of BoNT/A. Each compound was incubated at different molar excesses with a lethal dose of the toxin and then the mixture injected intravenously into mice. …
Repeated pull-through surgery for complicated Hirschsprung's disease--principles derived from clinical experience.
2007
Abstract Background In some patients, an initial pull-through procedure for Hirschsprung's disease fails, and obstructive symptoms persist or recur. Then a repeated pull-through operation may be necessary. Methods Seventeen patients with Hirschsprung's disease aged 2 to 9 years (median, 4.6 years) have undergone a repeated pull-through procedure because of unresponsive symptoms after an initial operation. The initial procedure was Soave in 3 patients, Rehbein in 13 patients, and Duhamel in 1 patient. Surgical revision was indicated by incomplete resection of the transition zone in 16 patients, anastomotic strictures in 9 patients, and fistulas in 2 patients. All 17 patients have undergone R…
Botulinum toxin in preparation of oral cavity for microsurgical reconstruction.
2010
CONCLUSIONS: Infiltration of botulinum toxin in the major salivary glands allows a temporary reduction of salivation that begins 8 days afterwards and returns to normal within 2 months. The inhibition of salivary secretion, carried out before the oral cavity reconstructive surgery, could allow a reduction of the incidence of oro-cutaneous fistulas and local complications. OBJECTIVES: Saliva stagnation is a risk factor for patients who have to undergo reconstructive microsurgery of the oral cavity, because of fistula formation and local complications in the oral cavity. The authors suggest infiltration of botulinum toxin in the major salivary glands to reduce salivation temporarily during th…
Inhibition of FcεRI-mediated Activation of Rat Basophilic Leukemia Cells by Clostridium difficile Toxin B (Monoglucosyltransferase)
1996
Abstract Treatment of rat basophilic leukemia (RBL) 2H3-hm1 cells with Clostridium difficile toxin B (2 ng/ml), which reportedly depolymerizes the actin cytoskeleton, blocked [3H]serotonin release induced by 2,4-dinitrophenyl-bovine serum albumin, carbachol, mastoparan, and reduced ionophore A23187-stimulated degranulation by about 55-60%. In lysates of RBL cells, toxin B 14C-glucosylated two major and one minor protein. By using two-dimensional gel electrophoresis and immunoblotting, RhoA and Cdc42 were identified as protein substrates of toxin B. In contrast to toxin B, Clostridium botulinum transferase C3 that selectively inactivates RhoA by ADP-ribosylation did not inhibit degranulation…
Botulinum Toxin Is Effective in the Management of Neurogenic Dysphagia. Clinical-Electrophysiological Findings and Tips on Safety in Different Neurol…
2017
Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated wi…