Toxicon : official journal of the International Society on Toxinology
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The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. ⋯ The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations.
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Envenomation syndromes induced by Atlantic cnidaria have been tabulated and their therapy discussed. The pharmacokinetics of the venom has been emphasized. Pain occurs instantly and reaches a zenith rapidly in the surf. ⋯ Antivenoms for Atlantic cnidaria are not available. The instances when verapamil might be employed are very rare. The reasons for the increasing case load of these injuries are discussed and the need to discover more effective therapeutic agents is emphasized.
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Botulinum toxins are not commonly thought of as adjuncts to surgical procedures. This article reviews some of the perioperative uses of botulinum toxins.
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Randomized Controlled Trial
Intra-articular Botulinum Toxin Type A: a new approach to treat arthritis joint pain.
There is a growing need for novel treatments of refractory arthritis joint pain as the aging population is expanding with many patients who are unable to undergo joint replacement surgery. We are studying the efficacy and safety of intra-articular injection of Botulinum Toxin Type A (IA-BoNT/A) into joints with arthritis pain. In several small open label studies, initial effects for IA-BoNT/A were encouraging because two thirds of the patients had more than 50% reduction in joint pain severity that was associated with a significant improvement in function. ⋯ Based on these initial studies of IA-BoNT/A we have gone 'back to the bench' to standardize a menu of pain behaviors for mice with acute inflammatory arthritis pain and chronic inflammatory arthritis pain. IA-BoNT/A significantly reduced arthritis joint tenderness (evoked pain score) in acute and chronic inflammatory arthritis and normalized impaired spontaneous wheel running in mice with chronic inflammatory arthritis but not in those with acute inflammatory arthritis. With these models of arthritis and pain behavior methods we will be able to screen potential intra-articular analgesics, define dose response curves and injection schedule, and study the relationships of articular pain and loss of function.
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The venom of cone snails (Conus spp.) is a rich source of peptides exhibiting a wide variety of biological activities. Several of these conopeptides are neuronal nicotinic acetylcholine receptor (nAChR) antagonists and belong to the A-, M-, S-, C and the recently described D-superfamily (alphaD-conopeptides). Here we describe the discovery and characterization of two alphaD-conopeptides isolated from the venom of Conus mustelinus and Conus capitaneus. ⋯ These peptides show close structural homology to the alphaD-VxXIIA, -B and -C conopeptides from the venom of Conus vexillum and are dimers (about 11kDa) of similar or identical peptides with 49 amino acid residues and a characteristic arrangement of ten conserved cysteine residues. These novel types of conopeptides specifically block neuronal nAChRs of the alpha7, alpha3beta2 and alpha4beta2 subtypes in nanomolar concentrations. Due to their high affinity, these new ligands may provide a tool to decipher the localisation and function of the various neuronal nAChRs.