Treatment of taipoxin with p-brcomophenacyl bromide resulted in modification of single histidine residues in the CI and P subunits. The modification decreased the neurotoxicity (lethality) 350-fold, but the inhibitory action on high-affinity choline transport was reduced only threefold. The phospholipase activity and Ca'+-association constants for taipoxin and its subunits were determined. A model for the neurotoxicity of taipoxin indicates the CI subunit as the ultimate cause of the disruption of synaptic transmission.Upon nervous stimulation, cholinergic nerke endings release quanta of acetylcholine packaged in small vesicles, apparently by an exocytotic mechanism [l]. By retrieval of the membrane, vesicles are reformed and reloaded with transmitter [2,3]. A membrane pump provides choline for the synthesizing enzyme choline acetyltransferase, and acetyl coenzyme A is probably furnished by the mitochondrion [4]. Snake venom neurotoxins, black widow spider venom and the bacterial botulinus toxin can interfere with different parts of this cycle.Black widow spider venom acts by releasing the transmitter as evidenced by an avalanche of miniature endplate potentials and the disappearance of vesicle structure [5,6]. Botulinus toxin inhibits the release process, probably directly, without visible ultrastructural alterations [7 -91. The snake venom neurotoxins have a slight enhancing action on the release process, but the final effect seems to be inhibited reformation of functional vesicles [lo, 111. The biochemical correlate may be inhibition of high-affinity choline uptake, as we have demonstrated on isolated nerve endings from Torpedo mavmovata [12] or as others have shown with brain synaptosomes [13].Taipoxin has been shown to be composed of three subunits, which are linked together by non-covalent forces [14]. Data on the nature of the interaction of the subunit polypeptide chains will be presented elsewhere (Fohlman et al., unpublished). The comchroic.Abbreviations. BrPhAc, p-bromophenacyl; CD, circular diEnzyme. Phospholipase A2 (EC 3.1.1.4).plete covalent structure of the polypeptide backbone of the y subunit has been determined and the attachment point of the carbohydrate moiety has been assigned [15]. It is homologous to pancreatic prophospholipase [16]. The N-terminal residues of the CI and P subunits have been shown to be highly homologous to each other and to vertebrate digestive-tract phospholipases including presynaptic toxins. Microheterogeneity, at least of the P subunits, is present and three very similar but clearly different amino acid compositions have been obtained [14] (and unpublished observation). Further sequence analysis of these polypeptides is under way. Fig.1 gives a schematic picture of the taipoxin complex and the derivatives used in this study.Four known presynaptic snake venom neurotoxins (crotoxin, P-bungarotoxin, notexin and taipoxin) have been used in neurochemical studies. Notexin, one of the chains of crotoxin and P-bungarotoxin and all three subunits of taipoxin are known to be s...
The aim of the study was to investigate the effect of delmopinol hydrochloride on the development of dental plaque and on newly established plaque. In addition, the influence of this compound on the composition of the microbiota colonizing the gingival mucous membrane was studied. 14 healthy male volunteers took part. After a 3 week pre-experimental period of intense oral hygiene, the participants refrained from all oral hygiene for 14 days. The buccal surfaces of cuspids and bicuspids on one side of the jaws were treated with a 1% aqueous solution of delmopinol hydrochloride (applied with a paint brush) 2 x a day for 7 days, while the contralateral side received placebo solution. On day 7, the application procedures were changed in that the test compound was applied on the teeth previously treated with placebo and vice versa. Plaque development was assessed clinically and by photo-based planimetric determination. The clinical recordings revealed that 89.3% of the placebo-treated surfaces displayed visible plaque on day 7, compared to 6.0% of the delmopinol hydrochloride treated surfaces. Delmopinol hydrochloride treatment of the previously placebo-treated surfaces resulted in a decrease in the number of surfaces with visible plaque from 89.3% on day 7 to 6% on day 14. These results were confirmed by the planimetric data. No significant change in the composition of the mucosal flora was observed during the experimental period. The present results indicate that delmopinol hydrochloride markedly reduces the formation of dental plaque on a clean tooth surface exposed to conditions which favour bacterial colonization. Furthermore, the substance appears to possess plaque-dissolving properties.
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