14 research outputs found

    Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder

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    The present study describes the isolation of the first neurotoxin (acantoxin IVa) from Acanthophis sp. Seram death adder venom and an examination of its activity at nicotinic acetylcholine receptor (naChR) subtypes. Acantoxin IVa (MW 6815; 0.1-1.0 muM) caused concentration-dependent inhibition of indirect twitches (0.1 Hz, 0.2 ms, supramaximal V) and inhibited contractile responses to exogenous nicotinic agonists in the chick biventer cervicis nerve-muscle, confirming that this toxin is a postsynaptic neurotoxin. Acantoxin IVa (1-10 nM) caused pseudo-irreversible antagonism at skeletal muscle nAChR with an estimated pA(2) Of 8.36 +/- 0.17. Acantoxin IVa was approximately two-fold less potent than the long-chain (Type 11) neurotoxin, alpha-bungarotoxin. With a pK(i) value of 4.48, acantoxin IVa was approximately 25,000 times less potent than a-bungarotoxin at alpha7-type neuronal nAChR. However, in contrast to alpha-bungarotoxin, acantoxin IVa completely inhibited specific [H-3]-methyllycaconitine (MLA) binding in rat hippocampus homogenate. Acantoxin IVa had no activity at ganglionic nAChR, alpha4beta2 subtype neuronal nAChR or cytisine-resistant [H-3]-epibatidine binding sites. While long-chain neurotoxin resistant [H-3]-MLA binding in hippocampus homogenate requires further investigation, we have shown that a short-chain (Type 1) neurotoxin is capable of fully inhibiting specific [H-3]-MLA binding. (C) 2004 Elsevier Inc. All rights reserved

    Biodegradable injectable polyurethanes: Synthesis and evaluation for orthopaedic applications

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    Copyright © 2008 Elsevier Ltd All rights reserved.Biodegradable polyurethanes offer advantages in the design of injectable or preformed scaffolds for tissue engineering and other medical implant applications. We have developed two-part injectable prepolymer systems (prepolymer A and B) consisting of lactic acid and glycolic acid based polyester star polyols, pentaerythritol (PE) and ethyl lysine diisocyanate (ELDI). This study reports on the formulation and properties of a series of cross linked polyurethanes specifically developed for orthopaedic applications. Prepolymer A was based on PE and ELDI. Polyester polyols (prepolymer B) were based on PE and dl-lactic acid (PEDLLA) or PE and glycolic acid (PEGA) with molecular weights 456 and 453, respectively. Several cross linked porous and non-porous polyurethanes were prepared by mixing and curing prepolymers A and B and their mechanical and thermal properties, in vitro (PBS/37 degrees C/pH 7.4) and in vivo (sheep bi-lateral) degradation evaluated. The effect of incorporating beta-tricalcium phosphate (beta-TCP, 5 microns, 10 wt.%) was also investigated. The cured polymers exhibited high compressive strength (100-190 MPa) and modulus (1600-2300 MPa). beta-TCP improved mechanical properties in PEDLLA based polyurethanes and retarded the onset of in vitro and in vivo degradation. Sheep study results demonstrated that the polymers in both injectable and precured forms did not cause any surgical difficulties or any adverse tissue response. Evidence of new bone growth and the gradual degradation of the polymers were observed with increased implant time up to 6 months.Raju Adhikari, Pathiraja A. Gunatillake, Ian Griffiths, Lisa Tatai, Malsha Wickramaratna, Shadi Houshyar, Tim Moore, Roshan T.M. Mayadunne, John Field, Margaret McGee and Tania Carbonehttp://www.elsevier.com/wps/find/journaldescription.cws_home/30392/description#descriptio
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