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K Needham

Publications and source records attributed to K Needham.

5 recordsLinked to original sources

Olivocochlear collaterals evoke excitatory effects in onset neurones of the rat cochlear nucleus.

Axons of medial olivocochlear neurones in the superior olivary complex terminate on the outer hair cells of the cochlea and also give off collaterals that terminate in the cochlear nucleus. Previous work in our laboratory, using extracellular recordings in the cochlear nucleus, has indicated that stimulation of the olivocochlear axons may have an excitatory effect on specific cell populations of the cochlear nucleus, such as onset-choppers, in contrast to the peripheral suppressive action of the same axons. We have investigated whether this excitation is produced by action of the olivocochlear collaterals in the cochlear nucleus or whether it is mediated via the peripheral suppression, by measuring intracellular responses in the rat cochlear nucleus to electrical stimulation of the olivocochlear axons in silence. The results demonstrate that single shocks applied to the olivocochlear axons can evoke excitatory postsynaptic potentials in onset neurones. We observed an inhibitory effect in one chopper only. In the same animals in all other neurones investigated (i.e. three primary-like neurones and eight choppers) the same stimulation was without any effect on cell membrane potential. We conclude that the excitatory effects in onset neurones are not caused by suppression in the auditory peripheral organ, but by activation of olivocochlear collaterals in the cochlear nucleus.

Animals↗

A comparative study of prothrombinase and thrombin inhibitors in a novel rabbit model of non-occlusive deep vein thrombosis.

A quantitative and non-occlusive deep vein thrombosis model was developed in rabbits. We used this model to test the antithrombotic activity of the prothrombinase complex inhibitors factor rXai and its chemical analog glutamyl-glycyl-arginyl chloromethyl ketone inactivated human factor Xa (EGR-Xai), along with the thrombin inhibitors D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) and heparin. Dose dependent effects of the inhibitors during constant infusion were monitored. Measurements included thrombus weights, hemostatic parameters and both cuticle and ear bleeding times. In this model, factor rXai and EGR-Xai had comparable in-vivo efficacy, and showed 80%-93% inhibition at plasma levels of 6.5 nM (rXai) and 8 nM (EGR-Xai). Effects on ex-vivo clotting times varied among the inhibitors. At 80-100% thrombus inhibition, factor rXai and EGR-Xai had no statistically significant effect, while PPACK extended thrombin clotting time (TCT) times 2.3-fold, and heparin prolonged both activated partial thromboplastin time (APTT), prothrombin time (PT) and TCT ex-vivo clotting times 6.9-, 1.2-, and 7-fold respectively. At these dosages, cuticle and ear bleeding times were prolonged for all inhibitors and showed increases of 177%-389% (cuticle) and 45%-129% (ear). Our results demonstrate that direct inhibition of prothrombinase complex assembly is effective in arresting venous thrombosis.

Amino Acid Chloromethyl Ketones↗