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Biomedical subjects

S Ramanadham

Publications and source records attributed to S Ramanadham.

60 records · Page 4Linked to original sources

Effect of insulin replacement on streptozotocin-induced effects in the rat heart.

Streptozotocin (65 mg/kg) was used to induce diabetes in male Sprague-Dawley rats. Isolated cardiac tissue exhibited a systematic depression in atrial pacemaker function and an enhancement in ventricular function accompanied by a supersensitivity to calcium relative to control animals. beta-Adrenoceptor density was found to be significantly lowered in the treated animals. However, no change in responsiveness of the tissues to isoproterenol was observed. The systematic changes in atria and ventricle were found to be completely and partially reversed respectively, by daily administration of 4-5 units of Ultralente (U-100) insulin, whereas the decrease in beta-adrenoceptor number and supersensitivity to calcium were completely reversed. These results suggest that STZ by itself might not have toxic effects in the heart and that its effects may be overcome by chronic insulin-replacement.

Animals↗

Chronotropic actions of bPTH-(1-34) in the right atrium of the rat.

Bovine parathyroid hormone and its N-terminal (1-34) peptide fragment (bPTH-(1-34] are known to possess direct hypotensive activity in the rat. The purpose of the present study was to determine if bPTH-(1-34) possessed a direct chronotropic action as well. In vivo studies revealed that bPTH-(1-34) did produce a chronotropic effect in the rat comprising both a direct component as well as a reflex tachycardia related to its hypotensive actions. In vitro studies of isolated right atria indicated that while bPTH-(1-34) had no positive inotropic effect, it did produce significant chronotropic effects which were direct and dose-dependent. The potency of bPTH-(1-34) was found to be similar to that of isoproterenol, however, it was only one-third as effective as isoproterenol in maximally increasing atrial rate. A slight but significant increase in atrial cyclic AMP was generated prior to the chronotropic actions of bPTH-(1-34).

Adrenergic Fibers↗

Alterations in cardiac performance in experimentally-induced diabetes.

Responses in cardiac tissue isolated from streptozotocin (STZ)-treated and age-matched control rats to isoproterenol (ISO) and calcium were studied. 4 weeks after STZ, atrial function was found to be depressed, whereas right ventricular function was enhanced. Neither tissue exhibited an alteration in sensitivity to ISO. In contrast, while sensitivity to calcium was found to be unaltered in atrial tissue, supersensitivity to calcium was observed in ventricles after STZ treatment. beta-Adrenoceptor number determination revealed a 36% decrease in Bmax with no change in affinity after STZ treatment. These results suggest that 4 weeks after STZ treatment pacemaker function is depressed, while enhancement in ventricular function is associated with an alteration in calcium utilization.

Animals↗

Potentiation of barbiturate- and halothane-induced hypnosis after probenecid or sulfinpyrazone pretreatment.

The uricosuric agent, probenecid, when administered prior to systemic administration of pentobarbital led to a decreased latency, to loss of righting reflex and to a potentiation of the duration of hypnosis. This potentiation was dose-related and doses of probenecid below 50 mg/kg (i.p.) were without effect. Pretreatment of rats with sulfinpyrazone, another uricosuric agent, yielded similar results. Pretreatment of animals with probenecid shortened the latency to onset of hypnosis induced by halothane (i.p.) and increased the duration of loss of righting reflex, 3-fold. Both sulfinpyrazone and probenecid, administered prior to 1.0% inhalation halothane exposure, shortened the latency to onset of hypnosis in doses as small as 10 mg/kg, much less than the doses required to affect significantly pentobarbital-induced hypnosis. The results, as yet, do not indicate a plausible mechanism of action, but do expose a potentially useful drug interaction which may be of clinical use.

Animals↗

Temporal analysis of retinal function in IRBP peptide-induced experimental autoimmune uveoretinitis (EAU).

Experimental autoimmune uveoretinitis (EAU) induced by interphotoreceptor retinoid binding protein (IRBP) is a complex and multifaceted disease mediated by several different immunopathogenic processes. There is a temporal progression of the disease affecting the anterior and posterior segments of the eye, culminating with destruction of the photoreceptor cells. In the present study, we investigated the effects of IRBP peptide-induced EAU on different cell types within the retina. The Muller cells of the peripheral retina are damaged at the onset of EAU at day 9. There is induction of glial fibrillary acidic protein (GFAP) in the peripheral retinal Muller cells with concomitant reduction in the electroretinogram (ERG) b-wave. By day 12 of EAU, intensely GFAP-positive Muller cells are detected throughout the peripheral and central retina and with maximal diminution of the ERG b-wave. There is a lag in the diminution of the ERG a-wave, first detected at day 12 of EAU, and reaching its maximum at day 15. This change in the ERG is associated with destruction of the tips of the photoreceptor cells. These results indicate that during IRBP peptide-induced EAU, there is a positive correlation between the temporal changes in retinal histology, GFAP expression by Muller cells, and loss of retinal function.

Amino Acid Sequence↗