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Biomedical subjects

R Shankar

Publications and source records attributed to R Shankar.

At least 91 records · Page 5Linked to original sources

Retardation of calcification of bovine pericardium used in bioprosthetic heart valves by phosphocitrate and a synthetic analogue.

The purpose of this study was to determine if phosphocitrate (PC), a naturally occurring inhibitor of calcification, and its synthetic analogue, N-sulpho-2-amino tricarballylate (SAT), administered either by daily injection or local delivery via Alzet osmotic minipump, could inhibit calcification of glutaraldehyde-preserved bovine pericardium used in bioprosthetic heart valves, subcutaneously implanted in rats. Local drug delivery, but not systemic administration, was effective. PC, administered by Alzet minipump (12 mg.kg-1.day-1), inhibited calcification significantly (tissue calcium = 5 +/- 2 micrograms/mg dry tissue, mean +/- SEM), compared with untreated or saline-treated controls (89 +/- 9 and 49 +/- 9 micrograms/mg, respectively). SAT, administered by the same route at both the same and a higher molar dosage, was less potent (tissue calcium = 26 +/- 9 micrograms/mg and 17 +/- 5 micrograms/mg, respectively). PC and SAT therapy were not associated with adverse effects. We conclude that locally administered PC and SAT can inhibit intrinsic calcification of bovine pericardium, with PC being more potent.

Animals↗

Reduction of infection stones in rats by combined antibiotic and phosphocitrate therapy.

The potential of phosphocitrate to inhibit infection stones in rats when combined with an antibiotic was studied. A significant reduction occurred in both the number and weight of recovered stones from rats receiving combined treatment with amoxycillin (50 mg./kg. body wt./day and phosphocitrate (112 mumol./kg. body wt./day) for four weeks. The inhibitory responses were attributed to the intact phosphocitrate molecule as administration of citrate in equimolar concentrations did not mimic the observed effects of phosphocitrate. In comparison with non-infected controls, antibiotic treatment alone failed to eliminate total stone growth. However, composition of the stone reverted from predominantly struvite to a mixture of struvite and newberyite as urinary parameters normalized. The studies highlight the usefulness of phosphocitrate to restrict magnesium salt deposition in vivo.

Amoxicillin↗

A possible antiatherogenic role for phosphocitrate through modulation of low density lipoprotein uptake and degradation in aortic smooth muscle cells.

The present study reports the influence of a phosphorylated polycarboxylic acid, phosphocitrate, on low density lipoprotein (LDL) metabolism in cultured rabbit aortic smooth muscle cells. Phosphocitrate profoundly influenced both LDL binding and degradation. At the maximal effective concentration (2 mM), phosphocitrate released approximately 90% of the receptor-bound [125I]LDL whilst the total amount of [125I]LDL degraded was reduced by 60%. Measurement of total cholesterol accumulation revealed that even in the presence of high concentrations of added LDL, phosphocitrate (2 mM) diminished cholesterol levels close to the basal levels seen in incubations in lipoprotein-deficient serum. Further, this inhibitory effect of phosphocitrate was demonstrable after 24 h at 37 degrees C. Phosphocitrate, a recognized anticalcifying agent, possesses a strong negative charge to size ratio at physiological pH. It is postulated that the observed effects probably arise from charge interference and/or its ability to modulate cellular calcium concentration.

Animals↗

Pentobarbitone stimulation of protein phosphorylation in rat brain in vitro.

Effect of pentobarbitone on protein phosphorylation in rat brain in vitro was investigated. It was observed that at short term incubations pentobarbitone greatly enhanced incorporation of 32P into cerebral phosphoproteins which came to lower level after prolonged incubation. Dose response curve of the drug on protein phosphorylation was unconventional. The drug did not appreciably affect lipid peroxidation in brain homogenates. Effect of pentobarbitone on protein phosphorylation is not due to its inhibition of mitochondrial electron flow which would have given opposite results.

Animals↗

Atherogenesis. Mitigation of monocyte adhesion to arterial endothelium in hyperlipidemic rats by phosphocitrate, a phosphorylated polycarboxylic acid.

Phosphocitrate, a phosphorylated polycarboxylic acid ameliorates two early events in atherogenesis. When administered to rats on an atherosclerotic diet (112 mumol/kg body wt./day), it reduced monocyte adhesion to aortic endothelium from 34 +/- 7 cells/HPF for untreated rats to 1 +/- 1 cell/HPF, a value seen in normal, non-atherosclerotic rats. Transmission electron microscopy of aortic sections showed no evidence of subendothelial lipid accumulation in phosphocitrate-treated rats despite the high circulating plasma lipid levels. The mechanisms of action of phosphocitrate are unknown but the indications are that its influence may be mediated through its polyanionic chemical nature and/or its ability to modulate cellular calcium accumulation. In addition to its possible therapeutic value as an anti-calcifying and anti-atherogenic compound, phosphocitrate may prove useful as an experimental probe for studying the cellular basis of atherogenesis.

Animals↗

Anti-ulcerogenic effect of banana powder (Musa sapientum var. paradisiaca) and its effect on mucosal resistance.

Orally administered banana pulp powder (Musa sapientum var. paradisiaca) was shown to have significant anti-ulcerogenic activity in rats subjected to aspirin, indomethacin, phenylbutazone, prednisolone and cysteamine and in guinea-pigs subjected to histamine. Banana powder not only increased mucosal thickness but also significantly increased [3H]thymidine incorporation into mucosal DNA. Relative to untreated control sections, histological studies showed that banana treatment increased staining by alcian blue in the apical cells with staining noted in the deeper layers of the mucosal glands. Banana-treated and control sections were also stained for DNA by the Feulgen reaction. The banana-treated sections showed a greater aggregation and intensity of pink spots when compared to controls. The present study suggests that banana powder treatment not only strengthens mucosal resistance against ulcerogens but also promotes healing by inducing cellular proliferation.

Animals↗