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Biomedical subjects

R R Sharma

Publications and source records attributed to R R Sharma.

At least 109 records · Page 6Linked to original sources

Serum thyroxine and triiodothyronine concentrations in rats receiving lithium carbonate.

Circulating thyroxine (T4) and triiodothyronine (T3) concentrations in rats were determined after various periods of lithium administration in diet. No significant change in serum T4 and T3 levels was observed after ten days of lithium treatment. However, lithium treatment for one month, two months and four months showed a significant decrease in serum T4 and T3 levels indicating the adverse effect of chronic lithium intake.

Animals↗

Effect of vitamin A deficiency on pulmonary and hepatic in vitro metabolism of benzo(a)pyrene in rat.

The metabolism of (3H)-benzo(a)pyrene and the activities of enzymes involved in its metabolism were studied in rat lung and liver in vitamin A deficiency. Deficiency of vitamin A resulted a significant decrease in the overall metabolism of benzo(a)pyrene in the liver in vitro, whereas no significant difference was evident in the lung. The ethyl acetate-soluble metabolites of benzo(a)pyrene formed by lung and liver preparations were unaltered qualitatively by vitamin A deficiency. However, quantitative analysis revealed that vitamin A deficiency decreased the yield of dihydrodiols, quinones and phenols in liver, and dihydrodiols in lung. The hepatic cytochrome P-450 content, arylhydrocarbon hydroxylase and uridine diphosphate-glucuronosyl transferase activities were reduced, whereas glutathione S-transferase activity was increased in the vitamin A deficient animals. Contrary to this, pulmonary cytochrome P-450 content was above the control values (p less than 0.01) and no alteration in pulmonary arylhydrocarbon hydroxylase activity was observed in vitamin A deficient rats. Uridine diphosphate-glucuronosyltransferase and glutathione S-transferase activities were impaired in lung by inducing vitamin A deficiency. However, no significant difference was evident in the overall metabolism of benzo(a)pyrene by lung supernatants from the two groups.

Animals↗

Effect of intratracheally instilled benzo(a)pyrene on the pulmonary and hepatic drug-metabolizing enzymes in normal and vitamin A deficient rats.

The effect of intratracheal instillation of different doses of benzo(a)pyrene (0.1, 1.0 and 2.0 mg) on the drug metabolizing enzymes of lung and liver was analysed in rats fed diet with or without vitamin A for 5-6 weeks. Benzo(a)pyrene exposure at 2.0 mg dose only elevated the level of cytochrome P-450 and b5, and activity of benzopyrene hydroxylase in liver, and extent of increase was similar in normal and vitamin A deficient groups. Contrary to this, pulmonary contents of cytochrome P-450 and b5, and benzopyrene hydroxylase activity increased over control values in both the groups even at lower doses of benzo(a)pyrene. Moreover, their values were higher in vitamin A deficient-treated groups compared to normal-treated controls. Increase in these parameters was greater in lung as compared to increase in liver. NADPH cytochrome C-reductase in lung and liver was not affected either by inducing vitamin A deficiency or exposing these rats further to benzo(a)pyrene. Uridine-diphospho-glucuronosyl-transferase (UDP-GT) activity in normal and vitamin A deficient groups was enhanced following exposure to benzo(a)pyrene both in lung and liver. However, activity of this enzyme remained impaired in vitamin A deficient groups, benzo(a)pyrene exposed or not exposed when compared to respective normal controls. Glutathione S-transferase activity remained unchanged following exposure to benzo(a)pyrene both in lung and liver. The apparent increase in hepatic glutathione S-transferase and decrease in pulmonary glutathione S-transferase activity in vitamin A deficiency was only due to vitamin A deficient status of rats with no further effect of benzo(a)pyrene.

Animals↗

Theoretical interpretation of extraction (in brain) of peptides including concentration variations.

The transport properties of several peptides across blood-brain barrier (BBB) have been investigated theoretically in terms of simple diffusion and facilitated diffusion processes. Comparison of the calculated results from the simple diffusion and the experimental data reveals the presence of the facilitated diffusion of these substances which we have conceived of as a carrier-mediated process. The values of the partition coefficients f for these peptides were in the range 7 X 10(-4) less than or equal to f less than or equal to 200 X 10(-4). The calculated f values gave permeabilities, Ps, in lipids between 10(-7) less than or equal to Ps less than or equal to 14 X 10(-7) cm/s. These values were then used to estimate the extraction for peptides from simple diffusion alone which vary from 0.3 to 3.5% compared with the experimental extraction (0.4-12%) indicating the inadequacy of the simple diffusion alone to explain the experimental data. As for the carrier-mediated facilitated diffusion process we have used the activated-complex theory. The extraction in this case depends on the maximal rate of transport (Tmax)f and the reciprocal of the affinity constant Kt for the transport of peptides through BBB. We have deduced that (Tmax)f approximately 0.46 X 10(-3) pmol/g X s and Kt approximately 0.35 nM for Met-enkephalin (Met-ENK), Leu-enkephalin (Leu-ENK), glutathione, carnosine, alpha-MSH and MIF and (Tmax)f approximately 10 X 10(-3) pmol/g X s and Kt approximately 7 nM for AVP, beta LT, beta E and alpha E to explain the observed results. We have also obtained the quantitative variation of extraction with concentration of peptides in the brain-capillary and have established that the extraction decreases with increasing concentration of peptides, tending to a small constant value at high concentrations. It has been inferred that carrier-mediated facilitated diffusion is important for the transport of peptides across BBB.

Animals↗

The effect of anti-cancer drugs on pharmacokinetics of antipyrine in vitamin A deficiency.

The pharmacokinetics of orally and intravenously administered antipyrine-14C in individual rats were investigated to examine the effects of vitamin A deficiency and/or cytotoxic anti-cancer drugs, like cyclophosphamide, methotrexate, 5-fluorouracil and actinomycin-D. Both vitamin A deficiency and pretreatment of rats with anti-cancer drugs led to impairment in the absorption from the gastro-intestinal tract and the plasma elimination of antipyrine. Pretreatment of vitamin A deficient rats with anti-cancer drugs further retarded the absorption and plasma clearance of antipyrine. Apparent volume of distribution of antipyrine was reduced (P less than 0.001) by inducing vitamin A deficiency in rats, whereas pretreatment of rats with anti-cancer drugs did not show any effect. Cytotoxic drugs, and vitamin A deficiency increased the area under the plasma concentration vs. time curve of orally administered antipyrine (AUCoral). In vitro findings suggest that the most probable cause of delayed clearance/prolonged half-life and increased AUCoral values was the reduction in hepatic cytochrome P-450 dependent mixed function oxidase system.

Animals↗

Effect of vitamin A deficiency on the pulmonary and hepatic drug-metabolizing enzymes in rat.

The effect of vitamin A deficiency on the drug-metabolizing enzyme system of the lung and liver was analyzed in rats fed diets with or without vitamin A for 5-6 weeks. The hepatic level of vitamin A was significantly reduced in vitamin A deficient animals. The hepatic cytochrome P-450 and b5 contents and activity of benzo(a)pyrene hydroxylase was significantly reduced in deficient animals. Contrary to this, pulmonary cytochrome P-450 and b5 contents were above the control values. No alteration in pulmonary benzo(a)pyrene hydroxylase was noted. The uridine diphosphate-glucuronosyltransferase activity of digitonin-treated microsomal membranes was below the control values both in lung and liver. However, the native uridine diphosphate-glucuronosyltransferase activity remained unchanged in the liver and was below control values in the lung.

Animals↗

Effect of vitamin A deficiency on the level of glutathione and glutathione S-transferase activity in rat colon and liver.

The effect of vitamin A status on colon and liver glutathione content and the activity of glutathione S-transferase was studied in rats. Animals were fed diets with or without vitamin A for 4-5 weeks. There was no difference in the weight gains of control and deficient animals. Hepatic and colonic level of vitamin A was significantly reduced in vitamin A deficient animals. Hepatic glutathione content was below control values (31%); whereas activity of glutathione S-transferase was enhanced in deficient animals (41.2%). Contrary to this, colon glutathione S-transferase activity was significantly reduced (40.7%) and glutathione content remained unchanged in vitamin A deficiency.

Animals↗

Effect of vitamin A deficiency on pulmonary and hepatic protective enzymes in rat.

Rats were fed diet with or without vitamin A for 5-6 weeks. Vitamin A deficiency had differential effect on the activities of protective enzymes in lung and liver. Superoxide dismutase activity was reduced significantly in lung, whereas remained unchanged in liver, in vitamin A deficient group. Catalase activity was reduced both in lung and liver by inducing vitamin A deficiency. On the other hand, vitamin A deficiency resulted in significant increase in the activity of glutathione peroxidase in lung and had little effect in liver. NADPH dependent lipid peroxidation, as measured by TBA products, remained unaltered, both in lung and liver in vitamin A deficient animals when compared to control group. These results suggest that vitamin A deficiency does not seem to predispose lung and liver to the injurious effects of oxygen toxicity in vivo.

Animals↗

Value and limitations of testicular scanning by in vivo labelling of RBC with 99mTc.

When a scrotal affection cannot be diagnosed confidently by correlation of clinical history and physical examination, testicular scanning with 99mTc is a useful adjunct diagnostic modality. In vivo labelling of red blood cells with 99mTc was achieved by prior oral administration of 200 mg of stannous chloride. This helped to obtain satisfactory scintigraphy with a rectilinear scanner. This procedure was found to be useful in the adult with recent tender testicle in whom the torsion of the testis could not be clinically differentiated from epididymo-orchitis. Another area of scan's valuable clinical application was in the early diagnosis of testicular abscess in patients with epididymo-orchitis not responding immediately to antibiotic therapy. The study also proved to be a useful, non-invasive method for follow-up assessment of a case of torsion of the testis where detorsion and orchiopexy was performed as well as in case of rupture of a testis after orchiorrhapy.

Erythrocytes↗