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Biomedical subjects

S K Sharma

Publications and source records attributed to S K Sharma.

At least 559 records · Page 31Linked to original sources

Megadoses of vitamin C prevent the development of tolerance and physical dependence on morphine in mice.

In mice ascorbate, when co-administered with morphine, suppresses the development of tolerance and physical dependence on the drug, without significantly affecting its analgesic properties as inferred from unaltered ED50 values. The duration of morphine-induced analgesia, however, is progressively reduced with an increase in the amounts of ascorbate. Ascorbate at 1g/kg body weight does not alter the pH of blood, and has no effect on the levels of lipid-peroxides in blood and brain. Studies presented in this paper suggest the potential use of ascorbate in the prevention of development of tolerance in therapeutic applications of narcotics as analgesics. Cultured Neuroblastoma X Glioma hybrid cells (NG 108-15) respond to opiates in two different ways. The rapid receptor mediated inhibition of adenylate cyclase is followed by a long-lived compensatory increase in its activity (1-4). In a recent report (5) we have shown that ascorbate suppresses the delayed etorphine-induced compensatory increase in cAMP levels in NG 108-15 cells without affecting the short-term inhibitory response of cells to the drug. It has been suggested that while the former may be the basis of narcotic dependence and tolerance, the latter is responsible for the analgesic effect. These observations, based on a model system, prompted us to examine the effect of ascorbate on the pharmacological properties of morphine at the organismal level.

Analgesia↗

Calyco-ureteroplasty in the management of selected renal calculi.

Calyco-ureteroplasty was performed in 15 renal calculi patients with grossly deformed upper tracts. The procedure aimed to achieve total clearance of calculi, preserve renal function and check stone recurrence. At follow-up from 6 months to 7 years, there was no stone recurrence and all the patients maintained sterile urine cultures. There was both biochemical and radiological improvement in renal function. It is felt that this procedure may have a role in rehabilitating diseased renal units, preserves renal function and involves no parenchymal loss.

Adolescent↗

A study of disseminated intravascular coagulopathy in hepatic coma complicating acute viral hepatitis.

Thirty cases of viral hepatitis with and without coma and 15 normal healthy age and sex matched controls were studied for disseminated intravascular coagulopathy (DIC). Cases of viral hepatitis with coma showed strong evidence of DIC in the form of increased plasma FDP (240 +/- 190.64 dilution), diminished fibrinogen half life (48.1 +/- 15.3 hours) and increased fractional catabolic rate (46.13 +/- 14.7% per day) with normal Euglobulin clot lysis time and reduced fibrinogen (147.33 +/- 43.5%) and platelet count (1.27 +/- 0.324 lakhs/cm.). The possible role of heparin in the reversal of coagulation abnormalities have been discussed.

Adult↗

Studies on the reproductive function in the male rat following combined administration of progestin and androgen.

Experiments were designed to test the effects of megestrol acetate (MA) and medroxyprogesterone acetate (provera) in combination with methyltestosterone (MT) and testosterone enanthate (TE), respectively, on sperm population and motility of spermatozoa in the ductus deferens, circulating androgens, mating behaviour, and fertility in male rats. One milligram of progestin and 100 micrograms of androgen, when administered for 70 days, impaired the fertility without any apparent effect on mating behaviour. Azoospermia or severe oligospermia coupled with asthenospermia was achieved in the majority of animals. Spermatozoa revealed changes in their pattern of motility after different medication intervals and these have been discussed in relation to androgen dependency of the reproductive tract. Transitory decline in serum androgen is observed after withdrawal of treatment.

Androgens↗

Studies on the effects of total nephrectomy in sheep.

Effects of total nephrectomy were studied in six sheep. There was no marked deterioration in the clinical condition of the animals except anorexia and reduced water intake. Three sheep survived the period of observation of 120 hours when they were euthanized. One animal suddenly died at each of 76, 80 and 100 hours. Progressive increase of blood urea nitrogen concentration was accompanied by severe metabolic acidosis in the later stages. Plasma creatinine rose significantly but the change was not marked. Plasma inorganic phosphorous and calcium decreased significantly. Unaffected plasma sodium levels were accompanied by hyperkalemia and hypochloremia. Plasma total proteins and albumin decreased significantly in the later stages. Results showed markedly different responses to total nephrectomy in sheep as compared to changes reported in cattle and nonruminants.

Acidosis↗

Acylation of the alanine149 N-terminal of alpha-chymotrypsin and its effect on catalytic function.

A novel, active derivative of alpha-chymotrypsin was prepared from alanine-neochymotrypsinogen in which the epsilon-amino groups and the alpha-amino group of N-terminal Ala149 were acetylated. The catalytic properties at neutral and alkaline pH of this enzyme derivative were compared with those of a control alpha-chymotrypsin derivative in which only the epsilon-amino groups were acetylated. While the Km (app) of the two derivatives were the same at pH 7 to 8, at more alkaline pH the derivative having the masked Ala149 had much lower Km (app) values than the control. It is concluded that the inactivation of alpha-chymotrypsin at high pH is linked, at least in part, to the ionization state of its N-terminal Ala149 group.

Acylation↗

Pancreatic function tests in tropical sprue is pancreas involved?

Pancreatic functions were studied in 15 patients with tropical sprue. The diagnosis of tropical sprue was made on accepted criteria of demonstrating malabsorption of at least two unrelated food substances in the absence of any other cause for malabsorption in patients residing in a tropical zone. Exogenous secretion (Boots) in a dose of one clinical unit per kg was employed for direct stimulation of exocrine pancreatic secretion. Of the 15 patients, 12 showed normal pancreatic functions. In two patients, volume output was marginally low i.e. 1.6 and 1.6 ml/kg/hr respectively (Normal value greater than 1.8 ml/kg/hr). In the third patient, volume output was normal but maximum bicarbonate concentration in pancreatic juice was 61.6 mEq/litre (Normal value greater than 80 mEq/litre). None of these three patients, however, had abnormalities in both the parameters of exocrine pancreatic function. Although pancreatic hyposecretion has been reported in patient with tropical sprue when indirect stimulation with Lundh meal was applied to pancreas, yet on direct stimulation with secretin, we found pancreatic functions to be normal. It is therefore concluded that the pancreas is not primarily involved in tropical sprue.

Adolescent↗

The role of amino-terminal alanine in the control of conformation and activity of alpha-chymotrypsin.

Novel acetylated derivatives of three different three-chained chymotrypsins were prepared from bovine chymotrypsinogen A and their catalytic properties and kinetics of denaturation in urea were compared with those of the corresponding non-acetylated enzymes. Measurements of the Km (apparent) as a function of pH confirmed earlier findings of Valenzuela and Bender [J. Biol. Chem. 248, 4909-4914 (1973)] that the alpha-species of chymotrypsin is much more sensitive to reversible inactivation at high pH compared to its sister three-chained chymotrypsins, alpha 1 and kappa-chymotrypsin. Similarly, the denaturation rate constants in 8 M urea of alpha-chymotrypsin were much more sensitive to high pH than alpha 1 and kappa-chymotrypsin. The urea denaturation study showed a transition at about pH 8 to a more urea-sensitive form of alpha-chymotrypsin, whereas alpha 1 and kappa-chymotrypsin were relatively insensitive to a change in pH from 6.5 to 10. When the N-terminal Ala149 of alpha-chymotrypsin was acetylated, thus preventing protonation of the N terminus, the active enzyme derivative displayed the same Km (app) vs pH profile as alpha 1 and kappa-chymotrypsin. Urea denaturation studies with this masked derivative also showed that the pH-dependent transition of native alpha-chymotrypsin at pH 8 was eliminated. These results demonstrate that it is the presence of the protonated Ala149 residue in alpha-chymotrypsin that accounts for much of the hypersensitivity of this enzyme species to inactivation and urea denaturation in the pH region 7.5-10.

Alanine↗