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Biomedical subjects

G Shah

Publications and source records attributed to G Shah.

68 records · Page 4Linked to original sources

Acute metabolic interaction of ethanol and drugs.

Addition of ethanol in vitro was found to inhibit the microsomal metabolism of a variety of drugs such as meprobamate, aminopyrine, pentobarbital and zoxazolamine. In all cases, a mixed type of inhibition was obtained. When the concentration of alcohols of different chain lengths required to inhibit 50% of the metabolism of drugs was plotted against their corresponding octanol-water partition coefficients (Po/w) it was found that the inhibitory potency of alcohols is linearly related to the partition coefficients, with a slope of 0.98. In vivo acute administration of ethanol also resulted in decreased whole body metabolism of meprobamate, aminopyrine, pentobarbital, zoxazolamine and aniline. In vitro addition of pentobarbital, phenobarbital and meprobamate had no significant effect on ethanol metabolism by liver slices. Acute pretreatment with these drugs also had no effect on the rate of ethanol metabolism in vivo as measured in the whole body or as estimated from the rate of decrease of blood ethanol concentration. It appears therefore that acute metabolic interaction of ethanol and drugs is a one sided phenomenon, i.e. ethanol inhibits drug metabolism, whereas drugs do not inhibit ethanol metabolism. Ethanol inhibition of drug metabolism in vitro appears to result from a modification of the lipophilic milieu that surrounds the cytochrome P-450 in the microsomal membrane. Interference with the hydrophobic sites may either directly or indirectly affect the catalytic activities of the microsomal enzyme.

Animals↗

Induction of labor in the high-risk pregnancy with PGF 2 alpha.

The induction of labor in the high-risk patient is accompanied by an increased incidence of cesarean section partly due to failed induction. A series of 50 high-risk patients induced with intravenous prostaglandin F 2 alpha is presented. Forty-five were successfully induced, 35 of whom delivered vaginally. Failed inductions occurred in 5 patients. The overall success rate was 90%, and cesarean section rate was 25.5%. There was an increased incidence of late decelerations in the PGF 2 alpha groups as compared to spontaneous and Pitocin-stimulated labors. While the success was high, the use of a drug which itself may caused fetal cardiovascular changes is not desirable, especially in those pregnancies already at risk.

Adolescent↗

Characterization of gastric mucosal membranes. VIII. The localization of peptides by iodination and phosphorylation.

Two fractions of gastric mucosal membranes obtained by Ficoll-sucrose density gradient centrifugation were studied by a variety of techniques to localize the polypeptides. Gel electrophoresis showed the presence of five major polypeptides and several minor ones. Only one of these, 82,000 daltons, was available for iodination in the intact tissue. The two membrane fractions differed in their accessibility to peroxidase. The denser fraction showed two major defined iodination peaks at 82,000 and 102,000 daltons. Freeze-thawing and iodinating with 131-I produced additional labeling of peaks as well as relabeling the 82,000-dalton component, showing it was accessible from both sides of the membrane. The two major components were also sensitive to cross-linking, the 102,000 polypeptide being especially sensitive to --SH oxidation. Proteolysis with trypsin removed both components in the denser membrane fraction, in addition to inhibiting the K+-ATPase and K+-p-nitrophenylphosphatase of that fraction. Phosphorylation with [gamma-32-P]ATP labeled the 102,000-dalton component and K+, HCO3- minus and p-nitrophenylphosphate reduced the level of labeling. Hence the 102,000 region contains a subunit of the ATPase, is readily iodinated in inside-out vesicles, and is the most available for interpeptide S--S cross-linking.

Adenosine Monophosphate↗

Comparison of sensitivity and alcohol consumption in four outbred strains of rats.

Differences in alcohol consumption and in sensitivity to the effects of ethanol were investigated in four outbred rat strains: Fischer 344, Long-Evans, Sprague-Dawley and Wistar. Alcohol consumption was measured in all four strains in three separate subgroups for each strain, using three different concentrations of ethanol (5, 10 and 20% v/v). An intermittent forced alternate-day ethanol presentation procedure (ethanol as the sole fluid for one day followed by only water the next day), as well as a two-bottle choice paradigm, were employed for this purpose. Ethanol-induced hypothermia and motor impairment (tilting plane test) were used to assess sensitivity. Significant differences in alcohol consumption were found among these strains. The Long-Evans strain consumed the highest and Fischer 344 the lowest amount of ethanol. Wistar and Sprague-Dawley were intermediate. However, the strains did not differ in sensitivity to ethanol. Similarly, determination of sensitivity to ethanol on day 0 in separate groups of these four strains (same age and weight, and obtained at the same time from the same supplier) did not reveal graded differences in sensitivity (hypothermia and motor impairment) corresponding to differences in alcohol consumption. These results suggest that sensitivity does not correlate with alcohol consumption.

Analysis of Variance↗

Effect of lipid solubility on the development of chronic cross-tolerance between ethanol and different alcohols and barbiturates.

Tolerance to ethanol and cross-tolerance to other alcohols (n-propanol, n-butanol, t-butanol, isobutanol, t-amyl alcohol, n-amyl alcohol, and benzyl alcohol) and barbiturates (pentobarbital, secobarbital, amobarbital, thiopental, barbital and phenobarbital) that differ in lipid:water partition coefficient was examined in rats after chronic pretreatment with ethanol. Tolerance and cross-tolerance were studied with three different measures (hypothermia, tilt-plane, and rotarod). Tolerance to ethanol resulted in significant cross-tolerance to alcohols with low lipid solubility (n-propanol and t-butanol), whereas no cross-tolerance was seen with alcohols of high lipid solubility (isobutanol, n-amyl alcohol, t-amyl alcohol and benzyl alcohol). Cross-tolerance to n-butanol (which has intermediate lipid solubility) appeared to be metabolic rather than functional. Tolerance to ethanol also resulted in significant cross-tolerance to barbital and phenobarbital, but not to pentobarbital, secobarbital, amobarbital or thiopental. These studies suggest that lipid solubility is an important factor in relation to specificity of cross-tolerance to alcohols and barbiturates.

Alcohols↗

Characterization of the Phenomenon of rapid tolerance to ethanol.

Motor impairment (tilt-plane) and hypothermia tests were used to further characterize the phenomenon of rapid tolerance to ethanol. Five experiments were carried out to clarify the relationship between rapid and chronic tolerance. The first experiment demonstrated that the extent of tolerance on day 2 produced by the single dose of 4 g/kg alcohol on day 1 was similar to that resulting from two divided doses, administered 2 h apart. In the second experiment, a linear relationship between treatment dose and rapid tolerance development was demonstrated in that higher day 1 treatment doses resulted in greater rapid tolerance development. In the third, a parallel dose-response relationship, similar to that known for chronic tolerance, was observed for rapid tolerance. In the fourth experiment, we compared the development of rapid tolerance under three different conditions: (a) in groups of rats that were not subjected to testing at all (no testing); on day 1, (b) in groups of rats that were not tested on the apparatus but handled at all test times on day 1 (dummy testing); and (c) in groups of rats that were tested at all test times on day 1 (testing or intoxicated group). No testing on day 1 failed to produce rapid tolerance to ethanol whereas testing and dummy testing of animals on day 1 after pretreatment with ethanol-produced rapid tolerance to ethanol on day 2. In the last experiment, immediate posttrial administration of ketamine was found not to block rapid tolerance development. These findings provide additional support for similarities between the mechanisms of rapid and chronic tolerance.

Animals↗

Misleading acute hypercalcemia due to hyperlipidemia: a method-dependent error.

OBJECTIVE: To report a case of artifactual hypercalcemia in a patient with hyperlipidemia. METHODS: We present clinical data and laboratory findings in a 33-year-old woman with generalized fatigue, a recent 5-kg weight loss, and a papular rash on the extremities as well as a history of diabetes and hypertension. RESULTS: Physical examination revealed an obese patient with eruptive xanthomas and lipemia retinalis. Laboratory tests showed hyperlipidemia, hypercalcemia (serum calcium measured by spectrophotometry), anemia, hyperproteinemia, hyperuricemia, and hyperbilirubinemia. After 4 days of a low-fat, low-cholesterol diet and gemfibrozil therapy, the serum triglyceride level decreased, and the serum calcium concentration returned to normal. CONCLUSION: In patients with hypercalcemia without an obvious cause, a spurious measurement should be considered.

Journal Article↗

Liquid chromatographic determination of oxfendazole in swine feeds.

A relatively simple analytical method is presented for determination of oxfendazole (2-(methoxycarbonylamino)-5-phenylsulfinyl-benzimidazole) at levels as low as 0.012% in swine feeds, using cation exchange liquid chromatography (LC). The sample was extracted with a solvent mixture of methanol-glacial acetic acid (90 + 10) at 45 degrees C, using a gyrorotory shaker. Plant pigments and other feed excipients were removed using zinc acetate treatment and pH-controlled extraction. Oxfendazole was further separated from the remaining interferences and quantitatively determined by LC on a Partisil SCX column with acetonitrile-0.01M phosphate buffer as mobile phase. The method is stability-specific, linear, precise, and accurate at 80-120% labeled strength (relative standard deviation 0.9-1.7 with mean recovery of 98-99%). Supporting data at a level of 0.0135% oxfendazole in swine feed indicated that this method is capable of complete recovery of oxfendazole from medicated swine feeds.

Animal Feed↗