Novel approach to ampullary cannulation.
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Biomedical subjects
Publications and source records attributed to S C Batra.
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First-pass metabolism (FPM) of orally ingested alcohol has been attributed to gastric alcohol dehydrogenase (ADH) activity in both humans and rats. To determine whether gastric alcohol dehydrogenase is essential for alcohol FPM, we sought a species lacking this enzyme. We found that Syrian golden hamsters have negligible gastric ADH yet alcohol FPM (265 +/- 25 mg ethanol/kg) was comparable to that of rats (251 +/- 31 mg/kg). To determine whether hamster gastric mucosal cells metabolize sufficient alcohol to account for this FPM, primary cultures were established, and these cells metabolized 1.99 +/- 0.84 mumol ethanol/10(6) cells/hr, an amount sufficient to account for the bulk of alcohol FPM. In contrast to alcohol dehydrogenase, catalase activity in hamster gastric mucosa (870 +/- 93 units/g tissue) was eightfold higher than in rat gastric mucosa (111 +/- 9 units/g tissue; P < 0.0001). FPM in hamsters treated with 3-aminotriazole was reduced from 242 +/- 24 to 130 +/- 22 mg/kg (P < 0.05) but was not reduced in rats. The results imply that catalase participates in gastric alcohol metabolism of hamsters.
BACKGROUND/AIMS: Several studies have shown that the stomach has sufficient alcohol dehydrogenase activity to metabolize a significant amount of alcohol and that cimetidine depresses this alcohol dehydrogenase activity. However, both gastric metabolism of ethanol and its inhibition by cimetidine remain controversial. Given the difficulty in assessing gastric metabolism of ethanol in vivo, this subject was investigated in vitro. METHODS: Cultured rat gastric epithelial cells were incubated with 200 mmol/L [1-14C]ethanol for 90 minutes with and without cimetidine (0.1-1 mmol/L) or omeprazole (1 mmol/L). The quantity of ethanol oxidized by gastric cells was measured by the amount of acetate produced using ion exchange chromatography. RESULTS: The majority of cells at confluency had typical features of mucous cells. The gastric cells metabolized significant amounts of ethanol, sufficient to account for in vivo first-pass metabolism of ethanol in rats. Cimetidine, but not omeprazole, reduced ethanol metabolism by 39.9% +/- 4.9% (P < 0.01), an inhibition comparable with that previously reported for first-pass metabolism in vivo. CONCLUSIONS: Gastric cells in tissue culture are capable of significant ethanol oxidation, the in vitro rates are sufficient to account for first-pass metabolism of ethanol in vivo, and cimetidine inhibits ethanol metabolism in tissue culture, an effect that parallels its decrease of first-pass metabolism in vivo.
The effects of the calcium antagonist prenylamine on intracellular calcium concentration were studied in a human ovarian carcinoma cell line, OVCAR-3. Exposure of cells to 100 microM prenylamine resulted in nearly a 10-fold increase in cytosolic free calcium concentration ([Ca2+]i) as measured by Fura-2 fluorescence. In calcium-free medium, although the increase in [Ca2+]i caused by prenylamine was smaller, it was still substantial compared with the basal level. Efflux experiments with 45Ca showed that 100 microM prenylamine increased calcium efflux by 70% compared with control, indicating active extrusion of the elevated [Ca2+]i. The sluggish nature of calcium release and its independence from the pool activated by ionomycin suggest that the calcium was probably not released from endoplasmic reticulum. These results, although paradoxical, provide a new insight into the possible mechanism of action of prenylamine in causing cancer cell death.
The effect of one, 4 and 8 weeks of continuous estrogenization of rabbit on peroxidase (PO) activity and on both cytoplasmic and nuclear estrogen receptors was studied in the uterus, vagina, urethra and urinary bladder. Whereas the peroxidase activity in the urogenital tissue of untreated controls was near zero, after one week of estrogen treatment it increased very substantially in the uterus and vagina and much less dramatically in the urethra or urinary bladder. With continuation of estrogen treatment for 4 or 8 weeks the PO decreased by 80-90% in the uterus and vagina and by only 40% in the urethra. After one week of estrogen treatment the density of both cytosolic and nuclear estrogen receptors decreased by several fold in both the uterus and vagina, whereas it decreased by 30-50% in the urethra and bladder. The concentration of both cytosolic and nuclear receptors decreased further although less dramatically with continuing estrogen treatment, up to 8 weeks, in all tissues. These data suggest that although the general pattern of responses to estrogen showing an initial increase in PO followed by a reduction with continuing estrogen treatment is the same in all urogenital tissues, the responses seem to have a prolonged time scale in the case of lower urinary tract tissues. The quantitative aspect of the response generally corresponds with the density of estrogen receptors in the urogenital tissues.
High concentrations of magnesium (12 and 24 mM) in the extracellular medium markedly inhibited both spontaneous activity and K+-induced contracture in strips of nonpregnant human myometrium. Net calcium influx measured by the uptake of 45Ca2+ in the myometrium was considerably decreased by high concentrations of magnesium. This was true for both resting (unstimulated) and K+-stimulated uptake of 45Ca2. While calcium uptake in K+-stimulated tissues exposed to 24 mM magnesium was significantly lower than in those exposed to 12 mM, no difference was found in the unstimulated tissues. These data indicate that the tocolytic action of magnesium most probably results from the inhibition of calcium entry into myometrial cells.
The binding properties of the calcium channel inhibitor [3H]-nitrendipine to membrane fragments prepared from nonpregnant and pregnant human myometrium were investigated. Specific binding sites with high affinity and low capacity were identified in both pregnant and nonpregnant myometrium. Whereas there was no significant difference in the concentration of binding sites in the two types of myometria, the Kd value for binding in pregnant myometrium was lower than that in nonpregnant myometrium (p less than 0.05). Although dihydropyridines effectively competed for [3H]-nitrendipine-binding sites, verapamil was a poor competitor. This was true for both the pregnant and nonpregnant myometrium. The inhibition of nitrendipine binding by dihydropyridines and also verapamil was significantly greater in pregnant than in nonpregnant myometrium. These data suggest that dihydropyridine-type calcium channel inhibitors might provide a useful alternative for treating premature labor.
When female estrogenized rabbits were injected i.v. with 3H-progesterone, the tritium concentration determined after one hour was about two to three times higher in urethra, urinary bladder and vagina than in the heart. High affinity progesterone receptors (KD = 1-2 nM) could be demonstrated in both cytoplasmic and nuclear fractions prepared from estrogenized rabbit urethra, bladder and vagina. The cytosolic receptor concentration in both urethra and bladder was about half of that in the vagina. The concentration of nuclear receptors in urethra was not significantly different from that in the vagina, but in the bladder the concentration was only about one fourth of that in the vagina or urethra. The mean KD of cytosolic receptors from bladder was significantly higher than the corresponding values in urethra and vagina. Progesterone binding sites in the bladder had a broader hormonal specificity than those in the urethra or vagina. The present demonstration of specific progesterone receptors in the female urethra might provide a possible link between estrogen progesterone interaction and the appearance of urinary incontinence during pregnancy in women.
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It is not uncommon to use estrogen therapy in patients with urinary stress incontinence. The possibility of a selective action of estrogen in the lower urinary tract was examined. Wet weight of the uterus, vagina and urethra increased significantly, and that of the urinary bladder insignificantly after estradiol treatment of ovariectomized rabbits. When ovariectomized rabbits were injected i.v. with 3H-estradiol, the tritium concentration, determined after 1 hour, was 3 to 4 times higher in urethra, urinary bladder and vagina than that in the muscle. High affinity estradiol receptors (KD approximately 1 X 10(-9) M) could be demonstrated in both the cytoplasmic and nuclear fractions prepared from the female rabbit urethra and bladder. The concentrations of estradiol receptors in the urethra and bladder were about 10 and 20 times lower respectively than those in the uterus. The present evidence for estradiol receptors in the lower urinary tract supports the case for estradiol therapy in urinary incontinence.
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