8 results match your criteria: "Bronx V.A. Medical Center[Affiliation]"

Site and quantitative importance of alcohol first-pass metabolism.

Alcohol Clin Exp Res

April 2000

Section of Liver Disease & Nutrition, Alcohol Research Center, Bronx V.A. Medical Center, New York 10468, USA.

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Background/aims: Polyenylphosphatidylcholine protects against alcoholic cirrhosis in the baboon. This study assesses whether the antifibrotic effect also pertains to a species other than the baboon and to agents other than alcohol.

Methods: Rats were injected with either CC14 in peanut oil or peanut oil alone, and pair-fed nutritionally adequate liquid diets, with or without polyenylphosphatidylcholine.

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To assess effects of repetitive alcohol drinking and pre-existing first-pass metabolism on the cimetidine-induced increase in blood alcohol concentrations, 20 healthy men (aged 20 to 40) of varied ethnicity and consuming less than 60 g alcohol per week underwent baseline quantitation of first-pass metabolism of alcohol. This was followed by oral administration of 0.6 g/kg ethanol given postprandially in 3 to 4 drinks spread over 135 min, before and after cimetidine (400 mg twice a day for 7 days).

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In most individuals, only part of the imbibed alcohol reaches the systemic blood. With doses relevant to social drinking, this is due mainly to gastric first-pass metabolism of alcohol, which acts as a barrier against toxic alcohol blood levels. The activity of gastric alcohol dehydrogenase can account for a substantial fraction of this metabolism.

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The possibility that cholinergic stimulation might directly activate a receptor-operated Ca2+ channel was investigated in the CA1 region of guinea pig hippocampus using intracellular recording techniques. Two cholinergic responses were studied: (1) the plateau depolarization evoked by cholinergic stimulation in the presence of Ba2+; and (2) the Ca2(+)-dependent component of membrane depolarization. Both of these responses were blocked by 1-5 microM of nifedipine, a blocker of voltage-dependent L-type Ca2+ channels.

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Alcohol dehydrogenase (ADH) isoenzymes different from those of the liver were shown to be present in the human gastric mucosa. Two ADH activity bands present in the gastric mucosa of surgical specimens from all 7 black and 11 white Americans studied were absent in 14 and barely detectable in 3 of 21 Japanese subjects evaluated. Similar ethnic differences pertained to both genders and were independent of the gastric pathology.

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Acute ethanol ingestion impairs memory in humans at concentrations associated with mild intoxication. A possible neurophysiological correlate of this effect is the suppression by ethanol of long-tem potentiation (LTP), a persistent increase in synaptic efficiency which has been proposed as a substrate for memory. However, in previous studies ethanol has been shown to impair LTP only at very high concentrations, near the lethal level in humans.

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The effect of the cholinergic agonist carbachol on a putative substrate for memory (long-term potentiation; LTP) was investigated in slices of rat hippocampus (CA1 region). Carbachol (5 microM) increased LTP when the presynaptic depression of the EPSP was controlled. The results indicate that carbachol enhances the effectiveness of the tetanus, probably through postsynaptic mechanisms.

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