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Biomedical subjects

S Schenker

Publications and source records attributed to S Schenker.

249 records · Page 14Linked to original sources
PubMedDate not supplied

Comparison of dietary protein with an oral, branched chain-enriched amino acid supplement in chronic portal-systemic encephalopathy: a randomized controlled trial.

A randomized study was conducted in 37 hospitalized patients at six cooperating hospitals in which protein-intolerant cirrhotic patients were fed increasing amounts of either dietary protein or a branched-chain enriched amino acid solution (BCAA) until they attained an intake of 80 gm protein per day or equivalent or until they developed stage 2 encephalopathy. All patients initially received 20 gm of dietary protein for 1 week, after which 20 gm of protein or BCAA were added weekly. Nitrogen balance improved from negative to positive in all patients in whom it was measured and increased equally in both groups. Seven of the 20 patients in the protein group and 1 of 17 in the BCAA group developed encephalopathy of stage 2 or greater (p less than 0.05). Changes in each component of the portal-systemic encephalopathy syndrome were compared, and differences were statistically significant for mental status grade (p less than 0.01), asterixis (p less than 0.05), Portal-systemic encephalopathy index (p less than 0.01), but insignificant for Number Connection Test, EEG or ammonia. Plasma amino acid profiles showed an increase in BCAA in the study group. Thus, oral BCAA supplements appear to induce positive nitrogen balance to approximately the same degree as an equivalent amount of dietary protein without inducing encephalopathy as frequently.

Adult↗
PubMedDate not supplied

The effect of cimetidine on hepatic drug elimination in cirrhosis.

Both cimetidine therapy and cirrhosis individually interfere with normal elimination of various drugs. Cimetidine is often prescribed in patients with cirrhosis but there is incomplete data on its effect on drug elimination in cirrhotics. The purpose of this study was to address this issue. Eight stable cirrhotics were studied prior to and following 7 days of cimetidine administration, (300 mg orally q.i.d.). Chlordiazepoxide (Librium), which is eliminated by the liver after demethylation, and indocyanine green, which is removed by the liver without biotransformation, were used as probes. Consistent with the concept that cimetidine interferes with drug metabolism by inhibiting microsomal oxidation, chlordiazepoxide clearance in the cirrhotics was inhibited by cimetidine (p less than 0.05), but indocyanine green clearance was unaffected. As shown by us previously (Roberts, R. K. et al., Gastroenterology 1978; 75:479-485), untreated cirrhotics had substantially lower chlordiazepoxide clearance than did controls. The inhibitory effect of cimetidine on chlordiazepoxide clearance was less in cirrhotics than in controls (p less than 0.05). In all subjects, there was excellent correlation between initial clearance and magnitude of depression in clearance after cimetidine, i.e., the larger the initial clearance, the larger the change (r = 0.97, p less than 0.0001). Forty-eight hours after stopping cimetidine, chlordiazepoxide clearance returned to baseline in cirrhotics and controls. Our data demonstrate that cimetidine and cirrhosis may act additively to impair drug metabolism. This effect of cimetidine on chlordiazepoxide clearance is smaller in cirrhotics than in controls, but, because of impaired initial drug elimination in cirrhosis, it may result in adverse clinical effects.

Aged↗
PubMedDate not supplied

Stimulatory effects of ethanol on amino acid transport by rat fetal hepatocytes.

Previous studies have indicated that acute, and especially chronic, maternal ethanol consumption can depress placental uptake of various amino acids. Since the fetal cell itself represents a second barrier to nutrients, one which may be altered by ethanol exposure, the effects of ethanol on amino acid net uptake by rat fetal hepatocytes was addressed. The present study determined that ethanol stimulated amino acid net uptake by fetal hepatocytes grown in monolayer culture. Fetal liver cells were grown in custom Williams' E medium (without L-arginine and with L-ornithine) and exposed to epidermal growth factor (0, 1, 2 or 5 ng per ml) and ethanol (1.7 +/- 0.1 or 3.9 +/- 0.2 mg per ml). Addition of ethanol (3.9 mg per ml) to the culture medium completely blocked measurable cell replication during a 48-hr exposure period. Fetal hepatocytes exposed to ethanol accrued both protein and water in a parallel fashion, both in excess of that by control cells. Ethanol (1.7 and 3.9 mg per ml) for 48 hr stimulated alpha-aminoisobutyric acid net uptake by fetal hepatocytes (p less than 0.05). Efflux was not affected (p greater than 0.05). The onset of this significant stimulation of net uptake was progressive and required in excess of 6 hr of contact with ethanol. This ethanol stimulation of alpha-aminoisobutyric acid net uptake persisted for at least 24 hr following ethanol withdrawal. The component(s) of alpha-aminoisobutyric acid net uptake stimulated by ethanol was independent of extracellular Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMedDate not supplied

Effects of nicotine and nicotine/ethanol on human placental amino acids transfer.

Ethanol abuse and smoking during pregnancy both result in decreased offspring weight. One explanation for this may be impaired placental nutrient transport. This study assessed this possibility utilizing the 4-hr perfused human placental system and human placental vesicles exposed to "physiological," 0.2 microM and large (about 20 microM) nicotine concentrations alone, as well as nicotine combined with ethanol, 200 or 400 mg/ml, for up to 48 hr. Two nonmetabolizable amino acids, alpha-aminoisobutyric acid (AIB) and cycloleucine (CLEU) were used as probes. Nicotine was measured by gas chromatography in the placental perfusion system and vesicles and verified as to concentration. There was no statistically significant evidence of decreased transport of these amino acids with exposure to nicotine alone or nicotine and ethanol together in either test system. Thus, brief exposure to nicotine and ethanol does not impair amino acid transport by the human placenta.

Amino Acids↗
PubMedDate not supplied

Ethanol-induced oxidative stress and enzymatic defenses in cultured fetal rat hepatocytes.

Previously, we have documented an ethanol (E)-induced oxidative stress (OS) in cultured fetal rat hepatocytes (FRH). The cause of this is uncertain, but an inhibition of key antioxidant enzymes could be a/the factor. OS was also observed in fetal liver (FL) during in utero E exposure, but not in maternal liver, a difference that might be related to selectively lower enzymatic defenses in the fetus. Here, we record effects of E on activities of catalase (Cat), superoxide dismutase (Cu, Zn SOD and Mn SOD), glutathione peroxidase (GPX), and glutathione-S-transferase (GST) in FRH isolated from 20-day-old fetuses and exposed to E (2 mg/ml) for up to 24 h and we compare these to adult rat liver data. E treatment decreased fetal liver reduced glutathione (GSH) pools by 23% (p < 0.05) and increased malondialdehyde (MDA) by 14% (p < 0.05) within 24 h of E exposure. E caused an increase in fetal liver Cat by 18%, 32%, and 47% by 3, 6, and 24 h of E, respectively (p < 0.05). A 24-h E exposure increased Cu, Zn SOD by 22% (p < 0.05) and Mn SOD by 21% (p < 0.05). A 24 h E treatment increased GPX by 18% (p < 0.05) and GST by 17% (p < 0.05). Cat in whole FL was 26% of adult (p < 0.05) whereas Cu, Zn SOD and Mn SOD in whole FL were 12% and 11% of adult levels (p < 0.05). GPX and GST in FL were 11% and 28% of adult values (p < 0.05). It is concluded that in FRH, E-induced OS is not caused by impaired activities of these enzymes, but their low basal activities (vs. adult) may predispose the fetus to OS.

Animals↗
PubMedDate not supplied

Portal hypertensive gastropathy.

Portal hypertensive gastropathy (PHG) is part of a complex syndrome which occurs as a complication of chronic liver disease and portal hypertension (PHTN). At endoscopy, the gastric mucosa shows that mosaic-like pattern and red marks, which are the source of gastric bleeding. Only the severe form of gastropathy is liable to bleed. The pathogenesis of PHG and the hemodynamic changes in PHTN are not completely understood, but chronic increase in portal pressure is a prerequisite for the development of this disorder. It has been suggested that an overproduction of endogenous vasodilators and a reduced vascular sensitivity to endogenous vasoconstrictors contribute to these circulatory disturbances. H2 receptor antagonists and sucralfate are ineffective in the management of bleeding PHG. Two small studies reported that propranolol is effective in arresting mucosal hemorrhage from severe PHG. Other feasible alternatives include transjugular intrahepatic portal-systemic shunt (TIPS) and portal-systemic shunt procedure.

Chronic Disease↗
PubMedDate not supplied

Extrahepatic glucuronidation of morphine in the dog.

The pharmacokinetic disposition of morphine was studied in sham-operated dogs, dogs with hepatic devascularization, and dogs with bile duct and ureter ligation after iv administration of 1 mg/kg of morphine. In sham-operated dogs, morphine is rapidly distributed and eliminated, with a terminal half-life of 65 +/- 30 min. Morphine glucuronide appeared in plasma within 5 min and rose rapidly to levels an order of magnitude higher than morphine levels, before both declined in parallel. In hepatic devascularized dogs, there was a marked delay in morphine elimination due to a 47% reduction in clearance. The appearance of morphine glucuronide in plasma was not delayed, but the AUC of morphine glucuronide was reduced by 56% compared to control for the first 180 min. In bile duct- and ureter-ligated dogs, elimination of morphine was increased and morphine glucuronide elimination from plasma was decreased, suggesting that glucuronide normally excreted in bile is hydrolyzed back to the parent compound and reabsorbed in sham-operated control animals. In conclusion, morphine was glucuronidated by both hepatic and extrahepatic glucuronyltransferases to an approximately equal extent in the dog.

Animals↗