PubMed Health⌕ Search

Biomedical subjects

A Hoyumpa

Publications and source records attributed to A Hoyumpa.

10 recordsLinked to original sources
PubMed1984

Kinetics of intestinal calcium transport during maturation in rats.

Young animals absorb and retain more calcium (Ca) than their older counterparts. The mechanism(s) for this age-related difference and the kinetics of intestinal calcium transport during maturation are not known. We determined, therefore, the unidirectional uptake and the transmural flux of [45Ca] in everted duodenal and jejunal sacs of suckling, weanling, adolescent, and adult rats using [3H] dextran as a marker of adherent mucosal volume. These measurements were carried out over a wide range of Ca concentrations (0.5-30 mM). Results indicate an evolving pattern of intestinal calcium transport with different kinetic characteristics emerging as the animals matured. The active component of transport became more pronounced with increasing age. In adult rats Km and Jmax of [45Ca] duodenal and jejunal uptake were several-fold greater than corresponding values for suckling rats. Transport at higher calcium concentrations (10-30 mM) was non-saturable, and the permeability coefficient decreased with age. The transition to a more saturable process occurred around the time of weaning. These findings suggest that intestinal calcium transport is characterized by a maturation pattern that starts with a predominantly passive system during infancy and changes to a saturable active mechanism during maturation.

Aging↗
PubMed1983

Effects of ethanol in vitro on rat intestinal brush-border membranes.

Ethanol, at concentrations found in the intestinal lumen after moderate drinking, has been shown to inhibit carrier-mediated intestinal transport processes. This inhibition could occur by direct interaction with membrane transporters, dissipation of the energy producing Na+ electrochemical gradient and/or nonspecific alteration of membrane integrity. The latter alteration may be reflected by changes in membrane fluidity, chemical composition or vesicular size. These possibilities were examined with studies in purified brush border membrane vesicles of rat intestine. Ethanol inhibited concentrative Na+-dependent D-glucose uptake in a dose-dependent manner. In contrast, ethanol did not inhibit concentrative D-glucose uptake under conditions of D-glucose trans-stimulation in the absence of a Na+ electrochemical gradient. Ethanol also inhibited initial, concentrative Na+-dependent taurocholic acid uptake, as well as equilibrium uptake. That ethanol exerted a dual effect on transport by increasing membrane conductance for Na+ while decreasing intravesicular space was supported by direct studies of Na+ uptake. Morphometric analysis confirmed that ethanol-treated membranes had a decreased intravesicular size when compared to untreated membranes. Finally, membrane fluidity measured by EPR showed that ethanol had a significant fluidizing effect without producing qualitative changes in membrane proteins, as determined by SDS gel electrophoresis. These results suggest that ethanol inhibits carrier-mediated transport by dissipation of the Na+ electrochemical gradient and alteration of membrane integrity rather than by direct interaction with membrane transporter.

Animals↗
PubMed1983

Developmental kinetics of colonic calcium transport.

Young animals absorb and retain more calcium (Ca) than their older counterparts. Our previous studies on small intestinal calcium transport indicated an evolving pattern with a change in the kinetics of calcium uptake. Whether the lower intestine also mirrors and participates in calcium transport is not known. Therefore, the unidirectional uptake of 45Ca was determined in everted colonic sacs of suckling, weanling and adolescent rats using 3H dextran as a marker of adherent mucosal volume. These measurements were carried out over a 0.5-30 mM Ca2+ concentrations. Results indicate an evolving pattern of intestinal calcium transport with different kinetic characteristics emerging as the animals matured. The mediated component of transport became more pronounced with increasing age. Actual Km and Jmax values for mediated colonic 45Ca uptake showed an evolving pattern. A steady rise in both Km and Jmax was noted with increasing age. Transport at higher concentrations (10-30 mM) was non-saturable. The transition to a more saturable process occurred around the time of weaning. These findings suggest that colonic calcium transport is characterized by a maturation pattern that starts with a predominately passive system during infancy and changes to a saturable mechanism during maturation.

Animals↗
PubMed1982

Differential effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism in the rat.

The effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism have been studied both in vivo and in vitro in the rat, using caffeine, phenacetin, antipyrine and aminopyrine as test substrates. N-Demethylation of aminopyrine (P-450 mediated) was increased both in vivo and in vitro in rats after chronic ethanol feeding (P less than 0.05) whereas in vivo N-demethylation of caffeine and O-dealkylation of phenacetin (P-448 mediated) were unchanged in the same animals. N-Demethylation of antipyrine was increased by both phenobarbital and 3-methylcholanthrene pretreatment and by chronic ethanol feeding (P less than 0.05), possibly due to cytochrome P-450 induction. Furthermore, the Michaelis affinity constants, Km, for hepatic microsomal aminopyrine N-demethylase and antipyrine N-demethylase were lower in chronic ethanol-fed animals (P less than 0.05), suggesting a qualitative change in the enzymes resulting in greater substrate affinity. These findings suggest a differential effect of chronic ethanol feeding on the induction of cytochrome P-450- and cytochrome P-448 mediated drug metabolism, with a greater effect on the former microsomal system.

Aminopyrine N-Demethylase↗
PubMed1981

Normal metabolism of morphine in cirrhosis.

Morphine disposition and elimination was studied in 6 healthy male subject s and 6 male patients with cirrhosis, to assess the role of differences, if any, on the reported intolerance of morphine in cirrhosis. In addition the elimination of indocyanine green was studied in the same subjects on a separate occasion. The elimination half-life of indocyanine green was increased and its plasma clearance was markedly reduced in patients with cirrhosis as compared with controls (p less than 0.05). In contrast the disposition and elimination of morphine were unaffected by moderate to severe cirrhosis. Furthermore, while marked sedation was observed in normal subjects, the cirrhotics demonstrated mild sedation with no clinical evidence of hepatic coma. The normal elimination of morphine in cirrhosis is in contrast to the decreased elimination of high clearance drugs metabolized by oxidation, such as lidocaine and meperidine. Morphine is also normally a high clearance drug that is detoxified by conjugation with glucuronic acid. Since intra- or extrahepatic shunting, or both, in cirrhosis do not significantly impair morphine clearance, we postulate that significant extrahepatic morphine conjugation may occur in both normal subjects and in patients with cirrhosis. Furthermore, the reported morphine intolerance to the central effects of morphine cannot be explained by impaired drug elimination and increased availability of morphine to cerebral receptors.

Adult↗
PubMed1975

The effects of age and liver disease on the disposition and elimination of diazepam in adult man.

This study investigates the separate effects of age and hepatocellular liver disease on the disposition and elimination of diazepam (Valium) in man. The drug was given either by rapid intravenous injection (0.1 mg/kg) or orally (10 mg) to 33 normal volunteers rnaging in age from 15 to 82 yr as well as to 9 individuals with alcoholic cirrhosis, 8 with acute viral hepatitis, and 4 with chronic active hepatitis. In the normal individuals, the terminal plasma half-life of diazepam, (t 1/2 (B)) exhibited a striking age-dependence; at 20 yr the t 1/2 (beta) was about 20 h, but it increased linearly with age to about 90 h at 80 yr. The plasma clearance of diazepam in the majority of the normal subjects was between 20 and 32 ml/min and showed no significant age-dependence. Cigarette smoking did not affect the half-life or the clearance. Additionally, neither the plasma binding (97.4 plus or minus 1.2%, mean plus or minus SD) nor the blood/plasma concentration ratio (0.58 plus or minus 0.16) of diazepam showed any age-related changes (P greater than 0.05). By contrast, analysis of the intravenous data according to a two-compartment open model indicated that both the initial distribution space (V1) and the volume of distribution at steady state [Vd(ss)] of diazepam increased linearly with age (P less than 0.005). The increase in Vd(ss) was secondary to the change in V1. It appears then that the prolongation of t 1/2 (beta) of diazepam with age is primarily dependent on an increase in the initial distribution volume of the drug. The plasma concentration/time course of the metabolite, desmethyldiazepam, was also affected by age. In older individuals, the initial presence and the peak values of desmethyldiazepam were observed later and the metabolite was present in lower concentrations. Despite the profound prolongation of t 1/2 (theta) with age, the constancy of diazepam clearance indicates that drug plasma concentrations will not accumulate any more in the old than the young, and chronic dosage more in the old than the young, and chronic dosage modifications based on pharmacokinetic considerations are unnecessary. Data obtained in patients with liver disease were compared with those found in age-matched control groups. Patients with cirrhosis showed a more than twofold prolongation in the half-life of diazepam (105.6 plus or minus 15.2 vs. 46.6 plus or minus 14.2 h, P less than 0.001).

Administration, Oral↗
PubMed1975

The effect of liver disease in man on the disposition of phenobarbital.

The disposition of phenobarbital (PB) was studied in normal individuals and in patients with cirrhosis or acute viral hepatitis to determine 1) if there is significant impairment of PB metabolism in hepatic disease and 2) to what extent such abnormal disposition of the drug affects its disappearance from blood. The diagnosis of liver disease was based on characteristic clinical findings, biochemical liver "function" tests and liver biopsy when necessary. All individuals had normal renal function and were free of other drug and alcohol intake for at least 3 weeks. With radiotracer methodology, PB and its principal metabolites, p-hydroxyphenobarbital (PBOH) and conjugated PBOH (PBOC), were monitored in blood and urine for 5 days after a single dose of 14-C-PBadministered intraduodenally. PB blood half-life (T1/2) in the control group was 86 plus or minus 3 hours (S.E.). In cirrhotics the T1/2 was prolonged to 130 plus or minus 15 hours (P less than .001) and this was accompanied by a 50% reduction in urinary PBOC excretion (P less than .05). Urinary excretion of PB and PBOH was unaltered by cirrhosis. In patients with acute viral hepatitis, PB T1/2 was not significantly prolonged and urinary excretion of PB and its metabolites was in the normal range (P greater than .05). No PBOH and only traces of PBOC were detected in the blood of either control individuals or patients with liver disease. Urinary excretion of unchanged PB was an important elimination pathway of the drug in all groups. As a result of this, PB T1/2 in cirrhosis was only moderately prolonged.

Adult↗