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Biomedical subjects

W B Strum

Publications and source records attributed to W B Strum.

At least 37 records · Page 2Linked to original sources
PubMed1984

Inhibitory effect of unconjugated bile acids on the intestinal transport of 5-methyltetrahydrofolate in rat jejunum in vitro.

The effect of the unconjugated bile acids, cholic, deoxycholic, chenodeoxycholic, and ursodeoxycholic acids, and of the conjugated bile acid taurocholic acid on the mucosal-to-serosal transport and tissue uptake of the naturally occurring folate derivative, 5-methyltetrahydrofolate (5-CH3H4PteGlu) was examined in everted sacs of rat jejunum. Each of the unconjugated bile acids examined inhibited the transport and tissue uptake of 5-CH3H4PteGlu in a concentration dependent manner. At low concentrations (0.01-0.1 mM) of cholic and deoxycholic acids, no structural or functional damage to the intestinal mucosa occurred and the transport of 5-CH3H4PteGlu was inhibited competitively with Ki values of 0.114 mM and 0.055 mM for cholic and deoxycholic acids, respectively. The greater inhibition of 5-CH3H4PteGlu transport by unconjugated bile acids at 1 mM can be attributed to observed structural and functional damage to the intestinal mucosa. The addition of 2 mM lecithin to the mucosal medium failed to prevent the inhibitory effect of 0.1 mM deoxycholic acid on the transport of 0.5 microM 5-CH3H4PteGlu. Compared with the effect of unconjugated bile acids, the conjugated bile acid taurocholic acid (0.01-5 mM) showed no effect on the transport and tissue uptake of 5-CH3H4PteGlu. The results of this study show that intestinal transport and tissue uptake of 5-CH3H4PteGlu are inhibited by unconjugated bile acids in a dose-dependent fashion. The clinical and physiological implications of these observations are discussed.

Animals↗
PubMed1984

Inhibitory effect of unconjugated bile acids on the enterohepatic circulation of methotrexate.

The effect of unconjugated cholic and deoxycholic acids on intestinal and hepatic transport and bile secretion of methotrexate was studied using everted sacs of rat proximal jejunum and isolated perfused rat liver. Cholic and deoxycholic acids competitively inhibit the mucosal-to-serosal transport of methotrexate (Ki, 0.08 and 0.06 mM, respectively). Cholic and deoxycholic acids also decrease intestinal tissue content of methotrexate in a concentration-dependent manner. Structural and functional damage to the intestinal mucosa does not occur in tissue treated with 0.1 mM and lower concentration of deoxycholic acid as assessed by histological studies, transmural potential difference measurements and the release of the cytoplasmic marker enzyme, lactate dehydrogenase. In the isolated liver, cholic and deoxycholic acids inhibit the uptake, retention and biliary secretion of methotrexate. At 1 mM cholic and deoxycholic acids, 72 and 80% inhibition in liver uptake and 93 and 99% inhibition in bile secretion of 1 microM methotrexate are observed, respectively. These studies demonstrate that unconjugated bile acids inhibit the enterohepatic circulation of methotrexate by impairing its intestinal transport and hepatic uptake and retention and biliary secretion.

Animals↗
PubMed1983

Ranitidine.

Ranitidine is an H2-receptor antagonist that was released recently for use in the treatment of acute duodenal ulcer disease, Zollinger-Ellison syndrome, and systemic mastocytosis with gastric hypersecretion. The pharmacokinetics, efficacy, adverse effects, and clinical utility of ranitidine are presented. The drug is similar in therapeutic effect to its predecessor, cimetidine, yet has certain advantages over cimetidine in clinical applications.

Aged↗
PubMed1983

Cyclic adenosine-3',5'-monophosphate and folate transport in rat jejunum.

The intestinal transport of 5-methyltetrahydrofolate and pteroylmonoglutamate was examined in everted sacs of rat jejunum exposed to compounds which increase intracellular cyclic adenosine-3', 5'-monophosphate. Adenyl cyclase stimulators (hydrocortisone and prostaglandin), phosphodiesterase inhibitors (3-isobutyl-l-methylxanthine, aminophylline and papaverine), and dibutyryl adenosine-3',5'-cyclicmonophosphate added to the mucosal medium inhibit the mucosal-to-serosal transport of physiological concentrations of 5-methyltetrahydrofalate and pteroylmonoglutamate. Transport inhibition is correlated with the ability of these agents to increase cellular cyclic adenosine-3', 5'-monophosphate. The active, carrier-mediated transport system of folate compounds is highly sensitive to the increase in cyclic adenosine-3', 5'-monophosphate level, while the diffusion system is insensitive. These data indicate that the active transport system of folates is modulated by cellular cyclic adenosine-3', 5'-monophosphate.

1-Methyl-3-isobutylxanthine↗
PubMed1983

A pH-dependent, carrier-mediated system for transport of 5-methyltetrahydrofolate in rat jejunum.

The intestinal transport of the naturally occurring folate coenzyme, 5-methyltetrahydrofolate, was studied using everted sacs of rat jejunum. The study provides evidence that intestinal transport of 5-methyltetrahydrofolate is composed of two systems: 1) an active, carrier-mediated system which is demonstrable at low concentrations; and 2) a diffusion system which is demonstrable at high concentrations. The active system is characterized by: 1) saturation kinetics with Km congruent to 0.3 microM; 2) accumulation against a concentration gradient with a serosal-to-mucosal ratio of 1.8; 3) inhibition by metabolic poisons; 4) inhibition by oxidized and reduced folate analogs; 5) temperature dependence; 6) sodium dependence; 7) glucose dependence; and 8) specificity for the jejunum. These features are strongly pH-dependent, and demonstration of active transport of 5-methyltetrahydrofolate requires a buffer pH of 6, glucose in the incubation medium and a substrate concentration of less than 10(-6) M. The diffusion process is characterized by: 1) linear increase in the mucosal-to-serosal transport of 5-methyltetrahydrofolate with increasing mucosal concentration to 10(-6) M and above; 2) energy independence; 3) pH independence; and 4) temperature independence. These studies clarify the mechanism of intestinal transport of 5-methyltetrahydrofolate, show the similarities to transport of other folate compounds and provide a unified concept of intestinal folate transport.

Animals↗
PubMed1982

Effects of haem infusion on biliary secretion of porphyrins, haem and bilirubin in man.

Employing a continuous bile collection, we measured the bile secretion of porphyrins, haem (iron protoporphyrin IX regardless of oxidation state) and bilirubin in five healthy subjects. The baseline values for the flow of porphyrins in the bile were: 4.7 +/- 1.9 nmol/h uroporphyrin, 27.3 +/- 3.8 nmol/h coproporphyrin and 39.2 +/- 11.7 nmol/h protoporphyrin. Bile haem flow was 59.7 +/- 12.6 nmol/h, and that of bilirubin 23.8 +/- 8.2 mumol/h. Following haem injection (6.4 mumol/kg) the flow of protoporphyrin but not of the other porphyrins was reduced, and the bile haem flow increased (232 +/- 109.5 nmol/h), while the flow of bilirubin did not increase significantly. A few patients with representative porphyrias showed the expected increase in copro- and protoporphyrin in the bile. The patient with coproporphyria exhibited a bile flow of coproporphyrin of 1470 +/- 133 nmol/h and of protoporphyrin of 334 +/- 29 nmol/h; haem infusion significantly reduced the bile flow of both porphyrins (to 649 +/- 101 for copro- and 215 +/- 36 nmol/for protoporphyrin). The patient with protoporphyria had an increased protoporphyrin flow, yet haem infusion caused no reduction in protoporphyrin flow (106 +/- 7 after v. 81.4 +/- 13 nmol/h before haem). In conclusion, we found that haem and porphyrins are normal constituents of bile, and that injected haem appears in bile. Bile bilirubin did not rise within 12 h after haem infusion a finding which warrants further investigation.

Adult↗
PubMed1981

Characteristics of the transport of pteroylglutamate and amethopterin in rat jejunum.

Intestinal transport of pteroylglutamate and amethopterin, a folate antagonist, was further characterized in everted sacs of rat jejunum. The system is composed of two distinguishable processes: active, pH-dependent, carrier-mediated transport and diffusion. The active process is specific for the pteroylglutamate molecule and requires sodium. When active transport is blocked completely by cyanide, iodoacetate, p-chloromercuriphenylsulfonate, the absence of sodium or high concentrations (50-100 microM) of the substrate, 20 to 30% of the total substrate available is transported by diffusion. In contrast to the active process, the diffusion component is not pH-dependent. Sulfasalazine inhibits pteroylglutamate (Ki congruent to 112 microM and amethopterin K congruent to 70 microM) transport competitively and reduces the quantity of pteroylglutamate converted to 5-methyltetrahydrofolate during intestinal transport. Studies using identical concentrations of amethopterin covalently bound to albumin and free drug indicate that the covalently bound amethopterin is transported 18% as well as free drug by jejunal and ileal sacs. Ethanol (3g/dl) has a mild inhibitory effect on pteroylglutamate and amethopterin transport. Cholestyramine (20 mg) adsorbs 95% of pteroylglutamate or amethopterin (100 micrograms) in vitro. These studies further clarify the mechanisms of intestinal folate transport and describe drug interactions which influence the transport process.

Animals↗
PubMed1980

Hepatic uptake, intracellular accumulation and biliary secretion of 5-methyltetrahydrofolate.

Transport of the reduced folate coenzyme, 5-methyltetrahydrofolate, from plasma to bile was studied in the isolated perfused rat liver. The system was inhibited by metabolic poisons, pteroylglutamate, 10-formylfolate, and amethopterin. The coenzyme was concentrated in hepatic parenchyma 1.3 fold over the concentration in the medium. After an initial delay of approximately 20 min the biliary secretion of the coenzyme nearly paralleled the hepatic uptake, and the coenzyme was concentrated in bile 15-19 times above the perfusion medium. The transport process was saturable with a Kt value of 0.45 mM and Vmax of 0.66 mumoles/hr/g liver. Chromatography of the bile revealed minimal biotransformation of the secreted coenzyme. In experiments in vivo 5-methyltetrahydrofolate was absorbed readily from the intestine, as demonstrated by the urinary excretion of 32-40% of the dose within 48 hr after peroral administration. These studies indicate that hepatic uptake and biliary secretion of 5-methyltetrahydrofolate occurs by an energy-dependent, carrier-mediated process in which the coenzyme accumulates in the liver, is secreted into bile against a high concentration gradient and undergoes enterohepatic circulation.

Animals↗
PubMed1979

Enzymatic reduction and methylation of folate following pH-dependent, carrier-mediated transport in rat jejunum.

Intestinal transport of [3H] folate was studied using everted sacs of rat jejunum. The proximal small intestine transports folate against a concentration gradient by a system which is saturable, pH-dependent, energy-dependent, sodium-dependent, sensitive to temperature, and appears to be a common transport system for folate compounds. Chromatographic analysis of folate compounds in the serosal compartment after a 60 min incubation with folate in the mucosal medium in sodium phosohate buffer indicated that metabolism of folate to 5-methyltetrahydrofolate was extensive at pH 6.0 and negligible at pH 7.5. The percent conversion of folate to 5-methyltetrahydrofolate at pH 6.0 was reduced by increasing the concentration of folate in the mucosal medium, thus indicating saturation of the reduction and methylation process. These findings indicate that folate transport in rat jejunum occurs by an energy-dependent, carried-mediated system and that both folate transport and intestinal conversion of folate to 5-methyltetrahydrofolate are pH-dependent.

Animals↗
PubMed1978

Eosinophilic esophagitis in a patient with vigorous achalasia.

A patient with vigorous achalasia is presented who had marked smooth muscle hypertrophy and eosinophilic infiltration of the esophagus identical to that seen in patients with eosinophilic gastroenteritis. Eosinophilic infiltration of the esophagus probably represents a variant of the eosinophilic gastroenteritis syndrome and may predispose to an esophageal motor disorder.

Adult↗