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Biomedical subjects

C H Halsted

Publications and source records attributed to C H Halsted.

At least 73 records · Page 4Linked to original sources
PubMed1982

Folate nutrition in the elderly.

The consensus of this panel is that average dietary intake of folate in the free-living elderly population is probably adequate in most. Certainly more good data are needed; in addition, safe and reasonable dietary goals for folate intake are required. However, patients who have diseases requiring hospitalization or conditions for which institutionalization are required are obviously at greater risk. In addition, there is some evidence that the elderly poor in the US may be at greater risk of deficiency. Similarly, the evidence for folate deficiency based on blood assay data would seem to focus on the lower socioeconomic (largely Black and Hispanic) populations in addition to the hospitalized and institutionalized elderly. An additional factor in the genesis of folate deficiency among the aged is the factor of alcohol use which probably represents the single most important risk factor in folate deficiency among the elderly as well as among the nonelderly population. Although certain drugs such as anticonvulsants and sulfasalazine, may interfere with folate absorption or utilization, the number of elderly patients who are taking these drugs is relatively small and therefore this factor is not considered to be a major contributor to the problem of folate deficiency in the elderly. The question of folate malabsorption in the elderly has been examined. It is our conclusion that disease in the elderly population including gastric surgery and intestinal malabsorption, etc can certainly interfere with folate absorption but these problems are not widespread among the elderly population. There is only limited evidence that the physiological process of aging influences the intestinal absorption of folate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1981

Human jejunal brush border folate conjugase. Characteristics and inhibition by salicylazosulfapyridine.

Human jejunal brush border folate conjugase (EC 3.4.22.-) was partially purified and characterized. Three drugs known to be associated with clinical folate deficiency were tested for inhibition of the partially purified enzyme. Using jejunal mucosa from obese patients undergoing intestinal bypass surgery, brush border folate conjugase was purified 50-80-fold by centrifugation, Triton X-100 solubilization and DEAE-Sephadex and Sephacryl S-200 chromatography. Using synthetic pteroyldiglutamyl[14C]glutamate as substrate, the enzyme was found to have a pH optimum of 6.5 and an apparent Km of 1.6 micro M. Incubation of the enzyme with synthetic pteroyl[14C]glutamylhexaglutamate resulted in a spectrum of shorter-chain 14C-labeled pteroylglutamates at 60 min. Pteroyl[14C]glutamate was the major product at 120 min, with quantitative recovery of free glutamate in the incubation medium. Salicylazosulfapyridine was a competitive inhibitor of the enzyme (Ki = 0.13 mM), while ethanol, diphenylhydantoin and salicylazosulfapyridine metabolites had no effect. These data suggest that brush border folate conjugase is an exopeptidase which progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport. Inhibition of brush border folate conjugase by salicylazosulfapyridine provides a mechanism for folate malabsorption and deficiency in chronic users of this drug.

Carboxypeptidases↗
PubMed1981

Ethanol, the liver, and the gastrointestinal tract.

Ethanol is easily absorbed from the intestine and diffuses quickly throughout body water. The bulk of ethanol is metabolized in the liver, where alcohol dehydrogenase, a complex mixture of isoenzymes, oxidizes ethanol to acetaldehyde. Ethanol abuse produces functional and structural changes in the gastrointestinal tract, such as in the stomach, small intestine, liver, and pancreas. Accumulating evidence suggests direct toxicity of ethanol and possibly of acetaldehyde. Fatty liver, alcoholic hepatitis, liver cirrhosis, acute and chronic gastritis, deranged structure and function of the small intestine, acute and chronic pancreatitis, and pancreatic lithiasis are some of the sequelae of ethanol abuse. Recent investigations have enhanced our understanding of the functional and structural changes of the gastrointestinal tract produced by the abuse of ethanol.

Alcoholism↗
PubMed1981

Intestinal absorption of [3H]folic acid in the chronic alcoholic monkey.

The intestinal absorption of labeled folic acid ([3H]pteroylmonoglutamate) was determined from urinary and fecal recoveries of tritium in pairs of monkeys fed control liquid diets or diets containing 50% of energy as ethanol for a 24-mo period. Weight gain, fecal fat excretion, nitrogen balance, D-xylose absorption, serum folate levels, jejunal histology, and intestinal enzyme activities were similar in each group. Liver biopsies obtained after 12 and 24 mo of feeding demonstrated steatosis and megamitochondria in the ethanol-fed group, with decreased hepatic levels of folate at 24 mo. Intestinal malabsorption of labeled folic acid in the ethanol-fed monkeys was indicated by decreased urinary recovery of tritium but increased fecal recovery of tritium after intragastric administration of [3H]pteroylmonoglutamate. These studies suggest that folic acid malabsorption follows the chronic administration of ethanol together with a nutritious diet.

Alcoholism↗
PubMed1981

Hepatic folate metabolism in the chronic alcoholic monkey.

To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of 3H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected.

Alcoholism↗
PubMed1979

The intestinal absorption of folates.

Dietary folates, existing primarily in the form of pteorylpolyglutamates, are absorbed in the jejunum by a process involving hydrolysis and subsequent intestinal transport of pterolymonoglutamyl folate. Current evidence indicates that one (or more) intestinal mucsoal enzyme(s), termed folate conjugase, is required for the hydrolysis of pteroylpolyglutamate to pteroylmonoglutamyl folate. Unresolved controversies include the mucosal location of hydrolysis (surface versus intracellular), whether the transport of pteroylmonoglutamate is active or passive, and the relation of intestinal mucosal metabolism of pteroylmonoglutamate to its intestinal transport.

Anemia, Megaloblastic↗
PubMed1978

Availability of monoglutamyl and polyglutamyl folates in normal subjects and in patients with coeliac sprue.

Intestinal folate absorption was assessed in six normal subjects and in four patients with coeliac sprue who were studied before and after treatment by dietary gluten exclusion. Comparisons were made of the luminal disappearance from the perfused jejunum of 3H-pteroylmonoglutamate and pteroyl 14C-glutamylhexaglutamate, and of the 48-hour urinary recovery of each isotope after perfusion and a tissue saturating dose of folic acid. The labelled urinary folates consisted of folic acid, 10-formyltetrahydrofolate, and 5-methyltetrahydrofolate. In each group urinary recovery of 3H was significantly greater than that of 14C, confirming the evidence from jejunal perfusion that the availability of monoglutamyl folate is greater than that of polyglutamyl folate. According to the urinary recovery data, both folates were poorly absorbed in untreated coeliac sprue, but were normally absorbed after treatment. Assuming uniform displacement of the absorbed labelled folates by the parenteral flushing dose, the finding of greater urinary isotope recovery than of luminal folate disappearance from the perfused proximal jejunal segment suggests an adaptation of the distal small bowel for folate absorption in coeliac sprue.

Adult↗
PubMed1977

Folate conjugase: two separate activities in human jejunum.

Previous perfusion studies of the human jejunum suggested that conjugated folate is hydrolyzed on the mucosal surface. The techniques of cell fractionation and DEAE and gel chromatography led to the identification of two separate folate conjugase activities in human jejunal mucosa: one membrane-bound and concentrated in the brush border, the other soluble and intracellular. These enzyme activities exhibit different pH optima, molecular weights, and inhibition characteristics. Folate conjugase in the brush border may accomplish the initial digestion of dietary pteroylpolyglutamates.

Carboxypeptidases↗
PubMed1977

Jejunal perfusion of simple and conjugated folates in celiac sprue.

The intestinal absorption of [3H]-pteroylmonoglutamate (simple folic acid) and pteroyl-micron[14C]glutamyl-gamma-hexaglutamate ([14C]PG-7, conjugated folic acid) was assessed by the method of jejunal perfusion in five patients with proven celiac sprue who were studied after a gluten-containing or a gluten-free diet, and in nine normal subjects. The luminal disappearance of each folate was markedly impaired after exposure of the patients to dietary gluten and improved by gluten restriction, but not to within the range found in the normal subjects. The luminal disappearance of each folate was markedly impaired after exposure of the patients to dietary gluten and improved by gluten restriction, but not to within the range found in the normal subjects. In each experiment, column chromatography of the luminal aspirates revealed similar spectra of hydrolytic products of [14C]PG-7, whereas the fraction of the distal aspirate chromatogram appearing as pteroyl-micron[14C]glutamyl-gamma-monoglutamate ([14C]-PG-1) was similar in all three groups. By accounting for the variable effects of absorption on the luminal appearance of [14C]PG-1 and by correcting for mucosal hydrolysis which was not followed by release of [14C]PG-1 to the luminal contents, the calculated rate of in vivo hydrolysis of [14C]PG-7 to [14C]PG-1 was found impaired in both celiac sprue groups, with significant improvement on treatment. In mucosal biopsies from the sprue patients, the in vitro activity of folate conjugase in whole homogenates was higher and the activity of disaccharidase lower than in a group of 12 normal mucosal biopsies. These in vitro data suggest that the predominant cellular location of mucosal folate conjugase is different from that of disaccharidase, whereas comparison with the results of in vivo hydrolysis suggests that measurement of the enzyme in whole mucosal homogenates overestimates its significant digestive activity. The present studies indicate that (a) the mucosal lesion of celiac sprue significantly limits the intestinal absorption of both simple and conjugated folate, and (b) malabsorption of conjugated folate results from a combination of impaired hydrolysis and decreased mucosal uptake of hydrolytic product.

Adult↗
PubMed1976

In vitro uptake and metabolism of pteroylpolyglutamate by rat small intestine.

The digestion and cellular uptake of 14C-pteroylheptaglutamate (14C-PG-7) was studied using an isolated cell preparation from rat small intestine and by assay of folate conjugase (EC 3.4.23.10) in whole homogenates and brush border fractions of rat small intestinal mucosa. In the cell preparation, 14C-pteroylmonoglutamate (14C-PG-1), the principal degradation product of 14C-PG-7, was concentrated earlier in the cell fraction than in the extracellular fraction, while the concentrations equalized after 15 minutes. Incubation of cells with equimolar 14C-PG-7 and 3H-PG-1 was followed by a threefold greater cellular concentration of 14C-PG-1 than 3H-PG-1. In subcellular fractionation studies, folate conjugase was minimally present in the brush border relative to the supernatant fraction. These data suggest that 14C-PG-7 is transported into the epithelial cell of the intestinal mucosa prior to its hydrolysis by intracellular folate conjugase.

Animals↗