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Biomedical subjects

J J Cerda

Publications and source records attributed to J J Cerda.

At least 55 records · Page 3Linked to original sources

Clinical studies of intestinal folate conjugases.

Clinical differences between the two human intestinal mucosal folate conjugases were assessed by measurement of their activities in normal individuals and in patients with chronic diarrhea of differing causes. Intracellular folate conjugase (ICFC) was 15-fold more active than brush border folate conjugase (BBFC) in jejunal mucosa from seven obese patients undergoing elective gastric bypass surgery. The activity of ICFC was similar among normal volunteers and patients with diarrhea of unknown origin (DUO), gluten-sensitive enteropathy (GSE), inflammatory bowel disease (IBD), and the short bowel syndrome (IBD-SBS). By contrast, BBFC, sucrase, and lactase were decreased significantly in GSE, and BBFC was increased in IBD-SBS. The activity of BBFC correlated with lactase and with sucrase in the normal subjects and in patients with DUO, whereas no correlations were found with the activity of ICFC in any group. Our clinical studies confirm that ICFC and BBFC are different enzymes. ICFC is not affected by intestinal disease, whereas the activity of jejunal BBFC, like that of other brush border enzymes, is decreased by mucosal injury and is also capable of adapting to distal small intestinal disease or surgical resection.

Adult↗

Bacterial endotoxin retention by inline intravenous filters.

Filters used in i.v. administration sets were tested for their ability to retain bacterial endotoxins for up to 96 hours of continuous infusion. Inline filters composed of cellulose ester, polyacrylate, polypropylene, polyethylene, or Posidyne Nylon 66 were used during continuous infusion of 5% dextrose injection at 83 mL/hr. One milliliter of inoculum containing 10(8) Escherichia coli was injected through a port upstream from the filter. A bacterial filter was used to monitor the sterility of effluent from the inline filters. The effluent was tested with limulus amebocyte lysate (LAL) that could detect endotoxin concentrations greater than 50 pg/mL. A control solution was monitored for viability of the bacteria throughout the course of the study, and positive endotoxin controls were used to confirm the sensitivity of the LAL. Samples of effluent were tested at 0, 4, 19, 24, 48, 72, and 96 hours. Effluent from all filters was sterile throughout the study. LAL assay indicated that only the effluent from filters containing Posidyne Nylon 66 was free of endotoxins for 96 hours. Effluent from the other filters contained endotoxins immediately after injection of the E. coli. Of the inline filters tested, only the one composed of Posidyne Nylon 66 was able to retain E. coli endotoxin for 96 hours. Further study is needed with E. coli and other microorganisms that are likely contaminants of i.v. infusions.

Drug Contamination↗

Hypocholesterolemic agents: a comparison of the relative effectiveness of cholestyramine and pectin in rats.

Studies were carried out to evaluate the comparative effectiveness of cholestyramine and pectin as hypocholesterolemic agents. Circulating levels of serum cholesterol and lipoprotein-associated cholesterol were measured in rats fed high cholesterol diet supplemented with either cholestyramine or pectin. When compared with controls, a significant decrease in the level of total cholesterol was observed in rats fed either cholestyramine or pectin (p less than 0.001, 43% reduction in cholesterol, and p less than 0.04, 25% reduction in cholesterol, respectively) and this was due exclusively to the lowering of low density lipoprotein. Further statistical evaluation of data revealed no significant difference between the cholesterol levels of rats fed either cholestyramine or pectin (p greater than 0.07). The data acquired in this study suggest that both cholestyramine and pectin are comparable and effective hypocholesterolemic agents and the observed hypocholesterolemic effect of these agents is mediated through lowering of cholesterol associated with the low density lipoprotein.

Animals↗

Urinary 4-pyridoxic acid excretion in 24-hour versus random urine samples as a measurement of vitamin B6 status in humans.

Urinary excretion of 4-pyridoxic acid (4PA) in 19 men (n = 5) and women (n = 14) was measured to evaluate the validity of determining the 4PA/creatinine ratio in random urine samples as an alternative to total 24-h 4PA excretion in assessing vitamin B6 nutritional status. The relationships among dietary vitamin B6 intake, 4PA excretion, plasma pyridoxal 5'-phosphate levels, and erythrocyte aspartate aminotransferase activity and in vitro stimulation by added plasma pyridoxal 5'-phosphate were examined. The subjects consumed all meals for 3 days in a metabolic unit, and protein intake was kept constant. Plasma pyridoxal 5'-phosphate concentration was positively correlated with vitamin B6 intake of the previous day (r = 0.61, p less than 0.01). There was a positive correlation (r = 0.59, p less than 0.01) between total 4PA and 4PA/creatinine in the 24-h urine samples. No difference (p greater than 0.05) in 4PA/creatinine between the 24-h samples and either morning or afternoon random samples taken the next day was found. These findings support the use of the 4PA/creatinine ratio in random urine samples as an alternative to 24-h urinary 4PA excretion.

Adolescent↗

Effect of age on poly- and monoglutamyl folacin absorption in human subjects.

Intestinal folacin absorption and mucosal conjugase activities were assessed in healthy male elderly (65-83 years) and young (20-29 years) human subjects. Luminal disappearance as measured simultaneously from the perfused jejunum of 3 mumol of both [3H]pteroylmonoglutamate [( 3H]PG-1) and pteroyl-[14C]glutamyl-hexaglutamate [( 14C]PG-7) as well as the urinary recovery of each isotope and mucosal conjugase activities were compared. Luminal disappearance of either [3H]PG-1 or [14C]PG-7 was not different for the two age groups (P greater than 0.05). The average (mean +/- SD) disappearance of [3H]PG-1 was 63 +/- 12% in the elderly and 67 +/- 6% in the young groups. In contrast, the disappearance of [14C]PG-7 averaged 51 +/- 6% in the elderly and 48 +/- 3% in the young group. Urinary recovery (percent in 48 hours) was not different for either isotope when the two age groups were compared (P greater than 0.05). The urinary recovery of 3H averaged 60 +/- 21% in the elderly and 59 +/- 13% in the young in contrast to 35 +/- 22% and 35 +/- 7% for 14C recovery in the elderly and young groups, respectively. Folacin conjugase activities measured at pH 6.5 and at pH 4.5 were not different between the groups (P greater than 0.05). The findings indicate that intestinal absorption of folacin and activity of folacin conjugases are not affected by the aging process.

Adult↗

Effect of dietary pectin on iron absorption and turnover in the rat.

The influence of dietary pectin on iron absorption and retention was studied in rats. Basal diet with low and normal iron levels were fed with and without addition of 2% citrus pectin. After 40 days rats were fasted for 24 hours and were given 59Fe in dilute HCl with or without 2% pectin by gavage. Whole-body counting techniques were employed to monitor 59Fe absorption and turnover. Rats maintained on low iron diet absorbed and retained a much higher proportion of 59Fe than rats maintained on normal level of iron. Dietary pectin at the level fed in this study had no influence on iron uptake and/or turnover in rats.

Absorption↗

Effect of dietary fiber on absorption of B-6 vitamers in a rat jejunal perfusion study.

Previous research has indicated that dietary fiber may affect the absorption and utilization of certain nutrients. To determine the effect of certain fiber materials on the absorption of B-6 vitamers, jejunal segments from young male adult rats were perfused in situ with a control solution containing 0.02 mM pyridoxine (PN), 0.02 mM pyridoxal (PL), and 0.02 mM pyridoxamine (PM), followed by a test solution containing the same vitamin B-6 mixture and one of five fiber-rich test materials (cellulose, pectin, lignin, homogenized fresh carrot, or carrot homogenized after 10 min boiling) added at a concentration of 1-3%. The mean absorption rates of PL, PN, and PM from the control solution were, respectively, 3.66 +/- 0.23, 2.06 +/- 0.23, and 1.74 +/- 0.37 nmole/min/20 cm jejunal segment. There were no significant differences between the absorption rates of B-6 vitamers from control and test solutions containing cellulose, pectin, and lignin. The absorption rates of PM and PL were significantly depressed (P less than 0.05 and P less than 0.01, respectively) by the presence of fresh or cooked carrot. The absorption rate of PN in presence of cooked carrot was also decreased relative to the control value but the difference was only marginally significant (P less than 0.10). When the concentration of fresh carrot in the test solution was increased to 10% by weight and the perfusion rate was decreased from 1.91 to 0.49 ml/min in a second perfusion experiment, there was a significant increase in variability and the differences between absorption rates of the B-6 vitamers in control and test solutions were not statistically significant. The limited evidence of adverse effect of carrot on absorption of vitamin B-6 suggested the need for further clarification of the influence of dietary fiber in an unrefined state on the bioavailability of vitamin B-6.

Animals↗

Nutritional aspects of malabsorption syndromes.

Therapy of the malabsorption syndrome centers on adequate diagnosis of the underlying pathology, with vigorous therapeutic efforts directed at correcting this and thereby preventing ongoing losses of nutrients. Dietary therapy includes a high-protein, high-calorie, low-fat diet often supplemented with MCTs in an effort to minimize steatorrhea. Water-soluble vitamin deficiency is rare, but supplementation with small daily doses is innocuous and probably should be prescribed. Significant fat-soluble vitamin deficiencies are seen more commonly and can be monitored by physical examination and the prothrombin time. Calcium, magnesium, and vitamin D deficiencies are more common than originally suspected. Adequate therapy requires monitoring of the serum calcium, magnesium, parathyroid hormone levels, and, optimally, 24-hour urinary collections for calcium. Supplementation of these mineral deficiencies requires ongoing close observation to prevent hypercalcemia. Iron deficiency can be easily diagnosed by available serum iron determination, and replacement with oral supplements is curative. Trace metal deficiencies occur, but our capabilities of detecting and treating them is still in its infancy. Figure 3 outlines our approach to the evaluation and treatment of the patients suspected of having the malabsorption syndrome.

Dietary Carbohydrates↗

The effect of diphenylhydantoin (phenytoin) on the sequential stages of intestinal folate absorption.

The drug diphenylhydantoin (phenytoin) (DPH) is thought to interfere with the bioavailability of dietary folate through an effect on intestinal folate deconjugation and/or monoglutamate folate transport. In order to determine whether DPH inhibition occurs in the sequential steps of folate deconjugation, uptake, or reduction-methylation, the effect of the drug on the intestinal absorption of hexaglutamate folate (PteGlu6), pteroylmonoglutamate folate (PGA), and N-5-methyltetrahydrofolate (CH3FH4) was studied. Folate absorption was directly quantified by the method of triple lumen tube perfusion in 12 subjects serving as their own controls. All 12 received PGA mixed with and without DPH (20 micrograms/ml), while 6 of the 12 subjects received hexaglutamate and 6 received reduced methylated folate with and without added DPH. With this model DPH was shown not to impair significantly folate absorption by any action upon the process of folate deconjugation, absorption, or reduction-methylation. The previously reported association between DPH intake and reduced levels of serum folate remains unexplained by these studies.

Adult↗

Giardiasis.

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Biopsy↗

Use of nutritional supplements in an ambulatory elderly population.

The use of nutritional supplements by 3,192 ambulatory elderly participants in a health screening program is described. The 2,009 women used vitamin (45.5 per cent) and mineral (22.4 per cent) products with significantly greater frequencies than did the 1,183 men (34.0 per cent and 15.0 per cent, respectively); chi-square, P less than 0.01. The most commonly used vitamin products were multiple vitamins, multiple vitamins with minerals, vitamin E, and vitamin C; for minerals, the ranking was potassium chloride, calcium salts, and ferrous sulfate. Eighty-two participants (2.5 per cent) reported the use of four or more supplements. Many older Americans are spending a great deal of money for nutritional supplements, whereas it would seem that the money could be better spent to improve the quality of their diet.

Age Factors↗

Pectin: its interaction with serum lipoproteins.

In vitro studies of interaction between grapefruit (Citrus paradisi) pectin and various human serum lipoproteins indicated that pectin interacts specifically with low-density lipoprotein. Examination of observed interaction between the pectin and low-density lipoprotein under variable experimental conditions revealed the electrostatic nature of this interaction. The results obtained from these studies suggest a possible biochemical basis by which dietary pectin may cause lowering of serum and/or tissue cholesterol levels.

Chemical Phenomena↗

Alcaptonuria and sucrase-isomaltase deficiency in three offspring of a consanguineous marriage.

Intestinal brush border membrane hydrolases and HLA lymphocyte antigens have been examined in three siblings with sucrose intolerance and alcaptonuria, and their consanguineous parents. Sucrase-isomaltase activity was absent in the three patients, and corresponded with the gel electrophoresis of SDS-solubilized brush border membranes, which failed to demonstrate the protein band normally associated with sucrase-isomaltase complex. The activities of all brush border membrane enzymes in the mother were normal, while those of the father were generally low. The use of hydrolytic capacity ratios, however, permitted the designation of both parents as heterozygotes. Significant homogentisic aciduria was found only in the three propositi, and no effect of homogentisic acid on the sucrase activities of two normal, unrelated children could be demonstrated in vitro. The HLA lymphocyte antigen profiles of all seven family members demonstrated remarkable histocompatibility in five of them.

Adolescent↗

Ultrasonographic demonstration of the pancreatic duct.

During a 4-year period, 375 patients with clinically suggestive pancreatic disease were examined with gray scale ultrasound. In 14 patients, the pancreatic duct itself was demonstrated. All of these had clinical or laboratory evidence for, and radiologically or surgically proven, pancreatic duct obstruction. Etiology of the obstruction was either tumor, chronic pancreatitis, pancreatic abscess, pseudocyst, or stricture of the duct at the papilla of Vater. Two patients had Crohn's disease of the duodenum.

Adult↗