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Biomedical subjects

J F Gregory

Publications and source records attributed to J F Gregory.

At least 73 records · Page 4Linked to original sources

Metabolic utilization of pyridoxine-beta-glucoside in rats: influence of vitamin B-6 status and route of administration.

[3H]5'-O-(beta-D-glucopyranosyl) pyridoxine (PN-glucoside) and [14C]pyridoxine (PN) were administered orally or intraperitoneally to vitamin B-6-adequate or -deficient rats. Analysis of intestinal contents and feces indicated effective intestinal absorption of PN-glucoside relative to PN. There was greater retention of 14C than 3H in the liver and carcass regardless of the route of administration of the radiolabeled vitamins. There was no major difference in the relative distribution of 3H and 14C among the vitamin B-6 metabolites in the liver between the treatment groups, and no [3H]PN-glucoside was detected in any of the livers. For all groups, the majority of the 3H administered was detected in the urine within 24 h. Less excretion of both 3H and 14C in the urine was observed for the deficient rats. There was no major difference in the relative proportion of urinary [3H]PN-glucoside or [3H]4-PA between rats fed or injected with the radiolabeled vitamins. These results indicate that vitamin B-6 status influences the clearance of metabolites derived from PN and PN-glucoside, as well as the clearance of intact PN-glucoside. Vitamin B-6 status, however, has little or no effect on the utilization of PN-glucoside. This study also suggests that the intestine is the primary site of the limited conversion of PN-glucoside to biologically active PN in the rat.

Administration, Oral↗

Incomplete utilization of pyridoxine-beta-glucoside as vitamin B-6 in the rat.

This research was conducted to determine the bioavailability of 5'-O-(beta-D-glucopyranosyl) pyridoxine (PN-glucoside) during chronic administration in a depletion-repletion bioassay. PN-glucoside was found previously to constitute a major portion of the total vitamin B-6 in many foods of plant origin. Following a 14-d depletion period, rats were fed diets containing graded levels of either free pyridoxine (PN) or PN-glucoside for 17 d. Slope ratio analysis of dose-response curves, on the basis of growth and plasma pyridoxal 5-phosphate (PLP) concentration, indicated 10-34% utilization of PN-glucoside relative to the molar response to PN. Erythrocyte aspartate amino-transferase (AspAT) activity and urinary 4-pyridoxic acid concentration were lower and the stimulation of AspAT activity by exogenous PLP was greater for rats fed PN-glucoside than for those fed PN, which indicated reduced vitamin B-6 nutriture in response to PN-glucoside. A constant 7-9% of the ingested PN-glucoside was detected in urine in intact form at all dosage levels. These results provide further evidence of incomplete bioavailability of PN-glucoside and indicate that its extent of utilization is not influenced by its level of dietary intake.

Administration, Oral↗

Comparison of pteroylpolyglutamate hydrolase (folate conjugase) from porcine and human intestinal brush border membrane.

1. A comparative study of pteroylpolygluatamte hydrolase (folate conjugase) of brush border membrane vesicles from human and porcine intestine was conducted. 2. The enrichment of conjugase activity during membrane isolation was 5-fold greater for the human than the pig. 3. Porcine and human conjugases exhibited similar Km values and could completely hydrolyze pteroyltriglutamate (PteGlu3) to PteGlu1 via an exohydrolytic process. 4. Pteroic acid, PteGlu1 and anionic polysaccharides did not inhibit human or porcine conjugase. 5. Apparent mol. wts for detergent-enzyme complexes were 237,000 (pig) and greater than 500,000 (human). 6. These results indicate similar kinetic properties and mode of action but differences in physical behavior between the intestinal brush border folate conjugases of human and pig.

Animals↗

Dosage form and formulation effects on the bioavailability of vitamin E, riboflavin, and vitamin B-6 from multivitamin preparations.

The effects of formulation factors and pharmaceutical dosage form on the bioavailability of RRR-alpha-tocopherol (d-alpha-tocopherol), riboflavin, and pyridoxine hydrochloride were studied after administration of two capsule formulations and a tablet to 12 normal humans. Absorption of RRR-alpha-tocopherol was increased from the Aquabiosorb soft elastic gelatin (SEG) capsule formulation compared with the modified standard-SEG capsule and the commercial tablet. There were no significant differences in bioavailability of riboflavin and pyridoxine hydrochloride between the SEG formulation and the tablet albeit a trend toward consistent absorption was seen from the SEG formulation. The modified-SEG formulation exhibited significantly lower bioavailability for these water-soluble vitamins. The enhanced bioavailability of vitamin E and the trend towards faster and more consistent absorption of riboflavin and vitamin B-6 from the SEG formulation may be related to the surfactant vehicle employed and the attendant wetting properties. The results also suggest ethnic differences in vitamin bioavailability.

Adult↗

Determination of folate bioavailability with a rat bioassay.

Variations of a recently proposed rat bioassay were examined and applied to the measurement of biologically available folate. The concentration of hepatic folate was found to be inconsistent as a response indicator, although fasting levels of plasma folate accurately reflected available dietary folate. Studies involving the control of coprophagy suggested that fecal folate significantly contributes to the folate status of the rat. Bioassays employing multiple dietary levels of dried orange juice solids or blanched cabbage without control of coprophagy were conducted to determined available folate by slope-ratio methods. The apparent bioavailability of endogenous folate in the dried orange juice and cabbage was 146 and 68%, respectively, relative to folic acid. The presence of dried orange juice solids or cabbage did not inhibit the utilization of folate pentaglutamate added to the diets. These results illustrate the usefulness and several limitations of the rat bioassay for evaluating the bioavailability of folate. However, the appropriateness of the rat as a model of human folate digestion and absorption requires further investigation.

Animals↗

Phrasing in the speech and reading of the hearing impaired.

The study reported here explored a partial explanation for the fourth-grade "bottleneck" in literacy advancement by hearing-impaired students. Speech samples from 21 deaf subjects were rated for degree of evident phrasal quality. Likewise, reading comprehension scores for each student were obtained under four reading conditions: reading in whole sentences, in phrases, in fragmented word groups, and in single words. Degree of rated speech phrasality was found to relate significantly and positively to correct recall answers to questions based upon silent reading of passages typed in meaningful word groups (but not when the passages were typed in whole sentences, fragmented word groups, or in single words). The results were taken to suggest that--whereas staccato-speaking deaf students may lack a sense of the phrase altogether--phrasal-speaking deaf youngsters fail to independently apply their phrase sense in the normal reading situation. Thus, both types of deaf youngsters have difficulty affecting the transition to phrase reading that is common for hearing students at or about the fourth-grade level. Finally, I argue that this phrase sense can be instilled in hearing-impaired students and that they can be trained to use it in reading.

Adolescent↗

Efficacy of the rat bioassay for the determination of biologically available vitamin B-6.

Research was conducted to evaluate the merits of rat bioassays in studies concerning the bioavailability of vitamin B-6. A protocol was devised, which included pair-feeding and prevention of coprophagy. Plasma pyridoxal 5'-phosphate (PLP) was measured by a rapid chromatographic method as an indicator of vitamin B-6 status. Pyridoxamine and pyridoxal exhibited 70% molar activity relative to pyridoxine at suboptimal dietary levels. Selected foods (spinach, cornmeal and potato) were evaluated at three dietary levels with this protocol. Analysis of dose-response curves (dietary vitamin B-6 vs. plasma PLP) by slope-ratio methods yielded imprecise estimates of the relative vitamin B-6 bioavailability. This low precision, in addition to the potential for interference by direct absorption of B-6 vitamers synthesized by intestinal microflora, indicates the need for improved methods for measurement of biologically available vitamin B-6. It was concluded that rat bioassay methods, even as modified here, may be frequently unsuitable for use in studies of vitamin B-6 bioavailability. Results presented provide further support for the use of plasma PLP as an indicator of vitamin B-6 nutriture.

Animals↗

Experimental efficacy of apalcillin and cefpiramide compared with that of six other antipseudomonal agents in Pseudomonas aeruginosa burn infections.

The therapeutic efficacy of cefpiramide and apalcillin was evaluated and compared with that of six other antipseudomonal beta-lactam antibiotics in an experimental mouse burn infection due to Pseudomonas aeruginosa. Both cefpiramide and apalcillin were as potent as cefsulodin and more potent than carbenicillin, cefotaxime, cefoperazone, piperacillin and gentamicin in protecting the infected mice from fatal bacteraemia and in eradicating Ps. aeruginosa from the infected site.

Ampicillin↗

A descriptive analysis of high school seniors with speech disabilities.

Of over 26,000 high-school seniors for whom survey data from the recent High School and Beyond study were complete, 278 identified themselves as having speech disabilities. The data on these latter students were compared to those on their nonimpaired peers with regard to demographic variables and measures of achievement, personal characteristics, and relationship to school and work. These orally handicapped pupils tended to be older, more often from linguistic minority groups, and tended to present more additional handicapping conditions. The data also showed the impaired group at a disadvantage regarding achievement, self-image, motivation, and career aspirations. Some possibilities for ameliorating these conditions are suggested.

Achievement↗

Effect of dietary selenium on the metabolism of aflatoxin B1 in turkeys.

To investigate the biochemical mechanism of the previously reported protective effect of dietary selenium against aflatoxin toxicity, the hepatic metabolism of aflatoxin B1 in turkey poults was examined at various dietary selenium concentrations. Diets were supplemented with 0.2, 2.0 or 4.0 ppm selenium (as sodium selenite) and 500 ng aflatoxin B1/g diet in an 18-day trial. Free and conjugated aflatoxin and metabolites were quantified using high-performance liquid chromatography. The proportion of liver aflatoxins in conjugated forms increased and the ratio of free aflatoxin B1/M1 decreased with increasing dietary selenium concentrations. These in vivo results provide evidence of selenium-induced enhancement of aflatoxin detoxification processes. In a similar experiment using 2.0 ppm selenium and 750 ng aflatoxin B1/g diet, the concentration of hepatic reduced glutathione, cytochrome P-450 and the activity of enzymes involved in the metabolism of aflatoxin B1 and glutathione were determined. Although the selenium supplement increased glutathione peroxidase activity, dietary selenium had no effect on reduced glutathione or cytochrome P-450 concentrations or on the activities of glutathione transferase E, glucuronyl transferase and cytochrome c reductase. These data indicate that the protective action of selenium is not mediated by an increase in glutathione availability for aflatoxin conjugation or by effects on the activities of these enzymes as measured in vitro.

Aflatoxin B1↗

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↗

Fluorometric determination of folacin in biological materials using high performance liquid chromatography.

A procedure was developed for the quantitation of the major folacin compounds present in foods and other biological materials. Extraction conditions were selected to provide conversion of 10-formyltetrahydrofolic acid (10-HCO-H4folic acid) to 5-HCO-H4folic acid. Polyglutamyl folates were deconjugated with hog kidney conjugase. The resulting folacin monoglutamates were separated by reverse-phase high performance liquid chromatography after extract purification on an anion exchange column. Detection of H4folic acid and its substituted derivatives was performed by monitoring the native fluorescence of the reduced folates in the acidic mobile phase. Folic acid, H2folic acid and also H4folic acid were measured fluorometrically by using an oxidative postcolumn derivatization system in series with the first fluorometer. Detection limits ranged from 0.03 to 2.3 pmol/100 microliters injection for the various folates. The validity of the method was supported by recovery and fluorescence spectral studies and by comparison with Lactobacillus casei assays for a variety of samples. Analysis of rat liver following a single pulse dose of 3H-labeled folic acid indicated large differences between the patterns of radiolabeled and endogenous folates.

Animals↗

Metabolite distribution and rate of residue clearance in turkeys fed a diet containing aflatoxin B1.

The retention of aflatoxin residues in tissues of turkey poults fed a diet containing aflatoxin B1 (500 ppb) for 18 days was determined. Free and conjugated aflatoxin metabolites were quantified using high-pressure liquid chromatography. Aflatoxin residue levels were greater in liver than muscle tissues, although all levels were low (range 0.01-1.19 ng/g tissue). Free and conjugated aflatoxins B1 and M1, a metabolite of B1, were the principal tissue residues. Other metabolites investigated included aflatoxicol, which was detected in certain samples, and aflatoxin Q1 which was not detected. Conjugated aflatoxins, hydrolysed and extracted from the aqueous tissue fractions, comprised 55-91% of the total detected aflatoxin residues. All aflatoxin residues were rapidly cleared following discontinuation of the dietary aflatoxin B1 (half-life 1.4 days for total aflatoxin clearance from liver). These results provide further evidence that tissues from animals maintained on diets containing aflatoxins do not provide a major source of aflatoxins when consumed by man.

Aflatoxin B1↗

Effects of food composition on the bioavailability of vitamin B-6 in the rat.

The effects of food composition and thermal processing on the relative bioavailability of vitamin B-6 in beef, spinach, potato, and cornmeal were assessed by a series of rat bioassays. The protein content of the basal diets was varied from 5 to 50%. Within each protein subgroup, graded levels of pyridoxine (PN) were added to basal diets to obtain standard PN dose-response curves. Poor correlation was observed between bioavailability values calculated from plasma pyridoxal 5'-phosphate (PLP) and the less specific bioassay criteria (growth and feed efficiency). Plasma PLP values indicated that: 1) the bioavailability of vitamin B-6 in beef was greater than that in cornmeal, spinach and potato; and 2) thermal processing of the tested foods or increasing dietary protein levels did not adversely affect, and often increased, the bioavailability of the vitamin. The results also showed that diet composition and food processing must be considered in evaluating the bioavailability of vitamin B-6.

Animals↗

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↗