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Biomedical subjects

V I Mathan

Publications and source records attributed to V I Mathan.

At least 91 records · Page 5Linked to original sources

Vitamin B12 synthesis by human small intestinal bacteria.

In man, physiological amounts of vitamin B12 (cyanocobalamin) are absorbed by the intrinsic factor mediated mechanism exclusively in the ileum. Human faeces contain appreciable quantities of vitamin B12 or vitamin B12-like material presumably produced by bacteria in the colon, but this is unavailable to the non-coprophagic individual. However, the human small intestine also often harbours a considerable microflora and this is even more extensive in apparently healthy southern Indian subjects. We now show that at least two groups of organisms in the small bowel, Pseudomonas and Klebsiella sp., may synthesise significant amounts of the vitamin.

Diet↗

Bacterial flora of the jejunum: a comparison of luminal aspirate and mucosal biopsy.

The aerobic and anaerobic bacterial flora grown from 40 human jejunal aspirates were compared with the flora grown from an intestinal mucosal biopsy obtained simultaneously from the same level. In four paired samples the flora was identical; in nine the flora differed by only one organism. In six pairs the flora differed by two organisms, and in 11 pairs by three or more organisms. In nine pairs the jejunal aspirate grew only one organism or was sterile, but the biopsy showed considerable numbers of organisms. In one pair the jejunal aspirate grew organisms, but there was no growth from the biopsy. It is apparent that for adequate bacteriological study of the intestine, the flora at both sites should be investigated.

Actinomycetaceae↗

A preliminary simulated iron fortification trial in South Indian preschool children.

1. The effect of fortification of food with iron to provide 10 mg elemental Fe/child per d was studied in preschool children maintained on a cereal diet, over a 5-month period. 2. The absorption of 5 mg Fe as ferrous sulphate mixed in one meal was 3.3% of the test dose and when 3.3 mg was given with each of three meals over a 2 d period the corresponding value was 4.8%. 3. The mean absorption of a test dose of ferrous ascorbate studied in twenty-four children midway through the trial was 42%. 4. The only beneficial effect of Fe fortification in this time-period in the experimental group was the prevention of the decrease in packed cell volume which occurred in the control groups.

Child, Preschool↗

WHO sponsored collaborative studies on nutritional anaemia in India. The effects of ascorbic acid and protein supplementation on the response of pregnant women to iron, pteroylglutamic acid and cyanocobalamin therapy.

1. A study was conducted in two centres in southern and northern India of the effects of the addition of ascorbic acid and protein supplements to iron, pteroyglutamic acid and cyanocobalamin, in the prophylaxis and treatment of anaemia of pregnancy. 2. A dose of 500 mg ascorbic acid/d had no beneficial effect. Women who received 15 g calcium caseinate/d showed a superior haematological response. The reasons for this are unknown, but are more likely attributable to an increased absorption of the supplemental iron than to the correction of a protein deficiency.

Anemia, Hypochromic↗

WHO sponsored collaborative studies on nutritional anaemia in India. The effect of parenteral iron administration in the control of anaemia of pregnancy.

1. The relative efficacy of oral and parenteral iron administration in the prophylaxis and treatment of Fe-deficiency anaemia of pregnancy has been studied. 2. Intravenous administration of Fe by total dose infusion of Fe dextran was not superior to oral Fe 120 mg/d, 6 d/week for 10-12 weeks. 3. Intramuscular Fe dextran, 100 mg twice per week for 10-12 weeks, produced a significantly greater rise in mean haemoglobin concentration than oral Fe therapy. 4. The superiority of intramuscular Fe as compared with intravenous Fe is probably related to the different handling of the Fe dextran by the reticulo-endothelial system. 5. In spite of the better response to intramuscular Fe dextran, it is not recommended for public health practice because of the risks associated with its use and the much higher cost of the preparation and its delivery.

Administration, Oral↗

Intestinal perfusion studies in tropical sprue. 1. Amino acid and dipeptide absorption.

Intestinal absorption of glycine 20 mmol/1, glycyl-glycine 10 mmol/1 plus L-leucine 10 mmol/1, and glycyl-L-leucine 10 mmol/1 has been studied by intestinal perfusion in 11 patients with tropical sprue and 10 control subjects. The patients with sprue had a significant reduction in the rate of absorption of glycine from a 20 mmol/1 solution, but there were no significant differences in the absorption of the other substances. The failure to demonstrate any difference in the absorption of these substances is probably related to their low concentration relative to the maximum absorptive capacity of the intestine. In both groups of subjects the kinetic advantage of glycyl-glycine absorption as compared with glycine absorption was maintained. When the dipeptides were perfused, free amino acids appeared in the perfusate presumably by "back diffusion" from the mucosal cells. In the case of glycyl-L-leucine considerably more glycine and leucine were found in the perfusate in patients with sprue than in the control subjects. There was no correlation between peptide absorption and the concentration of total glycly-glycine hydrolase and glycyl-L-leucine hydrolase, measured as combined brush border and cytosol enzymes. The concentrations of these enzymes were similar in both groups of subjects.

Amino Acids↗

Free intrinsic factor in the small intestine in man.

Human jejunal and ileal contents and ileostomy effluents were examined for the presence of free intrinsic factor. This was detected in 9 out of 10 jejunal and three out of five ileal aspirates and in one of three ileostomy effluents studied. The intrinsic factor in the ileal effluent was shown to be physiologically active. The presence of free intrinsic factor in the small intestine has considerable physiological significance in maintaining the enterophepatic circulation of vitamin B12. It would also permit the absorption of any free vitamin B12 produced by ileal bacteria.

Body Fluids↗

Pleomorphic virus-like particles in human faeces.

Pleomorphic fringed particles bearing some resemblance to orthomyxoviruses and coronaviruses were seen in 90 percent of stools from south Indian children and adults but not in stools from neonates. This finding may be related to the abnormalities of intestinal structure and function common in this region of India.

Adult↗

W.H.O. sponsored collaborative studies on nutritional anaemia in India. 1. The effects of supplemental oral iron administration to pregnant women.

A W.H.O. sponsored collaborative study of the effects of iron supplementation to pregnant women was carried out in Delhi (northern India) and Vellore (southern India). Supplementation was given under supervision from the 26th to the 36th or 38th week of pregnancy. A control group received only placebo; one group received vitamin B12 and folic acid alone; four groups received vitamin B12, folate and a daily iron supplement ranging from 30 to 240 mg of elemental iron as ferrous fumerate, and one further group received 120 mg of iron without B12 or folate. Groups receiving no iron showed a fall in mean stet concentration. Those receiving iron showed a rise in haemoglobin, the best results being in the groups receiving 120 and 240 mg of iron together with vitamin B12 and folate. Even in these groups however there was still a high prevalence of anaemia and iron deficiency at the end of the trial period. Iron alone did not produce as good results as iron plus vitamin B12 and folate. The supplementation had no detectable effect on the birth weight of the children, nor on the haemoglobin concentration of the infants at three months of age. The daily absorption of iron in the pregnant women, as judged from the increase in haemoglobin mass, was not as satisfactory as expected. Possible reasons for this are discussed. It is concluded that to provide these women with adequate iron a daily oral supplementation of 120 mg of elemental iron or more is needed. This can only be achieved by medicinal means. Before supplementation can be recommended on a public health scale, further information regarding the cost and expected benefits of such measures must be obtained.

Administration, Oral↗

An electron-microscopic study of jejunal mucosal morphology in control subjects and in patients with tropical sprue in southern India.

The ultrastructure of the jejunal mucosa obtained by peroral biopsy from 7 control subjects and 12 patients with tropical sprue was studied. Compared with biopsies from control subjects in temperature zones, southern Indian control subjects showed minimal increase in lysosomes in surface epithelial cells, an occasional dark-staining degenerating epithelial cell in the upper two-thirds of villi, and an increase in cellular infiltration of surface epithelium and lamina propria. The jejunal epithelial cells of tropical sprue patients had abnormal microvilli, marked increase in lysosomes, increase in intracellular fat, and degenerative changes in rough endoplasmic reticulum and mitochondria. Two types of degenerating epithelial cells, designated pale and dark based on their staining quality, were seen in the villi. Pale staining degenerating cells were also seen in the crypts. The basement membrane region showed an amorphous deposit with many collagen fibers and fat droplets. The epithelial layer and lamina propria showed increased cellular infiltration. In one biopsy from a patient with sprue, particles of possible viral origin were seen.

Adolescent↗

Kinetics of the attachment of intrinsic factor-bound cobamides to ileal receptors.

To determine whether the molecular configuration of vitamin B(12) influences the attachment of intrinsic factor-vitamin B(12) complex to ileal microvillous membrane receptor sites, we have examined the kinetics of uptake of intrinsic factor-bound cyanocobalamin by brush borders and microvillous membranes isolated from guinea pig ileum, and have compared this uptake with that of intrinsic factor alone and with that of intrinsic factor complexed with various analogs of cyanocobalamin. We first studied the kinetics of binding of cyanocobalamin and other cobamides to human gastric intrinsic factor. The binding of cyanocobalamin showed saturation kinetics and, at relatively high concentrations of cyanocobalamin, a Scatchard plot of binding was linear. The dissociation constant for the intrinsic factor-cyanocobalamin complex was 0.066 nM. When the binding of various vitamin B(12) analogs to intrinsic factor was determined by competition experiments, the analogs could be separated into two categories: those with affinities similar to that of cyanocobalamin and those with affinities much lower than that of cyanocobalamin. The affinity of cyanocobalamin for intrinsic factor was not altered by various substitutions at the -CN position, while removal of a single amido group on the corrin ring of substitution of the dimethylbenzimidazole base greatly reduced affinity. Removal of the base totally abolished binding. These findings, confirming those reported by others, are consistent with the concept that the cyanocobalamin molecule fits into a "pocket" in the intrinsic factor molecule, with the nucleotide base facing inward and the -CN side of the planar corrin ring facing outward. We then investigated the attachment of intrinsic factor-bound cyanocobalamin to ileal receptor. Attachment to microvillous membranes showed saturation kinetics with a dissociation constant of 0.25 nM. Attachment was rapid and was 70% complete within 5 min; the second-order rate constant for attachment was 1.3 x 10(6) M(-1) s(-1). The half-time for dissociation of intrinsic factor-bound cyanocobalamin from the ileal receptor was approximately 35 min. Free intrinsic factor inhibited the attachment of intrinsic factor-bound cyanocobalamin, but the rate of attachment of free intrinsic factor was slower than that of intrinsic factor bound to cyanocobalamin. When intrinsic factor was complexed with various analogs of cyanocobalamin, the affinities of these complexes for ileal microvillous membranes were similar to that of intrinsic factor-bound cyanocobalamin. These findings suggest that the molecular configuration of vitamin B(12) is not a major determinant in the interaction between intrinsic factor-bound vitamin B(12) and its ileal receptor site.

Animals↗

Iron, folate, and vitamin B 12 nutrition in pregnancy: a study of 1000 women from southern India.

As part of a WHO collaborative programme the prevalence of anaemia was studied and the serum concentrations of iron, folate, and vitamin B(12) were measured in 1 000 pregnant women from southern India. The results of the study show a high prevalence of anaemia, resulting from iron and folate deficiency with iron deficiency predominating. Interrelationships between these nutrients and their effect on pregnancy and the fetus were investigated. The results indicate that, in comparison with populations in developed countries, there was a high prevalence of iron and vitamin B(12) deficiency in the community, but the state of folate nutrition was similar to that found elsewhere.

Adolescent↗