PubMed HealthSearch

Biomedical subjects

V I Mathan

Publications and source records attributed to V I Mathan.

At least 19 recordsLinked to original sources

Analysis of the binding of polymyxin B to endotoxic lipid A and core glycolipid using a fluorescent displacement probe.

Dansylcadaverine, a cationic fluorescent probe binds to bacterial lipopolysaccharide and lipid A, and is displaced competitively by other compounds which possess affinity toward endotoxins. The binding parameters of dansylcadaverine for lipid A were determined by Scatchard analysis to be two apparently equivalent sites with apparent dissociation constants (Kd) ranging between 16 microM to 26 microM, while that obtained for core glycolipid from Salmonella minnesota Re595 yielded a Kd of 22 microM to 28 microM with three binding sites. The Kd of polymyxin B for lipid A was computed from dansylcadaverine displacement by the method of Horovitz and Levitzki (Horovitz, A., and Levitzki, A. (1987) Proc. Natl. Acad. Sci. USA 84, 6654-6658). The applicability of this method for analyzing fluorescence data was validated by comparing the Kds of melittin for lipid A obtained by direct Scatchard analysis, and by the Horovitz-Levitzki method. The displacement of dansylcadaverine from lipid A by polymyxin B was distinctly biphasic with Kds for polymyxin B-lipid A interactions corresponding to 0.4 microM and 1.5 microM, probably resulting as a consequence of lipid A being a mixture of mono- and di-phosphoryl species. This was not observed with core glycolipid, for which the Kd for polymyxin was estimated to range from 1.1 microM to 5.8 microM. The use of dansylcadaverine as a displacement probe offers a novel and convenient method of quantitating the interactions of a wide variety of substances with lipid A.

Binding, Competitive

Interaction of melittin with endotoxic lipid A.

Several amphipathic and cationic substances are known to bind lipid A, the toxic component of bacterial lipopolysaccharides. In this report, we have characterized, by fluorescence methods, the interaction of melittin, an amphipathic and basic 26-residue polypeptide isolated from bee venom, with lipid A. The stoichiometry of the complex appears to be two molecules of melittin to one of lipid A with a dissociation constant of 2.5 x 10(-6) M. The binding of melittin not only modifies the endotoxic properties of lipid A in a number of biological assays, but also results in abrogation of the hemolytic activity of melittin. A model of the complex is proposed based on the known structures of lipid A and melittin, and the observed stoichiometry of binding.

Animals

Effect of base precursors on water and electrolyte transport during oral hydration solution perfusion in secreting rat intestine.

In situ steady-state, single-pass small intestine perfusions in rats were carried out to compare the effect of the bicarbonate and citrate World Health Organization oral rehydration solutions and a base precursor-free solution on intestinal water and electrolyte transport after inducing intestinal secretion with purified heat-stable Escherichia coli enterotoxin. When toxin was not perfused, the rates of water, sodium, and bicarbonate absorption were significantly greater from the bicarbonate-containing solution than from the citrate or base precursor-free solutions. Chloride absorption was greater from the base precursor-free solution, but this might reflect the higher chloride concentration of the perfusate. When toxin was perfused, there was no significant difference among the solutions in the rates of water, potassium, or chloride absorption. Sodium absorption occurred at significantly greater rates from both the bicarbonate and the base precursor-free solutions than from the citrate solution. Base precursor-containing solutions may not provide any advantage over a base precursor-free solution in stimulating water and sodium absorption in 5'-cyclic guanosine monophosphate mediated acute diarrhea.

Administration, Oral

The relationship of microbial pathogens to acute infectious diarrhoea of childhood.

Bacterial, viral and parasitic enteric pathogens were detected in 692 of 916 children below 36 months of age with acute diarrhoea and in 289 of 587 matched controls. The rates of identification of only four groups of pathogens, rotavirus, Shigellae, Salmonella typhimurium and enterotoxigenic E. coli, were significantly higher in the patients. The prevalence of a variety of other enteric pathogens was similar in controls of patients. Shigellosis had a characteristic clinical profile but none of the other agents could be suspected on clinical grounds. The high prevalence of pathogens in controls suggested that the population may be partially protected against a variety of enteric pathogens and that final common pathways leading to diarrhoea may be activated by changes in the microbial ecology of the gut lumen.

Acute Disease

Tropical sprue.

Explore the source record for details and available documents.

Animals

Evaluation of the efficacy of oral rehydration solutions using human whole gut perfusion.

Whole gut perfusion in humans was used to compare the effect on intestinal water and electrolyte transport of the World Health Organisation oral rehydration solution (solution II, composition in mmol/l: glucose 111, sodium 90, bicarbonate 30, potassium 20; 308 mOsm/kg); a hypertonic commercial oral rehydration solution (solution III, glucose 188, sodium 50, bicarbonate 20, potassium 20 mmol/l; 335 mOsm/kg); and three experimental bicarbonate free, hypotonic oral rehydration solutions: solution IV (glucose 111, sodium 60, potassium 20 mmol/l; 260 mOsm/kg), solution V (glucose 80, sodium 60, potassium 20 mmol/l; 219 mOsm/kg), and solution VI (glucose 80, sodium 30, potassium 20 mmol/l; 177 mOsm/kg). Perfusion of the intestine with a standard cleansing solution (solution I, sodium 125, potassium 10, bicarbonate 20, sulphate 40, mannitol 80 mmol/l; 275 mOsm/kg) confirmed published data on minimal water and sodium absorption. Experimental solution VI produced maximum water absorption (mean (SE) +1660.0 (29.8) ml/h) significantly greater than solution II (+1195.3 (79.5) ml/h), III (+534.7 (140.3) ml/h), IV (+1498.0 (42.7) ml/h), and V (+1327.7 (24.4) ml/h; p less than 0.05). Sodium absorption was significantly greater with solution II (+97.4 (7.9) mmol/h) compared to VI (+43.3 (7.8) mmol/h; p less than 0.01) but not compared to IV (+67.2 (13.0) mmol/h). A hypotonic oral rehydration solution such as solution VI may provide optimal replacement treatment for patients with acute diarrhoea.

Adult

Jejunal and ileal glucose-stimulated water and sodium absorption in tropical enteropathy: implications for oral rehydration therapy.

Intestinal glucose and water absorption in response to glucose has been studied in tropical enteropathy with a view to determine the optimum glucose concentration in oral rehydration solutions for use in the tropics. Maximum jejunal water and sodium absorption occurred from an 80-mM glucose-sodium chloride solution (-285.7 +/- 46.0 ml/30 cm/h and -31.8 +/- 3.8 mM/30 cm/h, respectively) during in vivo steady-state jejunal perfusion. At perfusate glucose concentrations greater than 250 mM, however, jejunal water and sodium secretion occurred. In the ileum, maximum glucose-stimulated water absorption (-91.1 +/- 27.1 ml/30 cm/h) was significantly less than in the jejunum. Glucose absorption demonstrated saturation kinetics in both the jejunum and ileum. The half-saturation concentration was higher in the jejunum (167 mM) compared to the ileum (28 mM). This study suggests that the optimal glucose concentration for oral rehydration solutions used in the tropics should be 80 mM, as lower and higher concentrations result in diminished jejunal water absorption.

Adult

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

Diagnosis of Strongyloides and hookworm infections: comparison of faecal and duodenal fluid microscopy.

Faecal microscopical diagnosis of Strongyloides and hookworm infections is insensitive. We have therefore compared duodenal fluid and faecal microscopy for detection of these parasites in a group of 292 patients being investigated for gastrointestinal symptoms who were examined by both techniques. Thirty-three of these patients (8%) were infected with Strongyloides stercoralis and 88 (30%) had hookworm infections. Microscopical examination of up to 3 faecal specimens detected only 33% and 65% of patients with Strongyloides and hookworm infections, respectively. Microscopical examination of a single specimen of duodenal fluid was more sensitive for detection of strongyloidiasis, identifying 76% of patients; the parasite was found exclusively in duodenal fluid (and not in faeces) in 67% of patients. For hookworm, the diagnostic sensitivity was similar with both techniques but duodenal fluid microscopy detected some patients (35%) who had not been identified by faecal microscopy. This study confirms previous work indicating the insensitivity of faecal microscopy in these infections and emphasizes the need to consider routine examination of duodenal fluid to exclude chronic strongyloidiasis. This may have particular relevance for south-east Asian war veterans and immunocompromised patients.

Ancylostomatoidea