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Biomedical subjects

V I Mathan

Publications and source records attributed to V I Mathan.

At least 37 records · Page 2Linked to original sources
PubMed1995

Evaluation of a simplified HEp-2 cell adherence assay for Escherichia coli isolated from south Indian children with acute diarrhea and controls.

A simplified HEp-2 cell adhesion assay was performed with stored Escherichia coli isolates from 761 children with acute diarrhea and 531 matched controls, and the results were evaluated by means of fluorescent actin staining and hybridization with DNA probes. The prevalence rates of localized adherence and aggregative adherence were significantly higher for patients (9.9 and 7.6%, respectively) than for controls (3.7 and 3.9%, respectively).

Acute Disease↗
PubMed1994

Interaction of cationic amphiphilic drugs with lipid A: implications for development of endotoxin antagonists.

This report presents evidence for the interactions of several classes of cationic amphiphilic drugs including the phenothiazines, aminoquinolines, biguanides, and aromatic diamidines, with lipid A, the endotoxic principle of lipopolysaccharides. The interactions of the drugs were quantitatively assessed by fluorescence methods. The affinities of the drugs for lipid A parallel their endotoxin-antagonistic effects in the Limulus gelation assay. Dicationic compounds bind lipid A with greater affinity; the affinity of such molecules increases exponentially as a function of the distance between the basic moieties. The bis-amidine drug--pentamidine--examined in greater detail, binds lipid A with high affinity (apparent Kd: 0.12 microM), and LPS, probably due to simultaneous interactions of the terminal amidine groups with the anionic phosphates on lipid A. The sequestration of endotoxin by pentamidine reduces its propensity to bind to cells, and the complex exhibits attenuated toxicity in biological assays. These results have implications in the development of therapeutic strategies against endotoxin-related disease states.

Aminoquinolines↗
PubMed1994

Alteration of colonic absorption by long-chain unsaturated fatty acids. Influence of hydroxylation and degree of unsaturation.

Unabsorbed dietary unsaturated fatty acids may cause diarrhea in patients with steatorrhea, but their ability to cause colonic fluid secretion is not known. The present study investigated the effect of several dietary long-chain unsaturated fatty acids on colonic absorption and morphology in the rat colon in vivo. The fatty acids tested induced concentration-dependent net water secretion. The ability of these fatty acids to induce net water secretion varied as follows: linolenic acid (18:3) > linoleic acid (18:2), ricinoleic acid (18:1 OH) > oleic acid (18:1), palmitoleic acid (16:1). Net absorption of sodium and chloride were decreased in fatty acid perfusions. Mucosal activity of sodium potassium adenosine triphosphate and adenyl cyclase were not significantly altered by fatty acids. Epithelial cell damage was noted and correlated with the ability of the fatty acid to induce fluid secretion. Unsaturated fatty acids induce epithelial cell damage and fluid secretion in the colon, their effect being related to the degree of unsaturation.

Adenylyl Cyclases↗
PubMed1993

Enzyme-linked immunosorbent assay for quantification of anti-lipid A antibody. Enhancement of sensitivity by antigen immobilization at low pH.

An enzyme-linked immunosorbent assay (ELISA) to quantitate anti-lipid A antibodies in sera has been developed. The sensitivity of the ELISA was improved when the antigen (lipid A) was immobilized at pH 2.0, presumably by enhanced solid-phase adsorption of lipid A which is presumed to be aggregated at low pH. This was also verified by solid-phase immunoradiometry in which a four-fold improvement in the signal-to-noise ratio was observed when antigen coating was performed at pH 2.0 as compared to coating at pH 9.6. The enhanced sensitivity permitted the use of low concentrations of lipid A (10 micrograms/ml) for antigen coating of microtiter plates. The assay was able to clearly detect differences in IgG anti-lipid A levels between patients with chronic liver disease and normal controls.

Animals↗
PubMed1993

Electron microscopic study of the attachment and penetration of rabbit intestinal epithelium by Providencia alcalifaciens.

Ilea of adult rabbits with removable ileal ties (RITARD model) that developed diarrhoea and ileal loops of adult rabbits after inoculation with Providencia alcalifaciens, isolated from two patients with diarrhoea, were studied by transmission electron microscopy for enterocyte-bacterial interactions. Two modes of entry of bacteria into epithelial cells were seen: one directly by endocytosis associated with polymerization of cytoskeletal components and the other by disruption of tight junctions with entry into and proliferation in intercellular spaces.

Acute Disease↗
PubMed1993

Colonic dysfunction in acute diarrhoea: the role of luminal short chain fatty acids.

Faecal concentrations and output of short chain fatty acids (SCFA) were assessed on successive days by gas-liquid chromatography in 24 patients with acute watery diarrhoea. Absorption of water and sodium from the rectum was also measured by a dialysis technique in 17 of these patients and in nine normal subjects in the presence and absence of luminal SCFA. Faecal SCFA concentrations were low on the first day of diarrhoea (mean (SEM) 9.9 (5.8) mmol/kg) and increased to 94.8 (16.4) mmol/kg by the fifth day. Faecal output of SCFA corresponded to these figures. Net water absorption, in the absence of luminal SCFA, was stopped in patients with acute diarrhoea (-59 (81) nl/cm2/min) compared with healthy controls (+322 (63) nl/cm2/min) (p < 0.01). Luminal SCFA restored net water absorption to +184 (67) nl/cm2/min in patients with acute diarrhoea (p < 0.01). Net absorption of sodium decreased in patients with acute diarrhoea in the absence of luminal SCFA, but returned to normal with luminal SCFA. Net secretion of potassium increased in acute diarrhoea, and did not change in the presence of SCFA. Defective absorption from the rectum in acute diarrhoea is reversed by luminal SCFA. The reduction of luminal SCFA in acute diarrhoea treated conventionally may be a factor contributing to colonic dysfunction.

Acute Disease↗
PubMed1993

Enteric vascular endothelial response to bacterial endotoxin.

The response of enteric vasculature to endotoxin was examined at the ultrastructural level using a murine model of endotoxin-induced acute diarrhoea. Morphological changes indicative of endothelial damage were evident as early as 15 minutes following endotoxin challenge. These changes, characterized by widening of intercellular spaces, increased microvillous projections and the appearance of stress fibres, preceded the leucocytic response. Endothelial damage increased with time, being associated with progressive degenerative changes in the plasma membrane, cytoplasm and organelles, ultimately leading to desquamation. These latter changes were temporally associated with margination of neutrophils and platelet adhesion to the denuded subendothelium. The venules were the primary site of these changes while the capillaries were the least affected. The arterioles were markedly constricted with minimal endothelial damage. These changes suggest that the enteric vascular endothelium may be an important target organ, and the resultant endothelial injury may have implications in host responses to endotoxin.

Acute Disease↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

Tropical sprue.

Explore the source record for details and available documents.

Animals↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

Xylose transport in the human jejunum.

D-Xylose transport in the human jejunum was studied in vivo using a standard intestinal perfusion technique, and also in vitro in human jejunal brush border membrane vesicles. Initial D-xylose concentrations were linearly related to D-xylose absorption rates, a finding consistent with passive diffusion. Perfusion of D-xylose with varying D-glucose concentrations were aimed at examining D-xylose-D-glucose jejunal cotransport. D-Xylose absorption rates from a 30 mM D-xylose perfusate did not change significantly when 10, 30, or 60 mM glucose were added (-3.0 +/- 0.62 vs -3.34 +/- 0.71, -3.82 +/- 0.81, and -4.56 +/- 0.72 mM/30 cm/hr, respectively; minus indicates net absorption) suggesting an absence of a cotransport system. In brush border membrane vesicles, xylose uptake was partially inhibited by D-glucose and phlorizin. These data suggest that jejunal D-xylose absorption, at concentrations used clinically, is by passive diffusion, which process completely overrides a minor D-glucose cotransport component. The D-xylose tolerance test, therefore, reflects jejunal mucosal surface area and mucosal permeability to D-xylose and not nutrient carbohydrate absorption.

Adult↗
PubMed1989

Intestinal transit in healthy southern Indian subjects and in patients with tropical sprue.

Whole gut transit was measured in a group of 21 healthy volunteers and 21 patients with tropical sprue by radio-opaque marker technique, using mean transit time single (MTTS) and single stool transit (SST) method. Mean SST in controls was 25.8 (1.4) (SE) hours, which is considerably shorter than in controls in temperate zones. Mean SST (23.7 (0.6) h) correlated significantly with average MTTS (24.9 (1.6) h) (r = 0.88; p less than 0.001) confirming that SST is a valid method to measure intestinal transit in the tropics. Patients with tropical sprue had a mean SST similar to controls (24.4 (1.1) h), in spite of significantly higher faecal weights (580 (41.2) g v 252 (17.2) g; p less than 0.001).

Adolescent↗