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Biomedical subjects

V I Mathan

Publications and source records attributed to V I Mathan.

At least 55 records · Page 3Linked to original sources
PubMed1989

Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora.

The inactivation of digoxin by conversion to reduced metabolites (digoxin reduction products, or DRP), a function of the anaerobic gut flora, was studied in normal volunteers from southern India and the United States. Digoxin was metabolised to DRP by 28 (13.7%) of 204 healthy south Indians in contrast to 67 (36.0%) of 186 New Yorkers (p less than 1 X 10(-6)). Only 1.0% of Indians compared with 14.0% of Americans excreted large amounts of metabolites (greater than 40% DRP) in the urine (p less than 1 X 10(-5)). Of 104 urban Indians, 23 (22.1%) were metabolisers, in contrast with five of 100 rural villagers (p less than 0.001). Within the urban group, digoxin metabolism correlated with education, frequency of animal protein intake, and most significantly, personal income. Organisms capable of reducing digoxin in vitro were found with similar frequencies in stool cultures from Indians and Americans. In the cultures of some subjects, DRP production was inhibited at lower dilutions but expressed at higher dilutions. We conclude that variations in drug metabolism between population groups may result from differences in the metabolic activity of the anaerobic gut flora probably mediated by environmentally determined factors.

Adolescent↗
PubMed1988

Purification and chemical characterisation of the inhibitor of lipid peroxidation from intestinal mucosa.

The antioxidant previously isolated from intestinal mucosa has been subjected to further purification and identification. Although this inhibitor moved as a single spot on thin-layer chromatography in a number of different solvent systems, it proved to be a mixture of free carboxylic acids whose relative composition was similar in different batches. Detailed studies involving the use of high-pressure liquid chromatography, combined gas chromatography-mass spectrometry, high-field 360 MHz proton nuclear magnetic resonance spectroscopy, fast atom bombardment mass spectrometry and other techniques established that the inhibitor was a mixture of carboxylic acids of the following identity and relative composition (the major components comprising 92% of the total fatty acids): palmitic acid, 14.8%; palmitoleic acid, 3.6%; stearic acid, 7.0%; oleic acid, 21.0%; linoleic acid, 27.6% arachidonic acid, 18.0%. Mixtures of authentic fatty acids of the same relative concentration showed inhibition of peroxidation, comparable with the purified inhibitor from intestinal mucosa. A study of the inhibitory activity of the components of the mixture using malonaldehyde estimation, diene conjugation and arachidonic acid estimation showed that the inhibitory activity was due to palmitoleic and oleic acids only, the latter being the major component.

Animals↗
PubMed1988

An unidentified inhibitor of lipid peroxidation in intestinal mucosa.

Lipid peroxidation in vitro was tested by malonaldehyde production in gastrointestinal mucosa and compared with other tissues. It was observed that gastrointestinal mucosa was resistant to both non-enzymatic and enzymatic lipid peroxidation. This was due to the presence of an inhibitor of lipid peroxidation in the membranous fractions of intestinal mucosa. This inhibitor was capable of inhibiting other recognised peroxidation systems, such as liver mitochondria. This effect was confirmed by measurement of diene conjugation and utilisation of arachidonic acid as other markers of peroxidation, in addition to malonaldehyde production. Preliminary characterisation of this inhibitor revealed that it is resistant to proteolysis, non-diffusable and extractable from membranes by organic solvents. It was partially purified by methanol extraction of the mucosa and by three successive preparative thin-layer chromatography steps. The purified material gave a single spot on thin-layer chromatography, using a number of different solvent systems. Mobility of the inhibitor on thin-layer chromatography was different from that of authentic tocopherol, and it was present in the intestine of vitamin-E-deficient animals. These results suggest that the resistance of intestinal mucosa to lipid peroxidation is due to the presence of a novel inhibitor which is lipidic in nature.

Animals↗
PubMed1988

Tropical sprue in southern India.

Tropical sprue, a primary malabsorption syndrome affecting residents and visitors to several tropical regions, occurs in southern India in endemic and epidemic forms. The stomach, the small intestine and colon are affected and malabsorption results in nutrient deficiency. Enterocyte damage, the primary lesion in southern Indian tropical sprue, is the result of a persistent lesion of the stem cell compartment. This lesion occurs on a background of tropical enteropathy and the available evidence suggests that an immunity conferring agent may be responsible for initiating the damage.

Gastric Mucosa↗
PubMed1988

Rotavirus epidemiology in Vellore, south India: group, subgroup, serotype, and electrophoretype.

Rotaviruses were detected in 163 of 916 (17.8%) specimens collected from children under 3 years of age with gastroenteritis in Vellore, South India, between August 1983 and July 1985. Rotaviruses were detected throughout the study period, with a peak prevalence in December to February (winter) and June to August (southwest monsoon season). A total of 117 rotavirus strains were tested for subgroup, serotype, and rotavirus double-stranded RNA electrophoretic migration pattern; 24.8% of the strains were subgroup I, 69.2% were subgroup II, and 6.0% were neither subgroup I nor subgroup II. Subgroup I and II strains were circulating concurrently throughout the study. Of the 117 rotavirus strains, 32 (27.4%) were serotyped; 15 were serotype 1, 3 were serotype 2, 2 were serotype 3, and 12 were serotype 4. Three serotypes were circulating concurrently during the periods of peak rotavirus prevalence. In 100 of the 117 strains (85.4%) an RNA pattern was detected. One unusual subgroup I group A rotavirus with a long migration pattern and four atypical rotaviruses serologically related to group C were also detected.

Child↗
PubMed1988

Absorption of water and sodium and activity of adenosine triphosphatases in the rectal mucosa in tropical sprue.

In 10 southern Indian patients with tropical sprue, in vivo dialysis showed a defect of absorption of water and sodium from the rectum, when compared with 11 healthy volunteers. Sodium-potassium-ATPase activity, measured in homogenates of rectal biopsies, was significantly diminished in patients with sprue. Magnesium-ATPase and alkaline phosphatase were normal in biopsy homogenates. Decreased activity of colonic sodium-potassium-ATPase may contribute to diarrhoea in some patients with tropical sprue.

Humans↗
PubMed1988

Bacterial lipopolysaccharide-induced intestinal microvascular lesions leading to acute diarrhea.

Subcutaneous challenge of mice with lipopolysaccharide (LPS) from gram negative bacteria, produced an intestinal microvascular lesion causing fluid exudation into the lumen of the intestine and diarrhea. The microvascular lesion was characterized by endothelial cell damage and microthrombi in the venules and capillaries of the intestinal lamina propria. Marker organisms, given orally to challenged mice, grew in the exuded fluid and could invade the mucosa. Intravenous transfer of postchallenge plasma produced the lesion in normal mice and absorption of such plasma by Sepharose coupled to LPS-antibody abolished this effect. Instillation of large quantities of LPS into the lumen of the intestine produced scattered microvascular lesions, although none of these animals developed diarrhea. Since a similar microvascular lesion has been described in the rectal mucosal lamina propria of adults with acute diarrhea, it is suggested that LPS-induced vascular damage may be a novel mechanism in the pathogenesis of acute diarrhea.

Acute Disease↗
PubMed1987

Role of bacterial toxins, bile acids, and free fatty acids in colonic water malabsorption in tropical sprue.

Colonic perfusion studies in 10 southern Indian patients with tropical sprue and nine matched healthy adults revealed a defect of water and sodium absorption from the colon in sprue. Heat-labile and heat-stable enterotoxin production was not detected in coliforms cultured from the feces of any of the 19 subjects. The 24-hr fecal bile acid output was increased in patients with sprue, but fecal aqueous bile acid concentrations remained within normal limits, and these did not correlate with defects in colonic water and sodium absorption. Fecal free fatty acid excretion was markedly increased in sprue. There was a negative correlation between fecal excretion of unsaturated free fatty acids and colonic water and sodium absorption.

Adult↗
PubMed1986

Diagnosis of giardiasis by specific IgM antibody enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was used to detect serum IgM and IgG antibodies against Giardia in fifty-two patients with diarrhoea from the United Kingdom and south India. Serum anti-Giardia IgM responses occurred in patients with giardiasis; in two of three patients studied longitudinally IgM levels had fallen to normal 2-3 weeks after treatment. At serum dilutions of 1/200 to 1/400 there was almost complete separation of ELISA readings between patients with Giardia and Giardia-free controls; the sensitivity and specificity of the ELISA were both 96%. Serum anti-Giardia IgG was detected in patients and controls but was unable to distinguish current from previous infection.

Acute Disease↗
PubMed1986

Epithelial cell renewal and turnover and relationship to morphologic abnormalities in jejunal mucosa in tropical sprue.

A morphometric study confirmed that increasing severity of the jejunal mucosal morphologic lesion is accompanied by increased crypt height and reduced villus length in patients with tropical sprue. Mitotic activity in the crypts was increased. Pulse labeling of jejunal mucosal biopsies cultured in vitro with [3H]thymidine confirmed that there was increased uptake of label in tropical sprue with more rapid migration of labeled cells to the villi. The label was also lost more rapidly. Earlier ultrastructural studies have shown enterocyte damage and extrusion in the crypt and villus epithelium. The present data suggest that in the jejunal mucosa of patients with tropical sprue, the loss of damaged enterocytes leads to villus shortening and increased cell production in the crypts, with hypertrophy of the crypts.

Adult↗
PubMed1986

The prevalence of bacterial intestinal pathogens in a healthy rural population in southern India.

In a one-year prospective survey bacterial intestinal pathogens unassociated with diarrhoeal episodes were isolated from 20.5% of stool samples from 48.5% of a stratified random sample of the population of a village in southern India. Campylobacter jejuni was the pathogen most frequently isolated, followed by enteropathogenic serotypes of Escherichia coli. The incidence of diarrhoea in the study population was lower than the frequency of isolation of bacterial intestinal pathogens. It is necessary to understand the prevalence of intestinal pathogens in this ecosystem to know the dynamics of intestinal infection and the pathogenesis of diarrhoea.

Adolescent↗
PubMed1986

Ultrastructural pathology of the rectal mucosa in Shigella dysentery.

Colonocyte damage in the rectal mucosa in shigellosis is the result of bacterial invasion and leads to ulceration. Additional factors in colonocyte damage may be the Shigella cytotoxin and, especially in colonic crypt cells, bacterial endotoxin. A vascular lesion was present in the lamina propria of the rectal mucosa, which resembled endothelial damage secondary to bacterial endotoxins. In patients with longer duration of symptoms, relative vascular insufficiency, activated lymphocytes, eosinophil and mast cell degranulation, and antibody-mediated colonocyte damage may all play a role.

Adolescent↗
PubMed1985

Cryptosporidium and diarrhoea in southern Indian children.

Cryptosporidium was detected more frequently in stool samples from southern Indian children with acute diarrhoea than from matched controls. It was seldom the only pathogen detected and was not associated with clearcut clinical features. The frequency of the protozoon in children under six months of age was higher in controls than in patients with acute diarrhoea. These features suggest that Cryptosporidium is unlikely to be a major cause of acute diarrhoea in this population. Frequency of Cryptosporidium was higher in children who had been given antibiotics and in those with prolonged episodes of diarrhoea. Administration of antibiotics may lead to conditions within the intestinal lumen that favour colonisation by the organism and prolongation of diarrhoeal episodes.

Acute Disease↗
PubMed1985

Local Shwartzman reaction in the rectal mucosa in acute diarrhoea.

A microvascular lesion characterized by endothelial and platelet damage leading to intravascular coagulation, thrombosis and vascular dehiscence with haemorrhage was found in capillaries and venules in the rectal mucosal lamina propria of adults with acute diarrhoea. The lesion morphologically resembled the local Shwartzman reaction. There was no correlation between the prevalence of the vascular lesion and the presence of recognized enteric pathogens, but there was a significant correlation with the clinical severity of the illness. It is suggested that this vascular lesion could be the result of the failure of the epithelioluminal barrier in the colon and it may also be one of the determinants of the clinical severity of illness in adults with acute diarrhoea.

Acute Disease↗
PubMed1985

A comparison of the susceptibility of three human gut tumour-derived differentiated epithelial cell lines, primary monkey kidney cells and human rhabdomyosarcoma cell line to 66-prototype strains of human enteroviruses.

The growth of prototype strains of 31 serotypes of ECHO, 3 polio, 6 Coxsackie B, 24 Coxsackie A and enterovirus serotypes 70 and 71 were tested in parallel in primary monkey kidney cells (PMK), RD cells and three gut tumour-derived differentiated epithelial cell lines (HRT-18 HT-29 in SKCO-1). All 31 serotypes of ECHO viruses grew in HT-29, 27 and SKCO-1, 5 in HRT-18, 29 in PMK and 29 in RD. There was good growth of poliovirus serotypes in all five cell types. Coxsackie B viruses grew well in all the cell lines except RD. Fifteen of the Coxsackie A viruses grew in SKCO-1, 4 in HT-29, 3 in HRT-18 and 7 in RD. Enterovirus serotypes 70 and 71 grew only in RD cells after 3 serial passages. These results showed that 2 of the gut tumour-derived cell lines, HT-29 and SKCO-1 had a markedly wider susceptibility, with comparable or wider sensitivity, for enteroviruses, than PMK and RD. While their use for field isolation from clinical samples is not yet fully established HT-29 and SKCO-1 would appear to be ideal for a variety of laboratory manipulations of the majority of enteroviruses.

Animals↗
PubMed1985

An epidemic of acute diarrhoea in rural southern India associated with echovirus type 11 infection.

An epidemic of diarrhoea with two distinct waves affected a village of 1375 people in southern India in 1983. The first wave of the epidemic, from the last week of December 1982, had a sharp peak in January 1983 and was over by March. Echovirus type 11 was isolated from patients, who also had a serum antibody response to the virus. During the second wave of the epidemic, from May to September 1983, the clinical features were different and Shigella flexneri was isolated without significant viral isolates. Infection during the first wave did not protect from the second wave. Virus isolation was in human intestinal tumour-derived differentiated epithelial cell lines; such cell lines may be useful for the isolation and identification of enteroviruses in clinical samples.

Diarrhea↗
PubMed1985

Rectal mucosal morphologic abnormalities in normal subjects in southern India: a tropical colonopathy?

Electron dense bodies and vesicles were increased in undifferentiated crypt cells and differentiated colonocytes in the rectal mucosa of healthy volunteers in southern India. In addition, in the surface colonocytes lysosomes were increased, the cells were shorter with short irregularly grouped microvilli, there was evidence of cell immaturity and a high prevalence of spiral organism infestation. There was also alterations in goblet cell mucus granules, a reticulohistiocytic response in the subluminal lamina propria and residual evidence of vascular damage. These alterations indicate a non-specific response to mucosal injury. Such changes have not been observed in the rectal mucosa of temperate zone controls and could be designated tropical colonopathy.

Adult↗