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Biomedical subjects

B N Walia

Publications and source records attributed to B N Walia.

At least 19 recordsLinked to original sources

Study on the mechanism of Giardia lamblia induced diarrhoea in mice.

The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia infected mice in the presence or absence of phorbol-12-myristate-13-acetate (PMA), the activator of protein kinase C (PKC) or 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), the inhibitor of PKC or Ca(2+)-calmodulin. There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of ionophore or PMA resulted in net secretion of Na+ and Cl- in the control group while in the infected group there was no change in the fluxes of these ions. The selective potent inhibitor of protein kinase C, H-7, reversed the secretion of Na+ and Cl- in infected group to absorption. The addition of PMA and Ca(2+)-ionophore together in the infected group had a partial additive effect. This study suggests that G. lamblia induced fluid secretion involves protein kinase C and further protein kinase C acts in synergism with calcium.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

The prevention of Indian childhood cirrhosis.

Previous studies have led to the hypothesis that the gross hepatic copper storage characteristic of Indian childhood cirrhosis (ICC) is due to the early introduction of animal milk feeds which have been contaminated with copper from brass household utensils. Amongst the families of 100 cases of ICC, the incidence of ICC in children born after dietary advice had been given (1/86) was significantly lower than in older siblings (12/125). This study attempted to document the incidence of ICC and the usage of brass before and after an intervention programme in Pune District advising against this pattern of infant feeding. The study encountered numerous difficulties in data gathering, but documented a fall in ICC prevalence resulting in its virtual disappearance in Pune District. This contrasted with an unchanged incidence in Chandigarh. Although a fall in brass usage was seen in Pune District, this was actually a spontaneous sociological change rather than a result of health education.

Alloys

Multi-drug-resistant Salmonella typhi--a need for therapeutic reappraisal.

Enteric fever caused by Salmonella typhi resistant to all the standard first-line antibiotics is emerging as a major problem in developing countries. Fifteen such culture-proven cases were treated with ceftriaxone (6), cefotaxime (5) or ciprofloxacin (4). The earliest defervescence occurred with ceftriaxone (mean 3.3 days). Clinical cures were obtained with all three drugs with only one child having a relapse. Ciprofloxacin, by virtue of its cost and an oral route of administration, is the ideal choice in a developing country.

Cefotaxime

Effect of exogenous copper on lipid peroxidation in rat hepatocytes. Possible involvement of protein kinase C.

We have investigated the direct effect of copper on malondialdehyde formation in rat isolated hepatocytes. Copper was found to decrease the cell viability with concomitant production of malondialdehyde in a time related manner. In addition the protein kinase C activator, PMA, was found to have a synergistic effect with copper on rat hepatocytes. These results indicate that protein kinase C may be important in mediating hepatotoxicity after exposure to copper.

Animals

Reliability of skinfold calipers as a tool for measuring body fat in human beings.

Triceps skinfold thickness measured in ten adults aged 19 to 50 yr by a Holtain skinfold caliper, was compared with subcutaneous fat thickness obtained on cross-sections of the left upper arm by computerized axial tomography (CAT). The thickness of subcutaneous fat was measured on CAT scan film directly with the inbuilt computer graphic technique. The measurements taken on CAT scan film were found to be significantly higher (by 21-45%; P less than 0.001) than those by the skinfold calipers. Our findings suggest that skinfold calipers may not be very accurate tools for the assessment of body fat in human beings. Therefore, its use in the determination of body composition, for which great precision is required calls for re-thinking.

Adipose Tissue

Salmonella typhimurium enterotoxin mediated fluid secretion.

Unidirectional Na+ and Cl- fluxes were studied in rats treated with S. typhimurium enterotoxin (S-LT). There was net absorption of Na+ and Cl- in the control group, while in the toxin treated animals there was net secretion of Na+ and Cl- (P less than 0.001). There was no change in the transport of D-glucose in the toxin treated group as compared to the control animals. The Na+, K(+)-ATPase pump was unaltered in the S-LT treated animals (198.67 +/- 11.23 nmoles Pi/mg protein/min) as compared to the control group (189.93 +/- 10.09 nmoles Pi/mg protein/min). There was no change in the unidirectional fluxes of Ca+2 in the S-LT treated animals as compared to the control animals, suggesting no change in the permeability of the S-LT treated intestinal membrane to Ca+2.

Animals

Serological responses to hepatitis B virus infection in multi-transfused thalassemic children.

One hundred children with beta-thalassemia major were studied prospectively. A one time analysis of serum samples was carried out for a battery of hepatitis B viral markers viz., HBsAg, anti-HBs and anti-HBc. Seven mutually different serological patterns were observed. The commonest profile seen in 49 patients was a combined seropositivity for anti-HBc and anti-HBs indicating past HBV infection with persisting immunity. Definite evidence of active HBV infection (seropositivity for HBsAg and/or HBeAg) was demonstrated in 10 cases, six of these were HBsAg positive. Anti-HBc positivity alone was detected in 17 patients. The remaining 24 children were seropositive for anti-HBs alone suggesting a possible passive transmission of anti-HBs through blood transfusion.

Blood Transfusion

Studies on the mechanism of Salmonella typhimurium enterotoxin-induced diarrhoea.

The unidirectional fluxes of Na+ and Cl- were studied in Salmonella typhimurium enterotoxin-treated rats. There was net secretion of Na+ and Cl- in toxin-treated animals, while in control animals there was net absorption of these ions. In the presence of the Ca(2+)-ionophore, there was net secretion of Na+ and Cl- in the control group, while the ionophore enhanced the secretion of these ions in experimental animals. The calcium channel blocker, verapamil, decreased the secretion induced by salmonella toxin, but could not reverse the secretion to absorption. There was no difference in the net absorption of Ca2+ in both the control and experimental animals. There was a significant increase in the intracellular free calcium concentrations in enterocytes isolated from toxin-treated rat intestines as compared to that in enterocytes isolated from control animals. In the presence of PMA (phorbol-12-myristated-13-acetate) there was net secretion of Na+ and Cl- in the control group, while in the experimental group there was no change in the fluxes of these ions. The selective, potent inhibitor of protein kinase C, H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine) reversed the secretion of Na+ and Cl- in the toxin-treated group to absorption. The addition of indomethacin also inhibited the secretion induced by salmonella toxin, but failed to reverse it to absorption. However, the addition both H-7 and indomethacin to the experimental group had a partial additive effect. These studies demonstrate that the Salmonella enterotoxin-mediated fluid secretion involves protein kinase C and the arachidonic acid metabolites and perhaps does not involve the extracellular calcium pools.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Sequential histopathologic alterations in Indian childhood cirrhosis treated with d-penicillamine.

Eight children who satisfied all the diagnostic criteria of classic Indian childhood cirrhosis were treated with d-penicillamine. Clinical recovery in a 3- to 12-month period was accompanied histopathologically by accentuation of micronodules with regression of hepatocytic degenerative changes, Mallory's hyaline, pericellular fibrosis, lobular inflammation, and disappearance of hepatocytic copper staining protein. The nodules in the posttreatment biopsies were so small as to be categorized as "micronodular cirrhosis." In one case clinical recovery was associated with an almost normal liver histology after passing through a micronodular phase. This report is the first documentation of the histologic sequence of changes in Indian childhood cirrhosis on d-penicillamine treatment.

Copper

Assessment of preclinical vitamin A deficiency in children with persistent diarrhea.

To explore the relationship between vitamin A deficiency and persistent diarrhea among young children, we studied the vitamin A status of 23 children greater than 5 years of age with persistent diarrhea by performing conjunctival impression cytology (CIC) and the relative dose-response test (RDR) as a measure of liver reserve of vitamin A. The control group consisted of 23 age- and sex-matched children who were otherwise healthy in whom CIC was performed and fasting plasma retinol values were determined. The criteria for vitamin A deficiency in CIC were paucity of goblet cells and scanty, abnormal epithelial cells. None of these children had ocular manifestations of vitamin A deficiency. Among the children with persistent diarrhea, CIC characteristic of vitamin A deficiency was found in 17 (group 1) and CIC results were normal in six (group 2). In group 1, the serum retinol levels were 1 +/- 1 microgram/dl, and RDR was 88 +/- 14. In group 2, the serum retinol levels were 8 +/- 4 micrograms/dl (p less than 0.001) and the RDR was 16 +/- 12 (p less than 0.001). In the control group, the CIC results were normal in all the children and the plasma retinol levels in these children were 19 +/- 8 micrograms/dl. In conclusion, 17 of 23 children with persistent diarrhea had abnormal CIC results, significantly low serum retinol levels, and significantly high RDR results, although they had not yet manifested xerophthalmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool

The correlation of biochemical virulence factors and enterotoxin production with LD50 of Salmonella typhimurium in mice.

Five strains of Salmonella typhimurium were examined to determine the parameters of virulence. The virulent species significantly resisted the macrophage bactericidal activity (p less than 0.05). The chemiluminescent (CL) response was studied to determine the level of Oxygen-free radicals (OFR) generated and the antioxidant enzymes superoxidase dismutase (SOD), catalase and glutathione peroxidase were assayed to determine the antioxidant mechanism of S. typhimurium to subvert these microbicidal pathways. The levels of the various enzymes were correlated with the virulence (as determined by LD50) and the ability of the microorganisms to induce diarrhoea. Oxygen free radical (OFR) generation elicited by macrophages, in the presence of virulent and avirulent salmonellae was not statistically significant (p greater than 0.05). No correlation was found between the levels of the antioxidant enzymes and the LD50 values. Thus the oxygen-dependent pathways do not appear to play a role in the pathogenesis of salmonellosis, and do not specify the virulence of the microorganism. Immunological and biological assays revealed the virulent strain to be more toxigenic than the avirulent strain. Therefore, the basis of differing virulence in S. typhimurium may be the ability to make and release more toxin in vivo.

Animals

Role of calcium and calmodulin in Giardia lamblia-induced diarrhoea in mice.

The unidirectional fluxes of Na+, Cl- and Ca2+ across the small intestinal epithelium of normal and Giardia lamblia-infected mice were studied in vitro in short-circuited tissue. Net secretion of Na+ and Cl- was observed in infected animals, whereas in non-infected (control) animals there was net absorption of Na+ ions and marginal secretion of Cl- ions. In infected animals, net absorption of Ca2+ was observed as compared to little secretion observed in control animals. Although the presence of Ca(2+)-ionophore in the medium resulted in a net secretion of Na+ and Cl- in controls, it could not cause any change in the fluxes of these ions in infected animals. Verapamil, a calcium channel blocker, reversed the effects of infection and Ca(2+)-ionophore. Further W7 (n-(6-aminohexyl)-5 chloro-1-naphthalene sulphonamide), a calmodulin antagonist, also reversed the effects of infection. The addition of the neurotoxin, tetrodotoxin caused net absorption of Na+, Cl- and net secretion of Ca2+ in the control group, but it could not produce any effect on the fluxes of these ions in the infected group. These findings demonstrate that, in G. lamblia infection, the secretion of Na+ and Cl- is associated with an increase in absorption of Ca2+ and an increase in calmodulin activity in intestinal microvillar core. These findings further suggest that the enteric nervous system plays a marginal role in Giardia infection.

Animals

Immune status in ataxia telangiectasia.

Immune status of 22 patients of ataxia telangiectasia was studied over a period of 8 yr (mean age of patients: 9.5 +/- 3 yr; 9 of 22 were siblings). Low T-cell number was observed in 14 of 19 patients but the response to PHA challenge done in 10 patients was normal and migration inhibition to BCG antigen was positive in 6 of 6 patients. IgM defect was seen in 2 out of 18 patients and serum IgA was deficient in 10 out of 18 patients. Salivary IgA was also absent in these children. Four children had high spontaneous NBT reduction. None of the patients had lymphoma, leukemia or any other malignancy at the time of presentation. Candida killing was normal in all patients. The presenting feature related to the CNS in almost all children and gross infections were not seen.

Adolescent

Differences between the mechanisms of action of heat-stable and heat-labile enterotoxins of Escherichia coli.

The mucosal-to-serosal and serosal-to-mucosal fluxes of Na+ and Cl- were measured in control mice and mice treated with heat-stable (ST) and heat-labile (LT) enterotoxins in the presence or absence of: Ca2(+)-ionophore A23187, an activator of Ca2(+)-calmodulin; or phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C(PKC); or 1-(5-isoquinolinyl sulphonyl)-2-methyl piperazine (H-7), an inhibitor of PKC. There was net secretion of Na+ and CL- in both experimental groups in contrast to net absorption in the control group. The addition of ionophore or PMA or ionophore + PMA resulted in net secretion of Na+ and Cl- in the control group and the effect of ionophore and pMA was found to be additive. The addition of ionophore did not cause any change in electrolyte fluxes in the ST toxin treated group, however, it increased the net secretion of Na+ and Cl- in the LT toxin treated group. PMA increased the net secretion of Na+ and Cl- in the St toxin treated group, however, it did not cause any change in Na+ and Cl- fluxes in the LT toxin treated group. H-7 did not reverse the effect of ST toxin, however, it reversed the effect of LT toxin.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Fungal diarrhoea: association of different fungi and seasonal variation in their incidence.

A total of 854 patients (640 children and 214 adults) admitted with acute or chronic diarrhoea suspected of non-invasive overgrowth of fungi in intestine were screened during a period of 3 years. Fungal proliferation was noted in 54.8% of these patients (53.6% in children, 58.4% in adults). The predominant fungal species isolated were Candida albicans (64.5%), followed by C. tropicalis (23.3%) C. krusei (6.9%). Torulopsis glabrata (1.6%). Trichosporon sp. and Geotrichum sp. were found to be responsible in 2.3% of adults. As seen in bacterial diarrhoea, higher incidence was noted in children from April to August. No such seasonal variation was noted in adults.

Acute Disease

Psychosocial problems in families of disabled children.

Psychosocial problems faced by parents and other family members were studied in 50 families with a physically disabled child (PD group), 50 with a mentally retarded child (MR group) and 50 with a healthy child (control group). A semi-structured questionnaire assisted interview and standardized scales were used to measure social burden, marital adjustment and maternal neuroticism. Families with disabled children perceived greater financial stress, frequent disruption of family routine and leisure, poor social interaction, and ill effects on their physical and mental health as compared to families of control children. The overall social burden scores were significantly higher in both the groups with disabled children as compared to controls (mean scores PD 17.8, MR 14.6, C 0.72, p less than .001), and showed a significant inverse correlation with the socio-economic and educational status of parents. The neuroticism scores were also significantly higher (PD 23.7, MR 19.0, C 9.6, p less than .01), and the marital adjustment scores lower (PD 75, MR 79, C 86, p less than .01) in families with disabled children. Appropriate management of these problems should be part of rehabilitation programmes.

Adolescent