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Biomedical subjects

S K Mehta

Publications and source records attributed to S K Mehta.

At least 37 records · Page 2Linked to original sources

Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats.

The role of oxidative-stress as a mechanism of hepatotoxicity caused by combination of isoniazid (INH) and Rifampicin (RMP) was investigated in young growing rats. A successful model of hepatotoxicity was produced by giving 50 mg/kg/day each of INH and RMP in two weeks. Liver showed type II hepatocellular changes (microvesicular fat deposition) with mild portal triaditis. The glutathione and related thiols were significantly decreased in both blood and liver tissues with combination of INH and RMP treatment. Superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferases with CDNB and DCNB as substrates were decreased in the combination treated group. Glutathione reductase, glutathione-S-transferase with ethacrynic acid as substrate and lipid peroxidation exhibited a significant increase with treatment. The altered profile of antioxidant enzymes with increased lipid peroxidation indicated the enhanced oxidative-stress in combination of INH and RMP treatment. All the findings are faithfully reflected in the blood tissue except superoxide dismutase which showed significant enhancement in this tissue. INH and RMP hepatotoxicity is thus appeared to be mediated through oxidative-stress.

Animals↗

Normal values and methodologic recommendations for signal-averaged electrocardiography in children and adolescents.

Signal-averaged electrocardiography was performed in 153 normal children and adolescents (1 day to 18.3 years old) to examine the effects of age, sex, and race on different electrocardiographic variables, and to evaluate whether the current methods for analysis of the signal-averaged electrocardiogram are applicable to small children. Tracing with inaccurate automatic determination of the QRS end point or high noise levels were excluded. Filtered QRS duration, root-mean-square voltage, and low-amplitude signal duration were measured using 25, 40, and 80 Hz filters. All variables were significantly different (p <0.01) in infants compared with subjects aged >15 years. These differences gradually resolved with increasing age. Sex differences were present for some variables in adolescents only, and there was no significant race-related difference. Because of the shorter QRS duration, the terminal activities were more accurately reflected at the terminal duration of 30 ms in infants and 35 ms in children aged at least 1 year to <6 years. Normative data for filtered QRS duration, root-mean-square voltage, and low-amplitude signal duration are provided for different age groups.

Adolescent↗

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition.

The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive fat globules could be demonstrated in frozen sections stained with oil red O'. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O-2) and H2O2. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone.

Animals↗

Parental hypertension and cardiac alterations in normotensive children and adolescents.

The objective of this investigation was the examination of the relation of left ventricular mass (LVM) and function with cardiovascular response to exercise in normotensive adolescents at risk for hypertension. Carried out was a prospective, cross-sectional study of 47 subjects (age, 10 to 18 years), who underwent dynamic and isometric exercise, 24-hour Holter monitoring, and echocardiography. Twenty-nine had normotensive parents (group 2, "at risk"). Both groups were similar for age, race, sex, body mass index, blood pressures, and resting heart rates. Group 2 had a higher E/A ratio (2.3 +/- 0.5 vs 2.0 +/- 0.5; p = 0.039) and higher heart rates during stage IV of dynamic exercise (188 +/- 20 beats/min vs 176 +/- 18 beats/min; p = 0.046). The LVM, 24-hour heart rates, and exercise systolic blood pressures (SBP) were similar in both groups. Only in group 2, SBP at peak dynamic and isometric exercise correlated best with LVM (r = 0.74, p < 0.002; r = 0.82, p < 0.001). It is concluded that altered hemodynamic regulatory mechanisms may exist before the establishment of hypertension in normotensive subjects with parental hypertension.

Adolescent↗

Candida overgrowth after treatment of duodenal ulcer. A comparison of cimetidine, famotidine, and omeprazole.

Acid-reducing drugs can cause increased growth of microbes, including fungus, because of high gastric pH. Our purpose was to evaluate the occurrence of mycotic infection in patients with duodenal ulcer on anti-ulcer therapy and to compare the effects of cimetidine, famotidine, and omeprazole. Eighty patients with duodenal ulcer (62 males and 18 female patients, 16-65 years old) were evaluated for mycotic infection before and after 6 weeks of therapy (cimetidine, 20 patients; famotidine, 40 patients; omeprazole, 20 patients). Mycotic infection was diagnosed by endoscopic biopsy from the ulcer edge subjected to smear, culture, and histopathology and by endoscopic brush samples and gastric aspirate. On the basis of these studies, patients were categorized as having no fungal growth, saprophytic growth, or significant fungal growth. Thirty-five (43.8%) patients had evidence of fungus before ulcer therapy, and 16 of the 35 (20%) had significant fungal growth. The fungal isolation rate was higher in older patients (> and = 45 years of age) and in those with an ulcer size > and = 2 cm. While there was no significant increase in the total number of patients with evidence of fungus after therapy (n = 36), there was a significant increase in those with significant growth (n = 27, p < 0.05) compared with pretreatment status. We found that posttreatment gastric pH of > and = 4 was associated with a higher fungal positivity rate (59.4%) than pH values < 4 (32.4%, p < 0.05). However, neither the type of drug used nor the response in terms of ulcer healing correlated with the presence of fungus. Regardless of the type of drug used, acid-reducing therapy is associated with increased significant fungal growth.

Adult↗

Evaluation of three portable samplers for monitoring airborne fungi.

Airborne fungi were monitored at five sample sites with the Burkard portable, the RCS Plus, and the SAS Super 90 air samplers; the Andersen 2-stage impactor was used for comparison. All samplers were calibrated before being used simultaneously to collect 100-liter samples at each site. The Andersen and Burkard samplers retrieved equivalent volumes of airborne fungi; the SAS Super 90 and RCS Plus measurements did not differ from each other but were significantly lower than those obtained with the Andersen or Burkard samplers. Total fungal counts correlated linearly with Cladosporium and Penicillium counts. Alternaria species, although present at all sites, did not correlate with total count or with amounts of any other fungal genera. Sampler and location significantly influenced fungal counts, but no interactions between samplers and locations were found.

Aerosols↗

Protein-energy malnutrition and oxidative injury in growing rats.

1. Weaning rats were fed ad libitum isocaloric diets containing 5% and 20% casein based proteins. 5% protein diet was protein deficient diet. Pair fed rats with the 5% protein group were maintained simultaneously on 20% protein diet but the amount restricted to the amount taken up by PEM group. 2. Glutathione, antioxidative enzymes, lipid peroxidation and histopathological studies in liver and only glutathione and antioxidative enzymes in blood were carried out. 3. Rats fed the 5% protein diet developed a severe protein energy malnutrition (PEM) whereas those on pair-fed diet developed mild to moderate PEM. 4. Glutathione related thiols superoxide dismutase, glutathione peroxidase, catalase and glutathione-Stransferase with (1 Chloro 2,4-dinitro benzene (CDNB) substrate) were decreased in liver with concomitant increase of lipid peroxidation in severe PEM. In blood glutathione, glutathione peroxidase and catalase were decreased while superoxide dismutase was increased in severe PEM group. 5. Mild to moderate PEM (pair-fed group) also resulted in similar changes in liver except glutathione peroxidase, lipid peroxidation in liver and superoxide dismutase in blood. 6. Hepatic injury was detectable only in the severe PEM group. 7. Oxidative-stress and hepatic injury occurred in severe PEM and to a lesser degree in mild to moderate PEM.

Animals↗

Chloroquine for mild to moderately active ulcerative colitis: comparison with sulfasalazine.

Chloroquine and hydroxychloroquine have been used successfully in a number of immunological diseases because of their immunomodulatory effect. Preliminary studies have shown them to be effective in the treatment of idiopathic ulcerative colitis. We assessed the efficacy or oral chloroquine in the treatment of idiopathic ulcerative colitis of mild to moderate severity in a randomized, controlled, blinded trial. Forty patients were assigned to receive chloroquine phosphate (500 mg/day) or sulfasalazine (3 g/day). The outcome of therapy was monitored at the end of 2 wk and 4 wk by symptom assessment and sigmoidoscopic examination. An objective scoring system was used for the evaluation, and patients were categorized into those showing complete remission, partially responding, and nonresponders. There was a sequential improvement in the individual scores as well as total activity score in both groups at 2 wk and 4 wk. With chloroquine, 12 patients (60%) showed complete remission at 4 wk, whereas six (30%) had a partial response. With sulfasalazine, 11 patients (55%) had complete remission at 4 wk, and eight (40%) showed partial response. There was no significant difference in the response to the two drugs (p > 0.05). Five (25%) patients in the chloroquine group had side effects, compared with eight (40%) in the sulfasalazine group (p > 0.05). All side effects were minor and transient, not requiring withdrawal of the drug. We conclude that short-duration chloroquine therapy is a safe and effective alternative to sulfasalazine in the treatment of mild to moderately active ulcerative colitis.

Adjuvants, Immunologic↗

Hyperaggregation of platelets in intestinal tuberculosis: role of platelets in chronic inflammation.

Eighty-eight percent (38/43) patients of intestinal tuberculosis showed significant hyperaggregation of platelets (P < 0.001). Serum and plasma from 15 patients when incubated with normal platelets caused hyperaggregation. Gel filtered platelets from 2 patients suspended in normal plasma showed hyperaggregation of platelets with arachidonic acid. Tubercular protein had no effect on platelet aggregation. A role of hyperactive platelets in chronic inflammatory response is discussed.

Adolescent↗

Effect of mild malnutrition on disaccharidase activity and glucose uptake in intestinal brush border vesicles of growing monkeys.

BACKGROUND: The effect of severe malnutrition has been reported by some workers, but there is a paucity of information on milder forms even though 85% of pre-school children show evidence of mild to moderate malnutrition in India. METHODS: Mild to moderate protein energy malnutrition was induced in 12 monkeys, and 12 were kept as controls. After a 30-40% reduction in body weight as compared with their controls, the animals were killed, and brush border membrane vesicles were prepared from three small parts of the small intestine. Purified vesicles were used for the assay of lactase, sucrase, maltase and glucose uptake in vitro. RESULTS: The activity of lactase, sucrase, and maltase, and uptake of (U-14C)-D-glucose was decreased in all three parts of small intestine, and the lactose tolerance test result was also abnormal in the protein energy-malnourished group. On nutritional rehabilitation, the disaccharidase activities recovered completely. CONCLUSION: This study indicates that even mild to moderate malnutrition decreases the digestion and absorption of carbohydrates throughout the small intestine, and it should not be ignored during the developing stage.

Animals↗

Assessment of optimal dose of lactose for lactose hydrogen breath test in Indian adults.

To evaluate the possibility of using a 12.5 g or 25 g oral dose of lactose for hydrogen breath test for diagnosis of lactose intolerance instead of the usual 50 g dose. 35 patients with non-ulcer dyspepsia and an abnormal 50 g lactose breath hydrogen of more than 20 ppm over the base line were retested using 12.5 g and 25 g lactose. 32 (91.4%) and 15 (42.8%) of these 35 patients had an abnormal hydrogen breath test using 25 g (p = ns compared to 50 g dose) and 12.5 g (p < 0.001) lactose doses respectively. This study reveals that it may be possible to use a 25 g lactose dose instead of a 50 g dose for the lactose hydrogen breath test.

Breath Tests↗

Effect of protein energy malnutrition on the lipid composition and leucine uptake of small intestinal brush border vesicles of growing rhesus monkeys.

Mild to moderate protein energy malnutrition (PEM) was induced in young developing rhesus monkeys by giving them half of the casein-based synthetic diet which was given to control animals. After a body weight reduction of 30-40%, the PEM animals were sacrificed. The small intestine was removed, flushed with ice-cold saline, everted and divided into equal proximal, middle and distal segments. Brush border membrane vesicles (BBMV) were prepared from all three segments and assayed for marker enzymes, e.g. sucrase and alkaline phosphatase, to assess their purity. Sucrase was found to be purified 23-fold and alkaline phosphatase 12-fold compared to the respective homogenates in all three parts. In PEM animals, uptake of [U-14C]L-leucine into the BBMV was diminished in all three segments and cholesterol and phospholipid levels also decreased significantly. As a result there was an elevation in the molar ratio of cholesterol to phospholipid, and the sphingomyelin: phosphatidylcholine molar ratio also increased. This signified a decrease in lipid fluidity and amino acid uptake in PEM in the small intestine. Histologically, a mild to moderate grade of partial villus atrophy was observed in the intestine. The diminished uptake and lipid fluidity of the membrane and the histological changes returned to their control values after nutritional rehabilitation.

Alkaline Phosphatase↗

Differential tropism of EB rotavirus (serotype 3) to small intestine of homologous murine model.

The 4-5 days-old NMRI strain infant mice were orally inoculated with EB rotavirus (serotype 3). The intestinal disaccharidases activity was studied separately in three segments of the small intestine i.e. duodenum, jejunum and ileum on day 1 to 7 post inoculation (p.i.). The severity of EB rotavirus infection correlated with a significant decrease of small intestinal lactase, maltase and sucrase on day 3 p.i. The level of maltase after the initial decline increased in all the three segments of small intestine of infected mice. However, the lactase activity remained suppressed for a relatively longer period in ileum of infected mice than in controls. These enzymes began to approach to normal value by day 5 p.i., but in ileum, lactase activity continued to be severely depressed even on day 7 p.i. Rotavirus was consistently detected in intestinal contents by ELISA on days 1 to 7 p.i. The infected mice showed a significant increase in rotavirus (serotype 3)-specific serum IgG and IgM antibody level during the declining (days 5-7 p.i.) phase of infection. Diarrhoea was noted up to day 6 p.i. The protracted suppression of the lactase activity in ileum in comparison to duodenum and jejunum showed a differential tropism of EB rotavirus (serotype 3) strain to the small intestine of homologous murine model.

Animals↗