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Biomedical subjects

U C Garg

Publications and source records attributed to U C Garg.

At least 37 records · Page 2Linked to original sources

Inhibition of rat mesangial cell mitogenesis by nitric oxide-generating vasodilators.

Recent studies indicate that endothelium-derived relaxing factor (EDRF) may be identical with nitric oxide (NO). The purpose of this study was to investigate the antimitogenic effect of NO-generating drugs in cultured mesangial cells. S-nitroso-N-acetylpenicillamine, sodium nitroprusside, and isosorbide dinitrate, which generate NO, dose dependently inhibited serum-stimulated DNA synthesis. All three drugs also inhibited the rate of cell proliferation, whereas sodium nitroprusside and S-nitroso-N-acetylpenicillamine decreased cell density at confluence. The antimitogenic activity of S-nitroso-N-acetylpenicillamine was labile in culture medium and could be inhibited by hemoglobin, supporting the view that NO, in free or bound form, was the ultimate effector. All three vasodilators increased cellular guanosine 3',5'-cyclic monophosphate (cGMP) levels dose dependently; moreover, 8-bromo-cGMP mimicked the effects of the NO-generating drugs, suggesting that cGMP may be an intracellular mediator of antimitogenesis. The growth-inhibitory effect of S-nitroso-N-acetylpenicillamine was reversible and was not due to cell toxicity as shown by several criteria of cell viability. The results raise the possibility that EDRF/NO may be a modulator of mesangial cell growth in vivo.

Animals↗

Enzyme levels in bronchoalveolar lavage fluid and serum of active pulmonary tuberculosis patients.

Bronchoalveolar lavage (BALF) was found to be a useful index of cell damage. It has been observed that the enzymes in BALF could give an idea of cell damage in a pulmonary disease. Acid phosphatase, alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl-transpeptidase were assessed in mild, moderate, and severe pulmonary tuberculosis patients and Mantoux-negative normal controls. Activities of these enzymes were found to be higher in patients and were increasing with the severity of the disease. Increase in these enzymes in pulmonary tuberculosis patients could be attributed to lung tissue damage.

Acid Phosphatase↗

Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells.

Endothelium-derived relaxing factor has been recently identified as nitric oxide. The purpose of this study was to determine if vasodilator drugs that generate nitric oxide inhibit vascular smooth muscle mitogenesis and proliferation in culture. Three chemically dissimilar vasodilators, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate, dose-dependently inhibited serum-induced thymidine incorporation by rat aortic smooth muscle cells. Moreover, 8-bromo-cGMP mimicked the antimitogenic effect of the nitric oxide-generating drugs. The antimitogenic effect of S-nitroso-N-acetylpenicillamine was inhibited by hemoglobin and potentiated by superoxide dismutase, supporting the view that nitric oxide was the ultimate effector. Sodium nitroprusside and S-nitroso-N-acetylpenicillamine significantly decreased the proliferation of vascular smooth muscle cells. Moreover, the inhibition of mitogenesis and proliferation was shown to be independent of cell damage, as documented by several criteria of cell viability. These results suggest that endogenous nitric oxide may function as a modulator of vascular smooth muscle cell mitogenesis and proliferation, by a cGMP-mediated mechanism.

Animals↗

Calcium calmodulin in altered NaCl transport by heat-labile enterotoxin of Escherichia coli.

The mucosal-to-serosal and serosal-to-mucosal fluxes of Na+ and Cl- were carried out in control and experimental groups treated with different doses of heat-labile enterotoxin in the presence or absence of Ca2+-ionophore, Ca2+ channel blocker and calmodulin inhibitor. There was net secretion of Na+ and Cl- in 16 and 32 units of heat-labile enterotoxin treated groups in comparison to net absorption in control group, however, in animals treated with 8 units of heat-labile enterotoxin, no change in Na+ and Cl- fluxes was found when compared to control. Ca2+- ionophore increased net secretion of Na+ and Cl- in 16 and 32 units of heat-labile enterotoxin treated groups and also caused secretion in control group instead of net absorption. Ca2+ channel blocker and calmodulin inhibitor partially reversed the effect of heat-labile enterotoxin. The effect of Ca2+-ionophore was more pronounced in the control group while that of Ca2+ channel blocker and calmodulin inhibitor was more pronounced in 16 and 32 units of heat-labile enterotoxin treated groups. The findings suggest the involvement of Ca2+ and calmodulin in the action of heat-labile enterotoxin of Escherichia coli in mice.

Animals↗

Urinary excretion of renal brush-border enzymes in lepromatous leprosy--a preliminary investigation.

Activities of the brush-border enzymes, alkaline phosphatase, maltase, leucine aminopeptidase, and gamma-glutamyl transpeptidase, were measured in urine samples of 25 lepromatous leprosy patients and an equal number of age-matched healthy controls. None of the patients were shown to be suffering from any other systematic disease. The enzymatic activities were shown to be significantly elevated in leprosy patients when compared to controls.

Alkaline Phosphatase↗

Effect of heat-stable and heat-labile enterotoxins of Escherichia coli on intestinal brush border membrane enzymes of mice.

The activities of intestinal brush border membrane (BBM) enzymes alkaline phosphatase, maltase, lactase, sucrase, gamma-glutamyl transpeptidase and leucine aminopeptidase were determined in intestinal homogenates and purified BBMs from control, heat-stable and heat-labile enterotoxin treated mice. The activities of all the enzymes except lactase were decreased significantly (p less than 0.01) in homogenates while increased significantly (p less than 0.001) in BBMs of experimental groups as compared to controls. Calmodulin activities were increased significantly (p less than 0.01) as compared to control in heat-stable enterotoxin treated mice but remained unaltered in heat-labile enterotoxin treated mice. DNA contents of intestinal homogenates were decreased in experimental groups demonstrating the decrease in cell number in these groups. The altered BBM enzyme activities could not be attributed to changes in calmodulin activities. The increase in enzyme activities in BBMs may reflect a compensatory phenomenon in the remaining cells.

Alkaline Phosphatase↗

Effects on intestinal nutrient uptake and brush border membrane enzymes in response to atherogenic diet in rhesus monkeys.

Transport of nutrients and kinetic parameters (Vmax and Km) of brush border membrane (BBM) enzymes were studied in duodenum, jejunum, and ileum from atherogenic diet-fed monkeys. The Km remained unaltered while feeding of atherogenic diet resulted in higher Vmax of sucrase, maltase, and alkaline phosphatase and lower Vmax of gamma-glutamyltranspeptidase and leucine-aminopeptidase compared to controls. Na+-dependent D-glucose transport was higher in duodenum and jejunum and unaltered in ileum. In contrast to D-glucose transport, the transport of amino acids was decreased in all three intestinal segments from atherogenic diet-fed monkeys.

Alkaline Phosphatase↗

Role of Ca2(+)-calmodulin and protein kinase C in the secretory action of heat-labile enterotoxin of Escherichia coli in mice.

The mucosal-to-serosal and serosal-to-mucosal fluxes of Na+ and Cl- were carried out in control and heat-labile enterotoxin treated mice in the presence or absence of Ca2(+)-ionophore A23187, the activator of Ca2(+)-calmodulin or Phorbol-12-myristate-13-acetate (PMA), the 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 experimental group in comparison to net absorption in control group. The addition of ionophore or PMA resulted in net secretion of Na+ and Cl- in control group. In experimental group ionophore increased the net secretion of Na+ and Cl- while, PMA could not cause any change in Na+ and Cl- fluxes in experimental group. Calmodulin activity remained unaltered in heat-labile enterotoxin treated mice as compared to control. H-7, reversed the effects of PMA and heat-labile enterotoxin. These studies demonstrate that heat-labile enterotoxin primarily involves PKC in its action.

Animals↗

A novel biological effect of atrial natriuretic hormone: inhibition of mesangial cell mitogenesis.

We have investigated the effect of atrial natriuretic hormone on serum-induced mitogenesis in cultured rat mesangial cells. Synthetic peptides, atriopeptin 28 and atriopeptin 24, dose-dependently decreased thymidine incorporation, with a half-maximal effect at approximately 1 nM and a maximal inhibition of approximately 60%. Moreover, atriopeptin 28 significantly decreased the clonal proliferation of mesangial cells. Atriopeptin 28 also decreased resting cytosolic Ca but had no effect on the increase induced by serum, relative to the lower baseline established by atriopeptin 28. Nevertheless, the overall effect of atriopeptin 28 on Ca was to attenuate the serum-induced increase, relative to the original resting level. These results therefore provide evidence for a novel biological effect of atrial natriuretic hormone and suggest that the antimitogenic effect may be mediated by atriopeptin-induced alterations of intracellular Ca dynamics. We speculate that atrial natriuretic hormone may be a modulator of mesangial cell mitogenesis in vivo.

Animals↗

Physiological and histopathological changes in the intestines of mice challenged with S. typhi.

Transport of Na+, Cl-, Ca2+ and 3-0-methyl-D-glucose (a non-metabolizable analogue of D-glucose) was worked out in control, infected and immunized-infected animals along with histopathological studies of the intestines in these groups. There was significant decrease (p less than 0.01) in net absorption of Na+ and Cl- in the infected group as compared to that in the control group. There was also a significant decrease (p less than 0.01) in 3-0-methyl-D-glucose uptake in the infected group. However, no change was found in the immunized group in any of the electrolytes and non-metabolizable analogue of D-glucose. These findings correlated well with the histopathological studies as the infected intestines showed complete disorganization of mucosal tissues with loss of epithelial cells from the villi whereas the mucosal lining and epithelial cells from the intestines of immunized mice were normal looking.

3-O-Methylglucose↗

A spectrophotometric method for calmodulin assay.

The activity of calmodulin as an activator of cAMP phosphodiesterase was assayed. AMP was hydrolyzed by 5'-nucleotidase, and the adenosine formed was measured by both liquid scintillation counting and spectrophotometry at 265 nm. Calmodulin activities measured by the two methods were equivalent, indicating that spectrophotometric assay of calmodulin can be used in place of the isotopic method.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effect of various oxygen free radical scavengers in preventing tissue injury caused by Escherichia coli in pyelonephritic mice.

Reactive oxygen species have been found to be responsible for the tissue injury caused in experimental pyelonephritis in mice. The extent of lipid peroxidation (as assayed by malondialdehyde formation) was found to be increased significantly (p less than .001) in the infected group as compared to the normal mice. Superoxide dismutase and catalase (oxygen free radical scavengers) showed a significant decrease (p less than .001) in the extent of lipid peroxidation even in the presence of infection. Dimethyl sulfoxide, a hydroxyl ion scavenger, was however found to be effective only at 4 and 7 days postinfection (p less than .001). Allopurinol, an inhibitor of xanthine oxidase, did not significantly (p greater than .05) inhibit the formation of lipid peroxides, even upto 7 days postinfection. There was a significant decrease (p less than .05) in the activities of renal brush border membrane enzymes used as markers of renal tissue damage (i.e. alkaline phosphatase, leucine amino-peptidase and gamma-glutamyl transpeptidase) in the infected group as compared to the normal group. In the presence of superoxide dismutase, dimethylsulfoxide and catalase except allopurinol, the activities of all the enzymes but maltase were found to be increased significantly (p less than .05) as compared to the infected group. There was a significant increase (p less than .01) in the bacterial count in the presence of superoxide dismutase and DMSO in infected mice as compared to the infected control mice. However, no significant difference was observed in the catalase and allopurinol treated groups.

Allopurinol↗

Effect of excretory-secretory products of Giardia lamblia on glucose and phenylalanine transport in the small intestine of Swiss albino mice.

The transport of D-glucose and L-phenylalanine was measured in intestinal brush border membrane (BBM) vesicles treated with Excretory-secretory (ES) products of Giardia lamblia. Uptake was found to be significantly lower (P/0.01) in the treated vesicles than in the controls. Exposure of intestinal tissue to ES products resulted in net secretion (P/0.01) of Na+, C1- and 3-O-methyl-D-glucose. Both observations indicate that alterations in the absorptive functions of the intestine might be attributed to interaction of ES products with the BBM.

Animals↗

Studies on the mechanism of Escherichia coli heat-stable enterotoxin-induced diarrhoea in mice.

The unidirectional fluxes of Na+, Cl- and Ca2+ and activities of calmodulin in the intestinal microvillar core were studied in Escherichia coli heat-stable enterotoxin-treated mice. There was net secretion of Na+ and Cl- in toxin-treated animals, while in control animals there was net absorption of these ions. In both control and experimental animals, there was net absorption of Ca2+; however, the absorption was significantly higher (P less than 0.01) in experimental animals when compared to controls. In the presence of Ca2+-ionophore, there was a net secretion of Na+ and Cl- in controls, while the Ca2+-ionophore could not cause any change in the fluxes of these ions in experimental animals. The activity of calmodulin was significantly higher (P less than 0.01) in experimental animals. Verapamil, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, reversed the effects of Ca2+-ionophore and heat-stable enterotoxin. These studies demonstrate that the toxin acts through Ca2+-calmodulin, and secretion of Na+ and Cl- in experimental animals is due to an increase in calcium absorption and an increase in calmodulin activity in the intestinal microvillar core.

Animals↗

New sensitive markers for the detection of experimental ascending pyelonephritis.

Kinetic parameters (Km and Vmax) of renal brush border membrane (BBM) enzymes alkaline phosphatase, maltase, leucine-aminopeptidase and gamma-glutamyltranspeptidase were used as markers for the early detection of pyelonephritis. Km of all the enzymes studied remained unaltered. The Vmax of all the enzymes studied were found to be significantly decreased (p less than 0.05) 3 or 4 days postinfection and onwards in the left obstructed kidney. The Vmax of alkaline phosphatase and leucine-aminopeptidase was found to be significantly increased (p less than 0.05) in early stages and decreased (p less than 0.05) in later stages of infection in the right unobstructed kidney. No histopathological lesions confirming pyelonephritis could be seen 7 days postinfection in the left kidney and right kidney remained histopathologically unaltered. This demonstrated that BBM enzymes are much earlier disturbed as compared to histopathological changes.

Alkaline Phosphatase↗

Effect of different Giardia lamblia inocula on glucose and amino acids transport in the intestinal brush border membrane vesicles of infected mice.

The transport of D-glucose, L-phenyl-alanine, L-lysine and L-aspartic acid was measured in the brush border membrane vesicles prepared from intestines of Swiss albino mice infected with three different inocula of Giardia lamblia cysts (100, 1,000 and 10,000 cysts). A significantly low uptake of nutrients was observed in the infected animals as compared with the uninfected groups (P less than 0.05). However, the uptake of nutrients did not alter significantly with varying inoculum size. With D-glucose the respective peak uptakes at 30 seconds were 59.3 +/- 5.5, 60.4 +/- 3.8 and 60.5 +/- 4.02 pmoles mg-1 protein, while with L-phenyl-alanine they were 158.1 +/- 8.3, 151.7 +/- 17.3 and 140.7 +/- 6.0 pmoles mg-1 protein. The same trend was observed for L-lysine and L-aspartic acid. Therefore we conclude that inoculum size does not influence the uptake of nutrients.

Amino Acids↗

Antipili antibody affords protection against ascending pyelonephritis in rat: evaluated by renal brush border membrane enzymes.

Kinetic parameters (Km and Vmax) of renal brush border membrane (BBM) enzymes alkaline phosphatase, maltase, leucine aminopeptidase and gamma-glutamyltranspeptidase were worked out in control, infected and immunized-infected rats. There was no significant change in the Km of all the enzymes studied in three groups. The Vmax of all the enzymes studied decreased significantly (p less than 0.05) 3 or 4 days postinfection and onwards in the left obstructed kidney of infected and immunised-infected animals. However, in the right unobstructed kidney the Vmax of alkaline phosphatase and leucine aminopeptidase increased significantly (p less than 0.05) in the early stages and decreased (p less than 0.05) in later stages in both the experimental groups. The significant difference (p less than 0.05) in the Vmax of infected and immunized-infected groups at various stages of infection revealed the partial protective role of antipili antibody against ascending pyelonephritis.

Alkaline Phosphatase↗

Prevention of alterations in the transport of nutrients in pyelonephritic rats by immunization with pili.

The uptake of D-glucose, L-aspartate, L-lysine and L-proline was studied in renal brush border membrane vesicles prepared from control, infected and actively immunized-infected rats. The uptake of D-glucose, L-lysine and L-proline was decreased significantly (p less than 0.05) during the course of infection in the infected animals. However, the uptake of L-aspartate was increased significantly (p less than 0.05) in early stages and decreased significantly (p less than 0.05) in later stages of infection in the infected animals. When the animals were actively immunized with pili, still there were changes in the uptake of D-glucose and L-aspartate, but the changes appeared later and less pronounced. No change in the uptake of L-lysine and L-proline was observed in the immunized-infected animals. The findings demonstrated that active immunization with pili prevents alterations in the uptake of nutrients in pyelonephritic rats.

Animals↗