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Biomedical subjects

N Kaul

Publications and source records attributed to N Kaul.

29 records · Page 2Linked to original sources

Serologic markers of gluten-sensitive enteropathy in bullous diseases.

BACKGROUND AND DESIGN: Dermatitis herpetiformis (DH) is characterized immunologically by the presence of IgA immune deposits in the skin and by the presence of various serum antibodies. Of these, antibodies to gliadin, reticulin, and endomysium have been found to be significant. There are, however, conflicting reports as to the exact specificity and sensitivity of these serologic markers in diagnosing DH. We examined the disease specificity of these three antibody markers in 14 patients with DH, in 98 patients with pemphigus and pemphigoid, and in 26 normal subjects. Reticulin and endomysium antibodies were detected by indirect immunofluorescence and gliadin antibodies by means of the enzyme-linked immunosorbent assay method. RESULTS: Among the various bullous diseases, endomysial and reticulin antibodies were found to be disease specific for DH. Endomysial antibodies occurred in twice the number of DH patients (72%) compared with the occurrence of reticulin antibodies (36%). Antigliadin antibodies were detected in two thirds of DH patients and were not disease specific since increased frequencies of these antibodies were also detected in patients with pemphigus and pemphigoid. CONCLUSION: These studies support the earlier findings of the high degree of specificity of endomysial antibodies for DH and, thus, help to differentiate DH from other bullous disorders.

Antibodies↗

Collagen-stimulated superoxide production: evidence for coupled mobilization of calcium.

Superoxide production by human neutrophils was stimulated by rat liver collagen. The stimulation was exponentially related to the collagen concentration, with maximal effect at 150 micrograms/ml. The collagen-induced effect was significantly enhanced by the presence of Ca2+ in the medium. Verapamil--a calcium channel blocker--caused a dose-dependent inhibition of superoxide production by collagen-stimulated neutrophils. Collagen-induced stimulation was associated with a transient rise in cytosolic free Ca2+ independent of the presence of Ca2+ in the medium. Depletion of intracellular calcium caused a significant decrease in superoxide activity; however, replenishment of Ca2+ in the medium significantly overcame the inhibition. These changes were associated with a direct binding of [14C]collagen with the neutrophils. Our data suggest that collagen-neutrophil interaction couples superoxide production with the process of Ca2+ mobilization and that this interaction may play a physiologic role in neutrophil stimulation.

Animals↗

Effect of nifedipine on Leishmania donovani infection in-vivo and in-vitro: chemiluminescence responses of peritoneal macrophages and neutrophils.

After peritoneal macrophages had been exposed to different concentrations of nifedipine (10-120 ng mL-1) there was a significant increase (P less than 0.001) in the percentage of Leishmania donovani infected macrophages compared with controls. Parasite load was also significantly increased (P less than 0.001) in nifedipine-treated, L. donovani infected, BALB/c mice, compared with untreated, infected mice, post-inoculation. Peak chemiluminescence responses were significantly depressed (P less than 0.001) in nifedipine-treated infected mice compared with untreated mice post-inoculation. It is suggested that availability of intracellular calcium is a factor in the defense mechanism of inflammatory cells in L. donovani infections.

Animals↗

Standardization of ELISA for the detection of anti-cardiolipin antibodies--effect of non-specific IgG binding.

Various frequencies of anti-cardiolipin antibodies reported in patients with systemic lupus erythematosus and other autoimmune and infectious diseases necessitates the need for standardization of the immunoassay. We report here the usefulness of "no-antigen" control for each serum in determining the actual value of the anti-phospholipid antibodies. This non-specific "no-antigen" binding was quite variable from serum to serum and in general was higher in the patient population than in healthy individuals which served as controls. This non-specific binding may be associated with the increased IgG content of the sera as shown by the linear association of the absorbance of the back-ground readings to increases in IgG concentration (correlation coefficient 0.98).

Antigen-Antibody Reactions↗

Neutrophil oxygen free radical production proportionates with the degree of myocardial ischemia.

OBJECTIVE: To assess the production of oxygen free radicals by chemiluminescence and to assess leukocyte aggregation, in patients with acute myocardial infarction and angina pectoris, and to compare these to creatine kinase-MB levels. DESIGN: Prospective study with serial estimation at presentation and 72 h later. SETTING: Referral, tertiary care hospital. PATIENTS: Group 1, acute myocardial infarction (n = 18); group 2, stable angina pectoris (n = 8); and age-and sex-matched normal healthy persons (n = 12). All patients included had pain of less than 24 h duration with typical electrocardiographic and laboratory abnormalities. Patients or controls who had any inflammatory disease in the preceding two weeks or who were on anti-inflammatory drugs, calcium channel or beta-adrenoceptor blockers, were excluded. TESTS: Venous blood samples taken at presentation and 72 h later were analyzed for creatine kinase-MB using a standard kit, neutrophilic chemiluminescence and leukocyte aggregation. MAIN RESULTS: In group 1 there were significant rises in both creatine kinase-MB and chemiluminescence, which subsequently regressed (P less than 0.02). There was, however, no statistical correlation between the two. The qualitative pattern of the rise and fall of chemiluminescence was similar in group 2. Changes in leukergy in both groups were not significant. CONCLUSIONS: Oxygen free radical generation occurs early in myocardial ischemia with regression by 72 h. Neutrophilic chemiluminescence may provide an alternative method for assessment of myocardial ischemia.

Cell Aggregation↗

Altered calcium homeostasis in carbon tetrachloride exposed rat hepatocytes.

In situ perfusion of rat liver with carbon tetrachloride (10-15 mM at a final concentration of lul/ml of mineral oil) resulted in a significant (p less than 0.01) loss of microsomal Ca2+ over 5-15 min of exposure. Mitochondrial Ca2+ content increased sharply (2 fold) with concomitant increase in the cytosolic free Ca2+. The changes were associated with a significant (p less than 0.01) decrease in plasma membrane Ca2+ - ATPase activity, reflected by impaired Ca2+ efflux and Ca2+ exchange properties. Our data indicates that impairment of plasma membrane Ca2+ flux contributes substantially to the overall disruption of calcium homeostasis induced by carbon tetrachloride.

Animals↗

Probucol treatment reverses antioxidant and functional deficit in diabetic cardiomyopathy.

Earlier we reported that probucol treatment subsequent to the induction of diabetes can prevent diabetes-associated changes in myocardial antioxidants as well as function at 8 weeks. In this study, we examined the efficacy of probucol in the reversal of diabetes induced myocardial changes. Rats were made diabetic with a single injection of streptozotocin (65 mg/kg, i.v.). After 4 weeks of induction of diabetes, a group of animals was treated on alternate days with probucol (10 mg/kg i.p.), a known lipid lowering agent with antioxidant properties. At 8 weeks, there was a significant drop in the left ventricle (LVSP) and aortic systolic pressures (ASP) in the diabetic group. Hearts from these animals showed an increase in the thiobarbituric acid reacting substances (TBARS), indicating increased lipid peroxidation. This was accompanied by a decrease in the myocardial antioxidant enzymes activities, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). Myocardial catalase activity in the diabetic group was higher. In the diabetic + probucol group both LVSP and ASP showed significant recovery. This was also accompanied by an improvement in SOD and GSHPx activities and there was further increase in the catalase activity. Levels of the TBARS was decreased in this group. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit which can be reversed with probucol treatment. Improved cardiac function with probucol may be due to the recovery of antioxidants in the heart.

Animals↗

Significance of adaptation mechanisms in adriamycin induced congestive heart failure.

Natural history of myocardial dysfunction due to chronic contractile deficit consists of physiological and pathophysiological adaptations culminating in congestive heart failure. Among the mechanisms considered is the combination of compensatory as well as the harmful overcompensatory role of the adrenergic system during the genesis of a congestive heart failure "spiral" due to the chronic treatment with adriamycin. Refractoriness of this spiral to various inotropic agents may involve reduced sympathetic support of the myocardium, structural loss of contractile elements and abnormalities of the Ca2+ metabolism.

Adaptation, Physiological↗

Oxygen free radicals and protective effect of captopril on myocardial infarct size.

Captopril (0.25 mg/kg and 0.5 mg/kg, p.o.) decreased the myocardial infarct size and prevented the progressive decrease in voltage of the R wave in rats. It had no marked effect on systolic blood pressure at these dose levels but higher doses (1 mg/kg, p.o.) reduced systolic blood pressure. It also produced a concentration-dependent (50-700 ng/10(6) cells) decrease of chemiluminescence response from rat neutrophils and markedly reduced serum malonyldialdehyde levels, elevated as a consequence of left coronary artery ligation. It is suggested that the protective effect of captopril may be mediated through a decreased formation or scavenging of reactive oxygen species.

Animals↗

Probucol improves antioxidant activity and modulates development of diabetic cardiomyopathy.

To examine the role of free radicals in diabetic cardiomyopathy, myocardial antioxidants as well as lipid peroxide content were examined in rats made diabetic with a single injection of streptozotocin (65 mg/kg i.v). At 4 wk, the left ventricular peak systolic (LVSP) as well as aortic pressures were depressed in the diabetic group. Hearts from diabetic animals showed about a 100% increase in thiobarbituric acid reactive substances (TBARS), indicating increased lipid peroxidation. This was accompanied by about a 50% decrease in superoxide dismutase (SOD) and 60% decrease in glutathione peroxidase (GSHPx) enzyme activities. Catalase activity in these hearts showed a small but significant increase. Treatment with probucol (10 mg/kg i.p., on alternate days), a known lipid-lowering drug with strong antioxidant properties, was initiated 1 d after the induction of diabetes and was continued for 4 wk. In probucol-treated diabetic animals, LVSP was not different from controls. Probucol treatment caused a small but significant improvement in serum insulin and decrease in glucose levels as well as increased myocardial SOD, GSHPx, and catalase activities with a concomitant decrease in TBARS in the diabetic animals. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit, and a better cardiac function due to treatment with probucol may be related to the improved insulin levels as well as maintenance of the antioxidant status of the heart.

Animals↗