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Biomedical subjects

N Kaul

Publications and source records attributed to N Kaul.

At least 19 recordsLinked to original sources
PubMed2002

Vitamin E and carotene status in pre-eclamptic pregnant women from India.

BACKGROUND: The imbalance between oxidative stress and the protective antioxidant system of the body enhanced the free radical mediated membrane lipid peroxidation and possibly the vascular endothelial damage due to peroxidation plays a major role in the aetiology of pre-eclampsia. With present day awareness on micronutrient antioxidants, we did investigate vitamin E and carotene status in Indian pre-eclamptic pregnant and full term normotensive pregnant women. Fresh vegetables and oils are considered to be good sources of vitamin E and carotene. The subjects were used to have good intake of fresh vegetable and oil as per Indian standard prescribed by Indian council of Medical research (ICMR) for this sub-continent. METHODS: The blood samples were processed for RBC vitamin E, serum carotene and serum cholesterol analysis. Routine laboratory tests like hemogram, serum urea, urate, malonyldialdehyde, urine sugar and albumin were performed. RESULTS: All pregnant subjects, both cases and control were maternal and gestational age matched. Routine check up showed no significant differences in means of white blood cell count, Hb/hematocrit and platelets. Serum urate and malonyldialdehyde were significantly raised in pre-eclamptic cases. The severely affected pre-eclamptic cases (diastolic BP >100 mmHg with proteinuria 2+ and more) showed markedly low levels of vitamin E and carotene whereas their levels were comparable between mild cases (diastolic BP <100 mmHg with+/-trace albuminuria) and normotensive pregnant control. CONCLUSIONS: The study concluded that the levels of vitamin E and carotene were markedly lowered in severe pre-eclamptic pregnant women from India. The mild pre-eclamptic cases did not show noticeable changes from that of control pregnant women. Further studies are needed to verify their therapeutic and prophylatic roles against pre-eclamptic complication suring pregnancy.

Adult↗
PubMed2001

The effect of alpha-tocopherol on monocyte proatherogenic activity.

Atherosclerosis is the leading cause of morbidity and mortality in Westernized populations. The monocyte is a crucial cell in the genesis of the atherosclerotic lesion and is present during all stages of atherosclerosis. alpha-Tocopherol (AT) is the most active component of the vitamin E family and is the principal and most potent lipid-soluble antioxidant in plasma and LDL. With regard to monocyte function, AT supplementation (1200 IU/d) has been shown to decrease release of reactive oxygen species, lipid oxidation, release of cytokines such as interleukin-1ss (IL-1ss) and tumor necrosis factor-alpha (TNF-alpha) and decrease adhesion of monocytes to human endothelium. The mechanism of inhibition of superoxide and lipid oxidation by monocytes appears to be via inhibition of protein kinase C (PKC), the decrease in IL-1ss and TNF-alpha release by inhibition of 5-lipoxygenase and the inhibition of monocyte-endothelial cell adhesion via decrease in adhesion molecules on monocytes, CD11b and VLA-4 and by decreasing DNA-binding activity of nuclear transcription factor kappaB. Thus, in addition to the decrease in oxidative stress resulting from AT supplementation, as evidenced by decreased F(2)-isoprostanes and LDL oxidizability, AT is anti-inflammatory and exerts beneficial antiatherogenic effects on cells crucial in atherogenesis such as monocytes.

Animals↗
PubMed2001

Alpha-tocopherol and atherosclerosis.

Cardiovascular disease is the leading cause of morbidity and mortality in the Western world. There is compelling evidence incriminating oxidative stress in the pathogenesis of the atherosclerotic lesion. Several lines of evidence suggest that antioxidants, especially alpha-tocopherol, have potential beneficial effects with regard to cardiovascular disease. In vitro, alpha-tocopherol has been shown to inhibit platelet adhesion and aggregation and smooth muscle cell proliferation, exert anti-inflammatory effects on monocytes, and improve endothelial function. Also, supplementation with alpha-tocopherol has been shown to decrease lipid peroxidation, platelet aggregation, and pro-inflammatory activity of monocytes. However, clinical trials with alpha-tocopherol supplementation to date have been equivocal. Thus, although mounting in vitro evidence and animal models provide a sound scientific basis for alpha-tocopherol supplementation, further clinical trials are required before a definitive recommendation can be made with respect to the primary and secondary prevention of heart disease.

Animals↗
PubMed1998

Role of protein kinase C in basal and hydrogen peroxide-stimulated NF-kappa B activation in the murine macrophage J774A.1 cell line.

In macrophages, hydrogen peroxide appears to be a physiological activator of the transcription factor, nuclear factor kappa B (NF-kappa B); however, the molecular basis of H2O2-stimulated NF-kappa B activation is not well defined. The observations that NF-kappa B can be activated in cells by phorbol 12-myristate 13-acetate and in vitro by addition of protein kinase C (PKC) are suggestive of a role of PKC in NF-kappa B activation, which was investigated in the J774A.1 murine macrophage cell line. Basal NF-kappa B DNA-binding activity and nuclear localization were decreased by PKC inhibitors. Although PKC activity was modified by H2O2 with a similar time course as H2O2 activation of NF-kappa B, the H2O2-stimulated increase in NF-kappa B DNA binding and translocation to the nucleus was unaffected by PKC inhibitors. Furthermore, PKC down-regulation (through preincubation with phorbol esters) also affected only baseline NF-kappa B DNA binding but not H2O2-stimulated NF-kappa B activation. Buffering of changes in intracellular free calcium concentration also had no effect upon H2O2-stimulated NF-kappa B activation. Thus, classical PKC activity may modulate basal NF-kappa B activity but does not participate in H2O2-stimulated NF-kappa B activation.

Animals↗
PubMed1998

Transmembrane redox signaling activates NF-kappaB in macrophages.

In macrophages, NF-kappaB can be activated by H2O2 generated by the respiratory burst or added exogenously. The mechanism of H2O2 signaling may involve changes in the cellular redox state or a redox reaction at the plasma membrane; however, the site of H2O2 action cannot be readily ascertained because of its membrane permeability. Ferricyanide, a nonpermeable redox active anion, activated NF-kappaB in the macrophage cell line, J774A.1. In contrast with exogenous H2O2, activation by ferricyanide did not correlate with net oxidation of NAD(P)H or glutathione, suggesting that a transplasma membrane redox reaction itself was the first signaling process in NF-kappaB activation.

Animals↗
PubMed1996

Activation of NF kappa B by the respiratory burst of macrophages.

H2O2 and other reduced oxygen species have been proposed as activators of the transcription factor, NF Kappa B. Stimulated macrophages produce superoxide and H2O2 (the respiratory burst). We tested the hypothesis that production of these species could serve as part of the NF Kappa B activation pathway in rat alveolar macrophages and the J774A.1 mouse monocyte/macrophage cell line. Phorbol myristate acetate (PMA) and ADP, which stimulate the respiratory burst, caused NF Kappa B activation in both cells. Catalase abolished NF kappa B activation, while superoxide dismutase produced little inhibition. Thus, H2O2 was the principal agent of respiratory burst-associated NF kappa B activation. Abolition of NF kappa B activation by catalase also suggested that intermediate signaling pathways, such as protein kinase C activation or intracellular free calcium elevation must not be involved. Exogenous H2O2 added as a bolus > or = 50 microM (> or = 50 nmol/10(6) macrophages) also activated NF kappa B in macrophages. Nevertheless, the maximum endogenous production of H2O2 by stimulated alveolar macrophages during a 30-min incubation was < or = 1.3 nmol H2O2/10(6) cells for PMA stimulation and < or = 0.2 nmol H2O2/10(6) cells for ADP stimulation. Thus, relatively little endogenous H2O2 generation was required to produce NF kappa B activation compared to the required amount of exogenous H2O2. As H2O2 rapidly diffuses and is consumed, these results suggest that the site of action for endogenously generated H2O2 is probably close to its origin, the plasma membrane.

Adenosine Diphosphate↗
PubMed1996

Clinical significance of glycosylated haemoglobin (HbA1C) over fasting blood sugar for monitoring metabolic control in diabetic patients with or without complications.

Glycosylated haemoglobin was studied in 30 cases of mild to severe diabetes in the age group 12-60 years. Ten patients were keto-acidotic. Glycosylated haemoglobin and fasting blood sugar levels were studied in patients with various complications of diabetes like neuropathy, nephropathy, retinopathy, keto-acidosis, cardiac and respiratory complications. There was a significant correlation between fasting blood sugar and glycosylated haemoglobin in normal subjects as well as in diabetic patients. There was a significant correlation between levels of glycosylated haemoglobin and blood sugar over preceding 4-6 weeks. Most frequent complication being retinopathy and keto-acidosis was associated with maximum glycosylated haemoglobin with poor metabolic control.

Adolescent↗
PubMed1995

Hydrogen peroxide changes in ischemic and reperfused heart. Cytochemistry and biochemical and X-ray microanalysis.

Active oxygen species including hydrogen peroxide (H2O2) play a major role in ischemia-reperfusion injury. In the present study, changes in myocardial H2O2 content as well as its subcellular distribution were examined in rat hearts subjected to ischemia-reperfusion. Isolated perfused rat hearts were made globally ischemic for 20 or 30 minutes and were reperfused for different durations. H2O2 content in these hearts was studied biochemically and changes were correlated with the recovery of function. These hearts were also analyzed for subcellular distribution of H2O2. Optimal conditions of tissue processing as well as incubation medium were established for reacting cerium chloride with H2O2 to form cerium perhydroxide, an insoluble electron-dense product. The chemical composition of these deposits was confirmed by x-ray micro-analysis. Global ischemia caused complete contractile failure in minutes and after 30 minutes of ischemia, these was a > 250% increase in the myocardial H2O2 content. Depressed contractile function recovery in the early phase of reperfusion was accompanied by approximately a 600% increase in the myocardial H2O2 content. Brief pre-fixation with low concentrations of glutaraldehyde, inhibition of alkaline phosphatase, glutathione peroxidase, and catalase, post-fixation but no post-osmication, and no counterstaining yielded the best cytochemical definition of H2O2. In normal hearts, extremely small amounts of cerium hydroperoxide precipitates were located on the endothelial cells. X-ray microanalysis confirmed the presence of cerium in the reaction product. Ischemia resulted in a stronger reaction, particularly on the sarcolemma as well as abluminal side of the endothelial cells; and upon reperfusion, cerium precipitate reaction at these sites was more intense. In the reperfused hearts, the reaction product also appeared within mitochondria between the cristae as well as on the myofibrils, but Z-lines were devoid of any precipitate. The data support a significant increase in myocardial H2O2 during both the phase of ischemia and the first few minutes of reperfusion. A stronger reaction on the sarcolemma and abluminal side of endothelial cells may also indicate enhanced H2O2 accumulation as well as vulnerability of these sites to oxidative stress injury.

Animals↗
PubMed1994

Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats.

BACKGROUND: The potential usefulness of adriamycin (ADR) is restricted because of its cardiotoxic side effects. Since free radicals and lipid peroxidation are suggested to be involved in ADR cardiomyopathy, we examined the beneficial effects of probucol, a lipid-lowering drug with strong antioxidant properties. METHODS AND RESULTS: ADR was administered to rats in six equal intraperitoneal injections over a period of 2 weeks (cumulative dose of 15 mg/kg). After a 3-week posttreatment period, cardiomyopathy and congestive heart failure were characterized by ascites, congested liver, depressed cardiac function, elevated left ventricular end-diastolic pressure, and myocardial cell damage. Myocardial glutathione peroxidase (GSHPx) activity was decreased, and lipid peroxidation was increased. Probucol (cumulative dose, 60 mg/kg IP) was administered in six equal injections over a 2-week period on days alternating with ADR treatment. Probucol significantly attenuated the myocardial effects of ADR, improved left ventricular function, and lowered mortality as well as the amount of ascites. Treatment with probucol was also accompanied by an increase in myocardial GSHPx and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation. CONCLUSIONS: These data provide evidence that ADR cardiomyopathy is associated with an antioxidant deficit. Improved cardiac function resulting from treatment with probucol may be related to the maintenance of the antioxidant status of the heart. The study suggests potential usefulness of antioxidant (probucol) therapy in ADR cardiomyopathy.

Animals↗
PubMed1993

Effect of nifedipine administration on the functional capacity of neutrophils.

Administration of nifedipine to mice over a period of six months caused a significant (p < 0.05) decrease in neutrophilic functions viz superoxide generation, coupled to NADPH oxidase activity as well as NADPH production by HMP shunt. Properties like chemotaxis and phagocytosis showed a similar decrease. From this study, it is seen that nifedipine causes neutrophil functional abrogation which is therefore an apparent concern for the prolonged usage of the drug. However, relevance of the mouse model to clinical situation needs further investigation.

Animals↗
PubMed1993

Free radicals and the heart.

Because of the molecular configuration, most free radicals are highly reactive and can cause cell injury. Protective mechanisms have evolved to provide defense against free-radical injury. Any time these defense systems are overwhelmed, such as during disease states, cell dysfunction may occur. In this review we discuss cellular sources as well as the significance of free radicals, oxidative stress, and antioxidants. A probable role of oxidative stress in various cardiac pathologies has been also analyzed. Although some methods for the detection of free radicals as well as oxidative stress have been cited, better methods to study the quantity as well as subcellular distribution of free radicals are needed in order to understand fully the role of free radicals in both health and disease.

Animals↗
PubMed1992

Decrease of myocardial infarct size with desferrioxamine: possible role of oxygen free radicals in its ameliorative effect.

The ability of an iron chelator, desferrioxamine, to inhibit the infarct size in in vivo rat heart was assessed. Anaesthetised rats were subjected to coronary artery ligation (CAL) for 72 hr and infarct size was measured macroscopically using TTC staining. Systolic blood pressure and ECG were monitored. Desferrioxamine (10 mg/kg and 20 mg/kg i.v.) administered half an hour after CAL markedly reduced the infarct size. However, drug treatment did not alter the systolic blood pressure of animals. In addition, desferrioxamine in vitro and in vivo demonstrated an inhibition of rat PMN-evoked and luminol-enhanced chemiluminescence. The capacity of desferrioxamine to impair the generation or to scavenge directly oxygen free radicals may be responsible for its beneficial effect on myocardial infarct size in rats.

Animals↗
PubMed1992

Intracellular cAMP determines the extent of degradation and not the synthesis of collagen by rat hepatocytes.

Intracellular collagen degradation in normal rat hepatocytes was exponentially stimulated by db-cAMP (10-100 microM). The effect was manifested as a decrease (p less than 0.01) in net collagen production. The extent of degradation directly co-related with the intracellular cAMP levels, only up to a threshold concentration (16.2 +/- 1.3 p moles/10(6) cells) elicited by 100 microM of db-cAMP. Higher concentrations induced no further increment. Forskolin adenylate cyclase activator (10-50 microM), produced similar effects demonstrating cAMP dependence of the phenomenon. Both db-cAMP as well as Forskolin stimulated collagen degradation (p less than 0.05) in hepatocytes from rats administered CCL4. However, the extent of stimulation was significantly (p less than 0.01) less compared to that observed in normal hepatocytes. Our data demonstrates that elevated cAMP levels regulate net collagen content by signalling intracellular collagen degradation and not synthesis.

Animals↗
PubMed1992

Oxygen free radicals in essential hypertension.

Membrane abnormalities in essential hypertensives (EH) are well known. The respiratory burst enzyme, NADPH oxidase is located in the cell membrane of the neutrophil (PMNLs) and its activity is important in generation of oxygen derived free radical (OFR). Recently OFR have been implicated in vascular changes in variety of conditions. An attempt was made to delineate the status of OFR and antioxidants in EH. Ten, age and sex-matched, healthy controls (GpI) and 26 untreated EH (Gp IIA mild-8, Gp IIB Moderate-8, Gp IIC Severe-10) were studied. After clinical examination and basic laboratory evaluation of subjects, neutrophils isolated from their blood were studied. Chemiluminescence (CL) emitted by PMNLs after stimulation was measured (counts/min) in a luminometer and was taken as measure of OFR production and thereby of NADPH oxidase activity. The levels of antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH), were also estimated. Chemiluminescence was increased significantly (p less than 0.01) in Gp IIC (243.04 +/- 24.9 x 10(3) counts per minute) as compared to Gp IIA (2.80 +/- 1.87), Gp IIB (34.54 +/- 30.24) and Gp I (0.52 +/- 0.15) and SOD was reduced significantly (p less than 0.05) in all EH (Gp IIA 3.9 +/- 0.3 units per mg protein, Gp IIB 3.5 +/- 0.3 and Gp IIC 3.12 +/- 0.3) as compared to controls (4.1 +/- 0.2). Similarly GSH was reduced (p less than 0.05) in EH (Gp IIA 11.2 +/- 1.7 mg per gm protein, Gp IIB 8.5 +/- 1.1 and Gp IIC 6.6 +/- 0.3) as compared to Gp I (13.5 +/- 2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

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↗