Biomedical subjects

M Dikshit

Publications and source records attributed to M Dikshit.

At least 55 records · Page 3Linked to original sources

PubMed1998

Prothrombin time in retinitis pigmentosa.

The prothrombin time was recorded for 87 primary retinitis pigmentosa (RP) patients belonging to three different clinical categories. All categories showed prothrombin time higher than normal. There was no correlation between the age of onset and the prothrombin time, nor between duration of disease and the prothrombin time. The high prothrombin time in patients with RP suggests that further study of prothrombin time and related factors may help in better understanding of the pathogenesis of RP.

Adolescent↗

PubMed1997

Alterations in the free radical generation and nitric oxide release from rat peripheral polymorphonuclear leukocytes following thrombosis.

The present investigation was undertaken to study the alterations in free radical generation and release of nitric oxide (NO) from polymorphonuclear leukocytes (PMNLs) following thrombosis. Thrombosis was induced in rats by intravenous injection of collagen and adrenaline. PMNLs were separated from rat blood by using dextran sedimentation and Ficoll-Hypaque. Arachidonic acid (AA), formyl methionine leucine phenylalanine (FMLP) and opsonized zymosan (OZ) induced free radical generation was estimated as luminol (LCL) and Lucigenin (LUCDCL) dependent chemiluminescence. PMNLs nitric oxide synthase (NOS) activity and NO release were measured by using [14C] L-Arginine (L-Arg) and oxy-hemoglobin respectively. LCL and LUCDCL responses in rat PMNLs were significantly attenuated following thrombosis. There was no change in the release of myeloperoxidase enzyme (MPO) from PMNLs obtained following thrombosis. PMNLs NOS activity and NO release were also found to be increased after thrombosis. Pretreatment of rat PMNLs with 10 mM L-NAME (NO precursor) or 100 microM sodium nitroprusside (NO donor), resulted in significant reduction of AA induced LCL response. Results obtained indicate that NO release form PMNLs was augmented while free radical generation response was attenuated after the induction of thrombosis.

Animals↗

PubMed1997

Attenuation in rat brain nitric oxide synthase activity in the coarctation model of hypertension.

The correlation of brain nitric oxide synthase (NOS) activity with renal hypertension has been investigated in rats. NOS activity was measured by oxyhaemoglobin and by conversion of radioactive arginine to citrulline. There was significant elevation of blood pressure (54% increase) along with left ventricular hypertrophy (26% greater than the control) 8 weeks after coarctation. The brain NOS activity was also significantly reduced in coarctated animals (45% of the control value). Treatment with captopril (angiotensin converting enzyme inhibitor) or centhaquin (centrally acting antihypertensive agent) led to significant reduction of left ventricular hypertrophy and a marked recovery in the brain NOS activity (to 92% and 135% of the control, respectively). Nifedipine (a calcium channel blocker) also brought about normalization of blood pressure but the left ventricular hypertrophy was not prevented. The brain NOS activity in the nifedipine treated group also showed a significant trend of recovery (to 73% of the control NOS activity). The results suggested that there is an inverse correlation between brain NOS activity and blood pressure level.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Nitric oxide-dependent blood-brain barrier permeability alteration in the rat brain.

The role of nitric oxide (NO), a well known vasodilator, in the regulation of blood-brain barrier (BBB) permeability is not clear. Therefore, the present study was planned to assess the role of NO-releasing compounds like sodium nitroprusside (SNP) and the active metabolite of molsidomine, SIN-1, as well as a precursor on NO, L-arginine, on this physiological barrier. The permeability was assessed by using several tracers. All three agents increased the permeability of BBB to the tracer. The increase in permeability caused by L-arginine was not blocked by N-nitro-L-arginine methyl ester (L-NAME). L-Arginine-treated brains did not show an elevation of nitrite content, thus ruling out the possibility of NO generation and its involvement in BBB permeability alteration. It is concluded that NO itself causes an increase in the permeability of BBB. However, arginine-induced opening is not NO mediated.

Animals↗

PubMed1996

Interaction of nitric oxide synthase inhibitors and their D-enantiomers with rat neutrophil luminol dependent chemiluminescence response.

1. Formyl-methionyl-leucyl-phenylalanine (FMLP) or arachidonic acid (AA) induced luminol dependent chemiluminescence (LCL) response of rat polymorphonuclear leukocytes (PMNLs) was found to be inhibited by nitric oxide synthease inhibitors and their D-enantiomers. 2. Rat PMNLs LCL response was inhibited by NG-nitro-L-arginine methyl ester (L-NAME), D-NAME, NG-monomethyl-L-arginine (L-NMMA) or D-NMMA, in a concentration- and time-dependent manner. 3. It was observed that both L- and D-enantiomers of the arginine analogues (1000 microM) did not inhibit AA induced lucigenin-dependent chemiluminescence (LUCDCL) response and cytochrome c reduction, used for estimating the NADPH-oxidase activity in the cells and in the cell free system, respectively. 4. None of the L- and D-enantiomers had any effect on either rat basal PMNLs or AA-induced oxygen consumption. 5. In addition, neither the L nor D-enantiomers of NAME altered either AA-induced release or the activity of myeloperoxidase from rat PMNLs azurophilic granules. 6. The results obtained indicate that the attenuation of the LCL response by L- and D-enantiomers of arginine analogues, is a non-specific effect as there was no inhibition of NADPH-oxidase and MPO activity, MPO release or oxygen consumption. Therefore, the data obtained indicate that these agents should be used with caution to analyse the role of nitric oxide in rat PMNLs LCL response.

Animals↗

PubMed1996

Retinitis pigmentosa genetics: a study in Indian population.

A total of 151 retinitis pigmentosa (RP) patients from 83 families were screened and the frequencies of different genetic categories studied. One hundred and ten patients out of 151 had a positive inheritance pattern, and autosomal recessive (AR) emerged as the predominant (53 out of 151), genetic pattern followed by isolated or sporadic (41 out of 151) cases. Further study of autosomal recessive cases revealed consanguinity as the main characteristic (49 out of 53) in the Indian population studied. Early onset and severe progression of disease was seen in the consanguineous group.

Consanguinity↗

PubMed1995

Nitric oxide modulates blood-brain barrier permeability during infections with an inactivated bacterium.

The objective of the present investigation was to study the involvement of NO in regulating the permeability of the blood-brain barrier (BBB) during infections, since NOS is known to be induced following infections. The administration of inactivated Escherichia coli (a source of lipopolysaccharide) or poly (I:C), an interferon inducer, to rats increased the permeability of BBB significantly. This increase was found to be potentiated in the presence of L-arginine, a substrate for NOS, while D-arginine had no such effect. N-nitro L-arginine methyl ester, an inhibitor of NOS, and dexamethasone, an inhibitor of NOS induction, blocked the E. coli-induced effects. These results suggest that during infections, NOS inductions causes the release of large quantities of NO, resulting in increased BBB permeability.

Animals↗

PubMed1995

Status of antioxidants in brain microvessels of monkey and rat.

Levels of certain antioxidants namely reduced glutathione (GSH), ascorbic acid (Vit C), alpha-tocopherol (Vit E) and antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were compared in monkey and rat brain microvessels which constitute the blood-brain barrier (BBB). The BBB of both the species contains appreciable amounts of the antioxidants to protect against oxidative damage. The level of protection in rat seems to be more efficient than monkey since rat microvessels contain higher concentrations of some of the bio-antioxidants. The comparative status of enzymatic and non-enzymatic protective system against oxidation in the brain microvessels has been discussed.

Animals↗

PubMed1995

Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart.

Effect of myocardial ischaemia on the bioantioxidants levels in the cat heart was evaluated. In addition, effect of curcumin, an anti-inflammatory and anti-thrombotic drug, and quinidine, a standard antiarrhythmic drug, was also studied in the cat. Myocardial ischaemia was induced by the ligation of left descending coronary artery. Quinidine (1 mg/kg, iv) was administered 15 min prior to while curcumin (100 mg/kg, ip) was given 30 min before ligation. Hearts were removed 4 h post coronary artery ligation. Levels of glutathione (GSH), malonaldelhyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) were estimated in the ischaemic and non-ischaemic zones. Both the drugs protected the animals against decrease in the heart rate and blood pressure following ischaemia. In the ischaemic zone, after 4 h of ligation, an increase in the level of MDA and activities of MPO and SOD (cytosolic fraction) were observed. Quinidine and curcumin pretreatment prevented the ischaemia-induced elevation in MDA contents and LDH release. Curcumin pretreatment did not prevent the increase in MPO activity while quinidine did. Results obtained indicate alterations in the bioantioxidants following ischaemia and both curcumin and quinidine prevented ischaemia induced changes in the cat heart.

Animals↗

PubMed1994

Effect of platelet activating factor antagonists in different models of thrombosis.

Effect of three specific PAF antagonists, SR-27417, BN-50739 and ginkgolide derivative BN-52021 have been evaluated in models of thrombosis in the mouse, rat and cat. Thrombosis in the mouse was induced by intravenous infusion of collagen and adrenaline. In rats it was induced by inserting a metallic wire into the inferior vena cava. In the cat, thrombus formation was assessed in the extracorporeal shunt. All the antagonists offered a dose-dependent protection against pulmonary thromboembolism in mice (1, 3 and 10 mg/kg) and the thrombosis monitored in the extracorporeal shunt in cats (0.3, 1 and 3 mg/kg). In rats, no significant protection was observed with these antagonists even at the highest dose used.

Animals↗

PubMed1994

Modulation of rat peripheral polymorphonuclear leukocyte response by nitric oxide and arginine.

The effect of nitric oxide (NO) on the luminol-dependent chemiluminescence (LCL) response of rat polymorphonuclear leukocytes (PMNLs) was analyzed by using sodium nitroprusside (SNP), a NO donor, and L-arginine (L-arg), a NO precursor. A significant reduction in the LCL intensity was observed in presence of SNP (100 mumol/L) or L-arg (5 or 10 mmol/L) in arachidonic acid (AA) phorbol ester (PMA) and formyl-methionyl-leucyl-phenylalanine stimulated PMNLs. However, opsonized zymosan-induced LCL was not attenuated significantly. Reduction in hydroxyl radical and superoxide generation was also observed in SNP- or L-arg-pretreated cells. D-Arg (10 mmol/L) pretreatment did not inhibit PMNLs' LCL response. Furthermore, methylene blue (5 mumol/L) and L-NG-mono methyl-L-arginine (100 or 300 mumol/L) significantly attenuated the LCL response, as induced by various agonists. Cyclic GMP did not alter the reactive oxygen species generation from rat PMNLs. In addition, AA-induced release of myeloperoxidase, a marker of azurophilic granules, was found to be enhanced in L-arg- (10 mmol/L) pretreated PMNLs. The results suggest that NO inhibits free radical generation from rat PMNLs.

Animals↗

PubMed1994

Alterations in the bioantioxidants following thrombosis.

The role of free radicals in rat thrombosis has been demonstrated by studying its scavenging enzyme system. Changes in the bio-antioxidants (GSH-redox cycle, total thiol groups, vitamins E and C) that also offer protection against the free radicals, have, however, not been studied so far. This investigation was undertaken to understand the involvement of these antioxidants during thrombosis. The tissues investigated following thrombosis were blood, platelets, polymorphonuclear leukocytes (PMNLs), heart, and lung. Glutathione (GSH) content in the platelets was observed to be depleted. However, oxidized glutathione (GSSG) contents in the platelets, PMNLs, and blood remain unaltered. In addition, in the whole blood GSH levels were increased significantly, whereas there was no change in the GSSG level. Activity of glutathione reductase (GR) was decreased significantly in platelets and lungs with an increase in the total thiol groups in the lung homogenate. Activity of Glutathione peroxidase (Gpx) remained unaltered in all the tissues studied. In addition, 24% and 15% decrease in the alpha-tocopherol concentration was observed in thrombocytes and PMNLs, respectively, with no change in the ascorbate levels in these cells. Results of this investigation suggest alterations in the GSH-redox cycle in blood, platelets, and lung after thrombosis in the rat.

Animals↗

PubMed1993

Effect of molsidomine and free radical scavengers on the pulmonary thromboembolism in mice.

Molsidomine is a prodrug of nitric oxide (NO) and is used in the treatment of coronary heart disease. Recent studies with NO have shown that it can exert beneficial as well as toxic effects. It was, therefore, considered desirable to evaluate the effect of this drug in an animal model of thrombosis. It was administered to mice, one hour prior to the thrombotic challenge, in a dose range of 1 to 100 mg/kg ip. In lower doses (1-30 mg/kg), it offered protection by 24-38%, and at 50 and 100 mg/kg it protected 54% and 58% animals respectively. Mice pretreated with molsidomine (3, 10 and 30 mg/kg) and free radical scavengers (superoxide dismutase, catalase, mannitol and deferoxamine, suboptimal doses) together offered significantly more protection against thrombosis than either one of them alone. The results suggest that a combination of molsidomine and free radical scavengers should be more effective than molsidomine alone in the treatment of thrombosis and other ischemic disorders.

Animals↗

PubMed1993

Free radical scavenging mechanisms during pulmonary thromboembolism in rats.

In the present investigation alterations in the free radical generating and scavenging enzymes in platelets, neutrophils (PMNLs), heart and lung homogenates following rat pulmonary thromboembolism have been studied. Thrombosis was induced by intravenous infusion of collagen and adrenaline. Levels of malonaldehyde (MDA) were elevated in the PMNLs after thrombosis. Activities of superoxide dismutase (SOD) and catalase (CAT) were found to increase in platelets and PMNLs respectively. However, there was no significant alteration in the lactate dehydrogenase (LDH), lysozyme (LYS), ratio of xanthine oxidase to dehydrogenase (XO/XH) and PMNLs O2- generation before and after thrombosis. Migration of PMNLs following thrombosis was indicated by increased activity of myeloperoxidase (MPO) in the heart. In addition, pretreatment with allopurinol, a xanthine oxidase inhibitor and indomethacin, a cyclooxygenase inhibitor offered protection against thromboembolism induced death/paralysis. Results suggest the involvement of free radicals in thrombosis.

Allopurinol↗

PubMed1993

Alterations in free radical scavenging mechanisms following blood-brain barrier disruption.

It has been reported earlier that rat microvessels which constitute the blood-brain barrier (BBB) are rich in free radical scavenging enzymes. In the present investigation, BBB of rat was disrupted by intravenous infusion of the hypertonic saline and changes in enzymes--namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR)--were evaluated in the brain microvessels at 30 min after the intravenous administration of hypertonic saline, being the time of peak effect. There was a significant increase in the activities of CAT (40%), GPx (26%), and SOD (16%) over the control values. In addition, within 90 min BBB was found to be reestablished and the levels of enzymes reverted to normal. Malondialdehyde (MDA) levels and activity of lactate dehydrogenase (LDH) remained unaltered during and following disruption, suggesting that there was no change in the membrane lipid environment. Similarly, there was no cell lysis. The results suggest that the disruption of BBB following hypertonic saline administration might be due to an increase in the generation of free radicals in the brain microvessels.

Animals↗

PubMed1993

Centpropazine affinity to cortical noradrenergic receptors and effect on their responsiveness in the rat.

We have studied the in-vitro effect of centpropazine on cerebral cortical noradrenergic receptors measured as the accumulation of second messengers, cyclic AMP and inositol phosphate, stimulated by noradrenaline, and the binding to alpha 1- and beta-adrenoceptors. Centpropazine inhibited inositol phosphate, but not the cyclic AMP accumulation in the cerebral cortical slices of the rat. It moderately antagonized the specific binding of [3H]prazosin, but did not affect the specific binding of the beta-adrenoceptor ligand, [3H]CGP 12177, to cerebral cortical membranes.

Adrenergic beta-Antagonists↗

PubMed1993

Pulmonary thromboembolism-induced alterations in nitric oxide release from rat circulating neutrophils.

We have earlier reported that neutrophils play an important role in pulmonary thromboembolism. The effect of circulating polymorphonuclear leukocytes (PMNL) isolated from normal and thrombotic rats was, therefore, studied on platelet aggregation in platelet-rich plasma. PMNL inhibited the platelet aggregation in a concentration- and time-dependent manner at 37 degrees C. The platelet aggregation inhibitory response of PMNL was more pronounced in the presence of superoxide dismutase and was abolished by hemoglobin and methylene blue. These observations suggested that the inhibitory effect of PMNL on platelets was mediated by neutrophil-derived relaxing factor. PMNL, obtained after thromboembolism, inhibited the platelet aggregation response more strongly due to an increased release of nitric oxide from them. It is suggested that PMNL play an important role in the regulation of hemostasis.

Adenosine Deaminase↗

PubMed1992

Effect of pulmonary thromboembolism on circulating neutrophils in mice.

The role of free radical generation and its scavenging enzymes in circulating mice polymorphonuclear leukocytes (PMNLs) has been studied following pulmonary thromboembolism. Levels of malonaldehyde (MDA), 02- radical generation, activity of superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), myeloperoxidase (MPO) and lysozyme were estimated in lysed neutrophil preparations. Activities of SOD and CAT were increased in neutrophils, while animals showed 60 +/- 4% thrombocytopenia. Levels of MDA in PMNLs were also elevated significantly following thrombosis. However, there was no significant change in superoxide radical generation, after thrombotic challenge, in mice neutrophils. The present study provides evidence for the involvement of free radicals in mice pulmonary thromboembolism.

Animals↗