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Biomedical subjects

M Dikshit

Publications and source records attributed to M Dikshit.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nitrite content and antioxidant enzyme levels in the blood of schizophrenia patients.

RATIONALE: Recent studies have suggested augmentation in the inflammatory response as well as involvement of nitric oxide (NO) in mood disorders. Polymorphonuclear leukocytes (PMN), NO and free radicals have been associated with inflammatory response; however, the status of NO in the PMN has not been investigated so far in schizophrenia patients. OBJECTIVES: The present study was undertaken to investigate levels of nitrite (a metabolite of NO), malonaldehyde (MDA, lipid peroxidation product) and antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (Gpx) in the PMN of schizophrenia patients. METHODS: Patients with schizophrenia (n=62) were diagnosed according to DSM-IV and were free of anti-psychotic medications/ECT for at least 3 months. Mean age of the patients was 29.06+/-1.17 years, with a male to female ratio of 4:1, and mean duration of illness was 3.7+/-0.6 years. The control group consisted of 82 healthy subjects with a mean age of 37.0+/-1.26 and a male to female ratio of 5:1. PMN were isolated from the blood. Nitrite, MDA and antioxidant enzymes were estimated by standard biochemical techniques in the PMN of normal healthy controls and schizophrenia patients. Platelet and plasma nitrite levels were also estimated in controls and schizophrenia patients. RESULTS: Nitrite content in the PMN was reduced to 68%, while plasma and platelet nitrite content in schizophrenia patients was not significantly changed in comparison to controls. Malonaldehyde (MDA) content in PMN was significantly augmented in schizophrenia patients but activity of SOD, catalase and Gpx remain unaltered. CONCLUSION: Results obtained indicate a significant decrease in NO synthesis and an increase in MDA in the PMN of schizophrenia patients, while antioxidant enzyme activities were not altered in the PMN of schizophrenia patients. This suggests that the decrease in PMN NO synthesis by PMN might lead to oxidative stress in schizophrenia patients.

Adolescent↗
PubMed2001

Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives as potential antithrombotic agents.

A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best (r > 0.8) with electronic parameters (F, sigma or mu) having high statistical significance > 99.9% (F(2,22)>15.0; F(2,22alpha:0.001)=11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.

Animals↗
PubMed2001

Platelet 3H ketanserin binding in migraine.

Platelet 3H ketanserin binding was studied in 33 patients of migraine and 30 healthy controls. The binding characteristics: equilibrium dissociation constant (Kd) and maximal number of binding sites (Bmax) determined by Scatchard analysis revealed a significant decrease in Kd and no change in Bmax in migraine cases. No correlation was observed between the Kd and Bmax with the clinical features of migraine. The findings of the present study show that there is a decreased affinity of platelet 5-HT2 receptors in migraine.

Adult↗
PubMed2001

Blood nitrite levels in patients with migraine during headache-free period.

OBJECTIVE: To investigate blood nitrite levels after migraine attacks and to assess whether or not the change in nitric oxide levels observed during acute migraine persist after the attacks. BACKGROUND: Involvement of nitric oxide has been suggested in the initiation of acute migraine. Recent studies have shown alteration in the platelet response and platelet nitrite levels during migraine attacks. METHODS: Patients with migraine with aura and patients without aura were included in the study. The study was conducted on 50 patients with migraine and 90 healthy controls. Blood from the patients was collected at least 7 +/- 0.8 days after the last attack of migraine. Nitrite levels in the polymorphonuclear leukocytes, platelets, and plasma were estimated. Platelet aggregation response in some of these patients was also studied. RESULTS: No significant change in the polymorphonuclear leukocyte, platelet, and plasma nitrite levels in patients with migraine compared to controls was observed. Patients with migraine with aura had significantly lower polymorphonuclear leukocyte nitrite levels compared to those without aura (P<.05). In addition, no significant difference in the adenosine diphosphate-induced platelet aggregation was observed in the migraineurs compared to the healthy controls. CONCLUSIONS: Results obtained indicate that the platelet aggregation response and the blood nitrite levels were not altered significantly after an attack in the patients with migraine.

Adult↗
PubMed2001

Role of nitric oxide in a progressive neurodegeneration model of Parkinson's disease in the rat.

This study was undertaken to investigate the nitric oxide synthase (NOS) activity in the striatum following 6-hydroxydopamine (6-OHDA) induced neurodegeneration in rats. Constitutive NOS (cNOS) activity remained unaltered at 3, 7 and 14 days after lesion, while a 43% and 45% decrease was observed at 30 and 50 days, respectively. Inducible NOS (iNOS) activity was detected only on the 3rd day after lesion and not in subsequent days or the control striatum. N(G)-nitro-L-arginine methyl ester (L-NAME) pretreatment blocked the amphetamine-induced rotations and inhibited the iNOS activity at the 3rd day after the 6-OHDA injection. L-NAME pretreatment also significantly restored the striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in 6-OHDA treated rats. Thus a possible role of nitric oxide in 6-OHDA induced neurodegeneration is suggested.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Modulation of polymorphonuclear leukocytes function by nitric oxide.

Recognition of the endothelium-derived relaxation factor as nitric oxide (NO) gave rise to an impression that NO was synthesised only by the endothelial lining of the vessel wall. Later it was found that NO is synthesized constitutively by the enzyme nitric oxide synthase (NOS) in various cells. However, inflammatory cytokines can induce NOS (known as inducible NOS [iNOS]) activity in all the somatic cells. Blood cells, such as eosinophils, platelets, neutrophils, monocytes, and macrophages, also synthesize NO. Among them, polymorphonuclear leukocytes (PMNs) constitute an important proportion and are also the major participants in a number of pathological conditions with suggestive involvement of NO. PMNs can synthesize NO at rates similar to endothelial cells, thus suggesting the importance of PMN-derived NO in various physiological and pathological conditions. Most of the studies so far focus on the peripheral PMNs, while studies on PMNs after emigration are limited, thus warranting systematic studies on PMNs from both sources. The role of the endothelial NOS (eNOS) and functions of NO derived from the endothelial cells has been studied extensively. However, understanding of the PMNs NOS and its regulatory role in their function is unraveling. The present review summarizes the modulatory role of NO on PMNs functions and points out the discrepancies relating to presence of NOS in PMNs. This information will be helpful in understanding the importance of NO in physiological and pathological conditions associated with PMNs.

Animals↗
PubMed2000

Mechanisms involved in the augmentation of arachidonic acid-induced free-radical generation from rat neutrophils following hypoxia-reoxygenation.

Polymorphonuclear leukocytes are known to play an important role in hypoxia/ischemia and reoxygenation injury. The present study was undertaken to investigate the involvement of protein kinase C, calmodulin, and cyclic adenosine monophosphate in the augmentation of the free-radical generation observed after hypoxia-reoxygenation (H-R). Free-radical generation from the rat polymorphonuclear leukocytes was measured as the arachidonic acid (1-5x10(-5) M)-induced luminol-dependent chemiluminescence response, which was augmented following H-R. The increase in free-radical generation after H-R was completely blocked by the pretreatment of cells with PKC inhibitor H(7), whereas indomethacin (a cyclo-oxygenase inhibitor) or forskolin (an adenylate cyclase activator) failed to modulate the H-R-dependent response. However, W(7)-a calcium/calmodulin (Ca(2+)/CaM) antagonist-partially reduced the augmented free-radical generation observed in the H-R cells. Results obtained thus suggest the possible involvement of protein kinase C and calcium in the augmentation of the free-radical generation response following H-R.

Adenylyl Cyclases↗
PubMed2000

Immobilization stress-induced changes in brain acetylcholinesterase activity and cognitive function in mice.

In the present study, the effect of acute and chronic immobilization stress on brain acetylcholinesterase (AChE) enzyme activity and cognitive function in mice was investigated. Mice were immobilized by strapping for 150 min. One group of mice were only immobilized once (acute stress) while in another group mice were immobilized (150 min) daily for 5 consecutive days (chronic stress). Specific AChE enzyme activity (micromol min(-1)mg(-1)) was estimated by a spectrophotometric method in the whole brain of mice subjected to acute and chronic stress. In the acute stress group, AChE activity (0.24922 +/- 0.011) in the detergent-soluble fraction was found to be significantly decreased in comparison to the control group (0.33561 +/- 0.022). Chronic stress did not cause any significant change in AChE activity in the detergent-soluble fraction. In the salt-soluble fraction, AChE activity was significantly decreased only in the chronic stress group (0.08791 +/- 0.011) as compared to the control group (0.12051 +/- 0.011). A passive avoidance test was used to assess cognitive function. The transfer latency time (TLT) from a light to dark chamber was recorded in the control and acute stress groups (30 min after immobilization is over) on day 1 (Trial I) and the following day (Trial II). The acute stress group showed an increase (178%) in TLT from Trial I to Trial II, which was significantly higher than that of the non-stress control group (75%). In the chronic stress group, Trial I was undertaken 30 min after the last immobilization, i.e. on day 5 and 24 hr later, Trial II. However, the chronically stressed mice showed an increase (70%) in TLT similar to the control group. Thus this study shows that acute immobilization stress may enhance cognitive function in mice which may be attributed to a decrease in AChE activity leading to an increase in cholinergic activity in the brain.

Acetylcholinesterase↗
PubMed2000

Antioxidant levels in the rat brain after nitric oxide synthase inhibition: a preliminary report.

Protective effects of NOS inhibitors and free radical scavengers in cerebral ischemia are well documented. The present study was undertaken to determine the possible effects of NOS inhibition on brain antioxidants. Levels of both enzymatic [glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)] and non-enzymatic [reduced glutathione (GSH)] antioxidants following nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME), D-NAME or 7-nitroindazole (7-NI) have been investigated. NOS activity and antioxidant levels in the rat cerebellum and medulla were estimated 1 h after treatment with L-NAME (10, 30 and 100 mg/kg, i.p.), D-NAME (100 mg/kg, i.p.) or 7-NI (25 mg/kg, i.p.). L-NAME and 7-NI inhibited NOS activity in a dose-dependent manner. D-NAME also exhibited significant NOS inhibition. The activity of SOD and the GSH level remained unaltered following NOS inhibition. However, L-NAME and D-NAME at 100 mg/kg attenuated GPx activity in the cerebellum, though 7-NI had no effect. L-NAME inhibited catalase activity in medulla only at 30 mg/kg, but had no effect in cerebellum. However, 7-NI (25 mg/kg), D-NAME and L-NAME at 100 mg/kg did not affect catalase activity in the rat brain. Thus, NOS inhibition by the three agents did not have major effects on brain antioxidant levels.

Animals↗
PubMed1999

Nitric oxide-mediated augmentation of polymorphonuclear free radical generation after hypoxia-reoxygenation.

Polymorphonuclear leukocytes (PMNLs), nitric oxide (NO), calcium, and free radicals play an important role in hypoxia/ischemia and reoxygenation injury. In the present study, NO donors, sodium nitroprusside (SNP), and diethylamine-NO (DEA-NO) at low concentrations (10 and 100 nmol/L) potentiated, while higher (10 micromol/L to 10 mmol/L) concentrations inhibited free radical generation response in the rat PMNLs. Free radical generation response was found to be significantly augmented when hypoxic PMNLs were reoxygenated (hypoxia-reoxygenation [H-R]). This increase in free radical generation after reoxygenation or SNP (10 nmol/L) was blocked in the absence of extracellular calcium. SNP (10 nmol/L) or H-R-mediated increases in the free radical generation were prevented by the pretreatment of PMNLs with NO scavenger (hemoglobin), the polyadenine diphosphate (ADP)-ribosylation synthase inhibitor (benzamide) or the calcium channel antagonist (felodipine). A significant augmentation in the nitrite and intracellular calcium levels was observed during hypoxia. Hemoglobin pretreatment also blocked the increase in intracellular calcium levels due to SNP (10 nmol/L) or hypoxia. Thus, increased availability of NO during SNP treatment or H-R, may have led to an ADP-ribosylation-mediated increase in intracellular calcium, thereby increasing the free radical generation from the rat PMNLs.

Animals↗
PubMed1999

Effect of nitric oxide modulators on pylorus-ligation-induced ulcers in the rat.

In the present investigation, the effect of nitric oxide (NO) modulators on pylorus-ligation-induced gastric ulcers in rats was studied. Sodium nitroprusside (SNP, 1 mg kg-1), a NO donor, l-arginine (l-Arg, 300 mg kg-1), the NO precursor, nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor and lipopolysaccharide (LPS, 3 mg kg-1), a NOS inducer have been administered prior to pylorus ligation. The effects of these interventions on the gastric mucosal nitrite content, the incidence of ulcers, the ulcer index, the volume of gastric secretions and the free and total acidity 4 h after pylorus ligation were investigated. SNP, l-Arg and LPS pretreatment increased the mucosal nitrite contents and protected the animals against pyloric-ligation-induced increase in acidity and ulcer index. However, inhibition of NOS activity by l-NAME (10 mg kg-1) decreased the nitrite content and augmented the ulcer-induced increase in the gastric acid contents. Coadministration of l-Arg with l-NAME prevented the l-NAME-induced changes. Interventions which increased the mucosal nitrite content were found to be protective against ulcers. However, the NOS inhibitor l-NAME decreased mucosal nitrite levels and was ulcerogenic. Results obtained thus indicate the protective effect of NO on the pyloric-ligation-induced ulcers in the rat.

Animals↗
PubMed1999

Polymorphonuclear leukocyte nitrite content and antioxidant enzymes in Parkinson's disease patients.

OBJECTIVE: The present study was undertaken to evaluate the alteration in the peripheral neuronal nitric oxide synthase (NOS) activity in Parkinson's disease patients. Therefore, basal nitrite content in PMNs, platelets and in the plasma of PD and control Indian population were evaluated. MATERIALS AND METHODS: We estimated nitrite, the nitric oxide (NO) metabolite, in neutrophils (PMNs), platelets and in plasma of control and in L-dopa treated Parkinson's disease (PD) patients. We also measured the activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the PMNs. RESULTS: We observed a significant increase in the basal nitrite content in PMNs of PD patients without any alteration in the plasma and platelets. Thus, the change was specific to PMNs. Catalase activity was significantly less in the PMNs of PD patients, but SOD and GPx remained unaltered. CONCLUSION: Results obtained in the PD patients exhibit an increase in the NOS activity in PMNs. Thus, involvement of NO is suggested in PD.

Adult↗
PubMed1998

Inhibition of platelet aggregation by a protein factor present in rat peripheral polymorphonuclear leukocyte supernatant.

In the present investigation, effect of rat peripheral polymorphonuclear leukocyte (PMNL) supernatant was investigated on platelet aggregation. Rat PMNLs suspended in Hanks balanced salt solution (HBSS, pH 7.4) were incubated at 37 degrees C for different time intervals and cell-free supernatant was obtained by centrifugation. Supernatant was found to inhibit adenosine diphosphate (ADP), arachidonic acid (AA), and calcium ionophore-induced platelet aggregation. The inhibitory effect of PMNL supernatant on platelet aggregation was not blocked by methylene blue (10 microM) or adenosine deaminase (5 U ml(-1)) pretreatment, suggesting that the inhibitory effect of the supernatant on aggregation was not mediated by nitric oxide (NO) or ecto-ADPase. The effect of PMNL supernatant on platelet aggregation was abolished by preheating the supernatant at 95 degrees C for 5 minutes. Pretreatment of the supernatant with protease inhibitors abolished the inhibitory effect of supernatant on platelet aggregation suggesting that the factor may be a protein or peptide with protease activity. Partial purification of biologically active factor by fine particle liquid chromatography (FPLC) by using Superose 6B column yielded a peak with a molecular weight of approximately 30 kDa having antiaggregatory activity. The results obtained suggest that rat peripheral PMNLs release yet another factor(s) that inhibits platelet aggregation. The factor is a heat labile protein with a molecular weight of approximately 30 kDa.

Adenosine Deaminase↗
PubMed1998

Free radicals and antioxidant status following pylorus ligation induced gastric mucosal injury in rats.

The present investigation was undertaken to suggest the involvement of free radicals in the pathogenesis of pyloric ligation induced ulcers in rats. Lipid peroxidation product (MDA), antioxidant contents and secretory activity have been studied in the rat stomach at different time intervals after pylorus ligation induced ulcers. A time-dependent increase in the peptic activity, free and total acid content in the gastric juice was observed. MDA level, myeloperoxidase (a neutrophil maker) and catalase activity in the rat stomach homogenate were augmented 2, 4 and 19 h after pylorus ligation. While a significant and time-dependent decrease in the glutathione content, superoxide dismutase and glutathione peroxidase activity was observed after pyloric ligation. An increase in the acid and pepsin content in the gastric juice in N-ethyl maleamide (GSH depletor) or aminotriazole (catalase inhibitor) pretreated animals, further suggests that depletion in the antioxidant levels enhance ulceration. Thus the results obtained have shown alterations in the antioxidant status following ulceration, indicating that free radicals seems to be associated with the pylorus ligation induced ulceration in rats.

Amitrole↗
PubMed1998

Role of endothelial-derived reactive oxygen species and nitric oxide in norepinephrine-induced rat aortic ring contractions.

In the present investigation involvement of endothelial-derived reactive oxygen species (ROS) and their interaction with nitric oxide (NO), during norepinephrine (NE)-induced contraction of rat aortic rings was studied. NE (1x10(-10) M to 1x10(-5) M) caused concentration-dependent contractio n of the endothelium intact aortic rings. In the presence of hydroxyl radical scavengers, histidine (1x10(-3) M), mannitol (3x10(-3) M), dimethyl sulfoxide (50x10(-3) M) or thiourea (1x10(-3) m), superoxide dismutase (superoxide radical scavenger, SOD 10 or 100 U ml-1) or catalase (hydrogen peroxide inactivator 3, 10, or 100 U ml-1) the concentration-response curve of NE was shifted towards the right. Interestingly, in NG-nitro-l-arginine methyl ester (L-NAME) (1x10(-5) M, a NO synthase inhibitor) pretreated rings, NE-induced contractions were not inhibited by SOD or extracellular hydroxyl radical scavengers (mannitol and histidine). However, in these rings NE-induced contractions were found to be attenuated by endogenous hydroxyl radical scavengers (thiourea and DMSO) or catalase. In the endothelium denuded rings no significant effect of these scavengers on NE-induced contractions was observed. These results thus indicate the involvement of endothelium-derived hydrogen peroxide, superoxide and hydroxyl radicals in the NE-induced contractions. In addition, endothelial NO interacts with the ROS generated during rat aortic ring contractions.

Animals↗
PubMed1998

Cellular immune response of Mastomys and gerbils in experimental filariasis.

OBJECTIVE: To determine mitogenic and antigen-specific cellular immune responses of two species of rodents, viz. Meriones unguiculatus and Mastomys coucha to assess the usefulness of the A. viteae/Mastomys model for cellular immune studies in experimental filariasis. METHODS: Lymphocyte blast transformation test (LTT) using spleen cells of normal and A. viteae infected animals. RESULTS: The proliferative response of gerbils was much higher than that of Mastomys to both ConA and filarial antigens. Cells of both species of rodents did not respond to microfilarial (mf) antigen, however, their mitogenic response differed during infection. Some degree of nonspecific suppression was observed in gerbils during prepatent and patent stages of infection, while Mastomys revealed highest proliferation during patent microfilaraemia. Mastomys cells did not respond to adult or mf antigen, while adult-specific proliferation was detected in the case of gerbils. CONCLUSION: The A. viteae/gerbil model shows more similarity to human filarial infection regarding cellular immune response. Markedly low responsiveness of a high percentage of Mastomys and wide variations in the cellular response to nonspecific mitogen limit the usefulness of Mastomys coucha in immunological studies, especially cellular immunity.

Animals↗
PubMed1998

Alterations in the vasoreactivity of hypertensive rat aortic rings: role of nitric oxide and superoxide radicals.

OBJECTIVES: Present study was undertaken to investigate involvement of nitric oxide (NO) and superoxide radicals in the modulation of vasoreactivity in a model of renal hypertension. METHOD: Hypertension was induced in the male Sprague Dawley rats by aortic banding just above the left kidney. Relaxation or contraction following cumulative addition of acetylcholine (Ach, 1 x 10(-8) to 1 x 10(-5) M) or phenylephrine (PE, 1 x 10(-8) to 1 x 10(-5) mol/l) was studied in the aortic rings obtained from sham operated normotensive, hypertensive and captopril pretreated rats. Ach and PE responses were taken in the presence or absence of NO synthase inhibitor (L-NAME; 1 x 10(-5) and 1 x 10(-4) mol/l). Spontaneous release of NO from the aortic rings was evaluated by studying the inhibition of adenosine diphosphate stimulated platelet aggregation, while superoxide radicals were estimated by cytochrome c reduction method. RESULTS: Ach induced vasorelaxation in PE precontracted rings was impaired following 8 wk after aortic banding, while spontaneous release of NO remained unaffected. Captopril pretreatment restored the aortic ring responsiveness to Ach. An increase in the superoxide radical generation and PE induced contraction following L-NAME treatment in the hypertensive rat aortic rings was observed. CONCLUSION: Attenuation in the Ach induced NO release and augmentation in the superoxide radical generation seems to play an important role in the modulation of vasoreactivity following renal hypertension in rats.

Acetylcholine↗