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Biomedical subjects

P K Seth

Publications and source records attributed to P K Seth.

At least 37 records · Page 2Linked to original sources
PubMed2002

A study on nitric oxide, beta-adrenergic receptors and antioxidant status in the polymorphonuclear leukocytes from the patients of depression.

BACKGROUND: alterations in the polymorphonuclear leukocyte (PMNs) receptors, second messenger system and in their responses have been found associated with depression. Recently role of tetrahydrobiopterin and nitric oxide has also been reported in the depressive disorders. It was therefore considered worthwhile to investigate the NOS activity in the PMNs, which like neurons, also express neuronal NOS (nNOS), antioxidant enzyme levels [superoxide dismutase (SOD), catalase and glutathione peroxidase (Gpx)] and beta-adrenergic receptors in the patients of depression. METHODS: patients were diagnosed according to the DSM-IV and were medication free, while healthy age-matched controls were also included in the study to estimate nitrite content, beta-adrenergic receptors and antioxidant enzymes in the PMNs according to the standard methodologies. RESULTS: an analysis of 66 cases of depression and 114 controls revealed 73% decrease in nitrite content and 71% decrease in beta-adrenergic receptor binding in the patients as compared to the healthy controls. However, activities of SOD, catalase and Gpx were not significantly altered in the patients. CONCLUSION: the results of the present study for the first time indicate alterations the NOS activity in PMNs obtained form the patients of affective disorders.

Adolescent↗
PubMed2002

The role of dopamine in manganese-induced oxidative injury in rat pheochromocytoma cells.

Reactive dopamine (DA) metabolites have been implicated in both Parkinson's disease and manganese (Mn) neurotoxicity. Rat PC12 and genetically modified PC12 (PC12M) cells capable of producing higher DA content, on exposure to MnCl2 (10(-6) M) for 72 hours, exhibited a significant decrease in glutathione content. Activity of antioxidant enzyme catalase was also inhibited following 24- and 72-hour MnCl2 exposure. MnCl2 caused a concentration-dependent (10(-7) to 10(-3) M) loss in mitochondrial activity after 24 and 72 hours and an impaired DNA synthesis after 72 hours with changes being more marked in PC12M cells. The results indicate that the free-radical-mediated toxicity of Mn at cellular level involves down-regulation of antioxidants in normal and DA-rich PC12 cells. PC12M cells appeared to be more sensitive than PC12 cells.

Animals↗
PubMed2002

Neuropsychological studies on lead battery workers.

This study assessed the psychological status of 60 lead-acid battery workers occupationally exposed to low level lead and 30 referents in Lucknow. Digit spans and symbol, Bourdon-wiersma vigilance and Raven's Progressive matrices tests were administered. Significant impairments in concentration, attention, auditory and visual memory, psycho-motor speed, perceptual accuracy, and visual reasoning were observed in the workers compared to the referents. The deficits were not related to exposure duration since the magnitude of the impairments observed in workers with 1-y duration was the same as in those with more (up to 30 years) work duration. The blood lead of the battery workers was significantly elevated. There were functional deficits of the central nervous system in the lead-acid battery workers.

Adolescent↗
PubMed2001

Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression.

Studies initiated to characterise the catalytic activity and expression of CYP1A1 in rat blood lymphocytes revealed significant activity of 7-ethoxyresorufin-O-deethylase (EROD) in rat blood lymphocytes. Pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (NF) resulted in significant induction in the activity of lymphocyte EROD suggesting that like the liver enzyme, EROD activity in lymphocytes is inducible and is mediated by the MC inducible isoenzymes of P450. The increase in the activity of EROD was associated with a significant increase in the apparent Vmax and affinity of the substrate towards EROD. That this increase in the activity of EROD could be primarily due to the increase in the expression of CYP1A1 isoenzymes was demonstrated by RT-PCR and western immunoblotting studies indicating an increase in the expression of CYP1A1 in blood lymphocytes after MC pretreatment. Significant inhibition in the EROD activity of MC induced lymphocyte by anti-CYP1A1/1A2 and alpha-naphthoflavone further provided evidence that the CYP1A1/1A2 isoenzymes are involved in the activity of EROD in blood lymphocytes. The data indicating similarities in the regulation of CYP1A1 in blood lymphocytes with the liver isoenzyme suggests that factors which may affect expression of CYP1A1 in liver may also affect expression in blood lymphocytes and that blood lymphocytes could be used as a surrogates for studying hepatic expression of the xenobiotic metabolising enzymes.

Animals↗
PubMed2001

Neurodevelopmental consequences of gestational exposure (GD14-GD20) to low dose deltamethrin in rats.

Effect of low level in utero exposure to deltamethrin (DT) (1mg /kg wt.) during gestation day 14-20 was studied on selected neurobehavioral, neurochemical, immunohistochemical parameters in rats at 6 and 12 weeks postnatal period. The significant increase in acetylcholinesterase activity and decrease in (3)H-quinuclidinyl benzilate binding in the hippocampal region of DT exposed animals, suggesting impairment in cholinergic (muscarinic) receptors. A significant decrease in the learning and memory performances was also observed both at 6 and 12 weeks, which is directly correlated with decrease in muscarinic receptor binding. Immunohistochemistry and image analysis of growth associated protein-43, a neuron specific protein present in axonal growth cone and a marker for neuronal differentiation and synaptogenesis, exhibit aberrant increase in its expression in the hippocampus in DT exposed rats at both time periods. The data suggests that low level exposure to DT in utero during brain growth spurt period adversely affects the developing brain and the changes persist even up to 12 weeks postnatal period in rats. Although there is no significant recovery at 12 weeks assessment but still significant impairment persist on biochemical and behavioural parameters.

Acetylcholinesterase↗
PubMed2001

The effect of smoking and eating habits on DNA damage in Indian population as measured in the Comet assay.

This study was undertaken with the aim of assessing the status of DNA damage in a normal healthy Indian population. The 62 male volunteers in this study belonged to the smoking, non-smoking, vegetarian and non-vegetarian categories, were well educated and aged between 23 and 57 years. The data revealed significant differences in the extent of DNA damage in the smokers versus non-smokers as well as between the vegetarians and non-vegetarians. A significant difference was also observed amongst the different groups of smokers depending on the extent of smoking. An age-dependent effect in DNA damage was also observed. This preliminary study has, for the first time, revealed differences in the extent of DNA damage in the normal Indian population depending on their eating and smoking habits as well as age.

Adult↗
PubMed2001

Induction of rat brain cytochrome P450s (P450s) by deltamethrin: regional specificity and correlation with neurobehavioral toxicity.

Oral administration of 5 mg/kg body weight of deltamethrin, an alpha-cyano type II pyrethroid insecticide once a day for 1, 7, 15 and 21 consecutive days to young Druckerey rats (6- 8 weeks old) produced a time dependent increase in the activity of cytochrome P450 (P450) dependent 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) in rat brain microsomes. A significant induction was observed on prolonged exposure of deltamethrin for 15 or 21 days. The induction in the activity of cerebral P450 enzymes was associated with the time dependent increase in the spontaneous locomotor activity indicating accumulation of deltamethrin or its metabolites in brain with the increase in the duration of exposure. Administration of deltamethrin (5 mg/kg) for 21 days produced region specific changes in the dealkylation of ethoxyresorufin and pentoxyresorufin in rat brain with significant induction occurring in the activity of P450 1A1/2 dependent EROD in cerebellum, hippocampus, hypothalamus and medulla-pons and that of P450 2B1/2 mediated PROD in hippocampus, hypothalamus, corpus striatum and mid brain. The data suggests that the differences in the induction of individual P450 isoenzymes in diverse brain regions could play a role in regulating the response of brain to pyrethroid insecticides by modulating their concentration per se or their active metabolites at the target site(s).

Journal Article↗
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

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

In vitro cytotoxicity evaluation of plastic biomedical devices.

Cytotoxic potential of four plastic biomedical devices (intravenous transfusion sets, IV sets; dextrose normal saline bottles, DNS bottles; Ringer lactate bottles, RL bottles; and Ryle's tubes) including 17 different brands was evaluated by investigating growth inhibition, percent survival, mitotic index and colony-forming ability (cfa) in L929, an adherent type mouse fibroblast cell line. Experimental sets were exposed with leachates of biomedical products in serum-free minimum essential medium (MEM) for 1 h at 37 degrees C in a CO2 incubator. After 1 h, medium was replaced with serum rich MEM containing essential amino acids and reincubated up to 96 h. Cells in serum-free MEM only were processed under identical conditions and served as the control. The leachates from all types of biomedical devices evaluated exhibited reduction in the growth and survival of the cell line in the first 12 h postexposure followed by their gradual recovery up to 96 h. A significant reduction in cell growth was apparent in the six brands of IV sets from 24 h onwards up to 36 h (59% growth inhibition). Though the cfa was also reduced in all the brands tested, the magnitude of reduction was less compared to growth inhibition. The results indicate that leachates of IV sets were more toxic compared to other biomedical devices screened, and growth inhibition assay was found to be more sensitive and suitable for cytotoxicity evaluation of biomedical devices.

Animals↗
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↗
PubMed2000

Alterations in some membrane properties in rat brain following exposure to lead.

The effect of lead exposure on intracellular calcium levels, membrane fluidity, lipid peroxidation, acetylcholinesterase and monoamine oxidase activity and its accumulation in different regions of the brain were studied to understand the molecular mechanism of lead induced neurotoxicity. Lead treatment (20 mg/kg lead nitrate, intraperitoneally, once daily for 15 days) resulted in a significant accumulation of lead in all brain regions with the maximum being in the hippocampus. Levels of glutathione, lipid peroxidation, intracellular calcium and membrane fluidity, as well as the activity of the membrane bound enzymes, acetylcholinesterase and monoamine oxidase, increased to a significant level in certain areas of the rat brain. The results suggest that lead exerts neurotoxic effects by altering certain membrane bound enzymes and may cause oxidative stress.

Acetylcholinesterase↗
PubMed2000

Raised platelet thiobarbituric acid-reacting substances in proliferative Eales' disease.

BACKGROUND: Platelets are an elective site for oxidative stress owing to their high content of polyunsaturated fatty acid. Increased lipid peroxidation and elevated platelet thiobarbituric acid-reacting substances (TBARS) signal oxidative stress. This possibly leads to retinal neovascularization in Eales' disease. METHODS: TBARS levels were estimated in consecutive cases of Eales' disease with neovascularisation (n = 26), Eales' disease without neovascularisation (n = 17) and healthy controls (n = 17). RESULTS: Platelet TBARS levels in the cases of Eales' disease with neovascularisation, Eales' disease without neovascularisation, and healthy controls were 0.66 +/- 0.1, 0.57 +/- 0.11 and 0.42 +/- 0.14 n moles TBARS formed/hour/10(8) platelets respectively. Student's t-test showed a significant increase in platelet TBARS levels in cases with neovascularisation as compared to cases without neovascularization (p < 0.05) and healthy controls (p < 0.01). CONCLUSION: The increase in platelet TBARS levels in proliferative Eales' disease is consistent with an emerging view that lipid peroxides may be associated with retinal neovascularisation.

Adolescent↗
PubMed1999

Changes in neurotransmitter receptors and neurobehavioral variables in rats co-exposed to lead and ethanol.

The influence of lead (10 mg/kg) and ethanol (10% v/v, in drinking water) administration, either alone or in combination for 8 weeks was investigated on the uptake of lead in tissues, dopamine, benzodiazepine and cholinergic (muscarinic) receptors, motor activity, number of fighting episodes and several selected lead-sensitive biochemical indices in young rats. Lead or ethanol treatment did not elicit any appreciable influence on body weight gain, tissue weight, and food intake. However, a decreased amount of mean water intake was noticed in animals ingesting ethanol plus lead. Both lead and ethanol when administered individually exacerbate the decrease of blood delta-aminolevulinic acid dehydratase (ALAD) activity while lead and ethanol administered together exhibited a pronounced inhibition of ALAD activity. A significant increase in hepatic GSH levels, hepatic and brain MDA levels was also observed in animals co-exposed to lead and ethanol compared to lead alone treated rats. Simultaneous exposure to lead and ethanol also resulted in a significantly more pronounced decrease in binding of [3H]fluintrazepam in membranes prepared from the fronto-cortical region compared to the corresponding controls. The binding of [3H]spiroperidol to striatal and [3H]quinuclidinyl benzylate (QNB) to cerebellar membranes remained unaltered in all the exposed animals. Spontaneous locomotor activity and aggressive behaviour increased significantly in the group treated with both lead and ethanol compared to the control group. The lead concentrations in blood, liver, kidney and brain were significantly higher in rats exposed simultaneously to lead and ethanol compared to lead alone exposed group. The results indicate more pronounced neurotoxic and neurobehavioural changes in animals co-exposed to lead and ethanol; however, the exact mechanism or site of its action is still not clear.

Aggression↗
PubMed1999

Cholinergic and serotonergic alterations in the rat hippocampus following trimethyltin exposure and fetal neural transplantation.

Trimethyltin (TMT) apart from causing cholinergic denervation of the hippocampus, damages the serotonergic inputs into the hippocampus as well. In the present study, fetal cholinergic and serotonergic rich neuronal populations from septal and raphe regions, respectively, were transplanted alone or in combination (as co-grafts) in the hippocampus of TMT exposed rats. Neurotransmitter receptor binding and neurotransmitter levels were assayed 6 months post-transplantation. Fetal septal transplants (rich in cholinergic neurons) significantly restored the deficits in cholinergic (muscarinic) receptor binding and acetylcholinesterase activity caused by TMT exposure. Raphe transplants (rich in serotonergic neurons) restored the deficit in serotonergic receptor binding and serotonin levels caused by TMT. Co-grafts of fetal raphe and septal neurons restored both the cholinergic (muscarinic) and serotonergic receptor functions. The results suggest that co-grafting technique could provide a better restoration of functional deficits when more than one type of neuronal population is damaged.

Acetylcholine↗
PubMed1999

Cytochrome P450 (P450) isoenzyme specific dealkylation of alkoxyresorufins in rat brain microsomes.

Characterization of xenobiotic metabolizing cytochrome P450s (P450s) was carried out in rat brain microsomes using the specific substrates, 7-pentoxy- and 7-ethoxyresorufin (PR and ER), metabolized in the liver by P450 2B1/2B2 and 1A1/1A2 respectively and 7-benzyloxyresorufin (BR), a substrate for both the isoenzymes. Brain microsomes catalysed the O-dealkylation of PR, BR and ER in the presence of NADPH. The ability to dealkylate alkoxyresorufins varied in different regions of the brain. Microsomes from the olfactory lobes exhibited maximum pentoxyresorufin-O-dealkylase (PROD), benzyloxyresorufin-O-dealkylase (BROD) and ethoxyresorufin-O-dealkylase (EROD) activities. The dealkylation was found to be inducer selective. While pretreatment with phenobarbital (PB; 80 mg/kg; i.p. x 5 days) resulted in significant induction in PROD (3-4 fold) and BROD (4-5 fold) activities, 3-methylcholanthrene (MC; 30 mg/kg; i.p. x 5 days) had no effect on the activity of PROD and only a slight effect on that of BROD (1.4 fold). MC pretreatment significantly induced the activity of EROD (3 fold) while PB had no effect on it. Kinetic studies have shown that this increase in the activities following pretreatment with P450 inducers was associated with a significant increase in the velocity of the reaction (Vmax) of O-dealkylation. In vitro studies using organic inhibitors and antibodies have further provided evidence that the O-dealkylation of alkoxyresorufins is isoenzyme specific. While in vitro addition of alpha-naphthoflavone (ANF), an inhibitor of P450 1A1/1A2 catalysed reactions and antibody for hepatic P450 1A1/1A2 isoenzymes produced a concentration-dependent inhibition of EROD activity, metyrapone, an inhibitor of P450 2B1/2B2 and antibody for hepatic P450 2B1/2B2 significantly inhibited the activity of PROD and BROD in vitro. The data suggest that, as in the case of liver, dealkylation of alkoxyresorufins can be used as a biochemical tool to characterise the xenobiotic metabolising P450s and substrate selectivity of P450 isoenzymes in rat brain microsomes.

Alkylation↗