The Journal of the Association of Physicians of India, 2005
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been a... more Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the f...
The Journal of the Association of Physicians of India, 2002
Endothelial cell dysfunction may play a role in the pathobiology of pre-eclampsia and human essen... more Endothelial cell dysfunction may play a role in the pathobiology of pre-eclampsia and human essential hypertension. Vasodilators and platelet anti-aggregators such as prostacyclin and nitric oxide are produced by endothelial cells. The half-life of prostacyclin and nitric oxide are reduced by superoxide anion, whereas superoxide dismutase antagonizes its action. To estimate the plasma concentrations of nitric oxide and lipid peroxides and those of catalase and superoxide dismutase in patients with pre-eclampsia and essential hypertension. Patients of essential hypertension and pre-eclampsia were selected for the study. Nitric oxide and lipid peroxides were estimated in the plasma and anti-oxidants catalase and superoxide dismutase were estimated in the RBC membranes. The ratio between lipid peroxides and nitric oxide was elevated and the activity of superoxide dismutase reduced in patients with pre-eclampsia and uncontrolled essential hypertension. These results suggest that oxidant...
Experiments were performed to study the effect of various prostaglandins (PGs) and their precurso... more Experiments were performed to study the effect of various prostaglandins (PGs) and their precursors, gamma-linolenic acid (GLA) and arachidonic acid (AA) on gamma-radiation and benzo (a) pyrene (BP)-induced genetic damage to the bone marrow cells of mice, using the sensitive micronucleus (MN) test. Thromboxane B2 prostaglandin El and GLA completely prevented BP-induced and reduced to a great degree radiation-induced genetic damage., where as PGE2, PGF2alpha and AA were without any effect. Since GLA and AA are widely distributed in the cell membranes , and as PGs can be formed virtually in response to any type of stimulus., it is likely that GLA and PGEl may function as endogenous anti-mutagenic chemicals. utroduction Radiation can damage DNA, ultimately be carcinogenic, possibly cause mutations and thus may by the generation of free _ radicals, physically disrupting DNA or both and thus, induce mutations (1,2). Recently, it has been shown that radiation can, possibly by generating free radicals (3), can activate phospholipase A2 leading to the liberation of arachidonic acid (AA), such that excess of PGE2 and PGF2alpha formation occurs. In addition, it was also observed that FGI2 synthesis is decreased due to radiation (4). But, there were no reports on the liberation of gamma-linolenic JUNE1985VOL.29NO.6
Prostaglandins, Leukotrienes and Essential Fatty Acids, 1995
Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential h... more Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alapha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin El, (PGE0, prostacyclin (PGI2), and PGI3, which are potent platelet anti-aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians. Since insulin resistance and hyperinsulinemia and features of obesity, NIDDM, HTN and CHD, diseases that are common in Indians, and as decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids (PUFAs) in skeletal muscle phospholipids and, possibly, in the plasma, the possibility is raised that changes in the metabolism of EFAs may have a fundamental role in the pathobiology of these conditions. If this is true, this suggests that supplementation of GLA, DGLA, AA, EPA and/or DHA may be indicated to prevent CHD, HTN and NIDDM in Indians.
The ability of ethanol, copper, iron and viruses to alter prostaglandin (PG) metabolism may be re... more The ability of ethanol, copper, iron and viruses to alter prostaglandin (PG) metabolism may be responsible for their ability to induce cirrhosis of liver. PGs are known to regulate fibroblast proliferation, glycosaminoglycan and collagen synthesis and participate in immune response and inflammation. Thus, the beneficial effect of colchicine in cirrhosis could be due to its ability to enhance thromboxane A2 synthesis and normalise PG levels.
Prostaglandin E2, colchicine and imidazole, known to enhance and inhibit thromboxane A2 (TxA2) sy... more Prostaglandin E2, colchicine and imidazole, known to enhance and inhibit thromboxane A2 (TxA2) synthesis respectively and chloroquine, a PGE1 synthesis enhancer and PGE2 antagonist can alter the leukocyte alkaline phosphatase (LAP) enzyme activity. Thromboxane A2 and other related prostaglandins (PGs) are known to bind to DNA and thus possibly regulate DNA action. It is proposed here that prostaglandins are able to modify LAP activity by their action on the DNA and thus the Gene that codes for LAP. This hypothesis envisages that normally there are specific receptors on the genes for PGs. Taking LAP enzyme system as the model, it is proposed that the affinity of TxA1, TxA2, PGE2 and PGE1 to the operator is more than to that of the repressor. But when the levels of TxA2, PGE2 and PGE1 are in excess, all the receptors on the operator are not only completely occupied but they are also able to bind to repressor in sufficient amounts to transiently switch off the LAP synthesis by the structural gene. It is further envisaged that the affinity of the PG receptors on the operator and repressor systems of the operon is greatest for TxA1 and least for PGE2 (TxA1 greater than TxA2 greater than PGE1 greater than PGE2). This hypothesis though simply in its model explains all the variables obtained in our studies on the effect of PGs on the LAP activity. This concept by itself or a suitable modification, may explain the role of PGs in the pathogenesis of cancer. It will be interesting to study, in the light of this hypothesis, the role of the PG system on DNA repair mechanism, m-RNA and t-RNA synthesis and gene action in several systems.
Radiation is pro-inflammatory in nature in view of its ability to induce the generation of reacti... more Radiation is pro-inflammatory in nature in view of its ability to induce the generation of reactive oxygen species (ROS), cytokines, chemokines, and growth factors with associated inflammatory cells. Cells are efficient in repairing radiation-induced DNA damage; however, exactly how this happens is not clear. In the present study, GLA reduced DNA damage (as evidenced by micronuclei formation) and enhanced metabolic viability, which led to an increase in the number of surviving RAW 264.7 cells in vitro by reducing ROS generation, and restoring the activities of desaturases, COX-1, COX-2, and 5-LOX enzymes, TNF-α/TGF-β, NF-kB/IkB, and Bcl-2/Bax ratios, and iNOS, AIM-2, and caspases 1 and 3, to near normal. These in vitro beneficial actions were confirmed by in vivo studies, which revealed that the survival of female C57BL/6J mice exposed to lethal radiation (survival~20%) is significantly enhanced (to ~80%) by GLA treatment by restoring altered levels of duodenal HMGB1, IL-6, TNF-α, a...
The Journal of the Association of Physicians of India, 2006
Metabolics syndrome is common in SE Asian. An hypothesis that aberrant expression of perilipins a... more Metabolics syndrome is common in SE Asian. An hypothesis that aberrant expression of perilipins and 11-beta-hydroxysteroid dehydrogenase-1 (11-beta-HSD-1) enzyme plays a significant role in the development of metabolic syndrome X in Indians is proposed. Thus, methods designed to target perilipins and 11-beta-HSD-1 may form a novel approach in the prevention and management of metabolic syndrome X.
The Journal of the Association of Physicians of India, 2005
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been a... more Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the f...
The Journal of the Association of Physicians of India, 2002
Endothelial cell dysfunction may play a role in the pathobiology of pre-eclampsia and human essen... more Endothelial cell dysfunction may play a role in the pathobiology of pre-eclampsia and human essential hypertension. Vasodilators and platelet anti-aggregators such as prostacyclin and nitric oxide are produced by endothelial cells. The half-life of prostacyclin and nitric oxide are reduced by superoxide anion, whereas superoxide dismutase antagonizes its action. To estimate the plasma concentrations of nitric oxide and lipid peroxides and those of catalase and superoxide dismutase in patients with pre-eclampsia and essential hypertension. Patients of essential hypertension and pre-eclampsia were selected for the study. Nitric oxide and lipid peroxides were estimated in the plasma and anti-oxidants catalase and superoxide dismutase were estimated in the RBC membranes. The ratio between lipid peroxides and nitric oxide was elevated and the activity of superoxide dismutase reduced in patients with pre-eclampsia and uncontrolled essential hypertension. These results suggest that oxidant...
Experiments were performed to study the effect of various prostaglandins (PGs) and their precurso... more Experiments were performed to study the effect of various prostaglandins (PGs) and their precursors, gamma-linolenic acid (GLA) and arachidonic acid (AA) on gamma-radiation and benzo (a) pyrene (BP)-induced genetic damage to the bone marrow cells of mice, using the sensitive micronucleus (MN) test. Thromboxane B2 prostaglandin El and GLA completely prevented BP-induced and reduced to a great degree radiation-induced genetic damage., where as PGE2, PGF2alpha and AA were without any effect. Since GLA and AA are widely distributed in the cell membranes , and as PGs can be formed virtually in response to any type of stimulus., it is likely that GLA and PGEl may function as endogenous anti-mutagenic chemicals. utroduction Radiation can damage DNA, ultimately be carcinogenic, possibly cause mutations and thus may by the generation of free _ radicals, physically disrupting DNA or both and thus, induce mutations (1,2). Recently, it has been shown that radiation can, possibly by generating free radicals (3), can activate phospholipase A2 leading to the liberation of arachidonic acid (AA), such that excess of PGE2 and PGF2alpha formation occurs. In addition, it was also observed that FGI2 synthesis is decreased due to radiation (4). But, there were no reports on the liberation of gamma-linolenic JUNE1985VOL.29NO.6
Prostaglandins, Leukotrienes and Essential Fatty Acids, 1995
Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential h... more Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alapha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin El, (PGE0, prostacyclin (PGI2), and PGI3, which are potent platelet anti-aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians. Since insulin resistance and hyperinsulinemia and features of obesity, NIDDM, HTN and CHD, diseases that are common in Indians, and as decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids (PUFAs) in skeletal muscle phospholipids and, possibly, in the plasma, the possibility is raised that changes in the metabolism of EFAs may have a fundamental role in the pathobiology of these conditions. If this is true, this suggests that supplementation of GLA, DGLA, AA, EPA and/or DHA may be indicated to prevent CHD, HTN and NIDDM in Indians.
The ability of ethanol, copper, iron and viruses to alter prostaglandin (PG) metabolism may be re... more The ability of ethanol, copper, iron and viruses to alter prostaglandin (PG) metabolism may be responsible for their ability to induce cirrhosis of liver. PGs are known to regulate fibroblast proliferation, glycosaminoglycan and collagen synthesis and participate in immune response and inflammation. Thus, the beneficial effect of colchicine in cirrhosis could be due to its ability to enhance thromboxane A2 synthesis and normalise PG levels.
Prostaglandin E2, colchicine and imidazole, known to enhance and inhibit thromboxane A2 (TxA2) sy... more Prostaglandin E2, colchicine and imidazole, known to enhance and inhibit thromboxane A2 (TxA2) synthesis respectively and chloroquine, a PGE1 synthesis enhancer and PGE2 antagonist can alter the leukocyte alkaline phosphatase (LAP) enzyme activity. Thromboxane A2 and other related prostaglandins (PGs) are known to bind to DNA and thus possibly regulate DNA action. It is proposed here that prostaglandins are able to modify LAP activity by their action on the DNA and thus the Gene that codes for LAP. This hypothesis envisages that normally there are specific receptors on the genes for PGs. Taking LAP enzyme system as the model, it is proposed that the affinity of TxA1, TxA2, PGE2 and PGE1 to the operator is more than to that of the repressor. But when the levels of TxA2, PGE2 and PGE1 are in excess, all the receptors on the operator are not only completely occupied but they are also able to bind to repressor in sufficient amounts to transiently switch off the LAP synthesis by the structural gene. It is further envisaged that the affinity of the PG receptors on the operator and repressor systems of the operon is greatest for TxA1 and least for PGE2 (TxA1 greater than TxA2 greater than PGE1 greater than PGE2). This hypothesis though simply in its model explains all the variables obtained in our studies on the effect of PGs on the LAP activity. This concept by itself or a suitable modification, may explain the role of PGs in the pathogenesis of cancer. It will be interesting to study, in the light of this hypothesis, the role of the PG system on DNA repair mechanism, m-RNA and t-RNA synthesis and gene action in several systems.
Radiation is pro-inflammatory in nature in view of its ability to induce the generation of reacti... more Radiation is pro-inflammatory in nature in view of its ability to induce the generation of reactive oxygen species (ROS), cytokines, chemokines, and growth factors with associated inflammatory cells. Cells are efficient in repairing radiation-induced DNA damage; however, exactly how this happens is not clear. In the present study, GLA reduced DNA damage (as evidenced by micronuclei formation) and enhanced metabolic viability, which led to an increase in the number of surviving RAW 264.7 cells in vitro by reducing ROS generation, and restoring the activities of desaturases, COX-1, COX-2, and 5-LOX enzymes, TNF-α/TGF-β, NF-kB/IkB, and Bcl-2/Bax ratios, and iNOS, AIM-2, and caspases 1 and 3, to near normal. These in vitro beneficial actions were confirmed by in vivo studies, which revealed that the survival of female C57BL/6J mice exposed to lethal radiation (survival~20%) is significantly enhanced (to ~80%) by GLA treatment by restoring altered levels of duodenal HMGB1, IL-6, TNF-α, a...
The Journal of the Association of Physicians of India, 2006
Metabolics syndrome is common in SE Asian. An hypothesis that aberrant expression of perilipins a... more Metabolics syndrome is common in SE Asian. An hypothesis that aberrant expression of perilipins and 11-beta-hydroxysteroid dehydrogenase-1 (11-beta-HSD-1) enzyme plays a significant role in the development of metabolic syndrome X in Indians is proposed. Thus, methods designed to target perilipins and 11-beta-HSD-1 may form a novel approach in the prevention and management of metabolic syndrome X.
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