Ghrelin is a growth hormone secretagogue producedby the gut,and is expressed in the hypothalamusand other tissues as well.Ghrelin not only plays animportant role in the regulation of appetite,energy balance and glucos...Ghrelin is a growth hormone secretagogue producedby the gut,and is expressed in the hypothalamusand other tissues as well.Ghrelin not only plays animportant role in the regulation of appetite,energy balance and glucose homeostasis,but also shows antibacterial activity,suppresses pro-inflammatory cytokine production and restores gut barrier function.Inexperimental animals,ghrelin has shown significantbeneficial actions in preventing mortality from sepsis.In the critically ill,corticosteroid insufficiency as a resultof dysfunction of the hypothalamic-pituitary-adrenalaxis is known to occur.It is therefore possible that bothgut and hypothalamus play an important role in thepathogenesis of sepsis by virtue of their ability to produce ghrelin,which,in turn,could be a protective phenomenon to suppress inflammation.It remains to beseen whether ghrelin and its analogues are of benefit intreating patients with sepsis.展开更多
Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by...Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by appropriate vagal stimulation that is anti-inflammatory in nature. Acetylcholine, the principal vagal neurotransmitter, is a potent anti-inflammatory molecule. Polyunsaturated fatty acids (PUFAs) augment acetylcholine release, while acetylcholine can enhance the formation of prostacyclin, lipoxins, resolvins, protectins and maresins from PUFAs, which are anti-inflammatory and anti-arrhythmic molecules. Furthermore, plasma and tissue levels of PUFAs are low in those with CHD and atherosclerosis. Hence, vagal nerve stimulation is beneficial in the prevention of CHD and cardiac arrhythmias. Thus, measurement of catecholamines, acetylcholine, various PUFAs, and their products lipoxins, resolvins, protectins and maresins in the plasma and peripheral leukocytes, and vagal tone by heart rate variation could be useful in the prediction, prevention and management of CHD and cardiac arrhythmias.展开更多
Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are inc...Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6-/-mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E2 (PGE2). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE2 production. These results suggest that the activities of △6 and △5 desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could prevent NAFLD. This suggests that an imbalance between proand anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.展开更多
Scleritis and other autoimmune diseases are characterized by an imbalance in the levels of pro-inflammatory and anti-inflammatory molecules with the balance tilted more towards the former due to the failure of recogni...Scleritis and other autoimmune diseases are characterized by an imbalance in the levels of pro-inflammatory and anti-inflammatory molecules with the balance tilted more towards the former due to the failure of recognition of self. The triggering of inflammatory process could be ascribed to the presence of cytoplasmic DNA/chromatin that leads to activation of cytosolic DNA-sensing c GAS-STING(cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway and enhanced expression of NF-κB that results in an increase in the production of pro-inflammatory bioactive lipids. Bioactive lipids gamma-linolenic acid(GLA), dihomoGLA(DGLA), prostaglandin E1(PGE1), prostacyclin(PGI2) and lipoxin A4, resolvins, protectins and maresins have antiinflammatory actions, bind to DNA to render it non-antigenic and are decreased in autoimmune diseases. These results suggest that efforts designed to enhance the production of anti-inflammatory bioactive lipids may form a new approach to autoimmune diseases. Local injection or infusion of lipoxins, resolvins, protectins and maresins or their precursors such as arachidonic acid may be exploited in the prevention and management of autoimmune diseases including scleritis, uveitis and lupus/rheumatoid arthritis.展开更多
Action to Control Cardiovascular Risk in Diabetes(ACCORD),The Action in Diabetes and Vascular Disease:Preterax and Diamicron Modified Release Controlled Evaluation and the Veterans Affairs Diabetes Trial were designed...Action to Control Cardiovascular Risk in Diabetes(ACCORD),The Action in Diabetes and Vascular Disease:Preterax and Diamicron Modified Release Controlled Evaluation and the Veterans Affairs Diabetes Trial were designed to study whether older patients with type 2 diabetes mellitus could reduce the risk of heart attacks and stroke and thereby prolong their lives by maintaining their blood glucose levels at near-healthy levels but failed to demonstrate the hoped-for benef it.Why the trials failed,though,and why ACCORD saw significantly more deaths due to increased rates of cardiovascular events in the intensive therapy arm of the study are not clear.These data have now been confirmed by the results of the recently concluded NICE-SUGAR Study which again revealed that intensive gluc ose control increased mortality among adults in intensive care units.I propose that the negative results noted in these trials are due to altered brain serot o nin concentrations and autonomic dysregulation in addition to the low-grade systemic inflammation,decreased endothelial nitric oxide and enhanced free radical generation,diminished anti-oxidant defenses and altered metabol ism of essential fatty acids present in patients with type 2 diabetes.展开更多
文摘Ghrelin is a growth hormone secretagogue producedby the gut,and is expressed in the hypothalamusand other tissues as well.Ghrelin not only plays animportant role in the regulation of appetite,energy balance and glucose homeostasis,but also shows antibacterial activity,suppresses pro-inflammatory cytokine production and restores gut barrier function.Inexperimental animals,ghrelin has shown significantbeneficial actions in preventing mortality from sepsis.In the critically ill,corticosteroid insufficiency as a resultof dysfunction of the hypothalamic-pituitary-adrenalaxis is known to occur.It is therefore possible that bothgut and hypothalamus play an important role in thepathogenesis of sepsis by virtue of their ability to produce ghrelin,which,in turn,could be a protective phenomenon to suppress inflammation.It remains to beseen whether ghrelin and its analogues are of benefit intreating patients with sepsis.
文摘Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by appropriate vagal stimulation that is anti-inflammatory in nature. Acetylcholine, the principal vagal neurotransmitter, is a potent anti-inflammatory molecule. Polyunsaturated fatty acids (PUFAs) augment acetylcholine release, while acetylcholine can enhance the formation of prostacyclin, lipoxins, resolvins, protectins and maresins from PUFAs, which are anti-inflammatory and anti-arrhythmic molecules. Furthermore, plasma and tissue levels of PUFAs are low in those with CHD and atherosclerosis. Hence, vagal nerve stimulation is beneficial in the prevention of CHD and cardiac arrhythmias. Thus, measurement of catecholamines, acetylcholine, various PUFAs, and their products lipoxins, resolvins, protectins and maresins in the plasma and peripheral leukocytes, and vagal tone by heart rate variation could be useful in the prediction, prevention and management of CHD and cardiac arrhythmias.
基金Supported by Ramalingaswami Fellowship of the Department of Biotechnology, Indiaa grant from the Defense Research and Development Organisation, New Delhi, India
文摘Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6-/-mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E2 (PGE2). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE2 production. These results suggest that the activities of △6 and △5 desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could prevent NAFLD. This suggests that an imbalance between proand anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.
文摘Scleritis and other autoimmune diseases are characterized by an imbalance in the levels of pro-inflammatory and anti-inflammatory molecules with the balance tilted more towards the former due to the failure of recognition of self. The triggering of inflammatory process could be ascribed to the presence of cytoplasmic DNA/chromatin that leads to activation of cytosolic DNA-sensing c GAS-STING(cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway and enhanced expression of NF-κB that results in an increase in the production of pro-inflammatory bioactive lipids. Bioactive lipids gamma-linolenic acid(GLA), dihomoGLA(DGLA), prostaglandin E1(PGE1), prostacyclin(PGI2) and lipoxin A4, resolvins, protectins and maresins have antiinflammatory actions, bind to DNA to render it non-antigenic and are decreased in autoimmune diseases. These results suggest that efforts designed to enhance the production of anti-inflammatory bioactive lipids may form a new approach to autoimmune diseases. Local injection or infusion of lipoxins, resolvins, protectins and maresins or their precursors such as arachidonic acid may be exploited in the prevention and management of autoimmune diseases including scleritis, uveitis and lupus/rheumatoid arthritis.
文摘Action to Control Cardiovascular Risk in Diabetes(ACCORD),The Action in Diabetes and Vascular Disease:Preterax and Diamicron Modified Release Controlled Evaluation and the Veterans Affairs Diabetes Trial were designed to study whether older patients with type 2 diabetes mellitus could reduce the risk of heart attacks and stroke and thereby prolong their lives by maintaining their blood glucose levels at near-healthy levels but failed to demonstrate the hoped-for benef it.Why the trials failed,though,and why ACCORD saw significantly more deaths due to increased rates of cardiovascular events in the intensive therapy arm of the study are not clear.These data have now been confirmed by the results of the recently concluded NICE-SUGAR Study which again revealed that intensive gluc ose control increased mortality among adults in intensive care units.I propose that the negative results noted in these trials are due to altered brain serot o nin concentrations and autonomic dysregulation in addition to the low-grade systemic inflammation,decreased endothelial nitric oxide and enhanced free radical generation,diminished anti-oxidant defenses and altered metabol ism of essential fatty acids present in patients with type 2 diabetes.
