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Undurti N Das

Publications and source records attributed to Undurti N Das.

At least 37 records · Page 2Linked to original sources
PubMed2005

Pathophysiology of metabolic syndrome X and its links to the perinatal period.

It is proposed that metabolic syndrome X is initiated in the perinatal period as a low-grade systemic inflammatory condition. Increased consumption of energy-dense diets by pregnant women and lactating mothers suppresses the activities of Delta-6 and Delta-5 desaturases not only in maternal tissues but also in fetal liver and the placenta, resulting in decreased plasma and tissue concentrations of long-chain polyunsaturated fatty acids omega-6 arachidonic acid (AA), omega-3 eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA, DHA, and AA have negative feedback control on tumor necrosis factor-alpha and IL-6 synthesis. Hence, EPA, DHA, and AA deficiencies induced by an energy-dense diet increase generation of tumor necrosis factor-alpha and interleukin-6, markers of inflammation that in turn decrease production of endothelial nitric oxide and adiponectin to induce insulin resistance in maternal and fetal tissues. Increased concentrations of tumor necrosis factor-alpha and interleukin-6 enhance expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 enzyme, which produces abdominal obesity, insulin resistance, hyperlipidemia, hyperphagia, and hyperleptinemia, characteristic features of metabolic syndrome X. Continued consumption of an energy-dense diet in childhood aggravates these molecular events. This implies that supplementation of long-chain polyunsaturated fatty acids (especially AA, EPA, and DHA in appropriate ratios) from the perinatal period through adulthood could prevent, arrest, or postpone development of metabolic syndrome X.

Female↗
PubMed2005

Long-chain polyunsaturated fatty acids, endothelial lipase and atherosclerosis.

Endothelial lipase (EL), a new member of the lipase gene family, was recently cloned and has been shown to have a significant role in modulating the concentrations of plasma high-density lipoprotein levels (HDL). EL is closely related to lipoprotein and hepatic lipases both in structure and function. It is primarily synthesized by endothelial cells, functions at the cell surface, and shows phospholipase A1 activity. Overexpression of EL decreases HDL cholesterol levels whereas blocking its action increases concentrations of HDL cholesterol. Pro-inflammatory cytokines suppress plasma HDL cholesterol concentrations by enhancing the activity of EL. On the other hand, physical exercise and fish oil (a rich source of eicosapentaenoic acid and docosahexaenoic acid) suppress the activity of EL and this, in turn, enhances the plasma concentrations of HDL cholesterol. Thus, EL plays a critical role in the regulation of plasma HDL cholesterol concentrations and thus modulates the development and progression of atherosclerosis. The expression and actions of EL in specific endothelial cells determines the initiation and progression of atherosclerosis locally explaining the patchy nature of atheroma seen, especially, in coronary arteries. Both HDL cholesterol and EPA and DHA enhance endothelial nitric oxide (eNO) and prostacyclin (PGI2) synthesis, which are known to prevent atherosclerosis. On the other hand, pro-inflammatory cytokines augment free radical generation, which are known to inactivate eNO and PGI2. Thus, interactions between EL, pro- and anti-inflammatory cytokines, polyunsaturated fatty acids, and the ability of endothelial cells to generate NO and PGI2 and neutralize the actions of free radicals may play a critical role in atherosclerosis.

Animals↗
PubMed2005

A defect in the activity of Delta6 and Delta5 desaturases may be a factor predisposing to the development of insulin resistance syndrome.

GLUT-4 (glucose transporter) receptor, tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), daf-genes and PPARs (peroxisomal proliferation activator receptors) play a role in the development of insulin resistance syndrome and associated conditions. But, the exact interaction between these molecules/factors and the mechanism(s) by which they produce insulin resistance syndrome is not clear. I propose that a defect in the activity of the enzymes Delta6 and Delta5 desaturases that are essential for the formation of long chain metabolites of essential fatty acids, linoleic acid and alpha-linolenic acid, is a factor in the development of insulin resistance syndrome. Long chain polyunsaturated fatty acids (LCPUFAs) increase cell membrane fluidity and enhance the number of insulin receptors and the affinity of insulin to its receptors; suppress TNF-alpha, IL-6, macrophage migration inhibitory factor (MIF) and leptin synthesis; increase the number of GLUT-4 receptors, serve as endogenous ligands of PPARs, modify lipolysis, and regulate the balance between pro- and anti-oxidants, and thus, play a critical role in the pathogenesis of insulin resistance. In the nematode, Caenorhabditis elegans, the protein encoded by daf-2 is 35% identical to the human insulin receptor; daf-7 codes a transforming growth factor-beta (TGF-beta) type signal and daf-16 enhances superoxide dismutase (SOD) expression. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Calorie restriction enhances the activity of Delta6 and Delta5 desaturases, melatonin production, decreases daf-2 signaling, free radical generation, and augments anti-oxidant defenses that may explain the beneficial effect of diet control in the management of obesity, insulin resistance, and type II diabetes mellitus. These evidences suggest that the activities of Delta6 and Delta5 enzymes play a critical role in the expression and regulation of GLUT-4, TNF-alpha, IL-6, MIF, daf-genes, melatonin, and leptin by modulating the synthesis and tissue concentrations of LCPUFAs. Caloric restriction delays ageing by activating Sir 2 deacetylase in yeast, and expression of Sir 2 (SIRT1) in human cells. Both insulin and insulin-like growth factor-1 (IGF-1) attenuated this response. SIRT1 sequesters the proapoptotic factor Bax, prevents stress-induced apoptosis of cells, and thus, prolongs survival. In addition, SIRT1 repressed PPAR-gamma, and overexpression of SIRT1 attenuated adipogenesis, and upregulation of SIRT in differentiated fat cells triggered lipolysis and loss of fat, events that are known to attenuate insulin resistance and prolong life span. It remains to be seen whether LCPUFAs have a regulatory role in SIRT1 expression and control Sir 2 deacetylase activity. Thus, calorie restriction or reduced food intake has a role not only in the pathobiology of insulin resistance, but also in other associated conditions such as obesity, type II diabetes mellitus, ageing, and longevity.

Animals↗
PubMed2004

Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: The ATTICA Study.

OBJECTIVES: We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein (CRP), white blood cell counts, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, amyloid A, fibrinogen, and homocysteine. BACKGROUND: To the best of our knowledge, the mechanism(s) by which the Mediterranean diet reduces cardiovascular risk are not well understood. METHODS: During the 2001 to 2002 period, we randomly enrolled 1,514 men (18 to 87 years old) and 1,528 women (18 to 89 years old) from the Attica area of Greece (of these, 5% of men and 3% of women were excluded because of a history of cardiovascular disease). Among several factors, adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet. Higher values of the score meant closer adherence to the Mediterranean diet. RESULTS: Participants who were in the highest tertile of the diet score had, on average, 20% lower CRP levels (p = 0.015), 17% lower IL-6 levels (p = 0.025), 15% lower homocysteine levels (p = 0.031), 14% lower white blood cell counts (p = 0.001), and 6% lower fibrinogen levels (p = 0.025), as compared with those in the lowest tertile. The findings remained significant even after various adjustments were made. Borderline associations were found regarding TNF-alpha (p = 0.076), amyloid A levels (p = 0.19), and diet score. CONCLUSIONS: Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers. This may partly explain the beneficial actions of this diet on the cardiovascular system.

Adolescent↗
PubMed2004

Perinatal supplementation of long-chain polyunsaturated fatty acids, immune response and adult diseases.

Both omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) modulate TH1 and TH2 cell generation, their cytokine production, and cell proliferation and thus may serve as endogenous anti-inflammatory molecules. LCPUFAs suppress the production of tumor necrosis factor-alpha (TNF-alpha) (and so also of OX40, since it belongs to the family of TNFR) and the expression of Bcl-2, suggesting that these fatty acids have the ability to prevent/suppress autoimmune diseases. Human breast milk contains substantial amounts of both omega-3 and omega-6 fatty acids. This indicates that LCPUFAs present in human breast milk suppress the levels of OX40 and decrease the expression of Bcl-xL and Bcl-2 on exposure to self-antigens and thus, protects against the development of autoimmune diseases in later life. In view of this, I propose that supplementation of appropriate amounts of LCPUFAs during perinatal period protects against atopy, asthma, auto-immune diseases, type 1 and type 2 diabetes mellitus, hypertension, coronary heart disease, metabolic syndrome X, lymphomas, leukemias and other cancers, schizophrenia, depression and other adult diseases in which low-grade systemic inflammation plays a significant role. It is also likely that perinatal supplementation of LCPUFAs in adequate amounts modulates the expression of genes concerned with immune response, angiogenesis, central osmo/sodium and glucose sensors etc. This renders various tissues and organs including T cells and macrophages, endothelial cells, hypothalamic neurons, and various cardiovascular tissues to be able to counteract the pathological mechanisms that tend to induce various adult diseases by blunting the inflammatory responses in those who received adequate amounts of LCPUFAs during the perinatal period compared to those who did not.

Anti-Inflammatory Agents↗
PubMed2004

Metabolic syndrome X: an inflammatory condition?

Obesity, atherosclerosis, insulin resistance and hyperinsulinemia, hyperlipidemia, essential hypertension, type 2 diabetes mellitus, and coronary heart disease (CHD) are the components of metabolic syndrome X and are associated with elevated plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha, which are markers of inflammation. This suggests that metabolic syndrome X is a low-grade, systemic, inflammatory condition. Hence, instituting anti-inflammatory measures might be beneficial in preventing or halting the progress of metabolic syndrome X in high-risk populations.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2004

Effects of omega-3 fatty acid supplementation on tumor-bearing rats.

BACKGROUND: Dietary fish oil (rich in omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid) suppresses synthesis and activity of proinflammatory cytokines that induce anorexia. We hypothesized that dietary fish oil reverses the feeding pattern of tumor anorexia, increasing food intake and retarding tumor growth. STUDY DESIGN: Thirty-two Fischer rats were placed in Automated Eater Meter cages and randomly divided into four groups: tumor bearing (TB) rats eating normal chow diet (TB-Chow); TB rats eating chow diet supplemented with omega-3 fatty acids (TB-omega-3FA); Controls, non-tumor bearing (NTB) rats eating normal chow (NTB-Chow); and NTB rats with omega-3 fatty acid supplementation (NTB-omega-3FA). Doses of 10(6) methylcholanthrene (MCA) sarcoma cells were subcutaneously injected in TB rats. Daily food intake, meal size (MZ), meal number (MN), body weight, and tumor volume were measured, and rats were euthanized at onset of anorexia. Data were statistically analyzed using analyses of variance (ANOVA) and t-tests. Data are reported as mean +/- SE. RESULTS: Tumor appeared significantly earlier in TB-Chow than in TB-omega-3FA rats (7.5 +/- 0.3 days versus 11.6 +/- 0.8 days, p < 0.05). Daily food intake declined significantly in TB-Chow versus TB-omega-3FA rats 18 days after tumor inoculation and, at onset of anorexia, was 9.41 +/- 1.77 g/day versus 13.32 +/- 0.81 g/day, p < 0.05. Food intake decreased initially by decrease in meal number (at day 15) followed by a decrease in meal size (at day 18). At onset of anorexia, meal size and meal number were significantly decreased in TB-Chow versus TB-omega-3FA rats (0.75 +/- 0.067 g/meal versus 1.05 +/- 0.08 g/meal, p < 0.05) and (9.5 +/- 1.32 versus 12.79 +/- 0.93 meals/day, p < 0.05), respectively. Tumor volume was significantly smaller in TB-omega-3FA versus TB-Chow rats (7.6 +/- 0.6 cm(3) versus 16.5 +/- 1.0 cm(3), p < 0.05), as was tumor weight (7.5 +/- 2.2 g versus 18.1 +/- 1.6 g, p < 0.05). CONCLUSIONS: In TB rats, omega-3FA improved food intake; restored normal eating pattern, delayed onset of anorexia, tumor appearance, and growth; and prevented body weight loss. Supplementation of omega-3 fatty acids has therapeutic potential in cancer anorexia.

Animals↗
PubMed2004

Essential fatty acids in Huntington's disease.

Huntington's disease is an inherited neurodegenerative disorder due to a mutation in exon 1 of the Huntingtin gene that encodes a stretch of polyglutamine (polyQ) residues close to the N-terminus of the huntingtin protein. Aggregated polyQ residues are highly toxic to the neuronal cells when they enter the cell nucleus. The mechanisms by which aggregated polyQ induces neurodegeneration include the binding of abnormal huntingtin to cyclic adenosine monophosphate response element binding protein, which hampers its ability to turn on transcription of other genes; mutant huntingtin binding to the active site on the cyclic adenosine monophosphate response element binding protein, which is essential for its acetyltransferase activity and, hence, the drugs that inhibit histone deacetylase arrest polyQ-dependent neurodegeneration; and/or disrupting the ubiquitin-proteasome system. Transgenic R6/1 mice that incorporate a human genomic fragment containing promoter elements exon 1 and a portion of intron 2 of the huntingtin gene responsible for Huntington's disease develop late-onset neurologic deficits in a manner similar to the motor abnormalities of Huntington's disease and show increased survival rates and decreased neurologic deficits when supplemented with essential fatty acids throughout life. A randomized, placebo-controlled, double-blind study has shown that highly unsaturated fatty acids are beneficial to patients with Huntington's disease. These results raise the possibility that unsaturated fatty acids may prevent or arrest polyQ aggregation, inhibit histone deacetylase, and/or activate the ubiquitin-proteasome system. In view of the encouraging results with essential fatty acids in Huntington's disease, it is proposed that their possible use in other neurodegenerative conditions need to be explored.

Fatty Acids, Essential↗
PubMed2004

Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus.

Paraventricular (PVN) concentrations of neuropeptide Y (NPY), serotonin (5-HT) and dopamine (DA) in anorectic tumor-bearing (TB) rats were measured before and after tumor resection. At onset of anorexia in TB versus non-tumor bearing (NTB) Controls 5-HT increased from 12.19+/-0.49 pg/microg to 14.89+/-0.81 pg/microg ( P<0.05 ) while DA and NPY decreased from 7.34+/-0.42 pg/microg to 4.97+/-0.56 pg/microg and 23.47+/-4.27 pg/microg to 13.64+/-1.44 pg/microg, respectively ( P<0.05 ). After tumor resection, these neuromediators normalized when compared to sham-operated NTB rats. NTB pair-fed Controls were also studied. We conclude that the increased 5-HT and the decreased DA and NPY concentrations in PVN are associated with cancer anorexia and that the NPY food stimulatory effect is linked to serotoninergic and dopaminergic systems in hypothalamus.

Animals↗
PubMed2004

Occlusion of infusion vessels on gamma-linolenic acid infusion.

gamma-Linolenic acid (GLA) is known to have selective tumoricidal action. In this study, the effect of lithium salt of GLA conjugated to iodized lymphographic oil (LGIOC) was injected intra-arterially close to the origin of tumor-feeding vessel(s) was studied. Four patients with stage 4 cancer disease (2 with hepatocellular carcinoma, 1 with giant cell tumor of the bone, and one with renal cell carcinoma), were selected for the study. Angiography, radiography and computed axial tomography were performed prior to and immediately after the injection of LGIOC and at periodic intervals. All four patients tolerated the treatment well. The most significant observation was the complete occlusion of the tumor-feeding vessels after LGIOC injection. Follow-up angiograms performed in all the patients showed occlusion of the tumor-feeding vessels is more or less permanent. A significant reduction in the size of the tumor was also observed in these patients. LGIOC showed occlusion of tumor-feeding vessels after infusion, and further studies are needed to confirm these preliminary results.

Adult↗
PubMed2004

From bench to the clinic: gamma-linolenic acid therapy of human gliomas.

Malignant gliomas are among the most devastating of cancers and are a major cause of mortality in a young population with a median survival time of 9 months following cytoreductive surgery, radiotherapy and chemotherapy. Recent studies showed that polyunsaturated fatty acids especially gamma-linolenic acid (GLA) have selective tumoricidal action especially against malignant glioma cells both in vitro and in vivo. Limited open label clinical studies showed that intratumoral injection/infusion of GLA is safe and effective against malignant gliomas. In view of this, large-scale, double blind studies are needed to establish the usefulness of GLA in the treatment of malignant brain tumors.

Antineoplastic Agents↗
PubMed2004

Interleukin-1beta system in anorectic catabolic tumor-bearing rats.

PURPOSE OF REVIEW: The onset of cancer anorexia and the accompanying neurological symptoms and signs involve the general influence of cytokines on the brain. Using methylcholanthrene to induce tumors in Fischer 344 rats, we measured various specific components of the cytokine-induced anorectic reaction, including: (1) IL-1beta system components (ligand, signaling receptor, receptor accessory proteins, and receptor antagonist); (2) TNF-alpha; (3) TGF-beta1; and (4) IFN-gamma in the tumor tissue, the liver and the brain. RECENT FINDINGS: The data show that IL-1beta, TNF-alpha and IFN-gamma messenger RNA were detected in the tumor tissue of anorectic tumor-bearing rats. In brain regions, anorexia is associated with the upregulation of IL-1beta and its receptor mRNA. All other mRNA remained unchanged in the brain regions examined. SUMMARY: This suggests that IL-1beta and its receptor may play a significant role in this model of cancer-associated anorexia. In vivo, the characterization of cytokine components in the brain may provide data for potential pharmacological interventions to ameliorate the anorexia of disease.

Animals↗
PubMed2004

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevents schizophrenia in adult life?

It is suggested that perinatal supplementation of long-chain polyunsaturated fatty acids (LCPUFAs) especially; eicosapentaenoic and docosahexaenoic acids prevent schizophrenia in the adult. I propose that schizophrenia could be a low-grade systemic inflammatory disease with its origins in the perinatal period, probably triggered by maternal infection in a genetically susceptible individual that leads to excess production of pro-inflammatory cytokines both in the mother and the fetus. These cytokines, in turn, induce damage to the fetal neurons leading to the adult onset of schizophrenia. I suggest that maternal infection perse interferes with the metabolism of essential fatty acids (EFAs) resulting in deficiency of LCPUFAs that are known to have neuroprotective action. Alternatively, decreased formation of LCPUFAs as a result of decreased activity of D6 and D5 desaturases (due to prematurity) can result in neuronal damage due to the absence/decrease in the neuroprotective LCPUFAs. This is supported by the observation that LCPUFAs suppress the production of pro-inflammatory cytokines, have anti-inflammatory and neuroprotective actions. Furthermore, LCPUFAs are essential for brain growth and development. If this hypothesis is true, it implies that perinatal supplementation of appropriate amounts of LCPUFAs in the right combination is helpful in the prevention of schizophrenia in adult life.

Animals↗
PubMed2003

Can memory be improved? A discussion on the role of ras, GABA, acetylcholine, NO, insulin, TNF-alpha, and long-chain polyunsaturated fatty acids in memory formation and consolidation.

It is proposed that long-chain polyunsaturated fatty acids when given from the perinatal period will ensure proper development and growth of the brain and maintain the activity and/or concentrations of ras, nitric oxide, insulin, and various neurotransmitters and cytokines at physiological level and thus, improve memory and prevent learning deficits.

Acetylcholine↗
PubMed2003

Gamma-linolenic acid therapy of human gliomas.

OBJECTIVES: We investigated the effect of intratumoral administration of gamma-linolenic acid (GLA) in human gliomas. METHODS: We evaluated the effect of the administration of 1 mg of GLA for 7 d via a cerebral reservoir placed into the tumor bed or by direct intratumoral delivery in nine patients who had grade 4 disease and recurrent glioma after surgery, radiation, or chemotherapy. RESULTS: There was some, but not dramatic, improvement in patients' survival. No significant prolongation of life span was expected considering the advanced nature of the disease. Nevertheless, it was encouraging that GLA produced no significant side effects in any patient. Regression of the cerebral gliomas was visualized on computed tomography and magnetic resonance imaging. CONCLUSIONS: Based on results of the present and previous studies, we believe that GLA is a safe antitumor agent and that higher doses of GLA should be investigated in future studies.

Adolescent↗