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).

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.

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.

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.

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.

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.

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.

A perinatal strategy to prevent coronary heart disease.

I investigated whether metabolism of essential fatty acids and the concentrations of their long-chain metabolites (long-chain polyunsaturated fatty acids [LCPUFAs]) are altered in fetal or perinatal growth retardation, maternal hypercholesterolemia, low-grade systemic inflammation, insulin resistance, and atherosclerosis, conditions that predispose to the development of coronary heart disease (CHD).I critically reviewed the literature pertaining to the metabolism of essential fatty acids in CHD and conditions that predispose to it.LCPUFAs enhance endothelial nitric oxide synthesis, suppress the production of the proinflammatory cytokines tumor necrosis factor and interleukin-6, attenuate insulin resistance, and have antiatherosclerotic properties.

Insulin in sepsis and septic shock.

NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.

Insulin: an endogenous cardioprotector.

This review discusses the myocardial protective property of the insulin/glucose-insulin-potassium regimen and the mechanisms involved in this beneficial action. Several recent studies suggest that insulin not only is useful to control hyperglycemia and maintain glucose homeostasis but also may have the unique property to protect the myocardium from reperfusion injury and ischemia and prevent apoptosis of myocardial cells. The insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha, interleukin-6, macrophage migration inhibitory factor and other pro-inflammatory cytokines, and free radicals; and enhances the synthesis of endothelial nitric oxide and anti-inflammatory cytokines interleukin-4 and interleukin-10.

Current advances in sepsis and septic shock with particular emphasis on the role of insulin.

Sepsis and septic shock account for substantial morbidity and mortality in the intensive care units. NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-a (TNF-alpha), interleukin-1 (IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia are some of the factors that induce systemic inflammatory response and myocardial depression seen in sepsis. Conversely, adenosine, activated protein C, oxidized phospholipids, w-3 fatty acids, and insulin have beneficial effects in sepsis and septic shock.

Folic acid says NO to vascular diseases.

Objectives: The possible link between folic acid or folate and tetrahydrobiopterin (H(4)B), vitamin C, polyunsaturated fatty acids (PUFAs), and nitric oxide (NO), which may explain the beneficial actions of these nutrients in various vascular conditions, was investigated.

Methods: The literature pertaining to the actions of folic acid/folate, H(4)B, vitamin C, PUFAs, and NO was reviewed.

Results: Impaired endothelial NO (eNO) activity is an early marker for cardiovascular disease.

Metabolic alterations during inflammation and its modulation by central actions of omega-3 fatty acids.

Purpose Of Review: To discuss the possible relationship between long-chain polyunsaturated fatty acids, cytokines, anandamides, nitric oxide, leptin, various neurotransmitters in the brain, and their role in anorexia of acute and chronic inflammatory conditions and cancer.

Recent Findings: Recent studies have shown that long-chain polyunsaturated fatty acids, especially the omega-3 series, have antiinflammatory actions, increase the concentrations of anandamides, enhance the levels of acetylcholine and nitric oxide and modulate the concentrations and actions of various neurotransmitters, including leptin, in the brain. Patients suffering from acute and chronic inflammatory conditions have low tissue concentrations of various long-chain polyunsaturated fatty acids, and high levels of proinflammatory cytokines that can cause anorexia and decrease food intake.

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.

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.

Is metabolic syndrome X an inflammatory condition?

It is suggested that metabolic syndrome X is a low-grade systemic inflammatory condition.

Is insulin an endogenous cardioprotector?

Stress hyperglycemia and diabetes mellitus with myocardial infarction are associated with increased risk for in-hospital mortality, congestive heart failure, or cardiogenic shock. Hyperglycemia triggers free radical generation and suppresses endothelial nitric oxide generation, and thus initiates and perpetuates inflammation. Conversely, insulin suppresses production of tumor necrosis factor-alpha and free radicals, enhances endothelial nitric oxide generation, and improves myocardial function.