Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antihypertensive agents of first choice include ACE-inhibitors, angiotensin receptor blockers, beta blockers, calcium antagonists and diuretic agents. For the selection of medicaments, the individual patient risk profile of decisive importance. In particular a metabolic syndrome, diabetes mellitus, disturbed renal function and/or a disturbed electrolyte household must be considered. For initial treatment monotherapy or a low-dose combination regime is suggested. If the response is inadequate, possible options include increasing the dose, changing the medicament, (sequential monotherapy) or, in the sense of stepped treatment, introduction of further combination drugs. Resistance to therapy should prompt consideration of a number of causes, in particular noncompliance on the part of the patient.
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PMID:[Medical treatment of hypertension--what treatment for what patients?]. 1537 6

Long hydrocarbon chain ethers with bis-terminal hydroxyl or carboxyl groups have been synthesized and evaluated for their potential to favorably alter lipid disorders including metabolic syndrome. Compounds were assessed for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes as well as for their effects on lipid and glycemic variables in female obese Zucker fatty rats following 1 and 2 weeks of daily oral administration. The most active compounds were found to be symmetrical with four to five methylene groups separating the central ether functionality and the gem dimethyl or methyl/aryl substituents. Biological activity was found to be greatest for tetramethyl-substituted ether diols (e.g., 28 and 31), while bis(arylmethyl) derivatives (e.g., 10, 11, and 27), diethers (e.g., 49, 50, and 56), and diphenyl ethers (e.g., 35 and 36) were the least active. For the most biologically active compound 28, we observed as much as a 346% increase in serum HDL-cholesterol and a 71% reduction in serum triglycerides at the highest dose administered (100 mg/kg) after 2 weeks of treatment. For compound 31 we observed a 69% reduction in non-HDL-cholesterol, accompanied by a 131% increase in HDL-cholesterol and an 84% reduction in serum triglycerides under the same treatment conditions.
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PMID:Long hydrocarbon chain ether diols and ether diacids that favorably alter lipid disorders in vivo. 1545 61

There are a total of 17 families of drugs that are used for treating the heterogeneous group of cardiovascular diseases. We propose a comprehensive pharmacogenomic approach in the field of cardiovascular therapy that considers the five following sources of variability: the genetics of pharmacokinetics, the genetics of pharmacodynamics (drug targets), genetics linked to a defined pathology and its corresponding drug therapies, the genetics of physiologic regulation, and environmental-genetic interactions. Examples of the genetics of pharmacokinetics are presented for phase I (cytochromes P450) and phase II (conjugating enzymes) drug-metabolizing enzymes and for phase III drug transporters. The example used to explain the genetics of pharmacodynamics is glycoprotein IIIa and the response to antiplatelet effects of aspirin. Genetics linked to a defined pathology and its corresponding drug therapies is exemplified by ADRB1, ACE, CETP and APOE and drug response in metabolic syndrome. The examples of cytochrome P450s, APOE and ADRB2 in relation to ethnicity, age and gender are presented to describe genetics of physiologic regulation. Finally, environmental-genetic interactions are exemplified by CYP7A1 and the effects of diet on plasma lipid levels, and by APOE and the effects of smoking in cardiovascular disease. We illustrate this five-tiered approach using examples of cardiovascular drugs in relation to genetic polymorphism.
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PMID:Pharmacogenomics and drug response in cardiovascular disorders. 1546 3

To compare effects of antihypertensive and combined therapy on 24-hour blood pressure, biochemical parameters and chronic hyperinsulinemia in patients with metabolic syndrome. 54 patients with metabolic syndrome were observed during 8 weeks. 28 patients (group A) were treated with antihypertensive agents (calcium antagonists, and when required -- ACE inhibitors and diuretics). 26 patients (group B) received the same therapy plus metformin. There were no significant changes in parameters of lipid and carbohydrate metabolism in group A. In group B we found significant decrease in C-peptide (p<0.05) and triglyceride (p<0.1) levels and increase in high density lipoprotein cholesterol levels (p<0.01). The combined antihypertensive and metformin therapy has a significant effect on carbohydrate and lipid metabolism.
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PMID:[Assessment of efficacy of combined therapy with antihypertensive agents and biguanides in patients with metabolic syndrome]. 1547 88

Keto-substituted hydrocarbons with 11-19 methylene and bis-terminal hydroxyl and carboxyl groups have been synthesized and evaluated in both in vivo and in vitro assays for their potential to favorably alter lipid disorders including metabolic syndrome. Compounds were assessed for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes as well as for their effects on lipid and glycemic variables in obese female Zucker fatty rats [Crl:(ZUC)-faBR] following 1 and 2 weeks of oral administration. The most active compounds were found to be symmetrical with four to five methylene groups separating the central ketone functionality and the gem dimethyl or methyl/aryl substituents. Furthermore, biological activity was found to be greatest in both in vivo and in vitro assays for the tetramethyl-substituted keto diacids and diols (e.g., 10c, 10g, 14c), and the least active were shown to be the bis(arylmethyl) derivatives (e.g., 10e, 10f, 14f). Compound 14c dose-dependently elevated HDL-cholesterol, reduced triglycerides, and reduced NEFA, with a minimum effective dose of 30 mg/kg/day. Compound 1 g dose-dependently modified non-HDL-cholesterol, triglycerides, and nonesterified fatty acids, with a minimum effective dose of 10 mg/kg/day. At this dose, compound 10g elevated HDL-cholesterol levels 2-3 times higher than pretreatment levels, and a dose-dependent reduction of fasting insulin and glucose levels was observed.
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PMID:Long hydrocarbon chain keto diols and diacids that favorably alter lipid disorders in vivo. 1553 62

The focus of current diabetes research is the clarification of the pathogenetic relationships between subclinical inflammation, diabetes and arteriosclerosis. Even minimal disturbances in glucose tolerance are associated with a chronic, generalized inflammatory reaction that links components of the metabolic syndrome and contributes to the development of diabetic complications as well as to the development and progression of arteriosclerosis. The most important mediators and markers of this inflammation cascade are NF-kappaB, TNF-alpha, IL-6, CRP and PAI-1. For the treatment of subclinical inflammation, substances with anti-inflammatory properties such as statins or ACE inhibitors are of increasing importance.
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PMID:[Inflammation and diabetes]. 1554 May 36

The role of the RAAS in development and maintenance of blood pressure is well established. In addition, the deleterious effects of angiotensin II on the heart, vasculature, and kidneys have been clearly defined. There seems to be a close relationship between endothelial dysfunction, insulin resistance (a precursor to diabetes and coronary artery disease) and angiotensin II. The signaling pathways for insulin in the vascular wall interacts with the angiotensin signaling, giving rise to potential mechanisms for development of diabetes and resulting harmful effects. A large number of clinical trials using ACE inhibitors or ARBs have shown significant reduction in secondary endpoints in the development of new onset of diabetes. Ongoing prospective studies involving ARBs (eg, the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research trial) and ACE inhibitors (eg, the Diabetes Re-duction Assessment with Ramipril and Rosiglita-zone Medication trial) are testing the ability of certain agents to prevent type 2 diabetes. In the meantime, it is important to recognize insulin resistance and metabolic syndrome as entities that increase the risk for cardiovascular disease. In addition to lifestyle modifications, managing endothelial dysfunction and protecting the vasculature will help prevent diabetes and cardiovascular disease.
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PMID:The renin angiotensin system as a therapeutic target to prevent diabetes and its complications. 1569 45

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.
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PMID:Can brain dysfunction be a predisposing factor for metabolic syndrome? 1575 41

Prevalence of the Type 2 diabetes mellitus (DM2) has been rising in the whole word. It is assumed that before DM2 develops, patients undergo a stadium of impaired glucose tolerance (IGT) or they have impaired fasting glycaemia (IFG). The confirmed IFG or IGT represent strong predictors of DM2 manifestation and at the same time they are related with high cardiovascular risk, namely with IGT. Other significant risk factor (RF) of DM2 is the obesity and metabolic syndrome. Recent clinical studies have shown that some metabolic abnormalities, which precede development of DM2 can be positively influenced by the lifestyle changes, including improvement of the diet and increasing the physical activity. Such measures can prevent or at least to delay the development of type 2 diabetes mellitus and thus the development of cardiovascular diseases. Positive effect has also the administration of some drugs, already tested in clinical studies, namely glitasons, metromin, inhibitor of ACE, sartans and other.
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PMID:[Contemporary prospects of prevention of type 2 diabetes mellitus]. 1588 94

Metabolic syndrome represents a common risk factor for premature cardiovascular disease and cancer whose core cluster includes diabetes, hypertension, dyslipidaemia and obesity. The liver is a target organ in metabolic syndrome patients in which it manifests itself with non-alcoholic fatty liver disease spanning steatosis through hepatocellular carcinoma via steatohepatitis and cirrhosis. Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients, not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome. The available drug weaponry for metabolic syndrome includes aspirin, metformin, peroxisome proliferator-activated receptor agonists, statins, ACE (angiotensin I-converting enzyme) inhibitors and sartans, which are potentially or clinically useful also to the non-alcoholic fatty liver disease patient. Studies are needed to highlight the grey areas in this topic. Issues to be addressed include: diagnostic criteria for metabolic syndrome; nomenclature of non-alcoholic fatty liver disease; enlargement of the clinical spectrum and characterization of the prognosis of insulin resistance-related diseases; evaluation of the most specific clinical predictors of metabolic syndrome/non-alcoholic fatty liver disease and assessment of their variability over the time; characterization of the importance of new risk factors for metabolic syndrome with regard to the development and progression of non-alcoholic fatty liver disease.
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PMID:Review article: the metabolic syndrome and non-alcoholic fatty liver disease. 1622 69


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