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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (the so-called "class effect"). However, statins differ in multiple characteristics, including liver and renal metabolism, half-life, effects on several serum lipid components, bioavailability and potency. Some are fungal derivatives, and others are synthetic compounds. The percentage absorption of an oral dose, amount of protein binding, degree of renal excretion, hydrophilicity, and potency on a weight basis is variable. These differences may be even greater in diabetic patients, who may present diabetes-induced abnormalities in P450 isoforms and altered hepatic metabolic pathways. Thus, it is obvious that head-to-head comparisons between different statins are preferable than trial-to-trial comparisons. Such assessments are of utmost importance, especially in cases in which specific populations with a distinct lipid profile and altered metabolic pathways, like diabetics, are studied. It should be specially pinpointed that patients with metabolic syndrome and diabetes constitute also a special population regarding their atherogenic dyslipidemia, which is usually associated with low HDL-cholesterol, hypertriglyceridemia and predominance of small dense LDL-cholesterol. Therefore, these patients may benefit from fibrates or combined statin/fibrate treatment. This policy is not accomplished since in the real world things are more complex. Trials would require very large sample sizes and long-term follow-up to detect significant differences in myocardial infarction or death between two different statins. Moreover, the fact that new compounds are under several phases of research and development represents an additional drawback for performing the trials. Ideally, head-to-head trials regarding clinically important outcomes should be conducted for all drugs. Nonetheless, the desirability of performing such trials, which epitomize modern evidence-based medicine, is frequently superseded by the feasibility dictated by pragmatic and economic circumstances. In the latter case, in absence of solid systematic documentation of comparable health benefits and long-term safety, both researchers and practicing physicians should allude to the weight of scientific endorsement behind the arguments and seek for the possible strengths and weaknesses intrinsic to each specific study. In any case, conclusions based on surrogate endpoints cannot completely substitute head-to-head comparisons regarding patients' outcome.
Cardiovasc Diabetol 2005 Jun 07
PMID:Statins research unfinished saga: desirability versus feasibility. 1594 71

Adrenomedullin was originally discovered as a vasodilative peptide, but recent studies have revealed its pleiotropic effects. Among these studies, the antioxidative properties of adrenomedullin were observed in adrenomedullin knockout mice. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by high blood pressure, ischemia and aging. This indicates that antioxidants that can inhibit reactive oxygen species production but do not have a scavenging effect could be a new effective therapeutic target for organ protection in hypertension as well as metabolic syndrome, in which higher oxidative stress plays a pivotal role.
Timely Top Med Cardiovasc Dis 2005 Jun 01
PMID:Adrenomedullin as a potent antioxidative and antiatherosclerotic substance. 1594 48

Cardiovascular disease (CVD) and diabetes are growing public health burdens and remain one of the leading causes of morbidity and mortality in Canada (Heart and Stroke Foundation, 2003). It has become increasingly evident that individuals who present with a cluster of metabolic disorders, known as the metabolic syndrome, are at an increased risk of developing both CVD and type 2 diabetes (Ng, 2003). Due to the increased risk of morbidity and mortality associated with the metabolic syndrome, it is imperative for health care professionals to become familiar with the diagnostic criteria for this disorder. This will enable nurses to provide the appropriate primary and secondary prevention strategies in order to help reduce individual risk. With the help of a case study, this article will define metabolic syndrome, review its prevalence and risk factors, and discuss therapeutic interventions for this disorder.
Can J Cardiovasc Nurs 2005
PMID:Metabolic syndrome. 1597 60

Dyslipidemia, fundamental to the atherosclerotic process, is now a readily correctable risk factor with established efficacy of treatment for reducing risk of CHD and strokes. The current focus on LDL-cholesterol for risk assessment needs to be broadened to accommodate the two-way traffic of cholesterol entering and leaving the arterial intima reflected by the LDL/HDL ratio or the Total/HDL ratio. The choice of lipid therapy should be individualized to take into account the presence of the metabolic syndrome and the lipid profile of the patient. The intensity of therapy and goals should be linked to multivariable risk, particularly in those with modest lipid values. Cardiovascular risk factor clustering is pronounced for each lipid, is promoted by adiposity and greatly influences its CHD hazard. Global risk assessment taking clustering into account is essential for efficient preventive management of lipids. More attention needs to be afforded the absolute risk reduction attainable and must recognize that the number needed to treat to prevent one event increases the lower the lipid value, the lower global risk and the healthier the subject.
Curr Med Chem Cardiovasc Hematol Agents 2005 Jul
PMID:Risk stratification of dyslipidemia: insights from the Framingham Study. 1597 83

The vascular endothelial basement membrane and extra cellular matrix is a compilation of different macromolecules organized by physical entanglements, opposing ionic charges, chemical covalent bonding, and cross-linking into a biomechanically active polymer. These matrices provide a gel-like form and scaffolding structure with regional tensile strength provided by collagens, elasticity by elastins, adhesiveness by structural glycoproteins, compressibility by proteoglycans--hyaluronans, and communicability by a family of integrins, which exchanges information between cells and between cells and the extracellular matrix of vascular tissues. Each component of the extracellular matrix and specifically the capillary basement membrane possesses unique structural properties and interactions with one another, which determine the separate and combined roles in the multiple diabetic complications or diabetic opathies. Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel companion (atheroscleropathy) are associated with multiple metabolic toxicities and chronic injurious stimuli. The adaptable quality of a matrix or form genetically preloaded with the necessary information to communicate and respond to an ever-changing environment, which supports the interstitium, capillary and arterial vessel wall is individually examined.
Cardiovasc Diabetol 2005 Jun 28
PMID:The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded. 1598 57

Few treatments for obesity exist and improvements for treatment of hyperlipidemia are still desirable. Thyroid hormone receptors (TRs) regulate body weight, adiposity, and cholesterol levels. However, thyroid hormones can have deleterious effects, particularly cardiac acceleration, that limits the use of hormones in the treatment of obesity. There is evidence that the TRbeta subtype mediates lowering of blood cholesterol levels and possibly elevation of metabolic rate, whereas TRalpha appears to control heart rate. In studies, described in this review article, we examined the effects of selective TRbeta activation on metabolic rate and heart rate in mice, rats and monkeys. T3 had a greater effect on increasing heart rate in wild type (WT) than in TRalpha-/- mice (ED15 values of 34 and 469 nmol/kg/day, respectively). T3 increased metabolic rate (MVO2) in both WT and TRalpha-/- mice, but the effect on TRalpha-/- mice was less pronounced compared to WT mice. Stimulation of MVO2 is mediated by both TRalpha and TRbeta, but with different profiles. In cholesterol-fed rats, KB-141, a selective TRbeta agonist, increased MVO2 with a 10-fold selectivity and lowered cholesterol with a 27-fold selectivity vs. tachycardia. In primates, KB-141 caused significant, cholesterol, Lp(a) and body weight reduction after 1 week of treatment with no effect on heart rate. These data suggest that selective TRbeta agonists may represent a novel class of drugs for the treatment of obesity, hypercholesterolemia and elevated Lp(a), which may make them useful therapeutics for patients with metabolic syndrome.
Cardiovasc Drug Rev 2005
PMID:Development of the thyroid hormone receptor beta-subtype agonist KB-141: a strategy for body weight reduction and lipid lowering with minimal cardiac side effects. 1600 30

Atherosclerosis, myocardial infarction, and heart failure are cardiovascular complications in a continuum that begins with risk factors such as hypertension, diabetes, and dyslipidemia. These particular cardiovascular risk factors commonly occur together in obese individuals as components of the metabolic syndrome. In Asia, there is a trend toward an increase in the prevalence of the metabolic syndrome and cardiovascular disease. Abdominal adiposity is arguably the key factor underlying the development of insulin resistance and the metabolic syndrome. It is now known that adipose tissues secrete adipokines, and in obese subjects, there is a chronic low-grade inflammation. The inflammation and the associated endothelial dysfunction are reversible in the early stages. The Asian diet is low in animal fat but high in carbohydrates. Recent studies suggest that low-carbohydrate diets are more effective than low fat diets in inducing weight loss, suggesting that excessive carbohydrate rather than fat is the cause of obesity. Strategies to combat cardiovascular disease should now focus on tackling the epidemic of obesity and developing innovative and effective lifestyle and pharmacological interventions.
J Cardiovasc Pharmacol 2005 Aug
PMID:The cardiovascular continuum in Asia--a new paradigm for the metabolic syndrome. 1604 22

Diabetic patients may have aggressive coronary disease with an excessive rate of restenosis and accelerated atherosclerotic progression. This article reviews the different modalities of percutaneous treatment and their results in the diabetic population, from the early days of balloon angioplasty to the current implementation of drug-eluting stents. As restenosis may be virtually eradicated in the near future, plaque progression remains the cornerstone for interventional cardiologists and the medical community. In this regard, attempts to modify life habits, and a more accurate control of the components of the metabolic syndrome should be the main therapeutic objective.
Expert Rev Cardiovasc Ther 2005 Jul
PMID:Percutaneous coronary revascularization in diabetics: from balloon angioplasty to drug-eluting stents. 1607 74

Studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac disease.The introduction of HAART regimens, by preventing opportunistic infections and reducing the incidence of myocarditis, has reduced the prevalence of HIV-associated cardiomyopathy of about 30% and the prevalence of cardiac involvement of AIDS-associated malignancies of about 50%. However, HAART regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (approximately 1.4 cardiac events per 1000 years of therapy according to the Framingham score). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART according to the most recent clinical guidelines is needed.
Curr Drug Targets Cardiovasc Haematol Disord 2005 Aug
PMID:Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy. 1610 66

There are three peroxisome proliferator-activated receptors (PPARs) subtypes which are commonly designated PPAR alpha, PPAR gamma and PPAR beta/delta. PPAR alpha activation increases high density lipoprotein (HDL) cholesterol synthesis, stimulates "reverse" cholesterol transport and reduces triglycerides. PPAR gamma activation results in insulin sensitization and antidiabetic action. Until recently, the biological role of PPAR beta/delta remained unclear. However, treatment of obese animals by specific PPAR delta agonists results in normalization of metabolic parameters and reduction of adiposity. Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands. The new generation of dual-action PPARs--the glitazars, which target PPAR-gamma and PPAR-alpha (like muraglitazar and tesaglitazar) are on deck in late-stage clinical trials and may be effective in reducing cardiovascular risk, but their long-term clinical effects are still unknown. A number of glitazars have presented problems at a late stage of clinical trials because of serious side-effects (including ragaglitazar and farglitazar). The old and well known lipid-lowering fibric acid derivative bezafibrate is the first clinically tested pan--(alpha, beta/delta, gamma) PPAR activator. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile. Therefore, bezafibrate could be considered (indeed, as a "post hoc" understanding) as an "archetype" of a clinically tested pan-PPAR ligand. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. Clinical evidences obtained from bezafibrate-based studies strongly support the concept of pan-PPAR therapeutic approach to conditions which comprise the metabolic syndrome. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. More powerful new compounds with pan-PPAR activity and proven long-term safety should be highly effective in a clinical setting of patients with coexisting relevant lipid and glucose metabolism disorders.
Cardiovasc Diabetol 2005 Sep 16
PMID:Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. 1616 52


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