Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently there has been increased concern over the side effects of the atypical antipsychotic drugs, including diabetes, hyperlipidemia and obesity. The relationship between diabetes and antipsychotic drugs requires a careful analysis. Patients with schizophrenia are known to suffer from diabetes more often than the general population. In addition, a number of case reports indicate that the conventional antipsychotic as well as atypical antipsychotic drugs produce diabetes. Clozapine and olanzapine, in particular, have been implicated producing diabetes as well as diabetic ketoacidosis. Epidemiological surveys have supplemented the case reports, finding increased incidence of diabetes in patients treated with atypical antipsychotic agents, but these surveys have not yielded consistent results regarding the differential effects of the various atypical antipsychotic drugs. The mechanism by which antipsychotic agents produce diabetes is not elucidated. Weight gain and consequent alteration in triglycerides and cholesterol have been known to occur frequently with olanzapine and clozapine. The ensuing metabolic syndrome itself may cause insulin resistance and diabetes. In the absence of definitive scientific data on the differential effects of antipsychotic drugs in inducing diabetes, clinical prudence and careful monitoring of all patients on atypical antipsychotic drugs is necessary. Aripiprazole and ziprasidone have not been shown to increase weight or produce diabetes, but more information on the diabetogenic effects of ziprasidone and aripiprazole is needed. In order to assess the differential effects of atypical antipsychotic drugs in producing diabetes and the mechanisms by which they produce this reaction, further research is necessary.
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PMID:Side effects of atypical antipsychotic drugs. 1528 97

Metabolic syndrome is the latest moniker for an alliance of pathologic conditions that conspire to amplify the risk of atherosclerosis or type 2 diabetes. Several recent advances in the understanding of this condition have led to its widespread adoption in clinical practice, prompted by influential practice guidelines. In particular, guidelines relating to the management of hyperlipidemia and hypertension afford a prominent role for metabolic syndrome, as a risk factor and a target of therapy. In many ways, the scientific evidence base has not kept pace with the demand for treatment options, rendering therapy nebulous. Most prominently, we do not know whether to adopt a strategy based on a multi-pronged attack, or whether to concentrate our greatest efforts on attacking a critical weakness. We review the limited data available regarding metabolic syndrome, with a focus on expert opinion gleaned from clinical guidelines, and offer advice to the clinician from our own experience with this population.
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PMID:Slaying the metabolic syndrome. Are we battling the Hydra or the Chimera? 1528 43

The upstream stimulatory factor (USF) proteins are ubiquitously expressed and, as such, represent unusual candidates for involvement in disorders of carbohydrate and lipid metabolism. Nonetheless, a recent study has reported an association between specific alleles of USF1 and familial combined hyperlipidaemia, a common disorder that substantially increases the risk of premature atherosclerotic cardiovascular disease. USF1 might, therefore, also contribute to the metabolic syndrome. The use of chromatin immunoprecipitation methodologies combined with promoter microarray assays will help to define the transcriptional networks that underlie whole-body glucose and lipid homeostasis.
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PMID:USF1 implicated in the aetiology of familial combined hyperlipidaemia and the metabolic syndrome. 1531 Apr 55

Zucker diabetic fat (ZDF) rats with the metabolic syndrome and hyperlipidemia develop focal and segmental sclerosis. The role of oxidative and nitrosative stress in the nephropathy in ZDF was studied. Renal histology, function, and immunohistologic and biochemical parameters of oxidative and nitrosative stress were evaluated at 8 and 22 wk of age in ZDF and Zucker lean (ZL) rats and after chronic treatment with ebselen, an antioxidant and peroxinitrite scavenger. At 8 wk, ZDF rats showed hyperglycemia, no proteinuria or nephropathy, but higher levels of dihydrobiopterin and 3-nitrotyrosine (3-NT)-modified proteins compared with age-matched ZL rats. At 22 wk, ZDF rats developed focal and segmental sclerosis, proteinuria, decreased creatinine clearance, and renal tissue levels of glutathione and tetrahydrobiopterin with further elevation in dihydrobiopterin and 3-NT-modified proteins, in contrast to age-matched ZL rats. Renal immunohistologic expression of lipid peroxidation products and 3-NT-modified proteins also increased in 22-wk-old ZDF but not in ZL rats. Chronic ebselen treatment of ZDF rats restored renal tissue levels of glutathione and tetrahydrobiopterin; prevented significant accumulation of dihydrobiopterin, lipid peroxidation products, and 3-NT-modified proteins; and ameliorated focal and segmental sclerosis, proteinuria, and fall in creatinine clearance without affecting mean BP, body weight, and blood glucose, compared with the untreated ZDF rats. Chronic ebselen therapy also ameliorated vasculopathy with lipid deposits and tubulointerstitial scarring, inflammation, and upregulated alpha-smooth muscle actin expression. These findings suggest that ZDF rats develop a progressive nephropathy with glomerular, vascular, and tubulointerstitial pathology. Oxidative and nitrosative stress predates the nephropathy, which is improved by peroxinitrite scavenger ebselen, and thus considered its cause and not consequence.
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PMID:Nephropathy in Zucker diabetic fat rat is associated with oxidative and nitrosative stress: prevention by chronic therapy with a peroxynitrite scavenger ebselen. 1533 88

The adipose tissue produces a vast number of molecules called adipokines such as leptin, tumoral necrosis factor (TNFalpha), interleukins and adiponectin. Many of the metabolic disturbances associated with obesity and the metabolic syndrome may be due to citokine production by adipocytes. The adipose tissue increases the soluble fractions of TNFalpha leading to a rise in its biological activity. The activation of TNFalpha system causes insulin resistance through different mechanisms such as defects in receptor fosforilation and reduction in insulin-sensitive glucose transporters. TNFalpha is also involved in the pathophysiology of hypertension and dyslipidaemia associated with obesity and insulin resistance. More than one third of interleukin-6 (IL-6) concentrations come from the adipocytes. It has been demonstrated a role for IL-6 in the development of hyperlipidemia, diabetes and hypertension. In contrast to the rest of adipokines, adiponectin is reduced in obesity, diabetes or cardiovascular disease. Adiponectin improves insulin resistance, dyslipidaemia and adhesion to endothelial cells protecting from atherosclerosis development. Thus, adipokines have an important role in the pathophysiology of metabolic syndrome by different mechanisms involving metabolic and vascular effects.
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PMID:[Obesity and inflammation]. 1538 13

Metabolic syndrome also can be named insulin resistance syndrome. The main clinical manifestations include metabolic disorders of glucose and lipid and some diseases caused by the metabolic disorder, such as impaired glucose tolerance or diabetes, obesity, hyperlipemia, fatty liver, hypertension, coronary heart disease, microalbuminuria, etc. According to the theory of zang-fu organs (viscera) in traditional Chinese medicine, these diseases all result from the deficiency of spleen-qi. They are characterized by deficiency in the Ben (root) and excess in the Biao (branch). The Ben (root) is the failure of the spleen in transportation, and the Biao (branch) is stagnation of qi, blood, phlegm, fire, dampness and food. In the prevention and treatment of metabolic syndrome, it is advocated that the intervention of medicine should be used as early as possible, so as to slow down the occurrence and development of insulin resistance, and that emphasis should be transferred from decreasing blood glucose alone to comprehensive prevention of risk factors, especially to the prevention of cardiovascular events. The effect of traditional Chinese herbs is not as good as the western drugs in decreasing the blood pressure and glucose. However, the traditional Chinese herbs have distinctive superiority in ameliorating the insulin resistance, protecting the injury of vascular endothelial cells, regulating the metabolism of lipid, inhibiting the hypercoagulability, and treating the inflammation. Moreover, they are relatively safe. Therefore, the integration of the traditional Chinese medicine and western medicine is worth further research.
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PMID:[Prevention and treatment of metabolic syndrome with integrated traditional Chinese and western medicine]. 1538 69

Obesity is a multifactorial, chronic disorder that has reached epidemic proportions in most industrialized countries and is threatening to become a global epidemic. Obese patients are at higher risk from coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus, cancers, cerebrovascular accidents, osteoarthritis, restrictive pulmonary disease, and sleep apnoea. In particular, visceral fat accumulation is usually accompanied by insulin resistance or type 2 diabetes mellitus, hypertension, hypertriglyceridemia, high uremic acid levels, low high density lipoprotein (HDL) cholesterol to define a variously named syndrome or metabolic syndrome. Metabolic syndrome is now considered a major cardiovascular risk factor in a large percentage of population in worldwide. Both obesity and metabolic syndrome are particularly challenging clinical conditions to treat because of their complex pathophysiological basis. Indeed, body weight represents the integration of many biological and environmental components and relationships among fat and glucose tolerance or blood pressure are not completely understood. Efforts to develop innovative anti-obesity drugs, with benefits for metabolic syndrome, have been recently intensified. In general two distinct strategies can be adopted: first, to reduce energy intake; second, to increase energy expenditure. Here we review some among the most promising avenues in these two fields of drug therapy of obesity and, consequently, of metabolic syndrome.
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PMID:Emerging aspects of pharmacotherapy for obesity and metabolic syndrome. 1545 65

Childhood obesity is a major risk factor, especially for the metabolic syndrome and further cardiovascular diseases. The metabolic syndrome is defined by a combination of obesity, arterial hypertension, hyperlipidemia and dyslipidemia, insulin resistance or type 2 diabetes mellitus. Obesity in early childhood further increases the risk of premature illnesses and early death, therefore raising public health concerns. About one third of overweight or obese children and adolescents exhibit features of early metabolic syndrome. In view of the increasing issue of early-onset obesity, effective family- and school-based primary care programs in addition to sufficient weight-reducing therapeutic approaches are necessary in order to achieve a modification of our sedentary lifestyle. Local long-term therapeutic programs for obese young patients are an important tool to establish a more active and health-oriented life style in children and their families and to reduce the individual and public burden of obesity in childhood.
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PMID:[Obesity and the metabolic syndrome in children and adolescents]. 1552 25

The metabolic syndrome (MetS) is a huge public health problem worldwide, being one of the major causes of cardiovascular disease, responsible for a growing number of premature deaths throughout the world. MetS includes a cluster of anomalies, such as: abdominal obesity, insulin resistance, hyperinsulinemia, hypertension, type 2 diabetes mellitus or glucose intolerance, hypertriglyceridemia etc. The number of people with MetS increases with age, affecting more than 40% of people in their 60s and 70s. About 30% of European people over 50 have MetS. Some experts estimate that as many as two thirds of Americans may be suffering from MetS. The exact cause of MetS is not known: genetics play a minor role, acquired in-utero factors also play a role (prenatal malnutrition, toxin exposure, exposure to high levels of maternal cortisol). For most people, the MetS results primarily from lifestyle factors, such as: chronic stress, inadequate exercise. The MetS can be avoided and reversed in most cases. Weight loss is both a treatment and goal for MetS patients. Moderate weight loss, in the range of 5-10% of body weight, can help restore body's ability to recognize insulin and greatly reduce the chance that the syndrome will evolve into a more serious illness. In most people weight loss will lower blood pressure and improve triglyceride levels. Increased activity alone can improve insulin levels. Physical activity result in a weight loss, improved blood pressure, improved cholesterol and triglyceride level and reduced risk of developing diabetes. It is also important to treat: hyperlipidemia, hypertension, prothrombotic state.
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PMID:The metabolic syndrome--a multifaced disease. 1552 15

The metabolic reduction of 11-keto groups in glucocorticoid steroids such as cortisone leads to the nuclear receptor ligand cortisol. This conversion is an example of pre-receptor regulation and constitutes a novel pharmacological target for the treatment of metabolic disorders such as insulin resistance and possibly other derangements observed in the metabolic syndrome, such as hyperlipidemia, hypertension, and lowered insulin secretion. This reaction is carried out by the NADPH-dependent type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), an enzyme attached through an integral N-terminal transmembrane helix to the lipid bilayer and located with its active site within the lumen of the endoplasmic reticulum. Here we report the crystal structure of recombinant guinea pig 11beta-HSD1. This variant was determined in complex with NADP at 2.5 A resolution and crystallized in the presence of detergent and guanidinium hydrochloride. The overall structure of guinea pig 11beta-HSD1 shows a clear relationship to other members of the superfamily of short-chain dehydrogenases/reductases but harbors a unique C-terminal helical segment that fulfills three essential functions and accordingly is involved in subunit interactions, contributes to active site architecture, and is necessary for lipid-membrane interactions. The structure provides a model for enzyme-lipid bilayer interactions and suggests a funneling of lipophilic substrates such as steroid hormones from the hydrophobic membrane environment to the enzyme active site.
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PMID:The crystal structure of guinea pig 11beta-hydroxysteroid dehydrogenase type 1 provides a model for enzyme-lipid bilayer interactions. 1554 90


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