Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenously formed reactive oxygen species continuously damage cellular constituents including DNA. These challenges, coupled with exogenous exposure to agents that generate reactive oxygen species, are both associated with normal aging processes and linked to cardiovascular disease, cancer, cataract formation, and fatty liver disease. Although not all of these diseases have been definitively shown to originate from mutations in nuclear DNA or mitochondrial DNA, repair of oxidized, saturated, and ring-fragmented bases via the base excision repair pathway is known to be critical for maintaining genomic stability. One enzyme that initiates base excision repair of ring-fragmented purines and some saturated pyrimidines is NEIL1, a mammalian homolog to Escherichia coli endonuclease VIII. To investigate the organismal consequences of a deficiency in NEIL1, a knockout mouse model was created. In the absence of exogenous oxidative stress, neil1 knockout (neil1-/-) and heterozygotic (neil1+/-) mice develop severe obesity, dyslipidemia, and fatty liver disease and also have a tendency to develop hyperinsulinemia. In humans, this combination of clinical manifestations, including hypertension, is known as the metabolic syndrome and is estimated to affect >40 million people in the United States. Additionally, mitochondrial DNA from neil1-/- mice show increased levels of steady-state DNA damage and deletions relative to wild-type controls. These data suggest an important role for NEIL1 in the prevention of the diseases associated with the metabolic syndrome.
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PMID:The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. 1644 48

Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases, including diseases that do not primarily manifest as disorders of the locomotive apparatus. In this review we present the evidence for prescribing exercise therapy in the treatment of metabolic syndrome-related disorders (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, obesity), heart and pulmonary diseases (chronic obstructive pulmonary disease, coronary heart disease, chronic heart failure, intermittent claudication), muscle, bone and joint diseases (osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, chronic fatigue syndrome) and cancer, depression, asthma and type 1 diabetes. For each disease, we review the effect of exercise therapy on disease pathogenesis, on symptoms specific to the diagnosis, on physical fitness or strength and on quality of life. The possible mechanisms of action are briefly examined and the principles for prescribing exercise therapy are discussed, focusing on the type and amount of exercise and possible contraindications.
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PMID:Evidence for prescribing exercise as therapy in chronic disease. 1664 91

The insulin resistance syndrome refers to a constellation of findings, including glucose intolerance, obesity, dyslipidemia, and hypertension, that promote the development of type 2 diabetes, cardiovascular disease, cancer, and other disorders. Defining the pathophysiological links between insulin resistance, the insulin resistance syndrome, and its sequelae is critical to understanding and treating these disorders. Over the past decade, two approaches have provided important insights into how changes in insulin signaling produce the spectrum of phenotypes associated with insulin resistance. First, studies using tissue-specific knockouts or tissue-specific reconstitution of the insulin receptor in vivo in mice have enabled us to deconstruct the insulin resistance syndromes by dissecting the contributions of different tissues to the insulin-resistant state. Second, in vivo and in vitro studies of the complex network of insulin signaling have provided insight into how insulin resistance can develop in some pathways whereas insulin sensitivity is maintained in others. These data, taken together, give us a framework for understanding the relationship between insulin resistance and the insulin resistance syndromes.
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PMID:From mice to men: insights into the insulin resistance syndromes. 1646 Feb 69

Male sexual dysfunction-a term that is commonly used to refer to erectile dysfunction, premature ejaculation, decreased libido and impaired orgasm-is the primary complaint encountered by many urologists. Despite the high prevalence and bothersome nature of these complaints, they are frequently neglected in clinical practice. This paper highlights clinical situations in which urologists should systematically evaluate male sexual functioning. These include men who present with several common urologic disorders, such as pelvic trauma, malignancies, and lower urinary tract symptoms associated with benign prostatic hyperplasia, neurologic disorders and infertility. Studies have shown that erectile dysfunction might be a clinical marker of endothelial dysfunction, and consequently of undetected diabetes, hypertension, dyslipidemia, coronary artery disease and depression. We also address the question of whether urologists should adopt wide-ranging screening regimens for sexual dysfunction.
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PMID:How, why and when should urologists evaluate male sexual function? 1647 Feb 7

More than 500,000 US women die of cardiovascular disease (CVD) annually, exceeding deaths for cancer, accidents, and diabetes combined. Yet women are largely unaware of this and fear breast cancer more. One way of changing this number is to change the way we approach CVD, that is, to practice preventive healthcare. Until recently, guidelines for women with CVD were derived largely from research conducted primarily on white middle-aged men. Although evidence-based medicine is still lacking, guidelines and recommendations specifically for women are now available and include aggressive management of the risk factors of smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity. Unless women are educated regarding these risk factors and are enabled to make lifestyle changes, their chances of modifying and reducing their risks are severely impaired.
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PMID:Prevention: the key to reducing cardiovascular disease risk in women. 1648 28

Insulin-mediated glucose disposal varies widely in apparently healthy human beings, and the more insulin resistant an individual, the more insulin they must secrete in order to prevent the development of type 2 diabetes. However, the combination of insulin resistance and compensatory hyperinsulinemia increases the likelihood that an individual will be hypertensive, and have a dyslipidemia characterized by a high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentration. These changes increase risk of cardiovascular disease (CVD), and in 1988, this cluster of related abnormalities was designated as comprising a syndrome (X). Several other clinical syndromes are now known to be associated with insulin resistance and compensatory hyperinsulinemia. For example, polycystic ovary syndrome appears to be secondary to insulin resistance and compensatory hyperinsulinemia. More recently, studies have shown that the prevalence of insulin resistance/hyperinsulinemia is increased in patients with nonalcoholic fatty liver disease, and there are reports that certain forms of cancer are more likely to occur in insulin resistant/hyperinsulinemic persons. Finally, there is substantial evidence of an association between insulin resistance/hyperinsulinemia, and sleep disordered breathing. Given the rapid increase in the number of clinical syndromes and abnormalities associated with insulin resistance/hyperinsulinemia, it seems reasonable to suggest that the cluster of these changes related to the defect in insulin action be subsumed under the term of the insulin resistance syndrome. In addition to the identification of additional clinical syndromes related to insulin resistance/hyperinsulinemia, a number of new risk factors have been recognized that would increase CVD risk in these individuals. Thus, in addition to a high TG and a low HDL-C, the atherogenic lipoprotein profile in insulin resistant/hyperinsulinemic individuals also includes the appearance of smaller and denser low density lipoprotein particles, and the enhanced postprandial accumulation of remnant lipoproteins; changes identified as increasing risk of CVD. Elevated plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be associated with increased CVD, and there is evidence of a significant relationship between PAI-1 and fibrinogen levels and both insulin resistance and hyperinsulinemia. Evidence is also accumulating that sympathetic nervous system (SNS) activity is increased in insulin resistant, hyperinsulinemic individuals, and, along with the salt sensitivity associated with insulin resistance/hyperinsulinemia, increases the likelihood that these individuals will develop essential hypertension. The first step in the process of atherogenesis is the binding of mononuclear cells to the endothelium, and mononuclear cells isolated from insulin resistant/hyperinsulinemic individuals adhere with greater avidity. This process is modulated by adhesion molecules produced by endothelial cells, and there is a significant relationship between degree of insulin resistance and the plasma concentration of the several of these adhesion molecules. Further evidence of the relationship between insulin resistance and endothelial dysfunction is the finding that asymmetric dimethylarginine, an endogenous inhibitor of the enzyme nitric oxide synthase, is increased in insulin resistant/hyperinsulinemic individuals. Finally, plasma concentrations of several inflammatory markers are elevated in insulin resistant subjects. It is obvious that the cluster of abnormalities associated with insulin resistance and compensatory hyperinsulinemia contains many well-recognized CVD risk factors, choosing which one, or ones, that are primarily responsible for the accelerated atherogenesis that characterizes this syndrome is not a simple task. Indeed, efforts to try to do so by the use of multiple regression analysis of epidemiological data may be more misleading than helpful.
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PMID:Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. 1648 19

The importance of epigenetic alterations has been acknowledged in cancer for about two decades by an increasing number of molecular oncologists who contributed to deciphering the epigenetic codes and machinery and opened the road for a new generation of drugs now in clinical trials. However, the relevance of epigenetics to common diseases such as metabolic syndrome and cardiovascular disease was less conspicuous. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with metabolic syndrome (MetS)--combining disturbances in glucose and insulin metabolism, excess of predominantly abdominally distributed weight, mild dyslipidemia and hypertension, with the subsequent development of obesity, type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD)--have suffered improper "epigenetic programing" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their life-time. Moreover, as seen for obesity and T2D, MetS tends to appear earlier in childhood, to be more severe from generation to generation and to affect more pregnant women. Thus, in addition to maternal effects, MetS patients may display "transgenerational effects" via the incomplete erasure of epigenetic marks endured by their parents and grandparents. We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development throughout life. Increasing our understanding on epigenetic patterns significance and small molecules (nutrients, drugs) that reverse epigenetic (in) activation should provide us with the means to he obsolete human thrifty genotype into a "squandering" phenotype.
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PMID:[Nutritional epigenomics of metabolic syndrome]. 1659 5

Obesity has been described as an epidemic because of the rapid increase in the number of overweight and obese individuals over the past 20 yr. This increasing prevalence of obesity is a worldwide phenomenon affecting both children and adults. The metabolic syndrome is a constellation of central adiposity, impaired fasting glucose, elevated blood pressure, and dyslipidemia (high triglyceride and low HDL cholesterol). When three of these five criteria are present, the risk of cardiovascular disease and diabetes is increased 1.5- to 2-fold. As body weight, expressed as the BMI, rises, there are a number of other diseases that are associated with it. First, life span is shortened and the risk of sudden death increases. Second, the risk of diabetes, gall bladder disease, hypertension, heart disease, osteoarthritis, sleep apnea, and certain forms of cancer also increase.
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PMID:Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. 1662 98

Endocrine dysfunction and parameters of metabolic syndrome were assessed in 91 patients aged 4.3-32.5 years who underwent allogeneic or autologous BMT in childhood. Final short stature, found in five of the 35 patients who attained final height, was associated with the underlying disease (specifically, Fanconi anemia) (P=0.0013), previous cranial irradiation (P=0.0007), type of conditioning irradiation (P<0.05) and allogeneic BMT (P=0.05). Growth hormone deficiency (n=10) was associated with previous cranial irradiation (P<0.005) and conditioning total body irradiation (P<0.001). Twelve patients had primary hypothyroidism, one had hyperthyroidism and one papillary thyroid carcinoma. Hypothyroidism was associated with neck/mediastinal (P<0.005) and conditioning irradiation (P<0.05). Primary gonadal failure was found in 24 of the mature patients (62.5% females). Hypogonadism was associated with the underlying disease (especially hematological malignancies) (P<0.05), pretransplant treatment (P<0.05), irradiation conditioning (P<0.001), older age (P<0.005) and advanced pubertal stage at BMT (P<0.05). Obesity (body mass index >2 s.d.) was found in 4.4% and type II diabetes and impaired glucose tolerance in 3.3% each. Dyslipidemia was found in 27.9% of the 43 patients tested. These findings emphasize the need for long-term follow-up of endocrine and metabolic parameters in young patients after BMT in order to offer proper treatment and improve quality of life.
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PMID:Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence. 1669 34

The aim of this study was to determine the effect of metabolic syndrome on brachial-ankle pulse wave velocity (baPWV) by using the new guidelines for diagnosis of this syndrome in Japan. We examined 525 men and women without a history of cardiovascular disease or cancer, and an ankle-brachial index < 0.9. The baPWV was measured using a device (Form PWV/ABI) that simultaneously monitored bilateral brachial and ankle pressure wave forms. Metabolic syndrome was defined as a waist circumference > or = 85 (90) cm in men (women) and two or more of the following risk factors: hypertension, dyslipidemia, and glucose intolerance diagnosed by a 75 g oral glucose tolerance test. The baPWV showed a significant linear relationship with waist circumference, waist-to-hip ratio, body fat, systolic and diastolic blood pressure, triglycerides, fasting glucose, 2-h-postload glucose, fasting insulin, and glycosylated hemoglobin-A1c, after adjusting for sex and age. These factors were also strongly related to fasting insulin levels. When subjects were classified into six groups based on waist circumference and the number of risk factors for metabolic syndrome (0, 1, and > or =2), we found that more risk factors clearly increased the odds ratios for an elevated baPWV in those subjects in the highest quartile of the baPWV distribution in multivariate logistic models. An increase in odds ratio was observed despite a normal waist circumference and may well have been due to increased fasting insulin and blood pressure levels. An increase in the number of risk factors for metabolic syndrome was highly correlated with an increased baPWV, probably due to insulin resistance.
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PMID:Impact of metabolic syndrome on brachial-ankle pulse wave velocity in Japanese. 1671 51


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