Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Concentrations of leptin, an adipocyte-derived hormone, are elevated in obesity. Recently, leptin has been shown to participate in multiple biological actions including inflammation, reproduction, and angiogenesis. Leptin has also been documented as a critical component in the process of wound healing; however, leptin involvement in cardiovascular disease is poorly understood. We examined the expression of leptin (ob) and leptin receptor (ob-R) genes in the rat heart following ischemia/reperfusion, which was induced by coronary artery ligation, and mRNA was obtained from hearts 0.5 to 36 h after initiating reperfusion. Expressions of ob and ob-R mRNA were examined by real-time quantitative RT-PCR and immunohistochemistry. The ob and ob-Ra mRNA and protein expressions were significantly increased (p<0.01) and ob-Rb mRNA was significantly decreased (p<0.01) in hearts after 8 h of reperfusion. Furthermore, ob and ob-R proteins were expressed in injured myocytes where inflammatory cells infiltrated. In contrast, those expressions were not influenced in hearts after 8 h of ischemia stress only. To determine the functional effects of leptin on the ischemic/reperfused heart, rats were treated with anti-leptin antibodies prior to ischemia/reperfusion; however, this treatment did not affect the elevation of mRNA expression levels of inflammatory markers such as TNF-alpha and IL-1beta in ischemic hearts. Our results demonstrated for the first time that ischemia/reperfusion induced leptin and leptin receptor gene expression in the rat heart. This study helps to elucidate the mechanisms behind the onset and development of ischemic heart disease concomitant with obesity.
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PMID:Ischemia/reperfusion in rat heart induces leptin and leptin receptor gene expression. 1713 25

Heart failure with normal ejection fraction (HF-NEF) is frequently believed to be more common in women than in men. However, the interaction of gender and age has rarely been analyzed in detail, and knowledge of the distinction between pre- and postmenopausal women is lacking. Some of the studies that have described a higher prevalence of HF-NEF in women relied on clinical diagnoses of HF together with normal systolic function and did not measure diastolic function. This applies to the analysis of patients hospitalized for HF and some epidemiological investigations that agree on the greater prevalence of HF-NEF in women. Population-based studies with echocardiographic determination of diastolic function have suggested equal or greater prevalence of diastolic dysfunction in men. Major risk factors for HF-NEF include hypertension, aging, obesity, diabetes, and ischemia. Hypertension is more frequent in women and can contribute to left ventricular and arterial stiffening in a gender-specific way. Aging, obesity, and diabetes affect myocardial and vascular stiffness differently and lead to different forms of myocardial hypertrophy in women and men. In contrast, ischemia may play a greater role in men. Gender differences in ventricular diastolic distensibility, in vascular stiffness and ventricular/vascular coupling, in skeletal muscle adaptation to HF, and in the perception of symptoms may contribute to a greater rate of HF-NEF in women. The underlying molecular mechanisms include gender differences in calcium handling, in the NO system, and in natriuretic peptides. Estrogen affects collagen synthesis and degradation and inhibits the renin-angiotensin system. Effects of estrogen may provide benefit to premenopausal women, and the loss of its protective mechanisms may render the heart of postmenopausal women more vulnerable. Thus, a number of molecular mechanisms can contribute to the gender differences in HF-NEF.
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PMID:Role of gender in heart failure with normal left ventricular ejection fraction. 1718 12

This review summarizes the well-known clinical features of the obstructive sleep apnea-hypopnea syndrome (OSAHS) and emphasizes new research on this syndrome. Though described in the seventies, the prevalence OSAHS is known mainly in the US. A dramatic increasing in prevalence has been related to the increase prevalence of obesity, raising a substantial public health problem. Discussion continues on the proper definition of the syndrome and degrees of severity. Multiple factors are involved in the pathogenesis of sleep apnea: anatomic abnormalities, mechanical factors, nervous alterations, muscular imbalance between pharyngeal constrictor and dilator muscles or part of a metabolic syndrome? Indeed, obstructive sleep apnea with and without obesity is increasingly implicated in the initiation and progression of metabolic disorders and of cardiovascular diseases (hypertension, cardiac ischemia and probably congestive heart failure, cardiac arrhythmias and strokes). An extended literature reports the neural, humoral, thrombotic, metabolic and inflammatory mechanisms linking OSAHS to endocrinology and cardiovascular diseases. Daytime sleepiness, cognitive, memory and performance deficits with their risks are also stressed. These consequences require treating this syndrome as soon as possible. Multiple interventions (medical, mechanical-nasal positive airway pressure or oral appliances, and sometimes surgical management) can be used but nasal continuous positive airway pressure is the "gold standard" treatment in severe OSAHS. More often multiple interventions are appropriate in a given patient. Finally, there is growing evidence that genetic factors influence the expression of OSAHS. Numerous genetic studies have investigated the etiology of OSAHS with the goal of improving our understanding of its pathogenesis.
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PMID:[Obstructif sleep apnea-hypopnea syndrome: evolution of an old concept]. 1718 49

The aim of this study is to identify the risk factors for development of chronic critical limb ischemia (CLI) in diabetic and nondiabetic patients with peripheral arterial disease (PAD). 127 patients (pts) with PAD (63 with type 2 diabetes and 64 nondiabetic) were randomly included in a cross sectional study. Out of them 17 were with CLI. Population was investigated for age, height, weight, sex, duration of PAD and diabetes, arterial hypertension, hyperlipidemia, smoking, obesity, systolic blood pressure, value of ankle-brachial index, previous claudicating distance and peripheral intervention, amputation, medical treatment with prostanoids, insulin and antiplatelet drugs and histories of cerebrovascular disease, coronary artery disease and other concomitant diseases. After adjudging linear correlation between mentioned variables and presence of CLI, logistic regression model was built. There were no significant differences in demographic data between both populations. Hyperlipidemia was more frequent in nondiabetic population. Multiple regression model show ankle-brachial index < 0,5, measured in previous 1-3 years (OR 3.39 CI 95% 0.28-40.78), microvascular complication retinopathy (OR 12.98 CI 95% 1.76-95.58), heart failure (OR 1.91 CI 95% 0.29-2.72) and previous prostanoids treatment (OR 15.92 CI 95% 0.53-476.58) as predictors of development of CLI in diabetic population with PAD. After heart failure exclusion of model of nondiabetic pts, previous surgery (OR 3.14 CI 95% 0.61-16.09) and smoking (OR 0.35 CI 95% 0.78-1.62) were presented as prognostic factors for CLI's onset. Our results indicate differences between predictors of CLI's onset in diabetic and nondiabetic population with PAD. Presence of retinopathy, previous measured ankle-brachial index and prostanoids treatment are predictors of development of CLI in diabetic population. Previous surgery is independent predictor for CLI'onset in nondiabetics. Treating concomitant heart failure for both populations and modifying risk factor smoking in nondiabetic population, have an important clinical usefulness in risk assessment approach of peripheral arterial disease patients.
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PMID:Risk factors for development of critical limb ischemia -- a survey of diabetic vs. nondiabetic population. 1721 Dec 94

The immune response to foreign or self antigens mediates liver damage during viral or autoimmune hepatitis. However, it now appears that also specific antigen-independent liver diseases, where liver damage has been attributed to occur from oxygen radical formation, seem to be mediated by cells of the innate and adaptive immune response. These liver disorders include alcoholic liver disease, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis, and ischemia/reperfusion injury that impairs the function of liver grafts. Here it seems that breakdown of the gastrointestinal barrier might increase the concentration of bacterial toxins in the portal blood, which then activate cells of the innate immune system, e. g., Kupffer cells, but, depending on the nature of the toxin, probably also conventional T cells. Invariant NKT cells which specifically recognize glycolipid antigens were supposed to become activated during metabolic disorders related to obesity. However, both steatohepatitis as well as ischemia/reperfusion injury are associated with a Th1 cytokine response characterized by IFNgamma and TNFalpha elevation, that might reflect an NKT cell response on the one hand, but also conventional T lymphocytes, in particular CD4 (+) T cells, are critical for the pathophysiology of these disorders. In 1992 we described a model of T cell-dependent liver injury inducible by the T cell-mitogenic lectin concanavalin A. This model of immune-mediated liver injury was intensively used to study pathophysiological immune effector mechanisms as well as cytokine signaling important for hepatocellular apoptosis, inhibition of apoptosis and regeneration. Recently it became evident that the inflammatory response in this model is regulated by specific cytokine signals as well as by immune regulator cells. The immune-regulatory functions of the liver are of particular interest with respect to the scavenger function of this organ, being continuously exposed to foreign antigenic material from the gut which should be eliminated without causing chronic disease.
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PMID:Cellular and cytokine-mediated mechanisms of inflammation and its modulation in immune-mediated liver injury. 1723 22

Among the general heart failure (HF) population, over half have diastolic HF (DHF). The proportion of DHF increases with age, from 46% in patients younger than 45 years to 59% in patients older than 85 years. The diagnosis of DHF is made by the combination of signs and symptoms of HF with preserved systolic function (left ventricular ejection fraction >50%), and evidence of diastolic dysfunction obtained by echocardiographic Doppler examination, invasive hemodynamic evaluation, or an elevation of serum B-type natriuretic peptide. The most common risk factors for the development of diastolic dysfunction and DHF include long-standing hypertension, older age, female sex, obesity, diabetes, chronic kidney disease, and coronary artery disease. Acute decompensation occurs in the setting of pressure overload, volume overload, or superimposed cardiac ischemia. The cornerstones of in-hospital management include blood pressure and volume control, heart rate control, and correction of precipitating factors. Priorities in the outpatient clinic include optimal blood pressure control, maintenance of euvolemia with minimal or no diuretics, and, potentially, use of disease-modifying drugs including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aldosterone receptor blockers, beta-blockers, and digoxin. Long-term regression of left ventricular hypertrophy, improvement in diastolic filling parameters, and sustained reductions in B-type natriuretic peptide may be future treatment targets for this condition.
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PMID:Curriculum in cardiology: integrated diagnosis and management of diastolic heart failure. 1758 43

Neuropeptide Y (NPY) has long been known to be involved in stress, centrally as an anxiolytic neuromodulator, and peripherally as a sympathetic nerve- and in some species, platelet-derived vasoconstrictor. The peptide is also a vascular mitogen, via Y1/Y5, and is angiogenic via Y2/Y5 receptors. Arterial injury activates platelet NPY and vascular Y1 receptors, inducing medial hypertrophy and neointima formation. Exogenous NPY, dipeptidyl peptidase IV (DPPIV, forming an Y2/Y5-selective agonist) and chronic stress augment these effects and occlude vessels with atherosclerotic-like lesions, containing thrombus and lipid-laden macrophages. Y1 antagonist blocks stress-induced vasoconstriction and post-angioplasty occlusions, and hence may be therapeutic in angina and atherosclerosis/restenosis. Conversely, tissue ischemia activates neuronal and platelet-derived NPY, Y2/Y5 and DPPIV, which stimulate angiogenesis/arteriogenesis. NPY-Y2-DPPIV agonists may be beneficial for ischemic revascularization and wound healing, whereas antagonists may be therapeutic in retinopathy, tumors, and obesity. Since stress is an underestimated risk factor in many of these conditions, NPY-based drugs may offer new treatment possibilities.
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PMID:Stress, NPY and vascular remodeling: Implications for stress-related diseases. 1724 99

This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria.
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PMID:Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. 1725 93

DNA base damage results from a combination of endogenous sources, (normal metabolism, increased metabolism due to obesity, stress from diseases such as arthritis and diabetes, and ischemia) and the environment (ingested toxins, ionizing radiation, etc.). If unrepaired DNA base damage can lead to diminished cell function, and potentially diseases and eventually mutations that lead to cancer. Sophisticated DNA repair mechanisms have evolved in all living cells to preserve the integrity of inherited genetic information and transcriptional control. Understanding a system like DNA repair is greatly enhanced by using engineering methods, in particular modeling interactions and using predictive simulation to analyze the impact of perturbations. We describe the use of such a "nanosystem engineering" approach to analyze the DNA base excision repair pathway in human cells, and use simulation to predict the impact of varying enzyme concentration on DNA repair capacity.
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PMID:DNA base excision repair nanosystem engineering: model development. 1728 37

Cardiovascular disease is the leading cause of death among men and women in the United States. Silent myocardial ischemia, defined as documentation of ischemia in the absence of angina or anginal equivalents, affects up to 4 million Americans and carries a poor prognosis. The assessment of the presence of subclinical coronary atherosclerosis affords an opportunity to identify patients who may be at risk for coronary artery disease over the long term. In addition to traditional risk factors (such as lipid parameters, diabetes, hypertension, smoking, and age), a variety of novel factors (such as lipoprotein[a], homocysteine, and C-reactive protein) may enhance assessment of risk in specific populations. Risk modification should be aimed at achieving recommended levels of lipids and blood pressure, reducing obesity, facilitating optimal management of diabetes and the metabolic syndrome, and encouraging smoking cessation and physical activity. Clinicians should be knowledgeable regarding the application of national guidelines for the reduction of cardiovascular risk so as to maximize the prospects for both the primary and secondary prevention of coronary artery disease and associated adverse outcomes.
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PMID:Cardiovascular disease: strategies for risk assessment and modification. 1729 47


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