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)

Since the earliest reports of human immunodeficiency virus (HIV) disease, undernutrition has been associated with HIV infection, typically with the late stages of the disease (namely acquired immunodeficiency syndrome), and may advance to severe wasting and cachexia. Specific micronutrient deficiencies are also recognized to occur with HIV infection, but their actual effect on the clinical course of the disease is hard to assess. The studies reviewed provide more insight into the complex interface between undernutrition and, in some cases, obesity and HIV/acquired immunodeficiency syndrome and highlight the possibility of alleviating or curing undernutrition by means of simple and comparatively inexpensive dietary adjustments.
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PMID:Nutritional and metabolic abnormalities in pre-AIDS HIV infection. 1670 57

Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.
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PMID:Serum adiponectin and leptin concentrations in HIV-infected children with fat redistribution syndrome. 1686 9

There is a finely tuned interplay between immune and neuroendocrine systems. Metabolic disturbances like obesity will have serious consequences on immunity both at the cellular and at the cytokine expression levels. Our in vivo results confirm the immune deficiency of ob/ob mice, leptin deficient and massively obese, characterized by a reduced Ag-specific T cell proliferation after keyhole limpet hemocyanin immunization. In this report, we show that dendritic cells (DCs), major APCs involved in T lymphocyte priming, are affected in obese mice. Both their function and their steady-state number are disturbed. We demonstrate that DCs from ob/ob mice are less potent in stimulation of allogenic T cells in vitro. This impaired functionality is not associated with altered expression of phenotypic markers but with the secretion of immunosuppressive cytokines such as TGF-beta. Moreover, we show increased in vivo steady-state number of epidermal DCs in ob/ob mice, which is not due to a migratory defect. The ob/ob mice are characterized by the absence of functional leptin, a key adipokine linking nutrition, metabolism, and immune functions. Interestingly, intradermal injection of leptin is able to restore epidermal DC number in obese mice. Thus, DCs might be directly sensitive to metabolic disturbances, providing a partial explanation of the immunodeficiency associated with obesity.
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PMID:Impairment of dendritic cell functionality and steady-state number in obese mice. 1705 24

Interleukin (IL)-18 is a proinflammatory cytokine that plays an important role in both innate and adaptive immune responses against viruses and intracellular pathogens. Increased levels of circulating IL-18 from HIV-1 infected patients have been reported especially in the advanced and late stages of the disease, whereas in the initial stage serum levels of IL-18 were not increased. In contrast, low production of Il-18 was observed in vitro from peripheral blood mononuclear cells (PBMC) of HIV-1 infected patients, and these results were also observed in macaques infected with simian immunodeficiency virus (SIV). In addition, decreased IL-18 production from PBMC was significantly correlated with low production of IL-2. Furthermore, serum levels of IL-18 significantly decreased after highly active antiretroviral therapy. During the early stage of HIV-1 infection there is a decreased production of gamma interferon (IFN), IL-12 and IL-2 as well as not activation of IL-18 production and this leads to inhibition of Th1 immune response, whereas in the advanced stage of the disease, strong activation of IL-18 production along with persistent decreased production of gamma IFN, IL-12 and IL-2 may promote a Th2 immune response, which leads to persistent viral replication. Several studies have shown increased levels of IL-18 in HIV-seronegative subjects with obesity, insulin resistance and type II diabetes. Metabolic disorders, fat redistribution and cardiovascular manifestations are becoming more frequent in HIV-1 infected patients treated with antiretroviral drugs. Consequently, involvement of IL-18 in these disorders has been postulated and demonstrated in patients with lipodistrophy, or with hypertriglyceridemia. Finally, higher serum levels of IL-18 may represent an useful marker in HIV-1 infected patients with metabolic disorders and fat redistribution, as well as a sensitive predictor of cardiovascular complications in treated patients.
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PMID:Interleukin-18: a proinflammatory cytokine in HIV-1 infection. 1707 17

Precise spatial and temporal regulation of proteolytic activity is essential to human physiology. Modulation of protease activity with synthetic peptidomimetic inhibitors has proven to be clinically useful for treating human immunodeficiency virus (HIV) and hypertension and shows potential for medicinal application in cancer, obesity, cardiovascular, inflammatory, neurodegenerative diseases, and various infectious and parasitic diseases. Exploration of natural inhibitors and synthesis of peptidomimetic molecules has provided many promising compounds performing successfully in animal studies. Several protease inhibitors are undergoing further evaluation in human clinical trials. New research strategies are now focusing on the need for improved comprehension of protease-regulated cascades, along with precise selection of targets and improved inhibitor specificity. It remains to be seen which second generation agents will evolve into approved drugs or complementary therapies.
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PMID:Protease inhibitors and their peptidomimetic derivatives as potential drugs. 1709 88

There are few diseases whose incidence varies as greatly worldwide as that of diverticulosis. Its prevalence is largely age-dependent: the disease is uncommon in those under the age of 40, the prevalence of which is estimated at approximately 5%; this increases to 65% in those > or =65 years of age. Of patients with diverticula, 80-85% remain asymptomatic, while, for unknown reasons, only three-fourths of the remaining 15-20% of patients develop symptomatic diverticular disease. Traditional concepts regarding the causes of colonic diverticula include alterations in colonic wall resistance, disordered colonic motility and dietary fiber deficiency. Currently, inflammation has been proposed to play a role in diverticular disease. Goals of therapy in diverticular disease should include improvement of symptoms and prevention of recurrent attacks in symptomatic, uncomplicated diverticular disease, and prevention of the complications of disease such as diverticulitis. Diverticulitis is the most usual clinical complication of diverticular disease, affecting 10-25% of patients with diverticula. Most patients admitted with acute diverticulitis respond to conservative treatment, but 15-30% require surgery. Predictive factors for severe diverticulitis are sex, obesity, immunodeficiency and old age. Surgery for acute complications of diverticular disease of the sigmoid colon carries significant rates of morbidity and mortality, the latter of which occurs predominantly in cases of severe comorbidity. Postoperative mortality and morbidity are to a large extent driven by patient-related factors.
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PMID:Diverticular disease in the elderly. 1746 51

The aim of this study was to analyze LPIN1 adipose tissue gene expression levels in 3 clinical insulin-resistant conditions-obesity, type 2 diabetes mellitus, and human immunodeficiency virus (HIV)-associated lipodystrophy-and its relationship with adipogenic and inflammatory markers. Subcutaneous adipose tissue samples were obtained from 2 cohorts: 98 subjects with different degrees of adiposity and with or without the presence of type 2 diabetes mellitus and 37 HIV-infected patients. Real-time polymerase chain reaction was used to measure gene expression of LPIN1 and adipogenic (PPARgamma, SREBP1c) and inflammatory markers (IL6, TNFalpha, TNFR1, and TNFR2). LPIN1 messenger RNA expression levels were significantly lower in the obese group (P = .002), were similar in type 2 diabetes mellitus patients and control subjects (P = .211), and were significantly higher in HIV-infected patients (P < .001). LPIN1 messenger RNA levels positively correlated with insulin sensitivity in all subjects. Moreover, an inverse correlation with proinflammatory cytokines was observed.
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PMID:Human subcutaneous adipose tissue LPIN1 expression in obesity, type 2 diabetes mellitus, and human immunodeficiency virus--associated lipodystrophy syndrome. 1795 Jan 3

The systemic inflammatory response represents a coordinated set of physiologic actions that serve to fight infection, heal wounds, and promote recovery from external stressors. Thus, under most circumstances an intact systemic inflammatory response increases the likelihood of a successful outcome following acute injury or infection. However, under certain conditions, such as in major trauma, an excessive proinflammatory response may arise that worsens the prognosis. Conversely, protein calorie malnutrition can result in immunodeficiency, leaving the individual at risk of infection. Finally, low-grade chronic inflammation that is persistent, as can be seen in obesity, diabetes, and the metabolic syndrome, can lead to serious health risks. Thus, inflammatory states within a range from chronic low-grade to acute severe responses can have profound effects on morbidity and manifest an increased risk of mortality. Therapies to down-regulate the systemic inflammatory response by targeting the source of inflammation may dramatically improve patient outcome in chronic inflammatory states and some acute inflammatory conditions.
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PMID:Systemic response to inflammation. 1824 May 43

Human immunodeficiency virus (HIV) infection has become a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Metabolic complications such as dyslipidemia, insulin resistance, diabetes mellitus, obesity, and fat distribution abnormalities are associated with increased risk of cardiovascular disease. Cardiovascular disease is now a leading cause of death among HIV-infected patients. Lipid abnormalities, now often characteristically seen with HIV infection, include elevated triglycerides and low elevated total cholesterol (TC), and low high-density lipoprotein (HDL) levels of total and HDL cholesterol. Many antiretroviral drugs are associated with lipid abnormalities, which commonly include hypertriglyceridemia and increased total and low-density lipoprotein cholesterol levels. The management of dyslipidemia includes lifestyle modifications, lipid-lowering therapy, and switching antiretroviral therapy (ART). The increased prevalence of insulin resistance, impaired glucose tolerance, and diabetes is multifactorial in etiology. Management and goals of diabetes should follow the same practice guidelines in non-HIV-infected patients. Drug interactions and switching ART are additional management measures in diabetic HIV-infected patients. Since the treatment of lipodystrophy is a challenge, its prevention by selecting appropriate ART is the key.
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PMID:Diagnosis and management of common chronic metabolic complications in HIV-infected patients. 1902 Mar 62

Primary liver cancer (PLC) incidence trends from Africa are unknown. Using Kampala Cancer Registry data from 1960 to 1980 and 1991 to 2005, we identified 771 PLCs. Although rates were stable among men, PLC incidence among women increased >50%. Investigations of viral hepatitis, aflatoxin, obesity, and human immunodeficiency virus (HIV) may help to explain the increasing incidence of hepatocellular carcinomas (HCCs).
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PMID:Trends in the incidence of primary liver cancer in Central Uganda, 1960-1980 and 1991-2005. 1917 20


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