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)

In many Sub-Saharan African populations, in particular urban dwellers, there have been marked rises in the prevalences of obesity in women, hypertension, diabetes, and cerebral vascular disease. Yet there have been only slight rises in coronary heart disease. To learn more of the roles of the various influencing factors in the puzzling situations described, some aspects of the past and present occurrences of these diseases are described and discussed, with comparisons being made with corresponding situations in African Americans, as well as in certain white populations. Despite increases in the knowledge of influencing factors, such fail to explain fully the epidemiologic situations described. As to the future, judging from the experiences of other populations, despite continuing indigence, within the next generation significant rises in coronary heart disease in certain African populations seem to be inevitable. However, in many of those populations, in particular those in the South, the extent of changes, apart from those linked with level of socioeconomic state, will be strongly affected by the rising epidemic of human immunodeficiency virus and acquired immunodeficiency syndrome.
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PMID:Variations in occurrences of nutrition-related diseases in Sub-Saharan Africans in stages of transition: what of the future? 1182 75

Steatosis or fatty liver in individuals with human immunodeficiency virus (HIV) may result from HIV itself, the use of nucleoside analogues, concurrent infection with hepatitis B or C, alcohol use, diabetes mellitus, obesity, or combinations of these factors. Nucleoside analogues have been the focus of increasing concern, because several fatal cases of severe macrosteatosis, lactic acidosis, and hepatomegaly have been linked to the use of nucleoside analogues. Other classes of antiretroviral drugs, as well as opportunistic infections, can also cause hepatic injury without steatosis. The additive effect of these different risk factors, especially in the presence of underlying hepatic steatosis, likely contributes to the increased prevalence of hepatic abnormalities among HIV-infected individuals. The conditions under which some patients rapidly progress to hepatic failure and/or cirrhosis need to be defined. This is a US government work. There are no restrictions on its use.
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PMID:The fatty liver in AIDS. 1194 34

Appropriate preconception health care improves pregnancy outcomes. When started at least one month before conception, folic acid supplements can prevent neural tube defects. Targeted genetic screening and counseling should be offered on the basis of age, ethnic background, or family history. Before conception, women should be screened for human immunodeficiency virus and syphilis infection and begin treatment to prevent the transmission of disease to the fetus. Immunizations against hepatitis B, rubella, and varicella should be completed, if needed. Women should be counseled on ways to prevent infection with toxoplasmosis, cytomegalovirus, and parvovirus B19. Environmental toxins such as cigarette smoke, alcohol, and street drugs, and chemicals such as solvents and pesticides should be avoided. In women with diabetes, it is important to optimize disease control through intensive management before pregnancy. Medications for hypertension, epilepsy, thromboembolism, depression, and anxiety should be reviewed and changed, if necessary, before the patient becomes pregnant. Counseling about exercise, obesity, nutritional deficiencies, and the overuse of vitamins A and D is beneficial. Physicians may also choose to discuss occupational and financial issues related to pregnancy and to screen patients for domestic violence.
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PMID:Preconception health care. 1261 25

Human immunodeficiency virus protease inhibitors are associated with metabolic abnormalities that may increase risk of atherosclerotic vascular disease, including dyslipidemia, insulin resistance, and central obesity. Dyslipidemia, characterized by hypercholesterolemia and hypertriglyceridemia, small low- and high-density lipoprotein particles, and in some cases lipoprotein(a) excess, can be severe and has been associated with endothelial dysfunction and carotid atherosclerosis. The mechanisms underlying protease inhibitor-associated dyslipidemia have not been elucidated completely, but appear to involve hepatic overproduction of very low-density lipoproteins and to a lesser extent, impaired clearance. Insulin resistance appears to mediate part of the adverse lipoprotein changes observed in patients taking protease inhibitors. Ongoing epidemiological and surrogate endpoint studies are investigating the atherogenicity of these medications. Until the risk associated with use of protease inhibitors is better understood, identifying patients at high risk for adverse vascular events such as heart attacks, cardiac death, and stroke is a high priority. This article reviews the lipid and lipoprotein abnormalities associated with use of protease inhibitors, possible mechanisms for protease inhibitor-associated dyslipidemia, its potential atherogenicity, and use of the National Cholesterol Education Program Adult Treatment Panel III Guidelines for the management of patients with dyslipidemia.
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PMID:Dyslipidemia in the era of HIV protease inhibitors. 1263 93

Changes in body fat in persons infected with the human immunodeficiency virus (HIV) have been associated with deleterious changes in blood lipids and insulin resistance, raising concern that these changes will increase the risk for accelerated atherosclerosis. Changes in body fat are often identified in advanced disease but may also occur early after HIV infection is detected. Conflicting evidence suggests that fat maldistribution may be related to use of protease inhibitors, nonnucleoside reverse transcriptase inhibitors, or a combination of these two classes of drugs, but the etiologies of the various changes in body fat remain uncertain. To date there have been no remedies for the loss of subcutaneous fat, but recent evidence has suggested that discontinuation of stavudine or zidovudine therapy may be associated with limited restoration of extremity fat. For fat accumulation, a number of strategies have been attempted, including treatment with human growth hormone, androgens, or metformin, and changes in diet and exercise. As in persons not infected with HIV, it is expected that the cornerstone of management, especially in the presence of central obesity, dyslipidemia, and insulin resistance, will include a diet low in saturated fat, with low-glycemic index carbohydrates, and high in fiber. Very limited evidence in persons infected with HIV has suggested that a supervised exercise program may be beneficial.
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PMID:Body habitus changes related to lipodystrophy. 1265 76

Glucocorticoids have a broad array of life-sustaining functions and play an important role in the therapy of many diseases. Thus, changes of tissue sensitivity to glucocorticoids may be associated with and influence the course and treatment of many pathologic states. Such tissue sensitivity changes may present on either side of an optimal range, respectively as glucocorticoid resistance or hypersensitivity, and may be generalized or tissue-specific. Familial/sporadic glucocorticoid resistance syndrome caused by inactivating mutations of the glucocorticoid receptor (GR) gene is a classic monogenic disorder associated with congenital, generalized glucocorticoid insensitivity, while several autoimmune, inflammatory and allergic diseases are often associated with resistance of the inflamed tissues to glucocorticoids. On the other hand, glucocorticoid hypersensitivity has been suggested in visceral obesity-related insulin resistance associated with components of the metabolic syndrome, and in the acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus type-1 (HIV-1) infection. Here, we have reviewed the molecular analyses of five familial and three sporadic cases of the familial/sporadic glucocorticoid resistance syndrome and discussed the possible contribution of newly identified molecules, such as HIV-1 accessory proteins Vpr and Tat, FLICE-associated huge protein (FLASH) and chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), on the molecular regulation of GR activity, as well as their possible contribution to changes in tissue sensitivity to glucocorticoids in pathologic conditions.
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PMID:Tissue glucocorticoid resistance/hypersensitivity syndromes. 1294 36

The combination of immunodeficiency, inflammatory process and nutritional status that is characteristic of infective and food-borne illness is more evident in chronic diet- and environment-influenced chronic diseases such as diabetes, obesity, cardiovascular disease, cancer, arthritis and neuro-degeneration diseases. These chronic diseases tend to be oxidation-linked and may manifest in communities around the world, irrespective of income. In addressing the challenges of the above diseases, a significant role for dietary phytochemicals is emerging. Phytochemicals are required from a spectrum of food for at least their antioxidant role, if not for other properties, to protect tissues from activities that manifest themselves into what we call chronic disease. Among the diverse groups of phytochemicals, phenolic antioxidants and antimicrobials from food plants are being targeted for designed dietary intervention to manage major oxidation-linked diseases such as diabetes, cardiovascular diseases, arthritis, cognition diseases and cancer. Foods containing phenolic phytochemicals are also being targeted to manage bacterial infections associated with chronic diseases such as peptic ulcer, urinary tract infections, dental caries and food-borne bacterial infections. Plants produce phenolic metabolites as a part of growth, developmental and stress adaptation response. These stress and developmental responses are being harnessed to design consistent phytochemical profiles for safety and clinical relevancy using novel tissue culture and bioprocessing technologies. The biochemical strategy for harnessing phenolic phytochemicals for human health and wellness is based on the hypothesis that phenolic metabolites in plants are efficiently produced through an alternative mode of metabolism linking proline synthesis with pentose-phosphate pathway. In this model, stress-induced proline biosynthesis is coupled to pentose-phosphate pathway, driving the synthesis of NADPH(2) and sugar phosphates for anabolic pathways, including phenolic and antioxidant response pathways, while simultaneously providing reducing equivalents needed for mitochondrial oxidative phosphorylation in the form of proline as an alternative to NADH from Krebs/TCA cycle. Based on this model, tissue culture techniques and elicitation concepts have been used to stimulate phenolic metabolites with an antioxidant response in germinating seeds, sprouts and clonal lines of dietary plants. From our initial investigations, a model has been proposed in which the proline-linked pentose-phosphate pathway is suggested to be critical for modulating protective antioxidant response pathways in diverse biological systems, including biochemical and cellular pathways important for human health. The proposed proline-linked pentose-phosphate pathway model provides a mechanism for understanding the mode of action of phenolic phytochemicals in modulating antioxidant pathways and provides avenues by which dietary approaches may manage oxidation-linked chronic and infectious diseases. The model also has implications for the development of antimicrobial phenolic phytochemicals against bacterial pathogens in an era of increasing antibiotic resistance. Further, this model also has relevance for improving fungal and yeast-based food bioprocessing for designing functional foods and for environmental bioremediation using plant and microbial systems, as well as for improving agricultural and food systems in harsh environments.
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PMID:A model for the role of the proline-linked pentose-phosphate pathway in phenolic phytochemical bio-synthesis and mechanism of action for human health and environmental applications. 1500 10

Starting from the very simple molecule sulfamic acid, O-substituted-, N-substituted-, or di-/tri-substituted sulfamates may be obtained, which show specific biological activities which were or started to be exploited for the design of many types of therapeutic agents. Among them, sulfamate inhibitors of aminoacyl-tRNA synthetases (aaRSs) were recently reported, constituting completely new classes of antibiotics, useful in the fight of drug-resistant infections. Anti-viral agents incorporating sulfamate moieties have also been obtained, with at least two types of such derivatives investigated: the nucleoside/nucleotide human immunodeficiency virus (HIV) reverse transcriptase inhibitors, and the HIV protease inhibitors (PIs). In the increasing armamentarium of anti-cancer drugs, the sulfamates occupy a special position, with at least two important targets evidenced so far: the steroid sulfatases (STSs) and the carbonic anhydrases (CAs). An impressing number of inhibitors of STSs of the sulfamate type have been reported in the last years, with several compounds, such as 667COUMATE among others, progressing to clinical trials for the treatment of hormone-dependent tumors (breast and prostate cancers). This field is rapidly evolving, with many types of new inhibitors being constantly reported and designed in such a way as to increase their anti-tumor properties, and decrease undesired features (for example, estrogenicity, a problem encountered with the first generation such inhibitors, such as EMATE). Among the many isozymes of CAs, at least two, CA IX and CA XII, are highly overexpressed in tumors, being generally absent in the normal tissues. Inhibition of tumor-associated CAs was hypothesized to lead to novel therapeutic approaches for the treatment of cancer. Many sulfamates act as very potent (low nanomolar) CA inhibitors. The X-ray crystal structure of the best-studied isozyme, CA II, with three sulfamates (sulfamic acid, topiramate, and EMATE) has recently been reported, which allowed for a rationale drug design of new inhibitors. Indeed, low nanomolar CA IX inhibitors of the sulfamate type have been reported, although such compounds also act as efficient inhibitors of isozymes CA I and II, which are not associated with tumors. A large number of anti-convulsant sulfamates have been described, with one such compound, topiramate, being widely used clinically as anti-epileptic drug. By taking into consideration a side effect of topiramate, an anti-epileptic drug leading to weight loss in some patients, it has recently been proposed to use this drug and related sulfamates for the treatment of obesity. The rationale of this use is based on the inhibition of the mitochondrial CA isozyme, CA V, involved in lipogenesis. Some sulfamates were also shown to possess potent inhibitory activity against acyl coenzyme A:cholesterol acyltransferase, an enzyme involved in cholesterol metabolism. One such agent, avasimibe, is in advanced clinical trials for the treatment of hyperlipidemia and atherosclerosis. Thus, the sulfamate moiety offers very attractive possibilities for the drug design of various pharmacological agents, which are on one hand due to the relative ease with which such compounds are synthesized, and on the other one, due to the fact that biological activity of most of them is impressive.
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PMID:Sulfamates and their therapeutic potential. 1547 25

Type 2 diabetes mellitus and obesity have reached epidemic proportions in many developing and developed nations, leading to talk of the "twin epidemics." The latest projections from the International Diabetes Federation suggest that 190 million people worldwide currently have type 2 diabetes. In addition, > or = 300 million people worldwide have impaired glucose tolerance (IGT). These statistics represent an epidemic of major proportions--possibly the largest epidemic in human history--in terms of glucose intolerance and cardiovascular disease (CVD) risk because individuals with IGT are at substantially higher risk for diabetes and CVD than are members of the general population. Along with IGT, the metabolic syndrome comprises other major CVD risk factors, including insulin resistance, central obesity, and dyslipidemia; insulin resistance has been implicated as the single most common cause of the syndrome. Although the exact prevalence of the metabolic syndrome is unknown, the syndrome is widespread among adults in developed nations, becoming more prevalent with age. Epidemiologic data suggest that in patients with schizophrenia or affective disorders, both diabetes and obesity are 1.5 to 2.0 times more prevalent than in the general population. Furthermore, because adverse effects of certain therapies for human immunodeficiency virus (HIV) infection and psychiatric disorders increase the risk for developing diabetes, obesity, and the metabolic syndrome, such therapies should be carefully chosen, particularly considering CVD risk. Appropriate therapy may be determined via screening of patients for levels of fasting blood glucose and lipids, as well as other CVD risk factors, before initiating use of second-generation antipsychotic agents or highly active antiretroviral therapy.
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PMID:Epidemiology of diabetes mellitus and associated cardiovascular risk factors: focus on human immunodeficiency virus and psychiatric disorders. 1590 89

Insulin resistance is accepted as the underlying fundamental defect that predates and ultimately leads to the development of type 2 (adult onset) diabetes mellitus in the general non-human immunodeficiency virus (HIV)-infected population. Insulin resistance is also a major component of the metabolic syndrome that, in association with other factors such as hypertension, hypercholesterolemia, and central obesity, defines a pre-diabetic atherogenic state that leads to adverse cardiovascular events. Growing evidence now suggests that mitochondrial dysfunction in skeletal muscle may be the mechanism whereby insulin resistance is induced. The prevalence of insulin resistance, glucose intolerance, and diabetes in the HIV-infected population has dramatically increased following the common use of highly active antiretroviral therapy (HAART). The development of insulin resistance in the HIV-infected population is likely to be multifactorial reflecting genetic predisposition, direct and indirect effects of both the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral therapy, and a possible contribution from chronic inflammatory changes induced by HIV. Indirect effects of antiretroviral therapy on insulin resistance may be mediated through both the visceral adiposity and peripheral fat depletion components of lipodystrophy as well as through fatty infiltration in liver and muscle. Based on current knowledge, mitochondrial dysfunction can be hypothesized to play a key role in each of these components.
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PMID:Insulin resistance in the HIV-infected population: the potential role of mitochondrial dysfunction. 1618 Nov 44


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