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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson's disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders.
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PMID:Therapeutic potential of cannabinoids in CNS disease. 1261 97

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

Fat redistribution (lipodystrophy) and metabolic anomalies are reported increasingly in HIV-infected patients being treated with protease inhibitors. The incidence of these side effects ranges from 5% to 75% in such patients, who often complain of spontaneous fat wasting in the face, arms, or legs, with or without central obesity. Hyperlipidemia and insulin resistance are almost always associated with lipodystrophy. We review the metabolic complications of antiretroviral therapies and discuss possible therapeutic interventions.
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PMID:Metabolic effects of protease inhibitor therapy. 1273 15

Leptin is a an adipocyte-secreted hormone that regulates weight centrally. However, the leptin receptor is expressed not only in the central nervous system, but also in peripheral tissues, such as haematopoietic and immune systems. Therefore, the physiological role of leptin should not be limited to the regulation of food intake and energy expenditure. Moreover, the leptin receptor bears homology to members of the class I cytokine family, and recent data have demonstrated that leptin is able to modulate the immune response. Thus, the leptin receptor is expressed in human peripheral blood mononuclear cells, mediating the leptin effect on proliferation and activation. In vitro activation and HIV infection in vivo induce the expression of the long isoform of the leptin receptor in mononuclear cells. Also, leptin stimulates the production of proinflammatory cytokines from cultured monocytes and enhances the production of Th1 type cytokines from stimulated lymphocytes. Moreover, leptin has a trophic effect on monocytes, preventing apoptosis induced by serum deprivation. Leptin stimulation activates JAK-STAT, IRS-1-PI3K and MAPK signalling pathways. Leptin also stimulates Tyr-phosphorylation of the RNA-binding protein Sam68 mediating the dissociation from RNA. In this way, leptin signalling could modulate RNA metabolism. These signal transduction pathways provide possible mechanisms whereby leptin may modulate activation of peripheral blood mononuclear cells. Therefore, these data support the hypothesis regarding leptin as a proinflammatory cytokine with a possible role as a link between the nutritional status and the immune response. Moreover, these immunoregulatory functions of leptin could have some relevance in the pathophysiology of obesity.
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PMID:Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action. 1282 72

The presentation of the nutritional problems of HIV-infected children is changing over time with improved antiretroviral regimens. Early reports of HIV infection in the 1980s, included such problems as malnutrition and wasting. However, as treatment and prophylactic regimens improve, the current nutritional problems of HIV-infected children in developed countries include truncal obesity and insulin resistance in addition to malnutrition. Background data on the wasting syndrome, etiology of malnutrition, nutritional effects of highly active antiretroviral therapies, and nutritional intervention strategies for HIV-infected children will be presented.
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PMID:Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy. 1287 May 39

Metformin, a biguanide, has been available in the US for the treatment of type 2 diabetes mellitus for nearly 8 years. Over this period of time, it has become the most widely prescribed antihyperglycaemic agent. Its mechanism of action involves the suppression of endogenous glucose production, primarily by the liver. Whether the drug actually has an insulin sensitising effect in peripheral tissues, such as muscle and fat, remains somewhat controversial. Nonetheless, because insulin levels decline with metformin use, it has been termed an 'insulin sensitiser'. Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular outcomes in patients with diabetes. Cardiovascular disease, impaired glucose tolerance and the polycystic ovary syndrome are now recognised as complications of the insulin resistance syndrome, and there is growing interest in the management of this extraordinarily common metabolic disorder. While diet and exercise remain the cornerstone of therapy for insulin resistance, pharmacological intervention is becoming an increasingly viable option. We review the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits it provides over and above its effect on glucose levels alone. We also discuss its potential role for a variety of insulin resistant and prediabetic states, including impaired glucose tolerance, obesity, polycystic ovary syndrome and the metabolic abnormalities associated with HIV disease.
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PMID:Metformin: new understandings, new uses. 1293 Jan 61

The evolution in therapy for chronic hepatitis C virus (HCV) infection to the more recent use of peginterferons in combination with ribavirin has dramatically increased the sustained virological response (SVR) rates versus standard interferon/ ribavirin combination therapy. However, although peginterferon and ribavirin therapy has markedly improved treatment responses overall, factors such as high viral load, genotype 1 infection, obesity, HIV co-infection and African American race continue to pose challenges to optimizing SVR rates. Application of mathematical models may be helpful in understanding why these groups and/or individuals appear to be resistant to interferon (IFN)-based therapy. This article focuses on the viral kinetics and viral kinetic differences among patients infected with HCV genotypes 1 and 2, obese and nonobese patients, and African Americans and Whites.
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PMID:Viral kinetics in hepatitis C virus: special patient populations. 1293 66

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 life-stage approach, which views the behaviours and exposures of an individual from the preconceptual situation of the parent through pregnancy, infancy, childhood and adolescence, and into the advancing years through adulthood, is the basis of analysis of strategies to improve long-term health. Among the behaviours of note is the dietary selection pattern, conditioning our exposure to nutrients and dietary constituents that influences growth, nutriture, cognitive and physical performance, and disease resistance and susceptibility. The African Diaspora created a population displaced from Africa to the Western Hemisphere as part of the African slave trade from the 16th to 18th centuries. It continues to manifest distinct dietary and lifestyle practices in the context of a health experience that is different both from the population in their African countries of origin and from the other ethnicities in their countries of displacement and current residence. Afro-Americans are more susceptible to a series of diseases and conditions including low birth weight, violence, and HIV/AIDS, as well as the non-communicable diseases: obesity, diabetes mellitus, cardiovascular disease, hypertension, stroke, renal failure, breast cancer, prostate cancer and lead poisoning. The differential nature of dietary practices are conditioned at times by the poverty and marginalisation of the populace, resulting in either disadvantageous or beneficial outcomes relative to others' eating habits. Serious consideration must be given to the possibility that ethnic difference give rise to different requirements and tolerances for essential nutrients and distinct protective or adverse responses to foods and dietary substances. The major challenges to health improvement for the African Diaspora is coming to grips with the policy and programmatic nuances of differential treatment and the effecting the behavioural changes that would be needed in a population skeptical of the motives of media and of the power elites of their societies.
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PMID:Diet and long-term health: an African Diaspora perspective. 1450 96

GH and PRL are both implicated in adipose tissue development. Whilst direct effects of GH have been clearly demonstrated, direct effects of PRL have been subject to considerable debate. Recent studies have however provided compelling evidence for PRL receptors on adipocytes and in vitro effects on leptin and lipoprotein lipase activity have been demonstrated. Quantitatively however these effects of PRL are less significant than those of GH and the most pronounced effects of PRL on adipose tissue are indirect, for example, during lactation, when prolactin drives milk synthesis which results in a homeorhetic shift towards lipid mobilization from adipose tissue to support milk production. GH also exhibits such homeorhetic effects, most notably in ruminants, but also clearly has direct, insulin-antagonistic, metabolic effects. The roles of GH and PRL on adipocyte proliferation and differentiation have also been controversial, with GH stimulating adipocyte differentiation in vitro in cell lines whilst stimulating proliferation and inhibiting differentiation of primary cell cultures. Examination of adipose tissue development in PRLRko and GHRko mice has revealed roles for both hormones. PRLRko mice show impaired development of both internal and subcutaneous adipose tissue due to decreased numbers of adipocytes. In contrast, GHRko mice exhibit major decreases in the number of internal (parametrial) adipocytes whereas subcutaneous adipocytes develop almost normally. This leads to major changes in the sites of adipose tissue accretion and bears interesting parallels with the adipose tissue redistribution which occurs in HIV-induced lipodystrophy. Such individuals exhibit a central obesity which can be partially corrected by GH treatment. However, recent studies suggest that this may be a physiological response in which adipose tissue sites containing lymphoid tissue (such as mesenteric) show preservation of adipose tissue perhaps to support augmented immune responses.
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PMID:Effects of growth hormone and prolactin on adipose tissue development and function. 1470 19


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