Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines may be involved in weight loss and disturbances of metabolism associated with human immunodeficiency virus (HIV) infection. Dietary n-3 fatty acids reduce the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) in normal humans and prevent IL-1 and TNF anorexia in animals. Accordingly, we studied the nutritional and metabolic effects of a 10-week trial of dietary fish oil (MaxEPA 18 g/day) in men with weight loss due to acquired immune deficiency syndrome (AIDS). Twenty men were enrolled, and 16 completed the 10-week supplementation period. Prior weight loss was 13.7 +/- 1.8 kg(17.4 +/- 1.6% body weight, means +/- SE). Food intake, body composition, blood chemistries, serum cytokine concentrations, in vitro production of IL-1 and TNF by PBMC, and clinical course were followed. A subset of subjects (n=12) underwent stable isotope infusions to measure de novo hepatic lipogenesis (DNL), an in vivo metabolic index that is influenced by cytokine presence and has previously been found to be elevated in AIDS. An unsupplemented group of men with AIDS wasting (10.4 +/- 2.4 kg weight loss, 13.1 +/- 2.2% body weight) was monitored for 10 weeks as controls. Baseline food intake (2,395 +/- 177 kcal/day and 95.1 +/- 7.2 g protein/day), body weight, percent fat, and fat-free mass were unchanged over the 10-week supplementation period. Serum triglycerides were reduced in hypertriglyceridemic subjects, confirming compliance with fish oil supplementation and suggesting that their hypertriglyceridemia was at least in part due to overproduction. Serum TNF and IL-1 were undetectable before or after fish oil supplementation. Serum interferon alpha (IFN) was measurable but did not change. In vitro production of IL-1 and TNF by PBMC was markedly reduced both at baseline and after fish oil supplementation in this population, even in the presence of new AIDS complications, compared with normal controls. The metabolic measurement DNL fell and weight was gained (2.1 +/- 1.3 kg) in subjects who did not develop new AIDS-related complications, but further increases in DNL and further weight loss were observed in subjects who developed a new AIDS complication (p<0.05 for interaction between new complication and change in DNL). No changes in body weight, food intake, serum triglycerides, serum cytokines, or DNL were observed in the unsupplemented group. We conclude that fish oil is a weak anticytokine agent that is unable to overcome the metabolic and nutritional consequences of acute AIDS-related complications but may exert a clinical anticytokine effect in stable AIDS patients. Cytokine production by PBMC is not a useful or reliable marker of in vivo cytokine activity in AIDS patients with weight loss. In contrast, an integrative functional index that is sensitive to cytokine presence in tissues (hepatic DNL) correlated with clinical response. These findings are relevant to the design of future studies of more potent anticytokine agents, such as thalidomide.
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PMID:Effects of dietary n-3 fatty acid supplementation in men with weight loss associated with the acquired immune deficiency syndrome: Relation to indices of cytokine production. 860 62

Tissue wasting often occurs during human immunodeficiency virus infection and acquired immune deficiency syndrome. While weight-loss in the human immunodeficiency virus-infected individual can be seen as an isolated symptom, catabolism during acquired immune deficiency syndrome is usually associated with complications such as diarrhea, malabsorption, fever and secondary infection. Glutamine is an amino acid central to many important metabolic pathways and recent findings suggest that glutamine depletion may explain the progression of tissue wasting during human immunodeficiency virus infection.
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PMID:Glutamine deficiency as a cause of human immunodeficiency virus wasting. 867 62

The effects of stress on immunity and on the bacterial translocation from intestine to mesenteric lymph nodes, liver, and spleen were studied in a group of newborn CD1 mice. Animals were separated into three experimental groups. Mice from group I were stressed by intraperitoneal (i.p.) injections of heat-killed staphylococci for 4 weeks. Mice from group II were i.p. injected with saline solution only. The remaining mice, group III, were not injected. The clinical condition, presence of bacteria in abdominal organs, mitochondrial activity in splenic cells, lymphocyte proliferative response to Concanavalin-A and in vitro antibody production were evaluated in each mouse. Results showed that prolonged i.p. stressor challenge causes severe weight loss and immunodeficiency. The splenic lymphocytes from stressed mice exhibited a significant depression of both proliferative response to Concanavalin-A stimulation and anti-erythrocytes antibody synthesis. Instead, cultured in basal conditions, the splenic cells from stressed mice have an increased capacity to reduce the tetrazolium salts. Bacterial dissemination from intestine to mesenteric lymphoid nodes was also confirmed in the same group of mice. In contrast, mice in groups II and III presented no weight loss and no immunodeficiency. Results suggest that chronic biological stress induced in newborn mice could facilitate the translocation of Gram-negative bacteria. Probable pathogenic mechanisms are commented upon and a correlation is proposed between the bacterial dissemination and the wasting development.
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PMID:Bacterial translocation and wasting in stressed mice. 869 51

The clinicopathologic and immunologic features of 15 llamas affected with juvenile llama immunodeficiency syndrome (JLIDS) are described. Healthy adult (n = 10) and juvenile (n = 10) llamas served as controls. JLIDS llamas were characterized by wasting, and clinically apparent, repeated infections were frequently observed. The median age at which a health problem was first perceived was 11.6 months. All 15 affected llamas died or were killed, and JLIDS was confirmed at necropsy. The median duration of illness was 3.5 months. Lymphocyte blastogenesis assays showed suppressed responses (particularly to Staphylococcus sp. Protein A) in JLIDS llamas. No evidence of retroviral infection was detected. Mild, normocytic, normochromic, non-regenerative anemia, low serum albumin concentration and low to low-normal globulin concentrations were typically found on initial clinical evaluation. Lymph node biopsies showed areas of paracortical depletion. All llamas affected with JLIDS had low serum IgG concentrations, pre-vaccination titers against Clostridium perfringens C and D toxoids of < or = 1:100, and no titer increase following vaccination.
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PMID:Prospective characterization of the clinicopathologic and immunologic features of an immunodeficiency syndrome affecting juvenile llamas. 874 96

Loss of body mass, or wasting, is a major cause of morbidity and a contributor to mortality in human immunodeficiency virus-1 (HIV-1) infection. Dietary supplements and appetite adjuvants have had limited effectiveness in treating this condition. GH and insulin-like growth factor I (IGF-I) have been shown to be anabolic in many catabolic conditions, and limited data suggest similar efficacy in HIV wasting. In addition, it appears that GH and IGF-I may have complementary anabolic effects with opposing glucoregulatory effects. We report results from a 12-week randomized, placebo-controlled trial of combination recombinant human GH (rhGH; Nutropin; 0.34 mg, sc, twice daily) and rhIGF-I (5.0 mg, sc, twice daily) in individuals with HIV wasting and without active opportunistic infection, cancer, or gastrointestinal disease. A total of 142 subjects (140 males and 2 females) were randomized using a 2:1, double blind treatment scheme and assigned to receive either active treatment or placebo injections. Eighty subjects completed the 12-week protocol. Nutritional intake and demographic and clinical characteristics did not differ between the groups at any study time point. At 3 weeks, the treatment group had a significantly larger weight increase (P = 0.0003), but this difference was not observed at any later time point. Similarly, fat-free mass, calculated from skinfold measurements, increased transiently in the treatment group at 6 weeks (P = 0.002). No significant differences in isokinetic muscle strength or endurance testing or in quality of life were observed between the groups. Resting heart rate was significantly higher in the treatment group at each time point post-baseline. GH and IGF-binding protein-3 levels did not change; however, IGF-I levels were higher in the treatment group at 6 and 12 weeks. There were no significant between-group differences in any of the measured biochemical or immunological parameters. rhGH plus rhIGF-I treatment was associated with an increased incidence of peripheral edema and other side-effects, possibly related to fluid retention. We conclude that the combination of rhIGF-I and low dose rhGH used in this study had no significant anabolic effect in HIV wasting.
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PMID:A randomized, placebo-controlled trial of combined insulin-like growth factor I and low dose growth hormone therapy for wasting associated with human immunodeficiency virus infection. 876 60

The utility of the simian immunodeficiency virus of macaques (SIVmac) model of AIDS has been limited by the genetic divergence of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and the SIVs. To develop a better AIDS animal model, we have been exploring the infection of rhesus monkeys with chimeric simian/human immunodeficiency viruses (SHIVs) composed of SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rev. SHIV-89.6, constructed with the HIV-1 env of a cytopathic, macrophage-tropic clone of a patient isolate of HIV-1 (89.6), was previously shown to replicate to a high degree in monkeys during primary infection. However, pathogenic consequences of chronic infection were not evident. We now show that after two serial in vivo passages by intravenous blood inoculation of naive rhesus monkeys, this SHIV (SHIV-89.6P) induced CD4 lymphopenia and an AIDS-like disease with wasting and opportunistic infections. Genetic and serologic evaluation indicated that the reisolated SHIV-89.6P expressed envelope glycoproteins that resembled those of HIV-1. When inoculated into naive rhesus monkeys, SHIV-89.6P caused persistent infection and CD4 lymphopenia. This chimeric virus expressing patient isolate HIV-1 envelope glycoproteins will be valuable as a challenge virus for evaluating HIV-1 envelope-based vaccines and for exploring the genetic determinants of HIV-1 pathogenicity.
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PMID:A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. 879 35

In an effort to augment human immunodeficiency virus type 1 (HIV-1) gene expression in transgenic mice, an infectious proviral DNA clone was modified by deleting the two NF kappa B binding sites and some adjacent upstream LTR sequences and replacing them with the core enhancer of Moloney murine leukemia virus (MLV). Two independent lines of MLV/HIV transgenic mice were established that expressed HIV-1-specific RNA in lymphoid tissue, striated skeletal muscle, and the eye lens. Heterozygous animals from each transgenic line spontaneously developed an inflammatory disease of the eye associated with the production of copious amounts of purulent lacrimal secretions beginning at 2 weeks of age. Periorbital abscess formation became grossly apparent by 2 months of age and Pasteurella pneumotropica was cultured from the harderian glands and conjunctival surfaces of many of the MLV/HIV animals but not their nontransgenic, cohabiting littermates. This gram-negative commensal bacterium has been previously associated with a similar disease phenotype in immunocompromised (e.g., nude mice) rodent colonies. MLV/HIV mice developed normally until 15 weeks of age, when weight loss and wasting occurred, culminating in premature death (as earlier as 6 months of age). The cachexia was associated with an initially focal and subsequently progressive myopathy, coinciding with age-related increases of HIV gene expression in muscle.
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PMID:Myopathy and spontaneous Pasteurella pneumotropica-induced abscess formation in an HIV-1 transgenic mouse model. 886 75

Although anabolic effects of GH supplementation have been reported in acquired immune deficiency syndrome (AIDS) patients, the effects of human immunodeficiency virus (HIV) infection per se on GH secretion are unknown. Therefore, we evaluated the characteristics of GH secretion in eight asymptomatic HIV-infected men, eight clinically stable male AIDS patients, and eight healthy controls. Wasting AIDS patients were not included to circumvent the confounding effects of opportunistic disease on GH secretion. Samples for GH analysis were taken at 10-min intervals over 24 h. GH was measured by immunoradiometric assay (detection limit, 0.08 mU/L). Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 were measured every 6 h. The pulsatile secretion of GH was evaluated by Cluster and DESADE analyses. No differences in number of peaks, peak amplitude, peak length, peak interval, or GH secretion per 24 h were found among the studied groups. IGF-I and IGF-binding protein-3 concentrations were not different among groups. Circadian GH secretion in asymptomatic HIV infection and AIDS without wasting is not different from that in healthy subjects. Therefore, anabolic effects documented in clinical trials with recombinant human GH in AIDS patients are not merely explained by alterations in the GH/IGF-I axis induced by HIV infection per se.
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PMID:Circadian growth hormone secretion in asymptomatic human immune deficiency virus infection and acquired immunodeficiency syndrome. 892 55

Weight loss is commonly associated with increased morbidity and mortality in individuals with human immunodeficiency virus (HIV) infection. We performed a nested case-control study of 26 HIV-infected subjects recruited from a cohort of gay men enrolled in the Multicenter Acquired Immunodeficiency Syndrome Cohort Study. To test the hypothesis that hormonal changes precede and may induce the wasting syndrome, we performed a nested case-control study and analyzed serum gonadal steroids and GH in samples of HIV-infected men with or without weight loss, uncomplicated by diarrhea or ever having an opportunistic infection. We studied 13 cases (mean age +/- SD, 45 +/- 7.2 yr) with a mean weight loss of 13 +/- 3.6%, considered to have the wasting syndrome by Centers for Disease Control criteria (weight loss of > 10%) and 13 controls matched for age and duration of follow-up. Serum bioavailable testosterone (T) levels decreased in the case group (P < 0.05) before the definition of wasting was attained, although weight loss had already begun. More impressive declines occurred in serum T (P = 0.012), free T (P = 0.0025), and bioavailable T (P < 0.0001) during the 6 months immediately before documentation of wasting. These changes were concurrent with an increase in serum FSH (P = 0.0135) without a change in serum LH. We conclude that a decline in bioavailable T occurs early in the course of events leading to wasting, suggesting that changes in gonadal hormones may contribute to the multifactorial etiology of the wasting syndrome.
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PMID:Serum hormones in men with human immunodeficiency virus-associated wasting. 892 68

Infection with the human immunodeficiency virus (HIV) can lead to global alterations in metabolism as well as immunodeficiency. There is dysregulation of endocrine function in adults and children, the extent and magnitude correlating with disease progression. Some of the more prominent abnormalities occur in the thyroid, gonadal, and somatomedin axes. Clinical manifestations of these abnormalities are growth failure in children, which is one of the most sensitive indicators of disease progression, and a wasting syndrome in adults and children. Although there are case reports of growth hormone (GH) deficiency in HIV-infected children, most patients with growth failure have normal serum levels of GH and normal to low levels of insulin-like growth factor-I (IGF-I). Antiretrovial therapy can improve the growth rate in children for a period of time if there is a drop in viral titer, but as the viral load increases, the growth rate decreases again. Administration of GH or IGF-I to these patients can improve the growth rate and lean body mass, and in some patients improve immune function. Although studies on resting energy expenditure in HIV-infected patients have shown increases, these are not proportional to disease progression, but may be dependent upon cytokine activation and other abnormalities. Adult patients with wasting have been shown to have relatively normal total energy expenditure, but decreased intake. Appetite stimulants have been shown to have some benefit, but do not increase lean body mass. The most significant clinical benefit has come from administration of GH in short-term trials. GH and IGF-I are both able to inhibit apoptosis and reconstitute the immune system in rodents treated with ablative therapy. In addition, GH can modulate the marrow suppressive effects of zidovudine and may enhance its ability to inhibit viral reverse transcriptase. Current clinical trials are ongoing in both adults and children. GH and IGF-I may have a role in regimens intended for immune reconstruction, and could be useful as adjuvant therapy in selected patients with HIV infection.
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PMID:Use of human recombinant growth hormone and human recombinant insulin-like growth factor-I in patients with human immunodeficiency virus infection. 895 Jun 24


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