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)

The acquired immunodeficiency syndrome and (human immunodeficiency virus) infection loom as our major public health priorities for at least the next two decades. Despite the recent exciting early development of vaccines and newer drug therapies, we are all faced with a reservoir of almost one-quarter million cases in the United States and several times that worldwide. Since the vast majority of HIV-infected patients develop AIDS, which is a chronic progressive disease that produces gastrointestinal dysfunction and wasting, development of rational strategies for nutritional support of these patients should also be a high priority.
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PMID:Toward rational nutritional support of the human immunodeficiency virus-infected patient. 190 46

Cryptosporidiosis is a serious disease in malnourished children and in people with malignancies or AIDS. Current rodent models for evaluating drug therapy against cryptosporidiosis have many limitations, including the need for a high inoculum, the absence of symptoms resembling those seen in humans, and the need to maintain exogenous immunosuppression. We have developed a gamma interferon knockout (GKO) mouse model with which to evaluate therapies against C. parvum and have used paromomycin for evaluation of this model. The GKO model offers considerable improvements over other systems, since it requires no additional immunosuppression and adult mice can be infected with as few as 10 oocysts (compared with 10(7) for SCID mice). Infected mice develop profound gastrointestinal dysfunction due to extensive infection and severe mucosal damage involving the entire small intestine. Clinical symptoms, which include depression, anorexia, weight loss, and wasting, result in death within 2 to 4 weeks. The time of death depends on the oocyst challenge dose. Paromomycin modulated parasitological and clinical parameters in highly predictable and significant ways, including prevention of death. In addition, examination of the extensively infected gut provided an important insight into the dynamics between a specific drug treatment, its impact on the extent and the site of parasite distribution, and clinical outcome. These uniform symptoms of weight loss, wasting, and death are powerful new parameters which bring this model closer to the actual disease seen in humans and other susceptible mammalian species.
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PMID:The gamma interferon gene knockout mouse: a highly sensitive model for evaluation of therapeutic agents against Cryptosporidium parvum. 970 83

Enteropathogenic Escherichia coli (EPEC) was recognized as a common opportunistic pathogen of simian immunodeficiency virus-infected rhesus macaques (Macaca mulatta) with AIDS. Retrospective analysis revealed that 27 of 96 (28.1%) animals with AIDS had features of EPEC infection, and EPEC was the most frequent pathogen of the gastrointestinal tract identified morphologically. In 7.3% of animals dying with AIDS, EPEC represented the sole opportunistic agent of the gastrointestinal tract at death. In 20.8% of cases, it was seen in combination with one or more gastrointestinal pathogens, including Cryptosporidium parvum, Enterocytozoon bieneusi, Mycobacterium avium, Entamoeba histolytica, Balantidium coli, Strongyloides stercoralis, cytomegalovirus, and adenovirus. Clinically, infection was associated with persistent diarrhea and wasting and was more frequent in animals that died at under 1 year of age (P < 0.001, Fisher exact test). The organism was associated with the characteristic attaching and effacing lesion in colonic tissue sections and produced a focal adherence pattern on a HEp-2 assay but was negative for Shiga toxin production as assessed by PCR and a HeLa cell cytotoxicity assay. A 2.6-kb fragment encompassing the intimin gene was amplified and sequenced and revealed 99.2% identity to sequences obtained from human isolates (GenBank AF116899) corresponding to the epsilon intimin subtype. Further investigations with rhesus macaques may offer opportunities to study the impact of EPEC on AIDS pathogenesis and gastrointestinal dysfunction.
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PMID:Identification of enteropathogenic Escherichia coli in simian immunodeficiency virus-infected infant and adult rhesus macaques. 1123 Apr 13

Weight loss is a negative prognostic indicator in patients infected with HIV. Mortality rates rise measurably with as little as 3-5% weight loss over 6 months. The sensitivity of this measure is at least partly due to the correlation between weight loss and a metabolic cachexia that has been observed with other infections, trauma, and some cancers. However, the cachexia in patients with HIV, commonly termed wasting, may also be due to, or exacerbated by, reduced caloric intake, gastrointestinal dysfunction, or metabolic abnormalities independent of abnormal energy expenditure. In patients with HIV wasting, therapies should be directed both at reversing the underlying source of protein energy malnutrition and at other factors that may be contributing to weight loss.
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PMID:Pathogenesis and consequences of HIV-associated wasting. 1572 70

Gastrointestinal disease and inflammation are common sequelae of human and simian immunodeficiency virus (SIV) infection. Nevertheless, the molecular mechanisms that lead to gastrointestinal dysfunction remain unclear. We investigated regulation of the interleukin (IL)-6-JAK-STAT3 pathway in jejunum and colon, collected at necropsy, from 10 SIV-infected macaques with diarrhea (group 1), 10 non-SIV-infected macaques with diarrhea (group 2), and 7 control uninfected macaques (group 3). All group 1 and 2 macaques had chronic diarrhea, wasting, and colitis, but group 1 animals had more frequent and severe lesions in the jejunum. A significant increase in IL-6 and SOCS-3 gene expression along with constitutive STAT3 activation was observed in the colon of all group 1 and 2 macaques and in the jejunum of only group 1 macaques compared to controls. Further, in colon, histopathology severity scores correlated significantly with IL-6 (groups 1 and 2) and SOCS-3 (group 2) gene expression. In jejunum, a similar correlation was observed only in group 1 animals. Phosphorylated STAT3 (p-STAT3) was localized to lymphocytes (CD3+) and macrophages (CD68+), with fewer CD3+ lymphocytes expressing p-STAT3 in group 1 macaques. Despite high SOCS-3 expression, STAT3 remained constitutively active, providing a possible explanation for persistent intestinal inflammation and immune activation that may favor viral replication and disease pro-gression.
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PMID:Gastrointestinal disease in simian immunodeficiency virus-infected rhesus macaques is characterized by proinflammatory dysregulation of the interleukin-6-Janus kinase/signal transducer and activator of transcription3 pathway. 1805 58

Abstract Traumatic brain injury (TBI) is one of the most severe injuries encountered in intensive care units. TBI patients exhibit protein wasting and gastrointestinal dysfunction, which may be risk factors for a septic state. Specific nutritional support may be required for these patients, and we hypothesize that standard nutritional support does not allow restoration of the nutritional state of TBI patients. A well-validated rat model of TBI by fluid percussion was used. Rats were randomized into three groups: healthy rats receiving standard chow diet ad libitum (AL), rats sustaining TBI and receiving standard chow diet (TBI), and rats sustaining TBI and receiving a standard enteral diet (TBI-EN) for 4 days. TBI in rats was characterized by anorexia, body weight loss (AL: +15 +/- 5 g versus TBI: -11 +/- 4 g and TBI-EN: -8 +/- 4 g; p < 0.05), decrease in nitrogen balance (AL: 2.9 +/- 0.2 g versus TBI: 1.0 +/- 0.2 g and TBI-EN: 0.2 +/- 0.2 g, p < 0.05) associated with decrease in muscular protein content (extensor digitorum longus [EDL]: AL: 36 +/- 2 mg versus TBI: 26 +/- 3 mg and TBI-EN: 28 +/- 2 mg; p < 0.05), and intestinal atrophy (ileum: AL: 673 +/- 42 mg versus TBI: 442 +/- 23 mg and TBI-EN: 377 +/- 27 mg; p < 0.05). Interestingly, standard enteral nutrition was not effective in restoring any of these parameters. This work confirms that TBI is associated with profound nutritional alterations and has a major impact on nitrogen metabolism and on intestinal trophicity. It also demonstrates that using standard enteral nutrition cannot reverse this phenomenon. Thus, developing new nutritional strategies to cover TBI patients' specific nutritional requirements appears mandatory.
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PMID:Metabolic response and nutritional support in traumatic brain injury: evidence for resistance to renutrition. 1992 16

Protein wasting (PW) or protein-energy wasting (PEW) occurs commonly in patients with diabetes mellitus who have end-stage renal disease (ESRD) and are undergoing maintenance dialysis (MD) therapy. Some but not all studies indicate that PW or PEW is more prevalent in diabetic when compared with nondiabetic MD patients and that diabetic patients commencing maintenance hemodialysis (MHD) are more likely to lose fat-free, edema-free weight than are incident nondiabetic MHD patients. The causes of PW and PEW in diabetic MD patients are probably largely similar to those of nondiabetic MD patients. These causes include anorexia, reduced food intake, concurrent illnesses particularly when associated with inflammatory processes, physical or mental debility, removal of nutrients by dialysis procedure, acidemia, possibly physical deconditioning, and oxidant and carbonyl stress. However, diabetic MD patients are also at greater risk for PW or PEW from comorbidities related to diabetes per se. These disorders include ischemic vascular disease, hypertension, gastrointestinal dysfunction, and neuropathy. Metabolic disorders such as insulin deficiency or resistance to the actions of insulin, and elevated levels of counterregulatory hormones may also contribute to PW or PEW in diabetic MD patients. Mechanisms by which these metabolic disorders in diabetic ESRD patients may cause PW or PEW are discussed.
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PMID:Effect of diabetes mellitus on protein-energy wasting and protein wasting in end-stage renal disease. 2052 7