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)

1. Increased release of tumour necrosis factor is thought to contribute to human-immunodeficiency-virus-associated wasting syndrome. Elevated serum concentrations of tumour necrosis factor have, however, mainly been found during acute opportunistic infections and were not correlated with the degree of wasting. This finding may be explained by the paracrine release and the rapid inactivation of tumour necrosis factor. Serum levels of the two recently detected soluble tumour necrosis factor receptor proteins (p55 and p75) are assumed to reflect tumour necrosis factor release. 2. Serum levels of soluble tumour necrosis factor receptors 55 and 75 were measured by an enzyme-linked immunological and biological binding assay in 45 human-immunodeficiency-virus-infected patients and seven healthy control subjects. Patients were followed up for survival. Serum albumin, prealbumin, total iron-binding capacity (transferrin) and C-reactive protein concentrations were measured using standard laboratory methods. Body composition was determined by bioelectrical impedance analysis. 3. Serum concentrations of soluble tumour necrosis factor receptor 55 and 75 were both significantly increased in human-immunodeficiency-virus-infected patients as compared with the health control subjects (P < 0.05); soluble tumour necrosis factor receptor concentrations were even more increased in patients with elevated C-reactive protein levels (> or = 5mg/l) as compared with those with normal C-reactive protein levels (< 5mg/l; P < 0.0001 and P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumour necrosis factor receptor levels are linked to the acute-phase response and malnutrition in human-immunodeficiency-virus-infected patients. 816 42

In late 1988 in Ethiopia, a physician and a nutritionist examined 240 registered children in the village of Melkaye (Farmers' Association No. 34) in Darolobo District of Habro Province for vitamin A deficiency. These children had been dependent on food aid because of consistent drought and crop failures since, at least, 1982. The food aid, which was the main food source, included food deficient in vitamin A and beta-carotene: wheat flour, vegetable oil, butter-oil, and beans. 53.2% of the boys and 43.1% of the girls had at least 1 sign of vitamin A deficiency, especially night blindness, an early manifestation of vitamin A deficiency. 28.8% of all children had night blindness without signs of xerophthalmia compared with the WHO cut-off point of 1%. (The cut-off point is used to determine the public health significance of vitamin A deficiency.) 6.7% had Bitot's spots compared with a cut-off point of 0.5%. 7.1% had corneal xerosis/ulceration compared with a cut-off point of .01%. 5.8% had corneal scars compared with a cut-off point of .05%. 30.2% had a serum retinol level less than .35 mcmol/l compared with a cut-off point of 5%. 17 of 70 children (24.3%) who had died in the last 2 years had ruptured or damaged eye(s). The median levels of serum retinol-binding protein, iron, transferrin saturation, and ferritin were lower than normal levels. On the other hand, parameters of iodine status, total triiodothyronine, and total thyroxine and thyrotropin were all normal. 78.8% and 82.4% of the children experienced high levels of IgG and IgM, respectively. 42.4% had high C-reactive protein levels. Wasting was more common than stunting (33% vs. 10%). 8% suffered from both stunting and wasting. The severity of xerophthalmia was perhaps the most severe ever recorded and prompted health workers to distribute vitamin A capsules to all children in Melkaye and nearby villages.
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PMID:Severe vitamin A deficiency in a rural village in the Hararge region of Ethiopia. 843 88

The unusual amino acid composition of acute phase proteins may be relevant to our understanding of the mechanism of tissue wasting in chronic inflammatory disease. During periods in which demand for amino acids outstrips dietary supply, skeletal muscle protein may be mobilized to meet this demand. An imbalance in the amino acid composition of these proteins may thus be detrimental to the body's nitrogen economy. To address this problem, we have measured the synthetic rate of fibrinogen (perhaps the major acute phase protein) and plasma amino acid profiles in a group of patients with adenocarcinoma of the pancreas and an ongoing inflammatory response (serum C-reactive protein >10 mg/L in the absence of any other obvious infective or inflammatory cause). These were also measured in a control group with no evidence of inflammation. Fibrinogen synthesis was measured after an overnight fast, using a flooding dose of 2H5-phenylalanine. The fractional rate of fibrinogen synthesis was significantly elevated in the cancer group compared with healthy controls [39.3 (20.0-49.9) and 21.9 (13.2-37.7) %/d, respectively; median (range), P < 0.05]. The absolute rate of fibrinogen synthesis was also elevated [84 (33-143) and 26 (15-43) mg/(kg.d), respectively; median (range), P < 0.01]. We calculated that, in cancer patients with anorexia-cachexia (i.e., documented ongoing weight loss in the absence of an obvious cause such as obstruction or malabsorption), aromatic amino acid supply (predominantly tryptophan) most limits fibrinogen synthesis from skeletal muscle reserves. Demand for the nonessential amino acids serine and glycine was elevated. Assuming that tryptophan is limiting, up to 2.6 g muscle protein ( approximately 12 g skeletal muscle tissue) may be wasted to synthesize 1 g fibrinogen. Interpretation of the observation that circulating free tryptophan concentrations were significantly reduced in the cancer patients will have to await flux measurements. The metabolic changes accompanying the inflammatory response suggest that down-regulation of this process may be beneficial.
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PMID:Fibrinogen synthesis is elevated in fasting cancer patients with an acute phase response. 968 56

The presence of an acute-phase protein response (APPR) has been suggested to shorten survival and contribute to weight loss in patients with pancreatic cancer. Fatty acids derived from fish oil have been shown to alter proinflammatory cytokine production and acute-phase protein synthesis in vitro. The present study was designed to determine the effects of a fish oil-enriched nutritional supplement on the concentrations of a range of individual acute-phase proteins (APP) in patients with advanced pancreatic cancer. In a sequential series, 18 patients with pancreatic cancer received the supplement (providing 2 g eicosapentaenoic acid and 1 g docosahexaenoic acid/d) for 3 wk while another 18 received full supportive care alone. Six healthy subjects served as additional controls. Acute-phase proteins were measured before and after the 3-wk intervention period in cancer patients. At baseline, albumin, transferrin and pre-albumin were significantly reduced and fibrinogen, haptoglobin, alpha-1-acid glycoprotein, alpha-1-antitrypsin, ceruloplasmin and C-reactive protein (CRP) were significantly elevated in the cancer patients compared with healthy controls, reflecting their roles as negative and positive acute phase proteins, respectively. In the supplemented cancer group, the only significant change in APP concentrations over the 4-wk study period was an increase in transferrin. In the control cancer group there were further significant reductions in albumin, transferrin and pre-albumin, and a significant increase in CRP concentration. These results suggest that many positive and negative APP are altered in advanced pancreatic cancer. The APPR tends to progress in untreated patients but may be stabilized by the administration of a fish oil-enriched nutritional supplement. This may have implications for reducing wasting in such patients.
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PMID:Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer. 1035 75

Routine sodium bicarbonate-buffered dialysate is contaminated with predominantly gram-negative micro-organisms. These bacteria release pyrogenic substances such as endotoxins, peptidoglycans, exotoxins and fragments thereof. Pyrogens derived from contaminated dialysate either alone or in costimulation with activated complement components are the most important activators of circulating mononuclear cells in patients on chronic intermittent hemodialysis. Activated mononuclear cells release proinflammatory cytokines which are key mediators in acute and chronic inflammatory diseases associated with long-term hemodialysis therapy. Recent experimental and clinical data suggest that the use of pyrogen-free dialysate prevents activation of mononuclear cells and improves the state of chronic inflammation, as indicated by decreased plasma levels of C-reactive protein in chronic hemodialysis patients. Future clinical studies have to prove whether the use of pyrogen-free dialysate in combination with biocompatible dialyzer membranes and tubings reduces the incidence and severity of chronic inflammatory diseases (beta(2)-microglobulin amyloidosis, muscle protein wasting, atherosclerosis) in long-term hemodialysis patients.
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PMID:Chronic inflammation in hemodialysis: the role of contaminated dialysate. 1085 24

Malnutrition commonly occurs in patients with end-stage renal disease (ESRD), and hypoalbuminemia is considered the best clinical marker of malnutrition and mortality in this population. Recently, it has been recognized that a substantial number of patients with ESRD have serologic evidence of an augmented inflammatory response and moreover, inflammation may be as or more important than protein intake in causing hypoalbuminemia. In addition, the presence of inflammation may be a more powerful predictor of mortality than dietary protein intake. The presence of inflammation is often subtle and is detected by increased levels of the positive acute phase proteins, most notably C-reactive protein. The causes of the stimulation of the systemic inflammatory response may include reaction to dialyzer membranes, increased production of advanced glycosylated end-products, oxidative stress of uremia and overt and occult infections, especially unrecognized arteriovenous graft infections. There is a complex relationship between inflammation and nutritional status. Inflammation can cause both anorexia with protein-calorie malnutrition as well as wasting through mechanisms mediated by cytokines. Novel therapies will need to be developed to counter this systemic inflammation since it appears to be a major cause of mortality in patients with end-stage renal disease.
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PMID:Assessment of inflammation and nutrition in patients with end-stage renal disease. 1094 3

Tuberculosis patients often suffer from severe weight loss, which is considered to be immunosuppressive and a major determinant of severity and outcome of disease. Because leptin is involved in weight regulation and cellular immunity, its possible role in tuberculosis-associated wasting was investigated. In an urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte mass, appetite, C-reactive protein (CRP), tuberculin reactivity, and cytokine response were measured in tuberculosis patients and healthy controls. Plasma leptin concentrations were lower in patients than in controls (615 vs. 2,550 ng/liter; P < 0.001). Multivariate regression analysis showed that body fat mass and inflammation were two independent factors determining plasma leptin concentrations; there was a positive correlation between fat and leptin, whereas, unexpectedly, leptin was inversely associated with CRP and tumor necrosis factor-alpha production. Concentrations of both CRP and leptin were independently associated with loss of appetite. Our results do not support the concept that weight loss in tuberculosis is caused by enhanced production of leptin. Rather, loss of body fat leads to low plasma leptin concentrations, and prolonged inflammation may further suppress leptin production. Because leptin is important for cell-mediated immunity, low leptin production during active tuberculosis may contribute to increased disease severity, especially in cachectic patients.
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PMID:Decreased plasma leptin concentrations in tuberculosis patients are associated with wasting and inflammation. 1183 17

Undernutrition is a frequent complication of evolutive and chronic HIV (human immunodeficiency virus) infection characterized by bodyweight loss and changes in body composition. The Centers for Disease Control and Prevention define AIDS wasting as involuntary loss of more than 10% of body weight, plus more than 30 days of either diarrhea, or weakness and fever. Wasting syndrome has been considered as a case definition of the AIDS disease since 1987. Wasting syndrome is clearly linked to disease progression and death. Despite the progress under the era of highly active antiretroviral therapy (HAART), wasting is still a problem for people with AIDS. A small part of the weight lost is fat. More important is the loss of "lean body mass", which is mostly muscle. Body composition changes during HIV infection are different from those observed in food deprivation. Under the era of HAART, a HIV-associated adipose redistribution syndrome (HARS) was described that associates subcutaneous lipoatrophy and abdominal obesity linked to various metabolic disorders. Several factors contribute to wasting syndrome. Not only low food intake and poor nutrient absorption, but mainly altered metabolism (increased resting energy expenditure) and specific disturbances in protein turnover, which is also increased. Nutritional evaluation of HIV-infected patients should include the measurement of body composition and analysis of nutritional parameters, including albumin, transthyretin and C-reactive protein. Transthyretin seems to be particularly useful to follow the recovery period of malnutrition.
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PMID:Body composition and nutritional parameters in HIV and AIDS patients. 1255 39

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this population, inflammation (which is interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Indeed, several different inflammatory biomarkers, such as high sensitivity C-reactive protein (hs-CRP), have been shown to independently predict mortality in ESRD patients. As CRP is so strongly associated with vascular disease it has been suggested that this hepatic-derived protein is not only a marker, but also a mediator of vascular disease. Indeed, recent in vitro data from studies on endothelial cells, monocytes-macrophages and smooth muscle cells support a direct role for CRP in atherogenesis. The causes of the highly prevalent state of inflammation in ESRD are multiple, including decreased renal function, volume overload, comorbidity and intercurrent clinical events, factors associated with the dialysis procedure and genetic factors. Recent evidence suggests that several cytokine DNA polymorphisms may affect the inflammatory state as well as outcome in ESRD patients. As interventions directed towards traditional risk factors have, so far, not proven to be very effective, controlled studies are needed to evaluate if various pharmacological as well as non-pharmacological anti-inflammatory treatment strategies, alone or in combination, may be an option to affect the unacceptable high cardiovascular mortality rate in this patient group.
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PMID:Inflammation in end-stage renal disease--a fire that burns within. 1587 43

Although traditional risk factors for cardiovascular disease are common in dialysis patients, they alone cannot explain the unacceptably high prevalence of vascular disease in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, wasting, obesity, vascular calcification, and oxidative stress. In addition, genetic factors such as single nucleotide polymorphisms (SNPs) may significantly influence the immune response, the levels of inflammatory markers and body composition, as well as the prevalence of vascular calcification in this patient group. While genetic variations in the tumor necrosis factor (TNF)-alpha-308 and interleukin (IL)-10 -1082 SNPs seem to be consistently associated with adverse clinical outcome in end-stage renal disease (ESRD) patients, the results regarding genetic variations in the IL-6 gene have been conflicting. To elucidate the respective role of DNA polymorphisms in the IL-6 and C-reactive protein (CRP) genes, as well as genes that encode vascular calcification inhibitors (such as fetuin-A, matrix Gla protein, and osteoprotegerin), sufficiently powered studies are needed in which both the protein product and the specific phenotype are determined. In addition, polymorphisms in genes related to body composition may be excellent candidates for analysis in the ESRD population, since nutritional parameters are strongly associated with adverse events in these patients. It seems conceivable that in the future, prognostic or predictive multigene DNA assays (which allow a simultaneous and rapid assessment of multiple genetic variants) will provide nephrologists with a more precise approach for the identification of "high-risk" ESRD patients and the development of accurate individualized treatment strategies.
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PMID:Gene polymorphism association studies in dialysis: the nutrition-inflammation axis. 1607 56


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