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 techniques of prompt gamma neutron-activation analysis for the measurement of total-body nitrogen and whole-body counting for the measurement of total-body potassium were used to determine the mass of muscle and nonmuscle lean tissue and their protein content in 135 normal male and female subjects, 20-80 yr of age. Age-related changes in the size of the muscle and nonmuscle compartments and their protein content provide basic data for the investigation of protein metabolism in aging subjects and in individuals with various metabolic disorders, particularly wasting diseases such as cancer. Significant age-related changes in the size of various body compartments were noted. The loss of muscle mass and its protein content contrasts with the relative constancy of the nonmuscle lean tissue and suggests that skeletal muscle is particularly vulnerable to the aging process.
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PMID:Compartmental body composition based on total-body nitrogen, potassium, and calcium. 744 27

We investigated the use of ornithine alpha-ketoglutarate in treatment of rats bearing Morris hepatoma 7777. Rats received diets containing either ornithine alpha-ketoglutarate, which has been used in other catabolic states (i.e. injury, sepsis), or an isonitrogenous, isocaloric diet containing glycine. Untreated tumors grew to a mass of 11 g/100 g body weight over the 3-wk period after implantation and induced progressive anorexia, negative nitrogen balance, and body and tissue wasting. Compared with glycine, ornithine alpha-ketoglutarate had no effect on tumor growth, but also did not alter the catabolic effects of the tumor on its host. We hypothesized that capture of amino acids by the tumor limited the efficacy of supplemental nutrition here and in published reports in which tumor burden comprised 4-30% of body weight. This is supported by our observation that a 3-wk of implantation the rate of protein deposition plus amino acid oxidation by the tumor was equivalent to approximately 70% of the host's daily protein intake. To parallel the clinical situation in which tumor burden is small at diagnosis and initiation of treatment, the same diets were tested in rats treated by excision of the tumor at a limited stage of the disease. Rats received 3 d preoperative nutrition with ornithine alpha-ketoglutarate or glycine, and continued on the same diets for 3 or 6 d postoperatively. Compared with glycine-fed rats, ornithine alpha-ketoglutarate-fed rats showed a more positive nitrogen balance, higher concentrations of glutamine and branched-chain amino acids in muscle, and accelerated protein deposition in small intestine (P < 0.05). Our results explain the lack of success of nutritional support in untreated cancer and underline the need for clinically relevant animal models for further studies.
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PMID:Supplemental nutrition with ornithine alpha-ketoglutarate in rats with cancer-associated cachexia: surgical treatment of the tumor improves efficacy of nutritional support. 750 Jan 78

Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the sarcoma model, rats were implanted subcutaneously with tumour, and treated continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps. Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine treatment significantly lowered the tumour-induced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups respectively. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects could be the result of down-regulation of cytokine production and/or increased clearance of cytokines.
Br J Cancer 1995 Nov
PMID:Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. 757 64

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-alpha) are early perturbed after tumor transplantation (Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16-23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH0130 hepatoma probably account for this lack of effect.
Cancer Lett 1995 Oct 20
PMID:Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth. 758 74

The mechanisms leading to the development of cancer cachexia are still poorly understood. Recently, cytokines such as interleukin 1 and tumour necrosis factor-alpha have been involved as mediators of the tissue wasting consequent to tumour growth. The rat ascites hepatoma Yoshida AH-130 is a highly anaplastic tumour that causes in the host an early and marked depletion of both the skeletal muscle and the adipose tissue, mainly accounted for by a hypercatabolic state. Profound hormonal alterations and the release of tumour necrosis factor-alpha and interleukin 1 by the tumour cells likely concur in forcing the metabolic balance towards the catabolic side [1]. In order to possibly achieve the correction of this wasting condition, the AH-130 bearing rats were administered a daily s.c. dose of interleukin 1 receptor antagonist (IL-1ra; 2 mg/kg). This factor, however, was completely ineffective in either inhibiting tumour proliferation or in preventing the consequent tissue depletion and protein hypercatabolism. These observations suggest that interleukin 1 is not important, at least in this model system, for either the development of cachexia or tumour growth.
Cancer Lett 1995 Aug 16
PMID:Interleukin-1 receptor antagonist (IL-1ra) is unable to reverse cachexia in rats bearing an ascites hepatoma (Yoshida AH-130). 765 41

Cisplatin is an effective antineoplastic agent, but can cause renal tubular damage leading to urinary magnesium wasting and hypomagnesaemia. Cisplatin and 5-fluorouracil, when used in combination, have synergistic antitumour activity in upper gastrointestinal malignancies, but it is unclear whether they have additive effects on renal magnesium loss. To determine the optimal regimen for magnesium supplementation in these patients, we have conducted a randomised trial of routine intravenous magnesium supplements compared with magnesium given on an 'as required' basis. 32 patients were randomised to receive magnesium intravenously in prehydration and posthydration fluids with cisplatin chemotherapy, or to receive magnesium only when the serum level was low. 5-fluorouracil was given as a continuous infusion. Serum magnesium was measured on admission for each cycle of chemotherapy and an interim measurement performed between each cycle. 28 patients were evaluable. All patients randomised to receive magnesium on an 'as required' basis had at least one episode of hypomagnesaemia. On subsequent admissions for chemotherapy (cycles 2 and 3), the mean serum magnesium level was significantly lower in these patients compared with patients who received magnesium routinely (P < 0.05). After omission of magnesium from the first cycle of cisplatin, magnesium supplements were necessary in 50% of subsequent cycles, usually by the second or third cycle. Moreover, there were several instances of symptomatic hypomagnesaemia requiring further intravenous supplements in mid-cycle. Patients treated with a combination of cisplatin and 5-fluorouracil should be given intravenous magnesium supplements with each cycle of cisplatin chemotherapy. Nevertheless, episodes of hypomagnesaemia still occur, and additional intravenous supplements may be required, highlighting the importance of measuring this electrolyte.
Eur J Cancer 1995
PMID:A randomised study to determine whether routine intravenous magnesium supplements are necessary in patients receiving cisplatin chemotherapy with continuous infusion 5-fluorouracil. 771 21

Malignant histiocytosis (MH) and true histiocytic lymphoma (THL) are hematopoietic malignancies of the mononuclear phagocytic system distinguished from each other by clinical presentation and presumed cell of origin. THL present as a localized mass derived from the fixed tissue histiocyte which may or may not disseminate. MH originates from the circulating monocyte or tissue macrophage and is characterized by a syndrome of systemic symptoms, pancytopenia, adenopathy, hepatosplenomegaly, and wasting. The distinction between MH and THL is at times arbitrary and overlap exists between these syndromes. The clinicopathologic studies that defined these entities were performed prior to the development of immunophenotyping and other molecular techniques currently used to ensure proper classification of hematopoietic malignancies. Nine patients from the University of Minnesota originally diagnosed with MH were retrospectively analyzed using a panel of antibodies reactive against T cell, B cell, and myelomonocytic antigens. Only one patient was reclassified as a possible histiocytic malignancy after reevaluation. Similar immunophenotyping studies have also shown cases previously diagnosed as MH or THL express lymphoid antigens, and would now be classified as Ki-1 positive anaplastic large cell lymphoma (ALCL) or some other hematopoietic neoplasm. These results indicate true histiocytic neoplasms are extremely rare, and previous concepts concerning clinical presentation and therapeutic outcome of the entities are inaccurate. In this paper we summarize the results of multiple retrospective analyses of cases previously diagnosed as MH or THL, including our experience at University of Minnesota, to illustrate the overall rarity of these entities. The current literature on malignant histiocytic disorders is reviewed, and the clinical presentation of patients determined to have histiocytic malignancies using contemporary analytical techniques is discussed.
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PMID:Malignant histiocytosis: a reassessment of cases formerly classified as histiocytic neoplasms and review of the literature. 775 95

To investigate the mechanism causing cachexia and its association with shorter patient survival, we cloned weight-loss-inducing and -non-inducing sublines of murine colon 26 carcinoma (colon 26). One clone, clone 20, induced substantial weight loss, wasting of adipose tissue and muscle, and hypoglycemia in mice with a minimum tumor burden of 0.3 g (2 g per 100 g body weight). Clone-20-bearing mice had a median survival of 24.5 days with average tumor weight of 0.4 g. In contrast, clone 5 induced neither severe weight loss, wasting of adipose tissue and muscle, nor hypoglycemia; clone-5-bearing mice survived for a median of 70 days with average tumor weight of 12 g. These results clearly indicate that shorter survival is associated with the degree of cachexia and is independent of tumor size. Using this pair of colon 26 clones, we examined mediators of cachexia. Neither TNF alpha, IL-1 alpha nor IFN gamma was detected in the serum of mice bearing either clone, while IL-6 was detected in mice bearing both clones by ELISA and a bioassay. Administration of anti-IL-6 monoclonal antibody (MAb) partially but significantly suppressed cachexia induction in clone-20-bearing mice. These results point to the involvement of IL-6 in experimental cachexia. However, our finding of the presence of IL-6 in the serum of mice bearing clone 5, which does not induce weight loss, clearly indicates that IL-6 is not solely responsible for the induction of cachexia.
Int J Cancer 1995 May 16
PMID:Establishment and characterization of cachexia-inducing and -non-inducing clones of murine colon 26 carcinoma. 775 58

Ifosfamide and cisplatin are two commonly used cancer chemotherapeutic agents associated with significant acute and chronic renal toxicity. The clinical characteristics of ifosfamide-induced renal injury are proximal tubular wasting of glucose, phosphate, bicarbonate, sodium, potassium, and amino acids; proteinuria; and decreased glomerular filtration rate. Cisplatin administration may result in a dose-dependent reduction of glomerular filtration rate, hypomagnesemia, hypokalemia, and polyuria. The characteristics of renal toxicity associated with each of these agents are discussed with attention to possible mechanisms of injury and long-term clinical outcome.
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PMID:Renal toxicity of cancer chemotherapeutic agents in children: ifosfamide and cisplatin. 778 38

Rats bearing the Yoshida AH-130 ascites hepatoma, a cachectic rat tumour, showed signs of important muscle wasting with reduced muscle weights. This phenomenon was associated with a decreased rate of in vivo alanine oxidation as measured by the production of 14CO2 from [U-14C]alanine intragastrically administered. It was later found that the decreased amino acid oxidation was associated with a reduced uptake in skeletal muscle as measured in incubated soleus muscles, thus suggesting that the decreased in vivo oxidation is basically due to a reduced oxidation of the amino acid in skeletal muscle. The decrease in alanine oxidation in the tumour-bearing animals was also associated with higher circulating alanine concentrations in their blood. In addition, tumour-bearing rats presented a lower (26%) protein synthetic rate in skeletal muscle, as measured by the incorporation of [14C]phenylalanine into muscle protein. The addition of insulin to the incubation medium abolished the lower rate of protein synthesis, thus suggesting a greater response to this hormone by the muscle of tumour-bearing rats. In conjunction with a reduced protein synthesis, tumour-bearing rats showed a clearly enhanced rate of protein degradation in isolated skeletal muscles. The results presented confirm previous observations suggesting that the skeletal muscle of tumour bearing animals is in a profound negative nitrogen balance which partially accounts for the wasting observed in the tissue. In addition, the present study allows us to conclude that, in spite of the increased alanine utilization for both gluconeogenesis and tumour growth, the oxidation of alanine by the whole animal is decreased in the tumour-bearing rats. This seems to be associated with a decreased ability of skeletal muscle to handle this amino acid.
Cancer Lett 1994 Dec 09
PMID:Alanine metabolism in rats bearing the Yoshida AH-130 ascites hepatoma. 781 30


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