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At least 865 records · Page 48Linked to original sources
PubMed1993

Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.

Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.

Animals↗
PubMed1994

Systemic administration of ciliary neurotrophic factor induces cachexia in rodents.

Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra-neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting in death over a period of 7-10 d. This weight loss could not be explained by a reduction in food intake and involved losses of both fat and skeletal muscle. CNTF also induced the synthesis of acute phase proteins such as haptoglobin. Implantation of C6 lines expressing a nonsecreted form of CNTF, or the parental C6 line itself, did not result in wasting effects. Analysis of this CNTF-induced wasting indicates similarities with the previously described cachectins, tumor necrosis factor, interleukin 6, and leukemia inhibitory factor, but does not involve the induction of these cytokines.

Animals↗
PubMedDate not supplied

Cardiac cachexia: preoperative and postoperative nutrition management.

The present study examined the hemodynamic and metabolic effects of nutrition support in patients with malnutrition secondary to severe mitral valve disease and congestive heart failure. Pulmonary artery pressure measurements, echocardiographic studies, gas exchange measurements, immune function tests, and clinical evaluations were made on hospitalized patients 2 weeks before and 3 weeks after surgery for valve replacement or annuloplasty. All patients received a total daily energy intake of 20 to 30 kcal/kg, four of the patients preoperatively as a combination of oral food plus parenteral nutrition and these four patients plus two additional patients as only parenteral nutrition in the early postoperative period. All six patients received nutrition support as oral food plus parenteral nutrition in the late postoperative period. Compared with baseline, nutrition support was associated with stable hemodynamic function, unchanged whole-body oxygen consumption and carbon dioxide production, and improved clinical indices both before and after surgery. Comprehensive hemodynamic, metabolic, and clinical studies thus indicate that acceptable levels of nutrition support can be provided to malnourished patients with severe congestive heart failure, which improves their clinical status and does not adversely influence cardiac function.

Aged↗
PubMedDate not supplied

Effect of total parenteral nutrition on the protein kinetics of patients with cancer cachexia.

AIMS AND BACKGROUND: The question of whether TPN is able to reverse lean body mass depletion in cachectic cancer patients and, in particular, its effect on protein kinetics is a matter of some controversy. This study investigates the impact of TPN on protein kinetics in patients with gastric cancer. METHODS: The study involved three patients with 14-30% weight loss. They were administered a TPN regimen including 33-40 kcal/kg/day and 1.4-1.7 g amino acid/kg/day. The protein metabolism was studied before and during TPN using a stable amino acid isotope. RESULTS: Whole body protein turnover and breakdown did not change during TPN, whereas whole body protein synthesis increased from 3.39 +/- 1.04 to 6.05 +/- 0.48 g/kg/day (P = 0.03). However, the net balance, which was slightly negative prior to TPN, became positive during nutritional support. In the skeletal muscle compartment the synthesis improved with TPN (from 9.38 +/- 2.6 nmol/100 mL/min to 35.95 +/- 3.4 nmol/100 mL/min; P = 0.0143), whereas breakdown did not change significantly. CONCLUSIONS: TPN triggers a positive metabolic response in cachectic cancer patients. Whether this results in a clinical benefit for the patient requires further investigation.

Adult↗
PubMed2003

Dietary conjugated linoleic acid decreased cachexia, macrophage tumor necrosis factor-alpha production, and modifies splenocyte cytokines production.

The effect of conjugated linoleic acid (CLA) on macrophage functions were studied in vitro, in vivo, and ex vivo. In RAW macrophage cell line, CLA (mixed isomers) was shown to inhibit lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) production. Two CLA isomers, c9,t11 and t10,c12, were tested on RAW cells and it was found that the c9,t11 was the isomer responsible for the inhibition of LPS-induced TNF-alpha production. BALB/c mice were used to determine the effect of dietary CLA on body weight wasting and feed intake after LPS injection. CLA was protective against LPS-induced body weight wasting and anorexia. Plasma TNF-alpha levels after LPS injection were lower in the CLA group compared with the corn oil-fed control group 2 hr post-LPS injection. In a separate experiment, 30 mice were fed a CLA-supplemented diet or a corn oil-supplemented diet for 6 weeks and peritoneal resident macrophages were obtained for measuring TNF-alpha and nitric oxide production after in vitro exposure to interferon-gamma (IFN-gamma) and/or LPS. TNF-alpha production was not found to be different in peritoneal macrophages from mice fed the dietary treatments, but less nitric oxide was produced in macrophages from CLA-fed mice upon stimulation when compared with macrophages from control-fed mice. Splenocytes were also collected from the mice fed the dietary treatments and stimulated to produce cytokines in culture. Supernatant was used to run cytokine enzyme-linked immunoabsorbant assays. Interleukin-4 (IL-4) was decreased in CLA-fed mice when splenocytes were stimulated with concanavalin A (Con A) for 44 hr; however, IL-2 and the IL-2-to-IL-4 ratio were elevated.

Animals↗
PubMed1993

Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia.

PURPOSE: Several placebo-controlled randomized clinical trials have demonstrated that megestrol acetate can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia. The present trial was designed to compare megestrol acetate doses ranging from 160 to 1,280 mg/d. METHODS: This trial randomized 342 assessable patients with cancer anorexia/cachexia to receive oral megestrol acetate at doses of 160, 480, 800, or 1,280 mg/d. Patients were evaluated monthly by history, examination, patient-completed questionnaires, and serum albumin levels. RESULTS: The data demonstrate that there is a positive dose-response effect for megestrol acetate on appetite stimulation (P < or = .02). In concert, there was a trend for more nonfluid weight gain with higher drug doses. Megestrol acetate was well tolerated in this group of patients with advanced malignant disease. CONCLUSION: The positive dose-response effect that we observed for megestrol acetate on appetite stimulation supports both our prestudy hypothesis and other available literature. Nonetheless, based primarily on the cost and inconvenience associated with the use of higher doses of this drug, it is reasonable to use 160 mg/d for the initial treatment of cancer anorexia/cachexia in routine clinical practice.

Adult↗
PubMed2000

Anemia-inducing substance is related to elimination of lipolytic hyperactivity by cyclic plasma perfusion in human cancer cachexia.

We previously reported that cyclic plasma perfusion suppressed lipolytic activity in malignant tumor-bearing animals and reversed their body weight loss. In this study we investigated the relation between this phenomenon and interleukin (IL)-1 alpha, IL-1 beta, IL-6, interferon-gamma, leukemia inhibitory factor, tumor necrosis factor-alpha, and anemia-inducing substance (AIS) in vitro by examining changes in their levels in the plasma of advanced ovarian cancer patients. When the patients' plasma was incubated with noncoated charcoal for one hour, its lipolytic activity decreased by 39.0 +/- 2.4%, which was similar to the results obtained with the plasma of healthy subjects. IL-1 alpha, IL-1 beta, interferon-gamma, leukemia inhibitory factor, and tumor necrosis factor-alpha did not adsorb the charcoal. IL-6 was 3.7% adsorbed, but this did not cause a significant difference (p = 0.131). Nor was the recombinant form of these cytokines adsorbed to the charcoal. AIS, however, was 98.1% adsorbed. These results indicate that AIS is strongly associated with the reduction in lipolytic activity by cyclic plasma perfusion through noncoated charcoal resin.

Adult↗
PubMed2005

Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia.

Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R was shown, by immunocytochemistry, to be present in the human infundibular nucleus/median eminence, paraventricular nucleus, lateral hypothalamic area, and perifornical area, although in the latter two regions, only a few MCH1R-containing cells were found. In addition, MCH1R staining was found in nerve fibers in the periventricular nucleus, dorsomedial and ventromedial nucleus, suprachiasmatic nucleus, and tuberomammillary nucleus. A significant 1.6 times increase in the number of MCH1R cell body staining was found in the infundibular nucleus in postmortem brain material of cachectic patients, compared with matched controls, supporting a role for this receptor in energy homeostasis in the human.

Aged↗
PubMed1996

Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice.

Activins and inhibins, members of the transforming growth factor-beta superfamily, are involved in diverse physiological and developmental processes. We have previously shown that mice deficient in alpha-inhibin develop gonadal sex cord-stromal tumors at an early age. The tumor development is rapidly followed by a wasting syndrome that includes severe weight loss, hepatocellular necrosis around the central vein, and depletion of the parietal cells in the glandular stomach. The liver histology in inhibin-deficient mice is similar to the pathological effects of short-term treatment of rats and mice with recombinant activin A. Consistent with these findings, we have shown that the gonadal tumors in the inhibin-deficient mice secrete high levels of activins. In addition, Northern blot analysis has localized activin receptor type II (ActRII) to the liver. Based on these studies, we postulated that tumor-produced activins act through ActRII to cause the wasting syndrome in inhibin-deficient mice. To test this hypothesis and determine the significance of elevated levels of activin signaling through ActRII in vivo, we generated compound homozygous mutant mice deficient in both alpha-inhibin and ActRII. Despite the continued development of gonadal sex cord-stromal tumors and elevated serum levels of activin A and B, the compound homozygous mutant mice suffered no unusual weight loss, and the stomachs and livers of the majority of the mice were histologically normal. These results demonstrate that increased levels of activin signaling through ActRII in hepatocytes and the glandular stomach causes the hepatocellular necrosis and depletion of parietal cells in the glandular stomach as well as the severe weight loss in vivo.

Activin Receptors↗
PubMed1996

The clinical relevance of circulating tumor necrosis factor-alpha in acute decompensated chronic heart failure without cachexia.

STUDY OBJECTIVE: To evaluate the clinical relevance of circulating tumor necrosis factor-alpha (TNF alpha) in subjects with advanced acutely decompensated congestive heart failure (CHF) and to determine the modulatory effect of clinical interventions on short-term elaboration of this cytokine. DESIGN: Prospective, case-controlled study. SETTING: Inpatient and outpatient (hospital and clinic), at regional academic medical center. PATIENT INTERVENTIONS: Plasma concentrations of TNF alpha were determined in 25 healthy, normal control subjects and in 29 noncachectic patients with advanced CHF (mean ejection fraction = 16 +/- 6%) who required hospitalization for i.v. diuretic and/or inotropic therapy despite optimization of oral medical regimens. CHF patients were divided into two groups: diuretic responsive (group A; n = 6) and diuretic resistant requiring inotropic support (group B; n = 23). Group B was randomly allocated to receive either i.v. dobutamine (n = 13) or milrinone (n = 10) for 72 h. TNF alpha levels in CHF patients were measured serially at baseline, at 6 h, at 48 h, at 72 h, and at 1-week follow-up after hospital discharge. RESULTS: Plasma TNF alpha levels at baseline in CHF patients were 4.0 +/- 1.1 pg/mL (range, 0.5 to 6.5 pg/ mL) and 2.5 +/- 0.6 pg/mL (range, 0.5 to 6.8 pg/mL) in groups A and B, respectively, which were significantly different (p < 0.002) from normal subjects (0.89 +/- 0.40 pg/mL; range, 0.5 to 9.7 pg/mL). Despite clinically successful therapy with i.v. diuretics, dobutamine, or milrinone, plasma levels of this cytokine remained unchanged. Plasma TNF alpha in CHF patients measured in recovery (1 week after hospital discharge) was 5.1 +/- 1.2 pg/mL (range, 1.0 to 9.9 pg/mL) and 3.9 +/- 0.8 pg/mL (range, 0.5 to 8.7 pg/mL) in groups A and B, respectively. CONCLUSION: These findings suggest that although noncachectic patients with chronic heart failure who suffer acute decompensation elaborate significantly higher circulating levels of TNF alpha compared with healthy control subjects, no significant reduction or alteration in circulating TNF alpha is noted in the short-term follow-up despite clinical improvement.

Acute Disease↗
PubMed2004

Lepromatous leprosy with extensive unusual ulcerations and cachexia. Is it the first case of Lucio's phenomenon from Iran?

We report a 33-year-old Iranian woman with widespread ulcerative lesions in the setting of lepromatous leprosy. We think that the sudden appearance of the characteristic necrotic lesions in the absence of fever and other systemic manifestation, and in accordance with epidermal necrosis and the presence of large numbers of AFB in the endothelium are all in favor of the diagnosis of Lucio's phenomenon for this patient. To our knowledge this is the first patient who may have had this phenomenon reported from the Middle East.

Adult↗