Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an anaerobic physical exercise program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 M was seen after a program of anaerobic physical exercise. This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.Abbreviations BCM Body cell mass - HIV Human immunodeficiency virus type 1 - NAC N-Acetyl-cysteine     

Weight loss in patients with hematological neoplasias is associated with immune system stimulation

Summary Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon- and tumor necrosis factor- are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon- activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon- activity.Abbreviations NHL non-Hodgkin's lymphoma - HD Hodgkin's disease - MM multiple myeloma - MGUS monoclonal gammopathy of unknown significance - IFN- interferon- - TNF- tumor necrosis factor-     

恶性肿瘤患者肌肉减少症的诊断与营养干预

肌肉减少症是恶性肿瘤患者常见的临床综合征之一，可视为发病、死亡等不良预后的一项独立危险因素。主要评估方法为CT、MRI、PET等成像技术。肌肉减少症的发生、发展与肿瘤恶病质关系密切，且与抗肿瘤治疗相互影响。近年来，不断涌现出采取营养支持、药物和运动等综合干预手段的临床研究，其中不少取得了效果。肌肉减少症在恶性肿瘤治疗中具有不可忽视的临床价值，其发病机制复杂，疗效和安全性尚需更多高级别循证依据支持。     

ω-3多不饱和脂肪酸对改善肿瘤病人临床结局的研究进展

近年来,ω-3多不饱和脂肪酸对恶性肿瘤的发生和转归的影响逐渐引起人们的重视.改善病人的恶病质、纠正恶性营养不良效果确切,对某些肿瘤存在潜在的抑制作用,并在逆转多药耐药的研究领域中也显示了良好的发展前景.     

Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model

Background Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.Methods Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1–11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.Results Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.Conclusion Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.This study was financially supported by a grant from Ortho Biotech, a division of Janssen Cilag, Tilburg, the Netherlands     

Prevalence and predictors associated with severe pulmonary hypertension in COPD

Background

Pulmonary hypertension (PH) is one of the most common complications of COPD (chronic obstructive pulmonary disease), but its severe form is uncommon. Various factors play an important role in the occurrence and severity of pulmonary hypertension in patients.

Adipokines and ghrelin in gastric cancer cachexia

AIM： To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia.
METHODS： Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor （IGF-Ⅰ）, were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancerinduced cachexia and 30 served as a control group. The relationships between hormones, body mass index （BMI） loss ratio, age, gender, and Glasgow Prognostic Score （GPS） were investigated.
RESULTS： Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients （P 〈 0.05）. Ghrelin, resistin, leptin, adiponectin and IGF- Ⅰ, showed a significant correlation with BMI loss ratio and GPS （P 〈 0.05）. A strong correlation was seen between GPS and BMI loss （R = -0.570, P 〈 0.0001）. Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-Ⅰ （P 〈 0.05）. Existence of an important significant relationship between resistin and insulin resistance was also noted.
CONCLUSION： These results showed that serum ghrelin, leptin, adiponectin, and IGF-Ⅰ play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.