摘要:

The year 2001/2002 has been marked by a number of exciting new results for our understanding of anabolic and catabolic mediators and their participation in wasting states, as reflected by the contents of this section. It becomes ever more apparent that a clear understanding of how to shut off hypercatabolic and hypermetabolic processes is needed to underpin effective strategies for wasting syndromes. A particularly interesting development in the control of degradative processes in skeletal muscle is the discovery of several muscle-specific ubiquitin ligases. These enzymes, which confer specificity to the degradation of myofibrillar proteins and are situated in a pathway of proteolysis common to a variety of wasting states, may prove to be a valuable point of intervention in muscle atrophy. In the clinical arena, studies on non-small cell lung cancer patients as well as broader patient populations with solid tumours provide more evidence for a high incidence of hypermetabolism as well as low energy intake. The best therapies currently available for the cancer cachexia/anorexia syndrome have numerous limitations and tend mainly to attenuate losses rather than to promote a net gain of weight or lean body mass. Sustained hypermetabolism over the long course of disease progression constitutes an important contributor to negative energy balance, and its presence is likely to be a limiting factor to the success of current treatment approaches.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The reversal of catabolic processes remains a significant challenge related, in part, to their complexity and our incomplete understanding of the mechanisms involved. The eicosanoids are key players in the inflammatory process and have been implicated in the process of cancer cachexia. They are unsaturated C20 fatty acids which can be separated into two main groups: the lipoxygenase products including leukotrienes and lipoxins, and the prostanoids including prostaglandins, prostacyclin and thromboxane. This review examines the biology of the eicosanoids and the evidence of a role for the eicosanoids in cancer cachexia and wasting.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

This brief review discusses an exciting area in skeletal muscle research, namely the role of apoptosis in relation to muscle activity. Apoptotic cell death appears to occur during atrophy as a mechanism for removing part of the myofiber without affecting its viability. Recent developments in our understanding of the signaling of muscle catabolism and new insights into the therapeutic outlets are highlighted. The roles of mitochondria, Ca2+, and tumor necrosis factor α in activating the caspase cascade are discussed. We speculate that atrophy-induced apoptosis is a normal regulatory process that the cell can use to reduce the number of organelles, thus ensuring optimal cell function.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The nuclear factor κB family of inducible transcription factors regulates the expression of many genes. Nuclear factor κB has been implicated in autoimmune and inflammatory diseases, infection, cell survival, and cell transformation with subsequent promotion of cancer. In this review, we summarize features of nuclear factor κB regulation in several catabolic disorders, and describe its role in normal cellular function as well as provide an important link to the role of scaffold proteins, cellular receptors, and other cell signaling pathway kinases that converge on the nuclear factor κB signaling cascade. Subsequently, we focus on the role of nuclear factor κB in cell survival and oxidative stress. Finally, potential therapeutic strategies are discussed that may modify nuclear factor κB activity including endogenous antioxidant systems and the Fas/FasL system. However, challenges still remain in developing new therapeutic strategies that not only include identifying novel agents, but also by improving clinical endpoint definitions and by defining biological efficacy.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The uncoupling protein 1 homologue, uncoupling protein 3, is able to uncouple adenosine triphosphate production from mitochondrial respiration, thereby dissipating energy as heat and affecting the efficiency of energy metabolism. Uncoupling protein 3 is expressed predominantly in skeletal muscle, and has been associated with whole-body energy metabolism. However, on the basis of present evidence it has been concluded that the primary function of uncoupling protein 3 is not in the regulation of energy expenditure. For example, fasting, an energy expenditure attenuating condition, upregulates uncoupling protein 3 expression, and uncoupling protein 3 knockout mice have a normal metabolic rate. The exact function of uncoupling protein 3 remains to be elucidated, but at present putative roles for uncoupling protein 3 include involvement in the regulation of the production of reactive oxygen species, mitochondrial fatty acid transport and the regulation of glucose metabolism in skeletal muscle. Because all these putative functions assume that uncoupling protein 3 affects mitochondrial coupling, a secondary effect of the function of uncoupling protein 3 might still be that it influences (but not regulates) energy metabolism, consistent with observations in linkage and association studies. Therefore, uncoupling protein 3 remains an interesting target for pharmacological upregulation in the treatment of obesity and diabetes.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-α, interleukin-1β, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

This review summarizes evidence indicating that the sympathetic nervous system, through hormonal and neurotransmitter actions, produces anabolic, protein-sparing effects on skeletal muscle protein metabolism. Studies are reviewed which indicate that catecholamines secreted by the adrenal medulla have an inhibitory effect on muscle Ca2+-dependent protein degradation independently of other hormones. In addition, norepinephrine released from adrenergic terminals may increase the rate of protein synthesis in oxidative muscles, leading to increased protein accretion. Evidence is also presented that these effects seem to be mediated by β2-adrenoceptors and cyclic adenosine monophosphate-dependent pathways. The understanding of the precise mechanisms by which endogenous catecholamines promote muscle anabolic effects may bring new perspectives for efficient treatment of muscle-wasting conditions and enhancement of growth efficacy in farm species.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A critical review of recent international literature related to the use of intradialytic parenteral nutrition is given. The role of intradialytic parenteral nutrition as a therapy in malnourished hemodialysis patients is established and the need for systematic monitoring of this population at high risk of malnutrition is emphasized.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Most adult and pediatric liver transplantation candidates present several metabolic disturbances that lead to malnutrition. Because malnutrition may adversely affect morbidity and mortality of orthotopic liver transplantation, it is very important to carefully assess the nutritional status of the waiting list patients. Pretransplant nutritional therapy - enteral or parenteral - may positively influence liver metabolism, muscle function, and immune status. Nutrition therapy should continue in the short- and also in the long-term post-transplant periods. For malnourished patients, early post-transplant enteral or parenteral nutrition have been useful in improving nutritional status. Finally, the metabolic and nutritional care of the liver transplant donor must be considered to reduce allograft dysfunction indices.

ISSN:1363-1950    

出版商:OVID    

年代:2002

数据来源: OVID