Neuroendocrine Effects on the Heart and Targets for Therapeutic Manipulation in Heart Failure
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Chronic heart failure (CHF) involves derangements in multiple neurohormonal axes leading to a procatabolic state and wasting syndrome associated with significant mortality. Catabolic abnormalities include excess catecholamines and glucocorticoids. Anabolic defects include deficiencies of sex steroids, insulin resistance, and growth hormone (GH) resistance. These abnormalities are also correlated with increased morbidity and mortality in CHF. Anabolic axes have been augmented in pilot studies in CHF with testosterone, GH, insulin‐like growth factor‐1, and GH secretagogues. Results have been varied although some treatments have been associated with improved surrogate endpoints. This review article explores the current understanding of metabolic derangements in CHF and highlights potential neuroendocrine treatment strategies.Keywords:
Catabolism
Wasting Syndrome
There is a wide variability in the clinical presentation of the protein energy malnutrition often characterized as wasting in patients infected with HIV. Moreover, the clinical presentation has evolved over time. Initially, protein energy malnutrition was characterized by profound weight loss and depletion of body cell mass (BCM). Recently, unrelated concurrent metabolic abnormalities, such as lipodystrophy, may complicate the diagnosis of HIV wasting. Although measures of BCM are relatively accurate for the diagnosis of HIV wasting, the optimal tools for assessing BCM are not necessarily available to the clinician. From the practical standpoint, HIV wasting may be a self-evident diagnosis in advanced stages, but effective interpretation of the early signs of HIV wasting requires familiarity with other complications included in the differential diagnosis.
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Lipodystrophy
Mass wasting
Presentation (obstetrics)
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Intact human adult articular cartilage is central for the functioning of the articulating joints.This largely depends on the integrity of its extracellular matrix, given the high loading forces during movements in particular in the weight-bearing joints.Unlike the first impression of a more or less static tissue, articular cartilage shows -albeit in the adult organism -a slow tissue turnover.Thus, one of the most important questions in osteoarthritis research is to understand the balance of catabolic and anabolic factors in articular cartilage as this is the key to understand the biology of cartilage maintenance and degeneration.Anabolic and catabolic pathways are very much intermingled in articular cartilage.The balance between anabolism and catabolism is titrated on numerous levels, starting from the mediator-synthesizing cells which express either catabolic or anabolic factors.Also, on the level of the effector cells (i.e.chondrocytes) anabolic and catabolic gene expression compete for a balance of matrix homeostasis, namely the synthesis of matrix components and the expression and activation of matrix-degrading proteases.Also, there are multiple layers of intracellular cross-talks in between the anabolic and catabolic signalling pathways.Maybe the most important lesson from this overview is the notion that the anabolic-catabolic balance as such counts and not so much sufficient net anabolism or limited catabolism alone.Thus, it might be neither the aim of osteoarthritis therapy to foster anabolism nor to knock down catabolism, but the balance of anabolic-catabolic activities as a total needs proper titration and balancing.
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Summary Minced neoplasms and minced tissues of the host animals were incubated with xanthine-8-C 14 , hypoxanthine-8-C 14 , adenine-8-C 14 , or guanine-8-C 14 ; and aqueous alcoholic extracts of these mixtures were examined by means of the chromatographic-radioautographic technic. It was found that relatively less catabolism and more anabolism occurred in the neoplastic tissues than in most of the host tissues examined. The relevance of these findings to the possible roles of catabolism and anabolism in control of growth is discussed.
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Hypoxanthine
Purine metabolism
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Proteome
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The growth yields (Y(obs)) are greater under substrate-limited conditions than those under substrate-sufficient conditions in continuous cultures. This indicates that the excess substrate should cause uncoupling between anabolism and catabolism, which leads to energy spilling. Although the uncoupling between anabolism and catabolism has already been recognized in the microbiology literature, how to quantitatively describe such uncoupling remains unclear. Based on a balance on substrate reaction, a growth yield model was developed in relation to residual substrate concentration for substrate-sufficient continuous cultures. On the basis of that yield model, the concept of an uncoupling coefficient between anabolism and catabolism is defined in this work. A model describing the effect of the residual substrate concentration on the uncoupling coefficient of anabolism to catabolism is proposed. This model agrees very well with literature data.
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The HIV wasting syndrome and other HIV-associated weight loss is a major problem in HIV-infected patients. The available data strongly suggest that wasting is associated with decreased survival. It may also further impair immune function. A variety of etiologies probably contribute to this wasting, including hypermetabolism, alterations in metabolism, lessened oral intake, malabsorption, cytokine effects, and endocrine dysfunction. The relative contributions of each of these etiologies to wasting probably varies considerably from patient to patient. Successful treatment calls for identification of possible etiologies of wasting in the individual patient with AIDS. Further treatment may include treating underlying conditions and controlling such symptoms as diarrhea, nausea, or fever. Nutritional support, including both parenteral and enteral nutrition, has shown some promise of efficacy, and a variety of drugs appears to be helpful. Future treatment to reverse wasting may include the use of several of these agents in combination. Currently, there is much that clinicians can do to evaluate and treat the HIV wasting syndrome, with significant potential benefits to their patients.
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Hypermetabolism
Etiology
Enteral administration
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Metabolism is the term employed to embrace the various physical and chemical processes occurring within the tissues upon which the growth and heat production of the body depend and from which the energy for muscular activity, for the maintenance of vital activity and for the maintenance of vital functions is derived (Best & Taylor 1950). The destructive processes by which complex substances are converted by living cells into more simple compounds are called catabolism. Anabolism denotes the constructive processes by which simple substances are converted by living cells into more complex compounds, especially into living matter. Catabolism and anabolism are part of all metabolic processes, the carbohydrate, fat and protein metabolism. The term anabolic refers only to substances that exert an anabolic effect on protein metabolism and are unlikely to cause adverse androgenic effects. They shift the equilibrium between protein synthesis and degradation in the body as a whole in the direction of synthesis, either by promoting protein synthesis or reducing its breakdown. The protein anabolic effect of anabolic steroids is not restricted to single organs but is the result of stimulated biosynthesis of cellular protein in the whole organism.
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