Anabolic resistance

It is very probable that anabolic resistance to nutrition and/or exercise contributes to age-related muscle loss. More likely, sarcopenia is a very complex process caused by a multiplicity of events, some of... 

Interventions such as leucine supplementation, ingestion of an adequate amount of essential amino acids or protein following traditional resistance exercise, and low-load BFR to prevent and reverse muscle loss with aging seem hopeful. The key to all of these therapeutic techniques is in their ability to overcome anabolic resistance to exercise and nutrients by stimulating muscle protein synthesis and translation initiation through the mTORCl pathway. 

Insulin is a powerful anabolic hormone but it is unlikely that insulin deficiency causes skeletal muscle atrophy by direct action on muscle fibers (as opposed to neurogenic atrophy) except in chronic untreated cases. There is however a close parallel between the catabolic states induced by glucocorticoid excess and by insulin deficiency. Moreover, impaired insulin action is implicated in other endocrine myopathies as a contributory cause of muscle wasting. Both acromegaly and thyrotoxicosis are associated with insulin resistance due to a postreceptor defect, and secondary hyperparathyroidism due to hypophosphatemia also gives rise to insulin insensitivity. 

The production of both anabolic sex hormones and growth hormone decreases in aging and the result is muscle loss. Also the loss of neural motor cells gives rise to atrophy of the muscles. In the aging process an increased inflammatory activity can be seen and it causes degeneration of muscle tissue through insuline resistance and activation of protein breakdown enzymes. The increased inflammatory activity is due to both normal aging as well as the presence of multiple chronic diseases (Dutta 1997. 

Conversion of 4-aminopyrazolo [3,4-d] pyrimidine (VIII) to its ribonucleotide by mouse tumours and host tissues has been observed [118,119]. Although no evidence of the anabolism of A -methyladenine (111) [120] to the ribonucleotide was obtained in mice with Ehrlich ascites carcinoma [121, 122], it is anabolized by bacteria [123. 124] and the enzyme responsible was partially purified from Salmonella typhimurium [125]. Human epidermoid carcinoma No. 2 cells resistant to 2-fluoroadenine (H.Ep.-2/FA) have lost adenine phosphoribosyl-... 

Much information on the mechanism of action and cross-resistance of purine analogues has been obtained in bacteria, some of which are quite sensitive to certain of these compounds in vitro. There is a great deal of variation in response of the various bacteria to a particular agent and of a particular bacterium to the various cytotoxic purine analogues. Some, if not most, of these differences are probably due to differences in the anabolism of the various compounds. Despite the fact that certain purine analogues have quite a spectrum of antibacterial activity in vitro, none has been useful in the treatment of bacterial infections in vivo because their toxicity is not selective—the metabolic events whose blockade is responsible for their antibacterial activity are also blocked in mammalian cells and thus inhibition of bacterial growth can only be attained at the cost of prohibitive host toxicity. In contrast, the sulpha drugs and antibiotics such as penicillin act on metabolic events peculiar to bacteria. 

Brown, G. A., M. D. Vukovich, T. A. Reifenrath, et al. Effects of anabolic precursors on serum testosterone concentrations and adaptations to resistance training in young men. Int J... 

Anabolic steroids are also still used in refractory anemias, although with recombinant human erythropoietin now widely available they appear to be seen mainly as a means of increasing the response to erythropoietin in highly resistant cases combination treatment with erythropoietin, a glucocorticoid, and nandrolone has also been recommended for treating myelodysplastic syndromes (13). Again, in such exceptional situations the risks of anabolic steroids have to be accepted. 

Cohen JC, Hickman R. Insulin resistance and diminished glucose tolerance in powerlifters ingesting anabolic steroids. J Clin EndocrinolMetab. 1987 64 960-963. 

Anabolic steroids may be hazardous to both physical and mental health. They weaken resistance by unbalancing the body s hormonal system and predispose those who take them to weakness rather tlian strength in later life They commonly increase aggression, possibly encouraging violent behavior ( roid rage ). They may also undermine sexual potency and desire Women athletes who take steroids may become masculinized for example, they may develop deep voices and facial hair. 

Thioglucosyl ceramide and thiolactosyl ceramide also have been synthesized to study cellular glycolipid traffic and metabolism (162). Both pthiolactosyl ceramide and lactosyl pthioceramide were made. The thioglycocidic link is resistant to glycosidase degradation to ceramide, and these analogs therefore can be used as precursors to monitor cellular GSL anabolism alone. 

The 2 -azido group of cytarazid renders the nucleoside more resistant to deamination to the 2 -azidouridine derivative (153) by deoxycytidine deaminase, but was also observed to reduce substrate affinity for the deoxycytidine kinase necessary for anabolic phosphorylation to the active cytarazid 5 -triphosphate [180]. Conversely, cytarazid was a more potent inhibitor of the target DNA polymerases a and K = 0.6 and 0.7 //M, respectively) than the parent ara-C (.A = 10 and 17 fiM, respectively), and the dissimilar spectrum of antitumour activity exhibited by the two compounds was attributed to differences in stability, metabolic activation and inhibitory potency [180, 181]. Interestingly, the instability of cytarazid to thiols present in the assay media, was commented on but not pursued [180]. In view of previous discussions concerning the bioreduction of AZT... 

Urea, the end product of nitrogen metabolism, accumulates rapidly in ARF. Most patients with ARF have a primary stressful illness that results in ureagenesis, and thus protein breakdown is markedly accelerated. Protein catabolism in ARF may be stimulated as the result of insulin resistance, metabolic acidosis, circulating proteases and inflammatory mediators, and the effects of uremic toxins. The mechanism may be direct, via modulation of protein synthesis, or indirect, by inhibiting the action of anabolic hormones. ... 

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