Creatine plays a central role in energy metabolism and is synthesized in the liver, kidney and pancreas. In healthy patients, it is transported via the blood stream to the muscles, heart and brain with high and fluctuating energy demands by the molecule creatine transporter. Creatine, although naturally synthesized in the human body, can be ingested in the form of supplements and is commonly used by athletes. The purpose of this review was to assess the clinical applications of creatine supplementation on paediatrics. Creatine metabolism disorders have so far been described at the level of two synthetic steps, guanidinoacetate N-methyltransferase (GAMT) and arginine: glycine amidinotransferase (AGAT), and at the level of the creatine transporter 1(CrT1). GAMT and AGAT deficiency respond positively to substitutive treatment with creatine monohydrate whereas in CrT1 defect, it is not able to replenish creatine in the brain with oral creatine supplementation. There are also data concerning the short and long-term therapeutic benefit of creatine supplementation in children and adults with gyrate atrophy (a result of the inborn error of metabolism with ornithine delta- aminotransferase activity), muscular dystrophy (facioscapulohumeral dystrophy, Becker dystrophy, Duchenne dystrophy and sarcoglycan deficient limb girdle muscular dystrophy), McArdle's disease, Huntington's disease and mitochondria-related diseases. Hypoxia and energy related brain pathologies (brain trauma, cerebral ischemia, prematurity) might benefit from Cr supplementation. This review covers also the basics of creatine metabolism and proposed mechanisms of action.
"Indeed, although fibrosis is reduced in quadriceps and diaphragm of mdx mice lacking arginase-2, it seems that it is not the case for the soleus, the cardiac muscle and the longissimus dorsi. More importantly from the clinical perspective, long-term dietary supplementation with arginine increased skeletal and cardiac muscle fibrosis in dystrophic mice, in contrast to the reported benefits from short-term supplementation, thus suggesting caution is needed regarding dietary arginine supplementation for patients with DMD . Taken together, these studies indicate the crucial roles of macrophage polarization in both muscle repair and fibrogenesis, particularly in dystrophic muscle. "
[Show abstract][Hide abstract] ABSTRACT: The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells) is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair.
[Show abstract][Hide abstract] ABSTRACT: The repair of an injured tissue is a complex biological process involving the coordinated activities of tissue-resident and infiltrating cells in response to local and systemic signals. Following acute tissue injury, inflammatory cell infiltration and activation/proliferation of resident stem cells is the first line of defense to restore tissue homeostasis. However, in the setting of chronic tissue damage, such as in Duchenne Muscular Dystrophy, inflammatory infiltrates persist, the ability of stem cells (satellite cells) is blocked and fibrogenic cells are continuously activated, eventually leading to the conversion of muscle into nonfunctional fibrotic tissue. This review explores our current understanding of the cellular and molecular mechanisms underlying efficient muscle repair that are dysregulated in muscular dystrophy-associated fibrosis and in aging-related muscle dysfunction.
Current Topics in Developmental Biology 01/2011; 96:167-201. DOI:10.1016/B978-0-12-385940-2.00007-3 · 4.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This review is focused on creatine (CR) (methyl guanidine acetic acid) and its application in the form of a dietary supplement. It has been especially utilized by athletes, but its pronounced therapeutic potential is also discussed in the present article. It is supposed that human body uses CR for the formation of creatine phosphate (PCr), which is necessary for muscular work as a source of energy. The effects of supplemented CR on dynamics of methionine cycle and other related metabolic pathways have not been fully explained yet. The review is focused on the description of affects caused by its application on human body and metabolism. Already the application of small amounts of CR rapidly increases levels of thiodiglycolic acid (TDGA) in urine after its supplementation, which phenomenon can serve as a sensitive marker of disturbance in metabolic pathways of 2C units and of thiolic compounds. Strong differences between initial and terminal TDGA levels in urine indicate that CR disturbed the equilibria of redox processes, catalyzed by folates and vitamin B12. Some theories for explanation of these effects are described in this manuscript. Nevertheless, similarly as in other metabolic studies, the results are significantly affected by the probands' individual responses, which reflect their individual genetic makeup. The various methods such as voltammetric (generally electrochemical), chromatographic, mass spectrometric, enzymatic etc., which have been most frequently utilized for determination of discussed compounds in common laboratories, have been reported.
Current Organic Chemistry 09/2011; 15(17-17):3029-3042. DOI:10.2174/138527211798357083 · 2.16 Impact Factor
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