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R eferences 1. Hietbrink F, Koenderman L, Rijkers GT, Leenen LPH. Trauma: the role of the innate immune system. World J Emerg Surg, 2006;1:15. 2. Zhang G, Gurtu V, Kain SR, Yan G. Early detection of apoptosis using afluorescent conjugate of Annexin V. Bio Techniques. 1997;23:525-31. 3. Ulukaya E, Acilan C, Ari F, İkitimur E, Yilmaz Y. A glance at the methods for detection of apoptosis qualitatively and quantitatively. Turk J Biochem. 2011;36:261–9. 4. Rieger AM, Nelson KL, Konowalchuk JD, Barreda DR. Modified Annexin V/Propidium Iodide apoptosis assay for


Beta-hydroxy-beta-methylbutyrate (HMB) has been used extensively as a dietary supplement for athletes and physically active people. HMB is a leucine metabolite, which is one of three branched chain amino acids. HMB plays multiple roles in the human body of which most important ones include protein metabolism, insulin activity and skeletal muscle hypertrophy. The ergogenic effects of HMB supplementation are related to the enhancement of sarcolemma integrity, inhibition of protein degradation (ubiquitin pathway), decreased cell apoptosis, increased protein synthesis (mTOR pathway), stimulation of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and enhancement of muscle stem cells proliferation and differentiation. HMB supplementation has been carried out with various groups of athletes. In endurance and martial arts athletes, HMB supplementation revealed positive effects on specific aerobic capacity variables. Positive results were also disclosed in resistance trained athletes, where changes in strength, body fat and muscle mass as well as anaerobic performance and power output were observed. The purpose of this review was to present the main mechanisms of HMB action, especially related to muscle protein synthesis and degradation, and ergogenic effects on different types of sports and physical activities.

epidermal necrolysis: comparison with case–control analysis. Clin Pharmacol Ther 2010; 88:60–8. 4. Sharma VK, Sethuraman G, Kumar B. Cutaneous adverse drug reactions: clinical pattern and causative agents – a 6 year series from Chandigarh. India J Postgrad Med 2001; 47:95–9. 5. Viard-Leveugle I, Gaide O, Jankovic D et al. TNFα and IFNγ are potential inducers of Fasmediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol 2013; 133:489–98. 6. Caproni M, Antiga E, Parodi A et al. Elevated

REFERENCES 1. Colcott-Fox T. Ringed eruptions of the fingers. Br J Dermatol . 1895;7:91-95. 2. Radcliff-Crocker H. Granuloma annulare. Br J Dermatol . 1902;14:1-9. 3. Buechner SA, Winkelmann RK, Banks PM. Identification of T-cell subpopulations in granuloma annulare. Arch Dermatol . 1983;119:125-128. 4. Fayyazi A, Schweyer S, Eichmeyer B, et al. Expression of IFN-gamma, coexpression of TNF-alpha and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare. Arch Dermatol Res . 2000;292:384-390. 5. Umbert P, Winkelmann RK

. 2008;45:443–52. 32. Wannhoff A, Bölck B, Kübler AC, Bloch W, Reuther T. Oxidative and nitrosative stress and apoptosis in oral mucosa cells after ex vivo exposure to lead and benzo[a]pyrene. Toxicol In Vitro. 2013;27:915–21. 33. Hohl A, Gullo JDS, Silva CCP, et al. Plasma levels of oxidative stress biomarkers and hospital mortality in severe head injury: A multivariate analysis. J Crit Care. 2012;27:523.e11–523.e19. 34. Ji H-H, Huang G-L, Yin H-X, Xu P, Luo S-Y, Song J-K. Association between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs

al. Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J Natl Cancer Inst . 2003;95:1138-1149. 19. Miller RL, Gerster JF, Owens ML, Slade HB, Tomai MA. Imiquimod applied topically: a novel immune response modifier and new class of drug. Int J Immunopharmacol . 1999;21:1-14.

al. Constitutive Hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation. Am. J. Pathol. 2006; 168(1),321–330. 18. Italiano A, Le Cesne A, Bellera C et al. GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/ US and French National Cancer Institute Single-Arm Phase II Collaborative Study. Ann. Oncol. 2013; 24(11),2922–2926. 19. Sun Y, Guo W, Ren T et al. Gli1 inhibition suppressed cell growth and cell cycle progression and induced apoptosis as well as autophagy depending on ERK1/2 activity in human chondrosarcoma cells

decreases the levels of ROS by inhibiting mitochondrial complex IV and increasing SOD activities in cardiomyocytes under ischemia/reperfusion. Biochem Biophys Res Commun . 2012;421:164-169. 8. Somaio Neto F, Ikejiri AT, Bertoletto PR, et al. Gene expression related to oxidative stress in the heart of mice after intestinal ischemia. Arq Bras Cardiol . 2014;102:165-173. 9. Wang L, Huang H, Fan Y, et al. Effects of Downregulation of MicroRNA-181a on H 2 O 2 -Induced H9c2 Cell Apoptosis via the Mitochondrial Apoptotic Pathway. Oxid Med Cell Longev . 2014;2014:960362. 10

of 14-alpha-lipoyl andrographolide and various antibiotics on the formation of biofilms and production of exopolysaccharide and pyocyanin by Pseudomonas aeruginosa. Antimicrob Agents Chemother . 2011;55:3015-3017. 24. Jakobsen TH, van Gennip M, Phipps RK, et al. Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Antimicrob Agents Chemother . 2012;56:2314-2325. 25. Yang JY, Della-Fera MA, Nelson-Dooley C, et al. Molecular mechanisms of apoptosis induced by ajoene in 3T3-L1 adipocytes. Obesity . 2006;14:388-397. 26. Jakobsen

homocysteine levels and bone quality and bone mineral density parameters in older persons. Bone . 2014;63:141-146. 32. Ataie A, Ataee R, Mansoury Z, Aghajanpour M, Sciences M. Homocysteine Intracerebroventricular Injection Induces Apoptosis in the Substantia Nigra Cells and Parkinson’s Disease Like Behavior in Rats. Int J Mol Cell Med . 2013;(3):2-7. 33. Bertoia ML, Pai JK, Cooke JP, et al. Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease. Atherosclerosis . 2014;235(1):94-101. 34. Schnabel R, Lackner KJ, Rupprecht HJ, et