Scientific Papers and Patents on Substances with Unproven Effects

Author(s): Sergei V. Jargin*.

Journal Name: Recent Patents on Drug Delivery & Formulation

Volume 13 , Issue 1 , 2019

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Graphical Abstract:


It is evident from reviewing scientific literature that the quality of argumentation in some areas of medical research has deteriorated during the last decades. Publication of a series of questionable reliability has continued without making references to the published criticism; examples are discussed in this review. Another tendency is that drugs without proven efficiency are advertised, corresponding products patented and marketed as evidence-based medications. Professional publications are required to register drugs and dietary supplements to obtain permissions for the practical use; and such papers appeared, sometimes being of questionable reliability. Several examples are discussed in this review when substances without proven effects were patented and introduced into practice being supported by publications of questionable reliability. Some of the topics are not entirely clear; and the arguments provided here can induce a constructive discussion.

Keywords: Placebo, atherosclerosis, cardiovascular, hormesis, antioxidants, dietary supplements.

Le Fanu J. Mass medicalisation is an iatrogenic catastrophe. BMJ 2018; 361: k2794.
Mattson MP, Calabrese EJ, Eds. Hormesis A Revolution in Biology, Toxicology and Medicine. New York: Springer 2010.
Jargin SV. Hormesis: Umbrella mechanism only for agents present in the environment. Hum Exp Toxicol 2015; 34(4): 439-41.
Calabrese E, Iavicoli I, Calabrese V. Hormesis: Its impact on medicine and health. Hum Exp Toxicol 2013; 32: 120-52.
Calabrese EJ. Hormesis: Path and progression to significance. Int J Mol Sci 2018; 19(10)E2871
Calabrese EJ, Iavicoli I, Calabrese V. Hormesis: Why it is important to biogerontologists. Biogerontology 2012; 13: 215-35.
Chazov EI, Tertov VV, Orekhov AN, Lyakishev AA, Perova NV, Kurdanov KA, et al. Atherogenicity of blood serum from patients with coronary heart disease. Lancet 1986; 2: 595-8.
Orekhov AN, Pivovarova EM, Sobenin IA, Yakushkin VV, Tertov VV. Use of cell culture for optimisation of direct antiatherogenic therapy with verapamil. Drugs 1992; 44(Suppl. 1): 105-10.
Sobenin IA, Chistiakov DA, Bobryshev YV, Orekhov AN. Blood atherogenicity as a target for anti-atherosclerotic therapy. Curr Pharm Des 2013; 19(33): 5954-62.
Orekhov AN, Sobenin IA, Revin VV, Bobryshev YV. Development of antiatherosclerotic drugs on the basis of natural products using cell model approach. Oxid Med Cell Longev 2015; 2015463797
Shchelkunova TA, Morozov IA, Rubtsov PM, Samokhodskaya LM, Andrianova IV, Rudimov EG, et al. Effect of sex hormones on levels of mRNAs coding for proteins involved in lipid metabolism in macrophages. Biochemistry 2013; 78(12): 1342-53.
Orekhov AN, Tertov VV, Pokrovsky SN, Adamova IYu, Martsenyuk ON, Lyakishev AA. Blood serum atherogenicity associated with coronary atherosclerosis. Evidence for nonlipid factor providing atherogenicity of low-density lipoproteins and an approach to its elimination. Circ Res 1988; 62(3): 421-9.
Tertov VV, Orekhov AN, Sobenin IA, Gabbasov ZA, Popov EG, Yaroslavov AA, et al. Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation due to lipoprotein aggregation. Circ Res 1992; 71(1): 218-28.
Aksenov D, Orekhova D, Kireev R, Andrianova I, Smirnov A, Sobenin I, et al. Effects of sex hormones on intracellular cholesterol accumulation and LDL aggregation. Effect of sex hormones on intracellular cholesterol accumulation and LDL aggregation. Abstracts of the 77th Congress of the European Atherosclerosis Society, 26-29 April 2008, Istanbul. Atheroscler Suppl 2008; 9(1): 20.
Kireev RA, Kuvshinova E, Andrianova IV, Sobenin IA, Orekhov AN. Effect of sex hormones on atherosclerotic indices in primary culture of female cells. Abstracts of the XIV International Symposium on Atherosclerosis, 18-22 June 2006, Rome. Atheroscler Suppl 2006; 7(3): 250.
Nikitina NA, Sobenin IA, Myasoedova VA, Korennaya VV, Mel’nichenko AA, Khalilov EM. Antiatherogenic effect of grape flavonoids in an ex vivo model. Bull Exp Biol Med 2006; 141(6): 712-5.
Orekhov AN, Sobenin IA, Korneev NV, Kirichenko TV, Myasoedova VA, Melnichenko AA. Anti-atherosclerotic therapy based on botanicals. Recent Pat Cardiovasc Drug Discov 2013; 8(1): 56-66.
Ryong LH, Tertov VV, Vasil’ev AV, Tutel’yan VA, Orekhov AN. Antiatherogenic and antiatherosclerotic effects of mushroom extracts revealed in human aortic intima cell culture. Drug Dev Res 1989; 17: 109-17.
Orekhov AN, Sobenin IA, Kirichenko TV, Miasoedova VA, Melnichenko AA. Method for preventing and treating atherosclerosis. RU 2455016C1 (2011).
Orekhov AN, Sobenin IA, Kirichenko TV, Miasoedova VA. BobryshevIu, V., Melnichenko, A.A. Method of treating atherosclerosis having anti-cytokine action. RU 2539377C2 (2012).
Orekhov AN, Sobenin IA, Karagodin VP, Pshchezhetskii AV, Feoktistov AS. Method for prevention of atherosclerosis based on inhibition of atherogenic lipoprotein modification. RU 2484841C1 (2011).
Orekhov AN, Sobenin IA, Karagodin VP, Melnichenko AA, Mukhamedova NM. A method of preventing atherosclerosis, based on cholesterol efflux from cells of the vascular wall. RU 2011144524A (2011).
Vertkin AL, Li ED, Pyshkina IA, Orekhov AN. Role of fish food additives in the treatment and prophylaxis of atherogenic dyslipidemia. Kardiologiia 1994; 34(8): 22-8.
Sobenin IA. Principles of pathogenetic therapy of atherosclerosis. Dissertation. Research Institute for Pathology and Pathophysiology: Moscow; 2006.
Jargin SV. Development of antiatherosclerotic drugs on the basis of cell models: A comment. Int J Pharmacol Phytochem Ethnomed 2015; 1: 10-4.
Goldstein JL, Brown MS. Progress in understanding the LDL receptor and HMG-CoA reductase, two membrane proteins that regulate the plasma cholesterol. J Lipid Res 1984; 25(13): 1450-61.
Ricciarelli R, Zingg JM, Azzi A. Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger receptor expression in cultured aortic smooth muscle cells. Circulation 2000; 102(1): 82-7.
Llorente-Cortés V, Badimon L. LDL receptor-related protein and the vascular wall: Implications for atherothrombosis. Arterioscler Thromb Vasc Biol 2005; 25(3): 497-504.
Gong Q, Pitas RE. Synergistic effects of growth factors on the regulation of smooth muscle cell scavenger receptor activity. J Biol Chem 1995; 270(37): 21672-8.
Pirillo A, Norata GD, Catapano AL. LOX-1, OxLDL, and atherosclerosis. Mediators Inflamm 2013; 2013152786
Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P. LOX-1 in atherosclerosis: Biological functions and pharmacological modifiers. Cell Mol Life Sci 2013; 70(16): 2859-72.
Jargin SV. Testing of serum atherogenicity on cell cultures: Assessment of reliability. Gazz Med Ital 2011; 170(2): 159-63.
Eskin SG, Sybers HD, Lester JW, Navarro LT, Gotto AM, DeBakey ME. Human smooth muscle cells cultured from atherosclerotic plaques and uninvolved vessel wall. In Vitro 1981; 17(8): 713-8.
Brown MS, Goldstein JL, Krieger M, Ho YK, Anderson RG. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J Cell Biol 1979; 82(3): 597-613.
Jargin SV. Orekhov’s method: Reassessment of in vitro lipid uptake assays. Recent Adv Cardiovasc Drug Discov 2014; 9(2): 122-5.
Budzen S, Rymaszewska J. The biological role of carnosine and its possible applications in medicine. Adv Clin Exp Med 2013; 22: 739-44.
Cararo JH, Streck EL, Schuck PF, Ferreira Gda C. Carnosine and related peptides: Therapeutic potential in age-related disorders. Aging Dis 2015; 6: 369-79.
Boldyrev AA, Stvolinsky SL, Fedorova TN, Suslina ZA. Carnosine as a natural antioxidant and geroprotector: From molecular mechanisms to clinical trials. Rejuvenation Res 2010; 13: 156-8.
Babizhayev MA, Yegorov YE. Telomere attrition in human lens epithelial cells associated with oxidative stress provide a new therapeutic target for the treatment, dissolving and prevention of cataract with N-Acetylcarnosine lubricant eye drops. Kinetic, pharmacological and activity-dependent separation of therapeutic targeting: Transcorneal penetration and delivery of L-Carnosine in the aqueous humor and hormone-like hypothalamic antiaging effects of the instilled ophthalmic drug through a safe eye medication technique. Recent Pat Drug Deliv Formul 2016; 10(2): 82-129.
Babizhayev MA, Deyev AI, Yegorov YE. Non-hydrolyzed in digestive tract and blood natural L-carnosine peptide as a panacea of tomorrow for various flu ailments: Signaling activity attenuating nitric oxide (NO) production, cytostasis, and NO-dependent inhibition of influenza virus replication in macrophages in the human body infected with the virulent swine influenza A (H1N1) virus. J Basic Clin Physiol Pharmacol 2013; 24: 1-26.
Zhao J, Posa DK, Kumar V, Hoetker D, Kumar A, Ganesan S. Carnosine protects cardiac myocytes against lipid peroxidation products. Amino Acids 2019; 51: 123-38.
Bispo VS, de Arruda CIP, Di Mascio P, Medeiros MH. Structural elucidation of a carnosine-acrolein adduct and its quantification in human urine samples. Sci Rep 2016; 6: 19348.
Baba SP, Hoetker JD, Merchant M, Klein JB, Cai J, Barski OA. Role of aldose reductase in the metabolism and detoxification of carnosine-acrolein conjugates. J Biol Chem 2013; 288: 28163-79.
Hipkiss AR. Would carnosine or a carnivorous diet help suppress aging and associated pathologies? Ann N Y Acad Sci 2006; 1067: 369-74.
Hipkiss AR, Brownson C, Carrier MJ. Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev 2001; 122: 1431-45.
Ghodsi R, Kheirouri S. Carnosine and advanced glycation end products: A systematic review. Amino Acids 2018; 50(9): 1177-86.
Wang LW, Huang X. An approach to revolutionize cataract treatment by enhancing drug probing through intraocular cell line. Libyan J Med 2018; 13(1)1500347
Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Doroshenko VS. Efficacy of N-acetylcarnosine in the treatment of cataracts. Drugs R D 2002; 3: 87-103.
Dubois VD, Bastawrous A. N-acetylcarnosine (NAC) drops for age-related cataract. Cochrane Database Syst Rev 2017; 2CD009493
Menon K, Mousa A, de Courten B. Effects of supplementation with carnosine and other histidine-containing dipeptides on chronic disease risk factors and outcomes: protocol for a systematic review of randomised controlled trials. BMJ Open 2018; 8e020623
Furst T, Massaro A, Miller C, Williams BT, LaMacchia ZM, Horvath PJ. β-Alanine supplementation increased physical performance and improved executive function following endurance exercise in middle aged individuals. J Int Soc Sports Nutr 2018; 15(1): 32.
Mitry P, Wawro N, Rohrmann S, Giesbertz P, Daniel H, Linseisen J. Plasma concentrations of anserine, carnosine and pi-methylhistidine as biomarkers of habitual meat consumption. Eur J Clin Nutr 2019; 73(5): 692-702.
Rogerson D. Vegan diets: Practical advice for athletes and exercisers. J Int Soc Sports Nutr 2017; 14: 36.
Appleby PN, Allen NE, Key TJ. Diet, vegetarianism, and cataract risk. Am J Clin Nutr 2011; 93: 1128-35.
Das BN, Thompson JR, Patel R, Rosenthal AR. The prevalence of age related cataract in the Asian community in Leicester: A community based study. Eye (Lond) 1990; 4: 723-6.
Kilis-Pstrusinska K. Carnosine, carnosinase and kidney diseases. Postepy Hig Med Dosw (Online) 2012; 66: 215-21.
Hipkiss AR, Cartwright SP, Bromley C, Gross SR, Bill RM. Carnosine: Can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential? Chem Cent J 2013; 7: 38.
Fraser GE. Vegetarian diets: What do we know of their effects on common chronic diseases? Am J Clin Nutr 2009; 89: 1607S-2.
Singh PN, Sabaté J, Fraser GE. Does low meat consumption increase life expectancy in humans? Am J Clin Nutr 2003; 78(3)(Suppl.): 526S-32.
Baye E, Ukropcova B, Ukropec J, Hipkiss A, Aldini G, de Courten B. Physiological and therapeutic effects of carnosine on cardiometabolic risk and disease. Amino Acids 2016; 48(5): 1131-49.
Hipkiss AR. Possible benefit of dietary carnosine towards depressive disorders. Aging Dis 2015; 6: 300-3.
Jargin SV. Comment on Use of carnosine for oxidative stress reduction in different pathologies. Oxid Med Cell Longev 2016; 20165250386
Giorgio M. Oxidative stress and the unfulfilled promises of antioxidant agents. Ecancermedicalscience 2015; 9: 556.
de Courten B, Kurdiova T, de Courten MP, Belan V, Everaert I, Vician M. Muscle carnosine is associated with cardiometabolic risk factors in humans. PLoS One 2015; 10e0138707
Papas AM. Antioxidant Status, Diet, Nutrition, and Health. Boca Raton, Florida: CRC Press 1999.
Kaludercic N, Deshwal S, Di Lisa F. Reactive oxygen species and redox compartmentalization. Front Physiol 2014; 5: 285.
Conti V, Izzo V, Corbi G, Russomanno G, Manzo V, De Lise F. Antioxidant supplementation in the treatment of aging-associated diseases. Front Pharmacol 2016; 7: 24.
Soory M. Nutritional antioxidants and their applications in cardiometabolic diseases. Infect Disord Drug Targets 2012; 12: 388-401.
Ashor AW, Siervo M, Lara J, Oggioni C, Mathers JC. Antioxidant vitamin supplementation reduces arterial stiffness in adults: A systematic review and meta-analysis of randomized controlled trials. J Nutr 2014; 144: 1594-602.
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D. Oxidative stress, aging, and diseases. Clin Interv Aging 2018; 13: 757-72.
Edeas M. Anti-oxidants, controversies and perspectives: How can the failure of clinical studies using anti-oxidants be explained? J Soc Biol 2009; 203: 271-80.
Aldosari S, Awad M, Harrington EO, Sellke FW, Abid MR. Subcellular Reactive Oxygen Species (ROS) in cardiovascular pathophysiology. Antioxidants (Basel) 2018; 7(1)E14
Salehi B, Martorell M, Arbiser JL, Sureda A, Martins N, Maurya PK. Antioxidants: Positive or negative actors? Biomolecules 2018; 8(4): 124.
Calabrese V, Cornelius C, Cuzzocrea S, Iavicoli I, Rizzarelli E, Calabrese EJ. Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity. Mol Aspects Med 2011; 32(4-6): 279-304.
Khoroshilova IP, Babizhayev MA, Ilatovskaia LB, Kiseleva OA, Gankovskaia LN. Prevention method of proliferative vitreoretinopathy. RU 2175223 (2001).
Rodriguez-Coleman H, Spaide R. Ocular complications of needle perforations during retrobulbar and peribulbar injections. Ophthalmol Clin North Am 2001; 14: 573-9.
Shpak NI, Naritsyna NI, Konovalova NV. Taufon and emoksipin in the combined treatment of sclerotic macular dystrophies. Oftalmol Zh 1989; 7: 463-5.
Aleksandrova TE, Aleksandrov EI. Treatment method for chorioretina dystrophy developed after tuberculous chorioretinitis. RU 2463998 (2006).
Lialin AN, Zharov VV, Butolina OE. Method of treating involutional eye diseases. RU 2565840C2 (2011).
Avetisov SE, Iomdina EN, Vinetskaia MI, Tarutta EP, Khromov GL, Davydov AB, et al. Agent for antioxidant protection of eye media and tissues. RU 2070010C1 (1993).
Soustov LV, Chelnokov EV, Bitiurin NM, Nemov VV, Avetisov SE, Polunin GS, et al. Pharmaceutical composition for preventive maintenance of development and treatment of initial stage of age cataract (versions). RU 2352352C1 (2007).
Greenblatt HK, Greenblatt DJ. Meldonium (Mildronate): A performance-enhancing drug? Clin Pharmacol Drug Dev 2016; 5(3): 167-9.
Statsenko S, Turkin SV, Fabritskaya SV, Shilina NN. Efficacy of short-term therapy with meldonium in patients with chronic heart failure of ischemic etiology and type 2 diabetes mellitus. Kardiologiia 2017; 57(4): 58-63.
Lyamina NP, Razborov IB, Karpov ES. Clinical and economic aspects of Meldonium as part of physical rehabilitation programs in patients with coronary heart disease after percutaneous coronary interventions. Kardiologiia 2016; 56(8): 13-8.
Arduini A, Zammit VA. A tennis lesson: Sharp practice in the science behind the Sharapova case. Postgrad Med J 2016; 92: 429-30.
Klusa V, Beitnere U, Pupure J, Isajevs S, Rumaks J, Svirskis S. Meldonium and its neuroregulatory mechanisms: Targeting the mitochondria, neuroinflammation, and protein expression. Medicina (Kaunas) 2013; 49: 301-9.
Ovchinnikov AV, Chertorizhskii EA, Belyi PA. Pharmaceutical composition having a neuroprotective, nootropic, antiamnesic effect, and method for preventing and/or treating states associated with cerebral circulation disorders, cerebrovascular and neurodegenerative diseases. WO2014087231 A2 (2012).
Plotnikov MB, Chernysheva GA, Smoliakova VI, Shchetinin PV, Ploynikova TM, Kuchin AV. Anti-ischemic drug. RU 2499593C1 (2012).
Zagorii GV. Medicinal agent exhibiting cardioprotective effect. WO2015012781 A1 (2013).
Zagorii GV. Drug with cerebro-protective effect. WO2015023244A9 (2013).
Zagorii GV. Drug cerebroprotective action. RU2014130112A (2013).
Temnaia EV, Mikunis RI, Frantsuzova SB, Iurzhenko NN, Trinus EV. Method for supporting therapy of post-myocardial infarction patients at recovery phase. RU1814898C (1989).
Dambrova M, Makrecka-Kuka M, Vilskersts R, Makarova E, Kuka J, Liepinsh E. Pharmacological effects of meldonium: Biochemical mechanisms and biomarkers of cardiometabolic activity. Pharmacol Res 2016; 113(Pt B): 771-80.
Kuka J, Vilskersts R, Cirule H, Makrecka M, Pugovics O, Kalvinsh I, et al. The cardioprotective effect of Meldonium is diminished after co-treatment with L-carnitine. J Cardiovasc Pharmacol Ther 2012; 17(2): 215-22.
Liepinsh E, Konrade I, Skapare E, Pugovics O, Grinberga S, Kuka J, et al. Meldonium treatment alters γ-butyrobetaine and l-carnitine concentrations in healthy volunteers. J Pharm Pharmacol 2011; 63: 1195-201.
Reuter SE, Evans AM. Carnitine and acylcarnitines: Pharmacokinetic, pharmacological and clinical aspects. Clin Pharmacokinet 2012; 51(9): 553-72.
Schooneman MG, Vaz FM, Houten SM, Soeters MR. Acylcarnitines: Reflecting or inflicting insulin resistance? Diabetes 2013; 62: 1-8.
Lippi G, Mattiuzzi C. Misuse of the metabolic modulator meldonium in sports. J Sport Health Sci 2017; 6(1): 49-51.
DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: Systematic review and meta-analysis. Mayo Clin Proc 2013; 88(6): 544-51.
DiNicolantonio JJ, Niazi AK, McCarty MF, Lavie CJ, Liberopoulos E, O’Keefe JH. L-carnitine for the treatment of acute myocardial infarction. Rev Cardiovasc Med 2014; 15(1): 52-62.
Ferrari R, Merli E, Cicchitelli G, Mele D, Fucili A, Ceconi C. Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: A review. Ann N Y Acad Sci 2004; 1033: 79-91.
Gaby AR. Nutritional treatments for acute myocardial infarction. Altern Med Rev 2010; 15(2): 113-23.
Pauly DF, Pepine CJ. The role of carnitine in myocardial dysfunction. Am J Kidney Dis 2003; 41(4)(Suppl. 4): S35-43.
Tarantini G, Scrutinio D, Bruzzi P, Boni L, Rizzon P, Iliceto S. Metabolic treatment with L-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology 2006; 106(4): 215-23.
Brass EP, Hiatt WR. The role of carnitine and carnitine supplementation during exercise in man and in individuals with special needs. J Am Coll Nutr 1998; 17(3): 207-15.
Shang R, Sun Z, Li H. Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: A systematic review and meta-analysis. BMC Cardiovasc Disord 2014; 14: 88.
Aguer C, McCoin CS, Knotts TA, Thrush AB, Ono-Moore K, McPherson R, et al. Acylcarnitines: Potential implications for skeletal muscle insulin resistance. FASEB J 2015; 29: 336-45.
Dambrova M, Liepinsh E. Response to comment by Sergei V. Jargin: “Meldonium (Meldonium): primum non nocere. Pharmacol Res 2016; 114: 295-6.
McCoin CS, Knotts TA, Adams SH. Acylcarnitines- old actors auditioning for new roles in metabolic physiology. Nat Rev Endocrinol 2015; 11: 617-25.
Otsubo C, Bharathi S, Uppala R, Ilkayeva OR, Wang D, McHugh K, et al. Long-chain acylcarnitines reduce lung function by inhibiting pulmonary surfactant. J Biol Chem 2015; 290: 23897-904.
Rutkowsky JM, Knotts TA, Ono-Moore KD, McCoin CS, Huang S, Schneider D, et al. Acylcarnitines activate proinflammatory signaling pathways. Am J Physiol Endocrinol Metab 2014; 306(12): E1378-87.
Guasch-Ferré M, Zheng Y, Ruiz-Canela M, Hruby A, Martínez-González MA, Clish CB, et al. Plasma acylcarnitines and risk of cardiovascular disease: Effect of mediterranean diet interventions. Am J Clin Nutr 2016; 103: 1408-16.
Arutiunov GP, Dmitriev DV, Melentiev AS. Experience of Meldonium application for the treatmet of acute myocardial infarction. Klin Gerontol 1996; 1: 12-4.
Gleser MG, Kiseleva AE, Astashkin EI. Effect of L-Carnitine on QT dispersion in patients with acute coronary syndrome. Kardiologiia 2015; 55(3): 4-9.
Kalvinsh I, Visokinskas A, Bagdonas G, Knasene I, Lesaukaite V, Matsiyauskene I. Meldonium in geriatric patients with cardiac failure. Ter Arkh 2006; 78(9): 75-7.
Nechaeva GI, Zheltikova EN. Effects of meldonium in early postmyocardial infarction period. Kardiologiia 2015; 55(8): 35-42.
Statsenko ME, Shilina NN, Turkina SV. Use of Meldonium in the combination treatment of patients with heart failure in the early postinfarction period. Ter Arkh 2014; 86(4): 30-5.
Sakharchuk II, Denisenko GT, Grushko VS, Bodaretskaia OI, Pishchalenko AN. The use of mildronat in heart failure in patients with chronic ischemic heart disease. Vrach Delo 1989; 9: 21-3.
Liepinsh E, Vilskersts R, Loca D, Kirjanova O, Pugovichs O, Kalvinsh I, et al. Meldonium, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction. J Cardiovasc Pharmacol 2006; 48: 314-9.
Vilskersts R, Liepinsh E, Kuka J, Cirule H, Veveris M, Kalvinsh I, et al. Myocardial infarct size-limiting and anti-arrhythmic effects of Meldonium orotate in the rat heart. Cardiovasc Drugs Ther 2009; 23: 281-8.
Svalbe B, Zvejniece L, Vavers E, Pugovics O, Muceniece R, Liepinsh E, et al. Meldonium treatment improves functional recovery following middle cerebral artery occlusion in rats. Behav Brain Res 2011; 222: 26-32.
Jargin SV. Pathology in the former Soviet Union: Scientific misconduct and related phenomena. Dermatol Pract Concept 2011; 1: 75-81.
Jargin SV. Invasive procedures with questionable indications. J Surg Open Access 2017; 3(5): 1-6.
Jargin SV. Renal biopsy research with implications for therapy of glomerulonephritis. Curr Drug Ther 2012; 7: 263-7.
Schobersberger W, Dünnwald T, Gmeiner G, Blank C. Story behind meldonium-from pharmacology to performance enhancement: A narrative review. Br J Sports Med 2017; 51(1): 22-5.
Fu L, Huang M, Chen S. Primary carnitine deficiency and cardiomyopathy. Korean Circ J 2013; 43(12): 785-92.
Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, Donapetry-García C, Pedre-Piñeiro AM. Significance of l-carnitine for human health. IUBMB Life 2017; 69(8): 578-94.
Buist NR. Historical perspective on clinical trials of carnitine in children and adults. Ann Nutr Metab 2016; 68(Suppl. 3): 1-4.
Beaudet AL. Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis. BioEssays 2017; 39(8): 1-26.
Dambrova M, Liepinsh E, Kalvinsh I. Mildronate: Cardioprotective action through carnitine-lowering effect. Trends Cardiovasc Med 2002; 12(6): 275-9.
Dambrova M, Daiia D, Liepin’sh E, Kir’ianova O, Kalvin’sh I. Biochemical mechanisms of mildronate action during ischemic stress. Lik Sprava 2004; 2: 68-74.
KalvinshIIa. Meldonium and trimetazidine: Similarity and difference. Terra Medica 2002; 3: 3-5.
Jargin SV. Meldonium (Meldonium): Primum non nocere. Pharmacol Res 2016; 114: 294.
Malaguarnera M. Carnitine derivatives: Clinical usefulness. Curr Opin Gastroenterol 2012; 28(2): 166-76.
Solomatin II. Use of the Meldonium preparation in ophthalmology. In: VI Forum Ophtalmologicum Balticum. Riga: LMA; 1990; pp. 97–99.
Bratko VI, Chernykh VV, Liubarskii MS, Smagin AA, Lysikov AG, Kombantsev EA, et al. Method for treating diabetic retinopathy. RU 2270025C1 (2004).
Savenkov GA. Method of treating dystrophic diseases of cornea. RU 2421191C1 (2010).
Logai IM, Pavlovich RN. Possible complications of parabulbar injections. Oftalmol Zh 1992; 4: 252-3.
Weihrauch TR. Placebo treatment is effective differently in different diseases - but is it also harmless? A brief synopsis. Sci Eng Ethics 2004; 10: 151-5.
Stelmakh A, Abrahamovych O, Cherkas A. Highly purified calf hemodialysate (Actovegin®) may improve endothelial function by activation of proteasomes: A hypothesis explaining the possible mechanisms of action. Med Hypotheses 2016; 95: 77-81.
Ziegler D, Edmundson S, Gurieva I, Mankovsky B, Papanas N, Strokov I. Predictors of response to treatment with actovegin for 6 months in patients with type 2 diabetes and symptomatic polyneuropathy. J Diabetes Complications 2017; 31: 1181-7.
Derev’yannykh EA, Bel’skaya GN, Knoll EA, Krylova LG, Popov DV. Experience in the use of Actovegin in the treatment of patients with cognitive disorders in the acute period of stroke. Neurosci Behav Physiol 2008; 38: 873-5.
Skoog I, Korczyn AD, Guekht A. Neuroprotection in vascular dementia: A future path. J Neurol Sci 2012; 322: 232-6.
Saletu B, Grünberger J, Linzmayer L, Stöhr H. Functional improvement of the aging brain: Placebo controlled pharmaco-EEG and psychometric studies with a metabolically active hemoderivative (Actovegin). Z Gerontol 1984; 17: 271-9.
Bugrova SG. Efficacy of actovegin in the treatment of cognitive disturbances in discirculatory encephalopathy. Zh Nevrol Psikhiatr Im S S Korsakova 2008; 108(11): 93-5.
Konoplya AI, Laskov VB, Shul’ginova AA. Immune and oxygen disturbances in patients with chronic cerebral ischemia and their correction. Zh Nevrol Psikhiatr Im S S Korsakova 2015; 115(11): 28-32.
Guekht A, Skoog I, Edmundson S, Zakharov V, Korczyn AD. ARTEMIDA trial (a randomized trial of efficacy, 12 months international double-blind actovegin): A randomized controlled trial to assess the efficacy of actovegin in poststroke cognitive impairment. Stroke 2017; 48: 1262-70.
Shmatov VI, Litvinov AM. Method of cerebral ischemic insult treatment. RU2145895C1 (1996).
Karzakova LM, Saperov VN, Kashaeva LN. Method for treating acute cerebral stroke cases. RU2268064C1 (2005).
Zatolokin VD, Per’kov AA, Bezhin AI. Method of correcting ischemic liver affection. RU2394574C1 (2009).
Pavlov AP, Shishkina TV, Pavlov SS. Therapeutic method of peripheral nerves involvement. RU2360688C1 (2008).
Bykov AV, Korenevskii NA, Korenevskaia SN, Filatova OI. Method of complex therapy with combined ischemia of central hemodynamic system, lower extremities, heart and brain. RU2673481C1 (2017).
Smolianinov AB, Boiko IN, Khalaichev EE. Method for treating patients with ischemic cardiac disease. RU2284826C1 (2005).
Dutson TR, Orcutt MW. Chemical changes in proteins produced by thermal processing. J Chem Educ 1984; 61: 303-8.
Budzen S, Rymaszewska J. The biological role of carnosine and its possible applications in medicine. Adv Clin Exp Med 2013; 22: 739-44.
Lee P, Nokes L, Smith PM. No effect of intravenous Actovegin® on peak aerobic capacity. Int J Sports Med 2012; 33: 305-9.
Beetz A, Machicao F, Ried C, Ruzicka T, Michel G. Radioprotective effects of a protein-free hemodialysate in human epidermis. Skin Pharmacol 1996; 9: 197-202.
Wilmink JM, Stolk PW, van Weeren PR, Barneveld A. The effectiveness of the haemodialysateSolcoseryl for second-intention wound healing in horses and ponies. J Vet Med A Physiol Pathol Clin Med 2000; 47: 311-20.
Isler H, Bauen A, Hubler M, Oberholzer M. Morphometric assessment of wound healing in rats treated with a protein - free haemodialysate. Burns 1991; 17: 99-103.
Meilin S, Machicao F, Elmlinger M. Treatment with Actovegin improves spatial learning and memory in rats following transient forebrain ischaemia. J Cell Mol Med 2014; 18: 1623-30.
Elmlinger MW, Kriebel M, Ziegler D. Neuroprotective and anti-oxidative effects of the hemodialysateactovegin on primary rat neurons in vitro. Neuromol Med 2011; 13: 266-74.
Gariballa SE, Sinclair AJ. Assessment and treatment of nutritional status in stroke patients. Postgrad Med J 1998; 74: 395-9.
Safarova TP, Yakovleva OB, Sheshenin VS, Gavrilova SI. Methods of augmentation of antidepressant therapy (on the model of complex therapy with the inclusion of actovegin) in gerontopsychiatric hospital. Zh Nevrol Psikhiatr Im S S Korsakova 2018; 118(6 Part 2): 55-63.
Riobó SP, Sierra PR, Soldo RJ, Gómez-Candela C, García LPP, Serra-Majem L. Special considerations for nutritional studies in elderly. Nutr Hosp 2015; 31(Suppl. 3): 84-90.
Jargin SV. Scientific misconduct and international cooperation. Tidsskr Nor Laegeforen 2002; 122: 953.
Jargin SV. Some aspects of medical education in Russia. Am J Med Stud 2013; 1(2): 4-7.

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Article Details

Year: 2019
Page: [37 - 45]
Pages: 9
DOI: 10.2174/1872211313666190307162041

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