Preview

Медицинский Совет

Расширенный поиск

Астения и утомление при гипераммониемии: этиопатогенез и методы коррекции

https://doi.org/10.21518/2079-701X-2021-21-1-95-104

Полный текст:

Аннотация

Астения и утомляемость – это наиболее часто встречающиеся синдромы у пациентов с заболеваниями печени, которые существенно влияют на  качество жизни. Распространенность утомляемости при хронических заболеваниях печени составляет от 50 до 85%. Хотя был достигнут некоторый прогресс в понимании процессов, которые могут вызывать утомление в целом, основные причины утомляемости, связанной с заболеванием печени, остаются не совсем понятны. В частности, многие исследования предполагают, что утомляемость, связанная с  заболеванием печени, вероятно, возникает в  результате изменений нейротрансмиссии в головном мозге на фоне гипераммониемии. Гипераммонемия – это метаболическое состояние, характеризующееся повышенным уровнем аммиака – азотсодержащего соединения. В настоящем обзоре описывается гипераммониемия, которая, вероятно, важна в патогенезе утомляемости, связанной с заболеванием печени. Аммиак является сильнодействующим нейротоксином, его повышенное содержание в крови может вызывать неврологические признаки и симптомы, которые могут быть острыми или хроническими в зависимости от основной патологии. Гипераммониемию следует распознать на ранней стадии и немедленно начать лечение, чтобы предотвратить развитие опасных для жизни осложнений, таких как отек головного мозга и кома. В статье приводятся патофизиологические механизмы влияния гипераммониемии на состояние психовегетативного статуса пациентов с  заболеваниями печени, а  также перечисляются основные принципы лечения. Значительная часть статьи уделена L-орнитину-L-аспартату, который эффективен при астении и утомляемости для снижения уровня гипераммониемии при хронических заболеваниях печени с помощью множества хорошо изученных механизмов.

Об авторах

Е. Ю. Плотникова
Кемеровский государственный медицинский университет
Россия

Плотникова Екатерина Юрьевна, д.м.н., профессор кафедры поликлинической терапии, последипломной подготовки и сестринского дела, руководитель курса клинической гастроэнтерологии

650029, Кемерово, ул. Ворошилова, д. 22а



М. Н. Синькова
Кемеровский государственный медицинский университет
Россия

Синькова Маргарита Николаевна, к.м.н., доцент кафедры поликлинической терапии, последипломной подготовки и сестринского дела

650029, Кемерово, ул. Ворошилова, д. 22а



Л. К. Исаков
Кемеровский государственный медицинский университет
Россия

Исаков Леонид Константинович, к.м.н., доцент кафедры поликлинической терапии, последипломной подготовки и сестринского дела

650029, Кемерово, ул. Ворошилова, д. 22а



Список литературы

1. Дюкова Г.М. Астенический синдром: проблемы диагностики и терапии. Эффективная фармакотерапия. Неврология и психиатрия. 2012;(1):40–45. Режим доступа: https://umedp.ru/articles/astenicheskiy_sindrom_problemy_ diagnostiki_i_terapii.html.

2. Bates D.W., Schmitt W., Buchwald D., Ware N.C., Lee J., Thoyer E. et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993;153(24):2759–2765. https://doi. org/10.1001/archinte.1993.00410240067007.

3. Swain M.G. Fatigue in chronic disease. Clin Sci (Lond). 2000;99(1):1–8. Available at: https://pubmed.ncbi.nlm.nih.gov/10887052/.

4. Swain M.G. Fatigue in liver disease: pathophysiology and clinical management. Can J Gastroenterol. 2006;20(3):181–188. https://doi. org/10.1155/2006/624832.

5. Gerber L.H., Weinstein A.A., Mehta R., Younossi Z.M. Importance of fatigue and its measurement in chronic liver disease. World J Gastroenterol. 2019;25(28):3669–3683. https://doi.org/10.3748/wjg.v25.i28.3669.

6. Newton J.L. Systemic symptoms in non-alcoholic fatty liver disease. Dig Dis. 2010;28(1):214–219. https://doi.org/10.1159/000282089.

7. Swain M.G., Jones D.E.J. Fatigue in chronic liver disease: New insights and therapeutic approaches. Liver Int. 2019;39(1):6–19. https://doi. org/10.1111/liv.13919.

8. Chiang D.J., McCullough A.J. The impact of obesity and metabolic syndrome on alcoholic liver disease. Clin Liver Dis. 2014;18(1):157–163. https://doi.org/10.1016/j.cld.2013.09.006.

9. Patidar K.R., Bajaj J.S. Tired of Hepatitis B? Dig Dis Sci. 2016;61(4):953–954. https://doi.org/10.1007/s10620-016-4067-8.

10. Austin P.W., Gerber L., Karrar A.K. Fatigue in chronic liver disease: exploring the role of the autonomic nervous system. Liver Int. 2015;35(5):1489–1491. https://doi.org/10.1111/liv.12784.

11. Stinton L., Swain M.G. Fatigue in cirrhosis: is transplant the answer? Clin Gastroenterol Hepatol. 2012;10(2):103–105. https://doi.org/10.1016/j. cgh.2011.10.036.

12. D’Mello C., Swain M.G. Liver-brain interactions in inflammatory liver diseases: implications for fatigue and mood disorders. Brain Behav Immun. 2014;35:9–20. https://doi.org/10.1016/j.bbi.2013.10.009.

13. D’Mello C., Swain M.G. Liver-brain inflammation axis. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G749–G761. https://doi.org/10.1152/ ajpgi.00184.2011.

14. Upadhyay R., Bleck T.P., Busl K.M. Hyperammonemia: What Urea-lly Need to Know: Case Report of Severe Noncirrhotic Hyperammonemic Encephalopathy and Review of the Literature. Case Rep Med. 2016;8512721. https://doi.org/10.1155/2016/8512721.

15. Olde Damink S.W., Jalan R., Dejong C.H. Interorgan ammonia trafficking in liver disease. Metab Brain Dis. 2009;24(1):169–181. https://doi. org/10.1007/s11011-008-9122-5.

16. D’Amico G., Morabito A., Pagliaro L., Marubini E. Survival and prognostic indicators in compensated and decompensated cirrhosis. Dig Dis Sci. 1986;31(5):468–475. https://doi.org/10.1007/BF01320309. 17. Bajaj J.S., Reddy K.R., Tandon P., Wong F., Kamath P.S., Garcia-Tsao G. et al. The 3-month readmission rate remains unacceptably high in a large North American cohort of patients with cirrhosis. Hepatology. 2016;64(1):200–208. https://doi.org/10.1002/hep.28414.

17. Cordoba J., Ventura-Cots M., Simón-Talero M., Amorós À., Pavesi M., Vilstrup H. et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acuteon-chronic liver failure (ACLF). J Hepatol. 2014;60(2):275–281. https://doi. org/10.1016/j.jhep.2013.10.004.

18. Romero-Gómez M., Montagnese S., Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol. 2015;62(2):437–447. https://doi.org/10.1016/j. jhep.2014.09.005.

19. Matthews S.A. Ammonia, a causative factor in meat poisoning in Eck fistula dogs. Am J Physiol. 1922;59:459–460.

20. Sherlock S., Summerskill W.H., White L.P., Phear E.A. Portal-systemic encephalopathy; neurological complications of liver disease. Lancet. 1954;267(6836):454–457. https://doi.org/10.1016/S0140-6736(54)91874-7.

21. Bosoi C.R., Rose C.F. Identifying the direct effects of ammonia on the brain. Metab Brain Dis. 2009;24(1):95–102. https://doi.org/10.1007/ s11011-008-9112-7.

22. Martinez-Hernandez A., Bell K.P., Norenberg M.D. Glutamine synthetase: glial localization in brain. Science. 1977;195(4284):1356–1358. https://doi. org/10.1126/science.14400.

23. Norenberg M.D., Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 1979;161(2):303–310. https://doi.org/10.1016/0006-8993(79)90071-4.

24. Cooper A.J., Mora S.N., Cruz N.F., Gelbard A.S. Cerebral ammonia metabolism in hyperammonemic rats. J Neurochem. 1985;44(6):1716–1723. https://doi.org/10.1111/j.1471-4159.1985.tb07159.x.

25. Lavoie J., Giguère J.F., Layrargues G.P., Butterworth R.F. Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J Neurochem. 1987;49(3):692–697. https://doi.org/10.1111/j.1471-4159.1987. tb00949.x.

26. Cooper A.J., Plum F. Biochemistry and physiology of brain ammonia. Physiol Rev. 1987;67(2):440–519. https://doi.org/10.1152/physrev.1987.67.2.440.

27. Matheson D.F., van den Berg C.J. Ammonia and brain glutamine: inhibition of glutamine degradation by ammonia. Biochem Soc Trans. 1975;3(4):525–528. https://doi.org/10.1042/bst0030525.

28. Norenberg M.D. The Astrocyte in Liver Disease. Adv Cell Neurobiol. 1981;2:303–352. https://doi.org/10.1016/B978-0-12-008302-2.50013-4.

29. Bélanger M., Desjardins P., Chatauret N., Butterworth R.F. Loss of expression of glial fibrillary acidic protein in acute hyperammonemia. Neurochem Int. 2002;41(2–3):155–160. https://doi.org/10.1016/s0197-0186(02)00037-2.

30. Neary J.T., Whittemore S.R., Zhu Q., Norenberg M.D. Destabilization of glial fibrillary acidic protein mRNA in astrocytes by ammonia and protection by extracellular ATP. J Neurochem. 1994;63(6):2021–2027. https://doi. org/10.1046/j.1471-4159.1994.63062021.x.

31. Desjardins P., Bandeira P., Raghavendra Rao V.L., Ledoux S., Butterworth R.F. Increased expression of the peripheral-type benzodiazepine receptorisoquinoline carboxamide binding protein mRNA in brain following portacaval anastomosis. Brain Res. 1997;758(1–2):255–258. https://doi. org/10.1016/s0006-8993(97)00339-9.

32. Giguère J.F., Hamel E., Butterworth R.F. Increased densities of binding sites for the ‘peripheral-type’ benzodiazepine receptor ligand [3H]PK 11195 in rat brain following portacaval anastomosis. Brain Res. 1992;585(1–2):295–8. https://doi.org/10.1016/0006-8993(92)91222-z.

33. Hermenegildo C., Montoliu C., Llansola M., Muñoz M.D., Gaztelu J.M., Miñana M.D., Felipo V. Chronic hyperammonemia impairs the glutamatenitric oxide-cyclic GMP pathway in cerebellar neurons in culture and in the rat in vivo. Eur J Neurosci. 1998;10(10):3201–3209. https://doi. org/10.1046/j.1460-9568.1998.00329.x.

34. James I.M., Garassini M. Effect of lactulose on cerebral metabolism in patients with chronic portosystemic encephalopathy. Gut. 1971;12(9):702–704. https://doi.org/10.1136/gut.12.9.702.

35. Iversen P., Sørensen M., Bak L.K., Waagepetersen H.S., Vafaee M.S., Borghammer P. et al. Low cerebral oxygen consumption and blood flow in patients with cirrhosis and an acute episode of hepatic encephalopathy. Gastroenterology. 2009;136(3):863–871. https://doi.org/10.1053/j.gastro.2008.10.057.

36. Dam G., Keiding S., Munk O.L., Ott P., Vilstrup H., Bak L.K. et al. Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake. Hepatology. 2013;57(1):258–265. https://doi.org/10.1002/hep.25995.

37. McCandless D.W., Schenker S. Effect of acute ammonia intoxication on energy stores in the cerebral reticular activating system. Exp Brain Res. 1981;44(3):325–330. https://doi.org/10.1007/BF00236570.

38. Lockwood A.H., Murphy B.W., Donnelly K.Z., Mahl T.C., Perini S. Positronemission tomographic localization of abnormalities of brain metabolism in patients with minimal hepatic encephalopathy. Hepatology. 1993;18(5):1061–1068. https://doi.org/10.1002/hep.1840180508.

39. Felipo V., Butterworth R.F. Neurobiology of ammonia. Prog Neurobiol. 2002;67(4):259–279. https://doi.org/10.1016/s0301-0082(02)00019-9.

40. Bessman S.P., Bessman A.N. The cerebral and peripheral uptake of ammonia in liver disease with an hypothesis for the mechanism of hepatic coma. J Clin Invest. 1955;34(4):622–628. https://doi.org/10.1172/JCI103111.

41. Lai J.C., Cooper A.J. Neurotoxicity of ammonia and fatty acids: differential inhibition of mitochondrial dehydrogenases by ammonia and fatty acyl coenzyme A derivatives. Neurochem Res. 1991;16(7):795–803. https://doi. org/10.1007/BF00965689.

42. Kosenko E., Felipo V., Montoliu C., Grisolía S., Kaminsky Y. Effects of acute hyperammonemia in vivo on oxidative metabolism in nonsynaptic rat brain mitochondria. Metab Brain Dis. 1997;12(1):69–82. https://doi. org/10.1007/BF02676355.

43. Görg B., Karababa A., Shafigullina A., Bidmon H.J., Häussinger D. Ammoniainduced senescence in cultured rat astrocytes and in human cerebral cortex in hepatic encephalopathy. Glia. 2015;63(1):37–50. https://doi. org/10.1002/glia.22731.

44. Görg B., Karababa A., Schütz E., Paluschinski M., Schrimpf A., Shafigullina A. et al. O-GlcNAcylation-dependent upregulation of HO1 triggers ammoniainduced oxidative stress and senescence in hepatic encephalopathy. J Hepatol. 2019;71(5):930–941. https://doi.org/10.1016/j.jhep.2019.06.020.

45. Wright G., Davies N.A., Shawcross D.L., Hodges S.J., Zwingmann C., Brooks H.F. et al. Endotoxemia produces coma and brain swelling in bile duct ligated rats. Hepatology. 2007;45(6):1517–1526. https://doi.org/10.1002/hep.21599.

46. Pedersen H.R., Ring-Larsen H., Olsen N.V., Larsen F.S. Hyperammonemia acts synergistically with lipopolysaccharide in inducing changes in cerebral hemodynamics in rats anaesthetised with pentobarbital. J Hepatol. 2007;47(2):245–252. https://doi.org/10.1016/j.jhep.2007.03.026.

47. Marini J.C., Broussard S.R. Hyperammonemia increases sensitivity to LPS. Mol Genet Metab. 2006;88(2):131–137. https://doi.org/10.1016/j. ymgme.2005.12.013.

48. Rodrigo R., Cauli O., Gomez-Pinedo U., Agusti A., Hernandez-Rabaza V., Garcia-Verdugo J.M., Felipo V. Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology. 2010;139(2):675–684. https://doi.org/10.1053/j. gastro.2010.03.040.

49. Shawcross D.L., Wright G.A., Stadlbauer V., Hodges S.J., Davies N.A., WheelerJones C. et al. Ammonia impairs neutrophil phagocytic function in liver disease. Hepatology. 2008;48(4):1202–1212. https://doi.org/10.1002/hep.22474.

50. Kerbert A.J.C., Jalan R. Recent advances in understanding and managing hepatic encephalopathy in chronic liver disease. F1000Res. 2020;9:312. https://doi.org/10.12688/f1000research.22183.1.

51. Lockwood A.H. Blood ammonia levels and hepatic encephalopathy. Metab Brain Dis. 2004;19(3–4):345–349. https://doi. org/10.1023/b:mebr.0000043980.74574.eb.

52. Potnis A., VanMeter S., Stange J. Prevalence of Hepatic Encephalopathy from a Commercial Medical Claims Database in the United States. Int J Hepatol. 2021;8542179. https://doi.org/10.1155/2021/8542179.

53. Плотникова Е.Ю., Сухих А.С. Различные варианты гипераммониемии в клинической практике. Медицинский совет. 2018;(14):34–42. https://doi.org/10.21518/2079-701X-2018-14-34-42.

54. Summar M.L., Barr F., Dawling S., Smith W., Lee B., Singh R.H. et al. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin. 2005;21(4 Suppl.):S1–S8. https://doi.org/10.1016/j.ccc.2005.05.002.

55. Panlaqui O.M., Tran K., Johns A., McGill J., White H. Acute hyperammonemic encephalopathy in adult onset ornithine transcarbamylase deficiency. Intensive Care Med. 2008;34(10):1922–1924. https://doi.org/10.1007/ s00134-008-1217-2.

56. Yoshino M., Nishiyori J., Yamashita F., Kumashiro R., Abe H., Tanikawa K. et al. Ornithine transcarbamylase deficiency in male adolescence and adulthood. Enzyme. 1990;43(3):160–168. https://doi.org/10.1159/000468724.

57. Ghatak T., Azim A., Mahindra S., Ahmed A. Can Klebsiella sepsis lead to hyperammonemic encephalopathy with normal liver function? J Anaesthesiol Clin Pharmacol. 2013;29(3):415–416. https://doi. org/10.4103/0970-9185.117079.

58. Nott L., Price T.J., Pittman K., Patterson K., Fletcher J. Hyperammonemia encephalopathy: an important cause of neurological deterioration following chemotherapy. Leuk Lymphoma. 2007;48(9):1702–1711. https://doi. org/10.1080/10428190701509822.

59. Jiang S.M., Jia L., Zhang M.H. Probiotic and lactulose: influence on gastrointestinal flora and pH value in minimal hepatic encephalopathy rats. Int J Clin Exp Med. 2015;8(6):9996–10000. Available at: https://www.ncbi.nlm. nih.gov/pmc/articles/PMC4537956/.

60. Bajaj J.S., Saeian K., Christensen K.M., Hafeezullah M., Varma R.R., Franco J. et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol. 2008;103(7):1707–1715. https://doi. org/10.1111/j.1572-0241.2008.01861.x.

61. Shen T.C., Albenberg L., Bittinger K., Chehoud C., Chen Y.Y., Judge C.A. et al. Engineering the gut microbiota to treat hyperammonemia. J Clin Invest. 2015;125(7):2841–2850. https://doi.org/10.1172/JCI79214.

62. Wang W.W., Zhang Y., Huang X.B., You N., Zheng L., Li J. Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction. World J Gastroenterol. 2017;23(38):6983–6994. https://doi.org/10.3748/wjg.v23.i38.6983.

63. Butterworth R.F., Kircheis G., Hilger N., McPhail M.J.W. Efficacy of l-Ornithine l-Aspartate for the Treatment of Hepatic Encephalopathy and Hyperammonemia in Cirrhosis: Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Exp Hepatol. 2018;8(3):301–313. https://doi.org/10.1016/j.jceh.2018.05.004.

64. Häussinger D., Steeb R., Kaiser S., Wettstein M., Stoll B., Gerok W. Nitrogen metabolism in normal and cirrhotic liver. Adv Exp Med Biol. 1990;272:47–64. https://doi.org/10.1007/978-1-4684-5826-8_3.

65. Hadjihambi A., Khetan V., Jalan R. Pharmacotherapy for hyperammonemia. Expert Opin Pharmacother. 2014;15(12):1685–1695. https://doi.org/10.1517/ 14656566.2014.931372.

66. Kircheis G., Lüth S. Pharmacokinetic and Pharmacodynamic Properties of L-Ornithine L-Aspartate (LOLA) in Hepatic Encephalopathy. Drugs. 2019;79(1 Suppl.):23–29. https://doi.org/10.1007/s40265-018-1023-2.

67. Girard G., Butterworth R.F. Effect of portacaval anastomosis on glutamine synthetase activities in liver, brain, and skeletal muscle. Dig Dis Sci. 1992;37(7):1121–1126. https://doi.org/10.1007/BF01300297.

68. Desjardins P., Rao K.V., Michalak A., Rose C., Butterworth R.F. Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab Brain Dis. 1999;14(4):273–280. https://doi.org/10.1023/a:1020741226752.

69. Kumar A., Davuluri G., Silva R.N.E., Engelen M.P.K.J., Ten Have G.A.M., Prayson R. et al.. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis. Hepatology. 2017;65(6):2045–2058. https://doi.org/10.1002/hep.29107.

70. Butterworth R.F. L-Ornithine L-Aspartate (LOLA) for the Treatment of Hepatic Encephalopathy in Cirrhosis: Novel Insights and Translation to the Clinic. Drugs. 2019;79(1 Suppl.):1–3. https://doi.org/10.1007/s40265-018-1021-4.

71. Najmi A.K., Pillai K.K., Pal S.N., Akhtar M., Aqil M., Sharma M. Effect of l-ornithine l-aspartate against thioacetamide-induced hepatic damage in rats. Indian J Pharmacol. 2010;42(6):384–387. https://doi. org/10.4103/0253-7613.71926.

72. Staedt U., Leweling H., Gladisch R., Kortsik C., Hagmüller E., Holm E. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol. 1993;19(3):424–430. https://doi. org/10.1016/s0168-8278(05)80553-7.

73. Rose C., Michalak A., Rao K.V., Quack G., Kircheis G., Butterworth R.F. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology. 1999;30(3):636–640. https://doi.org/10.1002/hep.510300311.

74. Ijaz S., Yang W., Winslet M.C., Seifalian A.M. The role of nitric oxide in the modulation of hepatic microcirculation and tissue oxygenation in an experimental model of hepatic steatosis. Microvasc Res. 2005;70(3):129–136. https://doi.org/10.1016/j.mvr.2005.08.001.

75. Goh E.T., Stokes C.S., Sidhu S.S., Vilstrup H., Gluud L.L., Morgan M.Y. L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2018;5(5):CD012410. https://doi.org/10.1002/14651858.CD012410.pub2.

76. Лазебник Л.Б., Голованова Е.В., Алексеенко С.А., Буеверов А.О., Плотникова Е.Ю., Долгушина А.И. и др. Российский консенсус «Гипераммониемии у взрослых». Экспериментальная и клиническая гастроэнтерология. 2019;(12):4–23. https://doi.org/10.31146/1682-8658- ecg-172-12-4-23.

77. Nanchahal K., Ashton W.D., Wood D.A. Alcohol consumption, metabolic cardiovascular risk factors and hypertension in women. Int J Epidemiol. 2000;29(1):57–64. https://doi.org/10.1093/ije/29.1.57.

78. Mennen L.I., de Courcy G.P., Guilland J.C., Ducros V., Zarebska M., Bertrais S. et al. Relation between homocysteine concentrations and the consumption of different types of alcoholic beverages: the French Supplementation with Antioxidant Vitamins and Minerals Study. Am J Clin Nutr. 2003;78(2):334–338. https://doi.org/10.1093/ajcn/78.2.334.

79. Halsted C.H., Villanueva J.A., Devlin A.M., Chandler C.J. Metabolic interactions of alcohol and folate. J Nutr. 2002;132(8 Suppl.):2367S–2372S. https://doi.org/10.1093/jn/132.8.2367S.

80. Cravo M.L., Glória L.M., Selhub J., Nadeau M.R., Camilo M.E., Resende M.P. et al. Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. Am J Clin Nutr. 1996;63(2):220–224. https://doi.org/10.1093/ajcn/63.2.220.

81. Gibson A., Woodside J.V., Young I.S., Sharpe P.C., Mercer C., Patterson C.C. et al. Alcohol increases homocysteine and reduces B vitamin concentration in healthy male volunteers – a randomized, crossover intervention study. QJM. 2008;101(11):881–887. https://doi. org/10.1093/qjmed/hcn112.

82. Kamat P.K., Mallonee C.J., George A.K., Tyagi S.C., Tyagi N. Homocysteine, Alcoholism, and Its Potential Epigenetic Mechanism. Alcohol Clin Exp Res. 2016;40(12):2474–2481. https://doi.org/10.1111/acer.13234.


Рецензия

Для цитирования:


Плотникова Е.Ю., Синькова М.Н., Исаков Л.К. Астения и утомление при гипераммониемии: этиопатогенез и методы коррекции. Медицинский Совет. 2021;(21-1):95-104. https://doi.org/10.21518/2079-701X-2021-21-1-95-104

For citation:


Plotnikova E.Yu., Sinkova M.N., Isakov L.K. Asthenia and fatigue in hyperammonemia: etiopathogenesis and methods of correction. Meditsinskiy sovet = Medical Council. 2021;(21-1):95-104. (In Russ.) https://doi.org/10.21518/2079-701X-2021-21-1-95-104

Просмотров: 49


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)