Value of the pyridoxine of the hydrochloride and copper in prevention of atherosclerosis

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VALUE OF THE PYRIDOXINE OF THE HYDROCHLORIDE AND COPPER IN PREVENTION OF ATHEROSCLEROSIS

(Literary review)

Ochilova Dilorom Abdullayevna

Associate professor of department of pharmacology, normal and pathological physiology of the Bukhara state medical institute Bukhara. Republic of Uzbekistan

Komilova Bakhmal Odilovna

Candidate of Biology, the assistant to department ofpharmacology, normal and pathological physiology of the Bukhara state medical institute Bukhara. Republic of Uzbekistan

Annotation: The article provides a literature review of the importance of pyridoxine hydrochloride and copper in the prevention of atherosclerosis. Vitamin B6 deficiency and absolute or relative copper deficiency are affected by a common metabolic event, namely the function of lysyl oxidase in connective tissue maturation, which may be relevant in the initial lesion of atherosclerosis. The use of pyridoxine hydrochloride and copper is highly effective in preventing atherosclerosis. Fixed combinations of copper and pyridoxine in diseases associated with atherosclerosis, and their prevention provide effective results.

Keywords: atherosclerosis, prevention of atherosclerosis, pyridoxine hydrochloride, copper (Cu) as a necessary micronutrient

pyridoxine hydrochloride copper prevention atherosclerosis

Cardiovascular diseases of atherosclerotic genesis are the main cause of death in the world - (Bonow et al. 2002); The incidence of such diseases and mortality because of them increase at an urbanization and industrialization - (Global Atlas on Cardiovascular Disease Prevention and Control 2011). Diseases of a cardiovascular system are the main reason for disability and mortality around the world - [O.S. Pavlova 2012], according to many experts, this problem will proceed within several decades. The researches INTERHEART showed that 70% of primary myocardial infarction are connected by a dislipidemiya.

B6 vitamin is essentially micronutrient and for it norms of consumption are established. The recommended daily consumption of a pyridoxine is two -- 2.5 mg/days for men, 1.8 -- 2 mg/days for women (the pregnant 2.3 mg/days feeding 2.5 mg/days). At violations of a diet, a stress, various diseases the need of an organism for a pyridoxine increases - [29]. In a body of the person about 80% of B6 vitamin contain in muscles, in a liver, a myocardium and kidneys. The pyridoxine improves use by an organism of no saturated fatty acids, well influences functions of nervous system, liver, blood formation and function CCC.

The deficiency of B6 vitamin meets at patients with the coronary heart disease (CHD) -[28] authentically more often. Formation of early atherosclerosis in an aorta of a rat was connected with a giperhomocysteine emia and decrease in the antioxidant activity caused by low concentration of B6 in Vivo vitamin - [N. Endo, 2007]. The deficiency of B6 vitamin and absolute or relative deficiency of copper are surprised the general metabolic event, namely function of a lysyloxidase when maturing connecting fabric that it can matter at initial damage of atherosclerosis - [L.M. Klevay, 1971]. The pyridoxine contributes to normalization of fibrillation due to elimination of violations of lipid structure; decrease in a giperhomocysteineemiya and inflammation endothelia - [32]. Long reception of B6 in a dose of 4.6 mg/days is associated with reliable reduction of risk of development of SSZ for 33% - [29].

Treatment of patients with AG medicines of a pyridoxine allows reducing significantly systolic and diastolic arterial blood pressure, levels of adrenaline and noradrenaline in plasma of blood [30]. Treat the proved pharmacodynamics effects of a pyridoxine ant edematous and antihypertensive: reception of 5 mg/days of a pyridoxine during 4 weeks was followed by decrease HELL, increase in a diuresis, and loss of excess liquid, and decrease in a tone of a sympathetic part of the autonomic nervous system - [31]. Federal application of a pyridoxine in doses of five -- 10 mg/days at all types of the obliterating diseases of vessels and their thromboses is recommended to operating instructions of medicines - [33]. In a large Danish research with participation of 10,601 healthy volunteers (average age of 56 years) influence of all known vitamin of B6, folate, a cobalamin, Riboflavin on levels of the general homocysteine , tsistationin, cysteine, methionine and creatinine was analyzed. Among vitamin of B6 pyridoxal phosphate of blood showed the strongest return correlation with the general homocysteine and tsistationiny: at increase in levels of pyridoxal phosphate the level of a homocysteine decreased - [34].

Impact of a pyridoxine on neutralization of a homocysteine and elimination of chronic inflammation (including endothelia) was repeatedly confirmed in clinic-epidemiological researches. In a cohort research from 1205 people at the age of 45 -- 75 years levels of pyridoxal phosphate and C-jet protein (SRB) were measured in plasma. Statistically significant dose-dependent correlation between levels of pyridoxal phosphate and SRB is established.

Higher level of pyridoxal phosphate in plasma authentically corresponded to lower levels of glucose and glikirovanny hemoglobin - [35]. The research NHANES (National Health and Nutrition Examination Survey, the research review of health and food which is carried out by the Center of control of diseases of the USA) confirmed interrelation between low consumption of B6 vitamin and the pro-inflammatory status of patients - [36]. The pyridoxine and its derivatives pyridoxal and pyridoxamin are necessary for metabolism of carbohydrates, proteins and fats - [P.M.Abraham, 2010]. The pyridoxine takes part in maintenance sodium - potassium balance, and is necessary for synthesis of neurotransmitters of serotonin, a dopamine, noradrenaline and adrenaline. The pyridoxine plays an important role in regulation of synthesis and secretion of insulin. In a number of pilot and clinical trials the interrelation between security with V6, SD vitamin and MS was shown - [37].

It was noted that in a liver (which is depot of B6 vitamin) animals with model of diabetes had the same maintenance of a pyridoxine high, as well as in control - [38]. Pyridoxal phosphate, supporting secretion of insulin and reducing an oxidative stress, promoted protection of cells of islets of Langerhans - [39]. In clinical trials, the interrelation between risk of SD 2 types and decrease in level of a pyridoxine was confirmed [40]. Observations of groups of women with gestational diabetes in late pregnancy showed that reception of a pyridoxine (100 mg/days) even during rather short term (2 weeks) promoted statistically significant improvement of curve tolerance to glucose - [41, 42]. Effects of an excess homocysteine on HELL are caused probably by a vasoconstriction, dysfunction of kidneys and increase in a delay of sodium, increase in rigidity of walls of arteries owing to atherosclerotic changes. The Antihomocysteine e therapy including folate and folate-synergists a pyridoxine (B6) and cyanocobalamin (B12) promotes decrease HELL - [43].

Dietary supplement is executed in the form of a tablet and contains a pyridoxine a hydrochloride (B6 vitamin), cyanocobalamin (B12 vitamin), and acid folate (B9 vitamin), allows to support the normal level of a homocysteine in blood, without causing at the same time side effects. Besides, possesses a wide preventive range concerning atherosclerosis and diseases associated with it - [1].

Copper it is known to mankind from antiquity. From antiquity did ware of copper. Still, in the countries of Central Asia, in a copper cauldron cook wedding pilaf. This metal did not lose the value and in modern science and including medicine. Do intrauterine spirals, some surgical instruments of copper - [5]. Copper is carried to ten metals which are called "life metals". This element is necessary for normal functioning of a human body on the one hand, but with another - is toxic at the increased concentration - [Chasova E.V., 2012]. Copper is a part of the enzymes having oxidation-reduction activity and participating in iron metabolism stimulates digestion of proteins and carbohydrates, is involved in processes of providing body tissues of the person by oxygen. Besides, this microcell isa cofactor for a lysyloxidase and is necessary for inter- molecular communication of collagen and elastin. Copper - the main component of a myelin cover, participates in formation of collagen, a skeleton mineralization, synthesis of erythrocytes, formation of pigments of skin. As clinical manifestations of a lack of copper of an organism, serve violations of formation and function of a cardiovascular system, a skeleton, and development of a dysplasia of connecting fabric - [9].

Copper content in a human body fluctuates (on 100 g of dry weight) from 5 mg in a liver up to 0.7 mg in bones, in body liquids - from 100 mkg (on 100 ml) in blood up to 10 mkg in cerebrospinal fluid. And all copper in the adult's organism about 100 mg. Copper is a part of a number of enzymes - tyrosine elements, cy- tochromoxidases, stimulates the haematogenic function of marrow. About 90% of the copper which is contained in plasma are a part of ceruloplasmin. In blood serum copper is in two fractions. The most part (9296%) is strongly connected with proteins of serum of blood - connection with a-globulins (ceruloplasmin).

Small part of plasma copper is connected with albumin. Copper is necessary for processes of a formation of hemoglobin and cannot be replaced with any other element - [6]. The daily need for copper fluctuates from 0.9 to 3.0 mg/days. At the same time the physiological need for copper at adults makes 1.0 mg/days, children have from 0.5 to 1.0 mg/days. Sources of copper are chocolate, cocoa, a liver, nuts, sunflower seeds, mushrooms, mollusks, a salmon and spinach - [14]. Copper is the major element necessary for various functions. Change of level of copper is connected with numerous pathological states, including chronic ischemia, atherosclerosis and cancer. Therefore the copper homeostasis supported by a combination of two ions of copper (Cu () and Cu(2)), is crucial for health - [20].

In modern traditional medicine of copper, attribute many useful medicinal properties. Consider that at external application copper normalizes the general state, normalizes arterial blood pressure. Carrying copper bracelets, applying of copper plates, five-kopeck coins at a hypertension, presence of bruises are widely used, etc. - [I.D. Karomatov 2012]. Anti-inflammatory, immunomodulatory, antineoplastic, antimicrobic properties of cupriferous substances are revealed [A.I. Is- lamova, 2013]. Copper stimulates maturing of reticu- losit and their transformation into erythrocytes, promotes transfer of iron in marrow and to its transformation into integrally connected form. One of private consequences of a lack of an organism of copper is iron utilization violation (ferritine) and the increase in concentration of iron following it in a liver. At the same time anemia develops and also synthesis of phosphatide is broken and the activity of a cytochromoxidase decreases - [11]. It is established that under the influence of a therapy by copper secretory function of a stomach is normalized, the inflammatory phenomena decrease, and destructive, erosive sites disappear - [13].

Besides, as relative or absolute shortcomings of copper promote a hypercholesterolemia, this only dietary component, perhaps, connects initial and subsequent stages of pathogenesis of atherosclerosis - [15].

Cu necessary micronutrient, but supernormal Cu potentially toxic. The important tendency to involve between 2 states of an oxidation defines the frequent presence as a factor in many fizologichesky and psychologically of processes through Cu- contain enzymes, including mitochondrial products of energy, protection against an oxidative stress (through a superoxide dismutaza), and extracellular stability of a matrix (through an oxidase of a lizil). In a type of the fact that free, Cu Cu conveyors and chaperons of Cu. densely check potentially toxic, intracellular Cu. The latest data show that these transport systems of Cu play an important role in physiological reactions of cardiovascular cages, including growth of cages, migration, angiogenesis and restoration of wounds. In response to factors of growth, a citokina and a hypoxia their expression, subcellular localization and function are rigidly regulated. The transport systems of Cu and their regulators were also connected to various cardiovascular patofiziologiya as hypertension, inflammation, atherosclerosis, diabetes, a warm hypertrophy, and a cardiomyopathy. Deeper understanding of the central role of Cu conveyors and chaperons of Cu in the cellular alarm system and an expression of genes in cardiovascular biology gives the chance to identify new therapeutic targets for cardiovascular diseases - [16].

Though activation of cationic channels TRPV1 capsaitciny can reduce accumulation of lipids and formation of atherosclerotic defeats, clinical application of a capsaitciny was limited to its chronic toxicity. Compound of sulfide of copper (KS) of nanoparticles with targeting antibodies the act of TRPV1 as photothermic the alarm system TRPV1 switch in vascular of cages (VSMCs), using infrared light. At radiation, local temperature increase opens thermosensitive channels TRPV1 and causes inflow of Ca2. Increase in intracellular Ca2 activates an autophagy and interferes with formation of foamy cages in VSMCs processed by the oxidized lipoproteins of low density Together, it speaks about KC-TRPV1 can represent therapeutic means locally and temporarily weaken atherosclerosis - [17]. Oxidizing modification of LDL plays an important role in development of atherosclerosis. The lipoprotein of the high density (LPVP) provides protection against atherosclerosis, and antioxidant properties of a paraocsonaza 1 (PON1) as it was offered, promote this effect of LPVP. Copper of the ion-induced oxidation of LNP it was reduced to 48% to the cleaned Q192 of a paraocsonaza 1 on risk, but only 33% of equivalent activity of a paraocsonaza 1 on risk of R192. The isoenzyme of LPVP-PON1 Q192 caused 65% decrease while the isoenzyme of LPVP-PON1 R192 caused only 46% decrease in oxidation of LDL copper ions. These results reflect the fact that PON1 Q and PON1 R alloys can have various protective characteristics from oxidation of LDL - [18]. The theory briefly stated here, involving deficiency of Cu in an etiology and a pathophysiology of IBS explains more attributes of a disease, than any other theory. The most important is temporary communication between increase in the IBS level and decrease in maintenance of Cu in food from 1930th years along with parallel increase in additives to pregnant women with Fe, the antagonist of Cu. There are more than eighty anatomic, chemical and physiological similarities between animals to deficiency of Cu and people with IBS. The few from these similarities were made by other dietary manipulations because giving cholesterol directs deficiency of Cu in animals - [19].

High level of copper and lower level of zinc can contribute to the development of atherosclerosis and its consequences as factors of a multifactorial disease. Further researches are necessary to draw a conclusion whether high concentration of copper and zinc in serum of blood can be risk factor of development of atherosclerosis - [21].

Oxidation is an important way in pathogenesis of the coronary heart disease (CHD) through oxidation of lipoproteins of the low density (LDL) and education of free radicals. Cu necessary micronutrient for enzymes, which catalyze reactions of an oxidation of LDL. Therefore, Cu assessment in an atherosclerotic disease is important - [22]. Cellular copper (Cu) plays an important role in angiogenesis and an extracellular matrix a remodeling; was shown that the increased Cu in vascular equal muscle cells is connected with atherosclerosis and hypertension in animal experiments - [23]. Copper and its main transport protein ceruloplasmin were offered for assistance to development of atherosclerosis. The most part of data arrives from pilot and model studies on animals. Copper and mortality were not at the same time estimated at the patients who transferred coronary angiography. The increased concentration of copper and ceruloplasmin it is independently connected with the increased risk of mortality from all reasons and from the cardiovascular reasons - [24].

Intracellular copper causes activation redox - sensitive factors of a transcription and strengthening of regulation of mediators of inflammation in the endothelium cages. Chelation of copper by means of TTM can weaken the activation endothelia induced by TNFa and, therefore, inhibit vascular inflammation and atherosclerosis - [25]. Etiology factors of atherosclerosis are activation the endothelia, which is characterized by, increase in regulation of molecules of cellular adhesion and pro-inflammatory chemokine and sitokin and the subsequent receipt of monocytes in arterial to intima. Redox-active ions of transitional metals, such as copper and iron, can play an important role in activation endothelia, stimulating redox - sensitive alarm ways of cages - [26]. It is established that serumal levels of zinc and copper below at patients with atherosclerosis is reliable, than in control group, but reliable differences in the serumal Cu and Zn levels between heavy atherosclerosis and slight atherosclerosis it is not revealed - [27].

The way of receiving complex compound of copper with a pyridoxine consists in implementation of electrolysis of ethyl solution of a pyridoxine with copper electrodes in the presence of lithium chloride at the density of current from 6 to 10 ¹/tQ/cm2. Technical result - reduction of time of receiving complex compound of copper with a pyridoxine - [17].

Conclusion: It is possible to tell, application of a pyridoxine of a hydrochloride and copper has high efficiency in prevention of atherosclerosis. The fixed combinations of copper and a pyridoxine at the diseases connected with atherosclerosis, and their prevention provide effective results.

Literature

1. Алтамышев А. Лекарственные богатства Киргизии Фрунзе, Кыргызыстан 1976

2. Громова О.А., Торшин И.Ю., Назаренко А.Г., Калачева А.Г. Дефицит магния и пиридоксина как фактор риска развития ишемической болезни сердца Журнал. Кардиология, 2016.10.55-62

3. Дыдыкина И.С., Дыдыкина П.С., Алексеева О.Г. Вклад микроэлементов (меди, марганца, цинка, бора) в здоровье кости: вопросы профилактики и лечения остеопении и остеопороза- Эффективная фармакотерапия 2014, 3, 34-38

4. Зеленов В.И., Цокур М.Н., Шабанова И.В. Способ получения комплексного соединения меди с пиридоксином - Государственное образовательное учреждение высшего профессионального образования "Кубанский государственный университет" (ГОУ ВПО КубГУ), Номер патента: 2415860 Россия, 2011.

5. Исламова А.И., Мифтахова Р.Н., Абдрахманов А.С. Физиологическая роль меди и ее соединений - Инновационный потенциал молодежной науки - Материалы Всероссийской научной конференции 8 ноября 2013 г.-Уфа 2013, 115-118.

6. Кароматов И.Д. Простые лекарственные средства Бухара 2012

7. Кароматов И.Д. Медь и его значение в медицине Электронный научный журнал «Биология и интегративная медицина» 2017 №11

8. Мифтахова Р.Н., Исламова А.И., Абдрахманов А.С.Лечебные свойства меди и ее соединений - Инновационный потенциал молодежной науки - Материалы Всероссийской научной конференции 8 ноября 2013 г.-Уфа 2013, 176-179

9. Нормы физиологических потребностей в энергии и пищевых веществах для различных групп населения Российской Федерации. Методические рекомендации МР 2.3.1.2432-8 //

10. Павлова О.С. Современные возможности эффективной сердечно-сосудистой профилактики у пациентов с артериальной гипертензией и дисли- пидемией. Мед, новости. 2012; 1: 62-68.

11. Часова Э.В., В.В. Ивчук. Некоторые аспекты токсического воздействия тяжелых металлов на организм человека. Материалы II молодежной международной научно-практической конференции студентов, аспирантов, и молодых ученых «Наука XXI века: новый подход». - Санкт-Петербург, 28 сентября 2012 года. - С. 32-38

12. Persicov А.^, Brodsky B. Unstable molecules form stable tissues // Proc. Natl. Acad. Sci. USA. 2002. Vol. 99. № 3. P. 1101-1103.

13. Opsahl W., Zeronian H., Ellison M. et al. Role of copper in collagen cross-linking and its influence onselected mechanical properties of chick bone and tendon // J. Nutr. 1982. Vol. 112. № 4. P. 708-716.

14. Endo N., Nishiyama K., Okabe M., Matsumoto M., Kanouchi H., Oka T. Vitamin B6 suppresses apoptosis of NM-1 bovine endothelial cells induced by homocysteine and copper. Biochim Biophys Acta. 2007 Apr;1770(4):571-577.

15. Klevay, L.M.Allen, Vitamin B6, copper, and atherosclerosis. The lancet 1977.

16. Fukai T., Ushio-Fukai M., Kaplan J.H. Copper transporters and copper chaperones: roles in cardiovascular physiology and disease - Am J. Physiol Cell Physiol. C186-C201. doi: 10.1152/ajpcell.00132.2018. 2018, Jun 6.

17. Gao W., Sun Y., Cai M., Zhao Y., Cao W., Liu Z., Cui G., Tang B. Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis - Nat. Commun. 2018, Jan 15, 9(1), 231. doi: 10.1038/s41467-017-02657-z.

18. Bayrak A., Bayrak T., Bodur E., Kiling K., Demirpenge E. The effect of HDL-bound and free PON1 on copper-induced LDL oxidation-Chem Biol Interact. 2016,25,141-146. doi: 10.1016/j.cbi.2016.08.007.

19. Klevay L., M. IHD from copper deficiency: a unified theory- Nutr Res Rev. 2016, 29,172-179.

20. Seo Y., Cho Y., Huh Y., Park H. Copper Ion from Cu2O Crystal Induces AMPK-Mediated Autoph- agy via Superoxide in Endothelial Cells-Mol Cells. 2016, 39, 195-203. doi: 10.14348/molcells.2016.2198.

21. Tasic N., Tasic D., Otasevic P., Veselinovic M., Jakovljevic V., Djuric D., Radak D. Copper and zinc concentrations in atherosclerotic plaque and serum in relation to lipid metabolism in patients with carotid atherosclerosis- Vojnosanit Pregl. 2015,72,801-806.

22. Bagheri B., Akbari N., Tabiban S., Habibi V., Mokhberi V. Serum level of copper in patients with coronary artery disease. Niger Med J. 2015,56,39-42. doi: 10.4103/0300-1652.149169.

23. Zimnicka A., Tang H., Guo Q., Kuhr F., Oh M., Wan J., Chen J., Smith K., Fraidenburg D., Choudhury M., Levitan I., Machado R., Kaplan J., Yuan J. Upregulated copper transporters in hypoxia-induced pulmonary hypertension-PLoS One. 2014, 10, doi: 10.1371/journal.pone.0090544.

24. Grammer T., Kleber M., Silbernagel G., Pilz S., Scharnagl H., Lerchbaum E., Tomaschitz A., Koenig W., Mдrz W. Copper, ceruloplasmin, and longterm cardiovascular and total mortality (the Ludwigshafen Risk and Cardiovascular Health Study)- Free Radic Res. 2014, 48, 706-715. doi: 10.3109/10715762.2014.901510.

25. Wei H., Zhang W., Leboeuf R., Frei B. Copperinduces--and copper chelation by tetrathiomolybdate inhibits--endothelial activation in vitro-Redox Rep. 2014, 19, 40-48. doi: 10.1179/1351000213Y.0000000070.

26. Wei H., Zhang W., McMillen T., Leboeuf R., Frei B. Copper chelation by tetrathiomolybdate inhibits vascular inflammation and atherosclerotic lesion development in apolipoprotein E-deficient mice - Atherosclerosis. 2012, 223(2),306-313. doi: 10.1016/j.atherosclerosis.2012.06.013.

27. Islamoglu Y., Evliyaoglu O., Tekbas E., Cil H, Elbey M., Atilgan Z., Kaya H., Bilik Z., Akyuz A., Alan S. The relationship between serum levels of Zn and Cu and severity of coronary atherosclerosis- Biol Trace Elem Res. 2011, 144, 436-444. doi: 10.1007/s12011-011-9123-9.

28. Torshin I., Gromova O. Magnesium: fundamental studies and clinical practice. Nova Biomedical Publishers. NY, 2011.

29. Rimm E.B., Willett W.C., Hu F.B. et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998;279(5):359-364.

30. van Dijk R.A., Rauwerda J.A., Steyn M. et al. Long-term homocysteine lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothe- liumdependent vasodilation or carotid artery stiffness: a 2-year, randomized,placebo-control Arterioscler Thromb Vasc Biol 2001;21(12):2072-2079.

31. Komarov F.I., Novikov V.S., Onikienko B.A. Effect of vitamin B6 on diuresis in patients with marked circulatory disorders. Kardiologiia.1964;4:53-55. PMID: 1417978140.

32. Martinez M., Cuskelly G.J., Williamson J. et al. Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta- synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration. J Nutr 2000;130(5):1115--1123.

33. Ambrosch A., Dierkes J., Lobmann R. et al. Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus. Dia- bet Med 2001;18(3):185-192.

34. Midttun O., Hustad S., Schneede J. et al. Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr 2007;86(1):131-138.

35. Shen J., Lai C.Q., Mattei J. et al. Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. Am J Clin Nutr 2010;91(2):337-342.

36. Morris M.S., Sakakeeny L., Jacques P.F. et al. Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status. J Nutr 2010;140(1):103-110.

37. Abraham P.M., Kuruvilla K.P., Mathew J., Malat A., Joy S., Paulose C.S. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose. J. Biomed. Sci. 2010; 17:78.

38. Okada M., Shibuya M., Yamamoto E., Murakami Y. Effect of diabetes on vitamin B6 requirement in experimental animals. Diabetes Obes. Metab. 1999; 1(4):221-225.

39. Kiran S.G., Dorisetty R.K., Umrani M.R., Boindala S., Bhonde R.R., Chalsani M., Singh H., Ven- katesan V. Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction-in vitro and in vivo. Exp. Biol. Med (Maywood). 2011 ;236(4) :456-465.

40. Sharafetdinov Kh.Kh., Plotnikova O.A., Meshcheriakova V.A., Kodentsova V.M., Vrzhesin- skaia O.A., Spirichev V.B., Shatniuk L.N. Vitamin supply in patients with non-insulin-dependent diabetes mellitus. Klin. Med. (Mosk). 1999;77(4):26-8 (in Russ.)]

41. Spellacy W.N., Buhi W.C., Birk S.A. Vitamin B6 treatment of gestational diabetes mellitus: studies of blood glucose and plasma insulin. Am. J. Obstet. Gynecol. 1977;127(6):599-602.

42. Bennink H.J., Schreurs W.H. Improvement of oral glucose tolerance in gestational diabetes by pyri- doxine. Br. Med. J. 1975;3(5974):13--15.

43. Stehouwer C.D., van Guldener C. Does homocysteine cause hypertension? Clin. Chem. Lab. Med. 2003;41(11):1408--1411.

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