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Tüberküloz ve D Vitamini Arasındaki İlişkinin Değerlendirilmesi: Güncel Yaklaşımlar

Yıl 2019, Cilt: 9 Sayı: 4, 565 - 573, 16.12.2019
https://doi.org/10.31832/smj.549164

Öz

D vitamini güneş
ışınları aracılığıyla deride sentezlenen ve iskelet sistemi üzerinde olumlu
etkileri bulunan steroid yapıda bir hormondur. D vitamininin bağışıklık sistemi
üzerindeki rolü, bağışıklık hücrelerinde D vitamini reseptörlerinin belirlenmesi
ve makrofajlar, monositler ile aktive edilmiş T hücreleri gibi bağışıklık
hücrelerinde D vitamininin aktif formunun tanımlanmış olmasıyla saptanmıştır. D
vitamini, katelisidin ve defensin gibi antimikrobiyal peptidlerin salınımını
artırarak, otofajiyi uyararak, Toll benzeri reseptörlerin sinyalizasyonunu
değiştirerek, anti-inflamatuvar sitokinlerin salınımını artırarak ve dendritik
hücrelerle T ve B lenfositlerin regülasyonunu sağlayarak doğal ve kazanılmış
bağışıklık sistemini modüle etmektedir. Mycobacterium
tuberculosis
etkeninin sebep olduğu sistemik bir bakteriyel enfeksiyon olan
tüberküloza karşı, D vitamini bu mekanizmalarla olumlu etki göstermektedir. Bu
derlemede D vitamininin tüberküloz hastalığı üzerindeki etkilerinin son güncel
literatür verilerine göre incelenmesi amaçlanmıştır.

Kaynakça

  • 1. Gois P, Ferreira D, Olenski S, Seguro A. Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor? Nutrients 2017;9(7):651.
  • 2. Tellioğlu A, Başaran S. Güncel Bilgiler Işığında Vitamin D. ARŞİV 2013;22(2):259-71.
  • 3. White JH. Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity. Infect Immun 2008;76(9):3837-43.
  • 4. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010;10(4):482-96.
  • 5. White JH. Vitamin D as an Inducer of Cathelicidin Antimicrobial Peptide Expression: Past, Present and Future. J Steroid Biochem Mol Biol 2010;121(1-2):234-8.
  • 6. Souto Filho JTD, de Andrade AS, Ribeiro FM, Alves PAS, Simonini VRF. Impact of vitamin D deficiency on increased blood eosinophil counts. Hematol Oncol Stem Cell Ther 2018;11(1):25-9.
  • 7. Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A, et al. Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol 2018;175:125-35.
  • 8. Hossein-nezhad A, Holick MF. Vitamin D for Health: A Global Perspective. Mayo Clin Proc 2013;88(7):720-55.
  • 9. Wu S, Sun J. Vitamin D, Vitamin D Receptor, and Macroautophagy in Inflammation and Infection. Discov Med 2011;11(59):325.
  • 10. Özkan B, Döneray H. D vitamininin iskelet sistemi dışı etkileri. Cocuk Sag Hast Derg 2011;54(2):99-119.
  • 11. Brighenti S, Bergman P, Martineau AR. Vitamin D and tuberculosis: where next? J Intern Med 2018;284(2):145-62.
  • 12. Kempker JA, Tangpricha V, Ziegler TR, Martin GS. Vitamin D in sepsis: from basic science to clinical impact. Crit Care 2012;16(4):316.
  • 13. Korf H, Decallonne B, Mathieu C. Vitamin D for infections. Curr Opin Endocrinol Diabetes Obes 2014;21(6):431-6.
  • 14. Yamshchikov A, Desai N, Blumberg H, Ziegler T, Tangpricha V. Vitamin D for Treatment and Prevention of Infectious Diseases: A Systematic Review of Randomized Controlled Trials. Endocr Pract 2009;15(5):438-49.
  • 15. Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1, 25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 1983;57(6):1308-10.
  • 16. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 1983;221(4616):1181-3.
  • 17. Kempker JA, Han JE, Tangpricha V, Ziegler TR, Martin GS. Vitamin D and sepsis: An emerging relationship. Dermatoendocrinol 2014;4(2):101-8.
  • 18. Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, et al. Vitamin D-Directed Rheostatic Regulation of Monocyte Antibacterial Responses. J Immunol 2009;182(7):4289-95.
  • 19. Thoma-Uszynski S, Stenger S, Takeuchi O, Ochoa MT, Engele M, Sieling PA, et al. Induction of direct antimicrobial activity through mammalian toll-like receptors. Science 2001;291(5508):1544-7.
  • 20. Zasloff M. Fighting Infections With Vitamin D. Nat Med 2006;12(4):388.
  • 21. Wang T-T, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-Mendoza LE, et al. Direct and Indirect Induction by 1,25-Dihydroxyvitamin D3of the NOD2/CARD15-Defensin β2 Innate Immune Pathway Defective in Crohn Disease. J Biol Chem 2010;285(4):2227-31.
  • 22. Sundaram ME, Coleman LA. Vitamin D and Influenza. Adv Nutr 2012;3(4):517-25.
  • 23. Luo J, Zhang M, Yan B, Zhang K, Chen M, Deng S. Imbalance of Th17 and Treg in peripheral blood mononuclear cells of active tuberculosis patients. Braz J Infect Dis 2017;21(2):155-61.
  • 24. Organization WH. WHO Global Tuberculosis Report 2018 Executive Summary. 2018.
  • 25. Williams CJB. On the Use and Administration of Cod-Liver Oil in Pulmonary Consumption. Lond J Med 1849;1(1 (Jan., 1849)):1-18.
  • 26. Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol 2007;103(3-5):793-8.
  • 27. Huang SJ, Wang X, Liu ZD, Cao WL, Han Y, Ma AG, et al. Vitamin D deficiency and the risk of tuberculosis: a meta-analysis. Drug Des Devel Ther 2016;Volume11:91-102.
  • 28. Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, et al. IFN-γ- and TNF-Independent Vitamin D-Inducible Human Suppression of Mycobacteria: The Role of Cathelicidin LL-37. J Immunol 2007;178(11):7190-8.
  • 29. Rook GA, Steele J, Fraher L, Barker S, Karmali R, O'riordan J, et al. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 1986;57(1):159.
  • 30. Crowle AJ, Ross EJ, May MH. Inhibition by 1, 25 (OH) 2-vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages. Infect Immun 1987;55(12):2945-50.
  • 31. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin Dmediated human antimicrobial response. Science 2006;311(5768):1770-3.
  • 32. Krutzik SR, Hewison M, Liu PT, Robles JA, Stenger S, Adams JS, et al. IL-15 Links TLR2/1-Induced Macrophage Differentiation to the Vitamin D-Dependent Antimicrobial Pathway. J Immunol 2008;181(10):7115-20.
  • 33. Chen Y, Liu W, Sun T, Huang Y, Wang Y, Deb DK, et al. 1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of TLR Signaling via Targeting MicroRNA-155-SOCS1 in Macrophages. J Immunol 2013;190(7):3687-95.
  • 34. Rode AKO, Kongsbak M, Hansen MM, Lopez DV, Levring TB, Woetmann A, et al. Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion. Front Immunol 2017;8.
  • 35. Sly LM, Lopez M, Nauseef WM, Reiner NE. 1α,25-Dihydroxyvitamin D3-induced Monocyte Antimycobacterial Activity Is Regulated by Phosphatidylinositol 3-Kinase and Mediated by the NADPH-dependent Phagocyte Oxidase. J Biol Chem 2001;276(38):35482-93.
  • 36. Rahman S, Rehn A, Rahman J, Andersson J, Svensson M, Brighenti S. Pulmonary tuberculosis patients with a vitamin D deficiency demonstrate low local expression of the antimicrobial peptide LL-37 but enhanced FoxP3+ regulatory T cells and IgG-secreting cells. Clin Immunol 2015;156(2):85-97.
  • 37. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, et al. Vitamin D as Supplementary Treatment for Tuberculosis. Am J Respir Crit Care Med 2009;179(9):843-50.
  • 38. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 2011;377(9761):242-50.
  • 39. Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci 2012;109(38):15449-54.
  • 40. Ganmaa D, Giovannucci E, Bloom BR, Fawzi W, Burr W, Batbaatar D, et al. Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial. Am J Clin Nutr 2012;96(2):391-6.
  • 41. Ralph AP, Waramori G, Pontororing GJ, Kenangalem E, Wiguna A, Tjitra E, et al. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial. PLoS One 2013;8(8):e70032.
  • 42. Salahuddin N, Ali F, Hasan Z, Rao N, Aqeel M, Mahmood F. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'. BMC Infect Dis 2013;13(1):22.
  • 43. Daley P, Jagannathan V, John KR, Sarojini J, Latha A, Vieth R, et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2015;15(5):528-34.
  • 44. Mily A, Rekha RS, Kamal SMM, Arifuzzaman ASM, Rahim Z, Khan L, et al. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. PLoS One 2015;10(9):e0138340.
  • 45. Tukvadze N, Sanikidze E, Kipiani M, Hebbar G, Easley K, Shenvi N, et al. High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial. Am J Clin Nutr 2015;102(5):1059-69.
  • 46. Ganmaa D, Munkhzul B, Fawzi W, Spiegelman D, Willett W, Bayasgalan P, et al. High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial. Am J Respir Crit Care Med 2017;196(5):628-37.

Evaluation of the Association Between Tuberculosis and Vitamin D: Current Approaches

Yıl 2019, Cilt: 9 Sayı: 4, 565 - 573, 16.12.2019
https://doi.org/10.31832/smj.549164

Öz

Vitamin D is a steroid hormone synthesized in
the skin through sunlight and has positive effects on skeletal system. The role
of vitamin D on the immune system have been demonstrated with the detection of
vitamin D receptors in immune cells and the discovery that vitamin D can be
converted into active form in immune cells such as macrophages, monocytes,
activated T cells. Vitamin D modulates the innate and adapted immune system by
increasing the release of antimicrobial peptides such as cathelicidine and
defensin, stimulating autophagy, modifying Toll-like receptor signaling,
increasing the release of anti-inflammatory cytokines and regulating dendritic
cells, T and B lymphocytes. Against tuberculosis, a systemic bacterial infection
caused by Mycobacterium tuberculosis,
vitamin D has a positive effect through these mechanisms. In this review, the
effects of vitamin D on tuberculosis are aimed to be analyzed according to the
latest current literature.

Kaynakça

  • 1. Gois P, Ferreira D, Olenski S, Seguro A. Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor? Nutrients 2017;9(7):651.
  • 2. Tellioğlu A, Başaran S. Güncel Bilgiler Işığında Vitamin D. ARŞİV 2013;22(2):259-71.
  • 3. White JH. Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity. Infect Immun 2008;76(9):3837-43.
  • 4. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010;10(4):482-96.
  • 5. White JH. Vitamin D as an Inducer of Cathelicidin Antimicrobial Peptide Expression: Past, Present and Future. J Steroid Biochem Mol Biol 2010;121(1-2):234-8.
  • 6. Souto Filho JTD, de Andrade AS, Ribeiro FM, Alves PAS, Simonini VRF. Impact of vitamin D deficiency on increased blood eosinophil counts. Hematol Oncol Stem Cell Ther 2018;11(1):25-9.
  • 7. Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A, et al. Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol 2018;175:125-35.
  • 8. Hossein-nezhad A, Holick MF. Vitamin D for Health: A Global Perspective. Mayo Clin Proc 2013;88(7):720-55.
  • 9. Wu S, Sun J. Vitamin D, Vitamin D Receptor, and Macroautophagy in Inflammation and Infection. Discov Med 2011;11(59):325.
  • 10. Özkan B, Döneray H. D vitamininin iskelet sistemi dışı etkileri. Cocuk Sag Hast Derg 2011;54(2):99-119.
  • 11. Brighenti S, Bergman P, Martineau AR. Vitamin D and tuberculosis: where next? J Intern Med 2018;284(2):145-62.
  • 12. Kempker JA, Tangpricha V, Ziegler TR, Martin GS. Vitamin D in sepsis: from basic science to clinical impact. Crit Care 2012;16(4):316.
  • 13. Korf H, Decallonne B, Mathieu C. Vitamin D for infections. Curr Opin Endocrinol Diabetes Obes 2014;21(6):431-6.
  • 14. Yamshchikov A, Desai N, Blumberg H, Ziegler T, Tangpricha V. Vitamin D for Treatment and Prevention of Infectious Diseases: A Systematic Review of Randomized Controlled Trials. Endocr Pract 2009;15(5):438-49.
  • 15. Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1, 25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 1983;57(6):1308-10.
  • 16. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 1983;221(4616):1181-3.
  • 17. Kempker JA, Han JE, Tangpricha V, Ziegler TR, Martin GS. Vitamin D and sepsis: An emerging relationship. Dermatoendocrinol 2014;4(2):101-8.
  • 18. Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, et al. Vitamin D-Directed Rheostatic Regulation of Monocyte Antibacterial Responses. J Immunol 2009;182(7):4289-95.
  • 19. Thoma-Uszynski S, Stenger S, Takeuchi O, Ochoa MT, Engele M, Sieling PA, et al. Induction of direct antimicrobial activity through mammalian toll-like receptors. Science 2001;291(5508):1544-7.
  • 20. Zasloff M. Fighting Infections With Vitamin D. Nat Med 2006;12(4):388.
  • 21. Wang T-T, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-Mendoza LE, et al. Direct and Indirect Induction by 1,25-Dihydroxyvitamin D3of the NOD2/CARD15-Defensin β2 Innate Immune Pathway Defective in Crohn Disease. J Biol Chem 2010;285(4):2227-31.
  • 22. Sundaram ME, Coleman LA. Vitamin D and Influenza. Adv Nutr 2012;3(4):517-25.
  • 23. Luo J, Zhang M, Yan B, Zhang K, Chen M, Deng S. Imbalance of Th17 and Treg in peripheral blood mononuclear cells of active tuberculosis patients. Braz J Infect Dis 2017;21(2):155-61.
  • 24. Organization WH. WHO Global Tuberculosis Report 2018 Executive Summary. 2018.
  • 25. Williams CJB. On the Use and Administration of Cod-Liver Oil in Pulmonary Consumption. Lond J Med 1849;1(1 (Jan., 1849)):1-18.
  • 26. Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol 2007;103(3-5):793-8.
  • 27. Huang SJ, Wang X, Liu ZD, Cao WL, Han Y, Ma AG, et al. Vitamin D deficiency and the risk of tuberculosis: a meta-analysis. Drug Des Devel Ther 2016;Volume11:91-102.
  • 28. Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, et al. IFN-γ- and TNF-Independent Vitamin D-Inducible Human Suppression of Mycobacteria: The Role of Cathelicidin LL-37. J Immunol 2007;178(11):7190-8.
  • 29. Rook GA, Steele J, Fraher L, Barker S, Karmali R, O'riordan J, et al. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 1986;57(1):159.
  • 30. Crowle AJ, Ross EJ, May MH. Inhibition by 1, 25 (OH) 2-vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages. Infect Immun 1987;55(12):2945-50.
  • 31. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin Dmediated human antimicrobial response. Science 2006;311(5768):1770-3.
  • 32. Krutzik SR, Hewison M, Liu PT, Robles JA, Stenger S, Adams JS, et al. IL-15 Links TLR2/1-Induced Macrophage Differentiation to the Vitamin D-Dependent Antimicrobial Pathway. J Immunol 2008;181(10):7115-20.
  • 33. Chen Y, Liu W, Sun T, Huang Y, Wang Y, Deb DK, et al. 1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of TLR Signaling via Targeting MicroRNA-155-SOCS1 in Macrophages. J Immunol 2013;190(7):3687-95.
  • 34. Rode AKO, Kongsbak M, Hansen MM, Lopez DV, Levring TB, Woetmann A, et al. Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion. Front Immunol 2017;8.
  • 35. Sly LM, Lopez M, Nauseef WM, Reiner NE. 1α,25-Dihydroxyvitamin D3-induced Monocyte Antimycobacterial Activity Is Regulated by Phosphatidylinositol 3-Kinase and Mediated by the NADPH-dependent Phagocyte Oxidase. J Biol Chem 2001;276(38):35482-93.
  • 36. Rahman S, Rehn A, Rahman J, Andersson J, Svensson M, Brighenti S. Pulmonary tuberculosis patients with a vitamin D deficiency demonstrate low local expression of the antimicrobial peptide LL-37 but enhanced FoxP3+ regulatory T cells and IgG-secreting cells. Clin Immunol 2015;156(2):85-97.
  • 37. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, et al. Vitamin D as Supplementary Treatment for Tuberculosis. Am J Respir Crit Care Med 2009;179(9):843-50.
  • 38. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 2011;377(9761):242-50.
  • 39. Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci 2012;109(38):15449-54.
  • 40. Ganmaa D, Giovannucci E, Bloom BR, Fawzi W, Burr W, Batbaatar D, et al. Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial. Am J Clin Nutr 2012;96(2):391-6.
  • 41. Ralph AP, Waramori G, Pontororing GJ, Kenangalem E, Wiguna A, Tjitra E, et al. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial. PLoS One 2013;8(8):e70032.
  • 42. Salahuddin N, Ali F, Hasan Z, Rao N, Aqeel M, Mahmood F. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'. BMC Infect Dis 2013;13(1):22.
  • 43. Daley P, Jagannathan V, John KR, Sarojini J, Latha A, Vieth R, et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2015;15(5):528-34.
  • 44. Mily A, Rekha RS, Kamal SMM, Arifuzzaman ASM, Rahim Z, Khan L, et al. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. PLoS One 2015;10(9):e0138340.
  • 45. Tukvadze N, Sanikidze E, Kipiani M, Hebbar G, Easley K, Shenvi N, et al. High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial. Am J Clin Nutr 2015;102(5):1059-69.
  • 46. Ganmaa D, Munkhzul B, Fawzi W, Spiegelman D, Willett W, Bayasgalan P, et al. High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial. Am J Respir Crit Care Med 2017;196(5):628-37.
Toplam 46 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Yücel Büyükdere 0000-0003-2366-8735

Aylin Ayaz 0000-0002-3543-7881

Yayımlanma Tarihi 16 Aralık 2019
Gönderilme Tarihi 4 Nisan 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 9 Sayı: 4

Kaynak Göster

AMA Büyükdere Y, Ayaz A. Tüberküloz ve D Vitamini Arasındaki İlişkinin Değerlendirilmesi: Güncel Yaklaşımlar. Sakarya Tıp Dergisi. Aralık 2019;9(4):565-573. doi:10.31832/smj.549164

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