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Asymmetrıcal Dımethylargınıne (ADMA)

Year 2005, Volume: 7 Issue: 2, 36 - 41, 01.07.2005

Abstract

Asymmetric dimethylarginine (ADMA) is the principal endogenous inhibitor of nitric oxide synthase. It regulates rates of nitric oxide (NO) formation. There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide , which has been characterized as an "endogenous anti-atherosclerotic molecule". Thus, ADMA might be thought as a key role contributing to endothelial dysfunction. Recently, it was found that ADMA was significantly elevated in animals and humans with hypercholesterolemia. ADMA also participated in inflammatory reaction in atherosclerosis. Elevated plasma concentrations of ADMA are also present in hypercholesterolemic and hypertensive patients, in patients with chronic heart failure, and in other patient groups at high risk of developing cardiovascular disease. Elevation of ADMA induces dysfunction of the endothelium, which becomes clinically evident by impaired endothelium-dependent vasodilation, hyperaggregability of platelets, and enhanced monocyte adhesion. Recent prospective studies suggest that endothelial dysfunction indicates an increased risk of future cardiovascular events. Most of scientifics found that ADMA is a novel cardiovascular risk factor. Plasma ADMA is now available as a routine laboratory evaluation

References

  • Mugge A, Hanefeld C, Boger RH: Plasma concentration of asymmetric dimethylarginine and the risk of coronary heart disease: rationale and design of the multicenter CARDIAC study. Atheroscler Suppl. 4: 29-32, 2003.
  • Lenzen H, Tsikas D, Boger RH: Asymmetric dimethylarginine ( ADMA ) and the risk for coronary heart disease : the multicenter CARDIAC study. Eur J Clin Pharmacol. 8:1-5, 2005.
  • Leiper JM , Vallance P: The synthesis and metabolism of asymmetric dimethylarginine (ADMA) . Eur J Clin Pharamacol. 8: 1-6, 2005.
  • Cooke JP: Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 20: 2032-37, 2000.
  • Jiang J, Tang Y, Li N, Deng H, Li Y: Effect of simvastatin on endothelium-dependent vasorelaxation and endogenous nitric oxide synthase inhibitor. Acta Pharmacol. 25: 893- 901, 2004.
  • Sela BA: ADMA (Asymmetric dimethylarginine) the inhibitor of nitric oxide (NO) Snythesis: a new marker for vascular pathology. Harefuah. 144 : 655-9, 2005.
  • Endemann DH, Schiffrin E: Endothelial Dysfunction. J Am Soc. Nephrol. 15:1983-92, 2004.
  • Miyazaki H, Matsuoka H, Cooke JP: Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation. 99: 1141-46, 1999.
  • Gornik HL, Creager MA: Arginine, endothelial and vascular health. J of Nutr. 134: 2880S-87S, 2004.
  • Chauhan A, More RS, Mullins PA: Aging- associated endothelial dysfunction in humans is reversed by L-Arginine. J Am Coll Cardiol. 28: 1796-1804, 1996.
  • Celermajer DS: Endothelial dysfunction: does it matter? Is it reversible? J Am Cardiol. 30: 325-333, 1997.
  • Achan V, Ho HK, Heeschen C, Stuehlinger M, Jang JJ, Kimoto M, Vallance P, Cooke JP: ADMA regulates angiogenesis genetic and metabolic evidence. Vasc Med. 10 : 7-14, 2005.
  • Stühlinger M, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, Reaven GM, Tsao PS: Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. J Am.Med.Assoc. 287:1420-26,2002.
  • Lentz SR, Rodionow RN, Dayol S: Hyperhomocysteinemia, endothelial dysfunction and cardiovascular risk: the potential role of ADMA. Atherosclerosis Suppl. 4: 61-5, 2003.
  • Boger RH: Association of asymmetric dimethylarginine and endothelial dysfunction. Clin Chem Lab Med. 41 : 1467-72, 2003.
  • Holven KB, Haugstad TS, Holm T, Aurust P, Ose L, Nenseter MS: Folic acid treatment reduces elevated plasma levels of asymmetric dimethylarginine in hyperhomocysteinaemic subjects. Br J Nutr. 89:359-63, 2003.
  • Sydow K, Schwedhelm E, Arakawa N, Bode- Boger SM, Tsikas D, Hornig B, Frolich JC, Boger RH: ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocysteinemia: effects of L-arginine and B vitamins. Cardiovascular Res. 57: 244- 52,2003.
  • Teerlink T, Nijveldt RJ, Leewen V: Determination of arginine, ADMA, SDMA in human plasma and other biological samples by HPLC. Anal Biochem. 303:131-7, 2002.
  • Valtonen P, Karppi J, Nyyssonen K, Valkonen VP, Halonen T, Punnoven K: Comparison of HPLC method and commercial ELISA assay for asymmetric dimethylarginine (ADMA) determination in human serum. J Chromatogr B Analyt Technol Biomed Life Sci. 6: 1-5, 2005.
  • Marra M, Bonfigli AR, Testa R, Testa I, Gambini A, Coppa G: High-performance liquid chromatographic assay of asymmetrc dimethylarginine, symmetric dimethylarginine, and arginine in human plasma by derivatization with naphyhalene-2,3-dicarboxaldehyde. Anal Biochem. 318:13-7, 2003.
  • Martes-Lobenhoffere J, Krugo L, Bade-Boger SM: Determination of arginine and ADMA in human plasma by liquid chromatography/mass spectrometry with the isotope dilution techinque. J Mass Spectrom. 39: 1287-94, 2004.
  • Huang LF, Guo FQ, Liary YZ, Li B, Cheng BM: Simultaneus determination of L-arginine and its mono and dimethylated metabolites in human plasma by HPLC mass spectrometry. Anal Bioanal Chem. 380: 643-9, 2004.
  • Albsmeter J, Schwedhelm E, Sculze F, Kastner M, Boger RH: Determination of NG, NG-dimethyl L- arginine, an endogenous NO synthase inhibitor by gas chromaography – mass spectrometry. J Chromatogr B Analyt Technol Biomed Kife Sci. 809: 59-65, 2004.
  • Vishwanathan K, Tackett RL, Stewart JT, Bartlett MG: Determination of arginine and methylated arginine in human plasma by liquid chromotography tandem mass spectrometry. J Chromatog B Biomed Sci Appl.748:157-66, 2000.
  • Schulze F, Wesemann R, Schwedhelm E, Sydow K, Albsmeir J, Boger RH: Determination of asymmetric dimethylarginine (ADMA) using novel ELISA assay. Clin Chem Lab Med. 42: 1377-83, 2004.
  • Nonaka S, Tsunada M, Imai K, Funatsu T: High- performance liquid chromatographic assay of N(G)-monomethyl-L-arginine, N(G),N(G)- dimethyl-L-arginine, and N(G),N(G)'-dimethyl-L- arginine using 4-fluoro-7-nitro-2, 1,3- benzoxadiazole as a fluorescent reagent. J Choromatogr A. 1066: 41-5, 2005.
  • Marro M, Bonfgli AR, Testa R, Testa I, Gambini A, Coppa G: HPLC assay of ADMA, SDMA and Arginine in human plasma by derivation with naphthalene 2-3-dicarboxaldehde. Anal Biochem. 318:13-7, 2003.
  • Kielstein JT, Stefanie Mb, Frölich JC, Ritz E, Haller H, Fliser D: Asymmetric Dimethylarginine, blood pressure,and renal perfusion in elderly subjects. Circulation. 107:1891-99, 2003.
  • Lin KY, Ito A, Asagami S, Kimoto M, Tsuji H, Reaven GM, Cooke JP: Impaired nitric oxide synthase pathway in diabetes mellitus. Circulation. 106:987-92, 2002.
  • Tarnow L, Hovind P, Teerlink T, Stehouwer CDA, Parving H: Elevated plasma Asymmetric Dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in Type 1 diabetes. Diabetes Care. 27:765-69, 2004.
  • Makino N , Maeda T, Sugano M, Watanabe R, Abe N: High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated wtih eNOS down-regulation and apoptosis in endothelial cells. J Diabetes Complications. 19: 347- 55, 2005.
  • Xiong Y, Lei M, Fu S, Fu Y: Effect of diabetic duration on serum concentrations of endogenous inhibitor of nitric oxide synthase in patients and rats with diabetes. Life Sci. 77:149-59, 2005.
  • Sydow K, Hornig B, Arakawa N, Bode-Boger SM, Tsikas D, Munzel T, Boger RH: Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia : potential role of ADMA. Vasc Med. 9:93-101, 2004.
  • Kryzuzanowska K, Mittermayer F, KoppHP, Wolzt M, Schernthaner G: Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. J Clin Endocrinol Metab. 89:277-81, 2004.
  • Paiva H, Lehimaki T, Laakso J, Ruokonen I, Tervanen R, Metio S: Dieary composition as a determinant of plasma asymmetrical dimethylarginne in subjects with mild hypercholesteremia. Metabolism.53: 1072-5, 2004.
  • Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflat I: Relationship between obesity, smoking and the endogen ntric oxide synthase inhibitor, ADMA. Metabolism. 53 :1574-9, 2004.
  • Marliss EB, Chevalier S, Gougeon R, Morais JA, Lamarche M, Adegoke OA, Wu G: Elevations of plasma methylarginines in obesity and ageing are related to insulin ensitivity and rates of protein turnover. Diabetologia . 21: 1-9, 2005.
  • Fleck C, Schweitzer F, Karge E, Busch M, Stein G: Serum concentration of asymmetric ( ADMA) and symmetric ( SDMA) dimethylarginine in patients with chronic kidney diseases. Clin Chim Acta. 336:1-12, 2003.
  • Raconi P, Tripepi G, Malberti F, Testa S, Mallamaci F, Zoccali C: Asymmetrical Dimethylarginine Predicts Progression to Dialysis and Death in Patients with Chronic Kidney Disease: A Competing Risks Modeling Approach. J Am Soc Nephrol. 8 : 1-5, 2005.
  • Mallamaci F, Tripepi G, Cutrupi S, Malotino LS, Zoccali C: Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD. Kidney Int. 67 : 2330-7, 2005.
  • Yılmaz MI, Saglam M, Caglar K, Cakır E
  • Ozgurtas T, Sonmez A, Eyileten T, Yenicesu M, Acikel C, Oguz Y, Ozcan O, Bozlar U, Erbil K, Aslan I, Vural A: Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation. Transplantation. 80: 1660-66, 2005.

Asimetrik Dimetilarginin (ADMA)

Year 2005, Volume: 7 Issue: 2, 36 - 41, 01.07.2005

Abstract

Asimetrik dimetilarginin (ADMA), esas olarak endojen nitrik oksit sentaz inhibitörüdür. ADMA, nitrik oksit oluşum hızını düzenler. Vasküler tonus ve yapısının sürdürülmesinde temel rolü oynadığına dair çok miktarda kanıt bulunmaktadır. ‘Endojen anti-aterosklerotik molekül’ olarak bilinen nitrik oksit, major endotel kaynaklı vazoaktif mediatörüdür. Dolayısıyla ADMA’nın endotel disfonksiyonu ile ilgili anahtar rolü oynayabileceği düşünülmektedir. Son zamanlarda, ADMA hiperkolesterolemili insanlar ve hayvanlarda önemli oranda yüksek bulunmuştur. ADMA aterosklerozun inflamatuvar reaksiyon sürecine de katılmaktadır. ADMA plazma konsantrasyonları olan hasta grubunda kronik kalp yetmezliği ve diğer kardiyovasküler hastalıkların yanısıra hiperkolesterolemili ve hipertansif hastalarda da artmaktadır. Bozulan endotel bağımlı vazodilatasyon, plateletlerin agregabilite artışı ve monosit adezyonu artışının klinik delili olarak ortaya çıkan endotel disfonksiyonu, ADMA artışını uyarır. Son prospektif çalışmalar, ortaya çıkabilecek kardiyovasküler olayların endotel disfonksiyonunu desteklemektedir. Birçok bilim adamı ADMA’yı yeni bir kardiyovasküler risk faktörü olarak düşünmektedir. Günümüzde plazma ADMA’nın rutin laboratuvarlarda ölçümü mümkündür

References

  • Mugge A, Hanefeld C, Boger RH: Plasma concentration of asymmetric dimethylarginine and the risk of coronary heart disease: rationale and design of the multicenter CARDIAC study. Atheroscler Suppl. 4: 29-32, 2003.
  • Lenzen H, Tsikas D, Boger RH: Asymmetric dimethylarginine ( ADMA ) and the risk for coronary heart disease : the multicenter CARDIAC study. Eur J Clin Pharmacol. 8:1-5, 2005.
  • Leiper JM , Vallance P: The synthesis and metabolism of asymmetric dimethylarginine (ADMA) . Eur J Clin Pharamacol. 8: 1-6, 2005.
  • Cooke JP: Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 20: 2032-37, 2000.
  • Jiang J, Tang Y, Li N, Deng H, Li Y: Effect of simvastatin on endothelium-dependent vasorelaxation and endogenous nitric oxide synthase inhibitor. Acta Pharmacol. 25: 893- 901, 2004.
  • Sela BA: ADMA (Asymmetric dimethylarginine) the inhibitor of nitric oxide (NO) Snythesis: a new marker for vascular pathology. Harefuah. 144 : 655-9, 2005.
  • Endemann DH, Schiffrin E: Endothelial Dysfunction. J Am Soc. Nephrol. 15:1983-92, 2004.
  • Miyazaki H, Matsuoka H, Cooke JP: Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation. 99: 1141-46, 1999.
  • Gornik HL, Creager MA: Arginine, endothelial and vascular health. J of Nutr. 134: 2880S-87S, 2004.
  • Chauhan A, More RS, Mullins PA: Aging- associated endothelial dysfunction in humans is reversed by L-Arginine. J Am Coll Cardiol. 28: 1796-1804, 1996.
  • Celermajer DS: Endothelial dysfunction: does it matter? Is it reversible? J Am Cardiol. 30: 325-333, 1997.
  • Achan V, Ho HK, Heeschen C, Stuehlinger M, Jang JJ, Kimoto M, Vallance P, Cooke JP: ADMA regulates angiogenesis genetic and metabolic evidence. Vasc Med. 10 : 7-14, 2005.
  • Stühlinger M, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, Reaven GM, Tsao PS: Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. J Am.Med.Assoc. 287:1420-26,2002.
  • Lentz SR, Rodionow RN, Dayol S: Hyperhomocysteinemia, endothelial dysfunction and cardiovascular risk: the potential role of ADMA. Atherosclerosis Suppl. 4: 61-5, 2003.
  • Boger RH: Association of asymmetric dimethylarginine and endothelial dysfunction. Clin Chem Lab Med. 41 : 1467-72, 2003.
  • Holven KB, Haugstad TS, Holm T, Aurust P, Ose L, Nenseter MS: Folic acid treatment reduces elevated plasma levels of asymmetric dimethylarginine in hyperhomocysteinaemic subjects. Br J Nutr. 89:359-63, 2003.
  • Sydow K, Schwedhelm E, Arakawa N, Bode- Boger SM, Tsikas D, Hornig B, Frolich JC, Boger RH: ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocysteinemia: effects of L-arginine and B vitamins. Cardiovascular Res. 57: 244- 52,2003.
  • Teerlink T, Nijveldt RJ, Leewen V: Determination of arginine, ADMA, SDMA in human plasma and other biological samples by HPLC. Anal Biochem. 303:131-7, 2002.
  • Valtonen P, Karppi J, Nyyssonen K, Valkonen VP, Halonen T, Punnoven K: Comparison of HPLC method and commercial ELISA assay for asymmetric dimethylarginine (ADMA) determination in human serum. J Chromatogr B Analyt Technol Biomed Life Sci. 6: 1-5, 2005.
  • Marra M, Bonfigli AR, Testa R, Testa I, Gambini A, Coppa G: High-performance liquid chromatographic assay of asymmetrc dimethylarginine, symmetric dimethylarginine, and arginine in human plasma by derivatization with naphyhalene-2,3-dicarboxaldehyde. Anal Biochem. 318:13-7, 2003.
  • Martes-Lobenhoffere J, Krugo L, Bade-Boger SM: Determination of arginine and ADMA in human plasma by liquid chromatography/mass spectrometry with the isotope dilution techinque. J Mass Spectrom. 39: 1287-94, 2004.
  • Huang LF, Guo FQ, Liary YZ, Li B, Cheng BM: Simultaneus determination of L-arginine and its mono and dimethylated metabolites in human plasma by HPLC mass spectrometry. Anal Bioanal Chem. 380: 643-9, 2004.
  • Albsmeter J, Schwedhelm E, Sculze F, Kastner M, Boger RH: Determination of NG, NG-dimethyl L- arginine, an endogenous NO synthase inhibitor by gas chromaography – mass spectrometry. J Chromatogr B Analyt Technol Biomed Kife Sci. 809: 59-65, 2004.
  • Vishwanathan K, Tackett RL, Stewart JT, Bartlett MG: Determination of arginine and methylated arginine in human plasma by liquid chromotography tandem mass spectrometry. J Chromatog B Biomed Sci Appl.748:157-66, 2000.
  • Schulze F, Wesemann R, Schwedhelm E, Sydow K, Albsmeir J, Boger RH: Determination of asymmetric dimethylarginine (ADMA) using novel ELISA assay. Clin Chem Lab Med. 42: 1377-83, 2004.
  • Nonaka S, Tsunada M, Imai K, Funatsu T: High- performance liquid chromatographic assay of N(G)-monomethyl-L-arginine, N(G),N(G)- dimethyl-L-arginine, and N(G),N(G)'-dimethyl-L- arginine using 4-fluoro-7-nitro-2, 1,3- benzoxadiazole as a fluorescent reagent. J Choromatogr A. 1066: 41-5, 2005.
  • Marro M, Bonfgli AR, Testa R, Testa I, Gambini A, Coppa G: HPLC assay of ADMA, SDMA and Arginine in human plasma by derivation with naphthalene 2-3-dicarboxaldehde. Anal Biochem. 318:13-7, 2003.
  • Kielstein JT, Stefanie Mb, Frölich JC, Ritz E, Haller H, Fliser D: Asymmetric Dimethylarginine, blood pressure,and renal perfusion in elderly subjects. Circulation. 107:1891-99, 2003.
  • Lin KY, Ito A, Asagami S, Kimoto M, Tsuji H, Reaven GM, Cooke JP: Impaired nitric oxide synthase pathway in diabetes mellitus. Circulation. 106:987-92, 2002.
  • Tarnow L, Hovind P, Teerlink T, Stehouwer CDA, Parving H: Elevated plasma Asymmetric Dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in Type 1 diabetes. Diabetes Care. 27:765-69, 2004.
  • Makino N , Maeda T, Sugano M, Watanabe R, Abe N: High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated wtih eNOS down-regulation and apoptosis in endothelial cells. J Diabetes Complications. 19: 347- 55, 2005.
  • Xiong Y, Lei M, Fu S, Fu Y: Effect of diabetic duration on serum concentrations of endogenous inhibitor of nitric oxide synthase in patients and rats with diabetes. Life Sci. 77:149-59, 2005.
  • Sydow K, Hornig B, Arakawa N, Bode-Boger SM, Tsikas D, Munzel T, Boger RH: Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia : potential role of ADMA. Vasc Med. 9:93-101, 2004.
  • Kryzuzanowska K, Mittermayer F, KoppHP, Wolzt M, Schernthaner G: Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. J Clin Endocrinol Metab. 89:277-81, 2004.
  • Paiva H, Lehimaki T, Laakso J, Ruokonen I, Tervanen R, Metio S: Dieary composition as a determinant of plasma asymmetrical dimethylarginne in subjects with mild hypercholesteremia. Metabolism.53: 1072-5, 2004.
  • Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflat I: Relationship between obesity, smoking and the endogen ntric oxide synthase inhibitor, ADMA. Metabolism. 53 :1574-9, 2004.
  • Marliss EB, Chevalier S, Gougeon R, Morais JA, Lamarche M, Adegoke OA, Wu G: Elevations of plasma methylarginines in obesity and ageing are related to insulin ensitivity and rates of protein turnover. Diabetologia . 21: 1-9, 2005.
  • Fleck C, Schweitzer F, Karge E, Busch M, Stein G: Serum concentration of asymmetric ( ADMA) and symmetric ( SDMA) dimethylarginine in patients with chronic kidney diseases. Clin Chim Acta. 336:1-12, 2003.
  • Raconi P, Tripepi G, Malberti F, Testa S, Mallamaci F, Zoccali C: Asymmetrical Dimethylarginine Predicts Progression to Dialysis and Death in Patients with Chronic Kidney Disease: A Competing Risks Modeling Approach. J Am Soc Nephrol. 8 : 1-5, 2005.
  • Mallamaci F, Tripepi G, Cutrupi S, Malotino LS, Zoccali C: Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD. Kidney Int. 67 : 2330-7, 2005.
  • Yılmaz MI, Saglam M, Caglar K, Cakır E
  • Ozgurtas T, Sonmez A, Eyileten T, Yenicesu M, Acikel C, Oguz Y, Ozcan O, Bozlar U, Erbil K, Aslan I, Vural A: Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation. Transplantation. 80: 1660-66, 2005.
There are 42 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Güler Buğdaycı This is me

Erdinç Serin This is me

Publication Date July 1, 2005
Published in Issue Year 2005 Volume: 7 Issue: 2

Cite

APA Buğdaycı, G., & Serin, E. (2005). Asimetrik Dimetilarginin (ADMA). Duzce Medical Journal, 7(2), 36-41.
AMA Buğdaycı G, Serin E. Asimetrik Dimetilarginin (ADMA). Duzce Med J. July 2005;7(2):36-41.
Chicago Buğdaycı, Güler, and Erdinç Serin. “Asimetrik Dimetilarginin (ADMA)”. Duzce Medical Journal 7, no. 2 (July 2005): 36-41.
EndNote Buğdaycı G, Serin E (July 1, 2005) Asimetrik Dimetilarginin (ADMA). Duzce Medical Journal 7 2 36–41.
IEEE G. Buğdaycı and E. Serin, “Asimetrik Dimetilarginin (ADMA)”, Duzce Med J, vol. 7, no. 2, pp. 36–41, 2005.
ISNAD Buğdaycı, Güler - Serin, Erdinç. “Asimetrik Dimetilarginin (ADMA)”. Duzce Medical Journal 7/2 (July 2005), 36-41.
JAMA Buğdaycı G, Serin E. Asimetrik Dimetilarginin (ADMA). Duzce Med J. 2005;7:36–41.
MLA Buğdaycı, Güler and Erdinç Serin. “Asimetrik Dimetilarginin (ADMA)”. Duzce Medical Journal, vol. 7, no. 2, 2005, pp. 36-41.
Vancouver Buğdaycı G, Serin E. Asimetrik Dimetilarginin (ADMA). Duzce Med J. 2005;7(2):36-41.