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Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats

Yıl 2021, , 33 - 38, 21.01.2021
https://doi.org/10.33631/duzcesbed.739536

Öz

Aim: The aim of this study was to investigate the neuroprotective effect of metoprolol and its efficacy in reducing lipid peroxidation levels in the spinal cord ischemia-reperfusion model in rats.
Material and Methods: Twenty (20) Sprague-Dawley female rats weighing between 220 gr and 280 gr were randomly divided into 3 groups. Only laparotomy was performed in the control group, and the aorta abdominalis was revealed. In the groups other than the control group, clip compression was applied to the aorta abdominalis for 45 minutes. The ischemia group was not given any medication. Metoprolol was administered intraperitoneally at 0.5 mg/kg to the metoprolol group. Motor examination was made according to Tarlov scale at the 1st and 24th hours and then, spinal cords of all rat models were removed. Spinal cord tissue samples were collected for histopathological examination and for determining malondialdehyde (MDA) level. All rats were sacrificed by draining blood after their motor examinations.
Results: According to motor examination findings at the 1st and 24th hours, metoprolol resulted in a statistically significant improvement in recovery (p=0.045). Histopathological examinations revealed that metoprolol contributed to neurological recovery by reducing neuronal necrosis. MDA levels, which is an indicator of lipid peroxidation, were significantly lower in the metoprolol group when compared to the ischemia group (p=0.001).
Conclusion: Metoprolol was found to be significantly effective in reducing and/or preventing spinal cord ischemia-reperfusion injury.

Kaynakça

  • 1. Karacan I, Koyuncu H, Pekel O, Sümbüloğlu G, Kirnap M, Dursun H, et al. Traumatic spinal cord injuries in Turkey: a nation-wide epidemiological study. Spinal Cord. 2000; 38(11): 697-701. https://doi.org/10.1038/sj.sc.3101064.
  • 2. Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars). 2011; 71(2): 281-99.
  • 3. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991; 75(1): 15-26. https://doi.org/10.3171/jns.1991.75.1.0015.
  • 4. Kaptanoglu E, Caner HH, Sürücü HS, Akbiyik F. Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury. J Neurosurg. 1999; 91(Suppl 2): 200-4. https://doi.org/10.3171/spi.1999.91.2.0200.
  • 5. Ilhan A, Yilmaz HR, Armutcu F, Gurel A, Akyol O. The protective effect of nebivolol on ischemia/reperfusion injury in rabbit spinal cord. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(7): 1153-60. https://doi.org/10.1016/j.pnpbp.2004.06.023.
  • 6. Karatas Y, Cengiz SL, Esen H, Toker A, Savas C. Effect of carvedilol on secondary damage in experimental spinal cord injury in rats. Turk Neurosurg. 2015; 25(6): 930-5. https://doi.org/10.5137/1019-5149.JTN.11749-14.1
  • 7. Liu D, Huang Y, Li B, Jia C, Liang F, Fu Q. Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats. Clin Exp Pharmacol Physiol. 2015; 42(2): 202-12. https://doi.org/10.1111/1440-1681.12345
  • 8. Kazanci A, Seckin H, Karadeniz U, Kazanci D, Turan S, Kazanci B, et al. Comparison of the effect of mexiletine and methylprednisolone on neural function and histopathological damage after transient spinal cord ischemia in rabbits. Turk Neurosurg. 2010; 20(1): 43-9.
  • 9. Benfield P, Clissold SP, Brogden RN. Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. Drugs. 1986; 31(5): 376-429. https://doi.org/10.2165/00003495-198631050-00002.
  • 10. Mao Y, Tokudome T, Kishimoto I. Ghrelin as a treatment for cardiovascular diseases. Hypertension. 2014; 64(3): 450-4. https://doi.org/10.1161/HYPERTENSIONAHA.114.03726.
  • 11. Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JGF, et al. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014; 384(9961): 2235-43. https://doi.org/10.1016/S0140-6736(14)61373-8.
  • 12. Berg T. β1-Blockers lower norepinephrine release by inhibiting presynaptic, facilitating β1-adrenoceptors in normotensive and hypertensive rats. Front Neurol. 2014; 5: 51. https://doi.org/10.3389/fneur.2014.00051.
  • 13. Kalaycioglu S, Sinci V, Imren Y, Oz E. Metoprolol prevents ischemia-reperfusion injury by reducing lipid peroxidation. Jpn Circ J. 1999; 63(9): 718-21. https://doi.org/10.1253/jcj.63.718.
  • 14. Sharif H, Cotie LM, La Fountaine MF, Ditor DS. The influence of cardiac autonomic activity on the QT-variability index in able-bodied and incomplete spinal cord injured individuals. Auton Neurosci. 2015; 190: 46-52. https://doi.org/10.1016/j.autneu.2015.04.002.
  • 15. Gok HB, Solaroglu I, Okutan O, Cimen B, Kaptanoglu E, Palaoglu S. Metoprolol treatment decreases tissue myeloperoxidase activity after spinal cord injury in rats. J Clin Neurosci. 2007; 14(2): 138-42. https://doi.org/10.1016/j.jocn.2005.10.016.
  • 16. Tarlov IM, Klinger H. Spinal cord compression studies. II. Time limits for recovery after acute compression in dogs. AMA Arch Neurol Psychiatry. 1954; 71(3): 271-90.
  • 17. Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86(1): 271-8. https://doi.org/10.1016/0003-2697(78)90342-1.
  • 18. Nazli Y, Colak N, Alpay MF, Uysal S, Uzunlar AK, Cakir O. Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury. Clinics (Sao Paulo). 2015; 70(1): 52-60. https://doi.org/10.6061/clinics/2015(01)10.
  • 19. Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG. Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol. 2014; 6: 309-31. https://doi.org/10.2147/CLEP.S68889.
  • 20. Bravo-Esteban E, Taylor J, Aleixandre M, Simón-Martínez C, Torricelli D, Pons JL, et al. Longitudinal estimation of intramuscular Tibialis Anterior coherence during subacute spinal cord injury: relationship with neurophysiological, functional and clinical outcome measures. J Neuroeng Rehabil. 2017; 14(1): 58. https://doi.org/10.1186/s12984-017-0271-9.
  • 21. Noreau L, Noonan VK, Cobb J, Leblond J, Dumont FS. Spinal cord injury community survey: a national, comprehensive study to portray the lives of Canadians with spinal cord injury. Top Spinal Cord Inj Rehabil. 2014; 20(4): 249-64. https://doi.org/10.1310/sci2004-249
  • 22. Spinal Cord Injury (SCI) 2016 Facts and figures at a glance. J Spinal Cord Med. 2016; 39(4): 493-4. https://doi.org/10.1080/10790268.2016.1210925.
  • 23. Tanhoffer RA, Yamazaki RK, Nunes EA, Pchevozniki A, Pchevozniki AM, Nogata C, et al. Glutamine concentration and immune response of spinal cord-injured rats. J Spinal Cord Med. 2007; 30(2): 140-6. https://doi.org/10.1080/10790268.2007.11753925.
  • 24. Liverman CT, Altevogt BM, Joy JE, Johnson RT. Spinal cord injury: progress, promise, and priorities. Washington, DC: The National Academies Press; 2005. https://doi.org/10.17226/11253.
  • 25. Hall ED, Springer JE. Neuroprotection and acute spinal cord injury: A reappraisal. NeuroRx. 2004; 1(1): 80-100. https://doi.org/10.1602/neurorx.1.1.80.
  • 26. McTigue DM. Potential therapeutic targets for PPARgamma after spinal cord injury. PPAR Res. 2008; 2008: 517162. https://doi.org/10.1155/2008/517162.
  • 27. Azbill RD, Mu X, Bruce-Keller AJ, Mattson MP, Springer JE. Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury. Brain Res. 1997; 765(2): 283-90. https://doi.org/10.1016/s0006-8993(97)00573-8.
  • 28. Xiong Y, Rabchevsky AG, Hall ED. Role of peroxynitrite in secondary oxidative damage after spinal cord injury. J Neurochem. 2007; 100(3): 639-49. https://doi.org/10.1111/j.1471-4159.2006.04312.x.
  • 29. Xu W, Chi L, Xu R, Ke Y, Luo C, Cai J, et al. Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord. 2005; 43(4): 204-13. https://doi.org/10.1038/sj.sc.3101674.
  • 30. Hall ED. Inhibition of lipid peroxidation in CNS trauma. J Neurotrauma. 1991; 8(Suppl 1): S31-41.
  • 31. Anoopkumar-Dukie S, Walker RB, Daya S. A sensitive and reliable method for the detection of lipid peroxidation in biological tissues. J Pharm Pharmacol. 2001; 53(2): 263-6. https://doi.org/10.1211/0022357011775299.

Sıçanlarda Metoprololün Deneysel Omurilik İskemisi/Reperfüzyon Hasarı Üzerine Etkileri

Yıl 2021, , 33 - 38, 21.01.2021
https://doi.org/10.33631/duzcesbed.739536

Öz

Amaç: Bu çalışmanın amacı, metoprololün nöroprotektif etkisini ve sıçanlarda omurilik iskemisi/reperfüzyon modelinde lipid peroksidasyon düzeylerini azaltmadaki etkinliğini araştırmaktır.
Gereç ve Yöntemler: 220 gr ve 280 gr ağırlığında yirmi (20) Sprague-Dawley dişi sıçan rastgele 3 gruba ayrıldı. Kontrol grubunda sadece laparotomi yapıldı ve aort abdominalis ortaya konuldu. Kontrol grubu dışındaki gruplarda, aort abdominalise 45 dakika boyunca klips kompresyon uygulandı. İskemi grubuna herhangi bir ilaç verilmedi. Metoprolol grubuna intraperitonal olarak 0,5 mg/kg metoprolol uygulandı. Motor muayene 1. ve 24. saatlerde Tarlov ölçeğine göre yapıldı ve daha sonra tüm sıçanların omurilikleri çıkarıldı. Histopatolojik inceleme ve malondialdehit (MDA) seviyesini belirlemek için omurilik doku örnekleri toplandı. Tüm sıçanlar motor muayenelerinden sonra kansızlaştırma yoluyla sakrifiye edildi.
Bulgular: 1. ve 24. saatteki motor muayene bulgularına göre, metoprolol istatistiksel olarak anlamlı bir iyileşme sağladı (p=0,045). Histopatolojik incelemeler, metoprololün nöronal nekrozu azaltarak nörolojik iyileşmeye katkıda bulunduğunu ortaya koydu. Lipid peroksidasyonunun bir göstergesi olan MDA düzeyleri, metoprolol grubunda iskemi grubuna göre anlamlı olarak daha düşüktü (p=0,001).
Sonuç: Metoprololün omurilik iskemi/reperfüzyon hasarını azaltmada ve/veya önlemede önemli ölçüde etkili olduğu ortaya konulmuştur.

Kaynakça

  • 1. Karacan I, Koyuncu H, Pekel O, Sümbüloğlu G, Kirnap M, Dursun H, et al. Traumatic spinal cord injuries in Turkey: a nation-wide epidemiological study. Spinal Cord. 2000; 38(11): 697-701. https://doi.org/10.1038/sj.sc.3101064.
  • 2. Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars). 2011; 71(2): 281-99.
  • 3. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991; 75(1): 15-26. https://doi.org/10.3171/jns.1991.75.1.0015.
  • 4. Kaptanoglu E, Caner HH, Sürücü HS, Akbiyik F. Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury. J Neurosurg. 1999; 91(Suppl 2): 200-4. https://doi.org/10.3171/spi.1999.91.2.0200.
  • 5. Ilhan A, Yilmaz HR, Armutcu F, Gurel A, Akyol O. The protective effect of nebivolol on ischemia/reperfusion injury in rabbit spinal cord. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(7): 1153-60. https://doi.org/10.1016/j.pnpbp.2004.06.023.
  • 6. Karatas Y, Cengiz SL, Esen H, Toker A, Savas C. Effect of carvedilol on secondary damage in experimental spinal cord injury in rats. Turk Neurosurg. 2015; 25(6): 930-5. https://doi.org/10.5137/1019-5149.JTN.11749-14.1
  • 7. Liu D, Huang Y, Li B, Jia C, Liang F, Fu Q. Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats. Clin Exp Pharmacol Physiol. 2015; 42(2): 202-12. https://doi.org/10.1111/1440-1681.12345
  • 8. Kazanci A, Seckin H, Karadeniz U, Kazanci D, Turan S, Kazanci B, et al. Comparison of the effect of mexiletine and methylprednisolone on neural function and histopathological damage after transient spinal cord ischemia in rabbits. Turk Neurosurg. 2010; 20(1): 43-9.
  • 9. Benfield P, Clissold SP, Brogden RN. Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. Drugs. 1986; 31(5): 376-429. https://doi.org/10.2165/00003495-198631050-00002.
  • 10. Mao Y, Tokudome T, Kishimoto I. Ghrelin as a treatment for cardiovascular diseases. Hypertension. 2014; 64(3): 450-4. https://doi.org/10.1161/HYPERTENSIONAHA.114.03726.
  • 11. Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JGF, et al. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014; 384(9961): 2235-43. https://doi.org/10.1016/S0140-6736(14)61373-8.
  • 12. Berg T. β1-Blockers lower norepinephrine release by inhibiting presynaptic, facilitating β1-adrenoceptors in normotensive and hypertensive rats. Front Neurol. 2014; 5: 51. https://doi.org/10.3389/fneur.2014.00051.
  • 13. Kalaycioglu S, Sinci V, Imren Y, Oz E. Metoprolol prevents ischemia-reperfusion injury by reducing lipid peroxidation. Jpn Circ J. 1999; 63(9): 718-21. https://doi.org/10.1253/jcj.63.718.
  • 14. Sharif H, Cotie LM, La Fountaine MF, Ditor DS. The influence of cardiac autonomic activity on the QT-variability index in able-bodied and incomplete spinal cord injured individuals. Auton Neurosci. 2015; 190: 46-52. https://doi.org/10.1016/j.autneu.2015.04.002.
  • 15. Gok HB, Solaroglu I, Okutan O, Cimen B, Kaptanoglu E, Palaoglu S. Metoprolol treatment decreases tissue myeloperoxidase activity after spinal cord injury in rats. J Clin Neurosci. 2007; 14(2): 138-42. https://doi.org/10.1016/j.jocn.2005.10.016.
  • 16. Tarlov IM, Klinger H. Spinal cord compression studies. II. Time limits for recovery after acute compression in dogs. AMA Arch Neurol Psychiatry. 1954; 71(3): 271-90.
  • 17. Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86(1): 271-8. https://doi.org/10.1016/0003-2697(78)90342-1.
  • 18. Nazli Y, Colak N, Alpay MF, Uysal S, Uzunlar AK, Cakir O. Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury. Clinics (Sao Paulo). 2015; 70(1): 52-60. https://doi.org/10.6061/clinics/2015(01)10.
  • 19. Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG. Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol. 2014; 6: 309-31. https://doi.org/10.2147/CLEP.S68889.
  • 20. Bravo-Esteban E, Taylor J, Aleixandre M, Simón-Martínez C, Torricelli D, Pons JL, et al. Longitudinal estimation of intramuscular Tibialis Anterior coherence during subacute spinal cord injury: relationship with neurophysiological, functional and clinical outcome measures. J Neuroeng Rehabil. 2017; 14(1): 58. https://doi.org/10.1186/s12984-017-0271-9.
  • 21. Noreau L, Noonan VK, Cobb J, Leblond J, Dumont FS. Spinal cord injury community survey: a national, comprehensive study to portray the lives of Canadians with spinal cord injury. Top Spinal Cord Inj Rehabil. 2014; 20(4): 249-64. https://doi.org/10.1310/sci2004-249
  • 22. Spinal Cord Injury (SCI) 2016 Facts and figures at a glance. J Spinal Cord Med. 2016; 39(4): 493-4. https://doi.org/10.1080/10790268.2016.1210925.
  • 23. Tanhoffer RA, Yamazaki RK, Nunes EA, Pchevozniki A, Pchevozniki AM, Nogata C, et al. Glutamine concentration and immune response of spinal cord-injured rats. J Spinal Cord Med. 2007; 30(2): 140-6. https://doi.org/10.1080/10790268.2007.11753925.
  • 24. Liverman CT, Altevogt BM, Joy JE, Johnson RT. Spinal cord injury: progress, promise, and priorities. Washington, DC: The National Academies Press; 2005. https://doi.org/10.17226/11253.
  • 25. Hall ED, Springer JE. Neuroprotection and acute spinal cord injury: A reappraisal. NeuroRx. 2004; 1(1): 80-100. https://doi.org/10.1602/neurorx.1.1.80.
  • 26. McTigue DM. Potential therapeutic targets for PPARgamma after spinal cord injury. PPAR Res. 2008; 2008: 517162. https://doi.org/10.1155/2008/517162.
  • 27. Azbill RD, Mu X, Bruce-Keller AJ, Mattson MP, Springer JE. Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury. Brain Res. 1997; 765(2): 283-90. https://doi.org/10.1016/s0006-8993(97)00573-8.
  • 28. Xiong Y, Rabchevsky AG, Hall ED. Role of peroxynitrite in secondary oxidative damage after spinal cord injury. J Neurochem. 2007; 100(3): 639-49. https://doi.org/10.1111/j.1471-4159.2006.04312.x.
  • 29. Xu W, Chi L, Xu R, Ke Y, Luo C, Cai J, et al. Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord. 2005; 43(4): 204-13. https://doi.org/10.1038/sj.sc.3101674.
  • 30. Hall ED. Inhibition of lipid peroxidation in CNS trauma. J Neurotrauma. 1991; 8(Suppl 1): S31-41.
  • 31. Anoopkumar-Dukie S, Walker RB, Daya S. A sensitive and reliable method for the detection of lipid peroxidation in biological tissues. J Pharm Pharmacol. 2001; 53(2): 263-6. https://doi.org/10.1211/0022357011775299.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Uğur Yazar 0000-0003-4749-133X

Sabahattin Hızıroğlu Bu kişi benim 0000-0001-5317-3659

Süleyman Karahan Bu kişi benim 0000-0001-5091-081X

Mustafa Emre Ercın 0000-0002-7340-8045

Ali Rıza Güvercin 0000-0002-8689-0571

Serap Ozer Yaman 0000-0002-5089-0836

Yayımlanma Tarihi 21 Ocak 2021
Gönderilme Tarihi 20 Mayıs 2020
Yayımlandığı Sayı Yıl 2021

Kaynak Göster

APA Yazar, U., Hızıroğlu, S., Karahan, S., Ercın, M. E., vd. (2021). Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 11(1), 33-38. https://doi.org/10.33631/duzcesbed.739536
AMA Yazar U, Hızıroğlu S, Karahan S, Ercın ME, Güvercin AR, Ozer Yaman S. Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats. DÜ Sağlık Bil Enst Derg. Ocak 2021;11(1):33-38. doi:10.33631/duzcesbed.739536
Chicago Yazar, Uğur, Sabahattin Hızıroğlu, Süleyman Karahan, Mustafa Emre Ercın, Ali Rıza Güvercin, ve Serap Ozer Yaman. “Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats”. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 11, sy. 1 (Ocak 2021): 33-38. https://doi.org/10.33631/duzcesbed.739536.
EndNote Yazar U, Hızıroğlu S, Karahan S, Ercın ME, Güvercin AR, Ozer Yaman S (01 Ocak 2021) Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 11 1 33–38.
IEEE U. Yazar, S. Hızıroğlu, S. Karahan, M. E. Ercın, A. R. Güvercin, ve S. Ozer Yaman, “Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats”, DÜ Sağlık Bil Enst Derg, c. 11, sy. 1, ss. 33–38, 2021, doi: 10.33631/duzcesbed.739536.
ISNAD Yazar, Uğur vd. “Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats”. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 11/1 (Ocak 2021), 33-38. https://doi.org/10.33631/duzcesbed.739536.
JAMA Yazar U, Hızıroğlu S, Karahan S, Ercın ME, Güvercin AR, Ozer Yaman S. Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats. DÜ Sağlık Bil Enst Derg. 2021;11:33–38.
MLA Yazar, Uğur vd. “Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats”. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, c. 11, sy. 1, 2021, ss. 33-38, doi:10.33631/duzcesbed.739536.
Vancouver Yazar U, Hızıroğlu S, Karahan S, Ercın ME, Güvercin AR, Ozer Yaman S. Effects of Metoprolol on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rats. DÜ Sağlık Bil Enst Derg. 2021;11(1):33-8.