Araştırma Makalesi
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Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi

Yıl 2023, Cilt: 34 Sayı: 3, 189 - 194, 27.11.2023
https://doi.org/10.36483/vanvetj.1237613

Öz

LPS ile deneysel endotoksemi oluşturulan ratlarda marbofloksasin, diklofenak sodyum ve metilprednizolon kullanımının serum sitokin seviyeleri üzerine etkilerinin değerlendirilmesi amaçlanmıştır. Çalışmada 186 adet rat, kontrol grubu (n: 6) ayrıldıktan sonra rastgele 5 eşit gruba ayrıldı. Kontrol grubundan 0. Saat te kan örnekleri alındı. Ratlarda endotoksemi oluşturmak amacı ile intraperitoneal (IP) yolla LPS (4mg/rat) uygulandı. Endotoksemi sonrası gelişen sepsisi tedavi etmek için marbofloksasin 100 mg/kg, diklofenak sodyum 10 mg/kg, metilprednizolon 10 mg/kg dozlarında IP yolla uygulandı. İlaç uygulaması takiben 1, 2, 4, 8, 12 ve 24. saatler de tiyopental anestezisi altında kan örnekleri alınarak serum sitokin değerleri ölçüldü. Araştırmada elde edilen veriler doğal şekillenen sepsise büyük ölçüde benzerlik gösterdi. Sitokin seviyeleri incelendiğinde diklofenak sodyum ile marbofloksasin uygulamasının tek başlarına sepsisi tedavi etmede etkisinin olmadığı, ancak metilprednizolon uygulamasının tek ve kombine yapılması durumunda etkili olabileceği belirlendi. Sepsis ile yükselen sitokin düzeyleri için kortikosteroid uygulamasının tek veya antibiyotik ve NSAİİ’lerle kombine kullanılmasının faydalı olabileceği önerilmektedir.

Destekleyen Kurum

Van YYÜ BAP

Teşekkür

Bu araştırma Yüzüncü Yıl Üniversitesi Bilimsel Araştırma Projeleri Başkanlığı tarafından 2010-SBE-D174 no’lu proje ile desteklenmiştir.

Kaynakça

  • Akgül Y, Akgül Ö, Kozat S et al. (2019). Evaluation of intercellular adhesion molecule-1 (ICAM-1), Tumor necrosis factor α (TNF-α), Interleukins (IL-6, IL-8) and C-reactive protein (CRP) levels in neonatalcalves with presumed septicemia. Van Vet J, 30 (3), 167-173.
  • Akyüz E, Naseri A, Erkılıç ve ark. (2017). Neonatal Buzağı İshalleri ve Sepsis. Kafkas Üniv Fen Bil Enst Derg, 10 (2), 181-191.
  • Beydilli Y, Gökçe Hİ (2019). Sepsisli Neonatal Buzağılarda Bazı hematolojik ve Biyokimyasal Parametrelerin Araştırılması. MAKU J Health Sci Inst, 7 (2), 55-67.
  • Biniek K, Szuster-Ciesielka A, Kaminska T et al. (1998). Tumor necrosis factor and interferon activity in the circulation of calves after reated injection low doses of lipopolisacharide. Vet Immunol Immunop, 62 (4), 297-307.
  • Bone RC, Charles JF, Clemmer TP et al. (1989). Sepsis sydrome: A validclinicalentity. Crit Care Med, 17 (5), 389-393.
  • Coimbra R, Melbostad H, Loomis W, Tobar M, Hoyt DB (2005). Phosphodiesterase inhibition decreases nuclear factor-Kb activation and shiftsth cytokine response to ward anti-inflammatory activity in acute endotoxemia. J Trauma, 59 (3), 575-582.
  • Coşkun D, Corun O, Yazar E (2020). Effect of supportive therapy on the pharmaco kinetics of intravenous marbofloxacin in endotoxemic sheep. J vet Pharmacol Therap, 43, 288-296.
  • Creasey AA, Chang AC, Feigen L et al. (1993). Tissue factor path way inhibitor reduces mortality from Escherichiacoli septic shock. J Clin Invest, 91 (6), 2850-2860.
  • Doğan MD, Ataoglu H, Akarsu ES (2002). Nimesulide and diclofenac inhibit lipopolysaccharide-induced hypothermia and tumornecrosis factor-α elevation in rats. Fund Clin Pharmacol; 16(4), 303-309.
  • Erkayman BP (2020). Sepsis Oluşturmak İçin Kullanılan Deneysel Hayvan Modelleri. Atatürk Üniversitesi Vet Bil Derg, 15(2), 181-186.
  • Eroğlu MS, Kırbaş A (2020). Sistemik İnflamatuar Yanıt Sendromu ve Sepsis, F Ü Sağ Bil Vet Derg, 34 (1), 61-67.
  • Gardlund B, Sjölin J, Nilsson A et al. (1995). Plasmalevels of cytokines in primary septic shock in humans: Correlation with diseases everity. J Infect Dis, 172 (1), 296-301.
  • Gouwy M, Struyf S, Proost P, van Damme J (2005). Synergy in cytokine and chemokine network samplifies the inflammatory response. Cytokine Growth FR, 16 (6), 561-580.
  • Hasani A, Soljakova M, Jakupi M, Ustalar-Ozgen S (2011). Preemptive analgesic effects of midazolam and diclofenac in rat model. Bosn J Basic Med, 11 (2), 113-118.
  • Howard M, Muchamuel T, Andrade S, Menon S (1993). Interleukin 10 Protects Mice from Lethal Endotoxemia. J Exp Med; 177 (4), 1205-1208.
  • Itoh A, Nishihira J, Makita H, et al. (2003). Effects of IL-1beta, TNF-alpha, and macrophagemi gration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells. Respirology, 8 (4), 467-472.
  • Izumi T, Bakhle YS (1989). Out put of prostanoids from rat lung following endotoxin and its modification by methylprednisolone. Circ Shock, 28 (1), 9-21.
  • Karbian N, Abutbul A, El-Amore R, et al. (2020). Apoptotic cell therapy for cytokinestormassociated with acute severe sepsis, Cell Deathand Disease; 11, 535-549.
  • Kesteman AS, Aude A, Ferran AA et al. (2009). İnfluence of ınoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of klebsiella pneumoniae in a rat lung ınfection model. Antimicrob Agents Ch, 53 (11), 4740-4748.
  • Khan AA, Slifer TR, Araujo FG, Suzuki Y, Remington J (2000). Protectionagainst Lipopolysaccharide-Induced Death by Fluoroquinolones. Antimicrob Agents Chemother, 44 (11), 3169-3173.
  • Lelubre C, Vincent JL (2018). Mechanisms and treatment of organ failure in sepsis, Nat Rev Nephrol, 14(7), 417-427.
  • Lukashenko PV, Lukashenko TM, Savanovich II, Sandakov DB, Gerein V (2004). Granulocyte macrophage colony-stimulating factor regulates activity of the nervous system. Neuroimmunomodulation, 11 (1), 36-40.
  • Marik PE, Lipman J (2007). The definition of septicshock: implications for treatment, Crit Care Resusc, 9(1), 101-103.
  • Meduri GU (1999). An historical review of glucocorticoid treatment in sepsis. Disease pathophysiology and the design of treatment in vestigation. Sepsis, 3, 21-38.
  • Oberholzer A, Oberholzer C, Moldawer LL (2002). Interleukin-10: A complex role in the pathogenesis of sepsis syndromes and it spotential as an anti-inflammatory drug. Crit Care Med, 30 (1), 58-63.
  • Otto CM (2007). Sepsis in veterinary patients: what do we know and where can wego?. J Vet Emerg Crit Care, 17 (4), 329-332.
  • Öner AC, Şahin A (2021). Endotoksemi Şekillendirilmiş Ratlarda Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Serum Biyokimyasal Değerler Üzerine Etkisi. Van Vet J, 32 (3), 98-103.
  • Özcan C, Hasanoğlu A, Gülcüler M (1996). Sepsis ve inflamasyon mediatörleri. Turgut Özal Tıp Merkezi Dergisi, 3 (4), 374- 381.
  • Pardon B, Deprez P (2018). Rational antimicrobial therapy for sepsis in cattle in face of the new lagislation on critical lyimportant antimicrobials. Vlaams Diergenees kundig Tijdschrift, 87, 37-46.
  • Park YJ, Lee MJ, Bae J et al. (2022). Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model. Life, 12, 421.
  • Rasooli A, Abbasi M, Shani Z, Hajihosseini R (2022). Preventive Effects of NSAIDs on Lung Tissue Oxidative Damage in an Animal Sepsis Model. J Cell Mol Anesth, 7 (1), 2-8.
  • Remick DG (2007). Biological perspectives pathophysiology of sepsis. Am J Pathol, 170 (5), 1435-1444.
  • Rosenbloom AJ, Pinsky MR, Bryant JL et al. (1995). Leukocyteactivation in the peripheral blood of patients with cirrhosis of the liver and SIRS. Correlation with serum interleukin-6 levelsand organ dysfunction. JAMA, 274 (1), 58-65.
  • Sakaguchi S, Furusawa S (2006). Oxidative stres and septic shock: metabolic aspects of oxygen-derived free radicals generated in the liver during endotoxemia. Immunol Med Microbiol, 47 (2), 167-177.
  • Sun XY, Ding XF, Liang HY et al. (2020). Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies, Stem Cell Research & Therapy, 11, 214.
  • Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J (2005). Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit, 11 (3), 76-85.
  • Utomo MT, Sudarmo SM, Sudiana K (2020). Zinc Supplementation in Cytokine Regulation DuringLPS-induced Sepsis in Rodent. J Int Dent Med Res, 13 (1), 46-50.
  • Yarema TC, Yost S (2011). Low-Dose Corticosteroids to Treat Septic Shock: A Critical Literature Review. Crit Care Nurse; 31(6), 16-26.
  • Yazar E, Çöl R, Konyalıoğlu S et al. (2004). Effects of vitamin E and prednisolone on biochemical and haematological parameters in endotoxaemic New Zealand white rabbits. B Vet I Pulawy, 48 (2), 105-108.
  • Yazar E, Er A, Uney A, Altunok V, Elmas M (2007). Effect of flunixin meglumine on cytokine levels in experimental endotoxemia in mice. J Vet Med A, 54 (7), 352-355.
  • Yazar E, Er A, Uney K, et al. (2010). Effects of drugs used in endotoxic shock on oxidative stres and organ damage markers. Free Rad Res, 44 (4), 397-402.

Effect of Marbofloxacin, Diclofenac Sodium and Methylprednisolone on Serum Cytokine Levels in Systemic Endotoxemia

Yıl 2023, Cilt: 34 Sayı: 3, 189 - 194, 27.11.2023
https://doi.org/10.36483/vanvetj.1237613

Öz

It was aimed to evaluate the effects of using marbofloxacin, diclofenacsodium and methylprednisolone on serum cytokine levels in rats with experimental endotoxemia with LPS. In the study, 186 rats were randomly divided into 5 equal groups after the control group (n: 6) was separated. Blood samples were taken from the control group at 0 hour. LPS (4mg/rat) was administered intraperitoneally (IP) to induce endotoxemia in rats. To treat sepsis developing after endotoxemia, marbofloxacin 100mg/kg, diclofenacsodium 10 mg/kg, methylprednisolone 10 mg/kg were administered by IP route. Serum cytokine values were measured by taking blood samples under thiopental anesthesia at 1, 2, 4, 8, 12 and 24 hours following drug administration. The data obtained in the study showed a great deal of similarity to naturally occurring sepsis. When cytokine levels were examined, it was determined that the application of diclofenacsodium and marbofloxacin alone did not have an effect in the treatment of sepsis, but methylprednisolone application could be effective in case of single or combined application. It is suggested that corticosteroid administration alone or in combination with antibiotics and NSAIDs may be beneficial for increased cytokine levels with sepsis.

Kaynakça

  • Akgül Y, Akgül Ö, Kozat S et al. (2019). Evaluation of intercellular adhesion molecule-1 (ICAM-1), Tumor necrosis factor α (TNF-α), Interleukins (IL-6, IL-8) and C-reactive protein (CRP) levels in neonatalcalves with presumed septicemia. Van Vet J, 30 (3), 167-173.
  • Akyüz E, Naseri A, Erkılıç ve ark. (2017). Neonatal Buzağı İshalleri ve Sepsis. Kafkas Üniv Fen Bil Enst Derg, 10 (2), 181-191.
  • Beydilli Y, Gökçe Hİ (2019). Sepsisli Neonatal Buzağılarda Bazı hematolojik ve Biyokimyasal Parametrelerin Araştırılması. MAKU J Health Sci Inst, 7 (2), 55-67.
  • Biniek K, Szuster-Ciesielka A, Kaminska T et al. (1998). Tumor necrosis factor and interferon activity in the circulation of calves after reated injection low doses of lipopolisacharide. Vet Immunol Immunop, 62 (4), 297-307.
  • Bone RC, Charles JF, Clemmer TP et al. (1989). Sepsis sydrome: A validclinicalentity. Crit Care Med, 17 (5), 389-393.
  • Coimbra R, Melbostad H, Loomis W, Tobar M, Hoyt DB (2005). Phosphodiesterase inhibition decreases nuclear factor-Kb activation and shiftsth cytokine response to ward anti-inflammatory activity in acute endotoxemia. J Trauma, 59 (3), 575-582.
  • Coşkun D, Corun O, Yazar E (2020). Effect of supportive therapy on the pharmaco kinetics of intravenous marbofloxacin in endotoxemic sheep. J vet Pharmacol Therap, 43, 288-296.
  • Creasey AA, Chang AC, Feigen L et al. (1993). Tissue factor path way inhibitor reduces mortality from Escherichiacoli septic shock. J Clin Invest, 91 (6), 2850-2860.
  • Doğan MD, Ataoglu H, Akarsu ES (2002). Nimesulide and diclofenac inhibit lipopolysaccharide-induced hypothermia and tumornecrosis factor-α elevation in rats. Fund Clin Pharmacol; 16(4), 303-309.
  • Erkayman BP (2020). Sepsis Oluşturmak İçin Kullanılan Deneysel Hayvan Modelleri. Atatürk Üniversitesi Vet Bil Derg, 15(2), 181-186.
  • Eroğlu MS, Kırbaş A (2020). Sistemik İnflamatuar Yanıt Sendromu ve Sepsis, F Ü Sağ Bil Vet Derg, 34 (1), 61-67.
  • Gardlund B, Sjölin J, Nilsson A et al. (1995). Plasmalevels of cytokines in primary septic shock in humans: Correlation with diseases everity. J Infect Dis, 172 (1), 296-301.
  • Gouwy M, Struyf S, Proost P, van Damme J (2005). Synergy in cytokine and chemokine network samplifies the inflammatory response. Cytokine Growth FR, 16 (6), 561-580.
  • Hasani A, Soljakova M, Jakupi M, Ustalar-Ozgen S (2011). Preemptive analgesic effects of midazolam and diclofenac in rat model. Bosn J Basic Med, 11 (2), 113-118.
  • Howard M, Muchamuel T, Andrade S, Menon S (1993). Interleukin 10 Protects Mice from Lethal Endotoxemia. J Exp Med; 177 (4), 1205-1208.
  • Itoh A, Nishihira J, Makita H, et al. (2003). Effects of IL-1beta, TNF-alpha, and macrophagemi gration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells. Respirology, 8 (4), 467-472.
  • Izumi T, Bakhle YS (1989). Out put of prostanoids from rat lung following endotoxin and its modification by methylprednisolone. Circ Shock, 28 (1), 9-21.
  • Karbian N, Abutbul A, El-Amore R, et al. (2020). Apoptotic cell therapy for cytokinestormassociated with acute severe sepsis, Cell Deathand Disease; 11, 535-549.
  • Kesteman AS, Aude A, Ferran AA et al. (2009). İnfluence of ınoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of klebsiella pneumoniae in a rat lung ınfection model. Antimicrob Agents Ch, 53 (11), 4740-4748.
  • Khan AA, Slifer TR, Araujo FG, Suzuki Y, Remington J (2000). Protectionagainst Lipopolysaccharide-Induced Death by Fluoroquinolones. Antimicrob Agents Chemother, 44 (11), 3169-3173.
  • Lelubre C, Vincent JL (2018). Mechanisms and treatment of organ failure in sepsis, Nat Rev Nephrol, 14(7), 417-427.
  • Lukashenko PV, Lukashenko TM, Savanovich II, Sandakov DB, Gerein V (2004). Granulocyte macrophage colony-stimulating factor regulates activity of the nervous system. Neuroimmunomodulation, 11 (1), 36-40.
  • Marik PE, Lipman J (2007). The definition of septicshock: implications for treatment, Crit Care Resusc, 9(1), 101-103.
  • Meduri GU (1999). An historical review of glucocorticoid treatment in sepsis. Disease pathophysiology and the design of treatment in vestigation. Sepsis, 3, 21-38.
  • Oberholzer A, Oberholzer C, Moldawer LL (2002). Interleukin-10: A complex role in the pathogenesis of sepsis syndromes and it spotential as an anti-inflammatory drug. Crit Care Med, 30 (1), 58-63.
  • Otto CM (2007). Sepsis in veterinary patients: what do we know and where can wego?. J Vet Emerg Crit Care, 17 (4), 329-332.
  • Öner AC, Şahin A (2021). Endotoksemi Şekillendirilmiş Ratlarda Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Serum Biyokimyasal Değerler Üzerine Etkisi. Van Vet J, 32 (3), 98-103.
  • Özcan C, Hasanoğlu A, Gülcüler M (1996). Sepsis ve inflamasyon mediatörleri. Turgut Özal Tıp Merkezi Dergisi, 3 (4), 374- 381.
  • Pardon B, Deprez P (2018). Rational antimicrobial therapy for sepsis in cattle in face of the new lagislation on critical lyimportant antimicrobials. Vlaams Diergenees kundig Tijdschrift, 87, 37-46.
  • Park YJ, Lee MJ, Bae J et al. (2022). Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model. Life, 12, 421.
  • Rasooli A, Abbasi M, Shani Z, Hajihosseini R (2022). Preventive Effects of NSAIDs on Lung Tissue Oxidative Damage in an Animal Sepsis Model. J Cell Mol Anesth, 7 (1), 2-8.
  • Remick DG (2007). Biological perspectives pathophysiology of sepsis. Am J Pathol, 170 (5), 1435-1444.
  • Rosenbloom AJ, Pinsky MR, Bryant JL et al. (1995). Leukocyteactivation in the peripheral blood of patients with cirrhosis of the liver and SIRS. Correlation with serum interleukin-6 levelsand organ dysfunction. JAMA, 274 (1), 58-65.
  • Sakaguchi S, Furusawa S (2006). Oxidative stres and septic shock: metabolic aspects of oxygen-derived free radicals generated in the liver during endotoxemia. Immunol Med Microbiol, 47 (2), 167-177.
  • Sun XY, Ding XF, Liang HY et al. (2020). Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies, Stem Cell Research & Therapy, 11, 214.
  • Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J (2005). Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit, 11 (3), 76-85.
  • Utomo MT, Sudarmo SM, Sudiana K (2020). Zinc Supplementation in Cytokine Regulation DuringLPS-induced Sepsis in Rodent. J Int Dent Med Res, 13 (1), 46-50.
  • Yarema TC, Yost S (2011). Low-Dose Corticosteroids to Treat Septic Shock: A Critical Literature Review. Crit Care Nurse; 31(6), 16-26.
  • Yazar E, Çöl R, Konyalıoğlu S et al. (2004). Effects of vitamin E and prednisolone on biochemical and haematological parameters in endotoxaemic New Zealand white rabbits. B Vet I Pulawy, 48 (2), 105-108.
  • Yazar E, Er A, Uney A, Altunok V, Elmas M (2007). Effect of flunixin meglumine on cytokine levels in experimental endotoxemia in mice. J Vet Med A, 54 (7), 352-355.
  • Yazar E, Er A, Uney K, et al. (2010). Effects of drugs used in endotoxic shock on oxidative stres and organ damage markers. Free Rad Res, 44 (4), 397-402.

Ayrıntılar

Birincil Dil Türkçe
Konular Veteriner Farmakoloji
Bölüm Araştırma Makaleleri
Yazarlar

Ali ŞAHİN 0000-0003-4104-7131

Ahmet Cihat ÖNER 0000-0001-6614-4347

Proje Numarası 2010-SBE-D174
Erken Görünüm Tarihi 27 Kasım 2023
Yayımlanma Tarihi 27 Kasım 2023
Gönderilme Tarihi 18 Ocak 2023
Kabul Tarihi 24 Ekim 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 34 Sayı: 3

Kaynak Göster

APA ŞAHİN, A., & ÖNER, A. C. (2023). Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi. Van Veterinary Journal, 34(3), 189-194. https://doi.org/10.36483/vanvetj.1237613
AMA ŞAHİN A, ÖNER AC. Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi. Van Vet J. Kasım 2023;34(3):189-194. doi:10.36483/vanvetj.1237613
Chicago ŞAHİN, Ali, ve Ahmet Cihat ÖNER. “Marbofloksasin, Diklofenak Sodyum Ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi”. Van Veterinary Journal 34, sy. 3 (Kasım 2023): 189-94. https://doi.org/10.36483/vanvetj.1237613.
EndNote ŞAHİN A, ÖNER AC (01 Kasım 2023) Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi. Van Veterinary Journal 34 3 189–194.
IEEE A. ŞAHİN ve A. C. ÖNER, “Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi”, Van Vet J, c. 34, sy. 3, ss. 189–194, 2023, doi: 10.36483/vanvetj.1237613.
ISNAD ŞAHİN, Ali - ÖNER, Ahmet Cihat. “Marbofloksasin, Diklofenak Sodyum Ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi”. Van Veterinary Journal 34/3 (Kasım 2023), 189-194. https://doi.org/10.36483/vanvetj.1237613.
JAMA ŞAHİN A, ÖNER AC. Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi. Van Vet J. 2023;34:189–194.
MLA ŞAHİN, Ali ve Ahmet Cihat ÖNER. “Marbofloksasin, Diklofenak Sodyum Ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi”. Van Veterinary Journal, c. 34, sy. 3, 2023, ss. 189-94, doi:10.36483/vanvetj.1237613.
Vancouver ŞAHİN A, ÖNER AC. Marbofloksasin, Diklofenak Sodyum ve Metilprednizolonun Sistemik Endotoksemide Serum Sitokin Düzeylerine Etkisi. Van Vet J. 2023;34(3):189-94.

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