Seckin OZKANLAR, Zekai HALICI, Muhammet Hamidullah UYANIK, Fatih AKCAY

Antibiyotik, Steroid ve Vitamin K’nın Terapötik Etkilerinin Erken Dönem Sepsis Süresince Laboratuvar Hayvanlarında Karşılaştırılması

Sepsisin tedavisinde kortikosteroidlerin tek başına ya da antibiyotiklerle birlikte kullanımları halen anlaşılması güç bir konudur. Ayrıca, sepsiste kanamadan mikrovasküler tromboza kadar değişen koagülasyon anormalliklerinin Vitamin K (Vit K) bağımlılığı yönünden araştırılması gerekmektedir. Bu çalışmada antibiyotik, steroid ve Vit K'nın etkilerinin terapötik sonuçları şiddetli sepsiste araştırılmıştır. Sıçanlarda septik peritonitis oluşturmak için abdominal cerrahi ile çekal-bağlamadelme (CLP) yapıldı. Sıçanlar her grupta 12 sıçan olmak üzere 7 gruba ayrıldı. Gruplar Sham, CLP, CLP+IM (imipenem), CLP+MP (metilprednizolon), CLP+VK (vitamin K3, menadione), CLP+IM+MP ve CLP+IM+VK'dir. Her gruptan 6 hayvan 16'ncı saatte örneklerin elde edilmesi için sakrifiye edildi. Kalan hayvanlar yaşam sürelerinin kaydedilebilmesi için gözlemlendi. TNF-?, IL-1? ve IL-6 değerlerindeki en yüksek artış CLP ve CLP+VK gruplarında görüldü. Sitokinler CLP+IM+MP grubunda önemli derecede artmadı. Trombosit sayısı CLP ve CLP+MP gruplarında azaldı (P

Comparison of the Therapeutic Effects of Antibiotic, Steroid, and Vitamin K During Early Sepsis in Laboratory Animals

The use of corticosteroids alone or with antibiotics in the treatment of sepsis is still a subject of conflict. Besides, coagulation abnormalities in sepsis ranging from bleeding to microvascular thrombosis are needed to be evaluated with respect to Vitamin K (Vit K) dependence. The effects of antibiotic, steroid and Vit K on severe sepsis were investigated to compare therapeutic outcomes in this study. Cecal-ligation-puncture (CLP) was induced by abdominal surgery in rats to produce septic peritonitis. Rats were divided into 7 groups including 12 rats each. Groups were Sham, CLP, CLP+IM (imipenem), CLP+MP (methylprednisolone), CLP+VK (vitamin K3, menadione), CLP+IM+MP and CLP+IM+VK. Six animals from each group were sacrificed to obtain samples at the 16th h. The remaining ones were observed to record survival times. The highest increases in serum TNF-α, IL-1β and IL-6 levels were observed in Group CLP and CLP+VK. Cytokines did not significantly increase in Group CLP+IM+MP. The platelet count decreased in Group CLP and CLP+MP (P

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1. Aziz M., Jacob A., Yang WL., Matsuda A., Wang P., 2013. Current trends in inflammatory and immunomodulatory mediators in sepsis. Journal of Leukocyte Biology, 93, 329-342.
2. Chen F., Fan XH., Wu YP., Zhu JL., Wang F., Bo LL., Li JB., Bao R., Deng XM., 2014. Resolvin D1 improves survival in experimental sepsis through reducing bacterial load and preventing excessive activation of inflammatory response. European Journal of Clinical Microbiology, 33, 457-464.
3. Khamphommala L., Parc Y., Bennis M., Ollivier JM., Dehni N., Tiret E., Parc R., 2008. Results of an aggressive surgical approach in the management of postoperative peritonitis. Australian and New Zealand Journal of Surgery, 78, 881-888.
4. Delsesto D., Opal SM., 2011. Future perspectives on regulating pro-and anti-inflammatory responses in sepsis. Contributions to Microbiology, 17: 137-156. 5. Jaffer U., Wade RG., Gourlay T., 2010. Cytokines in the systemic inflammatory response syndrome: a review. HSR Proceedings in Intensive Care δ Cardiovascular Anesthesia, 2, 161-175.
6. Pinsky MR., Vincent JL., Deviere J., Alegre M., Kahn RJ., Dupont E., 1993. Serum cytokine levels in human septic shock. Relation to multiplesystem organ failure and mortality. Chest, 103, 565-575.
7. Cunneen J., Cartwright M., 2004. The puzzle of sepsis: fitting the pieces of the inflammatory response with treatment. American Association of Critical- Care Nurses, AACN Clinical Issues 15, 18-44.
8. Emmanuel K., Weighardt H., Bartels H., Siewert JR., Holzmann B., 2005. Current and future concepts of abdominal sepsis. World Journal of Surgery, 29, 3-9.
9. Koo DJ., Jackman D., Chaudry IH., Wang P., 2001. Adrenal insufficiency during the late stage of polymicrobial sepsis. Critical Care Medicine, 29, 618-622.
10. Burry LD., Wax RS., 2004. Role of corticosteroids in septic shock. The Annals of Pharmacotherapy, 38, 464-472.
11. Assfalg V., Huser N., Reim D., Kaiser-Moore S., Rossmann-Bloeck T., Weighardt H., Novotny AR., Stangl MJ., Holzmann B., Emmanuel KL., 2010. Combined immunosuppressive and antibiotic therapy improves bacterial clearance and survival of polymicrobial septic peritonitis. Shock, 33, 155-161.
12. Levi M., Schultz M., van der Poll T., 2013. Sepsis and thrombosis. Seminars in Thrombosis and Hemostasis, 39, 559-566.
13. Satran R., Almog Y., 2003. The coagulopathy of sepsis: pathophysiology and management. The Israel Medical Association Journal, 5, 516-520. 14. Esmon CT., 2004. Crosstalk between inflammation and thrombosis. Maturitas, 47, 305-314.
15. Singleton KD., Wischmeyer PE., 2003. Distance of cecum ligated influences mortality, tumor necrosis factor-alpha and interleukin-6 expression following cecal ligation and puncture in the rat. European Surgical Research, 35, 486- 491.
16. Rim KP., Kim K., Jo YH., Lee JH., Rhee JE., Kang KW., Suh GJ., Kwon WY., Lee MJ., Lee HS., 2012. Effect of therapeutic hypothermia according to severity of sepsis in a septic rat model. Cytokine 60, 755-761.
17. Akpinar E., Halici Z., Cadirci E., Bayir Y., Karakus E., Calik M., Topcu A., Polat B., 2014. What is the role of renin inhibition during rat septic conditions: preventive effect of aliskiren on sepsis-induced lung injury. NaunynSchmiedeberg's Archives of Pharmacology, 387, 969-978.
18. Fijen JW., Kobold AC., de Boer P., Jones CR., van der Werf TS., Tervaert JW., Zijlstra JG., Tulleken JE., 2000. Leukocyte activation and cytokine production during experimental human endotoxemia. European Journal of Internal Medicine, 11, 89-95.
19. Cadirci E., Altunkaynak BZ., Halici Z., Odabasoglu F., Uyanik MH., Gundogdu C., Suleyman H., Halici M., Albayrak M., Unal B., 2010. Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and punctureinduced sepsis model in rats. Shock, 33, 479-484.
20. Maier S., Traeger T., Entleutner M., Westerholt A., Kleist B., Huser N., Holzmann B., Stier A., Pfeffer K., Heidecke CD., 2004. Cecal ligation and puncture versus colon ascendens stent peritonitis: two distinct animal models for polymicrobial sepsis. Shock, 21, 505-511.
21.Orsal E., Halici Z., Bayir Y., Cadirci E., Bilen H., Ferah I., Aydin A., Ozkanlar S., Ayan AK., Seven B., Ozaltin S., 2013. The role of carnitine on ovariectomy and inflammation-induced osteoporosis in rats. Experimental Biology and Medicine, 238, 1406-1412.
22. Col R., Durgun Z., 2007. Sepsis, lökositler, sitokinler ve disseminant intravasküler koagulasyon. Veteriner Bilimleri Dergisi, 23, 97- 106.
23. Brooks HF., Osabutey CK., Moss RF., Andrews PL., Davies DC., 2007. Caecal ligation and puncture in the rat mimics the pathophysiological changes in human sepsis and causes multi-organ dysfunction. Metabolic Brain Disease, 22, 353-373.
24. de Oliveira, LM., Pires MG., Magrisso AB., Munhoz TP., Roesler R., de Oliveira JR., 2010. Fructose-1,6-bisphosphate inhibits in vitro and ex vivo platelet aggregation induced by ADP and ameliorates coagulation alterations in experimental sepsis in rats. Journal of Thrombosis and Thrombolysis, 29, 387-394.
25. Esmon CT., Taylor FB. Jr., Snow TR., 1991. Inflammation and coagulation: linked processes potentially regulated through a common pathway mediated by protein C. Thrombosis and Haemostasis, 66, 160-165.
26. Bernard GR., Vincent JL., Laterre PF., LaRosa SP., Dhainaut JF., Lopez-Rodriguez A., Steingrub JS., Garber GE., Helterbrand JD., Ely EW., Fisher CJ. Jr., 2001. Efficacy and safety of recombinant human activated protein C for severe sepsis. The New England Journal of Medicine, 344, 699-709.
27. Riedemann NC., Guo RF., Ward PA., 2003. Novel strategies for the treatment of sepsis. Nature Medicine, 9, 517-524.
28. Bevilacqua MP., Pober JS., Majeau GR., Fiers W., Cotran RS., Gimbrone MA. Jr., 1986. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proceedings of The National Academy of Sciences of the United States of America, 83, 4533-4537.
29. Conkling PR., Greenberg CS., Weinberg JB., 1988. Tumor necrosis factor induces tissue factor-like activity in human leukemia cell line U937 and peripheral blood monocytes. Blood, 72, 128- 133.
30. Stouthard JM., Levi M., Hack CE., Veenhof CH., Romijn HA., Sauerwein HP., van der Poll T., 1996. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thrombosis and Haemostasis, 76, 738-742.