Turkiye Klinikleri Journal of Veterinary Sciences

.: REVIEW
Neonatal Buzağı Septisemileri İçin Potansiyel Bir Biyobelirteç Adayı: Presepsin: Geleneksel Derleme
A Potential Biomarker Candidate for Neonatal Calf Septicemia: Presepsin: Traditional Review
Abdullah Murat ALTINSOYa , Vahdettin ALTUNOKa
aSelçuk Üniversitesi Veteriner Fakültesi, Veterinerlik Biyokimyası ABD, Konya, Türkiye
Turkiye Klinikleri J Vet Sci. 2024;15(1):23-9
doi: 10.5336/vetsci.2023-96107
Article Language: TR
Full Text
ÖZET
Neonatal buzağı septisemisi, genç buzağılarda genellikle pasif transfer yetersizliğinin bir sonucu olarak ortaya çıkmaktadır. İshal, pnömoni, omfalit, respiratuar distres sendromu gibi nedenlere bağlı olarak gelişebilmektedir. Son yapılan bir çalışma ile kritik hastalığa sahip buzağıların yaklaşık %34'ünde sepsis geliştiği ortaya konmuştur. Neonatal buzağı septisemilerine bağlı olarak ülke ve dünya genelinde, hayvancılık yapan işletmelerde ciddi ekonomik kayıplar meydana gelmektedir. Klinik pratikte, buzağılarda gelişen sepsisin tanısında kullanılan mevcut yöntemler çoğunlukla yetersiz kalmaktadır. Ayrıca yapılan çalışmalara rağmen buzağı septisemilerinin patofizyolojisi hakkında yeterli bilgi mevcut değildir. Sepsisin erken aşamada tespit edilmesi hâlinde mortalite oranları ciddi bir biçimde azalmaktadır. Veteriner hekimlik alanında, hastalığın teşhis ve seyri hakkında bilgi almak amacıyla biyobelirteçlerin kullanımı yaygınlık kazanmaktadır. CD14 glikoproteininin, bakteriyel enzimin etkisiyle parçalanması sonrasında presepsin adı verilen çözünür formda bir molekül açığa çıkmaktadır. Presepsinin beşerî hekimlikte, sepsisin erken tanısı ve tedaviye alınan yanıtı izlemek amacıyla kullanımı giderek yaygınlık kazanmaktadır. Presepsin molekülü, sepsis patofizyolojisinde direkt olarak yer alması sebebiyle yaygın kullanılan diğer biyobelirteçlerin önüne geçmektedir. Yenidoğan buzağı septisemisinde presepsin değerlerini ortaya koyan herhangi bir çalışma mevcut değildir. Bu derleme ile beşerî hekimlikte kullanımı giderek artan presepsin molekülünün, neonatal buzağı septisemilerinin teşhis ve seyri esnasında kullanılabilecek umut vadeden bir biyobelirteç olabileceği üzerinde durulmuştur.

Anahtar Kelimeler: Presepsin; neonatal buzağı septisemisi; biyobelirteç
ABSTRACT
Neonatal calf septicemia usually occurs as a result of passive transfer failure in young calves. It may develop due to causes such as diarrhea, pneumonia, omphalitis, and respiratory distress syndrome. A recent study revealed that approximately 34% of critically ill calves develop sepsis. Due to calf septicemia, serious economic losses occur in livestock enterprises throughout the country and the world. Current methods used to diagnose sepsis in calves are often scanty in clinical practice. In addition, despite the studies, there is not enough information about the pathophysiology of calf septicemia. Mortality rates are significantly reduced if sepsis is detected at an early stage. In veterinary medicine, biomarkers are becoming widespread to obtain information about the diagnosis and prognosis of the disease. After the CD14 glycoprotein is cleaved by the effect of the bacterial enzyme, a released soluble molecule called presepsin. The use of presepsin in human medicine for the early diagnosis of sepsis and monitoring the response to treatment is becoming increasingly common. Presepsin molecule is superior to other commonly used biomarkers as it is directly involved in the pathophysiology of sepsis. There is no study on the values of presepsin in calf septicemia. In this review, it was emphasized that the presepsin molecule, which is increasingly used in human medicine, maybe a promising biomarker that can be used during the diagnosis and prognosis of neonatal calf septicemia.

Keywords: Presepsin; neonatal calf septicemia; biomarker
REFERENCES:
  1. Guzelbektes H, Sen I, Aydogdu U, Er C, Coşkun A. Investigation of cytokine levels in calves with sepsis. J Hellenic Vet Med Soc. 2022;73(2):4113-8. [Crossref] 
  2. Lewis DH, Chan DL, Pinheiro D, Armitage-Chan E, Garden OA. The immunopathology of sepsis: pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T cells. J Vet Intern Med. 2012;26(3):457-82. [Crossref]  [PubMed]  [PMC] 
  3. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-10. [Crossref]  [PubMed]  [PMC] 
  4. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-247. [PubMed]  [PMC] 
  5. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200-11. [Crossref]  [PubMed]  [PMC] 
  6. Citil M, Gokce E. Neonatal septisemi [Neonatal septicemia]. Turkiye Klinikleri J Vet Sci. 2013;4(1):62-70. [Link] 
  7. Pas ML, Bokma J, Lowie T, Boyen F, Pardon B. Sepsis and survival in critically ill calves: Risk factors and antimicrobial use. J Vet Intern Med. 2023;37(1):374-89. [Crossref]  [PubMed]  [PMC] 
  8. Maden M. Hastalıkların teşhisi ve izlenmesinde biyobelirteçler [The biomarkers in the diagnosis and monitoring of diseases]. Turkiye Klinikleri J Vet Sci Pharmacol Toxicol-Special Topics. 2015;1(1):50-62. [Link] 
  9. López-Martínez MJ, Franco-Martínez L, Martínez-Subiela S, Cerón JJ. Biomarkers of sepsis in pigs, horses and cattle: from acute phase proteins to procalcitonin. Anim Health Res Rev. 2022;23(1):82-99. [Crossref]  [PubMed] 
  10. Fecteau G, Smith BP, George LW. Septicemia and meningitis in the newborn calf. Vet Clin North Am Food Anim Pract. 2009;25(1):195-208, vii-viii. [Crossref]  [PubMed] 
  11. Rubio I, Osuchowski MF, Shankar-Hari M, Skirecki T, Winkler MS, Lachmann G, et al. Current gaps in sepsis immunology: new opportunities for translational research. Lancet Infect Dis. 2019;19(12):e422-e36. [Crossref]  [PubMed] 
  12. Jarczak D, Kluge S, Nierhaus A. Sepsis-pathophysiology and therapeutic concepts. Front Med (Lausanne). 2021;8:628302. [Crossref]  [PubMed]  [PMC] 
  13. Otto GP, Sossdorf M, Claus RA, Rödel J, Menge K, Reinhart K, et al. The late phase of sepsis is characterized by an increased microbiological burden and death rate. Crit Care. 2011;15(4):R183. [Crossref]  [PubMed]  [PMC] 
  14. Komorowski M, Green A, Tatham KC, Seymour C, Antcliffe D. Sepsis biomarkers and diagnostic tools with a focus on machine learning. EBioMedicine. 2022;86:104394. [Crossref]  [PubMed]  [PMC] 
  15. Li ZL, Yang BC, Gao M, Xiao XF, Zhao SP, Liu ZL. Naringin improves sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis. Mol Ther Nucleic Acids. 2021;25:502-14. [Crossref]  [PubMed]  [PMC] 
  16. Yaegashi Y, Shirakawa K, Sato N, Suzuki Y, Kojika M, Imai S, et al. Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis. J Infect Chemother. 2005;11(5):234-8. [Crossref]  [PubMed] 
  17. Mussap M, Noto A, Fravega M, Fanos V. Soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein (LBP) in neonatal sepsis: new clinical and analytical perspectives for two old biomarkers. J Matern Fetal Neonatal Med. 2011;24 Suppl 2:12-4. [Crossref]  [PubMed] 
  18. Kollçaku F, Kayar A, Dokuzeylül B, Or E. Bir akut faz protein olan prokalsitoninin biyobelirteç olarak veteriner hekimlik klinik pratiğinde kullanımı ve önemi [The use and importance of procalcitonin as a biomarker in veterinary clinical practice]. Dicle Üniv Vet Fak Derg. 2022;15(2):116-20. [Crossref] 
  19. Barichello T, Generoso JS, Singer M, Dal-Pizzol F. Biomarkers for sepsis: more than just fever and leukocytosis-a narrative review. Crit Care. 2022;26(1):14. [Crossref]  [PubMed]  [PMC] 
  20. Pierrakos C, Velissaris D, Bisdorff M, Marshall JC, Vincent JL. Biomarkers of sepsis: time for a reappraisal. Crit Care. 2020;24(1):287. [Crossref]  [PubMed]  [PMC] 
  21. Ryoo SM, Han KS, Ahn S, Shin TG, Hwang SY, Chung SP, et al; Korean Shock Society (KoSS) Investigators. The usefulness of C-reactive protein and procalcitonin to predict prognosis in septic shock patients: A multicenter prospective registry-based observational study. Sci Rep. 2019;9(1):6579. [Crossref]  [PubMed]  [PMC] 
  22. Yogeshpriya S, Selvaraj P. C-reactive protein in veterinary practice. Dairy and Vet Sci J. 2019;13(2):555858. [Link] 
  23. Akgül Y, Akgül Ö, Kozat S, Özkan C, Kaya A, Yılmaz N. 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 neonatal calves with presumed septicemia. Van Vet J. 2019;30(3):167-73. [Crossref] 
  24. Coskun A, Sen I. Acute phase response and clinical changes in calves with lipopolysaccharide induced endotoxemia. Eurasian J Vet Sci. 2012;28(1):21-6. [Link] 
  25. Ballou MA, Cobb CJ, Hulbert LE, Carroll JA. Effects of intravenous Escherichia coli dose on the pathophysiological response of colostrum-fed Jersey calves. Vet Immunol Immunopathol. 2011;141(1-2):76-83. [Crossref]  [PubMed]  [PMC] 
  26. Basoglu A, Sen I, Sevinc M, Simsek A. Serum concentrations of tumor necrosis factor-alpha in neonatal calves with presumed septicemia. J Vet Intern Med. 2004;18(2):238-41. [Crossref]  [PubMed] 
  27. Karzai W, Oberhoffer M, Meier-Hellmann A, Reinhart K. Procalcitonin--a new indicator of the systemic response to severe infections. Infection. 1997;25(6):329-34. [Crossref]  [PubMed]  [PMC] 
  28. Shiferaw B, Bekele E, Kumar K, Boutin A, Frieri M. The role of procalcitonin as a biomarker in sepsis. J Infect Dis Epidemiol. 2016;2:006. [Crossref] 
  29. Ercan N, Tuzcu N, Basbug O, Gok K, Isıdan H, Ograk YZ. The evaluation of important biomarkers in healthy cattle. Kafkas Univ Vet Fak Derg. 2014;20(5):749-55. [Link] 
  30. Bonelli F, Meucci V, Divers TJ, Boccardo A, Pravettoni D, Meylan M, et al. Plasma procalcitonin concentration in healthy calves and those with septic systemic inflammatory response syndrome. Vet J. 2018;234:61-5. [Crossref]  [PubMed] 
  31. Akyüz E, Gökce G. Neopterin, procalcitonin, clinical biochemistry, and hematology in calves with neonatal sepsis. Trop Anim Health Prod. 2021;53(3):354. [Crossref]  [PubMed]  [PMC] 
  32. Matur E, Özcan M, Ergül Ekiz E, Ergen E, Erek M, Or E, et al. Use of serum procalcitonin (PCT) level and PCT mRNA expression as a potential clinical biomarker in cats with bacterial and viral infections. J Feline Med Surg. 2022;24(12):e595-e602. [Crossref]  [PubMed] 
  33. Zamani F, Zare Shahneh F, Aghebati-Maleki L, Baradaran B. Induction of CD14 expression and differentiation to monocytes or mature macrophages in promyelocytic cell lines: new approach. Adv Pharm Bull. 2013;3(2):329-32. [PubMed]  [PMC] 
  34. Ibeagha-Awemu EM, Lee JW, Ibeagha AE, Zhao X. Bovine CD14 gene characterization and relationship between polymorphisms and surface expression on monocytes and polymorphonuclear neutrophils. BMC Genet. 2008;9:50. [Crossref]  [PubMed]  [PMC] 
  35. Arroyo-Espliguero R, Avanzas P, Jeffery S, Kaski JC. CD14 and toll-like receptor 4: a link between infection and acute coronary events? Heart. 2004;90(9):983-8. [Crossref]  [PubMed]  [PMC] 
  36. de Aguiar BB, Girardi I, Paskulin DD, de Franca E, Dornelles C, Dias FS, et al. CD14 expression in the first 24h of sepsis: effect of -260C>T CD14 SNP. Immunol Invest. 2008;37(8):752-69. [Crossref]  [PubMed] 
  37. Klouche K, Cristol JP, Devin J, Gilles V, Kuster N, Larcher R, et al. Diagnostic and prognostic value of soluble CD14 subtype (Presepsin) for sepsis and community-acquired pneumonia in ICU patients. Ann Intensive Care. 2016;6(1):59. [Crossref]  [PubMed]  [PMC] 
  38. Ikegame A, Kondo A, Kitaguchi K, Sasa K, Miyoshi M. Presepsin production in monocyte/macrophage-mediated phagocytosis of neutrophil extracellular traps. Sci Rep. 2022;12(1):5978. [Crossref]  [PubMed]  [PMC] 
  39. Takai N, Kataoka M, Higuchi Y, Matsuura K, Yamamoto S. Primary structure of rat CD14 and characteristics of rat CD14, cytokine, and NO synthase mRNA expression in mononuclear phagocyte system cells in response to LPS. J Leukoc Biol. 1997;61(6):736-44. [Crossref]  [PubMed] 
  40. Wang Y, Zarlenga DS, Paape MJ, Dahl GE, Tomita GM. Functional analysis of recombinant bovine CD14. Vet Res. 2003;34(4):413-21. [Crossref]  [PubMed] 
  41. Kim JI, Lee CJ, Jin MS, Lee CH, Paik SG, Lee H, et al. Crystal structure of CD14 and its implications for lipopolysaccharide signaling. J Biol Chem. 2005;280(12):11347-51. [Crossref]  [PubMed] 
  42. Pal A, Sharma A, Bhattacharya TK, Chatterjee PN, Chakravarty AK. Molecular characterization and SNP detection of CD14 gene of crossbred cattle. Mol Biol Int. 2011;2011:507346. [Crossref]  [PubMed]  [PMC] 
  43. Park BS, Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med. 2013;45(12):e66. [Crossref]  [PubMed]  [PMC] 
  44. Bazil V, Horejsí V, Baudys M, Kristofová H, Strominger JL, Kostka W, et al. Biochemical characterization of a soluble form of the 53-kDa monocyte surface antigen. Eur J Immunol. 1986;16(12):1583-9. [Crossref]  [PubMed] 
  45. Moon HW, Park M, Hur M, Kim H, Choe WH, Yun YM. Usefulness of enhanced liver fibrosis, glycosylation isomer of mac-2 binding protein, galectin-3, and soluble suppression of tumorigenicity 2 for assessing liver fibrosis in chronic liver diseases. Ann Lab Med. 2018;38(4):331-7. [Crossref]  [PubMed]  [PMC] 
  46. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, et al. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005;4(6):2070-80. [Crossref]  [PubMed]  [PMC] 
  47. Sauter KS, Brcic M, Franchini M, Jungi TW. Stable transduction of bovine TLR4 and bovine MD-2 into LPS-nonresponsive cells and soluble CD14 promote the ability to respond to LPS. Vet Immunol Immunopathol. 2007;118(1-2):92-104. [Crossref]  [PubMed] 
  48. Chenevier-Gobeaux C, Bardet V, Poupet H, Poyart C, Borderie D, Claessens YE. Presepsin (sCD14-ST) secretion and kinetics by peripheral blood mononuclear cells and monocytic THP-1 cell line. Ann Biol Clin (Paris). 2016;74(1):93-7. [Crossref]  [PubMed] 
  49. Aulin LBS, Kleijburg A, Moerland M, van Hasselt JGC. Characterizing the kinetics of presepsin and associated inflammatory biomarkers in human endotoxemia. Inflamm Res. 2022;71(9):999-1001. [Crossref]  [PubMed]  [PMC] 
  50. Lee S, Song J, Park DW, Seok H, Ahn S, Kim J, et al. Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: a prospective observational study according to the Sepsis-3 definitions. BMC Infect Dis. 2022;22(1):8. [Crossref]  [PubMed]  [PMC] 
  51. Kondo Y, Umemura Y, Hayashida K, Hara Y, Aihara M, Yamakawa K. Diagnostic value of procalcitonin and presepsin for sepsis in critically ill adult patients: a systematic review and meta-analysis. J Intensive Care. 2019;7:22. [Crossref]  [PubMed]  [PMC] 
  52. Aliu-Bejta A, Atelj A, Kurshumliu M, Dreshaj S, Bar?ić B. Presepsin values as markers of severity of sepsis. Int J Infect Dis. 2020;95:1-7. [Crossref]  [PubMed] 
  53. Hay AN, Wagner B, Leeth CM, LeRoith T, Cecere TE, Lahmers KK, et al. Horses affected by EPM have increased sCD14 compared to healthy horses. Vet Immunol Immunopathol. 2021;242:110338. [Crossref]  [PubMed] 
  54. Tukia E, Wagner B, Vainio K, Mönki J, Kareskoski M. The effect of uterine lavage on soluble CD14, chemokine ligand 2, and interleukin 10 levels in mares with postpartum metritis. J Equine Vet Sci. 2021;98:103365. [Crossref]  [PubMed] 
  55. Silva A, Wagner B, McKenzie HC, Desrochers AM, Furr MO. An investigation of the role of soluble CD14 in hospitalized, sick horses. Vet Immunol Immunopathol. 2013;155(4):264-9. [Crossref]  [PubMed] 
  56. Okamura Y, Yokoi H. Development of a point-of-care assay system for measurement of presepsin (sCD14-ST). Clin Chim Acta. 2011;412(23-24):2157-61. [Crossref]  [PubMed] 
  57. Shirakawa K, Naitou K, Hirose J, Takahashi T, Furusako S. Presepsin (sCD14-ST): development and evaluation of one-step ELISA with a new standard that is similar to the form of presepsin in septic patients. Clin Chem Lab Med. 2011;49(5):937-9. [Crossref]  [PubMed]  [PMC] 
  58. Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses. Vet Immunol Immunopathol. 2009;127(3-4):242-8. [Crossref]  [PubMed] 
  59. Bonelli F, Meucci V, Divers TJ, Wagner B, Intorre L, Sgorbini M. Kinetics of plasma procalcitonin, soluble CD14, CCL2 and IL-10 after a sublethal infusion of lipopolysaccharide in horses. Vet Immunol Immunopathol. 2017;184:29-35. [Crossref]  [PubMed] 
  60. Fogle J, Jacob M, Blikslager A, Edwards A, Wagner B, Dean K, et al. Comparison of lipopolysaccharides and soluble CD14 measurement between clinically endotoxaemic and nonendotoxaemic horses. Equine Vet J. 2017;49(2):155-9. [Crossref]  [PubMed] 
  61. Wagner B, Ainsworth DM, Freer H. Analysis of soluble CD14 and its use as a biomarker in neonatal foals with septicemia and horses with recurrent airway obstruction. Vet Immunol Immunopathol. 2013;155(1-2):124-8. [Crossref]  [PubMed] 

.: Up To Date

.: Process List

Login



Contact


Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com