Journal of Literature Pharmacy Sciences

Yara Fizyolojisi ve Deneysel Yara Modelleri: Geleneksel Derleme
Wound Physiology and Experimental Wound Models: Traditional Review
Rabia Edibe PARLAR KÖPRÜLÜa, Gökçe MUTLUb, Esra İPEKCİb, Mehmet Evren OKURc
aİstanbul Medipol Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji ABD, İstanbul, Türkiye
bSağlık Bilimleri Üniversitesi Hamidiye Eczacılık Fakültesi, Farmasötik Teknoloji ABD, İstanbul, Türkiye
cSağlık Bilimleri Üniversitesi Hamidiye Eczacılık Fakültesi, Farmakoloji ABD, İstanbul, Türkiye
J Lit Pharm Sci. 2022;11(2):94-103
doi: 10.5336/pharmsci.2022-88482
Article Language: TR
Full Text
ÖZET
 Yara, vücuda gelebilecek bir yaralanma sonucu cildin epidermisinde hasar oluşması ve derinin normal anatomisinin ve fonksiyonlarının bozulması olarak tanımlanır. Yara iyileşmesi, kazayla veya kasıtlı olarak meydana gelen travma sonrası derinin bütünlüğünü korumak için önemli bir fizyolojik süreçtir. Normal yara iyileşmesi, hemostaz/inflamatuar faz, inflamasyon, proliferatif faz ve yeniden şekillenme fazı dâhil olmak üzere birbirini takip eden ve üst üste binen 4 fazı içerir. Yara iyileşmesi; yaş, eşlik eden hastalık, beslenme ve hijyen gibi birçok faktör tarafından etkilenmektedir. Aşırı yara iyileşmesi (hipertrofik skar ve keloid) veya kronik yara (ülser), bozulmuş fizyolojik yara iyileşme süreçlerinin göstergesidir. Yaraların temelde akut/kronik olarak ayrılmasının yanında, oluştuğu bölge (ağız, göz, deri vb.) ve oluşumuna göre (travmaya bağlı yara, diyabetik yara ve yanık yaraları) sınıflandırılması, bakımı ve tedavisi açısından farklılıklar oluşturmaktadır. Genel olarak topikal antiseptikler ile yapılan geleneksel yara bakımının yanında günümüzde otogreftler, allogreftler, kültürlü epitelyal otogreftler ve biyouyumlu ve biyobozunur polimerlere dayalı yara pansumanları gibi tedavi seçenekleri de bulunmaktadır. Deneysel yara modelleri, terapötik potansiyele sahip yeni ajanları test etmek, doku onarım mekanizmasının patogenezini incelemek ve yeni biyobelirteçleri saptamak için gereklidir. İn silico, in vitro ve in vivo dâhil olmak üzere yara iyileşme sürecini incelemek için çeşitli modeller kullanılmıştır. Bunun yanında, hiçbir deneysel yara modeli fizyolojik yara iyileşmesini tam olarak temsil etmediği için farklı modelleri içeren uygun bir kombinasyon kullanılmalıdır. Bu derlemede; yara tipleri, yara iyileşmesi, in vitro ve in vivo deneysel yara modelleri tartışılmaktadır.

Anahtar Kelimeler: Yara; yara bakımı; yara iyileşmesi; yara modelleri; yara tedavisi
ABSTRACT
 Wound is defined as damage to the epidermis of the skin and disruption of the normal anatomy and functions of the skin as a result of an injury to the body. Wound healing is an important physiological process to preserve the integrity of the skin after accidental or intentional trauma. Normal wound healing includes four consecutive and overlapping phases, including the hemostasis/inflammatory phase, the inflammation, the proliferative phase, and the remodeling phase. Wound healing; it is affected by many factors such as age, concomitant disease, nutrition and hygiene. Excessive wound healing (hypertrophic scar and keloid) or chronic wound (ulcer) is indicative of impaired physiological wound healing processes. In addition to the acute/chronic division of wounds, the classification according to the region (mouth, eye, skin etc.) and formation (traumatic wound, diabetic wound and burn wounds) creates differences in terms of care and treatment. In addition to traditional wound care with topical antiseptics in general, treatment options such as autografts, allografts, cultured epithelial autografts and wound dressings based on biocompatible and biodegradable polymers are now available. Experimental wound models are required to test new agents with therapeutic potential, to study the pathogenesis of tissue repair mechanism, and to detect new biomarkers. Various models have been used to study the wound healing process, including in silico, in vitro, and in vivo. In addition, an appropriate combination of different models should be used, as no experimental wound model is fully representative of physiological wound healing. In this review, wound types, wound healing, in vitro and in vivo experimental wound models are discussed.

Keywords: Wound; wound care; wound healing; wound models; wound treatment
REFERENCES:
  1. Joshi A, Joshi VK, Pandey D, Hemalatha S. Systematic investigation of ethanolic extract from Leea macrophylla: Implications in wound healing. J Ethnopharmacol. 2016;191:95-106. [Crossref]  [PubMed] 
  2. Gonzalez AC, Costa TF, Andrade ZA, Medrado AR. Wound healing-a literature review. An Bras Dermatol. 2016;91(5):614-20. [Crossref]  [PubMed]  [PMC] 
  3. Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Adv Ther. 2017;34(3):599-610. [Crossref]  [PubMed]  [PMC] 
  4. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219-29. [Crossref]  [PubMed]  [PMC] 
  5. Wynn M. The Benefits and harms of cleansing for acute traumatic wounds: a narrative review. Adv Skin Wound Care. 2021;34(9):488-92. [Crossref]  [PubMed] 
  6. Kaviyalakshmi M, Mekala M. Review on potency of encapsulated and unencapsulated form of vitamin C produced from agricultural wastes against acute and chronic wound healing. Int J Pharm Res. 2021;13(3). [Crossref] 
  7. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;25(1):9-18. [Crossref]  [PubMed] 
  8. Sen CK. Human wounds and its burden: an updated compendium of estimates. Adv Wound Care (New Rochelle). 2019;8(2):39-48. [Crossref]  [PubMed]  [PMC] 
  9. Thomas DC, Tsu CL, Nain RA, Arsat N, Fun SS, Sahid Nik Lah NA. The role of debridement in wound bed preparation in chronic wound: a narrative review. Ann Med Surg (Lond). 2021;71:102876. [Crossref]  [PubMed]  [PMC] 
  10. Mukherjee R, Tewary S, Routray A. Diagnostic and prognostic utility of non-invasive multimodal imaging in chronic wound monitoring: a systematic review. J Med Syst. 2017;41(3):46. [Crossref]  [PubMed] 
  11. Nasiri E, Mollaei A, Birami M, Lotfi M, Rafiei MH. The risk of surgery-related pressure ulcer in diabetics: a systematic review and meta-analysis. Ann Med Surg (Lond). 2021;65:102336. [Crossref]  [PubMed]  [PMC] 
  12. Agrawal K, Chauhan N. Pressure ulcers: back to the basics. Indian J Plast Surg. 2012;45(2):244-54. [Crossref]  [PubMed]  [PMC] 
  13. Greenhalgh DG. Wound healing and diabetes mellitus. Clin Plast Surg. 2003;30(1):37-45. [Crossref]  [PubMed] 
  14. Kido D, Mizutani K, Takeda K, Mikami R, Matsuura T, Iwasaki K, et al. Impact of diabetes on gingival wound healing via oxidative stress. PLoS One. 2017;12(12):e0189601. [Crossref]  [PubMed]  [PMC] 
  15. Li J, Du R, Bian Q, Zhang D, Gao S, Yuan A, et al Topical application of HA-g-TEMPO accelerates the acute wound healing via reducing reactive oxygen species (ROS) and promoting angiogenesis. Int J Pharm. 2021;597:120328. [Crossref]  [PubMed] 
  16. Zhou X, Guo Y, Yang K, Liu P, Wang J. The signaling pathways of traditional Chinese medicine in promoting diabetic wound healing. J Ethnopharmacol. 2022;282:114662. [Crossref]  [PubMed] 
  17. Ahmad W, Khan IA, Ghaffar S, Al-Swailmi FK, Khan I. Risk factors for diabetic foot ulcer. J Ayub Med Coll Abbottabad. 2013;25(1-2):16-8. [PubMed] 
  18. Ullah S, Mansoor S, Ayub A, Ejaz M, Zafar H, Feroz F, et al. An update on stem cells applications in burn wound healing. Tissue Cell. 2021;72:101527. [Crossref]  [PubMed] 
  19. Oryan A, Alemzadeh E, Alemzadeh E, Barghi M, Zarei M, Salehiniya H. Effectiveness of the adipose stem cells in burn wound healing: literature review. Cell Tissue Bank. 2021 Sep 24. [Crossref]  [PubMed] 
  20. Sadeghipour H, Torabi R, Gottschall J, Lujan-Hernandez J, Sachs DH, Moore FD Jr, et al. Blockade of IgM-mediated inflammation alters wound progression in a swine model of partial-thickness burn. J Burn Care Res. 2017;38(3):148-60. [Crossref]  [PubMed]  [PMC] 
  21. Patel PA, Bailey JK, Yakuboff KP. Treatment outcomes for keloid scar management in the pediatric burn population. Burns. 2012;38(5):767-71. [Crossref]  [PubMed] 
  22. Vrijman C, van Drooge AM, Limpens J, Bos JD, van der Veen JP, Spuls PI, et al. Laser and intense pulsed light therapy for the treatment of hypertrophic scars: a systematic review. Br J Dermatol. 2011;165(5):934-42. [Crossref]  [PubMed] 
  23. Edlich RF, Rodeheaver GT, Thacker JG, Lin KY, Drake DB, Mason SS, et al. Revolutionary advances in the management of traumatic wounds in the emergency department during the last 40 years: part II. J Emerg Med. 2010;38(2):201-7. [Crossref]  [PubMed] 
  24. Iheozor-Ejiofor Z, Newton K, Dumville JC, Costa ML, Norman G, Bruce J. Negative pressure wound therapy for open traumatic wounds. Cochrane Database Syst Rev. 2018;7(7):CD012522. [Crossref]  [PubMed]  [PMC] 
  25. Shi C, Wang C, Liu H, Li Q, Li R, Zhang Y, et al. Selection of appropriate wound dressing for various wounds. Front Bioeng Biotechnol. 2020;8:182. [Crossref]  [PubMed]  [PMC] 
  26. Blakytny R, Jude E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabet Med. 2006;23(6):594-608. [Crossref]  [PubMed] 
  27. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1-2):113-25. [Crossref]  [PubMed]  [PMC] 
  28. Qing C. The molecular biology in wound healing & non-healing wound. Chin J Traumatol. 2017;20(4):189-93. [Crossref]  [PubMed]  [PMC] 
  29. Schultz GS, Chin GA, Moldawer L, Diegelmann RF, Fitridge R, Thompson M. Principles of wound healing. Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists [Internet]. Adelaide: University of Adelaide Press; 2011. p.423-50. [Crossref] 
  30. Tsourdi E, Barthel A, Rietzsch H, Reichel A, Bornstein SR. Current aspects in the pathophysiology and treatment of chronic wounds in diabetes mellitus. Biomed Res Int. 2013;2013:385641. [Crossref]  [PubMed]  [PMC] 
  31. Ellis S, Lin EJ, Tartar D. Immunology of wound healing. Curr Dermatol Rep. 2018;7(4):350-8. [Crossref]  [PubMed]  [PMC] 
  32. Sinno H, Prakash S. Complements and the wound healing cascade: an updated review. Plast Surg Int. 2013;2013:146764. [Crossref]  [PubMed]  [PMC] 
  33. Ridiandries A, Tan JTM, Bursill CA. The role of chemokines in wound healing. Int J Mol Sci. 2018;19(10):3217. [Crossref]  [PubMed]  [PMC] 
  34. Shah A, Amini-Nik S. The role of phytochemicals in the inflammatory phase of wound healing. Int J Mol Sci. 2017;18(5):1068. [Crossref]  [PubMed]  [PMC] 
  35. Koh TJ, DiPietro LA. Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med. 2011;13:e23. [Crossref]  [PubMed]  [PMC] 
  36. Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration. Science. 2017;356(6342):1026-30. [Crossref]  [PubMed] 
  37. Wolf SJ, Melvin WJ, Gallagher K. Macrophage-mediated inflammation in diabetic wound repair. Semin Cell Dev Biol. 2021;119:111-8. [Crossref]  [PubMed]  [PMC] 
  38. Singh S, Young A, Mcnaught CE. The physiology of wound healing. Surg. 2017;35(9):473-7. [Crossref] 
  39. Mahdavian Delavary B, van der Veer WM, van Egmond M, Niessen FB, Beelen RH. Macrophages in skin injury and repair. Immunobiology. 2011;216(7):753-62. [Crossref]  [PubMed] 
  40. Su WH, Cheng MH, Lee WL, Tsou TS, Chang WH, Chen CS, et al. Nonsteroidal anti-inflammatory drugs for wounds: pain relief or excessive scar formation? Mediators Inflamm. 2010;2010:413238. [Crossref]  [PubMed]  [PMC] 
  41. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 2002;3(5):349-63. [Crossref]  [PubMed] 
  42. Eckes B, Nischt R, Krieg T. Cell-matrix interactions in dermal repair and scarring. Fibrogenesis Tissue Repair. 2010;3:4. [Crossref]  [PubMed]  [PMC] 
  43. Leite SN, Jordão Júnior AA, Andrade TAM de, Masson D dos S, Frade MAC. Modelos experimentais de desnutrição e sua influência no trofismo cutâneo. An Bras Dermatol. 2011;86(4):681-8. [Crossref]  [PubMed] 
  44. Zhou S, Salisbury J, Preedy VR, Emery PW. Increased collagen synthesis rate during wound healing in muscle. PLoS One. 2013;8(3):e58324. [Crossref]  [PubMed]  [PMC] 
  45. Ribatti D, Crivellato E. "Sprouting angiogenesis", a reappraisal. Dev Biol. 2012;372(2):157-65. [Crossref]  [PubMed] 
  46. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161(6):1163-77. [Crossref]  [PubMed]  [PMC] 
  47. Miettinen M, Rikala MS, Rys J, Lasota J, Wang ZF. Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. Am J Surg Pathol. 2012;36(4):629-39. [Crossref]  [PubMed]  [PMC] 
  48. Moustakas A, Heldin P. TGFβ and matrix-regulated epithelial to mesenchymal transition. Biochim Biophys Acta. 2014;1840(8):2621-34. [Crossref]  [PubMed] 
  49. Tsai HW, Wang PH, Tsui KH. Mesenchymal stem cell in wound healing and regeneration. J Chin Med Assoc. 2018;81(3):223-4. [Crossref]  [PubMed] 
  50. Finnerty CC, Jeschke MG, Branski LK, Barret JP, Dziewulski P, Herndon DN. Hypertrophic scarring: the greatest unmet challenge after burn injury. Lancet. 2016;388(10052):1427-36. [Crossref]  [PubMed]  [PMC] 
  51. Kim HS, Sun X, Lee JH, Kim HW, Fu X, Leong KW. Advanced drug delivery systems and artificial skin grafts for skin wound healing. Adv Drug Deliv Rev. 2019;146:209-39. [Crossref]  [PubMed] 
  52. Sami DG, Heiba HH, Abdellatif A. Wound healing models: a systematic review of animal and non-animal models. Wound Med. 2019;24(1):8-17. [Crossref] 
  53. Ud-Din S, Bayat A. Non-animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin. Wound Repair Regen. 2017;25(2):164-76. [Crossref]  [PubMed] 
  54. Yadav E, Yadav P, Verma A. In silico study of Trianthema portulacastrum embedded iron oxide nanoparticles on glycogen synthase kinase-3β: a possible contributor to its enhanced in vivo wound healing potential. Front Pharmacol. 2021;12:664075. [Crossref]  [PubMed]  [PMC] 
  55. van den Broek LJ, Limandjaja GC, Niessen FB, Gibbs S. Human hypertrophic and keloid scar models: principles, limitations and future challenges from a tissue engineering perspective. Exp Dermatol. 2014;23(6):382-6. [Crossref]  [PubMed]  [PMC] 
  56. Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol. 2007;127(5):998-1008. [Crossref]  [PubMed] 
  57. Cho H, Won CH, Chang SE, Lee MW, Park GH. Usefulness and limitations of skin explants to assess laser treatment. Med Lasers. 2013;2(2):58-63. [Crossref] 
  58. Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2(2):329-33. [Crossref]  [PubMed] 
  59. Vidmar J, Chingwaru C, Chingwaru W. Mammalian cell models to advance our understanding of wound healing: a review. J Surg Res. 2017;210:269-80. [Crossref]  [PubMed] 
  60. Zhang M, Li H, Ma H, Qin J. A simple microfluidic strategy for cell migration assay in an in vitro wound-healing model. Wound Repair Regen. 2013;21(6):897-903. [Crossref]  [PubMed] 
  61. Li J, Zhu L, Zhang M, Lin F. Microfluidic device for studying cell migration in single or co-existing chemical gradients and electric fields. Biomicrofluidics. 2012;6(2):24121-2412113. [Crossref]  [PubMed]  [PMC] 
  62. Wei Y, Chen F, Zhang T, Chen D, Jia X, Wang J, et al. A tubing-free microfluidic wound healing assay enabling the quantification of vascular smooth muscle cell migration. Sci Rep. 2015;5:14049. [Crossref]  [PubMed]  [PMC] 
  63. Remoué N, Bonod C, Fromy B, Sigaudo-Roussel D. Animal models in chronic wound healing research: for innovations and emerging technologies in wound care. Innov Emerg Technol Wound Care. 2020;197-224. [Crossref] 
  64. Sanapalli BKR, Yele V, Singh MK, Thaggikuppe Krishnamurthy P, Karri VVSR. Preclinical models of diabetic wound healing: a critical review. Biomed Pharmacother. 2021;142:111946. [Crossref]  [PubMed] 
  65. Sueki H, Gammal C, Kudoh K, Kligman AM. Hairless guinea pig skin: anatomical basis for studies of cutaneous biology. Eur J Dermatol. 2000;10(5):357-64. [PubMed] 
  66. Suckow MA, Brammer DW, Rush HG, Chrisp CE. Biology and diseases of rabbits. Lab Anim Med. 2002;329-64. [Crossref]  [PMC] 
  67. Ren HT, Hu H, Li Y, Jiang HF, Hu XL, Han CM. Endostatin inhibits hypertrophic scarring in a rabbit ear model. J Zhejiang Univ Sci B. 2013;14(3):224-30. [Crossref]  [PubMed]  [PMC] 
  68. Naldaiz-Gastesi N, Goicoechea M, Alonso-Martín S, Aiastui A, López-Mayorga M, García-Belda P, et al. Identification and characterization of the dermal panniculus carnosus muscle stem cells. Stem Cell Reports. 2016;7(3):411-24. [Crossref]  [PubMed]  [PMC] 
  69. Okur ME, Ayla Ş, Çiçek Polat D, Günal MY, Yoltaş A, Biçeroğlu Ö. Novel insight into wound healing properties of methanol extract of Capparis ovata Desf. var. palaestina Zohary fruits. J Pharm Pharmacol. 2018;70(10):1401-13. [Crossref]  [PubMed] 
  70. Gharaboghaz MNZ, Farahpour MR, Saghaie S. Topical co-administration of Teucrium polium hydroethanolic extract and Aloe vera gel triggered wound healing by accelerating cell proliferation in diabetic mouse model. Biomed Pharmacother. 2020;127:110189. [Crossref]  [PubMed] 
  71. Chithra P, Sajithlal GB, Chandrakasan G. Influence of aloe vera on the healing of dermal wounds in diabetic rats. J Ethnopharmacol. 1998;59(3):195-201. [Crossref]  [PubMed] 
  72. Okur ME, Ayla Ş, Yozgatlı V, Aksu NB, Yoltaş A, Orak D, et al. Evaluation of burn wound healing activity of novel fusidic acid loaded microemulsion based gel in male Wistar albino rats. Saudi Pharm J. 2020;28(3):338-48. [Crossref]  [PubMed]  [PMC] 
  73. Breen A, Mc Redmond G, Dockery P, O'Brien T, Pandit A. Assessment of wound healing in the alloxan-induced diabetic rabbit ear model. J Invest Surg. 2008;21(5):261-9. [Crossref]  [PubMed] 
  74. Shrivastav A, Mishra AK, Ali SS, Ahmad A, Abuzinadah MF, Khan NA. In vivo models for assesment of wound healing potential: a systematic review. Wound Med. 2018;20:43-53. [Crossref] 
  75. Vaena MLHT, Sinnecker JP, Pinto BB, Neves MFT, Serra-Guimarães F, Marques RG. Effects of local pressure on cutaneous blood flow in pigs. Rev Col Bras Cir. 2017;44(5):498-504. [Crossref]  [PubMed] 

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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