Turkiye Klinikleri Journal of Veterinary Sciences

.: REVIEW
Süt Sığırlarında Geçirgen Bağırsak Sendromu: Geleneksel Derleme
Leaky Gut Syndrome in Dairy Cattle: Traditional Review
Elif Zeynep OĞUZa, Fatma KARAKAŞ OĞUZa
aBurdur Mehmet Akif Ersoy Üniversitesi Veteriner Fakültesi, Hayvan Besleme ve Beslenme Hastalıkları ABD, Burdur, Türkiye
Turkiye Klinikleri J Vet Sci. 2023;14(2):67-76
doi: 10.5336/vetsci.2022-93491
Article Language: TR
Full Text
ÖZET
Süt sığırlarında ketozis, asidoz gibi verimliliği olumsuz etkileyen çeşitli stres faktörleri vardır. Bu faktörler, geçirgen bağırsak sendromuna neden olabilmektedir. Bağırsak, karmaşık ve sürekli değişen ortamı kalıcı olarak algılayan, işleyen ve ona tepki veren bir duyu organıdır. Bağırsak bir bariyer ve endokrin organ olmasının yanı sıra birincil lenfoid organdır. İntestinal sistem zararlı etkenlere karşı bariyer görevi görürken, besin maddelerinin ve diğer bileşiklerin seçici emilimini içeren birçok hayati fonksiyona sahiptir. Bağırsak duvarını koruyan fiziksel ve kimyasal olmak üzere 2 tür bariyer vardır. Fiziksel bariyerler, bağırsak mukozasını kaplayan goblet hücreleri tarafından salgılanan viskoz bir mukustan oluşur. Kimyasal bariyer ise bu mukus tabakası içerisinde bulunur. Mukus tabakası içinde, epitelde paneth hücreleri tarafından üretilen antimikrobiyal peptidler ve rejenere adacık kaynaklı 3 (Reg3) molekülü bulunur. Kimyasal bariyer molekülleri, bağırsak mikroorganizmalarının parçalanmasını ve bağırsak duvarına nüfuz etmesini engellemek için çalışır. Bağırsak yüzeyinde bariyer görevi gören başka faktörler de vardır. Bunlar, mukoza yüzeyindeki sıkı bağlantı odaklarını oluşturan fosfolipidler, proteinler ve lenfositlerin de dâhil olduğu bağırsak immün sistemi ve bağırsak mikrobiyotasıdır. Bağırsak bariyerinin bozulmasıyla birlikte lipopolisakkaridlerin kana geçmesi istenmeyen sonuçlara sebep olmaktadır. Bu stres faktörlerini önlemede besleme ön plana çıkmaktadır. Bu derlemede, geçirgen bağırsak sendromu ve bu sendroma sebep olan etkenleri önlemeye dair bilgi verilmesi amaçlanmıştır.

Anahtar Kelimeler: Stres faktörleri; besleme; geçirgen bağırsak sendromu; süt sığırı
ABSTRACT
Various stress factors adversely affect productivity, such as ketosis and acidosis in dairy cattle. These factors can cause leaky gut syndrome. The gut is a sensory organ that permanently perceives, processes and responds to the complex and ever-changing environment. In addition to being a barrier and endocrine organ, the intestine is the primary lymphoid organ. While the intestinal tract acts as a barrier against harmful agents, it has many vital functions, including selective absorption of nutrients and other compounds. Two types of barriers, physical and chemical, protect the intestinal wall. Physical barriers consist of a viscous mucus secreted by the goblet cells lining the intestinal mucosa. The chemical barrier is found in this mucus layer. Within the mucus layer are antimicrobial peptides produced by paneth cells in the epithelium and 3 (Reg3) molecules from regenerated islets. Chemical barrier molecules prevent intestinal microorganisms from breaking down and penetrating the intestinal wall. Other factors act as a barrier on the intestinal surface. These are the intestinal immune system and microbiota, including the phospholipids, proteins and lymphocytes forming tight junctional foci on the mucosal surface. With the deterioration of the intestinal barrier, the passage of lipopolysaccharides into the blood causes undesirable results. Nutrition comes to the fore in preventing these stress factors. This review aims to give information about leaky gut syndrome and the prevention of factors causing it.

Keywords: Stress factors; nutrition; leaky gut syndrome; dairy cattle
REFERENCES:
  1. Sanz-Fernandez MV, Stoakes SK, Johnson JS, Abuajamieh M, Seibert JT, Pearce SC, et al. Heat Stress: What's the Gut Got To Do With It? Herd Health and Nutrition Conferences. 2015. [Link] 
  2. Rodriguez-Jimenez S, Horst EA, Mayorga EJ, Kvidera SK, Abeyta MA, Goetz BM, et al. The what, why, and physiologic cost of leaky gut syndrome. American Association of Bovine Practitioners Proceedings of the Annual Conference. 2019;165-71. [Link] 
  3. Stewart AS, Pratt-Phillips S, Gonzalez LM. Alterations in Intestinal Permeability: The Role of the "Leaky Gut" in Health and Disease. J Equine Vet Sci. 2017;52:10-22. [Crossref]  [PubMed]  [PMC] 
  4. Tabakoğlu E, Durgut R. Veteriner hekimlikte oksidatif stres ve bazı önemli hastalıklarda oksidatif stresin etkileri [Oxidative stress in veterinary medicine and effects in some important diseases]. Avkae Derg. 2013;3(1):69-75. [Link] 
  5. Di Meo S, Reed TT, Venditti P, Victor VM. Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid Med Cell Longev. 2016;2016:1245049. [Crossref]  [PubMed]  [PMC] 
  6. Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94(2):329-54. [Crossref]  [PubMed]  [PMC] 
  7. Dam B, Misra, Banerjee S. Role of Gut Microbiota in Combating Oxidative Stress. In: Chakraborti S, Chakraborti T, Chattopadhyay D, Shaha C, eds. Oxidative Stress in Microbial Diseases. 1st ed. Singapore: Springer; 2019. p.45-9. [Link] 
  8. Odenwald MA, Turner JR. Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol. 2013;11(9):1075-83. [Crossref]  [PubMed]  [PMC] 
  9. Gareau MG, Silva MA, Perdue MH. Pathophysiological mechanisms of stress-induced intestinal damage. Curr Mol Med. 2008;8(4):274-81. [Crossref]  [PubMed] 
  10. Kvidera SK, Dickson MJ, Abuajamieh M, Snider DB, Fernandez MVS, Johnson JS, et al. Intentionally induced intestinal barrier dysfunction causes inflammation, affects metabolism, and reduces productivity in lactating Holstein cows. J Dairy Sci. 2017;100(5):4113-27. [Crossref]  [PubMed] 
  11. Boudry G, Péron V, Le Huërou-Luron I, Lallès JP, Sève B. Weaning induces both transient and long-lasting modifications of absorptive, secretory, and barrier properties of piglet intestine. J Nutr. 2004;134(9):2256-62. [Crossref]  [PubMed] 
  12. Moeser AJ, Klok CV, Ryan KA, Wooten JG, Little D, Cook VL, et al. Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig. Am J Physiol Gastrointest Liver Physiol. 2007;292(1):G173-81. [Crossref]  [PubMed] 
  13. Baumgard LH, Rhoads RP Jr. Effects of heat stress on postabsorptive metabolism and energetics. Annu Rev Anim Biosci. 2013;1:311-37. [Crossref]  [PubMed] 
  14. Ruiz-González A, Rico DE, Rico JE. Modulation of fecal metabolites by heat stress and diet, and their association with ınflammation and leaky gut markers in dairy cows. Metabolites. 2022;12(2):142. [Crossref]  [PubMed]  [PMC] 
  15. Pearce SC, Mani V, Boddicker RL, Johnson JS, Weber TE, Ross JW, et al. Heat stress reduces intestinal barrier integrity and favors intestinal glucose transport in growing pigs. PLoS One. 2013;8(8):e70215. [Crossref]  [PubMed]  [PMC] 
  16. Emmanuel DG, Madsen KL, Churchill TA, Dunn SM, Ametaj BN. Acidosis and lipopolysaccharide from Escherichia coli B:055 cause hyperpermeability of rumen and colon tissues. J Dairy Sci. 2007;90(12):5552-7. [Crossref]  [PubMed] 
  17. Khafipour E, Krause DO, Plaizier JC. A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation. J Dairy Sci. 2009;92(3):1060-70. [Crossref]  [PubMed] 
  18. Minuti A, Ahmed S, Trevisi E, Piccioli-Cappelli F, Bertoni G, Jahan N, et al. Experimental acute rumen acidosis in sheep: consequences on clinical, rumen, and gastrointestinal permeability conditions and blood chemistry. J Anim Sci. 2014;92(9):3966-77. [Crossref]  [PubMed] 
  19. Zhang S, Albornoz RI, Aschenbach JR, Barreda DR, Penner GB. Short-term feed restriction impairs the absorptive function of the reticulo-rumen and total tract barrier function in beef cattle. J Anim Sci. 2013;91(4):1685-95. [Crossref]  [PubMed] 
  20. Atrian P, Shahryar HA. Heat stress in dairy cows (a review). Research in Zoology. 2012;2(4):31-7. [Link] 
  21. Hall DM, Baumgardner KR, Oberley TD, Gisolfi CV. Splanchnic tissues undergo hypoxic stress during whole body hyperthermia. Am J Physiol. 1999;276(5):G1195-203. [Crossref]  [PubMed] 
  22. Hall DM, Buettner GR, Oberley LW, Xu L, Matthes RD, Gisolfi CV. Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. Am J Physiol Heart Circ Physiol. 2001;280(2):H509-21. [Crossref]  [PubMed] 
  23. Sammad A, Wang YJ, Umer S, Lirong H, Khan I, Khan A, et al. Nutritional Physiology and Biochemistry of Dairy Cattle under the Influence of Heat Stress: Consequences and Opportunities. Animals (Basel). 2020;10(5):793. [Crossref]  [PubMed]  [PMC] 
  24. Ceciliani F, Ceron JJ, Eckersall PD, Sauerwein H. Acute phase proteins in ruminants. J Proteomics. 2012;75(14):4207-31. [Crossref]  [PubMed] 
  25. Graber CD, Reinhold RB, Breman JG, Harley RA, Hennigar GR. Fatal heat stroke. Circulating endotoxin and gram-negative sepsis as complications. JAMA. 1971;216(7):1195-6. [Crossref]  [PubMed] 
  26. Leon LR. Heat stroke and cytokines. Prog Brain Res. 2007;162:481-524. [Crossref]  [PubMed] 
  27. Chen Y, Arsenault R, Napper S, Griebel P. Models and methods to investigate acute stress responses in cattle. Animals (Basel). 2015;5(4):1268-95. [Crossref]  [PubMed]  [PMC] 
  28. Pederzolli RA, Van Kessel AG, Campbell J, Hendrick S, Wood KM, Penner GB. Effect of ruminal acidosis and short-term low feed intake on indicators of gastrointestinal barrier function in Holstein steers. J Anim Sci. 2018;96(1):108-25. [Crossref]  [PubMed]  [PMC] 
  29. Bertoni G, Trevisi E, Han X, Bionaz M. Effects of inflammatory conditions on liver activity in puerperium period and consequences for performance in dairy cows. J Dairy Sci. 2008;91(9):3300-10. [Crossref]  [PubMed] 
  30. Abuajamieh M, Kvidera SK, Fernandez MV, Nayeri A, Upah NC, Nolan EA, et al. Inflammatory biomarkers are associated with ketosis in periparturient Holstein cows. Res Vet Sci. 2016;109:81-5. [Crossref]  [PubMed] 
  31. Humblet MF, Guyot H, Boudry B, Mbayahi F, Hanzen C, Rollin F, et al. Relationship between haptoglobin, serum amyloid A, and clinical status in a survey of dairy herds during a 6-month period. Vet Clin Pathol. 2006;35(2):188-93. [Crossref]  [PubMed] 
  32. Trevisi E, Minuti A. Assessment of the innate immune response in the periparturient cow. Res Vet Sci. 2018;116:47-54. [Crossref]  [PubMed] 
  33. Newby NC, Leslie KE, Dingwell HDP, Kelton DF, Weary DM, Neuder L, et al. The effects of periparturient administration of flunixin meglumine on the health and production of dairy cattle. J Dairy Sci. 2017;100(1):582-7. [Crossref]  [PubMed] 
  34. Enemark JM. The monitoring, prevention and treatment of sub-acute ruminal acidosis (SARA): a review. Vet J. 2008;176(1):32-43. [Crossref]  [PubMed] 
  35. Kleen JL, Hooijer GA, Rehage J, Noordhuizen JP. Subacute ruminal acidosis (SARA): a review. J Vet Med A Physiol Pathol Clin Med. 2003;50(8):406-14. [Crossref]  [PubMed] 
  36. Guo J, Chang G, Zhang K, Xu L, Jin D, Bilal MS, et al. Rumen-derived lipopolysaccharide provoked inflammatory injury in the liver of dairy cows fed a high-concentrate diet. Oncotarget. 2017;8(29):46769-80. [Crossref]  [PubMed]  [PMC] 
  37. Li S, Khafipour E, Krause DO, Kroeker A, Rodriguez-Lecompte JC, Gozho GN, et al. Effects of subacute ruminal acidosis challenges on fermentation and endotoxins in the rumen and hindgut of dairy cows. J Dairy Sci. 2012;95(1):294-303. [Crossref]  [PubMed] 
  38. Lambert GP, Schmidt A, Schwarzkopf K, Lanspa S. Effect of aspirin dose on gastrointestinal permeability. Int J Sports Med. 2012;33(6):421-5. [Crossref]  [PubMed] 
  39. Briggs NG, Brennan KM, Funnell BJ, Nicholls GT, Schoonmaker JP. Use of aspirin to intentionally induce gastrointestinal tract barrier dysfunction in feedlot cattle. J Anim Sci. 2020;98(9):skaa264. [Crossref]  [PubMed]  [PMC] 
  40. Takeuchi K, Amagase K. Roles of cyclooxygenase, prostaglandin E2 and EP receptors in mucosal protection and ulcer healing in the gastrointestinal tract. Curr Pharm Des. 2018;24(18):2002-11. [Crossref]  [PubMed] 
  41. Bjarnason I, Williams P, Smethurst P, Peters TJ, Levi AJ. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut. 1986;27(11):1292-7. [Crossref]  [PubMed]  [PMC] 
  42. Bjarnason I, Hayllar J, MacPherson AJ, Russell AS. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology. 1993;104(6):1832-47. [Crossref]  [PubMed] 
  43. Gingerich DA, Baggot JD, Yeary RA. Pharmacokinetics and dosage of aspirin in cattle. J Am Vet Med Assoc. 1975;167(10):945-8. [PubMed] 
  44. Bravo DM, Wall EH. The rumen and beyond: Nutritional physiology of the modern dairy cow. J Dairy Sci. 2016;99(6):4939-40. [Crossref]  [PubMed] 
  45. Bradford BJ, Yuan K, Ylioja C. Managing complexity: Dealing with systemic crosstalk in bovine physiology. J Dairy Sci. 2016;99(6):4983-96. [Crossref]  [PubMed] 
  46. Stoakes SK, Abuajamieh M, Sanz-Fernandez V, Seibert JT, Nolan E, Rhoads RP, et al. Evaluating compounds with influence in the gut. In Proceedings of the 75th annual Minnesota Nutrition Conference. 2014. p.33-48.
  47. Singleton KD, Wischmeyer PE. Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia. Shock. 2006;25(3):295-9. [Crossref]  [PubMed] 
  48. Caroprese M, Albenzio M, Marino R, Santillo A, Sevi A. Dietary glutamine enhances immune responses of dairy cows under high ambient temperature. J Dairy Sci. 2013;96(5):3002-11. [Crossref]  [PubMed] 
  49. Zhang B, Guo Y. Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1 (ZO-1) expression in weaning piglets. Br J Nutr. 2009;102(5):687-93. [Crossref]  [PubMed] 
  50. Wang X, Valenzano MC, Mercado JM, Zurbach EP, Mullin JM. Zinc supplementation modifies tight junctions and alters barrier function of CACO-2 human intestinal epithelial layers. Dig Dis Sci. 2013;58(1):77-87. [Crossref]  [PubMed] 
  51. Mao X, Qi S, Yu B, He J, Yu J, Chen D. Zn(2+) and L-isoleucine induce the expressions of porcine β-defensins in IPEC-J2 cells. Mol Biol Rep. 2013;40(2):1547-52. [Crossref]  [PubMed] 
  52. Chauhan SS, Rashamol VP, Bagath M, Sejian V, Dunshea FR. Impacts of heat stress on immune responses and oxidative stress in farm animals and nutritional strategies for amelioration. Int J Biometeorol. 2021;65(7):1231-44. [Crossref]  [PubMed] 
  53. Buffinton GD, Doe WF. Depleted mucosal antioxidant defences in inflammatory bowel disease. Free Radic Biol Med. 1995;19(6):911-8. [Crossref]  [PubMed] 
  54. Elli M, Aydin O, Bilge S, Bozkurt A, Dagdemir A, Pinarli FG, et al. Protective effect of vitamin A on ARA-C induced intestinal damage in mice. Tumori. 2009;95(1):87-90. [Crossref]  [PubMed] 
  55. Yang Y, Yuan Y, Tao Y, Wang W. Effects of vitamin A deficiency on mucosal immunity and response to intestinal infection in rats. Nutrition. 2011;27(2):227-32. [Crossref]  [PubMed] 
  56. Kucuk O, Sahin N, Sahin K. Supplemental zinc and vitamin A can alleviate negative effects of heat stress in broiler chickens. Biol Trace Elem Res. 2003;94(3):225-35. [Crossref]  [PubMed] 
  57. Singh PK, Wise SY, Ducey EJ, Fatanmi OO, Elliott TB, Singh VK. α-Tocopherol succinate protects mice against radiation-induced gastrointestinal injury. Radiat Res. 2012;177(2):133-45. [Crossref]  [PubMed] 
  58. Sahin K, Kucuk O, Sahin N, Sari M. Effects of vitamin C and vitamin E on lipid peroxidation status, serum hormone, metabolite, and mineral concentrations of Japanese quails reared under heat stress (34 degrees C). Int J Vitam Nutr Res. 2002;72(2):91-100. [Crossref]  [PubMed] 
  59. Alhidary IA, Shini S, Al Jassim RA, Gaughan JB. Effect of various doses of injected selenium on performance and physiological responses of sheep to heat load. J Anim Sci. 2012;90(9):2988-94. [Crossref]  [PubMed] 
  60. Al-Saiady MY, Al-Shaikh MA, Al-Mufarrej SI, Al-Showeimi TA, Mogawer HH, Dirrar A. Effect of chelated chromium supplementation on lactation performance and blood parameters of Holstein cows under heat stress. Animal Feed Science and Technology. 2004;117(3-4):223-33. [Link] 
  61. Tuncer Hİ. Karma yemlerde kullanimi yasaklanan hormon, antibiyotik, antikoksidiyal ve ilaçlar [To banned usage of hormones, antibiotics, anticoccidials and drugs in compound animal feed]. Lalahan Hayvancılık Araştırma Enstitüsü Dergisi. 2007;47(1):1-9. [Link] 
  62. Cronje P. Heat stress in livestock-the role of the gut in its aetiology and a potential role for betaine in its alleviation. Recent Advances in Animal Nutrition in Australia. 2005;15:107-22. [Link] 
  63. Kettunen H, Tiihonen K, Peuranen S, Saarinen MT, Remus JC. Dietary betaine accumulates in the liver and intestinal tissue and stabilizes the intestinal epithelial structure in healthy and coccidia-infected broiler chicks. Comp Biochem Physiol A Mol Integr Physiol. 2001;130(4):759-69. [Crossref]  [PubMed] 
  64. Hassan RA, Ebeid TA, Abd El-Lateif AI, Ismail NB. Effect of dietary betaine supplementation on growth, carcass and immunity of New Zealand White rabbits under high ambient temperature. Livestock Science. 2011;135(2-3):103-9. [Link] 
  65. Peterson SE, Rezamand P, Williams JE, Price W, Chahine M, McGuire MA. Effects of dietary betaine on milk yield and milk composition of mid-lactation Holstein dairy cows. J Dairy Sci. 2012;95(11):6557-62. [Crossref]  [PubMed] 
  66. Gabler N, Frouel S, Awati A, Owusu-Asiedu A, Amerah A, Patridge G, et al. Betaine mitigates intestinal permeability in growing pigs induced by heat stress. In: Australasian Pig Science Association, Pluske JR, Pluske JM, eds. Manipulating Pig Production XIV: Proceedings of the Fourteenth Biennial Conference of the Australasian Pig Science Association (APSA), Melbourne, Australia, 24th-27th November, 2013. Australia: Australasian Pig Science Association, Werribbee, Vic.; 2013. p.24-7.
  67. Shakeri M, Cottrell JJ, Wilkinson S, Zhao W, Le HH, McQuade R, et al. Dietary Betaine Improves Intestinal Barrier Function and Ameliorates the Impact of Heat Stress in Multiple Vital Organs as Measured by Evans Blue Dye in Broiler Chickens. Animals (Basel). 2019;10(1):38. [Crossref]  [PubMed]  [PMC] 
  68. Min Y, Ma X, Sankaran K, Ru Y, Chen L, Baiocchi M, et al. Sex-specific association between gut microbiome and fat distribution. Nat Commun. 2019;10(1):2408. [Crossref]  [PubMed]  [PMC] 
  69. Kurihara M, Shioya S. Dairy cattle management in a hot environment. Food and Fertilizer Technology Center. 2003. [Link] 

.: Up To Date



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