Journal of Literature Pharmacy Sciences

Alzheimer Hastalığının Gelişiminde Kimyasal Ajanların Olası Etkileri
The Possible Effects of Chemical Agents on the Development Of Alzheimer's Disease
Ayça ADALIa, Anıl YİRÜNa,b, Belma KOÇER GÜMÜŞELc, Pınar ERKEKOĞLUa
aFarmasötik Toksikoloji ABD, Hacettepe Üniversitesi Eczacılık Fakültesi, Ankara, TÜRKİYE
bFarmasötik Toksikoloji ABD, Çukurova Üniversitesi Eczacılık Fakültesi, Adana, TÜRKİYE
cFarmasötik Toksikoloji ABD, Lokman Hekim Üniversitesi Eczacılık Fakültesi, Ankara, TÜRKİYE
J Lit Pharm Sci. 2019;8(3):214-24
doi: 10.5336/pharmsci.2019-65605
Article Language: TR
Full Text
ÖZET
Demans, düşünme ve hatırlama yeteneğinde uzun süreli ve kademeli olarak azalmaya neden olan bir hastalıktır. Alzheimer hastalığı, yaşlılardaki demansın en sık nedenidir ve bilişsel işlevlerin genel kaybı ve ölümün izlendiği, genellikle yavaş ilerleyen, kısa erimli bellek kaybı ile karakterize kronik bir nörodejeneratif hastalıktır. Hastalık ilerledikçe ruh hâli değişimleri, motivasyon kaybı, konuşma işlevlerinde bozulma, özbakım yapamama ve davranış sorunları ortaya çıkabilmektedir. Dünya genelinde yaşlı nüfus oranının giderek artması, yaşam tarzında doğallıktan uzaklaşma ve kronik hastalıkların artması Alzheimer hastalığı görülme sıklığını artırmaktadır. Bu nedenle, Alzheimer hastalığına yol açması olası faktörlerin bilinmesi, hastalığa erken dönemde tanı konması ve tedaviye mümkün olduğunca erken başlanması açısından önemlidir. Kimyasal ajan olarak çevresel kirleticilerin nöropatolojik durumları indükleyerek Alzheimer hastalığına yol açabileceği belirtilmektedir. Bu konuda toksik metaller, endüstriyel kirleticiler, hava kirleticileri, pestisitler, antimikrobiyal ajanlar konularında farklı araştırma grupları tarafından, gerek in vivo gerekse in vitro birçok farklı araştırma yapılmıştır. Ayrıca, büyük cerrahi girişimler sırasında kullanılan genel anestezikler, yaşlı hastalarda postoperatif kognitif disfonksiyon komplikasyonuna yol açabilmektedir. Bu ilaçlar sinir dokusunda inflamasyona neden olabilmektedir, bu durumda sık cerrahi girişimde bulunulan hastalarda seneler sonra Alzheimer hastalığı ortaya çıkabileceği belirtilmektedir. Bu çalışmada, Alzheimer hastalığının genel özelliklerinden bahsedilmesi; bu hastalığın patofizyolojinde rol oynayabileceği bildirilen kimyasal ajanlardan ve bu konularda yapılmış çalışmalardan söz edilmesi amaçlanmıştır.

Anahtar Kelimeler: Alzheimer hastalığı; toksik metal; antimikrobiyal ajan; endustriyel kimyasal; anestezikler
ABSTRACT
Dementhia is a disease that causes long and gradual decreases in the thinking and remembering Alzheimer's disease is the main cause of ementhia in elderly. It is mainly a longlasting neurodegenerative condition characterized with short staged memory loss, a general loss of cognitive functions and finally death. As the disease proceeds, mood changes, motivation loss, deterioration of speech, self-care and behavior problems can arise. Throughout the world, increase in incidence of Alzheimer's disease are suggested to be caused by ageing of population, widespread chronical diseases and divergence of modern lifestyle from the nature. Therefore, it is important to know these factors affecting the incidence of Alzheimer's disease and it plays a vital role in early diagnosis and medical treatment. As chemical agents, environmental pollutants might trigger Alzheimer's disease by inducing the neuropathological conditions. Many research -both in vivo and in vitro- were conducted on air pollutants, toxic metals, antimicrobial agents and industrial pollutants. In addition, the general anesthetics that are used during vital surgical operations to old patients may cause post-operative cognitive-disfunction complications. These anesthetics can also result in inflamation in neural tissue. It has been stated that Alzheimer's disease might ocur in years in patients that had frequent surgical operations. In this review, we will discuss the general characteristics of the Alzheimer's disease; the chemical agents that plays role on the pato-physiology of Alzheimer's disease and we will give a general overview of previous research on stuides conducted on chemicals agents as a cause of Alzheimer's disease.

Keywords: Alzheimer's disease; toxic metal; antimicrobial agents; industrial chemical; anesthetics
REFERENCES:
  1. Burns A, Illiffe S. Alzheimer's disease. BMJ. 2009;338(5):b158. [Crossref]  [PubMed] 
  2. Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med. 2010;362(4):329-44. [Crossref]  [PubMed] 
  3. Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease-insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol. 2017;13(10):612-23. [Crossref]  [PubMed] 
  4. Hsu D, Marshall GA. Primary and secondary prevention trials in Alzheimer disease: looking back, moving forward. Curr Alzheimer Res. 2017;14(4):426-40.
  5. Salmon DP. Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease. Curr Top Behav Neurosci. 2012;10:187-212. [Crossref]  [PubMed] 
  6. Forstl H, Kurz A. Clinical features of Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci. 1999;249(6):288-90. [Crossref]  [PubMed] 
  7. Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology. 2004;62(11):1984-9. [Crossref]  [PubMed] 
  8. Martorana A, Esposito Z, Koch G. Beyond the cholinergic hypothesis: do current drugs work in Alzheimer's disease? CNS Neurosci Ther. 2010;16(4):235-45. [Crossref]  [PubMed]  [PMC] 
  9. Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci. 1991;12(10): 383-8. [Crossref] 
  10. Yegambaram M, Manivannan B, Beach TG, Halden RU. Role of environmental contaminants in the etiology of Alzheimer's disease: a review. Curr Alzheimer Res. 2015;12(2):116-46. [Crossref]  [PubMed]  [PMC] 
  11. Tchounwou P, Yedjou C, Patlolla A, Sutton D. Heavy metal toxicity and the environment. In: Luch A, ed. Molecular, Clinical and Environmental Toxicology. 1st ed. Suiza: Springer Basel; 2012. p.133-64. [Crossref]  [PubMed]  [PMC] 
  12. Kawahara M, Kato-Negishi M. Link between aluminum and the pathogenesis of Alzheimer's disease: the integration of the aluminum and amyloid cascade hypotheses. Int J Alzheimers Dis. 2011;2011:276393. [Crossref]  [PubMed]  [PMC] 
  13. Campbell A. The potential role of aluminium in Alzheimer's disease. Nephrol Dial Transplant. 2002;17 Suppl 2:17-20. [Crossref]  [PubMed] 
  14. Rondeau V, Commenges D, Jacqmin-Gadda H, Dartigues JF. Relation between aluminum concentrations in drinking water and Alzheimer's disease: an 8-year follow-up study. Am J Epidemiol. 2000;152(1):59-66. [Crossref]  [PubMed]  [PMC] 
  15. Rondeau V, Jacqmin-Gadda H, Commenges D, Helmer C, Dartigues JF. Aluminum and silica in drinking water and the risk of Alzheimer's disease or cognitive decline: findings from 15-year follow-up of the PAQUID cohort. Am J Epidemiol. 2009;169(4):489-96. [Crossref]  [PubMed]  [PMC] 
  16. Mirza A, King A, Troakes C. Exley C. Aluminium in brain tissue in familial Alzheimer's disease. J Trace Elem Med Biol. 2017;40:30-6. [Crossref]  [PubMed] 
  17. Sparks DL, Schreurs BG. Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2003;100(19):11065-9. [Crossref]  [PubMed]  [PMC] 
  18. Singh I, Sagare AP, Coma M, Perlmutter D, Gelein R, Bell RD, et al. Low levels of copper disrupt brain amyloid-β homeostasis by altering its production and clearance. Proc Natl Acad Sci U S A. 2013;110(36):14771-6. [Crossref]  [PubMed]  [PMC] 
  19. Squitti R, Polimanti R. Copper phenotype in Alzheimer's disease: dissecting the pathway. Am J Neurodegener Dis. 2013;2(2):46-56. [Crossref]  [PubMed]  [PMC] 
  20. Thompson CM, Markesbery WR, Ehmann WD, Mao YX, Vance DE. Regional brain trace-element studies in Alzheimer's disease. Neurotoxicology. 1988;9(1):1-7.
  21. House E, Collingwood J, Khan A, Korchazkina O, Berthon G, Exley C. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Abeta42 in a manner which may have consequences for metal chelation therapy in Alzheimer's disease. J Alzheimers Dis. 2004;6(3):291-301. [Crossref]  [PubMed] 
  22. Basha MR, Wei W, Bakheet SA, Benitez N, Siddiqi HK, Ge YW, et al. The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and β-amyloid in the aging brain. J Neurosci. 2005;25(4):823-9. [Crossref]  [PubMed]  [PMC] 
  23. Bakulski KM, Rozek LS, Dolinoy DC, Paulson HL, Hu H. Alzheimer's disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics. Curr Alzheimer Res. 2012;9(5):563-73. [Crossref]  [PubMed]  [PMC] 
  24. Kim JH, Gibb HJ, Howe PD. WHO Concise International Chemical Assessment Document 69. Cobalt and Inorganic Cobalt Compounds; 2006.
  25. Mates JM, Segura JA, Alonso FJ, Marquez J. Roles of dioxins and heavy metals in cancer and neurological diseases using ROS mediated mechanisms. Free Radical Biol Med. 2010;49(9):1328-41. [Crossref]  [PubMed] 
  26. Viaene MK, Masschelein R, Leenders J, De Groof M, Swerts LJ, Roels HA. Neurobehavioural effects of occupational exposure to cadmium: a cross sectional epidemiological study. Occup Environ Med. 2000;57(1):19-27. [Crossref]  [PubMed]  [PMC] 
  27. Jiang LF, Yao TM, Zhu ZL, Wang C, Ji LN. Impacts of Cd(II) on the conformation and self-aggregation of Alzheimer's tau fragment corresponding to the third repeat of microtubule-binding domain. Biochim Biophys Acta. 2007;1774(11):1414-21. [Crossref]  [PubMed] 
  28. Pigatto PD, Costa A, Guzzi G. Are mercury and Alzheimer's disease linked? Sci Total Environ. 2018;613-614:1579-80. [Crossref]  [PubMed] 
  29. Mutter J, Curth A, Naumann J, Deth R, Walach H. Does inorganic mercury play a role in Alzheimer's disease? A systematic review and an integrated molecular mechanism. J Alzheimers Dis. 2010;22(2):357-74. [Crossref]  [PubMed] 
  30. Nielsen FH. Importance of making dietary recommendations for elements designated as nutritionally beneficial, pharmacologically beneficial, or conditioinally essential. The J Trace Elements Exp Med. 2000;13(1):113-29. [Crossref] 
  31. Dani SU. Arsenic for the fool: an exponential connection. Sci Total Environ. 2010;408(8): 1842-6. [Crossref]  [PubMed] 
  32. O'Bryant SE, Edwards M, Menon CV, Gong G, Barber R. Long-term low-level arsenic exposure is associated with poorer neuropsychological functioning: a project FRONTIER study. Int J Environ Res Public Health. 2011;8(3):861-74. [Crossref]  [PubMed]  [PMC] 
  33. Gharibzadeh S, Hoseini SS. Arsenic exposure may be a risk factor for Alzheimer's disease. J Neuropsychiatry Clin Neurosci. 2008;20(4): 501. [Crossref]  [PubMed] 
  34. Craddock TJ, Tuszynski JA, Chopra D, Casey N, Goldstein LE, Hameroff SR, et al. The zinc dyshomeostasis hypothesis of Alzheimer's disease. PLoS One. 2012;7(3):e33552. [Crossref]  [PubMed]  [PMC] 
  35. Huang X, Cuajungco MP, Atwood CS, Moir RD, Tanzi RE, Bush AI. Alzheimer's disease, β-amyloid protein and zinc. J Nutr. 2000;130(5S Suppl):1488S-92. [Crossref]  [PubMed] 
  36. Bonda DJ, Lee HG, Blair JA, Zhu X, Perry G, Smith MA. Role of metal dyshomeostasis in Alzheimer's disease. Metallomics. 2011;3(3): 267-70. [Crossref]  [PubMed]  [PMC] 
  37. Estevez AO, Mueller CL, Morgan KL, Szewczyk NJ, Teece L, Miranda-Vizuete A, et al. Selenium induces cholinergic motor neuron degeneration in Caenorhabditis elegans. Neurotoxicology. 2012;33(5):1021-32. [Crossref]  [PubMed]  [PMC] 
  38. Wang P, Wang ZY. Metal ions influx is a double edged sword for the pathogenesis of Alzheimer's disease. Ageing Res Rev. 2017;35:265-90. [Crossref]  [PubMed] 
  39. Gong G, O'Bryant SE. The arsenic exposure hypothesis for Alzheimer disease. Alzheimer Dis Assoc Disord. 2010;24(4):311-6. [Crossref]  [PubMed] 
  40. Syme CD, Nadal RC, Rigby SEJ, Viles JH. Copper binding to the amyloid-β (Aβ) peptide associated with Alzheimer's disease: folding, coordination geometry, pH dependence, stoichiometry, and affinity of Aβ-(1-28): insights from a range of complementary spectroscopic techniques. J Biol Chem. 2004;279(18): 18169-77. [Crossref]  [PubMed] 
  41. Parthasarathy S, Yoo B, McElheny D, Tay W, Ishii Y. Capturing a reactive state of amyloid aggregates: NMR-based characterization of copper-bound alzheimer disease amyloid β-fibrils in redox cycle. J Biol Chem. 2014;289(14):9998-10010. [Crossref]  [PubMed]  [PMC] 
  42. Baldi I, Lebailly P, Mohammed-Brahim B, Letenneur L, Dartigues JF, Brochard P. Neurodegenerative diseases and exposure to pesticides in the elderly. Am J Epidemiol. 2003;157(5):409-14. [Crossref]  [PubMed] 
  43. Casida JE, Durkin KA. Neuroactive insecticides: targets, selectivity, resistance, and secondary effects. Ann Rev Entomol. 2013;58(1):99-117. [Crossref]  [PubMed] 
  44. Mwila K, Burton MH, Van Dyk JS, Pletschke BI. The effect of mixtures of organophosphate and carbamate pesticides on acetylcholinesterase and application of chemometrics to identify pesticides in mixtures. Environ Monit Assess. 2013;185(3):2315-27. [Crossref]  [PubMed] 
  45. Rouimi P, Zucchini-Pascal N, Dupont G, Razpotnik A, Fouche E, De Sousa G, et al. Impacts of low doses of pesticide mixtures on liver cell defence systems. Toxicology In Vitro. 2012;26(5):718-26. [Crossref]  [PubMed] 
  46. Laetz CA, Baldwin DH, Collier TK, Hebert V, Stark JD, Scholz NL. The synergistic toxicity of pesticide mixtures: implications for risk assessment and the conservation of endangered pacific salmon. Environ Health Perspect. 2008;117(3):348-53. [Crossref]  [PubMed]  [PMC] 
  47. Singh N, Chhillar N, Banerjee B, Bala K, Basu M, Mustafa M. Organochlorine pesticide levels and risk of Alzheimer's disease in north Indian population. Hum Exp Toxicol. 2013;32(1):24-30. [Crossref]  [PubMed] 
  48. Chhillar N, Singh NK, Banerjee BD, Bala K, Sharma D, Mustafa M, et al. Γγ-hexachlorocyclohexane as a risk for Alzheimer's disease: a pilot study in North Indian population. Am J Alzheimers Dis. 2013;1:60-71. [Crossref] 
  49. Terry AV Jr. Functional consequences of repeated organophosphate exposure: potential non-cholinergic mechanisms. Pharmacol Ther. 2012;134(3):355-65. [Crossref]  [PubMed]  [PMC] 
  50. Edwards FL, Yedjou CG, Tchounwou PB. Involvement of oxidative stress in methyl parathion and parathion-induced toxicity and genotoxicity to human liver carcinoma (HepG2) cells. Environ Toxicol. 2013;28(6):342-8. [Crossref]  [PubMed]  [PMC] 
  51. Viberg H, Fredriksson A, Eriksson P. Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Toxicol Appl Pharmacol. 2003;192(2):95-106. [Crossref] 
  52. Yegambaram M, Manivannan B, Beach TG, Halden RU. Role of environmental contaminants in the etiology of Alzheimer's disease: a review. Curr Alzheimer Res. 2015;12(2):116-46. [Crossref]  [PubMed]  [PMC] 
  53. Mates JM, Segura JA, Alonso FJ, Marquez J. Roles of dioxins and heavy metals in cancer and neurological diseases using ROS-mediated mechanisms. Free Radic Biol Med. 2010;49(9):1328-41. [Crossref]  [PubMed] 
  54. Tanner CM, Goldman SM, Ross GW, Grate SJ. The disease intersection of susceptibility and exposure: chemical exposures and neurodegenerative disease risk. Alzheimers Dement. 201;10(3 Suppl):S213-25. [Crossref]  [PubMed] 
  55. Calderon-Garcidue-as L, Reed W, Maronpot RR, Henriquez-Roldan C, Delgado-Chavez R, Calderon-Garcidue-as A, et al. Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Toxicol Pathol. 2004;32(6):650-8. [Crossref]  [PubMed] 
  56. Maqbool F, Mostafalou S, Bahadar H, Abdollahi M. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms. Life Sci. 2016;145:265-73. [Crossref]  [PubMed] 
  57. Sun W, Ban JB, Zhang N, Zu YK, Sun WX. Perinatal exposure to di-(2-ethylhexyl)-phthalate leads to cognitive dysfunction and phospho-tau level increase in aged rats. Environ Toxicol. 2014;29(5):596-603. [Crossref]  [PubMed] 
  58. Exley C. Does antiperspirant use increase the risk of aluminium-related disease, including Alzheimer's disease? Mol Med Today. 1998;4(3):107-9. [Crossref] 
  59. Ahn KC, Zhao B, Chen J, Cherednichenko G, Sanmarti E, Denison MS, et al. In vitro biological activities of the antimicrobials triclocarban, its analogues, and triclosan in bioassay screens: receptor-based bioassay screens. Environ Health Perspect. 2008;116(9):1203-10. [Crossref]  [PubMed]  [PMC] 
  60. Fox M, Knapp LA, Andrews PW, Fincher CL. Hygiene and the world distribution of Alzheimer's disease: epidemiological evidence for a relationship between microbial environment and age-adjusted disease burden. Evol Med Public Health. 2013;2013(1):173-86. [Crossref]  [PubMed]  [PMC] 
  61. Halden RU. On the need and speed of regulating triclosan and triclocarban in the United States. Environ Sci Technol. 2014;48(7):3603-11. [Crossref]  [PubMed]  [PMC] 
  62. Barse AV, Chakrabarti T, Ghosh TK, Pal AK, Kumar N, Raman RP, et al. Vitellogenin induction and histo-metabolic changes following exposure of cyprinus carpio to methyl paraben. Asian Australasian J Animal Sci. 2010;23(12):1557-65. [Crossref] 
  63. Kawaguchi M, Irie K, Morohoshi K, Watanabe G, Taya K, Morita M, et al. Maternal isobutyl-paraben exposure alters anxiety and passive avoidance test performance in adult male rats. Neurosci Res. 2009;65(2):136-40. [Crossref]  [PubMed] 
  64. Block ML, Calderon-Garcidue-as L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 2009;32(9): 506-16. [Crossref]  [PubMed]  [PMC] 
  65. Moulton PV, Yang W. Air pollution, oxidative stress, and Alzheimer's disease. J Environ Public Health. 2012;2012:472751. [Crossref]  [PubMed]  [PMC] 
  66. Kim S, Knight EM, Saunders EL, Cuevas AK, Popovech M, Chen LC, et al. Rapid doubling of Alzheimer's amyloid-β40 and 42 levels in brains of mice exposed to a nickel nanoparticle model of air pollution. F1000Res. 2012;1:70. [Crossref]  [PubMed]  [PMC] 
  67. Calderon-Garcidue-as L, Kavanaugh M, Block M, D'Angiulli A, Delgado-Chivez R, Torres-Jardin R, et al. Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and downregulation of the cellular prion protein in air pollution exposed children and young adults. J Alzheimers Dis. 2012;28(1):93-107. [Crossref]  [PubMed] 
  68. Bohnen N, Warner MA, Kokmen E, Kurland LT. Early and midlife exposure to anesthesia and age of onset of Alzheimer's disease. Int J Neurosci. 1994;77(3-4):181-5. [Crossref]  [PubMed] 
  69. Bohnen NI, Warner MA, Kokmen E, Beard CM, Kurland LT. Alzheimer's disease and cumulative exposure to anesthesia: a case-control study. J Am Geriatr Soc. 1994;42(2): 198-201. [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