Article Data

  • Views 124
  • Dowloads 0

Review

Open Access

Targeting the Endothelium

  • JOSE A. ADAMS1

1Mount Sinai Medical Center Div. Neonatology 3-BLUM

DOI: 10.22514/SV51.092010.4 Vol.5,Issue S1,September 2010 pp.17-23

Published: 07 September 2010

*Corresponding Author(s): JOSE A. ADAMS E-mail: tony-adams@msmc.com

PDF (63.4 kB)

Abstract

The endothelium is an active organ with paracrine-endocrine capabilities that directs a multitude of physiological actions both locally and remotely. Cardiac arrest and resuscitation is a model of whole body ischemia reperfusion injury, inter-ventions that have their basis in cytoprotection, reduction of the inflammatory cascade, fibrinolysis and improvement of microvasculature blood flow target the endothelium. This presentation will review pharmacologic, cell targeted therapies and periodic acceleration (pGz) interventions that have the endothelium in part as the target organ. The clinical potential of such interventions as preconditioning, conditioning and postconditioning strategies associated with cardiac arrest will be defined.

Key words

endothelium, periodic acceleration (pGz), cardiac arrest, cardiopulmonary resuscitation, ischemia reperfusion, nitric oxide, shear stress

Cite And Share

JOSE A. ADAMS. Targeting the Endothelium. Signa Vitae. 2010. 5(S1);17-23.

References

4. Hutcheson IR, Griffith TM. Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow. Am J Physiol 1991;261(1 Pt 2):H257-62.

5. Li H, Wallerath T, Forstermann U. Physiological mechanisms regulating the expression of endothelial-type NO synthase. Nitric Oxide 2002;7(2):132-47.

6. Li Y, Zheng J, Bird IM, Magness RR. Effects of pulsatile shear stress on signaling mechanisms controlling nitric oxide production, endothe-lial nitric oxide synthase phosphorylation, and expression in ovine fetoplacental artery endothelial cells. Endothelium 2005;12(1-2):21-39.

7. Wu H, Jin Y, Arias J, Bassuk J, Uryash A, Kurlansky P,et al. In vivo upregulation of nitric oxide synthases in healthy rats. Nitric Oxide 2009;21(1):63-8.

8. Malek A, Izumo S. Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium. Am J Physiol 1992;263(2 Pt 1):C389-96.

9. Ohura N, Yamamoto K, Ichioka S, Sokabe T, Nakatsuka H, Baba A, et al. Global analysis of shear stress-responsive genes in vascular endothelial cells. J Atheroscler Thromb 2003;10(5):304-13.

10. Cabrales P, Tsai AG, Frangos JA, Intaglietta M. Role of endothelial nitric oxide in microvascular oxygen delivery and consumption. Free Radic Biol Med 2005;39(9):1229-37.

11. Cooper CE, Giulivi C. Nitric oxide regulation of mitochondrial oxygen consumption II: Molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 2007;292(6):C1993-2003.

12. Loke KE, Laycock SK, Mital S, Wolin MS,Berstein R, Oz M, et al. Nitric oxide modulates mitochondrial respiration in failing human heart. Circulation. 1999;100(12):1291-7.

13. Zhao X, He G, Chen YR, Pandian RP, Kuppusamy P, Zweier JL. Endothelium-derived nitric oxide regulates postischemic myocardial oxy-genation and oxygen consumption by modulation of mitochondrial electron transport. Circulation 2005;111(22):2966-72.

14. Dudzinski DM, Michel T. Life history of eNOS: partners and pathways. Cardiovasc Res 2007;75(2):247-60.

15. Grumbach IM, Chen W, Mertens SA, Harrison DG. A negative feedback mechanism involving nitric oxide and nuclear factor kappa-B modulates endothelial nitric oxide synthase transcription. J Mol Cell Cardiol 2005;39(4):595-603.

16. Adams JA. Endothelium and cardiopulmonary resuscitation. Crit Care Med 2006;34(12 Suppl):S458-65.

17. Albrecht EW, Stegeman CA, Heeringa P, Henning RH, van Goor H. Protective role of endothelial nitric oxide synthase. J Pathol 2003;199(1):8-17.

18. Dudzinski DM, Igarashi J, Greif D, Michel T. The regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol 2006;46:235-76.

19. Schulz R, Kelm M, Heusch G. Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc Res 2004;61(3):402-13.

20. Burger DE, Lu X, Lei M, Xiang FL,Hammoud J, Jinag M, et al. Neuronal nitric oxide synthase protects against myocardial infarction-induced ventricular arrhythmia and mortality in mice. Circulation 2009;120(14):1345-54.

21. Danson EJ, Choate JK, Paterson DJ. Cardiac nitric oxide: emerging role for nNOS in regulating physiological function. Pharmacol Ther 2005;106(1):57-74.

22. Wiklund L, Sharma HS, Basu S. Circulatory arrest as a model for studies of global ischemic injury and neuroprotection. Ann N Y Acad Sci 2005;1053:205-19.

23. Adams JA, Wu D, Bassuk J, Arias J, Lozano H, Lamas G, et al. Nitric oxide synthase isoform inhibition before whole body ischemia reperfu-sion in pigs: Vital or protective? Resuscitation 2007;74(3):516-25.

24. Adams JA, Wu H, Bassuk JA, Arias J, Uryash A, Jorapur V, et al. Periodic acceleration (pGz) prior to whole body Ischemia reperfusion injury provides early cardioprotective preconditioning. Life Sci 6 2010;86:707-15.

25. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74(5):1124-36.

26. Saxena P, Newman MA, Shehatha JS, Redington AN, Konstantinov IE. Remote ischemic conditioning: evolution of the concept, mecha-nisms, and clinical application. J Card Surg 2010;25(1):127-34.

27. Schmidt MR, Smerup M, Konstantinov IE, Shimizu M, Li J, Cheung M, et al. Intermittent peripheral tissue ischemia during coronary isch-emia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol 2007;292(4):H1883-90.

28. Xin P, Zhu W, Li J, Ma S, Wang L, Liu M, et al. Combined local ischemic postconditioning and remote perconditioning recapitulate the cardioprotective effects of local ischemic preconditioning. Am J Physiol Heart Circ Physiol 2010;298:H1819 -31.

29. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion. Pharmacol Ther 2007;116(2):173-91.

30. Vinten-Johansen J, Zhao ZQ, Jiang R, Zatta AJ, Dobson GP. Preconditioning and postconditioning: innate cardioprotection from ischemia-reperfusion injury. J Appl Physiol 2007;103(4):1441-8.

31. Vinten-Johansen J, Zhao ZQ, Zatta AJ, Kin H, Halkos ME, Kerendi F. Postconditioning-A new link in nature’s armor against myocardial ischemia-reperfusion injury. Basic Res Cardiol Jul 2005;100(4):295-310.

32. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Gyton RA, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 2003;285(2):H579-88.

33. Zhao ZQ, Vinten-Johansen J. Postconditioning: reduction of reperfusion-induced injury. Cardiovasc Res May 1 2006;70(2):200-11.

34. Adams JA, Bassuk JA, Arias J, Wu H, Jorapur V, Lamas GA, et al. Acute effects of “delayed postconditioning” with periodic acceleration after asphyxia induced shock in pigs. Pediatr Res 2008;64(5):533-7.

35. Argaud L, Gateau-Roesch O, Raisky O, Loufouat J, Robert D, Ovize M. Postconditioning inhibits mitochondrial permeability transition. Circulation 2005;111(2):194-7.

36. Danielisova V, Nemethova M, Gottlieb M, Burda J. The changes in endogenous antioxidant enzyme activity after postconditioning. Cell Mol Neurobiol 2006;26(7-8):1181-91.

37. Dosenko VE, Nagibin VS, Tumanovskaya LV, Zagoriy VY, Moibenko AA, Vaage J. Proteasomal proteolysis in anoxia-reoxygenation, pre-conditioning and postconditioning of isolated cardiomyocytes. Pathophysiology 2006;13(2):119-25.

38. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: new strategies for cardioprotection. Diabetes Obes Metab 2008;10:451-9.

39. Penna C, Mancardi D, Tullio F, Pagliaro P. Postconditioning and intermittent bradykinin induced cardioprotection require cyclooxygenase activation and prostacyclin release during reperfusion. Basic Res Cardiol 2009; 104:390-402.

40. Vinten-Johansen J. Postconditioning: a mechanical maneuver that triggers biological and molecular cardioprotective responses to reperfu-sion. Heart Fail Rev 2007;12(3-4):235-44.

41. Zhu M, Feng J, Lucchinetti E, Fischer G, Xu L, Pedrazzini T, et al. Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway. Cardiovasc Res 2006;72(1):152-62.

42. Teschendorf P, Padosch SA, Del Valle YFD, Peter C, Popp E, Scbneider A, et al. Effects of activated protein C on post cardiac arrest microcirculation: an in vivo microscopy study. Resuscitation 2009;80(8):940-5.

43. Larmann J, Schmidt C, Gammelin H, Van Aken HK, Frenzel T,Lanckohr C, et al. Intercellular adhesion molecule-1 inhibition attenuates neurologic and hepatic damage after resuscitation in mice. Anesthesiology 2005;103(6):1149-55.

44. Callaway CW, Rittenberger JC, Logue ES, McMichael MJ. Hypothermia after cardiac arrest does not alter serum inflammatory markers. Crit Care Med 2008;36(9):2607-12.

45. Chen F, Kondo N, Sonobe M, Fujinaga T, Wada H, Bando T. Expression of endothelial cell-specific adhesion molecules in lungs after cardiac arrest. Interact Cardiovasc Thorac Surg 2008;7(3):437-40.

46. Haynes WG, Hamer DW, Robertson CE, Webb DJ. Plasma endothelin following cardiac arrest: differences between survivors and non-survivors. Resuscitation 1994;27(2):117-22.

47. Bottiger BW, Motsch J, Bohrer H, Motsch J, Soder M, Fleischer F,et al. Activation of blood coagulation after cardiac arrest is not balanced adequately by activation of endogenous fibrinolysis. Circulation 1995;92(9):2572-8.

48. Bottiger BW, Motsch J, Braun V, Martin E, Kirschfink M. Marked activation of complement and leukocytes and an increase in the concentra-tions of soluble endothelial adhesion molecules during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humans. Crit Care Med 2002;30(11):2473-80.

49. Geppert A, Zorn G, Delle-Karth G, Heinz G, Maurer G,Siostrzonek P, et al. Plasminogen activator inhibitor type 1 and outcome after suc-cessful cardiopulmonary resuscitation. Crit Care Med 2001;29(9):1670-7.

50. Geppert A, Zorn G, Karth GD, Haumer M,Gwechenberger M, Koller-Strametz J,et al. Soluble selectins and the systemic inflammatory response syndrome after successful cardiopulmonary resuscitation. Crit Care Med 2000;28(7):2360-5.

51. Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, et al. Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome. Circulation 2002;106(5):562-8.

52. Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Current Opinnion in Critical Care 2004;10(3):208-12.

53. Adrie C, Monchi M, Laurent I, Um S, Yan SB, Thuong M,et al. Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway. J Am CollCardiol 2005;46(1):21-8.

54. Ye Y, Lin Y, Atar S, Huang MH, Perez-Polo JR, Uretsky BF,et al. Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions. Am J Physiol Heart Circ Physiol 2006;291(3):H1158-69.

55. Ludman A, Venugopal V, Yellon DM, Hausenloy DJ. Statins and cardioprotection--more than just lipid lowering? Pharmacol Ther 2009;122(1):30-43.

56. Ye Y, Martinez JD, Perez-Polo RJ, Lin Y, Uretsky BF, Birnbaum Y. The role of eNOS, iNOS, and NF-kappaB in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin. Am J Physiol Heart Circ Physiol 2008;295(1):H343-51.

57. Gori T, Sicuro S, Dragoni S, Donati G, Forconi S, Parker JD. Sildenafil prevents endothelial dysfunction induced by ischemia and reperfu-sion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study. Circulation 15 2005;111(6):742-6.

58. Szabo G, Radovits T, Veres G, Krieger N, Loganathan S, Sandner P,et al. Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass. Eur J Cardiothorac Surg 2009;36(4):657-4.

59. Piqueras L, Sanz MJ, Perretti M, Morcillo E, Norling L, Mitchell JA, et al. Activation of PPARbeta/delta inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release. J Leukoc Biol 2009;86(1):115-22.

60. Yeh CH, Chen TP, Lee CH, Wu YC, Lin YM, Lin PJ. Cardiomyocytic apoptosis following global cardiac ischemia and reperfusion can be attenuated by peroxisome proliferator-activated receptor alpha but not gamma activators. Shock 2006;26(3):262-70.

61. Touyz RM, Schiffrin EL. Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications. Vascul Pharmacol 2006;45(1):19-28.

62. Bottiger BW, Arntz HR, Chamberlain DA, Bhlumki E,Belmans A, Danays T,et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med 2008;359(25):2651-62.

63. Spohr F, Bottiger BW. Thrombolysis during cardiopulmonary resuscitation: a pilot randomised trial of thrombolysis in cardiac arrest (the TICA trial). Resuscitation 2005;64(3):389.

64. Bogoyevitch MA. An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res 2004;63(2):208-16.

65. Brines M. The therapeutic potential of erythropoiesis-stimulating agents for tissue protection: a tale of two receptors. Blood Purif 2010;29(2):86-92.

66. Peterson TE, Katusic ZS. EPO tecting the endothelium. Br J Pharmacol 2007;150(7):823-5.

67. Mihov D, Bogdanov N, Grenacher B, Gassmann M, Zünd G, Bogdanova A, et al. Erythropoietin protects from reperfusion-induced myo-cardial injury by enhancing coronary endothelial nitric oxide production. Eur J Cardiothorac Surg 2009;35(5):839-46.

68. Besler C, Doerries C, Giannotti G, Luscher TF, Landmesser U. Pharmacological approaches to improve endothelial repair mechanisms. Expert review of cardiovascular therapy. Expert Rev Cardiovasc Ther 2008;6(8):1071-82.

69. Fliser D, Bahlmann FH. Erythropoietin and the endothelium - a promising link? Eur J Clin Invest 2008;38(7):457-61.

70. Burger DE, Xiang FL, Hammoud L, Jones DL, Feng Q. Erythropoietin protects the heart from ventricular arrhythmia during ischemia and reperfusion via neuronal nitric-oxide synthase. J Pharmacol Exp Ther 2009;329(3):900-7.

71. Incagnoli P, Ramond A, Joyeux-Faure M, Pepin JL, Levy P, Ribuot C. Erythropoietin improved initial resuscitation and increased survival after cardiac arrest in rats. Resuscitation 2009;80(6):696-700.

72. Singh D, Kolarova JD, Wang S, Ayoub IM, Gazmuri RJ. Myocardial protection by erythropoietin during resuscitation from ventricular fibril-lation. Am J Ther 2007;14(4):361-8.

73. Givehchian M, Beschorner R, Ehmann C, Frauenlob L, Morgalla M, Hashemi B,et al. Neuroprotective effects of erythropoietin during deep hypothermic circulatory arrest. Eur J Cardiothorac Surg 2010;37(3):662-8.

74. Popp E, Vogel P, Teschendorf P, Bottiger BW. Effects of the application of erythropoietin on cerebral recovery after cardiac arrest in rats. Resuscitation 2007;74(2):344-51.

75. Huang CH, Hsu CY, Tsai MS, Wang TD, Chang WT, Chen WJ. Cardioprotective effects of erythropoietin on postresuscitation myocardial dysfunction in appropriate therapeutic windows. Crit Care Med Nov 2008;36(11 Suppl):S467-73.

76. Cariou A, Claessens YE, Pene F, Marx JS, Spaulding C, Hababou C, et al. Early high-dose erythropoietin therapy and hypothermia after out-of-hospital cardiac arrest: a matched control study. Resuscitation 2008;76(3):397-404.

77. Grmec S, Strnad M, Kupnik D, Sinkovic A, Gazmuri RJ. Erythropoietin facilitates the return of spontaneous circulation and survival in victims of out-of-hospital cardiac arrest. Resuscitation 2009;80(6):631-7.

78. Janssens S, Pokreisz P, Schoonjans L,Pellens M, Vermeersch P, Tjwa M, et al. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ Res 14 2004;94(9):1256-62.

79. Melo LG, Gnecchi M, Pachori AS, Kong D, wang K, Liu X,et al. Endothelium-targeted gene and cell-based therapies for cardiovascular disease. Arterioscler Thromb Vasc Biol 2004;24(10):1761-74.

80. Morishita R, Sugimoto T, Aoki M, Kida I, Tomita N, Moriguchi A,et al. In vivo transfection of cis element “decoy” against nuclear factor-kappaB binding site prevents myocardial infarction. Nat Med 1997;3(8):894-9.

81. Adams JA, Mangino MJ, Bassuk J, Inman DM, Sackner MA. Noninvasive motion ventilation (NIMV): a novel approach to ventilatory support. J Appl Physiol 2000;89(6):2438-46.

82. Adams JA, Mangino MJ, Bassuk J, Kurlansky P, Sackner MA. Regional blood flow during periodic acceleration. Crit Care Med 2001;29(10):1983-8.

83. Adams JA, Mangino MJ, Bassuk J, Kurlansky P, Sackner MA. Novel CPR with periodic Gz acceleration. Resuscitation 2001;51(1):55-62.

84. Adams JA, Mangino MJ, Bassuk J, Sackner MA. Hemodynamic effects of periodic G(z) acceleration in meconium aspiration in pigs. J Appl Physiol 2000;89(6):2447-52.

85. Adams JA, Moore JE, Jr., Moreno MR, Coelho J, Bassuk J, Wu D. Effects of periodic body acceleration on the in vivo vasoactive response to N-omega-nitro-L-arginine and the in vitro nitric oxide production. Ann Biomed Eng 2003;31(11):1337-46.

86. Adams JA, Bassuk J, Wu D, Grana M, Kurlansky P, Sackner MA. Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation factors. J Appl Physiol 2005;98(3):1083-90.

87. Adams JA, Wu H, Bassuk JA, Arias J, Uryash A, Kurlansky P. Periodic acceleration (pGz) acutely increases endothelial and neuronal nitric oxide synthase expression in endomyocardium of normal swine. Peptides 2009;30(2):373-7.

88. Lozano H, Wu D, Bassuk J, Aria J, Kurlansky P, Lamas GA,et al. The effects of prostaglandin inhibition on whole-body ischemia-reperfusion in swine. Am J Emerg Med 2008;26(1):45-53.

89. Martinez A, Arias J, Bassuk JA, Wu H, Kurlansky P, Adams JA. Adrenomedullin is increased by pulsatile shear stress on the vascular endothelium via periodic acceleration (pGz). Peptides 2008;29(1):73-8.

90. Adams JA, Bassuk JA, Arias J, Wu H, Joarpur V, Lamas GA, et al. Acute Effects of “Delayed Postconditioning” with Periodic Acceleration (pGz) After Asphyxia Induced Shock in Pigs. Pediatr Res 2008;64:533-7.

91. Martinez-Murillo R, Serrano J, Fernandez AP, Martinez A. Whole-body periodic acceleration reduces brain damage in a focal ischemia model. Neuroscience 2009;158(4):1390-6.

92. Adams JA, Bassuk J, Wu D, Kurlansky P. Survival and normal neurological outcome after CPR with periodic Gz acceleration and vasopres-sin. Resuscitation 2003;56(2):215-21.

93. Adams JA, Bassuk JA, Arias J. Periodic acceleration (pGz) CPR in a swine model of asphyxia induced cardiac arrest Short-term hemody-namic comparisons. Resuscitation 2008; 77:132-8.

94. Nava G, Adams JA, Bassuk J, Wu D, Kurlansky P, Lamas GA. Echocardiographic comparison of cardiopulmonary resuscitation (CPR) using periodic acceleration (pGz) versus chest compression. Resuscitation 2005;66(1):91-7.

95. Wu D, Bassuk J, Arias J, Peschiera I, Lamet A, Kurlansky P, et al. Post-resuscitation reperfusion injury: comparison of periodic Gz accelera-tion versus Thumper CPR. Resuscitation 2006;70(3):454-62.

96. Fujita M, Tambara, K, Ikemoto, M, Sakamoto, S, Ogai, A. Periodic Acceleration Enhances Release of Nitric Oxide in Healthy Adults. Int J Angiol 2005;14:11-14.

97. Fukuda S, Shimada K, Kawasaki T, Kono Y,Jissho S, Taguchi H,et al. “Passive exercise” using whole body periodic acceleration: effects on coronary microcirculation. Am Heart J Apr 2010;159(4):620-6.

98. Kohler M, Amann-Vesti BR, Clarenbach CF, Vrack T, Noll G, Russi EW, et al. Periodic whole body acceleration: a novel therapy for cardio-vascular disease. Vasa 2007;36(4):261-6.

99. Sackner MA, Gummels E, Adams JA. Nitric oxide is released into circulation with whole-body, periodic acceleration. Chest 2005;127(1):30-9.

100. Sackner MA, Gummels EM, Adams JA. Say NO to fibromyalgia and chronic fatigue syndrome: an alternative and complementary therapy to aerobic exercise. Med Hypotheses 2004;63(1):118-23.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) The Science Citation Index (SCI) is a citation index originally produced by the Institute for Scientific Information (ISI) and created by Eugene Garfield. It (Science Citation Index Expanded) covers more than 8,500 notable and significant journals, across 150 disciplines in science and technology, from 1900 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

IndexCopernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time

Conferences

    Top