<?xml version="1.0" encoding="utf-8"?>
<XML>
<JOURNAL>
<YEAR>2015</YEAR>
<VOL>19</VOL>
<NO>3</NO>
<MOSALSAL>58</MOSALSAL>
<PAGE_NO>215</PAGE_NO>


<ARTICLES>

	<ARTICLE> 
		<TitleF>A comprehensive approach to investigate the contradictory effects of metformin therapy in cerebral ischemic injury</TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Ischemic brain injury involves a complex sequence of excitetoxic and oxidative events. Metformin is proposed as one of the potential candidates for returning the body to its basic homeostasis in ischemic situations. Metformin can either protect or damage cells by activating AMP-activated protein kinase (AMPK) and its downstream factors so, it has a dual role in the cerebral ischemia context, but more investigations are needed to define its exact underlying mechanism. Herein, we classify the controversial results of metformin therapy in the experimental models of brain ischemia central and peripheral injection of metformin, chronic and acute treatment, pre- and post-treatment with metformin, tissue-specific role of metformin, dose-specific effect of metformin, age-dependent aspects of metformin therapy. Categorizing different types of cerebral ischemia is important in investigating the dual role of metformin. Due to the variations in metformin therapy, it can be used for chronic treatment, but the patients must be informed about its harmful effects. Although the mechanisms in which AMPK protects/degenerates neurons against ischemic stress situation are still unknown.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>146</FPAGE>
			<TPAGE>157</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/1
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/5/10
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/1
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/8/10
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Ghorbangol</Name>
				<MidName></MidName>
				<Family>Ashabi</Family>
				<NameE>Ghorbangol</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Ashabi</FamilyE>
				<Organizations>
				<Organization>Physiology Research Center and Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>as_habi@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Fariba</Name>
				<MidName></MidName>
				<Family>Khodagholi</Family>
				<NameE>Fariba</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Khodagholi</FamilyE>
				<Organizations>
				<Organization>Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>Khodagholi@sbmu.ac.ir</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Shima</Name>
				<MidName></MidName>
				<Family>Zare-shahamati</Family>
				<NameE>Shima</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Zare-shahamati</FamilyE>
				<Organizations>
				<Organization>NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>SZS1992@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Negar</Name>
				<MidName></MidName>
				<Family>Ghadernezhad</Family>
				<NameE>Negar</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Ghadernezhad</FamilyE>
				<Organizations>
				<Organization>Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>negar.gh1986@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Mona</Name>
				<MidName></MidName>
				<Family>Maleki</Family>
				<NameE>Mona</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Maleki</FamilyE>
				<Organizations>
				<Organization>Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>monamaleki28@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Leila</Name>
				<MidName></MidName>
				<Family>Khalaj</Family>
				<NameE>Leila</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Khalaj</FamilyE>
				<Organizations>
				<Organization>Medical School, Alborz University of Medical Sciences, Alborz, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>lkhalaj@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Metformin</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>AMPK</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Glucose</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Brain</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Ischemia</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Abdelsaid M, Prakash R, Li W, Coucha M, Hafez S, Johnson MH, et al. Metformin treatment in the period after stroke prevents nitrative stress and restores angiogenic signaling in the brain in diabetes. Diabetes 64(2015) 1804-17.##Anyanwu EC. Neurochemical changes in the aging process: Implications in medication in the elderly. ScientificWorldJournal 7(2007) 1603-10.##Ashabi G, Khalaj L, Khodagholi F, Goudarzvand M, Sarkaki A. Pre-treatment with metformin activates nrf2 antioxidant pathways and inhibits inflammatory responses through induction of ampk after transient global cerebral ischemia. Metab Brain Dis 30(2015) 747-54.##Ashabi G, Khodagholi F, Khalaj L, Goudarzvand M, Nasiri M. Activation of amp-activated protein kinase by metformin protects against global cerebral ischemia in male rats: Interference of ampk/pgc-1alpha pathway. Metab Brain Dis 29(2014) 47-58.##Atherton PJ, Babraj J, Smith K, Singh J, Rennie MJ, Wackerhage H. Selective activation of ampk-pgc-1alpha or pkb-tsc2-mtor signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 19(2005) 786-8.##Athyros VG, Kakafika AI, Tziomalos K, Papageorgiou AA, Karagiannis A. Statins for the prevention of first or recurrent stroke. Curr Vasc Pharmacol 6(2008) 124-33.##Bailey CJ, Turner RC. Metformin. N Engl J Med 334(1996) 574-9.##Brathwaite S, Macdonald RL. Current management of delayed cerebral ischemia: Update from results of recent clinical trials. Transl Stroke Res 5(2013) 207-26.##Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21(2001) 2-14.##Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D. Characterization of amp-activated protein kinase gamma-subunit isoforms and their role in amp binding. Biochem J 346 Pt 3(2000) 659-69.##den Hertog HM, Vermeer SE, Zandbergen AA, Achterberg S, Dippel DW, Algra A, et al. Safety and feasibility of metformin in patients with impaired glucose tolerance and a recent tia or minor ischemic stroke (limit) trial - a multicenter, randomized, open-label phase ii trial. Int J Stroke (2013).##Dietrich WD, Alonso O, Busto R. Moderate hyperglycemia worsens acute blood-brain barrier injury after forebrain ischemia in rats. Stroke 24(1993) 111-6.##Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: An integrated view. Trends Neurosci 22(1999) 391-7.##Dorce VA, Palermo-Neto J. Behavioral and neurochemical changes induced by aging in dopaminergic systems of male and female rats. Physiol Behav 56(1994) 1015-9.##Du L, Hickey RW, Bayir H, Watkins SC, Tyurin VA, Guo F, et al. Starving neurons show sex difference in autophagy. J Biol Chem 284(2009) 2383-96.##Du L, Zhang X, Han YY, Burke NA, Kochanek PM, Watkins SC, et al. Intra-mitochondrial poly(adp-ribosylation) contributes to nad+ depletion and cell death induced by oxidative stress. J Biol Chem 278(2003) 18426-33.##El Messaoudi S, Rongen GA, de Boer RA, Riksen NP. The cardioprotective effects of metformin. Curr Opin Lipidol 22(2011) 445-53.##Elgebaly MM, Prakash R, Li W, Ogbi S, Johnson MH, Mezzetti EM, et al. Vascular protection in diabetic stroke: Role of matrix metalloprotease-dependent vascular remodeling. J Cereb Blood Flow Metab 30(2010) 1928-38.##Farbood Y, Sarkaki A, Khalaj L, Khodagholi F, Badavi M, Ashabi G. Targeting adenosine monophosphate-activated protein kinase by metformin adjusts post-ischemic hyperemia and extracellular neuronal discharge in transient global cerebral ischemia. Microcirculation 22(2015a) 534-41.##Farbood Y, Sarkaki A, Khalaj L, Khodagholi F, Badavi M, Ashabi G. Targeting ampk by metformin adjusts post-ischemic hyperemia and extracellular neuronal discharge in transient global cerebral ischemia. Microcirculation (2015b).##Faure P, Wiernsperger N, Polge C, Favier A, Halimi S. Impairment of the antioxidant properties of serum albumin in patients with diabetes: Protective effects of metformin. Clin Sci (Lond) 114(2008) 251-6.##Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J 36(2015) 2288-96.##Fujita-Hamabe W, Harada S, Tokuyama S. [effectiveness of metformin in prevention of development of hyperglycemia and neuronal damage caused by ischemic stress]. Yakugaku Zasshi 131(2011) 533-8.##Furlow TW, Jr. Cerebral ischemia produced by four-vessel occlusion in the rat: A quantitative evaluation of cerebral blood flow. Stroke 13(1982) 852-5.##Galardo MN, Riera MF, Pellizzari EH, Cigorraga SB, Meroni SB. The amp-activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-b-d-ribonucleoside, regulates lactate production in rat sertoli cells. J Mol Endocrinol 39(2007) 279-88.##Gray CS, Scott JF, French JM, Alberti KG, O\'Connell JE. Prevalence and prediction of unrecognised diabetes mellitus and impaired glucose tolerance following acute stroke. Age Ageing 33(2004) 71-7.##Ha HC, Snyder SH. Poly(adp-ribose) polymerase-1 in the nervous system. Neurobiol Dis 7(2000) 225-39.##Harada S, Fujita-Hamabe W, Tokuyama S. The importance of regulation of blood glucose levels through activation of peripheral 5\'-amp-activated protein kinase on ischemic neuronal damage. Brain Res 1351(2010) 254-63.##Harada S, Fujita-Hamabe W, Tokuyama S. Ischemic stroke and glucose intolerance: A review of the evidence and exploration of novel therapeutic targets. J Pharmacol Sci 118(2011) 1-13.##Harada S, Fujita WH, Shichi K, Tokuyama S. The development of glucose intolerance after focal cerebral ischemia participates in subsequent neuronal damage. Brain Res 1279(2009) 174-81.##Hardie DG, Hawley SA. Amp-activated protein kinase: The energy charge hypothesis revisited. Bioessays 23(2001) 1112-9.##He L, Sabet A, Djedjos S, Miller R, Sun X, Hussain MA, et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of creb binding protein. Cell 137(2009) 635-46.##He Z, Cui L, Meschia JF, Dickson DW, Brott TG, Simpkins JW, et al. Hippocampal progenitor cells express nestin following cerebral ischemia in rats. Neuroreport 16(2005) 1541-4.##He Z, He YJ, Day AL, Simpkins JW. Proestrus levels of estradiol during transient global cerebral ischemia improves the histological outcome of the hippocampal ca1 region: Perfusion-dependent and-independent mechanisms. J Neurol Sci 193(2002) 79-87.##Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359(2008) 1577-89.##Horman S, Vertommen D, Heath R, Neumann D, Mouton V, Woods A, et al. Insulin antagonizes ischemia-induced thr172 phosphorylation of amp-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of ser485/491. J Biol Chem 281(2006) 5335-40.##Hou X, Xu S, Maitland-Toolan KA, Sato K, Jiang B, Ido Y, et al. Sirt1 regulates hepatocyte lipid metabolism through activating amp-activated protein kinase. J Biol Chem 283(2008) 20015-26.##Jiang T, Yu JT, Zhu XC, Wang HF, Tan MS, Cao L, et al. Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre-activation of ampk-dependent autophagy. Br J Pharmacol 171(2014) 3146-57.##Kernan WN, Viscoli CM, Inzucchi SE, Brass LM, Bravata DM, Shulman GI, et al. Prevalence of abnormal glucose tolerance following a transient ischemic attack or ischemic stroke. Arch Intern Med 165(2005) 227-33.##Kim M, Tian R. Targeting ampk for cardiac protection: Opportunities and challenges. J Mol Cell Cardiol 51(2011) 548-53.##Kristensen JM, Larsen S, Helge JW, Dela F, Wojtaszewski JF. Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of ampk kinase dead but not wild type mice. PLoS One 8(2013) e53533.##Kuramoto N, Wilkins ME, Fairfax BP, Revilla-Sanchez R, Terunuma M, Tamaki K, et al. Phospho-dependent functional modulation of gaba(b) receptors by the metabolic sensor amp-dependent protein kinase. Neuron 53(2007) 233-47.##Labuzek K, Suchy D, Gabryel B, Bielecka A, Liber S, Okopien B. Quantification of metformin by the hplc method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol Rep 62(2010) 956-65.##Li J, Benashski SE, Venna VR, McCullough LD. Effects of metformin in experimental stroke. Stroke 41(2010) 2645-52.##Li J, McCullough LD. Effects of amp-activated protein kinase in cerebral ischemia. J Cereb Blood Flow Metab 30(2009) 480-92.##Li J, McCullough LD. Effects of amp-activated protein kinase in cerebral ischemia. J Cereb Blood Flow Metab 30(2010) 480-92.##Li J, Zeng Z, Viollet B, Ronnett GV, McCullough LD. Neuroprotective effects of adenosine monophosphate-activated protein kinase inhibition and gene deletion in stroke. Stroke 38(2007) 2992-9.##Li W, Prakash R, Kelly-Cobbs AI, Ogbi S, Kozak A, El-Remessy AB, et al. Adaptive cerebral neovascularization in a model of type 2 diabetes: Relevance to focal cerebral ischemia. Diabetes 59(2009) 228-35.##Li W, Qu Z, Prakash R, Chung C, Ma H, Hoda MN, et al. Comparative analysis of the neurovascular injury and functional outcomes in experimental stroke models in diabetic goto-kakizaki rats. Brain Res 1541(2013) 106-14.##Liu F, Benashski SE, Persky R, Xu Y, Li J, McCullough LD. Age-related changes in amp-activated protein kinase after stroke. Age (Dordr) 34(2011) 157-68.##Liu F, Yuan R, Benashski SE, McCullough LD. Changes in experimental stroke outcome across the life span. J Cereb Blood Flow Metab 29(2009) 792-802.##Liu XS, Chopp M, Zhang RL, Zhang ZG. Micrornas in cerebral ischemia-induced neurogenesis. J Neuropathol Exp Neurol 72(2013) 718-22.##Liu Y, Tang G, Li Y, Wang Y, Chen X, Gu X, et al. Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion. J Neuroinflammation 11(2014a) 177.##Liu Y, Tang G, Zhang Z, Wang Y, Yang GY. Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion. Neurosci Lett 579C(2014b) 46-51.##Love S. Apoptosis and brain ischaemia. Prog Neuropsychopharmacol Biol Psychiatry 27(2003) 267-82.##McCullough LD, Zeng Z, Li H, Landree LE, McFadden J, Ronnett GV. Pharmacological inhibition of amp-activated protein kinase provides neuroprotection in stroke. J Biol Chem 280(2005) 20493-502.##McGuinness ME, Talbert RL. Phenformin-induced lactic acidosis: A forgotten adverse drug reaction. Ann Pharmacother 27(1993) 1183-7.##Mielke JG, Taghibiglou C, Wang YT. Endogenous insulin signaling protects cultured neurons from oxygen-glucose deprivation-induced cell death. Neuroscience 143(2006) 165-73.##Modi G, Modi M, Mochan A. Stroke and hiv--causal or coincidental co-occurrence? S Afr Med J 96(2006) 1247-8.##Moler FW, Meert K, Donaldson AE, Nadkarni V, Brilli RJ, Dalton HJ, et al. In-hospital versus out-of-hospital pediatric cardiac arrest: A multicenter cohort study. Crit Care Med 37(2009) 2259-67.##Mukherjee P, Mulrooney TJ, Marsh J, Blair D, Chiles TC, Seyfried TN. Differential effects of energy stress on ampk phosphorylation and apoptosis in experimental brain tumor and normal brain. Mol Cancer 7(2008) 37.##Mulligan JD, Gonzalez AA, Kumar R, Davis AJ, Saupe KW. Aging elevates basal adenosine monophosphate-activated protein kinase (ampk) activity and eliminates hypoxic activation of ampk in mouse liver. J Gerontol A Biol Sci Med Sci 60(2005) 21-7.##Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the american diabetes association and the european association for the study of diabetes. Diabetes Care 32(2009) 193-203.##Ni Chroinin D, Asplund K, Asberg S, Callaly E, Cuadrado-Godia E, Diez-Tejedor E, et al. Statin therapy and outcome after ischemic stroke: Systematic review and meta-analysis of observational studies and randomized trials. Stroke 44(2013) 448-56.##Ostergaard L, Aamand R, Karabegovic S, Tietze A, Blicher JU, Mikkelsen IK, et al. The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. J Cereb Blood Flow Metab 33(2013) 1825-37.##Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: Possible role in insulin resistance. Science 300(2003) 1140-2.##Petticrew M. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (ukpds 34). Uk prospective diabetes study (ukpds) group. Lancet 352(1998) 854-65.##Pomfy M, Franko J. Validation of a four-vessel occlusion model for transient global cerebral ischemia in dogs. J Hirnforsch 39(1999) 465-71.##Prakash R, Li W, Qu Z, Johnson MA, Fagan SC, Ergul A. Vascularization pattern after ischemic stroke is different in control versus diabetic rats: Relevance to stroke recovery. Stroke 44(2013) 2875-82.##Price G. Metformin lactic acidosis, acute renal failure and rofecoxib. Br J Anaesth 91(2003) 909-10.##Qiang W, Weiqiang K, Qing Z, Pengju Z, Yi L. Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing ampkalpha. Exp Mol Med 39(2007) 535-43.##Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, et al. Aging-associated reductions in amp-activated protein kinase activity and mitochondrial biogenesis. Cell Metab 5(2007) 151-6.##Rojas J, Arraiz N, Aguirre M, Velasco M, Bermudez V. Ampk as target for intervention in childhood and adolescent obesity. J Obes 2011(2011) 252817.##Ronnett GV, Aja S. Amp-activated protein kinase in the brain. Int J Obes (Lond) 32 Suppl 4(2008) S42-8.##Ronnett GV, Ramamurthy S, Kleman AM, Landree LE, Aja S. Ampk in the brain: Its roles in energy balance and neuroprotection. J Neurochem 109 Suppl 1(2009) 17-23.##Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, et al. Heart disease and stroke statistics--2008 update: A report from the american heart association statistics committee and stroke statistics subcommittee. Circulation 117(2008) e25-146.##Rosen P, Wiernsperger NF. Metformin delays the manifestation of diabetes and vascular dysfunction in goto-kakizaki rats by reduction of mitochondrial oxidative stress. Diabetes Metab Res Rev 22(2006) 323-30.##Sanderson TH, Wider JM. 2-vessel occlusion/hypotension: A rat model of global brain ischemia. J Vis Exp (2013).##Sanossian N, Saver JL, Rajajee V, Selco SL, Kim D, Razinia T, et al. Premorbid antiplatelet use and ischemic stroke outcomes. Neurology 66(2006) 319-23.##Sarkaki A, Farbood Y, Badavi M, Khalaj L, Khodagholi F, Ashabi G. Metformin improves anxiety-like behaviors through ampk-dependent regulation of autophagy following transient forebrain ischemia. Metab Brain Dis (2015).##Seo-Mayer PW, Thulin G, Zhang L, Alves DS, Ardito T, Kashgarian M, et al. Preactivation of ampk by metformin may ameliorate the epithelial cell damage caused by renal ischemia. Am J Physiol Renal Physiol 301(2011) F1346-57.##Slemmer JE, Shacka JJ, Sweeney MI, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem 15(2008) 404-14.##Smiley D, Umpierrez G. Metformin/rosiglitazone combination pill (avandamet) for the treatment of patients with type 2 diabetes. Expert Opin Pharmacother 8(2007) 1353-64.##Snider BJ, Gottron FJ, Choi DW. Apoptosis and necrosis in cerebrovascular disease. Ann N Y Acad Sci 893(1999) 243-53.##Soraya H, Khorrami A, Garjani A, Maleki-Dizaji N, Garjani A. Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats. Pharmacol Rep 64(2012) 1476-84.##Szabo C, Dawson VL. Role of poly(adp-ribose) synthetase in inflammation and ischaemia-reperfusion. Trends Pharmacol Sci 19(1998) 287-98.##Takata F, Dohgu S, Matsumoto J, Machida T, Kaneshima S, Matsuo M, et al. Metformin induces up-regulation of blood-brain barrier functions by activating amp-activated protein kinase in rat brain microvascular endothelial cells. Biochem Biophys Res Commun 433(2013) 586-90.##Towfighi A, Saver JL. Stroke declines from third to fourth leading cause of death in the united states: Historical perspective and challenges ahead. Stroke 42(2011) 2351-5.##Tuerk RD, Thali RF, Auchli Y, Rechsteiner H, Brunisholz RA, Schlattner U, et al. New candidate targets of amp-activated protein kinase in murine brain revealed by a novel multidimensional substrate-screen for protein kinases. J Proteome Res 6(2007) 3266-77.##Turnley AM, Stapleton D, Mann RJ, Witters LA, Kemp BE, Bartlett PF. Cellular distribution and developmental expression of amp-activated protein kinase isoforms in mouse central nervous system. J Neurochem 72(1999) 1707-16.##Tziomalos K, Giampatzis V, Bouziana SD, Spanou M, Pavlidis A, Papadopoulou M, et al. Effect of prior treatment with different statins on stroke severity and functional outcome at discharge in patients with acute ischemic stroke. Int J Stroke 8(2013) E49.##Vancheri F, Curcio M, Burgio A, Salvaggio S, Gruttadauria G, Lunetta MC, et al. Impaired glucose metabolism in patients with acute stroke and no previous diagnosis of diabetes mellitus. QJM 98(2005) 871-8.##Venna VR, Li J, Hammond MD, Mancini NS, McCullough LD. Chronic metformin treatment improves post-stroke angiogenesis and recovery after experimental stroke. Eur J Neurosci 39(2014) 2129-38.##Vytla VS, Ochs RS. Metformin increases mitochondrial energy formation in l6 muscle cell cultures. J Biol Chem 288(2013) 20369-77.##Wang W, Guan KL. Amp-activated protein kinase and cancer. Acta Physiol (Oxf) 196(2009) 55-63.##Wang W, Yang X, Lopez de Silanes I, Carling D, Gorospe M. Increased amp:Atp ratio and amp-activated protein kinase activity during cellular senescence linked to reduced hur function. J Biol Chem 278(2003) 27016-23.##Wei RL, Teng HJ, Yin B, Xu Y, Du Y, He FP, et al. A systematic review and meta-analysis of buyang huanwu decoction in animal model of focal cerebral ischemia. Evid Based Complement Alternat Med 2013(2013) 138484.##Wellons JC, 3rd, Sheng H, Laskowitz DT, Mackensen GB, Pearlstein RD, Warner DS. A comparison of strain-related susceptibility in two murine recovery models of global cerebral ischemia. Brain Res 868(2000) 14-21.##Yenari MA, Han HS. Influence of therapeutic hypothermia on regeneration after cerebral ischemia. Front Neurol Neurosci 32(2013) 122-8.##Yeung CW, Chung HY, Fong BM, Tsai NW, Chan WM, Siu TS, et al. Metformin-associated lactic acidosis in chinese patients with type ii diabetes. Pharmacology 88(2011) 260-5.##Ying W, Garnier P, Swanson RA. Nad+ repletion prevents parp-1-induced glycolytic blockade and cell death in cultured mouse astrocytes. Biochem Biophys Res Commun 308(2003) 809-13.##Zou MH, Hou XY, Shi CM, Kirkpatick S, Liu F, Goldman MH, et al. Activation of 5\'-amp-activated kinase is mediated through c-src and phosphoinositide 3-kinase activity during hypoxia-reoxygenation of bovine aortic endothelial cells. Role of peroxynitrite. J Biol Chem 278(2003) 34003-10.#### ##</REF>
			</REFRENCE>
		</REFRENCES>

	</ARTICLE>


	<ARTICLE> 
		<TitleF>Long-term, high-dose aspirin therapy increases the specific activity of complex III of mitochondrial respiratory chain in the kidney of diabetic rats</TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Introduction: One of the main mechanisms by which diabetic complications occur is an alteration of the structure and function of proteins due to hyperglycemia. Aspirin (ASA) affects cellular pathways through different mechanisms, including glycation inhibition and antioxidant activity. The aim of the present study, as a follow up to our previous one, is to investigate the effect of long-term, high-dose ASA therapy on mitochondrial respiratory chain complexes in the kidneys and brain of streptozotocin-induced diabetic rats. Its effect on liver toxicity of the rats was also investigated. Materials and Methods: High dose of ASA (100 mg/kg in drinking water) was administered to streptozotocin-induced diabetic rats during the twelve-week study period. After that, the rats were sacrificed under anesthesia and the tissues were retained -80 °C. Then the activity of respiratory chain complexes and the mentioned enzyme were measured in the brain, kidney, liver and serum of rats. Results: Treatment of diabetic rats with ASA could significantly compensate for the decreased activity of complex III respiratory chain in the kidneys. In addition, the activity of the liver enzymes (ALT, AST, ALP and LDH) in the serum of diabetic rats was significantly reduced by administration of ASA. However, there were no other significant functional changes observed in the kidney and brain respiratory chains complexes and the mentioned enzymes in liver. Conclusion: In conclusion, ASA therapy has a beneficial effect on the mitochondrial complexes and some serum enzymes in diabetic rats.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>158</FPAGE>
			<TPAGE>166</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/12015/04/12
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/1/23
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/12015/10/22
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/7/30
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Mohammad Reza</Name>
				<MidName></MidName>
				<Family>Ashoori</Family>
				<NameE>Mohammad Reza</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Ashoori</FamilyE>
				<Organizations>
				<Organization>Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>ashoori_mr57@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>S. Zahra</Name>
				<MidName></MidName>
				<Family>Bathaie</Family>
				<NameE>S. Zahra</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Bathaie</FamilyE>
				<Organizations>
				<Organization>Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>zbatha2000@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Hamid</Name>
				<MidName></MidName>
				<Family>Heidarzadeh</Family>
				<NameE>Hamid</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Heidarzadeh</FamilyE>
				<Organizations>
				<Organization>Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>hami_heidarzadeh@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Aspirin</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Streptozotocin</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Respiratory Chain Complex</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Brain</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Kidney</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Liver Enzymes</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Angiolillo DJ, Suryadevara S. Aspirin and clopidogrel: Efficacy and resistance in diabetes mellitus. Best Pract Res Clin Endocrinol Metab 2009; 23: 375-88.##Arvanitakis C, Chen G, Folscroft J, Greenberger N. Effect of aspirin on intestinal absorption of glucose, sodium, and water in man. Gut 1977; 18: 187-90.##Bathaie S, Nikfarjam L, Rahmanpour R, Moosavi–Movahedi A. Spectroscopic studies of the interaction of aspirin and its important metabolite, salicylate ion, with DNA, A.T and G.C rich sequences. Spectrochimica Acta 2010; 77: 1-27.##Benard G, Faustin B, Passerieux E, Galinier A, Rocher C, Bellance N, et al. Physiological diversity of mitochondrial oxidative phosphorylation. Am J Physiol Cell Physiol 2006; 291: C1172-82.##Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 2002; 5: 561-8.##Bradford MM. A rapid and sensitive method for the quantitative of microgram quantities of protein utilizing the principal of protein-dye binding. Anal biochem 1976; 72:248-254: 248-254.##Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-20.##Caballero F, Gerez E, Batlle A, Vazquez E. Preventive aspirin treatment of streptozotocin induced diabetes: Blockage of oxidative status and revertion of heme enzymes inhibition. Chem Biol Interact 2000; 126: 215-25.##Chavez E, Castro-Sanchez L, Shibayama M, Tsutsumi V, Perez Salazar E, Moreno MG, et al. Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by ccl4. J Appl Toxicol 2012; 32: 51-9.##Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of reactive oxygen species by mitochondria: Central role of complex iii. J Biol Chem 2003; 278: 36027-31.##Chowdhury SK, Zherebitskaya E, Smith DR, Akude E, Chattopadhyay S, Jolivalt CG, et al. Mitochondrial respiratory chain dysfunction in dorsal root ganglia of streptozotocin-induced diabetic rats and its correction by insulin treatment. Diabetes; 59: 1082-91.##Dervisevik M, Dinevska-Kovkarovska S, Dimitrovska M, Cipanovska N, Miova B. High dose of aspirin moderates diabetes-induced changes of heart glycogen/glucose metabolism in rats. J Physiol Sci 2014; 64: 411-20.##Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the akt site. J Clin Invest 2001; 108: 1341-8##Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996; 19: 257-67.##Goldberg DM, Martin JV, Knight AH. Elevation of serum alkaline phosphatase activity and related enzymes in diabetes mellitus. Clin Biochem 1977; 10: 8-11.##Gredilla R, Phaneuf S, Selman C, Kendaiah S, Leeuwenburgh C, Barja G. Short-term caloric restriction and sites of oxygen radical generation in kidney and skeletal muscle mitochondria. Ann N Y Acad Sci 2004; 1019: 333-42.##Hadley J, Malik N, Meek K. Collagen as a model system to investigate the use of aspirin as an inhibitor of protein glycation and crosslinking. Micron 2001; 32: 307-15.##Hamden K, Carreau S, Boujbiha MA, Lajmi S, Aloulou D, Kchaou D, et al. Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: Protective effect of 17 beta-estradiol. Steroids 2008; 73: 495-501.##Hanna AN, Waldman WJ, Lott JA, Koesters SC, Hughes AM, Thornton DJ. Increased alkaline phosphatase isoforms in autoimmune diseases. Clin Chem 1997; 43: 1357-64.##Harding JJ, Ganea E. Protection against glycation and similar post-translational modifications of proteins. Biochim Biophys Acta 2006; 1764: 1436-46.##Hundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, et al. Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest 2002; 109: 1321-6.##Jafarnejad A, Bathaie SZ, Nakhjavani M, Hassan MZ. Effect of spermine on lipid profile and hdl functionality in the streptozotocin-induced diabetic rat model. Life Sci 2008a; 82: 301-7.##Jafarnejad A, Bathaie SZ, Nakhjavani M, Hassan MZ. Investigation of the mechanisms involved in the high-dose and long-term acetyl salicylic acid therapy of type i diabetic rats. J Pharmacol Exp Ther 2008b; 324: 850-7.##Jafarnejad A, Bathaie SZ, Nakhjavani M, Hassan MZ, Banasadegh S. The improvement effect of l-lys as a chemical chaperone on stz-induced diabetic rats, protein structure and function. Diabetes Metab Res Rev 2008c; 24: 64-73.##Kanwar M, Chan PS, Kern TS, Kowluru RA. Oxidative damage in the retinal mitochondria of diabetic mice: Possible protection by superoxide dismutase. Invest Ophthalmol Vis Sci 2007; 48: 3805-11.##Lapshina EA, Sudnikovich EJ, Maksimchik JZ, Zabrodskaya SV, Zavodnik LB, Kubyshin VL, et al. Antioxidative enzyme and glutathione s-transferase activities in diabetic rats exposed to long-term asa treatment. Life Sci 2006; 79: 1804-11.##Mastrocola R, Restivo F, Vercellinatto I, Danni O, Brignardello E, Aragno M, et al. Oxidative and nitrosative stress in brain mitochondria of diabetic rats. J Endocrinol 2005; 187: 37-44.##Moharib SA, El-Batran SA. Hypoglycemic effect of dietary fibre in diabetic rats. Research Journal of Agriculture and Biological Sciences 2008; 4: 455-461.##Morin C, Zini R, Simon N, Tillement JP. Dehydroepiandrosterone and alpha-estradiol limit the functional alterations of rat brain mitochondria submitted to different experimental stresses. Neuroscience 2002; 115: 415-24.##Munusamy S, Saba H, Mitchell T, Megyesi JK, Brock RW, Macmillan-Crow LA. Alteration of renal respiratory complex-iii during experimental type-1 diabetes. BMC Endocr Disord 2009; 9: 1-9.##Nathan DM. Prevention of long-term complications of non-insulin-dependent diabetes mellitus. Clin Invest Med 1995; 18: 332-9.##Noguchi H. Stem cells for the treatment of diabetes. Endocr J 2007; 54: 7-16.##Oberle; S, Polte; T, Abate; A, Podhaisky; H-P, Schröder H. Aspirin increases ferritin synthesis in endothelial cells a novel antioxidant pathway Circulation Research 1998; 82: 1016-1020.##Rabbani N, Thornalley PJ. Dicarbonyls linked to damage in the powerhouse: Glycation of mitochondrial proteins and oxidative stress. Biochem Soc Trans 2008; 36: 1045-50.##Rosca MG, Mustata TG, Kinter MT, Ozdemir AM, Kern TS, Szweda LI, et al. Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Renal Physiol 2005; 289: F420-30.##Rossignol R, Malgat M, Mazat JP, Letellier T. Threshold effect and tissue specificity. Implication for mitochondrial cytopathies. J Biol Chem 1999; 274: 33426-32.##Saeed MK, Deng Y, Dai R. Attenuation of biochemical parameters in streptozotocin-induced diabetic rats by oral administration of extracts and fractions of cephalotaxus sinensis. J Clin Biochem Nutr 2008; 42: 21-8.##Shi X, Ding M, Dong Z, Chen F, Ye J, Wang S, et al. Antioxidant properties of aspirin: Characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, nf-κb activation, and tnf-α production Molecular and Cellular Biochemistry 1999; 199: 93-102.##Shojaeian S, Bathaie SZ. The effect of aspirin on the interaction of histone h5 and h5-DNA. Physiology and pharmacology 2004; 2: 157-168.##Turko I, Murad F. Quantitative protein profiling in heart mitochondria from diabetic rats. J Biol Chem 2003; 278: 35844-9.##Urios P, Grigorova-Borsos AM, Sternberg M. Aspirin inhibits the formation of pentosidine, a cross-linking advanced glycation end product, in collagen. Diabetes Res Clin Pract 2007a; 77: 337-40.##Urios P, Grigorova-Borsos AM, Sternberg M. Flavonoids inhibit the formation of the cross-linking age pentosidine in collagen incubated with glucose, according to their structure. Eur J Nutr 2007b; 46: 139-46.## ##</REF>
			</REFRENCE>
		</REFRENCES>

	</ARTICLE>


	<ARTICLE> 
		<TitleF>Carbon nanotubes prolong the regulatory action of nerve growth factor on the endocannabinoid signaling </TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Introduction: Carbon nanotubes (CNTs) have shown enormous potential in neuroscience. Nerve growth factor (NGF)-CNTs complex promotes the neuronal growth, however, the underlying mechanism(s) have remained elusive. Based on the interplay between NGF and the endocannabinoid system, involvement of the neuroprotective endocannabinoid, 2-arachidonoyl glycerol (2-AG), was investigated in the mechanism of action of NGF. Materials and Methods: Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs. MWCNTs were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). In vitro cytotoxicity was evaluated by MTT assay. Following three times daily intracerebroventricular injections of NGF solution (2, 5, and 10 &#38;mug), and 5, 10, and 20 &#38;mug of acid- or amine-modified MWCNTs, or MWCNTs-NGF complex for either one or 7 days, 2-AG contents were quantified in the frontal cortex and hippocampus of rats by isotope-dilution liquid chromatography/mass spectrometry. Results: FTIR confirmed the amino-functionalization of COOH-MWCNTs and NGF immobilization on the aminated MWCNTs. Aminated MWCNTs and MWCNTs-NGF complex showed less cytotoxicity than COOH-MWCNTs (P&#60;0.05, P&#60;0.01, and P&#60;0.01). Chronic, but not acute, administration of MWCNTs-NGF complex and NGF solution at the highest dose tested led to the elevation of 2-AG at 1 h from the last injection (P&#60;0.01 and P&#60;0.001). 2-AG enhancement induced by MWCNTs-NGF complex lasted for up to 5 and 12 h post-injection (P&#60;0.01 and P&#60;0.001). 2-AG contents remained at the baseline level in the sham and groups receiving vehicle, acid- or amine-modified MWCNTs (P&#62;0.05). Conclusion: Functionalized MWCNTs-NGF complex induces a long-lasting increase of brain 2-AG content indicating the efficiency of this nanostructure to provide a sustained concentration of NGF. Implication of 2-AG in the mechanism of action of NGF might be of great therapeutic significance in the neurological disorders.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>167</FPAGE>
			<TPAGE>176</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/12015/04/122015/05/26
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/3/5
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/12015/10/222015/10/22
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/7/30
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Parichehr</Name>
				<MidName></MidName>
				<Family>Hassanzadeh</Family>
				<NameE>Parichehr</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Hassanzadeh</FamilyE>
				<Organizations>
				<Organization>Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>hassanzadehparichehr4@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Elham</Name>
				<MidName></MidName>
				<Family>Arbabi</Family>
				<NameE>Elham</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Arbabi</FamilyE>
				<Organizations>
				<Organization>Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>arbabiavalelham@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Fatemeh</Name>
				<MidName></MidName>
				<Family>Rostami</Family>
				<NameE>Fatemeh</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Rostami</FamilyE>
				<Organizations>
				<Organization>Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>frostamii@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Fatemeh</Name>
				<MidName></MidName>
				<Family>Atyabi</Family>
				<NameE>Fatemeh</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Atyabi</FamilyE>
				<Organizations>
				<Organization>Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email></Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Rassoul</Name>
				<MidName></MidName>
				<Family>Dinarvand</Family>
				<NameE>Rassoul</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Dinarvand</FamilyE>
				<Organizations>
				<Organization>Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email></Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Carbon nanotubes</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Nerve growth factor</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Endocannabinoid signaling</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Dr. Abolhassan Ahmadiani##Dr. Mohammad Reza Zali##Dr. Fatemeh Atyabi##Dr. Rassoul Dinarvand## ##</REF>
			</REFRENCE>
		</REFRENCES>

	</ARTICLE>


	<ARTICLE> 
		<TitleF>Gap junctions of the hippocampal CA1 area are crucial for memory consolidation</TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Introduction: Gap junctions are specialized cell–cell contacts between eukaryotic cells through which they communicate. This type of communication has the potential to modulate memory process. We evaluated the effects of the gating of the hippocampal CA1 area gap junction channels on memory consolidation, using passive avoidance task. Materials and Methods: 72 adult male Wistar rats were distributed into 9 groups of 8 each. Two guiding cannulas were bilaterally implanted in the hippocampal CA1 area of all rats. One week after surgery, the animals received an electrical shock with the intensity and duration of 0.3 mA and 1s, respectively. Immediately after training 25, 75 or 150 nM doses of carbenoxolone, a non-selective blocker of gap junction channels or 50, 150 and 1500 nM doses of trimethylamine, an opener of gap junction channels were injected. Another group received 50 nM trimethylamine and 10 min later 75 nM carbenoxolone, immediately post-training. 24 hours later, memory retrieval was assessed. Results: Post-training injection of carbenoxolone significantly and dose- dependently decreased step-through latency, whereas post-training injection of trimethylamine showed a tendency toward increasing step-through latency. Post-training injection of trimethylamine (50 nM) increased step-through latency, significantly compared with post-training injection of carbenoxolone (75 nM and 150 nM). Post-training injection of trimethylamine (50 nM) before carbenoxolone (75 nM) reversed the effects of carbenoxolone on inhibition of memory consolidation. Conclusion: These data suggest that the intercellular coupling via gap junction channels in the hippocampal CA1 cells is crucial for memory consolidation in the passive avoidance task.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>177</FPAGE>
			<TPAGE>184</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/12015/04/122015/05/262015/07/19
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/4/28
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/12015/10/222015/10/222015/10/5
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/7/13
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Siamak</Name>
				<MidName></MidName>
				<Family>Beheshti</Family>
				<NameE>Siamak</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Beheshti</FamilyE>
				<Organizations>
				<Organization>Division of Animal Sciences, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>siamak.beheshti@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Mehdi</Name>
				<MidName></MidName>
				<Family>Eivani</Family>
				<NameE>Mehdi</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Eivani</FamilyE>
				<Organizations>
				<Organization>Division of Animal Sciences, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>bioomehdi@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Jamal</Name>
				<MidName></MidName>
				<Family>Moshtaghian</Family>
				<NameE>Jamal</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Moshtaghian</FamilyE>
				<Organizations>
				<Organization>Division of Animal Sciences, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>jamalmoshtaghian@gmail.com</Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Gap junction</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Memory</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Hippocampal CA1 area</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Passive avoidance task</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Abel T, Lattal KM. Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol 2001; 11: 180-7.##Allen K, Fuchs EC, Jaschonek H, Bannerman DM, Monyer H. Gap junctions between interneurons are required for normal spatial coding in the hippocampus and short-term spatial memory. J Neurosci 2011; 31: 6542-52.##Beheshti S, Hosseini SA, Noorbakhshnia M, Eivani M. Role of hippocampal CA1 area gap junction channels on morphine state-dependent learning. Eur J Pharmacol 2014; 745: 196-200.##Bissiere S, Zelikowsky M, Ponnusamy R, Jacobs NS, Blair HT, Fanselow MS. Electrical synapses control hippocampal contributions to fear learning and memory. Science 2011; 331: 87-91.##Bocian R, Posluszny A, Kowalczyk T, Golebiewski H, Konopacki J. The effect of carbenoxolone on hippocampal formation theta rhythm in rats: In vitro and in vivo approaches. Brain Res Bull 2009; 78: 290-8.##Bocian R, Posluszny A, Kowalczyk T, Kazmierska P, Konopacki J. Gap junction modulation of hippocampal formation theta and local cell discharges in anesthetized rats. Eur J Neurosci 2011; 33: 471-81.##Buhl DL, Harris KD, Hormuzdi SG, Monyer H, Buzsaki G. Selective impairment of hippocampal gamma oscillations in connexin-36 knock-out mouse in vivo. J Neurosci 2003; 23: 1013-8.##Chepkova AN, Sergeeva OA, Haas HL. Carbenoxolone impairs LTP and blocks NMDA receptors in murine hippocampus. Neuropharmacology 2008; 55: 139-47.##Chrobak JJ, Buzsaki G. High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely behaving rat. J Neurosci 1996; 16: 3056-66.##Colgin LL, Moser EI. Gamma oscillations in the hippocampus. Physiology (Bethesda) 2010; 25: 319-29.##Dere E, Zlomuzica A. The role of gap junctions in the brain in health and disease. Neurosci Biobehav Rev 2012; 36: 206-17.##Draguhn A, Traub RD, Schmitz D, Jefferys JG. Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature 1998; 394: 189-92.##Duzel E, Penny WD, Burgess N. Brain oscillations and memory. Curr Opin Neurobiol 2010; 20: 143-9.##Gajda Z, Gyengesi E, Hermesz E, Ali KS, Szente M. Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo. Epilepsia 2003; 44: 1596-600.##Hanslmayr S, Staudigl T. How brain oscillations form memories: a processing based perspective on oscillatory subsequent memory effects. Neuroimage 2014; 85 Pt 2: 648-55.##Herve JC, Sarrouilhe D. Connexin-made channels as pharmacological targets. Curr Pharm Des 2005; 11: 1941-58.##Hormuzdi SG, Pais I, LeBeau FE, Towers SK, Rozov A, Buhl EH, et al. Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron 2001; 31: 487-95.##Hosseinzadeh H, Asl MN, Parvardeh S, Tagi Mansouri SM. The effects of carbenoxolone on spatial learning in the morris water maze task in rats. Med Sci Monit 2005; 11: BR88-94.##Katche C, Cammarota M, Medina JH. Molecular signatures and mechanisms of long-lasting memory consolidation and storage. Neurobiol Learn Mem 2013; 106: 40-7.##Konopacki J, Kowalczyk T, Golebiewski H. Electrical coupling underlies theta oscillations recorded in hippocampal formation slices. Brain Res 2004; 1019: 270-4.##Lorenzini CA, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat\'s passive avoidance response: A tetrodotoxin functional inactivation study. Brain Res 1996; 730: 32-9.##Nassiri-Asl M, Zamansoltani F, Zangivand A-A. The inhibitory effect of trimethylamine on the anticonvulsant activities of quinine in the pentylenetetrazole model in rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2008; 32: 1496-1500.##Paxinos G, Watson, C. The rat brain in stereotaxic coordinates. New York: Academic Press, 2007.##Rekling JC, Shao XM, Feldman JL. Electrical coupling and excitatory synaptic transmission between rhythmogenic respiratory neurons in the prebotzinger complex. J Neurosci 2000; 20: RC113.##Rouach N, Segal M, Koulakoff A, Giaume C, Avignone E. Carbenoxolone blockade of neuronal network activity in culture is not mediated by an action on gap junctions. J Physiol 2003; 553: 729-45.##Rozental R, Srinivas, M., Spray, D.C., . How to close a gap junction channel: Efficacies and potencies of uncoupling agents. Connexin methods and protocols: Humana Press, 2001: 447–476.##Salameh A, Dhein S. Pharmacology of gap junctions. New pharmacological targets for treatment of arrhythmia, seizure and cancer? Biochim Biophys Acta 2005; 1719: 36-58.##Sohl G, Maxeiner S, Willecke K. Expression and functions of neuronal gap junctions. Nat Rev Neurosci 2005; 6: 191-200.##Tovar KR, Maher BJ, Westbrook GL. Direct actions of carbenoxolone on synaptic transmission and neuronal membrane properties. J Neurophysiol 2009; 102: 974-8.##Traub RD, Kopell N, Bibbig A, Buhl EH, LeBeau FE, Whittington MA. Gap junctions between interneuron dendrites can enhance synchrony of gamma oscillations in distributed networks. J Neurosci 2001; 21: 9478-86.##Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, Guldenagel M, et al. Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem 2002; 383: 725-37.##Zola-Morgan S, Squire LR, Amaral DG. Human amnesia and the medial temporal region: Enduring memory impairment following a bilateral lesion limited to field ca1 of the hippocampus. J Neurosci 1986; 6: 2950-67.###### ##</REF>
			</REFRENCE>
		</REFRENCES>

	</ARTICLE>


	<ARTICLE> 
		<TitleF>Effects of doxepin on spatial memory, TNF-α and Bcl-2 family genes expression in rat hippocampus</TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Introduction: Although the initial hypothesis for the action of doxepin was based on the inhibition of the reuptake of neurotransmitters, it has been suggested that it may also involve other mechanisms. Therefore, this study aims to investigate the effect of doxepin on spatial memory, tumor necrosis factor alpha (TNF-&#59;alpha) level, expression of pro-apoptotic (Bad and Bax) and anti-apoptotic (Bcl-2) genes in the rat hippocampus. Materials and Methods: Male rats were divided randomly into three groups the control, the doxepin 1 and 5 mg/kg, respectively). Rats received i.p injection of doxepin for 21 days. Spatial memory was evaluated by Morris water maze test. Then the hippocampi were dissected for measurement of the expression of Bcl2, Bad and Bax genes and the TNF-&#59;alpha level. Results: Our results showed no significant effects of doxepin on spatial memory. Doxepin significantly decreased expression of Bad gene, but had no significant/considerable effects on Bcl2 and Bax gene expression. Also, the ratio of TNF-&#59;alpha to total protein (%) did not show significant differences in the rat hippocampus. Conclusion: These results did not show any significant impact of doxepin on the factors affecting the neuronal functions in intact animals. However, Since a significant reduction in the hippocampal Bad mRNA levels was observed It is our assumption that doxepin has neuroprotective effects.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>185</FPAGE>
			<TPAGE>192</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/12015/04/122015/05/262015/07/192015/09/14
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/6/23
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/12015/10/222015/10/222015/10/52015/11/14
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/8/23
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Nastaran</Name>
				<MidName></MidName>
				<Family>Eidelkhani</Family>
				<NameE>Nastaran</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Eidelkhani</FamilyE>
				<Organizations>
				<Organization>Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>na.eidelkhani@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Maryam</Name>
				<MidName></MidName>
				<Family>Radahmadi</Family>
				<NameE>Maryam</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Radahmadi</FamilyE>
				<Organizations>
				<Organization>Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>m_radahmadi@med.mui.ac.ir</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Laleh</Name>
				<MidName></MidName>
				<Family>Rafiee</Family>
				<NameE>Laleh</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Rafiee</FamilyE>
				<Organizations>
				<Organization>Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>rafiee.laleh@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Mahsa</Name>
				<MidName></MidName>
				<Family>Gharzi</Family>
				<NameE>Mahsa</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Gharzi</FamilyE>
				<Organizations>
				<Organization>Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>mahsagharzi@gmail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Hojjatallah</Name>
				<MidName></MidName>
				<Family>Alaei</Family>
				<NameE>Hojjatallah</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Alaei</FamilyE>
				<Organizations>
				<Organization>Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>alaei@med.mui.ac.ir</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Parham</Name>
				<MidName></MidName>
				<Family>Reisi</Family>
				<NameE>Parham</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Reisi</FamilyE>
				<Organizations>
				<Organization>Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>p_reisi@med.mui.ac.ir</Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Doxepin</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Memory</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Hippocampus</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Bcl-2 family</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>TNF-α.</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Abdel-Salam OM, Baiuomy AR, Arbid MS. Studies on the anti-inflammatory effect of fluoxetine in the rat. Pharmacological Research 2004; 49: 119-131.##Bianchi M, Sacerdote P, Panerai AE. Chlomipramine differently affects inflammatory edema and pain in the rat. Pharmacology Biochemistry and Behavior 1994; 48: 1037-1040.##Djordjevic A, Djordjevic J, Elaković I, Adzic M, Matić G, Radojcic MB. Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat prefrontal cortex. European journal of pharmacology 2012; 693: 37-44.##Drake LA, Fallon JD, Sober A. Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. Journal of the American Academy of Dermatology 1994; 31: 613-616.##Duman RS, Malberg J, Thome J. Neural plasticity to stress and antidepressant treatment. Biological psychiatry 1999; 46: 1181-1191.##Engel D, Zomkowski AD, Lieberknecht V, Rodrigues AL, Gabilan NH. Chronic administration of duloxetine and mirtazapine downregulates proapoptotic proteins and upregulates neurotrophin gene expression in the hippocampus and cerebral cortex of mice. J Psychiatr Res 2013; 47: 802-8.##Gharzi H, Reisi P, S Haghjooye Javanmard M. Dose related effects of doxepin on passive avoidance learning in rats. Research in Pharmaceutical Sciences 2012; 7: S35.##Gray VC, Hughes RN. Drug-, dose- and sex-dependent effects of chronic fluoxetine, reboxetine and venlafaxine on open-field behavior and spatial memory in rats. Behav Brain Res 2015; 281: 43-54.##Hajak G, Rodenbeck A, Voderholzer U, Riemann D, Cohrs S, Hohagen F, et al. Doxepin in the treatment of primary insomnia: A placebo-controlled, double-blind, polysomnographic study. Journal of Clinical Psychiatry 2001; 62: 453-463.##Ji B-S, Ji H, Liu G-Q. Doxepin protects cultured neurons against oxidative stress-induced injury. Acta pharmacologica Sinica 2004; 25: 297-300.##Jin Y, Lim C-M, Kim S-W, Park J-Y, Seo J-S, Han P-L, et al. Fluoxetine attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. Brain research 2009; 1281: 108-116.##Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, et al. Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci U S A 2010; 107: 8434-9.##Lee MM, Reif A, Schmitt AG. Major depression: A role for hippocampal neurogenesis? Behavioral Neurobiology of Depression and Its Treatment 2013: 153-179.##Lin C-Y, Huang C-S, Huang C-Y, Yin M-C. Anticoagulatory, antiinflammatory, and antioxidative effects of protocatechuic acid in diabetic mice. Journal of agricultural and food chemistry 2009; 57: 6661-6667.##Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J biol Chem 1951; 193: 265-275.##Paumier KL, Sortwell CE, Madhavan L, Terpstra B, Daley BF, Collier TJ. Tricyclic antidepressant treatment evokes regional changes in neurotrophic factors over time within the intact and degenerating nigrostriatal system. Exp Neurol 2015; 266: 11-21.##Richardson J, Keegan D, Bowen R, Blackshaw S, Cebrian-Perez S, Dayal N, et al. Verbal learning by major depressive disorder patients during treatment with fluoxetine or amitriptyline. International clinical psychopharmacology 1994.##Roumestan C, Michel A, Bichon F, Portet K, Detoc Ml, Henriquet C, et al. Anti-inflammatory properties of desipramine and fluoxetine. Respir Res 2007; 8: 35.##Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2005; 29: 201-217.##Sun X-Y, Zhang L, Wei C-X, Piao H-R, Quan Z-S. Characterization of the anticonvulsant activity of doxepin in various experimental seizure models in mice. Pharmacological reports: PR 2009; 61: 245.##Watanabe Y, Gould E, Daniels DC, Cameron H, McEwen BS. Tianeptine attenuates stress-induced morphological changes in the hippocampus. European journal of pharmacology 1992; 222: 157-162.##Xu H, Richardson JS, Li X-M. Dose-related effects of chronic antidepressants on neuroprotective proteins bdnf, bcl-2 and cu/zn-sod in rat hippocampus. Neuropsychopharmacology 2003; 28: 53-62.##Yau JL, Noble J, Hibberd C, Rowe WB, Meaney MJ, Morris RG, et al. Chronic treatment with the antidepressant amitriptyline prevents impairments in water maze learning in aging rats. The Journal of neuroscience 2002; 22: 1436-1442.##Zamani Z, Reisi P, Alaei H, Pilehvarian AA. Effect of royal jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic alzheimer\'s disease. Advanced biomedical research 2012; 1.##Zarei G, Reisi P, Alaei H, Javanmard SH. Effects of amitriptyline and fluoxetine on synaptic plasticity in the dentate gyrus of hippocampal formation in rats. Adv Biomed Res 2014; 3: 199.## ##</REF>
			</REFRENCE>
		</REFRENCES>

	</ARTICLE>


	<ARTICLE> 
		<TitleF>Evaluation of wound healing and post-operative intra-abdominal adhesions in opium addicted rats</TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Introduction: Opium addiction can change immune response to Types of stress such as injury or trauma due to alterations in the in secretion status of cytokines in the body. In this study, effects of opium addiction on wound healing and post-operative adhesion bands were assessed after laparotomy. Materials and Methods: Male rats (n=20) were randomly divided into opium addicted (documented with Naloxone test) and control group. Three weeks after surgery, site of abdominal incision was excised elliptically and sent for wound healing grading assessment by pathologist and an intra-abdominal adhesion band assessment was done. The concentrations of three cytokines (TNF , IFN and IL10) were also measured before, immediately after surgery and 24 hour after surgery. Results: Post-operative intra-abdominal adhesion was decreased in opium addicted group in comparison to control group (p value = 0.014). No statistically significant difference was found in the wound healing phase in two groups (P value = 0.057). Our findings showed that serum level of TNF , IFN and IL10 in two groups measured in all phases of examination (before surgery, within 30-60 min after surgery and 24h after surgery), were not statistically different/significant (p&#62;0.05). Conclusion: Since opium addiction can decrease post-operative intra-abdominal adhesions in rats, they may be susceptible to increased inflammation and these effects may be due to decreased post-operative pain.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>193</FPAGE>
			<TPAGE>199</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/12015/04/122015/05/262015/07/192015/09/142015/08/23
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/6/1
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/12015/10/222015/10/222015/10/52015/11/142015/11/15
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/8/24
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Mohammad Reza</Name>
				<MidName></MidName>
				<Family>Lashkarizadeh</Family>
				<NameE>Mohammad Reza</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Lashkarizadeh</FamilyE>
				<Organizations>
				<Organization>Department of Surgery, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>lashkarizadeh@kmu.ac.ir</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Mohammad</Name>
				<MidName></MidName>
				<Family>Garshasbi</Family>
				<NameE>Mohammad</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Garshasbi</FamilyE>
				<Organizations>
				<Organization>Department of Surgery, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>mohammadgarshasbi1356@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Shahriar</Name>
				<MidName></MidName>
				<Family>Dabiri</Family>
				<NameE>Shahriar</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Dabiri</FamilyE>
				<Organizations>
				<Organization>Department of Pathology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>shabanimoh@gail.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Mahdieh</Name>
				<MidName></MidName>
				<Family>Lashkarizadeh</Family>
				<NameE>Mahdieh</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Lashkarizadeh</FamilyE>
				<Organizations>
				<Organization>Department of Pathology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>shabanimoh@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Mohammad</Name>
				<MidName></MidName>
				<Family>Shabani</Family>
				<NameE>Mohammad</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Shabani</FamilyE>
				<Organizations>
				<Organization>Department of Neuroscience, Institute of Neuropharmacology, Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>shabani@kmu.ac.ir</Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Opium Addiction</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Laparotomy</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Wound healing</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Adhesion</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Rats</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Abbasizade Z, Galehdari H, Rezai A, Seyednezhad SM and Torabi M (2014) Evaluation of the relationship between serum levels of insulin, cortisol and growth hormones and wound healing in normal and diabetic rats. Physiology and Pharmacology 18:92-100.##Alizadeh AM, Sohanaki H, Khaniki M, Mohaghgheghi MA, Ghmami G and Mosavi M (2011) The Effect of Teucrium Polium Honey on the Wound Healing and Tensile Strength in Rat. Iranian Journal of Basic Medical Sciences 14:499.##Asadikaram G, Asiabanha M, Sayadi A, Jafarzadeh A and Hassanshahi G (2010) Impact of Opium on the serum levels of TGF-β in diabetic, addicted and addicted-diabetic rats. Iran J Immunol 7:186-192.##Bunicard FC, Anderson D, Billiav TR, Dunn DL, Hunter JG, Mathews JB and Pollack RE (2010) in Schwartz Principles of Surgery pp 59, 224, The McGraw-Hill Company.##Camara CR, Guzman FJ, Barrera EA, Cabello AJ, Garcia A, Fernandez NE, Caballero E and Ancer J (2008) Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats. World J Gastroenterol 14:5192-5196.##Cassidy V, Uum V, Stan HM, O\'Dell LE, Lutfy K and Freidman TC (2010) The effects of opioids and opioid analogs on animal and human endocrine systems. Endocrin Rev 31:98-132.##Condon ET, Cahill RA, O\'Malley DB, Aherne NJ and Redmond HP (2007) Evaluation of post operative peritoneal adhesion formation following perioperative Nicotine administration. J Surg Res:135-138.##Efron PA and Moldawer LL (2004) Cytokines and wound healing: the role of cytokine and anticytokine therapy in the repair response. Journal of Burn Care &#38; Research 25:149-160.##Eming SA, Krieg T and Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. Journal of Investigative Dermatology 127:514-525.##Ezzatabadipour M, Majidi M, Malekpour-afshar R, Eftekharvaghefi SH and Nematollahi-mahani SN (2011) The Effects of Morphine on Tissue Structure of the Growth Plate in Male Rats. Iranian Journal of Basic Medical Sciences 14:514.##Finley M, Happel C, Kaminsky D and Rogers T (2008) Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Cellular immunology 252:146-154.##Haney A (2000) Identification of macrophages at the site of peritoneal injury: evidence supporting a direct role for peritoneal macrophages in healing injured peritoneum. Fertility and sterility 73:988-995.##Järvinen PM and Laiho M (2012) LIM-domain proteins in transforming growth factor β-induced epithelial-to-mesenchymal transition and myofibroblast differentiation. Cellular signalling 24:819-825.##Kämpfer H, Paulukat J, Mühl H, Wetzler C, Pfeilschifter J and Frank S (2000) Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing. Molecular Medicine 6:1016.##Kawanishi K, Yamato M, Sakiyama R, Okano T and Nitta K (2013) Peritoneal cell sheets composed of mesothelial cells and fibroblasts prevent intra‐abdominal adhesion formation in a rat model. Journal of tissue engineering and regenerative medicine.##Khaksari M, Razmi Z, Hekmat AS, Naderi V and Rostami S (2012) The Effects of Cyclooxygenase Inhibitors on the Brain Inflammatory Response Following Traumatic Brain Injury in Rats. Iranian Journal of Basic Medical Sciences 15:1102.##Khorram-Manesh A, Ardakani JV, Behjati HR, Nylund G and Delbro D (2006) The effect of opioids on the development of postoperative intra-abdominal adhesions. Digestive diseases and sciences 51:560-565.##Khorram Manesh A, Ardakani JV, Behjati HR, Nylund G and Delbro D (2006) The effect of opioids on the development of post operative intra-abdominal adhesions. Digest Dis and Sci 51:560-565.##King A, Balaji S, Le LD, Crombleholme TM and Keswani SG (2014) Regenerative Wound Healing: The Role of Interleukin-10. Advances in wound care 3:315-323.##Kuang Y, Zhu Y, Kuang Y, Sun Y, Hua C and He W (2007) Changes of the immune cells, cytokines and growth hormone in teenager drug addicts]. Xi bao yu fen zi mian yi xue za zhi= Chinese journal of cellular and molecular immunology 23:821.##Labat M, Pouchelet M, Gouhier N, Boireau P and Milhaud G (2001) Regulation by phagic T-lymphocytes of a (pluripotent?) organ stem cell present in adult human blood. A beneficial exception to self-tolerance. Biomedicine &#38; pharmacotherapy 55:79-90.##Lovallo WR (2006) The hypothalamic–pituitary–adrenocortical axis in addiction. International journal of psychophysiology: official journal of the International Organization of Psychophysiology 59:193.##Malviya A, Negi N, Mandora M and Yadav J (2011) Perioperative Status and Complications in Opium Addicts in Western Rajasthan. Indian Journal of Surgery 73:346-351.##Mansourian A, Askarzadeh M, Shabani M and Divsalar K (2012) Comparison of Duration of Spinal Anesthesia with Lidocaine or Lidocaine Plus Epinephrine between Addicts and Non-addicts. Addiction and Health 4:95-101.##McGuire L, Heffner K, Glaser R, Needleman B, Malarkey W, Dickinson S, Lemeshow S, Cook C, Muscarella P and Melvin WS (2006) Pain and wound healing in surgical patients. Annals of behavioral medicine 31:165-172.##Nabati S, Asadikaram G, Arababadi MK, Shahabinejad G, Rezaeian M, Mahmoodi M and Kennedy D (2013) The plasma levels of the cytokines in opium-addicts and the effects of opium on the cytokines secretion by their lymphocytes. Immunology letters 152:42-46.##Nemati MH, Astaneh B and Safaee Ardekani G (2010) Effects of opium addiction on bleeding after coronary artery bypass graft surgery: report from Iran. Gen Thorac Cardiovasc Surg:456-460.##Parsania Shahrnaz, Shabani Mohammad, Moazzami Kasra , Razavinasab Moazamehosadat, Larizadeh Mohammad Hassan, Nazeri Masoud, Asadi-Shekaari Majid and Moein K (2014) Gender difference in motor impairments induced by chronic administration of Vinblastine. Iranian Journal of Basic Medical Sciences In Press.##Salmon-Ehr V, Ramont L, Godeau G, Birembaut P, Guenounou M, Bernard P and Maquart F-X (2000) Implication of interleukin-4 in wound healing. Laboratory investigation 80:1337-1343.##Sido B, Teklote J, Hartel M, Friess H and Buchler MW (2004) Inflammatory response after abdominal surgery. Best Pract Res Clin Anaesthesiol:439-454.##Wadji MB, Rohban M, Shabani M and Bahrampour A (2005) The effect of Opium addiction on response to major operation stress. Journal of Kerman University of Medical Sciences 12:159-164.## ##</REF>
			</REFRENCE>
		</REFRENCES>

	</ARTICLE>


	<ARTICLE> 
		<TitleF>The interactive effect of aerobic-resistance training and estrogen therapy on metabolic syndrome indices and omentin-1</TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Introduction: Obesity and visceral fat accumulation after menopause are associated with insulin resistance and cardiovascular diseases. We investigated the interactive effect of aerobic-resistance training and estrogen replacement therapy on visceral fat, omentin-1 and HOMA-IR in ovariectomized rats. Materials and Methods: Fifty female Wistar rats were ovariectomized (OVX) and divided into 5 groups (n=10 rats per group): Ovx+sedentary (Sedentary), aerobic-resistance training (Ovx+Exe), aerobic-resistance training+estrogen replacement therapy (Ovx+Exe+Est), estrogen replacement therapy (Ovx+Est) and sesame oil (Ovx+Oil). The exercise consisted of 8-week aerobic-resistance training (20 m/min, 3 days/week, 60 min/day, 10% slope, Load 3% body weight).17b-estradiol valerate (30 &#59;mug/kg bw in 0.2 ml sesame oil) were injected subcutaneously, three days a week during 8 weeks and the Ovx+Est+Est received both exercise protocol and estradiol as previous groups. Obtained data were analyzed by ANOVA and post hoc Tukey test. Results: Omentin-1showed significant increase in Ovx+Exe compared to Ovx+Exe+Est and Ovx+Est (P&#60;0.05). HOMA-IR and visceral fat was decreased in Ovx+Exe, Ovx+Exe+Est compared to Sedentary (P&#60;0.05). Conclusion: Eight-week aerobic-resistance training, 17-b estradiol replacement and co-treatment of exercise+estrogen successfully decreased visceral fat and insulin resistance probably via elevation in omentin-1 in ovaryectomized rats. Regarding the risk of hormone replacement therapy this study suggests that 2- month aerobic-resistance training is more effective in treating metabolic syndrome, rather than estrogen replacement therapy.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>200</FPAGE>
			<TPAGE>207</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/12015/04/122015/05/262015/07/192015/09/142015/08/232015/06/28
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/4/7
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/12015/10/222015/10/222015/10/52015/11/142015/11/152015/10/5
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/7/13
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Parvin</Name>
				<MidName></MidName>
				<Family>Babaei</Family>
				<NameE>Parvin</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Babaei</FamilyE>
				<Organizations>
				<Organization>Department of Physiology, Guilan University of Medical Sciences, Rasht, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>P_babaei@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Ameneh</Name>
				<MidName></MidName>
				<Family>Pourrahim Ghouroghchi</Family>
				<NameE>Ameneh</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Pourrahim Ghouroghchi</FamilyE>
				<Organizations>
				<Organization>Department of Physical Education and Sport Sciences, University of Guilan, Rasht, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>amenehpoorrahim@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Arsalan</Name>
				<MidName></MidName>
				<Family>Damirchi</Family>
				<NameE>Arsalan</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Damirchi</FamilyE>
				<Organizations>
				<Organization>Department of Physical Education and Sport Sciences, University of Guilan, Rasht, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>Arsalan388@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Bahram</Name>
				<MidName></MidName>
				<Family>Soltani Tehrani</Family>
				<NameE>Bahram</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Soltani Tehrani</FamilyE>
				<Organizations>
				<Organization>Cellular and Molecular Research Center, Guilan University of Medical Sciences, Rasht, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>soltani@gums.ac.ir</Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Combined Exercise</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Hormone Therapy</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>HOMA-IR</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Omentin-1</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Visceral Adipose</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Aguiar AF, Agati LB, Muller SS, Pereira OC, Silva MD, Effects of physical training on the mechanical resistance of rat femur proximal thirds. Acta Ortop Bras 18 (2010) 245- 9. ##     Babaei P, Mehdizadeh R,  Ansar MM, Damirchi A, Effects of ovariectomy and estrogen replacement therapy on visceral adipose tissue and serum adiponectin levels in rats. Menopause International 16 (2010) 100–104.##     Barros RP, Machado UF, Warner M, Gustafsson JA, Muscle GLUT4 regulation by estrogen receptors ERA and ER. Proc Natl Acad Sci U S A 103 (2006) 1605–8.##     Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Pray J, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 56 (2007)1655-1661.##     Cai RC, Wei L, Di JZ, Yu HY, Bao YQ, Jia WP, Expression of omentin in adipose tissues in obese and type 2 diabetic patients. Zhonghua Yi Xue Za Zhi 89 (2009) 381-384.##     Christiansen T, Paulsen SK, Bruun JM, Overgaard K, Ringgaard S, Pedersen SB, et al. Comparable reduction of the visceral adipose tissue depot after a diet-induced weight loss with or without aerobic exercise in obese subjects: a12-week randomized intervention study. European Journal of Endocrinology 160 (2009) 759–767. ##     Damirchi A, Mehdizade R, Ansar MM, Soltani B, Babaei P, Effects of aerobic exercise training on visceral fat and serum adiponectin concentration in ovariectomized rats. Climacteric 13 (2010)171–8.##     Davidson LE, Influence of exercise modality on body composition, insulin resistance and functional fitness in aging:A Randomized controlled trail. [dissertation]. St. 2007, Queen’s University Kingston, Ontario,Canada.##     Dieli-conwright CM, Spektror TM, Rice JC, Sattler FR, Schroeder ET, Hormone replacement therapy and messenger RNA expression of estrogen receptor coregulators after exercise in postmenopausal women. Med Sci Sports Exerc 42 (2010) 422-429.##     Fu M, Gong DW, Damcott C, Sabra M, Yang R, Pollin TI, et al. Systematic analysis of omentin 1 and omentin 2 on 1q23 as candidate genes for type 2 diabetes in the Old Order Amish. Diabetes 53 (2004) 59.##     Green JS, Stanforth PR, RankinenT, Leon AS, Rao DC, Skinner JS, et al. The effects of exercise training on abdominal visceral fat, body composition, and indicators of the metabolic syndrome in postmenopausal women with and without estrogen replacement therapy. Metabolism 53 (2004) 1192-1196.##     Gürsoy G, Kırnap NG, Ebah O, Acar Y,  Demirba B, Akçayöz S, et al. The relationship between plasma omentin-1 levels and insulin resistance in newly diagnosed type 2 diabetıc women. Clinical Reviews and Opinions 2 (2010) 49-54.##     Jialal, I, Devaraj S, Kaur H, Adams-Huet B, Bremer AA, Increased chemerin and decreased Omentin-1 in both adipose tissue and plasma in nascent metabolic syndrome. J Clin Endocrinol Metab 98 (2013) 514–517.##     Kanaley J, Sames C, Swisher L, Swick AG, Pioutz-Synder LL, Steppan CM, et al. Abdominal fat distribution in pre-and postmenopausal women: The impact of physical activity, age and menopausal status. Metabolism 50 (2001) 976-982.##     Malin SK, Gerber R, Chipkin SR, Independent and Combined Effects of Exercise Training and Metformin on Insulin Sensitivity in Individuals With Prediabetes. Diabetes Care 35 (2012) 131–136.##     Moreno-Navarrete JM, Catalán V, Ortega F, Gómez-Ambrosi J, Ricart W, Frühbeck G, et al. Circulating omentin concentration increases after weight loss. Nutrition &#38; Metabolism 7 (2010) 27.##    O’Leary VB,  Marchetti CM, Krishnan RK, Stetzer BP, Gonzalez F, Kirwan JP, Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat. J Appl Physiol 100 (2006) 1584–1589.##     Pan HY, Guo L, Li Q, Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes Res Clin Pract 88 (2010) 29–33.##     Ryan AS, Nicklas BJ, Berman DM, Hormone Replacement Therapy, insulin sensitivity, and abdominal obesity in postmenopausal women. Diabetes Care 25 (2002) 127-133.##     Saengsirisuwan V, Pongseeda S, Prasannarong M, Vichaiwong K, Toskulkao C, Modulation of insulin resistance in ovariectomized rats by endurance exercise training and estrogen replacement. Metabolism Clinical and Experimental 58 (2009) 38–47.##     Saremi A, Asghari M, Ghorbani A, Effects of aerobic training on serum omentin-1 and cardiometabolic risk factors in overweight and obese men. Journal of Sports Sciences 28 (2010) 993-8. ##     Schaffler A, Neumeier M, Herfarth H, Furst A, Scholmerich J, Buchler C, Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta (2005) 1732:96–102.##     Shibata R,  Ouchi N, Takahashi R, Terakura Y,  Ohashi K,  Ikeda N, et al. Omentin as a novel biomarker of metabolic risk factors. Diabetology &#38; Metabolic Syndrome 4 (2012) 37.##     Slentz CA,  Bateman LA, Willis LH,  Shields AT, Tanner CJ, Piner LW, et al. Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT. Am J Physiol Endocrinol Metab 301 (2011) 1033-1039. ##     Tan BK, Adya R, Farhatullah S, Lewandowski KC, O\'Hare P, Lehnert H, et al. Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome. Ex vivo and in vivo regulation of Omentin-1by insulin and glucose. Diabetes 57 (2008) 801-808.##     Tan BK, Adya R, Randeva HS, Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med 20 (2010) 143-148.##     Toth MJ, Tchernof A, Sites CK, Poehlman ET, Effect of menopausal status on body composition and abdominal fat distribution. Int J Obes 24 (2000) 226-231.##     Urbanova M, Dostalova I, Trachta P, Drapalova J, Kavalkova P, Haluzikova D, et al. Serum concentrations and subcutaneous adipose tissue mRNA expression of omentin in morbid obesity and type 2 diabetes mellitus: the effect of very-low-calorie diet, physical activity and laparoscopic sleeve gastrectomy. Physiol. Res 63 (2014) 207-218.##     Visseres D, Hens W, Taeymas J, Baeyens JP, Poortmas J, Gaal  LV, The effect of exercise on visceral adipose tissue in overweight adults: A systematic review and meta-analysis. Diabetes and Metabolism 8 (2013) 56415.##     Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, et al. Identification of omentin as a novel depotspecificadipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 290 (2006) 1253-1261.##     Yu D, Gong DW, Omentin Activates AMP-activated Protein  Kinase and Plays a Role in Energy Metabolism and Immune Response [Phd thesis]. Endocrinology, Diabetes and Nutrition University of Maryland, Baltimore (2011) 39-57.##     Zoth N, Weigt C, Laudenbach-Leschowski U, Diel P, Physical activity and estrogen treatment reduce visceral body fat and serumlevels of leptin in an additive manner in a diet induced animal model of obesity. Journal of Steroid Biochemistry &#38; Molecular Biology 122 (2010) 100–105.##     Zoth N, Weigt C, Zengin S, Selder O,  Selke N,  Kalicinski M,   et al.  Metabolic   effects   of   estrogen   substitution   in combination with   targeted   exercise training   on   the   therapy   of   obesity   in   ovariectomized Wistar rats. Journal  of  Steroid  Biochemistry  &#38;  Molecular  Biology 130 (2012) 64–72.## ##</REF>
			</REFRENCE>
		</REFRENCES>

	</ARTICLE>


	<ARTICLE> 
		<TitleF>Busulfan induces oxidative stress- and Bcl-2 family gene-related apoptosis in epididymal sperm and testis of adult male mice</TitleF>
		<TitleE></TitleE>
		<TitleLang_ID>2</TitleLang_ID>
		<ABSTRACTS>
			<ABSTRACT>
			<Language_ID>2</Language_ID>
			<CONTENT>Introduction: Busulfan as a chemotherapeutic agent causes testicular germinal epithelium depletion and cytotoxicity in germ cells. The aim of this study was to assess antioxidant status, reactive oxygen species (ROS) generation and apoptosis-related genetic markers of adult male mouse sperm following busulfan treatment. Materials and Methods: Forty adult NMRI mice (30 &#177; 5 g) were divided into two groups. Control and busulfan treated group were administered with 100 &#38;muL dimethyl sulfoxide and 3.2 mg/kg/day busulfan for 4 days, respectively. The superoxide dismutase and glutathione peroxidase assays were used for analyzing antioxidant status. Then, the levels of Bcl-2 family gene expression, lipid peroxidation and cytotoxicity were evaluated by Real-Time PCR, thiobarbituric and lactate dehydrogenase assays, respectively. Results: The results showed significant decrease on antioxidant status, increase on lipid peroxidation and lactate dehydrogenase in epididymal sperm and testis of busulfan treated mice in comparison with control (P&#60; 0.05). Real Time PCR demonstrated significantly increased-Bax gene expression and decreased-Bcl-2 gene expression in epididymal sperm of treated group (P&#60; 0.05). Conclusion: The high levels of lipid peroxidation and lactate dehydrogenase revealed increased-ROS and severe cytotoxicity in epididymal sperm and testis tissue following busulfan treatment at clinical dose. The oxidative stress and increased-ROS may induce Bcl-2 family gene expression-related apoptosis following busulfan therapy in normal cells.</CONTENT>
			</ABSTRACT>
		</ABSTRACTS>

		<PAGES>
			<PAGE>
			<FPAGE>208</FPAGE>
			<TPAGE>215</TPAGE>
			</PAGE>
		</PAGES>

		<RECEIVE_DATE>
			2015/08/12015/04/122015/05/262015/07/192015/09/142015/08/232015/06/282015/07/28
		</RECEIVE_DATE>

		<RECEIVE_DATE_FA>
			1394/5/6
		</RECEIVE_DATE_FA>

		<ACCEPT_DATE>
			2015/11/12015/10/222015/10/222015/10/52015/11/142015/11/152015/10/52015/10/22
		</ACCEPT_DATE>

		<ACCEPT_DATE_FA>
			1394/7/30
		</ACCEPT_DATE_FA>

		<AUTHORS>
			<AUTHOR>
				<Name>Parva</Name>
				<MidName></MidName>
				<Family>Nasimi</Family>
				<NameE>Parva</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Nasimi</FamilyE>
				<Organizations>
				<Organization>Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>parvanasimi62@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Mohammad Reza</Name>
				<MidName></MidName>
				<Family>Tabandeh</Family>
				<NameE>Mohammad Reza</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Tabandeh</FamilyE>
				<Organizations>
				<Organization>Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>m.tabandeh@scu.ac.ir</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Akbar</Name>
				<MidName></MidName>
				<Family>Vahdati</Family>
				<NameE>Akbar</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Vahdati</FamilyE>
				<Organizations>
				<Organization>Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>avahdatim@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>

			<AUTHOR>
				<Name>Saeed</Name>
				<MidName></MidName>
				<Family>Khatamsaz</Family>
				<NameE>Saeed</NameE>
				<MidNameE></MidNameE>
				<FamilyE>Khatamsaz</FamilyE>
				<Organizations>
				<Organization>Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran</Organization>
				</Organizations>
				<Countries>
				<Country></Country>
				</Countries>
				<EMAILS>
				<Email>Saeed1617@yahoo.com</Email>
				</EMAILS>
			</AUTHOR>
		</AUTHORS>


		<KEYWORDS>
			<KEYWORD>
				<KeyText>Apoptosis</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Bcl-2 family genes</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Busulfan</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Epididymal sperm</KeyText>
			</KEYWORD>

			<KEYWORD>
				<KeyText>Oxidative stress.</KeyText>
			</KEYWORD>
		</KEYWORDS>

		<REFRENCES>
			<REFRENCE>
				<REF>Ahar NH, Khaki A, Akbari G, Novin MG, The Effect of Busulfan on Body Weight, Testis Weight and MDA Enzymes in Male Rats. Intern J Women’s Heal and Reprod Sc 2 (2014) 316-319.##Bairey OD, Zimra Y, Shaklai M, Okon E, Rabizadeh E, Bcl-2, Bcl-X, Bax and Bak Expression in Short- and Long-Lived Patients with Diffuse Large B-Cell Lymphomas. Clin Cancer Res 5 (1999) 2860-2866. ##Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O, Oxidative Stress and Antioxidant Defense. WAO Journal 5 (2012) 9-19.##Chabner BA, Longo DL, editors. Cancer Chemotherapy and Biotherapy: Principle and Practice. Philadelphia: Lippincott Williams &#38; Wilkins, 2011. ##Choi YJ, Ok DW, Kwon DN, Chung JI, Kim HC, Yeo SM, Kim TM, Seo HG, Kim GH, Murine male germ cell apoptosis induced by busulfan treatment correlates with loss of c-kit-expression in a Fas/FasL- and p53-independent manner. FEBS Letters 575 (2004) 41-51.##Choudhary R, Chawala VK, Soni ND, Kumar J, Vyas RK, Oxidative stress and role of antioxidants in male infertility. Pak J Physiol 6 (2010) 54-59.##Dehghani F, Hassanpour A, Poost-Pasand A, Noorafshan A, Karbalay-Doust S, Protective effects of L-carnitine and homogenized testis tissue on the testis and sperm parameters of busulfan-induced infertile male rats. Iran J Reprod Med,11 (2013) 693-704.##Dev G, Gross A, Mc-Donnell JM, Korsmeyer SJ, BCL-2 family members and the mitochondria in apoptosis 13 (1999) 1899-1911.##Esposito F, Ammendola R, Faraonio R, Russo T, Cimino F, Redox control of signal transduction, gene expression and cellular senescence. Neurochem Res 29 (2004) 617-628.##Evenson DP, Wixon R, Clinical aspects of sperm DNA fragmentation detection and male infertility. Theriogenology 65 (2006) 979-991.##Fernandez HF, Tran HT, Albrecht F, Lennon S, Caldera H, Goodman MS, Evaluation of safety and pharmacokinetics of administering intravenous busulfan in a twice-daily or daily schedule to patients with advanced hematologic malignant disease undergoing stem cell transplantation. Biol Blood Marrow Transplant 8 (2002) 486-492. ##Gross A, Jockel J, Wei MC, Korsmeyer SJ, En-forced dimerization of BAX results in its translocation, mi-tochondrial dysfunction and apoptosis. EMBO J 17 (1998) 3878-3885.##Kawashima A, Osman BAH, Takashima M, Kikuchi A, Kohchi S, Satoh E, Tamba M, Matsuda M, Okamura N, CABS1 is a Novel Calcium-Binding Protein Specifically Expressed in Elongate Spermatids of Mice. Biology of reproduction 80 (2009) 1293-1304.##Kontos CK, Christodoulou ML, Scorilas A, Apoptosis-related BCL2-family Members: Key Players in Chemotherapy. Anticancer Agents Med Chem 13 (2013) 1-22. ##Meng A, Wang Y, Van Zant G, Zhou D, Ionizing radiation and busulfan induce premature senescence in murine bone marrow hematopoietic cells. Cancer Res 63 (2003) 5414-5419. ##Mihara M, Uchiama M, Determination of malonaldheyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86 (1978) 271-278.##Mohammad-Ghasemi F, Soleimanirad J, Ghanbari AA, An Ultrastructural Study on the Apoptotic Features of Spermatogenic Cells following Busulfan Treatment in Adult Mice. J Reprod Infertil 4 (2008) 319-329.##Mohammad-Ghasemi F, Bahadori MH, Faghani M, Nasiri E, Soleimani-Rad J, Buserelin Inhibits Apoptosis in Male Germ Cells Induced by Busulfan in Mouse Testis. J of Iran Anat Sci 7 (2009) 45-54.##Nieto Y, Thall P, Valdez B, Andersson B, Popat U, ,Anderlini P, Shpall EJ, Bassett R, Alousi A, Hosing C, Kebriaei P, Qazilbash M, Frazier E, Gulbis A, Chancoco C, Bashir Q, Ciurea S, Khouri I, Parmar S, Shah N, Worth L, Rondon G, Champlin R, Jones RB, High-Dose Infusional Gemcitabine Combined with Busulfan and Melphalan with Autologous Stem-Cell Transplant in Patients with Refractory Lymphoid Malignancies. Biol Blood Marrow Transplant 11 (2012) 1677-1686.##Nasimi P, Roohi S, editors. Cell death in animals and plants; Apoptosis, Necrosis &#38; Autophagy. Masjed Soleyman: Islamic Azad University of Masjed Soleyman press, 2012.##Probin V, Wang Y, Bai A, Zhou D, Busulfan selectively induces cellular senescence but not apoptosis in WI38 fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38 mitogen- activated protein kinase-dependent mechanism. J Pharmacol Exp Ther 319 (2006) 551-560. ##Probin V, Wang Y, Zhou D, Busulfan-induced up senescence is dependent upon ROS production upstream of the MAPK pathway. Free Radic Biol Med 12 (2007) 1858-1865.##Suriapraba E, Mani PR, Kumar RA, Karunya RR, Manigandan R, Brindha B, Saraswathi SD, Protective effect of NAC on busulfan induced clastogenesis in human peripheral blood lymphocytes. Intern J Inst Pharm and Life Sc 1 (2012) 172-177.##Torres M, Mitogen-activated protein kinase pathways in redox signaling. Front Biosci 8 (2003) 369-391.##Vahdati A, Fathi AR, Nasimi P, Saki GH, Busulfan induces apoptotic and cytotoxic effects on testis and epididymal sperm of adult male mouse following low dose treatment. Int J Bio 5 (2015) 70-78.##Wolter KG, Hsu CL, Smith CL, Nechushtan A, Xi XG, Youle RJ, Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol 139 (1997) 1281-1292.## ##</REF>
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