2017 21 3 66 259

A case of ciprofloxacin-associated Achilles tendinitis 2 2 Achilles tendinitis is a rare adverse effect of the fluoroquinolone antibiotics. Fluoroquinolone antibiotics have widespread usage for treatment of Gram-negative-related infections particularly urinary tract and respiratory infections. Due to the prevalent usage of this family of antibiotics, it is necessary to be careful about their side effects including Achilles tendinitis, which can ensue tendon rupture. This case report introduces an 84-year-old man diagnosed with Achilles tendinitis due to consumption of ciprofloxacin for treatment of urethritis. The patient experienced pain on posterior region of the left ankle after three days of antibiotic therapy onset and the pain was alleviated within a week following ciprofloxacin cessation along with treatment with nonsteroidal anti-inflammatory drugs. The Naranjo score was determined seven for this patient; accordingly, ciprofloxacin was the probable cause of this reaction. Early diagnosis of fluoroquinolones-associated Achilles tendinitis and stopping the treatment may prevent tendon rupture. 172 174 2017/03/11 1395/12/21 2017/07/26 1396/5/4 Vahid Pirhajati Mahabadi Vahid Pirhajati Mahabadi Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Vpirhajati.1@gmail.com Somayyeh Nasiripour Somayyeh Nasiripour Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran nasiripours@yahoo.com Maryam Farasatinasab Maryam Farasatinasab School of Pharmacy International Campus, Iran University of Medical Sciences, Tehran, Iran maryfarasati@gmail.com Shabnam Nadjafi Shabnam Nadjafi Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran najafi.sh@iums.ac.ir Achilles Tendinitis Ciprofloxacin Fluoroquinolones Grandvuillemin A, Contant E, Fedrizzi S, Gras V, Dautriche A. Tendinopathy after ofloxacin ear drops. Eur J Clin Pharmacol. 2015; 71: 1407-1408.##Haddow LJ, Chandra Sekhar M, Hajela V, Gopal Rao G. Spontaneous Achilles tendon rupture in patients treated with levofloxacin. J Antimicrob Chemother. 2003; 51: 747-748.##Kocsis B, Domokos J, Szabo D. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin. Ann Clin Microbiol Antimicrob. 2016; 15: 34.##Lewis T, Cook J. Fluoroquinolones and tendinopathy: a guide for athletes and sports clinicians and a systematic review of the literature. J Athl Train. 2014; 49: 422-427.##Shimatsu K, Subramaniam S, Sim H, Aronowitz P. Ciprofloxacin-induced tendinopathy of the gluteal tendons. J Gen Intern Med. 2014; 29: 1559-1562.##Singh D. Cholesterol level in non-insertional Achilles tendonopathy. Foot (Edinb). 2015; 25: 228-231.##Weinfeld SB. Achilles tendon disorders. Med Clin North Am. 2014; 98: 331-338.##Wise BL, Peloquin C, Choi H, Lane NE, Zhang Y. Impact of age, sex, obesity, and steroid use on quinolone-associated tendon disorders. Am J Med. 2012; 125: 1228.e23-1228. e28.##Yu C, Giuffre B. Achilles tendinopathy after treatment with fluoroquinolone. Australas Radiol. 2005; 49: 407-410.##Zenda T, Araki I, Nakamiya O, Tokuumi Y, Shimada Y, Komai K, et al. Achilles tendinitis as a rare extraintestinal manifestation of ulcerative colitis. Clin J Gastroenterol. 2016; 9: 129-133.#### ##

Study of cation imbalance in patients of malaria 2 2 Introduction: During its life cycle, malaria parasite has to traverse successfully through widely diverse environmental milieu of mosquito mid gut, RBC cytosol and human circulatory system where it is exposed to dramatic changes of extracellular milieu in terms of pH, osmolarity and ionic constituents. Therefore, the aim of this study was to examine the possible changes in the cations (Na+, K+, Mg2+, Ca2+, Cu2+ and Zn2+) in patients of malaria. Methods: Blood samples were collected in EDTA bulb at the time of admission (day-1) and on third day (day-3). The samples were analyzed within 24 hours of collection. Plasma sodium and potassium were measured by flame photometry and calcium, magnesium, copper, and zinc were measured by end point kit method. Results: The mean levels of plasma sodium, magnesium, calcium and zinc in the patients of malaria were significantly reduced (P<0.001) as compared to those in the control group. The levels of potassium and copper are significantly increased (P<0.001) in the malaria patients as compared to those in the control group. In the follow up study, the same parameters were studied in patients after antimalarial treatment and antimalarial + antioxidant treatment day-3. The levels of cations were reversed in the plasma. Conclusion: It concluded that the antimalarial drug regimen must be supported by antioxidants and trace elements supplementation to avoid grave penalty of reactive oxygen species and cations imbalance and also to improve the status of deviated biochemical parameters towards normalcy. 175 184 2017/03/112016/12/12 1395/9/22 2017/07/262017/08/22 1396/5/31 Rupal A Tyagi Rupal A Tyagi Department of Biochemistry, GMERS Medical College, Junagadh, Gujarat, India ami_tyagi2001@yahoo.com Amit G Tyagi Amit G Tyagi Department of Biochemistry, GMERS Medical College, Junagadh, Gujarat, India ami_tyagi2001@yahoo.com Prema Ram Choudhary Prema Ram Choudhary Department of Physiology, C.U. Shah Medical College, Surendranagar, Gujarat, India prema5252@gmail.com Jaidev singh shekhawat Jaidev singh shekhawat Department of Anatomy, C.U. Shah Medical College, Surendranagar, Gujarat, India jaygr1976@gmail.com Sodium Potassium Magnesium Calcium Copper Zinc Malaria. 1. Pillai AD, Addo R, Sharma P, Nguitragool W, Srinivasan P, Desai SA. Malaria parasites tolerate a broad range of ionic environments and do not require host cation remodelling. Molecular Microbiology 2013; 88(1):20-34.##2. Kakkilaya BS. Malaria-Disease information. Internet site:http//www.malariasite.com, 2007.##3. Bennett TN, Patel J, Ferdig MT, Roepe PD. Plasmodium falciparum Na+/H+ exchanger activity and quinine resistance. Mol Biochem Parasitol 2007; 153: 48-58.##4. Bosia A, Ghigo D, Turrini F, Nissani E, Pescarmona GP, Ginsburg H.Kinetic characterization of Na+/H+ antiport of Plasmodium falciparum membrane. J Cell Physiol 1993; 154: 527-34.##5. Boyd LO. Role of zinc plasma membrane functions. J. Nutr.2000; (130) 5:1432S-1436S.##6. Cabantchik ZI. Properties of permeation pathways induced in the human red cell membrane by malaria parasites. Blood Cells. 1990; 16(2-3):421-32.##7. Desai SA, Bezrukov SM, Zimmerberg J. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature.2000; 406: 1001-05.##8. Elford BC, Cowan GM, Ferguson, DJ. Parasite-regulated membrane transport processes and metabolic control in malaria-infected erythrocytes Biochem. J.1995; 308, 361-74##9. Gero AM, Kirk K. Nutrient transport pathways in Plasmodium-infected erythrocytes: what and where are they.Parasitol today.1994; 10:395-99##10. Gero AM, Upston JM. Altered membrane permeability: a new approach to malaria chemotherapy. Parasitol Today. 1992; 8:283-86##11. Ginsburg H, Handeli S, Friedman S, Gorodetsky R, Krugliak M. Effects of red blood cell potassium and hypertonicity on the growth of Plasmodium falciparum in culture. Z Parasitenkd 1986; 72: 185-99.##12. Ginsburg H. In Biomembranes. In: Benga Gh, Tager JM, (Editors). Basic and Medical Research. Berlin. 4th edition. Springer-Verlag, 1988:188-203##13. Ginsburg H. Alterations caused by the intra-erythrocytic malaria parasite in the permeability of its host cell membrane. Comp. Biochem. Physiol. 1990; 95A, 31-39##14. Ginsburg H.Transport pathways in the malaria-infected erythrocyte. Their characterization and their use as potential targets for chemotherapy. Biochem. Pharmacol.1994; 48:1847-56##15. Heinz Mehlhorn. Parasitology in Focus. In: Mehlhorn, (editor). Heidelberg-Berlin, 8th edition. Springer-Verlag .2002; 1: 18-45.##16. Karena LW, Sean M, McBride, Kami KK. Thomas VM. Characterization of two putative potassium channels in Plasmodium falciparum. Malar J.2008; (1) 7: 19.##17. Kirk K, Horner HA. Novel Anion Dependence of Induced Cation Transport in Malaria-infected Erythrocytes. The Journal of Biological Chemistry. 1995; 270 (41):24270-75. ##18. Kirk K. Membrane transport in the malaria-infected erythrocyte. Physiological Reviews 2001; 81(2): 495-537.##19. Topley and Wilson’s. Microbiology and Microbial infections. In: Collier L, Balows A, Sussman M, (editors).9th edition. London: Arnold.1998; 5 (20):361-405.##20. Lee P, Ye Z, Van Dyke K, Kirk RG. X-ray microanalysis of Plasmodium falciparum and infected red blood cells: effects of qinghaosu and chloroquine on potassium, sodium, and phosphorus composition. Am.J. Trop. Med. Hyg. 1988;39:157-65.##21. Martin RE, Kirk K. Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Blood 2007; 109:2217-24.##22. Nguitragool W, Bokhari AA, Pillai AD, Rayavara K, Sharma P, Turpin B, et al. Malaria parasite clag3genes determine channel-mediated nutrient uptake by infected red blood cells. Cell 2011; 145: 665-77.##23. Spillman NJ, Allen RJW, McNamara CW, Yeung BKS, Winzeler EA, Diagana TT. Sodium Regulation in the Malaria Parasite Plasmodium falciparum Involves the Cation ATPase PfATP4 and is a Target of the Spiroindolone Antimalarials. Cell Host and Microbe 2013; 13: 227-37. ##24. Overman RR. Reversible cellular permeability altera tions in disease. In vivo studies on sodium, potassium and chloride concentrations in erythrocytes of the malarious monkey. Am J Physiol 1948; 152: 113-21.##25. Pillai AD, Nguitragool W, Lyko B, Dolinta K, Butler MM, Nguyen ST, et al. Solute restriction reveals an essential role for clag3-associated channels in malaria parasite nutrient acquisition. Mol. Pharmacol. 2012; 82:1104-14.##26. Godkar PB. Textbook of Medical Laboratory Technology. Mumbai (India). 1st edition. Bhalani Publication. 1994; 245-48.##27. Saliba KJ, Horner HA, Kirk K. Transport and metabolismof the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum. J. Biol. Chem. 1998; 273:10190-95.##28. Staines HM, Alkhalil A, Allen RJ, De Jonge, HR, Derbyshire E, Egee S, et al. Electrophysiological studies of malaria parasite-infected erythrocytes: current status. Int J Parasitol 2007; 37: 475-82.##29. Tanabe K. Ion metabolism in malaria-infected erythrocyte. Blood cells 1990; 16(3):437-49.#### ##

The effects of acute, sub-chronic and chronic psychical stress on the brain electrical activity in male rats 2 2 Introduction: Stress is a main factor influencing brain functions as revealed by the electroencephalogram (EEG) recordings. Moreover, different stress durations seemingly cause perturbations in brain waves and lead to mental disorders. This study investigates the effects of acute, sub-chronic and chronic stress on EEG in rats.  Methods: Twenty-eight Wistar adult male rats were randomly allocated to one control and three experimental groups subjected to 6 hr/day of acute (1d), sub-chronic (7d) and chronic (21d) stress. At the end of each period, 20 minutes of EEG recording was taken of each subject. Results: Percentages of delta, theta and alpha frequencies of the baseline in the chronic stress group showed significant differences from those of the control (P<0.05). Theta waves increased in the chronic stress group compared to the acute and sub-chronic (P<0.05 and P<0.01; respectively) ones. This is while, compared to the control, the acute and sub-chronic stress groups exhibited significantly increased percentages of beta waves (P<0.05 in both). Conclusion: The data indicate that different stress durations have different impacts on the EEG rhythm. Acute and sub-chronic stress durations led to changed cortical activity, indicating the inability of the subjects to cope with the stress imposed. Also, chronic stress caused irregularities in the EEG rhythm (delta, theta and alpha waves). EEG recording seems to be useful for measuring stress levels and for predicting abnormalities due to different stress durations. 185 192 2017/03/112016/12/122017/03/11 1395/12/21 2017/07/262017/08/222017/07/26 1396/5/4 Maryam Radahmadi Maryam Radahmadi Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran m_radahmadi@med.mui.ac.ir Azadehalsadat Hosseini Dastgerdi Azadehalsadat Hosseini Dastgerdi Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran azade.hoseini@yahoo.com Neda Fallah Neda Fallah Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran nedafallah1992@gmail.com Hojjatallah Alaei Hojjatallah Alaei Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran alaei@ med.mui.ac.ir Stress Electroencephalogram (EEG) Adrenal gland Rat. References##Andrzejak RG, Lehnertz K, Mormann F, Rieke C, David P, Elger CE: Indications of nonlinear deterministic and finite-dimensional structures in time series of brain electrical activity: Dependence on recording region and brain state. Phys Rev E Stat Nonlin Soft Matter Phys 2001;64:061907.##Arıkanoğlu A: Current approach to differential diagnosis of epileptic seizures and pseudo-seizures. J Clin Exp Invest 2011;2:330-34.##Avishai-Eliner S, Eghbal-Ahmadi M, Tabachnik E, Brunson KL, Baram TZ: Down-regulation of hypothalamic corticotropin-releasing hormone messenger ribonucleic acid (mrna) precedes early-life experience-induced changes in hippocampal glucocorticoid receptor mrna. Endocrinology 2001;142:89-97.##Basar E, Guntekin B: A short review of alpha activity in cognitive processes and in cognitive impairment. Int J Psychophysiol 2012;86:25-38.##Blackhart GC, Minnix JA, Kline JP: Can EEG asymmetry patterns predict future development of anxiety and depression? A preliminary study. Biol Psychol 2006;72:46-50.##Dringenberg HC, Rubenstein ML, Solty H, Tomaszek S, Bruce A: Electroencephalographic activation by tacrine, deprenyl, and quipazine: Cholinergic vs. Non-cholinergic contributions. Eur J Pharmacol 2002;447:43-50.##Freedman R: Schizophrenia. N Engl J Med 2003;349:1738-49.##Hanslmayr S, Volberg G, Wimber M, Raabe M, Greenlee MW, Bauml KH: The relationship between brain oscillations and bold signal during memory formation: A combined EEG-fMRI study. J Neurosci. 2011;31:15674-80.##Heim C, Nemeroff CB: Neurobiology of early life stress: Clinical studies. Semin Clin Neuropsychiatry 2002;7:147-159.##Jena SK: Examination stress and its effect on EEG. Int J Med Sci Public Health 2015;11:1493-97.##Jurkowlaniec E, Tokarski J, Trojniar W: Effect of unilateral ibotenate lesions of the ventral tegmental area on cortical and hippocampal EEG in freely behaving rats. Acta Neurobiol Exp 2003;63:369-75.##Khasina EI, Kurilenko LA, Kirillov OI: Adrenal hypertrophy in rats during a long-term movement restrain. Z Mikrosk Anat Forsch 1985;99:603-10.##Knyazev GG, Savostyanov AN, Levin EA: Alpha synchronization and anxiety: Implications for inhibition vs. Alertness hypotheses. Int J Psychophysiol 2006;59:151-58.##Lagopoulos J, Xu J, Rasmussen I, Vik A, Malhi GS, Eliassen CF, Arntsen IE, Saether JG, Hollup S, Holen A, Davanger S, Ellingsen O: Increased theta and alpha EEG activity during nondirective meditation. J Altern Complement Med 2009;15:1187-92.##Loganathan S, Rathinasamy S: Alteration in memory and electroencephalogram waves with sub-acute noise stress in albino rats and safeguarded by scoparia dulcis. Pharmacogn Mag 2016;12:S7-S13.##Magariños AM, Verdugo JMG, McEwen BS: Chronic stress alters synaptic terminal structure in hippocampus. Proc Natl Acad Sci U S A. 1997;94:14002-8.##Miki Stein A, Munive V, Fernandez AM, Nunez A, Torres Aleman I: Acute exercise does not modify brain activity and memory performance in app/ps1 mice. PloS one 2017;12:e0178247.##Moore N, Tucker K, Brin F, Merai P, Shillcutt S, Coburn K: Positive symptoms of schizophrenia: Response to haloperidol and remoxipride is associated with increased alpha EEG activity. Human Psychopharmacology: Clinical and Experimental 1997;12:75-80.##Mrdalj J, Pallesen S, Milde AM, Jellestad FK, Murison R, Ursin R, Bjorvatn B, Gronli J: Early and later life stress alter brain activity and sleep in rats. PloS one 2013;8:e69923.##Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S: Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology 2009;34:501-8.##Paxinos G, Watson C: The rat brain in stereotaxic coordinates, ed 5th ed. Amsterdam ; London, Elsevier Academic, 2005.##Peng H, Hu B, Zheng F, Fan D, Zhao W, Chen X, Yang Y, Cai Q: A method of identifying chronic stress by EEG. Personal and ubiquitous computing 2013;17:1341-47.##Radahmadi M, Alaei H, Sharifi MR, Hosseini N: The effect of synchronized forced running with chronic stress on short, mid and long- term memory in rats. Asian J Sports Med 2013;4:54-62.##Radahmadi M, Alaei H, Sharifi MR, Hosseini N: Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats. J Bodyw Mov Ther 2015a;19:238-45.##Radahmadi M, Alaei H, Sharifi MR, Hosseini N: Effects of different timing of stress on corticosterone, bdnf and memory in male rats. Physiol Behav. 2015b;139:459-67.##Radahmadi M, Alaei H, Sharifi MR, Hosseini N: Stress biomarker responses to different protocols of forced exercise in chronically stressed rats. J Bodyw Mov Ther2017;21:63-68.##Radahmadi M, Hosseini N, Nasimi A: Effect of chronic stress on short and long-term plasticity in dentate gyrus; study of recovery and adaptation. Neuroscience 2014;280:121-29.##Ranjbar H, Radahmadi M, Alaei H, Reisi P: Effect of different duration of stress on spatial and cognitive memory in male rats. JIMS. 2015;32(309):1933-43 [In Persian].##Ranjbar H, Radahmadi M, Alaei H, Reisi P, Karimi S: The effect of basolateral amygdala nucleus lesion on memory under acute,mid and chronic stress in male rats. Turk J Med Sci. 2016;46:1915-25.##Ranjbar H, Radahmadi M, Reisi P, Alaei H: Effects of electrical lesion of basolateral amygdala nucleus on rat anxiety-like behaviour under acute, sub-chronic, and chronic stresses. Clin Exp Pharmacol Physiol. 2017;44:470-79.##Reisi P, Eidelkhani N, Rafiee L, Kazemi M, Radahmadi M, Alaei H: Effects of doxepin on gene expressions of bcl-2 family, tnf-alpha, map kinase 14, and akt1 in the hippocampus of rats exposed to stress Res Pharm Sci. 2017;12:15-20.##Schacter DL: EEG theta waves and psychological phenomena: A review and analysis. Biol Psychol. 1977;5:47-82.##Seo S-H, Lee J-T: Stress and EEG, INTECH Open Access Publisher, 2010.##Tang X, Yang L, Sanford LD: Interactions between brief restraint, novelty and footshock stress on subsequent sleep and EEG power in rats. Brain Res 2007;1142:110-18.##Uhlhaas PJ, Singer W: Neural synchrony in brain disorders: Relevance for cognitive dysfunctions and pathophysiology. Neuron 2006;52:155-68.##Ulrich-Lai YM, Figueiredo HF, Ostrander MM, Choi DC, Engeland WC, Herman JP: Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner. Am J Physiol Endocrinol Metab. 2006;291:E965-73.#### ##

Nogo receptor blockade enhances subventricular zone’s stem cells proliferation and differentiation in demyelination context 2 2 Introduction: Nogo-A and Nogo receptor (NgR) are expressed in the subventricular zone (SVZ) stem cells. NgR plays critical inhibitory roles in axonal regeneration and remyelination. However, the role of NgR in SVZ niche behaviors in demyelination context is still uncertain. Here we investigated the effects of NgR inhibition on SVZ niche reaction in a local model of demyelination in adult mouse optic chiasm. Methods: Demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. We injected siRNAs against NgR intracerebroventricularly via a permanent cannula over 14 days to knockdown NgR. To trace SVZ stem cells and assess the effect of NgR inhibition on their reaction, BrdU was injected to the animals prior to the demyelination induction. Immunohistochemistry and histological analysis was carried out 3, 7 and 14 days post demyelination lesion. Results: NgR inhibition significantly increased the numbers of proliferating cells in SVZ in response to demeylination. The number of BrdU+/Olig2+progenitor cells in the neurogenic zone of the lateral ventricles was enhanced when NgR was blocked. These progenitor cells (Olig2+, GFAP+ or PSA-NCAM) were mobilized away from this SVZ as a function of time. Inhibition of NgR significantly reduced demyelination extension in optic chiasm. Conclusion: Our findings reveal that inhibition of NgR potentiates adult SVZ progenitor cells proliferation and differentiation in demyelination condition and facilitates remyelination in the optic chiasm. Therefore, inhibition of NgR function could have therapeutic potential for demyelinating disease like multiple sclerosis. 193 205 2017/03/112016/12/122017/03/112017/07/10 1396/4/19 2017/07/262017/08/222017/07/262017/08/24 1396/6/2 Fereshteh Pourabdolhossein Fereshteh Pourabdolhossein Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran pourabdolhossein@gmail.com Samaneh Dehghan Samaneh Dehghan Physiology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran dehghans62@gmail.com Barbara Demeneix Barbara Demeneix Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, Muséum National ďHistoire Naturelle, Paris, France bdem@mnhn.fr Mohammad Javan Mohammad Javan Physiology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran mjavan@modares.ac.ir Demyelination NgR SVZ Progenitor cells Multiple Sclerosis Alvarez-Palazuelos LE, Robles-Cervantes MS, Castillo-Velazquez G, Rivas-Souza M, Guzman-Muniz J, Moy-Lopez N, Gonzalez-Castaneda RE, Luquin S, Gonzalez-Perez O. Regulation of neural stem cell in the human SVZ by trophic and morphogenic factors. Curr Signal Transduct Ther. 2011; 6(3): 320–326.##Baer AS, Syed YA, Kang SU, Mitteregger D, Vig R, Ffrench-Constant C, Franklin RJ, Altmann F, Lubec G, Kotter MR. Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of FYN-RHOA and protein kinase C signalling. Brain J. Neurol. 2009; 132: 465-481. ##Chitnis T, Imitola J, Wang Y, Elyman W, Chawla P, Sharukh M, Raddussi K, Bronson RT, Koury SJ. Elevated neural expression of CD 200 protects wlds mice from inflammation-mediated neurodegeneration. Am J Pathol. 2007; 170: 1695-1712.##Chong SY, Rosenberg SS, Fancy SP, Zhao C, Shen YA, et al. Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. PNAS. 2012; 109: 1299-1304.##Crespel A, Rigau V, Coubes P, Rousset MC, de Bock F, Okano H, Baldy-Moulinier M, Bockaert J, Lerner-Natoli M. Increased number of neural progenitors in human temporal lobe epilepsy. Neurobiol Dis. 2005; 19(3):436-450.##Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RL. Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. PNAS. 2003; 100(15): 9023-2027.##Decherf S, Seugnet I, Kouidhi S, Lopez-Juarez A, Clerget-Froidevaux MS, et al. Thyroid hormone exerts negative feedback on hypothalamic type 4 melanocortin receptor expression. PNAS. 2010; 107: 4471–4476.##Decker L, Picard-Riera N, Lachapelle F, Baron-Van Evercooren A. Growth factor treatment promotes mobilization young but not aged adult subventricular zone precursors in response to demyelination. J Neurosci Res. 2002; 69: 763-771.##Dehghan S, Javan M, Pourabdolhossein F, Mirnajafi-Zadeh J, Baharvand H. Basic fibroblast growth factor potentiates myelin repair following induction of experimental demyelination in adult mouse optic chiasm and nerves. J Mol Neurosci. 2012; 48(1):77-85.##Fischer D, He Z, Benowitz LI. Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J Neurosci. 2004; 24:1646-1651.##Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature. 2001; 409:341–346.##Fry EJ, Ho C, David S. A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron. 2007; 53: 649–662.##Guazzo EP. A technique for producing demyelination of the rat optic nerves. J Clin Neurosci. 2005; 12: 54-58.##Harvey PA, Lee DH, Qian F, Weinreb PH, Frank E. Blockade of Nogo receptor ligands promotes functional regeneration of sensory axons after dorsal root crush. J Neurosci. 2009; 29: 6285–6295.##Huang JY, Wang YX, Gu WL, Fu SL, Li Y, et al. Expression and function of myelin-associated proteins and their common receptor NgR on oligodendrocyte progenitor cells. Brain res. 2012; 1437: 1–15.##Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA. Increased hippocampal neurogenesis in Alzheimer's disease. PNAS. 2004; 101(1):343-347.##Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, et al. The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination. Nat. Neurosci. 2004; 7: 736-744.##Kotter MR, Li WW, Zhao C, Franklin RJ. Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J. Neurosci. 2006; 26: 328–332.##Kremer, D.; Gottle, P.; Hartung, H.P.; Kury, P. Pushing forward: Remyelination as the new frontier in CNS diseases. Trends Neurosci. 2016, 39, 246-263.##Li X, Su H, Fu QL, Guo J, Lee DH, So KF, Wu W. Soluble NgR fusion protein modulates the proliferation of neural progenitor cells via the notch pathway. Neurochem Res. 2011; 36:2363-2372.##Mathis C, Schro¨ter A, Thallmair M, Schwab ME. Nogo-A regulates neural precursor migration in the embryonic mouse cortex. Cereb Cortex. 2010; 20:2380–2390.##Mingorance A, Fontana X, Sole´ M, Burgaya F, Uren ˜a JM, Teng FY, Tang BL, Hunt D, Anderson PN, Bethea JR, Schwab ME, Soriano E, del Río JA. Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions. Mol Cell Neurosci. 2004; 26:34-49.##Mohajeri M, Sadeghizadeh M, Najafi F, Javan M. Polymerized nano-curcumin attenuates neurological symptoms in EAE model of multiple sclerosis through down regulation of inflammatory and oxidative processes and enhancing neuroprotection and myelin repair. Neuropharmacol. 2015; 99:156-167.##Mozafari S, Sherafat MA, Javan M, Mirnajafi-Zadeh J, Tiraihi T. Visual evoked potentials and MBP gene expression imply endogenous myelin repair in adult rat optic nerve and chiasm following local lysolecithin induced demyelination. Brain Res. 2010; 1351: 50-56.##Mozafari S, Javan M, Sherafat MA, Mirnajafi-Zadeh J, Heibatollahi M, Pour-Beiranvand S, Tiraihi T, Ahmadiani A. Analysis of structural and molecular events associated with adult rat optic chiasm and nerves demyelination and remyelination: possible role for 3rd ventricle proliferating cells. Neuromolecular Med. 2011; 13(2):138-150.##Nait-Oumesmar B, Decker L, Lachapelle F, Avellana-Adalid V, Bachelin C, Baron-Van Evercooren A. Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur J Neurosci. 1999; 11: 4357-4366.##Nait-Oumesmar B, Picard-Riera N, Kerninon C, Deccker L, Seilhean D, HÖlinger GU, Hirsch EC, Reynolds R, Baron-Van Evercooren A. Activation of the subventricular zone in multiple sclerosis: Evidence for early glial progenitors. PNAS. 2007; 104 (11): 4694-4699.##Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis. New Engl J Med. 2000; 343: 938-952. ##Paxinos GF, Franklin KBJ. The mouse brain in stereotaxic coordinates. 2004, San Diego, California: Academic Press##Pazhoohan S, Satarian L, Asghari AA, Salimi M, Kiani S, Mani AR, Javan M. Valproic Acid attenuates disease symptoms and increases endogenous myelin repair by recruiting neural stem cells and oligodendrocyte progenitors in experimental autoimmune encephalomyelitis. Neurodegener. Dis. 2014; 13(1):45-52.##Petratos S, Ozturk E, Azari MF, Kenny R, Lee JY, et al. Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation. Brain. 2012; 135: 1794-1818.##Picard-Riera N, Decker L, Delarasse C, Goude K, Nait-Oumesmar B, Liblau R, Pham-Dinh D, Baron-Van Evercooren A. Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice. PNAS. 2002; 99 (20): 13211-13216.##Picard-Riera N, Nait-Oumesmar B, Baron-Van Evercooren A. Endogenous adult neural stem cells: limits and potential to repair the injured central nervous system. J Neurosci Res. 2004; 15; 76(2): 223-231.##Pourabdolhossein F, Mozafari S, Javan M, Mirnajafizadeh S J, Ahmadiani A. Electrophysiological and Histological Study of Lysolecithin-Induced Local Demyelination in Adult Mice Optic Chiasm. Physiol Pharmacol. 2011; 14 (4) :324-336.##Pourabdolhossein F, Mozafari S, Morvan-Dubois G, Mirnajafi-Zadeh J, Lopez-Juarez A, Pierre-Simons J, Demeneix BA, Javan M. Nogo receptor inhibition enhances functional recovery following lysolecithin-induced demyelination in mouse optic chiasm. PLoS One. 2014 Sep 3;9(9):e106378.##Pourabdolhossein F, Gil-Perotín S, Garcia-Belda P, Dauphin A, Mozafari S, Tepavcevic V, Manuel Garcia Verdugo J, Baron-Van Evercooren A. Inflammatory demyelination induces ependymal modifications concomitant to activation of adult (SVZ) stem cell proliferation. Glia. 2017; 65(5):756-772.##Ramasamy S, Yu F, Hong Yu Y, Srivats H, Dawe GS, Ahmed S. NogoR1 and PirB signaling stimulates neural stem cell survival and proliferation. Stem Cells. 2014; 32(6):1636-1648.##Remaud S, Lopez-Juarez SA, Bolcato-Bellemin AL, Neuberg P, Stock F, et al. Inhibition of Sox2 Expression in the Adult Neural Stem Cell Niche In Vivo by Monocationic-based siR Delivery. Mol Ther Nucleic acids. 2013; 2: e89.##Rolando C, Parolisi R, Boda E, Schwab ME, Rossi F, Buffo A. Distinct roles of Nogo-A and Nogo receptor 1 in the homeostatic regulation of adult neural stem cell function and neuroblast migration. J Neurosci. 2012; 32(49):17788-17799. ##Satoh J, Onoue H, Arima K, Yamamura T. Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis. J Neuropathol. Exp. Neurol. 2005; 64: 129–138.##Sherafat MA, Javan M, Mozafari S, Mirnajafi-Zadeh J, Motamedi F. Castration attenuates myelin repair following lysolecithin induced demyelination in rat optic chiasm: an evaluation using visual evoked potential, marker genes expression and myelin staining. Neurochem Res. 2011; 36(10):1887-1895.##Sherafat MA, Heibatollahi M, Mongabadi S, Moradi F, Javan M, Ahmadiani A. Electromagnetic field stimulation potentiates endogenous myelin repair by recruiting subventricular neural stem cells in an experimental model of white matter demyelination. J Mol Neurosci. 2012; 48(1):144-53.## Steinbach K, McDonald CL, Reindl M, Schweigreiter R, Bandtlow C, Martin R. Nogo-Receptors NgR1 and NgR2 Do Not Mediate Regulation of CD4 T Helper Responses and CNS Repair in Experimental Autoimmune Encephalomyelitis. PLoS One. 2011; 6(11): e26341.##Su Z, Cao L, Zhu Y, Liu X, Huang Z, et al. Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration. J. Cell. Sci. 2007; 120: 1877–1887.##Syed YA, Baer AS, Lubec G, Hoeger H, Widhalm G, et al. Inhibition of oligodendrocyte precursor cell differentiation by myelin-associated proteins. Neurosurgical focus. 2008; 24: E5.##Wang B, Xiao Z, Chen B, Han J, Gao Y, et al. Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTORSTAT3 pathway. PloS one. 2008: 3; e1856.##Wang F, Zhu Y. The interaction of Nogo-66 receptor with Nogo-p4 inhibits the neuronal differentiation of neural stem cells. Neurosci. 2008; 151:74-81.##Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, et al. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature. 2002; 417:941–944.##Wang T, Wang J, Yin C, Liu R, Zhang JH, et al. Down-regulation of Nogo receptor promotes functional recovery by enhancing axonal connectivity after experimental stroke in rats. Brain Res. 2010; 1360: 147-158.##Wang X, Chun SJ, Treloar H, Vartanian T, Greer CA, Strittmatter SM. Localization of Nogo-A and Nogo-66 Receptor proteins at sites of axonmyelin and synaptic contact. J Neurosci. 2002;##22:5505–5515.##Yang Y, Liu Y, Wei P, Peng H, Winger R, et al. Silencing Nogo-A promotes functional recovery in demyelinating disease. Ann. Neurol. 2010; 67: 498-507.##Yu P, Huang L, Zou J, Yu Z, Wang Y, et al. Immunization with recombinant Nogo-66 receptor (NgR) promotes axonal regeneration and recovery of function after spinal cord injury in rats. Neurobiol. Dis. 2008; 32: 535-542.#### ##

PKMζ contributes in consolidation, retrieval and maintenance of amygdala dependent fear memory in rats 2 2 Introduction: Protein kinase M zeta (PKMζ) is assumed to be actively involved in retainig long-term potentiation. The goal of this study was to investigate the role of PKMζ in basolateral amygdala (BLA) upon acquisition, consolidation, retention and retrieval of memory using a specific inhibitor of PKMζ. Methods: Sixty male wistar rats underwent stereotaxic surgery and were cannulated bilaterally at the BLA nucleus. Then animals were divided into 4 groups of receiving BLA microinjection of zeta inhibitory peptide (ZIP) in different time courses: 30 min before and after training, 30 min before the testing (on the day after the learning) and 30 min after testing (but testing 10 days later). Memory was assessed using step through passive avoidance. Results: ZIP infusion in BLA had no significant change on acquisition (P=0.06), however significantly impaired consolidation, retrieval and maintenance of passive avoidance memory (P=0.012). Conclusion: Findings indicate that PKMζ activity in the BLA plays an important role in retaining amygdala dependent avoidance memory interfering the process of consolidation, retrieval and maintenance of learned task. 206 215 2017/03/112016/12/122017/03/112017/07/102017/02/23 1395/12/5 2017/07/262017/08/222017/07/262017/08/242017/06/29 1396/4/8 Bentolhoda Amirshabani Bentolhoda Amirshabani Department of Physiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran Hoda.amirshabani94@gmail.com Mohammad Rostampoor Mohammad Rostampoor Department of Physiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran rost_v@yahoo.com Parvin Babaei Parvin Babaei Department of Physiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran p_babaei@yahoo.com Protein kinase Mζ(PKMζ) Learning Fear memory zeta inhibitory peptide (ZIP) 1. Giese KP. Long-term potentiation and memory. Memory mechanisms of health of disease (ed Giese KP). 2012:1-17.##2. Stewart MG, Popov VI. Structural synaptic and dendritic spine plasticity in the hippocampus. Memory mechanisms in health and disease (ed Giese KP). 2012:19-52.##3. Papoutsi A, Sidiropoulou K, Poirazi P. Memory beyond synaptic plasticity: the role of intrinsic neuronal excitability. Memory mechanisms in health and disease (ed Giese KP). 2012:53-80.##4. Kim SY, Jung Y, Hwang GS, Han H, Cho M. Phosphorylation alters backbone conformational preferences of serine and threonine peptides. Proteins: Structure, Function, and Bioinformatics. 2011;79(11):3155-65.##5. Giese KP, Mizuno K. The roles of protein kinases in learning and memory. Learning & memory. 2013;20(10):540-52.##6. Schwartz JH, Greenberg SM. Molecular mechanisms for memory: second-messenger induced modifications of protein kinases in nerve cells. Annual review of neuroscience. 1987;10(1):459-76.##7. Hernandez AI, Blace N, Crary JF, Serrano PA, Leitges M, Libien JM, et al. Protein Kinase Mζ Synthesis from a Brain mRNA Encoding an Independent Protein Kinase Cζ Catalytic Domain IMPLICATIONS FOR THE MOLECULAR MECHANISM OF MEMORY. Journal of Biological Chemistry. 2003;278(41):40305-16.##8. Madroñal N, Gruart A, Sacktor TC, Delgado-García JM. PKMζ inhibition reverses learning-induced increases in hippocampal synaptic strength and memory during trace eyeblink conditioning. PLos one. 2010;5(4):e10400.##9. Sacktor TC. How does PKMζ maintain long-term memory? Nature Reviews Neuroscience. 2011;12(1):9-15.##10. Wang D-C, Liu P-C, Hung H-S, Chen T-J. Both PKMζ and KIBRA are closely related to reference memory but not working memory in a T-maze task in rats. Journal of Comparative Physiology A. 2014;200(1):77-82.##11. Hara Y, Punsoni M, Yuk F, Park CS, Janssen WG, Rapp PR, et al. Synaptic distributions of GluA2 and PKMζ in the monkey dentate gyrus and their relationships with aging and memory. The Journal of Neuroscience. 2012;32(21):7336-44.##12. Xue Y-X, Zhu Z-Z, Han H-B, Liu J-F, Meng S-Q, Chen C, et al. Overexpression of protein kinase Mζ in the prelimbic cortex enhances the formation of long-term fear memory. Neuropsychopharmacology. 2015;40(9):2146-56.##13. Muslimov IA, Nimmrich V, Hernandez AI, Tcherepanov A, Sacktor TC, Tiedge H. Dendritic Transport and Localization of Protein Kinase Mζ mRNA IMPLICATIONS FOR MOLECULAR MEMORY CONSOLIDATION. Journal of Biological Chemistry. 2004;279(50):52613-22.##14. Tiunova A, Bezryadnov D, Anokhin K. Involvement of Protein Kinase Mζ in the Maintenance of Long-Term Memory for Taste Aversion Learning in Young Chicks. Bulletin of experimental biology and medicine. 2015;158(5):592-4.##15. Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC. Storage of spatial information by the maintenance mechanism of LTP. Science. 2006;313(5790):1141-4.##16. LeBlancq MJ, McKinney TL, Dickson CT. ZIP It: Neural Silencing Is an Additional Effect of the PKM-Zeta Inhibitor Zeta-Inhibitory Peptide. The Journal of Neuroscience.8-6193:(23)36;2016.##17. Migues PV, Hardt O, Wu DC, Gamache K, Sacktor TC, Wang YT, et al. PKM [zeta] maintains memories by regulating GluR2-dependent AMPA receptor trafficking. Nature neuroscience. 2010;13(5):630-4.##18. Yao Y, Shao C, Jothianandan D, Tcherepanov A, Shouval H, Sacktor TC. Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKMζ in neurons. Neuropharmacology. 2013;64:37-44.##19. Xue Y-X, Luo Y-X, Wu P, Shi H-S, Xue L-F, Chen C, et al. A memory retrieval-extinction procedure to prevent drug craving and relapse. Science. 2012;336(6078):241-5.##20. Moncada D, Viola H. PKMζ inactivation induces spatial familiarity. Learning & Memory. 2008;15(11):810-4.##21. Crary JF, Shao CY, Mirra SS, Hernandez AI, Sacktor TC. Atypical protein kinase C in neurodegenerative disease I: PKMζ aggregates with limbic neurofibrillary tangles and AMPA receptors in Alzheimer disease. Journal of Neuropathology & Experimental Neurology. 2006;65(4):319-26.##22. Paxinos G, Watson C. The rat brain in stereotaxic coordinates 2nd ed. Academic: New York, NY, USA. 1986.##23. Serrano P, Yao Y, Sacktor TC. Persistent phosphorylation by protein kinase Mζ maintains late-phase long-term potentiation. The Journal of neuroscience. 2005;25(8):1979-84.##24. Crespo JA, Stöckl P, Ueberall F, Jenny M, Saria A, Zernig G. Activation of PKCzeta and PKMzeta in the nucleus accumbens core is necessary for the retrieval, consolidation and reconsolidation of drug memory. PloS one. 2012;7(2):e30502.##25. Shema R, Sacktor TC, Dudai Y. Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKMζ. Science. 2007;317(5840):951-3.##26. Morris R, Anderson E, Lynch Ga, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP 5. Nature. 1986;319(6056):774-6.##27. Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361(6407):31.##28. Stanton PK, Bramham C, Scharfman HE. Synaptic plasticity and transsynaptic signaling: Springer Science & Business Media; 2006.##29. McGaugh JL. Memory--a century of consolidation. Science. 2000;287(5451):248-51.##30. Serrano P, Friedman EL, Kenney J, Taubenfeld SM, Zimmerman JM, Hanna J, et al. PKMζ maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biol. 2008;6(12):e318.##31. Edelman AM, Blumenthal DK, Krebs EG. Protein serine/threonine kinases. Annual review of biochemistry. 1987;56(1):567-613.##32. Abel T, Nguyen PV, Barad M, Deuel TA, Kandel ER, Bourtchouladze R. Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell. 1997;88(5):615-26.##33. Alberini CM. Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends in neurosciences. 2005;28(1):51-6.##34. Reis DS, Jarome TJ, Helmstetter FJ. Memory formation for trace fear conditioning requires ubiquitin-proteasome mediated protein degradation in the prefrontal cortex. 2013.##35. Murchison CF, Zhang X-Y, Zhang W-P, Ouyang M, Lee A, Thomas SA. A distinct role for norepinephrine in memory retrieval. Cell. 2004;117(1):131-43.##36. Mamou CB, Gamache K, Nader K. NMDA receptors are critical for unleashing consolidated auditory fear memories. Nature neuroscience. 2006;9(10):1237-9.##37. Shema R, Hazvi S, Sacktor TC, Dudai Y. Boundary conditions for the maintenance of memory by PKMζ in neocortex. Learning & Memory. 2009;16(2):122-8.##38. Parsons RG, Davis M. Corrigendum: Temporary disruption of fear-potentiated startle following PKM [zeta] inhibition in the amygdala. Nature Neuroscience. 2011;14(12):1617-.##39. Zhang Y, Zong W, Zhang L, Ma Y, Wang J. Protein kinase M ζ and the maintenance of long-term memory. Neurochemistry International. 2016;99:215-20.##40. Kwapis JL, Jarome TJ, Gilmartin MR, Helmstetter FJ. Intra-amygdala infusion of the protein kinase Mzeta inhibitor ZIP disrupts foreground context fear memory. Neurobiology of learning and memory. 2012;98(2):148-53.##41. Hernández AI, Oxberry WC, Crary JF, Mirra SS, Sacktor TC. Cellular and subcellular localization of PKMζ. Phil Trans R Soc B. 2014;369(1633):20130140.##42. Balaban PM, Roshchin M, Timoshenko AK, Zuzina AB, Lemak M, Ierusalimsky VN, et al. Homolog of protein kinase Mζ maintains context aversive memory and underlying long-term facilitation in terrestrial snail Helix. Frontiers in cellular neuroscience. 2015;9.##43. Yoshihama Y, Hirai T, Ohtsuka T, Chida K. KIBRA co-localizes with protein kinase Mζ (PKMζ) in the mouse hippocampus. Bioscience, biotechnology, and biochemistry. 2009;73(1):147-51.##44. Yao Y, Kelly MT, Sajikumar S, Serrano P, Tian D, Bergold PJ, et al. PKMζ maintains late long-term potentiation by N-ethylmaleimide-sensitive factor/GluR2-dependent trafficking of postsynaptic AMPA receptors. The Journal of neuroscience. 2008;28(31):7820-7.##45. Ko H-G, Kim J-i, Sim S-E, Kim T, Yoo J, Choi S-L, et al. The role of nuclear PKMζ in memory maintenance. Neurobiology of Learning and Memory2016.1350:50-56.#### ##

Central administration of resistin into the paraventricular nucleus (PVN) produces significant cardiovascular responses 2 2 Introduction: Resistin, a complex multimeric structure which is secreted by adipose tissue and circulates in the blood, acts on the hypothalamus to increase sympathetic nerve activity, inhibit appetite and is associated with obesity, insulin resistance and cardiovascular disorders. In this study, we survey the cardiovascular effects of direct injection of resistin into specific cell group of the paraventricular nucleus (PVN) that is known as one of the centers which control the baseline of arterial pressure and heart rate. Methods: Adult male rats were anesthetized with urethane (1.4g/kg intraperitoneally). Arterial pressure (AP) and heart rate (HR) were monitored before and after treatment. Resistin (1, 3 and 5μg/rat), norepinephrine (2.5 nM), muscimol (250ng/rat) and saline as control (vehicle solution, 1μl) were injected into the PVN parvocellular neurons. Results: The results showed that resistin (3 and 5μg/rat) caused a significant increase in AP, HR and high QRS compared to control group and prior to its injection. Injection of norepinephrine into the PVN evoked a significant increase in AP, HR and QRS amplitude, whereas injection of muscimol significantly decreased these parameters. In the control group, saline injection into the PVN had no significant effect on these parameters. Conclusion: It can be concluded that the PVN can be one of the important central areas for actions of resistin which had obvious effects on HR and AP. These results provide a base for future studies to explore the role of resistin in cardiovascular responses in conditions like metabolic syndrome and hypertension. 216 224 2017/03/112016/12/122017/03/112017/07/102017/02/232017/02/1 1395/11/13 2017/07/262017/08/222017/07/262017/08/242017/06/292017/06/7 1396/3/17 Abolfazl Akbari Abolfazl Akbari Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran Gholamali Jelodar Gholamali Jelodar Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran jelodar@shirazu.ac.ir Resistin Paraventricular Nucleus Heart Rate Arterial Pressure Allen AM. Inhibition of the hypothalamic paraventricular nucleus in spontaneously hypertensive rats dramatically reduces sympathetic vasomotor tone. Hypertension 2002; 39: 275-280.##Benaroch EE. Paraventricular nucleus, stress response, and cardiovascular disease. Clinical Autonomic Research 2005; 15: 254-263.##Bhalla V, Kalogeropoulos A, Georgiopoulou V & Butler J. Serum resistin: physiology, pathophysiology and implications for heart failure. Biomarkers 2010; 4: 445-452.##Brunetti L, Orlando G, Recinella L, Michelotto B, Ferrante C, Vacca M.. Resistin, but not adiponectin, inhibits dopamine and norepinephrine release in the hypothalamus. European journal of pharmacology 2004; 493: 41-44.##Busanardo C, Crestni CC, Tavares RF, Resstel LB, Correa FM.. Cardiovascular responses to L-glutamate microinjection into the hypothalamic paraventricular nucleus are mediated by a local nitric oxide-guanylate cyclase mechanism. Brain research 2010; 1344: 87-95.##Busanardo C, Tavares RF, Correa F.. Role of N‐methyl‐D‐aspartate and non‐N‐methyl‐D‐aspartate receptors in the cardiovascular effects of L‐glutamate microinjection into the hypothalamic paraventricular nucleus of unanesthetized rats. Journal of neuroscience research 2009; 87: 2066-2077.##Chen Q, Li DP, Pan HL.. Presynaptic α1 adrenergic receptors differentially regulate synaptic glutamate and GABA release to hypothalamic presympathetic neurons. Journal of Pharmacology and Experimental Therapeutics 2006; 316: 733-742.##Chen QH, Haywood JR, Toney GM.. Sympathoexcitation by PVN-injected bicuculline requires activation of excitatory amino acid receptors. Hypertension 2003; 42: 725-731.##Coote J, Yang Z, Pyner S, Deering J.. Control of sympathetic outflows by the hypothalamic paraventricular nucleus. Clinical and experimental pharmacology and physiology 1998; 25: 461-463.##Daftary S, Boudaba C, Tasker J.. Noradrenergic regulation of parvocellular neurons in the rat hypothalamic paraventricular nucleus. Neuroscience 2000; 96: 743-751.##Dampney R. Functional organization of central pathways regulating the cardiovascular system. Physiological reviews 1994; 74: 323-364.##Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Isoproterenol inhibits resistin gene expression through a GS‐protein‐coupled pathway in 3T3‐L1 adipocytes. FEBS letters 2001a; 500: 60-63.##Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Tumor necrosis factor α is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes. Biochemical and biophysical research communications 2001b; 288: 1027-1031.##Frankel DS, Vasan RS, D'agostino RB, Benjamin EJ, Levy D, Wang TJ, Meigs JB.. Resistin, adiponectin, and risk of heart failure: the Framingham offspring study. Journal of the American College of Cardiology 2009; 53: 754-762.##Guyenet PG. The sympathetic control of blood pressure. Nature Reviews Neuroscience 2006; 7: 335-346.##HILL, J. W. 2012. PVN pathways controlling energy homeostasis. Indian journal of endocrinology and metabolism, 16, 627.##Hwang KR, Chans SH, Chan JY.. Noradrenergic neurotransmission at PVN in locus ceruleus-induced baroreflex suppression in rats. American Journal of Physiology-Heart and Circulatory Physiology 1998; 274: H1284-H1292.##Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM. Resistin gene expression in human adipocytes is not related to insulin resistance. Obesity research 2002; 10: 1-5.##Kannan H, Niijima A, Yamashita H.. Effects of stimulation of the hypothalamic paraventricular nucleus on blood pressure and renal sympathetic nerve activity. Brain research bulletin 1988; 20: 779-783.##Kos K, Harte AL, Dasilva NF, Tonchev A, Chaldakov G, James S, Snead DR, Hoggart B, O’hare JP, Mcternan PG. Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus. The Journal of Clinical Endocrinology & Metabolism 2007; 92: 1129-1136.##Kosari S, Rathner J, Chen F, Kosari S, Badoer E.. Centrally administered resistin enhances sympathetic nerve activity to the hindlimb but attenuates the activity to brown adipose tissue. Endocrinology 2011;152: 2626-2633.##Li YF, Jakson KL, Stern JE, Rabeler B, Patel KP. Interaction between glutamate and GABA systems in the integration of sympathetic outflow by the paraventricular nucleus of the hypothalamus. American Journal of Physiology-Heart and Circulatory Physiology 2006; 291: H2847-H2856.##Ling C, Kindblom J, Wennbo H, Billing H. Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels. FEBS letters 2001; 507: 147-150.##Lu SC, Shieh WY, Chen CY, Hsu SC, Chen HL. Lipopolysaccharide increases resistin gene expression in vivo and in vitro. FEBS letters 2002; 530: 158-162.##Marsh AJ, Fontes MA, Killinger S, Pawlak DB, Polson JW, Dampney RA. Cardiovascular responses evoked by leptin acting on neurons in the ventromedial and dorsomedial hypothalamus. Hypertension 2003; 42: 488-493.##Morash BA, Ur E, Wiesner G, Roy J, Wilkinson M. Pituitary resistin gene expression: effects of age, gender and obesity. Neuroendocrinology, 2004; 79: 149-156.##Nagaev I & Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochemical and biophysical research communications 2001; 285: 561-564.##Papay R, Gaivin R, Mccune DF, Rorabaugh BR, Macklin WB, Mcgath JC, Perez DM. Mouse α1B‐adrenergic receptor is expressed in neurons and NG2 oligodendrocytes. Journal of Comparative Neurology 2004;478: 1-10.##Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA. Resistin is expressed in human macrophages and directly regulated by PPARγ activators. Biochemical and biophysical research communications 2003; 300: 472-476.##Ranson R, Motawei K, Pyner S, Coote J. The paraventricular nucleus of the hypothalamus sends efferents to the spinal cord of the rat that closely appose sympathetic preganglionic neurones projecting to the stellate ganglion. Experimental brain research 1998; 120: 164-172.##Rinman L. Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and behavioral functions. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2011; 300: R222-R235.##Rodriguez-Pacheco F, Vazquez-Martinez R, Martinez-Fuentes AJ, Pulido MR, Gahete MD, etal. Resistin regulates pituitary somatotrope cell function through the activation of multiple signaling pathways. Endocrinology 2009; 150: 4643-4652.##Samuels E & Szabadi E. Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organisation. Current neuropharmacology 2008; 6: 235-253.##Savage DB, Sewter CP, Klenk ES, Segal DG, et al.. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator–activated receptor-γ action in humans. Diabetes 2001; 50: 2199-2202.##Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312.##Steppan CM, Wang J, Whiteman EL, Birnbaum MJ, Lazard MA. Activation of SOCS-3 by resistin. Molecular and cellular biology 2005; 25: 1569-1575.##Stone EA, Quartermain D, Lin Y, Lehmann ML. Central α 1-adrenergic system in behavioral activity and depression. Biochemical pharmacology 2007; 73: 1063-1075.##Takeishi Y, Niizeki T, Arimoto T, Nozaki N, Hirono O, et al. Serum Resistin is Associated With High Risk in Patients With Congestive Heart Failure A Novel Link Between Metabolic Signals and Heart Failure. Circulation Journal 2007; 71: 460-464.##Tovar S, Nogueras R, Tung LY, Castaneda TR, et al. Central administration of resistin promotes short-term satiety in rats. European Journal of Endocrinology 2005; 153: R1-R5.##Vazquez MJ, Gonzalez CR, Varela L, Lage R, Tovar S, et al. Central resistin regulates hypothalamic and peripheral lipid metabolism in a nutritional-dependent fashion. Endocrinology 2008; 149: 4534-4543.##Viengchareun S, Zennaro MC, Tallec PL, Lmbes M. Brown adipocytes are novel sites of expression and regulation of adiponectin and resistin. FEBS letters 2002; 532: 345-350.##Watson C & Paxinos G. The Rat Brain in Stereotaxic Coordinates. Elsevier 2005; 39-48.##Yura S., Sagawa N, Itoh H, Kakui K, Nuamah MA,et al.. Resistin is expressed in the human placenta. The Journal of Clinical Endocrinology & Metabolism 2003; 88: 1394-1397.#### ##

Mechanical activity of isolated aorta strips after prolonged exposure to low frequency electromagnetic fields and its interaction with the cholinergic and adrenergic systems in male rat 2 2 Introduction: Public concern about the potential effects of electromagnetic field (EMF) on human health is increased by progressive usage of electrical devices in modern life. The aim of this study was to investigate the effect of prolonged exposure to low frequency EMF on the mechanical activity of isolated thoracic aorta strips in rats. Methods: Fourteen male rats were randomly allocated into sham and experimental groups. Experimental group was continuously exposed to 1mT, 50Hz EMF, for 75 days in a magnetic coil box. Sham group was kept under conditions similar to experimental group, without being exposed to EMF. After 75 days, the rats were anaesthetized and the thoracic aorta was dissected and cut into 1cm strips. Aortic strips were suspended in organ bath chambers containing of Krebs’ buffer and were bubbled with a gas mixture (5% CO2, 95% O2). Then the aortic isometric tension was measured during 20-min equilibration period and after cumulative administration of acetylcholine and phenylephrine in different concentrations. Results: Increased vasocontraction responses to 10-6 M phenylephrine were observed in experimental group compared to sham group (P<0.05). Moreover, reduced vasorelaxation responses to 8×10-5 M acetylcholine were observed in the experimental group compared to sham group (P<0.05). Conclusion: It can be suggested that prolonged exposure to EMF have an effect on the vascular sensitivity to cholinergic and adrenergic system, can lead to alteration of the vascular resistance. 225 233 2017/03/112016/12/122017/03/112017/07/102017/02/232017/02/12016/09/1 1395/6/11 2017/07/262017/08/222017/07/262017/08/242017/06/292017/06/72017/07/2 1396/4/11 Maryam Owjfard Maryam Owjfard Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran : maryam.owjfard@yahoo.com Aminollah Bahaodini Aminollah Bahaodini Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran bahaodini@shirazu.ac.ir Amin Tamadon Amin Tamadon Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran amintamaddon@yahoo.com Electromagnetic field Thoracic aorta Phenylephrine Acetylcholine Gnus J, Czerski A, Ferenc S, Zawadzki W, Witkiewicz W, Rusiecka A, et al. Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro. Acta Veterinaria Brunensis 2013; 82: 331–336.##Graham RM, Perez DM, Hwa J, Piascik MT. Alpha 1-adrenergic receptor subtypes. Molecular structure, function, and signaling. Circulation Research 1996; 78: 737-749.##Ichioka S, Minegishi M, Iwasaka M, Shibata M, Nakatsuka T, Harii K, et al. High-intensity static magnetic fields modulate skin microcirculation and temperature in vivo. Bioelectromagnetics 2000; 21: 183-188.##Kobbert C, Berndt A, Bierbaum T, Sontag W, Breithardt G, Weissen-Plenz G, et al. Low-energy electromagnetic fields promote proliferation of vascular smooth muscle cells. Electromagnetic Biology and Medicine 2008; 27: 41-53.##Mayrovitz HN, Groseclose EE. Effects of a static magnetic field of either polarity on skin microcirculation. Microvascular Research 2005; 69: 24-27.##Mayrovitz HN, Groseclose EE, King D. No effect of 85 mt permanent magnets on laser-doppler measured blood flow response to inspiratory gasps. Bioelectromagnetics 2005; 26: 331-335.##McNamee D, Corbacio M, Weller J, Brown S, Stodilka R, Prato F, et al. The response of the human circulatory system to an acute 200-μt, 60-hz magnetic field exposure. International Archives of Occupational and Environmental Health 2011 84: 267-277.##Miura M, Okada J. Non-thermal vasodilatation by radio frequency burst-type electromagnetic field radiation in the frog. Journal of Physiology 1991: 257-273.##Miura M, Takayama K, Okada J. Increase in nitric oxide and cyclic gmp of rat cerebellum by radio frequency burst-type electromagnetic field radiation. Journal of Physiology## 1993; 461: 513-524.##Monfrecola G, Moffa G, Procaccini EM. Non-ionizing electromagnetic radiations, emitted by a cellular phone, modify cutaneous blood flow. Dermatology 2003; 207: 4-10.##Morris C, Skalak T. Static magnetic fields alter arteriolar tone in vivo. Bioelectromagnetics 2005; 26: 1-9.##Öcal I, Günay I. The effects of chronic ac magnetic field on contraction and relaxation of isolated thoracic aorta rings of healthy and diabetic rats. Brazilian Archives of Biology and Technology 2004; 47: 733-738.##Ohkubo C, Xu S. Acute effects of static magnetic fields on cutaneous microcirculation in rabbits. In Vivo 1997; 11: 221-225.##Okano H, Gmitrov J, Ohkubo C. Biphasic effects of static magnetic fields on cutaneous microcirculation in rabbits. Bioelectromagnetics 1999; 20: 161-171.##Okano H, Ohkubo C. Modulatory effects of static magnetic fields on blood pressure in rabbits. Bioelectromagnetics 2001a; 22: 408-418.##Okano H, Ohkubo C. Modulatory effects of static magnetic fields on blood pressure in rabbits. Bioelectromagnetics 2001b; 22: 408-418.##Rapoport RM, Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cgmp. Circulation Research## 1983; 52: 352-357.##Roshangar B, Soleimani-Rad J, Roya A, Leila R. Effect of low frequency electromagnetic field on cardiovascular system: An ultrastructural and immunohistochemical study. Annals of Biological Research 2012; 3: 81.##Schuhfried O, Vacariu G, Rochowanski H, Serek M, Fialka-Moser V. The effects of low-dosed and high-dosed low-frequency electromagnetic fields on microcirculation and skin temperature in healthy subjects. International Journal of Sports Medicine 2005; 26: 886-890.##Smith TL, Wong-Gibbons D, Maultsby J. Microcirculatory effects of pulsed electromagnetic fields. Journal of Orthopaedic Research 2004; 22: 80-84.##Tamadon A, Kafi M, Saeb M, Ghavami M. Association of milk yield and body condition score indices with the commencement of luteal activity after parturition in high producing dairy cows. Iranian Journal of Veterinary Research 2011; 12: 184-191.##Tepper OM, Callaghan MJ, Chang EI, Galiano RD, Bhatt KA, Baharestani S, et al. Electromagnetic fields increase in vitro and in vivo angiogenesis through endothelial release of fgf-2. FASEB J 2004; 18: 1231-1233.##Traikov L, Ushiyama A, Lawlor G, Sasaki R, Ohkubo C. Subcutaneous arteriolar vasomotion changes during and after elf-emf exposure in mice in vivo. Environmentalist 2005; 25: 93-101.##Wanstall JC, Jeffery TK, Gambino A, Lovren F, Triggle CR. Vascular smooth muscle relaxation mediated by nitric oxide donors: A comparison with acetylcholine, nitric oxide and nitroxyl ion. British Journal of Pharmacology 2001; 134: 463-472.##Wu D, Katz A, Lee CH, Simon MI. Activation of phospholipase c by alpha 1-adrenergic receptors is mediated by the alpha subunits of gq family. J Biol Chem 1992; 267: 25798-25802.##Yen-Patton GPA, Patton WF, Beer DM, Jacobson BS. Endothelial cell response to pulsed electromagnetic fields: Stimulation of growth rate and angiogenesis in vitro. Journal of Cellular Physiology 1988; 134: 37-46.##Yoshikawa T, Tanigawa M, Tanigawa T, Imai A, Hongo H, Kondo M. Enhancement of nitric oxide generation by low frequency electromagnetic field. Pathophysiology 2000a; 7: 131-135.##Yoshikawa T, Tanigawa M, Tanigawa T, Imai A, Hongo H, Kondo M. Enhancement of nitric oxide generation by low frequency electromagnetic field. Pathophysiology 2000b; 7: 131-135.##Zhong H, Minneman KP. Alpha1-adrenoceptor subtypes. European Journal of Pharmacology 1999; 375: 261-276.#### ##

Sodium hydrosulfide: A new potential candidate for treating delayed gastric emptying in diabetes 2 2 Introduction: Sodium hydrosulfide (NaHS) has shown to enhance the gastric emptying rate in normal rats but till now its effect on gastric emptying of food stuffs in diabetic rats was not investigated. Therefore, this study designed to determine the role of an oral administration of NaHS on gastric emptying rate (GER) of glucose, albumin and olive oil in gastroparetic and normal rats. Methods: To evaluate the effect of NaHS on the gastric emptying of glucose, albumin and olive oil in normal rats, thirty-six normal rats randomly assigned in six experimental groups (6 per group). Three groups of rats considered as control. They received albumin, glucose or olive oil orally. Three other normal groups considered as NaHS-treated animals. These groups received NaHS (320 μg/kg, orally) 30 min prior to food stuffs. To investigate the effect of NaHS on the gastric emptying of food stuffs in diabetic rats, the same protocols carried out. Thirty min after intragastric administration of food stuffs, animals received acetaminophen (as a marker for gastric emptying rate). Results: The results showed that in normal and gastroparetic rats, an oral administration of NaHS accelerated gastric emptying of glucose, albumin and olive oil. The increased gastric emptying of glucose, albumin and olive oil in NaHS-pretreated gastroparetic rats was 89.9, 92.3 and 60% respectively more than in corresponding’s controls. 234 240 2017/03/112016/12/122017/03/112017/07/102017/02/232017/02/12016/09/12017/02/18 1395/11/30 2017/07/262017/08/222017/07/262017/08/242017/06/292017/06/72017/07/22017/08/17 1396/5/26 Seyyed Ali Mard Seyyed Ali Mard Research Center for Infectious Diseases of Digestive System [Alimentary Tract Research Center], Physiology Research Center, Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran mard-sa@ajums.ac.ir Iraj Ahmadi Iraj Ahmadi Research Center for Infectious Diseases of Digestive System [Alimentary Tract Research Center], Physiology Research Center, Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran ahmadiiraj57@yahoo.com Mohammad Kazem Gharib-Naseri Mohammad Kazem Gharib-Naseri Physiology Research Center, Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran mgharibnaseri@yahoo.com Feryal Savary Feryal Savary Research Center for Infectious Diseases of Digestive System [Alimentary Tract Research Center], Physiology Research Center, Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran savari.f@ajums.ac.ir Sodium hydrosulfide Gastric emptying rate Gastroparesis Diabetic rat Barrett K. Gastrointestinal physiology. Lange physiology series. Lange Medical Books/McGraw-‎Hill, Medical Pub Division, New York. http:// www.accessmedicine. com/ resourceTOC. aspx; ‎‎2006.‎##Damgaard M, Graff J, Fuglsang S, Holst JJ, Rehfeld JF, Madsen JL. Effects of oleic acid and olive ‎oil on gastric emptying, gut hormone secretion and appetite in lean and overweight or obese males. ‎e-SPEN Journal. 2013; 8(1):e8-e14.‎##De Smet B, Mitselos A, Depoortere I. Motilin and ghrelin as prokinetic drug targets. Pharmacology ‎& therapeutics. 2009; 123(2):207-23.‎##Fiorucci S, Distrutti E, Cirino G, Wallace JL. The Emerging Roles of Hydrogen Sulfide in the ‎Gastrointestinal Tract and Liver.Gastroenterology. 2006; 131(1): 259-271.‎##Fomenko I, Sklyarov A, Bondarchuk T, Biletska L, Panasyuk N, Wallace JL. Effects of ‎conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with ‎stress-induced and epinephrine-induced gastric damage. Stress. 2014; 17(6):528-537.‎##Horowitz M, Maddox AF, Wishart JM, Harding PE, Chatterton BE, Shearman DJ. Relationships ‎between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus. European ‎journal of nuclear medicine. 1991; 18(4):229-34.‎##Jansen J, Fried M, Hopman W, Lamers C, Meyer J. Relation between gastric emptying of albumin-‎dextrose meals and cholecystokinin release in man. Digestive diseases and sciences. 1994; ‎‎39(3):571-6.‎##Koch KL, Calles-Escandon J. Diabetic gastroparesis. Gastroenterology clinics of North America. ‎‎2015; 44(1):39-57.‎##Mard SA, Ashabi A, Badavi M, Dianat M. Protective effects of vitamin B6 alone and in ‎combination with L-cysteine and NaHS on ethanol and indomethacin-induced gastric lesions in ‎mice. Iranian journal of basic medical sciences. 2015; 18(3):253-8.‎##Mard SA, Askari H, Neisi N, Veisi A. Antisecretory effect of hydrogen sulfide on gastric acid ‎secretion and the involvement of nitric oxide. BioMed research international. 2014; 2014:480921.‎##Mard SA, Gharib-Naseri MK, Badavi M. Delayed gastric emptying in diabetic rats caused by ‎decreased expression of cystathionine gamma lyase and H2S synthesis: in vitro and in vivo studies. ‎Neurogastroenterol Motil. 2016;Accepted to be published.‎##Mard SA, Neisi N, Solgi G, Hassanpour M, Darbor M, Maleki M. Gastroprotective effect of NaHS ‎against mucosal lesions induced by ischemia-reperfusion injury in rat. Dig Dis Sci. 2012; ‎‎57(6):1496-503.‎##Medeiros JV, Bezerra VH, Lucetti LT, Lima-Junior RC, Barbosa AL, Tavares BM, et al. Role of ‎KATP channels and TRPV1 receptors in hydrogen sulfide-enhanced gastric emptying of liquid in ‎awake mice. European journal of pharmacology. 2012; 693(1-3):57-63.‎##Nagai Y, Tsugane M, Oka J, Kimura H. Hydrogen sulfide induces calcium waves in astrocytes. ‎FASEB J 2004; 18:557–559.‎##NR S. Acetaminophen absorption kinetics in altered gastric emptying: establishing a relevant ‎pharmacokinetic surrogate using published data. J Pain Palliat Care Pharmacother. 2015; 29:115-9.‎##Qiu WC, Wang ZG, Lv R, Wang WG, Han XD, Yan J, et al. Ghrelin improves delayed ‎gastrointestinal transit in alloxan-induced diabetic mice. World journal of gastroenterology. 2008; ‎‎14(16):2572-7.‎##Schirra J, Katschinski M, Weidmann C, Schäfer T, Wank U, Arnold R, et al. Gastric emptying and ‎release of incretin hormones after glucose ingestion in humans. Journal of Clinical Investigation. ‎‎1996; 97(1):92.‎##Wallace JL. Hydrogen sulfide: a rescue molecule for mucosal defence and repair. Dig Dis Sci. ‎‎2012; 57(6):1432-4.‎##Yamano M, Kamato T, Nagakura Y, Miyata K. Effects of gastroprokinetic agents on gastroparesis ‎in streptozotocin-induced diabetic rats. Naunyn-Schmiedeberg's archives of pharmacology. 1997; ‎‎356(1):145-50.‎##Yonezawa D, Sekiguchi F, Miyamoto M, Taniguchi E, Honjo M, Masuko T, et al. A protective role ‎of hydrogen sulfide against oxidative stress in rat gastric mucosal epithelium. Toxicology. 2007; ‎‎241(1-2):11-8.‎## ##

Effect of tempol, a synthetic antioxidant, on renal complications of L-NAME induced preeclampsia in rat 2 2 Introduction: It has been suggested that oxidative stress has a crucial role in the pathophysiology of preeclampsia. In the present study, the effect of tempol, a synthetic antioxidant, on kidney injuries and oxidative stress was investigated in an experimental model of preeclampsia in rats. Methods: Preeclampsia was induced by oral administration of L-NAME to the rats on the day 10 of pregnancy. Animals were randomly divided into six groups (10-15 rats in each group); (I) normal pregnant (II) preeclamptic (III, IV, V) preeclamptic + tempol 20, 60 and 180 mg/kg/day, respectively, (VI) preeclamptic + hydralazine 10 mg/kg/day. Urine levels of sodium, potassium, creatinine, lactate dehydrogenase and 24 h protein, blood levels of creatinine and urea, in addition to malondialdehyde concentration in blood and kidney, as well as histological glomeruli changes were assessed. Results: L-NAME administration caused proteinuria and glomerular pathological changes. Tempol (20 and 60 mg/kg/day) significantly reduced plasma and renal (P<0.001) malondialdehyde levels and proteinuria (the biggest calculated P-value was less than 0.05) in preeclamptic rats. Tempol at the dose of 20 mg/kg/day improved the histological changes in preeclamptic animals, but the dose of 60 mg/kg/day restored histological findings. L-NAME did not change the other measured parameters. Hydralazine and highest dose of tempol (180 mg/kg/day) failed to affect biochemical and histological changes in experimental preeclampsia. Conclusion: Renal complications of experimental preeclampsia such as proteinuria and glomerular injuries can be prevented by tempol. The desired effects of tempol depend on its dose. 241 250 2017/03/112016/12/122017/03/112017/07/102017/02/232017/02/12016/09/12017/02/182017/01/12 1395/10/23 2017/07/262017/08/222017/07/262017/08/242017/06/292017/06/72017/07/22017/08/172017/05/31 1396/3/10 Mohammad Sharif Talebianpoor Mohammad Sharif Talebianpoor Herbal Medicine Research Center, School of Medicine, Yasouj University of Medical Sciences, Yasouj, Iran m.talebianpoor @yums.ac.ir Seyed Mohammad Owji Seyed Mohammad Owji Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran smowji@sums.ac.ir Mohsen Goharinia Mohsen Goharinia Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran gohariniam@sums.ac.ir Hossein Mirkhani Hossein Mirkhani Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran mirkhan@sums.ac.ir Tempol Rats Preeclampsia Oxidative Stress Proteinuria. Ardanaz N, Beierwaltes WH, Pagano PJ. Distinct hydrogen peroxide-induced constriction in multiple mouse arteries: Potential influence of vascular polarization. Pharmacol Rep 2008; 60: 61-7.##Bolte AC, van Geijn HP, Dekker GA. Management and monitoring of severe preeclampsia. Eur J Obstet Gynecol Reprod Biol 2001; 96: 8-20.##Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254.##Chatterjee PK, Cuzzocrea S, Brown PA, Zacharowski K, Stewart KN, Mota-Filipe H, et al. Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Kidney Int 2000; 58: 658-73.##Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, et al. Major congenital malformations after first-trimester exposure to ace inhibitors. N Engl J Med 2006; 354: 2443-51.##Datta PK, Sharma M, Duann P, Lianos EA. Effect of nitric oxide synthase inhibition on proteinuria in glomerular immune injury. Exp Biol Med 2006; 231: 576-84.##Dave A, Maru L, Jain A. Ldh (lactate dehydrogenase): A biochemical marker for the prediction of adverse outcomes in pre-eclampsia and eclampsia. J Obstet Gynaecol India 2016; 66: 23-9.##DeRubertis FR, Craven PA, Melhem MF. Acceleration of diabetic renal injury in the superoxide dismutase knockout mouse: Effects of tempol. Metabolism 2007; 56: 1256-64.##Elmarakby AA, Williams JM, Imig JD, Pollock JS, Pollock DM. Synergistic actions of enalapril and tempol during chronic angiotensin ii-induced hypertension. Vascul Pharmacol 2007; 46: 144-51.##García-Redondo AB, Briones AM, Beltrán AE, Alonso MJ, Simonsen U, Salaices M. Hypertension increases contractile responses to hydrogen peroxide in resistance arteries through increased thromboxane a2, ca2+, and superoxide anion levels. J Pharmacol Exp Ther 2009; 328: 19-27.##Harmon AC, Cornelius DC, Amaral LM, Faulkner JL, Cunningham Jr MW, Wallace K, et al. The role of inflammation in the pathology of preeclampsia. Clin Sci 2016; 130: 409-19.##Hoffmann DS, Weydert CJ, Lazartigues E, Kutschke WJ, Kienzle MF, Leach JE, et al. Chronic tempol prevents hypertension, proteinuria, and poor feto-placental outcomes in bph/5 mouse model of preeclampsia. Hypertension 2008; 51: 1058-65.##Karataş Y, Seçilmiş MA, Karayaylali I, Doran F, Büyükafşar K, Singirik E, et al. Effect of tempol (4-hydroxy tempo) on gentamicin-induced nephrotoxicity in rats. Fundam Clin Pharmacol 2004; 18: 79-83.##Knight SF, Yuan J, Roy S, Imig JD. Simvastatin and tempol protect against endothelial dysfunction and renal injury in a model of obesity and hypertension. Am J Physiol Renal Physiol 2010; 298: F86-94.##Leach M, Frank S, Olbrich A, Pfeilschifter J, Thiemermann C. Decline in the expression of copper/zinc superoxide dismutase in the kidney of rats with endotoxic shock: Effects of the superoxide anion radical scavenger, tempol, on organ injury. Br J Pharmacol 1998; 125: 817-25.##Lu H, Zhen J, Wu T, Peng A, Ye T, Wang T, et al. Superoxide dismutase mimetic drug tempol aggravates anti-gbm antibody-induced glomerulonephritis in mice. Am J Physiol Renal Physiol 2010; 299: F445-52.##Mathai M. Pre-eclampsia. Ceylon Med J 1996; 41: 7-9.##Maybury H, Waugh J. Proteinuria in pregnancy–just what is significant? Fet Mater Med Rev 2005; 16: 71-95.##Naghibi B, Ghafghazi T, Hajhashemi V, Talebi A, Taheri D. The effect of 2,3-dihydroxybenzoic acid and tempol in prevention of vancomycin-induced nephrotoxicity in rats. Toxicology 2007; 232: 192-9.##Noris M, Perico N, Remuzzi G. Mechanisms of disease: Pre-eclampsia. Nat Clin Pract Nephrol 2005; 1: 98-114.##Preti SC, Da Cunha V, Vassallo DV, Stefanon I. The superoxide dismutase mimetic, tempol, reduces the bioavailability of nitric oxide and does not alter l‐name‐induced hypertension in rats. Basic & clinical pharmacology & toxicology 2005; 97: 29-34.##Rafikova O, Salah EM, Tofovic SP. Renal and metabolic effects of tempol in obese zsf1 rats--distinct role for superoxide and hydrogen peroxide in diabetic renal injury. Metabolism 2008; 57: 1434-1444.##Sedeek M, Gilbert JS, LaMarca BB, Sholook M, Chandler DL, Wang Y, et al. Role of reactive oxygen species in hypertension produced by reduced uterine perfusion in pregnant rats. Am J Hypertens 2008; 21: 1152-6.##Sharma M, McCarthy ET, Savin VJ, Lianos EA. Nitric oxide preserves the glomerular protein permeability barrier by antagonizing superoxide. Kidney Int 2005; 68: 2735-44.##Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: Roles of oxidative stress and sgk1. Hypertension 2007; 49: 355-364.##Sones JL, Davisson RL. Preeclampsia, of mice and women. Physiol Genomics 2016; 48: 565-72.##Sverrisson K, Axelsson J, Rippe A, Gram M, Akerstrom B, Hansson SR, et al. Extracellular fetal hemoglobin induces increases in glomerular permeability: Inhibition with alpha1-microglobulin and tempol. Am J Physiol Renal Physiol 2014; 306: F442-8.##Talebianpoor MS, Mirkhani H. The effect of tempol administration on the aortic contractile responses in rat preeclampsia model. ISRN Pharmacol 2012; 2012: 187-208.##Tang Z, Shou I, Wang LN, Fukui M, Tomino Y. Effects of antihypertensive drugs or glycemic control on antioxidant enzyme activities in spontaneously hypertensive rats with diabetes. Nephron 1997; 76: 323-30.##Tanir HM, Sener T, Inal M, Akyuz F, Uzuner K, Sivri E. Effect of quercetine and glutathione on the level of superoxide dismutase, catalase, malonyldialdehyde, blood pressure and neonatal outcome in a rat model of pre-eclampsia induced by ng-nitro-l-arginine-methyl ester. Eur J Obstet Gynecol Reprod Biol 2005; 118: 190-5.##Teke Z, Kabay B, Ozden A, Yenisey C, Bir F, Demirkan NC, et al. Effects of tempol, a membrane-permeable radical scavenger, on local and remote organ injuries caused by intestinal ischemia/reperfusion in rats. J Surg Res 2008; 149: 259-71.##Yanes L, Romero D, Iliescu R, Cucchiarelli VE, Fortepiani LA, Santacruz F, et al. Systemic arterial pressure response to two weeks of tempol therapy in shr: Involvement of no, the ras, and oxidative stress. Am J Physiol Regul Integr Comp Physiol 2005; 288: R903-8.##Yoshida S, Hashimoto T, Kihara M, Imai N, Yasuzaki H, Nomura K, et al. Urinary oxidative stress markers closely reflect the efficacy of candesartan treatment for diabetic nephropathy. Nephron Exp Nephrol 2009; 111: e20-30.## ##

Single administrations of high and low doses of acetaminophen causes different effects on COX-2 gene expression and on tissue damage in liver and kidneys 2 2 Introduction: High dose of acetaminophen (APAP) is known to have hepatotoxic and nephrotoxic effects and studies show that this toxicities are dependent on the function of phase I bioactivation enzymes- Cyp450- and phase II biotransformation enzymes especially glucuronosylation and sulfonation pathways. However, the role of cyclooxygenase (COX) as an inflammatory mediator in toxic effects of APAP has not been explained satisfactorily yet. Methods: In this study, we aimed to find out if there is any association between APAP hepatotoxicity and COX-2 expression at mRNA levels. Male Balb/C mice were treated with a single high dose (300 mg/kg BW) or low dose (30 mg/kg BW) of APAP. Results: Following APAP treatment, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes were measured as the biochemical markers of hepatocellular damage. Then liver and kidney biopsies were processed and examined for histolopathogical changes as well as for total RNA extraction and COX-2 gene expression. Serum ALT/AST levels were significantly (P<0.05) higher and there were hepatotoxic damages after 24 hours in mice exposed to high dose of APAP (300 mg/kg BW). However, no obvious nephrotoxicity was observed in mice treated with either low or high doses of APAP. Based on RT-PCR data, the COX-2 specific mRNA was not expressed in liver tissues of either control or APAP-treated mice, while, it was expressed in kidney tissues of both control and APAP-treated mice. Conclusion: These data may suggest that unlike in liver, COX-2 expression in kidney may play a protective role in APAP-related hepatotoxicity. 251 259 2017/03/112016/12/122017/03/112017/07/102017/02/232017/02/12016/09/12017/02/182017/01/122017/03/17 1395/12/27 2017/07/262017/08/222017/07/262017/08/242017/06/292017/06/72017/07/22017/08/172017/05/312017/06/21 1396/3/31 Morteza Hatamzadeh Khaneghahi Morteza Hatamzadeh Khaneghahi Department of Biology, Kurdistan Science and Research Branch, Islamic Azad University, Sanandaj, Iran mortaza_1983@yahoo.com Sorour Shojaeian Sorour Shojaeian Department of Clinical Biochemistry, Medical Genetics, Nutrition, Alborz University of Medical Sciences, Karaj, Iran s_ssir@yahoo.com Abdolamir Allameh Abdolamir Allameh Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran allameha@modares.ac.ir Acetaminophen (APAP) Cyclooxygenase COX-2 gene expression Hepatotoxicity 1. Hinz B, Brune K. Paracetamol and cyclooxygenase inhibition: is there a cause for concern? Annals of the rheumatic diseases. 2012;71(1):20-5.##2. Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. The FASEB Journal. 2004;18(7):790-804.##3. Botting R. Paracetamol-inhibitable COX-2. Journal of physiology and pharmacology: an official journal of the Polish Physiological Society. 2000;51(4 Pt 1):609-18.##4. Lucas R, Warner TD, Vojnovic I, Mitchell JA. Cellular mechanisms of acetaminophen: role of cyclo-oxygenase. The FASEB journal. 2005;19(6):635-7.##5. Botting R, Ayoub SS. COX-3 and the mechanism of action of paracetamol/acetaminophen. Prostaglandins, leukotrienes and essential fatty acids. 2005;72(2):85-7.##6. Bessems JG, Vermeulen NP. Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. CRC Critical Reviews in Toxicology. 2001;31(1):55-138.##7. Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. The Journal of clinical investigation. 2009;119(2):305.##8. Rowden AK, Norvell J, Eldridge DL, Kirk MA. Updates on acetaminophen toxicity. Medical Clinics of North America. 2005;89(6):1145-59.##9. Liu Z-X, Govindarajan S, Kaplowitz N. Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity. Gastroenterology. 2004;127(6):1760-74.##10. Liu ZX, Han D, Gunawan B, Kaplowitz N. Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology. 2006;43(6):1220-30.##11. Aleksunes LM, Slitt AM, Cherrington NJ, Thibodeau MS, Klaassen CD, Manautou JE. Differential expression of mouse hepatic transporter genes in response to acetaminophen and carbon tetrachloride. Toxicological Sciences. 2005;83(1):44-52.##12. Dinarello CA. Proinflammatory cytokines. Chest Journal. 2000;118(2):503-8.##13. Jaeschke H, McGill MR, Williams CD, Ramachandran A. Current issues with acetaminophen hepatotoxicity—a clinically relevant model to test the efficacy of natural products. Life sciences. 2011;88(17):737-45.##14. Jeong S-Y, Lim J-S, Park H-J, Cho J-W, Rana S, Yoon S. Effects of acetaminophen on hepatic gene expression in mice. Physiological chemistry and physics and medical NMR. 2005;38(2):77-83.##15. Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. The FASEB journal. 2008;22(2):383-90.##16. Botting RM. Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clinical Infectious Diseases. 2000;31(Supplement 5):S202-S10.##17. Allameh A, Vansoun EY, Zarghi A. Role of glutathione conjugation in protection of weanling rat liver against acetaminophen-induced hepatotoxicity. Mechanisms of ageing and development. 1997;95(1):71-9.##18. Rouzer CA, Marnett LJ. Cyclooxygenases: structural and functional insights. Journal of lipid research. 2009;50(Supplement):S29-S34.##19. Lee Y-S, Kim H, Brahim JS, Rowan J, Lee G, Dionne RA. Acetaminophen selectively suppresses peripheral prostaglandin E 2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007;129(3):279-86.##20. Reilly TP, Brady JN, Marchick MR, Bourdi M, George JW, Radonovich MF, et al. A protective role for cyclooxygenase-2 in drug-induced liver injury in mice. Chemical research in toxicology. 2001;14(12):1620-8.##21. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, et al. Cyclooxygenase in biology and disease. The FASEB journal. 1998;12(12):1063-73.##22. Harrill AH, Ross PK, Gatti DM, Threadgill DW, Rusyn I. Population-based discovery of toxicogenomics biomarkers for hepatotoxicity using a laboratory strain diversity panel. Toxicological sciences. 2009:kfp096.##23. Tee LB, Davies DS, Seddon CE, Boobis AR. Species differences in the hepatotoxicity of paracetamol are due to differences in the rate of conversion to its cytotoxic metabolite. Biochemical pharmacology. 1987;36(7):1041-52.##24. Gregus Z, Madhu C, Klaassen CD. Species variation in toxication and detoxication of acetaminophen in vivo: a comparative study of biliary and urinary excretion of acetaminophen metabolites. Journal of Pharmacology and Experimental Therapeutics. 1988;244(1):91-9.#### ##