Recent concepts about sense of smell, odorant receptors and physiology of olfaction- an insight 2 2 The sense of olfaction reached its zenith in development much earlier than other special senses. Olfaction is much more acute than the other senses, exhibits both high sensitivity for odours and high discrimination between them. This plays a very important role even in the social and behavioral aspects of human beings. Recent studies using molecular genetics, electrophysiology and behavioral analysis have elucidated the mechanism, connectivity and functions of olfaction in different organisms. 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Association of two polymorphisms in MSH2 and XRCC1 genes with multiple sclerosis in Iranian population 2 2 Introduction: To protect genomes of all organisms from internal and external damages and maintain the genome integrity and the continuity of life, repair system has been developed in all living cells. Defects in repair system are responsible for various kinds of disease including cancers and neurodegenerative diseases such as Multiple sclerosis (MS). The relationship between various components of the repair system and MS has been confirmed by investigations on separate cohorts in independent research. The main aim of this study was to discover the genetic association of two functional polymorphisms of rs1799782 in XRCC1 and rs2303425 in MSH2 genes as the key players in DNA repair system; with MS. Methods: The genotypes of 105 MS patients and 102 age and sex matched healthy controls for these polymorphisms were determined by a PCR-RFLP technique. Results: Genotype and allele frequencies of rs1799782 in patients with MS compared to the control group demonstrated a significant difference and a possible role for this polymorphism in MS pathogenesis (P value (0.02) and OR (3.4)). The rs2303425 polymorphism showed no significant correlation (P value = 0.41 and OR=1.5) with the risk of MS in Iranian population. Conclusion: Our results suggest a possible role for repair system genes and their significance in the pathogenesis of multiple sclerosis. 83 89 2016/03/212016/04/27 1395/2/8 2016/06/132016/05/9 1395/2/20 Zahra Abedi Kichi Zahra Abedi Kichi Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran zahraabedi38@yahoo.com Fatemeh Khani-Habibabadi Fatemeh Khani-Habibabadi Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran f.khani90@yahoo.com Mohammadali Sahraian Mohammadali Sahraian MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran sahraian1350@yahoo.com Rosita Doosti Rosita Doosti MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran sahraian150@yahoo.com Mehrdad Behmanesh Mehrdad Behmanesh Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran behmanesh@modares.ac.ir DNA repair Multiple Sclerosis Association study XRCC1 MSH2 Breslin C, Hornyak P, Ridley A, Rulten SL, Hanzlikova H, Oliver AW, et al. 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Study of pulmonary functions in patients with metabolic syndrome 2 2 Introduction: Metabolic syndrome (MetS) and impaired lung functions have been associated with an increased risk for coronary heart disease. The aim of this study was to investigate the pulmonary functions in patients with MetS. Methods: This cross-sectional study included 200 subjects with MetS in the study group and 100 subjects without MetS in the control group. Participants were examined at M.P. Shah Medical College, Jamnagar, India between 2013 to 2016. MetS was assessed according to the National Cholesterol Education Program’s-Adult Treatment Panel III Criteria. Pulmonary function, fasting glucose, insulin and lipid profile levels were measured and homeostatic model assessment was used to assess insulin resistance. Pulmonary function and components of MetS were examined using independent Student's t-test, analysis of variance and chi-square test. Results: The overall prevalence of pulmonary functions impairment in patients with MetS was 50% with high prevalence of restrictive ventilatory patterns (33%). Insulin resistance was significantly (P<0.001) higher in the study group than in control group, while pulmonary functions variables of study group were significantly (P<0.001) lower than those of control group. There were significant differences in the body mass index, waist circumference, blood glucose, and insulin resistance (P<0.05) between ventilatory pattern of subgroups. Conclusion: We found that components of MetS and insulin resistance were significantly related to the impairment of pulmonary function. Therefore present study suggests that increased components of MetS and insulin resistance are risk factors for decline pulmonary functions in subjects with MetS. 90 97 2016/03/212016/04/272016/03/31 1395/1/12 2016/06/132016/05/92016/05/4 1395/2/15 Prema Ram Choudhary Prema Ram Choudhary Department of Physiology, C.U. Shah Medical College, Surendranagr Gujarat, India prema5252@gmail.com Rameshchandra D Jani Rameshchandra D Jani Department of Physiology, C.U. Shah Medical College, Surendranagr Gujarat, India dr.rdjani@gmail.com Metabolic syndrome Pulmonary functions Insulin resistance Prevalence • Chen R, Tunstall-Pedoe H, Bolton-Smith C, Hannah MK, Morrison C. Association of dietary antioxidants and waist circumference with pulmonary function and airway obstruction. Am J Epidemiol 2001; 153: 157-63.##• Chen WL, Wang CC, Wu LW, Kao TW, Chan JYH, Chen YJ et al. Relationship between Lung Function and Metabolic Syndrome. PLoS One 2014; 9(10): 1-7.##• Choi JH, Park S, Shin YH, Kim MY, Lee YJ. Sex differences in the relationship between metabolic syndrome and pulmonary function: The 2007 Korean National Health and Nutrition Examination Survey. 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Minocycline did not prevent the neurotoxic effects of amyloid β on intrinsic electrophysiological properties of hippocampal CA1 pyramidal neurons in a rat model of Alzheimer’s disease 2 2 Introduction: Although aging is the most important risk factor for Alzheimer's disease (AD), there is evidence indicating that neuroinflammation may contribute to the development and progression of the disease. Several studies indicated that minocycline may exert neuroprotective effects in rodent models of neurodegenerative diseases. Nevertheless, there are also other studies implying that minocycline has no positive beneficial effects. Thus, the aim of the present study was to assess the preventive effect of minocycline against Aβ-induced changes in intrinsic electrophysiological properties in a rat model of AD. Methods: The present study extended this line of research by examining whether inhibition of microglial activation may alter the intrinsic electrophysiological properties of CA1 pyramidal neurons in a rat model of Aβ neurotoxicity, using whole cell patch clamp. Results: Findings showed that bilateral injection of the Aβ (1-42) into the prefrontal cortex caused membrane hyperpolarization, action potential (AP) narrowing and after hyperpolarization (AHP) amplitude enhancement. It was also resulted in a faster decay time of AP, higher rheobase current, lower firing frequency and smaller post stimulus AHP amplitude. Administration of minocycline (45mg/kg, i.p) not only failed to prevent Aβ-induced alterations in the intrinsic electrophysiological properties, but also enhanced the effects of Aβ on neuronal firing behavior. Conclusion: It can be concluded that minocycline, as a microglial inhibitor, may enhance the disruption of electrophysiological properties of CA1 pyramidal neurons induced by Aβ neurotoxin, including AP parameters and intrinsic neuronal excitability. 98 107 2016/03/212016/04/272016/03/312016/03/27 1395/1/8 2016/06/132016/05/92016/05/42016/06/12 1395/3/23 Sharareh Daryani Sharareh Daryani Neuroscience Research Centre and Dept. of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran shararehdar@yahoo.com Alireza Farzaei Alireza Farzaei Dept. of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran alirezafarzaei@gmail.com Narges Hosseinmardi Narges Hosseinmardi Neuroscience Research Centre and Dept. of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran nargeshosseinmardi@gmail.com Farideh Bahrami Farideh Bahrami Neuroscience Research Centre and Department of Physiology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran farideh_bahrami@yahoo.com Mahyar Janahmadi Mahyar Janahmadi Neuroscience Research Centre and Dept. of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran Janahmadi@sbmu.ac.ir Amyloid Beta (Aβ) Neurotoxicity Minocycline Microglial Cells CA1 Pyramidal Neurons Intrinsic properties Ahmad M, Zakaria A, Almutairi KM. 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Protective effect of ginger against the pentylenetetrazole-induced seizure threshold model in streptozocin treated-diabetic mice 2 2 Introduction: There is evidence that diabetes affects seizure susceptibility. Ginger (Zingiber officinale Roscoe) which is used in traditional medicine has antioxidant activity and neuroprotective effects. The aim of this study was to evaluate the seizure threshold induced by pentylenetetrazole (PTZ) in diabetic mice after induction of diabetes with streptozocin and to examine the possible role of ginger extract in this manner. Methods: The anticonvulsant effect of ginger was investigated using i.v. PTZ-induced seizure models in non-diabetic and diabetic mice. Different doses of the hydroethanolic extract of ginger (50 and 100 mg/kg; i.p.) were administered daily for 2 weeks before PTZ challenge. The effect of ginger on the appearance of three separate seizure endpoints e.g. myoclonic, generalized clonic, and tonic extension phase were recorded. Results: The results showed that the ginger extract has anticonvulsant effects in the experimental model of seizure tested as it significantly increased the seizure threshold. Diabetic animal’s shows high blood glucose level and lower seizure threshold compared with non-diabetic control animals. Hydroethanolic extract of ginger significantly increased the onset time of myoclonic seizure (p<0.001) and significantly prevented generalized clonic (p<0.001) and forelimb tonic extension (p<0.001) seizure induced by PTZ in both non-diabetic and diabetic animals compared with control group. Conclusion: Based on the results, the hydroethanolic extract of ginger has anticonvulsant effects in diabetic mice, possibly through hypoglycemic effect, antioxidant mechanisms, and oxidative stress inhibition. 108 116 2016/03/212016/04/272016/03/312016/03/272016/04/21 1395/2/2 2016/06/132016/05/92016/05/42016/06/122016/05/30 1395/3/10 Abdolkarim Hosseini Abdolkarim Hosseini Department of Physiology, Faculty of Biological Science, Shahid Beheshti University, Tehran, Iran ab_hosseini@sbu.ac.ir Naser Mirazi Naser Mirazi Department of Biology, Faculty of Basic science, Bu-Ali Sina University, Hamedan, Iran mirazi@basu.ac.ir Ali Gomar Ali Gomar Department of Biology, Science & Research Institute, Islamic Azad University, Tehran, Iran gomar.ucla@gmail.com Seizure Ginger Diabetes PTZ Mice Akhani SP, Vishwakarma SL, Goyal RK. Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats. J Pharm Pharmacol 2004; 56: 101-105.##Arablou T, Aryaeian N, Valizadeh M, Sharifi F, Hosseini A, Djalali M. The effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus. Int J Food Sci Nutr 2014; 65(4): 515-20.##Benzie IFF, Wachtel-Galor S. Herbal Medicine Biomolecular Clinical Aspects. 2nd ed. New York, USA: CRC Press. 2011.##Berkovic SF, Johns JA, Bladin PF. Focal seizures and systemic metabolic disorders. Aust N Z J Med 1982; 12: 620-3.##Brick JF, Gutrecht JA, Ringel RA. Reflex epilepsy and nonketotic hyperglycemia in the elderly: a specific neuroendocrine syndrome. Neurology 1989; 39: 394-399.##Bush GH, Steward DJ. Can persistent cerebral damage be caused by hyperglycaemia? Paediatr Anaesth 1995; 5: 385-387.##Chung-Hsing C, Jiann-Chyun L, Giia-Sheun P. Status epilepticus associated with initiation of theophylline in an elderly patient with diabetic ketoacidosis. Neurol India. 2007; 55: 154-6.##Clark ME, Payton JE, Pittiglio LI. Acute ischemic stroke and hyperglycemia. Crit Care Nurs Q 2014; 37(2): 182-7.##Edraki M, Akbarzadeh A, Hosseinzadeh M, Tanideh N, Salehi A, Koohi-Hosseinabadi O. Healing effect of sea buckthorn, olive oil, and their mixture on full-thickness burn wounds. Adv Skin Wound Care 2014; 27(7): 317-23.##El-Akabawy G, El-Kholy W. Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats. Ann Anat 2014; 196(2-3): 119-28.##Engel JJ, Pedley TA, Aicardi J, Dichter MA, Moshé S, Perucca E, et al. Epilepsy: A comprehensive textbook. 2nd ed. Philadelphia, USA: Lippincott Williams & Wilkins. 2007.##Esteghamati A, Khalilzadeh O, Anvari M, Meysamie A, Abbasi M, Forouzanfar M, et al. The economic costs of diabetes: A population-based study in Tehran, Iran. Diabetologia 2009; 52(8): 1520-7.##Felipe CFB, Fonsêca KS, dos Reis Barbosa AL, Bezerra JNS, Neto MA, de Franc a Fonteles MM, et al. Alterations in behavior and memory induced by the essential oil of Zingiber officinale Roscoe (ginger) in mice are cholinergic-dependent. J Med Plants Res 2008; 2: 163-170.##Garthwaite J, Boulton CL. Nitric oxide signaling in the central nervous system. Annu Rev Physiol 1995; 57: 683-706.##Ghasemi M, Shafaroodi H, Karimollah AR, Gholipour T, Nezami BG, Ebrahimi F, et al. ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. Seizure 2010; 19(1): 53-8.##Ghasemzadeh A, Jaafar HZ, Rahmat A. Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules 2010; 15: 4324-4333.##Giacco F, Brownlee M. Oxidative Stress and Diabetic Complications. Circ Res 2010; 107: 1058-70.##Go KG, Prenen GH, Korf J. Protective effect of fasting upon cerebral hypoxic-ischemic injury. 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Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats. Brain Res 2013; 1535: 148-55.##Ippoushi K, Azuma K, Ito H, Horie H, Higashio H. [6]-gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions. Life Sci 2003; 73: 3427-37. ##Jeena K, Liju VB, Kuttan R. Antioxidant, anti-inflammatory and antinociceptive activities of essential oil from ginger. Indian J Physiol Pharmacol 2013; 57(1): 51-62.##Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. J Ethnopharmacol 2003; 84: 105-108.##King GL, Loeken MR. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol 2004; 122: 333-338.##Koltai M, Minker E. Changes of electro-shock seizure threshold in alloxan diabetic rats. Experientia 1975; 31: 1369.##Mandhane SN, Aavula K, Rajamannar T. Timed pentylenetetrazol infusion test: a comparative analysis with s.c. PTZ and MES models of anticonvulsant screening in mice. Seizure 2007; 16: 636-44.##Margineanu DG, Niespodziany I, Wulfert E. Hippocampal slices from long-term streptozotocin-injected rats are prone to epileptiform responses. Neurosci Lett 1998; 252: 183-186.##Markowitz GJ, Kadam SD, Smith DR, Johnston MV, Comi AM. Different effects of high- and low-dose phenobarbital on post-stroke seizure suppression and recovery in immature CD1 mice. Epilepsy Res 2011; 94: 138-148.##Mascolo N, Jain R, Jain SC, Capasso F. Ethnopharmacologic investigation of ginger (Zingiber officinale). J Ethnopharmacol 1989; 27: 129-140.##Messing RO, Simon RP. Seizures as a manifestation of systemic disease. Neurol Clin 1986; 4: 563-584.##Ni Dhi G, Balakri Shnan S, Pandhi P. Role of nitric oxide in electroshock and pentylenetetrazole seizure threshold in rats. Meth Find Exp Clin Pharmacol 1999; 21: 609-612.##Ojewole JA. 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Artemether effect and its interaction with vincristine and doxorubicin on human breast carcinoma MCF-7 cells 2 2 Introduction: For thousands of years, plants have been used as the main source of drug worldwide. Recently, it has been found out that the plant Artemisia annua and especially its derivatives such as artemether have anticancer properties. Methods: In this study, the anticancer effect of artemether on MCF-7 breast cancer cell line was examined. MTT assay was used to assess the viability of cancer cells. Results: The data showed that artemether (100-300 nM) resulted in MCF-7 growth inhibition. Artemether plus vincristine or doxorubicin compared to each drug alone showed significant cytotoxic effects. Over 50 percent of cells were killed in combination of non-effective doses of artemether and doxorubicin (50 and 160 nM, respectively). Conclusion: Taken together, the combined therapy of artemether and anticancer drugs would be a promising strategy for breast cancer but the effectiveness of such combination therapy needs to be verified by experimental and clinical investigations. 117 121 2016/03/212016/04/272016/03/312016/03/272016/04/212016/02/23 1394/12/4 2016/06/132016/05/92016/05/42016/06/122016/05/302016/06/9 1395/3/20 Mohammad Rasoul Samandari-Bahraseman Mohammad Rasoul Samandari-Bahraseman Research Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, GraduateUniversity of Advanced Technology, Kerman, Iran m.r.samandari@gmail.com Solmaz Sarhadi Solmaz Sarhadi Research Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, GraduateUniversity of Advanced Technology, Kerman, Iran sosa1360@yahoo.com Saeed Esmaeili-Mahani Saeed Esmaeili-Mahani Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman semahani@yahoo.com Breast cancer cell line MCF-7 Artemether Cell viability Chemotherapy Aggarwal, B. B., Y. Takada, et al. From chemoprevention to chemotherapy: common targets and common goals. Expert Opin Investig Drugs 2004;13:1327-1338.##Barnabé, N., J. A. Zastre, et al. Deferiprone protects against doxorubicin-induced myocyte cytotoxicity. Free Radical Biology and Medicine 2002; 33: 266-275.##Barnes, K., P. Chanda, et al. Impact of the large-scale deployment of artemether/lumefantrine on the malaria disease burden in Africa: case studies of South Africa, Zambia and Ethiopia. Malar J 2009; 8: 1-7.##Bhakuni, R. S., D. C. Jain, et al. Secondary metabolites of Artemisia annua and their biological activity. Current Science 2001; 80: 35-48.##Cragg, G. M. and D. J. Newman, Plants as a source of anti-cancer agents. Journal of Ethnopharmacology 2005; 100: 72-9.##Dobbs, N. A., C. J. Twelves, et al. Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry. Cancer chemotherapy and pharmacology 1995; 36: 473-476.##Frederick, C. A., L. D. Williams, et al. Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin. Biochemistry 1990; 29: 2538-2549.##Guerin, P. J., P. Olliaro, et al. Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development. The Lancet Infectious Diseases 2002; 2: 564-73.##Hanahan, D. and A. Weinberg Robert, Hallmarks of Cancer: The Next Generation. Cell 2011; 144: 646-674.##Himes, R. H., R. N. Kersey, et al. Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. Cancer Research 1976; 36: 3798-802.##Holland, J. F., C. Scharlau, et al. Vincristine treatment of advanced cancer: a cooperative study of 392 cases. Cancer research 1973; 33: 1258-1264.##Jiao, Y., C. M. Ge, et al. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin 2007; 28: 1045-1056.##Karuppusamy, S. A. A review on trends in production of secondary metabolites from higher plants by in vitro tissue, organ and cell cultures. Journal Med Plants Res 2009; 3: 1222-1239.##Kaufman, I. A., F. H. Kung, et al. Overdosage with vincristine. Journal of pediatrics 1976; 89: 671-674.##Pan, L., H. Chai, et al. The continuing search for antitumor agents from higher plants. Phytochemistry Letters 2010; 3: 1-8.##Russo, M., C. Spagnuolo, et al. Phytochemicals in Cancer Prevention and Therapy: Truth or Dare?. Toxins 2010; 2: 517-51.##Siegel R, Naishadham D, Jemal A.. Cancer Statistics, 2012. CA: CA Cancer J Clin. 2012; 62(1):10-29.##Stratton, M. R. Exploring the Genomes of Cancer Cells: Progress and Promise. Science 2011; 331: 1553-1558.##Surh, Y. J. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003; 3: 768-780.##Wu, Z. P., C. W. Gao, et al. Inhibitory effect of artemether on tumor growth and angiogenesis in the rat C6 orthotopic brain gliomas model. Integrative Cancer Therapies 2009; 8: 88-92.## ##

The antinociceptive effect of 17β-estradiol in the nucleus paragigantocellularis lateralis of male rats may be mediated by the NMDA receptors 2 2 Introduction: The nucleus paragigantocellularis lateralis (LPGi) is involved in the descending pain modulation. The neurostreoid, 17β-estradiol found in the PGi nucleus and modulates nociception by binding to estrogen receptors and also by allosteric interaction with NMDA receptors. In this study, the role of NMDA receptors in the 17β-estradiol-induced pain modulation was investigated by assessing the inflammatory pain responses changes after blockade of the LPGi nucleus’ NMDA receptors. Methods: In order to study the antinociceptive effect of intra-LPGi microinjection of 17β-estradiol, a guide cannula was implanted into the right LPGi nucleus. 500 nl of drugs were administered 15 minutes prior to formalin (50 μl of 4%) injection. Then, formalin-induced paw jerking behaviour was recorded for 60 min. For assessing the role of the NMDA receptors in the pain modulation by 17β-estradiol, it was injected 15 min after the intra-LPGi administration of 0.5 nmol of AP5 (the NMDA receptor antagonist); and paw jerking frequency was recorded for 1 h. Results: The results of the present study showed that intra-LPGi injection of 0.8 μmol of 17β-estradiol attenuated the chronic phase (P<0.001) of paw jerking behaviour. AP5 significantly reduced the antinociceptive effect of intra-LPGi 17β-estradiol both in the acute (P<0.001) and in the chronic phase (P<0.001) of formalin test. Conclusion: According to the results of this study, it can be concluded that the analgesic effect of intra-LPGi injection of 17β-estradiol on the formalin-induced inflammatory pain might be mediated via NMDA receptors. 122 129 2016/03/212016/04/272016/03/312016/03/272016/04/212016/02/232016/02/21 1394/12/2 2016/06/132016/05/92016/05/42016/06/122016/05/302016/06/92016/05/25 1395/3/5 Roghaieh Khakpay Roghaieh Khakpay Department of Animal Science, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran rkhakpai@gmail.com Maryam Azaddar Maryam Azaddar Department of Animal Science, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran maryam.azaddar@yahoo.com Fatemeh Khakpay Fatemeh Khakpay Institute for Cognitive Science Studies (ICSS), Tehran, Iran khakpai@gmail.com 17β-Estradiol Paragigantocellularis lateralis nucleus NMDA receptor Pain Aloisi A, Ceccarelli I. 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Trends in neurosciences. 2006;29,241-249.##Brooks J, Jenkinson M, Beckmann CF, Miller K, Wise R, Clare S, Schweinhardt P, Wilson G, Tracey I. Non-invasive functional imaging of the human spinal cord. In5th Congress of the European Federation of IASP Chapters, Istanbul, Turkey 2006; 1819. ##Coderre TJ and Van Empel I. The utility of excitatory amino acid (EAA) antagonists as analgesic agents. I. Comparison of the antinociceptive activity of various classes of EAA antagonists in mechanical, thermal and chemical nociceptive tests. Pain. 1994;59,345-352.##Craft RM, Mogil JS, Aloisi AM. Sex differences in pain and analgesia: the role of gonadal hormones. European Journal of Pain. 2004;8,397-411.##Dubuisson D and Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1978; 4,161-174.##Erami E, Azhdari-Zarmehri H, Ghasemi-Dashkhasan E, Esmaeili M-H, Semnanian S. 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Colistin, an option for treatment of multiple drug resistant Pseudomonas aeruginosa 2 2 Introduction: Multi-drug resistant (MDR) P. aeruginosa is constantly increasing and causing severe issues in combatting widely spread health problems. The aim of this study was to assess colistin susceptibility in MDR P. aeruginosa isolates obtained from different infection sites. Methods: Ninety clinical isolates of P. aeruginosa were collected from different hospitals of the Tabriz University of Medical Sciences. All isolates were identified using standard microbiology tests. The disk diffusion susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Antibiotic disks used in this study included ciprofloxacin, levofloxacin, ceftazidime, amikacin, gentamicin, cefepime, imipenem, meropenem, ticarcillin/clavulanic acid, piperacillin, aztreonam, and colistin. The MIC (Minimum Inhibitory Concentration) of colistin was determined by the agar dilution method according to CLSI guidelines. Results: MDR isolates were found in 75.6%, in which there was a high frequency in wound specimens (23.3%), followed by blood (17.8%), urine (15.6%), trachea (13.3%), and peritoneum (5.6%). High resistance rate (above 50%) was observed with piperacillin, aztreonam, ceftazidime, cefepime, meropenem, gentamicin, amikacin, ciprofloxacin, and levofloxacin. All isolates were found to be susceptible to colistin through the disk diffusion method; however, two isolates were non-susceptible in the agar dilution method. Conclusion: The present study shows a high frequency of MDR P. aeruginosa in our subjects, the limitations of empirical therapy, and the need for susceptibility testing. The most effective antibiotic against MDR P. aeruginosa was colistin. Therefore, colistin may be an alternative antimicrobial agent for infections due to MDR P. aeruginosa. 130 136 2016/03/212016/04/272016/03/312016/03/272016/04/212016/02/232016/02/212016/01/25 1394/11/5 2016/06/132016/05/92016/05/42016/06/122016/05/302016/06/92016/05/252016/06/9 1395/3/20 Mohammad Yousef Memar Mohammad Yousef Memar Department of Microbiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran y.memar@yahoo.com Rahman Pormehrali Rahman Pormehrali Department of Microbiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Nasser Alizadeh Nasser Alizadeh Department of Microbiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran alizade.naser@ymail.com Reza Ghotaslou Reza Ghotaslou Department of Microbiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran rzgottaslo@yahoo.com Hossein Bannazadeh Baghi Hossein Bannazadeh Baghi Department of Microbiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Colistin Multi-drug resistant P.aeruginosa Akhi MT, Ghotaslou R, Beheshtirouy S, Asgharzadeh M, Pirzadeh T, Asghari B, et al. Antibiotic susceptibility pattern of aerobic and anaerobic bacteria isolated from surgical site infection of hospitalized patients. Jundishapur Journal of Microbiology 2015; 8.##Akingbade O, Balogun S, Ojo D, Afolabi R, Motayo B, Okerentugba P, et al. Plasmid profile analysis of multidrug resistant pseudomonas aeruginosa isolated from wound infections in south west, nigeria. World Applied Sci J 2012; 20: 766-75.##Bayani M, Siadati S, Rajabnia R, Taher AA. Drug resistance of pseudomonas aeruginosa and enterobacter cloacae isolated from icu, babol, northern iran. International journal of molecular and cellular medicine 2013; 2: 204.##Bialvaei AZ, Samadi Kafil H. Colistin, mechanisms and prevalence of resistance. Current Medical Research & Opinion 2015; 31: 707-721.##Burjanadze I, Kurtsikashvili G, Tsereteli D, Tsertsvadze E, Kekelidze M, Imnadze P, et al. Pseudomonas aeruginosa infection in an intensive care unit. International Journal of Infection Control 2007; 3.##Cao B, Wang H, Sun H, Zhu Y, Chen M. Risk factors and clinical outcomes of nosocomial multi-drug resistant pseudomonas aeruginosa infections. Journal of Hospital Infection 2004; 57: 112-118.##D'Souza BB, Padmaraj SR, Rekha PD, Tellis RC, Prabhu S, Pothen P. In vitro synergistic activity of colistin and ceftazidime or ciprofloxacin against multidrug-resistant clinical strains of pseudomonas aeruginosa. Microbial Drug Resistance 2014; 20: 550-554.##De Francesco M, Ravizzola G, Peroni L, Bonfanti C, Manca N. Prevalence of multidrug-resistant acinetobacter baumannii and pseudomonas aeruginosa in an italian hospital. Journal of infection and public health 2013; 6: 179-185.##Falagas ME, Kasiakou SK, Saravolatz LD. Colistin: The revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clinical infectious diseases 2005; 40: 1333-1341.##Gunderson BW, Ibrahim KH, Hovde LB, Fromm TL, Reed MD, Rotschafer JC. Synergistic activity of colistin and ceftazidime against multiantibiotic-resistant pseudomonas aeruginosa in an in vitro pharmacodynamic model. Antimicrobial agents and chemotherapy 2003; 47: 905-909.##Igumbor E, Gwanzura L, Chirara M, Obi C, Muza D, Chihara M. Antibiotic sensitivity and plasmid profiles of pseudomonas aeruginosa. The Central African journal of medicine 2000; 46: 296-300.##Keen EF, Robinson BJ, Hospenthal DR, Aldous WK, Wolf SE, Chung KK, et al. Prevalence of multidrug-resistant organisms recovered at a military burn center. Burns 2010; 36: 819-825.##Lee J-Y, Ko KS. Mutations and expression of pmrab and phopq related with colistin resistance in pseudomonas aeruginosa clinical isolates. Diagnostic microbiology and infectious disease 2014; 78: 271-276.##Li J, Nation RL, Milne RW, Turnidge JD, Coulthard K. Evaluation of colistin as an agent against multi-resistant gram-negative bacteria. International journal of antimicrobial agents 2005; 25: 11-25.##Lo-Ten-Foe JR, de Smet AMG, Diederen BM, Kluytmans JA, van Keulen PH. Comparative evaluation of the vitek 2, disk diffusion, etest, broth microdilution, and agar dilution susceptibility testing methods for colistin in clinical isolates, including heteroresistant enterobacter cloacae and acinetobacter baumannii strains. Antimicrobial agents and chemotherapy 2007; 51: 3726-3730.##Magiorakos AP, Srinivasan A, Carey R, Carmeli Y, Falagas M, Giske C, et al. Multidrug‐resistant, extensively drug‐resistant and pandrug‐resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clinical Microbiology and Infection 2012; 18: 268-281.##Maita P, Boonbumrung K. Association between biofilm formation of pseudomonas aeruginosa clinical isolates versus antibiotic resistance and genes involved with biofilm. 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Risk factors for acquisition of multidrug-resistant pseudomonas aeruginosa producing spm metallo-β-lactamase. Antimicrobial agents and chemotherapy 2005; 49: 3663-3667.##Rossolini G, Mantengoli E. Treatment and control of severe infections caused by multiresistant pseudomonas aeruginosa. Clinical Microbiology and Infection 2005; 11: 17-32.##Saderi H, Owlia P. Detection of multidrug resistant (mdr) and extremely drug resistant (xdr) p. Aeruginosa isolated from patients in tehran, iran. Iranian Journal of Pathology 2015; 10: 265-271.##Song W, Woo H, Kim J, Lee K. In vitro activity of β-lactams in combination with other antimicrobial agents against resistant strains of pseudomonas aeruginosa. International journal of antimicrobial agents 2003; 21: 8-12.##Tacconelli E, Tumbarello M, Bertagnolio S, Citton R, Spanu T, Fadda G, et al. Multidrug-resistant pseudomonas aeruginosa bloodstream infections: Analysis of trends in prevalence and epidemiology. Emerging infectious diseases 2002; 8: 220-221.##Tan TY, Ng LSY. Comparison of three standardized disc susceptibility testing methods for colistin. Journal of Antimicrobial Chemotherapy 2006; 58: 864-867.##Tunyapanit W, Pruekprasert P, Laoprasopwattana K, Chelae S. In vitro activity of colistin against multidrug-resistant pseudomonas aeruginosa isolates from patients in songklanagarind hospital, thailand. The Southeast Asian journal of tropical medicine and public health 2013; 44: 273-80.##Vitkauskienė A, Skrodenienė E, Dambrauskienė A, Macas A, Sakalauskas R. Pseudomonas aeruginosa bacteremia: Resistance to antibiotics, risk factors, and patient mortality. Medicina (Kaunas) 2010; 46: 490-5.##Wayne P. Clinical and laboratory standards institute; 2011. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; 21.##Yoon MY, Lee K-M, Jeong SH, Kim J, Yoon SS. Heterogeneous virulence potential and high antibiotic resistance of pseudomonas aeruginosa strains isolated from korean pneumonia patients. The Journal of Microbiology 2010; 48: 518-525.##Yousefi S, Farajnia S, Nahaei MR, Akhi MT, Ghotaslou R, Soroush MH, et al. Detection of metallo-β-lactamase–encoding genes among clinical isolates of pseudomonas aeruginosa in northwest of iran. Diagnostic microbiology and infectious disease 2010; 68: 322-325.##Zavascki AP, Goldani LZ, Li J, Nation RL. Polymyxin b for the treatment of multidrug-resistant pathogens: A critical review. Journal of antimicrobial chemotherapy 2007; 60: 1206-1215.#### ##