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Diabetes mellitus linked Alzheimer’s disease – A review on sporadic form of Alzheimer’s disease 2 2 This review mainly deals with scientific data related to sporadic Alzheimer’s disease (AD) particularly related to diabetes mellitus (DM). AD is divided into sporadic AD and familial AD. It is known to be the most common cause of dementia. Sporadic form of AD results from multiple etiologic factors including metabolic, environmental and genetic factors. DM linked AD is known to be one of major challenges to health care system in these days. Both type 1 and type 2 DM is strongly related to cognitive impairment and known to be a major risk factor in the development of probable Alzheimer’s disease. In this review, the various mechanisms involved in the development of neuronal degeneration associated with chronic hyperglycaemia are discussed. 141 145 2018/01/11 1396/10/21 2018/09/20 1397/6/29 Ramu Sathiya Ramu Sathiya Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India sathiya.pg.ph@msruas.ac.in Anita Murali Anita Murali Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India anitamurali.pg.ph@msruas.ac.in Jayaraman Anbu Jayaraman Anbu Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India anbu.pg.ph@msruas.ac.in Diabetes mellitus Alzheimer’s disease Hyperglycemia Ariza L, Pages G, Garcia-Lareu B, Cobianchi S, Otaegui j, Ruberte J et al. Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy. Neurosci. 2014;274:250-259.##Bancher C, Grundke-Iqbal I, Iqbal K, Fried VA, Smith HT, Wisniewski HM. Abnormal phosphorylation of tau precedes ubiquitination in neurofibrillary pathology of Alzheimer disease. Brain Res. 1991;539 (1):11–18.##Belluti F, Rampa A, Gobbi S, Bisi A. 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Urban traffic noise pollution disturbs spatial learning and memory and increases anxiety-like behavior in adult male rats 2 2 Introduction: Noise pollution is an unwanted inevitable distribution of the modern and industrialized life of mankind. With the expansion of urban life, humans are daily exposed to noise pollution which can cause anxiety and disorders in cognitive activities. The present study was aimed to investigate the impact of sub-chronic urban traffic noise pollution on learning, memory and anxiety-like behavior in adult male rats. Methods: Thirty two adult male Wistar rats (weighing 275-300g) were used in the present experimental study. The animals were divided into two groups: the control and the noise-exposed. The rats in the test group were exposed to a 90dB noise recorded from a crowded street traffic for 6h/10 days. Control rats were intact. Morris water maze (MWM) and an elevated plus maze (EPM) were used to assess spatial learning and memory and anxiety-like behavior in rats. Results: The findings displayed that both control and noise-exposed group improved their maze steering over 4 days of experiment in MWM; however, noise-exposed group had more latency and traveled-distance in MWM to find the hidden platform in probe trial compared to those of control (P<0.05). Moreover, noise-exposed group showed a significant increase in weight gain compared to the control group (P<0.05). In addition, the spent time in open arm of the EPM was significantly decreased compared to controls (P<0.05). Conclusion: Urban traffic noise pollution for a short-term period causes a meaningful increase on weight gain, disorders in retrieval memory and increase in anxiety-like behavior in rats. 146 154 2018/01/112018/02/10 1396/11/21 2018/09/202018/08/20 1397/5/29 Mohammad Reza Afarinesh Mohammad Reza Afarinesh Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran r.afarinesh@kmu.ac.ir Baharak Akhtardanesh Baharak Akhtardanesh Clinical Science Department, Veterinary Faculty, Shahid Bahonar University, Kerman, Iran B.akhtardanesh@mail.uk.ac.ir Tahereh Haghpanah Tahereh Haghpanah Department of Anatomy, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran t.haghpah@kmu.ac.ir Fatemeh Golshan Fatemeh Golshan Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran faly.golshan@gmail.com Gholam Hossein Meftahi Gholam Hossein Meftahi Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran hossein.meftahi@bmsu.ac.ir Niousha Ghanbarpour Niousha Ghanbarpour National Organization for Development of Exceptional Talents, School For Gifted Students, Education Department, Part 1 N.ghanbarpour@gmail.com Ayoob Fakhri Ayoob Fakhri Clinical Science Department, Veterinary Faculty, Shahid Bahonar University, Kerman, Iran ayoobfakhri@gmail.com Saeed Sheikhshoaei Saeed Sheikhshoaei Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran shoaeesaeed@yahoo.com Vahid Sheibani Vahid Sheibani Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran v.sheibani@kmu.ac.ir Noise pollution Learning Anxiety Male rats Babisch W. 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Changes in the levels of hippocampal BDNF expression are accompanied with inflammatory dental pain-induced learning and memory impairment 2 2 Introduction: Learning and memory requires a brain-derived neurotrophic factor (BDNF)-dependent phase in the hippocampus. It has been reported that chronic pain decreases hippocampal BDNF levels. We have also previously reported that noxious stimulation of the rat tooth pulp impairs learning and memory. Therefore, we decided to find the changes in the hippocampal BDNF expression which are associated with tooth pain and learning and memory impairment. Methods: Dental pulp nociception was induced by intradental injection of capsaicin (100μg) in male Wistar rats. BDNF expression levels were determined by semi-quantitative RT-PCR and western blotting. Results: The data indicated that capsaicin elicited pain behaviors and impaired learning and memory in Morris water maze test. The protein and mRNA levels of BDNF were significantly (P<0.05) decreased in capsaicin-treated rats as compared with control animals. Furthermore, iboprofen (120mg/kg, ip) treatment caused a significant (P<0.05) up-regulation of the BDNF protein and mRNA in the hippocampus of capsaicin-injected animals. Conclusion: These findings suggest that inflammatory dental pain induces hippocampal function impairments by decreasing in BDNF expression. 155 162 2018/01/112018/02/102018/02/4 1396/11/15 2018/09/202018/08/202018/08/2 1397/5/11 Saeed Esmaeili-Mahani Saeed Esmaeili-Mahani Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran semahani@uk.ac.ir Maryam Raoof Maryam Raoof Endodontology Research Center, Kerman University of Medical Sciences, Kerman, Iran mraoof@kmu.ac.ir Mehdi Abbasnejad Mehdi Abbasnejad Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran mabbas@uk.ac.ir Mahdieh Nourzadeh Mahdieh Nourzadeh Iranian Center for Endodontic Research, Research Institute of Dental Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran m_nourzadeh@sbmu.ac.ir Dental pain Learning and memory Hippocampus BDNF expression Amirkhosravi L, Raoof M, Raoof R, Abbasnejad M, Esmaeili Mahani S, Ramezani M, et al. 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The effect of curcumin against 6-hydroxydopamine induced cell death and Akt/GSK disruption in human neuroblastoma cells 2 2 Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disease, characterized by the continuous deficit of dopaminergic neural cells in the substantia nigra pars compacta. The natural compounds from plant extracts, such as turmeric, have been proposed as alternative sources for anti-PD drugs. Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line used as an in vitro model for the study of dopaminergic cells. The neurotoxin 6-hydroxydopamine (6-OHDA) has been known to induce cell death in dopaminergic neural cells. Curcumin, as the main ingredient of turmeric, has been shown to protect against some animal models of PD. The purpose of the present study was to assess the potential neuroprotective effect of curcumin against the 6-OHDA-induced cell death in SH-SY5Y cells and to delineate its effect on Akt/GSK-3β signaling. Methods: The cells were exposed to 6-OHDA with/without different doses of curcumin and their viability was examined via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and morphological observations. According to the MTT results, the protective doses of curcumin (2 and 2.5μM) were selected for further studies. Western blot assay was done to determine the phosphorylated and total amount of Akt and GSK-3β proteins. Results: 6-OHDA induced cell death and declined Akt/GSK-3β phosphorylation, while curcumin co-treatment partially restored these effects. Conclusion: Taken together, these findings suggest that curcumin protects the SH-SY5Y cells from 6-OHDA-induced cell death and Akt/GSK-3β signaling alteration. Thus, our study indicates that curcumin has a partial cytoprotective effect in dopaminergic cell culture systems. 163 171 2018/01/112018/02/102018/02/42018/04/3 1397/1/14 2018/09/202018/08/202018/08/22018/08/2 1397/5/11 Maryam Moosavi Maryam Moosavi Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran marmoosavi@sums.ac.ir Majid Reza Farrokhi Majid Reza Farrokhi Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran farokhim@sums.ac.ir Narges Tafreshi Narges Tafreshi Department of Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA Narges.Tafreshi@moffitt.org Parkinson’s disease 6-OHDA SH-SY5Y Curcumin Akt GSK-3β Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: The indian solid gold. Adv Exp Med Biol 2007; 595: 1-75.##Amiri E, Ghasemi R, Moosavi M. 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The effects of rapamycin on the symptoms of cerebral ischemia due to changing the expression of miR-1 and its target genes, Bad and Bcl-w 2 2 Introduction: Stroke is the major cause of long-term disability in adults. The precise role of the mTOR signaling pathway in neural viability due to rapamycin effect in the animal model of middle cerebral artery occlusion (MCAO) remained elusive. Since the relationship between mTOR and miR-1, especially in neurons, is unknown, we have evaluated the effect of rapamycin as a post-ischemic treatment on improving stroke symptoms. Methods: Rats were divided into three groups including sham, control and rapamycin treatment group. Each contains four subgroups (n=7). One hour after MCAO, rats were received intravenously 0.1ml normal saline or 0.1ml rapamycin in the control and treatment groups, respectively. After 24 hours, neurologic deficit score, infarct volume, brain edema, and blood-brain barrier (BBB) permeability were measured in the control and treatment group. The expression of miR-1, Bcl-w and Bad were analyzed using quantitative RT-PCR in all groups. Results: Our results indicate that post-treatment with rapamycin, significantly reduces neurological deficits, infarct volume, brain edema and BBB permeability. It also decreases the level of miR-1 and Bad expression and increases the level of Bcl-w expression. Conclusion: According to our findings, post-ischemic treatment with rapamycin can be effective in improving symptoms of stroke using changing in the expression of the miR-1 gene and consequently, a changing in the expression of the target genes of this miRNA (i.e., Bad and Bcl-w). In summary, we unravel for the first time a link between mTOR, miRNA-1, Bcl-w and Bad in brain ischemia. 172 182 2018/01/112018/02/102018/02/42018/04/32018/04/13 1397/1/24 2018/09/202018/08/202018/08/22018/08/22018/08/28 1397/6/6 Anis Talebi Anis Talebi Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Mehdi Rahnema Mehdi Rahnema Department of Biology, Islamic Azad University-Zanjan Branch, Zanjan, Iran Mehdi.rahnema@iauz.ac.ir Mohammad reza Bigdeli Mohammad reza Bigdeli Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran mr_bigdeli@sbu.ac.ir miR-1 antagomir Stroke Bad Bcl-w Rapamycin Bansal S, Sangha KS, Khatri P. Drug treatment of acute ischemic stroke. Am J Cardiovasc Drugs. 2013; 13(1):57-69.##Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116: 281 297.##Bigdeli MR, Hajizadeha S, Froozandeh M, Rasulian B, Heidarianpour A, et al. 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Anti-cancer properties of the methanol extract of Boswellia serrata gum resin: Cell proliferation arrest and inhibition of angiogenesis and metastasis in BALB/c mice breast cancer model 2 2 Introduction: Boswellia serrata is a medicinal plant with immense potential in combating cancer. Since many cancers therapeutics have their roots in natural products, we investigated the inhibitory effect of B. serrata gum resin alcoholic extract (BSE) on tumor growth, metastasis and angiogenesis in 4T1 breast cancer mouse model. Methods: Cell viability of BSE on triple negative cancer cell line, 4T1, was measured by MTT assay. In the anti-breast cancer study, female BALB/c mice in four groups (n=5) were implanted into the mammary fat pad with 4T1 cells (1×105 cells/0.1 ml) and treated by BSE (50, 150 and 250mg/kg) and distilled water for 21 days. Anti-proliferation and anti-angiogenesis effects of BSE in tumor tissues were evaluated by immunohistochemical (IHC) analysis for Ki-67 and CD31 expression. The metastatic rate was investigated in the liver and lung tissues by histopathological analysis. Results: In in-vitro toxicity study, 4T1 cells line were sensitive to BSE treatment with reduced cell viability. BSE suppression of 4T1 tumor growth correlated with reduced cell proliferation as revealed by IHC analysis for Ki-67 expression. Analyses of the vasculature in the tumor tissues indicated smaller vessel area in BSE250 group compared to control tumors based on IHC for angiogenesis marker CD31. BSE only significantly decreased the metastatic rate in the lung tissue. Conclusion: From the outcome of our investigation, it is possible to conclude that BSE induces cell-specific cytotoxicity and suppresses cell proliferation, angiogenesis and metastasis rate in breast cancer cells and can be effective for advanced breast cancer. 183 194 2018/01/112018/02/102018/02/42018/04/32018/04/132018/07/4 1397/4/13 2018/09/202018/08/202018/08/22018/08/22018/08/282018/08/25 1397/6/3 Hiva Alipanah Hiva Alipanah Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran h_alipanah@sbu.ac.ir Parvin Zareian Parvin Zareian Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran p.zareian@ajaums.ac.ir Boswellia serrata Cell proliferation Cytotoxicity Tumor Growth Breast Cancer Agrawal, S., Saraswati, S., Mathur, R., & Pandey, M. Antitumor properties of Boswellic acid against Ehrlich ascites cells bearing mouse. Food and chemical toxicology,2011;49(9), 1924-1934. ##Al-Hajj, M., Wicha, M. 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Boswellia serrata, a potential antiinflammatory agent: an overview. Indian journal of pharmaceutical sciences,2011; 73(3), 255. ##Streffer, J., Bitzer, M., Schabet, M., Dichgans, J., & Weller, M. Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15. Neurology,2001; 56(9), 1219-1221. ##Suhail, M. M., Wu, W., Cao, A., Mondalek, F. G., Fung, K.-M., Shih, P.-T., . . . Lin, H.-K. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells. BMC Complementary and Alternative Medicine,2001; 11(1), 129. ##Syrovets, T., Gschwend, J. E., Büchele, B., Laumonnier, Y., Zugmaier, W., Genze, F., & Simmet, T. Inhibition of IκB kinase activity by actyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo. Journal of Biological Chemistry, 2004.##Thummuri, D., Jeengar, M. K., Shrivastava, S., Areti, A., Yerra, V. G., Yamjala, S., . . . 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Inhibition of Candida albicans yeast– hyphal transition by combination of fluconazole with amphotericin B 2 2 Introduction: Candidiasis represents a major threat to the life and health in immune-compromised individuals. The number of antifungal drugs is limited for the treatment of candidiasis. Combination therapy is one of the most frequently used techniques to alleviate this problem. Methods: Clinical isolates of Candida albicans were obtained from the immune-compromised patients. Antifungal susceptibilities to fluconazole and amphotericin B alone and in combination were performed by broth microdilution method. Eventually direct microscopic observation, time-kill kinetic assay, biomass and metabolic activity of the hypha, Sap enzyme activity and expression of SAP3 gene were carried out in C. albicans. Results: Combination of fluconazole with amphotericin B demonstrated synergistic and partial synergistic effects with fractional inhibitory concentration index ranged from 0.031 to 0.75. The data indicated that combination of fluconazole with amphotericin B exerted antifungal effects through reducing time-kill kinetic, yeast– hyphal transition, biomass and metabolic activity of the hypha and Sap enzyme activity in C. albicans. Additionally, the expression levels of the SAP3 gene were significantly down regulated (P<0.001) in C. albicans treated with combination of fluconazole with amphotericin B. Conclusion: Taken together, these events may confirm the potential uses of combination of fluconazole with amphotericin B against C. albicans. The results suggest that SAP3 gene could be probable target of synergistic interaction of fluconazole and amphotericin B in C. albicans. 195 204 2018/01/112018/02/102018/02/42018/04/32018/04/132018/07/42018/01/18 1396/10/28 2018/09/202018/08/202018/08/22018/08/22018/08/282018/08/252018/09/3 1397/6/12 Alireza Khodavandi Alireza Khodavandi Department of Biology, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran khodavandi@iaug.ac.ir Fahimeh Alizadeh Fahimeh Alizadeh Department of Microbiology, Yasooj Branch, Islamic Azad University, Yasooj, Iran f.alizadeh@iauyasooj.ac.ir Fatemeh Khezrian Fatemeh Khezrian Department of Microbiology, Yasooj Branch, Islamic Azad University, Yasooj, Iran f.Khezrian@iauyasooj.ac.ir Amphotericin B Candida albicans Fluconazole SAP3 Alizadeh F, Khodavandi A, Zalakian S. Quantitation of ergosterol content and gene expression profile of ERG11 gene in fluconazole-resistant Candida albicans. Curr Med Mycol 2017; 3: 13-9.##Borelli C, Ruge E, Schaller M, Monod M, Korting HC, Huber R, et al. The crystal structure of the secreted aspartic proteinase 3 from Candida albicans and its complex with pepstatin A. Proteins 2007; 68: 738–48. ##Calderone RA, Fonzi WA. Virulence factors of Candida albicans. Trends Microbiol 2001; 9: 327–35.##Chin VK, Lee TY, Rusliza B, Chong PP. Dissecting Candida albicans infection from the perspective of C. albicans virulence and omics approaches on host–pathogen interaction: a review. Int J Mol Sci 2016; 17: E1643.##CLSI (Clinical and Laboratory Standards Institute). Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard M27-A3. 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2008. ##Dalle F, Wächtler B, L'Ollivier C, Holland G, Bannert N, Wilson D, et al. Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes. Cell Microbiol 2010; 12: 248–71.##Gray KC, Palacios DS, Dailey I, Endo ME, Uno BE, Wilcock BC, et al. Amphotericin primarily kills yeast by simply binding ergosterol. Proc Natl Acad Sci 2012; 109: 2234–9.##Gu W, Guo D, Zhang L, Xu D, Sun S. The synergistic effect of azoles and fluoxetine against resistant Candida albicans strains is attributed to attenuating fungal virulence. Antimicrob Agents Chemother 2016; 60: 6179–88.##Haque F, Alfatah M, Ganesan K, Bhattacharyya MS. Inhibitory effect of sophorolipid on Candida albicans biofilm formation and hyphal growth. Sci Rep 2016; 6: 23575. ##Harmal NS, Khodavandi A, Alshawsh MA, Farida J, Sekawi Z, Ng K.P et al. Simplex and triplex polymerase chain reaction (PCR) for identification of three medically important Candida species. Afr J Biotechnol 2012; 11: 12895–902.##Hosseini SS, Yadegari MH, Rajabibazl M, Ghaemi EA. Inhibitory effects of carvacrol on the expression of secreted aspartyl proteinases 1-3 in fluconazole-resistant Candida albicans isolates. Iran J Microbiol 2016; 8: 401–9.##Khodavandi A, Alizadeh F, Aala F, Sekawi Z, Chong PP. In vitro investigation of antifungal activity of allicin alone and in combination with azoles against Candida Species. Mycopathologia 2010; 169: 287–95.##Khodavandi A, Alizadeh F, Harmal NS, Sidik SM, Othman F, Sekawi Z, et al. Expression analysis of SIR2 and SAPs1-4 gene expression in Candida albicans treated with allicin compared to fluconazole. Trop Biomed 2011; 28: 589–98.##Klepser ME, Ernst EJ, Lewis RE, Ernst ME, Pfaller MA. Influence of test conditions on antifungal time-kill curve results: proposed for standardized methods. Antimicrob Agents Chemother 1998; 42: 1207–12.##Lass-Flörl C. Triazole antifungal agents in invasive fungal infections: a comparative review. Drugs 2011; 71: 2405–19.##Lewis RE, Lund BC, Klepser ME, Ernst EJ, Pfaller MA. Assessment of antifungal activities of fluconazole and amphotericin B administered alone and in combination against Candida albicans by using a dynamic in vitro mycotic infection model. Antimicrob Agents Chemother 1998; 42: 1382–6.##Macdonald F, Odds FC. Inducible proteinase of Candida albicans in diagnostic serology and in the pathogenesis of systemic candidosis. J Med Microbiol 1980; 13: 423–35. ##Mardani M, Badiee P, Gharibnavaz M, Jassebi A, Jafarian H, Ghassemi F. Comparison of anti-Candida activities of the ancient plants Lawsonia inermis and Ziziphus spina christi with antifungal drugs in Candida species isolated from oral cavity. J Conserv Dent 2018; 21: 359-62.##Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence 2013; 4: 119–28.##Odds FC. Fluconazole plus amphotericin b combinations are not contraindicated and may add benefit for the treatment of candidemia. Clin Infect Dis 2003; 36: 1229–31. ##Paterson PJ, McWhinney PHM, Potter M, Kibbler CC, Prentice HG. The combination of oral amphotericin B with azoles prevents the emergence of resistant Candida species in neutropenic patients. Br J Haematol 2001; 112: 175–80.##Peeters E, Nelis HJ, Coenye T. Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates. J Microbiol Methods 2008; 72: 157–65.##Pianalto KM, Alspaugh JA. New horizons in antifungal therapy. J Fungi (Basel) 2016; 2: pii: E26. ##Rex JH, Pappas PG, Karchmer AW, Sobel J, Edwards JE, Hadley S, et al. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis 2003; 36: 1221–8. ##Ripeau JS, Aumont F, Belhumeur P, Ostrosky-Zeichner L, Rex JH, de Repentigny L. 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The rate of resistance to tetracyclines and distribution of tetA, tetB, tetC, tetD, tetE, tetG, tetJ and tetY genes in Enterobacteriaceae isolated from Azerbaijan, Iran during 2017 2 2 Introduction: Enterobacteriaceae are the heterogeneous group of Gram-negative bacteria, which cause different infections. The incidence of resistance to antibiotics among the Enterobacteriaceae is growing. This study investigated antibiotic resistance features and tetracycline resistance genes distribution in Enterobacteriaceae isolates from Hospitals of Azerbaijan, Iran. Methods: The disc diffusion agar and agar dilution methods were used for assessment of antibiotics susceptibility patterns and minimum inhibitory concentration determination of tetracycline and minocycline. To detect eight tetracycline resistance genes (tetA, tetB, tetC, tetD, tetE, tetG, tetJ, and tetY), the PCR was performed in tetracycline-resistant isolates. Results: The resistance rate to tetracycline, minocycline, doxycycline, and tigecycline by the disc diffusion agar method were 58.8%, 24%, 43.6% and 0.4%, respectively. Fifty-one (20.4%) isolates were multiple drugs resistant. The minimum inhibitory concentration results showed 52% resistance to tetracycline and 22% for minocycline. The percentage of tet genes distribution was tetA (14.4%), tetB (18.4%), tetC (2%) and tetD (4.4%). However, tetE, tetG, tetJ and tetY genes were not detected in the present study. Conclusion: There is a moderate-high resistance rate to tetracycline among Enterobacteriaceae in Azerbaijan. The most effective antibiotic against Enterobacteriaceae was tigecycline followed by fosfomycin, imipenem and meropenem. The tet genes family especially tetA and tetB were prevalent among tetracycline-resistant isolates. 205 212 2018/01/112018/02/102018/02/42018/04/32018/04/132018/07/42018/01/182018/03/24 1397/1/4 2018/09/202018/08/202018/08/22018/08/22018/08/282018/08/252018/09/32018/09/20 1397/6/29 Elham Sheykhsaran Elham Sheykhsaran Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran Sheikhsarane@tbzmed.ac.ir Hossein Bannazadeh Baghi Hossein Bannazadeh Baghi Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran hbannazadeh@tbzmed.ac.ir Mohammad Hossein Soroush Barhaghi Mohammad Hossein Soroush Barhaghi Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran soroush@tbzmed.ac.ir Naser Alizadeh Naser Alizadeh Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran Alizaden@tbzmed.ac.ir Mohammad Yousef Memar Mohammad Yousef Memar Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran memarm@tbzmed.ac.ir Shima Etemadi Shima Etemadi Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran Etemadish@tbzmed.ac.ir Reza Ghotaslou Reza Ghotaslou Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran gottasloreza@tbzmed.ac.ir Enterobacteriaceae Tetracyclines Suceptibility patterns tet genes Akhi MT, Ghotaslou R, Memar MY, Asgharzadeh M, Varshochi M, Pirzadeh T, et al. Frequency of mrsa in diabetic foot infections. International Journal of Diabetes in Developing Countries 2017; 37: 58-62.##Akram M, Shahid M, Khan AU. Etiology and antibiotic resistance patterns of community-acquired urinary tract infections in jnmc hospital aligarh, india. Annals of clinical microbiology and antimicrobials 2007; 6: 4.##Aminov R, Chee-Sanford J, Garrigues N, Teferedegne B, Krapac I, White B, et al. Development, validation, and application of pcr primers for detection of tetracycline efflux genes of gram-negative bacteria. Applied and Environmental Microbiology 2002; 68: 1786-1793.##Aminov R, Garrigues-Jeanjean N, Mackie R. Molecular ecology of tetracycline resistance: Development and validation of primers for detection of tetracycline resistance genes encoding ribosomal protection proteins. Applied and environmental microbiology 2001; 67: 22-32.##Andrews JM. Determination of minimum inhibitory concentrations. Journal of antimicrobial Chemotherapy 2001; 48: 5-16.##Chopra I, Roberts M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiology and molecular biology reviews 2001; 65: 232-260.##Connell SR, Tracz DM, Nierhaus KH, Taylor DE. Ribosomal protection proteins and their mechanism of tetracycline resistance. Antimicrobial agents and chemotherapy 2003; 47: 3675-3681.##Control CfD, Prevention. Antibiotic resistance threats in the united states, 2013: Centres for Disease Control and Prevention, US Department of Health and Human Services, 2013.##Cunha B. Oral doxycycline for non-systemic urinary tract infections (utis) due to p. Aeruginosa and other gram negative uropathogens: Springer, 2012.##Deng M, Zhu M-H, Li J-J, Bi S, Sheng Z-K, Hu F-S, et al. Molecular epidemiology and mechanisms of tigecycline resistance in clinical isolates of acinetobacter baumannii from a chinese university hospital. 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