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Does anthropometric measurements correlate with hematological parameters after the adolescent growth period? 2 2 Introduction: Musculoskeletal growth is variable during adolescent period and reaches its maximum by 18 years, whereas hemopoietic parameters reach adult values by 15 years. After adolescence period, the blood parameters may vary with nutrition and built of the individual. The purpose of this study was to find out any correlation between anthropometric and hematological parameters after the adolescent growth period. Methods: Total of 81 subjects (males: 20; females: 61), 18-22 years were analyzed for 4 anthropometric measures and 19 hematological markers. Blood was collected in citrate tubes and analyzed for hematological parameters. Results: Difference between BMI sub-groups with respect to hemoglobin (Hb), red cell distribution width-standard deviation (RDW-SD) and red cell distribution width-coefficient of variation (RDW-CV) in males and females was not significant. In males, height showed negative correlation with mean corpuscular hemoglobin concentration (MCHC) and weight showed positive correlation with hematocrit. BMI positively correlated with Hb. Body surface area (BSA) correlated with red blood cell count (RBC) and hematocrit. In females, height, weight and BSA did not show significant correlation with any of the blood parameters. BMI correlated positively with mid-cell fraction and negatively with mean platelet volume. RDW-SD and RDW-CV did not reveal any statistically significant correlation with height, weight, BMI and BSA in both males and females. Conclusion: In male subjects, hemoglobin concentration positively correlated with BMI whereas RBC count and hematocrit correlated with BSA. In females no such association was noted. RDW did not show any correlation with anthropometric measures in both genders. 137 146 2016/03/9 1394/12/19 2016/08/13 1395/5/23 Mehnaaz Sameera Arifuddin Mehnaaz Sameera Arifuddin Department of Physiology, Deccan College of Medical Sciences, Hyderabad, Telangana, India mehnaaz@deccancollegeofmedicalsciences.com Mohammed Abdul Hannan Hazari Mohammed Abdul Hannan Hazari Department of Physiology, Deccan College of Medical Sciences, Hyderabad, Telangana, India hannanhazari@deccancollegeofmedicalsciences.com BMI Body surface area Hematological parameters RDW Anthropometry 1. Stanford Children's Health. Available from http://www.stanfordchildrens.org/en/topic/default?id=the-growing-child-adolescent-13-to-18-years-90-P02175. (Last accessed on 25th February 25, 2016).##2. Center for academic research and training in anthropogeny. Available from https://carta.anthropogeny.org/moca/topics/adolescent-growth-spurt. (Last accessed on 25th February, 2016).##3. El-Hazmi MAF and Warsy AS. Normal reference values for hematological parameters, red cell indices, HbA2 and HbF from early childhood through adolescence in Saudis. Ann Saudi Med. 2001; 21(3-4):165-9.##4. Housman DB, Johnson MA, Davey A, Poon LW. Body mass index is associated with dietary patterns and health conditions in Georgia centenarians. Journal of Aging Research. 2011; doi:10.4061/2011/138015.##5. Peter R, Kumar R, Sangwan L, Pandey S. Prevalence of anemia and its correlation to body mass index: study among unmarried girls. International Journal of Basic and Applied Medical Sciences. 2012; 2:58-62.##6. Montagnana M, Cervellin G, Meschi T, Lippi G. The role of red blood cell distribution width in cardiovascular and thrombotic disorders. Clin Chem Lab Med. 2012; 50:635-41.##7. Skjelbakken T, Lappegård J, Ellingsen TS, Barrett-Connor E, Brox J, Løchen ML, Njølstad I, Wilsgaard T, Mathiesen EB, Brækkan SK, Hansen JB. Red cell distribution width is associated with incident myocardial infarction in a general population: the Tromsø Study. J Am Heart Assoc. 2014; 3(4). pii: e001109. doi: 10.1161/JAHA.114.001109.##8. Chen PC, Sung FC, Chien KL, Hsu HC, Su TC, Lee YT. Red blood cell distribution width and risk of cardiovascular events and mortality in a community cohort in Taiwan. Am J Epidemiol. 2012; 171:214-20.##9. Perlstein TS, Weuve J, Pfeffer MA, Beckman JA. Red blood cell distribution width and mortality risk in a community-based prospective cohort. Arch Intern Med 2009; 169:588-94.##10. Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med. 2009; 169:515-23.##11. Martin Söderholm, Yan Borné, Bo Hedblad, Margaretha Persson, and Gunnar Engström. Red cell distribution width in relation to incidence of stroke and carotid atherosclerosis: a population-based cohort study. PLoS One. 2015; 10(5): e0124957. doi: 10.1371/journal.pone.0124957.##12. Li W, Li X, Wang M, Xuan GE, Li F, Huang B, Peng J, Li G, Lu L, Yu Z, Ma J, Xu L, Jin M, Si H, Wan R. Association between red cell distribution width and the risk of heart events in patients with coronary artery disease. Experimental and Therapeutic Medicine. 2015; 9:1508-14.##13. Cheng CK, Chan J, Cembrowski GS, van Assendelft OW. Complete blood count reference interval diagrams derived from NHANES III: stratification by age, sex, and race. Lab Hematol. 2004; 10(1):42-53.##14. Nordin G, Mårtensson A, Swolin B, Sandberg S, Christensen NJ, Thorsteinsson V, Franzson L, Kairisto V, Savolainen ER. A multicentre study of reference intervals for haemoglobin, basic blood cell counts and erythrocyte indices in the adult population of the Nordic countries. Scand J Clin Lab Invest. 2004; 64(4):385-98.##15. Qiao R, Yang S, Yao B, Wang H, Zhang J, Shang H. Complete blood count reference intervals and age- and sex-related trends of North China Han population. Clinical Chemistry and Laboratory Medicine (CCLM). 2014; 52(7):1025-32.##16. Kelishadi R, Hashemipour M, Ashtijou P, Mirmoghtadaee P, Poursafa P, Khavarian N, Ghatrehsamani S. Association of cell blood counts and cardiometabolic risk factors among young obese children. Saudi Med J. 2010; 31(4):406-12.##17. Aypak C, Türedi O, Bircan MA, Yüce A. Could mean platelet volume among complete blood count parameters be a surrogate marker of metabolic syndrome in pre-pubertal children? Platelets. 2014; 25(6):393-8.##18. Centers for disease control and prevention. Available from http://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/. (Last accessed on 25th February, 2016).##19. Halls SB. Available from http://halls.md/body-surface-area/bsa.htm. (Last accessed on 20th February, 2016).##20. Hanson CA. Peripheral blood and bone marrow: Morphology, counts and differentials, and reactive disorders, Chapter 40, Section VII, Hematology. In: Clinical laboratory medicine, 2nd edn, McClatchey KD (Ed), Philadelphia (PA): Lippincott Williams & Wilkins, 2002, p.804.##21. Perrotta G, Roberts L, Glazier J, Schumacher HR. Use of sodium citrate anticoagulant for routine hematology analysis on the CELL-DYN® 4000: An opportunity to enhance efficiency in the clinical laboratory. Laboratory Hematology. 1998, 4:156-62.##22. Briggs C and Bain BJ. Basic haematological techniques, Chapter 3. In: Dacie and Lewis Practical Haematology, 11th ed., Bain BJ, Bates I, Laffan M, Lewis SM (Eds). Philadelphia, PA: Churchill Livingstone/Elsevier; 2012. ##23. Vajpayee N, Graham SS, Bem S. Basic examination of blood and bone marrow. In: Henry's Clinical Diagnosis and Management by Laboratory Methods, 22nd ed., McPherson RA, Pincus MR (Eds). Philadelphia, PA: Elsevier/Saunders; 2011.##24. Curry CV and Staros EB. Red Cell Distribution Width (RDW). Available from http://emedicine.medscape.com/article/2098635-overview (Last accessed on 28th February 2016).##25. Wikipedia. Red blood cell distribution width. Available from https://en.wikipedia.org/wiki/Red_blood_cell_distribution_width (Last accessed on 28th February 2016)##26. WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. WHO/NMH/NHD/MNM/11.1, 2011. Available from http://www.who.int/vmnis/indicators/haemoglobin.pdf (Last accessed on 28th February 2016)##27. Qin Y, Melse-Boonstra A, Pan X, Yuan B, Dai Y, Zhao J, Zimmermann MB, Kok FJ, Zhou M, Shi Z. Anemia in relation to body mass index and waist circumference among Chinese women. Nutr J. 2013; 12:10. doi: 10.1186/1475-2891-12-10.##28. Moafi A, Rahgozar S, Ghias M, Ahar EV, Borumand A, Sabbaghi A, Sameti A, Hashemi M. A study on body mass index, blood pressure, and red blood cell indices in new entering students of the University of Isfahan. Int J Prev Med. 2011; 2(4):280-5.##29. Fujita B, Strodthoff D, Fritzenwanger M, Pfeil A, Ferrari M, Goebel B, Figulla HR, Gerdes N, Jung C. Altered red blood cell distribution width in overweight adolescents and its association with markers of inflammation. Pediatr Obes. 2013; 8(5):385-91.##30. Barazzoni R, Cappellari GG, Semolic A, Chendi E, Ius M, Situlin R, Zanetti M, Vinci P, Guarnieri G. The association between hematological parameters and insulin resistance is modified by body mass index - results from the North-East Italy MoMa population study. PLoS One. 2014; 9(7):e101590. doi: 10.1371/journal.pone.0101590.##31. Ghadiri-Anari A, Nazemian N, Vahedian-Ardakani HA. Association of body mass index with hemoglobin concentration and iron parameters in Iranian population. ISRN Hematol. 2014; 2014:525312. doi: 10.1155/2014/525312.##32. Ausk KJ and Ioannou GN. Is obesity associated with anemia of chronic disease? A population-based study. Obesity (Silver Spring). 2008; 16(10):2356-61.##33. Saxena Y, Shrivastava A, Saxena V. Effect of gender on correlation of anaemia with body mass index in medical students. Indian J Physiol Pharmacol. 2011; 55(4):364-9.##34. Oliveira TM, de Faria FR, de Faria ER, Pereira PF, Franceschini SC, Priore SE. Nutritional status, metabolic changes and white blood cells in adolescents. Rev Paul Pediatr. 2014; 32(4):351-9. [Article in Portuguese].##35. Marzullo P, Minocci A, Giarda P, Marconi C, Tagliaferri A, Walker GE, Scacchi M, Aimaretti G, Liuzzi A. Lymphocytes and immunoglobulin patterns across the threshold of severe obesity. Endocrine. 2014; 45(3):392-400.##36. Vuong J, Qiu Y, La M, Clarke G, Swinkels DW, Cembrowski G. Reference intervals of complete blood count constituents are highly correlated to waist circumference: should obese patients have their own "normal values?". Am J Hematol. 2014; 89(7):671-7.##37. Charles LE, Fekedulegn D, McCall T, Burchfiel CM, Andrew ME, Violanti JM. Obesity, white blood cell counts, and platelet counts among police officers. Obesity (Silver Spring). 2007; 15(11):2846-54.## ##

Morphine-induced analgesic tolerance is associated with alteration of protein kinase Cγ and transient receptor potential vanilloid type 1 genes expression in rat lumbosacral cord and midbrain 2 2 Introduction: Transient receptor potential vanilloid type 1 (TRPV1) and protein kinase Cγ (PKCγ) are involved in sensitization/desensitization to noxious stimuli. We aimed to examine the gene expression levels of TRPV1 and PKCγ in rat lumbosacral cord and midbrain on days 1, 4 and 8 of induction of morphine analgesic tolerance. Methods: Two groups of male Wistar rats received twice daily saline (1 ml/kg) or morphine (10 mg/kg) for eight days and were monitored for analgesic tolerance with a hotplate test on days 1, 4 and 8 of the injections. Six independent groups in three sets were also treated with saline or morphine, decapitated on days 1, 4 or 8 of the schedule, respectively and their lumbosacral cord and midbrain were dissected. Results: The result of the hotplate test revealed induction of analgesic tolerance on days 4 and 8 of morphine injections. The TRPV1 gene expression in the lumbosacral cord was significantly increased only on day 4 of morphine injections, but the PKCγ gene expression remained with no significant changes on days 1, 4 and 8. In the midbrain, the TRPV1 gene expression was significantly increased only on day 1; however, the PKCγ gene expression was significantly increased on days 4 and 8 of morphine injections. Conclusion: It can be concluded that the TRPV1 gene expression changes in the lumbosacral cord and midbrain is associated with early phase of morphine-induced analgesic tolerance but the PKCγ gene expression is altered only in midbrain at the later phase of process. 147 156 2016/03/92016/04/8 1395/1/20 2016/08/132016/07/28 1395/5/7 Shamseddin Ahmadi Shamseddin Ahmadi Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran sh.ahmadi@uok.ac.ir Neda Parvini Neda Parvini Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran n.parvini@uok.ac.ir Morphine Analgesic tolerance Gene expression Spinal cord Midbrain TRPV1 PKCγ Ahmadi S, Amiri S, Rafieenia F, Rostamzadeh J. Gene expression profile of calcium/calmodulin-dependent protein kinase iialpha in rat's hippocampus during morphine withdrawal. Basic Clin Neurosci 2013; 4: 146-52.##Ahmadi S, Karami Z, Mohammadian A, Khosrobakhsh F, Rostamzadeh J. Cholestasis induced antinociception and decreased gene expression of mor1 in rat brain. Neuroscience 2015a; 284: 78-86.##Ahmadi S, Poureidi M, Rostamzadeh J. Hepatic encephalopathy induces site-specific changes in gene expression of glun1 subunit of nmda receptor in rat brain. Metab Brain Dis 2015b; 30: 1035-41.##Ahmadi S, Rashdi A. Gene expression profile of calcium/calmodulin-dependent protein kinase iiα in rat spinal cord and midbrain during induction of morphine analgesic tolerance Gene Cell Tissue 2016; 3: In Press. DOI: 10.17795/gct-38142 ##Ammon-Treiber S, Hollt V. Morphine-induced changes of gene expression in the brain. Addict Biol 2005; 10: 81-9.##Bailey CP, Smith FL, Kelly E, Dewey WL, Henderson G. How important is protein kinase c in mu-opioid receptor desensitization and morphine tolerance? Trends Pharmacol Sci 2006; 27: 558-65.##Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, et al. Opioid complications and side effects. Pain Physician 2008; 11: S105-20.##Bilsky EJ, Bernstein RN, Wang Z, Sadee W, Porreca F. Effects of naloxone and d-phe-cys-tyr-d-trp-arg-thr-pen-thr-nh2 and the protein kinase inhibitors h7 and h8 on acute morphine dependence and antinociceptive tolerance in mice. J Pharmacol Exp Ther 1996; 277: 484-90.##Cantrell AR, Catterall WA. Neuromodulation of na+ channels: An unexpected form of cellular plasticity. Nat Rev Neurosci 2001; 2: 397-407.##Chen SR, Prunean A, Pan HM, Welker KL, Pan HL. Resistance to morphine analgesic tolerance in rats with deleted transient receptor potential vanilloid type 1-expressing sensory neurons. Neuroscience 2007; 145: 676-85.##Chen Y, Geis C, Sommer C. Activation of trpv1 contributes to morphine tolerance: Involvement of the mitogen-activated protein kinase signaling pathway. J Neurosci 2008; 28: 5836-45.##Dogrul A, Bilsky EJ, Ossipov MH, Lai J, Porreca F. Spinal l-type calcium channel blockade abolishes opioid-induced sensory hypersensitivity and antinociceptive tolerance. Anesth Analg 2005; 101: 1730-5.##DuPen A, Shen D, Ersek M. Mechanisms of opioid-induced tolerance and hyperalgesia. Pain Manag Nurs 2007; 8: 113-21.##Granados-Soto V, Kalcheva I, Hua X, Newton A, Yaksh TL. Spinal pkc activity and expression: Role in tolerance produced by continuous spinal morphine infusion. Pain 2000; 85: 395-404.##Hakimizadeh E, Kazemi Arababadi M, Shamsizadeh A, Allahtavakoli M, Rezvani ME, Roohbakhsh A. Morphine reduces expression of trpv1 receptors in the amygdala but not in the hippocampus of male rats. Iran J Med Sci 2014; 39: 261-7.##Hosseini M, Taiarani Z, Hadjzadeh MA, Salehabadi S, Tehranipour M, Alaei HA. Different responses of nitric oxide synthase inhibition on morphine-induced antinociception in male and female rats. Pathophysiology 2011; 18: 143-9.##Igumenova TI. Dynamics and membrane interactions of protein kinase c. Biochemistry 2015; 54: 4953-68.##Immke DC, Gavva NR. The trpv1 receptor and nociception. Semin Cell Dev Biol 2006; 17: 582-91.##Jin WY, Yu LC. Involvement of protein kinase c in morphine tolerance at spinal levels of rats. ACS Chem Neurosci 2010; 1: 122-8.##Kauer JA, Gibson HE. Hot flash: Trpv channels in the brain. Trends Neurosci 2009; 32: 215-24.##Keil GJ, 2nd, Delander GE. Time-dependent antinociceptive interactions between opioids and nucleoside transport inhibitors. J Pharmacol Exp Ther 1995; 274: 1387-92.##Klecha AJ, Genaro AM, Gorelik G, Barreiro Arcos ML, Silberman DM, Schuman M, et al. Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: Thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase c signaling pathway. J Endocrinol 2006; 189: 45-55.##Koch T, Hollt V. Role of receptor internalization in opioid tolerance and dependence. Pharmacol Ther 2008; 117: 199-206.##Lee MC, Wanigasekera V, Tracey I. Imaging opioid analgesia in the human brain and its potential relevance for understanding opioid use in chronic pain. Neuropharmacology 2014; 84: 123-30.##Mandadi S, Tominaga T, Numazaki M, Murayama N, Saito N, Armati PJ, et al. Increased sensitivity of desensitized trpv1 by pma occurs through pkcepsilon-mediated phosphorylation at s800. Pain 2006; 123: 106-16.##Mao J. Opioid-induced abnormal pain sensitivity. Curr Pain Headache Rep 2006; 10: 67-70.##Mao J, Sung B, Ji RR, Lim G. Chronic morphine induces downregulation of spinal glutamate transporters: Implications in morphine tolerance and abnormal pain sensitivity. J Neurosci 2002; 22: 8312-23.##Martini L, Whistler JL. The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence. Curr Opin Neurobiol 2007; 17: 556-64.##Mayer DJ, Mao J, Price DD. The development of morphine tolerance and dependence is associated with translocation of protein kinase c. Pain 1995; 61: 365-74.##Narita M, Feng Y, Makimura M, Hoskins B, Ho IK. A protein kinase inhibitor, h-7, inhibits the development of tolerance to opioid antinociception. Eur J Pharmacol 1994a; 271: 543-5.##Narita M, Makimura M, Feng Y, Hoskins B, Ho IK. Influence of chronic morphine treatment on protein kinase c activity: Comparison with butorphanol and implication for opioid tolerance. Brain Res 1994b; 650: 175-9.##Naziroglu M, Demirdas A. Psychiatric disorders and trp channels: Focus on psychotropic drugs. Curr Neuropharmacol 2015; 13: 248-57.##Newton AC. Regulation of the abc kinases by phosphorylation: Protein kinase c as a paradigm. Biochem J 2003; 370: 361-71.##Nguyen TL, Kwon SH, Hong SI, Ma SX, Jung YH, Hwang JY, et al. Transient receptor potential vanilloid type 1 channel may modulate opioid reward. Neuropsychopharmacology 2014; 39: 2414-22.##Nguyen TL, Nam YS, Lee SY, Kim HC, Jang CG. Effects of capsazepine, a transient receptor potential vanilloid type 1 antagonist, on morphine-induced antinociception, tolerance, and dependence in mice. Br J Anaesth 2010; 105: 668-74.##Ossipov MH, Harris S, Lloyd P, Messineo E, Lin BS, Bagley J. Antinociceptive interaction between opioids and medetomidine: Systemic additivity and spinal synergy. Anesthesiology 1990; 73: 1227-35.##Roberts JC, Davis JB, Benham CD. [3h]resiniferatoxin autoradiography in the cns of wild-type and trpv1 null mice defines trpv1 (vr-1) protein distribution. Brain Res 2004; 995: 176-83.##Spicarova D, Palecek J. The role of spinal cord vanilloid (trpv1) receptors in pain modulation. Physiol Res 2008; 57 Suppl 3: S69-77.##Szallasi A. Autoradiographic visualization and pharmacological characterization of vanilloid (capsaicin) receptors in several species, including man. Acta Physiol Scand Suppl 1995; 629: 1-68.##Szallasi A, Nilsson S, Farkas-Szallasi T, Blumberg PM, Hokfelt T, Lundberg JM. Vanilloid (capsaicin) receptors in the rat: Distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment. Brain Res 1995; 703: 175-83.##Wang Z, Chabot JG, Quirion R. On the possible role of erk, p38 and camkii in the regulation of cgrp expression in morphine-tolerant rats. Mol Pain 2011; 7: 68.##Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, et al. Regulation of mu-opioid receptors: Desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 2013; 65: 223-54.##Woo DH, Jung SJ, Zhu MH, Park CK, Kim YH, Oh SB, et al. Direct activation of transient receptor potential vanilloid 1(trpv1) by diacylglycerol (dag). Mol Pain 2008; 4: 42.#### ##

The demyelination and altered motor performance following electrolytic lesion in the ventrolateral white matter of spinal cord in male rats: benefit of post-injury administration of estradiol 2 2 Introduction: Spinal cord injuries are accompanied with significant demyelination of axons and subsequent locomotor dysfunction. To identify the extent of damage following electrolytic lesion of ventrolateral white matter, essential area for initiation of locomotor activity, we assessed demyelination as well as alteration in motor performance. Moreover, the protective effect of estradiol as a candidate treatment for preservation of myelin and locomotor activity after injury was examined due to its anti-apoptotic and anti-inflammatory activities. Methods: A unilateral electrolytic lesion positioned in the right ventrolateral funiculus (VLF) was applied following laminectomy at T8-T9. In the estradiol-treated injury group, animals received a pharmacological single dose of estradiol valerate (4 mg/kg) at 30min post injury. Locomotor function was assessed using rotarod and open field tasks during 4 weeks after injury. Results: Obtained results showed significant demyelination at the site of injury and caudal areas following lesion as well as altered motor performance. Post-spinal cord injury administration of estradiol enhanced white matter maintenance at the site of lesion, restored the level of myelin basic protein (MBP), decreased TUNEL positive cells and improved functional recovery. Conclusion: Taken together, these results indicate that demyelination after lesion in VLF may be a contributing factor to limited motor performance, and suggest that pharmacological doses of estradiol may have an early protective effect through sparing of white matter. 157 171 2016/03/92016/04/82016/05/3 1395/2/14 2016/08/132016/07/282016/06/12 1395/3/23 Mina Afhami Mina Afhami Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran mina.afhammi@gmail.com Fatemeh Abbaszadeh Fatemeh Abbaszadeh Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran f.abbaszadehm@gmail.com Elham Saghaei Elham Saghaei Department of Physiology and pharmacology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran saghaei.e@skums.ac.ir Kobra Naseri Kobra Naseri Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran naseri@bums.ac.ir Mohammad Javan Mohammad Javan Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran mjavan@modares.ac.ir Masoumeh Jorjani Masoumeh Jorjani Shahid Beheshti Medical University Department of Pharmacology & Neuroscience Research Center msjorjani@sbmu.ac.ir Spinal cord injury Estradiol Demyelination Arvanian, V. L., L. Schnell, L. Lou, R. Golshani, A. Hunanyan, A. Ghosh, D. D. Pearse, J. K. Robinson, M. E. Schwab, J. W. Fawcett and L. M. Mendell. Chronic spinal hemisection in rats induces a progressive decline in transmission in uninjured fibers to motoneurons. Exp Neurol 2009;216: 471-480.##Barres, B. A., I. K. Hart, H. S. Coles, J. F. Burne, J. T. Voyvodic, W. D. Richardson and M. C. Raff. Cell death and control of cell survival in the oligodendrocyte lineage. Cell 1992;70: 31-46.##Barriere, G., H. Leblond, J. Provencher and S. Rossignol. Prominent role of the spinal central pattern generator in the recovery of locomotion after partial spinal cord injuries. J Neurosci 2008;28: 3976-3987.##Basso, D. M. Neuroanatomical substrates of functional recovery after experimental spinal cord injury: implications of basic science research for human spinal cord injury. Phys Ther 2000;80: 808-817.##Baumann, N. and D. Pham-Dinh. Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 2001;81: 871-927.##Beattie, M. S. Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 2004;10: 580-583.##Beattie, M. S., A. A. Farooqui and J. C. Bresnahan. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma 2000;17: 915-925.##Beattie, M. S., G. E. Hermann, R. C. Rogers and J. C. Bresnahan. Cell death in models of spinal cord injury. Prog Brain Res 2002;137: 37-47.##Biewenga, E., L. Cabell and T. Audesirk. Estradiol and raloxifene protect cultured SN4741 neurons against oxidative stress. Neurosci Lett 2005;373: 179-183.##Blight, A. R. Cellular morphology of chronic spinal cord injury in the cat: analysis of myelinated axons by line-sampling. Neuroscience 1983;10: 521-543.##Brown, L. T. Rubrospinal projections in the rat. J Comp Neurol 1974;154: 169-187.##Brown, L. T., Jr. Projections and termination of the corticospinal tract in rodents. Exp Brain Res 1971;13: 432-450.##Bunge, R. P., W. R. Puckett and E. D. Hiester. Observations on the pathology of several types of human spinal cord injury, with emphasis on the astrocyte response to penetrating injuries. Adv Neurol 1997;72: 305-315. ##Cao, Q., et al., Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat. Exp Neurol, 2005. 191 Suppl 1: p. S3-S16.##Casha, S., W. R. Yu and M. G. Fehlings. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 2001;103: 203-218.##Crowe, M. J., J. C. Bresnahan, S. L. Shuman, J. N. Masters and M. S. Beattie. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med 1997;3: 73-76.##Donnelly, D. J. and P. G. Popovich. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol 2008;209: 378-388.##Dunham, N. W. and T. S. Miya. A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Am Pharm Assoc (Baltim) 1957;46: 208-209.##Emery, E., P. Aldana, M. B. Bunge, W. Puckett, A. Srinivasan, R. W. Keane, J. Bethea and A. D. Levi. Apoptosis after traumatic human spinal cord injury. J Neurosurg 1998;89: 911-920.##Farooque, M., Z. Suo, P. M. Arnold, M. J. Wulser, C. T. Chou, R. W. Vancura, S. Fowler and B. W. Festoff. Gender-related differences in recovery of locomotor function after spinal cord injury in mice. Spinal Cord 2006;44: 182-187.##Gledhill, R. F., B. M. Harrison and W. I. McDonald. Demyelination and remyelination after acute spinal cord compression. Exp Neurol 1973;38: 472-487.##Hauben, E., T. Mizrahi, E. Agranov and M. Schwartz. Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity? Eur J Neurosci 2002;16: 1731-1740. ##Hedges VL, Ebner TJ, Meisel RL, Mermelstein PG. The cerebellum as a target for estrogen action. Front Neuroendocrinol 2012;33:403-11.##Hendriks, J. J., C. E. Teunissen, H. E. de Vries and C. D. Dijkstra. Macrophages and neurodegeneration. Brain Res Brain Res Rev 2005;48: 185-195.##Houle, J. D. and Y. Jin. Chronically injured supraspinal neurons exhibit only modest axonal dieback in response to a cervical hemisection lesion. Exp Neurol 2001;169: 208-217.##Hulsebosch, C. E. Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ 2002;26: 238-255.##Jasmin, L., G. Janni, T. M. Moallem, D. A. Lappi and P. T. Ohara. Schwann cells are removed from the spinal cord after effecting recovery from paraplegia. J Neurosci 2000;20: 9215-9223.##Jung-Testas, I., M. Renoir, H. Bugnard, G. L. Greene and E. E. Baulieu. Demonstration of steroid hormone receptors and steroid action in primary cultures of rat glial cells. J Steroid Biochem Mol Biol 1992;41: 621-631.##Kachadroka, S., A. M. Hall, T. L. Niedzielko, S. Chongthammakun and C. L. Floyd. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats. J Neurotrauma 2010;27: 611-626.##Katoh, K., T. Ikata, S. Katoh, Y. Hamada, K. Nakauchi, T. Sano and M. Niwa. Induction and its spread of apoptosis in rat spinal cord after mechanical trauma. Neurosci Lett 1996;216: 9-12.##Kotter MR, Li WW, Zhao C, Franklin RJ. Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation. J Neurosci 2006;26:328-32.##Krenz, N. R. and L. C. Weaver. Nerve growth factor in glia and inflammatory cells of the injured rat spinal cord. J Neurochem 2000;74: 730-739.##Lasiene, J., L. Shupe, S. Perlmutter and P. Horner. No evidence for chronic demyelination in spared axons after spinal cord injury in a mouse. J Neurosci 2008;28: 3887-3896.##Li, G. L., M. Farooque, A. Holtz and Y. Olsson. Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord. Acta Neuropathol 1999;98: 473-480.##Li, Y., P. M. Field and G. Raisman. Death of oligodendrocytes and microglial phagocytosis of myelin precede immigration of Schwann cells into the spinal cord. J Neurocytol 1999;28: 417-427.##Liu, X. Z., X. M. Xu, R. Hu, C. Du, S. X. Zhang, J. W. McDonald, H. X. Dong, Y. J. Wu, G. S. Fan, M. F. Jacquin, C. Y. Hsu and D. W. Choi. Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci 1997;17: 5395-5406.##Loy, D. N., D. S. Magnuson, Y. P. Zhang, S. M. Onifer, M. D. Mills, Q. L. Cao, J. B. Darnall, L. C. Fajardo, D. A. Burke and S. R. Whittemore. Functional redundancy of ventral spinal locomotor pathways. J Neurosci 2002;22: 315-323.##Ludwin, S. K. The pathobiology of the oligodendrocyte. J Neuropathol Exp Neurol 1997;56: 111-124.## Majczyński H, Sławińska U. Locomotor recovery after thoracic spinal cord lesions in cats, rats and humans. Acta Neurobiol Exp (Wars) 2007;67:235-57##Mathis, C., N. Denisenko-Nehrbass, J. A. Girault and E. Borrelli. Essential role of oligodendrocytes in the formation and maintenance of central nervous system nodal regions. Development 2001;128: 4881-4890.##McDonald, J. W. and C. Sadowsky. Spinal-cord injury. Lancet 2002;359: 417-425.##Meredith, G. E. and U. J. Kang. Behavioral models of Parkinson's disease in rodents: a new look at an old problem. Mov Disord 2006;21: 1595-1606.##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;13:138-50.##Naseri, K., E. Saghaei, F. Abbaszadeh, M. Afhami, A. Haeri, F. Rahimi and M. Jorjani. Role of Microglia and Astrocyte in Central Pain Syndrome Following Electrolytic Lesion at the Spinothalamic Tract in Rats. J Mol Neurosci 2012.##Norenberg, M., J. Smith and A. Marcillo. The pathology of human spinal cord injury: defining the problems. J Neurotrauma. 2004;21: 429-440.##Pang, Y., B. Zheng, L. R. Campbell, L. W. Fan, Z. Cai and P. G. Rhodes. IGF-1 can either protect against or increase LPS-induced damage in the developing rat brain. Pediatr Res 2010;67: 579-584.##Pistorio, A. L., S. H. Hendry and X. Wang. A modified technique for high-resolution staining of myelin. J Neurosci Methods 2006;153: 135-146.##Pomeroy, I. M., P. M. Matthews, J. A. Frank, E. K. Jordan and M. M. Esiri. Demyelinated neocortical lesions in marmoset autoimmune encephalomyelitis mimic those in multiple sclerosis. Brain 2005;128: 2713-2721.##Profyris, C., S. S. Cheema, D. Zang, M. F. Azari, K. Boyle and S. Petratos. Degenerative and regenerative mechanisms governing spinal cord injury. Neurobiol Dis 2004;15: 415-436.##Ritz, M. and O. Hausmann. Effect of 17beta-estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats. Brain Res. 2008;8: 177-188.##Samantaray, S., E. A. Sribnick, A. Das, N. P. Thakore, D. Matzelle, S. P. Yu, S. K. Ray, L. Wei and N. L. Banik. Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats. Ann N Y Acad Sci 2010;1199: 90-94.##Sherafat, M. A., Heibatollahi, M., Mongabadi, S., Moradi, F., Javan, M., & Ahmadiani, (2012). A electromagnetic field stimulation potentiates endogenous myelin repair by recruiting subventricular neural stem cells in an experimental model of white matter demyelination. Journal of Molecular Neuroscience, 48, 144–153.##Shuman, S. L., J. C. Bresnahan and M. S. Beattie. Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats. J Neurosci Res 1997;50: 798-808.##Sim, F. J., G. L. Hinks and R. J. Franklin. The re-expression of the homeodomain transcription factor Gtx during remyelination of experimentally induced demyelinating lesions in young and old rat brain. Neuroscience 2000;100: 131-139.##Sribnick EA, Matzelle DD, Ray SK and B. NL. Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. J Neurosci Res 2006;84: 1064-1075.##Sribnick, E. A., S. Samantaray, A. Das, J. Smith, D. D. Matzelle, S. K. Ray and N. L. Banik. Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats. J Neurosci Res 2010;88: 1738-1750.##Sribnick, E. A., J. M. Wingrave, D. D. Matzelle, G. G. Wilford, S. K. Ray and N. L. Banik. Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats. J Neurosci Res 2005;82: 283-293.##Steeves JD, J. L. Localization of a descending pathway in thespinal cord which is necessary for controlled treadmill locomotion. Neurosci Lett 1980;20: 283–288.##Sur, P., E. A. Sribnick, J. M. Wingrave, M. W. Nowak, S. K. Ray and N. L. Banik. Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells. Brain Res 2003;971: 178-188. ##Suyama K, Watanabe M, Sakai D, Osada T, Imai M, Mochida J. Nkx2.2 expression in differentiation of oligodendrocyte precursor cells and inhibitory factors for differentiation of oligodendrocytes after traumatic spinal cord injury. J Neurotrauma 2007;24:1013–1025. ##Takao, T., N. Flint, L. Lee, X. Ying, J. Merrill and K. J. Chandross. 17beta-estradiol protects oligodendrocytes from cytotoxicity induced cell death. J Neurochem 2004;89: 660-673.##Totoiu, M. O. and H. S. Keirstead. Spinal cord injury is accompanied by chronic progressive demyelination. J Comp Neurol 2005;486: 373-383.##Waxman, S. G. Demyelination in spinal cord injury. J Neurol Sci 1989;91: 1-14.##Webb, A. A., C. B. Chan, A. Brown and T. M. Saleh. Estrogen reduces the severity of autonomic dysfunction in spinal cord-injured male mice. Behav Brain Res 2006;171: 338-349.##Webb, A. A. and G. D. Muir. Course of motor recovery following ventrolateral spinal cord injury in the rat. Behav Brain Res 2004;155: 55-65.##Weidner, N., A. Ner, N. Salimi and M. H. Tuszynski. Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc Natl Acad Sci U S A 2001;98: 3513-3518.##Xu, G., S. Liu, Michael G. Hughes and D. J. McAdooab. Glutamate-Induced Losses of Oligodendrocytes and Neurons and Activation of Caspase-3 in the Rat Spinal Cord. Neuroscience 2008;153: 1034–1047.##Xu, G. Y., M. G. Hughes, Z. Ye, C. E. Hulsebosch and D. J. McAdoo. Concentrations of glutamate released following spinal cord injury kill oligodendrocytes in the spinal cord. Exp Neurol 2004;187: 329-336.##Young, W. (1988). Recovery mechanisms in spinal cord injury:implications for regenerative therapy. Neural Regeneration and Transplantation. A. R. L. F.J. Seil (ed). New York: 157–169.##Yune TY, Kim SJ, Lee SM, Lee YK, Oh YJ, Kim YC, Markelonis GJ and O. TH. Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats.. J Neurotrauma 2004;21: 293-306.#### ##

Lack of association between coding region of KCNE2 gene and the congenital long QT syndrome in an Iranian population 2 2 Introduction: Congenital long QT syndrome (LQTS) is a cardiac disorder characterized by QT interval prolongation at basal ECG. Different LQTS genes encode ion channel subunits or proteins involved in regulating cardiac ionic currents. Long QT syndrome type 6 (LQT6) is caused by mutation in the KCNE2 gene. Our research aimed to analyze genetic variants of KCNE2 gene causing the disease in Iranian population. Methods: Twenty nine patients consented for participation in the study. They were diagnosed based on Schwartz's criteria. After DNA extraction from peripheral blood cells, two exons of the KCNE2 gene were amplified. Afterwards, PCR-SSCP was carried out for screening the possible mutated gene variants. As the last verification step, direct sequencing was done to determine the sequence. Results: All samples were detected by PCR-SSCP and sequenced. None of the patients had the mutation in the KCNE2 gene. Conclusion: Investigating a genetic variant associated with LQTS, in Iranian patients clinically diagnosed with LQT6, no association was found between the disease and KCNE2 gene. Other previously identified genes, especially the major genes, should be considered for further investigation. 172 178 2016/03/92016/04/82016/05/32016/03/27 1395/1/8 2016/08/132016/07/282016/06/122016/07/1 1395/4/11 Pedram Torabian Pedram Torabian Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran pedram_torabian@yahoo.com Ayyoob Khosravi Ayyoob Khosravi Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran khosravia@goums.ac.ir Mehdi Gholizadeh Mehdi Gholizadeh Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran mehdi2ghde@yahoo.com Mehdi Zahedi Mehdi Zahedi Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran dr_zahedi@hotmail.com Majid Haghjoo Majid Haghjoo Shahid Rajaei Cardiovascular, Medical and Research Center Echocardiography Research Center, Tehran University of Medical Sciences, Tehran, Iran majid.haghjoo@gmail.com Morteza Oladnabi Morteza Oladnabi Department of Human Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran oladnabidozin@yahoo.com Yahya Jand Yahya Jand Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran Vahid Khori Vahid Khori Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran dr.khoori@goums.ac.ir KCNE2 gene Long QT syndrome Polymorphism Single-stranded conformational 1. G. Michael Vincent. The molecular genetics of the long QT syndrome: genes causing fainting and sudden death. Annual Review of Medicine. 1998 49: 263-274##2. Mohler PJ, Schott J-J, Gramolini AO, Dilly KW, Guatimosim S, Song L-S, et al. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature. 2003;421(6923):634-9.##2. Straus S, Bleumink G, Dieleman J, Stricker BC, Sturkenboom M. The incidence of sudden cardiac death in the general population. Journal of clinical epidemiology. 2004;57(1):98-102.##3. Abriel H, Cabo C, Wehrens XH, Rivolta I, Motoike HK, Memmi M, et al. Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in the cardiac Na+ channel. Circulation research. 2001;88(7):740-5.##4. Goldenberg I, Zareba W, Moss AJ. Long QT syndrome. Current problems in cardiology. 2008;33(11):629-94.##5. Aizawa Y, Kohno T, Yuasa S, Fukuda K. The Role of Circadian Rhythms in Fatal Arrhythmias and the Potential Impact of Intervention for Sleep-Disordered Breathing. Current pharmaceutical design. 2015;21(24):3512-22.##6. Summers KM, Bokil NJ, Lu FT, Low JT, Baisden JM, Duffy D, et al. Mutations at KCNQ1 and an unknown locus cause long QT syndrome in a large Australian family: implications for genetic testing. American Journal of Medical Genetics Part A. 2010;152(3):613-21.##7. Kloth J, Pagani A, Verboom M, Malovini A, Napolitano C, Kruit W, et al. Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors. British journal of cancer. 2015;112(6):1011-6.##8. Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman‐Smook J, Brink PA, et al. The genetic basis of long QT and short QT syndromes: a mutation update. Human mutation. 2009;30(11):1486-511.##9. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, et al. Spectrum of mutations in long-QT syndrome genes KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000;102(10):1178-85.##10. Nakajo K, Kubo Y. KCNQ1 channel modulation by KCNE proteins via the voltage‐sensing domain. The Journal of physiology. 2015.##11. Leung KH, Yip SP. Single Strand Conformation Polymorphism (SSCP) Analysis. Molecular Biomethods Handbook: Springer; 2008. p. 117-31.##12. Schwartz PJ. Idiopathic long QT syndrome: progress and questions. American heart journal. 1985;109(2):399-411.##13. Schwartz PJ, Crotti L, Insolia R. Long-QT Syndrome From Genetics to Management. Circulation: Arrhythmia and Electrophysiology. 2012;5(4):868-77.##14. Allegue C, Gil R, Sanchez‐Diz P, Torres M, Quintela I, Carracedo A, et al. A new approach to long QT syndrome mutation detection by Sequenom MassARRAY® system. Electrophoresis. 2010;31(10):1648-55.##15. Watanabe H, Darbar D, Kaiser DW, Jiramongkolchai K, Chopra S, Donahue BS, et al. Mutations in sodium channel β1-and β2-subunits associated with atrial fibrillation. Circulation: Arrhythmia and Electrophysiology. 2009;2(3):268-75.##16. Medlock MM, Tester DJ, Will ML, Bos JM, Ackerman MJ. Repeat long QT syndrome genetic testing of phenotype-positive cases: prevalence and etiology of detection misses. Heart Rhythm. 2012;9(12):1977-82.##17. Hoshino S, Kimura A, Fukuda Y, Dohi K, Sasazuki T. Polymerase chain reaction—single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple, economical, and rapid method for histocompatibility testing. Human immunology. 1992;33(2):98-107.##18. Gasser RB, Hu M, Chilton NB, Campbell BE, Jex AJ, Otranto D, et al. Single-strand conformation polymorphism (SSCP) for the analysis of genetic variation. Nature Protocols. 2006;1(6):3121-8.##19. Gordon E, Panaghie G, Deng L, Bee KJ, Roepke TK, Krogh-Madsen T, et al. A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance. Cardiovascular research. 2007.##20. Digby G, MacHaalany J, Malik P, Methot M, Simpson CS, Redfearn D, et al. Multifactorial QT interval prolongation. Cardiology journal. 2010;17(2):184-8.##21. Bennett PB, Guthrie HR. Trends in ion channel drug discovery: advances in screening technologies. Trends in biotechnology. 2003;21(12):563-9.##22. Wilde AA, Pinto YM. Cost-Effectiveness of Genotyping in Inherited Arrhythmia Syndromes Are We Getting Value for the Money? Circulation: Arrhythmia and Electrophysiology. 2009;2(1):1-3.##23. Larsen LA, Andersen PS, Kanters J, Svendsen IH, Jacobsen JR, Vuust J, et al. Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRP1 ion channel: implications for acquired and congenital long QT syndrome. Clinical Chemistry. 2001;47(8):1390-5.##24. Koo S, Teo W, Ching C, Chan S, Lee EJ. Mutation screening in KCNQ1, HERG, KCNE1, KCNE2 and SCN5A genes in a long QT syndrome family. ANNALS-ACADEMY OF MEDICINE SINGAPORE. 2007;36(6):394.##25. Du R, Tian L, Yuan G, Li J, Ren F, Gui L, et al. Mutation analysis of KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes in Chinese patients with long QT syndrome. Frontiers of medicine in China. 2007;1(3):312-5.##26. Christiansen M, Hedley PL, Theilade J, Stoevring B, Leren TP, Eschen O, et al. Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p. F29L in KCNH2. BMC medical genetics. 2014;15(1):31.##27. Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, et al. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. Jama. 2005;294(23):2975-80.##28. Iwasa H, Itoh T, Nagai R, Nakamura Y, Tanaka T. Twenty single nucleotide polymorphisms (SNPs) and their allelic frequencies in four genes that are responsible for familial long QT syndrome in the Japanese population. Journal of human genetics. 2000;45(3):182-3.##29. Sesti F, Abbott GW, Wei J, Murray KT, Saksena S, Schwartz PJ, et al. A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proceedings of the National Academy of Sciences. 2000;97(19):10613-8.##30. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell. 1999 16;97(2):175-87.##31. Tester DJ, Will ML, Haglund CM, Ackerman MJ. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 May; 2(5):507-17.##32. Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ. Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 ;6(9):1297-303. ##33. Yang Y1, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y, Liang B, Lin J, Liu Y, Liu B, Zhou Q, Zhang D, Wang R, Ma N, Su X, Niu K, Pei Y, Xu W, Chen Z, Wan H, Cui J, Barhanin J, Chen Y. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet. 2004;75(5):899-905. ##34. Millat G, Chevalier P, Restier-Miron L, Da Costa A, Bouvagnet P, Kugener B, Fayol L, Gonzàlez Armengod C, Oddou B, Chanavat V, Froidefond E, Perraudin R, Rousson R, Rodriguez-Lafrasse C. Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 Sep;70(3):214-27.##35. Isbrandt D, Friederich P, Solth A, Haverkamp W, Ebneth A, Borggrefe M, Funke H, Sauter K, Breithardt G, Pongs O, Schulze-Bahr E. Identification and functional characterization of a novel KCNE2 (MiRP1) mutation that alters HERG channel kinetics.J Mol Med (Berl). 2002 Aug;80(8):524-32.##36. Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005; 294(23):2975-80.##37. Gordon E, Panaghie G, Deng L, Bee KJ, Roepke TK, Krogh-Madsen T, Christini DJ, Ostrer H, Basson CT, Chung W, Abbott GW. A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance. Cardiovasc Res. 2008;77(1):98-106.#### ##

Synovial fractalkine plays important role in cytokines’ related knee edema variation in rat arthritis model 2 2 Introduction: The systemic and local content of inflammatory cytokines and chemokines play substantial roles in pathophysiology of arthritis. This study was purposed to verify the roles of synovial TNF-α, IL-6 and fractalkine (Fkn) in edema changes during different stages of Complete Freund’s Adjuvant (CFA)-induced knee arthritis in rats. Methods: 168 male Wistar rats were divided in 7 groups and each group was divided to 4 subgroups. Each subgroup contains 6 male rats. Arthritis was evoked into the right knee joint. Changes in knee edema were evaluated by caliper and synovial TNF-α and IL-6 levels were assayed by rat standard ELISA kit in homogenized synovial tissues on days 0, 7, 14 and 21 of study. Synovial Fkn content was assessed during different stages of study using western blot. For analysis of within-groups differences, ANOVA followed by post hoc Tukeys was used. Unpaired student t-test was used for analysis of differences between groups. Results: CFA injection caused intense knee edema which was reduced by anti-TNF-α and anti-Fkn administration. In anti-IL-6 treated rats, knee edema was reduced in the first two weeks but increased on day 21 of study. Remarkable increase in synovial TNF-α, IL-6 and Fkn levels were observed after CFA treatment. Anti-TNF-α treatment reduced synovial levels of IL-6 and Fkn. Anti-IL-6 administration caused a reduction in synovial IL-6 level and an increase in TNF-α synovial level. Anti-Fkn administration caused a reduction in Fkn and TNF-α level. Conclusion: It seems that Fkn plays an important role in modulating the TNF-α and IL-6 effects on edema changes in CFA-induced inflammation. 179 188 2016/03/92016/04/82016/05/32016/03/272016/05/30 1395/3/10 2016/08/132016/07/282016/06/122016/07/12016/07/18 1395/4/28 Sahar Golabi Sahar Golabi Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran sgolabister@gmail.com Jalal Zaringhalam Jalal Zaringhalam Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran jzaringhalam@yahoo.com Homa Manaheji Homa Manaheji Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran hshardimanaheji@yahoo.com Inflammation TNF-α IL-6 Fractalkine Complete Freund’s Adjuvant (CFA) Boehme BA, Lio FM, Maciejewski-Lenoir D, Bacon KB, Conlon PJ. The chemokine Fractalkine inhibits Fas-mediated cell death of brain microglia. J Immunol 2000; 165: 397-403.##Bradford MM. 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.##Cahill CM, Morinville A, Hoffert C, Odonnell D, Beaundet A. Up-regulation and trafficking of δ opioid receptor in a model of chronic inflammation: implications for pain control. Pain 2003; 101: 199-208.##Cicala C, Innaro A, Fiorucci S. No-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freunds adjuvant Arthiritis. Br J Pharmacol 2000; 130: 490-7.##Eskandari F, Webster JI, Sternberg EM. Neural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther 2003; 5: 251-265.##Foyet HS, Tsala DE, Bodo JCZE, Carine AN, Fabrice NH, Heroyne LT, et al. Anti-arthritic and anti-inflammatory propensity of catechins from Vitellaria paradoxa. Pharmacognosy Res 2014; 7: 367-377.##Garcia GE, Xia Y, Chen S, Wang Y, Ye RD, Harrison JK, et al. NF-kappa- B-dependent Fractalkine induction in rat aortic endothelial cells stimulated by IL-1beta, TNF-alpha, and LPS. J Leukoc Biol 2000; 67: 577-84.##Gilory DW. The endogenous control of acute inflammation from onset to resolution. Drug Discov Today Ther Strategics 2004; 1: 313-319.##Hyc A, Osiecka-Iwan A, Dziunycz P, Moskalewski S. Preparation of rat synovial membrane for studies of cytokine secretion. Follia histochem cyto 2007; 45: 57-60.##Jones B, Koch AE, Ahmed S. Pathological role of Fractalkine/CX3CL1 in rheumatic diseases: a unique chemokine with multiple functions. Front immunol 2012; 2: 1-22.##Kastenbauer S, Koedel U, Wick M, Kieseier BC, Hartung HP, Pfister HW. CSF and serum levels of soluble Fractalkine (CX3CL1) in inflammatory diseases of the nervous system. J Neuroimmunol 2003; 137: 210-217.##Katsikis PD, Chu CQ, Brennan FM, Maini RN, Feldmann M. Immunoregulatory role of Interleukin 10 in rheumatoid arthritis. J Exp Med 1994; 179: 1517-1527.##Liao YC, Liang WG, Chen FW, Hsu JH, Yang JJ, Chang MSH. IL-19 Induces Production of IL-6 and TNF- α and results in cell apoptosis through TNF- α. J Immunol 2002; 169: 4288-4297.##Lin MT, Juan CHY, Chang KJ, Chen WJ, Kuo ML. IL-6 inhibits apoptosis and retains oxidative DNA lesions in human gastric cancer AGS cells through up-regulation of anti-apoptotic gene mcl-1. Carcinogenesis 2001; 22: 1947-1953.##Matsumiya T, Imaizumi T, Fujimoto K, Cuib X, Shibatab T, Tamob W, et al. Soluble interleukin-6 receptor α inhibits the cytokine-induced Fractalkine/CX3CL1 expression in human vascular endothelial cells in culture. Exp Cell Res 2001; 269: 35-41.##McLoughlin RM, Hurst SM, Nowell MA, Harris DA, Horiuchi S, Morgan LW, et al. Differential regulation of neutrophil-activating chemokines by IL-6 and its soluble receptor isoforms. J Immunol 2016; 172: 5676-5683.##Multag SH. Dose dependent anti-inflammatory effect of Ammi majus alcoholic extract in rat: chronic study. Iraqi J pharm sci 2012; 21: 82-86.##Rodriguez Vita J, Lawrence T. The resolution of inflammation and cancer. Cytokine Growth Factor Rev 2010; 21: 61-65.##Rose-John S, Scheller J, Elson G, Jones SA. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukocyte Biol 2006; 80: 227-236.##Ruth JH, Volin MV, Haines GK, Woodruff DC, Katschke KJ, Woods JM, et al. Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum 2001; 44: 1568-1581.##Santora K, Rasa C, Visco D, Steinetz BG, Bagnell CA. Antiarthritic effects of relaxin, in combination with estrogen, in rat adjuvant-induced arthritis. J Pharmacol Exp Ther 2007; 322: 887-893.##Sukkar MB, Issa R, Xie SH, Oltmanns U, Newton R, Chung KF. Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids. Am J Physiol Lung Cell Mol Physiol 2004; 287: L1230–L1240.##Taniguchi N, Kanai S, Kawamoto M, Endo H, Higashino H. Study on application of static magnetic field for adjuvant arthritis rats. J Evid Based Complementary Altern Med 2004; 1: 187-191.##Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 2006; 86: 515–581.##Tekieh E, Zaringhalam J, Manaheji H, Maghsoudi N, Alani B, Zardooz H. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis. EXCLI J 2011; 10: 23-33.##Tekieh E , Zaringhalam J, Akhtari Z. Relationship between cytokines and spinal mu opioid receptor expression during adjuvant-induced arthritis in rats. Annu res rev boil 2014; 4: 1854-1866.##Yoshida K, Ochiai A, Matsuno H, Gabriel S, Panayi GS, Corrigall VM. Binding immunoglobulin protein resolves rheumatoid synovitis: a xenogeneic study using rheumatoid arthritis synovial membrane transplants in SCID mice. Arthritis Res Ther 2011; 13: 1-6.##Zaringhalam J, Tekieh E, Manaheji H, Akhtari Z. Cellular events during arthritis-induced hyperalgesia is mediated by Interleukin-6 and p38 MAPK and their effects on the expression of spinal mu-opioid receptors. Rheumatol Int 2013; 33: 2291-2299.##Zaringhalam J, Akhtari Z, Eidi A, Haeri Ruhani A, Tekieh E. Relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects of variation of hyperalgesia during different stages of arthritis in rats. Inflammopharmacol 2014; 22: 37–44.##Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983; 16: 109-110.## ##

Anti-nociceptive effect of Tanacetum Fisherae on formalin-induced inflammatory pain in rats 2 2 Introduction: The management of pain and inflammation related problem is a real challenge that people face daily. Although several drugs are available for these conditions, medicinal plants are believed to be an important source of new chemical substances with potential therapeutic effects. The objective of current study was to investigate the anti-nociceptive effect of Tanacetum Fisherae which has been traditionally used for treatment of pain. Methods: In this experimental study, formalin test was performed with drug (Tanacetum Fisherae) or DMSO pretreatment 30 min prior to formalin injection in 40 male Wistar rats. Fifty microliters of 2.5% formalin was injected into the plantar surface of the right hind paw. Immediately after injection, licking and flinching number and paw-shaking responses were observed at 5-min intervals for 1 h. Animals were divided into five experimental groups. There were 8 animals in each group. Each group received vehicle (7% DMSO) or Tanacetum Fisherae essential oil (25, 50 or 100 μg) or morphine (5 mg/kg). Two-way and one-way ANOVA were used for data analysis. Differences were considered significant at the level of P<0.05 (with 95% confidence interval). Results: Results showed that Tanacetum Fisherae essential oil dose dependently reduced licking and flinching number and also pain score in the late (15-35 min) and recovery phase (35-60 min) of formalin test (p<0.05, p<0.01, and p<0.001). It had no anti-nociceptive effect (p>0.05) in early (0-5 min) phase and interphase (5-15 min). Conclusion: Results demonstrate the effectiveness of Tanacetum Fisherae to mitigate the inflammatory pain. 189 196 2016/03/92016/04/82016/05/32016/03/272016/05/302016/04/16 1395/1/28 2016/08/132016/07/282016/06/122016/07/12016/07/182016/08/14 1395/5/24 Mohsen Fathi Mohsen Fathi Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran fathi@yahoo.com Narges Hosseinmardi Narges Hosseinmardi Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran nargeshosseinmardi@yahoo.com Kambiz Rohampour Kambiz Rohampour Department of Physiology, Guilan University of Medical Science, Rasht, Iran rohampour@yahoo.com Mahyar Janahmadi Mahyar Janahmadi Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran janahmadi@yahoo.com Ali Sonboli Ali Sonboli Department of Physiology, Guilan University of Medical Science, Rasht, Iran sonboli@yahoo.com Jalal Zaringhalam Jalal Zaringhalam Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran zaringhalam@yahoo.com Pain Formalin test Tanacetum Fisherae Abbott FV. Peripheral and central antinociceptive actions of ethylketocyclazocine in the formalin test. Eur J Pharmacol. 1988; 152:93-100.##Afsharypour S, Jahromy MM. Constituents of the essential oil of Tanacetum lingulatum (Boiss.) Bornm. J Essent Oil Res. 2003; 15: 74-76.##Bukhari IA, Khan RA, Gilani AU, Shah AJ, Hussain J, Ahmad VU. The analgesic, anti-inflammatory and calcium antagonist potential of Tanacetum artemisioides. Archive of Pharmacal Research. 2007; 30: 303-12.##Chau TT. Analgesic Testing In Animal Models. In: Pharmacological Methods in the Control of Inflammation. Chang JY, Lewis AJ (eds), pp 195-212. New York: Alan R. Liss, Inc., 1989.##Costa-Lotufo LV, De Lucena DF, Andrade-Neto M, Bezerra JN, Leal LK, De Sousa FC, De Barros Viana GS. Analgesic, Antiinflammatory and Central Depressor Effects of the Hydroalcoholic Extract and Fractions from Aeolanthus suaveolens. Biol Pharm Bull. 2004; 27: 821-824.##Courteix C, Bourget P, Caussade F, Bardin M, Coudore F, Fialip J, Eschalier A. Is the Reduced Efficacy of Morphine in Diabetic Rats Caused by Alterations of Opiate Receptors or of Morphine Pharmacokinetics. JPET. 1998; 285:63-70.##Da Cunha FM, Duma D, Assreuy J, Buzzi FC, Niero R, Campos MM. Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties. Free Radic Res 2004; 38:1241-53.##Damaj MI, Glassco W, Aceto MD, Martin BR. Antinociceptive and pharmacological effects of metanicotine, a selective nicotinic agonist. J Pharmacol Exp Ther. 1999; 291: 390–398.##Djavadi SB. Three new records Tanacetum for the flora of Iran. Rostaniha. 2008; 9: 23-32.##Dubisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine and brain stem stimulation in rats and cats. Pain. 1997; 4:161–174.##Esmaeili MA, Sonboli A, Ayyari Noushabadi M. Antioxidant and protective properties of six Tanacetum species against hydrogen peroxide-induced oxidative stress in K562 cell line: A comparative study. Food Chem. 2010; 121, 148-155.##Gupta M, Mazumder UK, Gomathi P, Thamil Selvan V. Antiinflammatory evaluation of leaves of Plumeria acuminate. BMC Complement Altern Med. 2006; 6: 36.##Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain. 1987; 30: 103–114.##Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Scientific World J. 2013; 29: 1-16.##Le Bars D, Manuela G, Cadden SW. Animal Models of Nociception. Pharmacol Rev. 2001; 53: 597-652.##Loeser J D, Butler S H, Chapman C R, Turk K C, editors. Bonica's Management of Pain. Philadelphia: Lippincott; 2001.##Malmberg AB, Yaksh TL. Antinociceptive Actions of Spinal Nonsteroidal Antiinflammatory Agents on the Formalin Test in the Rat. JPET. 1992; 263:136-146.##Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008; 24:428-35. ##Nakamura-Craig M, Follenfant RL. Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE2 and in the chronic hyperalgesia in rats with streptozotocin-induced diabetes. Pain. 1995; 63: 33–37.##Nathan C. Points of control in inflammation. Nature. 2002; 420: 846-852.##Norata GD, Marchesi P, Passamonti S, Pirillo A, Violi F, Catapano AL. Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis 2007; 191: 265-271.##Stevenson DE, Hurst RD. Polyphenolic phytochemicals - Just antioxidants or much more? Cel. Mol. Life Sci. 2007; 64: 2900–2916.##Oberprieler C, Vogt R, Watson LE. Tribe Anthemideae Cass. In The families and genera of vasicular plants, Flowering Plants, Eudicots, Asterales. Vol. 8, Kadereit JW, Jeffrey C. (Eds). 2006; Springer, Berlin, Germany. 342-374. ##Podlech D. Tanacetum. In Flora Iranica. Vol. 158, Rechinger, KH. (Ed). Akademische Druck-u. 1986; Verlagsanstalt, Graz,Austria. 88-148.##Rajaei P, Mohamadi N. Ethnobotanical Study of Medicinal Plants of Hezar Mountain Allocated in South East of Iran. IJPR. 2012; 11: 1153-1167.##Rajaei P, Nejadsattari T, Maassoumi AA, Mozaffarian V, Sonboli A. Micromorphology of glandular hairs, biological activity and composition of the essential oil of Tanacetum fisherae (Asteraceae-Anthemideae) from Iran. Nat Prod Commun. 2011; 6: 259-62.##Santos AR, Calixto JB. Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice. Neuropeptides. 1997; 31: 381–389. ##Santos FA, Rao VS. Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytother Res. 2000; 14: 240–244.##Sawynok J. Topical and peripherally acting analgesics. Pharmacol Rev. 2003; 55: 1–20.##Sonboli A, Kazempour Osaloo S, Riahi H, Mozaffarian V. Tanacetum joharchii sp. nov. (Asteraceae-Anthemideae) from Iran, and its phylogenetic status basd on molecular data. Nord J Bot. 2010; 28: 74-78. ##Szolcsanyi J, Bolcskei K, Szabo A, Pinter E, Petho G, Elekes K, Borzsei R, Almasi R, Szuts T, Keriand G, Helyes Z. Analgesic effect of TT-232, a heptapeptide somatostatin analogue, in acute pain models of the rat and the mouse and in streptozotocin-induced diabetic mechanical allodynia. Eur J Pharmacol. 2004; 498: 103-109.##Vissers K, Hoffmann V, Geenen F, Biermans R, Meert T. Is the Second Phase of the Formalin Test Useful to Predict Activity in Chronic Constriction Injury Models ? A Pharmacological Comparison in Different Species. Pain Pract. 2003; 3: 298-309.##Wheeler-Aceto H, Porreca F, Cowan A. The rat formalin test: comparison of noxious agents. Pain. 1990; 40:229-238.##Yashpal K, Coderre TJ. Influence of formalin concentration on the antinociceptive effects of antiinflammatory drugs in the formalin test in rats:seperate mechanisms underlying the nociceptive effects of low and high-concentration formalin. Eur J Pain. 1998; 2: 63-68.## ##

Magnesium oxide nanoparticles reduce anxiety induced by morphine withdrawal in adult male mice 2 2 Introduction: Our previous study has showed that chronic administration of magnesium oxide nanoparticles (MgO NP) can reduce anxiety in adult male rat. In this study the effects of MgO NP on anxiety induced by morphine withdrawal were investigated in adult male mice. Methods: Adult male NMRI mice (weighing 27 ± 3 g) divided into groups: control, receiving intraperitoneal (i.p.) injection of MgO NP (1, 2.5, 5 mg/kg), morphine withdrawal groups that receiving saline or MgO NP (2.5, 5 &10 mg/kg) as acute (a single injection at the test day) and chronic (co-injected with morphine for 4 days). To develop morphine dependency, increasing doses of morphine (20, 40, 80 mg/kg( injected subcutaneously for 4 days. Mice received a final morphine injection (40 mg/kg) 3 hours prior to naloxone (5 mg/kg (i.p.) on the day of testing (day 4). In addicted groups, after naloxone injection, morphine withdrawal signs were evaluated. In all groups, anxiety like behavior was assessed by the elevated plus maze apparatus. Results: MgO NP (2.5 & 5 mg/kg) reduced anxiety like behavior (P<0.05). Acute and chronic MgO NP injections (5&10 mg/kg) could significantly improve/alleviate anxiety like behavior (p<0.05 & p<0.01 respectively) and reduce locomotor activity (p<0.05, acute; p<0.05, & p<0.01, chronic), rearing, climbing and weight loss in morphine withdrawn mice. Conclusion: Due to the positive effect of MgO NP on anxiety like behavior and morphine withdrawal signs and symptoms, this nanoparticle can be a potential candidate for reducing the side effects of chronic usage of morphine and morphine withdrawal. 197 205 2016/03/92016/04/82016/05/32016/03/272016/05/302016/04/162016/03/2 1394/12/12 2016/08/132016/07/282016/06/122016/07/12016/07/182016/08/142016/07/18 1395/4/28 Mahnaz Kesmati Mahnaz Kesmati Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran m.kesmati@scu.ac.ir Maryam Konani Maryam Konani Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran m.koohnany@gmail.com Mozhhgan Torabi Mozhhgan Torabi Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran mozhgan.torabii@yahoo.com Lotfollah Khajehpour Lotfollah Khajehpour Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran khajehpour@scu.ac.ir Anxiety Nanoparticles Magnesium oxide Morphine withdrawal Barr GA, McPhie-Lalmansingh A, Perez J, Riley M. Changing mechanisms of opiate tolerance and withdrawal during early development: animal models of the human experience. ILAR J. 2011; 52(3): 329-41. ##Bhalla S , Andurkar SV , Gulati A.Neurobiology of opioid withdrawal: Role of the endothelin system. Life Sci. 2016; S0024-3205(16): 30016-9.##Cappendijk SLT, Vries R, Dzoljic MR. Inhibitory effect of nitric oxide (NO) synthase inhibitors on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. Neurosci Lett 1993; 162(1-2): 97-100. ## Castilho VM, Borelli KG, Brandão ML, Nobre MJ. Anxiety-like symptoms induced by morphine withdrawal may be due to the sensitization of the dorsal periaqueductal grey. Physiol Behav 2008; 94: 552–62.## Esmaeili MH, Haghdoost Yazdy H,Sofiabadi M, Ajdari Zarmehri H. The effect of magnesium on morphine withdrawal sings in rats. J Sabzevar Uni Med Sci 2010; 17(1): 6-12. ## Faria MP, Miguel TT, Gomes KS, Nunes-de Souza RL. Anxiety-like responses induced by nitric oxide within the BNST in mice: Role of CRF1 and NMDA receptors. Horm Behav 2016; 79: 74–83. ##Gamage TF, Ignatowska-Jankowska BM, Muldoon PP, Cravatt BF, Damaj MI, Lichtman AH. Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice. Drug Alcohol Depend 2015; 1(146): 7–16. ## Gao H. Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharmaceutica Sinica B 2016; In press.##Ghasemi A, Saberi M, Ghasemi M, Shafaroodi H, Moezi L, Bahremand A, Montaser-Kouhsari L, Ziai P, Dehpour AR. Administration of lithium and magnesium chloride inhibited tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice. Epilep Behav 2010; 19: 568–74.## Habibi-Asl B, Ghanbarzadeh S, Vaez H, Khodabandeh M. Effects of magnesium sulfate and bupropion on morphine induced tolerance in mice. Adv Biosci Clin Med 2015a; 3(2): 21-9. ##Habibi-Asl B, Hassanzadeh K, Moosazadeh S. Effect of ketamine and magnesium on morphine induced tolerance and dependence in mice. Drug 2005; 13(3): 110-15.##Habibi-Asl B, Hassanzadeh K, Vafai H, Mohammadi S. Development of morphine induced tolerance and withdrawal symptoms is attenuated by lamotrigine and magnesium sulfate in mice. Pak J Biol Sci 2009;12: 798–803. ##Habibi-Asl B, Vaez H, Aghaie N, Hasanpour-Aghdam S, Parvizpur A, Charkhpur M, Mahmoudi J, Eteraf-Oskouei T, Pishdad S, Ghanbarzadeh S. Attenuation of morphine-induced tolerance and dependency by pretreatment with magnesium sulfate and amitriptyline in male mice. Pharm Sci 2015 b;21: 192-8.##Hajhashemi V, Rabbania M, Asgharib GR, Karami-Saravi Z.Effects of Otostegia persica (Burm.) Boiss on morphine withdrawal syndrome in mice. Iran J Pharm Res 2004; 3: 171- 5.## Jacka FN, Overland S, Stewart R, Tell GS, Bjelland I, Mykletun A. Association between magnesium intake and depression and anxiety incommunity-dwelling adults: the Hordaland Health Study. Aust N .Z. J. Psychiatry 2009; 43: 45–52.##Jahangiri L, Kesmati M, Najafzadeh H. Evaluation analgesic and anti-inflammatory effect of nanoparticles of magnasium oxide in mice with and without ketamin. Eur Rev Med Pharmacol Sci. 2013:17; 2706-10.##Jain R, Mukherjee K, Mohan D. effects of nitric oxide synthase inhibitors in attenuating nicotine withdrawal in rats. Pharmacol Biochem Behav 2008; 88: 473–80.##Karami M, Rahimpour M, Karimi S, Sahraei H. Nitric oxide in central amygdala potentiates expression of conditioned withdrawal induced by morphine. Indian J Pharmacol 2014;46(1):57-62.## ##Karami R, Hosseini M, Khodabandehloo F. Khatami L, Taiarani Z. Different effects of L arginine on morphine tolerance in sham and ovariectomized female mice. J Zhejiang Univ-Sci B (Biomed Biotechnol) 2011; 12(12):1016-23. ##Kesmati M, Galedari H, Massah A. Comparison between C-FOS Expression in Male and Female Mice During Morphine Withdrawal in the Presence and Absence of Acute Administration of Matricaria Recutita. Tbib shargh 2009; 11(2):1-9.[ Article in Persian].##Kesmati M, Torabi M. Benefits and Harms of Nanoparticles in the Body (with approach of the central nervous system). First Edition, Tehran, Shellak . 2014a.[Book in Persian]. ##Kesmati M, Torabi M, Teymuri Zamaneh H, Malekshahi Nia H. Interaction between anxiolytic effects of magnesium oxide nanoparticles and exercise in adult male rat. Nanomed J 2014b; 1(5): 324-30. ##Kesmati M. Sargholi notarki Z, Issapareh N, Torabi M. Comparison the effect of zinc oxide and magnesium oxide nano particles on long term memory in adult male mice. Zahedan J Res Med Sci 2016; in press.## Kheiry M, Kesmati M, Najafzadeh H, Fatemi SR. Effects of nano-ZnO and bulk ZnO on the expression of morphine-induced conditioned place preference in mice. Iran Vet J 2015; 11(1): 56-63. [Article in Persian]. ## Kumar K, Sharma S, Kumar P, Deshmukh R. Therapeutic potential of GABAB receptor ligands in drug addiction, anxiety, depression and other CNS disorders. Pharmacol Biochem Behav 2013; 110: 174–84.##Laarakker MC, van Lith HA, Ohl F. Behavioral characterization of A/J and C57BL/6J mice using a multidimensional test: Association between blood plasma and brain magnesium-ion concentration with anxiety. Physiol Behav 2011; 102: 205-19. ##Liu KS, Chen SJ, Chen YW, Sung KC, Wang JJ. A dose response study on the efficacy of tricyclic antidepressants on reducing morphine-withdrawal symptoms. Acta Anaesthesiol Taiwanica 2013; 51:18-21. ##Mahmoud A, Ezgi Ö, Merve A, Özhan G. In vitro toxicological assessment of magnesium oxide nanoparticle exposure in several mammalian cell types. Int J Toxicol 2016; 35(4):429-37.##Miladi-Gorji H, Rashidy-Pour A, Fathollahi Y. Anxiety profile in morphine-dependent and withdrawn rats: Effect of voluntary exercise. Physiol Behav 2012; 105 : 195–202.## Młyniec K, Davies CL, Sa´nchez IGDAE, Pytka K, Budziszewska B, Nowak G. Essential elements in depression and anxiety. Part I. Pharmacol Rep 2014; 66: 534–44. ##Poleszak E. Benzodiazepine/GABA (A) receptors are involved in magnesium induced anxiolytic-like behavior in mice. Pharmacol Rep 2008; 60(4): 483-9. ##Shaikh SM, Shyama SK, Desai PV. Absorption, LD50 and Effects of CoO, MgO and PbO Nanoparticles on Mice “Mus musculus”. IOSR J Environ Sci Toxicol Food Technol (IOSR-JESTFT) 2015; 9(2): 32-8.##Slutsky I, Nashat Abumaria N, Wu J, Huang C, Zhang L, et al. Enhancement of learning and memory by elevating brain magnesium .Neuron 2010; 65(2): 143-4.##Sun WD, Zang G, Hao L, Liu X, YU F, Ma C, Cong B. Cholecystokinin octapeptide induces endogenous opioid- dependent anxiolytic effects in morphine –withdrawal rats. Neuroscience 2014; 277: 14–25. ##Toda N, Kishioka S, Hatano Y, Toda H. 2009. Modulation of opioid actions by nitric oxide signaling. Anesthesiology 2009; 110(1):166-81.## ##Torabi M, Kesmati, M, Eshagh Harooni, H, Najafzadeh Varzi H. Different efficacy of nanoparticle and ZnO in an animal model of anxiety. Neurophysiology 2013;45 (4): 299-305.##Torabi M, Kesmati M, Eshagh Harooni H, Najafzadeh Varzi H. The effect of local and intraperitoneal administration of opioid receptors modulating agents on anxiolytic properties of nano and conventional ZnO in male rats. Cell J 2014; 16(1): 37-61.##Vahidi S, Khalili M, Kiasalari Z, Yaghoutpoor E. Effect of methadone and valproate combination on morphine withdrawal-induced anxiety and depression in male mice. J Gorgan Uni Med Sci 2015; 16(4): 21-27. [Article in Persian].##Vural H, Demirin H, Kara Y, Eren I, Delibas N. Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte Antioxidant enzymeactivities in patients with Alzheimer’s disease. J Trace Elem Med Biol 2010; 24(3):169–73. ## Zhu H, Barr GA. Inhibition of morphine withdrawal by the NMDA receptor antagonist MK-801 in rat is age-dependent. Synapse 2001; 40: 282–93. #### ##

Sandifish (Holothuria scabra) ameliorates aging in menopausal women by increasing estradiol hormones 2 2 Introduction: Sandfish (Holothuria scabra) is a marine species generally sold as a raw material that has been dried even though the meat contains steroid hormone with high economic value, which has the potential to become a source of safe natural steroid hormone. This study was aimed to look at the potency of sandfish as an anti-aging for menopausal women. Sandfish could become a source of natural steroid for hormone replacement therapy to replace synthetic hormone that is proven to have negative impacts on health. Methods: This study used female rats (Rattus norvegicus) Sprague-Dawley Strain Variety II that were twelve weeks old and ovariectomized. In these animals, the bioassay test was conducted with the treatment of sandfish meat powder (SP) containing 30, 40, and 50 μg steroid/100 g. At the end of the treatment, the examination was carried out toward the concentration of steroid in blood serum using radioimmunoassay (RIA) and the uterine weight. Results: The treatment with SP in 30 μg steroid/100 g could increase the estradiol hormone in blood serum of test animals that were ovariectomized and produce the highest concentration of uterine weight. Conclusion: This study showed that a dose of SPcontaining 30 μg steroid/100 g body weight had the highest potential as an anti-aging in menopausal women. 206 214 2016/03/92016/04/82016/05/32016/03/272016/05/302016/04/162016/03/22016/04/20 1395/2/1 2016/08/132016/07/282016/06/122016/07/12016/07/182016/08/142016/07/182016/07/18 1395/4/28 Etty Riani Etty Riani Department of Aquatic Resources Management, Faculty of Fishery and Marine Science, Bogor Agricultural University. Jl. Lingkar Akademik, Kampus IPB Darmaga, Bogor, West Java, Indonesia etty_riani_harsono@yahoo.com Chairunissa Chairunissa Faculty of Veterinary Medicine, Bogor Agricultural University, Jl. Agatis, Kampus IPB Darmaga, Bogor, West Java, Indonesia chnisa@yahoo.com Hera Maheswari Hera Maheswari Faculty of Veterinary Medicine, Bogor Agricultural University, Jl. Agatis, Kampus IPB Darmaga, Bogor, West Java, Indonesia hera_maheshwari@yahoo.com Muhammad Dzikrifishofa Muhammad Dzikrifishofa Regional General Hospital of Leuwiliang, Regency of Bogor, Cibeber I, Leuwiliang, Bogor, West Java, Indonesia dzikrifishofa@gmail.com Nastiti Kusumorini Nastiti Kusumorini Faculty of Veterinary Medicine, Bogor Agricultural University, Jl. Agatis, Kampus IPB Darmaga, Bogor, West Java, Indonesia ntitik@yahoo.com Anti-aging Menopause Sandfish Steroid Berga SLm, Parry BL. Psychiatry and Reproductive Medicine. Kaplan and Kaplan Sadock’s Comprehensive Textbook of Psychiatry. Sadock BJ, Sadock VA editor. 7th edition. Philadelphia: Lipincott William and Willkins. 2000. ##Craig CR, Stitzel RE. Modern Pharmacology with Clinical Applications. Boston: Little Brown and Company. 1997. ##Diorio C, Lemieux J, Provencher L, Hogue JC, Vachon E. Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels. Breast Cancer Res Treat. 2012;136:573–579. ##Dodson LG, Steiner E. The perimenopause transition. Clinics in Family Practice 2002;4(1): 13-26. ##Eisenlohr-Moula TA, DeWalla CN, Girdlerb SS, Segerstrom SC. 2015. Ovarian hormones and borderline personality disorder features. Biological Psychology Preliminary evidence for interactive effects of estradiol and Progesterone. Biological Psychology 2015;109:37–52. ##Gao W, Stalder T, Kirschbaum C. Quantitative analysis of estradiol and six other steroid hormones in human saliva using a high through put liquid chromatography–tandem mass spectrometry assay. Talanta 2015;143:353–358. ##Guyton AC. Textbook of Medical Physiology, vol. 3. Jakarta: EGC. 1994. ##Hansen M. Effect of estrogen on protein synthesis in tendon and skeletal muscle: At rest and in response to exercise. PhD thesis, University of Copenhagen. 2008. ##Holzer H, Casper RF, Tulandi T. A new era in ovulation induction. Fertility and sterility 2006;85(2):277-284. ##Knowlton AA, Lee AR. Estrogen and the Cardiovascular System. Pharmacology & Therapeutics 2012;135:54–70.##Kocoska-Maras L, Rådestad AF, Carlström K, Bäckström T, von Schoultz B, Hirschberg AL. Cognitive function in association with sex hormones in postmenopausal women. Gynecological Endocrinology, 2013;29(1):59–62. ##Lee AR, Pechenino AS, Dong H, Hammock BD, Knowlton AA. Aging, Estrogen Loss and Epoxyeicosatrienoic Acids (EETs). PLOS ONE. 2013;8(8):1-8. ##Lu FC. Basic Toxicology. Fundamentals, target organs and risk assessment. 2nd ed. Jakarta: University of Indonesia; 1995.##Manson JE, Bassuk SS. Hot Flashes, Hormones and Your Health. New York: Mc Graw Hill. 2007.##Nakajima N, Nozak N, Ishihara A, Tsuji H. Analysis of isoflavone content in tempeh, a fermented soybean, and preparation of new isoflavone-enriched tempeh. Journal of Bioscience and Bioengineering. 2005;100(6):685-687.##Riani 2010. Steroid extract of sandfish (Holothuria scabra) as a hormone replacement therapy for menopausal and postmenopausal woman as well as for antiaging. Seminar of research results of Bogor Agricultural University, in IICC-IPB, 13-14 December, 2010. [In Indonesian]##Riani E, Kusumorini N, Nurjanah S. Steroid extract of sandfish (Holothuria scabra) as a hormone replacement therapy for menopausal and postmenopausal woman. National strategic grant reports. Bogor Agricultural University. 2010. [In Indonesian]##Riani E, Syamsu K, Kaseno, Nurjanah S, Dewi KH, Kustiariyah. Use of Steroid as Natural Aphrodisiac in Human. Report of Graduate Research Grant. Bogor: Bogor Agricultural University. 2005. [In Indonesian]##Riani E, Syamsu K, Kaseno, Nurjanah S, Dewi KH, Kustiariyah. Use of Sandfish Steroid as Sex Reversal in Commercial Aquatic Biota and Natural Aphrodisiac to Human. Report of Graduate Research Grant. Bogor: Bogor Agricultural University. 2006. [In Indonesian]##Riani E, Syamsu K, Kaseno, Nurjanah S, Dewi KH, Kustiariyah. Use of Sandfish Steroid as Sex Reversal in Commercial Aquatic Biota and Natural Aphrodisiac to Human and its Field Application. Report of Graduate Research Grant. Bogor: Bogor Agricultural University. 2007. [In Indonesian]##Riani E. Fish for health, intelligence, welfare and implementation of 21st Agenda. Technical Presentation of IPB Innovation: National competitiveness enhancement through the supply of cheap and qualified animal protein. Theater 7 Hall B. JCC Jakarta 10 July 2010. [In Indonesian]##Riani E. Sandfish (Holothuria scabra) steroid for male animal reproductive system. Proceding on Animal reproductive system technology for Indonesian food self-sufficiency. Bogor 6-7 October 2010. [In Indonesian]##Ruggiero RJ, Pharm D, Frances EL. Estrogen: Physiology, Pharmacology, and formulations of replacement therapy. J Midwifery and Women Health 2002;47(3): 130-138.##Shah A, Frazer A. Influence of acute or chronic administration of ovarian hormones on the effects of desipramine in the forced swim test in female rats. Psychopharmacology 2014;231:3685–3694. ##Sherwood L. Human Physiology: From Cells to Systems. 2nd ed. Jakarta: ECG. 2001. ##Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinselwood MM, Graham LS, Amaneh B, Ito Y, Fischer CR, Michael MD, Mendelson CR, Bulun SE. Aromatase cytochrom P450, the enzyme responsible for estrogen biosynthesis. Endoc. Rev. 1994;3:342-355.##Steinweg KK. Menopause, bone physiology, and osteoporosis prevention. Clinic in Family Practice 2002;(1):89-111. ##Sylvia AP, Lorraine MW. Pathophysiology: Clinical Concepts of Disease Processes. Volume 2. Jakarta: EGC; 2005. ##Thompson MM, Oyama TT, Kelly FJ, Kennefick TM, Anderson S. Activity and responsiveness of the renin-angiotensin system in the aging rat: Am J Physiol Regulatory Integrative Comp Physiol. 2000; 279: 1787-1794.##Thompson Z, Maibach H I. Biological effects of estrogen on skin. In: Farage MA, Miller KW, Maibach HI, editor. Textbook of Aging Skin. Berlin: Springer. 2010, p. 361-367. ##Tietz N. Clinical Guide to Laboratory Test. 3rd edition. Philadelphia: WB Saunders Company. 1995.##Turner, Bagara. Hormonal enchantment of growth in fish physiology. Vol. 8. New York: Academic Press; 1976, p. 456-597.##Wylie JR. Menopause, micronutrients, and hormone therapy. Am J. clin Nutr 2005;81:1223-1231. ##Zang H, Sahlin L, Masironi B, Hirschberg AL. Effects of testosterone and estrogen treatment on the distribution of sex hormone receptors in the endometrium of postmenopausal women. Menopause 2008;5(2): 233-239. ## ##