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51-57 1384 4 3 2 1*. :... BALB/c 81 (Clinical trial) :. 6 (30 g (30 mg/kg) (45 mg/kg) /.. Duncan LSD ANOVA...p<0.05 :... :. ( ).. : 60. : -1 Email: talaeit@sums.ac.ir 0711 2304372: 0711 2304372 : -2-3 -4-3 4 84/7/7: 83/6/6 :

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( ) ANOVA.* Duncan LSD.. ( )..(P<0.05). +.(1 1 ). (Merck ) S 3 (Microme ). 37 KOH.(1) S :1.. :1. ± ± ± ± ± ± 0/05±0/46 0/27±1/ 56 0/27±3/ 35 0/05±0/ 41 0/19±1/ 31 0/39±3/ 18 * 0/07±0/39 0/1±1/ 23 0/45±3/ 15 0/05±0/ 38 0/23±1/ 05 0/45±2/ 72 * 0/04±0/39 0/17±1/ 32 0/17±3/ 36 * 0/04±0/ 37 0/15±1/ 16 0/17±3/ 14 0/04±0/46 0/2±1/ 48 0/26±3/ 2 0/04±0/ 4 0/18±1/ 15 0/25±2/ 9 0/05±0/42 0/23±1/ 4 0/21±3/ 33 0/05±0/ 39 0/17±1/ 21 0/2±3/ 08 + 0/05±0/44 0/28±1/ 54 0/38±3/ 45 0/04±0/ 4 0/22±1/ 31 0/37±3/ 25 +.. :.(P<0.05) + * 1384

... 4 3.5 (1 3 2.5 2 1.5 1 0.5 0 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 * control phenytoin phenobarbital folic acid phenytoin+folic acid phenobarbital+folic acid :1.(P<0.05) + * :2 * * control phenytoin phenobarbital folic acid phenytoin+folic acid phenobarbital+folic acid :2 + *. %3 4 %7.(p<0.05).. (17 18)....p<0.05 + + p<0.05.(1 2)... 1384

. D (20 23 24 25 26) D... (27)... :... (19 20). (19).. (21). Ahn Chang. (1994) (22). (22).... References: 1. Klipstein FA. Subnormal serum folate and macrocytosis associated with anticonvulsant drug therapy.blood. 1964; 23: 68-83. 2. Sadler TW. Langman s medical embryology. 9th edition, Lippincott Williams & Wilkins, 2004; NY, 149, 154. 3. Delgado-Escueta AV, Jans D. Pregnancy and teratogenesis in the epilepsy. Neurology. 1992; 42(supplement5): 7. 4. Gally E, Granstrom ML, Hiilesmaa V, Bardy 1384

... A. Minor anomalies in offspring of epileptic mothers. J pediatric. 1988; 112: 520-529. 5. Holmes LB, Harvey EA, Brown KS, Hayes AM, Khoshbin S. Anticonvulsant teratogenesis: I. A study design for newborn infants. Teratology. 1994; 49: 202-207. 6. Loughnan PM, Gold H, Vance JC. Phenytoin teratogenecity in man. Lancet. 1973; 1: 70-72. 7. Hanson JW, Smith DW. The fetal hydantoin syndrome. J Pediateric. 1975; 87(2): 285-290. 8. Rengasamy P, Padmanabhan RR. Experimental studies on cervical and lumbar ribs in mouse embryos. Congenit Anom (Kyoto). 2004; 44(3):156-71. 9. Sullivan FM, Melhatton PR. A comparision of the teratogenic activity of the antiepileptic drugs carbamazepine, clonazepam, Ethosuximide, Phenobarbital, phenytoin and primidone in mice. Taxicol Appl Pharmacol. 1977; 40: 365-378 10. Bokhari A, Connolly S, Coull BA, Harvey EA, Holmes LB. Effects on toes from prenatal expose to anticonvoulsant drugs. Teratology. 2002; 66(3): 122-6. 11. Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM, et al. The teratology of anticonvulsant drugs. N Engl J Med. 2001; 344(15): 1132-8. 12. Mallow DW, Herrick, MK, Gathman G. Fetal exposure to anticonvulsant drugs. Arch Pathol Lab Med. 1980; 104: 215-18. 13. Schardein JL, Dresner AJ, Hentez DL, Petrere A, Fitzgerald JE. The modifying effect in folic acid and the diphenylhydantoin induced teratogenecity in mice. Toxicol Appl Pharmacol. 1973; 24: 150-158. 14. Kondo A, Kimura K, Isobe Y, Kamihira O, Matsuura O, Gotoh M, et al. Folic acid reduces risks of having fetus affected with neural tube defects: dietary folate and plasma folate concentration. Nioopn Hinyokikai Gakkai Zasshi. 2003; 94(5): 551-9. 15. Reynold JEF. Editor Martindale. The extrapharmacopia. 31 st edition, Royal pharmaceutical Society. 1996; 335-366. 16. Mcleod MJ. Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. Teratology. 1950; 22: 299-301. 17. Ishizaki T, Yokochi K, Chiba K, Tabuchi T, Wagatsuma T. Placental transfer of anticonvulsants (phenobarbital, phenytoin, valproic acid) and the elimination from neonates. Pediatr Pharmacol (New York). 1981; 1(4): 291-303. 18. Mirkin BL, Diphenylhydantoin: Placental transport, fetal localization, neonatal metabolism and possible teratogenic effects. J Pediatr. 1971; 78: 329-337. 19. Pack AM, Morrell Mj. Epilepsy and bone health in adults. Epilepsy Behav. 2004;5 Suppl 2:S24-9. 20. Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002; 14;58(9):1348-53. 21. Filardi S, Guerreiro CA, Magna LA, Marques Neto JF. Bone mineral density, vitamin D and anticonvulsant therapy. Arq Neuropsiquiatr. 2000;58(3A):616-20. 22. Chung S, Ahn C. Effects of anti-epileptic drug therapy on bone mineral density in ambulatory epileptic children. Brain Dev. 1994 Sep- Oct;16(5):382-5. 23. Schmitt BP, Nordlund DJ, Rodgers LA. Prevalence of hypocalcemia and elevated serum alkaline phosphatase in patients receiving chronic anticonvulsant therapy. J Fam Pract. 1984;18(6):873-7. 24. Marchesoni C, De Marco P, Ronconi GF, Miottello PG. Anomalies of phospho-calcium 1384

metabolism during antiepileptic treatment. Pediatr Med Chir. 1983 ;5(6):571-3. 25. Lindout D. Pharmacogenetic and drug interaction: role in antiepileptic drug induced teratogenesis. Neurology. 42 (suppl 5): 43-47. 26. Voudris K, Moustaki M, Zeis PM, Dimou S Vagiakou E, Tsagris B, et al. Alkaline phosphatase and its isoenzyme activity for the evaluation of bone metabolism in children receiving anticonvulsant monotherapy. Seizure. 2002;11(6):377-80. 27. Moor KL. The developing human: Clinically oriented embryology. 6th edition; Philadelphia: WB Sadler Company: 1998: 164-169. 1384