Objective Infantile spasms ( IS ) is the most common intractable epileptic encephalopathy during infancy,but there is the lack of animal experiment. By building IS animal model, the study discusses whether high-dose methylprednisolone has the protective effect on the immature rats of infantile spasms. Meth-ods Sprague-Dawley immature rats were randomly assigned to 3 groups on postnatal day 10 ( P10 ):control group、model groupⅠand model groupⅡ,thirty rats in each group. Immature rats in model groupⅠand mod-el group Ⅱ were injected NMDA intraperitoneally to induce seizures. The rats in the model groupⅡwere injec-ted intraperitoneally methylprednisolone on postnatal day 11,12 and 13. The clinical behavior of rats were ob-served and recorded. Neuronal apoptosis was detected by TUNEL. Immunohistochemistry and real-time PCR were used to analyze the expression of Bax,Bcl-2,caspase-3 in hippocampus. Results (1)83. 3% of rats in model groupⅠhad seizures,and none of rats in model groupⅡhad seizures on postnatal day 13. (2)The apop-totic cell number of brain tissues:model group Ⅱ( 14. 37 ± 2. 02 ) were lower than model group Ⅰ( 25. 67 ± 1. 52)and higher than control group(9. 00 ± 2. 50),the difference was statistically significant(all P<0. 05). (3)Bax protein and mRNA expression levels in model group Ⅱ(44. 55 ± 3. 58,2. 35 ± 1. 01)were lower than model group Ⅰ(58. 05 ± 4. 62,3. 27 ± 0. 95)and higher than control group (28. 90 ± 5. 14,1. 68 ± 0. 50),there was significant difference(all P<0. 05);(4)Caspase-3 expression levels of mRNA in model groupⅡ(5. 99 ± 1. 75) were lower than those in group model group Ⅰ(7. 88 ± 1. 60) and higher than those in control group (3. 60 ± 1. 70),there was significant difference(all P<0. 05). Conclusion High-dose methylprednisolone can reduce NMDA-induced seizures in the IS immature rats. High-dose methylprednisolone has protective effect on the NMDA-induced IS immature rats,which may be relation to weakening seizures and decreasing apoptosis.

OBJECTIVETo analyze genetic mutations and explore its molecular pathogenesis for an hereditary protein C (PC) deficiency pedigree.

METHODSThe pedigree has included 15 individuals from 4 generations. Plasma levels of PC activity (PC:A), PC antigen (PC:Ag) and other coagulant parameters were determined for members of the family. The 9 exons and intron-exon boundaries of protein C gene (PROC) of the proband were amplified with PCR and analyzed with direct sequencing. Detected mutations were confirmed with reverse sequencing. Corresponding PCR fragments from the family members were also directly sequenced.

RESULTSPlasma PC:A and PC:Ag for the proband was 26% and 18.60%, respectively, both being lower than normal references. Seven members from the pedigree also had lower PC:A, six had lower PC:Ag. A compound heterozygous missense mutation, including a T to G transition at position 6128 of exon 7, which results in Phe139Val, and a G to C transition at position 8478 in exon 9, which results in Asp255His, were identified in the proband. The paternal grandma, father and two aunts were heterozygous for g.6128 T to G, whilst the mother, the second uncle, sister and son were heterozygous for g.8478 G to C. There were lower PC:A in family members with g.8478 G to C.

CONCLUSIONThe proband had inherited two independent mutations of the PROC gene including g.6128 T to G in exon 7 and g.8478 G to C in exon 9 from her father and mother, respectively. The resulting compound heterozygous mutation has caused a serious hereditary protein C deficiency.

Humans ; Mutation ; Pedigree ; Protein C ; genetics ; Protein C Deficiency ; genetics