Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology.

Outbreaks of sexually transmitted hepatitis C virus (HCV) infections have been recently reported in HIV-

Approximately one-fourth of HIV-infected Taiwanese patients developed metabolic syndrome in the HAART era. Receipt of HAART and prolonged exposure to PI and nucleoside reverse transcriptase inhibitor(s) were associated with metabolic syndrome.

The purpose of this prospective cohort study was to compare the serologic response between human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) receiving two and three doses of hepatitis A virus (HAV) vaccine and HIV-uninfected MSM receiving two doses of HAV vaccine. Between June 2009 and December 2010, 582 MSM aged 18 to 40 years who were seronegative for HAV were enrolled in the study. HIV-infected MSM received either two doses of HAV vaccine (1,440 enzyme-linked immunosorbent assay units) (n 5 140) with the second dose given at week 24 or three doses (n 5 225) with the second and third dose given at weeks 4 and 24, respectively, while HIVuninfected MSM (n 5 217) received two doses. The primary endpoint was seroconversion at week 48. The geometric mean concentration (GMC) of anti-HAV antibody was determined at weeks 48 and 72. At week 48, the seroconversion rate was 75.7%, 77.8%, and 88.5% in intention-to-treat analysis for two-dose HIV-infected, three-dose HIV-infected, and two-dose HIV-uninfected MSM, respectively. The GMC of anti-HAV antibody at week 48 for three-dose HIV-infected MSM (2.29 6 0.73 log 10 mIU/mL) was significantly higher than that for two-dose HIV-infected MSM (1.94 6 0.66; P < 0.01), but was lower than HIV-uninfected MSM (2.49 6 0.42; P < 0.01). Multivariate analysis revealed higher CD4 counts (adjusted odds ratio [AOR] for per 50 cells/lL increase, 1.13; 95% confidence interval [CI], 1.05-1.21) and undetectable plasma HIV RNA load (AOR, 1.90; 95% CI, 1.10-3.28) before HAV vaccination were predictive of seroconversion in HIV-infected patients. Conclusion: Serologic response rate to three and two doses of HAV vaccine was similar in HIV-infected MSM, which was lower than that in HIV-uninfected MSM receiving two doses. HAV vaccination in HIV-infected patients with a higher CD4 count and suppression of HIV replication increased the seroconversion rate. (HEPATOLOGY

Lactoferrin is a metal-binding glycoprotein exhibiting multifunctional immunoregulation of antibacterial, antioxidant, anti-endotoxin and antiviral activities. Uptake of porcine lactoferrin (PLF) has been shown to enhance resistance to diarrhea and anemia in neonatal piglets. In this study, the methylotrophic yeast, Pichia pastoris, was used to express a recombinant PLF (rPLF) gene from swine mammary gland. A synthetic secretion cassette was constructed using the inducible promoter of the alcohol oxidase-1 gene (AOX1) and the yeast α-mating factor signal peptide. After electroporation and Zeocin selection, several clones expressed high levels of rPLF protein which constitutes more than 30% of the total protein. A time-course study showed that rPLF mRNA transcripts are stably expressed during 120 h of culture induction. rPLF was exported into the culture supernatant at approximately 87 mg/l and a large portion of rPLF was accumulated in the cell cytoplasm at approximately 760 mg/l after 72 h of methanol induction. Recombinant PLF protein was purified via a heparin column using a fast protein liquid chromatography system. The glycosylation of P. pastoris-derived rPLF was analyzed and similar patterns to milk PLF were observed. Pepsin hydrolysate of rPLF displayed high bactericidal activity against Escherichia coli ATCC 25922 under scanning electron microscopy observation and minimal inhibitory concentration and minimal bactericidal concentration tests. Our results suggested that the methylotrophic yeast-inducible system is suitable for large-scale production of active antibacterial rPLF glycoprotein.

HIV-positive MSM have a higher seroprevalence rate of HBV and HCV infection than HIV-negative MSM in Taiwan. Vaccination and safe-sex counseling should be provided to prevent the transmission of hepatitis viruses among MSM who may be engaged in high-risk behaviors.

No abstract

No abstract