Long-term therapeutic efficacy of lamivudine compared with interferon-alpha in children with chronic hepatitis B: the younger the better.

OBJECTIVES: To assess and compare the long-term therapeutic response to lamivudine compared with interferon-alpha (IFN-alpha) in children with chronic hepatitis B. METHODS: A total of 40 children (27 male; age, 1.3-18 y, mean, 7.7 y) with chronic hepatitis B who received lamivudine for at least 12 months were followed for a mean period of 39 (24-76) months. Their treatment efficacy was historically compared with that of 19 children (14 male; age, 2.1-17 y; mean, 10 y) who had been treated with IFN-alpha and were followed for a mean period of 39 (24-104) months. Therapeutic responses were compared at 2 y after the initiation of either of the treatment methods. RESULTS: Two years after the initiation of treatment, the results for children treated with lamivudine versus IFN-alpha were as follows: hepatitis B e antigen (HBeAg) seroconversion occurred in 26 (65%) of the 40 children versus 7 (37%) of the 19 children, P < 0.05. In the lamivudine-treated group, the results for children treated before the age of 7 versus age >7 were as follows: HBeAg seroconversion occurred in 17 (89%) of the 19 children versus 9 (43%) of the 21 children, P < 0.01, and loss of hepatitis B surface antigen (HBsAg) occurred in 8 (42%) versus 0%, P < 0.001. CONCLUSIONS: Long-term treatment of lamivudine led to significant improvement in the seroconversion rate of HBeAg in children with chronic hepatitis B compared with IFN-alpha therapy. Furthermore, in preschool-age children, it led to significant improvement in the seroconversion rate of HBeAg and HBsAg compared with school-age children.

Transgenic potato expressing Abeta reduce Abeta burden in Alzheimer's disease mouse model.

Beta amyloid (Abeta) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of Abeta is considered a primary therapeutic target. Immunization with Abeta can reduce Abeta burden and pathological features in transgenic AD model mice. Transgenic potato plants were made using genes encoding 5 tandem repeats of Abeta1-42 peptides with an ER retention signal. Amyloid precursor protein transgenic mice (Tg2576) fed with transgenic potato tubers with adjuvant showed a primary immune response and a partial reduction of Abeta burden in the brain. Thus, Abeta tandem repeats can be expressed in transgenic potato plants to form immunologically functional Abeta, and these potatoes has a potential to be used for the prevention and treatment of AD.

Amyloid precursor protein processing is separately regulated by protein kinase C and tyrosine kinase in human astrocytes.

Regulation of amyloid precursor protein (APP) processing by protein kinase C (PKC) and phosphotyrosine pathways was investigated in cultured human astrocytes. Phorbol 12, 13-dibutyrate (PDBu), a PKC activator, increased secretion of APPalpha 2-3-fold over control values, and GF109203X, a PKC inhibitor, blocked this effect. Similarly, platelet derived growth factor (PDGF) increased the secreted form of APPalpha (sAPPalpha) level two-fold, and genistein, a tyrosine kinase inhibitor, blocked the stimulatory effect of PDGF. Co-treatment of PDGF and PDBu resulted in a five-fold increase in the sAPPalpha production, and genistein and GF109203X did not block the stimulatory effects of PDBu and PDGF, respectively. These results indicate that both PKC and phosphotyrosine pathways are involved in APP processing in human astrocytes, but they act independently. The two pathways appear to converge to mitogen-activated protein kinase (MAPK) because PD98059, a MAPK inhibitor, blocked the effects of PDBu and PDGF on APPalpha secretion.