Low rates of active hepatitis B and C infections among adults and children living with HIV and taking antiretroviral therapy: A multicenter screening study in Lesotho

Lesotho presents the second-highest adult human immunodeficiency virus (HIV) prevalence globally. Among people living with HIV, data on hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection are limited. We report HBV and HCV coinfection data from a multicentre cross-sectional study among adult and pediatric patients taking antiretroviral therapy in 10 health facilities in Lesotho. Among 1318 adults screened (68% female; median age, 44 years), 262 (20%) had immunologically controlled HBV infection, 99 (7.6%) tested anti-HBs positive and anti-HBc negative, indicating vaccination, and 57 (4.3%) had chronic HBV infection. Among the patients with chronic HBV infection, 15 tested hepatitis B envelope antigen (HBeAg) positive and eight had detectable HBV viremia (median, 2 477 400 copies/mL; interquartile range, 205-34 400 000) with a mean aspartate aminotransferase-to-platelet ratio index of 0.48 (SD, 0.40). Prevalence of HCV coinfection was 1.7% (22 of 1318), and only one patient had detectable HCV viremia. Among 162 pediatric patients screened, three (1.9%) had chronic HBV infection, whereby two also tested HBeAg-positive, and one had detectable HBV viral load (210 copies/mL). Six of 162 (3.7%) had anti-HCV antibodies, all with undetectable HCV viral loads. Overall prevalence of chronic HBV/HIV and HCV/HIV coinfection among adults and children was relatively low, comparable to earlier reports from the same region. But prevalence of immunologically controlled HBV infection among adults was high. Of those patients with chronic HBV infection, a minority had detectable HBV-DNA.     

包膜活性炭吸附血液灌流清除人血浆中毒鼠强的实验

目的:观察包膜活性炭对血浆中毒鼠强的清除率及吸附规律。方法:实验于2004-05/2006-04在军事医学科学院毒物药物研究所国家重点实验室完成。采用包膜活性炭灌流器对毒鼠强血浆样进行血液灌流吸附,在灌流的1,2,3h分别取样,经乙酸乙酯萃取后,用气相色谱氮磷检测器法(GC/NPD)测定其含量并计算清除率。结果:活性炭对毒鼠强的吸附作用在血液灌流1h最高,灌流2h后毒鼠强质量浓度无明显变化。400,200μg/L毒鼠强血液灌流1h清除率分别为(57.83±1.85)%,(48.18±1.81)%。结论:用包膜活性炭吸附剂进行血浆的灌流吸附,能清除大部分毒物,迅速降低血浆中毒鼠强的质量浓度。     

Production and characterization of a mouse/human chimeric antibody directed against human neuroblastoma

Hybridoma CE7 produces a murine antibody (yl/k) which binds to a 190-kDa cell-surface glycoprotein of human neuroblas-toma. Because of its tumor specificity, it has been used routinely in clinical pathology to confirm diagnosis of neuroblastoma. We have Isolated the gene segments coding for the variable regions of the immunoglobulin Hand L chain of this hybridoma. These V genes were used to construct mouse/human chimeric H and L chain genes (yl/K) which were then expressed in SP2/0 cells. A cell-blnding inhibition assay showed that the specificity of the chimeric CE7 antibody (chCE7) is identical to that of the original CE7. Radioiodinated chCE7 binds to approximately 43,000 sites per neuroblastoma cell with an affinity of IOIO M-I. In neuroblastoma-bearing nude mice, biodistribution studies with [I25I]ch-CE7 were performed and tumor accumulations of up to 32% of injected dose/g tissue together with low blood and organ uptake were found.     

Dopamine precursors and brain function in phenylalanine hydroxylase deficiency

Phenylalanine and tyrosine constitute the two initial steps in the biosynthesis of dopamine, which, in its turn, is the metabolic precursor of noradrenaline and adrenaline. The extracellular phenylalanine concentration influences brain function in phenylalanine deficiency (PHD) by decreased dopamine synthesis. It has been shown to induce EEG slowing, and prolonged the performance time on neuropsychological tests. The tyrosine concentration in the CNS is reduced in PHD, possibly implying insufficient substrate (= tyrosine) for catecholamine synthesis due to competition inhibition, for instance across the blood brain barrier. In experimental studies it has been shown that the synthesis and release of dopamine can be influenced by an increase in the availability of tyrosine. In PHD an extra dietary intake of three doses of tyrosine (160mg/kg/24h) induced a shortsning of reaction time and decreased variability, and in a double-blind crossover study a similar dose has been reported to induce an improvement on psychological tests. In a study with lower doses of tyrosine (110mg/kg/24h) no effect was found on reaction time tests. These findings need to be substantiated, and more detailed information should be obtained.     

Pharmacokinetics and safety of recombinant anti-RhD in healthy RhD-negative male volunteers

In this first-in-man study, we assessed the pharmacokinetics, safety and tolerability of MonoRho, a human recombinant monoclonal anti-RhD immunoglobulin G1 (IgG1) antibody. Eighteen RhD-negative healthy male volunteers were randomized in two groups to receive a single administration of 300 micro g of MonoRho either intravenously or intramuscularly. There were no symptoms of allergic or anaphylactic type reaction in any subject, and there was no evidence of any MonoRho-related changes in laboratory safety parameters. None of the subjects mounted a detectable immune response to MonoRho. Serum samples were obtained up to 91 days after injection to measure anti-D IgG concentrations by flow cytometry. After intramuscular administration of MonoRho, anti-D IgG concentrations gradually increased reaching peak levels after a mean of 3.4 days. After 3 weeks, the mean anti-D IgG concentrations after intravenous and intramuscular administration became virtually equal to each other and remained so thereafter. In both the treatment groups, the mean elimination half-life was about 18 days and thus similar to that described for plasma-derived anti-D IgG. The bioavailability of MonoRho after intramuscular administration was estimated as 46%. The excellent tolerability and safety of MonoRho as well as its expected elimination half-life supports the continued clinical development of this compound.