Pharmacokinetics and pharmacodynamics of recombinant human growth hormone by subcutaneous jet- or needle-injection in patients with growth hormone deficiency

Eighteen growth hormone (GH) deficient children and adolescents (11 6/12–20 9/12 y) participated in a randomized open, two-period (4 weeks) cross-over study to evaluate the pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) administered daily, either by subcutaneous jet-injection or conventional needle-injection. Plasma growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), glucose, insulin, HbAlc and serum-free fatty acids (FFA) levels were analysed repeatedly. GH absorption characteristics, expressed as AUC_0-x, Cmax and Tmax ratio (%) jet-injected over needle-injected were similar in both groups. IGF-I and IGFBP-3 plasma levels were identical in both groups. Serum FFA concentrations were comparable after GH administration with either injection device. Surprisingly nocturnal blood glucose decreased to asymptomatic hypoglycaemic levels in all patients. The results of this study showed equal responses concerning absorption and bioavailability of growth hormone administered daily for 4 weeks by either a jet or a needle-injection device in GH-deficient children and adolescents.     

Ad-HGF修饰MSCs异体移植对烧伤创面愈合的作用

目的：探讨携带人肝细胞生长因子基因的重组腺病毒（Ad—HGF）修饰的骨髓间充质干细胞（MSCs）局部异体移植对烧伤创面愈合的作用。方法：密度梯度离心法体外分离培养雄性Wistar大鼠MSCs，并以感染复数（MOI=100）体外转染Ad—HGF。30只雌性Wistar大鼠随机分为：MSCs治疗组（A组）。Ad—HGF修饰MSCs治疗组（B组），Ad—GFP修饰MSCs治疗组（C组），Ad—HGF治疗组（D组）。空白对照组（E组）。复制大鼠深Ⅱ度烧伤模型，将细胞悬液、病毒悬液及生理盐水于创面下多点注射。伤后3、5、7、14、21d观察创面收缩率并采集创面标本，行HE染色观察创面愈合情况。结果：伤后7、14dB组与A组、C组、D组、E组比较，创口收缩率显著提高（P〈0．05）；HE染色可见B组表皮明显厚于其他各组。并可见钉脚下伸。结论：Ad—HGF修饰MSCs异体移植可显著提高烧伤创面愈合速度和质量，为烧伤创面修复提供了新的策略。     

Limited T Helper Cell Activity in C57BL/10 (B10) Mice with Inherited Low IgG Responsiveness

Due to limitations in antigen processing, mice of the C57BL/10ScSn (B10) strain exhibit a low IgG production against a variety of T-dependent antigens. To characterize the T-cell functions, the authors studied antigen-specific T-cell proliferation and cytokine production in vitro . The response of B10 mice was compared with that of the high IgG producing strain A/J. A highly restricted proliferative response and almost no interleukin-2 (IL-2) and interleukin-3 (IL-3) production was detected in lymph node (LN) cells of B10 mice primed in vivo by protein antigens and subjected to a specific restimulation in vitro , whilst A/J cells responded by significant proliferation and cytokine production. The antigen-specific T-cell response of B10 mice could not be increased by lipopolysaccharide treatment in vivo or by in vitro cultivation with IL-2. However, the T cells of B10 mice produced high levels of IL-2 and IL-4 when stimulated by phorbol myristate acetate (PMA) and Ca²⁺ ionophore, proving the existence of a functionally intact signal transduction pathway downstream of protein kinase C (PKC). The results suggest that the in vivo antigen priming does not effectively activate the T cells in B10 mice. The limited activation consequently leads to the low IgG response described in B10 mice.     

Immunocytochemical localization of the Menkes copper transport protein (ATP7A) to the trans-Golgi network

We have generated polyclonal antibodies against the amino-terminal third of the Menkes protein (ATP7A; MNK) by immunizing rabbits with a histidine-tagged MNK fusion construct containing metal-binding domains 1-4. The purified antibodies were used in Western analysis of cell lysates and in indirect immunofluorescence experiments on cultured cells. On Western blots, the antibodies recognized the approximately 165 kDa MNK protein in CHO cells and human fibroblasts. No MNK signal could be detected in fibroblasts from a patient with Menkes disease or in Hep3B hepatocellular carcinoma cells, confirming the specificity of the antibodies. Immunocytochemical analysis of CHO cells and human fibroblasts showed a distinct perinuclear signal corresponding to the pattern of the Golgi complex. This staining pattern was similar to that of alpha-mannosidase II which is a known resident enzyme of the Golgi complex. Using brefeldin A, a fungal inhibitor of protein secretion, we further demonstrated that the MNK protein is localized to the trans- Golgi network. This data provides direct evidence for a subcellular localization of the MNK protein which is similar to the proposed vacuolar localization of Ccc2p, the yeast homolog of MNK and WND (ATP7B), the Wilson disease gene product. In light of the proposed role of MNK both in subcellular copper trafficking and in copper efflux, these data suggest a model for how these two processes are linked and represent an important step in the functional analysis of the MNK protein.      

6种药物对部队进入海拔5200m急性高原反应预防效果的对比观察

目的 :筛选预防急性高原反应的药物。方法 :进驻海拔 5 2 0 0m哨卡的某部 118名士兵随机分为 6组。将复方红景天、银杏叶片、酪氨酸、复方党参、乙酰唑胺、异叶青兰组列为A、B、C、D、E、F组 ,每组 18～ 2 0人。于进入高原前 4天开始 ,每日早晚各服药 1次 ,到哨卡第 3天停药 ,连服 12d。部队进驻哨卡第 1～ 7天 ,以军用卫生标准GJB10 98- 91《急性高原反应的诊断和处理原则》随访记录受试者每天的急性高原反应症状 ,然后分度评分。分值高者 ,高原反应症状重。结果 :部队进入哨卡第 1天 ,A组症状评分较C、D、E、F组低 ,C组较A、D、E、F组高 (P <0 .0 1或P <0 .0 5 )。第 3天 ,除F组外 ,C组均高于其它 4组 ,B和E组较D组低 (P <0 .0 5或P <0 .0 1)。第 5天 ,A和B组较C组低 ,A组较D组低 (P <0 .0 5或P <0 .0 1)。第 7天 ,B组较A、C和D组低 ,F组较A、C和B组高 (P <0 .0 5或P <0 .0 1)。结论 :银杏叶片预防急性高原反应效果最好 ,乙酰唑胺和复方红景天次之 ,复方党参较异叶青兰好 ,酪氨酸最差     

Some peculiarities of hepatobiliary diseases in Vietnam

The most frequent hepatobiliary diseases in Vietnam are chronic hepatitis and cirrhosis, liver abscess, hepatobiliary ascaridiasis, angiocholitis, biliary lithiasis and primary liver cancer. The principal causes of chronic hepatitis and cirrhosis are HBV and HCV infections. Alcohol and chemicals (drugs, agricultural, industrial, war herbicides) also play an important role. Malaria causes hepatitis and fibrosis lesions, however no cirrhotic lesions were observed. There are two categories of liver abscess, amoebic and cholangitic, often caused by ascaridiasis. Treatment of amoebic abscesses is, at first, non-surgical for small abscesses, often combined with ultrasound guided abscess puncture. Cholangitis abscesses are more serious and often require surgical intervention. Among the gallstones, only 15% are of the gall-bladder, the majority are choledocho- and intrahepatic-lithiasis, composed largely of calcium bilirubinate and are frequently caused by Ascaris -related cholangitis and the nucleation of Ascaris eggs. Forty-seven per cent of acute cholecystitis are acalculous, showing a higher frequency than in Western countries. Primary liver cancer is one of the most frequent malignancies in Vietnam. More than 90% of liver cancers are hepatocellular carcinomas. The principal causes are HBV infection, followed by HCV infection, aflatoxin, alcohol and chemicals. Recent efforts aiming at earlier diagnosis, by selective screening in high-risk groups, have used clinical surveillance, abdominal sonography and AFP level determination. Promising results were obtained in prevention trials by reducing the high AFP level of cirrhotic patients using a vegetal drug, Gacavit, and by treatment with percutaneous ethanol injection therapy, as an alternative therapeutic measure for liver tumour resection.     

肝细胞生长因子对兔骨髓基质细胞生物学特性的影响

目的　观察腺病毒携带肝细胞生长因子cDNA(adHGF)转染兔骨髓基质细胞 (MSC)后的主要生物学特性。方法　抽取成年雄性新西兰白兔骨髓 ,密度梯度离心获得MSC。取兔膝关节软骨 ,体外培养软骨细胞至第 3代。adHGF转染第 5代MSC ,噻唑蓝 (MTT)法检测细胞增生活力 ,阿尔新蓝法检测细胞培养上清液中氨基己糖多糖 (GAG)含量。酶联免疫吸附实验 (ELISA)检测adHGF转染MSC后HGF的表达。免疫组织化学染色及反转录 聚合酶链反应 (RT PCR)检测Ⅰ、Ⅱ型胶原表达。结果　原代MSC为短梭形、簇状生长 ,传代细胞呈长梭形、旋涡样生长。adHGF转染前后细胞增生状态差异无显著性。MSC转染后GAG含量增加。免疫组织化学染色MSC转染前后I型胶原阳性 ,转染后Ⅱ型胶原弱阳性。转染后HGF表达量在转染 1周内最高 ,达 12 0 5ng/ml,并可持续至 6周。RT PCR表明MSC在adHGF转染前后均表达I型胶原 ,转染后微量表达Ⅱ型胶原。结论　MSC在体外培养过程中的自然转归是趋向于成骨。MSC不仅是HGF的源细胞 ,而且可作为靶细胞接受外源目的基因的转染并有效表达     

Risk of iatrogenic human immunodeficiency virus infection through transfusion of blood tested by inappropriately stored or expired rapid antibody assays in a Zambian hospital

BACKGROUND: The purpose of this study was to estimate the risk of human immunodeficiency virus (HIV) infection via the transfusion of blood tested by inappropriately stored or expired rapid antibody assays in Zambia. STUDY DESIGN AND METHODS: Surgical patients (n = 370) were tested with antibody assays (HIV-spot and HIV 1+2) that had expired 3 to 6 months previously. Blood donors (n = 211) were tested by inappropriately stored but non-expired HIV-spot assay. Serum samples from both groups were retested with enzyme immunoassays, and the seropositivity of samples was confirmed by immunoblotting. RESULTS: Seroprevalence in surgical patients and blood donors was 19.8 and 11.6 percent, respectively. Sensitivity and specificity of HIV-spot (expired) were 88.2 and 98.1 percent; those of HIV 1+2 (expired) were 82.1 and 94.7 percent; and those of HIV-spot (non-expired) were 91.7 and 98.8 percent, respectively. The risk of HIV infection via the transfusion of blood tested by HIV-spot (expired), HIV-spot (nonexpired), or HIV 1+2 (expired) was calculated to be 1.4, 1.0, and 3.2 percent, respectively. CONCLUSION: Manufacturers of the HIV-spot and HIV 1+2 assays claim sensitivity and specificity of 98.8 and 100 percent and 100 and 99.5 percent, respectively. In this study, sensitivity and specificity were 11 to 18 percent lower. Moreover, in- date reagents also performed less well than the manufacturers claimed, but the worst results were with expired or improperly stored reagents. According to the manufacturers of HIV-spot and HIV 1+2, the risk of HIV infection would be 0.2 and 0 percent, respectively. However, the risk of contracting HIV through transfusion is at least six times higher than expected.