盐酸左氧氟沙星眼用即型凝胶治疗兔金黄色葡萄球菌角膜炎

目的 盐酸左氧氟沙星眼用即型凝胶治疗兔金黄色葡萄球菌角膜炎的药效学研究.方法 选取60只双眼均正常的新西兰大白兔,给予左眼角膜基质内注射10μL含105个菌落形成单位(colony-forming unit,CFU)的金黄色葡萄球菌菌液,建立角膜炎动物模型.挑选炎症程度相近的48只兔,采用完全随机设计方法分为4组,即24 h基线组、磷酸盐缓冲液(PBS)空白对照组、盐酸左氧氟沙星滴眼液组及盐酸左氧氟沙星眼用即型凝胶组,每组12只.观察24 h基线组兔眼临床炎症情况并评分,观察角膜病理变化及进行细菌菌落计数;其余3组每日治疗3次,至第7天最后一次给药后2h对3组兔的处理同24 h基线组.各组角膜临床炎症评分和角膜细菌菌落计数值比较均使用多个样本均数比较中的完全随机设计资料的方差分析,即F检验.结果 第7天时,相对于PBS空白对照组,盐酸左氧氟沙星滴眼液与盐酸左氧氟沙星眼用即型凝胶均降低角膜炎感染的临床症状(P=0.00),角膜炎临床评分分别为4.21±1.10和3.63±0.86;第7天时,盐酸左氧氟沙星滴眼液组与盐酸左氧氟沙星眼用即型凝胶组兔眼角膜菌落数均降低(P=0.00),角膜菌落计数分别为(4.87±0.05)和(4.64±0.10)CFU,差异有统计学意义(P=0.00).结论 盐酸左氧氟沙星眼用即型凝胶局部给药治疗金黄色葡萄球菌角膜炎可明显改善临床症状、降低角膜菌落数,其作用优于常用的盐酸左氧氟沙星滴眼液,是一种有效的新型眼用制剂.     

近交系小鼠核心群和生产群遗传质量监测

目的:对常用的近交系小鼠核心群和生产群进行遗传质量监测,观察2者之间的遗传质量差异,为近交系小鼠保种繁殖方法的改进提供理论依据.方法:采用生化标记法和微量细胞毒实验对3个近交系小鼠BALB/c、C57BL/6、DBA/2的核心群(n=6)和生产群(n=30)进行遗传质量监测.生化标记法检查的位点有Idh-1、Car-2、Gpd-1、Hbb、Es-1、Es-2、Mod-1、Es-3和Akp-1;微量细胞毒实验检查的位点有Thy-1、H-2K和H-2D.结果:在所监测的9个生化标记位点上,核心群和生产群都符合品系标准.在免疫学位点上,3个品系的核心群和DBA/2品系的生产群符合品系标准,C57BL/6和BALB/c的生产群中分别发现2个(Thy-1a/b和H-2Db/d)和4个(H-2Kd/b)变异的个体;H-2Kb抗血清对BALB/c的细胞毒指数明显升高.结论:近交系小鼠核心群和生产群在遗传质量上可能出现差异,生产群的遗传质量问题应引起高度重视.     

In vitro and in vivo effects of JAK2 inhibition in chronic myelomonocytic leukemia

In chronic myelomonocytic leukemia (CMML), colony‐forming units granulocyte/macrophage (CFU‐GM), which grow in vitro in the absence of exogenous growth factors, arise from the abnormal clone that is responsible for the overproduction of granulomonocytic cells. Previous in vitro findings including ours suggest that divergent molecular aberrations in CMML seem to converge within the GM‐CSF signaling pathway. As JAK2 is a sentinel kinase in this pathway, JAK2 inhibition may be an attractive treatment approach in CMML. We investigated the in vitro effects of the specific JAK2 inhibitor TG101209 on the autonomous CFU‐GM formation from peripheral blood mononuclear cells of patients with CMML. TG101209 was found to either block or strongly inhibit spontaneous CFU‐GM growth in all 10 patients tested. This inhibitory effect was dose dependent and significantly more pronounced as compared to the inhibitory effect on stimulated CFU‐GM growth from normal individuals. In a CMML patient with splenomegaly, who was treated with the JAK1/2 inhibitor ruxolitinib off label, we can demonstrate a spleen response and the disappearance of constitutional symptoms which was associated with a decrease in autonomous CFU‐GM formation ex vivo. Pharmacological JAK2 inhibition may be an interesting approach to be systematically studied in patients with CMML.     

A case of pulmonary alveolar proteinosis treated with whole lung lavage

Pulmonary alveolar proteinosis represents a rare syndrome characterized by the accumulation of proteinaceous phospholipid-laden material in the alveoli. This leads to impaired gas exchange and arterial hypoxemia of varying degrees. The diagnosis is confirmed by lung biopsy. Sequential whole-lung lavage (WLL) first described in 1963 is the standard of care. We report a case of a male diagnosed of having pulmonary alveolar proteinosis (PAP) on transbroncial lung biopsy (TBLB). He was treated with sequential WLL (Left followed by right, Left being more involved on chest X-ray) followed by recombinant GM-CSF, with good result.     

Human Antibody Fragments Specific for the Epidermal Growth Factor Receptor Selected from Large Non-immunised Phage Display Libraries

Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2 nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (k_a and k_d). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.     

Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, Inc.     

Insecticide and fungicide effect on thermal and olfactory behavior of bees and their disappearance in bees’ tissues

Plant protection products may affect the behavior of organisms which are not a target of control. The effect of Karate Zeon 050 CS (λ-Cyhalothrin -based insecticide; λ-CBI) and Amistar 250 SC (Azoxystrobin-based fungicide; ABF) was determined on Apis mellifera worker attraction towards their own colony odour, along with temperature preferences. Bees exposed to pesticides prefer the environment with the odour of their nest less often than the control group, and that insecticide-treated bees chose warmer environments than the control insects. The observed differences in the bees, especially with attraction towards their own colony, were dependent on the time of day. Chromatographic analyses indicated that λ-Cyhalothrin elimination was half that of Azoxystrobin in bee organisms, and both agents retarded each other’s clearance. Mathematical modeling estimated that despite a relatively high disappearance rate, both compounds might have been bio-accumulated at relatively high level.