Fiber shaft extension in combination with HI loop ligands augments infectivity for CAR-negative tumor targets but does not enhance hepatotropism in vivo

Recent studies demonstrate that the fiber shaft length, which ranges from six beta-repeats to 23 beta-repeats in human adenoviruses (Ads), influences viral tropism. We have previously shown that artificial extension of the shaft length inhibits infectivity in CAR (coxsackievirus and Ad receptor)-positive cell lines, but does not affect infectivity in a CAR-independent, integrin-dependent cell entry pathway. On the basis of these findings, we hypothesized that Ad vectors with shaft extension might display lower infectivity in liver, which expresses high levels of CAR. We also postulated that infectivity of Ad vectors with shaft extension in CAR-negative tumors could be increased by exploiting a CAR-independent cell entry by incorporation of an RGD4C motif into the fiber knob HI-loop. We thus compared gene transfer efficiencies of our Ad serotype 5 (Ad5) capsid-based 'longer-shafted' Ad vector with or without an RGD4C motif in the HI-loop of the fiber knob (Ad5long and Ad5RGDlong, 32 beta-repeats) to wild-type Ad vector (Ad5, 22 beta-repeats) in vitro and in vivo. In this study, Ad5long showed similar infectivity in CAR-negative tumors (69.7%, P = 0.098), but significantly reduced infectivity in CAR-positive tumors (19.1%, P = 0.000038) and in liver (12.5%, P = 0.0047) compared with Ad5. On the other hand, Ad5RGDlong demonstrated similar infectivity in CAR-positive tumors (70.5%, P = 0.012) and in liver (83.4%, P = 0.51), but significantly increased infectivity in CAR-negative tumors (327%, P = 0.0000042) compared with Ad5. Importantly, Ad5RGDlong demonstrated an augmented gene transfer capacity for CAR negative tumors, but no enhanced hepatotropism in vivo. We suggest that Ad vectors with artificial fiber shaft extension in combination with HI loop ligands may be useful for gene therapy applications.     

Reappraisal of optimal hemoglobin standards for female blood donors in Canada

BACKGROUND: A hemoglobin (Hb) standard of 115 g per L on the copper sulfate test has been in use by the Canadian Red Cross Society Blood Services for female blood donor predonation screening since 1989. STUDY DESIGN AND METHODS: To determine if this lowered Hb standard results in increased iron deficiency in repeat blood donors, a study was conducted to evaluate the performance of the copper sulfate test and predonation capillary and venous Hb assays in a population of female blood donors most at risk of developing iron deficiency. RESULTS: Of the 174 donors who were of childbearing age, who were not taking iron supplements, and who had made at least three blood donations per year, 45 (25.9%) were iron deficient, and 64 (36.8%) had reduced iron stores; only 65 (37.3%) had normal iron stores. This study showed that capillary blood is more likely to have a higher Hb concentration (3.2 +/− 7.8 g/L) than venous blood samples, which could affect the performance of predonation screening assays that are based on capillary blood samples at a given discriminating value. With an Hb standard of 115 g per L, both the copper sulfate and capillary Hb assays were not sensitive enough to screen for iron deficiency (sensitivity, 27% and 33%; specificity, 96% and 93%, respectively) and were comparable only to the performance of a venous Hb assay with a cutoff value of 110 g per L (sensitivity, 27%; specificity, 99%). In contrast, an Hb standard of 125 g per L in the copper sulfate test could achieve a more optimal sensitivity of 79 percent and specificity of 78 percent. CONCLUSION: This study supports the use of a higher Hb cutoff value of 125 g per L for female blood donors in the predonation fingerstick copper sulfate test.     

术前肌电图和脑干听觉诱发电位与面肌痉挛微血管减压术后迟发性面瘫发生的关系(英文)

Background Delayed facial palsy ( DFP) after microvascular decompression ( MVD) in patients with hemifacial spasm ( HFS) is not uncommon,but the cause remains unknown. Objectives To assess whether intraoperative electromyography ( EMG) and brainstem auditory evoked potential ( BAEP) can predict DFP after MVD. Methods Between September 2009 and February 2011 we examined 86 patients,9 of whom ( 10. 4% ) developed DFP after MVD on the same side. All patients underwent MVD and were followed - up for a median period of 13 months ( range 6-22) . We retrospectively examined intraoperative facial EMG and BAEP findings using our MVD patients’ registry. We excluded secondary HFS and immediate postoperative facial palsy after MVD in this study. We assessed the prevalence and clinical characteristics of DFP and compared EMG and BAEP findings between DFP and non-DFP groups. Results: All pa- tients recovered completely,with a mean time to recovery of 37. 8 days ( range 22-57) . There were no significant differences between DFP and non - DFP patients in terms of the amplitude and latency of intraoperative EMG and BAEP. Conclusion The usefulness of intraoperative facial EMG and BAEP is limited and cannot predict DFP after MVD for HFS. We speculate that DFP after MVD is not associated with permanent nerve damage according to the EMG findings.     

Lactogenic Activity of Rats Stimulated by Gunnera Perpensa L. (Gunneraceae) from South Africa

Gunnera perpensa L. (Gunneraceae) is a medicinal plant used by Zulu traditional healers to stimulate milk production. The effect of an aqueous extract of the rhizome of the plant on milk production in rats was investigated. Female lactating rats that received oral doses of the extract of G.perpensa significantly (p<0.05) produced more milk than controls. The plant extract did not however, significantly influence the levels of prolactin, growth hormone, progesterone, cortisol, ALT, AST and albumin in the blood. The mammary glands of rats treated with the extract showed lobuloalveolar development. The extract (0.8 µg/ml) was also found to stimulate the contraction of the uterus and inhibit (23%) acetylcholinesterase activity. The cytotoxicity of the extract (LC₅₀) to two human cell lines (HEK293 and HepG2) was 279.43 µg/ml and 222.33µg/ml, respectively. It is inferred that the plant extract exerts its activity on milk production and secretion by stimulating lobuloalveolar cell development and the contraction of myoepithelial cells in the alveoli. It is concluded that Gunnera perpensa contains constituents with lactogenic activity that apparently contribute to its effectiveness in folk medicine.     

《亚洲男性学杂志》“21 世纪精液分析特刊”后序

精液分析成为不育研究的重要部分经历了一个极其漫长的历史变迁过程,并声名狼藉,曾经被排除在常规的病理学检查之外,直到近些年才引起学术界的重视.精液分析起源于19世纪,那时对精子的认识仅仅局限于检测性交后宫颈黏液中是否存在精子,曾认为是"有失体面的,不自重的[1].     

血小板激活因子对大鼠脑血管通透性的影响及药物的保护作用

颈内动脉注射血小板激活因子(PAF),再给伊文思蓝,可见脑实质染色程度加深,而颈内动脉只注射伊文思蓝,脑实质未见染色。而我们合成的新药SZ-1可剂量依赖性地抑制PAF诱导的脑实质伊文思蓝染色程度的加深。在体外培养的脑微血管平滑肌细胞上,PAF能显著刺激~(14)-花生四烯酸的释放,而SZ-1能剂量依赖性地抑制这种释放,提示PAF在脑内产生的损害除与其他因素相关外,还与其刺激花生四烯酸释放有密切关系,SZ-1对PAF引起的脑部损害有保护作用。