Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool

The use of livers from anti-hepatitis B core (HBc) positive donors can alleviate donor shortage. Nineteen of 367 (6%) adults receiving anti-HBc positive allografts [three were hepatitis B antigen (HBsAg) negative, hepatitis B antibody (HBsAb) positive; four were HBsAg positive and 12 were not exposed to hepatitis B viral (HBV) infection] were retrospectively reviewed. In HBsAg negative recipients, immunoprophylaxis (IP) was guided by viral serology and immunohistochemistry (IH) of day 0 and day 7 liver biopsies. If IH was negative, IP was stopped. None of three HBsAg negative, HBsAb positive recipients infected; one (replicating) of four HBsAg positive recipients reinfected and seven of eight (87.5%) HBsAg, HBsAb negative recipients, who did not receive long-term IP, infected after a median time of 2 years (range 1-5); one patient died of liver failure. Four HBsAg, HBsAb negative recipients, receiving life-long IP, remained infection free. Anti-HBc positive donor livers must be directed selectively first to HBsAg positive recipients, next to recipients having HBV antibodies and finally to HBV-naive recipients. Identification of both donor and recipient risk factors for HBV infection before transplantation allows indiscriminate use of antiviral prophylaxis. The necessity for IP therapy should be guided by HBV-DNA testing of donor liver tissue and serum. IH of early liver biopsies is an unreliable marker for predicting antiviral treatment requirements.     

Improvements in healthcare and cost benefits associated with botulinum toxin treatment of spasticity and muscle overactivity

Spasticity is a widespread, disabling form of muscle overactivity affecting patients with central nervous system damage resulting in upper motor neurone syndrome. There is a range of effective therapies for the treatment of spasticity (e.g. physical, anaesthetic, chemodenervation and neurolytic injections, systemic medication and surgery), but all therapies must be based on an individualized, multidisciplinary programme targeted to achieve patient goals. Appropriate therapy should be based on the extent and severity of spasticity, but spasticity and its consequences, regardless of presentation or cause, are commonly treated with systemic agents. This may be ill-advised as systemic treatment is associated with many undesirable effects. In particular, elderly patients with post-stroke spasticity are at risk from the central adverse effects of systemic medication (e.g. sedation and gait disturbance), which make them more susceptible to falling, with an associated increased risk of fracture. The rising costs of fracture care and its sequelae are fast becoming an international problem contributing to high healthcare expenditure. Botulinum toxin type-A (BoNT-A) treatment is highly effective for some of the more common forms of spasticity and muscle overactivity, and has a favourable profile when compared with systemic agents and other focal treatments. Therefore, the clinical benefits of BoNT-A treatment outweigh the apparent high costs of this intervention, showing it to be a cost-effective treatment.     

A trip through the signaling pathways of melanoma

Many cellular signaling pathways are involved in the development of cancer. Depending on the tumor entity, the nature as well as the mode of activation can differ. Some signaling pathways frequently show changes as all tumor cells have to fulfill some basic requirements such as independence from growth factors or insensitivity against apoptosis. In this review, the possibilities of a tumor to manipulate signaling pathways to reach these goals are exemplified based on an archetypical melanoma cell. In addition, new therapeutic options based on the knowledge of signaling pathways will be discussed.     

△LuxS的表型分析及其在GBS毒力调控机制研究中的应用

目的采用LuxS缺失突变株模型对B型链球菌中数量感应相关分子LuxS的功能及与其相关的自诱导因子-2数量感应通路进行研究，以探索其毒力调控机制。方法采用RT-PCR法、菌落印迹分析、生长曲线测定、cAMP因子测定等方法对该缺失突变菌株的表型特性进行了研究。最后应用哈氏弧菌作为报告菌株，通过生物发光测定法分析了突变株对B型链球菌诱导报告菌株中的生物发光活性的影响。结果发现此缺失突变可导致B型链球菌中scpB基因表达的上调；与野生株相比，突变株的生物发光诱导活性比野生株降低了大约两倍。结论本研究结果证实了LuxS在GBS中AI-2数量感应通路中的重要性，并为GBS中毒力调控机制的进一步研究提供了新的线索。     

增强子Ⅰ对乙型肝炎病毒DNA疫苗免疫应答的影响

目的 研究乙型肝炎病毒（HBV）自身增强子I（enhancerI，ENHI）对HBV DNA疫苗免疫应答的影响。方法 采用PCR法以HBVadr亚型全基因DNA序列为模板分别扩增表面抗原（HBsAg）和HBsA-ENHI基因片段，重组到载体VR1012中，构建两种HBV DNA疫苗，转染CADS-7细胞及HepG2细胞并免疫BALB／c小鼠。采用蛋白印迹、ELISA、ELISPOT等方法检测其在COS-7和HepG2细胞内的表达及小鼠的体液及细胞免疫应答效果。结果 转染的HepG2和COS-7细胞均表达HBsAg;连接ENHI的HBV DNA疫苗转染HepG2细胞后HBsAg表达量明显升高，两种疫苗转染COS-7细胞表达HBsAg无明显差异；免疫小鼠后第2周产生HBsAb及HBsAg特异性细胞毒T淋巴细胞（CTL），两种疫苗免疫产生的HBsAb及HBsAg特异性CTL无明显差异。结论ENHI可使HBV DNA疫苗转染HepG2细胞表达HBsAg明显增加，对转染COS-7细胞表达HBsAg及接种BALB／C小鼠引起的免疫应答无明显影响。     

Leber’s hereditary optic neuropathy and vitamin B12 deficiency

Background Leber’s hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON.Methods A case series was observed.Results Three patients who developed bilateral optic neuropathy are presented. All patients had a primary LHON mutation in their mtDNA, but also a subnormal vitamin B12 serum level at the time of presentation.Conclusions The clinical picture of optic neuropathy associated with vitamin B12 deficiency shows similarity to that of LHON. Both involve the nerve fibres of the papillomacular bundle. The present case reports suggest that optic neuropathy in patients carrying a primary LHON mtDNA mutation may be precipitated by vitamin B12 deficiency. Therefore, known carriers should take care to have an adequate dietary intake of vitamin B12 and malabsorption syndromes like those occurring in familial pernicious anaemia or after gastric surgery should be excluded.     

巯基化合物对内毒素诱导大鼠枯否细胞NF—kB活性和肿瘤坏死因子释放的影响

目的 观察巯基化合物对内毒素诱导大鼠枯否细胞（KC）NF-kB活性和肿瘤坏死因子-a（TNF-a）释放的影响。方法采用胶原酶灌注和percoll密度梯度离心法分离得到高纯度大鼠KC，在过夜培养后冲洗两遍（不含血清），加入内毒素（LPS）10ng／ml刺激原代培养的KC，观察不同浓度谷胱甘肽乙基酯（GSHEE）及N-乙酰半胱氨酸（NAC）对大鼠KCTNF-a释放和KC内谷胱甘肽（GSH）及NF-kB活性的影响。并观察使用谷胱甘肽合成抑制剂BSO后，对NAC抑制炎症因子的影响，采用凝胶滞留电泳法测NF-kB活性，采用高效液相色谱分析法测GSH水平。结果 LPS诱导KC中GSH水平无变化；GSHEE和NAC可提高KC中GSH水平（P〈0．05），降低NF-kB活性和TNF-a释放（P〈0．05）。NAC与BSO合用时KC中GSH水平无变化，TNF-a释放降低（P〈0．05）。结论 NAC通过抑制KC中NF-kB的激活和TNF-a的释放调节KC功能，但这种抑制作用并非通过增加GSH介导。     

Safety and efficacy of botulinum toxin type A following long-term use

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX^®. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.     

Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression

The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.