Evaluation of lithium as an inhibitory agent of herpes simplex virus in cell cultures and during reactivation of latent infection in rabbits.

Lithium carbonate inhibited plaque formation of herpes simplex virus types 1 and 2 in rabbit kidney and Vero cells (50% effective dose, 435.5 to 490 micrograms/ml). Plasma lithium levels of 67 to 134 micrograms/ml were achieved by oral therapy in rabbits. However, neither ocular virus shedding nor virus-positive trigeminal ganglia were reduced after intentional reactivation of latent herpes simplex virus infection.     

Antibody-dependent enhancement of HSV-1 infection by anti-gK sera

We previously reported that vaccination of BALB/c mice with the baculovirus expressed HSV-1 glycoprotein K (gK) or passive transfer of gK purified IgG to naive BALB/c mice causes severe exacerbation of HSV-1 induced corneal scarring following ocular challenge. In addition, a productive chronic infection, rather than a latent infection, is found in most trigeminal ganglia. These phenomena are accompanied by a very high T(H)1+T(H)2 response in the eye (Ghiasi, H., Cai, S., Nesburn, A.B., Wechsler, S.L., 1996. Vaccination with herpes simplex virus type 1 glycoprotein K impairs clearance of virus from the trigeminal ganglia resulting in chronic infection. Virology 224, 330-333; Ghiasi, H., Cai, S., Slanina, S., Nesburn, A. B., Wechsler, S.L., 1997. Nonneutralizing antibody against the glycoprotein K of herpes simplex virus type-1 exacerbates herpes simplex virus type-1-induced corneal scarring in various virus-mouse strain combinations. Invest. Ophthalmol. Vis. Sci. 38, 1213-1221; Ghiasi, H., Hofman, F.M., Cai, S., Perng, G.C., Nesburn, A.B., Wechsler, S.L., 1999. Vaccination with different HSV-1 glycoproteins induces different patterns of ocular cytokine responses following HSV-1 challenge of vaccinated mice. Vaccine 17, 2576-2582). In the studies reported here, we investigated the hypothesis that anti-gK serum produces antibody-dependent enhancement (ADE) of ocular HSV-1 infection. We found that gK vaccinated mice had significantly higher HSV-1 titers in their eyes than gD or mock-vaccinated mice and that anti-gK sera enhanced HSV-1 infection in the macrophage cell line U937. In addition, passive transfer of anti-gK sera to naive mice 24 h prior to ocular HSV-1 challenge also increased viral replication. These results were consistent with ADE of HSV-1 by sera to gK. This suggests that the severely exacerbated corneal disease seen following HSV-1 ocular challenge of gK vaccinated mice is a result of ADE. The ability of gK sera to cause harmful ADE may impact HSV-1 vaccine development.     

产后出血的预防和处理指南

目的:为产后出血(PPH)的预防和临床处理作一综述,为临床医师提供预防和处理产后出血的指南。涉及方面:预防、适当干预、使其影响最小化的方法。结果:建立常规,便于临床医师鉴别可能的高危人群,一旦发生产后过多出血,可指导临床如何迅速处理。证据:遵循加拿大定期健康检查办公室制定的证据等级。评估:由产科专家完善。利弊和成本:评估子宫收缩药和其他积极处理措施的方便性、正确性、有效性和安全性。建议:根据证据的等级,本指南分等级列出了12条建议。确认:按照MeSH词表推荐的postpartum haemorrhage在medline上查询相关文献,在Cochrane图书馆查找相关研究文献,并参考the ALARMcourse Manual。发起人:由产科临床实践委员会制定和综述,并由SOGC(加拿大妇产科协会)委员会批准。     

The role of natural killer cells in protection of mice against death and corneal scarring following ocular HSV-1 infection

C57BL/6 mice depleted of NK (natural killer) cells with anti-asialo-GM1 antibody were more susceptible to lethal HSV-1 ocular challenge (12% survival) than control C57BL/6 mice (100% survival), CD4+ depleted mice (100% survival), CD8+ depleted mice (80% survival), or macrophage depleted mice (85% survival). NK depletion also resulted in significantly higher levels of HSV-1 induced corneal scarring than was seen with any of the other groups. C57BL/6 mice depleted of NK cells with PK136 (anti-NK1.1 antibody which is more specific for NK cells than is anti-asialo-GM1 antibody) were also more susceptible to HSV-1 ocular challenge than T cell or macrophage depleted mice. Vaccination completely protected NK depleted mice against death and corneal scarring. In contrast to C57BL/6 mice, in BALB/c mice, NK depletion had no effect on survival or corneal scarring following ocular HSV-1 challenge. Experiments with IFN-gamma knockout mice (IFN-gamma(o/o) mice) suggested that IFN-gamma played a minor role in protection of na?ve mice against death following HSV-1 challenge. However, IFN-gamma did not appear to be an important factor in protection against HSV-1 induced eye disease. Thus, protection against HSV-1 induced corneal scarring in naive mice appeared to be due to a non-INF-gamma NK function. Our results therefore suggest that NK cells were very important in protecting naive C57BL/6 mice but not vaccinated C57BL/6 mice against corneal scarring and death following ocular HSV-1 challenge.     

Psoriasis: is the impairment to a patient’s life cumulative?

Psoriasis is associated with significant physical and psychological burden affecting all facets of a patient’s life – relationships, social activities, work and emotional wellbeing. The cumulative effect of this disability may be self‐perpetuating social disconnection and failure to achieve a ‘full life potential’ in some patients. Health‐related quality of life studies have quantified the burden of psoriasis providing predominantly cross‐sectional data and point‐in‐time images of patients’ lives rather than assessing the possible cumulative disability over a patient’s lifetime. However, social and economic outcomes indicate there are likely negative impacts that accumulate over time. To capture the cumulative effect of psoriasis and its associated co‐morbidities and stigma over a patient’s life course, we propose the concept of ‘Cumulative Life Course Impairment’ (CLCI). CLCI results from an interaction between (A) the burden of stigmatization, and physical and psychological co‐morbidities and (B) coping strategies and external factors. Several key aspects of the CLCI concept are supported by data similar to that used in health‐related quality of life assessments. Future research should focus on (i) establishing key components of CLCI and determining the mechanisms of impairment through longitudinal or retrospective case–control studies, and (ii) assessing factors that put patients at increased risk of developing CLCI. In the future, this concept may lead to a better understanding of the overall impact of psoriasis, help identify more vulnerable patients, and facilitate more appropriate treatment decisions or earlier referrals. To our knowledge, this is a first attempt to apply and develop concepts from ‘Life Course Epidemiology’ to psoriasis research.