Recombinant IFN-γ abrogates allograft tolerance induced by donor-specific blood transfusion by restoring alloantibody production

Donor-specific tolerance to heart allograft was induced in adult Lewis rats by pregraft donor-specific blood transfusion (DST). We previously showed that this tolerant state is characterized by a dramatic inhibition of T cell and macrophage activation. In addition, tolerant animals could not mount an efficient anti-donor humoral response whereas transfer of sera from rejecting animals triggered rejection in tolerant animals. This tolerance can be abrogated by daily post-graft administration of recombinant IFN-γ (rIFN-γ). To elucidate the mechanisms of action of rIFN-γ, T cell, macrophage and B cell functions were assessed in allograft recipients. IFN-γ did not restore the expression of Th1-related cytokine mRNA or the activated macrophage product inducible nitric oxide synthase in allografts. Importantly, rIFN-γ treatment promptly restored the anti-donor humoral response in DST-treated recipients. We conclude that rIFN-γ treatment in DST-treated allograft recipients cannot reverse the unresponsive state of Th1 cells and macrophages infiltrating the graft, but can provide B cell help for IgG alloantibody production which is lacking in these animals.     

气象因素对农田鼠类数量影响的典型相关分析

目的探讨气象因素对农田鼠类数量的影响。方法采用典型相关分析对开江县1978—1993年农田鼠密度与气象因素进行统计分析。结果1978—1993年开江县农田总鼠密度为5．58％～26．57％,黑线姬鼠、褐家鼠、四川短尾嗣密度分别为1．91％～18．41％、0．68％10．86％、0．47％～9．50％。气温、湿度、降雨量、日照数等12种气象因素与总鼠密度,黑线姬鼠、褐家鼠、四川短尾鼢密度4个因变量的典型相关系数中,第1对（r=1．0000）有统计学意义（X＾2=248．7032,P〈O．01）,鼠类数量以总鼠密度标准系数最大（4．7748）,气象因素标准系数最大的依次为7—8月平均日照数（-3．1532）、7—8月平均湿度（-1．6177）和7—8月平均降雨量（-1．4652）,且全部为负相关。结论农田鼠类数量主要受7—8月平均日照数、平均湿度和平均降雨量的影响。     

Pretreatment with Δ9-tetrahydrocannabinol (THC) increases cocaine-stimulated activity in adolescent but not adult male rats

Marijuana (Cannabis sativa) remains one of the most widely used illegal drugs, with adolescents being particularly vulnerable to its use and abuse. In spite of this, most studies are conducted in adult animals even though the effects might be quite different in adolescents. Additionally, the use of marijuana often precedes the use of other psychoactive drugs including cocaine, especially when marijuana exposure begins during early adolescence. The purpose of this study was to examine the effects of repeated Δ9-tetrahydrocannabinol (THC), the major active ingredient in marijuana, in adolescents compared to adults and to determine its subsequent effects on cocaine-stimulated activity. To this end, adolescent (postnatal day PND 34) and adult (PND 66) rats were administered 3 mg/kg/day THC for 8 days and locomotor activity was measured on days 1, 2, 7 and 8 after dosing. On day 12 (4 days after the last dose of THC), rats were injected with escalating doses of cocaine and behavior was recorded. Results show that THC depressed locomotor activity in adult rats but not in adolescents. However, following a cocaine challenge, adolescents exposed to THC showed increased locomotor responses to cocaine compared to chronic vehicle-injected controls. This was not seen in adults. These results show that the effects of cocaine are enhanced after THC in adolescents, but not adults, and that this might account for the greater transition to cocaine after early, as opposed to later, marijuana use.     

Immunotargeting of insulin reactive CD8 T cells to prevent Diabetes

We have previously demonstrated, in the collagen-induced arthritis model (CIA), that repetitive injections of immature bone-marrow-derived dendritic cells (iDCs) induce the expansion of a population of CD4CD49b-expressing cells, and that their adoptive transfer results in protection against CIA in a prophylactic setting. However, the in vivo mechanism responsible for their expansion, as well as their therapeutic potential in established disease remains to be defined. In the present study, we show that expression of the MHC class II molecules on iDCs is required for their expansion thus identifying these cells as MHC class II-restricted T cells. Using adoptive transfer of Thy1.1 positive cells, it is shown that iDC-induced CD4⁺CD49b⁺ T cells home to the lymph nodes draining the inflamed tissue. The high immunomodulatory potential of these cells was underscored following their adoptive transfer in a model of contact hypersensitivity. Finally, we assessed and compared the therapeutic potential of iDC-inducible CD4⁺CD49b⁺ T cells with that of iDCs in established CIA. Repetitive injections of iDCs in arthritic mice failed to decrease the severity of established disease. In contrast however, a single injection of iDC-induced CD4⁺CD49b⁺ T cells reversed clinical symptoms of arthritis and provided long-lasting protection. Together, our data indicate that iDC-induced CD4⁺CD49b⁺ T cells are bona fide T regulatory cells with strong immunomodulatory properties that are not only able to prevent disease onset, but also to interfere with an ongoing inflammatory immune response.     

Prolonged exposure of dendritic cells to maturation stimuli favors the induction of type-2 cytotoxic T lymphocytes

Dendritic cell (DC) maturation influences the priming and polarization of T lymphocytes. We recently found that early activated DC (i.e. DC exposed to pro-maturation stimuli for 8 h) were more prone to prime in vivo a type-1 cytotoxic T cell (Tc1) response than DC exposed to pro-maturation stimuli for 48 h (48h-DC). We investigated whether 48h-DC, conversely, allowed the induction of Tc2 cells. Antigen-pulsed mouse bone-marrow-derived DC at any maturation stage, in the presence of exogenous IL-12, skewed in vitro naive CD8(+) T cells towards Tc1 cells, but 48h-DC most potently, in the presence of exogenous IL-4, favored the induction of Tc2 cells. In vivo, full maturation of DC promoted expansion of Tc2 and fall of Tc1 cells. Tc2 cells maintained a high cytolytic activity and produced significant amounts of IL-4, IL-5, IL-10 and TGF-beta. Our results indicate that polarization of naive CD8(+) T cells to Tc2 cells is dependent on the amount of time DC have been exposed to maturation stimuli, and might be favored in late and/or chronic phases of an immune response.     

黑龙江省农区村屯鼠害防治与持续控制试验研究

目的防控黑龙江省农区村屯鼠害。方法以村屯为核心和最小单位、以抗凝血灭鼠剂（溴敌隆）和毒饵保护器（水泥毒饵站）为主要技术手段,以褐家鼠、小家鼠主要集中在村屯的秋冬季为防控的切入时机,长期投放水泥毒饵站。结果从毒饵取食量上看,在一年半的村屯鼠害防控试验中毒饵消耗量下降了95.65%;在处理后4个月通过夹夜法调查夹捕率下降了83.67%;次年的毒饵消耗量最大反弹高度仅相当于前一年同期最大量的23%。结论解决了村屯灭鼠中最为关键的技术环节,同时探索出较为简单的灭鼠方式,达到了对村屯鼠害持续控制的目的,且对人、畜、禽安全。     

南昌市鼠类种群分布及主要鼠传疾病发生风险的关系研究

目的了解南昌市不同生境的鼠密度及主要鼠传疾病流行情况,并对鼠传疾病发生的风险进行评估。方法鼠种调查采用夹夜法,主要鼠传疾病资料来自传染病疫情报告系统;风险评估采用风险评价指数矩阵法。结果 2006-2008年南昌市平均鼠密度为1.03%,褐家鼠为优势种,占52.55%;其次为小家鼠和黄胸鼠,分别占18.88%和17.35%。3种生境中以农村自然村鼠密度最高,达1.83%;其次是特殊行业,为0.89%;居民区最低,为0.56%。2006-2008年南昌市肾综合征出血热（HFRS）的年平均发病率为0.68/10万,3年未见人间鼠疫及鼠间疫情,未来HFRS在南昌市发生的风险为很有可能,鼠疫为有可能发生。结论科学的风险评估体系,有助于预测疾病发生的风险。     

饵料消耗率检验口岸范围鼠类侵害程度的可行性研究

目的通过鼠类对不同饵料消耗率的比较,对口岸范围鼠类侵害程度进行研究。方法以盐城＂陆、海、空＂口岸范围内各类型单位室内外鼠类活动作为研究对象,根据食饵消耗率,分析阳性频度分布趋势,确立鼠类侵害程度指标值。结果根据鼠征阳性率范围均值、离散度及频度分布理论,考虑卫生检疫实践,提出盐城口岸范围内鼠征法侵害程度分级标准：Ⅰ级（不足为害）侵害率0～2%;Ⅱ级（轻度侵害）侵害率〉2%～10%;Ⅲ级（中度侵害）侵害率〉10%～30%;Ⅳ级（重度侵害）侵害率〉30%。结论提出用饵料消耗率区分口岸范围鼠类侵害程度分级标准,可与鼠征法同时或单独使用,适合口岸大范围监测要求。     

The effects of maternal antidepressant use on offspring behaviour and brain development: Implications for risk of neurodevelopmental disorders

Approximately 10% of pregnant women are prescribed antidepressant drugs (ADDs), with selective serotonin reuptake inhibitors (SSRIs) the most widely prescribed. SSRIs bind to the serotonin transporter (SERT), blocking the reabsorption of serotonin by the presynaptic neuron and increasing serotonin levels in the synaptic cleft. The serotonergic system regulates a range of brain development processes including neuronal proliferation, migration, differentiation and synaptogenesis. Given the presence of SERT in early brain development, coupled with the ability of SSRIs to cross the placenta and also enter breast milk, concerns have been raised regarding the effects of SSRI exposure on the developing foetus and newborns. In this review, we evaluate preclinical and clinical studies that have examined the effects of maternal SSRI exposure and the risk for altered neurodevelopment and associated behaviours in offspring. While the current body of evidence suggests that maternal SSRI treatment may cause perturbations to the neurobiology, behaviour and ultimately risk for neurodevelopmental disorders in exposed offspring, conflicting findings do exist and the evidence is not conclusive. However, given the increasing incidence of depression and number of women prescribed ADDs during pregnancy, further investigation into this area is warranted.