梅毒螺旋体血行播散机制的研究进展

【摘要】 梅毒是由梅毒螺旋体进入循环系统进行血行播散导致的多系统损害，但目前其全身播散的具体机制尚未完全明确。基于国内外的研究进展，本文从梅毒螺旋体黏附与细胞外基质降解、细胞间连接和细胞骨架系统破坏、血管生成、炎症细胞浸润等多方面探讨梅毒螺旋体血行播散的机制，为进一步研究提供理论基础。     

MRI T1、T2相对比值对新生儿高胆红素脑损害的定量诊断

目的 探讨苍白球(globus pallidum,GP)与额叶白质(frontal white matter,FWM) T1、T2比值在足月新生儿胆红素脑病早期诊断中的价值.方法 收集75例临床确诊高胆红素血症(hyperbilirubinemia,HB)的新生儿,根据苍白球T1WI信号分为46例信号正常组(HBn组)和29例信号升高组(HBh组);同期收集44例健康新生儿作为健康对照组(healthy control,HC组).测量双侧GP与FWM的信号强度并计算GP/FWM的T1、T2信号强度比值(简称T1比值、T2比值).比较3组间各比值差异并绘制ROC曲线评估诊断效能,AUCs比较采用Delong检验.分析各比值与血清总胆红素(total serum bilirubin,TSB)的相关性.结果 3组间T1比值存在显著性差异(H=112.254,P＜0.001),HC、HBn、HBh组T1比值中位值依次增高,为2.14(1.87,2.52)、2.41(2.10,2.60)、3.08(2.81,3.43).ROC曲线分析显示,当T1比值分别以2.675、2.655、2.155作为阈值时,HC-HBh组、HBn-HBh组、HC-HBn组之间曲线下面积(AUC)最大(0.973、0.926、0.633),敏感性和特异性分别为0.948、0.898;0.983、0.795;0.707、0.528.此外,HBh组T2比值[0.66(0.65,0.68)]显著低于HBn组[0.69(0.66,0.72)]和HC组[0.70(0.68,0.73)],调整后P＜0.001,ROC曲线分析表明,T2比值具有一定鉴别诊断能力(AUC=0.726、0.798).HB组T1、T2比值与TSB水平均无相关性(P＞0.05).结论 T1和T2相对比值可用于新生儿胆红素脑病的早期诊断,其中T1比值诊断效能最佳,尤其能够提高对内眼不可见的早期病变的检出率.     

梅毒螺旋体溶血素生物信息学分析

目的本研究旨在对梅毒螺旋体(Tp)的5种溶血素进行进一步的生物信息学分析,为后续研究溶血素家族蛋白在Tp致病过程中的致病机制提供依据。 方法通过使用NCBI、BLAST、CDD、BioEdit、ExPASy、SignalP、TMHMM、MEGA、PSORTb 3.0、ABCpred等生物信息学分析方法分析梅毒螺旋体溶血素家族蛋白的一般性质、信号肽、糖基化、磷酸化位点、亚细胞位置、二级结构、功能结构域及抗原表位。 结果预测了Tp中5个溶血素家族蛋白一般性质,Tp1037功能结构域不同于其余4种,Tp0028含有1个信号肽,Tp0027含有1个糖基化位点,Tp0027和Tp1037有多个跨膜结构域,5个溶血素家族蛋白均含有多个磷酸化位点和B细胞、T细胞表位。 结论Tp含有5个溶血素家族蛋白基因,提示Tp入侵宿主时这些基因产物极有可能通过其膜成孔毒性损伤靶细胞,从而致病。     

5334例住院患者HBsAg、抗-HCV、抗-HIV1/2和TP-Ab的检测结果分析

目的 检测5334例住院患者HBsAg、抗-HCV、抗-HIV1/2和TP-Ab并分析检测结果.方法 采用ELISA法检测5334例住院患者HBsAg、抗-HCV、抗-HIV1/2和TP-Ab阳性情况,并分析HBsAg、抗-HCV、抗-HIV1/2和TP-Ab检测阳性者性别和年龄分布.结果 5334例住院患者HBsAg阳性率最高(7.56％),抗-HIV1/2阳性率最低(0.52％);男性患者HBsAg、抗-HCV、TP-Ab检测阳性率与女性患者比较,差异无统计学意义(P＞0.05);男性患者抗-HIV1/2检测阳性率显著高于女性患者,差异具有统计学意义(P＜0.05);成年组患者HBsAg和抗-HCV阳性率均显著高于青少年组,差异具有统计学意义(P＜0.05);老年组患者HBsAg、抗-HCV和TP-Ab阳性率均显著高于青少年组,差异具有统计学意义(P＜0.05);老年组患者HBsAg、TP-Ab阳性率均显著高于成年组,差异具有统计学意义(P＜0.05);不同年龄组患者抗-HIV1/2阳性率比较,差异无统计学意义(P＞0.05).结论 住院患者乙型肝炎感染率较高,艾滋病感染存在性别分布差异,乙肝、丙肝和梅毒感染在年龄分布上存在差异.     

Increasing Endocannabinoid Levels in the Ventral Pallidum Restore Aberrant Dopamine Neuron Activity in the Subchronic PCP Rodent Model of Schizophrenia

Background:

Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide. In addition, increasing endocannabinoid levels (by blockade of enzymatic degradation) has been reported to attenuate social withdrawal in a preclinical model of schizophrenia. Here we examine the effects of increasing endogenous cannabinoids on dopamine neuron activity in the sub-chronic phencyclidine (PCP) model. Aberrant dopamine system function is thought to underlie the positive symptoms of schizophrenia.

Methods:

Using in vivo extracellular recordings in chloral hydrate–anesthetized rats, we now demonstrate an increase in dopamine neuron population activity in PCP-treated rats.

Results:

Interestingly, endocannabinoid upregulation, induced by URB-597, was able to normalize this aberrant dopamine neuron activity. Furthermore, we provide evidence that the ventral pallidum is the site where URB-597 acts to restore ventral tegmental area activity.

Conclusions:

Taken together, we provide preclinical evidence that augmenting endogenous cannabinoids may be an effective therapy for schizophrenia, acting in part to restore ventral pallidal activity.     

Stability and Dynamics of Forebrain Vasopressin Receptor and Oxytocin Receptor During Pregnancy in Prairie Voles

During pregnancy, females undergo several physiologically driven changes that facilitate adaptive behaviours and prepare the mother to care for her developing offspring. The nonapeptide hormone oxytocin is best recognised for its involvement in mammalian pregnancy and has been tightly associated with maternal care, in addition to its roles in pregnancy, parturition and lactation. A closely-related nonapeptide hormone, arganine vasopressin, has received considerably less attention for its role in pregnancy, although it has recently been implicated in modulating maternal care and aggression. In the present study, we examined the expression patterns of receptors for oxytocin (OXTR) and vasopressin (V1aR) over the course of pregnancy, ranging from non-mated virgin to immediately postpartum female prairie voles (Microtus ochrogaster). Unexpectedly, we found that OXTR was highly stable in all measured structures in the forebrain. V1aR was also stable throughout most of the brain. Two exceptions to this were found in the ventral pallidum (VPall) and the paraventricular nucleus of the hypothalamus (PVN); both significantly correlated with the length of time that females were pregnant. Changes in the PVN may reflect functional feedback in vasopressin release, or preparatory changes for ensuing maternal behaviour. The results also indicate an unappreciated role for VPall V1aR in pregnancy, which may relate to the function of the VPall in hedonic ‘liking’ and motivational ‘wanting.’ Taken together, our data indicate that, with a few compelling exceptions, nonapeptide dynamics during prairie vole pregnancy are largely limited to changes in the synthesis and release of oxytocin and vasopressin, and not the receptors to which they bind.     

Current status of syphilis in pregnant women in Japan

We examined the current status of syphilis-infected pregnant Japanese women, according to the results of syphilis screening and confirmation tests of women who gave birth in Japan between October, 2015 and March, 2016. We requested 2458 obstetrical facilities to provide information of syphilis screening tests and 78.1% of them responded. Considering the response rate and the rate of implementation of confirmation tests, the number of syphilis-infected pregnant Japanese women was estimated to be 250 (1/4022) per year.     

Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates

Background

Syphilis is resurgent in many developed countries and still prevalent in developing nations. Current and future control campaigns would benefit from the development of a vaccine, but although promising vaccine candidates were identified among the putative surface-exposed integral outer membrane proteins of the syphilis spirochete, immunization experiments in the rabbit model using recombinant antigens have failed to fully protect animals upon infectious challenge. We speculated that such recombinant immunogens, purified under denaturing conditions from Escherichia coli prior to immunization might not necessarily harbor their original structure, and hypothesized that enhanced protection would result from performing similar immunization/challenge experiments with native antigens.

Chemogenetic manipulation of ventral pallidal neurons impairs acquisition of sign‐tracking in rats

Cues associated with rewarding events acquire value themselves as a result of the incentive value of the reward being transferred to the cue. Consequently, presentation of a reward‐paired cue can trigger reward‐seeking behaviours towards the cue itself (i.e. sign‐tracking). The ventral pallidum (VP) has been demonstrated to be involved in a number of motivated behaviours, both conditioned and unconditioned. However, its contribution to the acquisition of incentive value is unknown. Using a discriminative autoshaping procedure with levers, the effects of disrupting VP activity in rats on the emergence of sign‐tracking was investigated using chemogenetics, i.e. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Transient disruption of VP neurons [activation of the inhibitory hM4D(Gi) DREADD through systemic injections of clozapine N‐oxide (CNO) prior to each autoshaping session] impaired acquisition of sign‐tracking (lever press rate) without having any effect on approach to the site of reward delivery (i.e. goal‐tracking) or on the expression of sign‐tracking after it was acquired. In addition, electrophysiological recordings were conducted in freely behaving rats following VP DREADD activation. The majority of VP units that were responsive to CNO injections exhibited rapid inhibition relative to baseline, a subset of CNO‐responsive units showed delayed excitation, and a smaller subset displayed a mixed response of inhibition and excitation following CNO injections. It is argued that disruption of VP during autoshaping specifically disrupted the transfer of incentive value that was attributed to the lever cue, suggesting a surprisingly fundamental role for the VP in acquiring, compared with expressing, Pavlovian incentive values.