Understanding how Listeria monocytogenes targets and crosses host barriers

Human listeriosis is caused by the Gram-positive bacterium Listeria monocytogenes. In humans, this pathogen has the ability to cross the intestinal, placental and blood-brain barriers, leading to gastroenteritis, maternofetal infections and meningoencephalitis, respectively. The entry of L. monocytogenes into cultured human epithelial cells is mediated by the interaction of an L. monocytogenes surface protein, internalin, with its human receptor, E-cadherin. The internalin-E-cadherin interaction is species-specific, and relies on the nature of a single amino-acid in the E-cadherin molecule, which is proline in permissive species such as humans, and glutamic acid in non-permissive species such as the mouse. In a transgenic mouse model that expresses human E-cadherin in enterocytes, internalin allows L. monocytogenes to cross the intestinal barrier. Epidemiological evidence also supports a role for internalin in human listeriosis, not only for crossing the intestinal barrier, but also for targeting and crossing the placental and blood-brain barriers. Consistent with these epidemiological data, infection with L. monocytogenes of trophoblastic cell lines, primary trophoblast cultures and human placental villous explants demonstrates that bacterial invasion of the syncytiotrophoblast barrier is mediated by the internalin-E-cadherin interaction, leading to histopathological lesions that mimic those seen in the placentas of women with listeriosis. Thus, the internalin-E-cadherin interaction that plays a key role in the crossing of the intestinal barrier in humans is also exploited by L. monocytogenes to target and cross the placental barrier. Further investigations are currently focusing on the molecular mechanisms by which L. monocytogenes targets and crosses the blood-brain barrier.     

大鼠创伤性肠粘连模型的制备及黄厚排气颗粒对其粘连程度的影响

为筛选出操作方法简便，结果稳定可控的大鼠创伤性肠粘连模型，观察中药复方黄厚排气颗粒对其粘连程度的影响，选用SD大鼠，手术造成肠粘连模型，用中药复方2．5、5．0、10．0g/kg连续治疗7d后观察肠粘连程度。结果表明，以盲肠型动物模型的制备较为理想，手术易于操作，结果稳定可控。用中药复方治疗后模型动物的肠粘连程度得到明显改善。提示黄厚排气颗粒对术后肠粘连有一定的预防作用。     

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01–1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.Supported by NIH MH42803 and RCMI Grants RR03061 and RR01825     

脑动静脉畸形实验动物模型的建立

脑动静脉畸形是一种比较常见的严重威胁人们生命安全和生存质量的脑血管疾病，目前人们主要是通过尸体解剖以及CT、MRI等影像学的方法认识。近年来，学者们应用各种动物模型来研究脑动静脉畸形的血流动力学，病理生理学以及脑动静脉畸形栓塞材料的评估，栓塞后临床疗效评价，放射照射剂量对脑动静脉畸形的影响等。本文就脑动静脉畸形实验动物的常用种类，动物模型的建立方法以及动物模型的实际应用进行了综述。     

激素性股骨头缺血坏死MRI诊断的实验研究

目的：建立股骨头缺血坏死(ANFH)动物模型，将磁共振成像(MRI)表现与组织病理学结果对照，探讨早期ANFH的病理变化和删表现的病理学基础。方法：成年新西兰兔36只，随机均分成三组。A组：为正常对照组，静脉注射生理盐水。B、C组为实验组，B组：单纯静脉注射地塞米松10mg／kg／d连续7天，间隔两周再重复一次。C组；马血清与激素共用，先静脉注射马血清10g／kg，间隔2周再重复一次；继之重复B组给药。之后4、8、16、26周后分别从3组随机各取3只，先拍X线平片再进行删，然后取双侧股骨头做组织病理检查。结果：实验组兔股骨头第8周T1WI信号强度明显降低，T2WI呈不均匀高信号，对应病理改变为骨髓水肿，骨髓腔内少量出血和少量骨细胞坏死。16、26周T1WI信号强度增高，病理显示骨髓脂肪细胞肥大并融合成大泡状，大量骨细胞坏死，骨小梁变细、中断。16、26周兔股骨头X线平片示骨质稀疏，骨小梁模糊。C组上述变化较B组显著。结论：1．采用马血清和肾上腺皮质激素共用，比单纯用肾上腺皮质激素更易诱导出较典型的ANFH动物模型。2．删能够较全面反映早期激素性ANFH的病理变化。     

骨质疏松动物实验骨折风险性分析

目的:评价骨质疏松动物模型发生骨折的风险性.方法:健康雌性SD大鼠36只,随机分为实验组和对照组各18只.实验组切除双侧卵巢,对照组仅切开皮肤.于术后2、4、8周两组处死6只大鼠,作松质骨(腰椎)和皮质骨(股骨干)骨密度(BMD)组织形态学和力学测定.结果:与对照组相比,手术组松质骨BMD 2、4、8周均明显下降,2周皮质骨无明显差异,4、8周则明显下降;股骨中段骨皮质厚度变薄;骨小梁体积(TBV)占全部骨组织体积(TTV)的百分比明显减少;成骨细胞和破骨细胞明显增多;股骨最大弯曲载荷、腰椎最大压缩载荷下降.     

肌腱结嵌压固定法重建前交叉韧带生物力学实验研究

目的探讨绳肌腱结嵌压固定法重建前交叉韧带(ACL)影响初始固定效果的相关因素及对策。方法采用猪膝关节模拟重建ACL不同术式,即绳肌腱结股骨隧道嵌压固定和胫骨端肌腱编织缝合骨桥打结固定法,与骨-髌腱-骨两端界面螺钉固定法,比较其生物力学初始固定最大拔出载荷、抗拉刚度和位移等生物力学指标。结果最大抗拉载荷肌腱结组与正常ACL组接近,无显著性差异;肌腱结组大于骨-髌腱-骨界面螺钉固定组。抗拉载荷在100N和400N时的位移两组无显著性差异。胫骨端肌腱编织缝合骨桥上打结固定组最大抗拉载荷大于BPTB界面螺钉固定组和肌腱编织缝合后界面螺钉固定组。抗拉刚度正常ACL组>骨-髌腱-骨组>绳肌腱结组。最大位移正常ACL<髌腱骨组<肌腱结组。结论绳肌腱结嵌压固定法抗拉强度和刚度完全可以满足重建后ACL的生理需求;术中克服位移因素,是有效防止ACL重建术后松弛的关键。     

神经根慢性嵌压损伤的动物模型建立

目的：建立一种由自身骨性增生造成神经根慢性嵌压损伤的动物模型，为相关实验提供造模方法一方法：30只健康家猫，手术显露右侧C7、C8和L5、L6冲经根及其椎问孔内口，用牙髓钻破坏椎间孔周围骨皮质后，将“V”形松质骨块沿骨壁嵌于神经根通道的骨性管道内及侧隐窝后方，左侧做正常对照。在造模术前和术后第2、4、8、12、24周行磁刺激运动诱发电位(MEP)检测，每次随机选6只，4～5只行影像学检查，以确定神经根通道的狭窄程度和神经根受压状态，6只均做病理组织学检查和椎间孔截面积测量。结果：术后早期实验侧肢体出现行为异常：而后有不同程度肌萎缩；后期部分肢体远端出现溃疡。影像学检查随着嵌压时间延长．实验侧椎间孔骨痂增多，狭窄加重。神经根受压变形，椎间孔骨性截面积8周后明显减小，与对照侧比较有显著性差异。术后2周，神经根组织学检查主要表现为神经束膜、内膜的水肿。髓鞘肿胀；4周后发生节段性脱髓鞘：8周时神经轴突增粗、断裂，远端瓦勒氏变性；12周后变性冲经结构崩解、吸收，形成空洞：24周时整个神经干纤维化。术后4周时实验侧MEP开始出现潜伏期延长；8周时伴有波形分化不清；12周波幅明显下降：24周MEP的引出困难，部分电位消失。结论：采用椎问孔内自体松质骨植入，造成神经根慢性嵌压性损伤模型成功率高，操作简单，适用于脊柱各个节段，其损伤部位和形式与临床更为接近。     

天冬胶作为血管栓塞剂毒性实验的初步报告

目的:从其毒性和相关特性方面研究天冬胶作为血管栓塞剂的可行性。方法:昆明小鼠腹腔注射天冬胶后观察外貌行为、食物消耗、体重情况。最后检测WBC、血小板、RBC和Hb浓度;测定血清ALT、肌酐和尿素氮浓度。病理检查心、肝、肾、脾、脑、腹膜、生精组织及腹壁肌肉。大腿肌肉注射天冬胶的小鼠1、3、7 d后各处死,取局部肌肉标本送病理检查。结果:1.仅实验组给药后第1天反应稍差及食量显著低于对照组(P<0.001)外,第2天起各组外貌行为无异常、食量无显著差异(均P>0.05)。2.各组小鼠的体重随时间而增加,除实验组2于实验1周后增长速度显著低于实验组1(P<0.02)和对照组(P<0.001)外,其他无显著差异。3.各组血WBC、血小板、RBC、Hb及血清ALT、肌酐和尿素氮浓度无显著差别。4.仅1个实验组小鼠肝脏内可见多灶性淋巴细胞和其他炎症细胞浸润区,其他组肝脏表现正常。实验组腹膜出现少许慢性炎症细胞的浸润和间皮细胞的增生。其他均无病理改变。大腿肌肉内仅见少许残留异物,无病理改变。结论:天冬胶使用安全、生物相容性较好,作为血管栓塞剂有较好的前景。