Recurrent Herpetic Stromal Keratitis in Mice,a Model for Studying Human HSK

Herpetic eye disease, termed herpetic stromal keratitis (HSK), is a potentially blinding infection of the cornea that results in over 300,000 clinical visits each year for treatment. Between 1 and 2 percent of those patients with clinical disease will experience loss of vision of the infected cornea. The vast majority of these cases are the result of reactivation of a latent infection by herpes simplex type I virus and not due to acute disease. Interestingly, the acute infection is the model most often used to study this disease. However, it was felt that a recurrent model of HSK would be more reflective of what occurs during clinical disease. The recurrent animal models for HSK have employed both rabbits and mice. The advantage of rabbits is that they experience reactivation from latency absent any known stimulus. That said, it is difficult to explore the role that many immunological factors play in recurrent HSK because the rabbit model does not have the immunological and genetic resources that the mouse has. We chose to use the mouse model for recurrent HSK because it has the advantage of there being many resources available and also we know when reactivation will occur because reactivation is induced by exposure to UV-B light. Thus far, this model has allowed those laboratories using it to define several immunological factors that are important to this disease. It has also allowed us to test both therapeutic and vaccine efficacy.     

大鳄龟感染蛙病毒的PCR检测及组织病理分析

2013年3月成都市某海洋馆送检2只发病大鳄龟(Macrochelys temminckii),临床特征表现为:精神状态萎靡,爬行无力,对外界刺激反应迟钝;颈部和四肢局部红肿,腹甲溃烂,严重部位甚至穿孔,最后死亡。为明确患病大鳄龟的病因,进行了细菌学、组织病理学和PCR检查。细菌学检查阴性;病理组织学观察发现,大鳄龟多组织、器官均发生严重病变,尤其是肾、肝、肺和心的损伤最为严重,表现为明显的变性、坏死和炎症细胞浸润,并在一些病变组织细胞浆内见嗜酸性或嗜碱性包涵体。针对蛙病毒(Ranavirus)病毒的特异性PCR检测扩增出蛙病毒主要衣壳蛋白(MCP)基因500 bp目的片段,测序后的DNA序列与Gen Bank中已知核酸序列进行Blast比对,发现其与Gen Bank中的蛙病毒主要衣壳蛋白基因同源性达95%~99%。根据组织病理特点及PCR检测结果推测大鳄龟的死亡是感染蛙病毒所致。     

Infection,inflammation and exercise in cystic fibrosis

Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF).Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health.In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF.     

Inhibition of Plasmodium sporozoites infection by targeting the host cell

There is a great need of new drugs against malaria because of the increasing spread of parasite resistance against the most commonly used drugs in the field. We found that monensin, a common veterinary antibiotic, has a strong inhibitory effect in Plasmodium berghei and Plasmodium yoelii sporozoites hepatocyte infection in vitro. Infection of host cells by another apicomplexan parasite with a similar mechanism of host cell invasion, Toxoplasma tachyzoites, was also inhibited. Treatment of mice with monensin abrogates liver infection with P. berghei sporozoites in vivo. We also found that at low concentrations monensin inhibits the infection of Plasmodium sporozoites by rendering host cells resistant to infection, rather than having a direct effect on sporozoites. Monensin effect is targeted to the initial stages of parasite invasion of the host cell with little or no effect on development, suggesting that this antibiotic affects an essential host cell component that is required for Plasmodium sporozoite invasion.     

Active K+ transport in Mycoplasma mycoides var. Capri. Net and unidirectional K+ movements

Analysis of the cation composition of growing Mycoplasma mycoides var. Capri indicates that these organisms have a high intracellular K⁺ concentration ($\text{K}{}_{\mathrm{<mtext>i</mtext>}}\text{: 200–300}\text{mM}$) which greatly exceeds that of the growth medium, and a low Na⁺ concentration ($\text{Na}{}_{\mathrm{<mtext>i</mtext>}}{}^{\mathrm{+}}\text{: 20}\text{mM}$). Unlike $\text{Na}{}_{\mathrm{<mtext>i</mtext>}}{}^{\mathrm{+}}\text{, K}{}_{\mathrm{<mtext>i</mtext>}}{}^{\mathrm{+}}$ varies with cell aging.The K⁺ transport properties studied in washed organisms resuspended in buffered saline solution show that cells maintain a steady and large K⁺ concentration gradient across their membrane at the expense of metabolic energy mainly derived from glycolysis. In starved cells, $\text{K}{}_{\mathrm{<mtext>i</mtext>}}{}^{\mathrm{+}}$ decreases and is partially compensated by a gain in Na⁺. This substitution completely reverses when metabolic substrate is added (K⁺ reaccumulation process). Kinetic analysis of K⁺ movement in cells with steady K⁺ level shows that most of K⁺ influx is mediated by an autologous K⁺-K⁺ exchange mechanism. On the other hand, during K⁺ reaccumulation by K⁺-depleted cells, a different mechanism (a K⁺ uptake mechanism) with higher transport capacity and affinity drives the net K⁺ influx. Both mechanisms are energy-dependent.Ouabain and anoxia have no effect on K⁺ transport mechanisms; in contrast, both processes are completely blocked by dicyclohexylcarbodiimide, an inhibitor of the Mg²⁺-dependent ATPase activity.     

肺炎支原体感染对川崎病的影响及机制探讨

目的 分析肺炎支原体感染对川崎病的影响及其机制,以期指导临床诊疗。 方法 回顾性分析2013年8月至2018年8月我科住院的496例川崎病患儿临床资料,其中合并肺炎支原体感染组193例,未合并肺炎支原体感染组303例。应用倾向评分匹配法1∶1校正2组的年龄、性别、是否为不完全型川崎病、是否使用糖皮质激素、丙种球蛋白使用时间、丙种球蛋白使用方法和阿司匹林初始剂量,比较2组患儿的总发热天数、冠状动脉直径、冠状动脉扩张发生率、冠状动脉瘤发生率和丙种球蛋白无反应发生率。 结果 川崎病合并肺炎支原体感染组男性患儿多,更易发生颈部淋巴结肿大,年龄、中性粒细胞百分比、血沉和低密度脂蛋白高于川崎病未合并肺炎支原体感染组,血钾、血钙、高密度脂蛋白和白蛋白低于川崎病未合并肺炎支原体感染组,差异有统计学意义(均P2=5.516,P结论 肺炎支原体感染可能引起川崎病患儿脂质代谢及电解质的紊乱,其炎症反应更强,持续时间更长,对冠状动脉损伤更大。     

泌尿生殖道非淋菌性感染的病原学以及耐药性分析

目的：探究泌尿生殖道非淋茵性感染的病原学以及耐药性,指导临床合理用药。方法：对我院2006年3月．2011年12月确诊的2136例非淋菌性泌尿生殖道感染患者进行标本采集,对病原体及其耐药性进行检测分析。结果：淋茵感染泌尿生殖道病原茵主要为CT及支原体,男性患者CT感染率高于女性患者,女性患者支原体感染率高于男性患者,此外,念珠茵、滴虫及其他难以检出细菌亦属于致病病原茵的一种;在12种抗生素中,多西环素、米诺环素及交沙霉素敏感率较高,均〉80％,罗红霉素、红霉素及环丙沙星敏感度较低,均〈20％。结论：非淋茵感染泌尿生殖道病原菌主要为CT及支原体,男性患者CT感染率高于女性患者,女性患者支原体感染率高于男性患者,病原茵对多西环素、米诺环素及交沙霉素耐药性较低,但不同地域病原茵耐药性亦存在差异,应按照实际情况进行耐药性检测,指导临床合理用药。     

Adenine aminohydrolase from Leishmania donovani: unique enzyme in parasite purine metabolism

Adenine aminohydrolase (AAH) is an enzyme that is not present in mammalian cells and is found exclusively in Leishmania among the protozoan parasites that infect humans. AAH plays a paramount role in purine metabolism in this genus by steering 6-aminopurines into 6-oxypurines. Leishmania donovani AAH is 38 and 23% identical to Saccharomyces cerevisiae AAH and human adenosine deaminase enzymes, respectively, catalyzes adenine deamination to hypoxanthine with an apparent K(m) of 15.4 μM, and does not recognize adenosine as a substrate. Western blot analysis established that AAH is expressed in both life cycle stages of L. donovani, whereas subcellular fractionation and immunofluorescence studies confirmed that AAH is localized to the parasite cytosol. Deletion of the AAH locus in intact parasites established that AAH is not an essential gene and that Δaah cells are capable of salvaging the same range of purine nucleobases and nucleosides as wild type L. donovani. The Δaah null mutant was able to infect murine macrophages in vitro and in mice, although the parasite loads in both model systems were modestly reduced compared with wild type infections. The Δaah lesion was also introduced into a conditionally lethal Δhgprt/Δxprt mutant in which viability was dependent on pharmacologic ablation of AAH by 2'-deoxycoformycin. The Δaah/Δhgprt/Δxprt triple knock-out no longer required 2'-deoxycoformycin for growth and was avirulent in mice with no persistence after a 4-week infection. These genetic studies underscore the paramount importance of AAH to purine salvage by L. donovani.     

迷迭香酸抗穿透支原体脂蛋白诱导巨噬细胞凋亡的作用研究

探讨迷迭香酸对穿透支原体脂蛋白诱导巨噬细胞凋亡的保护作用。方法:以穿透支原体脂蛋白损伤RAW264．7细胞为模型,用MTT法检测细胞存活状况,DNA片断化分析观察穿透支原体脂蛋白对RAW264．7细胞DNA降解的影响,碘化丙啶染色流式细胞术检测细胞凋亡率。结果:7．5mg/L穿透支原体脂蛋白可引起RAW264．7细胞存活率降低,出现细胞凋亡特征性“DNA梯带”,流式细胞术检测细胞出现凋亡亚G1期峰,凋亡率为31．9%;100μmol/L迷迭香酸预处理1小时后可以升高RAW264．7细胞的存活率,凋亡细胞特征性的梯状梯带消失,细胞凋亡亚G1期峰消失,并使RAW264．7细胞的凋亡率下降为7．9%。结论:迷迭香酸有抗穿透支原体脂蛋白诱导RAW264．7细胞凋亡的作用。