Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

马兜铃酸对大鼠肾功能和组织病理学影响及川芎嗪与苯那普利的干预作用

目的:通过动物实验,观察大鼠灌胃马兜铃酸(AA)后,肾功能及肾脏组织病理学改变,及川芎嗪、苯那普利对肾损害的干预作用.方法:雄性Wistar大鼠98只,SPF级,随机分为4组:正常对照组20只,实验组分为模型组、川芎嗪组、苯那普利组,每组26只;各实验组按AA 20 mg·kg-1·d-1关木通浸膏灌胃,2 h后按分组灌胃给药.川芎嗪50 mg·kg-1·d-1,苯那普利1.8 mg·kg-1·d-1;正常对照组、模型组灌胃饮用水.各组每周测量体重,分别于第4、8、12周处死动物;腹主动脉采血分离血清,检测肾功能;取肾组织进行病理形态学检查.结果:AA灌胃4周后各组血肌酐/体重水平明显增加,与正常对照组比较有统计学差异;与模型组比较,川芎嗪、苯那普利组血肌酐/体重水平显著降低,提示有改善肾功能作用.肾脏组织病理学可见模型组早期有明显的肾小管坏死,部分小管结构紊乱较严重,空泡变性明显;后期出现间质灶性纤维化,纤维化面积＞30%.川芎嗪、苯那普利治疗组的肾功能和组织学损害程度较轻微,纤维化程度约15%～20%.结论:马兜铃酸对大鼠肾脏具有肾毒性,可导致小管间质损害和肾纤维化.川芎嗪、苯那普利对马兜铃酸肾损害有保护作用,能减轻马兜铃酸造成的肾组织病理损害,减少肾纤维化程度.     

运动员动态心电图观察

目的:评价运动员动态心电图中特殊事件的意义。方法:为30名身体健康无自觉症状的运动员作动态心电图检查。然后对检查结果进行统计分析。结果:ST抬高18人,ST下移4人,室性早搏(VE)9人,室速(VT)1人,室上性早搏(SVE)12人,室上速(SVT)2人,I°房室传导阻滞(I°AVB)1人,Ⅱ°房室传导阻滞(Ⅱ°AVB)4人。结论:动态心电图中特殊事件的临床意义与事件出现的时间、频度有关。     

Effects of Platelet Factor 4 on Expression of Bone Marrow Heparan Sulfate in Syngenic Bone Marrow Transplantation Mice

Platelet factor 4 ( PF4) is a negativehematopoietic factor.It can inhibit the prolifera-tion of endothelial cells and hematopoietic stem/progenitor cells,particularly megakaryoryocyticcells,reversibly[1] ,inhibit DNA synthesis,blockcell cycle progression during S phase and reducethe sensibility of normal hematopoietic stem/pro-genitor cells,but not some cancer or leukemia celllines,to cytotoxic drugs and ionizing radia-tion[2 - 3] ,and it also can cause a population in-crease of the stem cel…     

Reframing climate change as a public health issue: an exploratory study of public reactions

Background  

Climate change is taking a toll on human health, and some leaders in the public health community have urged their colleagues to give voice to its health implications. Previous research has shown that Americans are only dimly aware of the health implications of climate change, yet the literature on issue framing suggests that providing a novel frame - such as human health - may be potentially useful in enhancing public engagement. We conducted an exploratory study in the United States of people's reactions to a public health-framed short essay on climate change.     

氟烷吸入麻醉引起c—fos基因在中枢神经系统的表达与分布

研究氟烷吸入麻醉在中枢神经系统作用部位。应用ｃ－ｆｏｓ基因免疫组织化学方法。ＳＤ大鼠在吸入氟烷浓度为０．７５％．１。５％和２％麻醉１ｈ后，Ｆｏｓ阳性神经元主要分布于端脑；梨状皮层，杏仁核簇，伏核，外侧隔核，终纹麻核、海马ＣＡＩ区，海马回嗅觉小岛；     

Changes of circulating TNF and its effects on Pseudomonas aeruginosa septic shock in rabbits

Itiswellknownthatcertaincytokinesplayapivotalroleinthedevelopmentoftraumaandshock.Tumornecrosisfactor(TNF)isapolypep-tiedcytokinesynthesizedinmonocytesandmacrophagesinresponsetolipopolysaccharide(LPS)stimulation-TherelationshipbetweenTNFandendotoxic-septicshockbecomesafocusoftheresearchofshockmediators[1'2].Alargeamountofexperimentalandclinicaldata[3-9JsuggestthatTNFplaysanimportantroleinthepathogenesisofendotoxic-septicshockbuttheprecisemechanismandtherelationshipofTNFtoshockseverityrem…     

呼吸道感染与气象因素的关系

呼吸道感染是呼吸系统常见病、多发病。利用杭州地区1990年1月～1992年12月气象资料作了统计分析，并对同期来海军杭州疗养院门诊就诊的呼吸道感染病人进行了调查。结果为1～3、11、12月发病率高，与5～9月相比有非常显著差异（P＜0．001），呼吸道感染与气温低，湿度高，温差大，天气骤变等气象因素密切相关。潮冷天气（气温在10℃以下），频繁降温（每月3次以上），大幅度降温（4℃以上）三种气象因素共同存在情况下可导致呼吸道感染性疾病的高发。同时从气象学角度提出了预防该病的一些措施。     

马兜铃酸致肾小管上皮细胞损害及释放内皮素与血管紧张素的实验研究

目的:探讨马兜铃酸(AA)对培养的肾小管上皮细胞的损害,及释放内皮素(ET)、血管紧张素(Ang-Ⅱ)的影响. 方法:5?S RPMI-1640培养肾小管上皮细胞(LLC-PK1),采用结晶紫染色法观察细胞增殖;荧光染色观察活细胞数目;酶动力学检测LDH活性,比色法检测NAG水平;透射电镜观察细胞超微结构;放射免疫法测定ET、Ang-Ⅱ的浓度.结果: (1) AA 40、80、160 μg/ml可明显抑制细胞增殖,结晶紫OD值显著减少,与无AA对照组比较P<0.01.在AA 40 μg/ml作用下,随着时间延长,活细胞数目逐渐下降,显示AA对细胞损伤有一定的延续性;增加LDH释放率和NAG酶水平,与无AA对照组比较P<0.01.细胞超微结构观察:AA 40 μg/ml作用24 h后,细胞超微结构发生显著改变,以核变异最突出, 出现染色质浓染、核边集、核缺失、核膜卷曲增厚,线粒体肿胀等严重细胞损伤改变.AA( 40、80、160 μg/ml)可明显刺激细胞释放ET、Ang-Ⅱ,与无AA对照组比较P<0.01.[ HT5"H 结论:马兜铃酸对肾小管上皮细胞有明显的细胞毒性损害作用,使细胞超微结构发生显著损伤性改变,刺激肾小管上皮细胞分泌和释放ET、Ang-Ⅱ,此作用可能与 AA的毒性有关.