Toxicological evaluation of a chicory root extract.

An Ames test and a 28-day sub-chronic toxicity study in male and female Sprague-Dawley rats were conducted to evaluate the safety of a chicory root extract being investigated as a therapeutic for inflammation. Chicory extract had no mutagenic activity in the Ames test although it was cytotoxic to certain strains of Salmonella at higher doses with and without metabolic activation. For the 28-day rat study, measurements included clinical observations, body weights, food consumption, clinical pathology, gross necropsy and histology. There were no treatment-related toxic effects from chicory extract administered orally at 70, 350, or 1000 mg/kg/day. Since there were no observed adverse effects of chicory extract in these studies, the NOAEL for the extract is 1000 mg/kg/g administered orally for 28 days.     

骨骼肌再灌流损伤无再流的研究

目的：探讨一氧化氮与肢体骨骼肌再灌流损伤无再流变化的关系。方法：选兔２４只,随机分为实验组（硝普钠组和Ｌ－精氨酸组）及对照组,测定血清中肌酸磷酸激酶（ＣＰＫ）、一氧化氮（ＮＯ）含量;组织一氧化氮合成酶（ＮＯＳ）活性和肌组织局部血流量的变化;光镜、电镜观测组织结构变化。结果：实验组ＣＰＫ含量较对照组显降低;实验组肌原纤维溶解程度减轻;实验组局部血流量显升高。结论：应用促进ＮＯ合成的药物可减少骨骼     

Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms

Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite envenoming. In this study, we investigated the inhibiting effects of the small molecules varespladib (nonspecific phospholipase A₂ inhibitor), marimastat (broad spectrum matrix metalloprotease inhibitor) and dimercaprol (metal ion chelator) against coagulopathic toxins found in Crotalinae (pit vipers) snake venoms. Venoms from Bothrops asper, Bothrops jararaca, Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography, followed by nanofractionation and mass spectrometry identification undertaken in parallel. Nanofractions of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under study. Anticoagulant venom toxins were mostly identified as phospholipases A₂, while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine proteases. Varespladib was found to effectively inhibit most anticoagulant venom effects, and also showed some inhibition against procoagulant toxins. Contrastingly, marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant toxins. The information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates, and highlights their potential as future snakebite treatments.     

少或无脂肪型肾血管平滑肌脂肪瘤CT误诊原因探讨

目的探讨少或无脂肪型肾血管平滑肌脂肪瘤的误诊原因及对策。方法结合文献对临床经手术及病理证实的6例肾血管平滑肌脂肪瘤进行回顾性分析。结果少或无脂肪型肾血管平滑肌脂肪瘤CT及临床缺乏特征性,6例均误诊为肾癌。结论少或无脂肪型肾血管平滑肌脂肪瘤诊断困难,应结合多种影像学特点,采取薄层平扫及局部放大可以提高本病的诊断率。对于确实难以诊断的,应采取手术的方法切除肿瘤。     

丹红注射液合并硝酸甘油对急性心肌梗死患者PCI治疗中无复流现象及C-反应蛋白的影响

目的:研究急性心肌梗死(AMI)患者经皮冠状动脉介入(PCI)前静脉注射丹红注射液对术中无复流血流的改善及C-反应蛋白(CRP)的影响。方法:对120例AMI患者术前均给予阿司匹林300 mg、氯吡格雷300 mg等治疗。随机分成A组与B组两组,各60例。A组PCI术前予以丹红注射液,术中出现无复流2例,再予以硝酸甘油冠脉内给药;B组直接行PCI术,术中出现无复流8例,再予以硝酸甘油冠脉内给药,对比两组患者冠脉血流恢复情况。同时两组患者均在术前及术后监测CRP。结果:A组全部冠脉血流恢复TIMI3级,B组有4例冠脉血流恢复TIMI3级,且用丹红注射液组术后CRP降低更明显。结论:PCI术前静脉注射丹红注射液可以降低AMI患者的CRP值,且联合硝酸甘油后较单一给予硝酸甘油可更有效恢复无复流血管的TIMI血流值。     

Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs

Introduction: Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk–benefit profiles. This results in more complex albeit more promising treatment selection and choices.

Areas covered: The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented.

Expert opinion: Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.     

17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响

目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。     

恒河猴视觉分辨的反应抑制任务的行为训练及其应用

目的 训练恒河猴学习视觉分辨的go/no go任务（反应抑制任务的一种），以便进行认知神经科学、心理药理学、精神病学等领域的研究。方法 训练恒河猴一手不动，另一只手按压微动开关启动训练，并对屏幕上呈现的“□”做持续按压开关1s的反应，对“△”做松开开关的反应。应用该方法对两只恒河猴分三步进行训练（no go反应训练、go反应训练和go/no go反应训练。结果 经过30天左右的训练，两只猴正确反应率均可达85％以上，go反应的反应时为0．3－0．6秒。结论 此行为训练的方法简单、易行，是一种较好的go/no go任务的行为训练方法。     

Development of a novel method to measure the elastic properties of skin including subcutaneous tissue: New age‐related parameters and scope of application

Background/purpose: We have developed a new apparatus to measure the elastic properties of skin without contact using an air blown technique. Methods: Real‐time measurements of skin movement induced by air blown on the surface were measured at various times. We investigated age‐related changes in the displacement of the skin surface caused by air using various parameters. Ninety‐eight female Japanese volunteers, aged from 10 to 70 years, were used in this study. Results: The maximum distance (the denting state) that cheek skin moved reached 2–5 mm within 10–15 ms. After that, the skin generally recovered to its original state within 40–50 ms. The average maximum speed of movement was 0.49±0.08 (average±SD) m/s and the average recovery speed was 0.25±0.06 m/s. Significant changes with age were not observed in the denting state, but significant correlations with age were observed in the recovery state. The maximum recovery speed decreased significantly with age and the time required for recovery increased significantly with age. Although similar results were obtained at the corner of the mouth or the inner upper arm, different results were obtained at the below eyes and the forehead. Conclusions: This apparatus differs from other conventional instruments in that it measures the elastic properties of skin including subcutaneous tissue without contact.