Lipofibromatous hamartoma of a digital nerve. A case report

Lipofibromatous hamartoma is a rare, benign tumor, most often affecting the median nerve. Our case involved the volar radial digital nerve of the index finger, treated with a partial excision of the tumor. Important nerve branches should not be sacrificed in order to achieve radical excision.     

Fatal intoxications in Denmark following intake of morphine from opium poppies

Summary In Denmark it is legal to grow opium poppies for the production of poppy seeds and until 1986 for decoration purposes, too. Danish poppy capsules contain 0.3–5 mg morphine per capsule and the content of morphine in opium exuded from the capsules may amount to 24%. This has resulted in misuse as both fresh and dried poppy capsules have been used for the production of opium tea. During the period 1982–1985, seven casualties occurred among drug addicts in Denmark which were solely or partly caused by these opium poppies.     

Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis-dependent mechanism

AIM: In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis. EXPERIMENTAL DESIGN: Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax. RESULTS: Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In. CONCLUSION: The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis.     

TK-GFP fusion gene virus vectors as tools for studying the features of HSV-TK/ganciclovir cancer gene therapy in vivo

The fusion gene of herpes simplex virus thymidine kinase and green fluorescent protein (TK-GFP) was shown to be a versatile tool for examining the features of thymidine kinase/ganciclovir gene therapy in vitro. In this study, we used viral vectors carrying the fusion gene to characterize the aspects of this gene therapy form in rodent tumor models. Growth of subcutaneous 9L rat tumors transduced ex vivo with TK-GFP gene was prevented when ganciclovir (GCV) treatment was initiated immediately after tumor inoculation. Established tumors (>100 mm(3)), however, were untreatable despite the initial 55% proportion of TK-GFP positive cells. This was due to a rapid clearance of TK-GFP positive cells, but not GFP positive cells. Propidium iodide staining revealed that TK-GFP lentivirus vector was able to induce apoptosis/necrosis in 9L cells, as opposed to the respective GFP vector. Furthermore, when a subcutaneous nude mouse tumor model was used, the percentage of TK-GFP positive cells in vivo was maintained similarly as in cultured cells, suggesting contribution of a fully functional immune response to the disappearance of fusion gene positive cells. In vivo gene transfer studies: adenovirus TK-GFP vector injections resulted in about 25% gene transfer efficiency to 9L tumors and showed that their growth could be significantly reduced even when the tumor volumes were already >120 mm(3). Part of the effect was shown to be due to cytotoxicity of the vector. In summary, our results demonstrate the utility of TK-GFP fusion gene-carrying viral vectors in animal studies and show that readily detectable therapeutic genes can help us to understand the complicated nature of in vivo cancer gene therapy experiments.     

Molecular epidemiology of an outbreak caused by methicillin-resistant Staphylococcus aureus in a health care ward and associated nursing home

Our point-prevalence survey followed an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a long-term care facility and identified five MRSA strains, of which two possessed an outbreak genotype not encountered previously and three had another profile. All of them possessed SCCmec type V. Six methicillin-sensitive S. aureus strains were genotypically related to the epidemic strains.     

Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat

Summary Copulatory behavior in the ovariectomized rat, the lordotic response (L. R.), was induced by estrogen followed by progesterone. L. R. is inhibited by lysergic acid diethylamide (LSD) (0.05 mg/kg) and by Levo-5-hydroxytryptophan (L-5-HTP) (2.5 mg/kg). The effects of the putative 5-HT antagonists lisuride, metergoline, methysergide, mianserin, cinanserin, cyproheptadine, pirenperone and altanserin on the LSD-induced inhibition of L. R. were tested. Lisuride, metergoline, methysergide and mianserin were found to have no LSD-blocking effect. In contrast, cinanserin, cyproheptadine and pirenperone acted antagonistically to LSD, within a critical dose range. The selective 5-hydroxytryptamine₂ (5-HT₂) receptor antagonist altanserin effectively prevented the LSD-induced inhibition of L. R., and the doses required (0.05–0.20 mg/kg) indicated a comparatively high antagonistic potency. In addition altanserin (0.2 mg/kg) effectively prevented the lordosis inhibitory effect induced by L-5-HTP (2.5 mg/kg), after pretreatment with pargyline and RO4-4602. It is suggested that the suppression of copulatory behavior caused by LSD and L-5-HTP is mediated by 5-HT₂ receptors.     

基于UHPLC-QE-MS分析结合网络药理学探讨小叶黄杨生物碱治疗阿尔茨海默病的作用机制

目的 鉴定小叶黄杨中生物碱类化学成分，探讨治疗阿尔茨海默病的物质基础和作用机制。方法 表征小叶黄杨生物碱成分，并利用PubChem、SwissADME、Swiss Target Prediction、Genecards和OMIM等数据库获取小叶黄杨生物碱的活性成分和对应靶点，以及阿尔茨海默病的相关靶点；运用Cytoscape3.9.0软件绘制“成分-靶点”网络图；运用String平台构建蛋白互作网络图；运用微生信在线绘图工具进行通路富集分析可视化；用AutodockTools-1.5.6软件对筛选出的核心成分做分子对接。结果 鉴定小叶黄杨生物碱成分23个，筛选有效成分19个，对应靶点216个；筛选阿尔茨海默病靶点880个，药物-疾病交集靶点49个；GO富集分析主要相关的生物过程有化学性突触传递，顺行跨突触信号，跨突触信号等；KEGG通路富集分析中神经活性配体-受体相互作用，5-羟色胺能突触，cAMP信号等为主要信号通路。分子对接显示筛选的核心靶点和核心成分均有较强结合力。结论 本研究初步证明了小叶黄杨生物碱成分可以多成分、多靶点、多通路共同作用治疗阿尔茨海默病，为进一步深入研究小叶黄杨生物碱对阿尔茨海默病作用的物质基础以及作用机制提供参考。     

基于方剂数据分析的中药用量历史变迁规律研究

目的：分析不同朝代方剂中药剂量单位及其用量的历史演变规律，为中药临床用量提供参考。方法：对《中医方剂大辞典》中收载的九万余首方剂信息进行结构化和标准化处理，构建方剂数据库，并参考文献，对不同年代的用量单位按照现代单位进行了换算，采用断代史研究方法，分析方剂中药用量的演变规律。结果：筛选有中药组成的方剂8万4千余首，涉及用量单位375个，体积单位包括升、合等149种；数量单位86种；重量单位有两、钱等63种；长度单位包括寸、尺等7种，面积单位3种；历代使用频数最多的用量单位是“两”，达一半以上，其次是钱，以清代和民国时期使用频率最高。为了探究中药每日内服用量的规律，我们筛选了13,834首能代表每日服用剂量的内服方剂，有确切用量记载的药物频次81 830次，其中以长度为单位的中药平均长度为10.19 cm；以体积为单位的中药平均体积为753.24 mL；以重量为单位的中药频次是80 135次，平均重量为21.46 g。不同朝代内服方剂单味药一日平均用量唐朝最大，达到82.53 g，其后用量减少，至明以后用量与现代相差不大，多为10 g左右。结论：本研究首次基于大样本量的方剂数据，采用剂量换算和断代史研究方法，分析了不同历史时期中药用量的概貌和演变规律，发现了历代中药用量差异很大，是受诸多因素的影响。现代临床的中药用量，不应局限于古代文献记载，而应根据当前药物的特点，药材性效毒性的变化以及病人的病情、体质等灵活运用，方能达到药到病除，发挥中药的原创优势。