Gemfibrozil absorption and elimination in kidney and liver disease

Summary The disposition of the lipid-lowering drug gemfibrozil was studied in patients with either renal (n= 8) or hepatic disease (n= 8) and compared to those of healthy volunteers (n= 6). Gemfibrozil was determined in plasma and urine by means of a HPLC method. Urine was also analyzed for gemfibrozil conjugates.Following oral administration of 900 mg gemfibrozil, maximal plasma levels of the parent drug were 46.1±15.8 g/ml, attained after 2.2±1.1 h. In chronic renal failure and in liver cirrhosis the plasma concentrations of gemfibrozil did not significantly differ from that of controls except in those patients who were comedicated with antacids. These patients had significantly lower C_max and AUC values. The elimination half-life of the drug was 1.5 h in controls, 2.4 h in renal failure, and 2.1 h in liver disease. In healthy volunteers, only 0.02 to 0.15% of the given dose was recovered in the urine as parent gemfibrozil, while conjugates made up 7–14%. In patients with renal failure also, only traces of parent gemfibrozil could be detected, and conjugates accounted for 0.5–9.8%. In those with liver disease, however, about 0.1–0.2% were recovered in urine as parent gemfibrozil and up to 50% as conjugates. Strikingly, the amount of excreted conjugates in the urine was positively correlated to the direct bilirubin plasma concentration. It can be concluded that the elimination of gemfibrozil is not significantly influenced by renal failure. However, comedication with antacids markedly reduced plasma disposition of the drug. Patients with severe liver disease excreted more conjugated gemfibrozil via the kidney than did healthy controls. Thus, transfer across the canalicular cell membrane to the bile duct, rather than drug metabolization, is primarily disturbed in liver disease. Gemfibrozil accumulation is unlikely to occur in either kidney or liver disease.Abbreviations Cl_r creatinine clearance (ml/min) - HPLC high pressure liquid chromatography - C_max maximal plasma concentration (g/ml) - t_max time (h) after which C_max is attained - k_e elimination rate constant (h^–1) - t_1/2 elimination half-life (h) - A_e amount of drug excreted into the urine (% of given dose) - MRT mean residence time (h) - AUMC area under the first moment curve (g h²/ml) - AUC area under the plasma level time curve (g·h/ml) - ANOVA analysis of variance The paper is gratefully dedicated to G.W. Löhr     

ICD-11与DSM-5关于排泄障碍诊断标准的异同

本文目的是对《精神障碍诊断与统计手册（第5版）》（DSM-5）和《国际疾病分类（第11版）》（ICD-11）中排泄障碍诊断标准的异同进行比较。排泄障碍的临床特征是不恰当的尿液和粪便的排泄,明显引起患者痛苦或功能损害。为了提高精神心理工作者对相应内容的理解,本文对排泄障碍的在两套诊断系统中的诊断要点进行总结和对比。     

2－芳基丙酸类消炎镇痛药物的研究5 羟醛缩合法合成酮基布洛芬

以环己酮为起始原料，经Ｓｔｏｒｋ烯胺反应、羟醛缩合、消除、芳构化制得酮基布洛芬，总收率４３．２％。     

山东省消除疟疾行动计划中期评估报告

山东省属于单一疟疾流行区,间日疟流行于全省各地。在上世纪60年代和70年代初期发生两次疟疾暴发流行。1988年通过原卫生部考核率先在全国范围内达到了基本消灭疟疾的标准。1989年以来,疟疾疫情有所波动,但均不超过1/10万。2010年山东省启动消除疟疾工作,原省卫生厅下发消除疟疾工作实施方案,提出到2018年全省达到消除疟疾的目标。连续两年下发消除疟疾考核评估方案,目前已顺利完成82个县和2个市的消除疟疾考核评估工作。自启动消除疟疾工作以来,山东省认真实施中央补助地方公共卫生专项疟疾项目,圆满完成项目规定的各项任务。另外,省财政每年列出专项经费用于疟防工作。2010—2015年山东省疟疾防治经费累计投入5 092.49万元,从经费上保证了消除疟疾工作顺利实施。为满足消除疟疾工作需要,该省通过分级培训的方式开展了各种技术培训,累计培训各级镜检员15 494人次,临床医生56 382人次,疟疾防治人员34 624人次。全省基本建成较为完善的省、市、县、乡四级疟疾镜检网络系统,每年均按照指标要求开展血检工作,2010—2015年共血检发热病人1 774 321人,检出疟疾病人747例,检出率为0.42‰。严格按照"1-3-7"工作管理要求开展病例的管理和疫点调查处置工作,2010—2015年山东省共报告疟疾病例819例,开展疫点处置819个,有效避免了疫情扩散及二代病例的发生。为动员全社会共同关注和支持消除疟疾工作,广泛宣传疟疾危害和防治知识,全省各级疾控机构结合"4.26"全国疟疾宣传日,每年均开展大规模的宣传活动,2010—2015年山东省累计发放健教材料7 040 504份。山东省已连续三年无本地感染病例,但逐年增加的境外输入性疟疾病例为消除疟疾工作带来新的挑战。针对当前疟疾形势,山东省在继续做好消除疟疾工作的同时必须加强对输入性疟疾的监测和管理,确保全省如期实现消除疟疾目标。     

鹅不食草水煎剂对绿脓杆菌R质粒体外消除作用的实验研究

目的 探讨中药鹅不食草水煎剂对绿脓杆菌R质粒的消除作用。方法 对临床分离的绿脓杆菌R质粒进行了检测,并选用中药鹅不食草水煎剂对该质粒进行了体外消除试验。结果 体外药物作用24h、48h、72h,R质粒消除率分别为0.7％、4.7％、46.3％,SDS对照组分别为0.3％、0.7％、1.7％。结论 鹅不食草对耐药质粒有较强的消除作用。     

监测与响应: 中国消除疟疾后的核心干预措施

2021年6月,我国顺利通过WHO消除疟疾认证。但我国每年仍有数千例境外输入疟疾病例,因输入性疟疾病例引起的死亡病例每年均有报告;由输入性疟疾导致的继发病例时有发生,由于原疟疾流行区传疟媒介依然存在,在疟疾消除地区由输入性病例再次引起本地传播的风险依然较大。本文就消除后阶段我国疟疾防控工作面临的风险、监测与响应工作中面临的挑战进行分析,并对今后工作重点提出相应建议。     

2019年江苏省疟疾疫情分析

目的　分析2019年江苏省疟疾疫情,为制订防止疟疾输入再传播监测策略和措施提供科学依据。方法　收集2019年江苏省疟疾病例报告信息、流行病学个案调查、疫点调查与处置结案报告等疟疾疫情资料,并采用描述性方法进行分析。结果　2019年江苏省累计报告疟疾病例244例,均为实验室确诊的境外感染输入性病例,其中间日疟4例、恶性疟206例、三日疟12例、卵形疟22例;11例发展为重症病例,1例死亡。全省13个设区市报告病例数居前5位的依次为南京、南通、连云港、泰州、常州,报告的疟疾病例数占全省报告病例总数的59.84%。2019年报告的244例疟疾病例中,2例感染地为大洋洲巴布亚新几内亚、1例为亚洲巴基斯坦,其他241例均为非洲的27个国家或地区,其中输入来源较多的国家为安哥拉、刚果民主共和国、尼日利亚、赤道几内亚和科特迪瓦。244例疟疾病例中,在发病当天和发病后1～3 d就诊分别有77例（31.55%）和146例（59.84%）,首次就诊和就诊后1～3 d确诊分别有149例（61.06%）和77例（31.55%）,从就诊到确诊平均时间为（0.80 ± 1.59）d,较2018年的（1.34 ± 2.59）d显著缩短（U = 2.53,P < 0.05）。结论　江苏省应继续加强输入性疟疾监测和管理,提高输入性疟疾诊断能力和危重疟疾病例救治能力,以巩固消除疟疾成果。     

The global epidemiological situation of schistosomiasis and new approaches to control and research

While the distribution of schistosomiasis has changed over the last 50 years and there have been successful control programmes, the number of people estimated to be infected or at risk of infection has not been reduced. Today, 85% of the number of infected people are estimated to be on the African continent where few control efforts are made. In terms of disease burden, there is therefore a growing discrepancy between sub-Saharan Africa and the rest of the world. WHO has now developed a dual strategy for the control of schistosomiasis: a strategy for morbidity control adapted to the public health context in high burden areas, and a strategy to consolidate control in areas where a low endemic level has been reached and elimination may be feasible. Related to this new vision, some research needs are pointed out.     

Cellular uptake,elimination and toxicity of CdSe/ZnS quantum dots in HepG2 cells

In this work, the cellular uptake, elimination and toxicity of CdSe/ZnS QDs in HepG2 cells were comprehensively studied using inductively coupled plasma mass spectrometry (ICP-MS), MTT assay, AO/EB staining, and glutathione level and gene expression analysis. ICP-MS analytical results showed that the uptake efficiency of CdSe QDs by HepG2 cells was lower than that of Cd(II) and Se(IV), and the uptake was dose- and time-dependent. The uptake amount was related to the physicochemical properties of QDs, and NH₂-QDs with smaller size were more easily taken up by cells. In combination with various biochemical methodologies, a systematic and thorough quantitative analysis of the in vitro effects of CdSe/ZnS QDs with different coatings was conducted, along with that of Cd (II) and Se (IV). Although Cd(II) above 8.9 μM exhibited obvious toxicity to the cells, no obvious toxicity of four CdSe/ZnS QDs was observed within the tested concentration range (10–100 nM), most likely due to the protection of the ZnS shell and the PEG coating. From the molecular level's point of view, QDs at concentration of 100 nM exhibit obvious impact on the cells, such as increased gene expression (MT1A and CYP1A1), which was positively correlated with the intracellular concentration of QDs.