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Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

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World Journal of Hepatology 2014年第1期6卷 17-32页

作者： rolf Teschke Albrecht Wolff Christian Frenzel Alexander Schwarzenboeck Johannes Schulze Axel Eickhoff Department of Internal Medicine Ⅱ Klinikum Hanau Academic Teaching Hospital of the Medical Faculty of the Goethe University of Frankfurt/Main Department of Internal Medicine Ⅱ Division of Gastroenterology Hepatology and Infectious Diseases Friedrich Schiller University Jena Department of Medicine Ⅰ University Medical Center Hamburg Eppendorf Institute of Industrial Environmental and Social Medicine Medical Faculty Goethe University

Causality assessment of suspected drug induced liver injury(DILI) and herb induced liver injury(HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences(CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved. 2014 Baishideng Publishing Group Co., Limited. All

关键词： Drug induced liver injury Drug hepatotox-icity Herb induced liver injury Herbal hepatotoxicity Causality assessment

Design,synthesis and biological evaluation of pyridyl substituted benzoxazepinones as potent and selective inhibitors of aldosterone synthase

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Chinese Chemical Letters 2021年第7期32卷 2327-2332页

作者： Haichao Zhu Meihua Liu Haiyan Li Ting Guan Qi Zhang Yang Chen Yingxiang Liu rolf RHartmann Lina Yin Qingzhong Hu School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhou 51006China Pharmaceutical and Medicinal Chemistry Saarland UniversityCampus C2.3D-66123SaarbruckenGermany

Exorbitant aldosterone is closely associated with various severe diseases,including congestive heart failure and chronic kidney *** aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis,its inhibition constitutes a promising treatment for these *** a structure-based approach,a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2 H)-ones were designed as inhibitors of aldosterone *** compounds(5 j,5 l,5 m 5 w,5 x and 5 y)distinguished themselves with potent inhibition(IC50<100 nmol/L)and high selectivity over homogenous 11β-*** the most promising compound,5 x exhibited an IC_(50) of 12 nmol/L and an excellent selectivity factor(SF)of157,which are both superior to those of the re ference fadrazole(IC_(50)=21 nmol/L,SF=7).Importantly,5 x showed no inhibition against steroidogenic CYP17,CYP19 and a panel of hepatic CYP enzymes indicating an outstanding sa fety *** it manifested satis factory pharmacokinetic pro perties in rats,compound5 x was considered as a drug candidate for further development.

关键词： Aldosterone synthase Selective inhibitors Benzoxazepinones Heart failure Renal diseases

Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study

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World Journal of Hepatology 2017年第29期9卷 1141-1157页

作者： Dieter Melchart Stefan Hager Sabine Albrecht Jingzhang Dai Wolfgang Weidenhammer rolf Teschke Institute for Complementary and Integrative Medicine University Hospital Zurich and University of Zurich Competence Centre for Complementary Medicine and Naturopathy (Co Co Nat) University Hospital Munich rechts der Isar Technical University of Munich Hospital for Traditional Chinese Medicine Beijing University of Chinese Medicine Department of Internal Medicine Ⅱ Division of Gastroenterology and Hepatology Klinikum Hanau Teaching Hospital of the Medical Faculty of the Goethe University

AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver *** Patients with normal values of alanine aminotransferase(ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method(RUCAM) was *** This report presents for the first time liver injury data derived from a prospective, hospital-based and largescale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal(ULN) in 844 patients(3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients(0.12%) experienced higher ALT values of ≥ 5 × ULN(300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26(0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.

关键词： Traditional Chinese Medicine Herbal medicine Liver injury Roussel Uclaf Causality Assessment Method Herb induced liver injury

Impact of Colonization of an Invasive Species on Genetic Differentiation in New Environments: A Study on American Artemia franciscana (Crustacea: Anostraca) in the United Arab Emirates

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Journal of Ocean University of China 2021年第4期20卷 911-920页

作者： ASEM Alireza SCHUSTER rolf EIMANIFAR Amin LU Hao LIU Chunwei WU Xiaofang YAO Liping MENG Xinyu LI Weidong WANG Peizheng College of Fisheries and Life Science Hainan Tropical Ocean UniversitySanya 572022China College of Ecology and Environment Hainan UniversityHaikou 570208China Central Veterinary Research Laboratory Dubai 597United Arab Emirates Independent Senior Research Scientist Industrial District21601 EastonMaryland 21601USA College of Ecology and Environment Hainan Tropical Ocean UniversitySanya 572022China

Artemia franciscana,native to America,has recently colonized as non-indigenous population in Asia,Europe,North Africa,and *** evaluated the effects of the colonization of *** on genetic differentiation in new environments in the United Arab Emirates(UAE).We used the COI marker to determine the genetic structure and origins of exotic populations in the *** confirmed the colonization of *** in two *** populations of *** had significantly lower genetic variation than native populations in the Great Salt Lake and San Francisco *** showed that the studied populations could not have colonized directly from natural American habitats,and they possibly were from secondary introduction events of other non-indigenous *** analysis yielded different demographic patterns for the studied invasive *** population in Al Wathba Wetland Reserve(AWWR)demonstrated demographic expansion,whereas in Godolphin Lakes(GL),it reached a demographic *** tests showed an excess of recent and historical mutations in the COI gene pool of invasive AWWR Artemia in the new *** results suggest that different ecological conditions in new environments can exert selective pressures during the introduction of an exotic population,which can affect genetic variation.

关键词： Artemia franciscana non-native population mtDNA-COI genetic variation biodiversity UAE

Two-photon lithography for 3D magnetic nanostructure fabrication

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Nano Research 2018年第2期11卷 845-854页

作者： Gwilym Williams Matthew Hunt Benedikt Boehm Andrew May Michael Taverne Daniel Ho Sean Giblin Dan Read John Rarity rolf Allenspach Sam Ladak School of Physics and Astronomy Cardiff University Cardiff UK IBM Research - Zurich Rüschlikon Switzerland Department of Electrical and Electronic Engineering University of Bristol Bristol UK

Ferromagnetic materials have been utilized as recording media in data storage devices for many decades. The confinement of a material to a two-dimensional plane is a significant bottleneck in achieving ultra-high recording densities, and this has led to the proposition of three-dimensional （3D） racetrack memories that utilize domain wall propagation along the nanowires. However, the fabrication of 3D magnetic nanostructures of complex geometries is highly challenging and is not easily achieved with standard lithography techniques. Here, we demonstrate a new approach to construct 3D magnetic nanostructures of complex geometries using a combination of two-photon lithography and electrochemical deposition. The magnetic properties are found to be intimately related to the 3D geometry of the structure, and magnetic imaging experiments provide evidence of domain wall pinning at the 3D nanostructured junction.

关键词： magnetism spintronics nanomagnefism three-dimensional (3D)lithography

Genotype frequency of gelatinase B C-1562 T polymorphism in coronary heart disease and myocardial infarction

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Journal of Geriatric Cardiology 2004年第2期1卷 114-118页

作者： Dieter Niederacher Roger Marx Thomas Scheffold rolf Michael Klein Molecular Genetics Laboratory of the Gynecology Division Henrich-Heine University DuesseldorfGermany Heart Center Wuppertal University of Witten-HerdeckeWuppertalGermany

Background One of the characteristics of atherosclerosis is a change in the content of extracellular matrix in the arterial wall. Gelatinase B, a member of the family of matrix metalloproteinase, can regulate extracellular matrix metabolismand play a role in the pathogenesis of atherosclerosis, coronary heart disease (CHD) and myocardial infarction (MI). Gelatinase B is polymorphic due to a C to T change at the position -1562 bp in the promoter *** relationship with gene product concentration in serum and its role in mediating the risk of CHD and MI in Germans is still unknown. Methods We enrolled 102 controls and 322 patients with angiographically documented CHD,including a sub-group of 173 patients with acute or chronic MI and 80 patients with acute coronary syndrome (ACS).All patients and controls were Germans and genotyped by polymerase chain reaction and digestion with SphI. Results We found that several classical risk factors for CHD and MI, including hypercholesterolemia and cigarette smoking,were significantly increased in CHD and MI patients compared with controls. Serum levels of gelatinase B and tissue inhibitor of metalloproteinase-1 were increased in the peripheral blood of patients with acute coronary syndrome. No significant differences in genotype or allelic frequencies between CHD, MI and control subjects of either men or women were found. Our search for a possible association of the polymorphisms with CHD and MI by logistic regression analysis was also negative. The serum concentrations of gelatinase B showed no differences between genotypes. Conclusions Our data showed that gelatinase B might provide an index of plaque activity in ACS, but gelatinase B protein was not affected by genotypes. Also, the T variant of gelatinase B was not associated with CHD or MI in Germans. (J Geriatr Cardiol 2004;1(2):114-118.)

关键词： gelatinase B gene polymorphism coronary heart disease myocardial infarction gelatinase B protein

Alleviating Bottlenecks in Power Interconnectors by Means of FACTS

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Journal of Energy and Power Engineering 2012年第12期6卷 2046-2053页

作者： rolf Grunbaum Talivaldis Podins ABB AB FACTS Vasteras SE-721 64 Sweden ABB S1A Riga 1058 Latvia

Power interconnections are becoming increasingly important in various parts of the world, as incentives for power exchange between countries are growing. A current example is that the Baltic Energy Market Interconnection Plan is launched by the European Council. For a variety of reasons, it is desirable to keep transmission corridors as slender as possible, i.e. keeping the number of lines as limited as possible, while still keeping adequate stability and power transmission capacity over the corridor. This is true, no matter whether it concerns a green-field project, or if it is a question of expanding an existing transmission corridor into higher power transmission capability. To achieve this, FACTS （flexible AC transmission systems）, based on state of the art high power electronics, is a highly useful option, from technical, economical and environmental points of view, to increase the utilization and stability of a transmission system or intertie. The paper presents salient design features as well as benefits of recently installed FACTS devices, more specifically SVC （static var compensators） and series capacitors, for enabling or improving cross-border as well as interregional power transfer in a cost-effective and environmentally friendly way.

关键词： FACTS power transmission stability SVC series compensation transient stability voltage stability.

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智能神经假体:心理与技术问题

生命科学 2009年第2期21卷 226-233页

作者： ECKMILLER rolf 德国波恩大学计算机系

近年来,微系统技术、神经计算和生物系统等高新技术的发展,为新型植入式智能神经假体装置的发展、生产和应用提供了巨大的可能。其中一项特别引人关注的进展就是智能视觉假体。虽然通过中枢视觉系统到知觉域的机制还未完全了解,但视觉... 详细信息

近年来,微系统技术、神经计算和生物系统等高新技术的发展,为新型植入式智能神经假体装置的发展、生产和应用提供了巨大的可能。其中一项特别引人关注的进展就是智能视觉假体。虽然通过中枢视觉系统到知觉域的机制还未完全了解,但视觉假体是通过电刺激视觉通路的不同部位来产生有用的视觉感受。许多年前,哲学和心理物理学研究都强调视觉感受可能是由不同的原因所引起。为了研制视觉假体,我们使用两张映射图来描述中枢视觉系统的功能是如何实现的。我们提出一种具有自学习功能且包括几个阶段的视网膜编码器(retina encoder,RE)。视网膜模块的RE模拟视网膜的功能并假定其实现了模式P1从物理域到神经域的映射操作M1。与此相对应的,中枢视觉系统模块则实现另一个映射操作M2,即M1在神经域的输出信号被转换到知觉域而产生视觉感受P2。在设定的迭代和基于感受的学习过程中,一名拥有正常视力的被试参与实验来提供由P1而产生P2的感性的相似性估计作为学习算法的输入,该算法反过来调整RE的参数矢量使得P2足够接近P1。更具体的说,全部RE时空滤波器可以借助遗传算法与被试交互式的实现调节。另一种视网膜编码器RE*使用特殊的时空滤波器组、决策树算法以及仿真的微小眼动算法组合构成。这种新编码器可以显著提高调节的结果。近期RE的研究集中在试图增强RE本身基于P1模式预处理的特性、模式分割、时间模式表达的选择性调整以及刺激电极簇的选择性控制。随着神经假体技术研究的不断深入和成熟,将会有越来越多的人受益。

关键词：智能神经假体视知觉

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可燃粉尘爆炸基础研究综述

安全与环境学报 2021年第3期21卷 1068-1075页

作者： ECKHOFF rolf K 李刚卑尔根大学物理和技术系挪威卑尔根NO-5007 东北大学火灾&爆炸防治实验室沈阳110819

对工业可燃粉尘爆炸基础研究进行了综述。对粉尘爆炸领域有史以来的主要基础研究成果进行了高度概括,内容涉及引起粉尘爆炸的可燃物质、影响粉尘云可燃性和爆炸性的因素、粉尘云在空气中的燃烧、引发粉尘爆炸的点火源、一次和二次粉尘... 详细信息

对工业可燃粉尘爆炸基础研究进行了综述。对粉尘爆炸领域有史以来的主要基础研究成果进行了高度概括,内容涉及引起粉尘爆炸的可燃物质、影响粉尘云可燃性和爆炸性的因素、粉尘云在空气中的燃烧、引发粉尘爆炸的点火源、一次和二次粉尘爆炸、粉尘闪燃、杂混物的爆炸及粉尘云爆轰8个方面。回顾了粉尘爆炸的预防和缓解措施进展,指出了本质安全设计的意义。最后针对纳米颗粒粉尘的爆炸特性进行了探讨,通常粉尘的最小点火能随粉尘粒径减小而减小、爆炸指数随粉尘粒径减小而增大,这种趋势直到粉尘粒径减小到1~10μm一直存在,但这种趋势可能不会持续到纳米粉体级别,可能的两个原因是纳米粉体的难于分散和凝并作用。

关键词：安全工程粉尘爆炸引燃源二次粉尘爆炸爆炸预防爆炸缓解