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Effects of endothelin ETA receptor blocker LU 135252 on cardiac remod-eling and survival in a hypertensive rat model of chronic heart failure

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Acta Pharmacologica Sinica 2006年第11期27卷 1417-1422页

作者： Alexander REINECKE Marc DORENKAMP Mat Jap DAEMEN Reichiger SIMON thomas unger Clinic of Cardiology Christian-Albrechts-University of Kiel24105 KielGermany Institute of Pharmacology Christian-Albrechts University of Kiel24105 KielGermany Department of Pathology University of MaastrichtMaastrichtthe Netherlands

Aim:To investigate whether the endothelin ETAreceptor blocker provides similarbenefit on cardiac remodeling and survival in a hypertensive rat model of chronicheart failure（CHF）.Methods:Male stroke-prone spontaneously hypertensive（SHR-SP）rats were subjected to permanent ligation of the left coronary artery andwere treated for 6 weeks with the endothelin ETAreceptor blocker LU 135252(***-1.d-1)starting 24 h after ligation or ***-operated rats servedas normal *** mean arterial blood pressure（MAP）,heart rate（HR）,leftventricular end-diastolic pressure（LVEDP）,left ventricular contractility(LVdp/dtmax),left ventricular inner diameter（LVD）and circumference（LVC）,septalthickness,left ventricular interstitial collagen content（ICC）and heart weight（HW）were measured at the end of the ***:Compared with the untreatedgroup,LU 135252 tended to increase HW（1.43±0.03 vs 1.38±0.04 g;P>0.05）,increased LVD（7.65±0.24 mm vs 6.58±0.14 mm;P0.05）,reduced LVEDP（144mmHg vs 27±4 mmHg;P<0.05）andimproved LV dp/dtmax（4230±450 mmHg/s vs 1950±400 mmHg/s;P<0.05）;survivalwas not prolonged significantly（13% vs 11%;P=NS）.Conclusion:In this hyper-tensive rat model of CHF,chronic endothelin ETA receptor blockade with LU 135252improves cardiac hemodynamics,however,it does not affect long-term survivaland worsens cardiac ***,endothelin ETAreceptor antagonists areunlikely to have an important role in the management of patients with CHF.

关键词： myocardial infarction heart failure endothelin ET_A receptor antagonism LU 135252 cardiac remodeling ventricular function SHR-SP rats

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缓激肽在ACE抑制剂改善心肌梗塞后缺血边缘区血供中的作用

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中国药理学通报 2001年第5期17卷 581-584页

作者：茅建春金莹朱依纯仰礼真 thomas unger 上海市龙华医院内科上海200032 复旦大学基础医学院生理学教研室.肾脏与高血压研究中心上海200032 上海市岳阳医院内科上海200437 德国基尔大学药理系

目的　研究血管紧张素转换酶抑制剂 (ACEⅠ )介导的缓激肽 (bradykinin)对急性心肌梗塞后缺血边缘区组织血流量的影响。方法　♂Wistar大鼠被随机分成 4组 :雷米普利、雷米普利加icatibant、络沙坦以及喂水对照组。用药 1wk后结扎冠状... 详细信息

目的　研究血管紧张素转换酶抑制剂 (ACEⅠ )介导的缓激肽 (bradykinin)对急性心肌梗塞后缺血边缘区组织血流量的影响。方法　♂Wistar大鼠被随机分成 4组 :雷米普利、雷米普利加icatibant、络沙坦以及喂水对照组。用药 1wk后结扎冠状动脉左前降支 ,在结扎前后分别测定心率、血2 0 0 1 0 2 0 6收稿 ,2 0 0 1 0 5 17再修回1 复旦大学基础医学院生理学教研室·肾脏与高血压研究中心 ,上海　 2 0 0 0 322 上海市岳阳医院内科 ,上海　 2 0 0 4373德国基尔大学药理系作者简介 :茅建春 ,男 ,主治医师 ,Tel:0 2 1 64 0 4190 2 198压、缺血边缘区组织血流量的变化 ,成活的大鼠饲养 3wk后测定心肌梗死面积。结果　用雷米普利预处理 1wk能改善急性心梗心脏缺血边缘带的组织血流量并缩小心肌梗死面积 ,icatibant能使以上作用明显减弱 ,而单用络沙坦则无效。结论　ACEI类药物可改善急性心梗心脏缺血区边缘的血供并使梗塞面积缩小。

关键词：心肌梗塞血管紧张素缓激肽 ACE抑制剂组织血流量

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雷米普利对心肌梗死后心脏血管紧张素受体基因转录的影响(英文)

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中国药理学报 1999年第6期20卷 481-485页

作者：朱依纯朱依谆李军 HeinerSCHAFER Wolfgang ESCHMIDT thomas unger 姚泰上海医科大学生理学教研室 Department of Pharmacology University of Kiel DepartmentofInternalMedicineUniversityHospitalofKiel Department of InternalMedicineUniversityHospital of Kiel Kiel24105Germany

在慢性给予血管紧张素转换酶抑制剂雷米普利后的大鼠中观察心肌梗死（ＭＩ）后早期心肌组织中血管紧张素 Ⅱ（Ａｕｇ Ⅱ）受体基因转录的改变．方法：通过冠状动脉结扎建立大鼠ＭＩ模型，手术前１周即开始给予雷米普利或水，术后在存... 详细信息

在慢性给予血管紧张素转换酶抑制剂雷米普利后的大鼠中观察心肌梗死（ＭＩ）后早期心肌组织中血管紧张素 Ⅱ（Ａｕｇ Ⅱ）受体基因转录的改变．方法：通过冠状动脉结扎建立大鼠ＭＩ模型，手术前１周即开始给予雷米普利或水，术后在存活大鼠中继续治疗至处死大鼠；用定量ＲＴ－ＰＣＲ法检测大鼠心间隔组织的Ａｎｇ Ⅱ受体ｍＲＮＡ水平．结果：大鼠ＭＩ后心间隔组织中ＡＴ１和ＡＴ２受体ｍＲＮＡ水平升高，在１ｄ时达到高峰．给予雷米普利的大鼠ＭＩ后心间隔组织中Ａｎｇ Ⅱ受体ＩｎＲＮＡ水平与给予水的大鼠相比无显著差别．结论：非梗死区心肌组织中Ａｎｇ Ⅱ受体基因转录的特征性改变可能与ＭＩ后心肌重构过程有关而与ＡＣＥ抑制无关．

关键词：心肌梗塞血管紧张素Ⅱ 受体雷米普利基因转录

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Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone spontaneously hypertensive rats

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Acta Pharmacologica Sinica 2004年第6期 61-66页

作者： Alexander REINECKE,Marc DORENKAMP,Christain STORZ,Havvo BITTERLING,Susanne PENZ,Jack CLEUTJENS,Mat JAP DAEMEN,Reichiger SIMON,thomas unger Institute of Pharmacology University of Kiel 24105 Kiel Germany Institute of Pharmacology University of Kiel 24105 Kiel Germany Clinic of Cardiology Institute of Pharmacology University of Kiel 24105 Kiel Germany Institute of Pharmacology University of Kiel 24105 Kiel Germany University of Kiel Department of Pathology University ofMaastricht Maastricht The Netherlands Clinic of Cardiology University of Kiel 24105 Kiel Germany 24105 Kiel Institute of Pharmacology University of Kiel 24105 Kiel Germany Germany Institute of Pharmacology University of Kiel 24105 Kiel Germany

AIM: To elucidate the cardioprotective effects of T-type calcium channel blocker mibefradil and compare with that of the angiotensin-converting enzyme inhibitor ramipril in a stroke-prone spontaneously hypertensive rats (SHR- SP) model of congestive heart failure (CHF) after myocardial infarction (MI). METHODS: SHR-SP rats were subjected to permanent ligation of the left anterior decending coronary artery. Treatment with mibefradil (10 mg·kg-1·d-1), ramipril (10 mg·kg-1·d-1), or placebo was initiated 4 weeks before surgery and continued up to 6 weeks after induction of MI. Sham-operated rats served as controls. RESULTS: In placebo-treated MI rats, six weeks after MI, left ventricular circumference, inner diameter, and left ventricular end-diastolic pressure (LVEDP) were increased, whereas mean arterial blood pressure (MAP) and maximum rate of rise of left ventricular pressure (dp/ dtmax) were decreased compared with sham-operated controls (P05), and dp/dtmax was improved (P<0.01) compared with placebo-treated MI rats. In contrast, in mibefradil-treated MI rats, heart weight, heart weight to body weight ratio were slightly but not signifi- cantly reduced, LVEDP was slightly elevated compared with placebo-treated MI rats, and was elevated (P<0.05) compared with ramipril-treated MI rats, although interstitial collagen content were reduced (P<0.01) compared with placebo-treated MI ***: Chronic treatment with ramipril diminishes cardiac remodeling of heart failure after MI to a greater extent than mibefradil. Moreover, 6 weeks after MI, mibefradil treatment results in a slight rise in LVEDP compared with placebo-treated rats. Therefore, treatment with mibefradil might be deleterious rather than beneficial compared with ramipril or even placebo treatment in experim

关键词： mibefradil ramipril angiotensin-converting enzyme inhibitors calcium channel blockers myocar- dial infarction heart failure cardiac remodeling ventricular function SHR-SP rats

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LONG-TERM INHIBITION OF Na~+/H~+ EXCHANGE ATTENUATES CARDIAC REMODELING AFTER MYOCARDIAL INFARCTION IN RATS

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2001年第4期 80-85页

作者： XIA Qin-gui\+*L, Oliver Chung, Heidi Spitznagel, thomas unger (Institute of Pharmacology, Christian-Albrechts-University of Kiel, Hospitalstrasse 4, 24105 Kiel, Germany)\%

Objective: In addition to pH regulation, Na\++/H\++ exchanger (NHE) has been shown to facilitate cell growth and proliferation. However, the effects of long-term inhibition of Na\++/H\++ exchange on cardiac structural and functional remodeling post myocardial infarction (MI) are still controversial. The present study was therefore carried out to further investigate the effects of long-term treatment with cariporide, a specific inhibitor of NHE-1, on cardiac remodeling after MI in rats; Methods: Male Wistar rats that underwent coronary ligation were randomly selected for cariporide treatment starting 6 h after induction of MI or no *** was continued up to 6 weeks post MI, after which, the arterial, venous and left ventricular catheters were chronically implanted. Twenty-four h later, after hemodynamic signals were recorded in conscious rats, they were sacrificed and hearts were taken out for morphological examinations; Results: Cariporide treatment decreased the heart weight and heart weight to body weight ratio (both \%P\%<0.05), decreased left ventricular end-diastolic pressure (\%P\%<0.001), improved myocardial contractility (d\%P\%/d\%t\%\-\{max\}) (\%P\%<0.05) and tended to increase the survival of treated rats compared to that of untreated infarct rats; Conclusion: The results of the present study indicate that the long-term inhibition of NHE with cariporide can attenuate cardiac structural remodeling and improve left ventricular dysfunction in infarcted rats, and suggest that Na\++/H\++ exchange inhibition could be an effective therapeutic strategy for myocardial infarction-induced heart failure.

关键词： myocardial infarction Na\++/H\++ exchange inhibitor remodeling ventricular function

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Insights into carbon dioxide sequestration into coal seams through coupled gas flow-adsorption-deformation modelling

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第1期16卷 26-40页

作者： Hywel thomas Min Chen Geoenvironmental Research Centre Cardiff School of EngineeringCardiff UniversityQueen’s BuildingsThe ParadeNewport RoadCardiffCF243AAUK Key Laboratory of Marine Geology Tongji UniversityShanghai200092China

Injecting carbon dioxide(CO_(2))into coal seams may unlock substantial carbon sequestration *** the coal acts like a carbon filter,it can preferentially absorb significant amounts of CO_(2).To explore this further,desorption of the adsorbed gas due to pressure drop is investigated in this paper,to achieve an improved understanding of the long-term fate of injected CO_(2) during post-injection *** paper presents a dual porosity model coupling gas flow,adsorption and geomechanics for studying coupled processes and effectiveness of CO_(2) sequestration in coals.A new adsorption?desorption model derived based on thermodynamics is incorporated,particularly,the desorption hysteresis is *** reliability of the proposed adsorption-desorption isotherm is examined via validation *** is indicated that occurrence of desorption hysteresis is attributed to the adsorption-induced pore *** injection ceases,the injected gas continues to propagate further from the injection well,while the pressure in the vicinity of the injection well experiences a significant *** the adsorbed gas near the well also decreases,this decrease is less compared to that in pressure because of desorption *** unceasing spread of CO_(2) and drops of pressure and adsorbed gas depend on the degree of desorption hysteresis and heterogeneity of coals,which should be considered when designing CO_(2) sequestration into coal seams.

关键词： CO_(2)geological storage Coal seam Adsorption Desorption hysteresis

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CLASSIFICATIONS OF DUPIN HYPERSURFACES IN LIE SPHERE GEOMETRY

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Acta Mathematica Scientia 2024年第1期44卷 1-36页

作者： thomas E.CECIL Department of Mathematics and Computer Science College of the Holy CrossWorcesterMA01610USA

This is a survey of local and global classification results concerning Dupin hypersurfaces in S^(n)(or R^(n))that have been obtained in the context of Lie sphere *** emphasis is on results that relate Dupin hypersurfaces to isoparametric hypersurfaces in *** with these classification results,many important concepts from Lie sphere geometry,such as curvature spheres,Lie curvatures,and Legendre lifts of submanifolds of S^(n)(or R^(n)),are described in *** paper also contains several important constructions of Dupin hypersurfaces with certain special properties.

关键词： Dupin hypersurfaces isoparametric hypersurfaces Lie sphere geometry Lie sphere transformations Lie curvatures

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Proximity-dependent protein (de)stabilization: screening the human ORFeome for protein degraders and stabilizers

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3161-3162页

作者： thomas Hermanns Kay Hofmann Institute for Genetics University of CologneCologneGermany

In a recent study published in Nature,Poirson et *** an unbiased screen for proteins that can either bring about-or prevent-the destruction of proteinaceous model substrates in a proximity-dependent *** of such protein degraders and stabilizers will be instrumental in the development of new drug classes that specifically regulate the abundance of their target proteins.

关键词： al. stabilization stabilizers

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How to enhance agricultural plastic waste management in China?Insights from public participation

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Journal of Integrative Agriculture 2024年第6期23卷 2127-2143页

作者： Aibo Hao thomas Dogot Changbin Yin State Key Laboratory of Efficient Utilization of Arid and Semi-arid Arable Land in Northern China Institute of Agricultural Resources and Regional PlanningChinese Academy of Agricultural SciencesBeijing 100081China Economics and Rural Development Laboratory TERRA Teaching and Research CentreGembloux Agro-Bio TechUniversity of LiègeGembloux B-5030Belgium Research Center for Agricultural Green Development in China Beijing 100081China

Agricultural plastics play a pivotal role in agricultural ***,due to expensive costs,agricultural plastic waste management(APWM)encounters a vast funding *** one of the crucial stakeholders,the public deserves to make appropriate efforts for ***,identifying whether the public is willing to pay for APWM and clarifying the decisions’driving pathways to explore initiatives for promoting their payment intentions are essential to address the dilemma confronting *** this end,by applying the extended theory of planned behavior(TPB),the study conducted an empirical analysis based on 1,288 residents from four provinces(autonomous regions)of northern *** illustrate that:1)respondents hold generally positive and relatively strong payment willingness towards APWM;2)respondents’attitude(AT),subjective norm(SN),and perceived behavioral control(PBC)are positively correlated with their payment intentions(INT);3)environmental cognition(EC)and environmental emotion(EE)positively moderate the relationships between AT and INT,and between SN and INT,posing significant indirect impacts on *** study’s implications extend to informing government policies,suggesting that multi-entity cooperation,specifically public payment for APWM,can enhance agricultural non-point waste management.

关键词： agricultural plastic waste extended theory of planned behavior public payment environmental cognition environmental emotion

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Theory and classification of mass extinction causation

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National Science Review 2024年第1期11卷 16-36页

作者： thomas J.Algeo Jun Shen State Key Laboratory of Biogeology and Environmental Geology China University of Geosciences—Wuhan State Key Laboratory of Geological Processes and Mineral Resources China University of Geosciences—Wuhan Department of Geosciences University of Cincinnati

Theory regarding the causation of mass extinctions is in need of systematization, which is the focus of this contribution. Every mass extinction has both an ultimate cause, i.e. the trigger that leads to various climato-environmental changes, and one or more proximate cause(s), i.e. the specific climato-environmental changes that result in elevated biotic mortality. With regard to ultimate causes, strong cases can be made that bolide(i.e. meteor) impacts, large igneous province(LIP) eruptions and bioevolutionary events have each triggered one or more of the Phanerozoic Big Five mass extinctions, and that tectono-oceanic changes have triggered some second-order extinction events. Apart from bolide impacts, other astronomical triggers(*** flares, gamma bursts and supernova explosions) remain entirely in the realm of speculation. With regard to proximate mechanisms, most extinctions are related to either carbon-release or carbon-burial processes, the former being associated with climatic warming, ocean acidification, reduced marine productivity and lower carbonate δ13C values, and the latter with climatic cooling, increased marine productivity and higher carbonate δ13C values. Environmental parameters such as marine redox conditions and terrestrial weathering intensity do not show consistent relationships with carbon-cycle *** this context, mass extinction causation can be usefully classified using a matrix of ultimate and proximate factors. Among the Big Five mass extinctions, the end-Cretaceous biocrisis is an example of a bolide-triggered carbon-release event, the end-Permian and end-Triassic biocrises are examples of LIP-triggered carbon-release events, and the Late Ordovician and Late Devonian biocrises are examples of bioevolution-triggered carbon-burial events. Whereas the bolide-impact and LIP-eruption mechanisms appear to invariably cause carbon release, bioevolutionary triggers can result in variable carbon-cycle changes, e.g. carbon burial durin

关键词： biocrisis ultimate cause proximate cause bolide large igneous province bioevolutionary event

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