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Jennifer C. Sasaki Ashley Allemang Steven M. Bryce Laura Custer Kerry L. Dearfield Yasmin Dietz Azeddine Elhajouji Patricia A. Escobar Albert J. Fornace Jr Roland Froetschl Sheila Galloway Ulrike Hemmann Giel Hendriks Heng-Hong Li Mirjam Luijten Gladys Ouedraogo Lauren Peel Stefan Pfuhler Daniel J. Roberts Véronique Thybaud Jan van Benthem Carole L. Yauk Maik Schuler 《Environmental and molecular mutagenesis》2020,61(1):114-134
In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc. 相似文献
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Dr. Arni Raghavendrarao Raghuram M.Ch. Subbiah Kumar MD Kathamuthu Balamurugan DA Arulmurugan DA Ramiah Krishnan M.Ch. Perichiappan Sivakami BS Eluvathingal Varghese John M.Ch. 《Indian Journal of Thoracic and Cardiovascular Surgery》2006,22(3):178-181
Background Beating heart surgery has now become the commonest technique of doing Coronary Artery Bypass Graft Surgery (CABG) in our country.
It is being used even in such high risk situations like diffuse coronary disease and Critical Left Main stem Stenosis (LMCS)
with good results. The aim of this study is to retrospectively review our results in Off-Pump Coronary Artery Bypass Surgery
(OPCAB) in patients with critical left main stem stenosis.
Methods This study is a retrospective analysis of the data of patients who underwent primary coronary artery bypass surgery. During
the period from April 2003 to September 2005 a total of 64 patients underwent OPCAB procedure for critical LMCS. During the
same period 10 patients underwent CABG on Cardio Pulmonary Bypass (CPB). The age range was 36–77yrs. The sex distribution
was M: F 53∶10. Ten patients were done as emergency. 2 of them were on Intra Aortic Balloon Pump (IABP) support preoperatively.
10 patients were high risk with a Euro score of ≥5.
Results Left Internal Mammary Artery (LIMA) was used in 78% of cases. Average grafts per patient was 2.96. The median ventilation
time was 5.91 hrs. New IABP insertion in postoperative period was required in 1 patient. One patient was reexplored for bleeding.
There was one perioperative myocardial infarction. 57% of patients did not need any blood transfusion. There was no conversion
to CPB. There was no operative mortality. Inotropes were used in ten cases.
Conclusions OPCAB is a safe method of revascularization in patients with critical LMCS. Preoperative IABP is useful in patients with cardiogenic
shock. However, there is a place for CPB in patients needing additional procedures like Mitral Valve repair (MV repair) or
Dor's procedure or when the vessels are very diffusely diseased. Those patients who are unstable despite IABP support may
be managed by Beating heart On Pump (BHOP) technique. 相似文献
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Richard B Thompson Ewout J van den Bos Bryce H Davis Yoshihisa Morimoto Damian Craig Brad S Sutton Donald D Glower Doris A Taylor 《The Journal of heart and lung transplantation》2005,24(2):205-214
BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction. 相似文献
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氟西汀与阿米替林治疗105例抑郁障碍病人的双盲对照试验 总被引:6,自引:4,他引:2
目的:评价国产氟西汀的抗抑郁作用及安全性。方法:采用随机、双盲对照、多中心研究,分为国产氟西汀组57例(男性22例,女性35例;年龄40±s13a),口服氟西汀20mg,qd,阿米替林57例(男性27例,女性30例;年龄40±14a),口服阿米替林75mg,bid,疗程6wk。结果:氟西汀治疗抑郁障碍的疗效与阿米替林相当,总有效率分别为85%及92%(P>0.05);氟西汀组的主要副作用有口干、便秘、恶心、心动过速等,但较之阿米替林程度轻且发生率低。结论:氟西汀的抗抑郁作用与阿米替林相当,副作用少,服用方便。 相似文献
10.
Reeve Bryce B. Hays Ron D. Chang Chih-Hung Perfetto Eleanor M. 《Quality of life research》2007,16(1):1-8
Background Health-related quality of life (HRQL) is an accepted outcome measure in patients with mood and anxiety disorders. Yet, surprisingly
little attention has been paid to the determinants. In this paper we test the hypothesis that it is associated with personality
traits while controlling for mental disorders.
Methods A large sample of outpatients (n=640) with mood and anxiety disorders was studied. The empirically supported five factor model
of normal personality traits was assessed using the NEO-FFI and includes: neuroticism, extraversion, openness to experience,
agreeableness, and conscientiousness. Mental disorders were assessed with the CIDI, and HRQL with the SF-36.
Results Regression analyses revealed that the NEO-FFI scores, with the exception of conscientiousness, were significantly associated
with SF-36 subscales and summary scores, independently from the mental disorders. The percentage of explained variance due
to the personality traits was highest for the subscales Vitality (10.0%), Mental Health (13.3%) and the Mental Health Summary
Score (9.5%). Furthermore, specific personality traits were related to specific SF-36 subscales.
Conclusions A low HRQL of patients with mood or anxiety disorders is not only determined by the disease or the current health but is also
shaped by personality traits that are relatively stable throughout an individual's life time. 相似文献