Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

儿童外科教学方法实践及探讨

目的探讨儿童外科的教学特点及教学方法,提高儿外科医生的总体执业水平,促进儿童外科学的发展。方法通过分析四川大学华西医院多年儿童外科疾病的临床教学实践经验,总结出适合医学生、初级儿童外科专科医生的实用的教学方法及经验。结果结合儿童外科特有的疾病特点所总结出的故事式讲述教学、典型病例教学、漫画形式学习、比较学习法及多媒体素材教学五种方式是非常适合儿童外科教学的方法。能够加深记忆,提高兴趣,轻松快捷,事半功倍的掌握相关医学专业知识。结论独特有趣的儿童外科教学方法可提高医学生及儿童外科初级从业者的学习兴趣、专业知识和执业水平。     

Clinical implications,diagnosis,and management of diabetes in patients with chronic liver diseases

Diabetes mellitus(DM) negatively affects the development and progression of chronic liver diseases(CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma(HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.     

Effect of group reminiscence therapy on depression and perceived meaning of life of veterans diagnosed with dementia at veteran homes

ABSTRACT

Most senior veterans who live in veteran homes in Taiwan have few interpersonal relationships. Aging is often accompanied by solitude and illness, which causes senior veterans to doubt the meaning of life and to lose confidence in the value of life. This study tested the effectiveness of a group reminiscence therapy protocol on the depression and meaning of life among elderly institutionalized veterans. A quasi-experimental design was applied. A convenience sample of older adults was drawn from two veteran homes in southern Taiwan. Participants were assigned to intervention or control groups based on the veterans' homes they attended. The participants in the intervention group carried out group reminiscence therapy for 8 weeks in addition to their daily activities. The participants in the comparison group maintained their daily activities. Both groups were evaluated using the GDS-SF and MLS scale including two aspects of depression mood and meaning of life in weeks 1 and 8. The overall life satisfaction increased significantly over time for the intervention group compared to the comparison group from week 1 to week 8. The group reminiscence therapy programs showed promising effects in improving the depression and meaning of life of older veterans living in veteran homes.     

PBL教学法在临床心肺复苏术教学中的应用分析

目的 分析重症医学科PBL教学法在临床心肺复苏术教学中的应用效果.方法 本次实验的开展基础数据选择2016年9月—2018年7月进入医院重症医学科实习学生64例,按照学生自身意愿以及学校安排将参与实验学生分为均数相同的两个小组(对照组、观察组),每组实验人数均为32例,其中对照组(n=32)采用传统教学方法 ,观察组(n=32)则应用PBL教学法教学,对比两组学生在学期结束后整体的学习质量情况和教学满意率.结果 观察组学生经过测试后理论知识和专业技能得分均对比对照组更高,教学效果更加理想,观察组学生对于教学的满意率评价更高,P<0.05.结论 重症医学科临床心肺复苏术教学中应用PBL教学法,将理论与实践进行结合,对教学方法 进行改进,全面提升学生的思维理解能力,培养良好的动手能力,促进理论教学与实践的结合,为学生以后的职业生涯提供更加理想的条件.