Modulation of the expression of ABC transporters in murine (J774) macrophages exposed to large concentrations of the fluoroquinolone antibiotic moxifloxacin

Long-term exposure to pharmacological agents can select for cells that overexpress efflux transporters. We previously showed that mouse J774 macrophages cultivated for a prolonged period of time with toxic concentrations of the fluoroquinolone ciprofloxacin overexpress the efflux transporter Mrp4 and display a reduced accumulation of this antibiotic, but no change in the accumulation of moxifloxacin, a closely related molecule (Antimicrob. Agents Chemother. [2006] 50, 1689-1695 and [2009] 53, 2410-2416). Because of this striking difference between the two fluoroquinolones, we have now examined the modifications in the expression of ABC efflux transporters induced by the prolonged exposure of J774 macrophages to high concentrations of moxifloxacin. The resulting cell line showed (i) no difference in the accumulation of moxifloxacin but an increased accumulation and decreased efflux of ciprofloxacin; (ii) an overexpression of the multidrug transporters Abcb1a (P-gp), Abcc2 (Mrp2) and Abcg2 (Bcrp1), and a decreased expression of Abcc4 (Mrp4). While P-gp and Bcrp1 were functional, they did not modify the cellular accumulation of fluoroquinolones. The data show that exposing cells to high concentrations of a drug that is not affected by active efflux can trigger a pleiotropic response leading to a modulation in the expression of several transporters. These changes, however, are not sufficient to protect cells against the toxicity that fluoroquinolones may exert at large concentrations. They could also cause unanticipated drug interactions in vivo, should the drug exposure grossly exceed what is anticipated from its current registered use.     

Nurse migration: the effects on nursing education

This paper is an opinion piece based on experience and supported where possible with literature, which addresses an issue of both national and international interest. It focuses on one aspect of the multifaceted social phenomenon of nurse migration, i.e. nurse education.
Background:  Much has been written about the direct effects of nurse migration on the nurse migrant, the delivery of health care in the countries that supply the nurses, and the countries that receive them. However, there is little information regarding the direct effects of migration on nurse education within the literature.
Aim:  The aim of this paper is to raise awareness of the positive and negative effects of nurse migration on nurse education both in the countries that supply nurses and those which receive them.
Methods:  Both scholarly and 'grey' literature is used to support the discussion on the 'real' challenges faced by nurse educators and clinical nurses in those countries that supply or receive nurses. In addition, practical recommendations for nurse educators are presented. Furthermore, the nursing profession is challenged to become politically active, to become involved and to take responsibility for the decisions made about nurse education in order to protect the integrity of nurse education and patient safety.
Conclusion:  The quality of nurse education in many countries has been undermined as a result of rapid, mass migration. There is an urgent need to take practical steps to maintain the integrity of nurse education and the nurse's preparation for practice in order to protect patients' safety.     

Coronary Artery Spasm Induced by Ergonovine in an Infarct Related Coronary Artery Late After Primary Angioplasty

We report two cases with induced coronary spasm of the culprit lesion in the infarct related coronary artery in the chronic phase after primary percutaneous transluminal coronary angioplasty (PTCA). To our knowledge, there are few data on the response of the angioplasty site to ergonovine in human coronary arteries after primary PTCA. It is important to note that chest pain recurring after successful primary PTCA is not automatically related to restenosis, and coronary spasm in patients with previous myocardial infarction, should also be considered . (J Interven Cardiol 2000;31–34)     

儿童肱骨髁上骨折的治疗研究进展

肱骨髁上骨折在儿童肢体骨折中发生率极高,是儿童最常见的骨折之一,约占小儿全部肘关节损伤的60%.髁上骨折不仅常见而且经常有合并症发生,致使多次反复复位,神经损伤、手术探查及预后不佳等发生率较任何其他部位骨折都高.     

基于气相色谱-质谱和网络药理学探讨蒙药嘎拉图呼和挥发油成分抗胃癌的作用机制

【摘要】 目的 通过提取蒙药嘎拉图呼和挥发油部位，进行化学成分鉴定，结合网络药理学分析探讨传统蒙药复方嘎拉图呼和抗胃癌潜在作用机制。方法 采用气相色谱-质谱（GC-MS) 联用法定性分析嘎拉图呼和挥发油部位成分，并结合 Pubchem 和 Swiss Target Prediction 数据库，进行活性成分靶点的筛选；在 Gene Cards、OMIM、Pharm Gkb、TTD、DrugBank 数据库中检索胃癌相关的靶点；利用在线 Venn 将查到的靶点信息取交集；Cytoscape 3.9.0 软件构建成分-靶点-疾病网络图筛选关键成分；STRING 11.0数据库构建蛋白互作网络筛选核心作用靶点，利用DAVID 数据库进行 GO 功能和 KEGG通路富集分析；利用 Discovery Studio 2019进行核心靶点与相应小分子化合物之间分子对接。结果 通过 GC-MS 共鉴定出嘎拉图呼和挥发油部位中56种成分；以GC-MS 结果为基础，通过化学成分靶点预测数据库搜索并获得 46个活性成分，150 个活性靶点；化学成分靶点与胃癌相关靶点取交集，获得 135 个潜在治疗基因；进行 GO 功能富集与 KEGG 通路分析，获得包括 G 蛋白偶联信号通路、乙酰胆碱受体信号通路等多条胃癌相关信号通路；PPI 蛋白互作筛选核心基因，结果显示VEGFA、KDR、PTGS2和MAPK14为挥发油治疗胃癌的潜在作用靶点。结论 蒙药嘎拉图呼和挥发油中的46个有效成分可能通过调控 VEGFA、KDR、PTGS2和MAPK14参与多条信号通路共同发挥抗胃癌作用。本研究为进一步探讨蒙药复方抗胃癌作用机制提供数据依据。     

牙周病治疗进展

牙周病是世界范围内广泛流行的一种口腔疾 病。临床主要表现为牙龈肿胀出血，牙周袋形成，牙 周袋溢浓，牙齿松动甚至缺失等，X 线可见牙槽骨吸 收[1]。在我国，牙周病（包括牙龈病和牙周炎）是造成 我国居民牙齿丧失的主要原因之一，且牙周病可引 发并促进多种全身性疾病，如心脑血管病、糖尿病 等，对健康的危害较大，治疗比较复杂，时间和金钱 花费较多[2]。长期以来中西医均对牙周病的发病机制 和治疗方法进行了大量研究，两者各有其特点，但中 医辨证施治和标本兼治的理念更有其独到之处，现 就中西医对牙周病的研究进展做一综述。     

水痘-带状疱疹病毒的致病机制与防治

水痘-带状疱疹病毒(VZV)属人类疱疹病毒α亚科,具有嗜神经性,人类是该病毒的唯一自然宿主.初次感染可引起水痘,日后宿主免疫力低下时,病毒可再次激活引起带状疱疹.VZV感染易引起诸多并发症,对临床的诊治造成一定干扰.本文就VZV的分子结构、感染机制及途径、流行病学、临床特点和防治原则等方面进行综述,为疾病预防、诊断及合...     

不同TI-RADS指南预测甲状腺囊实性结节恶性风险分层价值的对比研究

目的 比较ACR TI-RADS、ATA指南及KSThR指南预测甲状腺囊实性结节恶性风险分层的价值。方法 回顾性分析经病理证实的293个甲状腺囊实性结节（良性210个，恶性83个）的超声表现特征，应用不同TI-RADS指南对甲状腺囊实性结节进行恶性风险分层，多因素Logistic回归筛选甲状腺囊实性恶性结节的危险因素；绘制受试者工作特征（ROC）曲线分析不同TI-RADS对甲状腺囊实性结节良恶性的预测效能。结果 甲状腺囊实性良恶性结节大小、结构成分及实性成分为低回声、实性成分为偏心位、偏心位实性成分与囊壁成锐角、微钙化、边界不规则占比比较差异均有统计学意义（均P<0.05）。ACR TI-RADS将良性结节分为极低危135个、低危46个、中危27个、高危2个，恶性结节分为极低危9个、低危13个、中危47个、高危14个；ATA指南将良性结节分为极低危158个、低危38个、高危14个，恶性结节分为极低危22个、低危8个、高危53个；KSThR指南将良性结节分为中危14个、低危187个、良性9个，恶性结节分为中危53个、低危28个、良性2个。多因素Logistic回归分析显示，实性成分...     

Machine learning for non-invasive sensing of hypoglycaemia while driving in people with diabetes

Aim

To develop and evaluate the concept of a non-invasive machine learning (ML) approach for detecting hypoglycaemia based exclusively on combined driving (CAN) and eye tracking (ET) data.

Materials and Methods

We first developed and tested our ML approach in pronounced hypoglycaemia, and then we applied it to mild hypoglycaemia to evaluate its early warning potential. For this, we conducted two consecutive, interventional studies in individuals with type 1 diabetes. In study 1 (n = 18), we collected CAN and ET data in a driving simulator during euglycaemia and pronounced hypoglycaemia (blood glucose [BG] 2.0-2.5 mmol L⁻¹). In study 2 (n = 9), we collected CAN and ET data in the same simulator but in euglycaemia and mild hypoglycaemia (BG 3.0-3.5 mmol L⁻¹).

Results

Here, we show that our ML approach detects pronounced and mild hypoglycaemia with high accuracy (area under the receiver operating characteristics curve 0.88 ± 0.10 and 0.83 ± 0.11, respectively).

Conclusions

Our findings suggest that an ML approach based on CAN and ET data, exclusively, enables detection of hypoglycaemia while driving. This provides a promising concept for alternative and non-invasive detection of hypoglycaemia.     

氯霉素泼尼松搽剂治疗小鼠特应性皮炎的实验研究

目的:研究氯霉素泼尼松搽剂对小鼠急性特应性皮炎的治疗效果.方法:选取48只小鼠,分为空白组、模型组、对照组及实验低、中、高剂量组共6组,每组8只,除空白组外,其余5组小鼠均用二硝基氯苯丙酮溶液建立特应性皮炎模型,空白组、模型组给予生理盐水,对照组给予1％吡美莫司乳膏,实验组低、中、高剂量组分别给予相应浓度的氯霉素泼尼松...