Elevated Reactive Oxygen Species but not Glutathione Regulate Mercury Resistance to AML-2/DX100 Cells

The multidrug resistance-associated protein (MRP1) mediates cellular efflux of various xenobiotics and cellular resistance to heavy metals. Previously we reported that MRP1 mediates resistance to mercury exposure and possible mechanism mediating MRP1 expression after mercury exposure. This study was designed to investigate the role of reactive oxygen species (ROS) and glutathione on the resistance of AML-2/DX100 cells to mercuric chloride. The MRP1 overexpressing cells (AML-2/DX100) cells showed less scavenging activity to ROS induced by mercury while no difference in the basal glutathione levels between AML-2/WT and AML-2/DX100 cells. Mercury induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) but not c-jun-N-terminal kinase in AML-2/DX100 cells. The specific inhibitor for p38 MAPK and ERK, and antioxidant decreased the production of MRP1 and therefore resistance of AML-2/DX100 cells against mercury exposure. These results suggest that induction of ROS and downstream p38 MAPK and ERK were involved in the resistance of cells to mercury by expression MRP1 in AML-2/DX100 cells.     

Industrial separation of oxygen isotopes by oxygen distillation

¹⁸O‐labeled water (Water‐¹⁸O) is a widely used starting material of ¹⁸F‐labeled diagnostic agents in positron emission tomography (PET). Conventionally, Water‐¹⁸O has been separated from other stable oxygen isotope species (¹⁶O, ¹⁷O) by water distillation or nitric oxide distillation. However, conventional methods are costly and may have safety issues. In 2004, we developed the first unit of our novel oxygen isotope separation process by cryogenic oxygen distillation to overcome these issues. To meet the needs of the market, we built a second unit in 2013 and a third in 2016. We are now operating three commercially viable separation units with a total capacity of 600 kg of Water‐¹⁸O per year.     

PNU282987对烧伤休克犬复苏时脂质过氧化损伤和组织含水率的影响

目的：研究α7烟碱型乙酰胆碱受体（α7nAChR）激动剂PNU282987对致死性烧伤休克犬脂质过氧化损伤和组织含水率的影响.方法：成年雄性Beagle犬12只,按完全随机数字表法分为烧伤补液组和烧伤PNU282987组,每组6只.采用凝固汽油燃烧法造成50%总体表面积Ⅲ度烧伤.于伤后0.5 h分别通过颈静脉补液,烧伤补液组给予林格液,烧伤PNU282987组给予等量含有PNU282987 （0.38 mg/kg）的林格液.补液量和速率均根据Parkland公式确定.于伤前和伤后2、4、8、12和24 h颈静脉取血,测定丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性,并于伤后24 h处死动物,留取心、肝、脾、肺、肾和回肠组织,测定组织含水率.结果：两组犬伤后SOD水平显著降低;伤后4 h起烧伤PNU282987组SOD水平显著高于烧伤补液组（P＜0.05）,而单纯烧伤组SOD水平持续降低.两组犬伤后MDA水平均上升,伤后4h起烧伤PNU282987组血浆MDA水平均显著低于烧伤补液组（P＜0.05）.烧伤PNU282987组脏器含水率显著低于烧伤补液组[心：（68.6±1.1）% vs.（78.3±1.8）%;肝：（70.0±1.4）% vs.（ 79.8±0.7）%;脾：（67.2±1.2）% vs.（78.8±0.8）%;肺：（74.3±0.5）% vs.（ 80.2±1.6）%;肾：（71.2±0.8）% vs.（ 80.1±0.9）%;回肠：（68.9±1.1）% vs.（ 78.7±0.8）%],差异均有统计学意义（P＜0.05）.结论：PNU282987能抑制烧伤休克犬复苏时引起的脏器氧自由基生成,减轻组织水肿,具有潜在临床应用价值.     

Stability of Oxygen Transmissibility During Ischemia

Abstract

Simultaneous measurements of oxygen availability (O₂a) and partial pressure (PO₂) were made by the double noble metal electrode system designed by Erdmann and Krell in an attempt to monitor the oxygen transmissibility (Dk) with respect to time before and after ischemic episodes in the brain cortex. Available current equations can appropriately describe the performance of the electrode in a homogeneous nonconsuming medium, and with some experimental error this electrode system can be used to estimate oxygen transmissibility changes in the brain based on the different chararcteristics of the O₂a (rod-type, flush-ended bare tip) and the PO₂ (rod-type, recessed tip) cathodes. Our method monitors the oxygen transmissibility within the diffusion sphere of the bare tip as the ratio of the currents related to O₂a and PO₂. We find with this system that even prolonged global cerebral ischemia does not alter the oxygen transmissibility of the brain tissue. Therefore, alteration of the oxygen transmissibility can not be a contributing factor to postischemic cerebral malfunction.     

Effect of Maximal Oxygen Pulse on Patients with Chronic Obstructive Pulmonary Disease

ObjectiveThis study evaluated the effect of maximal oxygen pulse (O₂P_max) on patients with chronic obstructive pulmonary disease (COPD) and confirmed the predictive effect on acute exacerbations of COPD (AECOPD).MethodsThis retrospective study included 91 participants who underwent cardiopulmonary exercise testing (CPET), lung function testing, a dyspnea scale assessment, and a 3-year follow-up. The participants were divided into two groups according to the O₂P_max value. Exercise capacity, ventilatory conditions, gas exchange efficiency, and dyspnea symptoms were compared, and the correlations between O₂P_max and these indices were evaluated. The ability of O₂P_max to predict AECOPD was examined.ResultsExercise capacity, ventilatory conditions, and gas exchange efficiency were lower, and dyspnea symptom scores were higher in the impaired O₂P_max group (P < 0.05). O₂P_max was positively correlated with forced vital capacity (FVC)%, forced expiratory volume in 1 sec (FEV-₁)%, FEV₁/FVC%, anaerobic threshold (AT), work rate (WR)%, aximal oxygen uptake (VO_2max)%, VO₂/kg_max, VO₂/kg_max%, WR_AT, WR_max, VO_2AT, VO_2max, and V_Emax, and was negatively correlated with EqCO_2AT, and EqCO_2max (P < 0.05). Most importantly, O₂P_max could be used to predict AECOPD, and the best cut-off value was 89.5% (area under the curve, 0.739; 95% CI, 0.609–0.869).ConclusionO₂P_max reflected exercise capacity, ventilation capacity, gas exchange capacity, and dyspnea symptoms in patients with COPD and may be an independent predictor of AECOPD.     

Experimental strategies to improve in vitro models of renal ischemia

Ischemia has elicited a great deal of interest among the scientific community due to its role in life-threatening pathologies such as cancer, stroke, acute renal failure, and myocardial infarction. Oxygen deprivation (hypoxia) associated with ischemia has recently become a subject of intense scrutiny. New investigators may find it challenging to induce hypoxic injury in vitro. Researchers may not always be aware of the experimental barriers that contribute to this phenomenon. Furthermore, ischemia is associated with other major insults, such as excess carbon dioxide (hypercapnia), nutrient deprivation, and accumulation of cellular wastes. Ideally, these conditions should also be incorporated into in vitro models. Therefore, the motivation behind this review is to: i. delineate major in vivo ischemic insults; ii. identify and explain critical in vitro parameters that need to be considered when simulating ischemic pathologies; iii. provide recommendations to improve experiments; and as a result, iv. enhance the validity of in vitro results for understanding clinical ischemic pathologies. Undoubtedly, it is not possible to completely replicate the in vivo environment in an ex vivo model system. In fact, the primary goal of many in vitro studies is to elucidate the role of specific stimuli during in vivo pathological events. This review will present methodologies that may be implemented to improve the applicability of in vitro models for understanding the complex pathological mechanisms of ischemia. Finally, although these topics will be discussed within the context of renal ischemia, many are pertinent for cellular models of other organ systems and pathologies.     

Automated live cell screening system based on a 24-well-microplate with integrated micro fluidics

In research, pharmacologic drug-screening and medical diagnostics, the trend towards the utilization of functional assays using living cells is persisting. Research groups working with living cells are confronted with the problem, that common endpoint measurement methods are not able to map dynamic changes. With consideration of time as a further dimension, the dynamic and networked molecular processes of cells in culture can be monitored. These processes can be investigated by measuring several extracellular parameters. This paper describes a high-content system that provides real-time monitoring data of cell parameters (metabolic and morphological alterations), e.g., upon treatment with drug compounds. Accessible are acidification rates, the oxygen consumption and changes in adhesion forces within 24 cell cultures in parallel. Addressing the rising interest in biomedical and pharmacological high-content screening assays, a concept has been developed, which integrates multi-parametric sensor readout, automated imaging and probe handling into a single embedded platform. A life-maintenance system keeps important environmental parameters (gas, humidity, sterility, temperature) constant.     

Theoretical estimation of retinal oxygenation during retinal detachment

The aim of the present work was to simulate the oxygenation of the whole retina during different degrees of retinal detachment. A differential equation describing the oxygenation of the whole retina, at different degrees of detachment, was set up and solved numerically. The results show that the choroid can supply the outer retina with a fairly large amount of oxygen as long as the detachment height is lower than about 1mm. This study thus supports the view that hyperoxia may well prove to be clinically beneficial.