The Relationship Between Exercise Intensity and Affective Responses Demystified: To Crack the 40-Year-Old Nut,Replace the 40-Year-Old Nutcracker!

Background A causal chain linking exercise intensity, affective responses (e.g., pleasure–displeasure), and adherence has long been suspected as a contributor to the public health problem of physical inactivity. However, progress in the investigation of this model has been limited, mainly due to inconsistent findings on the first link between exercise intensity and affective responses. Purpose The purpose was to reexamine the intensity–affect relationship using a new methodological platform. Methods Thirty young adults (14 women and 16 men) participated in 15-min treadmill exercise sessions below, at, and above their ventilatory threshold. The innovative elements were the following: (a) Affect was assessed in terms of the dimensions of the circumplex model; (b) assessments were made repeatedly during and after exercise; (c) patterns of interindividual variability were examined; (d) intensity was determined in relation to the ventilatory threshold; and (e) hypotheses derived from the dual-mode model were tested. Results Intensity did not influence the positive changes from pre- to post-exercise, but it did influence the responses during exercise, with the intensity that exceeded the ventilatory threshold eliciting significant and relatively homogeneous decreases in pleasure. Conclusions Exceeding the intensity of the ventilatory threshold appears to reduce pleasure, an effect that could negatively impact adherence.     

Electrodiffusion of Cl− and K+ in epithelial membranes reconstituted into planar lipid bilayers

An electrodiffusive permeability for Cl^–, its activation by low extracellular Cl^–-concentrations and the interaction between electrodiffusive fluxes of Cl^– and K⁺ are demonstrated in the ventricular membranes from the epithelium of the bovine choroid plexus. Membranes were fused into artificial lipid bilayers formed at the tip of micropipettes. What is thought to be the cytoplasmic side of the membrane (the trans-side or the inside of pipette) was clamped at negative potentials (0 to –90 mV). Under these conditions the current was discrete, fluctuating less than 2 pA. With Cl^– as the only conducting ion on the two sides we observed a small electrodiffusive permeability which was reduced by bumetanide or furosemide by 62%. When the outside solution was rendered Cl^–-free then the permeability to Cl^– increased by a factor of 2–5; this activation was reduced by bumetanide or furosemide by about 80%. We observed an interaction between inwards movements of K⁺ and outwards movements of Cl^– via the activated permeability: The total current was smaller than the sum of the expected inward K⁺-current and the expected outward activated Cl^–-current. Bumetanide or furosemide increased the total current; apparently the loss of current carried by Cl^– was smaller than the gain in current carried by K⁺. The presence of K⁺ on both sides of the membrane was a condition for this interaction.     

天麻素注射液的稳定性研究

作者用化学动力学方法测得天麻素注射液的水解反应速度与天麻素浓度的一次方成正比,属假一级反应;测得天麻素水解反应的活化能:pH≤2.5的酸性介质中E_a=29.54±0.55kcal·mol~(-1),pH≥10.5的碱性介质中E_a=14.79±1.74kcal·mol~(-1);天麻素注射液稳定的pH值约为6.8,稳定的pH范围为5.5～7.5。     

The adenosine A<Subscript>2A</Subscript> antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure

Rationale  Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Research involving choice tasks has shown that rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements and instead select less effortful food-seeking behaviors. Objective  Previous work showed that adenosine A_2A antagonism can reverse the effects of the DA antagonist haloperidol in an operant task that assesses effort-related choice. The present work used a T-maze choice procedure to assess the effects of adenosine A_2A and A₁ antagonism. Materials and methods  With this task, the two arms of the maze have different reinforcement densities (four vs. two food pellets), and a vertical 44 cm barrier is positioned in the arm with the higher density, presenting the animal with an effort-related challenge. Untreated rats strongly prefer the arm with the high density of food reward and climb the barrier in order to obtain the food. Results  Haloperidol produced a dose-related (0.05–0.15 mg/kg i.p.) reduction in the number of trials in which the rats chose the high-barrier arm. Co-administration of the adenosine A_2A receptor antagonist MSX-3 (0.75, 1.5, and 3.0 mg/kg i.p.), but not the A₁ antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.75, 1.5, and 3.0 mg/kg i.p.), reversed the effects of haloperidol on effort-related choice and latency. Conclusions  Adenosine A_2A and D2 receptors interact to regulate effort-related decision making, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia that can be observed in depression, parkinsonism, and other disorders.     

An automated near-real time computational method for induction and treatment of scar-related ventricular tachycardias

Catheter ablation is currently the only curative treatment for scar-related ventricular tachycardias (VTs). However, not only are ablation procedures long, with relatively high risk, but success rates are punitively low, with frequent VT recurrence. Personalized in-silico approaches have the opportunity to address these limitations. However, state-of-the-art reaction diffusion (R-D) simulations of VT induction and subsequent circuits used for in-silico ablation target identification require long execution times, along with vast computational resources, which are incompatible with the clinical workflow. Here, we present the Virtual Induction and Treatment of Arrhythmias (VITA), a novel, rapid and fully automated computational approach that uses reaction-Eikonal methodology to induce VT and identify subsequent ablation targets. The rationale for VITA is based on finding isosurfaces associated with an activation wavefront that splits in the ventricles due to the presence of an isolated isthmus of conduction within the scar; once identified, each isthmus may be assessed for their vulnerability to sustain a reentrant circuit, and the corresponding exit site automatically identified for potential ablation targeting. VITA was tested on a virtual cohort of 7 post-infarcted porcine hearts and the results compared to R-D simulations. Using only a standard desktop machine, VITA could detect all scar-related VTs, simulating activation time maps and ECGs (for clinical comparison) as well as computing ablation targets in 48 minutes. The comparable VTs probed by the R-D simulations took 68.5 hours on 256 cores of high-performance computing infrastructure. The set of lesions computed by VITA was shown to render the ventricular model VT-free. VITA could be used in near real-time as a complementary modality aiding in clinical decision-making in the treatment of post-infarction VTs.     

流式细胞术测定冠心病血小板活化状态的研究

目的：检测冠心病患者全血血小板活化程度与冠状动脉病变程度,研究血小板活化在冠心病（CHD）中的作用。方法：采用流式细胞术（FCM）测定28例稳定型心绞痛（SAP组）、26例不稳定型心绞痛（UAP组）和16例急性心肌梗死（AM I组）患者的外周血中血小板糖蛋白（CD 62P）、溶酶体膜糖蛋白（CD 63）的阳性表达,并与20例非冠心病患者对照。结果：经冠状动脉造影的90例病例中70例为阳性,CD 62P表达率不稳定型心绞痛组与非冠心病对照组及稳定型心绞痛组比较、冠脉二支以上病变与无病变及一支病变比较差异有显著性;CD 63阳性表达率不稳定型心绞痛组与其余三组比较差异有显著性,二支病变与无病变及一支病变比较差异有显著性。结论：不稳定型心绞痛体内血小板活化程度明显增高,血小板活化状态与冠脉病变的严重程度相关。     

实验性瘙痒脑机制的功能性磁共振成像系统评价

目的通过Meta分析更全面地概括描绘实验性瘙痒所激活脑区,以更明确瘙痒相关高级中枢处理过程。材料与方法检索Pubmed、Cochrane中心、Wiley Online Library、Springer Link、Science Direct、Embase、CNKI和中国生物医学文献数据库,收集建库以来至2016年8月使用功能性磁共振成像(functional magnetic resonance imaging,f MRI)观察瘙痒状态下脑区激活的研究。使用Ginger-ALE 2.3.6软件计算脑区激活似然评估(activation likelihood estimation,ALE)分布,Mango软件进行图像整合。结果共有8篇文献纳入研究,样本量100。岛叶、丘脑内侧背核、屏状核、壳核、扣带前回、额上回、扣带后回、楔前叶、额中回、额下回和中央后回激活增加。结论通过对既往瘙痒f MRI研究的整合分析,认为外周瘙痒信息经脊髓的上行传导束传入中枢,主要激活中央后回、楔前叶、岛叶、扣带回、前运动和辅助运动区及前额叶等脑区,可能涉及感觉分辨加工、情绪反应、运动规划及认知评价等心理反应,从而实现瘙痒高级中枢处理过程。     

Abrupt Termination of an Ethanol Regimen Provokes Ventricular Arrhythmia and Enhances Susceptibility to the Arrhythmogenic Effects of Epinephrine in Rats

Background: Pathologists examining victims of sudden unexpected death encounter alcoholics more often than expected; alcohol may play a role in sudden arrhythmic death. Here we determine whether a pattern of alcohol consumption, chronic ethanol intake, and withdrawal increases the incidence of malignant ventricular arrhythmia and modulates susceptibility to the arrhythmogenic potential of sympathetic stimulation from an epinephrine test in rats. Methods: Male Wistar rats were treated with a continuous ethanol liquid diet for 7 weeks, and then subjected to 1-day withdrawal or 21-day abstinence. Ventricular ectopy was evaluated by 24-hour electrocardiographic telemetry recording; whole-body sympathetic activation, cardiac sympathovagal balance, and susceptibility to ventricular arrhythmia induced by sympathetic stimulation were evaluated based on blood noradrenalin metabolite concentrations, heart rate variability, and a 3-step epinephrine test. Results: Ventricular arrhythmia and related death were observed only in rats at 1 day of withdrawal, but not in nonalcoholic, continuous ethanol intake or 21-day abstinence rats. One-day withdrawal after a 7-week continuous ethanol regimen elevated circulating noradrenalin metabolite levels and induced cardiac sympathovagal imbalance. Deaths related to the epinephrine test and ventricular arrhythmia induced by low doses of epinephrine were observed only in 1-day withdrawal rats. However, all anomalies were normalized by 21-day abstinence. Conclusions: Abrupt termination of a 7-week continuous ethanol regimen is sufficient to enhance the whole-body sympathetic activation and cardiac sympathovagal imbalance that contribute to ventricular arrhythmia and sudden death in alcoholic rats. Those providing medical care for alcoholics, including in cases of legal imprisonment, should be aware of the possibility of enhanced susceptibility to sudden arrhythmic death due to the abrupt termination of a chronic ethanol regimen.     

Intralaboratory validation of four in vitro assays for the prediction of the skin sensitizing potential of chemicals

Allergic contact dermatitis is induced by repeated skin contact with an allergen. Assessment of the skin sensitizing potential of chemicals, agrochemicals, and especially cosmetic ingredients is currently performed with the use of animals. Animal welfare and EU legislation demand animal-free alternatives reflected in a testing and marketing ban for cosmetic ingredients beginning in 2013. The underlying mechanisms of induction and elicitation of skin sensitization are complex and a chemical needs to comply several properties being skin sensitizing. To account for the multitude of events in the induction of skin sensitization an in vitro test system will consist of a battery of various tests.Currently, we performed intralaboratory validations of four assays addressing three different events during induction of skin sensitization. (1) The Direct Peptide Reactivity Assay (DPRA) according to Gerberick and co-workers (Gerberick et al., 2004) using synthetic peptides and HPLC analysis. (2) Two dendritic cell activation assays based on the dendritic cell like cell lines U-937 and THP-1 and flow cytometric detection of the maturation markers CD54 and/or CD86 ( [Ashikaga et al., 2006], [Python et al., 2007] and [Sakaguchi et al., 2006]). (3) Antioxidant response element (ARE)-dependent gene activity in a HaCaT reporter gene cell line (Emter et al., 2010). We present the results of our intralaboratory validation of these assays with 23 substances of known sensitizing potential. The sensitivity, specificity, and accuracy of the individual tests were obtained by comparison to human epidemiological data as well as to data from animal tests such as the local lymph node assay.     

Lower concentrations of methyl-β-cyclodextrin combined with interleukin-2 can preferentially induce activation and proliferation of natural killer cells in human peripheral blood

Previous studies have demonstrated that high concentrations of methyl-β-cyclodextrin (MβCD, 10-15 mM) can interfere with the formation of lipid rafts and inhibit activation of lymphocytes. In this report, we determined that lower concentrations of MβCD (1-4 mM) could accelerate the proliferation of lymphocytes in human peripheral blood mononuclear cells (PBMCs). In the expanded cells, CD3(-)CD56(+) natural killer (NK) cells were the dominant subpopulation, and a significant dose-effect relationship existed between the proportion of NK cells and the concentration of MβCD. In the groups treated with 3-4 mM MβCD, the proportions of NK cells reached a level of more than 60%. When PBMCs were treated with MβCD, CD69 was more preferentially expressed on CD3(-)CD56(+) cells than on CD3(+) cells at 48 and 72 hours. The expression of CD25 had no distinct difference at 48 hours, but when recombinant human interleukin-2 (IL-2) was added for a further 24 hours, it was also preferentially expressed on NK cells. MβCD and IL-2 synergistically could also induce interferon-γ (IFN-γ) production in CD56(+) human PBMCs. Mechanistic studies revealed that IFN-γ production in response to MβCD plus IL-2 was IL-12 independent but depended on endogenous IL-18 and IL-1β, and CD56(+)CD14(+) dendritic cell-like cells and B cells might mediate the ability of MβCD to activate NK cells. The MβCD-activated NK cells also had high cytotoxicity against the natural killer cell-sensitive K562 cells or lymphokine-activated killer cell-sensitive DAUDI cells in vitro. These studies indicated that lower concentrations of MβCD combined with IL-2 can preferentially induce activation and proliferation of NK cells in PBMCs.