Inhibitory effects of the atypical antipsychotic,clozapine, on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an half-inhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06. Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapine-induced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentration- and use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapine-induced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.     

Phenotype of Asthma-COPD Overlap in COPD and Severe Asthma Cohorts

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.MethodsPatients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL).ResultsThe prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) – 9.1%; group B (light smoker with low BEC) – 3.7%; group C (moderate to heavy smoker with high BEC) – 73.8%; and group D (moderate to heavy smoker with low BEC) – 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.ConclusionThe prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.     

富氧水对高原移居青年心肺功能的影响

目的：探讨在高原服用富氧水对移居青年心肺功能的影响。方法：对进驻海拔3700m1年的10名青年在服用富氧水前和服用富氧水（每次500mL,一日2次）15天后分别用EGM-II型踏车功量计做坐位踏车运动,初始负荷功率为50W,每3min递增50W,以60r/min连续踏车至200W,3min后终止。用直线回归法计算每位受试者功率200W时的心率（HR）及血氧饱和度（SaO2）,记录运动终止5min后恢复HR,按公式计算心功能指数。结果：服用富氧水15天后,心功能指数增高,功率200W时SaO2增高;功率200W时的HR和运动终止5min恢复HR降低,差别有非常显著性意义（P〈0.01）。结论：服用富氧水能提高高原移居青年的心肺功能。     

一种新的T细胞相关分子IBP表达水平定量检测方法的建立

目的 建立一种定量检测IBP表达水平的方法 ,为研究IBP在免疫细胞分化以及在免疫性疾病当中的作用奠定基础.方法 利用反转录PCR和PCR技术获得目的 基因和内参基因片段,构建重组质粒,以重组质粒为标准品,建立实时PCR标准曲线;测定外周血白细胞IBP和β-actin表达水平.以β-actin为内参照,均一化检测结果 .结果 重组质粒的阳性克隆经PCR扩增,0.8%琼脂糖凝胶电泳鉴定,目的 基因片段插入载体内;建立起实时PCR标准曲线.检测20例正常人全血标本,得到比较稳定的检测结果 .结论 成功建立了用实时PCR定量检测IBP mRNA表达水平方法 ,为进一步研究IBP奠定了基础.     

Total arch repair versus hemiarch repair in the management of acute DeBakey type I aortic dissection

Objective: In acute DeBakey type I aortic dissection, it is still controversial whether to perform extended aortic replacement to improve long-term outcome or to use a conservative strategy with ascending aortic and hemiarch replacement to palliate a life-threatening condition. Methods: Between 1999 and 2009, 188 consecutive patients (93 women; mean age, 57.4 ± 11.7 years) with acute DeBakey type I aortic dissection underwent hemiarch (Hemiarch group; n = 144) or total arch replacement (Total arch group; n = 44) in conjunction with ascending aorta replacement. Clinical outcomes were compared after adjustment for baseline characteristics using inverse-probability-of-treatment weighting. Results: Median follow-up was 47.5 months (range 0–130.4 months) and was 92.0% (n = 173) complete. Five-year unadjusted survival and permanent-neurologic-injury-free survival rates were 65.8 ± 8.3% and 43.1 ± 9.7% in the Total arch group, and 83.2 ± 3.3% and 75.2 ± 4.0% in the Hemiarch group, respectively (P = 0.013 and <0.001). After adjustment, the Total arch group patients were at greater risks of death (hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.21–4.67; P = 0.012), and permanent neurologic injury (HR 3.25, 95% CI 1.31–8.04; P = 0.011) compared to the Hemiarch group patients. The risks of the re-operation for aortic pathology or distal aortic dilatation (>55 mm) were similar for both groups (HR 0.33, 95% CI 0.08–1.43; P = 0.14). Conclusions: Total arch repair was associated with greater morbidity and mortality compared with hemiarch repair in acute DeBakey type I aortic dissection. Rates of aortic re-operation or aortic dilatation were not significantly different between the two surgical strategies. These findings support a conservative surgical approach to circumvent this life-threatening situation.     

三康胶囊对高原移居青年体力作业效率的影响

目的探讨在高原服用三康胶囊对移居青年体力作业效率的影响。方法对进驻海拔3 700 m 1年的10名青年在服药前和服药15d后分别用EGM-Ⅱ型踏车功量计做坐位踏车运动,初始负荷功率为50 W,每3 m in递增50 W,以60 r/m in连续踏车至200 W 3 m in后终止。用直线回归法计算每位受试者的PMC170,HR90w、功率200 W时的HR及SaO2,运动终止5 m in后恢复HR,按公式计算心功能指数。结果服药后各项检测指标较服药前均有非常显著性差异(P<0.01)。结论服用三康胶囊能明显提高高原移居青年的体力作业效率。     

海拔1400m某部官兵睡眠呼吸暂停低通气综合征患病率调查

目的调查某部官兵睡眠呼吸暂停低通气综合征(SAHS)的患病率,为进一步了解移居不同海拔高度不同时间人群的患病情况提供参照,并为制定该病的防治策略提供依据。方法采用整群抽样的方法对驻守海拔1 400 m的某部官兵进行睡眠问卷调查,根据打鼾程度及日间嗜睡评分保守估计人群SAHS患病率。结果在调查的348人中打鼾的发生率为39.08%,中度打鼾者占5.17%,无重度鼾症患者。吸烟和饮酒与打鼾程度相关。有高原接触史的被调查者打鼾发生率高于未曾上过高原者(χ2=7.122,P=0.028)。不同程度的打鼾患者,日间的嗜睡评分有显著性差异(F=3.689,P=0.013)。结论如果仅依据日间Epworth嗜睡量表(ESS)评分≥9分为标准,保守估计驻守海拔1 400 m某部官兵的SAHS患病率为4.02%,打鼾及SAHS是严重危害健康的疾病之一,但未引起人们的重视,需要搞好宣传教育工作。     

Three-Point Bending Properties of Hybrid Multi-Materials Using Adhesive Bonding Dependent on Strength Difference between Steel and Aluminum

The mechanical behaviors of two multi-materials, DP590 (steel sheet)–A356 (cast aluminum alloy) and SS330 (steel sheet)–A5052 (aluminum sheet), were studied. A structural adhesive was used for the joining of steel and aluminum at adhesion strengths of 10, 22, and 30 MPa. To demonstrate that the three-point bending properties depend on the difference in strength between steel and aluminum and adhesion strength, optical microscopy (OM), scanning electron microscopy (SEM), and finite-element analysis (FEA) were performed. According to the results of the bending tests on both multi-materials under the same stacking conditions, the flexural stress increased with the improvement in the adhesion strength until interface separation or aluminum fracture. At the same adhesion strength, the DP590 (lower)–A356 (upper) and SS330 (upper)–A5052 (lower) configurations exhibited a tendency to decrease in the sudden stress drop due to aluminum fracture and interface separation. The bending results were analyzed through the FEA and the stress distribution as a function of the stacking and adhesion strength was confirmed.     

口服富氧水对高原移居者肺功能的影响

目的探讨在海拔3 700 m和5 200 m高原口服富氧水对肺功能的影响。方法（1）在海拔3 700 m将20名已习服半年的男性志愿者分为实验组和对照组,实验组口服5%葡萄糖注射液制成的富氧水,对照组口服5%葡萄糖注射液,均每次500 m l,2次/d。饮用3 d后检测其肺功能,检测指标包括FVC、FEV1、FEV1%、MMEF、PEF和MVV。（2）对首次进驻海拔5 200 m的36名男性志愿者,自海拔1 400 m驻地乘汽车2 d到达海拔3 700 m当日随机分实验组和对照组,同前服用富氧水或生理盐水,直至进入海拔5 200 m某哨卡第6天,共服9d后检测肺功能。结果习服志愿者口服富氧水3 d和初进高原志愿者口服富氧水9 d,肺功能指标中FVC、FEV、MMEF、PEF、MVV均显著增高（P〈0.01,或P〈0.05）,FEV1%无显著性变化（P〉0.05）。结论在高原口服富氧水能提高移居者的肺通气功能。