Contractile dysfunction in hypertrophied hearts with deficient insulin receptor signaling: possible role of reduced capillary density

Diabetics have worse outcomes than nondiabetics after a variety of cardiac insults. We tested the hypothesis that impaired insulin receptor signaling in myocytes worsens cardiac remodeling and function following injury, even in the absence of hyperglycemia. Mice with cardiomyocyte-restricted knock out of the insulin receptor (CIRKO) and wild type (WT) mice were treated with isoproterenol (ISO) for 2 or 5 days. Heart rates and cardiac mass increased comparably following ISO in WT and CIRKO mice. After 5 days, WT hearts were hyperdynamic by echocardiographic and left ventricular pressure measurements. However, CIRKO hearts had a blunted increase in contractility and relaxation following ISO. Interestingly, single myocytes isolated from both CIRKO ISO and WT ISO hearts had increased cellular shortening with prolonged time to peak shortening vs. respective shams. Thus, loss of myocytes or extramyocyte factors, rather than intrinsic dysfunction of surviving myocytes, caused the blunted inotropic response in ISO treated CIRKO hearts. Indeed, CIRKO ISO mice had increased troponin release after 2 days and greater interstitial and sub-endocardial fibrosis at 5 days than did ISO WT. Apoptosis assessed by TUNEL and caspase staining was increased in CIRKO ISO compared to WT ISO hearts; however, very few of the apoptotic nuclei were clearly in cardiac myocytes. After 5 days of ISO treatment, VEGF expression was increased in WT but not in CIRKO hearts. In keeping with this finding, capillary density was reduced in CIRKO ISO relative to WT ISO. Basal expression of hypoxia-inducible factor-1alpha was lower in CIRKO vs. WT hearts and may explain the blunted VEGF response. Thus, absence of insulin receptor signaling in the cardiac myocyte worsens catecholamine-mediated myocardial injury, at least in part, via mechanisms that tend to impair myocardial blood flow and increase ischemic injury.     

毛细管气相色谱法测定酒石酸托特罗定中有机溶剂的残留量

摘 要 目的： 建立毛细管气相色谱法测定酒石酸托特罗定中8种有机溶剂残留量的方法。 方法: 采用CP sil 5CB色谱柱（60.0 m×0.32 mm,5 μm）;进样口温度为200℃;FID检测器温度为250℃;载气流速为1.2 ml·min^-1;柱温120℃;顶空瓶平衡温度85℃,时间30 min,以二甲基甲酰胺 水（1∶4）混合溶液为溶解介质,测定酒石酸托特罗定中甲醇,乙醇,乙腈,丙酮,乙酸乙酯,三氯甲烷和四氢呋喃的残留量;采用HP 1色谱柱（30.0 m×0.53 mm,5 μm）,进样口温度为220℃;FID检测器温度为250℃;载气流速为3.0 ml·min^-1;柱温80℃;顶空瓶平衡温度85℃,时间30 min,以二甲亚砜 氢氧化钠溶液（17∶13）混合溶液为溶解介质,测定酒石酸托特罗定中吡啶的残留量。结果:在各色谱条件下,被测溶剂峰之间均分离良好,8种溶剂的标准曲线线性良好,相关系数均大于0.999;平均回收率为86.0%～100.2%,RSD为1.7%～3.5%(n=9);甲醇,乙醇,乙腈,丙酮,乙酸乙酯,三氯甲烷,四氢呋喃和吡啶的检测限分别为0.63,0.43,0.30,0.18,0.079,0.36,0.18,0.89 μg·ml^-1。结论: 该法适用于酒石酸托特罗定中这8种有机溶剂残留量的测定。     

气相色谱法测定厄贝沙坦中9种残留溶剂

目的:建立厄贝沙坦原料药中9种残留溶剂(甲醇,乙醇,丙酮,异丙醇,乙腈,二氯甲烷,甲基叔丁基醚,乙酸乙酯及甲苯)的检测方法。方法:色谱柱为Kromat KB-624(30 m×0.53 mm,3.0μm);程序升温;载气为氮气,流速为5.0 ml·min-1;进样口温度为200℃;检测器为氢火焰离子化检测器,检测器温度为250℃;顶空进样,顶空瓶平衡温度为80℃,平衡时间20min。以二甲基亚砜为溶剂,用外标法测定9种残留溶剂的量,进样量为1 ml。结果:在本色谱条件下,9种残留溶剂分离良好。在各自的浓度范围内线性关系良好(r≥0.999 1),平均回收率为99.08%~105.14%,RSD为1.1%~3.3%(n=9);定量限分别为15.68,25.45,1.09,10.61,4.54,5.73,1.04,10.58,1.89μg。结论:本方法简便,准确,重复性好,可用于厄贝沙坦原料药中多种残留溶剂的同时测定。     

Clinical characteristics of influenza virus-induced lower respiratory infection during the 2015 to 2016 season

Background

Influenza A(H1N1)pdm09 virus infections often manifest severe respiratory symptoms, particularly in patients with a past history of allergic disease. Most of these findings were reported during the 2009 pandemic. The purpose of this study was to detail the clinical characteristics of influenza virus-induced lower respiratory infection (LRI) during the A(H1N1)pdm09-predominant 2015–2016 season.

普米克令舒和可必特雾化吸入治疗哮喘性支气管炎的临床分析

目的：探讨普米克令舒和可必特雾化吸入治疗哮喘性支气管炎的临床效果。方法：选取2012年10月～2013年10月在我院治疗的哮喘性支气管炎患者96例,随机分组,观察组48例采用普米克令舒联合可必特雾化吸入治疗,对照组单纯采用普米克令舒雾化吸入治疗,观察疗效并对比分析。结果：观察组的总有效率为97.8%,对照组总有效率为71.7%,差异显著（P＜0.05）,具有统计学意义。对比治疗期间两组患者临床症状好转时间,观察组优于对照组,指标差异显著（P＜0.05）,具有统计学意义。结论：临床治疗哮喘性支气管炎采用普米克令舒联合可必特雾化吸入治疗,具有见效快、效率高的优势。     

Circulating intercellular adhesion molecule 1 in rheumatoid arthritis — Relationship to systemic vasculitis and microvascular injury in nailfold capillary microscopy

Summary Intercellular adhesion molecule-1 (ICAM-1) is a membrane bound molecule that plays an important role in the pathogenic inflammatory responses observed in vasculitis. The aim of this study was to determine whether levels of soluble ICAM-1 sICAM-1) shedding into the circulation reflect the vascular injury found in nailfold capillaroscopy as well as systemic vasculitis in RA patients. We determined serum levels of sICAM-1 and soluble interleukin-2 receptor (sIL-2R) by an enzyme-linked immunosorbent assay in 79 RA patients. Serum level of sICAM-1 were significantly increased in RA patients compared to 30 healthy controls. RA patients with clinical signs of systemic vasculitis showed significantly higher levels of sICAM-1 than those without vascular involvement. Although no significant correlation between sICAM-1 levels and the capillaroscopy findings were found, 75% of the patients with severe vascular changes in capillaroscopy exceeded normal sICAM-1 cut off value. Serum sICAM-1 concentrations correlated significantly with the erythrocyte sedimentation rate and serum sIL-2R, but not with the duration of RA, radiological stages, Ritchie index, age or type of treatment. These findings suggest that increased levels of sICAM-1 in serum of RA patients reflect systemic vascular involvement rather than a local vascular injury.     

Imaging of Ca2+ Transients in Endothelial Cells of Single Perfused Capillaries: Correlation of Peak [Ca2+]i with Sites of Macromolecule Leakage

Objective: To investigate the mechanisms responsible for variation in the macromolecular leakage (formation of localized leaky sites) in venular microvessels with increased permeability, we examined the hypothesis that cytoplasmic calcium concentration [Ca²⁺]_i, does not increase uniformly within microvessel endothelial cells. Methods: We loaded the endothelial cells forming the walls of venular microvessels in frog mesentery with fura-2, and imaged [Ca²⁺]_i using a cooled CCD camera. Results: Control [Ca²⁺]_i was close to 60 nM in all regions. Control permeability was uniformly low in all microvessels. Exposure to ionomycin (5 mM) increased [Ca²⁺]_i in a biphasic manner, but not uniformly. There was variation in both time to peak (bimodal distribution) and peak [Ca²⁺]_i (274 ± 13 nM; mean variation above or below the peak value was 110 nM). Raising extracellular calcium from 1.1 to 5 mM increased the mean variation of [Ca²⁺]_i about peak values. Extravascular leakage of fluorescently labeled albumin or low-density lipoproteins was most prominent at sites where increases in [Ca²⁺]_i were largest. Conclusions: These data indicate that variation in [Ca²⁺]_i within individual endothelial cells or groups of cells could account, at least in part, for the distribution of localized leakage sites for macromolecules in venular microvessels in the high-permeability state.     

治咳川贝枇杷滴丸治疗慢性支气管炎（单纯型）急性发作（痰热郁肺证）的多中心随机双盲对照研究

目的 观察治咳川贝枇杷滴丸治疗慢性支气管炎（单纯型）急性发作（痰热郁肺证）有效性和安全性。方法 160例西医诊断为慢性支气管炎（单纯型）急性发作、中医辨证痰热郁肺证患者随机分为试验组120例和对照组40例。试验组口服治咳川贝枇杷滴丸,6丸/次,3次/d;对照组口服枇杷止咳胶囊,2粒/次,3次/d;两组疗程均为10 d。以临床疗效为主要观察指标。结果 治疗后试验组咳嗽、咯痰症状减轻的起效中位时间为102.0 h（FAS数据集,下同）、对照组为123.5 h,试验组咳嗽、咯痰症状痊愈中位时间为199.0 h、对照组为未痊愈,两组比较差异均具有统计学意义（P<0.05）;两组治疗后中医证候评分均较治疗前均明显减少,组内治疗前后比较,差异均具有统计学意义（P<0.01）,但治疗后中医证候评分与基线差值的组间比较无统计学差异（P>0.05）;治疗满10 d,试验组总愈显率为64.17%,对照组为45.00%,两组比较,差异具有统计学意义（P<0.05）;试验组发生不良事件10例（6.67%）,对照组发生不良事件3例（7.50%）,两组比较差异无统计学意义（P>0.05）;试验期间无严重不良事件发生。结论 治咳川贝枇杷滴丸治疗慢性支气管炎（单纯型）急性发作（痰热郁肺证）的临床疗效确切,安全性较好,具有较好的临床应用前景。     

Unidentified Bacterial Microorganisms Entrapped Within Blood Capillary Spaces of Tissue From Different Epidemiological Types of Kaposi's Sarcoma

Tissue specimens of different epidemiological types of Kaposís sarcoma (KS) from various geographical regions were investigated by transmission electron microscopy. Freshly fixed KS biopsies originated from 9 German patients: 3 classic KS cases, 5 AIDS-associated KS cases, and 1 atypical classic KS case. Additionally, KS autopsy material from the brain of a German AIDS patient was examined. Further biopsies came from 29 Ugandan patients: 16 endemic KS cases and 13 AIDS-associated KS cases. While investigating the ultrastructure, we discovered relatively small-sized bacterial microorganisms within blood capillary spaces of tumor tissue from 5 KS cases of different epidemiological type. The microorganisms often occurred in clusters. They were of coccoid-bacillary form and limited by a wrinkled multilayered cell wall. Many of them were encapsulated. They were not observed outside of the capillary lumen. The bacterial structures were often seen attached to capillary endothelial cells, which sometimes showed blistering into the capillary lumen. The observed bacterial microorganisms obviously represented agents of a bloodstream infection and must have been entrapped and accumulated within capillary spaces of KS tissue. The bacteria, which had an almost identical morphology in all 5 KS cases, could not be identified. If they are of pathogenic significance, it remains unknown.     

循证护理在改善慢性支气管炎并肺部感染患者睡眠质量中的应用

目的:探讨循证护理在改善慢性支气管炎并肺部感染患者睡眠质量中的应用。方法:选取2018年5月至2019年5月石景山医院收治的慢性支气管炎并肺部感染患者60例作为研究对象,按照随机数表法分为观察组和对照组,每组30例。观察组实施循证护理,对照组实施常规护理,比较护理效果。结果:护理前观察组2组匹兹堡睡眠质量指数(PSQI)、简化舒适状况量表(GCQ)评分与对照组比较差异有统计学意义(P<0.05);护理后观察组心理评分均低于对照组(P<0.05)。结论:循证护理在改善慢性支气管炎并肺部感染患者睡眠质量中的应用效果显著,可降低心理压力,提高睡眠质量,值得推广。