Characterizing Changes in the Excitability of Corticospinal Projections to Proximal Muscles of the Upper Limb

BackgroundThere has been an explosion of interest in methods of exogenous brain stimulation that induce changes in the excitability of human cerebral cortex. The expectation is that these methods may promote recovery of function following brain injury. To assess their effects on motor output, it is typical to assess the state of corticospinal projections from primary motor cortex to muscles of the hand, via electromyographic responses to transcranial magnetic stimulation. If a range of stimulation intensities is employed, the recruitment curves (RCs) obtained can, at least for intrinsic hand muscles, be fitted by a sigmoid function.Objective/hypothesisTo establish whether sigmoid fits provide a reliable basis upon which to characterize the input–output properties of the corticospinal pathway for muscles proximal to the hand, and to assess as an alternative the area under the (recruitment) curve (AURC).MethodsA comparison of the reliability of these measures, using RCs obtained for muscles that are frequently the targets of rehabilitation.ResultsThe AURC is an extremely reliable measure of the state of corticospinal projections to hand and forearm muscles, which has both face and concurrent validity. Construct validity is demonstrated by detection of widely distributed (across muscles) changes in corticospinal excitability induced by paired associative stimulation (PAS).Conclusion(s)The parameters derived from sigmoid fits are unlikely to provide an adequate means to assess the effectiveness of therapeutic regimes. The AURC can be employed to characterize corticospinal projections to a range of muscles, and gauge the efficacy of longitudinal interventions in clinical rehabilitation.     

Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia

Key points

• Raised arterial blood CO₂ (hypercapnia) is a feature of many lung diseases.
• CO₂ has been shown to act as a cell signalling molecule in human cells, notably by influencing the levels of cell signalling second messengers: cAMP and Ca²⁺.
• Hypercapnia reduced cAMP‐stimulated cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid transport in Calu‐3 cells and primary human airway epithelia but did not affect cAMP‐regulated HCO₃ ⁻ transport via pendrin or Na⁺/HCO₃ ⁻ cotransporters.
• These results further support the role of CO₂ as a cell signalling molecule and suggests CO₂‐induced reductions in airway anion and fluid transport may impair innate defence mechanisms of the lungs.

Abstract

Hypercapnia is clinically defined as an arterial blood partial pressure of CO₂ of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist‐stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP‐regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin‐stimulated elevations in intracellular cAMP as well as both adenosine‐ and forskolin‐stimulated increases in CFTR‐dependent transepithelial short‐circuit current, in polarised cultures of Calu‐3 human airway cells. This CO₂‐induced reduction in anion secretion was not due to a decrease in HCO₃ ⁻ transport given that neither a change in CFTR‐dependent HCO₃ ⁻ efflux nor Na⁺/HCO₃ ⁻ cotransporter‐dependent HCO₃ ⁻ influx were CO₂‐sensitive. Hypercapnia also reduced the volume of forskolin‐stimulated fluid secretion over 24 h, yet had no effect on the HCO₃ ⁻ content of the secreted fluid. Our data reveal that hypercapnia reduces CFTR‐dependent, electrogenic Cl⁻ and fluid secretion, but not CFTR‐dependent HCO₃ ⁻ secretion, which highlights a differential sensitivity of Cl⁻ and HCO₃ ⁻ transporters to raised CO₂ in Calu‐3 cells. Hypercapnia also reduced forskolin‐stimulated CFTR‐dependent anion secretion in primary human airway epithelia. Based on current models of airways biology, a reduction in fluid secretion, associated with hypercapnia, would be predicted to have important consequences for airways hydration and the innate defence mechanisms of the lungs.     

放射性同位素示踪技术在药物研发过程中的应用

药物的吸收、分布、代谢和排泄过程决定了药物分子在体内的过程和命运。作为常规生物样本检测技术的有效补充,放射性同位素标记示踪技术如今也被广泛应用于药物发现和开发过程中的各个阶段。特别是其高灵敏性、适用范围广的特点使其具有不可比拟的优势。通过对近年来放射性标记技术在药物评价领域中的应用进行了归纳和梳理,为药物研发相关领域研究人员提供可借鉴的参考。     

鼻中隔矫正术对变应性鼻炎伴鼻中隔偏曲患者生活质量的影响

目的评价鼻中隔偏曲矫正术对持续性变应性鼻炎（allergicrhinitis,AR）伴鼻中隔偏曲患者症状和生活质量的影响。方法应用症状视觉模拟评分量表（Visual Analogue Scale,VAs）和鼻结膜炎生存质量量表（Rhinocon junctivitis Quality of Life Questionnaire,RQI。Q）对62例持续性变应性鼻炎伴鼻中隔偏曲患者行鼻中隔偏曲术前、术后1个月、术后6个月临床症状和生活质量进行研究。结果鼻中隔偏曲矫正术后1个月、6个月患者症状、生活质量较术前均得到改善。术后1个月、6个月RQI．Q量表中各个维度的得分较术前明显降低,差异有统计学意义（P〈0．05）;术后6个月除总评分外,其余各维度与术后1个月比较,差异无统计学意义（P〉0．05）。VAS量表显示：术后患者症状较术前均有不同程度的改善,但改善最明显的为鼻塞,其次为打喷嚏。结论变应性鼻炎伴鼻中隔偏曲患者的生活质量降低,鼻中隔偏曲矫正术能明显的改善患者症状同时能提高患者的生活质量。     

藏族初中生心理健康状况与应对方式的关系研究

目的 了解应对方式对藏族初中生心理健康状况的影响。方法 采用自编的一般资料,中学生心理健康评定量表、简易应对方式问卷对786名藏族初中生进行问卷调查。结果 分层回归分析显示,第一层人口变量中上学方式、年级、家庭人均月收入、是否留守、学习成绩进入藏族初中生心理健康状况的回归方程(F=8.526,P=0.000),控制人口变量后,应对方式能独立解释心理健康状况21.70%的方差变异。结论 住校、初一、留守、学习成绩差、家庭收入低的藏族初中生心理健康状况差;管理者加强应对技巧的培训,能改善藏族初中生的心理健康状况。     

细菌快速检测试纸片法与传统方法培养结果的比较

目的比较细菌快速检测试纸片法与传统的方法在细菌检测结果上的差异。方法用试纸片法对物体表面污染菌总数和大肠杆菌进行检测,同时与传统方法作平行比较。结果检测细菌总数,用常规方法培养48 h后,细菌生长正常;而纸片法培养48 h,营养琼脂平板上无菌生长,继续培养至72 h才出现菌落。大肠菌群检测中,传统9管发酵法培养24h即有菌生长,国产大肠菌群快速检测试纸法培养36 h和日本产试纸片培养48 h才出现肉眼可见菌落。结论细菌快速检测试纸片虽能简化操作,但存在技术缺陷,且成本高。     

血管紧张素Ⅱ1型受体基因A1166C多态性与高血压肾脏损害相关性研究

目的:探讨血管紧张素Ⅱ1型受体(AT1R)A1166C多态性与高血压、高血压肾脏损害的关系。方法:入选188例原发性高血压患者进行尿微量白蛋白和AT1R基因A1166C多态性测定。结果:AA基因型与AC基因型收缩压分别为(149·1±20·8)mmHg(1mmHg=0·133kPa)和(137·8±22·6)mmHg,2组间差异有显著性(P=0·013)。AC基因型携带者尿微量白蛋白尿异常者明显增多,差异有显著性(P=0·006)。结论:AT1R基因A1166C多态性可能与原发性高血压和高血压肾脏损害有关。     

胃食管反流病与阻塞性睡眠呼吸暂停低通气综合征的相关性研究

目的探讨胃食管反流病(GERD)与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)间的关系。方法选取解放军第三五九医院2009年3月至2012年5月收治的OSAHS患者163例,根据研究对象是否存在GERD分为伴有GERD组和无GERD组,分析两组间体质量指数(BMI)、睡眠呼吸紊乱指数(AHI)和GERD症状评分;根据研究对象OSAHS的严重程度分为三组:轻度组、中度组和重度组,对组间GERD症状评分、睡眠分期及动脉血氧饱和度(SaO2)进行分析。结果 OSAHS患者中GERD发生率为59.5%,伴有GERD患者的GERD症状积分、AHI和BMI均高于无GERD者,差异有统计学意义(P<0.01)。重度组OSAHS患者GERD症状积分显著高于轻度和中度组,缺氧程度也重于轻度组,差异有统计学意义(P<0.05)。结论 OSAHS与GERD关系密切,但它们的关系是因果还是伴随关系仍需进一步研究。