网络建模研究生物质烟雾引起的导致慢性阻塞性肺病的炎症反应动力学

慢性阻塞性肺病（COPD）是一种由慢性炎症引起的气道阻塞和渐进性的肺组织损伤.目前在全球范围内大概有30亿人使用生物质燃料进行烹饪和加热取暖,生物质烟雾被认为是慢性阻塞性肺病一个重要的危险因素.最近的临床数据表明,与吸烟引起的慢性阻塞性肺病不同,生物质烟雾引起的慢性阻塞性肺病（BS-COPD）病人有Th2类型的抗炎反应特征.然而,由于促炎反应是慢性阻塞性肺病的一个基本特征,人们对生物质烟雾引起的慢性阻塞性肺病的Th2类型的抗炎特征形成机理还不是很清楚.本文应用多尺度网络模型计算研究了生物质烟雾引起的炎症反应动力学.本文的网络模型涉及几个不同的正反馈通路,激活这些正反馈通路分别对应不同的慢性阻塞性肺病临床表现的形成机制.建模研究确定在一部分BS-COPD病人具有混合的M1（促炎）和Th2炎症反应特征.本文的计算结果与临床试验吻合得很好,而且计算敲除模拟显示几种重要的网络组成部分对COPD疾病形成起着重要作用.研究对BS-COPD的形成机制提供了新的见解,为未来利用标靶和个性化治疗慢性阻塞性肺病提供了可能的理论基础.     

网络建模研究生物质烟雾引起的导致慢性阻塞性肺病的炎症反应动力学（英文）

慢性阻塞性肺病(COPD)是一种由慢性炎症引起的气道阻塞和渐进性的肺组织损伤.目前在全球范围内大概有30亿人使用生物质燃料进行烹饪和加热取暖,生物质烟雾被认为是慢性阻塞性肺病一个重要的危险因素.最近的临床数据表明,与吸烟引起的慢性阻塞性肺病不同,生物质烟雾引起的慢性阻塞性肺病(BS-COPD)病人有Th2类型的抗炎反应特征.然而,由于促炎反应是慢性阻塞性肺病的一个基本特征,人们对生物质烟雾引起的慢性阻塞性肺病的Th2类型的抗炎特征形成机理还不是很清楚.本文应用多尺度网络模型计算研究了生物质烟雾引起的炎症反应动力学.本文的网络模型涉及几个不同的正反馈通路,激活这些正反馈通路分别对应不同的慢性阻塞性肺病临床表现的形成机制.建模研究确定在一部分BS-COPD病人具有混合的M1(促炎)和Th2炎症反应特征.本文的计算结果与临床试验吻合得很好,而且计算敲除模拟显示几种重要的网络组成部分对COPD疾病形成起着重要作用.研究对BS-COPD的形成机制提供了新的见解,为未来利用标靶和个性化治疗慢性阻塞性肺病提供了可能的理论基础.     

以吖啶橙为荧光探针研究士的宁和布鲁辛与小牛胸腺DNA的相互作用

以吖啶橙(AO)为荧光探针,应用各种光谱法和热力学方法研究士的宁和布鲁辛与小牛胸腺DNA(ct-DNA)的相互作用情况。实验结果表明,在模拟人体生理环境下,把士的宁和布鲁辛这两种药物加入到DNA-AO体系中时,DNA-AO的光谱特征发生了明显的变化:在200nm和260nm处的紫外光谱吸收峰均有明显的减色效应,但没有红移和蓝移现象,表明药物与DNA不是典型的嵌插作用结合;DNA-AO的荧光光谱被药物显著的猝灭,根据Stern-Volmer方程可计算出士的宁和布鲁辛与DNA的成键常数分别是9.85×103L.mol-1和4.76×103L.mol-1。热变性温度,离子强度法和黏度法进一步证明药物与DNA不是嵌插结合,而是以沟槽作用的方式结合。     

青光眼药物跨角膜输运特性实验研究

青光眼是导致眼睛失明的疾病之一。局部用药是治疗青光眼的一种有效方法,但角膜的低渗透性限制了药物快速输运至病变组织,因此亟待研究青光眼药物跨角膜输运特性。本文选用质量分数ω=0.01与质量分数ω=0.05两种不同质量分数的毛果芸香碱水溶液作为青光眼药物制剂,对其作用在猪角膜上进行了药物渗透的离体实验。实验结果表明:质量分数ω=0.05实验组接收池内药物浓度增长速率明显高于ω=0.01实验组,药物浓度增长速率与初始给药浓度成正比例;药物累积过程主要由非稳态与伪稳态两个阶段组成,得出了伪稳态阶段药物累积量与给药浓度,时间,角膜厚度以及药物扩散系数满足的函数;毛果芸香碱水溶液跨角膜输运的扩散系数约为2.47×10~(-6) cm~2/s。本文的研究将有助于后续进行建立青光眼药物跨角膜输运特性数学描述方程的工作,从而优化青光眼药物的药物设计。     

癌细胞信号网络动力学研究

癌症不仅是一种基因突变疾病,更是一种涉及诸如增殖、分化、凋亡和侵袭等多条细胞命运抉择的信号转导通路疾病.癌细胞内的信号通路虽然非常复杂但我们可以专注于关键蛋白的信号网络建模,定量研究癌细胞核心信号通路的动力学和功能调控机理.本文结合一些具体网络模型,介绍癌细胞信号网络动力学的研究进展.首先介绍信号网络的基序动力学研究,然后讨论细胞存活、增殖、侵袭、凋亡等单个功能模块的网络建模,以及几个模块耦合的信号网络,和以癌细胞为整体的癌细胞信号网络建模.这些研究表明,基于核心信号通路动力学的研究确实能促进对肿瘤发生发展机理的了解,为肿瘤的治疗和药物靶点的设计提供线索和思路,这些令人振奋的研究将激发未来更多类似的工作.     

抑制剂8CA与脂肪细胞脂肪酸结合蛋白(A-FABP)结合模式的分子动力学研究

脂肪细胞脂肪酸结合蛋白A-FABP(Adipocyte fatty-acid binding protein)是治疗脂质调节生物过程相关疾病的重要靶标.采用分子动力学模拟和MM-PBSA方法研究抑制剂8CA与A-FABP结合模式,结果表明静电相互作用和范德华作用驱动了抑制剂8CA与A-FABP的结合.基于残基的能量分解表明抑制剂8CA与R126间的极性相互作用为抑制剂与A-FABP的结合提供了重要贡献,该残基与8CA的相互作用较好地稳定了抑制剂与A-FABP复合物的稳定性.期望该研究可为治疗炎症、动脉硬化和代谢病药物设计提供一定的理论指导.     

抑制剂8CA与脂肪细胞脂肪酸结合蛋白(A-FABP)结合模式的分子动力学研究

摘要：脂肪细胞脂肪酸结合蛋白A-FABP(Adipocyte fatty-acid binding protein)是治疗脂质调节生物过程相关疾病的重要靶标. 分子动力学模拟和MM-PBSA方法被采用研究抑制剂8CA与A-FABP结合模式. 研究结果表明静电相互作用和范德华作用驱动了抑制剂8CA与A-FABP的结合。基于残基的能量分解表明抑制剂8CA与R126间的极性相互作用为抑制剂与A-FABP的结合提供了重要贡献. 该残基与8CA的相互作用较好地稳定了抑制剂与A-FABP复合物的稳定性. 我们期望这个研究能为治疗炎症、动脉硬化和代谢病药物设计提供一定的理论指导。     

抑制剂8CA与脂肪细胞脂肪酸结合蛋白(A-FABP)结合模式的分子动力学研究

摘要：脂肪细胞脂肪酸结合蛋白A-FABP(Adipocyte fatty-acid binding protein)是治疗脂质调节生物过程相关疾病的重要靶标. 分子动力学模拟和MM-PBSA方法被采用研究抑制剂8CA与A-FABP结合模式. 研究结果表明静电相互作用和范德华作用驱动了抑制剂8CA与A-FABP的结合。基于残基的能量分解表明抑制剂8CA与R126间的极性相互作用为抑制剂与A-FABP的结合提供了重要贡献. 该残基与8CA的相互作用较好地稳定了抑制剂与A-FABP复合物的稳定性. 我们期望这个研究能为治疗炎症、动脉硬化和代谢病药物设计提供一定的理论指导。     

荧光光谱法研究奥美拉唑和埃索美拉唑与牛血清白蛋白的相互作用

首次应用荧光光谱法研究外消旋体奥美拉唑和其中的一个单体S-奥美拉唑(埃索美拉唑)分别与牛血清白蛋白(BSA)的相互作用机制的异同.利用荧光猝灭反应求出了在pH7.4、pH8.0、pH9.0这三种环境中两个药物结合常数KA和结合位点数n,进一步根据热力学参数判断出它们的主要作用力类型.发现两个药物引起的BSA内源荧光的猝灭均是由静态猝灭引起的.在相同情况下埃索美拉唑对BSA的结合能力强于奥美拉唑,结合位点数部是1.两种药物分子与BSA之间的作用力类型主要为疏水作用力和静电作用力.可以得出结论:两个药物除了结合常数的差异外并无不同.     

4种中成药中Fe、Zn和Mg含量分析

对4种临床常用治疗泌尿系统疾病的中成药物中金属元素Fe、Zn和Mg含量进行测定,为研究该类药物中微量元素的作用及与治疗泌尿系统疾病的关系提供依据.选取4种临床上常用的补肾药物壮腰健肾丸、颐和春胶囊、全鹿丸和知柏地黄丸,粉碎、干燥至恒重,用分析天平准确称量1.0000g,每种平行取3份,采用HNO3-HClO4湿法消化,用原子吸收分光光度计测定其微量元素Fe、Zn和Mg的含量,观察不同药物中Fe、Zn和Mg元素的含量差别.结果表明,这4种中成药物中含有丰富的微量元素;测定结果为研究微量元素与治疗肾病提供了有用的数据.     

Paradoxical vocal fold motion: Presentation and treatment options

Paradoxical vocal fold motion is a rare disorder in which adduction of the folds occurs on inspiration. The disorder presents with signs of airway obstruction and often airway distress, so proper diagnosis by the otorhinolaryngologist is critical to subsequent management. We present a retrospective review of 10 patients with the diagnosis of paradoxical vocal fold motion seen over a 6-year period. Eight patients were females, and 6 required an acute airway intervention at presentation; 3 patients eventually underwent tracheotomy for respiratory decompensation. Six patients had a prior diagnosis of asthma, and this was determined to contribute to their respiratory status. Five patients were treated with botulinum toxin and 2 with flexible nasolaryngoscopic biofeedback, which improved the outcome. A review of the literature confirms a female predominance of patients presenting with paradoxical adduction and airway distress, often with a history of asthma and psychopathology. Our experience with botulinum toxin and biofeedback suggests that these procedures are viable treatment options in the management of patients with this disorder.     

Episodic paroxysmal laryngospasm: Voice and pulmonary function assessment and management

Episodic paroxysmal laryngospasm (EPL) is a sign of laryngeal dysfunction, often without a specific organic etiology, which can masquerade as asthma, vocal fold paralysis, or a functional voice disorder. The intermittent respiratory distress of EPL may precipitate an apparent upper airway obstructive emergency, resulting in unnecessary endotracheal intubation, cardiopulmonary resuscitation, or tracheostomy. During 27 months, seven women and three men, ages 30–76 years, were assessed by a high diagnostic index of suspicion, an intensive history including psychosocial factors, physical examination of the airways, provocative asthma testing, and swallowing studies. Videolaryngoscopy, stroboscopy, and pulmonary flow-volume loop testing were definitive. The classic appearance was paradoxic inspiratory adduction of the anterior vocal folds with a posterior diamond-shaped glottic gap. During an attack of stridor or wheezing, attenuation of the inspiratory flow rate as depicted by the flow-volume loop suggested partial extrathoracic upper airway obstruction. Swallowing evaluation by videolaryngoscopy and videoesophagography may uncover gastroesophageal reflux disease. Hallmarks of management include patient and family education by observation of laryngoscopic videos, a specific speech therapy program, psychotherapy, and medical treatment of associated disorders. Electromyography may become a valuable future adjunct. Unlike laryngeal dystonia, patients with EPL do not benefit from botulinum toxin type A.     

Grape seed extract attenuates lung parenchyma pathology in ovalbumin-induced mouse asthma model: an ultrastructural study

Due to the growing incidence of asthma and because of the non-specificity and side effects of the conventional drugs, the development of novel agents for the treatment of asthma has become considerably important. Natural plant products offer promising alternatives for the development of effective and safe treatments. Grape seed extract (GSE) is one such phytochemical supplement that has been shown to have potent antioxidant and anti-inflammatory effects. Thus, the present study aimed to investigate the effect of GSE to suppress lung parenchyma pathology and inflammation in ovalbumin-induced murine asthma model. Ovalbumin exposure was associated with many pathological and morphometric alterations in the lungs of asthmatic mice. The alterations involved alveolar size reduction, alveolar wall thickening, cellular infiltration and blood capillary congestion, as well as significant increase in the number of type II pneumocytes and lamellar bodies. However, GSE significantly ameliorated of the pathological changes of ovalbumin-induced asthma. The results support the possibility of GSE as an effective, safe anti-inflammatory dietary supplement to attenuate the pathogenicity of asthma. While these preliminary results appear promising, further studies are required to elucidate the precise mechanism of the modulatory effect of GSE on asthma remodeling.     

PVCM, PVCD, EPL, and irritable larynx syndrome: What are we talking about and how do we treat it?

Paroxysmal vocal cord movement/motion (PVCM), paroxysmal vocal cord dysfunction (PVCD), episodic paroxysmal laryngospasm (EPL), and irritable larynx syndrome (ILS) are terms used to describe laryngeal dysfunction masquerading as asthma, upper airway obstruction, or functional and organic voice disorders. The differential diagnosis of PVCM, PVCD, EPL, and ILS is critical to successful medical and behavioral management of the patient. During the past 10 years, 27 subjects, ages 15–79 years, were identified to have paroxysms of inspiratory stridor, acute respiratory distress, associated aphonia and dysphonia, resulting in misdiagnosis and unnecessary emergency treatments, including endotracheal intubation, cardiopulmonary resuscitation, massive pharmacotherapy, or tracheostomy. A multifactorial management program is proposed utilizing principles of motor learning, neurolinguistic programming model, respiratory and phonatory synchronization, relaxation techniques, concurrent monitoring of behavioral adjustments, and formal psychological counseling.     

The Relationship Between Chronic Cough and Paradoxical Vocal Fold Movement: A Review of the Literature

SUMMARY: Chronic cough (CC) and paradoxical vocal fold movement (PVFM) are debilitating conditions. PVFM has been given many labels, including vocal cord dysfunction, Munchausen's stridor, functional inspiratory stridor, nonorganic functional or psychogenic upper airway obstruction, factitious asthma, psychogenic stridor, emotional laryngeal wheezing, and episodic laryngeal dyskinesia. Although CC and PVFM have been considered separate entities in many reports, there is preliminary support for the notion that there may be an underlying link between these two conditions. Speech pathologists have become increasingly involved in the treatment of these patients and therefore need to understand the theoretical background of these disorders, the pathophysiological links between the two, and the impact of voice disorders on these populations. The aim of this article is to review the current literature on CC and PVFM from a speech pathology perspective to provide a model for defining and conceptualizing the disorders and to provide a framework for management and future research.     

Collection and X-ray microanalysis of airway surface liquid in the mouse using ion exchange beads

The airway surface liquid (ASL) is a thin layer of liquid covering the airway epithelium. The ionic composition of the ASL is assumed to be important for airway function and may be altered in diseases such as cystic fibrosis and exercise-induced asthma. A method for collection of ASL is presented in which the fluid is collected using small dextran ion-exchange beads. The beads are equilibrated with the ASL in a humidity chamber, collected under silicon oil, dried and analyzed by X-ray microanalysis. Analysis of standard beads prepared by exposure to different salt solutions shows that linear calibration lines can be obtained, but that beads absorb different elements to a different extent. The results show that the ASL in mice is hypotonic, and that the mucus component of the ASL has an elemental composition that is different from that of the periciliary fluid.     

Efficacy of Singing Bowls in Childhood Asthma—A Pilot and Feasibility Study

The potential use of sound and vibration for diagnostic and therapeutic purposes remains largely under-explored and under-estimated. Sound and vibrational energy has great positive impact on the mind and body. It could be particularly useful for psychosomatic diseases as a complementary therapy. Singing bowls, the spiritual ancient therapy has been claimed to aid in mind relaxation and painful and inflammatory conditions. Childhood asthma is an inflammatory airway disease and a psychosomatic disorder. The psychological management in it is often neglected leading to under-treatment or a relapse. Hence, we hypothesized that sound therapy with singing bowls might be useful as complementary therapy in management of childhood asthma. We aimed to study the effect of singing bowl session on child’s asthma severity and control and on the psychological well-being. Children <18 years of age and suffering from childhood asthma were recruited after informed written consent of parents. At the baseline, demographic and clinical details were noted. Anthropometric parameters, PEFR readings, asthma severity, parental and child’s subjective feeling of well-being, asthma control score, and pediatric symptom checklist score (based on age) were determined. The child was given 15 min of singing bowl session as per the set protocol. The subjective and objective evaluation of asthma control and psychological assessment was repeated at 1 month and 3 months follow-up and compared with the baseline results for clinical significance. Eighteen children formed the study group with a mean age of 9.13 ± 2.15 years (range 2–15.25 years). 4 children had psychological issues on initial screening. There was a significant improvement in asthma severity, subjective feeling of well-being and asthma control score at 3 months (p < 0.05). Singing bowl therapy could be a useful, low-cost complementary therapy in childhood asthmatics.     

Laryngeal Botulinum Toxin Injection: Can It Be a Cause of Obstructive Sleep Apnea as an Adverse Effect?

Spasmodic dysphonia is a chronic voice disorder that is characterized by involuntary spasms of the laryngeal muscles during speech production. Botulinum toxin injection into to the laryngeal muscles is the most common and effective treatment of choice for symptoms of spasmodic dysphonia. We present a 44-year-old man with adductor spasmodic dysphonia who was diagnosed as having upper airway obstruction in a polysomnographic examination during sleep after a botulinum toxin injection.     

The Complex Structure of the Pharmacological Drug–Disease Network

The complexity of drug–disease interactions is a process that has been explained in terms of the need for new drugs and the increasing cost of drug development, among other factors. Over the last years, diverse approaches have been explored to understand drug–disease relationships. Here, we construct a bipartite graph in terms of active ingredients and diseases based on thoroughly classified data from a recognized pharmacological website. We find that the connectivities between drugs (outgoing links) and diseases (incoming links) follow approximately a stretched-exponential function with different fitting parameters; for drugs, it is between exponential and power law functions, while for diseases, the behavior is purely exponential. The network projections, onto either drugs or diseases, reveal that the co-ocurrence of drugs (diseases) in common target diseases (drugs) lead to the appearance of connected components, which varies as the threshold number of common target diseases (drugs) is increased. The corresponding projections built from randomized versions of the original bipartite networks are considered to evaluate the differences. The heterogeneity of association at group level between active ingredients and diseases is evaluated in terms of the Shannon entropy and algorithmic complexity, revealing that higher levels of diversity are present for diseases compared to drugs. Finally, the robustness of the original bipartite network is evaluated in terms of most-connected nodes removal (direct attack) and random removal (random failures).