Pharmacologic and cellular therapies in the treatment of traumatic spinal cord injuries: A systematic review

ObjectiveThe objective of this review is to synthesize and consolidate the existing literature on the treatment of SCI, focusing on drugs in development and cellular therapeutics, including stem-cell treatments.MethodsStudies were identified through a systemic search of PubMed, Ovid MEDLINE, Embase and the Cochrane database from their respective inceptions through January 1, 2020. We used the keywords “spinal cord injuries”, “therapeutics”, “stem cells”, and “pharmacology.”Study selectionStudies that assessed treatment strategies for SCI were included.Data extraction and synthesisData on SCIs were processed according to the Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) guidelines.FindingsIn total, 62 articles were found in the literature search and 13 clinical trials were identified and included in this study. This review article discusses the management and treatment of SCI with an emphasis on the pharmacology, molecular approaches, and the use of stem cells. Presently, none of the treatments examined has shown to be clearly effective.ConclusionsPresent management strategies of SCI are focused on improving spinal cord perfusion and decreasing secondary injuries such as hypoxia, inflammation, edema, excitotoxicity and disturbances of ion homeostasis. This review hopes to demonstrate the significant advances made in the field of SCI and the new methodologies and practices being employed by researchers to improve our knowledge of the pathology. Our hope is that by consolidating the past and current research, improvements can be made in the management, treatment, and outcomes for these patients and other who suffer from spinal pathologies.     

Translational paradigms in pharmacology and drug discovery

The translational sciences represent the core element in enabling and utilizing the output from the biomedical sciences and to improving drug discovery metrics by reducing the attrition rate as compounds move from preclinical research to clinical proof of concept. Key to understanding the basis of disease causality and to developing therapeutics is an ability to accurately diagnose the disease and to identify and develop safe and effective therapeutics for its treatment. The former requires validated biomarkers and the latter, qualified targets. Progress has been hampered by semantic issues, specifically those that define the end product, and by scientific issues that include data reliability, an overt reductionistic cultural focus and a lack of hierarchically integrated data gathering and systematic analysis. A necessary framework for these activities is represented by the discipline of pharmacology, efforts and training in which require recognition and revitalization.     

基于网络药理学的大果木姜子油治疗心力衰竭作用机制研究

目的:揭示大果木姜子油治疗心力衰竭的作用机制。方法:首先从动物药理学实验验证疗效,采用异丙肾上腺素(ISO)诱导复制心力衰竭大鼠模型,造模成功后应用大果木姜子油治疗4周,监测血流动力学指标,分析血清BNP水平和心肌组织形态学变化;然后基于文献检索和TCMSP数据库获取大果木姜子油活性成分及作用靶点,从CTD和Drugbank数据库筛选心力衰竭的已知治疗靶点,将疾病治疗靶点与大果木姜子油活性成分作用靶点进行Venn分析,运用SYBYL软件进行分子对接验证,运用STRING数据库分析蛋白互作关系,再利用DAVID数据库进行GO分子功能和KEGG通路富集分析。结果:大果木姜子油可显著升高ISO诱导的心衰大鼠LVSP、±dp/dtmax,降低LVEDP和BNP水平,改善心肌组织形态学变化;获得大果木姜子油20个活性成分,其中7个活性成分(沉香螺旋醇、芳樟醇、萜品烯-4-醇等)可能通过调控一个蛋白互作网络治疗心力衰竭,该网络中的靶点有PTGS1、PTGS2、NOS2、NOS3、GSK3B;由蛋白富集分析发现,这些靶点与前列腺素内过氧化物合酶活性和一氧化氮合酶活性有关。结论:大果木姜子油可改善心衰大鼠的血流动力学紊乱及心肌组织形态学变化;其治疗心力衰竭的机制可能与调控前列腺素内过氧化物合酶活性和一氧化氮合酶活性有关。     

头孢哌酮钠及其复方制剂的配伍禁忌

目的了解头孢哌酮钠及其复方制剂的配伍禁忌，供临床用药参考，避免其不良反应的发生。方法通过检索2009—2011年期间公开发表的头孢哌酮钠及其复方制剂配伍禁忌文献，进行总结归纳。鳍果头孢哌酮钠及其复方制剂与很多药物配伍试验均存在不同程度的配伍反应。结论头孢哌酮钠及其复方制剂的配伍禁忌较多，联合应用时应该谨慎，促进用药合理有效。     

The Effects of Guanfacine and Phenylephrine on a Spiking Neuron Model of Working Memory

We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate two drugs that affect WM: guanfacine (GFC) and phenylephrine (PHE). In this model, the loss of information over time results from changes in the spiking neural activity through recurrent connections. We reproduce the standard forgetting curve and then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating functional, neural, and biophysical properties of the model. In particular, applying GFC causes increased activity in neurons that are sensitive to the information currently being remembered, while applying PHE leads to decreased activity in these same neurons. Interestingly, these differential effects emerge from network-level interactions because GFC and PHE affect all neurons equally. We compare our model to both electrophysiological data from neurons in monkey dorsolateral prefrontal cortex and to behavioral evidence from monkeys performing the DRT.     

天茄子不同提取部位止血作用研究

目的研究天茄子不同提取部位的止血药理作用。方法依次以环己烷（T1）、水（T2）和乙醇（T3）为溶剂进行提取并对乙醇提取物依次用石油醚（T4）、乙酸乙酯（T5）、正丁醇（T6）进行萃取得到相应的部位以及水部位（T7）,采用毛细玻管法、玻片法、剪尾法和测定血浆复钙时间检测其止血作用。结果 T3、T6、T7可缩短小鼠玻片法凝血时间,T3、T5、T6、T7可显著缩短小鼠毛细管法凝血时间,T3、T4、T5、T6、T7可显著缩短小鼠断尾法出血时间,T3、T6、T7可显著缩短小鼠血浆复钙时间。结论天茄子95%醇总提物、乙酸乙酯部位、正丁醇部位、水部位凝血效果显著,其中95%醇总提物、正丁醇部位、水部位凝血效果极其显著。