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Cristiano Colalto 《Drug development research》2020,81(8):950-968
COVID-19 is a novel coronavirus disease with a higher incidence of bilateral pneumonia and pleural effusion. The high pulmonary tropism and contagiousness of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have stimulated new approaches to combat its widespread diffusion. In developing new pharmacological strategies, the chemical characteristic of volatility can add therapeutic value to the hypothetical drug candidate. Volatile molecules are characterized by a high vapor pressure and are consequently easily exhaled by the lungs after ingestion. This feature could be exploited from a pharmacological point of view, reaching the site of action in an uncommon way but allowing for drug delivery. In this way, a hypothetical molecule for COVID-19 should have a balance between its lung exhalation characteristics and both antiviral and anti-inflammatory pharmacological action. Here, the feasibility, advantages, and disadvantages of a therapy based on oral administration of possible volatile drugs for COVID-19 will be discussed. Both aerosolized antiviral therapy and oral intake of volatile molecules are briefly reviewed, and an evaluation of 1,8-cineole is provided in view of a possible clinical use and also for asymptomatic COVID-19. 相似文献
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目的:通过生物信息学技术比较哮喘患者与健康人的基因芯片数据,初步鉴定与哮喘相关的基因以及治疗哮喘的潜在药物。方法:从基因表达数据库下载GSE74986基因芯片,使用GEO2R分析得出差异表达基因,采用Morpheus制作差异表达基因的热图;通过DAVID 6.8对差异表达基因进行基因本体及京都基因与基因组百科全书分析,使用String 10.5构建蛋白质-蛋白质相互作用网络,筛选核心基因。进一步使用Cytoscape 3.6.1的插件MCODE对差异表达基因进行模块分析。通过医学本体信息检索平台筛选治疗哮喘的小分子药物。结果:筛选出510个差异表达基因,包括29个上调基因和481个下调基因。差异表达基因生物过程与通路主要富集在染色质沉默、核糖核酸聚合酶Ⅱ启动子的转录调节、蛋白质转运、信使核糖核酸加工、核糖核酸剪接以及泛素介导的蛋白水解、内质网中的蛋白质加工、核糖核酸转运、髓样分化因子依赖性Toll样受体信号通路、血小板激活、核苷酸结合寡聚化结构域样受体信号通路等。共得出9个核心基因,包括T-复合蛋白1θ亚基(CCT8),T复合物蛋白1α亚单位(TCP1),26S蛋白酶调节亚单位S10B(PSMC6),热休克蛋白90α(HSP90A) A1,细胞周期蛋白C(CCNC),HSP90AB1,26S蛋白酶体非ATP酶调节亚基6(PSMD6),泛素特异性蛋白酶14(USP14),真核细胞翻译起始因子4E(EIF4E)。得出2个重要模块,模块里的基因主要涉及剪接体和泛素介导的蛋白水解、蛋白修饰以及核糖核酸修饰等生物过程。治疗哮喘的潜在小分子药物有茴香霉素和金雀异黄素等。结论:差异表达基因和核心基因促进了对哮喘发病分子机制的理解,为哮喘的诊治提供了潜在的基因靶标与治疗药物。 相似文献
75.
目的:药学干预对喹诺酮类抗菌药物临床合理用药的影响效果。方法:选取2017年4月~2018年3月、2018年4月~2019年3月两时段就诊的患者,分别设为对照阶段、观察阶段,在两个阶段内于某院就诊且接受喹诺酮类抗菌药物治疗患者各选取115例,分别作为观察组及对照组,实施或未实施药学干预,分析组间干预效果差异。结果:观察组干预后喹诺酮类抗菌药物引发的不良反应发生率低于对照组(P<0.05);观察组干预后不合理使用率均低于对照组(P<0.05)。结论:药学干预对喹诺酮类抗菌药物临床合理用药能够产生积极影响效果。 相似文献
76.
It is hypothesized that persons who use drugs (PWUD) in Vietnam who are also HIV-positive may face additional challenges in psychosocial outcomes, and these challenges may extend to their family members. In this study, we examined depressive symptoms, stigma, social support, and caregiver burden of HIV-positive PWUD and their family members, compared to the outcomes of HIV-negative PWUD and their family members. Baseline, 3-month, and 6-month assessment data were gathered from 83 PWUD and 83 family members recruited from four communes in Phú Th? Province, Vietnam. For PWUD, although we observed a general decline in overall stigma over time for both groups, HIV-positive PWUD consistently reported significantly higher overall stigma for all three periods. Depressive symptoms among family members in both groups declined over time; however, family members of HIV-positive PWUD reported higher depressive symptoms across all three periods. In addition, family members of HIV-positive PWUD reported lower levels of tangible support across all three periods. Caregiver burden among family members of HIV-positive PWUD increased significantly over time, whereas the reported burden among family members of HIV-negative PWUD remained relatively unchanged. The findings highlight the need for future interventions for PWUD and family members, with targeted and culturally specific strategies to focus on the importance of addressing additional stigma experienced by PWUD who are HIV-positive. Such challenges may have direct negative impact on their family members' depressive symptoms, tangible support, and caregiver burden. 相似文献
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Luke Witherspoon Sean O'Reilly Jeremiah Hadwen Nafisa Tasnim Alex MacKenzie Faraz Farooq 《CTS Clinical and Translational Science》2015,8(4):298-304
Myotonic dystrophy type 1 (DM1) is caused by an expanded trinucleotide (CTG)n tract in the 3′ untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) gene. This results in the aggregation of an expanded mRNA forming toxic intranuclear foci which sequester splicing factors. We believe down‐regulation of DMPK mRNA represents a potential, and as yet unexplored, DM1 therapeutic avenue. Consequently, a computational screen for agents which down‐regulate DMPK mRNA was undertaken, unexpectedly identifying the sodium channel blockers mexiletine, prilocaine, procainamide, and sparteine as effective suppressors of DMPK mRNA. Analysis of DMPK mRNA in C2C12 myoblasts following treatment with these agents revealed a reduction in the mRNA levels. In vivo analysis of CD1 mice also showed DMPK mRNA and protein down‐regulation. The role of DMPK mRNA suppression in the documented efficacy of this class of compounds in DM1 is worthy of further investigation. 相似文献
79.
Anneli Uusküla Don C. Des Jarlais Mait Raag Steven D. Pinkerton Jonathan Feelemyer 《AIDS care》2015,27(1):105-111
The study was undertaken to assess the potential effectiveness of combined HIV prevention on the very high seroprevalence epidemic among persons who inject drugs (PWID) in Tallinn, Estonia, a transitional country. Data from community-based cross-sectional (respondent-driven sampling) surveys of PWID in 2005, 2007, 2009, and 2011 were used together with mathematical modeling of injection-associated HIV acquisition to estimate changes in injection-related HIV incidence during these periods. Utilization of one, two, or three of the interventions available in the community (needle and syringes exchange program, antiretroviral treatment [ART], HIV testing, opioid substitution treatment) was reported by 42.5%, 30.5%, and 11.5% of HIV+ and 34.7%, 36.4%, and 5.7% of HIV– PWIDs, respectively, in 2011. The modeling results suggest that the combination of needle/syringe programs and provision of ART to PWID in Tallinn substantially reduced the incidence of HIV infection in this population, from an estimated 20.7/100 person-years in 2005 to 7.5/100 person-years in 2011. In conclusion, combined prevention targeting HIV acquisition and transmission-related risks among PWID in Tallinn has paralleled the downturn of the HIV epidemic in this population. 相似文献
80.