银屑病治疗的小分子药物研究进展

银屑病是一种复杂的炎性皮肤疾病,其发病机制尚不完全清楚,且反复发作,治疗难度很大,严重影响了患者的生活和工作,这给新药研究和筛选带来一定的困难。尽管如此,抗银屑病新药一直是皮肤病药物治疗学研究的一个热点。国际上在寻找新的抗银屑病药物方面一直在做不懈努力,拟用于治疗的新候选药物不断出现,旨在继续提高疗效和降低毒副作用。目前,可用于治疗银屑病药物的作用靶点较多,主要集中在核激素受体的配体、免疫信号转导通路中的相关细胞因子和酶,以及作用于表皮的天然药用药材。针对治疗银屑病效果较佳、作用机制较明确的小分子药物进行总结,为开发抗银屑病的新药提供研究思路。     

他汀类药物的安全性风险评价

他汀类药物是最广泛的可用药物治疗降低胆固醇水平,并控制其发展的处方药。所有的他汀类药物,如阿托伐他汀、氟伐他汀、洛伐他汀、匹伐他汀、普伐他汀、瑞舒伐他汀和辛伐他汀可用于心血管疾病事件的预防。众所周知,在治疗过程中一些服用他汀类药物的患者出现不良反应,如肝损害、癌症的风险和骨骼肌损害。因此,认识他汀类药物的安全性风险是很重要的。根据发表的他汀类药物的临床研究文献数据,分析和认识这类药物的安全性、不良反应及毒性的风险,并简要介绍了由美国心脏协会和美国心脏病学院基于4年评述而制定的2013年他汀类降胆固醇药物新使用指南。     

2011—2013年312例医院抗感染类药物不良反应分析

目的分析抗感染类药物的不良反应与药物种类和给药途径的关系,为临床抗感染类药物的安全使用提供参考。方法回顾性分析2011—2013年右江民族医学院附属医院发生抗感染类药物不良反应患者312例,统计药物不良反应的主要类型,并分析患者发生不良反应与药物的种类和给药途径的关系。结果临床患者抗感染药物不良反应的类型主要为皮肤损害症状、消化系统症状以及神经系统症状,发生率分别为50.96%、20.83%、9.94%;发生不良反应的抗感染类药物前3位为头孢菌素类、喹诺酮类和复方类,发生率分别为32.37%、18.27%、14.42%;发生不良反应前3种途径分别为静滴、口服、肌注,其发生率分别为86.22%、10.90%、2.24%。结论在临床进行抗感染治疗时,应充分了解药物的不良反应,选择恰当用药方式,医护工作者应密切关注患者情况,防止不良反应的发生。     

2012—2013年钦州市第一人民医院脑外重症监护室特殊级抗菌药物的使用情况分析

目的了解医院脑外重症监护室(ICU)特殊使用级抗菌药物的应用情况。方法采用医院信息管理系统(HIS)汇集2012—2013年钦州市第一人民医院脑外ICU使用的所有特殊使用级抗菌药物的数据进行统计分析。结果 2012—2013年脑外ICU特殊使用级抗菌药物中,送检率均在85%以上,达到卫生部的要求。其中,亚胺培南/西司他丁的使用金额、使用量、用药频度(DDDs)和药物利用指数(DUI)均排在首位,DUI值大于1,日剂量偏大。同步性比值为1.0,同步性良好。大多数药物DUI合理,用药特点以治疗肺部感染为主而非神经系统,其中特殊级抗真菌药的使用在患者营养状况实验室指标上有相当体现,特别是与血清白蛋白相关性较明显。结论脑外ICU特殊使用级抗菌药物主要用于肺部感染,且用于院外带进的感染居多,防治真菌感染应及时纠正患者的基础营养。     

Review of the Applications of Biomedical Compositions Containing Hydroxyapatite and Collagen Modified by Bioactive Components

Regenerative medicine is becoming a rapidly evolving technique in today’s biomedical progress scenario. Scientists around the world suggest the use of naturally synthesized biomaterials to repair and heal damaged cells. Hydroxyapatite (HAp) has the potential to replace drugs in biomedical engineering and regenerative drugs. HAp is easily biodegradable, biocompatible, and correlated with macromolecules, which facilitates their incorporation into inorganic materials. This review article provides extensive knowledge on HAp and collagen-containing compositions modified with drugs, bioactive components, metals, and selected nanoparticles. Such compositions consisting of HAp and collagen modified with various additives are used in a variety of biomedical applications such as bone tissue engineering, vascular transplantation, cartilage, and other implantable biomedical devices.     

Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes

Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.     

A Bioluminescent Biosensor for Quantifying the Interaction of SARS-CoV-2 and Its Receptor ACE2 in Cells and In Vitro

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus–host interactions in order to quickly evaluate the infectious ability of mutant viruses and to develop or validate virus-inhibiting drugs. Here, we developed an ultrasensitive bioluminescent biosensor to evaluate virus–cell interactions by quantifying the interaction between the SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid, and HTP biosensor tool will significantly expedite the detection of viral mutants and the anti-COVID-19 drug discovery process.     

Clinical inertia in patients with type 2 diabetes treated with oral antidiabetic drugs: Results from a Japanese cohort study (JDDM53)

Aims/IntroductionTreatment intensification is commonly delayed in people with type 2 diabetes, resulting in poor glycemic control for an unacceptable length of time and increased risk of complications.Materials and MethodsThis retrospective study investigated clinical inertia in 33,320 Japanese adults with type 2 diabetes treated with oral antidiabetic drugs (OADs) between 2009 and 2018, using data from the Computerized Diabetes Care (CoDiC^®) database.ResultsThe median time from first reported glycated hemoglobin (HbA1c) ≥7.0% (≥53 mmol/mol) to treatment intensification was considerably longer and HbA1c levels were higher the more OADs the patient was exposed to. For patients receiving three OADs, the median times from HbA1c ≥7.0% (53 mmol/mol) to intensification with OAD, glucagon‐like peptide‐1 receptor agonist or insulin were 8.1, 9.1 and 6.7 months, with a mean HbA1c level at the time of intensification of 8.4%, 8.9% and 9.3%, respectively. The cumulative incidence for time since the first reported HbA1c ≥7.0% (≥53 mmol/mol) to intensification confirmed the existence of clinical inertia, identifying patients whose treatment was not intensified despite poor glycemic control. HbA1c levels ≥7.0% (≥53 mmol/mol) after ≥6 months on one, two or three OADs were observed in 42%, 51% and 58% of patients, respectively, showing that approximately 50% of patients are above HbA1c target regardless of how many OADs they take.ConclusionsReal‐world data here show clinical inertia in Japanese adults with type 2 diabetes from early diabetes stages when they are receiving OADs, and illustrate a need for earlier, more effective OADs or injectable treatment intensification and better communication around the existence of clinical inertia.     

Targeting ageing and preventing organ degeneration with metformin

BackgroundAgeing is characterized by a decline in cognitive and bodily functions. Metformin, the most commonly prescribed antidiabetic agent today, has proved to be able to modulate oxidative stress, several inflammatory pathways and cellular senescence to promote anti-ageing. This review aims to explore and summarize the effects of metformin on ageing.ResultsMetformin, a longstanding treatment for diabetes, has been shown to increase lifespan in both vertebrate and mammalian models. This pleiotropic effect is hypothesized to mimic calorie restriction, a currently proven means of slowing ageing, by decreasing insulin and insulin-like growth factor (IGF)-1 levels and improving insulin sensitivity. However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair. Clinical studies, such as those supported by the UK Clinical Practice Research Datalink service, have reported that diabetes patients treated with metformin live longer than patients without diabetes. Metformin use can also reduce type 2 diabetes mellitus (T2DM) incidence among those at risk, lower cancer incidence, and improve cognitive function, cardiovascular disease (CVD) risk factors and atherosclerosis.ConclusionVarious studies have found that metformin can target several nutrient-sensing, anti-ageing and immune pathways, leading to reductions in oxidative stress, inflammation and DNA damage as well as providing effects similar to those of calorie restriction. However, further trials are still needed to confirm these findings.