Thymosin as a possible therapeutic drug for COVID-19: A case report

BACKGROUNDThere are no effective antiviral therapies for coronavirus disease 2019 (COVID-19) at present. Although most patients with COVID-19 have a mild or moderate course of disease, up to 5%-10% of patients may have a serious and potentially life-threatening condition, indicating an urgent need for effective therapeutic drugs. The therapeutic effect of thymosin on COVID-19 has not been previously studied. In this paper, for the first time we report a case of thymosin treatment of COVID-19.CASE SUMMARYA 51-year-old man with imported COVID-19 was admitted with definite symptoms of chest tightness, chest pain, and fatigue. The polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 were negative. The antibody test was positive, confirming the diagnosis of COVID-19. As many orally administered drugs were not well tolerated due to gastrointestinal symptoms, an emergency use of thymosin, a polypeptide consisting of 28 amino acids, was administered by injection. Finally, after the implementation of the treatment program, symptoms and lung imaging improved significantly.CONCLUSIONIn this case report, it is confirmed that thymosin may help alleviate the severity of COVID-19 symptoms.     

广东省慢性化脓性中耳炎患者耳分泌物的病原体分布及药物敏感性分析

目的分析广东省慢性化脓性中耳炎(CSOM)患者耳分泌物的病原体分布及药物敏感性情况,为临床CSOM的诊断和治疗提供依据。方法回顾性分析2015—2019年1892例确诊为CSOM患者耳分泌物标本的微生物学培养结果,对病原体分布、临床常用抗感染药物的敏感性进行分析。结果共检出1054株条件致病菌,检出率位于前3位的细菌是金黄色葡萄球菌、凝固酶阴性葡萄球菌和铜绿假单胞菌,真菌是近平滑念珠菌、聚多曲霉和黄曲霉。葡萄球菌对红霉素、青霉素G的敏感率较低,对其他常用抗菌药物的敏感率均高于70.0%,铜绿假单胞菌对于常用抗假单胞菌药物的敏感率均高于85.0%。近平滑念珠菌和白色念珠菌对氟康唑、伏立康唑均具有较高的敏感率;黄曲霉、土曲霉对两性霉素B的最小抑菌浓度(MIC)值较高,橘青霉对于伏立康唑的MIC值较高。结论广东省CSOM患者耳分泌物中病原体以葡萄球菌、铜绿假单胞菌、念珠菌和曲霉菌为主;真菌的检出率较其他地区高;检出的病原体对常用的治疗药物具有较高的敏感性。     

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC_0–∞, AUC_0–t, and C_max) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The C_max and AUC_0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments.FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin C_max was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported.ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.     

Gastrointestinal safety of coxibs: systematic review and meta‐analysis of observational studies on selective inhibitors of cyclo‐oxygenase 2

Prior meta‐analyses have shown a higher gastrointestinal risk of nonselective NSAIDs versus placebo and a lower gastrointestinal risk of coxibs versus nonselective NSAIDs. However, the available data about gastrointestinal risk for coxibs versus placebo are scarce. The aim of this study was to review the current evidence on the use of coxibs and to evaluate the risk of gastrointestinal adverse outcomes (GAO) associated with coxibs versus nonexposed. Search was conducted on PubMed and Embase databases. We selected cohort observational, case‐control, nested case‐control and case‐crossover studies that reported the risk of GAO associated with coxibs versus nonexposed as relative risk (RR), odds ratio (OR), hazard ratio (HR) or incidence rate ratio (IRR). It was estimated the pooled RR and the 95% confidence interval (CI) for coxibs both individually and as a whole by the DerSimonian and Laird method. Twenty‐eight studies met inclusion criteria. Overall, coxibs were associated with a significant increment in the risk of GAO [RR 1.64 (95% CI 1.44–1.86)]. The analysis by individual drugs showed that etoricoxib [RR 4.85 (95% CI 2.64–8.93)] presented the highest gastrointestinal risk, followed by rofecoxib [RR 2.02 (95% CI 1.56–2.61)] and celecoxib [RR 1.53 (95% CI 1.19–1.97)]. Gastrointestinal risk was also high for the subgroups aged <65 years and low‐dose coxibs. The use of coxibs is associated with a statistically significant increased risk of GAO, which would be high even for low‐dose coxibs and <65‐year‐old subgroups. The risk would be higher for etoricoxib than for celecoxib and rofecoxib.     

载三氧化二砷脑胶质瘤靶向纳米递药系统i RGD/TGN-PEG-PAMAM/ATO的构建及体外研究

目的以树状大分子为载体材料并修饰血脑屏障(blood brain barrier,BBB)靶向短肽TGN和肿瘤靶向短肽i RGD构建脑胶质瘤靶向递药系统(i RGD/TGN-PEG-PAMAM/ATO),旨在解决三氧化二砷(arsenictrioxide,As2O3,ATO)在治疗脑胶质瘤过程中分布缺乏特异性、透BBB难等问题,使其具有更好抗脑胶质瘤作用。方法核磁共振图谱(1H-NMR)、透射电子显微镜(TEM)等考察载体的理化性质;电感耦合等离子发射光谱(ICP)、透析袋法分析其包封率及体外释放情况;通过激光共聚焦及流式细胞仪分析i RGD、TGN对细胞摄取的影响;MTT法考察纳米载体对脑微血管内皮细胞(HBMEC)和脑胶质瘤U87细胞的毒性及BBB模型中递药系统抑制U87细胞生长的情况。结果成功合成了i RGD/TGN-PEG-PAMAM载体,其形态规整,大小均匀,测得其粒径(24.87±0.84)nm,电位(17.26±1.64)m V;该载体对HBMEC和U87细胞均具有较小的毒性;递药系统i RGD/TGN-PEG-PAMAM/ATO的包封率为(71.92±1.17)%,体外释放表明ATO经载体包载后呈现一种缓慢释放趋势,且在酸性条件下更有利于ATO的释放;细胞摄取结果提示iRGD/TGN的修饰有利于U87细胞对递药系统的摄取;体外跨BBB抑制U87细胞生长实验结果表明,i RGD/TGN-PEG-PAMAM/ATO组具有更好的跨BBB抑制U87细胞生长效果。结论 i RGD/TGN-PEG-PAMAM/ATO脑胶质瘤靶向递药系统具有较好的体外跨BBB抑制U87细胞生长的效果,为脑胶质瘤治疗提供了新的策略。