Structural and some medicinal characteristics of the copper(II)–hydroxychloroquine complex

In the first phase of this study, the binding of hydroxychloroquine to the copper(II) cation is examined using liquid chromatography–mass spectrometry (LC–MS), matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), Fourier transform-ion cyclotron resonance spectrometry (FT-ICR) and nuclear magnetic resonance (¹H and ¹³C NMR) in one and two dimensions. The data suggest the metal–ligand complex is a polarity adaptive molecule. In the second phase of the study, the complexes activity is tested against the National Cancer Institute’s 60 cell line panel. Its anti-cancer activity is compared to quinine, Cu(II)–quinine and hydroxychloroquine. It serves as a base line for future anti-cancer complexes in which hydroxychloroquine is utilized for its ability to impact cell autophagy.     

甲氨蝶呤联合羟基氯喹对类风湿关节炎合并糖尿病患者糖化血红蛋白水平的影响

目的:观察类风湿关节炎(rheumatoid arthritis,RA)合并糖尿病(diabetes mellitus,DM)患者使用甲氨蝶呤(methotrexate,MTX)联合羟基氯喹(hydroxychloroquine,HCQ)治疗前后糖化血红蛋白(glycosylated hemoglobin,HbA1C)水平的变化。方法:通过回顾性分析,选取联合使用MTX+HCQ或单独使用MTX治疗的RA合并DM患者,且在治疗前及开始治疗12个月内分别至少有1次HbA1C值,记录其年龄、性别、诊断、体重指数、使用糖皮质激素情况。计算用药前到用药后12个月内HbA1C最低值的变化。结果:40例使用HCQ+MTX和45例使用MTX患者符合入选标准。两组间年龄、性别、体重指数、用药前HbA1C水平相似,MTX+HCQ组糖皮质激素使用比例(40.00%)比HCQ组更多(26.67%)(P=0.25)。MTX+HCQ组治疗后HbA1C有明显下降(0.42%,P=0.00),且MTX+HCQ组HbA1C降低幅度高于MTX组(0.42%,0.12%,P=0.02)。结论:与单独使用MTX相比,RA合并DM患者联合使用HCQ+MTX可明显降低HbA1C水平。     

Cell line studies and analytical measurements of three paclitaxel complex variations

The copper(II) cation, sucrose, and hydroxychloroquine were complexed with the chemotherapy agent paclitaxel and studied for medicinal activity. Data (GI₅₀, LD₅₀) from single dose and five dose National Cancer Institute sixty cell line panels are presented. Analytical measurements of different complexes were made using Nuclear Magnetic Resonance (¹H NMR), Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) and Fourier Transform-Ion Cyclotron Resonance (FT-ICR). Molecular modeling is utilized to better understand the impact that species could have on physical parameters associated with Lipinski’s Rule of Five, such as log P and TPSA. On average, Cu(II) and hydroxychloroquine decreased GI₅₀ values, while sucrose increased GI₅₀ values of paclitaxel.     

Zinc's protective role against hydroxychloroquine-induced cardiac effects in adult male albino rats

BackgroundLong exposure to Hydroxychloroquine (HCQ) has been complicated by some dangerous though infrequent cardiotoxicity.MethodsA total of 40 normal adult male albino rats dispersed into 4 groups were used. Group 1 (Control group), Group II (HCQ treated group), Group III (zinc [Zn]-treated group), and Group IV (HCQ and Zn treated group). Once the experimentation ended, rats were sacrificed and cardiac soft tissue sections were processed twenty-four hours at the end of the experiment for histological study.ResultsCardiac-stained sections revealed that HCQ induced widespread necrosis, dilatation, and vacuolar degeneration. However, the combination of HCQ with Zn ameliorated these damaging effects. Cardiac enzyme parameters were also studied in the 4 groups and revealed CK-MB and troponin were considerably elevated in groups II associated to the control group.ConclusionIt was concluded that Zn revealed a protective role against HCQ cardiomyopathy in adult male albino rats. This might signify an appreciated means for Zn-based treatment in the upcoming subsequent clinical records to adjust doses and guarantee patient safeguard.     

沙参麦冬汤联合硫酸羟氯喹治疗气阴两虚型原发性干燥综合征的疗效及对Th17/Treg免疫失衡的影响

摘要 目的：观察沙参麦冬汤联合硫酸羟氯喹治疗气阴两虚型原发性干燥综合征（pSS）的疗效及对辅助性T细胞（Th17）/调节性T细胞（Treg）免疫失衡的影响。方法：选择2020年3月~2021年5月期间我院收治的pSS患者80例作为研究对象,采用随机数字表法进行分组,将患者分为对照组和研究组,各为40例。对照组接受硫酸羟氯喹治疗,研究组接受沙参麦冬汤联合硫酸羟氯喹治疗。观察两组疗效、中医证候积分、症状相关指标及Th17/Treg免疫失衡指标,评价两组用药安全性。结果：研究组的临床总有效率较对照组高（P<0.05）。治疗后,两组口干咽燥、两目干涩、唇舌紫暗、关节疼痛、皮肤干涩证候积分下降,且研究组低于对照组（P<0.05）。治疗后,两组红细胞沉降率（ESR）、欧洲抗风湿病联盟干燥综合征疾病活动指数（ESSDAI）评分、免疫球蛋白G（IgG）、类风湿因子（RF）、欧洲抗风湿病联盟干燥综合征患者报告指数（ESSPRI）评分下降,且研究组低于对照组（P<0.05）,基础泪液分泌Ⅰ试验（SIt）、唾液流率升高,且研究组高于对照组（P<0.05）。治疗后,两组白介素-17（IL-17）、Th17下降,白介素-10（IL-10）、Treg升高（P<0.05）,研究组治疗后IL-17、Th17低于对照组,IL-10、Treg高于对照组（P<0.05）。两组不良反应发生率对比无显著性差异（P>0.05）。结论：沙参麦冬汤联合硫酸羟氯喹治疗气阴两虚型pSS疗效显著,可有效改善患者临床症状,阻止病情进展,调节机体Th17/Treg免疫失衡,具有一定的临床应用价值。     

Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis

BackgroundAmong many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin.AimsThis meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19.MethodsA comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio.ResultsA total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59–17.82%, I² – 92%), 10.22% (6.01–16.85%, I² – 79%), and 0.72% (0.34–1.51, I² – 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22–15.52, I² – 59%) and 8.61% (4.52–15.79, I² – 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77–1.93, I² – 0%) & 1.51 (0.79–2.87, I² – 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition).ConclusionThe use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.