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World Journal of Clinical Cases 2019年第24期7卷 4377-4383页

作者： Song-Zhao Wu Xiang Liang Jian Geng Meng-Bi Zhang Na Xie Xiao-Yan Su Nephrology Department Tungwah Hospital of Sun Yat-Sen UniversityDongguan 523000Guangdong ProvinceChina Department of Pathology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

BACKGROUND Fabry disease is a kind of lysosomal storage disease resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A(GLA). A mutation in the GLA gene leads to a loss of activity of alpha-galactosidase A. Some drugs,such as hydroxychloroquine, can cause pathological changes similar to those usually seen in Fabry *** SUMMARY We report the case of a 41-year-old female patient who was diagnosed with undifferentiated connective tissue disease in 2008. hydroxychloroquine treatment started 2 years ago, and proteinuria and hematuria increased. Renal biopsy demonstrated renal phospholipidosis. Zebra bodies and myelin figures were found by renal electron microscopy and were initially thought to be indicators of Fabry disease. A genetic analysis of the patient and her family members did not reveal mutations in the GLA gene, supporting a diagnosis of hydroxychloroquine-induced renal *** This report reveals one of the adverse effects of hydroxychloroquine. We should pay more attention to hydroxychloroquine-induced renal phospholipidosis.

关键词： Fabry disease Undifferentiated connective tissue disease hydroxychloroquine Renal phospholipidosis Case report

hydroxychloroquine serum concentration in coronavirus disease 2019(COVID-19)patients:a retrospective study

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Forensic Sciences Research 2021年第4期6卷 215-217页

作者： Saadi Fatima Zohra Lachgueur Nassima Department of Toxicology University hospitaloranalgeria Pharmacy Department Faculty of Medicineoranalgeria Faculty of Medicine environmental health research Laboratoryoranalgeria

Algeria has adopted a therapeutic protocol using hydroxychloroquine(HCQ)as a first-line treatment for patients with coronavirus disease 2019(COVID-19).The administration of HCQ must be accompanied by appropriate cardiac and therapeutic pharmacological monitoring to avoid side effects and *** work is a retrospective descriptive study aiming to estimate the HCQ levels of COVID-19 *** concentrations in blood samples from COVID-19 patients were determined using high performance liquid chromatography with diode array detector(HPLC-DAD)after liquid-liquid extraction of *** coefficient of determination(r2)of this method was *** limits of quantification and detection were 0.05 mg/L and 0.02 mg/L,respectively,with coefficients of variance less than 6%.Patient monitoring was performed following recommendations for the therapeutic pharmacological monitoring of HCQ in patients treated for SARS-CoV-2(COVID-19)infection validated by the coordinated action(AC43)of the National Agency for Research on AIDS and Viral Hepatitis(ANRS)and Therapeutic Pharmacological Monitoring and Personalization of Treatments(STP-PT)group.A total of 267 blood samples from 240 patients were analyzed,49%for males and 51%for *** than a third of the patients were 60-80 years *** majority(68%)of the HCQ concentrations were between 0.1 and 1 mg/***,more than 20%were between 0.05 and 0.1 mg/L,while only 7.5%were less than 0.05mg/L and 1.5%were greater than 1 mg/*** summary,patients with COVID-19 showed a good tolerance to HCQ in the majority of cases.

关键词： Forensic sciences concentration COVID-2019 hydroxychloroquine HPLC-DAD plasma

Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis

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Animal Models and Experimental Medicine 2019年第2期2卷 98-106页

作者： Na Shi Shuangyue Zhang Gregg Silverman Mengtao Li Jun Cai Haitao Niu NHC Key Laboratory of Human Disease Comparative Medicine (The Institute of Laboratory Animal Sciences CAMS&PUMC) Key Laboratory of Human Diseases Animal Model State Administration of Traditional Chinese Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases Beijing China Department of Rheumatology Langone Medical Center New York University New York City New York Peking Union Medical College Hospital Beijing China Fuwai Hospital Chinese Academy of Medical Sciences Beijing China

Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width.

关键词： atherosclerosis autoimmunity hydroxychloroquine intestinal microbiota rheumatoid arthritis

Use of hydroxychloroquine and azithromycin combination to treat the COVID-19 infection

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World Journal of Experimental Medicine 2022年第3期12卷 44-52页

作者： Jyoti Bajpai Akshyaya Pradhan Ajay Kumar Verma Surya Kant Department of Respiratory Medicine King George's Medical UniversityLukcnowLucknow 226003Uttar PradeshIndia Department of Cardiology King George's Medical UniversityLukcnowLucknow 226003Uttar PradeshIndia Department of Respiratory Medicine King George Medical UniversityLucknow 226003Uttar PradeshIndia

Coronavirus disease 2019(COVID-19)infection is unequivocally the worst crisis in recent decades,which is caused by a severe acute respiratory virus ***,there is no effective therapy for the COVID-19 *** countries have different guidelines for treating COVID-19 in the absence of an approved therapy for ***,there is an imminent need to identify effective treatments,and several clinical trials have been conducted *** hydroxychloroquine[HCQS],chloroquine,and azithromycin(AZ)have been widely used for management based on in vitro studies favoring antiviral effects against the COVID-19 ***,there is evidence both in favor and against the use of hydroxychloroquine and azithromycin(HCQS+AZ)combination therapy to manage the COVID-19 *** combination of hydroxychloroquine and azithromycin was significantly associated with increased adverse ***,the inference of these findings was from observational ***,large randomized trials are imperative to show the future path for the use of HCQS+AZ combination ***,owing to the ban on HCQS use in COVID-19,this may no longer be *** review is on the pharmacology,trials,regimens,and side effects of hydroxychloroquine and azithromycin combination therapy.

关键词： hydroxychloroquine Azithromycin Antiviral effects QT interval Randomized controlled trial

hydroxychloroquine: A Safe, Effective and Inexpensive Maintenance Therapy for Chronic Spontaneous Urticaria

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International Journal of Clinical Medicine 2024年第6期15卷 225-232页

作者： Kamel El-Reshaid Shaima Al-Bader Abdulla Al-Refaee Department of Medicine Faculty of Medicine Kuwait University Kuwait Kuwait Asad Al-Hamad Dermatology Center Ministry of Health Kuwait Kuwait

Background: Chronic spontaneous urticaria (CSU) is an autoimmune skin disorder that lasts for >6 weeks and may last for years. It is a disabling skin disease that impairs quality of life. Set-up treatment with antihistamines, immunosuppressives, immune modulators and lately Omalizumab are expensive or have significant side effects. In this retrospective study, we describe our experience with the use of hydroxychloroquine (HCQ) as a maintenance therapy for those with severe forms of CSU after Corticosteroids (C) induction phase. Patients and Methods: 16 adult patients (aged 44 ± 7) with severe CSU for 5 ± 1 months, were included in the study. Eight patients had attacks of angioneurotic oedema. Their previous treatments were antihistaminic and short-courses of C. Results: After 2 weeks of remission with C and HCQ 200 mg twice daily, the dose of C was tapered down and discontinued by the end of the first month. The seven days Urticaria Activity Score decreased from 30 ± 3 to 6 ± 1 by the first month and remained low at 3 ± 1 by the end of 2 years of follow-up. Moreover, IgE levels and CRP had similar trends. Remission persisted after 37 ± 9 months of follow-up. Conclusion: HCQ is a safe, efficacious and inexpensive drug for the treatment of CSU.

关键词： Autoimmune Disease Chronic Spontaneous Urticaria Corticosteroids hydroxychloroquine Omalizumab

Can hydroxychloroquine be used for COVID-19-induced arthritis? A debatable hypothesis

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World Journal of Experimental Medicine 2022年第6期12卷 108-110页

作者： Raktim Swarnakar Sankha Subhra Roy Shiv Lal Yadav Department of Physical Medicine and Rehabilitation All India Institute of Medical SciencesNew Delhi 110029DelhiIndia

hydroxychloroquine(HCQ)is a known disease-modifying antirheumatic drug for rheumatoid *** is also being used in viral arthritis on many *** is also being used to treat coronavirus disease 2019,but the results are not *** has been shown to have antiviral *** this context,we have a hypothesis that HCQ may be used as a treatment option in post-coronavirus disease 2019 arthritis.

关键词： COVID-19 Arthritis hydroxychloroquine DMARDS SARS-CoV-2 Post-COVID-19 arthritis

hydroxychloroquine in SARS-CoV-2 infection:Understanding the misadventure

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Journal of Acute Disease 2024年第2期13卷 45-52页

作者： David Banji Otilia J F Banji Department of Pharmacology&Toxicology College of PharmacyJazan UniversitySaudi Arabia Department of Clinical Pharmacy College of PharmacyJazan UniversitySaudi Arabia

The widespread outbreak of SARS-CoV-2 was declared a public health emergency by the World Health Organization and various governments *** prompted the implementation of stringent infection control measures to curb the spread of the *** this,the medical community faced the challenge of treating the virus without specific therapies or a vaccine,leading to reliance on empirical treatment *** this context,hydroxychloroquine,an antimalarial and antirheumatic drug,gained attention as a potential treatment *** its theoretical benefits,such as inhibiting viral entry,reducing inflammation,and modulating immune responses,empirical studies yielded inconsistent *** indicated a potential for symptom relief,while others showed no significant improvement in patient *** initial enthusiasm waned as the lack of substantial evidence led to revoking its Emergency Use Authorization,and several clinical trials were prematurely *** review in question critically examines the factors contributing to the ineffectiveness of hydroxychloroquine in treating SARS-CoV-2 infection,highlighting the complexities of drug repurposing during a rapidly evolving pandemic.

关键词： SARS-CoV-2 hydroxychloroquine Pharmacogenomics TLR signaling Cardiotoxicity

hydroxychloroquine alone or in combination with azithromycin and corrected QT prolongation in COVID-19 patients:A systematic review

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World Journal of Meta-Analysis 2021年第6期9卷 557-567页

作者： Haleh Ashraf Parham Ghafouri Sina Kazemian Abbas Soleimani Azadeh Sadat Naseri Shahrokh Karbalai Ali Kazemi Saeid Research Development Center Sina HospitalTehran University of Medical SciencesTehran 11367-46911Iran Cardiac Primary Prevention Research Center(CPPRC) Tehran Heart CenterTehran University of Medical SciencesTehran 11367-46911Iran Students'Scientific Research Center(SSRC) Tehran University of Medical SciencesTehran 11367-46911Iran School of medicine Tehran University of Medical ScienceTehran 11367-46911Iran Department of Cardiology Sina HospitalTehran University of Medical SciencesTehran 11367-46911Iran

BACKGROUND Despite the controversies about the effectiveness of the current drug regimens for coronavirus disease 2019(COVID-19),these drugs are still the only options ***,the safety of these drugs is yet to be confirmed.A serious concern is the occurrence of various cardiac arrhythmias,particularly QT *** To summarize the incidence and estimate the risk of QT interval prolongation in patients scheduling for conventional treatment(hydroxychloroquine alone or in combination with azithromycin)for *** We comprehensively searched Medline,Web of Knowledge,Google Scholar,Scopus,and Cochrane Central Register of Controlled Trials databases until October 31,2020 for all eligible studies under the considered keywords COVID19,arrhythmia,QT interval,therapy,azithromycin,and hydroxychloroquine *** study protocols were established in compliance with PRISMA-P guidelines(Preferred Reporting Items for Systematic Review and Meta-Analysis–Protocols),and a nine-star Newcastle-Ottawa Scale scoring system was used to assess the methodological quality of all eligible *** measures were corrected QT(QTc)prolongation,cardiac arrhythmias,or sudden cardiac *** Fifteen studies enrolling 8298 patients with targeted COVID-19 therapeutic regimes were *** eligible studies found a significant increase in the mean QTc interval following treatment with the described medications compared to baseline QTc with weighted standard differences in means of *** pooled prevalence rate of QTc prolongation was estimated to be 9.2%(95%confidence interval:4.5%to 18.1%).CONCLUSION hydroxychloroquine±azithromycin regimen can significantly increase the risk of developing QTc prolongation.

关键词： Azithromycin COVID-19 hydroxychloroquine QTc interval

Update on hydroxychloroquine use in pregnancy

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World Journal of Experimental Medicine 2023年第4期13卷 99-101页

作者： Wassan Nori Nabeeha Najatee Akram Raid M Al-Ani Department of Obstetrics and Gynecology Mustansiriyah UniversityBaghdad 10052Iraq Department of Pediatrics Mustansiriyah UniversityBaghdad 10052Iraq Department of Surgery/Otolaryngology University of AnbarAnbar 31001Iraq

It is well-known that hydroxychloroquine(HCQ)treats malaria,systemic lupus erythematosus,and rheumatoid arthritis in women for its immunomodulatory and anti-inflammatory ***,HCQ was used in cases with refractory antiphospholipid *** safety was reinforced in pregnant women owing to insignificant reports of adverse pregnancy outcomes and major congenital ***,HCQ was tested in cases with chronic placental inflammation with a promising result of increased life birth;however,its benefit needs further *** aimed to highlight the recent updates for HCQ use in various conditions in pregnancy.

关键词： Pregnancy hydroxychloroquine Preeclampsia Antiphospholipid syndrome Chronic placental inflammation COVID-19

hydroxychloroquine induces long QT syndrome by blocking hERG channel

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Frigid Zone Medicine 2023年第2期3卷 105-113页

作者： Xin Zhao Lihua Sun Chao Chen Jieru Xin Yan Zhang Yunlong Bai Zhenwei Pan Yong Zhang Baoxin Li Yanjie Lv Baofeng Yang Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular Medicine ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150086China

Objective:In March 2022,more than 600 million cases of Corona Virus Disease 2019(COVID-19)and about 6 million deaths have been reported ***,while effective antiviral therapy has not yet been available,chloroquine(CQ)/hydroxychloroquine(HCQ)has been considered an option for the treatment of *** many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients'lives,controversial results have also been *** concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval(LQT),an electrophysiological substrate for the induction of lethal ventricular ***,the mechanisms for this cardiotoxicity of HCQ remained incompletely *** and methods:Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel ***-293T cells with sustained overexpression of human-ether-a-go-go-related gene(hERG)K+channels were used for whole-cell patch-clamp recordings of hERG K+channel current(IhERG).Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels,***:electrocardiogram(ECG)recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in ***-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation *** suppressed the expression of hERG and hindered the formation of the heat shock protein 90(Hsp90)/hERG ***,the expression levels of connexin 43(CX43)and Kir2.1,the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias,were decreased by HCQ,while those of Cav1.2,the main Ca2+handling proteins,remained unchanged and SERCA2a was ***:HCQ could induce LQT but did not induce arrhythmi

关键词： COVID-19 hydroxychloroquine LQT hERG Hsp90