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chloroquine AND cardiomyopathy

Xun Yuan, Yi-Chuan Xiao, Gui-Ping Zhang, Ning Hou, Xiao-Qian Wu, Wen-Liang Chen, Jian-Dong Luo, Gen-Shui Zhang
Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14 days after CQ (ip 60 mg/kg/d) administration...
2016: Drug Design, Development and Therapy
Nejc Pavsic, Jerca Mraz, Zvezdana Dolenc Strazar, Jasmina Gabrijelcic, Janez Toplisek, Mirta Kozelj, Katja Prokselj
No abstract text is available yet for this article.
July 15, 2016: International Journal of Cardiology
Hiromitsu Kanamori, Genzou Takemura, Kazuko Goto, Akiko Tsujimoto, Atsushi Mikami, Atsushi Ogino, Takatomo Watanabe, Kentaro Morishita, Hideshi Okada, Masanori Kawasaki, Mitsuru Seishima, Shinya Minatoguchi
Little is known about the association between autophagy and diabetic cardiomyopathy. Also unknown are possible distinguishing features of cardiac autophagy in type 1 and type 2 diabetes. In hearts from streptozotocin-induced type 1 diabetic mice, diastolic function was impaired, though autophagic activity was significantly increased, as evidenced by increases in microtubule-associated protein 1 light chain 3/LC3 and LC3-II/-I ratios, SQSTM1/p62 (sequestosome 1) and CTSD (cathepsin D), and by the abundance of autophagic vacuoles and lysosomes detected electron-microscopically...
2015: Autophagy
Christoph Scheurle, Maximilian Dämmrich, Jan U Becker, Martin W Baumgärtel
A 76-year-old male Caucasian patient was treated in our hospital for acutely decompensated heart failure due to restrictive cardiomyopathy. Acute-on-chronic kidney failure developed with serum creatinine rising from 160 to 345 μmol/L (1.8-3.9 mg/dL); therefore, a kidney biopsy was performed. Besides secondary focal-segmental glomerulosclerosis and minimal amyloidosis, histological analysis showed zebra bodies in the cytoplasm of some podocytes, suggesting renal phospholipidosis (PL). Possible causes for this storage disorder encompass Fabry's disease, in rare cases silicosis, and an iatrogenic drug-induced aetiology...
February 2014: Clinical Kidney Journal
Haran Yogasundaram, Brendan N Putko, Julia Tien, D Ian Paterson, Bibiana Cujec, Jennifer Ringrose, Gavin Y Oudit
Drug-induced heart and vascular disease remains an important health burden. Hydroxychloroquine and its predecessor chloroquine are medications commonly used in the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders. Hydroxychloroquine interferes with malarial metabolites, confers immunomodulatory effects, and also affects lysosomal function. Clinical monitoring and early recognition of toxicity is an important management strategy in patients who undergo long-term treatment with hydroxychloroquine...
December 2014: Canadian Journal of Cardiology
Nilson Lopez-Ruiz, Carlos Esteban Uribe
A 36-year-old woman who had received long-term treatment with chloroquine for systemic lupus erythematosus developed a third degree atrioventricular block and required a permanent pacemaker. Notably, left ventricular thickening and mild systolic dysfunction were noticed on echocardiography as well as on cardiac MRI. As there was no clear explanation for myocardial findings, the patient underwent an endomyocardial biopsy that demonstrated vacuolar degeneration of myocytes on light microscopy and curvilinear bodies on electron microscopy, both findings consistent with chloroquine toxicity...
2014: BMJ Case Reports
B E Smid, C E M Hollak, B J H M Poorthuis, M A van den Bergh Weerman, S Florquin, W E M Kok, R H Lekanne Deprez, J Timmermans, G E Linthorst
Fabry disease' (FD) phenotype is heterogeneous: alpha-galactosidase A gene mutations (GLA) can lead to classical or non-classical FD, or no FD. The aim of this study is to describe pitfalls in diagnosing non-classical FD and assess the diagnostic value of plasma globotriaosylsphingosine. This is a case series study. Family 1 (p.A143T) presented with hypertrophic cardiomyopathy (HCM), absent classical FD signs, high residual alpha-galactosidase A activity (AGAL-A) and normal plasma globotriaosylsphingosine. Co-segregating sarcomeric mutations were found...
August 2015: Clinical Genetics
Zongpei Song, Lin An, Yong Ye, Jian Wu, Yunzeng Zou, Lin He, Hongxin Zhu
AIMS: Ultraviolet irradiation resistance-associated gene (UVRAG) is a tumour suppressor candidate that regulates cell autophagy and endocytosis. However, the in vivo function of UVRAG remains poorly understood. We sought to determine the physiological role of UVRAG in the heart. METHODS AND RESULTS: We characterized mice with disruption of the UVRAG gene by piggyBac (PB) transposon insertion. PB construct was inserted into intron 14 of the UVRAG gene and disruption of UVRAG transcript was confirmed by reverse transcript-polymerase chain reaction...
January 1, 2014: Cardiovascular Research
Brianne H Daniels, Rodney D McComb, Bret C Mobley, Sakir Humayun Gultekin, Han S Lee, Marta Margeta
Autophagic vacuolar cardiomyopathy is an underrecognized, but potentially fatal, complication of treatment with chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), which are used as therapy for malaria and common connective tissue disorders. Currently, the diagnosis of autophagic vacuolar cardiomyopathy is established through an endomyocardial biopsy and requires electron microscopy, which is not widely available and has a significant potential for sampling error. Recently, we have reported that immunohistochemistry for autophagic markers LC3 and p62 can replace electron microscopy in the diagnosis of HCQ-induced and colchicine-induced autophagic vacuolar skeletal myopathies...
July 2013: American Journal of Surgical Pathology
Ernst Tönnesmann, Reinhard Kandolf, Thorsten Lewalter
Chloroquine and hydroxychloroquine are still used for the prevention and treatment of malaria. Moreover, they are experiencing a renaissance in the long-term therapy of connective tissue diseases (particularly in systemic lupus erythematosus). They induce a lysosomal dysfunction with an accumulation of pathologic metabolic products, which can be seen in ultrastructural histology as pathognomonic cytoplasmic inclusion bodies. Due to its lower toxicity, hydroxychloroquine is the form used predominantly today...
June 2013: Immunopharmacology and Immunotoxicology
András Vereckei, Adám Fazakas, Timea Baló, Béla Fekete, Mária Judit Molnár, István Karádi
The authors report a case of rare chloroquine cardiotoxicity mimicking connective tissue disease heart involvement in a 56-year-old woman with mixed connective tissue disease (MCTD) manifested suddenly as third degree A-V block with QT(c) interval prolongation and short torsade de pointes runs ultimately degenerating into ventricular fibrillation. Immunological tests suggested an MCTD flare, implying that cardiac arrest had resulted from myocardial involvement by MCTD. However, QT(c) prolongation is not a characteristic of cardiomyopathy caused by connective tissue disease, unless anti-Ro/SSA positivity is present, but that was not the case...
April 2013: Immunopharmacology and Immunotoxicology
Morteza Azimian, Sakir H Gultekin, Jessica L Hata, James B Atkinson, Kim A Ely, Howard A Fuchs, Bret C Mobley
Chloroquine and hydroxychloroquine are used to chronically treat certain rheumatologic diseases and are generally considered safe. We describe 2 patients with skeletal myopathy and fatal cardiomyopathy-uncommon and underrecognized adverse effects of these agents. Both patients developed arrhythmias and heart failure, and 1 patient had documented diaphragmatic involvement. Muscle specimens showed typical vacuolar myopathy (indicative of impaired autophagy) with myeloid bodies in both patients and curvilinear bodies in 1 patient...
October 2012: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
Vincent M Figueredo
The heart is a target of injury for many chemical compounds, both medically prescribed and not medically prescribed. Pathophysiologic mechanisms underlying the development of chemical-induced cardiomyopathies vary depending on the inciting agent, including direct toxic effects, neurohormonal activation, altered calcium homeostasis, and oxidative stress. Numerous chemicals and drugs are implicated in cardiomyopathy. This article discusses examples of medication and nonprescribed drug-induced cardiomyopathies and reviews their pathophysiologic mechanisms...
June 2011: American Journal of Medicine
Maurizio Pieroni, Costantino Smaldone, Antonia Camporeale, Carolina Ierardi, Giacomo Dell'Antonio, Fulvio Bellocci, Filippo Crea
No abstract text is available yet for this article.
January 25, 2011: Journal of the American College of Cardiology
Jae Hak Lee, Woo-Baek Chung, Ju Hyun Kang, Hyung Woo Kim, Jin Jin Kim, Ji Hyun Kim, Hui-Jeong Hwang, Jea Beom Lee, Jong Won Chung, Hyo Lim Kim, Yun Seok Choi, Chul Soo Park, Ho-Joong Youn, Man Young Lee
A 52-year-old woman with rheumatoid arthritis who had been treated with prednisone and hydroxychloroquine for >12 years presented with chest discomfort and a seizure. She was diagnosed with restrictive cardiomyopathy combined with sick sinus syndrome. A myocardial muscle biopsy was performed to identify the underlying cardiomyopathy, which showed marked muscle fiber hypertrophy, fiber dropout, slightly increased interstitial fibrous connective tissue, and extensive cytoplasmic vacuolization of the myocytes under light microscopy...
November 2010: Korean Circulation Journal
Carlos Gorbea, Kimberly A Makar, Matthias Pauschinger, Gregory Pratt, Jeathrina L F Bersola, Jacquelin Varela, Ryan M David, Lori Banks, Chien-Hua Huang, Hua Li, Heinz-Peter Schultheiss, Jeffrey A Towbin, Jesús G Vallejo, Neil E Bowles
The innate antiviral response is mediated, at least in part, by Toll-like receptors (TLRs). TLR3 signaling is activated in response to viral infection, and the absence of TLR3 in mice significantly increases mortality after infection with enteroviruses that cause myocarditis and/or dilated cardiomyopathy. We screened TLR3 in patients diagnosed with enteroviral myocarditis/cardiomyopathy and identified a rare variant in one patient as well as a significantly increased occurrence of a common polymorphism compared with controls...
July 23, 2010: Journal of Biological Chemistry
Gabriele Fragasso, Francesca Sanvito, Francesca Baratto, Sabina Martinenghi, Claudio Doglioni, Alberto Margonato
Previous reports on antimalarial toxicity have only been related to long-term continuous treatments for nonmalarial indications, which require prolonged use of large doses, up to 1000 g or more every year. We describe a patient with recurrent malaria, prophylactically treated with low-dose chloroquine, who developed heart failure due to biventricular cardiac dysfunction. The right ventricle endomyocardial biopsy was suggestive of chloroquine toxicity. The heart failure improved after drug withdrawal. As a consequence, the potential for reversibility and the severity in undiagnosed cases of these toxic cardiomyopathies emphasize the importance of recognizing early signs of toxicity in order to withdraw antimalarials before the occurrence of life-threatening cardiac toxicity...
September 2009: Heart and Vessels
Puja K Puri, Nektarios I Lountzis, William Tyler, Tammie Ferringer
We report two cases of hydroxychloroquine-induced hyperpigmentation presenting in a 50-year-old Caucasian female (case 1) and a 78-year-old female (case 2), both receiving 400 mg per day. Case 1 had an arthritis predominant undifferentiated connective tissue disease, which was treated with hydroxychloroquine for 4-5 years. She presented with a mottled, reticulated macular gray pigmentation involving the upper back and shoulders. Case 2 had a history of systemic lupus erythematosus and rheumatoid arthritis, treated with hydroxychloroquine for 1...
December 2008: Journal of Cutaneous Pathology
T Rinda Soong, Lili A Barouch, Hunter C Champion, Frederick M Wigley, Marc K Halushka
Hydroxychloroquine- or chloroquine -induced cardiomyopathy is a rare but potentially fatal condition. Hydroxychloroquine and chloroquine are often used for long-term treatment of rheumatic diseases and for malaria prophylaxis. Hydroxychloroquine- and chloroquine-induced cardiomyopathy have well-described microscopic features, with the classic electron microscopic findings of myelin figures (myeloid bodies). We report on 2 new cases with novel findings. The first case, in a patient with systemic lupus erythematosus, was found to have megamitochondria in addition to myelin figures seen by electron microscopy...
December 2007: Human Pathology
Anita K Siddiqui, Seymour I Huberfeld, Karen M Weidenheim, Kenneth R Einberg, Linda S Efferen
Chloroquine and hydroxychloroquine (HCQ) are commonly prescribed antimalarial agents used for a variety of systemic diseases. HCQ neuromyotoxicity is a rare complication characterized by proximal muscle weakness, normal creatinine kinase levels, and characteristic ultrastructural changes on muscle biopsy of curvilinear body formation. In this report, we describe a patient with rheumatoid arthritis and respiratory failure associated with proximal myopathy secondary to HCQ. Characteristic changes on muscle biopsy were present...
February 2007: Chest
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