Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroquine, an agent used in treatment and prophylaxis of malaria, and also known for its antiinflammatory effects in dermatological, rheumatological, and connective tissue disorders, has been reported to cause toxicity, most commonly in the retina and the cardiovascular system. We describe a 60-year-old woman with longstanding rheumatoid arthritis receiving multidrug treatment, including prolonged administration of chloroquine. She developed complete heart block requiring a permanent pacemaker, congestive heart failure, and progressive myopathy. During hospital investigations for her myopathy, she died of acute pulmonary thromboembolism. Although hypertension and possibly amyloidosis were thought to be the cause of her cardiac disease, cardiac and skeletal muscle changes characteristic of chloroquine toxicity were observed. Chloroquine may be an important unsuspected contributing cause of cardiac dysfunction in patients with rheumatological disease. Endomyocardial biopsy should be considered early in the course of diagnosis and management.
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PMID:Chloroquine related cardiac toxicity. 963 91

Chloroquine, an anti-malaria drug, is known to cause myopathy with rimmed vacuole formation. Although it disrupts the lysosomal degradation of proteins, the precise mechanism underlying muscle fiber degeneration has remained unclear. We investigated the temporal profiles of muscle fiber degeneration in chloroquine-treated rats, paying special attention to endoplasmic reticulum (ER) stress and autophagy. Male Wistar rats were intraperitoneally injected with chloroquine diphosphate at a dosage of 50 mg/kg body weight every day. We examined the localization and levels of proteins related to ER stress and autophagy in soleus muscle by means of immunohistochemistry and Western blotting at 3, 5, and 7 weeks after the beginning of the treatment. At 3 weeks, the levels of LC3-II and amyloid-beta (Abeta) were increased. At 5 weeks, an unfolded protein response took place. At 7 weeks, rimmed vacuole formation became obvious. Interestingly, SERCA2, a Ca2+ -pump ATPase located in the endoplasmic/sarcoplasmic reticulum membrane was up-regulated at 5 weeks after treatment, but declined to the control level by 7 weeks. Taken together, these findings suggest that Abeta accumulation (at 3 weeks) caused by the disruption of lysosomal enzymes precedes an unfolded protein response (at 5 weeks). Next, activation of autophagy occurs (at 7 weeks), probably using sarcoplasmic reticulum membrane, the amount of which was increased. Chloroquine-treated rats could be useful for investigating the pathogenesis of diseases related to Abeta accumulation.
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PMID:Amyloid-beta accumulation caused by chloroquine injections precedes ER stress and autophagosome formation in rat skeletal muscle. 1919 58

Hydroxychloroquine (HCQ) and chloroquine are used worldwide for malaria as well as connective and rheumatological disorders. They have been reported to be linked to myopathy in patients. We report four patients who were receiving HCQ as part of treatment for connective tissue disorder and who presented with myopathy. The muscle biopsy in these patients was consistent with findings of HCQ toxicity. HCQ muscle toxicity is usually self-limiting after discontinuation of the drug. It also usually tends to be under-reported due to presence of various confounding factors. This warrants close monitoring and consideration of muscle biopsy as part of initial work up of patients who present with myopathy while receiving HCQ.
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PMID:Hydroxychloroquine-induced autophagic vacuolar myopathy with mitochondrial abnormalities. 3041 12