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)

TNF, a potent immunoregulatory cytokine, is associated with inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and cerebral malaria when produced in excess. Antimalarial agents such as chloroquine and hydroxychloroquine have been used to treat some rheumatic diseases. Chloroquine was reported to inhibit production of TNF, although the underlying mechanism is poorly understood. In RAW 264.7 cells stimulated with LPS, addition of chloroquine at nontoxic concentrations did not inhibit induction of TNF mRNA and NF-kappaB activity. In the same cells, synthesis and steady state level of 26-kDa pro-TNF were also not significantly reduced by addition of chloroquine, while only small amount of 17-kDa mature TNF was detected in the medium. A pulse-chase experiment of pro-TNF produced in chloroquine-treated cells showed significant inhibition of processing of prohormone. Hydroxychloroquine showed similar inhibitory effect, whereas other lysosomal inhibitors such as ammonium chloride and methylamine had no effect on the production of TNF. Our results suggest that chloroquine inhibits production of TNF at the step of processing of membrane-bound pro-TNF to make soluble mature protein in a lysosome-independent manner.
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PMID:Chloroquine inhibits processing of tumor necrosis factor in lipopolysaccharide-stimulated RAW 264.7 macrophages. 914 7

A new 4-month long study is testing the combination of hydroxychloroquine and AZT in HIV-positive people. Hydroxychloroquine has been used for treating malaria, rheumatoid arthritis, and lupus. Participants must be 18 years old or older with a T4 cell count between 200 and 500. Two groups will be studied, one using both drugs, and the other using AZT only.
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PMID:Treatment for HIV-related inflammation. 1136 90

A well-known malaria drug, Hydroxychloroquine, has shown some modest anti-HIV activity in laboratory and human studies, and volunteers are being recruited for a small phase I/II trial in Los Angeles. The drug will be studied in combination with ddI and Hydroxyurea, to determine if a less expensive and more tolerable regimen can be found. The study is sponsored by the AIDS Research Alliance (formerly Search Alliance) and funded by Bristol Myers. Sanofi will donate the Hydroxychloroquine. Study enrollment criteria and contact information are included.
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PMID:Hydroxychloroquine+ddI+Hydroxyurea antiretroviral trial, AIDS Research Alliance, Los Angeles. 1136 31

Chloroquine and its derivative, hydroxychloroquine sulfate, have been used in treating malaria, dermatitides of systemic lupus erythematosus and rheumatoid arthritis. Hydroxychloroquine retinopathy is uncommon in Taiwan. Here we report a patient with hydroxychloroquine retinopathy which progressed even after discontinuation of hydroxychloroquine. A 42-year-old woman had systemic lupus erythematosus for twenty years. She had been treated with 200 to 400 mg of hydroxychloroquine per day (4 to 8 mg/kg of body weight/day) with a cumulative dose of 657 g. After bull's-eye maculopathy was found, hydroxychloroquine was discontinued. Her medical history revealed no chloroquine administration and no other systemic disease. Five years after cessation of the therapy, her visual acuity and visual fields continued to deteriorate. Ophthalmoscopic examination revealed the hydroxychloroquine retinopathy had advanced. To the best of our knowledge, the progression of hydroxychloroquine retinopathy after discontinuation of medications is a rare phenomenon. Regular ophthalmologic examinations should be performed for patients on hydroxychloroquine regimens because there is no satisfactory treatment for hydroxychloroquine retinal toxicity. Ophthalmologists, dermatologists and rheumatologists should monitor for ocular toxicity of hydroxychloroquine carefully.
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PMID:Progression of hydroxychloroquine retinopathy after discontinuation of therapy: case report. 1148 Mar 31

Chloroquine (CHQ), an antimalarial, is also used as an anti-inflammatory drug for systemic lupus erythematosus and rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) reduces the frequency of organ involvement and disease flares, and relieves skin and joint symptoms. CHQ reduces the immunologically-mediated inflammation of the joints. HCQ and combination therapies have a significant benefit on synovitis, pain and physical disability on RA. We advocate the investment of resistance Plasmodium prevalence determinations in countries beset by malaria, and to match thereafter the quantity of persons administered CHQ. Follow-up investigations are essential to diagnose and prevent visual damage.
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PMID:Chloroquine has not disappeared. 1805 74

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. The second report describes the first case of hydroxychloroquine cardiomyopathy described in a patient with scleroderma. These novel findings will add to the present knowledge of hydroxychloroquine-induced cardiomyopathy in its pathology and its implication for treatment of rheumatic diseases.
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PMID:New clinical and ultrastructural findings in hydroxychloroquine-induced cardiomyopathy--a report of 2 cases. 1806 91

Hydroxychloroquine (HCQ) is an antimalarial drug used as chemoprophylaxis against malaria caused by Plasmodium vivax in the Republic of Korea Army (ROKA). In this study, we evaluated the pharmacokinetics (PK) of HCQ and its metabolites and the relationship between the PK of HCQ and the effect of treatment of HCQ on vivax malaria in South Koreans. Three PK studies of HCQ were conducted with 91 healthy subjects and patients with vivax malaria. Plasma concentrations were analyzed by noncompartmental and mixed-effect modeling approaches. A two-compartment model with first-order absorption best described the data. The clearance and the central and peripheral volumes of distribution were 15.5 liters/h, 733 liters, and 1,630 liters, respectively. We measured the plasma concentrations of HCQ in patients with prophylactic failure of HCQ and compared them with the prediction intervals of the simulated concentrations for HCQ from the final PK model built in this study. In 71% of the patients with prophylactic failure, the plasma concentrations of HCQ were below the lower bounds of the 95% prediction interval, while only 8% of them showed higher levels than the upper bounds of the 95% prediction interval. We report that a significant cause of prophylactic failure among the individuals in ROKA was ascribed to plasma concentrations of HCQ lower than those predicted by the PK model. However, prophylactic failure despite sufficient plasma concentrations of HCQ was confirmed in several individuals, warranting continued surveillance to monitor changes in the HCQ susceptibility of Plasmodium vivax in the Republic of Korea.
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PMID:Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. 1918 92

Hydroxychloroquine (HCQ) was initially indicated for the treatment of malaria, but more recently its anti-inflammatory and immune modulating properties have been utilized for treatment of multiple dermatologic and rheumatologic diseases. Mucocutaneous bluish-gray dyschromia is a rare side effect with HCQ and little information exists regarding its duration after drug discontinuation. The few existing case reports primarily describe small focal areas of discoloration. More extensive dyschromia has very rarely been reported with HCQ. We report a case of HCQ induced dyschromia diffusely involving the extremities, with minimal resolution one year after treatment discontinuation.
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PMID:Persistent cutaneous hyperpigmentation due to hydroxychloroquinone one year after therapy discontinuation. 2004 Feb 65

Hydroxychloroquine (HCQ) is a 4-aminoquinoline compound used to treat malaria and chronic autoimmune disorders and is not uncommonly found in the medical examiner setting. Studies have shown HCQ to have a long half-life (32-56 days in blood), high volume of distribution (580-815 L/kg), and therapeutic concentrations ranging from 0.03 to 15 mg/L, depending on the chronicity of treatment. Previous reports have shown that the toxic concentration of HCQ ranges from 3 to 26 mg/L, whereas the lethal concentration ranges from 20 to 104 mg/L. A report addressing nontoxic postmortem concentrations of HCQ in individuals known to be taking the medication, and in whom there is no evidence of toxicity, has not been previously undertaken. This study found that postmortem concentrations in nontoxic cases can range from 0.3 to 39 mg/L, which is well within the reported range of both lethal and toxic concentrations. It is recommended that all investigative and autopsy data be considered and that the cause of death not be certified based purely on blood HCQ concentrations.
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PMID:Postmortem hydroxychloroquine concentrations in nontoxic cases. 2146 94

Resisting cell death is one of the six hallmarks of cancer. Autophagy is a highly adaptable metabolic process that plays an important role in stressful conditions, such as nutrient deprivation and hypoxia. In these conditions, it is becoming evident that autophagy protects cells, by providing an alternative energy source and by eliminating dysfunctional organelles or proteins. In tumourigenesis, autophagy plays a dual role, which may be related to the different stages in cancer development. The autophagy-mediated removal of damaged proteins and organelles may prevent cancer initiation by limiting tissue inflammation. In contrast, autophagy has been shown to allow established tumours to survive in nutrient-deprived or hypoxic conditions during cancer progression. Key regulators of the autophagy pathway are modulated or aberrantly expressed in cancer and modulating autophagy is an attractive concept for cancer therapy. The difficulties, however, lie in the complexity of the crosstalk between apoptosis and autophagy and the lack of robust tissue biomarkers and in vivo assessment of autophagic flux. Currently there are 19 clinical trials in both solid and haematogenous cancers investigating the efficacy and toxicity of adding an autophagy inhibitor to standard treatment. Hydroxychloroquine, a drug routinely used in the treatment of malaria and autoimmune disorders, is the most common autophagy inhibitor under investigation due to its more favourable toxicity profile. This overview summarises the role of autophagy in cancer initiation, progression and resistance to treatment and thereby the therapeutic benefit that may be gained by modulating its effects.
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PMID:The role of autophagy in clinical practice. 2203 64


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