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)

WR 33063, a phenanthrene methanol, was studied in human volunteers for tolerance and toxicity. In normal volunteers, it was possible to give 4.6 g in four divided doses without adverse effect for 10 days. At this dose level, there was neither evidence of photosensitivity nor adverse renal or cardiac effect. At a dose level of 1.6 g in four divided doses for 6 days, WR 33063 cured 18 of 23 nonimmune volunteers infected with the Smith strain of Plasmodium falciparum from Vietnam. In addition, infections due to the Marks and Braithwaite Vietnam strains were also treated because these strains represent a major therapeutic challenge to chloroquine; six of six and two of three volunteers, respectively, were cured. With the Malayan Camp strain, 1.6 g in four divided doses for 6 days cured all of five volunteers. The African Uganda I strain of chloroquine-responsive malaria was even more responsive to WR 33063; all of six men who received 1.6 g in four divided doses for 6 days were cured, and all of three men who received this same dosage for 3 days were cured. One subject infected with a Haitian strain of P. falciparum was treated and cured. Blood-induced infections with the Chesson strain of P. vivax also responded well to WR 33063 with four of five men cured. In all, 52 men received WR 33063 in tolerance trials, and 59 men with experimental malaria and one man with clinical malaria were treated with WR 33063.
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PMID:A phenanthrene methanol (WR 33063) for treatment of acute malaria. 459 14

Two new investigational antimalarial drugs developed by the U.S. Army Malaria Research Program were tested in patients with multi-drug-resistant falciparum malaria from Vietnam. WR 33063, a phenanthrene methanol, cured 13 patients treated in the United States. All of these patients had suffered multiple recrudescences after treatment with standard antimalarial drugs. In addition, 23 of 25 patients with acute attacks of falciparum malaria treated in Vietnam were cured. The rate of clinical response was prompt. WR 30090, a quinoline methanol, similarly cured eight patients with multiple recrudescences in the United States and 23 of 26 patients in Vietnam. Adverse effects associated with the drugs were not seen. These drugs signify a major advance in the chemotherapy of drug-resistant falciparum malaria.
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PMID:Treatment of falciparum malaria from Vietnam with a phenanthrene methanol (WR 33063) and a quinoline methanol (WR 30090). 459 17

The spread of multiresistant strains of Plasmodium falciparum in south-east Asia and South America and the appearance of chloroquine resistance in Africa indicates the urgent need for alternative drugs against these parasites. Mefloquine, a 4-quinoline methanol, is the only new drug that is currently at an advanced stage of development.Studies in animal models and in the clinic have shown that it is highly active as a blood schizontocide against strains that are resistant to many established antimalarials, e.g., chloroquine and pyrimethamine. It is not, however, effective as a causal prophylactic agent. Preclinical toxicological, teratological, and carcinogenicity studies do not indicate any major contraindications to its use.Intensive clinical studies have been carried out in Africa, North and South America, south-east Asia, and Europe. These studies have indicated that the compound is generally well tolerated, safe, and effective in the treatment of malaria, particularly infections with chloroquine-resistant parasites.In order to protect this new and promising drug against the development of resistance to it in endemic areas, it is important that its introduction should be accomplished in a rational and deliberate manner. Appropriate precautionary measures include the development of mefloquine combinations (a combination of mefloquine with pyrimethamine-sulfadoxine is presently under investigation), its use with primaquine as a gametocytocidal drug to prevent transmission, and its deployment primarily for treatment, being used for prophylaxis only in special risk groups.
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PMID:Development of mefloquine as an antimalarial drug. UNDP/World Bank/WHO update. 640 67

Polymerase chain reaction (PCR) primered with primers 3,4 and 5,6 was performed using DNA extracted from dried blood spot of a falciparum malaria patient from Mengpeng Township, Yunnan using four different methods, including STE-proteinase K-SDS, methanol-proteinase K-SDS, Chelex-100 and Chelex-100-proteinase K to amplify DNA of apical membrane antigen 1 (AMA-1). A 900 bp DNA band could be seen on the ethidium bromide-stained agarose gel electrophoresis of the PCR products when DNA was extracted using all the above-mentioned methods except STE-proteinase K-SDS method. DNA extracted with Chelax-100 was recommended.
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PMID:[Application of Plasmodium falciparum DNA extract from dried blood spot of falciparum malaria patient in polymerase chain reaction]. 755 60

A reversed-phase high-performance liquid chromatographic method using acetonitrile-methanol-(1M) perchloric acid-water (30:9:0.8:95, v/v/v/v) at a flow of 1.5 ml min-1 on mu-Bondapak C18 column with UV (254 nm) detection has been developed for the separation of sulphadoxine, sulphalene and sulphamethoxazole from other antimalarials. Calibration curves were linear in the range 0.5-100 micrograms ml-1. The limit of quantitation was 50 ng ml-1. Within-day and day-to-day coefficients of variation averaged 2.1 and 6.45%, respectively. The extraction recovery of sulphadoxine from plasma, red blood cells and whole blood was 90.28, 92.05 and 94.69%, respectively. The method has been used for the determination of sulphadoxine concentrations in plasma, red blood cells and whole blood of eight healthy and 50 Plasmodium falciparum malaria cases after administration of two tablets of Fansidar. Mean sulphadoxine concentration in plasma was higher than red blood cells or whole blood. Sulphadoxine concentration in plasma and whole blood of P. falciparum malaria cases was significantly higher as compared to healthy volunteers while it was the same in red blood cells. Sulphadoxine was absorbed much less in red blood cells than in plasma or whole blood.
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PMID:Sulphadoxine concentrations in plasma, red blood cells and whole blood in healthy and Plasmodium falciparum malaria cases after treatment with Fansidar using high-performance liquid chromatography. 784 Dec 29

Twenty residue peptides from the 185-200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium falciparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone-methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphteria toxoid, and in particular a pronounced type III (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide-diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations.
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PMID:Antibody and clinical responses in volunteers to immunization with malaria peptide-diptheria toxoid conjugates. 785 Oct 7

The preparation of artemether from artemisinin is reviewed. Firstly, the extraction of artemisinin from Artemisia annua is described and an estimation of the yield per hectare based on literature data is given. Artemisinin is reduced with sodium borohydride to produce dihydroartemisinin as a mixture of epimers. The mixture is treated with methanol and an acid catalyst to provide artemether. Increasing demand for use of artemether places pressure on the supply of artemisinin, and an alternative means of preparing the drug from artemisinic acid, an abundant constituent of A. annua, which could triple current yields, is described. In anticipation of problems of drug resistance emerging with the continued use of artemether and artesunate to treat malaria, development of new derivatives of artemisinin which have enhanced stability is required. Examples of such derivatives which have been prepared in our laboratories, or proposed, are described.
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PMID:Extraction of artemisinin and artemisinic acid: preparation of artemether and new analogues. 805 18

A sensitive, selective and rapid reversed-phase high-performance liquid chromatographic method was developed for the simultaneous analysis of dapsone, monoacetyldapsone and pyrimethamine in human whole blood and plasma. The procedure involved extraction of the compounds and the internal standard, monopropionyldapsone, with tert.-butylmethyl ether under alkaline conditions. A newly marketed column, Supelcosil LC-ABZ (Supelco, 15 cm x 4.6 mm I.D.), was employed. The mobile phase, consisting of acetonitrile-methanol-phosphate buffer (2:1:7, v/v/v), was delivered at a flow-rate of 1.2 ml/min, and ultraviolet absorbance was monitored at 286 nm. The limit of determination using a 150-microliters sample was 10 ng/ml (40 nM) for dapsone and pyrimethamine and 8 ng/ml (28 nM) for monoacetyldapsone. Given that only a small amount of blood is required in this method, it could now be applied in studies involving blood level monitoring and pharmacokinetics in children on Maloprim (dapsone-pyrimethamine) prophylaxis in malaria endemic areas.
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PMID:Simultaneous determination of dapsone, monoacetyldapsone and pyrimethamine in whole blood and plasma by high-performance liquid chromatography. 849 23

A normal-phase high-performance liquid chromatographic method using dichloromethane-methanol-1 M perchloric acid (100:9:0.4, v/v) at a flow-rate of 0.8 ml/min on a Zorbax-Sil column with fluorescence detection has been developed for the separation of quinine and quinidine from other antimalarials. Within-day and day-to-day coefficients of variation averaged 0.74 and 7.56%, respectively. The extraction recovery of quinine for plasma, serum, red blood cells and whole blood (filter paper) was 88.13, 87.12, 78.0 and 77.5%, respectively. The method is capable of separating quinine from dihydroquinine, a compound usually found as an impurity in authentic quinine samples. The method has been used for the determination of quinine in plasma, serum, red blood cells and whole blood (filter paper) of six healthy and twenty Plasmodium falciparum malaria cases. The average quinine concentration in P. falciparum malaria cases was three to four times higher than that in healthy volunteers. Quinine was absorbed much less in red blood cells than in plasma or serum.
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PMID:Determination of quinine in serum, plasma, red blood cells and whole blood in healthy and Plasmodium falciparum malaria cases by high-performance liquid chromatography. 849 90

A novel solid-phase extraction and a robust high-performance liquid chromatographic (HPLC) separation procedure for artesunate and alpha- and beta-dihydroartemisinin, using post-column alkali decomposition and UV detection is described. Extraction was performed with Bond-Elut Phenyl solid-phase extraction cartridges and analysis by HPLC was carried out using a Waters Symmetry C8 5-microns 150 x 3.9 mm I.D. column. The mobile phase was 50% acetonitrile in 0.1 M acetate buffer (pH 4.8) delivered at a flow-rate of 0.7 ml/min. The column eluate was mixed with 1.2 M potassium hydroxide in 90% methanol delivered at 0.3 ml/min, in a 1-ml reaction coil at 69 degrees C, to form UV-absorbing chromophores which were detected at 290 nm. The recovery of all analytes was greater than 80%. There was no significant difference in the peak-area ratio of alpha- and beta-dihydroartemisinin in plasma. Preliminary pharmacokinetic data from six adult Vietnamese patients who received 120 mg of artesunate by intravenous injection for the treatment of acute falciparum malaria are presented. Despite limited data, the mean half-life of artesunate was approximately 3.5 min while that for dihydroartemisinin was 34 min. These data confirm the relatively rapid clearance of both artesunate and its principle active metabolite, dihydroartemisinin.
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PMID:Selective high-performance liquid chromatographic determination of artesunate and alpha- and beta-dihydroartemisinin in patients with falciparum malaria. 870 40


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