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)

Ferriprotoporphyrin IX (FPIX) forms a coordination complex with chloroquine, an anti-malarial drug. The FPIX-chloroquine complex strongly promotes the peroxidative cleavage of phospholipid membrane. Iron in the complex is essential for the complex to induce lipid peroxidation. In this paper a more detailed mechanism of the complex promoted lipid peroxidation was investigated. Apotransferrin exhibited no apparent inhibition of the complex evoked lipid peroxidation, indicating no mobilization of iron from the complex. No significant inhibitory effect by superoxide dismutase, catalase and sodium benzoate on the complex induced lipid peroxidative reaction, suggesting little involvement of superoxide anion, hydrogen peroxide and hydroxyl radical in the reaction. Quinine and mefroquine, blood shizontocidal drugs as well as chloroquine, formed a complex with FPIX and each complex more rapidly induced lipid peroxidation than FPIX alone. Primaquine, which is not as effective as quinine or mefroquine on an intraerythrocytic malaria parasite, neither coordinated to FPIX nor promoted lipid peroxidation. The complex formation between FPIX and chloroquine, quinine or mefroquine could play a key role in their anti-malarial actions.
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PMID:The chemical basis for the ferriprotoporphyrin IX-chloroquine complex induced lipid peroxidation. 204 70

The malaria-induced surface antigens on Plasmodium falciparum-infected erythrocytes from West African patients were characterized by agglutination of infected cells by human sera, surface immunofluorescence of live infected cells, inhibition of cytoadherence to C32 melanoma cells by human sera, immunoelectron microscopy (immunoEM), and immunoprecipitation. In a nonimmune individual, serum antibody reactivity to surface antigens of infected cells was acquired during convalescence, as tested by all five methods, and was generally parasite isolate-specific. By contrast, adult hyperimmune West African sera reacted with many isolates, including isolates from geographically distinct regions. A quantitative correlation was established between agglutination and surface immunofluorescence assay titers, and between surface immunofluorescence assay and immunoEM reactivity, suggesting that a single antigen or a set of coexpressed antigens is being detected. Surface iodination of infected cells identified trypsin-sensitive high M, antigens in the sodium dodecyl sulfate extract. All sera tested that agglutinated infected cells also immunoprecipitated these antigens. The same surface antigens were immunoprecipitated by the homologous convalescent serum as by adult sera. By immunoEM these antigens were localized exclusively at the knob-like protrusions of infected cells, where they may participate in adherence to vascular endothelium.
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PMID:Characterization and localization of Plasmodium falciparum surface antigens on infected erythrocytes from west African patients. 207 55

Malaria parasites of the genus Plasmodium spend much of their asexual life cycle inside the erythrocytes of their vertebrate hosts. Parasites presumably have to exploit metabolic and transport mechanisms to adapt themselves to the host erythrocyte's physicochemical environment. This review surveys the metabolism and transport of Ca2+, alkali cations, and H+ in malaria-infected erythrocytes. The Ca2+ content of Plasmodium-infected erythrocytes increases as the parasite matures. An increase in the influx of extracellular Ca2+ into infected erythrocytes is evident at later stages of parasite development. In infected erythrocytes, Ca2+ is almost exclusively localized in the parasite compartment and changes but little in the cytosol of the host cell. The importance of Ca2+ in supporting the growth of intraerythrocytic parasites and the invasion of erythrocytes by the merozoite has been assessed by depletion of extracellular Ca2+ with chelators, or by disturbance of the metabolism and transport of Ca2+ with a variety of Ca2+ modulators. Membranes of malaria-infected erythrocytes change their permeability to alkali cations. Hence, levels of K+ decrease and levels of Na+ increase in the cytosol of infected erythrocytes. Intraerythrocytic parasites maintain a high K+, low Na+ state, suggesting a mechanism for transporting K+ inward and Na+ outward against concentration gradients of the alkali cations across the parasite plasma membrane and/or the parasitophorous vacuole membrane (PVM). Concomitantly, P. falciparum can grow in Na(+)-enriched human erythrocytes. Experimental evidence suggests that Plasmodium possesses in its plasma membrane a proton pump which is very sensitive to orthovanadate, carbonylcyanide m-chlorophenylhydrazone, a protonophore, and dicyclohexylcarbodiimide, an inhibitor of H(+)-ATPase, but is only slightly sensitive to inhibitors of bacterial and mitochondrial respiration, such as antimycin A, CN-, or N3-, and ouabain, a Na+, K(+)-ATPase inhibitor. By operating this proton pump, parasites extrude H+ and thus generate an electrochemical gradient of protons (an internal negative membrane potential and a concentration gradient of protons) across the parasite plasma membrane. The electrochemical gradient apparently drives inward movement of Ca2+ and, possibly, glucose from the cytosol of infected erythrocytes. Little is known about the transport properties of the PVM. Recent sequence studies suggest that Plasmodium contains a cation-transporting ATPase which exhibits a high homology to the Ca2(+)-ATPase of rabbit skeletal muscle sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ion metabolism in malaria-infected erythrocytes. 209 86

Artemisinin (Qinghaosu) is a potent antimalarial sesquiterpene lactone isolated from the Chinese herb Artemisia annua. Arteether, a potent semisynthetic analogue of dihydroartemisinin is being developed by the World Health Organization as the artemisinin derivative of choice for the treatment of malaria. All three agents in doses of 400 and 600 mg/kg body weight were found to exhibit marked suppression of humoral responses, as measured by the hemolytic plaque assay, with arteether being the most potent. These agents did not alter the delayed-type hypersensitivity response to sheep erythrocytes at the same dose levels. In addition, all three agents were found not to possess any anti-inflammatory activity when tested on carrageenan-induced oedema. These results indicated that these agents have a selective immunosuppressive activity. They did not exhibit immunostimulating activity in contrast to what has been reported for sodium artesunate.
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PMID:Effects of artemisinin, dihydroartemisinin and arteether on immune responses of normal mice. 220 89

Data on a technique for the detection of antigen from arthropod vectors in a dot immunobinding assay are presented. In this system, antigen present in the vector was first solubilized in sodium dodecyl sulfate. The homogenate from this process was microfiltered through a two-membrane sandwich; target antigen molecules passed through the first membrane and were immobilized on the second one. The first membrane was nonbinding and served to impinge debris. The second membrane was a high-protein-binding-capacity hydrophobic polyvinylidene difluoride membrane. High signal-to-noise ratios were produced by this method, which is readily adaptable for field use. This assay was used for malaria sporozoites, but it can serve as a general technique that is applicable to other arthropod vectors and etiologic agents.
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PMID:Processing and microfiltration of mosquitoes for malaria antigen detection in a rapid dot immunobinding assay. 220 8

Qinghaosu (QHS), also known as artemisinine and arteannuin, is isolated from the Chinese herb Artemisia annua L. It is highly active against both chloroquine-sensitive and chloroquine-resistant strains of P. berghei and has been approved by the Ministry of Health for the treatment of malaria. When QHS is treated with sodium borohydride, dihydroqinghaosu (DH QHS) is resulted with the antimalarial activity enhanced several fold. This paper reports the pharmacokinetics of DHQHS studied with the radioimmunoassay method. When the drug was given orally in tablet form to rabbits at doses of 10, 20 and 30 mg/kg, peak serum levels of 0.03, 0.05 and 0.13 micrograms/ml, respectively, were obtained in 1 to 2 h. The corresponding T1/2 of the drug were found to be 1.19, 1.00 and 1.10 h and the MRTs were 1.73, 1.36 and 1.53 h. No significant difference between dosages used was observed. When dogs were given DHQHS tablets at the dose of 20 mg/kg, a peak serum concentration of 0.13 micrograms/ml wes reached in about 2 h with a T1/2 of 2.10 h and an MRT of 3.04 h. However, when dogs were given QHS tablets at the dose of 70 mg/kg, no drug was detected in the serum. It would appear that the bioavailability of DHQHS tablets is much higher than that of QHS when given orally to the dog.
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PMID:[The pharmacokinetics of dihydroqinghasu given orally to rabbits and dogs]. 223 23

A non-polymorphic antigen associated with the rhoptry organelles of Plasmodium falciparum has been purified by immunoaffinity chromatography. The antigen, RAP-1 (rhoptry associated protein-1), which is defined by monoclonal antibodies which inhibit parasite growth in vitro, is a multi-component antigen consisting of four major proteins of 80, 65, 42 and 40 kDa and two minor proteins of 77 and 70 kDa. These proteins were electro-eluted from preparative sodium dodecyl sulphate polyacrylamide gels and protected Saimiri sciureus monkeys from a lethal blood-stage infection of P. falciparum malaria. Sera from the protected animals recognized only proteins of the RAP-1 antigen when used to probe a Western blot of total parasite protein extract, confirming that RAP-1 is responsible for eliciting the protective immune response.
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PMID:A rhoptry antigen of Plasmodium falciparum is protective in Saimiri monkeys. 226 13

N,N'-Bis(benzyl)polyamine analogs were found to be substrates for highly purified polyamine oxidase. Metabolism of these analogs was apparently dependent on molecular O2 and resulted in the formation of benzaldehyde, H2O2, and a polyamine analog with free terminal amines. The debenzylation reaction was optimal between pH 9 and 10, identical to the pH optimum for polyamine oxidase activity when N1-acetylspermine was used as the substrate. On a molecular sieve column the debenzylating activity co-eluted with N1-acetylspermine oxidizing activity, at an apparent molecular mass of approximately 65 kDa. The purified enzyme also appeared to have a molecular mass of approximately 65 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Debenzylation of the bis(benzyl)polyamines was competitively inhibited by N1-acetylspermine and N1-acetylspermidine. The specific irreversible inhibitor of polyamine oxidase, N1,N4-bis(buta-2,3-dienyl)butanediamine also inhibited the debenzylation, whereas inhibitors of diamine and monoamine oxidases did not. The evolution of benzaldehyde from bis(benzyl)polyamine analogs by polyamine oxidase allowed the development of a simple rapid spectrophotometric assay for use in the measurement of polyamine oxidase activity in partially purified tissue or cell extracts. Further, metabolism of a bis(benzyl)polyamine analog by polyamine oxidase was found to be an important element in the growth inhibitory properties of the compound in a mouse model of malaria.
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PMID:Bis(benzyl)polyamine analogs as novel substrates for polyamine oxidase. 229 9

Following previous studies of verapamil reversal of chloroquine resistance in malaria and multi-drug resistance in cancer cells, the effect of verapamil was investigated on nifurtimox-resistant Trypanosoma cruzi in vitro and antimony-resistant Leishmania donovani in vitro and in vivo. Verapamil alone was not active against either parasite, but in combination with nifurtimox it reversed the drug resistance of T. cruzi and in combination with sodium stibogluconate reversed the drug resistance of L. donovani.
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PMID:Reversal of drug resistance in Trypanosoma cruzi and Leishmania donovani by verapamil. 255 33

Qinghaosu, also known as artemisinin and arteannuin, is a new type of antimalarial drug isolated from Artemisa annua L. Its low solubility in water and oil limited its widespread clinical use. Artesunate (sodium dihydroqinghaosu hydrogen hemisuccinate monoester) is easily soluble in water and is used iv in the treatment of acute cerebral and malignant malaria. However, artesunate was shown to have a very short half-life when given iv in animals as well as in human beings. A transdermal dosage form of artesunic acid had been prepared and was reported to have reliable suppressing and killing effects on plasmobium berghei in mice. This paper reports results of pharmacokinetic studies of this preparation when applied onto a fixed area of the shaved skin of mice and rabbits. Serum concentration of the drug was determined by a method of radioimmunoassay. The drug was found to be easily absorbed from the skin. The serum concentration-time curve is depicted in figures 1. Peak concentration of 1.8 micrograms/ml was reached at about 2 h when a dose of 25 mg/kg was given to rabbits. For mice, peak serum concentrations of 2.05 and 7.11 micrograms/ml were attained in about 0.5 h after doses of 31.3 and 71.4 mg/kg, respectively, while at a dose of 6.7 mg/kg a peak level of 0.82 micrograms/ml (a concentration more than 5000 times the IC50 of artesunate in in vitro tests on plasmodium berghei for antimalarial activity) was attained at about 4 h after application of the drug. The half-lives of the drug were found to be more than 2 h for both mice and rabbits.
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PMID:[The pharmacokinetics of a transdermal preparation of artesunate in mice and rabbits]. 261 77


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