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)

Lactate dehydrogenase, the terminal enzyme of anerobic Embden-Meyerhoff glycolysis, plays an important role in the carbohydrate metabolism of human malaria parasites. Based on the ability of malarial lactate dehydrogenase to use 3-acetylpyridine NAD as a coenzyme in a reaction leading to the formation of pyruvate from L-lactate, the enzymatic activity of fresh clinical isolates of Plasmodium falciparum and Plasmodium vivax was determined in relation to incubation time, asexual stages, and parasitemia and applied to a drug susceptibility assay. Lactate dehydrogenase activity was detectable at a parasitemia > 0.4%, at a hematocrit of 1.5%, and increased with parasitemia. Maximal lactate dehydrogenase activity was generally observed between 36 and 48 hr, when the trophozoites and schizonts predominated. The results of the in vitro drug susceptibility assays based on the inhibition of lactate dehydrogenase activity and on the incorporation of tritium-labeled hypoxanthine were correlated. For an optimal performance against fresh clinical malaria isolates, however, the enzymatic assay requires an initial parasitemia between 1 and 2% at a hematocrit of 1.5%.
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PMID:Plasmodium falciparum and Plasmodium vivax: lactate dehydrogenase activity and its application for in vitro drug susceptibility assay. 789 36

Genetically controlled enzyme variation exists within and between four sibling species of the Anopheles culicifacies complex of malaria vectors in India. A study on electrophoretic variation of nine enzymes in An. culicifacies sibling species revealed that the lactate dehydrogenase (Ldh) locus has Fast (F) and Slow (S) allozymes distinguishing species A+D from species B+C with a probability of c. 95%.
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PMID:Lactate dehydrogenase allozyme differentiation of species in the Anopheles culicifacies complex. 802 21

This report compares the use of the lactate dehydrogenase (pLDH) assay with 3H-hypoxanthine incorporation and Giemsa microscopy for the evaluation of anti-malaria drug inhibition of the growth of P. falciparum in vitro. The inhibition profiles and IC50 determinations of the pLDH assay were directly comparable to those determined by the radioactive uptake and microscopic methods. Furthermore, the pLDH culture sensitivity assay is reproducible, easily interpreted, rapid and inexpensive to perform, suggesting field applicability.
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PMID:Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity. 833 66

This report describes an enzyme assay for the detection of Plasmodium falciparum. The assay is based on the observation that the lactate dehydrogenase (LDH) enzyme of P. falciparum has the ability to rapidly use 3-acetyl pyridine NAD (APAD) as a coenzyme in the reaction leading to the formation of pyruvate from lactate. Human red blood cell LDH carries out this reaction at a very slow rate in the presence of APAD. We measured the development of APADH and found that the formation of this product could establish the basis of an assay that detected the presence of P. falciparum from in vitro cultures at parasitemia levels of 0.02%. We also had occasion to use this assay with clinical samples. We found a correlation between levels of parasitemia and the activity of parasite LDH. Parasite LDH (pLDH) activity could be measured in blood hemolysates and in plasma and serum from patients with malaria. We used the serum assay for pLDH and followed the level of pLDH in a patient with cerebral malaria prior to antimalarial treatment and during the recovery period. From these initial studies, it is evident that the measurement of pLDH has a correlation with parasitemia and may offer a method that can be developed into a simple test for the detection of Plasmodium parasitemia.
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PMID:Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. 844 24

The measurement of parasite lactate dehydrogenase (pLDH) has been presented as an easy and rapid method for the diagnosis of malaria in humans. In order to evaluate the sensitivity and specificity of such a test we examined blood samples from 429 Ugandan patients. While pLDH activity was significantly linked to parasitaemia, sensitivity and specificity were found to be rather low at 58.8 and 62.2% respectively. The positive and negative predictive values failed to meet necessary standards. We conclude that the methods of measurement of pLDH activity in malaria infection, although potentially useful for the fast diagnosis of malaria, need to be improved to be of true value in endemic areas.
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PMID:Parasite-specific lactate dehydrogenase for the diagnosis of Plasmodium falciparum infection in an endemic area in west Uganda. 866 89

Syntheses for the new photosensitizers HOSiPcOSi(CH3)2(CH2)3N(CH1)1 or 3(CH3)2, Pc 34 and Pc 25, have been developed and the order of activity of these photosensitizers and the previously reported photosensitizer Pc 4, HOSiPcOSi(CH3)2(CH2)3N(CH3)2, in the dark and with broad-band red light toward Plasmodium falciparum in red blood cell (RBC) suspensions has been studied. The order of activity has been found to be Pc 4 > Pc 34 > Pc 25. Thus, the activity of the photosensitizers under both sets of conditions is inversely proportional to the length of their terminal amino alkyl chains. The 50% inhibition dye concentration (IC50) in the dark for the parasites in RBC suspension with Pc 4 is 24 nM and the dye concentration and light fluence that yield > or = 3 log10 of parasite inactivation with Pc 4 are 2 microM and 3 J/cm2, respectively. The synthesis of DNA and proteins by the parasites in culture was strongly inhibited by Pc 4 in the dark while parasite lactate dehydrogenase (pLDH) activity was unaffected. With Pc 4 and light, DNA and protein synthesis of the parasites in culture was strongly inhibited, pLDH activity of the parasites was moderately inhibited and ribosome density of the parasite cells was reduced. Gel electrophoresis studies showed that synthesis of all parasite proteins was inhibited to a similar extent. These results suggest that Pc 4 both in the dark and with light inactivates the cells by disturbing their machinery for the synthesis of not just one but a whole series of proteins. It is concluded that Pc 4 and light may be able to serve as a practical sterilization combination not only for HIV and other viruses but also for malaria parasites in RBC concentrates, and that Pc 4 by itself may have potential as a chemotherapeutic agent toward malaria.
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PMID:Structure-activity and mechanism studies on silicon phthalocyanines with Plasmodium falciparum in the dark and under red light. 927 50

Currently 40% of the world's population is still at risk of becoming infected with malaria, which is an even more worrisome disease because of drug resistance and multidrug resistance. Research on drug resistance is suggesting new ways to attack the parasite by designing selectively toxic compounds. At Washington University, a study has been centering on how malarial parasites developed resistance to antimalarial drugs. A new class of compounds have been developed that block haem polymerization to haemazoin and kill the parasite. These hexadentate metal complexes that bypass the current resistance mechanisms are made from aspirin and are being tested in animals. A new resistance gene also been identified that transports chloroquine out of the parasite or blocks the drug's influx, leaving the parasite unharmed. In addition, a gene associated with mefloquine resistance was isolated at Harvard University. A large number drug transporter inhibitors have also been identified, but none is sufficiently selective for the parasite's transporter. In Oxford, UK, recently, the low-resolution structure of the human multidrug resistant P-glycoprotein was also solved, which might permit the design of modified antimalarial drugs. Exploiting the differences between parasite and human enzymes may also provide new drug targets. The crystal structure of a complex between plasmepsin, a parasite aspartate protease that initiates the digestion of hemoglobin, and an inhibitor has also been revealed. The crystal structure of lactate dehydrogenase (LDH) from Plasmodium falciparum has also been determined finding a big difference around the active site of the malarial enzyme and mammalian LDH. Parasite enzymes are being researched by other scientists elsewhere. At the University of Montpellier, France, the work on the parasite's choline carrier is more advanced. One of three compounds that kill parasites will be chosen for clinical studies.
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PMID:Beating the malaria parasite at its own game. 928 Aug 13

The correlation of P. falciparum lactate dehydrogenase (pLDH) activities and patent infections was evaluated for monitoring therapeutic responses and drug resistance in 70 patients with microscopically confirmed P. falciparum malaria in Nigeria. Each patient was treated with standard dosages of artemether (53 patients), chloroquine (7 patients), sulfadoxine-pyrimethamine (6 patients), or halofantrine (4 patients). Response of infection to treatment was monitored by microscopic examination of thick and thin blood smears, clinical symptoms, and levels of pLDH activities in blood products. pLDH activity was determined using an antibody capture technique and 3-acetyl pyridine adenine dinucleotide developed to enhance sensitivity of the enzyme detection. All patients treated with artemether were cured while 5 patients treated with chloroquine, 1 treated with sulfadoxine-pyrimethamine, and 2 treated with halofantrine suffered recrudescent infections after treatment. pLDH activity was detected in blood products obtained from patients with patent or recrudescent infections determined by microscopy and clinical symptoms. Levels of pLDH activities in whole blood and packed cells from the patients correlated with qualitative detection of parasites in blood smears and in patients with high gametocyte counts. Gametocyte counts in the patients after treatment ranged from 40 gametocytes/microliter of blood to 4923 gametocytes/microliter of blood. There is a consistent relationship between patent infection and pLDH activities that could easily be determined in whole blood and packed cells from the patients. Further development of the procedure will enhance its valuable application in clinical management of drug-resistant malaria in the endemic areas.
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PMID:Plasmodium falciparum: evaluation of lactate dehydrogenase in monitoring therapeutic responses to standard antimalarial drugs in Nigeria. 937 Oct 95

The development of rapid and specific diagnostic tests to identify individuals infected with malaria is of paramount importance in efforts to control the severe public health impact of this disease. This study evaluated the ability of a newly developed rapid malaria diagnostic test, OptiMAL (Flow Inc., Portland, Oreg.), to detect Plasmodium vivax and Plasmodium falciparum malaria during an outbreak in Honduras. OptiMAL is a rapid (10-min) malaria detection test which utilizes a dipstick coated with monoclonal antibodies against the intracellular metabolic enzyme parasite lactate dehydrogenase (pLDH). Differentiation of malaria parasites is based on antigenic differences between the pLDH isoforms. Since pLDH is produced only by live Plasmodium parasites, this test has the ability to differentiate live from dead organisms. Results from the OptiMAL test were compared to those obtained by reading 100 fields of traditional Giemsa-stained thick-smear blood films. Whole-blood samples were obtained from 202 patients suspected of having malaria. A total of 96 samples (48%) were positive by blood films, while 91 (45%) were positive by the OptiMAL test. The blood films indicated that 82% (79 of 96) of the patients were positive for P. vivax and 18% (17 of 96) were infected with P. falciparum. The OptiMAL test showed that 81% (74 of 91) were positive for P. vivax and 19% (17 of 91) were positive for P. falciparum. These results demonstrated that the OptiMAL test had sensitivities of 94 and 88% and specificities of 100 and 99%, respectively, when compared to traditional blood films for the detection of P. vivax and P. falciparum malaria. Blood samples not identified by OptiMAL as malaria positive normally contained parasites at concentrations of less than 100/microl of blood. Samples found to contain P. falciparum were further tested by two other commercially available rapid malaria diagnostic tests, ParaSight-F (Becton Dickinson, Cockeysville, Md.) and ICT Malaria P.f. (ICT Diagnostics, Sydney, Australia), both of which detect only P. falciparum. Only 11 of the 17 (65%) P. falciparum-positive blood samples were identified by the ICT and ParaSight-F tests. Thus, OptiMAL correctly identified P. falciparum malaria parasites in patient blood samples more often than did the other two commercially available diagnostic tests and showed an excellent correlation with traditional blood films in the identification of both P. vivax malaria and P. falciparum malaria. We conclude that the OptiMAL test is an effective tool for the rapid diagnosis of malaria.
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PMID:Evaluation of the OptiMAL test for rapid diagnosis of Plasmodium vivax and Plasmodium falciparum malaria. 943 47

A Plasmodium lactate dehydrogenase dipstick designed to separately detect P. falciparum and P. vivax malaria was evaluated in two Honduran populations where both species are endemic. The dipstick was compared to thick film microscopy; the polymerase chain reaction (PCR) was used to analyze discordant results. The dipstick had a sensitivity of 100% and a specificity of 95% compared with microscopy in the diagnosis of Plasmodium infections in a hospital population; the mean parasite density was approximately 590/mm3. In a field sample of mostly asymptomatic volunteers, the sensitivity of the dipstick for Plasmodium infection varied with parasite density. Additionally, the sensitivity and specificity of the dipstick was similar to thick film microscopy in the diagnosis of vivax malaria compared with the PCR. The dipstick was unable to detect P. vivax in the presence of P. falciparum because of cross-reactivity in the pan-specific band. Accurate species identification in mixed infections remains a problem in malaria diagnosis.
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PMID:Malaria diagnosis by dipstick assay in a Honduran population with coendemic Plasmodium falciparum and Plasmodium vivax. 988 91


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