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)

We conducted this study to determine efficacy of Parasight-F (an HRP-II antigen dipstick method to detect P. Falciparum) in children. A total of 30 children were enrolled in the age group of 2 months to 12 years whose peripheral smear showed asexual forms of Plasmodium falciparum. All patients were tested for presence of HRP-II antigen of Plasmodium falciparum in their blood by the Parasight-F dipstick test by either an EDTA sample or a finger prick blood sample. The sensitivity of Parasight-F was 83.3 % However, the sensitivity of Parasight-F to detect Plasmodium Falciparum in case of mixed Plasmodium (Vivax + Falciparum) infection was only 25 %. Also, all patients less than 6 months of age had a negative Parasight-F test. Parasitic index, prior treatment with antimalarials or severity of Falciparum malaria have no effect on the sensitivity of Parasight-F test. We conclude that Parasight-F is an effective tool for diagnosis of Plasmoduim falciparum malaria in children.
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PMID:A bedside dipstick method to detect Plasmodium falciparum. 1587 15

The aim of this study was to determine the frequency of G6PD deficiency and assess its impact on morbidity, especially anemia, in preschool-aged children in Cambodia. A total of 151 children including 82 boys and 69 girls from the Kandal province near Phnom Penh were studied. Ages ranged from 8 to 69 months. Blood was collected in EDTA-coated tubes. Blood counts were performed with an ABX Micros 60 system and G6PD in red blood cells was measured with a Roche Cobas Mira Plus system using Gamma reagents. G6PD deficiency was found in 14 cases (13.4% of boys and 4.3% of girls). Deficiency was complete in 7.3% of children and partial in 2%. Anemia defined as hemoglobin concentration less than 110 g/l was detected in 29.1% of children. No case of anemia could be attributed to enzyme deficiency since no sign of hemolysis was observed in any of the three children presenting both conditions. Further study is needed on G6PD deficiency in Cambodia including malaria-endemic areas and on the frequency and severity of jaundice due to enzyme deficiency in newborns.
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PMID:[Frequency of G6PD deficiency in a group of preschool-aged children in a centrally located area of Cambodia]. 1561 86

The human malaria parasite Plasmodium falciparum possesses a single gene with high similarity to the metalloproteins arginase and agmatinase. The recombinant protein reveals strict specificity for arginine, and it has been proposed that its function in ornithine production is as a precursor for polyamine biosynthesis. The specific activity of the plasmodial arginase was found to be 31 micromol min(-1) mg(-1) protein and the k(cat) was calculated as 96 (s-1) . The Km value for arginine and Ki value for ornithine were determined as 13 mM and 19 mM, respectively. The active arginase is a homotrimer of ca. 160 kDa. Dialysis of the arginase against EDTA results in monomers of approximately 48 kDa; however, the quaternary structure can be restored by addition of Mn 2+ . Mutagenic analyses of all the amino acid residues proposed to be involved in metal binding led to complex dissociation, except for the His-193-Ala mutant, which was also inactive but retained the trimeric structure. Substitution of His-233, which has been suggested to be in charge of proton shuttling within the active site, disrupted the trimeric structure and thereby the activity of the Pf arginase. Northern blot analysis identified a stage-specific expression pattern of the plasmodial arginase in the ring/young trophozoite stage, which guarantees the provision of ornithine for essential polyamine biosynthesis.
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PMID:Structural metal dependency of the arginase from the human malaria parasite Plasmodium falciparum. 1584 55

Aspartic proteases of human malarial parasites are thought to play key roles in essential pathways of merozoite release, invasion and host cell hemoglobin degradation during the intraerythrocytic stages of their life cycle. Therefore, we have purified and characterized Plasmodium vivax aspartic protease, to determine if this enzyme can be used as potential drug target/immunogen, and its inhibitors as potential antimalarial drug. The P. vivax aspartic protease has been purified by a combination of ion exchange and size exclusion chromatographies and HPLC. Its properties were examined in order to define a role in the hemoglobin degradation process. The purified enzyme migrated as a single band on native PAGE and SDS/PAGE with a molecular mass of 40 kDa. Gelatin zymogram analyses revealed a clear zone of proteolytic activity corresponding to the band obtained on native PAGE and SDS/PAGE. The enzyme has an optimal pH of 4.0 and exhibits its highest activity at 37 degrees C. The enzyme is inhibited by pepstatin, but not by other inhibitors including o-phenanthroline, EDTA, PMSF or E-64, supporting its designation as an aspartic protease; its IC50 value was found to be 3.0 microM. A Lineweaver Burk double reciprocal plot with pepstatin shows that the inhibition is competitive with respect to the substrate. Ca2+ and Mg2+ ions enhance the protease activity, whereas Cu2+ and Hg2+ ions were found to be inhibitory. The pivotal role of aspartic protease in initiating hemoglobin degradation in P. vivax malaria parasite is also demonstrated.
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PMID:Purification and characterization of a hemoglobin degrading aspartic protease from the malarial parasite Plasmodium vivax. 1604 50

Iron is crucial for many biochemical reactions involved in the growth and multiplication of the malaria parasite Plasmodium falciparum. There are many reports indicating that the iron chelators have antimalarial activity in vitro, in vivo and in human studies. However, these compounds suffer from a number of serious problems such as limited membrane permeability, short half-life and require long subcutaneous infusions. To circumvent these drawbacks we have designed a new class of iron chelators, wherein EDTA is tethered to 4-aminoquinoline. Here 4-aminoquinoline scaffold is used as a carrier to penetrate biological membrane and facilitate targetting the compounds to acidic food vacuole of the parasite. This study describes the synthesis of novel iron chelators and their in vitro antimalarial activity against P. falciparum strain of NF-54. The calculated LogP values of these compounds suggest the importance of lipophilicity for the antimalarial activity. The EDTA esters are more active than the corresponding acids. The biophysical studies suggest that these compounds may inhibit the parasite growth by iron chelation mechanism.
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PMID:Design, synthesis and antimalarial activity of a new class of iron chelators. 1678 62

Cerebral malaria (CM) is a life-threatening disorder and a major medical problem in developing countries. It is caused by the sequestration of malaria-infected erythrocytes onto brain endothelia, followed by blood-brain barrier (BBB) damage and neurological deficit. In the present study, matrix metalloproteinases (MMPs) were analysed in a mouse model of CM with Plasmodium berghei ANKA. Increased numbers of gelatinase B (MMP-9)-positive cells, which were also CD11b(+), were detected in the brain. In addition, activation of gelatinase B occurred in CM brains, and not in brains of mice with non-CM. However, selective genetic knockout of gelatinase B did not alter the clinical evolution of experimental CM. To study other protease balances, the mRNA expression levels of nine matrix metalloproteinases (MMPs), five membrane-type MMPs, TNF-alpha converting enzyme (TACE) and the four tissue inhibitors of metalloproteinases (TIMPs) were analysed during CM in different organs. Significant alterations in expression were observed, including increases of the mRNAs of MMP-3, -8, -13 and -14 in the spleen, MMP-8, -12, -13 and -14 in the liver and MMP-8 and -13 in the brain. Net gelatinolytic activity, independent of gelatinase B and inhibitable with EDTA, was detected in situ in the endothelia of blood vessels in CM brains, but not in brains of mice with non-CM, suggesting that metalloproteases, different from gelatinase B, are active in the BBB environment in CM. The increase in MMP expression in the brain was significantly less pronounced after infection of C57Bl/6 mice with the noncerebral strain P. berghei NK65, but it was similar in CM-susceptible C57Bl/6 and CM-resistant Balb/C mice upon infection with P. berghei ANKA. Furthermore, in comparison with C57Bl/6 mice, a larger increase in TIMP-1 and a marked, >30-fold induction in MMP-3 were found in the brains of Balb/C mice, suggesting possible protective roles for TIMP-1 and MMP-3.
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PMID:Matrix metalloproteinases, tissue inhibitors of MMPs and TACE in experimental cerebral malaria. 1686 90

Artificial membrane feeding (AMF) assays are used to determine malaria transmission-blocking activity in Anopheles. The purpose of this study was to determine the effect of the most widely used anticoagulants, EDTA and heparin, on development of the Plasmodium vivax sporogonic cycle. Blood samples collected from 60 patients carrying P. vivax infections were used to feed An. albimanus using AMF. Seven days after feeding, mosquitoes were dissected to assess mosquito infection. Mosquitoes fed with blood containing EDTA showed a lower mean oocyst number as compared with those fed blood with heparin. However, this effect was minimized upon reduction of EDTA concentrations in the serum. This result may be explained by the fact that microgametocytes require Ca(2+), Mn(2+), and Mg(+2) to activate enzymes important for exflagellation process and for motility of ookinetes. We therefore recommend that heparin be used as the anticoagulant of choice for blood used in AMF assays.
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PMID:Effects of anticoagulants on Plasmodium vivax oocyst development in Anopheles albimanus mosquitoes. 1769 Mar 93

Malaria in pregnancy jeopardizes the outcome of pregnancy, affecting both the mother and the foetus. The prevalence of placental malaria in women, who routinely attended ante-natal clinics in Owerri, south-eastern Nigeria, was assessed using three hospitals between March 2004 and August 2005. Placental blood was collected in EDTA bottles from incisions made on cleaned basal plate of the placenta, within an hour of delivery. Blood collected was used to assess ABO blood group, haemoglobin level as well as malaria parasitaemia. Malaria parasitaemia was determined from thick and thin smears stained with Giemsa, while the haemoglobin level was measured using the cyanomethaemoglobin method. A total of 586 pregnant women were involved in this study with written consents. Malaria parasites were observed in 175 (29.9%) of the women on delivery. Of these women, 64 (36.6%) were anaemic. A significant relationship at P<0.05 variation, was observed between the prevalence of malaria parasites in the placenta and gravidity, age and blood group. The rate of occurrence of malaria parasitaemia, in the placenta of women who were on a weekly prophylaxis against malaria is alarming and calls for more serious efforts in the prevention of malaria especially in this vulnerable group.
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PMID:Placental malaria in Owerri, Imo State, south-eastern Nigeria. 1808 96

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate and plays an important role in nucleotide metabolism and DNA replication controlling relative cellular levels of dTTP/dUTP, both of which can be incorporated into DNA. Isothermal titration calorimetry has been applied to the determination of the kinetic and thermodynamic parameters of the trimeric Plasmodium falciparum dUTPase, a potential drug target against malaria. The role of divalent ions in binding, and inhibition by different uridine derivatives has been assessed. When dUTP hydrolysis in the presence of EDTA was evaluated, a 105-fold decrease and a 12-fold increase of the k(cat) and Km values, respectively, were observed when compared with the dUTP.Mg2+ complex. Calculation of the activation energy, E(a), and the thermodynamic activation parameters showed that the energetic barrier was approximately 4-fold higher when Mg2+ was depleted. Other divalent ions such as Co2+ or Mn2+ can substitute the physiological cofactor, however the k(cat) was significantly reduced compared to dUTP.Mg2+. Binding and inhibition by dU, dUMP, dUDP, and alpha,beta-imido-dUTP were analysed by ITC and compared with data obtained by spectrophotometric methods and binding equilibrium studies. Product inhibition (Kip dUMP: 99.34 microM) was insignificant yet Ki values for dUDP and alpha,beta-imido-dUTP were in the low micromolar range. The effect of ionic strength on protein stability was also monitored. DSC analysis evidenced a slight increase in the unfolding temperature, Tm, with increasing salt concentrations. Moreover, the thermal unfolding pathway in the presence of salt fits adequately to an irreversible two-state model (N3-->3D).
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PMID:Kinetic and thermodynamic characterization of dUTP hydrolysis by Plasmodium falciparum dUTPase. 1858 21

Rapid determination of glucose-6-phosphate dehydrogenase (G6PD) status is desirable when it is necessary to use a drug contraindicated in G6PD-deficient persons, such as use of primaquine for malaria prevention or treatment. The purpose of this study was to compare a new, rapid, qualitative enzyme chromatographic test for deficiency of G6PD to a standard reference method. Samples from 196 G6PD-normal persons and 50 G6PD-deficient persons were evaluated. The sensitivity of the experimental rapid test was 0.98 and the specificity was 0.98 using specimens preserved in heparin, and 0.98 and 0.97, respectively, for specimens preserved in EDTA. Positive and negative predictive values were 0.72 and 1.00, respectively, for the test for heparinized specimens and 0.65 and 1.00, respectively, for the EDTA-preserved samples. This rapid test for G6PD deficiency is a sensitive method for screening of G6PD deficiency that requires minimal training and equipment and enables rapid identification of G6PD-deficient persons.
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PMID:Evaluation of a rapid qualitative enzyme chromatographic test for glucose-6-phosphate dehydrogenase deficiency. 2013 93


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