Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The usefulness of malaria diagnosis by Plasmodium falciparum GDH (NADP+), obtained by affinity chromatography, is demonstrated in ELISA assays, testing IgG antibodies against GDH (NADP+) from patients with acute malaria, who have had two or more episodes of malaria, or from sera of hyperimmune patients. GDH (NADP+) thermal stability was demonstrated in a high heat resistance assay. The immunofluorescence assay demonstrated that anti-culture (P. falciparum) supernatant serum and anti-GDH (NADP+) of Proteus spp. recognized epitopes in Venezuelan isolates, and Colombian and Brasilian malarial strains. The antigen is soluble, with high specificity, is a potent immunogen and is thermoresistant.
 ...
PMID:Glutamate dehydrogenase antigen detection in Plasmodium falciparum infections. 901 9

The major aim of this study was to characterize a soluble Plasmodium falciparum antigen from the plasma of malaria-infected humans and Plasmodium falciparum culture supernatants, using immunoabsorbent techniques and Western blotting. An Mr 60-kDa protein was isolated from the plasma of patients with Plasmodium falciparum malaria by affinity chromatography using rabbit anti-Proteus spp GDH(NADP+) serum as ligand. This protein, present in plasma of patients with acute Plasmodium falciparum infection, in Plasmodium falciparum culture supernatants, and in immune complexes, was tested with Plasmodium falciparum malaria hyperimmune serum from patients living in hyperendemic areas and rabbit anti-Proteus spp GDH(NADP+) serum prepared in the laboratory. In this report, we describe the results of a study showing that parasite GDH(NADP+) can be used to detect the presence of Plasmodium falciparum. It appears that this technique permits the chromatographic detection of a Plasmodium falciparum excretion antigen that may be used in the production of monoclonal antibodies to improve immunodiagnostic assays for the detection of antigenemia, and opens the possibility of its use as a non-microscopic screening method.
 ...
PMID:Characterization of Plasmodium falciparum glutamate dehydrogenase-soluble antigen. 987 82

We describe the separation of an active glutamate dehydrogenase [GDH (NADP+)] enzyme from the plasma of patients with P. falciparum infection using columns of sepharose anti-GDH (NADP+) of Proteus spp. The activity of this enzyme was also detected in P. falciparum culture supernatant. The parasitic origin of this enzyme was suggested by western blot analysis using anti-P. falciparum culture supernatant and anti-whole parasite antibodies. The differential inhibition of the P. falciparum GDH (NADP+) indicates that some epitopes recognised by the antibodies in both preparations may be different. The determination of P. falciparum GDH (NADP+) activity could be developed into a specific technique for the diagnosis of falciparum malaria.
 ...
PMID:Detection of glutamate dehydrogenase enzyme activity in Plasmodium falciparum infection. 1040 63

With the rapid spread of drug-resistant strains of Plasmodium falciparum, the development of new antimalarials is an urgent need. As malaria parasites live in a highly pro-oxidant environment, their anti-oxidant defences have frequently been suggested as candidate drug targets. A key point in such defences is the production of NADPH e.g. for maintaining anti-oxidant glutathione in the reduced state. Some authors have attributed this function in P. falciparum to a glutamate dehydrogenase, therefore proposed as a potential drug target. Here we show that isophthalic acid inhibits both Plasmodium GDH and bovine GDH but showing marked discrimination (70-fold lower K(i) for the parasite GDH). Isophthalic acid impairs intra-erythrocytic growth of P. falciparumin vitro whilst o-phthalic acid, not a GDH inhibitor, shows no effect. This offers hope that with careful design or thorough screening it should be possible to find inhibitors with the necessary selectivity between parasite and human GDHs.
 ...
PMID:Susceptibility of Plasmodium falciparum to glutamate dehydrogenase inhibitors--a possible new antimalarial target. 2039 10

Accurate and timely diagnosis is very critical for management, control and elimination of the malaria. Malaria rapid diagnostic tests (RDTs) have improved the diagnosis and management of malaria in remote areas, community and places where microscopy is not available for diagnosis. According to WHO report 2018, Plasmodium falciparum malaria constitutes more than 50% of malaria cases in India. Most of the RDTs used for diagnosis of falciparum malaria today employ HRP2 as a target antigen. However, low density parasitemia and deletion of hrp-2 gene in P. falciparum leads to false negative results and necessitates the development of alternative/ new or improved RDT for malaria diagnosis. We have analysed the genetic diversity and homology modelling of Pfgdh (glutamate dehydrogenase), ldh (lactate dehydrogenase) and aldolase genes in P. falciparum isolates from the eight endemic states of India to assess their potential as antigen for RDT development. We observed negligible sequence diversity in Pfgdh in comparison to the low level of diversity in ldh and aldolase gene. No structural or functional changes were observed in modelling studies and all three genes were under negative purifying selection pressure. The highly conserved nature of pfgdh gene suggests that GDH could be a potential target molecule for Pan/Pf diagnostic test for malaria.
 ...
PMID:Plasmodium falciparum glutamate dehydrogenase is genetically conserved across eight malaria endemic states of India: Exploring new avenues of malaria elimination. 3119 42