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)

Insects of the order Diptera are vectors for parasitic diseases such as malaria, sleeping sickness and leishmania. In the search for genes encoding proteins involved in the antiparasitic response, we have used the protozoan parasite Octosporea muscaedomesticae for oral infections of adult Drosophila melanogaster. To identify parasite-specific response molecules, other flies were exposed to virus, bacteria or fungi in parallel. Analysis of gene expression patterns after 24 h of microbial challenge, using Affymetrix oligonucleotide microarrays, revealed a high degree of microbe specificity. Many serine proteases, key intermediates in the induction of insect immune responses, were uniquely expressed following infection of the different organisms. Several lysozyme genes were induced in response to Octosporea infection, while in other treatments they were not induced or downregulated. This suggests that lysozymes are important in antiparasitic defence.
 ...
PMID:Parasite-specific immune response in adult Drosophila melanogaster: a genomic study. 1474 22

Infectious diseases are responsible for >25% of the global disease toll. The new Disease Control Priorities in Developing Countries Project (DCPP) aims to decrease the burden of these diseases by producing science-based analyses from demographic, epidemiologic, disease intervention, and economic evidence for the purpose of defining disease priorities and implementing control measures. The DCPP recently reviewed selected tropical infectious diseases, examined successful control experiences, and defined unsettled patient treatment, prevention, and research issues. Disease elimination programs against American trypanosomiasis (Chagas disease), onchocerciasis, lymphatic filariasis, leprosy, trachoma, and measles are succeeding. Dengue, leishmaniasis, African trypanosomiasis, malaria, diarrheal diseases, helminthic infections, and tuberculosis have reemerged because of inadequate interventions and control strategies and the breakdown of health delivery systems. Application of technologies must be cost-effective and intensified research is essential if these and other scourges are to be controlled or eliminated in the 21st century.
 ...
PMID:Combating tropical infectious diseases: report of the Disease Control Priorities in Developing Countries Project. 1499 34

Infections by parasitic protozoans and helminths are a major world-wide health concern, but no vaccines exist to the major human parasitic diseases, such as malaria, African trypanosomiasis, amebiasis, leishmaniasis, schistosomiasis, and lymphatic filariasis. Recent studies on a number of parasites indicate that immune responses to parasites in infected animals and humans are directed to glycan determinants within cell surface and secreted glycoconjugates and that glycoconjugates are important in host-parasite interactions. Because of the tremendous success achieved recently in generating carbohydrate-protein conjugate vaccines toward microbial infections, such as Haemophilus influenzae type b, there is renewed interest in defining parasite-derived glycans in the prospect of developing conjugate vaccines and new diagnostics for parasitic infections. Parasite-derived glycans are compelling vaccine targets because they have structural features that distinguish them from mammalian glycans. There have been exciting new developments in techniques for glycan analysis and the methods for synthesizing oligosaccharides by chemical or combined chemo-enzymatic approaches that now make it feasible to generate parasite glycans to test as vaccine candidates. Here, we highlight recent progress made in elucidating the immunogenicity of glycans from some of the major human and animal parasites, the potential for developing conjugate vaccines for parasitic infections, and the possible utilization of these novel glycans in diagnostics.
 ...
PMID:Antigenic glycans in parasitic infections: implications for vaccines and diagnostics. 1515 69

Three new naphthylisoquinoline alkaloids, the 7,3'-coupled ancistrotanzanine C (6), the 5,1'-coupled O-methylancistrocladinine (7), and the likewise 5,1'-coupled O,N-dimethylancistrocladine (8, previously known only as a partial-synthetic compound), have been isolated from the highland liana Ancistrocladus tanzaniensis, along with the two known 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (4) and ancistrotectorine (5). All of the compounds are S-configured at C-3 and bear an oxygen at C-6, and thus belong to the so-called Ancistrocladaceae type, similar to 1-3 previously isolated from this newly discovered plant species. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. The biological activities of the alkaloids against the pathogens causing malaria tropica, leishmaniasis, Chagas' disease, and African sleeping sickness were evaluated.
 ...
PMID:Ancistrotanzanine C and related 5,1'- and 7,3'-coupled naphthylisoquinoline alkaloids from Ancistrocladus tanzaniensis. 1516 31

Brothers 9 and 14 years of age presented in London with fever and skin lesions after a safari in East Africa. Malaria films were negative, but trypanosomes were seen in blood films and chancre fluid. Sleeping sickness should be considered in children returning from East Africa.
 ...
PMID:Sleeping sickness in brothers in london. 1536 33

The aromatic diamidines represent a class of compounds with broad-spectrum antimicrobial activity; however, their development is hindered by a lack of understanding of their mechanism of antimicrobial action. DB75 [2,5-bis(4-amidinophenyl)furan] is a trypanocidal aromatic diamidine that was originally developed as a structural analogue of the antitrypanosomal agent pentamidine. DB289, a novel orally active prodrug of DB75, is undergoing phase IIb clinical trials for early-stage human African trypanosomiasis, Pneumocystis jiroveci carinii pneumonia, and malaria. The purpose of this study was to investigate mechanisms of action of DB75 using Saccharomyces cerevisiae as a model organism. The results of this investigation suggest that DB75 inhibits mitochondrial function. Yeast cells relying upon mitochondrial metabolism for energy production are especially sensitive to DB75. DB75 localizes (by fluorescence) within the mitochondria of living yeast cells and collapses the mitochondrial membrane potential in isolated yeast mitochondria. Furthermore, addition of DB75 to yeast cells or isolated rat liver mitochondria results in immediate uncoupling of oxidative phosphorylation and subsequent inhibition of respiration. We conclude that the mitochondrion is a cellular target of DB75 in yeast cells and anticipate that the results of this study will aid in the target-based design of new antimicrobial aromatic diamidines.
 ...
PMID:DB75, a novel trypanocidal agent, disrupts mitochondrial function in Saccharomyces cerevisiae. 1538 60

A new axially chiral naphthylisoquinoline alkaloid, ancistroheynine B (7), has been isolated from the leaves of the Indian liana Ancistrocladus heyneanus Wall., along with two known related alkaloids, ancistrocladidine (3) and ancistrotanzanine C (6), which are 7,3'-coupled, too. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. Biological activities of ancistroheynine B against the pathogens of malaria, leishmaniasis, Chagas' disease, and African sleeping sickness were evaluated.
 ...
PMID:Ancistroheynine B and two further 7,3'-coupled naphthylisoquinoline alkaloids from Ancistrocladus heyneanus Wall. 1550 Dec 59

Herein we report the synthesis and evaluation of a series of thiosemicarbazones as potential inhibitors of cysteine proteases relevant to parasitic diseases. Derivatives of thiosemicarbazone 1 were discovered to be potent inhibitors of cruzain and rhodesain, crucial proteases in the life cycles of Trypanosoma cruzi and T. brucei rhodesiense, the organisms causing Chagas' disease and sleeping sickness. However, the entire series had only modest potency against falcipain-2, an essential protease for Plasmodium falciparum, the organism causing malaria. Among the active inhibitors, several potently inhibited proliferation of cultures of T. brucei. However, only modest activity was observed in inhibition of proliferation of T. cruzi or P. falciparum.
 ...
PMID:Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain. 1558 23

Parasitic diseases such as sleeping sickness, Chagas' heart disease, and malaria are major health problems in poverty-stricken areas. Antiparasitic drugs that are not only active but also affordable and readily available are urgently required. One approach to finding new drugs and rediscovering old ones is based on enzyme inhibitors that paralyze antioxidant systems in the pathogens. These antioxidant ensembles are essential to the parasites as they are attacked in the human host by strong oxidants such as peroxynitrite, hypochlorite, and H2O2. The pathogen-protecting system consists of some 20 thiol and dithiol proteins, which buffer the intraparasitic redox milieu at a potential of -250 mV. In trypanosomes and leishmania the network is centered around the unique dithiol trypanothione (N1,N8-bis(glutathionyl)spermidine). In contrast, malaria parasites have a more conservative dual antioxidative system based on glutathione and thioredoxin. Inhibitors of antioxidant enzymes such as trypanothione reductase are, indeed, parasiticidal but they can also delay or prevent resistance against a number of other antiparasitic drugs.
 ...
PMID:Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. 1565 67

HIV and tropical infections affect each other mutually. HIV infection may alter the natural history of tropical infectious diseases, impede rapid diagnosis, or reduce the efficacy of antiparasitic treatment. Tropical infections may facilitate the transmission of HIV and accelerate progression from asymptomatic HIV infection to AIDS. This article reviews data on known interactions for malaria, leishmaniasis, human African trypanosomiasis, Chagas' disease, schistosomiasis, onchocerciasis, lymphatic filariasis, and intestinal helminthiases.
 ...
PMID:The impact of HIV infection on tropical diseases. 1570 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>