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hypericum lanceolatum (hypericaceae) as a potential source of new anti-malarial agents: a bioassay-guided fractionation of the stem bark.malaria is a major public health threat in africa, and traditional medicine continues to play a key role in its control especially in rural areas. a bioassay-guided fractionation was carried out in order to evaluate the anti-malarial potential and the safety of the methanol extract of the hypericum lanceolatum stem bark.201121682873
[tgrom4 and tgama1: a checkpoint in parasite replication]. 201121718637
identification of a highly antigenic linear b cell epitope within plasmodium vivax apical membrane antigen 1 (ama-1).apical membrane antigen 1 (ama-1) is considered to be a major candidate antigen for a malaria vaccine. previous immunoepidemiological studies of naturally acquired immunity to plasmodium vivax ama-1 (pvama-1) have shown a higher prevalence of specific antibodies to domain ii (dii) of ama-1. in the present study, we confirmed that specific antibody responses from naturally infected individuals were highly reactive to both full-length ama-1 and dii. also, we demonstrated a strong association betwe ...201121713006
polymorphic variability in the 3' untranslated region (utr) of il12b is associated with susceptibility to severe anaemia in kenyan children with acute plasmodium falciparum malaria.abstract:201121819616
duffy negative antigen is no longer a barrier to plasmodium vivax--molecular evidences from the african west coast (angola and equatorial guinea).plasmodium vivax shows a small prevalence in west and central africa due to the high prevalence of duffy negative people. however, duffy negative individuals infected with p. vivax have been reported in areas of high prevalence of duffy positive people who may serve as supply of p. vivax strains able to invade duffy negative erythrocytes. we investigated the presence of p. vivax in two west african countries, using blood samples and mosquitoes collected during two on-going studies.201121713024
plasmodium falciparum and helminth coinfections among schoolchildren in relation to agro-ecosystems in mvomero district, tanzania.in sub-saharan africa, some individuals infected with malaria are also infected with helminths. however, the magnitude and distribution of such coinfections in relation to eco-systems remains poorly defined. this study was undertaken to determine the prevalence of plasmodium falciparum and helminth coinfections among schoolchildren in relation to agro-ecosystems in mvomero district, tanzania.201121741929
antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in plasmodium berghei-infected mice.artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (acts). however, acts are expensive and some of the non-artemisinin components are not well-tolerated by patients. there are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. mature leaves of carica papaya is widely used to treat malaria in several african countries. an act involving a medicin ...201121715732
anti-inflammatory cytokines predominate in acute human plasmodium knowlesi infections.plasmodium knowlesi has entered the human population of southeast asia. naturally acquired knowlesi malaria is newly described with relatively little available data, including data on the host response to infection. therefore pre-treatment cytokine and chemokine profiles were determined for 94 p. knowlesi, and for comparison, 20, p. vivax and 22 p. falciparum, patients recruited in malaysian borneo. nine, five and one patient with p. knowlesi, p. falciparum and p. vivax respectively had complica ...201121687657
volutin granules of eimeria parasites are acidic compartments and have physiological and structural characteristics similar to acidocalcisomes.the structural organization of parasites has been the subject of investigation by many groups and has lead to the identification of structures and metabolic pathways that may represent targets for anti-parasitic drugs. a specific group of organelles named acidocalcisomes has been identified in a number of organisms, including the apicomplexan parasites such as toxoplasma and plasmodium, where they have been shown to be involved in cation homeostasis, polyphosphate metabolism, and osmoregulation. ...201121699625
chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.malaria remains a devastating disease largely because of widespread drug resistance. new drugs and a better understanding of the mechanisms of drug action and resistance are essential for fulfilling the promise of eradicating malaria. using high-throughput chemical screening and genome-wide association analysis, we identified 32 highly active compounds and genetic loci associated with differential chemical phenotypes (dcps), defined as greater than or equal to fivefold differences in half-maximu ...201121817045
effectiveness of acts in cases of resistance to partner drugs. 201121700240
a systematic analysis of the early transcribed membrane protein family throughout the life cycle of plasmodium yoelii.the early transcribed membrane proteins (etramps) are a family of small, highly charged transmembrane proteins unique to malaria parasites. some members of the etramp family have been localized to the parasitophorous vacuole membrane that separates the intracellular parasite from the host cell and thus presumably have a role in host-parasite interactions. although it was previously shown that two etramps are critical for rodent malaria parasite liver-stage development, the importance of most etr ...201121819513
toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent il-1╬▓ secretion enhances parasite replication.abstract: alternatively activated macrophages (aam) are a key feature th2 immunity and have been associated with a variety of roles during helminth infection. the role this cell subset plays in protzoan infection remain relatively unexplored, herein we describe the effects of a redox enzyme (rtgprx) derived from toxoplasma gondii on murine macrophage phenotype in vitro. rtgprx has been previously associated with the maintainence of parasite oxidative balance. here our experiments show that rtgpr ...201121707997
functional haplotypes of fc gamma (fc+¦) receptor (fc+¦riia and fc+¦riiib) predict risk to repeated episodes of severe malarial anemia and mortality in kenyan children.development of protective immunity against plasmodium falciparum is partially mediated through binding of malaria-specific igg to fc gamma (+¦) receptors. variations in human fc+¦riia-h/r-131 and fc+¦riiib-na1/na2 affect differential binding of igg sub-classes. since variability in fc+¦r may play an important role in severe malarial anemia (sma) pathogenesis by mediating phagocytosis of red blood cells and triggering cytokine production, the relationship between fc+¦riia-h/r131 and fc+¦riiib-na1 ...201121818580
gestational malaria associated to plasmodium vivax and plasmodium falciparum placental mixed-infection followed by foetal loss: a case report from an unstable transmission area in brazil.gestational malaria is a multi-factorial syndrome leading to poor outcomes for both the mother and foetus. although an unusual increasing in the number of hospitalizations caused by plasmodium vivax has been reported in brazil, mortality is rarely observed. this is a report of a gestational malaria case that occurred in the city of manaus (amazonas state, brazil) and resulted in foetal loss. the patient presented placental mixed-infection by plasmodium vivax and plasmodium falciparum after diagn ...201121708032
binding of +¦,+¦-disubstituted amino acids to arginase suggests new avenues for inhibitor design.arginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine to form l-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. accordingly, arginase inhibitors may be therapeutically useful. continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-l-ornithine to human arginase i, we now report the first s ...201121728378
linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in plasmodium yoelii.plasmodium yoelii is an excellent model for studying malaria pathogenesis that is often intractable to investigate using human parasites; however, genetic studies of the parasite have been hindered by lack of genome-wide linkage resources. here, we performed 14 genetic crosses between three pairs of p. yoelii clones/subspecies, isolated 75 independent recombinant progeny from the crosses, and constructed a high-resolution linkage map for this parasite. microsatellite genotypes from the progeny f ...201121690382
in vitro activity of antifungal drugs against plasmodium falciparum field isolates.the increasing resistance of the malaria parasite plasmodium falciparum to currently available drugs necessitates a continuous effort to develop new antimalarial agents. we therefore aimed to assess the in vitro activity of the antifungal drugs clotrimazole, fluconazole, ketoconazole, itraconazole, voriconazole, flucytosine, amphotericin b, and caspofungin against field isolates of p. falciparum from lambar+®n+®, gabon. using the histidin-rich protein 2 (hrp-2) assay we determined the drug susce ...201121739204
support vector machine based prediction of p. falciparum proteasome inhibitors and development of focused library by molecular docking.the emergence and spread of plasmodium falciparum resistance to existing antimalarials emphasize the impelling search for novel drug targets and chemotherapeutic compounds. the ubiquitin-proteasome system plays a major role in overall protein turnover, in eukaryotic cells including plasmodia. 20s +¦ subunit is the catalytic core of this proteolytic machinery, and hence most of the inhibitors developed are being targeted towards this component. inhibition of the proteasome is established as a pro ...201121843142
synthesis and antimalarial evaluation of novel benzopyrano[4,3-b]benzopyran derivatives.7-methoxyflavenes and 5,7,8-trimethoxyflavenes were found to undergo stereoselective acid-catalyzed rearrangement to generate the benzopyrano[4,3-b]benzopyran ring system present in the natural product, dependensin. dependensin and its analogs were subjected to antimalarial growth inhibition assays against plasmodium falciparum and found to have ic(50) values ranging between 1.9 and 3.9++m.201121824783
endectocides for malaria control.systemic endectocidal drugs, used to control nematodes in humans and other vertebrates, can be toxic to anopheles spp. mosquitoes when they take a blood meal from a host that has recently received one of these drugs. recent laboratory and field studies have highlighted the potential of ivermectin to control malaria parasite transmission if this drug is distributed strategically and more often. there are important theoretical benefits to this strategy, as well as caveats. a better understanding o ...201121727027
apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in toxoplasma gondii.apicomplexa are important pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. apicomplexan parasites contain a relict chloroplast, the apicoplast. the apicoplast is indispensable and an attractive drug target. the apicoplast is home to a 1-deoxy-d-xylulose-5-phosphate (doxp) pathway for the synthesis of isoprenoid precursors. this pathway is believed to be the most conserved function of the apicoplast, and fosmidomycin, a specific inhibitor of the pathwa ...201121690250
phylogenomic analyses of malaria parasites and evolution of their exported proteins.abstract:201121676252
plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa.glucose is the primary source of energy and a key substrate for most cells. inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. for malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. plasmodium falciparum is the most d ...201121676209
prevalence of avian haematozoa in wild birds in a high-altitude forest in japan.the infection dynamics of avian haematozoa, which includes the genera plasmodium, haemoproteus, and leucocytozoon, are complicated by a variety of environmental factors and host-parasite interactions. in japan, the prevalence of haematozoa in wild birds has recently been determined in several local areas. however, no information on the annual prevalence of avian haematozoa in a single study site has been reported. here, we investigated the long-term infection dynamics of haematozoa in wild birds ...201121831523
pg12, a phospholipid analog with potent antimalarial activity, inhibits plasmodium falciparum ctp:phosphocholine cytidylyltransferase activity.in the human malaria parasite plasmodium falciparum, the synthesis of the major and essential membrane phospholipid, phosphatidylcholine, occurs via the cdp-choline and the serine decarboxylase phosphoethanolamine methylation (sdpm) pathways, which are fueled by host choline, serine, and fatty acids. both pathways share the final two steps catalyzed by two essential enzymes, p. falciparum ctp:phosphocholine cytidylyltransferase (pfcct) and choline-phosphate transferase (pfcept). we identified a ...201121705805
anaesthetic management of caesarean delivery in a parturient with malaria.malaria is a life-threatening illness with significant maternal and infant morbidity and mortality worldwide. due to the rarity of its diagnosis in the uk population, there is little information about the number of pregnant women affected by malaria. this report describes a primiparous woman requiring a category-1 emergency caesarean section for severe sepsis, in whom the cause of sepsis was found to be plasmodium vivax malaria. a brief overview of malaria in pregnancy as relevant to this case a ...201121840208
prevalence and risk factors of plasmodium falciparum infections in pregnant women of luanda, angola.pregnant women are at increased risk of malaria, but in angola, epidemiologic data from this group is almost inexistent. we conducted a cross-sectional study to determine the prevalence and risk factors of plasmodium falciparum infections in 567 pregnant angolan women living in luanda province. one in five women had p.-áfalciparum at delivery, diagnosed by pcr assay. age, residence and history of malaria during pregnancy were significantly associated with p.-áfalciparum infection, but gravidity ...201121729222
rapid diagnostic tests for diagnosing uncomplicated p. falciparum malaria in endemic countries.rapid diagnostic tests (rdts) for plasmodium falciparum malaria use antibodies to detect either hrp-2 antigen or pldh antigen, and can improve access to diagnostics in developing countries.201121735422
protein arginine methylation in parasitic protozoa.protozoa constitute the earliest branch of the eukaryotic lineage, and several groups of protozoans are serious parasites of humans and other animals. better understanding of biochemical pathways that are either in common with or divergent from those of higher eukaryotes is integral in the defense against these parasites. in yeast and humans, the posttranslational methylation of arginine residues in proteins affects myriad cellular processes, including transcription, rna processing, dna replicat ...201121685318
transgene optimization, immunogenicity and in vitro efficacy of viral vectored vaccines expressing two alleles of plasmodium falciparum ama1.apical membrane antigen 1 (ama1) is a leading candidate vaccine antigen against blood-stage malaria, although to date numerous clinical trials using mainly protein-in-adjuvant vaccines have shown limited success. here we describe the pre-clinical development and optimization of recombinant human and simian adenoviral (adhu5 and chad63) and orthopoxviral (mva) vectors encoding transgene inserts for plasmodium falciparum ama1 (pfama1).201121698193
toward a surrogate marker of malaria exposure: modeling longitudinal antibody measurements under outbreak conditions.biomarkers of exposure to plasmodium falciparum would be a useful tool for the assessment of malaria burden and analysis of intervention and epidemiological studies. antibodies to pre-erythrocytic antigens represent potential surrogates of exposure.201121818270
plasmodium falciparum serine repeat antigen 5 (se36) as a malaria vaccine candidate.a devastating disease spread by mosquitoes with high-efficiency, malaria imposes an enormous burden for which no licensed vaccine currently exists. although the genome complexity of the parasite has made vaccine development tenuous, an effective malaria vaccine would be a valuable tool for control, elimination and eventual eradication. the plasmodium serine repeat antigen 5 (sera5) is an abundant asexual blood stage antigen that does not show any antigenic variation and exhibits limited polymorp ...201121718740
caspase-1 activation of interleukin-1{beta} (il-1{beta}) and il-18 is dispensable for induction of experimental cerebral malaria.malaria infection is initiated by sporozoite invasion of hepatocytes and asexual reproduction of liver stages, processes that are regarded to be "clinically and diagnostically silent." merozoites, which egress from hepatocytes, infect erythrocytes in periodic cycles and induce disease. how the host innate immune system contributes to disease outcomes and to the induction of effector cells during malaria remains unclear. likewise, how the initial liver stages may shape responses to blood-stage pa ...201121708993
hippoboscid-transmitted haemoproteus parasites (haemosporida) infect galapagos pelecaniform birds: evidence from molecular and morphological studies, with a description of haemoproteus iwa.haemosporidian parasites are widely distributed and common parasites of birds, and the application of molecular techniques has revealed remarkable diversity among their lineages. four haemosporidian genera infect avian hosts (plasmodium, haemoproteus, leucocytozoon and fallisia), and haemoproteus is split into two sub-genera based on morphological evidence and phylogenetic support for two divergent sister clades. one clade (haemoproteus (parahaemoproteus)) contains parasites developing in birds ...201121683082
linear amplification for deep sequencing.linear amplification for deep sequencing (lads) is an amplification method that produces representative libraries for illumina next-generation sequencing within 2 d. the method relies on attaching two different sequencing adapters to blunt-end repaired and a-tailed dna fragments, wherein one of the adapters is extended with the sequence for the t7 rna polymerase promoter. ligated and size-selected dna fragments are transcribed in vitro with high rna yields. subsequent cdna synthesis is initiated ...201121720315
proteases as regulators of pathogenesis: examples from the apicomplexa.the diverse functional roles that proteases play in basic biological processes make them essential for virtually all organisms. not surprisingly, proteolysis is also a critical process required for many aspects of pathogenesis. in particular, obligate intracellular parasites must precisely coordinate proteolytic events during their highly regulated life cycle inside multiple host cell environments. advances in chemical, proteomic and genetic tools that can be applied to parasite biology have led ...201121683169
plasmodium falciparum uses a key functional site in complement receptor type-1 for invasion of human erythrocytes.the plasmodium falciparum adhesin pfrh4 binds to complement receptor type-1 (cr1) on human erythrocytes and mediates a glycophorin-independent invasion pathway. cr1 is a complement regulator and immune-adherence receptor on erythrocytes required for shuttling of c3b/c4b-opsonized particles to liver and spleen for phagocytosis. using recombinant cr1 constructs, we mapped the recognition site for pfrh4 to complement control protein modules 1 to 3 (ccp1-3) at the membrane-distal amino terminus of c ...201121685372
antibodies to plasmodium falciparum erythrocyte-binding antigen-175 are associated with protection from clinical malaria.background:: antibodies to blood-stage plasmodium falciparum antigens have been associated with protection against clinical malaria in some studies but not others. many of these studies have not assessed whether high-titer antibodies are associated with protection and have not adjusted for differences in malaria exposure. methods:: the presence of high-titer antibodies to apical membrane antigen-1, erythrocyte-binding antigen-175 (eba-175), and merozoite surface protein-119 (msp-119) was assesse ...201121817955
cananginones a-i, linear acetogenins from the stem bark of cananga latifolia.nine linear c23 and c21 acetogenins, named cananginones a-i (1-9), were isolated from stem bark of cananga latifolia. their structures were established by spectroscopic methods. these compounds showed cytotoxicity against three cancer cell lines (kb, mcf7 and nci-h187) with ic(50) values in the range 16.6-129.7++m. only 5 showed weak antimalarial activity against plasmodium falciparum. in addition, 8 and 9 exhibited weak antifungal activity against candida albicans.201121714976
lessons from sickle cell disease in the treatment and control of malaria. 201121714653
evaluation of the safety and immunogenicity in rhesus monkeys of a recombinant malaria vaccine for plasmodium vivax with a synthetic toll-like receptor 4 agonist formulated in an emulsion.plasmodium vivax is the major cause of malaria outside sub-saharan africa and inflicts debilitating morbidity and consequent economic impacts in developing countries. in order to produce a p. vivax vaccine for global use, we have previously reported the development of a novel chimeric recombinant protein, vmp001, based on the circumsporozoite protein (csp) of p. vivax. very few adjuvant formulations are currently available for human use. our interest is to evaluate second-generation vaccine form ...201121690242
substrate-induced conformational changes in plasmodium falciparum guanosine monophosphate synthetase.gmp synthetase is a glutamine amidotransferase that incorporates ammonia derived from glutamine into the nucleotide xanthosine 5'-monophosphate (xmp) to form guanosine 5'-monophosphate (gmp). functional coordination of domains in glutamine amidotransferases leads to upregulation of glutamine hydrolysis in the presence of acceptor substrates and is a common feature in this class of enzymes. we had shown earlier that binding of substrates to the acceptor domain of plasmodium falciparum gmp synthet ...201121827625
cd8+ t effector memory cells protect against liver-stage malaria.identification of correlates of protection for infectious diseases including malaria is a major challenge and has become one of the main obstacles in developing effective vaccines. we investigated protection against liver-stage malaria conferred by vaccination with adenoviral (ad) and modified vaccinia ankara (mva) vectors expressing pre-erythrocytic malaria ags. by classifying cd8(+) t cells into effector, effector memory (t(em)), and central memory subsets using cd62l and cd127 markers, we fou ...201121715686
in vitro antiplasmodial activity of sesquiterpene lactones from ambrosia tenuifolia.the in vitro antiplasmodial activity of ambrosia tenuifolia organic extract and its isolated sesquiterpene lactones, psilostachyin and peruvin, has been evaluated against plasmodium falciparum f32 and w2 strains. the cytotoxicity of both compounds was determined on lymphoid cells, and their corresponding selectivity indexes (sis) were calculated. peruvin was the most active compound on f32 strain of p. falciparum with a 50% inhibitory concentration value (ic(50)) of 0.3ôçë++g/ml (1.1ôçë++m) wher ...201121716685
plasmodium falciparum soluble extracts potentiate the suppressive function of polyclonal t regulatory cells through activation of tgf+¦-mediated signals.increased numbers of t regulatory cells (tregs), key mediators of immune homeostasis, were reported in human and murine malaria and it is current opinion that these cells play a role in balancing protective immunity and pathogenesis during infection. however, the mechanisms governing their expansion during malaria infection are not completely defined. in this article we show that soluble extracts of plasmodium falciparum (pfses), but not equivalent preparation of uninfected erythrocytes, induce ...201121699642
identification of plant-like galactolipids in chromera velia, a photosynthetic relative of malaria parasites.apicomplexa are protist parasites that include plasmodium spp., the causative agents of malaria, and toxoplasma gondii, responsible for toxoplasmosis. most apicomplexa possess a relict plastid, the apicoplast, which was acquired by secondary endosymbiosis of a red alga. despite being nonphotosynthetic, the apicoplast is otherwise metabolically similar to algal and plant plastids and is essential for parasite survival. previous studies of toxoplasma gondii identified membrane lipids with some str ...201121712377
investigations on the role of a lysozyme from the malaria vector anopheles dirus during malaria parasite development.a cdna encoding a lysozyme was obtained by rapid amplification of cdna ends-polymerase chain reaction (race-pcr) from females of the malaria vector anopheles dirus a (diptera: culicidae). the 623bp lysozyme (adlys c-1) cdna encodes the 120 amino acid mature protein with a predicted molecular mass of 13.4kda and theoretical pi of 8.45. six cysteine residues and a potential calcium binding motif that are present in adlys c-1 are highly conserved relative to those of c-type lysozymes found in other ...201121741400
susceptibility of anopheles stephensi to plasmodium gallinaceum: a trait of the mosquito, the parasite, and the environment.vector susceptibility to plasmodium infection is treated primarily as a vector trait, although it is a composite trait expressing the joint occurrence of the parasite and the vector with genetic contributions of both. a comprehensive approach to assess the specific contribution of genetic and environmental variation on "vector susceptibility" is lacking. here we developed and implemented a simple scheme to assess the specific contributions of the vector, the parasite, and the environment to "vec ...201121694762
safety and immunogenicity of multi-antigen ama1-based vaccines formulated with covaccine htôäó and montanide isa 51 in rhesus macaques.increasing the breadth of the functional antibody response through immunization with plasmodium falciparum apical membrane antigen 1 (pfama1) multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. this study assesses the safety and immunogenicity of three pfama1 diversity-covering (dico) vaccine candidates formulated as an equimolar mixture (dico mix) in covaccine htôäó or montanide isa 51, as well as that of a pfama1-msp1ôéüôéë fusion protein formulated in ...201121726452
detection of malarial byproduct hemozoin utilizing its unique scattering properties.the scattering characteristics of the malaria byproduct hemozoin, including its scattering distribution and depolarization, are modeled using discrete dipole approximation (dda) and compared to those of healthy red blood cells. scattering (or dark-field) spectroscopy and imaging are used to identify hemozoin in fresh rodent blood samples. a new detection method is proposed and demonstrated using dark-field in conjunction with cross-polarization imaging and spectroscopy. snrs greater than 50:1 ar ...201121716456
prevalence of malaria parasitemia amongst asymptomatic pregnant women attending a nigerian teaching hospital.malaria parasitemia among pregnant women is associated with complications to mother and the unborn fetus. there is paucity of data on asymptomatic malaria parasitemia, particularly in the northwest region of nigeria. the objectives of this study were to determine the prevalence of malaria parasitemia in asymptomatic pregnant women and to estimate the packed cell volume (pcv) of this group of pregnant women.201121691026
glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites.our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen plasmodium falciparum in culture and against plasmodium berghei in infected mice. with respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initia ...201121682307
natural haemozoin modulates matrix metalloproteinases and induces morphological changes in human microvascular endothelium.severe malaria, including cerebral malaria (cm), is characterized by the sequestration of parasitized erythrocytes in the microvessels after cytoadherence to endothelial cells. products of parasite origin, such as haemozoin (hz), contribute to the pathogenesis of severe malaria by interfering with host inflammatory response. in human monocytes, hz enhanced the levels of matrix metalloproteinase-9 (mmp-9), a protease involved in neuroinflammation. here the effects of hz on the regulation of mmps ...201121707906
pattern of malaria transmission along the rahad river basin, eastern sudan.understanding malaria vector mosquitoes and their infectivity dynamics is of importance in setting up intervention and control programmes. patterns of malaria transmission have been shown to differ between non-irrigated and irrigated semi-arid areas of eastern sudan. however, very little information is available regarding malaria transmission dynamics along the seasonal river's basin. such information is required for the design of effective vector control strategies.201121679459
enhancing immunogenicity to plga microparticulate systems by incorporation of alginate and rgd-modified alginate.poly-lactide-co-glycolide acid (plga) and alginate represent two different families of polymers widely used for microencapsulation application, even more, for vaccination purposes as particulate delivery/adjuvant systems. combination of these polymers has been previously considered for tissue engineering and drug delivery, however there is currently no report regarding their combination for vaccine application. in the present work, a w/o/w solvent extraction technique was developed to prepare no ...201121699977
bestatin-based chemical biology strategy reveals distinct roles for malaria m1- and m17-family aminopeptidases.malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. peptidases are a promising class of drug targets and perform several important roles during the plasmodium falciparum erythrocytic life cycle. herein, we report a multidisciplinary effort combining activity-based protein profiling, biochemical, and peptidomic approaches to functionally analyze two genetica ...201121844374
comparison of the antibody responses to plasmodium vivax and plasmodium falciparum antigens in residents of mandalay, myanmar.abstract:201121819610
in vitro sensitivity of plasmodium falciparum field isolates to extracts from cameroonian annonaceae plants.in a search for new plant-derived antimalarial extracts, 19 fractions were obtained from three annonaceae species, uvariopsis congolana (leaf, stem), polyalthia oliveri (stem bark), and enantia chlorantha (stem, stem bark) with yields ranging from 0.33% to 4.60%. the extracts were prepared from 500-ág of each plant part, using organic solvents to afford five methanolic fractions (acetogenin rich), five water fractions, five hexane fractions, and four interface precipitates. evaluation of the act ...201121739316
plasmodium falciparum merozoite invasion is inhibited by antibodies that target the pfrh2a and b binding domains.plasmodium falciparum, the causative agent of the most severe form of malaria in humans invades erythrocytes using multiple ligand-receptor interactions. the p. falciparum reticulocyte binding-like homologue proteins (pfrh or pfrbl) are important for entry of the invasive merozoite form of the parasite into red blood cells. we have analysed two members of this protein family, pfrh2a and pfrh2b, and show they undergo a complex series of proteolytic cleavage events before and during merozoite inva ...201121698217
characterization of a new phosphatase from plasmodium.plasmodium falciparum malaria is the most important parasitic disease worldwide, responsible for an estimated 1 million deaths annually. two p. falciparum genes code for putative phosphoglycerate mutases (pgmases), a widespread protein group characterized by the involvement of histidine residues in their catalytic mechanism. pgmases are responsible for the interconversion between 2 and 3-phosphoglycerate, an intermediate step in the glycolysis pathway. we have determined the crystal structures o ...201121689687
high-speed shaking of frozen blood clots for extraction of human and malaria parasite dna.abstract:201121824391
[immunopathological mechanism of cerebral malaria].cerebral malaria is a severe complication of malaria. early studies suggest that cerebral malaria is related to cytoadherence of parasitized red blood cells to the microvessel endothelium of brain. however, more and more evidence supported that the cause of cerebral malaria is uncontrolled inflammatory cytokines and infiltration of lymphocytes in brain microvessel. the article summarizes the research progress on immunological mechanism of cerebral malaria.201121823329
characterization and application of the fe(ii) and +¦-ketoglutarate dependent hydroxylase frbj.the fe(ii) and +¦-ketoglutarate-dependent hydroxylase frbj was previously demonstrated to utilize fr-900098 synthesizing a second phosphonate fr-33289. here we assessed its ability to hydroxylate other possible substrates, generating a library of potential antimalarial compounds. through a series of bioassays and in vitro experiments, we identified two new antimalarials.201121829824
environmental constraints guide migration of malaria parasites during transmission.migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. during transmission of malaria, parasite motility in the skin is important for plasmodium sporozoites to reach the blood circulation. here we show that sporozoite migration varies in different skin environments the parasite encounters at the arbitrary sites of the mosquito bite. in order to systematically examine how sporozoite migration depends on the structure of the ...201121698220
[new malaria drugs: screening against the entire parasite or target-based - which is the right path?]. 201121698606
6questionnaire-based approach to assess schoolchildren's physical fitness and its potential role in exploring the putative impact of helminth and plasmodium spp. infections in c+¦te d'ivoire.abstract:201121702903
long-term humoral and cellular immune responses elicited by a heterologous plasmodium vivax apical membrane antigen 1 protein prime/adenovirus boost immunization protocol.apical membrane antigen 1 (ama-1) is an invasion-related plasmodium antigen that is expressed during both intracellular and extracellular asexual stages of the parasite's life cycle, making it an ideal target for induction of humoral and cellular immune responses that can protect against malaria. we show here that when it is administered as a recombinant protein (p) in montanide isa720 adjuvant, followed by a recombinant human type 5 adenovirus (ad), intense and long-lasting plasmodium vivax ama ...201121730090
synthesis and in vitro antiplasmodial activity of quinoline-ferrocene esters.new 4-aminoquinoline-derived esters containing the redox-active ferrocene group brought in by either ferrocenyformic or 4-ferrocenylbutanoic acids were synthesized and tested in vitro for their antiplasmodial activity. the results revealed that only esters derived from ferrocenylformic acid were active against both chloroquine (cq)-resistant dd2 and cq-sensitive d10 strains of plasmodium falciparum. however, none of these showed higher actvity than cq against the sensitive strain. ester 16, whic ...201121827047
improvement of the observational method for plasmodium berghei oocysts in the midgut of mosquitoes.there is a need for improving the method for counting oocysts of plasmodium berghei in the midgut of anopheles mosquitoes. the two methods currently used, the formalin fixation method and the mercurochrome staining method, have contradicting advantages and disadvantages. in the formalin fixation method, the specimen can be preserved but unstained oocysts were often indistinct from the insect tissue. while in the mercurochrome staining method, stained oocysts can be clearly distinguished from ins ...201121707972
microbiology. exploiting malaria drug resistance to our advantage. 201121817037
interaction between ciprofloxacin and chloroquine in mice infected with chloroquine resistant plasmodium berghei : interaction between ciprofloxacin and chloroqune.the increasing spread of chloroquine resistant malaria has intensified the search for new antimalarial treatment, especially drugs that can be used in combination. ciprofloxacin (cfx) a fluoroquinolone commonly used to treat bacterial infections has been shown to possess significant antimalarial activity both in vitro and in vivo. thus efforts in this study were devoted to evaluating the antimalarial activity of combination of chloroquine (cq) with varying doses (10, 20, 40 80, 160-ámg/kg body w ...201121826489
worldwide genetic variability of the duffy binding protein: insights into plasmodium vivax vaccine development.the dependence of plasmodium vivax on invasion mediated by duffy binding protein (dbp) makes this protein a prime candidate for development of a vaccine. however, the development of a dbp-based vaccine might be hampered by the high variability of the protein ligand (dbp(ii)), known to bias the immune response toward a specific dbp variant. here, the hypothesis being investigated is that the analysis of the worldwide dbp(ii) sequences will allow us to determine the minimum number of haplotypes (m ...201121829672
real-time pcr assay and rapid diagnostic tests for the diagnosis of clinically suspected malaria patients in bangladesh.abstract:201121703009
ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of plasmodium falciparum and p. vivax.ferroquine (fq; ssr97193), a ferrocene-containing 4-aminoquinoline derivate, has potent in vitro efficacy against chloroquine (cq)-resistant plasmodium falciparum and cq-sensitive p. vivax. in the current study, ex vivo fq activity was tested in multidrug-resistant p. falciparum and p. vivax field isolates using a schizont maturation assay. although fq showed excellent activity against cq-sensitive and -resistant p. falciparum and p. vivax (median 50% inhibitory concentrations [ic(50)s], 9.6 nm ...201121730116
new insights into the mechanism of odorant detection by the malaria - transmitting mosquito anopheles gambiae.anopheles gambiae mosquitoes that transmit plasmodium falciparum malaria use a series of olfactory cues present in human sweat to locate their hosts for a blood meal. recognition of these odor cues occurs through the interplay of odorant receptors and odorant binding proteins (obps) that bind to odorant molecules and transport and present them to the receptors. recent studies have implicated potential heterodimeric interactions between two obps, obp1 and obp4, as important for perception of indo ...201121816826
measuring single-cell density.we have used a microfluidic mass sensor to measure the density of single living cells. by weighing each cell in two fluids of different densities, our technique measures the single-cell mass, volume, and density of approximately 500 cells per hour with a density precision of 0.001 g ml(-1). we observe that the intrinsic cell-to-cell variation in density is nearly 100-fold smaller than the mass or volume variation. as a result, we can measure changes in cell density indicative of cellular process ...201121690360
antiplasmodial indole alkaloids from leuconotis griffithii.a new indole alkaloid, leucoridine a n-oxide (1), consisting of two units of a strychnan type of skeleton, was isolated from the leaves of leuconotis griffithii. its structure was elucidated by various spectroscopic means such as nmr and ms, and also by chemical means. antiplasmodial activity against plasmodium falciparum 3d7 of indole alkaloids isolated from l. griffithii was investigated.201121830090
interaction between sulphur mobilisation proteins sufb and sufc: evidence for an iron-sulphur cluster biogenesis pathway in the apicoplast of plasmodium falciparum.the plastid of plasmodium falciparum, the apicoplast, performs metabolic functions essential to the parasite. various reactions in the plastid require the assembly of [fe-s] prosthetic groups on participating proteins as well as the reductant activity of ferredoxin that is converted from its apo-form by the assembly of [fe-s] clusters inside the apicoplast. the [fe-s] assembly pathway involving sulphur mobilising suf proteins has been predicted to function in the apicoplast with one component (p ...201121722645
medicinal chemistry perspectives of trioxanes and tetraoxanes.trioxane based compounds such as artemisinin and its synthetic and semi-synthetic analogues constitute promising class of antimalarial agents. the pharmaceutical development of artemisinin was started in 1971 after the isolation from chinese medicinal plant artemisia annua and this compound has drawn much attention from medical chemist and pharmacologist worldwide. researchers from across the globe have independently and collaboratively conducted various studies on the artemisinin system in an a ...201121824099
the potent antimalarial peptide cyclosporin a induces the aggregation and permeabilization of sphingomyelin-rich membranes.cyclosporin a (csa) is a hydrophobic peptide drug produced by the fungus tolypocladium inflatum. csa is commonly used as an immunosuppressive drug, but it also has antimalarial activity. the immunosuppressive activity of csa is clearly due to its association with specific proteins of immune cells such as cyclophilins. by contrast, the antimalarial properties of this peptide are completely independent of the association with a parasite's cyclophilins. because of its hydrophobicity, csa may intera ...201121692492
characterization of treatment failure in efficacy trials of drugs against plasmodium vivax by genotyping neutral and drug resistance-associated markers.plasmodium vivax intervention trials customarily report uncorrected treatment failure rates. application of recrudescence-reinfection genotyping and drug resistance single-nucleotide polymorphism typing to a 4-arm comparative efficacy trial illustrated that molecular approaches can assist in understanding the relative contributions of true drug resistance (recurrent with same genotype) and new infections to treatment failure. the pcr-corrected adequate clinical and parasitologic response may con ...201121709097
a randomized controlled phase ib trial of the malaria vaccine candidate gmz2 in african children.gmz2 is a fusion protein of plasmodium falciparum merozoite surface protein 3 (msp3) and glutamate rich protein (glurp) that mediates an immune response against the blood stage of the parasite. two previous phase i clinical trials, one in na+»ve european adults and one in malaria-exposed gabonese adults showed that gmz2 was well tolerated and immunogenic. here, we present data on safety and immunogenicity of gmz2 in one to five year old gabonese children, a target population for future malaria v ...201121829466
imported malaria in belgrade, serbia, between 2001 and 2009.since 2000, travel of serbian citizens to tropical areas has been slowly but steadily increasing. to determine the epidemiological and clinical characteristics of imported malaria in serbia, we analyzed clinical history data of all travelers who presented at the clinic for infectious and tropical diseases in belgrade after their return from tropical and subtropical areas between 2001 and 2009. the study series involved a total of 2981 travelers, and included both those with (847) and without (21 ...201121826415
etiopathogenesis of burkitt's lymphoma: a lesson from a bl-like in cd1 mouse immune to plasmodium yoelii yoelii.abstract:201121740585
potential of a khaya ivorensis -alstonia boonei extract combination as antimalarial prophylactic remedy.the decoction of the combined stem barks of khaya ivorensis a. chev. (meliaceae) and alstonia boonei de wild (apocynaceae) has a history of use in traditional medicine of central cameroon for malaria treatment but also for the prevention of the disease.201121742022
from the cover: rerooting the evolutionary tree of malaria parasites.malaria parasites (plasmodium spp.) have plagued humans for millennia. less well known are related parasites (haemosporida), with diverse life cycles and dipteran vectors that infect other vertebrates. understanding the evolution of parasite life histories, including switches between hosts and vectors, depends on knowledge of evolutionary relationships among parasite lineages. in particular, inferences concerning time of origin and trait evolution require correct placement of the root of the evo ...201121730128
the influence of mosquito resting behaviour and associated microclimate for malaria risk.abstract:201121736735
protein translation in plasmodium parasites.the protein translation machinery of the parasite plasmodium is the target of important anti-malarial drugs, and encompasses many promising targets for future drugs. plasmodium parasites have three subcellular compartments that house genomes; the nucleus, mitochondrion and apicoplast, and each requires its own compartmentalized transcription and translation apparatus for survival. despite the availability of the complete genome sequence that should reveal the requisite elements for all three com ...201121741312
a sub-microscopic gametocyte reservoir can sustain malaria transmission.novel diagnostic tools, including pcr and high field gradient magnetic fractionation (hfgmf), have improved detection of asexual plasmodium falciparum parasites and especially infectious gametocytes in human blood. these techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (lm).201121695129
rodent blood-stage plasmodium survive in dendritic cells that infect naive mice.plasmodium spp. parasites cause malaria in 300 to 500 million individuals each year. disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. infected individuals can also suffer relapses after several years, from plasmodium vivax and plasmodium ovale surviving in hepatocytes. plasmodium falciparum and plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood ...201121690346
insulin-like peptides in the mosquito anopheles stephensi: identification and expression in response to diet and infection with plasmodium falciparum.insulin-like peptides (ilps) regulate a multitude of biological processes, including metabolism and immunity to infection, and share similar structural motifs across widely divergent taxa. insulin/insulin-like growth factor signaling (iis) pathway elements are similarly conserved. we have shown that iis regulates reproduction, innate immunity, and lifespan in female anopheles stephensi, a major mosquito vector of human malaria. to further explore iis regulation of these processes, we identified ...201121703270
azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy.introduction: the first-line therapy for the intermittent preventive treatment of malaria in pregnancy (iptp) is sulphadoxine-pyrimethamine (sp). there is an urgent need to identify safe, well-tolerated and efficacious alternatives to sp due to widespread plasmodium falciparum resistance. combination therapy using azithromycin and chloroquine is one possibility that has demonstrated adequate parasitological response > 95% in clinical trials of non-pregnant adults in sub-saharan africa and where ...201121736423
multi-targeted activity of maslinic acid as an antimalarial natural compound.most drugs against malaria that are available or under development target a single process of the parasite infective cycle, favouring the appearance of resistant mutants which are easily spread in areas under chemotherapeutic treatments. maslinic acid (ma) is a low toxic natural pentacyclic triterpene for which a wide variety of biological and therapeutic activities have been reported. previous work revealed that plasmodium falciparum erythrocytic cultures were inhibited by ma, which was able to ...201121689375
in vitro and in vivo antimalarial activity assays of seeds from balanites aegyptiaca: compounds of the extract show growth inhibition and activity against plasmodial aminopeptidase.balanites aegyptiaca (balanitaceae) is a widely grown desert plant with multiuse potential. in the present paper, a crude extract from b. aegyptiaca seeds equivalent to a ratio of 1ôçë:ôçë2000 seeds to the extract was screened for antiplasmodial activity. the determined ic(50) value for the chloroquine-susceptible plasmodium falciparum nf54 strain was 68.26ôçë++g/++l -¦ 3.5. analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(h)-1,2,4-triazin-5-one oxime, an inhib ...201121687598
the nucleosome (histone-dna complex) is the tlr9-specific immunostimulatory component of plasmodium falciparum that activates dcs.the systemic clinical symptoms of plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. we recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (dcs) by tlr9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. we also de ...201121687712
non-apical membrane antigen 1 (ama1) iggs from malian children interfere with functional activity of ama1 iggs as judged by growth inhibition assay.apical membrane antigen 1 (ama1) is one of the best-studied blood-stage malaria vaccine candidates. when an ama1 vaccine was tested in a malaria na+»ve population, it induced functionally active antibodies judged by growth inhibition assay (gia). however, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in gia at baseline, ...201121695140
resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness.the greatest impediment to effective malaria control is drug resistance in plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy.201121698180
how selection forces dictate the variant surface antigens used by malaria parasites.red blood cells infected by the malaria parasite plasmodium falciparum express variant surface antigens (vsas) that evade host immunity and allow the parasites to persist in the human population. there exist many different vsas and the differential expression of these vsas is associated with the virulence (damage to the host) of the parasites. the aim of this study is to unravel the differences in the effect key selection forces have on parasites expressing different vsas such that we can better ...201121733875
microvascular sequestration of plasmodium falciparum. 201121823261
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