| synthesis and antimalarial evaluation of cyclic beta-amino acid-containing dipeptides. | this paper describes an efficient synthesis and the antiparasitic evaluation of cyclic beta-amino acid-containing dipeptides 3.1-3.6 and 4.1-4.5. the antimalarial properties of all these dipeptides have been evaluated in vitro against plasmodium falciparum and in vivo against plasmodium berghai. compounds 4.4 and 4.5 have been found to be very effective in this respect, with ic50 values of 3.87 and 3.64 microg/ml in the in vitro test, while 4.5 has also been found to be active in the in vivo eva ... | 2008 | 18305429 |
| the mechanism of antimalarial action of the ruthenium(ii)-chloroquine complex [rucl(2)(cq)] (2). | the mechanism of antimalarial action of the ruthenium-chloroquine complex [rucl(2)(cq)](2) (1), previously shown by us to be active in vitro against cq-resistant strains of plasmodium falciparum and in vivo against p. berghei, has been investigated. the complex is rapidly hydrolyzed in aqueous solution to [rucl(oh(2))(3)(cq)](2)[cl](2), which is probably the active species. this compound binds to hematin in solution and inhibits aggregation to beta-hematin at ph approximately 5 to a slightly low ... | 2008 | 18305967 |
| host cell traversal is important for progression of the malaria parasite through the dermis to the liver. | the malaria sporozoite, the parasite stage transmitted by the mosquito, is delivered into the dermis and differentiates in the liver. motile sporozoites can invade host cells by disrupting their plasma membrane and migrating through them (termed cell traversal), or by forming a parasite-cell junction and settling inside an intracellular vacuole (termed cell infection). traversal of liver cells, observed for sporozoites in vivo, is thought to activate the sporozoite for infection of a final hepat ... | 2008 | 18312843 |
| synthesis, antimalarial activity, structure-activity relationship analysis of thieno-[3,2-b]benzothiazine s,s-dioxide analogs. | an improved procedure for the synthesis of 3-amino-9-arylsubstituted-thieno[3,2-b]benzothiazine s,s-dioxide 2-decarboxylated is reported. thieno-[3,2-b]benzothiazine s,s-dioxide derivatives were investigated for their abilities to inhibit beta-hematin formation, hemoglobin hydrolysis and in vivo for their efficacy in rodent plasmodium berghei. compounds 5j-o were the most promising as inhibitors of hemoglobin hydrolysis, however, the compounds are not as efficient as chloroquine. a structure-act ... | 2008 | 18314337 |
| murine model for assessment of plasmodium falciparum transmission-blocking vaccine using transgenic plasmodium berghei parasites expressing the target antigen pfs25. | currently, there is no animal model for plasmodium falciparum challenge to evaluate malaria transmission-blocking vaccines based on the well-established pfs25 target antigen. the biological activity of transmission-blocking antibodies is typically assessed using an assay known as the membrane feeding assay (mfa). it is an in vitro method that involves mixing antibodies with cultured p. falciparum gametocytes and feeding them to mosquitoes through an artificial membrane followed by assessment of ... | 2008 | 18316385 |
| sporozoite-mediated hepatocyte wounding limits plasmodium parasite development via myd88-mediated nf-kappa b activation and inducible no synthase expression. | plasmodium sporozoites traverse several host cells before infecting hepatocytes. in the process, the plasma membranes of the cells are ruptured, resulting in the release of cytosolic factors into the microenvironment. this released endogenous material is highly stimulatory/immunogenic and can serve as a danger signal initiating distinct responses in various cells. thus, our study aimed at characterizing the effect of cell material leakage during plasmodium infection on cultured mouse primary hep ... | 2008 | 18322208 |
| no mirna were found in plasmodium and the ones identified in erythrocytes could not be correlated with infection. | the transcriptional regulation of plasmodium during its complex life cycle requires sequential activation and/or repression of different genetic programmes. micrornas (mirnas) are a highly conserved class of non-coding rnas that are important in regulating diverse cellular functions by sequence-specific inhibition of gene expression. what is know about double-stranded rna-mediated gene silencing (rnai) and posttranscriptional gene silencing (ptgs) in plasmodium parasites entice us to speculate w ... | 2008 | 18328111 |
| fitness of transgenic anopheles stephensi mosquitoes expressing the sm1 peptide under the control of a vitellogenin promoter. | three transgenic anopheles stephensi lines were established that strongly inhibit transmission of the mouse malaria parasite plasmodium berghei. fitness of the transgenic mosquitoes was assessed based on life table analysis and competition experiments between transgenic and wild-type mosquitoes. life table analysis indicated low fitness load for the 2 single-insertion transgenic mosquito lines vd35 and vd26 and no load for the double-insertion transgenic mosquito line vd9. however, in cage exper ... | 2008 | 18334506 |
| anti-malarial activity of eclipta alba against plasmodium berghei infection in mice. | the anti-malarial activity of eclipta alba leaves extract was evaluated against plasmodium'berghei anka strain in mice. a standard inoculum of 1 x 10(6) infected erythrocytes was used. the methanolic leaf extract (250-750 mg/kg) produced a dose-dependant chemosupression or schizontocidal effect during early and established infection and high mean survival time (m.s.t.) values particularly in the group administered 750 mg/kg/day of extract. the plant extract also exhibited repository activity. th ... | 2007 | 18338686 |
| two-step synthesis of achiral dispiro-1,2,4,5-tetraoxanes with outstanding antimalarial activity, low toxicity, and high-stability profiles. | a rapid, two-step synthesis of a range of dispiro-1,2,4,5-tetraoxanes with potent antimalarial activity both in vitro and in vivo has been achieved. these 1,2,4,5-tetraoxanes have been proven to be superior to 1,2,4-trioxolanes in terms of stability and to be superior to trioxane analogues in terms of both stability and activity. selected analogues have in vitro nanomolar antimalarial activity and good oral activity and are nontoxic in screens for both cytotoxicity and genotoxicity. the synthesi ... | 2008 | 18341274 |
| chemokine receptor cxcr3 and its ligands cxcl9 and cxcl10 are required for the development of murine cerebral malaria. | cerebral malaria is a significant cause of global mortality, causing an estimated two million deaths per year, mainly in children. the pathogenesis of this disease remains incompletely understood. chemokines have been implicated in the development of cerebral malaria, and the ifn-inducible cxcr3 chemokine ligand ip-10 (cxcl10) was recently found to be the only serum biomarker that predicted cerebral malaria mortality in ghanaian children. we show that the cxcr3 chemokine ligands ip-10 and mig (c ... | 2008 | 18347328 |
| truncation of plasmodium berghei merozoite surface protein 8 does not affect in vivo blood-stage development. | merozoite surface protein 8 (msp8) has shown promise as a vaccine candidate in the plasmodium yoelii rodent malaria model and has a proposed role in merozoite invasion of erythrocytes. however, the temporal expression and localisation of msp8 are unusual for a merozoite antigen. moreover, in plasmodium falciparum the msp8 gene could be disrupted with no apparent effect on invitro growth. to address the invivo function of full-length msp8, we truncated msp8 in the rodent parasite plasmodium bergh ... | 2008 | 18359107 |
| artesunate-erythropoietin combination for murine cerebral malaria treatment. | cerebral malaria is the most severe and rapidly fatal complication of plasmodium falciparum infection. despite appropriate anti-malarial treatment using quinine or artemisinin derivatives, 10-20% of mortality still occurs during the acute phase. to improve cerebral malaria outcome, adjunctive therapies are clearly needed. most experiments in this area have been dedicated to immuno-modulation with various successes. since erythropoietin has been shown to be highly effective in human ischemic stro ... | 2008 | 18359468 |
| malaria liver stage susceptibility locus identified on mouse chromosome 17 by congenic mapping. | host genetic variants are known to confer resistance to plasmodium blood stage infection and to control malaria severity both in humans and mice. this work describes the genetic mapping of a locus for resistance to liver stage parasite in the mouse. first, we show that decreased susceptibility to the liver stage of plasmodium berghei in the balb/c mouse strain is attributable to intra-hepatic factors and impacts on the initial phase of blood stage infection. we used qtl mapping techniques to ide ... | 2008 | 18365019 |
| the conserved plant sterility gene hap2 functions after attachment of fusogenic membranes in chlamydomonas and plasmodium gametes. | the cellular and molecular mechanisms that underlie species-specific membrane fusion between male and female gametes remain largely unknown. here, by use of gene discovery methods in the green alga chlamydomonas, gene disruption in the rodent malaria parasite plasmodium berghei, and distinctive features of fertilization in both organisms, we report discovery of a mechanism that accounts for a conserved protein required for gamete fusion. a screen for fusion mutants in chlamydomonas identified a ... | 2008 | 18367645 |
| plasmodium-induced inflammation by uric acid. | infection of erythrocytes with the plasmodium parasite causes the pathologies associated with malaria, which result in at least one million deaths annually. the rupture of infected erythrocytes triggers an inflammatory response, which is induced by parasite-derived factors that still are not fully characterized. induced secretion of inflammatory cytokines by these factors is considered a major cause of malaria pathogenesis. in particular, the inflammatory cytokine tumor necrosis factor (tnf) is ... | 2008 | 18369465 |
| reverse genetics analysis of antiparasitic responses in the malaria vector, anopheles gambiae. | anopheles mosquitoes are the major vectors of human malaria parasites. mosquito-parasite interactions are critical for disease transmission and therefore represent a potential target for malaria control strategies. mosquitoes mount potent antiparasitic responses, and identification of mosquito factors that limit parasite development is one of the major objectives in the field. to address this question, we have developed a convenient reverse genetics approach by injection of double-stranded rna ( ... | 2008 | 18370165 |
| antiparasitic activities and toxicities of individual enantiomers of the 8-aminoquinoline 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate. | 8-aminoquinolines are an important class of antiparasitic agents, with broad utility and excellent efficacy, but also limitations due to hematological toxicities, primarily methemoglobinemia and hemolysis. one representative from this class, (+/-)-8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate (npc1161c), proved extremely efficacious in animal models of malaria and pneumocystis pneumonia. this racemic mixture was separated into its component enanti ... | 2008 | 18378716 |
| antiplasmodial effects of the aqueous extract of phyllantus amarus schumach and thonn against plasmodium berghei in swiss albino mice. | phyllantus amarus schumach and thonn is a medicinal plant used commonly for the treatment of malaria-related symptoms by the general public in southeastern nigeria. the present study determines the possible antiplasmodial effects of the aqueous extract of the leaves and stem of the plant against plasmodium berghei infection using swiss albino mice as models. the blood schizonticidal activity of the aqueous extract in early infection and in established plasmodium berghei infection was assessed an ... | 2007 | 18379613 |
| cxcr3 determines strain susceptibility to murine cerebral malaria by mediating t lymphocyte migration toward ifn-gamma-induced chemokines. | cerebral malaria (cm) results from the binding of infected erythrocytes and leukocytes to brain endothelia. the precise mechanisms underlying lymphocyte recruitment and activation in cm remain unclear. therefore, the expression of various chemokines was quantified in brains of mice infected with plasmodium berghei anka (pba). several chemokines attracting monocytes and activated t-lymphocytes were expressed at high levels. their expression was almost completely abrogated in ifn-gamma ligand and ... | 2008 | 18383042 |
| hepatocyte permissiveness to plasmodium infection is conveyed by a short and structurally conserved region of the cd81 large extracellular domain. | invasion of hepatocytes by plasmodium sporozoites is a prerequisite for establishment of a malaria infection, and thus represents an attractive target for anti-malarial interventions. still, the molecular mechanisms underlying sporozoite invasion are largely unknown. we have previously reported that the tetraspanin cd81, a known receptor for the hepatitis c virus (hcv), is required on hepatocytes for infection by sporozoites of several plasmodium species. here we have characterized cd81 molecula ... | 2008 | 18389082 |
| mast cell-mediated immune responses through ige antibody and toll-like receptor 4 by malarial peroxiredoxin. | in this study, 2-cys plasmodium berghei anka (pba) peroxiredoxin (prx) was identified as an antigenic protein recognized by an anti-pba ige antibody using two-dimensional polyacrylamide gel electrophoresis and proteomic analysis. innate immune responses to pbaprx were examined using cells from mice deficient in toll-like receptors (tlr) or related molecules, and it was demonstrated that responses were severely impaired in tlr4(-/-), myd88(-/-) and md-2(-/-) mice, but not in toll/il-1 receptor do ... | 2008 | 18398934 |
| high mobility group protein hmgb2 is a critical regulator of plasmodium oocyst development. | the sexual cycle of plasmodium is required for transmission of malaria from mosquitoes to mammals, but how parasites induce the expression of genes required for the sexual stages is not known. we disrupted the plasmodium yoelii gene encoding high mobility group nuclear factor hmgb2, which encodes a dna-binding protein potentially implicated in transcriptional regulation of malaria gene expression. we investigated its function in vivo in the vertebrate and invertebrate hosts. deltapyhmgb2 parasit ... | 2008 | 18400754 |
| male fertility of malaria parasites is determined by gcs1, a plant-type reproduction factor. | malaria, which is caused by plasmodium parasites, is transmitted by anopheline mosquitoes. when gametocytes, the precursor cells of plasmodium gametes, are transferred to a mosquito, they fertilize and proliferate, which render the mosquito infectious to the next vertebrate host. although the fertilization of malaria parasites has been considered as a rational target for transmission-blocking vaccines, the underlying mechanism is poorly understood. here, we show that the rodent malaria parasite ... | 2008 | 18403203 |
| disruption of the plasmodium berghei 2-cys peroxiredoxin tpx-1 gene hinders the sporozoite development in the vector mosquito. | to investigate the physiologic role of cytosolic 2-cys peroxiredoxin of plasmodium berghei (pbtpx-1), we infected the vector mosquito anopheles stephensi with a parasite carrying a targeted knockout of pbtpx-1 (prx-ko). the number of prx-ko midgut oocysts at 14-15 days post-feeding (pf) was comparable to that of the parent strain (wt); however, the numbers of sporozoites that formed in midgut oocysts and accumulated in the salivary gland of prx-ko-infected mosquitoes by 21 days pf were decreased ... | 2008 | 18417228 |
| cognitive dysfunction in mice infected with plasmodium berghei strain anka. | cerebral malaria complicated by cognitive sequelae is a major cause of morbidity in humans infected with plasmodium falciparum. to model cognitive function after malaria, we created a rodent model of cerebral malaria by infecting c57bl/6 mice with plasmodium berghei strain anka. after 7 days, an object-recognition test of working memory revealed a significant impairment in the visual memory of infected mice. this impairment was observed in the absence of confounding effects of infection. the cog ... | 2008 | 18419550 |
| expression and processing of plasmodium berghei sera3 during liver stages. | cysteine proteases mediate liberation of plasmodium berghei merozoites from infected hepatocytes. in an attempt to identify the responsible parasite proteases, we screened the genome of p. berghei for cysteine protease-encoding genes. rt-pcr analyses revealed that transcription of four out of five p. berghei serine repeat antigen (pbsera) genes was strongly upregulated in late liver stages briefly before the parasitophorous vacuole membrane ruptured to release merozoites into the host cell cytop ... | 2008 | 18419771 |
| c5 deficiency and c5a or c5ar blockade protects against cerebral malaria. | experimental infection of mice with plasmodium berghei anka (pba) provides a powerful model to define genetic determinants that regulate the development of cerebral malaria (cm). based on the hypothesis that excessive activation of the complement system may confer susceptibility to cm, we investigated the role of c5/c5a in the development of cm. we show a spectrum of susceptibility to pba in a panel of inbred mice; all cm-susceptible mice examined were found to be c5 sufficient, whereas all c5-d ... | 2008 | 18426986 |
| critical role of a k+ channel in plasmodium berghei transmission revealed by targeted gene disruption. | regulated k(+) transport across the plasma membrane is of vital importance for the survival of most cells. two k(+) channels have been identified in the plasmodium falciparum genome; however, their functional significance during parasite life cycle in the vertebrate host and during transmission through the mosquito vector remains unknown. we hypothesize that these two k(+) channels mediate the transport of k(+) in the parasites, and thus are important for parasite survival. to test this hypothes ... | 2008 | 18434537 |
| antiplasmodial activity of sesquiterpene lactone from carpesium rosulatum in mice. | in the previous work, methanol extracts of carpesium rosulatum (compositae) were found to have high antiplasmodial activity against plasmodium falciparum in vitro, this activity being largely attributable to a ineupatorolides a (i-a). in the present study, encouragingly, i-a was also found to have potential antimalarial activity in vivo when tested against plasmodium berghei in mice. i-a (2, 5, 10 mg kg(-1) day(-1)) exhibited a significant blood schizontocidal activity in 4-day early infection, ... | 2008 | 18437422 |
| functional characterization of a redundant plasmodium trap family invasin, trap-like protein, by aldolase binding and a genetic complementation test. | efficient and specific host cell entry is of exquisite importance for intracellular pathogens. parasites of the phylum apicomplexa are highly motile and actively enter host cells. these functions are mediated by type i transmembrane invasins of the trap family that link an extracellular recognition event to the parasite actin-myosin motor machinery. we systematically tested potential parasite invasins for binding to the actin bridging molecule aldolase and complementation of the vital cytoplasmi ... | 2008 | 18441124 |
| processing of the circumsporozoite protein in infected hepatocytes is not dependent on aspartic proteases. | cd8(+) t cells play a major role in the protective immune response against the liver stage of malaria. it was previously shown that the circumsporozoite protein (csp) is processed and presented to specific t cells by both traversed and infected hepatocytes, but their respective antigen processing requirements were not completely defined. in the present study, we show that in vitro processing of the plasmodium berghei csp by infected mouse primary hepatocytes is exclusively dependent on proteasom ... | 2008 | 18444957 |
| liposomal polyethyleneglycol and polyethyleneglycol-peptide combinations for active targeting to liver in vivo. | this report describes the development and evaluation of a range of polyethyleneglycol and polyethyleneglycol-peptide liposome formulations that effectively target liver in vivo. a 19-amino-acid sequence from the n-terminal region of the circumsporozoite protein of plasmodium berghei was attached to the distal end of di22:1-aminopropane-polyethyleneglycol(3400), and incorporated into liposomes containing di22:1-phosphatidylcholine and di22:1-phosphatidylethanolamine-polyethyleneglycol(5000). by s ... | 2008 | 18446566 |
| [a new view of malaria provided by parasite imaging]. | infection by plasmodium, the causative agent of malaria, starts when the parasite, injected by a mosquito vector, reaches and invades the liver, where it transforms into a stage that is capable of infecting erythrocytes and that causes the symptoms and complications of the disease. this phase of the infection, called pre-erythrocytic stage, is the most elusive of the parasite's life cycle, yet it was identified more than fifty years ago as a primary target of vaccine strategies aimed at avoiding ... | 2007 | 18447048 |
| pbsr is synthesized in macrogametocytes and involved in formation of the malaria crystalloids. | crystalloids are transient organelles that form in developing malaria ookinetes and disappear after ookinete-to-oocyst transition. their origins and functions remain poorly understood. the plasmodium berghei scavenger receptor-like protein pbsr is essential for mosquito-to-host transmission of the parasite: pbsr knockout parasites produce normal numbers of oocysts that fail to form sporozoites, pointing to a role for pbsr in the oocyst during sporogony. here, using fluorescent protein tagging an ... | 2008 | 18452513 |
| coinfection with nonlethal murine malaria parasites suppresses pathogenesis caused by plasmodium berghei nk65. | mixed infection with different plasmodium species is often observed in endemic areas, and the infection with benign malaria parasites such as plasmodium vivax or p. malariae has been considered to reduce the risk of developing severe pathogenesis caused by p. falciparum. however, it is still unknown how disease severity is reduced in hosts during coinfection. in the present study, we investigated the influence of coinfection with nonlethal parasites, p. berghei xat (pb xat) or p. yoelii 17x (py ... | 2008 | 18453608 |
| influence of no synthase inhibitor l-name on parasitemia and survival of plasmodium berghei infected mice. | accelerated suicidal death or eryptosis of infected erythrocytes may delay development of parasitemia in malaria. eryptosis is inhibited by nitric oxide (no). the present study has been performed to explore, whether inhibition of no synthase by l-name modifies the course of malaria. we show here that l-name (>or=10 microm) increased phosphatidylserine exposure of plasmodium falciparum infected human erythrocytes, an effect significantly more marked than in noninfected human erythrocytes. we furt ... | 2008 | 18453756 |
| heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection. | the clinically silent plasmodium liver stage is an obligatory step in the establishment of malaria infection and disease. we report here that expression of heme oxygenase-1 (ho-1, encoded by hmox1) is upregulated in the liver following infection by plasmodium berghei and plasmodium yoelii sporozoites. ho-1 overexpression in the liver leads to a proportional increase in parasite liver load, and treatment of mice with carbon monoxide and with biliverdin, each an enzymatic product of ho-1, also inc ... | 2008 | 18474360 |
| common strategies to prevent and modulate experimental cerebral malaria in mouse strains with different susceptibilities. | cerebral malaria (cm) is a severe complication of plasmodium falciparum infection, predominantly experienced by children and nonimmune adults, which results in significant mortality and long-term sequelae. previous studies have reported distinct susceptibility gene loci in cba/cah (cba) and c57bl/6 (b6) mice with experimental cm (ecm) caused by infection with plasmodium berghei anka. here we present an analysis of genome-wide expression profiles in brain tissue taken from b6 and cba mice with ec ... | 2008 | 18474652 |
| parasite burden and cd36-mediated sequestration are determinants of acute lung injury in an experimental malaria model. | although acute lung injury (ali) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (cm); however, no model of malaria-induced lung injury has been definitively established. this study used bronchoalveolar lavage (bal), histopathology and gene expression analysis to examine the development of ali in mice infect ... | 2008 | 18483551 |
| conserved mosquito/parasite interactions affect development of plasmodium falciparum in africa. | in much of sub-saharan africa, the mosquito anopheles gambiae is the main vector of the major human malaria parasite, plasmodium falciparum. convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, p. berghei. here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of p. berghei development are also pertinent to a. gambiae/p. falciparum inter ... | 2008 | 18483558 |
| design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids. | a series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. each compound was tested in vitro against the protozoa trichomonas vaginalis, giardia lamblia, entamoeba histolytica, leishmania mexicana, and plasmodium berghei, in comparison with pentamidine and metronidazole. some analogues showed high bioactivity in the low micromolar range (ic(50)<1 microm) against the first four protozoa, which make them significantly more potent than either stand ... | 2008 | 18486471 |
| malaria and obesity: obese mice are resistant to cerebral malaria. | the relationship between malaria and obesity are largely unknown. this is partly due to the fact that malaria occurs mainly in tropical areas where, until recently, obesity was not prevalent. it now appears, however, that obesity is emerging as a problem in developing countries. to investigate the possible role of obesity on the host-parasite response to malarial infection, this study applied a murine model, which uses the existence of genetically well characterized obese mice. | 2008 | 18489748 |
| the microneme proteins ctrp and soap are not essential for plasmodium berghei ookinete to oocyst transformation in vitro in a cell free system. | two plasmodium berghei ookinete micronemal proteins, circumsporozoite and trap related protein (ctrp) and secreted ookinete adhesive protein (soap) both interact with the basal lamina component laminin. following gene disruption studies it has been proposed that, apart from their role in motility, these proteins may be required for interactions leading to ookinete-to-oocyst transformation. | 2008 | 18489758 |
| transmission blocking immunity in the malaria non-vector mosquito anopheles quadriannulatus species a. | despite being phylogenetically very close to anopheles gambiae, the major mosquito vector of human malaria in africa, anopheles quadriannulatus is thought to be a non-vector. understanding the difference between vector and non-vector mosquitoes can facilitate development of novel malaria control strategies. we demonstrate that an. quadriannulatus is largely resistant to infections by the human parasite plasmodium falciparum, as well as by the rodent parasite plasmodium berghei. by using genetics ... | 2008 | 18497855 |
| antimalarial activity of novel pyrrolizidinyl derivatives of 4-aminoquinoline. | two pyrrolizidinylalkyl derivatives of 4-amino-7-chloroquinoline (mg2 and mg3) were prepared and tested in vitro against cq-sensitive and cq-resistant strains of plasmodium falciparum and in vivo in a plasmodium berghei mouse model of infection. both compounds exhibited excellent activity in all tests and low toxicity against mammalian cells. preliminary studies of the acute toxicity and of the metabolism of the most active compound mg3 indicate a promising profile as a new antimalarial drug can ... | 2008 | 18538567 |
| imidazolidin-4-one peptidomimetic derivatives of primaquine: synthesis and antimalarial activity. | the synthesis of imidazolidin-4-one derivatives of primaquine containing the five-membered ring at the c-terminus of a dipeptide backbone coupled to the parent drug is described. these peptidomimetic derivatives were active against a chloroquine-resistant plasmodium falciparum strain and inhibited the development of the sporogonic cycle of plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. the novel imidazolidin-4-ones are extremely stable, both in human pl ... | 2008 | 18539459 |
| a plasmodium falciparum host-targeting motif functions in export during blood stage infection of the rodent malarial parasite plasmodium berghei. | plasmodium falciparum (p. falciparum) secretes hundreds of proteins--including major virulence proteins--into the host erythrocyte. in order to reach the host cytoplasm, most p. falciparum proteins contain an n terminal host-targeting (ht) motif composed of 11 amino acids. in silico analyses have suggested that the ht motif is conserved throughout the plasmodium species but experimental evidence only exists for p. falciparum. here, we show that in the rodent malaria parasite plasmodium berghei ( ... | 2008 | 18545649 |
| a sporozoite asparagine-rich protein controls initiation of plasmodium liver stage development. | plasmodium sporozoites invade host hepatocytes and develop as liver stages (ls) before the onset of erythrocytic infection and malaria symptoms. ls are clinically silent, and constitute ideal targets for causal prophylactic drugs and vaccines. the molecular and cellular mechanisms underlying ls development remain poorly characterized. here we describe a conserved plasmodium asparagine-rich protein that is specifically expressed in sporozoites and liver stages. gene disruption in plasmodium bergh ... | 2008 | 18551171 |
| plasmodium lipid rafts contain proteins implicated in vesicular trafficking and signalling as well as members of the pir superfamily, potentially implicated in host immune system interactions. | plasmodium parasites, the causal agents of malaria, dramatically modify the infected erythrocyte by exporting parasite proteins into one or multiple erythrocyte compartments, the cytoplasm and the plasma membrane or beyond. despite advances in defining signals and specific cellular compartments implicated in protein trafficking in plasmodium-infected erythrocytes, the contribution of lipid-mediated sorting to this cellular process has been poorly investigated. in this study, we examined the prot ... | 2008 | 18563749 |
| depletion of plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite. | proliferation of the pathogenic plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. this function is achieved by a complex antioxidant defence system composed of redox-active proteins and low mw antioxidants. here, we disrupted the p. berghei plasmoredoxin gene that encodes a parasite-specific 22 kda member of the thioredoxin superfamily. the successful generation of plasmoredoxin knockout mutants in the ro ... | 2008 | 18575607 |
| rodent plasmodium: population dynamics of early sporogony within anopheles stephensi mosquitoes. | early sporogony of plasmodium parasites involves 2 major developmental transitions within the insect vector, i.e., gametocyte-to-ookinete and ookinete-to-oocyst. this study compared the population dynamics of early sporogony among murine rodent plasmodium (plasmodium berghei, plasmodium chabaudi, plasmodium vinckei, and plasmodium yoelii) developing within anopheles stephensi mosquitoes. estimates of absolute densities were determined for gametocytes, ookinetes, and oocysts for 108 experimental ... | 2008 | 18576764 |
| antimalarial activity in mice of resveratrol derivative from pleuropterus ciliinervis. | | 2008 | 18577334 |
| simple and sensitive antimalarial drug screening in vitro and in vivo using transgenic luciferase expressing plasmodium berghei parasites. | we report two improved assays for in vitro and in vivo screening of chemicals with potential anti-malarial activity against the blood stages of the rodent malaria parasite plasmodiumberghei. these assays are based on the determination of luciferase activity (luminescence) in small blood samples containing transgenic blood stage parasites that express luciferase under the control of a promoter that is either schizont-specific (ama-1) or constitutive (eef1alphaa). assay 1, the in vitro drug lumine ... | 2008 | 18590736 |
| chloroquine mediated modulation of anopheles gambiae gene expression. | plasmodium development in the mosquito is crucial for malaria transmission and depends on the parasite's interaction with a variety of cell types and specific mosquito factors that have both positive and negative effects on infection. whereas the defensive response of the mosquito contributes to a decrease in parasite numbers during these stages, some components of the blood meal are known to favor infection, potentiating the risk of increased transmission. the presence of the antimalarial drug ... | 2008 | 18596975 |
| ampelozyziphus amazonicus ducke (rhamnaceae), a medicinal plant used to prevent malaria in the amazon region, hampers the development of plasmodium berghei sporozoites. | most medicinal plants used against malaria in endemic areas aim to treat the acute symptoms of the disease such as high temperature fevers with periodicity and chills. in some endemic areas of the brazilian amazon region one medicinal plant seems to be an exception: ampelozyziphus amazonicus, locally named "indian beer" or "saracura-mira", used to prevent the disease when taken daily as a cold suspension of powdered dried roots. in previous work we found no activity of the plant extracts against ... | 2008 | 18599059 |
| malaria-specific and nonspecific activation of cd8+ t cells during blood stage of plasmodium berghei infection. | cerebral malaria is one of the severe complications of plasmodium falciparum infection. studies using a rodent model of plasmodium berghei anka infection established that cd8(+) t cells are involved in the pathogenesis of cerebral malaria. however, it is unclear whether and how plasmodium-specific cd8(+) t cells can be activated during the erythrocyte stage of malaria infection. we generated recombinant plasmodium berghei anka expressing ova (ova-pba) to investigate the parasite-specific t cell ... | 2008 | 18606696 |
| in vivo antiplasmodial activity of 11(13)-dehydroivaxillin from carpesium ceruum. | the whole plants of carpesium genus are used in traditional medicine as anti-pyretic, analgesic and vermifugic, including a topical application for sores and inflammation. a previous study on carpesium genus suggested that the antiplasmodial activity against plasmodium falciparum was due to the existence of 11(13)- dehydroivaxillin (ddv) from etoac extracts of c. ceruum (compositae). here, the antimalarial activity of ddv was evaluated against plasmodium berghei in mice. the ld(50) of the compou ... | 2009 | 18608780 |
| solid microemulsion preconcentrate (nanosorb) of artemether for effective treatment of malaria. | a microemulsion preconcentrate was formulated on the basis of solubility of artemether (arm) in the various oily phases and surfactants and phase diagrams. various solid adsorbents were evaluated for their ability yield solid microemulsion preconcentrates (nanosorb-arm). nanosorb-arm on dilution yielded microemulsion with average globule size of 183 nm and polydispersity index of 0.498 when determined using photon correlation spectroscopy. the antimalarial activity of nanosorb-arm, arm solution ... | 2008 | 18611435 |
| both functional ltbeta receptor and tnf receptor 2 are required for the development of experimental cerebral malaria. | tnf-related lymphotoxin alpha (ltalpha) is essential for the development of plasmodium berghei anka (pba)-induced experimental cerebral malaria (ecm). the pathway involved has been attributed to tnfr2. here we show a second arm of ltalpha-signaling essential for ecm development through ltbeta-r, receptor of ltalpha1beta2 heterotrimer. | 2008 | 18612394 |
| antimalarial activity of a new stilbene glycoside from parthenocissus tricuspidata in mice. | a novel stilbene glycoside [piceid-(1-->6)-beta-d-glucopyranoside; pbg] from parthenocissus tricuspidata was tested in vivo against plasmodium berghei. pbg exhibited significant blood schizontocidal activity in a 4-day early infection, a repository evaluation, and an established infection, with a significant mean survival time comparable to that obtained with the standard drug, chloroquine (5 mg x kg(-1) x day(-1)). | 2008 | 18625780 |
| genistein-supplemented diet decreases malaria liver infection in mice and constitutes a potential prophylactic strategy. | in tropical regions millions of people still live at risk of malaria infection. indeed the emergence of resistance to chloroquine and other drugs in use in these areas reinforces the need to implement alternative prophylactic strategies. genistein is a naturally occurring compound that is widely used as a food supplement and is thought to be effective in countering several pathologies. results presented here show that genistein inhibits liver infection by the plasmodium parasite, the causative a ... | 2008 | 18628947 |
| thymic alterations in plasmodium berghei-infected mice. | the primary function of the thymus is to develop immature t-cells into cells that further in the periphery will be able to carry out immune functions. the literature has shown that thymus can be a target for many pathogens and severe structural alterations take place in this organ during infectious diseases. here, we investigated if thymus is also a target organ during experimental malaria infection by analyzing the presence of parasites inside the organ and histological alterations in thymuses ... | 2008 | 18635160 |
| [maturation of dendritic cells and activation of b-lymphocytes in spleens of icr mice infected with chloroquine-resistant plasmodium berghei]. | to investigate the relation between activation of b-cells and maturation of dendritic cells (dc) in the spleens of icr mice infected with chloroquine-resistant (rc) or chloroquine-sensitive (n) strain of plasmodium berghei. | 2008 | 18637575 |
| host biomarkers and biological pathways that are associated with the expression of experimental cerebral malaria in mice. | cerebral malaria (cm) is a primary cause of malaria-associated deaths among young african children. yet no diagnostic tools are available that could be used to predict which of the children infected with plasmodium falciparum malaria will progress to cm. we used the plasmodium berghei anka murine model of experimental cerebral malaria (ecm) and high-density oligonucleotide microarray analyses to identify host molecules that are strongly associated with the clinical symptoms of ecm. comparative e ... | 2008 | 18644885 |
| antimalarial activity of phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors. | the antimalarial activity and pharmacology of a series of phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors (hdacis) was evaluated. in in vitro growth inhibition assays approximately 50 analogs were evaluated against four drug resistant strains of plasmodium falciparum. the range of 50% inhibitory concentrations (ic(50)s) was 0.0005 to >1 microm. five analogs exhibited ic(50)s of <3 nm, and three of these exhibited selectivity indices of >600. the most potent compound, wr3 ... | 2008 | 18644969 |
| global metabolic responses of nmri mice to an experimental plasmodium berghei infection. | we present a metabolism-driven top-down systems biology approach to characterize metabolic changes in the mouse resulting from an infection with plasmodium berghei, using high-resolution (1)h nmr spectroscopy and multivariate data analysis techniques. twelve female nmri mice were infected intravenously with approximately 20 million p. berghei-parasitized erythrocytes. urine and plasma samples were collected 4-6 h before infection, and at days 1, 2, 3, and 4 postinfection. multivariate analysis o ... | 2008 | 18646786 |
| imc1b is a putative membrane skeleton protein involved in cell shape, mechanical strength, motility, and infectivity of malaria ookinetes. | membrane skeletons are cytoskeletal elements that have important roles in cell development, shape, and structural integrity. malaria parasites encode a conserved family of putative membrane skeleton proteins related to articulins. one member, imc1a, is expressed in sporozoites and localizes to the pellicle, a unique membrane complex believed to form a scaffold onto which the ligands and glideosome are arranged to mediate parasite motility and invasion. imc1b is a closely related structural paral ... | 2008 | 18650444 |
| development of smedds using natural lipophile: application to beta-artemether delivery. | the objective of the present investigation was to formulate self-microemulsifying drug delivery systems (smedds) using a novel, indigenous natural lipophile (n-lct) as an oily phase. smedds based on n-lct and commercially available modified oil (capryol 90) were formulated and their application in improving the delivery of a lipophilic anti-malarial drug, beta-artemether (bam) was also evaluated. bam-loaded smedds were characterized with respect to mean globule size and in vitro drug release pro ... | 2008 | 18652886 |
| concurrent gastro-intestinal nematode infection does not alter the development of experimental cerebral malaria. | concurrent helminth infections have been suggested to be associated with protection against cerebral malaria in humans, a condition characterised by systemic inflammation. here we show that a concurrent chronic gastro-intestinal nematode infection does not alter the course of murine cerebral malaria. mice infected with heligmosomoides polygyrus, and co-infected with plasmodium berghei anka 14 days later, developed malaria parasitemia, weight loss and anemia, at the same rate as mice without nema ... | 2008 | 18656411 |
| gene expression, antiparasitic activity, and functional evolution of the drosomycin family. | drosophila employs various antimicrobial peptides as effective weapons to defend against diverse pathogens. drosomycin is an inducible antifungal peptide initially isolated from the drosophila melanogaster haemolymph. here we report the expression pattern of seven drosomycin genes in four different developmental stages (egg, larva, pupa and adult). results show that drosomycin and drosomycin-2 are expressed in larva, pupa and adult, whereas drosomycin-1 and drosomycin-6 were not detected in all ... | 2008 | 18657321 |
| electrospray ionization-ion trap mass spectrometry study of pqaapro and pqproaa mimetic derivatives of the antimalarial primaquine. | electrospray ionization-ion trap mass spectrometry (esi-ms) of imidazolidin-4-one peptidomimetic derivatives of the antimalarial drug primaquine (pq) is reported. these compounds contain the imidazolidin-4-one moiety either at the n- or the c-terminal of a dipeptide backbone, thus respectively mimicking pq-amino acid-proline (pqaapro) and pqproaa derivatives of pq. both the peptidomimetics and precursors previously developed by us are promising drug candidates, as they were found to be active ag ... | 2008 | 18657994 |
| control of pathogenic cd8+ t cell migration to the brain by ifn-gamma during experimental cerebral malaria. | previous studies have shown that ifn-gamma is essential for the pathogenesis of cerebral malaria (cm) induced by plasmodium berghei anka (pba) in mice. however, the exact role of ifn-gamma in the pathway (s) leading to cm has not yet been described. here, we used 129p2sv/ev mice which develop cm between 7 and 14 days post-infection with pba. in this strain, both cd4(+) and cd8(+) t cells were involved in the effector phase of cm. when 129p2sv/ev mice deficient in the ifn-gamma receptor alpha cha ... | 2008 | 18665903 |
| chemically attenuated plasmodium sporozoites induce specific immune responses, sterile immunity and cross-protection against heterologous challenge. | vaccination with plasmodium sporozoites attenuated by irradiation or genetic manipulation induces a protective immune response in rodent malaria models. recently, vaccination with chemically attenuated p. berghei sporozoites (cas) has also been shown to elicit sterile immunity in mice. here we show that vaccination with cas of p. yoelii also protects against homologous infection and that a p. berghei cas vaccine cross protects against heterologous challenge with p. yoelii sporozoites. vaccinatio ... | 2008 | 18672017 |
| synthesis, antimalarial activity, and intracellular targets of mefas, a new hybrid compound derived from mefloquine and artesunate. | a new synthetic antimalarial drug, a salt derived from two antimalarial molecules, mefloquine (mq) and artesunate (as), here named mefas, has been tested for its pharmacological activity. combinations of as plus mq hydrochloride are currently being used in areas with drug-resistant plasmodium falciparum parasites; although as clears parasitemia in shorter time periods than any other antimalarial drug, it does not cure infected patients; in addition, mq causes side effects and is rather expensive ... | 2008 | 18710907 |
| recombinant scorpine: a multifunctional antimicrobial peptide with activity against different pathogens. | scorpine is an antimicrobial peptide whose structure resembles a hybrid between a defensin and a cecropin. it exhibits antibacterial activity and inhibits the sporogonic development of parasites responsible for murine malaria. in this communication we report the production of scorpine in a heterelogous system, using a specific vector containing its cloned gene. the recombinantly expressed scorpine (rscp) in (anopheles gambie) cells showed antibacterial activity against (bacillus subtilis) and (k ... | 2008 | 18726072 |
| a role of ige and cd23/no immune pathway in age-related resistance of lewis rats to plasmodium berghei anka? | in contrast to young rats, adult rats given i.p. plasmodium berghei anka (pba) control the parasitaemia and repair their anaemia. here, we investigated whether ige and cd23/no immune pathway could be implicated in this age-related resistance of adult rats to pba. eight-week-old rats displayed significantly higher levels of plasma total ige (p=0.01) and soluble cd23 (p=0.003) during the peak of parasitaemia, compared to 4-week-old rats. ige fc-binding antibody or aminoguanidine administration to ... | 2008 | 18761417 |
| reverse genetics screen identifies six proteins important for malaria development in the mosquito. | transmission from the vertebrate host to the mosquito vector represents a major population bottleneck in the malaria life cycle that can successfully be targeted by intervention strategies. however, to date only about 25 parasite proteins expressed during this critical phase have been functionally analysed by gene disruption. we describe the first systematic, larger scale generation and phenotypic analysis of plasmodium berghei knockout (ko) lines, characterizing 20 genes encoding putatively sec ... | 2008 | 18761621 |
| design and in vivo pharmacodynamic evaluation of nanostructured lipid carriers for parenteral delivery of artemether: nanoject. | the objective of the present investigation was to explore the potential of nanostructured lipid carriers (nlc) for the intravenous delivery of artemether (arm), a poorly water-soluble antimalarial agent. the nlc of arm (nanoject) were formulated by employing a microemulsion template technique. the nlc were evaluated for particle size, encapsulation efficiency, in vitro drug release and in vitro hemolysis. the antimalarial activity of the nanoject and conventional arm injectable formulation was e ... | 2008 | 18765274 |
| influence of chlorpromazine on eryptosis, parasitemia and survival of plasmodium berghe infected mice. | chlorpromazine has previously been shown to trigger suicidal erythrocyte death or eryptosis, which is characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. premature suicidal death of infected erythrocytes is in turn considered to delay development of parasitemia and thus favourably influence the clinical course of malaria. the present experiments have been performed to explore whether chlorpromazine influences in vitro parasite growth and eryptosis of pl ... | 2008 | 18769053 |
| hyperbaric oxygen prevents early death caused by experimental cerebral malaria. | cerebral malaria (cm) is a syndrome characterized by neurological signs, seizures and coma. despite the fact that cm presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. hyperbaric oxygen (hbo) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis. | 2008 | 18769544 |
| computational analysis of constraints on noncoding regions, coding regions and gene expression in relation to plasmodium phenotypic diversity. | malaria-causing plasmodium species exhibit marked differences including host choice and preference for invading particular cell types. the genetic bases of phenotypic differences between parasites can be understood, in part, by investigating constraints on gene expression and genic sequences, both coding and regulatory. | 2008 | 18769675 |
| immunological profile of a plasmodium vivax ama-1 n-terminus peptide-carbon nanotube conjugate in an infected plasmodium berghei mouse model. | we have covalently conjugated an n-terminus plasmodium vivax apical membrane antigen-1 (ama-1) peptide to functionalized carbon nanotubes (f-cnt). immunological characterization of this molecular conjugate revealed that the immunogen-ama-1 peptide was appropriately presented after being conjugated to cnts as well as being recognized by balb/c polyclonal antibodies. subsequent experiments lead us to assess the ama-1 peptide alone, as well as the cnt-peptide conjugate regarding rodent malarial inf ... | 2008 | 18771700 |
| intracellular calcium levels in the plasmodium berghei ookinete. | ookinetes are the motile and invasive stages of plasmodium parasites in the mosquito host. here we explore the role of intracellular ca2+ in ookinete survival and motility as well as in the formation of oocysts in vitro in the rodent malaria parasite plasmodium berghei. treatment with the ca2+ ionophore a23187 induced death of the parasite, an effect that could be prevented if the ookinetes were co-incubated with insect cells before incubation with the ionophore. treatment with the intracellular ... | 2008 | 18775093 |
| memory cd8 t cell responses exceeding a large but definable threshold provide long-term immunity to malaria. | infection of mice with sporozoites of plasmodium berghei or plasmodium yoelii has been used extensively to evaluate liver-stage protection by candidate preerythrocytic malaria vaccines. unfortunately, repeated success of such vaccines in mice has not translated readily to effective malaria vaccines in humans. thus, mice may be used better as models to dissect basic parameters required for immunity to plasmodium-infection than as preclinical vaccine models. in turn, this basic information may aid ... | 2008 | 18780790 |
| oxidative folding of synthetic polypeptides s-protected as tert-butylthio derivatives. | a new method for oxidative folding of synthetic polypeptides assembled by stepwise solid phase synthesis is introduced. folding is obtained in excellent yields by reacting s-tert-butylthiolated polypeptides with a 100-fold molar excess of cysteine at 37 degrees c in a slightly alkaline buffer containing chaotropic salts, and in the presence of air-oxygen. this novel protocol has been applied to the folding of s-tert-butylthiolated human thymus and activation-regulated chemokine (hu-tarc) derivat ... | 2008 | 18781562 |
| effect of cyclosporine on parasitemia and survival of plasmodium berghei infected mice. | cyclosporine triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. the present study explored whether cyclosporine influences eryptosis of plasmodium infected erythrocytes, development of parasitemia and thus the course of the disease. annexin v binding was utilized to depict phosphatidylserine exposure and forward scatter in facs analysis to estimate erythrocyte volume. in vitro infection of huma ... | 2008 | 18789889 |
| plasmodium berghei: lack of antimalarial activity of an analogue of folate precursor, 2,4-diamino-6-hydroxymethylpteridine in a mouse model. | it was earlier hypothesized that the malarial parasite may convert precursors of folate analogues to synthesize de novo inhibitors toxic to itself, but not to the mammalian cell. it was suggested that one such analogue, 2,4-diamino-6-hydroxymethylpteridine (dap) may be converted to aminopterin (amp), a known dihydrofolate reductase inhibitor. in the present study, we evaluated the ability of dap to inhibit proliferation of plasmodium berghei nk65 in mice, with(out) folinic acid rescue. cumulativ ... | 2008 | 18789931 |
| use of a drosophila model to identify genes regulating plasmodium growth in the mosquito. | we performed a forward genetic screen, using drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, plasmodium gallinaceum. we identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. presumptive mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. none of the identified genes have been previously implicated in innate immune responses ... | 2008 | 18791251 |
| growth-inhibitory effect of a fucoidan from brown seaweed undaria pinnatifida on plasmodium parasites. | the present study was undertaken to investigate the inhibitory effects of fucoidan, a sulfated polysaccharide isolated from the edible brown seaweed undaria pinnatifida, on the growth of plasmodium parasites. in order to assess the anti-malarial activity of fucoidan, growth inhibition activities were evaluated using cultured plasmodium falciparum parasites in vitro and on plasmodium berghei-infected mice in vivo. fucoidan significantly inhibited the invasion of erythrocytes by p. falciparum mero ... | 2009 | 18791738 |
| blood-stage plasmodium infection induces cd8+ t lymphocytes to parasite-expressed antigens, largely regulated by cd8alpha+ dendritic cells. | although cd8(+) t cells do not contribute to protection against the blood stage of plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ecm). at present, there is no direct evidence that the cd8(+) t cells mediating ecm are parasite-specific or, for that matter, whether parasite-specific cd8(+) t cells are generated in response to blood-stage infection. to resolve this and to define the cellular requirements for such priming, ... | 2008 | 18799734 |
| the analgesic and antiplasmodial activities and toxicology of vernonia amygdalina. | vernonia amygdalina possesses several bioactive compounds and is used in traditional medicines of southwestern uganda, along with other regions. its analgesic potential has not been investigated thus far. the present study examines the antinociceptive potential of the aqueous leaf extract (50-200 mg/kg) using three models of nociception (acetic acid-induced writhing, formalin test, and tail-flick test), antiplasmodial activity, and toxicology of the extract. the results show the extract signific ... | 2008 | 18800909 |
| complete protection against p. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing salmonella type iii secretion system and bordetella adenylate cyclase toxoid. | sterile immunity against malaria can be achieved by the induction of ifngamma-producing cd8(+) t cells that target infected hepatocytes presenting epitopes of the circumsporozoite protein (csp). in the present study we evaluate the protective efficacy of a heterologous prime/boost immunization protocol based on the delivery of the cd8(+) epitope of plasmodium berghei csp into the mhc class i presentation pathway, by either a type iii secretion system of live recombinant salmonella and/or by dire ... | 2008 | 18804138 |
| carbonic anhydrase inhibitors: inhibition of plasmodium falciparum carbonic anhydrase with aromatic/heterocyclic sulfonamides-in vitro and in vivo studies. | a library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds has been assayed for inhibition of the carbonic anhydrase (ca, ec 4.2.1.1) from the malaria parasite plasmodium falciparum (pfca). low micromolar and submicromolar in vitro inhibitors were detected, whereas several compounds showed ex vivo anti-p. falciparum activity, in cell cultures. one derivative, that is, 4-(3,4-dichlorophenylureido)thioureido-benzenesulfonamide was an effective in vitro pfca inhibitor ... | 2008 | 18805693 |
| transgenic rodent plasmodium berghei parasites as tools for assessment of functional immunogenicity and optimization of human malaria vaccines. | | 2008 | 18806208 |
| localisation of laminin within plasmodium berghei oocysts and the midgut epithelial cells of anopheles stephensi. | abstract: | 2008 | 18808667 |
| rapid identification of plasmodium-carrying mosquitoes using loop-mediated isothermal amplification. | with an aim to develop a quick and simple method to survey pathogen-transmitting vectors, lamp (loop-mediated isothermal amplification) was applied to the identification of plasmodium-carrying mosquitoes, specifically a plasmodium-transmitting experimental model using rodent malaria parasite (plasmodium berghei) and anopheline mosquitoes (anopheles stephensi). the detection sensitivity limit of the lamp reaction amplifying the spect2 gene was determined to be 1 x 10(2) purified plasmodium parasi ... | 2008 | 18809384 |
| synthesis and antimalarial activity of pyrazolo and pyrimido benzothiazine dioxide derivatives. | a series of phenylsubstituted pyrazolo and pyrimido benzothiazine dioxide derivatives were synthesized and investigated for their abilities to inhibit beta-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent plasmodium berghei. compounds 3-amino-7-chloro-9-(2'-methylphenyl)-1,9-dihydro-pyrazolo-[4,3-b]benzothiazine 4,4-dioxide 2b and 2,4-diamino-8-chloro-10h-phenyl-pyrimido-[5,4-b]benzothiazine 5,5-dioxide 3a were the most promising as inhibitors of hem ... | 2009 | 18835067 |
| protective cd8 t cells against plasmodium liver stages: immunobiology of an 'unnatural' immune response. | summary: immunization with high doses of irradiated sporozoites delivered by the bites of infected mosquitoes has been shown to induce protective responses against malaria, mediated in part by cd8(+) t cells. in contrast, natural transmission involving low exposure to live sporozoite antigen fails to elicit strong immunity. in this review, we examine how irradiated sporozoite immunization breaks the natural host-parasite interaction and induces protective cd8(+) t cells. upon biting, the malaria ... | 2008 | 18837788 |
| complement factors c1q, c3 and c5 in brain and serum of mice with cerebral malaria. | the patho-mechanisms leading to brain damage due to cerebral malaria (cm) are yet not fully understood. immune-mediated and ischaemic mechanisms have been implicated. the role of complement factors c1q, c3 and c5 for the pathogenesis of cm were investigated in this study. | 2008 | 18847493 |