Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| recombinant human ifn-alpha inhibits cerebral malaria and reduces parasite burden in mice. | most c57bl/6 mice infected i.p. with plasmodium berghei anka (pba) die between 7 and 14 days with neurologic signs, and the remainder die later (>15 days) with severe anemia. daily i.p. injections of a recombinant human ifn-alpha (active on mouse cells) prevented death by cerebral malaria (87% deaths in the control mice vs 6% in ifn-alpha-treated mice). the mechanisms of this ifn-alpha protective effect were multiple. ifn-alpha-treated, pba-infected mice showed 1) a marked decrease in the number ... | 2007 | 17475871 |
| minimum requirements for ookinete to oocyst transformation in plasmodium. | during their passage through a mosquito vector, malaria parasites undergo several developmental transformations including that from a motile zygote, the ookinete, to a sessile oocyst that develops beneath the basal lamina of the midgut epithelium. this transformation process is poorly understood and the oocyst is the least studied of all the stages in the malaria life cycle. we have used an in vitro culture system to monitor morphological features associated with transformation of plasmodium ber ... | 2007 | 17482621 |
| synthesis and antimalarial activity of new analogues of amodiaquine. | in order to determine the real significance of the 4'-phenolic group in the antimalarial activity and/or cytotoxicity of amodiaquine (aq), analogues for which this functionality was shifted or modified were synthesized. good in vitro antimalarial activity was obtained for compounds unable to form intramolecular hydrogen bond. among the compounds synthesized, new amino derivative 5 displayed the greatest selectivity index towards the most cq-resistant strain tested and was active in mice infected ... | 2008 | 17485145 |
| comparative antimalarial activities of six pairs of 1,2,4,5-tetraoxanes (peroxide dimers) and 1,2,4,5,7,8-hexaoxonanes (peroxide trimers). | six tetraoxanes had 50% inhibitory concentrations in the range of 10 to 100 ng/ml against plasmodium falciparum, whereas the corresponding hexaoxonanes had minimal antimalarial activity. the lack of iron-mediated reactivity of the hexaoxonanes may explain their low activity compared to the tetraoxanes, the latter of which are able to undergo iron(ii)-mediated activation. | 2007 | 17485500 |
| antimalarial activity of some plants traditionally used in meru district of kenya. | ten plant extracts commonly used by the meru community of kenya were evaluated for the in vitro antiplasmodial, in vivo antimalarial, cytotoxicity and animal toxicity activities. the water and methanol extracts of ludwigia erecta and the methanol extracts of fuerstia africana and schkuhria pinnata exhibited high antiplasmodial activity (ic(50) < 5 microg/ml) against chloroquine sensitive (d6) and resistant (w2) plasmodium falciparum clones. the cytotoxicity of these highly active extracts on ver ... | 2007 | 17486688 |
| heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. | cerebral malaria claims more than 1 million lives per year. we report that heme oxygenase-1 (ho-1, encoded by hmox1) prevents the development of experimental cerebral malaria (ecm). balb/c mice infected with plasmodium berghei anka upregulated ho-1 expression and activity and did not develop ecm. deletion of hmox1 and inhibition of ho activity increased ecm incidence to 83% and 78%, respectively. ho-1 upregulation was lower in infected c57bl/6 compared to balb/c mice, and all infected c57bl/6 mi ... | 2007 | 17496899 |
| germinal center architecture disturbance during plasmodium berghei anka infection in cba mice. | immune responses to malaria blood stage infection are in general defective, with the need for long-term exposure to the parasite to achieve immunity, and with the development of immunopathology states such as cerebral malaria in many cases. one of the potential reasons for the difficulty in developing protective immunity is the poor development of memory responses. in this paper, the potential association of cellular reactivity in lymphoid organs (spleen, lymph nodes and peyer's patches) with im ... | 2007 | 17506896 |
| identifying and characterising the plasmodium falciparum rhoph3 plasmodium vivax homologue. | four plasmodium species cause malaria in humans, plasmodium falciparum being the most widely studied to date. all plasmodium species have paired club-shaped organelles towards their apical extreme named rhoptries that contain many lipids and proteins which are released during target cell invasion. p. falciparum rhoph3 is a rhoptry protein triggering important immune responses in patients from endemic regions. it has also been shown that anti-rhoph3 antibodies inhibit in vitro invasion of erythro ... | 2007 | 17511961 |
| clip proteases and plasmodium melanization in anopheles gambiae. | melanization is a potent immune response mediated by phenoloxidase (po). multiple clip-domain serine proteases (clip) regulate po activation as part of a complex cascade of proteases that are cleaved sequentially. the role of several clip as key activators or suppressors of the melanization responses of anopheles gambiae to plasmodium berghei (murine malaria) has been established recently using a genome-wide reverse genetics approach. important differences in regulation of po activation between ... | 2007 | 17512801 |
| plasmodium berghei-infected primary hepatocytes process and present the circumsporozoite protein to specific cd8+ t cells in vitro. | a substantial and protective response against malaria liver stages is directed against the circumsporozoite protein (csp) and involves induction of cd8(+) t cells and production of ifn-gamma. csp-derived peptides have been shown to be presented on the surface of infected hepatocytes in the context of mhc class i molecules. however, little is known about how the csp and other sporozoite ags are processed and presented to cd8(+) t cells. we investigated how primary hepatocytes from balb/c mice pro ... | 2007 | 17513754 |
| plasmodium yoelii sporozoites with simultaneous deletion of p52 and p36 are completely attenuated and confer sterile immunity against infection. | malaria infection starts when sporozoites are transmitted to the mammalian host during a mosquito bite. sporozoites enter the blood circulation, reach the liver, and infect hepatocytes. the formation of a parasitophorous vacuole (pv) establishes their intracellular niche. recently, two members of the 6-cys domain protein family, p52 and p36, were each shown to play an important albeit nonessential role in plasmodium berghei sporozoite infectivity for the rodent host. here, we generated p52/p36-d ... | 2007 | 17517871 |
| allelic penetrance approach as a tool to model two-locus interaction in complex binary traits. | many binary phenotypes do not follow a classical mendelian inheritance pattern. interaction between genetic and environmental factors is thought to contribute to the incomplete penetrance phenomena often observed in these complex binary traits. several two-locus models for penetrance have been proposed to aid the genetic dissection of binary traits. such models assume linear genetic effects of both loci in different mathematical scales of penetrance, resembling the analytical framework of quanti ... | 2007 | 17551528 |
| a recombinant 19 kda plasmodium berghei merozoite surface protein 1 formulated with alum induces protective immune response in mice. | we investigated the immunogenicity of recombinant rmsp1 (rpbmsp1) that was generated from plasmodium berghei. the rpbmsp1 formulated in alum was found to be immunogenic which induced high levels of specific anti-rpbmsp1 antibody. the igg2a response predominated over igg1 during the challenge infection in the vaccinated mice. mice vaccinated with rpbmsp1 in alum mounted significant protective immunity against challenge infection (p < 0.01). on day 121 after the booster, three out of ten mice immu ... | 2007 | 17568385 |
| plasmodium berghei: antiparasitic effects of orally administered hypoestoxide in mice. | hypoestoxide (he) is a diterpene isolated from hypoestes rosea (acanthaceae), a plant indigenous to nigeria. previous studies demonstrated that he exhibited potent anti-inflammatory and anti-cancer activities in well established animal models but weak in vitro activities in both the anti-inflammation and anti-cancer in vitro screening systems. we now report a similar observation in the in vitro and in vivo screening systems for antimalarial activity. the results indicate that while he exhibits a ... | 2007 | 17568581 |
| antimalarial activity of some plants traditionally used in treatment of malaria in kwale district of kenya. | methanolic and water extracts of five medicinal plant species used for treatment of malaria in traditional/cultural health systems of kwale people in kenya were tested for antimalarial activity against plasmodium falciparum and plasmodium berghei, respectively and for their cytotoxic effects. the most active extracts (ic(50)<10 microg/ml) screened against chloroquine (cq) sensitive (d6) and resistant (w2) p. falciparum clones, were the water and methanol extracts of maytenus undata (thunb.) blak ... | 2007 | 17572031 |
| the role of dna mismatch repair in generating genetic diversity and drug resistance in malaria parasites. | although the mechanisms by which malaria parasites develop resistance to drugs are unclear, current knowledge suggests a main mechanism of resistance is the alteration of target enzymes by point mutation. in other organisms, defects in dna mismatch repair have been linked to increased mutation rates and drug resistance. we have identified an unusual complement of mismatch repair genes in the plasmodium genome. an initial functional test of two of these genes (pfmsh2-1 and pfmsh2-2) using a domin ... | 2007 | 17583362 |
| development of a pharmacodynamic model of murine malaria and antimalarial treatment with dihydroartemisinin. | antimalarial treatment strategies based on in vitro studies are limited by the paucity of pharmacodynamic information for dosage regimen design. we postulated that a murine model could be used for pre-clinical stages of drug development, especially in dose-response studies and evaluation of combination therapies. swiss mice infected with plasmodium berghei parasites (2-5% starting parasitaemia) were given dihydroartemisinin (0-100 mg/kg single dose). parasite density was regularly determined fro ... | 2007 | 17585920 |
| genetically attenuated plasmodium berghei liver stages persist and elicit sterile protection primarily via cd8 t cells. | live-attenuated plasmodium liver stages remain the only experimental model that confers complete sterile protection against malaria. irradiation-attenuated plasmodium parasites mediate protection primarily by cd8 t cells. in contrast, it is unknown how genetically attenuated liver stage parasites provide protection. here, we show that immunization with uis3(-) sporozoites does not cause breakthrough infection in t and b-cell-deficient rag1(-/-) and ifn-gamma(-/-) mice. however, protection was ab ... | 2007 | 17591958 |
| plasmodium berghei induced biochemical alterations in pregnant mice. | malaria leads to pathophysiological and biochemical alterations in placenta and blood of pregnant mice. a significant decrease in the sugar, protein and lipid levels in the placental homogenate of pregnant-infected mice was observed compared to the pregnant mice. however, serum protein content was not altered much in the pregnant-infected mice as compared to the levels in control mice. the serum lipid level enhanced significantly in both pregnant and non pregnant-infected mice. the enzymatic act ... | 2007 | 17593679 |
| a role for natural regulatory t cells in the pathogenesis of experimental cerebral malaria. | cerebral malaria (cm) is a serious complication of plasmodium falciparum infection that is responsible for a significant number of deaths in children and nonimmune adults. a failure to control blood parasitemia and subsequent sequestration of parasites to brain microvasculature are thought to be key events in many cm cases. here, we show for the first time, to our knowledge, that cd4(+)cd25(+)foxp3(+) natural regulatory t (treg) cells contribute to pathogenesis by modulating immune responses in ... | 2007 | 17600128 |
| plasmodium berghei xat: contribution of gammadelta t cells to host defense against infection with blood-stage nonlethal malaria parasite. | we examined a potential role of gammadelta t cells in protective immunity to blood-stage plasmodium berghei xat infection. plasmodium berghei xat is an attenuated variant of the lethal strain p. berghei nk65 and its infection is self-resolving in immune competent mice. to determine whether gammadelta t cells are essential for the resolution of p. berghei xat malaria, mice were depleted of gammadelta t cells with anti-tcrgammadelta antibody treatment. although mice that had received control antib ... | 2007 | 17601562 |
| the antiplasmodial activity of spermine alkaloids isolated from albizia gummifera. | in the present study the methanolic extract of albizia gummifera was fractionated into various fractions. these fractions were tested against choroquine sensitive (nf54) and resistant (ent30) strains of plasmodium falciparum. all other fractions apart from the alkaloidal fraction showed low activity with ic 50 above 3 microg/ml. the alkaloidal fraction exhibited strong activity against nf54 and ent30 with ic 50 of 0.16+/-0.05 and 0.99+/-0.06 microg/ml, respectively. five known spermine alkaloids ... | 2007 | 17601685 |
| genetically attenuated p36p-deficient plasmodium berghei sporozoites confer long-lasting and partial cross-species protection. | immunisation with live, radiation-attenuated sporozoites (ras) or genetically attenuated sporozoites (gas) of rodent plasmodial parasites protects against subsequent challenge infections. we recently showed that immunisation with plasmodium berghei gas that lack the microneme protein p36p protects mice for a period of up to 4 months. here, we show that the period of full protection induced by p36p(-)-sporozoites lasts 12 and 18 months in c57bl6 and balb/c mice, respectively. full protection is a ... | 2007 | 17604034 |
| efficacy, pharmacokinetics, and metabolism of tetrahydroquinoline inhibitors of plasmodium falciparum protein farnesyltransferase. | new antimalarials are urgently needed. we have shown that tetrahydroquinoline (thq) protein farnesyltransferase (pft) inhibitors (pftis) are effective against the plasmodium falciparum pft and are effective at killing p. falciparum in vitro. previously described thq pftis had limitations of poor oral bioavailability and rapid clearance from the circulation of rodents. in this paper, we validate both the caco-2 cell permeability model for predicting thq intestinal absorption and the in vitro live ... | 2007 | 17606674 |
| structural basis for conserved complement factor-like function in the antimalarial protein tep1. | thioester-containing proteins (teps) are a major component of the innate immune response of insects to invasion by bacteria and protozoa. teps form a distinct clade of a superfamily that includes the pan-protease inhibitors alpha(2)-macroglobulins and vertebrate complement factors. the essential feature of these proteins is a sequestered thioester bond that, after cleavage in a protease-sensitive region of the protein, is activated and covalently binds to its target. recently, tep1 from the mala ... | 2007 | 17606907 |
| co-infection with trypanosoma cruzi protects mice against early death by neurological or pulmonary disorders induced by plasmodium berghei anka. | the objective of this study was to investigate whether the infection of c57bl/6 mice by p. berghei anka, which causes severe malaria, was modulated by co-infection with trypanosoma cruzi. | 2007 | 17620126 |
| genetically attenuated plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex class i-dependent interferon-gamma-producing cd8+ t cells. | at present, radiation-attenuated plasmodia sporozoites ( gamma -spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. however, gamma -spz are not without risks. for example, the heterogeneity of the gamma -spz could explain occasional breakthrough infections. to avoid this possibility, we constructed a double-knockout p. berghei parasite by removing 2 genes, uis3 and uis4, that are up-regulated in infective spz. we evaluated the doub ... | 2007 | 17624847 |
| aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence. | human and rodent erythrocytes are known to be highly permeable to glycerol. aquaglyceroporin aquaporin (aqp)3 is the major glycerol channel in human and rat erythrocytes. however, aqp3 expression has not been observed in mouse erythrocytes. here we report the presence of an aquaglyceroporin, aqp9, in mouse erythrocytes. aqp9 levels rise as reticulocytes mature into erythrocytes and as neonatal pups develop into adult mice. mice bearing targeted disruption of both alleles encoding aqp9 have eryth ... | 2007 | 17636116 |
| [expression and immunogenicity evaluation of ectodomain and subdomains of plasmodium berghei apical membrane antigen 1]. | to express and evaluate the immunogenicity of ectodomain and its subdomains of plasmodium berghei apical membrane antigen i (pbama-1). | 2007 | 17639690 |
| in vivo imaging of malaria parasites in the murine liver. | the form of the malaria parasite inoculated by the mosquito, called the sporozoite, transforms inside the host liver into thousands of a new form of the parasite, called the merozoite, which infects erythrocytes. we present here a protocol to visualize in vivo the behavior of plasmodium berghei parasites in the hepatic tissue of the murine host. the use of gfp-expressing parasites and a high-speed spinning disk confocal microscope allows for the acquisition of four-dimensional images, which prov ... | 2007 | 17641649 |
| functional characterization of both map kinases of the human malaria parasite plasmodium falciparum by reverse genetics. | the kinome of the human malaria parasite plasmodium falciparum includes two genes encoding mitogen-activated protein kinase (mapk) homologues, pfmap-1 and pfmap-2, but no clear orthologue of the mapk kinase (mapkk) family, raising the question of the mode of activation and function of the plasmodial mapks. functional studies in the rodent malaria model plasmodium berghei recently showed the map-2 gene to be dispensable for asexual growth and gametocytogenesis, but essential for male gametogenesi ... | 2007 | 17651389 |
| induction of experimental cerebral malaria is independent of tlr2/4/9. | the contribution of the toll-like receptor (tlr) cascade to the pathogenesis of cerebral malaria (cm) is controversially discussed. tlr2 and tlr9 were reported to be involved in the induction of cm in a study while recently tlr signaling was shown to be dispensable for the development of cm. using plasmodium berghei anka (pba) infection of mice as a model of cm, we demonstrate here that the induction of cm is independent of tlr2, 4 and 9. using triple tlr2/4/9-deficient mice, we exclude synergis ... | 2008 | 17668237 |
| disruption of plasmodium falciparum development by antibodies against a conserved mosquito midgut antigen. | malaria parasites must undergo development within mosquitoes to be transmitted to a new host. antivector transmission-blocking vaccines inhibit parasite development by preventing ookinete interaction with mosquito midgut ligands. therefore, the discovery of novel midgut antigen targets is paramount. jacalin (a lectin) inhibits ookinete attachment by masking glycan ligands on midgut epithelial surface glycoproteins. however, the identities of these midgut glycoproteins have remained unknown. here ... | 2007 | 17673553 |
| synthesis and antimalarial activity of novel chiral and achiral benzenesulfonamides bearing 1, 3, 4-oxadiazole moieties. | a series of new benzenesulfonamides, most of which are chiral, incorporating 1, 3, 4-oxadiazole and amino acid moieties have been synthesized. some of these compounds were screened for antimalarial activity and also evaluated for their ability to inhibit hem polymerization. the electrophoretic analysis indicated that one compound was effective in inhibiting the degradation of hemoglobin. the synthesized compounds were tested in mice infected with plasmodium berghei. these derivatives have the po ... | 2007 | 17674812 |
| calcium channel antagonist (nifedipine) attenuates plasmodium berghei-specific t cell immune responses in balb/c mice. | nifedipine and verapamil (martin et al. science 1987;235:899-901) are a class of calcium channel blockers involved in the reversal of chloroquine (cq) drug resistance in cq-sensitive plasmodium spp. nifedipine alters calcium-dependent functions of macrophages and neutrophils during plasmodium berghei malaria. however, knowledge of nifedipine-induced immunomodulation of t cell functions during p. berghei malaria is still limited. we investigated the effect of nifedipine on the immune status of sp ... | 2007 | 17696947 |
| exposure of plasmodium sporozoites to the intracellular concentration of potassium enhances infectivity and reduces cell passage activity. | malaria sporozoites migrate through several cells prior to a productive invasion that involves the formation of a parasitophorous vacuole (pv) where sporozoites undergo transformation into exo-erythorcytic forms (eefs). the precise mechanism leading to sporozoite activation for invasion is unknown, but prior traversal of host cells is required. during cell migration sporozoites are exposed to large shifts in k(+) concentration. we report here that incubation of sporozoites to the intracellular k ... | 2007 | 17714805 |
| protective effect of antilymphocyte serum on mice infected with plasmodium berghei. | rabbit antiserum to mouse lymphocytes prolonged the survival of mice infected with plasmodium berghei. since antilymphocyte serum has a well-defined, potent immunosuppressive effect, the immune response of the host to the parasite actually may contribute to the death of the animal with an acute malarial infection. | 1969 | 17749380 |
| ultrastructural pathological changes in mice kidney caused by plasmodium berghei infection. | malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. this work reports under electron microscopy studies serious ultrastructural kidney damage such as extensive cytoplasmic vacuolation, vesiculation and autophagic vacuoles in proximal tubular cells. a thickened endothelial wall on peritubular capillary, interdigitation disorganization and significant decrease of their number in some areas were detected. swollen rough endoplasmic reticulum, s ... | 2006 | 17784642 |
| direct microscopic quantification of dynamics of plasmodium berghei sporozoite transmission from mosquitoes to mice. | the number of malaria sporozoites delivered to a host by mosquitoes is thought to have a significant influence on the subsequent course of the infection in the mammalian host. we did studies with anopheles stephensi mosquitoes with salivary gland infections of plasmodium berghei sporozoites expressing a red fluorescent protein. after individual mosquitoes fed on an ear pinna or the ventral abdomen of a mouse, fluorescence microscopy was used to count numbers of sporozoites. mosquitoes allowed to ... | 2007 | 17785479 |
| systemic tumor necrosis factor generated during lethal plasmodium infections impairs dendritic cell function. | dendritic cells (dcs) initiate innate and adaptive immune responses including those against malaria. although several studies have shown that dc function is normal during malaria, other studies have shown compromised function. to establish why these studies had different findings, we examined dcs from mice infected with two lethal species of parasite, plasmodium berghei or p. vinckei, and compared them to dcs from nonlethal p. yoelii 17xnl or p. chabaudi infections. these studies found that dcs ... | 2007 | 17785836 |
| ligation of b and t lymphocyte attenuator prevents the genesis of experimental cerebral malaria. | b and t lymphocyte attenuator (btla; cd272) is a coinhibitory receptor that is predominantly expressed on t and b cells and dampens t cell activation. in this study, we analyzed the function of btla during infection with plasmodium berghei anka. infection of c57bl/6 mice with this strain leads to sequestration of leukocytes in brain capillaries that is associated with a pathology resembling cerebral malaria in humans. during the course of infection, we found an induction of btla in several organ ... | 2007 | 17785848 |
| plasmodium berghei: enhanced protective immunity after vaccination of white rats born of immune mothers. | young white rats born of immune mothers had a significantly higher level of immunity to plasmodium berghei after immunization with a nonliving antigen than either unvaccinated littermates or vaccinated rats born of normal nonimmune mothers. | 1971 | 17839823 |
| the salivary glands and saliva of anopheles gambiae as an essential step in the plasmodium life cycle: a global proteomic study. | proteins synthesized in the salivary glands of the anopheles gambiae mosquito are thought to be important in the life cycle of the malaria parasite plasmodium. to describe a. gambiae salivary gland and saliva contents, we combined several techniques: 1-de, 2-de and lc ms/ms. this study has identified five saliva proteins and 122 more proteins from the salivary glands, including the first proteomic description for 89 of these salivary gland proteins. since the invasion and sporozoite maturation t ... | 2007 | 17849406 |
| malaria infection modulates effects of genotoxic chemicals in the mouse bone-marrow micronucleus test. | malaria has been reported to modulate the activity of cytochrome-p450 enzymes (cyp). since cyps are involved both in the activation and detoxication of xenobiotics, we investigated whether malaria would modify the effects of chemical carcinogens in the bone-marrow micronucleus assay. female c57bl6 mice were infected with plasmodium berghei (anka) and treated (ip route) with cyclophosphamide (cpa, 25 mg/kg body weight), 7,12-dimethylbenz[a]anthracene (dmba, 50mg/kg body weight) or ethyl methanesu ... | 2008 | 17851116 |
| flow cytometric analysis of micronuclei in peripheral blood reticulocytes iii. an efficient method of monitoring chromosomal damage in the beagle dog. | erythrocyte-based micronucleus tests have traditionally analyzed bone marrow because splenic filtration in most species removes micronucleated cells from peripheral blood. we have evaluated a flow cytometric method for monitoring micronucleated reticulocyte frequencies (%mn-ret) in the peripheral blood of beagle dogs treated with cyclophosphamide (cp) and have found that analysis of micronucleated reticulocytes (mn-rets) in peripheral blood is a suitable surrogate for bone marrow analysis. the t ... | 2007 | 17872896 |
| pharmacodynamics of doxycycline in a murine malaria model. | doxycycline is reported to impair second-generation parasite schizogony. the effects of doxycycline alone and combined with dihydroartemisinin were investigated in a murine malaria model. doxycycline lowered the rate of parasite growth within 2 days, with maximum effect in 6 days. addition of dihydroartemisinin led to an additive antimalarial effect. | 2007 | 17876000 |
| deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives(1). | the synthesis of deoxycholic acid (dca)- and cholic acid (ca)-derived mixed tetraoxanes revealed that n-(2-dimethylamino)ethyl derivatives are potent antimalarials in vitro and in vivo. the tetraoxanes presented in this paper are dual inhibitors: besides curing mice in vivo without observed toxic effects, they kill cancer cell lines at very low concentrations. for example, dca and ca derivatives 16 and 25 cured 3/5 (160 mg/kg/day) and 2/5 (40 mg/kg/day, mtd >960 mg/kg), respectively, and they we ... | 2007 | 17887664 |
| lead decreases parasitemia and enhances survival of plasmodium berghei-infected mice. | malaria, a disease accounting for more than one million deaths per year, is caused by intraerythrocytic growth of plasmodia. parasitemia may be blunted by suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and phosphatidylserine exposure. triggers of eryptosis include lead nitrate (pb(no3)2). as shown here, pb(no3)2 (> or = 10 microm) increased phosphatidylserine exposure of plasmodium falciparum-infected human erythrocytes, an effect significantly more marked than ... | 2007 | 17888870 |
| vesicle trafficking during sporozoite development in plasmodium berghei: ultrastructural evidence for a novel trafficking mechanism. | oocysts from anopheles stephensi mosquitoes fed on murine blood infected with plasmodium berghei berghei, were fixed for electron microscopy 6-12 days post-feeding. ultrastructural analysis focused on golgi-related trafficking pathways for rhoptry and microneme formation during sporogony. a small golgi complex of 1-3 cisternae is formed close to the spindle pole body from coated vesicles budded from the nuclear envelope which is confluent with the endoplasmic reticulum. rhoptries begin as small ... | 2008 | 17908361 |
| combination of protein and viral vaccines induces potent cellular and humoral immune responses and enhanced protection from murine malaria challenge. | the search for an efficacious vaccine against malaria is ongoing, and it is now widely believed that to confer protection a vaccine must induce very strong cellular and humoral immunity concurrently. we studied the immune response in mice immunized with the recombinant viral vaccines fowlpox strain fp9 and modified virus ankara (mva), a protein vaccine (cv-1866), or a combination of the two; all vaccines express parts of the same preerythrocytic malaria antigen, the plasmodium berghei circumspor ... | 2007 | 17908809 |
| in vitro and in vivo antiplasmodial activity of 'saye', an herbal remedy used in burkina faso traditional medicine. | 'saye', a traditional medicine used in burkina faso, which consists of extracts of cochlospermum planchonii (rhizome), cassia alata (leaf) and phyllanthus amarus (whole plant), showed a significant effect against plasmodium falciparum and plasmodium berghei parasites grown in vivo (ic(50) = 80.11 +/- 3.40 microg/ml; ed(50) = 112.78 +/- 32.32 mg/kg). in vitro the activity was lower. | 2008 | 17926335 |
| c3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against plasmodium berghei. | immune response against circumsporozoite protein (csp) of plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. engineered dna vaccine encoding csp and 3 copies of c3d caused an unexpected loss in protection attributed to the binding of c3d to the c-terminal region of csp. because the c3d region known as p28 represents the complement receptor (cr) 2-binding motif, we developed a csp-3 copies of p28 dna construct (csp-3p28). csp-3p28-i ... | 2007 | 17931754 |
| plasmodium falciparum: effect of radiation on levels of gene transcripts in sporozoites. | humans immunized by the bites of irradiated plasmodium falciparum (pf) sporozoite-infected mosquitoes are protected against malaria. radiation attenuates the sporozoites preventing them from fully developing and replicating in hepatocytes, but the effects of radiation on gene expression in sporozoites are unknown. we used rt-pcr (35 cycles of pcr followed by densitometry) to assess the expression of ten genes in pf sporozoites, and in sporozoites irradiated with 15,000cgy. irradiation reduced ex ... | 2008 | 17935717 |
| il-12p40-independent induction of protective immunity upon multiple plasmodium berghei irradiated sporozoite immunizations. | both ifn-gamma and il-12 play critical roles in defence against malaria. in a previous study, using plasmodium yoelii model, c57bl/6 ifn-gamma receptor deficient mice (ifn-gammar-/-) failed to develop protective immunity after a single immunization with irradiated sporozoites, but were protected after multiple immunizations. in contrast, in another study, balb/c ifn-gamma gene knockout mice (ifn-gamma-/-) and balb/c il-12-deficient mice (il-12p40-/- and il-12p35-/-) were unable to mount protecti ... | 2007 | 17944743 |
| cross-protection between attenuated plasmodium berghei and p. yoelii sporozoites. | an attenuated plasmodium falciparum sporozoite (pfspz) vaccine is under development, in part, based on studies in mice with p. berghei. we used p. berghei and p. yoelii to study vaccine-induced protection against challenge with a species of parasite different from the immunizing parasite in balb/c mice. one-hundred percent of mice were protected against homologous challenge. seventy-nine percent immunized with attenuated p. berghei sporozoite (pbspz) (six experiments) were protected against chal ... | 2007 | 17944745 |
| spiro- and dispiro-1,2-dioxolanes: contribution of iron(ii)-mediated one-electron vs two-electron reduction to the activity of antimalarial peroxides. | fourteen spiro- and dispiro-1,2-dioxolanes were synthesized by peroxycarbenium ion annulations with alkenes in yields ranging from 30% to 94%. peroxycarbenium ion precursors included triethylsilyldiperoxyketals and -acetals derived from geminal dihydroperoxides and from a new method employing triethylsilylperoxyketals and -acetals derived from ozonolysis of alkenes. the 1,2-dioxolanes were either inactive or orders of magnitude less potent than the corresponding 1,2,4-trioxolanes or artemisinin ... | 2007 | 17949067 |
| pharmacokinetics and pharmacodynamics of piperaquine in a murine malaria model. | piperaquine (pq) is an important partner in antimalarial treatment strategies. however, there is a paucity of detailed preclinical and pharmacokinetic data to link pq serum concentrations and toxicity or efficacy. the aim of this study was to investigate the pharmacokinetics and pharmacodynamics of pq in a murine malaria treatment model. the study comprised three arms. (i) pq pharmacokinetic parameters were determined in healthy and malaria-infected mice (90 mg/kg pq phosphate [pqp]). (ii) for d ... | 2008 | 17984231 |
| expression microarray analysis implicates apoptosis and interferon-responsive mechanisms in susceptibility to experimental cerebral malaria. | specific local brain responses, influenced by parasite sequestration and host immune system activation, have been implicated in the development of cerebral malaria. this study assessed whole-brain transcriptional responses over the course of experimental cerebral malaria by comparing genetically resistant and susceptible inbred mouse strains infected with plasmodium berghei anka. computational methods were used to identify differential patterns of gene expression. overall, genes that showed the ... | 2007 | 17991715 |
| the parasite invasion marker srpn6 reduces sporozoite numbers in salivary glands of anopheles gambiae. | for malaria transmission to occur, plasmodium sporozoites must infect the salivary glands of their mosquito vectors. this study reports that anopheles gambiae srpn6 participates in a local salivary gland epithelial response against the rodent malaria parasite, plasmodium berghei. we showed previously that srpn6, an immune inducible midgut invasion marker, influences ookinete development. here we report that srpn6 is also specifically induced in salivary glands with the onset of sporozoite invasi ... | 2008 | 18005239 |
| heparan sulfate proteoglycans provide a signal to plasmodium sporozoites to stop migrating and productively invade host cells. | malaria infection is initiated when anopheles mosquitoes inject plasmodium sporozoites into the skin. sporozoites subsequently reach the liver, invading and developing within hepatocytes. sporozoites contact and traverse many cell types as they migrate from skin to liver; however, the mechanism by which they switch from a migratory mode to an invasive mode is unclear. here, we show that sporozoites of the rodent malaria parasite plasmodium berghei use the sulfation level of host heparan sulfate ... | 2007 | 18005753 |
| toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host. | infection with plasmodium berghei anka is a well-established model of human cerebral malaria (cm). we show herein that toll-like receptor (tlr) signaling influences the development of lethal cm in p. berghei anka-infected mice. modulation of outcome was dependent on genetic background, such that deletion of myeloid differentiation factor (myd) 88 on the susceptible c57bl/6 background resulted in resistance to cm, whereas deletion of myd88 on the resistant balb/c background led to increased morta ... | 2007 | 18008236 |
| plasmodium berghei: parasite clearance after treatment with dihydroartemisinin in an asplenic murine malaria model. | clinical reports indicate that malaria-infected asplenic patients have a reduced capacity for parasite clearance despite intensive antimalarial therapy. the aim of this study was to evaluate the efficacy of dihydroartemisinin in an asplenic murine malaria model. mice were inoculated with plasmodium berghei parasitised erythrocytes and received a single dose of dihydroartemisinin 56 h later, at 2-5% parasitaemia. haematology, liver biochemistry and histopathology of key organs were performed to e ... | 2008 | 18023429 |
| potential antimalarial activity of indole alkaloids. | new antimalarial treatments are now urgently required, following the emergence of resistance to the most used drugs. natural products contribute greatly to the therapeutic arsenal in this area, including artemisinin and quinine (and atovaquone, semi-synthetic). among the natural products, indole alkaloids represent an interesting class of compounds. screening carried out to date has revealed several substances active in vitro under the micromolar range and with a good selectivity index. this rev ... | 2008 | 18035385 |
| [cloning and optimized prokaryotic expression of a pbmag-1 cdna fragment from plasmodium berghei anka]. | to clone and express a novel gene cdna fragment, pbmag-1, from plasmodium berghei anka strain. | 2007 | 18038803 |
| continuous exposure to plasmodium results in decreased susceptibility and transcriptomic divergence of the anopheles gambiae immune system. | plasmodium infection has been shown to compromise the fitness of the mosquito vector, reducing its fecundity and longevity. however, from an evolutionary perspective, the impact of plasmodium infection as a selective pressure on the mosquito is largely unknown. | 2007 | 18053261 |
| gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice. | microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. to better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (cm-r) and cm-susceptible (cm-s) mice, upon infection by plasmodium berghei anka (pba). we investigated mouse transcriptional responses at early and late stages of infection by use of cdna microarrays. | 2007 | 18062806 |
| the in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the meru community in kenya. | the use of herbal drugs as combinations has existed for centuries in several cultural systems. however, the safety and efficacy of such combinations have not been validated. in this study, the toxicity, anti-plasmodial and antimalarial efficacy of several herbal drug combinations were investigated. lannea schweinfurthii, turraea robusta and sclerocarya birrea, used by traditional health practitioners in meru community, were tested for in vitro anti-plasmodial and in vivo anti-malarial activity s ... | 2008 | 18065175 |
| reactive oxygen species modulate anopheles gambiae immunity against bacteria and plasmodium. | the involvement of reactive oxygen species (ros) in mosquito immunity against bacteria and plasmodium was investigated in the malaria vector anopheles gambiae. strains of an. gambiae with higher systemic levels of ros survive a bacterial challenge better, whereas reduction of ros by dietary administration of antioxidants significantly decreases survival, indicating that ros are required to mount effective antibacterial responses. expression of several ros detoxification enzymes increases in the ... | 2008 | 18065421 |
| [study of the binding of nuclear proteins from plasmodium berghei strains with different chloroquine sensitivity to oligonucleotides corresponding to regulatory elements of multidrug resistance (mdr1) gene]. | using electrophoretic mobility shift assay we first revealed in the nuclear extracts of the rodent malaria parasite plasmodium berghei (p. berghei) proteins, which bind specifically to the double-stranded oligonucleotides reproducing the binding sites of the transcription factors of ap1 family, nf-il6 and sp1 involved in the up-regulation of human multidrug resistance (mdr1) gene and to the oligonucleotide corresponding to the element responsive for the stimulation by serum (sre). the nuclear pr ... | 2007 | 18078069 |
| serial analysis of gene expression in plasmodium berghei salivary gland sporozoites. | the invasion of anopheles salivary glands by plasmodium sporozoites is an essential step for transmission of the parasite to the vertebrate host. salivary gland sporozoites undergo a developmental programme to express genes required for their journey from the site of the mosquito bite to the liver and subsequent invasion of, and development within, hepatocytes. a serial analysis of gene expression was performed on anopheles gambiae salivary glands infected or not with plasmodium berghei and we r ... | 2007 | 18093287 |
| integrin alphadbeta2 is dynamically expressed by inflamed macrophages and alters the natural history of lethal systemic infections. | the leukocyte integrins have critical roles in host defense and inflammatory tissue injury. we found that integrin alphadbeta2, a novel but largely uncharacterized member of this family, is restricted to subsets of macrophages and a small population of circulating leukocytes in wild-type mice in the absence of inflammatory challenge and is expressed in regulated fashion during cytokine-induced macrophage differentiation in vitro. alphadbeta2 is highly displayed on splenic red pulp macrophages an ... | 2008 | 18097061 |
| a conserved u-rich rna region implicated in regulation of translation in plasmodium female gametocytes. | translational repression (tr) plays an important role in post-transcriptional regulation of gene expression and embryonic development in metazoans. tr also regulates the expression of a subset of the cytoplasmic mrna population during development of fertilized female gametes of the unicellular malaria parasite, plasmodium spp. which results in the formation of a polar and motile form, the ookinete. we report the conserved and sex-specific regulatory role of either the 3'- or 5'-utr of a subset o ... | 2008 | 18158300 |
| hemolytic c-type lectin cel-iii from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development. | the midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. here we generate transgenic anopheles stephensi mosquitoes that express the c-type lectin cel-iii from the sea cucumber, cucumaria echinata, in a midgut-specific manner. cel-iii has strong and rapid ... | 2007 | 18159942 |
| class ii-restricted protective immunity induced by malaria sporozoites. | the irradiated-sporozoite vaccine elicits sterile immunity against plasmodium parasites in experimental rodent hosts and human volunteers. based on rodent malaria models, it has been proposed that cd8+ t cells are the key protective effector mechanism required in sporozoite-induced immunity. to investigate the role of class ii-restricted immunity in protective immunity, we immunized beta2-microglobulin knockout (beta2m-/-) mice with irradiated plasmodium yoelii or p. berghei sporozoites. sterile ... | 2008 | 18160479 |
| can transgenic mosquitoes afford the fitness cost? | in a recent study, sm1-transgenic anopheles stephensi, which are resistant partially to plasmodium berghei, had higher fitness than non-transgenic mosquitoes when they were maintained on plasmodium-infected blood. this result should be interpreted cautiously with respect to malaria control using transgenic mosquitoes because, despite the evolutionary advantage conferred by the transgene, a concomitant cost prevents it from invading the entire population. indeed, for the spread of a resistance tr ... | 2008 | 18164248 |
| progression of plasmodium berghei through anopheles stephensi is density-dependent. | it is well documented that the density of plasmodium in its vertebrate host modulates the physiological response induced; this in turn regulates parasite survival and transmission. it is less clear that parasite density in the mosquito regulates survival and transmission of this important pathogen. numerous studies have described conversion rates of plasmodium from one life stage to the next within the mosquito, yet few have considered that these rates might vary with parasite density. here we e ... | 2007 | 18166078 |
| chemical attenuation of plasmodium berghei sporozoites induces sterile immunity in mice. | radiation and genetic attenuation of plasmodium sporozoites are two approaches for whole-organism vaccines that protect against malaria. we evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. sporozoites were treated with the dna sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits plasmodium falciparum growth in vitro. here we show that treatment of plasmo ... | 2008 | 18174336 |
| recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria. | cerebral malaria (cm) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. in children cm induces cognitive impairment in about 10% of the survivors. erythropoietin (epo) has - besides of its well known haematopoietic properties - significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. the neurobiological responses to exogenously injected epo during murine cm were examine ... | 2008 | 18179698 |
| protection against cerebral malaria by the low-molecular-weight thiol pantethine. | we report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in plasmodium berghei anka-infected mice. the protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. parasite development was unaffected. pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer tra ... | 2008 | 18195363 |
| antiplasmodial triterpenoids from ekebergia capensis. | from the stem bark of ekebergia capensis, 10 new triterpenoid compounds, ekeberins a (1), b (2), c1 (3), c2 (4), c3 (5), d1 (6), d2 (7), d3 (8), d4 (9), and d5 (10), were isolated together with 17 known compounds. the structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the mosher ester method. several of these compounds were scr ... | 2008 | 18220356 |
| synthesis and antimalarial activity of semicarbazone and thiosemicarbazone derivatives. | seventeen semicarbazone and thiosemicarbazone derivatives were prepared and tested in vitro against a chloroquine resistant strain of plasmodium falciparum (w2) to evaluate their antiplasmodial potential. three thiosemicarbazones were found to be active against the parasite and non-toxic to human peripheral blood mononuclear cells (pbmc). among these, compound 5b presented the lowest ic50 value against p. falciparum (7.2 microm) and was the least toxic in the pbmc proliferation assay (ic50=73.5 ... | 2008 | 18222568 |
| synthesis and antimalarial activity of carbamate and amide derivatives of 4-anilinoquinoline. | a series of 4-anilinoquinolines bearing an amino side chain linked to the aromatic ring with a carbamate or an amide bond were synthesized and evaluated for their antimalarial activity and their cytotoxicity upon mrc-5 cells. among the 17 compounds, a majority was found to be active in the low nanomolar range against both chloroquine-sensitive and -resistant strains of plasmodium falciparum in vitro with relative low cytotoxicity. two compounds were then tested on mice infected by plasmodium ber ... | 2008 | 18226428 |
| inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease. | from the inoculation of plasmodium sporozoites via anopheles mosquito bites to the development of blood-stage parasites, a hallmark of the host response is an inflammatory reaction characterized by elevated histamine levels in the serum and tissues. given the proinflammatory and immunosuppressive activities associated with histamine, we postulated that this vasoactive amine participates in malaria pathogenesis. combined genetic and pharmacologic approaches demonstrated that histamine binding to ... | 2008 | 18227221 |
| malaria-infected mice are cured by oral administration of new artemisinin derivatives. | in four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. the clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. in comparison, animals receiving no drug die typically on day 6-7 postinfection. at only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of mala ... | 2008 | 18232653 |
| beta-hematin interaction with the hemopexin domain of gelatinase b/mmp-9 provokes autocatalytic processing of the propeptide, thereby priming activation by mmp-3. | gelatinase b or matrix metalloproteinase-9 is involved in inflammation and in autoimmune and vascular diseases. in contrast to the constitutive and homeostatic matrix metalloproteinase-2, matrix metalloproteinase-9 is an inducible enzyme. furthermore, it needs tight regulation, and a major control mechanism of its enzymatic activity is the activation of the latent enzyme by proteolysis of the 87 residue propeptide. activated matrix metalloproteinase-9 is detected in many vascular or hematologica ... | 2008 | 18237197 |
| the gram-negative bacteria-binding protein gene family: its role in the innate immune system of anopheles gambiae and in anti-plasmodium defence. | gram-negative bacteria-binding proteins (gnbps) are pattern recognition receptors which contribute to the defensive response against plasmodium infection in anopheles. we have characterized the gnbp gene family in anopheles gambiae at the molecular level, and show that they are functionally diverse components of the a. gambiae innate immune system. gnbpb4 is a major factor in the defence against a broad range of pathogens, while the other gnbps have narrower defence specificities. gnbpb4 is asso ... | 2008 | 18237283 |
| new bis(2-aminoimidazoline) and bisguanidine dna minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity. | a series of 75 guanidine and 2-aminoimidazoline analogue molecules were assayed in vitro against trypanosoma brucei rhodesiense stib900 and plasmodium falciparum k1. the dicationic diphenyl compounds exhibited the best activities with ic 50 values against t. b. rhodesiense and p. falciparum in the nanomolar range. five compounds (7b, 9a, 9b, 10b, and 14b) cured 100% of treated mice upon ip administration at 20 mg/kg in the difficult to cure t. b. rhodesiense stib900 mouse model. overall, the com ... | 2008 | 18247550 |
| mutation underlying resistance of plasmodium berghei to atovaquone in the quinone binding domain 2 (qo(2)) of the cytochrome b gene. | the anti-malarial agent atovaquone specifically targets the cytochrome bc(1) complex and inhibits the parasite respiration. resistance to this drug, a coenzyme q analogue, is associated with mutations in the mitochondrial cytochrome b gene. we previously reported atovaquone resistant mutations in plasmodium berghei, in the first quinone binding domain (qo(1)) of the cytochrome b gene (m133i and l144s) with v284f in the sixth transmembrane domain. however, in p. falciparum the most common mutatio ... | 2008 | 18248769 |
| single-dose protection against plasmodium berghei by a simian adenovirus vector using a human cytomegalovirus promoter containing intron a. | human adenovirus serotype 5 (adh5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. we designed adh5 vectors expressing antigen under the control of a human cytomegalovirus (hcmv) immediate-early promoter containing its intron a sequence. the transcriptional levels of antigen and immune responses to antigen for vectors with the hcmv promoter with the intron a sequence (lp) were greater than those for adh5 vectors using the hcmv p ... | 2008 | 18256155 |
| the guanylhydrazone cni-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase. | malaria is still a major cause of death in the tropics. there is an urgent need for new anti-malarial drugs because drug-resistant plasmodia frequently occur. over recent years, we elucidated the biosynthesis of hypusine, a novel amino acid contained in eukaryotic initiation factor 5a (eif-5a) in plasmodium. hypusine biosynthesis involves catalysis of deoxyhypusine synthase (dhs) in the first step of post-translational modification. in a screen for new inhibitors of purified plasmodium dhs, cni- ... | 2008 | 18256853 |
| antimalarial dual drugs based on potent inhibitors of glutathione reductase from plasmodium falciparum. | plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. as a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant ... | 2008 | 18260613 |
| single-dose immunogenicity and protective efficacy of simian adenoviral vectors against plasmodium berghei. | simian adenoviral vectors (sad) offer an attractive alternative to standard human adenovirus serotype 5 (adh5) subunit vaccination, due to pre-existing immunity affecting vaccine performance. we have used a mouse model of liver-stage malaria to test the efficiency of three chimpanzee-origin adenoviral vectors, adc6, adc7 and adc9 containing me.trap as an insert. adc7 and adc9 elicited strong immunogenicity ( approximately 20% of cd8(+) t cells in spleen), equivalent to or outperforming adh5 and ... | 2008 | 18266272 |
| simvastatin treatment shows no effect on the incidence of cerebral malaria or parasitemia during experimental malaria. | 2008 | 18268089 | |
| pregnancy outcome and placenta pathology in plasmodium berghei anka infected mice reproduce the pathogenesis of severe malaria in pregnant women. | pregnancy-associated malaria (pam) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. the physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. here, we describe a comprehensive mouse experimental model that recapitulates many of the patholog ... | 2008 | 18270595 |
| plasmodium berghei merozoite surface protein-9: immunogenicity and protective efficacy using a homologous challenge model. | merozoite surface protein-9 (msp-9) from plasmodium is considered a promising vaccine candidate due to its location and possible role in erythrocyte invasion. we report the identification and characterization of plasmodium berghei msp-9 (pbmsp-9) and its properties as an immunogen using a recombinant pbmsp-9 fragment to immunize balb/c mice. pbmsp-9 was found to harbor erythrocyte binding and serine protease activity. pbmsp-9 formulation in alum was highly immunogenic in balb/c mice. to evaluate ... | 2008 | 18272263 |
| a contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional mri. | human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with mri, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional mri. ligand-induced binding sites (libs) on activated platelet glycoprotein iib/iiia receptors were detected in the brains of m ... | 2008 | 18274670 |
| design, synthesis, and structure-activity relationship studies of 4-quinolinyl- and 9-acrydinylhydrazones as potent antimalarial agents. | malaria is a major health problem in poverty-stricken regions where new antiparasitic drugs are urgently required at an affordable price. we report herein the design, synthesis, and biological investigation of novel antimalarial agents with low potential to develop resistance and structurally based on a highly conjugated scaffold. starting from a new hit, the designed modifications were performed hypothesizing a specific interaction with free heme and generation of radical intermediates. this ap ... | 2008 | 18278859 |
| clotrimazole scaffold as an innovative pharmacophore towards potent antimalarial agents: design, synthesis, and biological and structure-activity relationship studies. | we describe herein the design, synthesis, biological evaluation, and structure-activity relationship (sar) studies of an innovative class of antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole and easy to synthesize by low-cost synthetic procedures. sar studies delineated a number of structural features able to modulate the in vitro and in vivo antimalarial activity. a selected set of antimalarials was further biologically investigated and displayed low ... | 2008 | 18278860 |
| anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo. | pyronaridine is a mannich base anti-malarial with demonstrated efficacy against drug resistant plasmodium falciparum, p. vivax, p. ovale and p. malariae. however, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. the aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against p. falciparum in vitro and in rodent malaria models in vivo to s ... | 2008 | 18279817 |
| implications of imaging malaria sporozoites. | the sporozoites of plasmodium parasites undergo several transmigrations before their establishment in the hepatocytes of a vertebrate host. techniques that illustrate parasite intra-vital migration and their interaction with host cells will advance the understanding of parasite biology. in a recent publication, amino et al. provided a detailed protocol for in vivo imaging of plasmodium berghei sporozoites in the dermis. the report has important implications in the dissection of malaria parasite ... | 2008 | 18280209 |