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synthesis, structure-activity relationship, and mode-of-action studies of antimalarial reversed chloroquine compounds.we have previously shown that a "reversed chloroquine (rcq)" molecule, composed of a chloroquine-like moiety and a resistance reversal-like moiety, can overcome chloroquine resistance in p. falciparum ( burgess , s. j. ; selzer , a. ; kelly , j. x. ; smilkstein , m. j. ; riscoe , m. k. ; peyton , d. h. j. med. chem. 2006 , 49 , 5623 . andrews , s. ; burgess , s. j. ; skaalrud , d. ; kelly , j. x. ; peyton , d. h. j. med. chem. 2010 , 53 , 916 ). here, we present an investigation into the structu ...201020684562
curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.in the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. for the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (mct) as liquid lipid. scanning electron microscopy (sem) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measur ...201020688493
an early commitment to expression of a particular tcrvbeta chain on cd8(+) t cells responding to attenuated plasmodium berghei sporozoites is maintained following challenge with infectious sporozoites.protection induced by irradiated plasmodium berghei sporozoites (pbgamma-spz) in mice is linked to cd8(+) t cells specific for exo-erythrocytic-stage ags, and intrahepatic memory cd8(+) t cells are associated with protracted protection. however, the ag specificity of the protective cd8(+) t cells remains largely unknown. in this study, we characterized the tcr vbeta usage by intrahepatic cd8(+) t cells during gamma-spz immunization and after the challenge with infectious pb sporozoites. the repe ...201020691016
artemisone effective against murine cerebral malaria.artemisinins are the newest class of drug approved for malaria treatment. due to their unique mechanism of action, rapid effect on plasmodium, and high efficacy in vivo, artemisinins have become essential components of malaria treatment. administration of artemisinin derivatives in combination with other anti-plasmodials has become the first-line treatment for uncomplicated falciparum malaria. however, their efficiency in cases of cerebral malaria (cm) remains to be determined.201020691118
differential expression of proteins in the midgut of anopheles albimanus infected with plasmodium berghei.the main vector for transmission of malaria in mexico is the anopheles albimanus mosquito. the midgut of disease-transmitting mosquitoes carries out a variety of functions that are related to blood feeding. we analyzed the midgut of a. albimanus infected with plasmodium berghei (resistant mosquito) using a proteomic approach to identify putative short peptides that are enriched in the midgut after blood feeding. mosquito midguts were analyzed by two-dimensional electrophoresis to determine the c ...201020692341
novel inhibitors of plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in the mouse model.plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. dihydroorotate dehydrogenase (dhodh) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy. a high throughput screen and subsequent medicinal chemistry program identified a series of n-alkyl-5-(1h-benzimidazol-1-yl)thiophene-2-carboxamides with low nan ...201020702404
the effect of nitric oxide and hydrogen peroxide in the activation of the systemic immune response of anopheles albimanus infected with plasmodium berghei.the expression of genes encoding the antimicrobial peptides (amps) attacin, cecropin and gambicin, as well as the effects of no and h(2)o(2) on their expression was investigated in midguts and fat bodies of anopheles albimanus during the midgut infection with plasmodium berghei. midgut infection induced an increase in the expression of the three amps in both tissues; while no and h(2)o(2) were present in haemolymph. treatment with l-name and vitamin c reduced the effect of p. berghei infection o ...201120708028
schistosoma co-infection protects against brain pathology but does not prevent severe disease and death in a murine model of cerebral malaria.co-infections of helminths and malaria parasites are common in human populations in most endemic areas. it has been suggested that concomitant helminth infections inhibit the control of malaria parasitemia but down-modulate severe malarial disease. we tested this hypothesis using a murine co-infection model of schistosomiasis and cerebral malaria. c57bl/6 mice were infected with schistosoma mansoni and 8-9 weeks later, when schistosoma infection was patent, mice were co-infected with plasmodium ...201120708623
functional immunogenicity of baculovirus expressing pfs25, a human malaria transmission-blocking vaccine candidate antigen.we have focused on development of a novel vaccine vector based on "baculophage", a baculovirus display system for expression of proteins on the surface of the viral envelope, as a non-pathogenic and non-vertebrate insect virus. in the present study, recombinant baculovirus (acnpv-pfs25surf) were generated, which displayed pfs25, a potent plasmodium falciparum transmission-blocking vaccine candidate. both intranasal and intramuscular immunizations of mice with acnpv-pfs25surf induced high levels ...201020709008
dialkylaminoalkyl derivatives of bicyclic compounds with antiplasmodial activity.dialkylaminoalkyl derivatives of 2-azabicyclo[3.2.2]nonanes and of bicyclo[2.2.2]octanes were prepared and their activities determined in vitro against the multiresistant k1 strain of plasmodium falciparum. several of the new compounds exhibited very promising antiplasmodial activity and selectivity. the results were compared to those of formerly synthesized analogues and of drugs in use. structure-activity relationships were detected. some of the more potent compounds were tested in vivo agains ...201020709557
phosphatidylinositol 3-phosphate, an essential lipid in plasmodium, localizes to the food vacuole membrane and the apicoplast.phosphoinositides are important regulators of diverse cellular functions, and phosphatidylinositol 3-monophosphate (pi3p) is a key element in vesicular trafficking processes. during its intraerythrocytic development, the malaria parasite plasmodium falciparum establishes a sophisticated but poorly characterized protein and lipid trafficking system. here we established the detailed phosphoinositide profile of p. falciparum-infected erythrocytes and found abundant amounts of pi3p, while phosphatid ...201020709789
immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria.cerebral malaria is a severe complication of malaria. sequestration of parasitized rbcs in brain microvasculature is associated with disease pathogenesis, but our understanding of this process is incomplete. in this study, we examined parasite tissue sequestration in an experimental model of cerebral malaria (ecm). we show that a rapid increase in parasite biomass is strongly associated with the induction of ecm, mediated by ifn-gamma and lymphotoxin alpha, whereas tnf and il-10 limit this proce ...201020720206
key factors regulating plasmodium berghei sporozoite survival and transformation revealed by an automated visual assay.malaria is transmitted to the host when plasmodium sporozoites are injected by a mosquito vector. sporozoites eventually enter hepatocytes, where they differentiate into liver-stage parasites. during the first hours after hepatocyte invasion, the crescent-shaped sporozoites transform into spherical intracellular exoerythrocytic parasites. this process, which precedes genome replication, can be mimicked in vitro in the absence of host cells. here, we developed an automated method to follow transf ...201020798246
effect of amphotericin b on parasitemia and survival of plasmodium berghei-infected mice.premature death of plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. amphotericin b has previously been shown to trigger suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. phosphatidylserine-exposing cells are rapidly cleared from circulating blood. the present study thus tested whether amphotericin b exerts a direct effect on plasmodium falcip ...201020798519
effect of anandamide in plasmodium berghei-infected mice.eryptosis, the suicidal death of erythrocytes, is characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. triggers of eryptosis include anandamide. enhanced eryptosis of infected human erythrocytes is expected to delay the development of parasitaemia during infection with plasmodium, the parasite causing malaria. the present experiments aimed to test, whether anandamide influences eryptosis, parasite growth and/or host survival during in vitro or in vivo in ...201020798520
persistent cognitive and motor deficits after successful antimalarial treatment in murine cerebral malaria.human cerebral malaria causes neurological and behavioral deficits which persist long after resolution of infection and clearance of parasites with antimalarial drugs. previously, we demonstrated that during active infection, mice with cerebral malaria demonstrated negative behavioral outcomes. here we used a chloroquine treatment model of cerebral malaria to determine whether these abnormal outcomes would be persistent in the mouse model. c57bl/6 mice were infected with plasmodium berghei anka, ...201020800692
immunization with pre-erythrocytic antigen celtos from plasmodium falciparum elicits cross-species protection against heterologous challenge with plasmodium berghei.the plasmodium protein cell-traversal protein for ookinetes and sporozoites (celtos) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. celtos is highly conserved among the plasmodium species, suggesting an important functional role across all species. therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protec ...201020808868
spiroindolones, a potent compound class for the treatment of malaria.recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. the spirotetrahydro-beta-carbolines, or spiroindolones, are potent drugs that kill the blood stages of plasmodium falciparum and plasmodium vivax clinical isolates at low nanomolar concentration. spiroindolones rapidly inhibit protein synthesis in p. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the ge ...201020813948
gene deletion from plasmodium falciparum using flp and cre recombinases: implications for applied site-specific recombination.the ability to manipulate the genome and induce site-specific recombination using either flippase (flp) or cre recombinase has been useful in many systems including plasmodium berghei for specific deletion events or to obtain conditional gene expression. to test whether these recombinases are active in plasmodium falciparum we constructed gene knockouts that contain sequences recognised as templates for site-specific recombination. we tested the ability of flp and cre recombinases, expressed con ...201120816845
reduced activity of the epithelial sodium channel in malaria-induced pulmonary oedema in mice.lung complications during malaria infection can range from coughs and impairments in gas transfer to the development of acute respiratory distress syndrome (ards). infecting c57bl/6 mice with plasmodium berghei k173 strain (pbk) resulted in pulmonary oedema, capillaries congested with leukocytes and infected red blood cells (irbcs), and leukocyte infiltration into the lungs. this new model of malaria-associated lung pathology, without any accompanying cerebral complications, allows the investiga ...201120816846
coincident parasite and cd8 t cell sequestration is required for development of experimental cerebral malaria.cerebral malaria (cm) is a fatal complication of plasmodium falciparum infection. using a well defined murine model, we observed the effect on disease outcome of temporarily reducing parasite burden by anti-malarial drug treatment. the anti-malarial treatment regime chosen decreased parasitaemia but did not cure the mice, allowing recrudescence of parasites. these mice were protected against cm, despite their parasitaemia having increased, following treatment cessation, to levels surpassing that ...201120828575
hemocyte differentiation mediates innate immune memory in anopheles gambiae mosquitoes.mosquito midgut invasion by ookinetes of the malaria parasite plasmodium disrupts the barriers that normally prevent the gut microbiota from coming in direct contact with epithelial cells. this triggers a long-lived response characterized by increased abundance of granulocytes, a subpopulation of hemocytes that circulates in the insect's hemocoel, and enhanced immunity to bacteria that indirectly reduces survival of plasmodium parasites upon reinfection. in mosquitoes, differentiation of hemocyt ...201020829487
heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of hsp90 from plasmodium falciparum and trypanosoma evansi and evaluation of its inhibitor as a candidate drug.using a pharmacological inhibitor of hsp90 in cultured malarial parasite, we have previously implicated plasmodium falciparum hsp90 (pfhsp90) as a drug target against malaria. in this study, we have biochemically characterized pfhsp90 in terms of its atpase activity and interaction with its inhibitor geldanamycin (ga) and evaluated its potential as a drug target in a preclinical mouse model of malaria. in addition, we have explored the potential of hsp90 inhibitors as drugs for the treatment of ...201020837488
polar alkaloids from the caribbean marine sponge niphates digitalis.a method involving flash chromatography, semi-preparative phenylhexyl rp hplc-dad-elsd combined with analytic polar-rp hplc-dad, was applied to separate and purify six highly nitrogenated bases and a bicyclic amidine alkaloid, the major components of the marine sponge niphates digitalis. their structures were identified as 1,8-diazabicyclo[5.4.0]undec-7-ene (1), deoxycytidine (2), phenylalanine (3), adenosine (4), deoxyguanosine (5), adenine (6) and thymidine (7) on the basis of spectroscopic da ...201020839615
naturally occurring triggers that induce apoptosis-like programmed cell death in plasmodium berghei ookinetes.several protozoan parasites have been shown to undergo a form of programmed cell death that exhibits morphological features associated with metazoan apoptosis. these include the rodent malaria parasite, plasmodium berghei. malaria zygotes develop in the mosquito midgut lumen, forming motile ookinetes. up to 50% of these exhibit phenotypic markers of apoptosis; as do those grown in culture. we hypothesised that naturally occurring signals induce many ookinetes to undergo apoptosis before midgut t ...201020844583
antiplasmodial activity of two marine polyherbal preparations from chaetomorpha antennina and aegiceras corniculatum against plasmodium falciparum.the ocean covers more than 70% of earth surface and hosts most 300,000 described species of plants and animals to use, which have been virtually unexploited for the development of medicines. marine plants are the good source of biologically active entities which exhibit therapeutic properties, when applied single or in combination of different plant extracts (polyherbal). polyherbal preparations are always a complex mixture of different forms and thus different compounds, which might act as agon ...201120844892
antimalarial activity of traditionally used western ghats plants from india and their interactions with chloroquine against chloroquine-tolerant plasmodium berghei.an ethnopharmacological investigation was undertaken on western ghats plants traditionally used to treat malaria; 50 plants were very carefully selected from total of 372 plants, and 216 extracts were prepared and tested for in vivo antiplasmodial activity alone and in combination with chloroquine (cq) against cq-tolerant plasmodium berghei (strain nk65). in in vivo antiplasmodial activity when plant extract alone is used, 81 extracts (or 37.5%) gave 52.90% significant parasitemia inhibition on ...201120846029
molecular genetics evidence for the in vivo roles of the two major nadph-dependent disulfide reductases in the malaria parasite.malaria-associated pathology is caused by the continuous expansion of plasmodium parasites inside host erythrocytes. to maintain a reducing intracellular milieu in an oxygen-rich environment, malaria parasites have evolved a complex antioxidative network based on two central electron donors, glutathione and thioredoxin. here, we dissected the in vivo roles of both redox pathways by gene targeting of the respective nadph-dependent disulfide reductases. we show that plasmodium berghei glutathione ...201020852334
functional significance of the intermediate conductance ca2+-activated k+ channel for the short-term survival of injured erythrocytes.increased cytosolic ca(2+) concentrations activate gardos k(+) channels in human erythrocytes with membrane hyperpolarization, efflux of k(+), cl⁻, and osmotically obliged h₂o resulting in cell shrinkage, a phenomenon referred to as gardos effect. we tested whether the gardos effect delays colloid osmotic hemolysis of injured erythrocytes from mice lacking the ca(2+)-activated k(+) channel k(ca)3.1. to this end, we applied patch clamp and flow cytometry and determined in vitro as well as in vivo ...201020857305
plasmodium berghei k173: selection of resistance to naphthoquine in a mouse model.naphthoquine (nq), as a component of arco® which composed of nq and artemisinin, is a new 4-aminoquinoline antimalarial synthesized by our institute. here, a naphthoquine-resistant line of rodent malaria parasite was selected through exposing plasmodium berghei keyberg 173 strain to progressively increased drug pressure. the selected strain showed a more than 200-fold decreased susceptibility to nq with a stable resistance phenotype after 10 serial passages without drug pressure or when cryopres ...201020868687
simultaneous administration of vitamin a and dtp vaccine modulates the immune response in a murine cerebral malaria model.the world health organisation recommends vitamin a supplementation (vas) to children aged 6 months to 5 years in low-income countries, and for logistic reasons, this has been linked to routine childhood immunizations. observational studies suggest that vas given with diphtheria-tetanus-pertussis (dtp) vaccine may increase mortality from non-targeted diseases. we investigated the non-targeted effect of pretreatment with vas and dtp vaccine in a murine model of experimental cerebral malaria. our a ...201020883315
the armadillo repeat protein pf16 is essential for flagellar structure and function in plasmodium male gametes.malaria, caused by the apicomplexan parasite plasmodium, threatens 40% of the world's population. transmission between vertebrate and insect hosts depends on the sexual stages of the life-cycle. the male gamete of plasmodium parasite is the only developmental stage that possesses a flagellum. very little is known about the identity or function of proteins in the parasite's flagellar biology. here, we characterise a plasmodium pf16 homologue using reverse genetics in the mouse malaria parasite pl ...201020886115
development of the malaria parasite in the skin of the mammalian host.the first step of plasmodium development in vertebrates is the transformation of the sporozoite, the parasite stage injected by the mosquito in the skin, into merozoites, the stage that invades erythrocytes and initiates the disease. the current view is that, in mammals, this stage conversion occurs only inside hepatocytes. here, we document the transformation of sporozoites of rodent-infecting plasmodium into merozoites in the skin of mice. after mosquito bite, ∼50% of the parasites remain in t ...201020921402
transgenic plasmodium that expresses hiv-1 gag elicits immunity and protects mice against vaccinia virus-gag and malarial parasites.malaria and human immunodeficiency virus type 1 (hiv-1) infection overlap in many regions of the world. our goal was to determine the feasibility of developing transgenic plasmodium berghei that expresses hiv-1 gag, pbgag, as a conceptual bivalent vaccine against both hiv-1 infection and malaria. immunization of mice with pbgag induced specific responses to the hiv-1 gag. importantly, mice vaccinated with pbgag were significantly protected from challenge with vaccinia virus-gag (vv-gag) with an ...201020933565
sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria?the sequestration of plasmodium falciparum-infected red blood cells (irbcs) in the microvasculature of organs is associated with severe disease; correspondingly, the molecular basis of irbc adherence is an active area of study. in contrast to p. falciparum, much less is known about sequestration in other plasmodium parasites, including those species that are used as models to study severe malaria. here, we review the cytoadherence properties of irbcs of the rodent parasite plasmodium berghei ank ...201020941396
the systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission.although eukaryotic protein kinases (epks) contribute to many cellular processes, only three plasmodium falciparum epks have thus far been identified as essential for parasite asexual blood stage development. to identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of epks in the genetically tractable rodent parasite plasmodium berghei. modeling domain signatures of conventional epks identified 66 put ...201020951971
a single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice.four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). when administered orally to malaria-infected mice using a single dose of only 6mg/kg body weight along with 18mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and beh ...201020952197
a rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.cerebral malaria (cm) is a neurological syndrome that includes coma and seizures following malaria parasite infection. the pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to cm, even if the underlying parasite infection has resolved. to that effect, there is no known adjuvant therapy for cm. current murine cm (mcm) models do not allow for rapid clinical identification of affected animals following infection. an animal model that more ...201020957049
selective accumulation of a novel antimalarial rhodacyanine derivative, ssj-127, in an organelle of plasmodium berghei.ssj-127, a novel antimalarial rhodacyanine derivative, has shown potent antimalarial activity against chloroquine-resistant plasmodium strains in vitro and subcutaneous administration of ssj-127 results in a complete cure of a mouse malaria model. ssj-127 was detected by fluorescence microscopy in the mouse malaria parasites plasmodium berghei after exposure of infected red blood cells to the compound in vitro and in vivo. selective accumulation of ssj-127 in an organelle is observed in all bloo ...201020970347
histopathological studies in two strains of semi-immune mice infected with plasmodium berghei anka after chronic exposure.to mimic a human malaria infection in the endemic condition, two strains of mice (balb/c and cba) were infected and treated several times to generate so-called semi-immune status. as previously reported, neither mice (balb/c and cba) strain showed cerebral malaria, even in the susceptible c57bl/6 (b6). the significant difference between the mice strains in our previous study was the rate of destruction of uninfected red blood cells (urbcs) at infection. after the established repeated cycles of i ...201020978790
development of experimental cerebral malaria is independent of il-23 and il-17.cerebral malaria (cm) is the most severe complication of plasmodium infection. although inappropriate immune responses to plasmodium falciparum are reported as the major causes of cm, the precise mechanisms for development remain unclear. il-23 and il-17 have critical roles in the onset of autoimmunity and inflammatory diseases triggered by microbial infections. thus, we investigated the influence of il-23 and il-17 on experimental cm (ecm) using plasmodium berghei anka infection of c57bl/6 mice ...201021036146
cutting edge: adaptive versus innate receptor signals selectively control the pool sizes of murine ifn-γ- or il-17-producing γδ t cells upon infection.γδ t lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. contributing to this is their responsiveness to pathogen products, either with or without the involvement of the tcr and its coreceptors. this study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ t cells. thus, myd88 deficiency severely impaired the response to malaria infection of cd27((-)), il-17a ...201021037088
plasmodium berghei anka: erythropoietin activates neural stem cells in an experimental cerebral malaria model.cerebral malaria (cm) causes substantial mortality and neurological sequelae in survivors, and no neuroprotective regimens are currently available for this condition. erythropoietin (epo) reduces neuropathology and improves survival in murine cm. using the plasmodium berghei model of cm, we investigated if epo's neuroprotective effects include activation of endogenous neural stem cells (nsc). by using immunohistochemical markers of different nsc maturation stages, we show that epo increased the ...201021044627
identification and characterization of a liver stage-specific promoter region of the malaria parasite plasmodium.during the blood meal of a plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. the plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel t ...201021048918
population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions.the combined effects of multiple density-dependent, regulatory processes may have an important impact on the growth and stability of a population. in a malaria model system, it has been shown that the progression of plasmodium berghei through anopheles stephensi and the survival of the mosquito both depend non-linearly on parasite density. these processes regulating the development of the malaria parasite within the mosquito may influence the success of transmission-blocking interventions (tbis) ...201021050427
production of ifn-γ by cd4(+) t cells in response to malaria antigens is il-2 dependent.t-cell immune responses are critical for protection of the host and for disease pathogenesis during infection with plasmodium species. we examined the regulation of cd4(+) t-cell cytokine responses during infection with plasmodium berghei anka (pba). cd4(+) t cells from pba-infected mice produced ifn-γ, il-4 and il-10 in response to tcr stimulation at levels higher than those from uninfected mice. this altered cytokine response was dependent on parasitemia. to examine the specificity of the resp ...201021059770
plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines.two current leading malaria blood-stage vaccine candidate antigens for plasmodium falciparum, the c-terminal region of merozoite surface protein 1 (msp1(19)) and apical membrane antigen 1 (ama1), have been prioritized because of outstanding protective efficacies achieved in a rodent malaria plasmodium yoelii model. however, p. falciparum vaccines based on these antigens have had disappointing outcomes in clinical trials. discrepancies in the vaccine efficacies observed between the p. yoelii mode ...201021060850
in vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins a-c, produced by penicillium sp. fki-4410.in the course of screening for antimalarial agents, five tropolone compounds were isolated from the culture broth of penicillium sp. fki-4410. two were known compounds, puberulic acid and stipitatic acid. three were new analogs of puberulic acid, designated viticolins a-c. among them, puberulic acid exhibited potent antimalarial inhibition, with ic(50) values of 0.01 μg ml(-1) against chloroquine-sensitive and -resistant plasmodium falciparum strains in vitro. furthermore, puberulic acid showed ...201021063422
apolipophorin-iii mediates antiplasmodial epithelial responses in anopheles gambiae (g3) mosquitoes.apolipophorin-iii (apolp-iii) is known to play an important role in lipid transport and innate immunity in lepidopteran insects. however, there is no evidence of involvement of apolp-iiis in the immune responses of dipteran insects such as drosophila and mosquitoes.201021072214
c-jun n terminal kinases (jnk) are activated in the brain during the pathology of experimental cerebral malaria.experimental cerebral malaria (ecm) resulting from plasmodium berghei anka (pba) infection in c57bl/6j mice manifests cell death in the brain. however, the precise molecular and biochemical mechanisms regulating cell death during ecm remains unknown. in this study we have examined, the role of a stress activated protein kinase called c-jun n terminal kinase during the pathology of ecm. we report in this study, for the first time the activation of all key elements in the jnk pathway like p-mkk4, ...201021073918
median lethal dose, antimalarial activity, phytochemical screening and radical scavenging of methanolic languas galanga rhizome extract.the methanolic extract of languas galanga rhizomes was investigated for antimalarial activity against plasmodium berghei (nk65) infections in mice. the median lethal dose was determined to ascertain the safety of the extract in icr mice of both sexes. the antimalarial activities during early and established infections, as well as the prophylactic activity were evaluated. phytochemical screening and radical scavenging activity of the extract were also investigated to elucidate the possible mechan ...201021081857
dematin, a component of the erythrocyte membrane skeleton, is internalized by the malaria parasite and associates with plasmodium 14-3-3.the malaria parasite invades the terminally differentiated erythrocytes, where it grows and multiplies surrounded by a parasitophorous vacuole. plasmodium blood stages translocate newly synthesized proteins outside the parasitophorous vacuole and direct them to various erythrocyte compartments, including the cytoskeleton and the plasma membrane. here, we show that the remodeling of the host cell directed by the parasite also includes the recruitment of dematin, an actin-binding protein of the er ...201021084299
increased levels of glutamate in the central nervous system are associated with behavioral symptoms in experimental malaria.cerebral malaria (cm) is a severe complication resulting from plasmodium falciparum infection. this condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. the underlying mechanisms of cm are incompletely understood. glutamate and other metabolites such as lactate have been implicated in its pathogenesis. in the present study, we investigated the involvement of glutamate in the behavioral symptoms of cm. seventeen female c57bl/6 mice (20-25 g) aged 6-8 ...201021085889
[mechanisms of liver invasion by malaria sporozoites]. 200921089536
malaria imc1 membrane skeleton proteins operate autonomously and participate in motility independently of cell shape.plasmodium imc1 (inner membrane complex 1) proteins comprise components of the subpellicular network, a lattice of intermediate filaments that form a structural part of the pellicle in the zoite stages of malaria parasites. family members imc1a and imc1b are differentially expressed in sporozoites and ookinetes, respectively, but have functionally equivalent roles affecting cell morphology, strength, motility, and infectivity. because of the coincident effects of previous imc1 gene disruptions o ...201021098480
the effect of vitamin a supplementation and diphtheria-tetanus-pertussis vaccination on parasitaemia in an experimental murine malaria model.vitamin a supplementation (vas) decreases overall child mortality in low-income countries. for logistical reasons, vas has been linked to routine childhood immunizations. however, several recent studies have indicated that vas may increase mortality and morbidity from infectious diseases when given with the diphtheria-tetanus-pertussis (dtp) vaccine. the immunological effects of combining the 2 treatments are unknown.201021105844
intravital microscopy of the mouse brain microcirculation using a closed cranial window.this experimental model was designed to assess the mouse pial microcirculation during acute and chronic, physiological and pathophysiological hemodynamic, inflammatory and metabolic conditions, using in vivo fluorescence microscopy. a closed cranial window is placed over the left parieto-occipital cortex of the mice. local microcirculation is recorded in real time through the window using epi and fluorescence illumination, and measurements of vessels diameters and red blood cell (rbc) velocities ...201021113121
antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.in an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (g6pd) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. the new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against plasmodium falciparum cell growth. the new age ...201021141892
molecular correlates of experimental cerebral malaria detectable in whole blood.cerebral malaria (cm) is a primary cause of deaths caused by plasmodium falciparum in young children in sub-saharan africa. laboratory tests based on early detection of host biomarkers in patient blood would help in the prognosis and differential diagnosis of cm. using the plasmodium berghei anka murine model of experimental cerebral malaria (ecm), we have identified over 300 putative diagnostic biomarkers of ecm in the circulation by comparing the whole-blood transcriptional profiles of resista ...201021149594
intradermal immunization of mice with radiation-attenuated sporozoites of plasmodium yoelii induces effective protective immunity.intravenous injection of mice with attenuated plasmodium berghei sporozoites induces sterile immunity to challenge with viable sporozoites. non-intravenous routes have been reported to yield poor immunity. because intravenous immunization has been considered to be unacceptable for large scale vaccination of humans, assessment was made of the results of intradermal immunization of mice with plasmodium yoelii, a rodent malaria parasite whose infectivity resembles that of human malaria.201021159170
fret peptides reveal differential proteolytic activation in intraerythrocytic stages of the malaria parasites plasmodium berghei and plasmodium yoelii.malaria is still a major health problem in developing countries. it is caused by the protist parasite plasmodium, in which proteases are activated during the cell cycle. ca(2+) is a ubiquitous signalling ion that appears to regulate protease activity through changes in its intracellular concentration. proteases are crucial to plasmodium development, but the role of ca(2+) in their activity is not fully understood. here we investigated the role of ca(2+) in protease modulation among rodent plasmo ...201021168413
a constitutive pan-hexose permease for the plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs.glucose is considered essential for erythrocytic stages of the malaria parasite, plasmodium falciparum. importance of sugar and its permease for hepatic and sexual stages of plasmodium, however, remains elusive. moreover, increasing global resistance to current antimalarials necessitates the search for novel drugs. here, we reveal that hexose transporter 1 (ht1) of plasmodium berghei can transport glucose (k(m)~87 μm), mannose (k(i)~93 μm), fructose (k(i)~0.54 mm), and galactose (k(i)~5 mm) in l ...201021169382
cd4+ natural regulatory t cells prevent experimental cerebral malaria via ctla-4 when expanded in vivo.studies in malaria patients indicate that higher frequencies of peripheral blood cd4(+) foxp3(+) cd25(+) regulatory t (treg) cells correlate with increased blood parasitemia. this observation implies that treg cells impair pathogen clearance and thus may be detrimental to the host during infection. in c57bl/6 mice infected with plasmodium berghei anka, depletion of foxp3(+) cells did not improve parasite control or disease outcome. in contrast, elevating frequencies of natural treg cells in vivo ...201021170302
engineering the chloroplast targeted malarial vaccine antigens in chlamydomonas starch granules.malaria, an anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. despite the incidence of malaria, which remains one of the most severe infections of human populations, there is no licensed vaccine against this life-threatening disease. in this context, we decided to explore the expression of plasmodium vaccine antigens fused to the granule bound starch synthase (gbss), the major protein associate ...201021179538
genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice.plasmodium falciparum has exerted tremendous selective pressure on genes that improve survival in severe malarial infections. systemic lupus erythematosus (sle) is an autoimmune disease that is six to eight times more prevalent in women of african descent than in women of european descent. here we provide evidence that a genetic susceptibility to sle protects against cerebral malaria. mice that are prone to sle because of a deficiency in fcγriib or overexpression of toll-like receptor 7 are prot ...201021187399
antimalarial activity of methanolic leaf extract of piper betle l.the need for new compounds active against malaria parasites is made more urgent by the rapid spread of drug-resistance to available antimalarial drugs. the crude methanol extract of piper betle leaves (50-400 mg/kg) was investigated for its antimalarial activity against plasmodium berghei (nk65) during early and established infections. the phytochemical and antioxidant potentials of the crude extract were evaluated to elucidate the possibilities of its antimalarial effects. the safety of the ext ...201021189459
in vivo antimalarial activities of ethanolic crude extracts and fractions of leaf and root of carpolobia lutea.carpolobia lutea (leaves and root) is used traditionally as malarial remedy by the ibibios of niger delta of nigeria and benin. this study was aimed to investigate the antiplasmodial potentials of the crude leaf and root extracts of this plant as well as their fractions in vivo in plasmodium berghei berghei-infected mice to give scientific proof to the ethnobotanical claims and correlate with the reported in vivo activity. the ethanolic extracts of carpolobia lutea leaf (245-735 mg/kg/day) and r ...201121190920
the functional domain of gcs1-based gamete fusion resides in the amino terminus in plant and parasite species.fertilization is one of the most important processes in all organisms utilizing sexual reproduction. in a previous study, we succeeded in identifying a novel male gametic transmembrane protein gcs1 (generative cell specific 1), also called hap2 (hapless 2) in the male-sterile arabidopsis thaliana mutants, as a factor critical to gamete fusion in flowering plants. interestingly, gcs1 is highly conserved among various eukaryotes covering plants, protists and invertebrates. of these organisms, chla ...201021209845
triclosan is minimally effective in rodent malaria models. 201121217674
artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain.the murine model of cerebral malaria (ecm) caused by plasmodium berghei anka (pba) infection in susceptible mice has been extensively used for studies of pathogenesis and identification of potential targets for human cm therapeutics. however, the model has been seldom explored to evaluate adjunctive therapies for this malaria complication. a first step toward this goal is to define a treatment protocol with an effective antimalarial drug able to rescue mice presenting late-stage ecm. we evaluate ...201121220531
protein kinase c-theta is required for development of experimental cerebral malaria.cerebral malaria is the most severe neurologic complication in children and young adults infected with plasmodium falciparum. t-cell activation is required for development of plasmodium berghei anka (pba)-induced experimental cerebral malaria (cm). to characterize the t-cell activation pathway involved, the role of protein kinase c-theta (pkc-θ) in experimental cm development was examined. pkc-θ-deficient mice are resistant to cm development. in the absence of pkc-θ, no neurologic sign of cm dev ...201021224058
malaria crystalloids: specialized structures for parasite transmission?malaria parasites possess many unique subcellular structures and organelles that are essential for the successful completion of the complex life cycle of plasmodium in the vertebrate host and mosquito vector. among these are the crystalloids: transient structures whose presence is restricted to the mosquito-specific ookinete and young oocyst stages of the parasite. nearly five decades after they were first described, the crystalloids are back in the spotlight, with recent discoveries pointing to ...201121237711
beta interferon suppresses the development of experimental cerebral malaria.cerebral malaria (cm) is a major complication of plasmodium falciparum infection, particularly in children. the pathogenesis of cerebral malaria involves parasitized red blood cell (rbc)-mediated vascular inflammation, immune stimulation, loss of blood-brain barrier integrity, and obstruction of cerebral capillaries. therefore, blunting vascular inflammation and immune cell recruitment is crucial in limiting the disease course. beta interferon (ifn-β) has been used in the treatment of diseases, ...201121245265
anxiety-like behavior and proinflammatory cytokine levels in the brain of c57bl/6 mice infected with plasmodium berghei (strain anka).cerebral malaria (cm) is a severe complication resulting from plasmodium falciparum infection. the underlying mechanisms of cm pathogenesis remain incompletely understood. the imbalance between the release of proinflammatory and anti-inflammatory cytokines has been associated with central nervous system dysfunction found in human and experimental cm. the current study investigated anxiety-like behavior, histopathological changes and release of brain cytokines in c57bl/6 mice infected with plasmo ...201121256928
the malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host.plasmodium sporozoites make a remarkable journey from the mosquito midgut to the mammalian liver. the sporozoite's major surface protein, circumsporozoite protein (csp), is a multifunctional protein required for sporozoite development and likely mediates several steps of this journey. in this study, we show that csp has two conformational states, an adhesive conformation in which the c-terminal cell-adhesive domain is exposed and a nonadhesive conformation in which the n terminus masks this doma ...201121262960
screening of antiplasmodial efficacy of ajuga bracteosa wall ex. benth.the rising problem of plasmodium resistance to the classical antimalarial drugs stresses the need to look for newer antiplasmodial components with effective and new mode of action. in the present study, the traditional medicinal plant ajuga bracteosa has been screened for its antiplasmodial efficacy. the extract was found to possess significant in vitro antiplasmodial efficacy with an ic(50) of 10.0 µg/ml. thus, the extract was further evaluated for its in vivo schizontocidal activity and effica ...201121264476
a chemotype that inhibits three unrelated pathogenic targets: the botulinum neurotoxin serotype a light chain, p. falciparum malaria, and the ebola filovirus.a 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype a light chain metalloprotease. subsequently, a variety of derivatives of this chemotype were synthesized to develop structure-activity relationships, and all are inhibitors of the bont/a lc. three-dimensional analyses indicated that half of the originally discovered 1,7-daac structure superimposed well with 4-amino-7-chloroquinoline-based antimalarial agents. thi ...201121265542
evaluation of the use of cocos nucifera as antimalarial remedy in malaysian folk medicine.white flesh extract of cocos nucifera (coconut) was studied to ascertain the ethnopharmacological standing of its antimalarial usage in malaysian folk medicine.201121277969
new imidazolidinedione derivatives as antimalarial agents.a series of new n-alky- and n-alkoxy-imidazolidinediones was prepared and assessed for prophylactic and radical curative activities in mouse and rhesus monkey models. new compounds are generally metabolically stable, weakly active in vitro against plasmodium falciparum clones (d6 and w2) and in mice infected with plasmodium berghei sporozoites. representative compounds 8e and 9c showed good causal prophylactic activity in rhesus monkeys dosed 30 mg/kg/day for 3 consecutive days by im, delayed pa ...201021282058
in vitro biotransformation, in vivo efficacy and pharmacokinetics of antimalarial chalcones.4'-n-butoxy-2,4-dimethoxy-chalcone (mbc) has been described as protecting mice from an otherwise lethal infection with plasmodium yoelii when dosed orally at 50 mg/kg/dose, daily for 5 days. in contrast, we found that oral dosing of mbc at 640 mg/kg/dose, daily for 5 days, failed to extend the survivability of p. berghei-infected mice. the timing of compound administration and metabolic activation likely contribute to the outcome of efficacy testing in vivo. microsomal digest of mbc yielded 4'-n ...201121282967
anti-malarial activity of holarrhena antidysenterica and viola canescens, plants traditionally used against malaria in the garhwal region of north-west himalaya.the increasing number of multidrug-resistant plasmodium strains warrants exploration of new anti-malarials. medicinal plant research has become more important, particularly after the development of chinese anti-malarial drug artemisnin from artemisia annua. the present study shows evaluation of anti-malarial effects of two plants commonly used against malaria in the garhwal region of north-west himalaya, in order to discover the herbal-based medicine.201121288335
evidence that mutant pfcrt facilitates the transmission to mosquitoes of chloroquine-treated plasmodium gametocytes.resistance of the human malarial parasite plasmodium falciparum to the antimalarial drug chloroquine has rapidly spread from several independent origins and is now widely prevalent throughout the majority of malaria-endemic areas. field studies have suggested that chloroquine-resistant strains might be more infective to mosquito vectors. to test the hypothesis that the primary chloroquine resistance determinant, mutations in pfcrt, facilitates parasite transmission under drug pressure, we have i ...201121288823
small-scale in vitro culture and purification of plasmodium berghei for transfection experiment.the standard protocol for genetic modification of the rodent malaria parasite plasmodium berghei requires infected blood from one or more laboratory mice, followed by large-scale in vitro parasite culture and purification of mature schizonts. here, protocols are described for small-scale in vitro culture from 20 µl of mouse tail blood and purification of mature p. berghei schizonts sufficient for a single transfection experiment. all procedures are performed in 1.5-ml microcentrifuge tubes. we c ...201121291917
in vitro and in vivo antiplasmodial activity and cytotoxicity of water extracts of phyllanthus emblica, terminalia chebula, and terminalia bellerica.to evaluate the in vitro and in vivo antiplasmodial activity and the cytotoxicity of phyllanthus emblica linn, terminalia chebula retz, and terminalia bellerica (gaertn) roxb extracts.201021294406
synthetic ozonide drug candidate oz439 offers new hope for a single-dose cure of uncomplicated malaria.ozonide oz439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. oz439 has successfully completed phase i clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing phase iia trials in malaria patients. herein, we describe the discovery of oz439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. in vitro, oz439 is fast-ac ...201121300861
in vivo and in vitro antimalarial activity of 4-nerolidylcatechol.4-nerolidylcatechol (4-nc) isolated from piper peltatum l. (piperaceae) was evaluated for in vitro antiplasmodial activity against plasmodium falciparum (cultures of both standard cqr (k1) and cqs (3d7) strains and two amazonian field isolates) and for in vivo antimalarial activity using the plasmodium berghei-murine model. 4-nc exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4-nc administered orally and subcutaneously at doses of 200, 400 and 600?mg/kg/day suppressed ...201121302338
therapeutical targeting of nucleic acid-sensing toll-like receptors prevents experimental cerebral malaria.excessive release of proinflammatory cytokines by innate immune cells is an important component of the pathogenic basis of malaria. proinflammatory cytokines are a direct output of toll-like receptor (tlr) activation during microbial infection. thus, interference with tlr function is likely to render a better clinical outcome by preventing their aberrant activation and the excessive release of inflammatory mediators. herein, we describe the protective effect and mechanism of action of e6446, a s ...201121303985
ratt: rapid annotation transfer tool.second-generation sequencing technologies have made large-scale sequencing projects commonplace. however, making use of these datasets often requires gene function to be ascribed genome wide. although tool development has kept pace with the changes in sequence production, for tasks such as mapping, de novo assembly or visualization, genome annotation remains a challenge. we have developed a method to rapidly provide accurate annotation for new genomes using previously annotated genomes as a refe ...201121306991
energy metabolism affects susceptibility of anopheles gambiae mosquitoes to plasmodium infection.previous studies showed that anopheles gambiae l3-5 females, which are refractory (r) to plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (s) g3 females. our studies revealed that r females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial state-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. furthermore, ...201121320598
gene profiling analysis reveals the contribution of cd24 and p2y6r to the susceptibility of young rats to plasmodium berghei infection.our previous studies have shown that plasmodium berghei infection induces distinct clinical, parasitological and immunological states in young susceptible rats versus adult resistant rats. this susceptibility was mainly found to be related to inadequate cellular responses. in this study we first identified the altered genes in young susceptible rats. unexpectedly, transcriptome analysis did not reveal any alteration of effector cytokines or their receptors. at day 13 p.i., six transcripts corres ...201121323829
synthesis and biological evaluation of benzimidazole-5-carbohydrazide derivatives as antimalarial, cytotoxic and antitubercular agents.a series of n'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3h-benzo[d]imidazole-5-carbohydrazide derivatives were synthesized and investigated for their abilities to inhibit ß-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent plasmodium berghei. selected analogues were screened for their antitubercular activity against sensitive mtb h(37)rv and multidrug-resistant mdr-mtb strains, and cytotoxic activity against a panel of human tumor cell lin ...201121334900
calcium signal regulates temperature-dependent transformation of sporozoites in malaria parasite development.the infection by the malaria parasite of its mammalian host is initiated by the asexual reproduction of the parasite within the host hepatocyte. before the reproduction, the elongated sporozoites undergo a depolarizing morphogenesis to the spherical exo-erythrocytic form (eef). this change can be induced in vitro by shifting the environmental conditions, in the absence of host hepatocytes. using rodent malaria parasites expressing a fret-based calcium sensor, yc3.60, we observed that the intrace ...201121335005
high parasite burdens cause liver damage in mice following plasmodium berghei anka infection independently of cd8(+) t cell-mediated immune pathology.infection of c57bl/6 mice with plasmodium berghei anka induces a fatal neurological disease commonly referred to as experimental cerebral malaria. the onset of neurological symptoms and mortality depend on pathogenic cd8(+) t cells and elevated parasite burdens in the brain. here we provide clear evidence of liver damage in this model, which precedes and is independent of the onset of neurological symptoms. large numbers of parasite-specific cd8(+) t cells accumulated in the liver following p. b ...201121343349
aryl piperazine and pyrrolidine as antimalarial agents. synthesis and investigation of structure-activity relationships.piperazine and pyrrolidine derivatives were synthesised and evaluated for their capacity to inhibit the growth of plasmodium falciparum chloroquine-resistant (fcr-3) strain in culture. the combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmodial activity. five compounds of the aryl-alcohol series inhibited 50% of parasite growth at doses =10 µm. the most active compound 1-(4-fluoronaphthyl)-3-[4-(4-nitro-2-trifluoromethylphenyl)piperazin- ...201121354139
cutting edge: attrition of plasmodium-specific memory cd8 t cells results in decreased protection that is rescued by booster immunization.sterile protection against infection with plasmodium sporozoites requires high numbers of memory cd8 t cells. however, infections with unrelated pathogens, as may occur in areas endemic to malaria, can dramatically decrease pre-existing memory cd8 t cells. it remains unknown whether unrelated infections will compromise numbers of plasmodium-specific memory cd8 t cells and thus limit the duration of antimalarial immunity generated by subunit vaccination. we show that p. berghei circumsporozoite-s ...201121357257
in vitro and in vivo antiplasmodial activities of risedronate and its interference with protein prenylation in plasmodium falciparum.the increasing resistance of malarial parasites to almost all available drugs calls for the identification of new compounds and the detection of novel targets. here, we establish the antimalarial activities of risedronate, one of the most potent bisphosphonates clinically used to treat bone resorption diseases, against blood stages of plasmodium falciparum (50% inhibitory concentration [ic50] of 20.3±1.0 µm). we also suggest a mechanism of action for risedronate against the intraerythrocytic sta ...201121357292
activation of a pak-mek signalling pathway in malaria parasite-infected erythrocytes.merozoites of malaria parasites invade red blood cells (rbcs), where they multiply by schizogony, undergoing development through ring, trophozoite and schizont stages that are responsible for malaria pathogenesis. here, we report that a protein kinase-mediated signalling pathway involving host rbc pak1 and mek1, which do not have orthologues in the plasmodium kinome, is selectively stimulated in plasmodium falciparum-infected (versus uninfected) rbcs, as determined by the use of phospho-specific ...201121371233
characterization of plasmodium berghei glutathione synthetase.plasmodium berghei contained 0.454±0.031 u/mg of glutathione synthetyase (gs). gs was purified using solid ammonium sulfate and sephadex g-200 from p. berghei infected mouse erythrocytes. sds-page showed purified gs as a single band protein of 70 kda and its km for ?-glutamylcysteine, glycine and atp being 0.33 mm, 8.3 mm and 0.43 mm respectively with noncompetitive inhibition by gsh. the malaria parasite enzyme was optimally active at 37°c and ph 8.0-8.5. heavy metals significantly inhibited pa ...201121377539
[cryopreservation of plasmodia with malaria models and establishment of a cryobank.]objective: cryopreservation is simply a method of keeping living cells frozen with the chance of regaining cellular viability, functions and antigenic structures whenever required, after heating. methods: in the present study, dimethyl sulphoxide (dmso) was mixed with the red blood cells having 20% of parasitemia obtained from the mice infected with plasmodium yoelii and plasmodium berghei at a final concentration of 15%. for cryopreservation: both test tubes containing each plasmodium species w ...201021391181
anopheles stephensi saliva enhances progression of cerebral malaria in a murine model.malaria accounts for the greatest morbidity and mortality of any arthropod-borne disease globally. recently, it was determined that the protective antisporozoite cd8+ t-cell response originates predominantly from cutaneous lymph nodes draining the site of parasite inoculation by an anopheles mosquito. the female mosquito inoculates sporozoites along with an assortment of salivary proteins into the skin of its mammalian host. mosquito saliva has demonstrable antihemostatic as well as various immu ...201121395422
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