comparative susceptibility of different mouse strains to liver-stage infection with plasmodium berghei sporozoites assessed using in vivo imaging. | the liver stages of plasmodium parasites are important targets for the discovery and development of prophylactic drugs. | 2017 | 28291500 |
rhesus macaque and mouse models for down-selecting circumsporozoite protein based malaria vaccines differ significantly in immunogenicity and functional outcomes. | non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. transgenic rodent parasites expressing genes of human plasmodium are now routinely used for efficacy studies of human malaria vaccines. mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are suffi ... | 2017 | 28288639 |
transdermal delivery of oleanolic acid attenuates pro-inflammatory cytokine release and ameliorates anaemia in p. berghei malaria. | malaria remains a major health problem in many tropical areas. severe malaria infection is associated with secondary complications including anaemia leading to a need for the search of affordable antimalarial agents that can clear the parasitaemia and ameliorate anaemia during infection. the current study investigated the effects of transdermally delivered oa on malaria parasites, hct and selected plasma cytokine concentrations in p. berghei-infected male sprague-dawley rats. the study was carri ... | 2017 | 28283442 |
quantitative characterization of hemozoin in plasmodium berghei and vivax. | the incidence and global distribution of chloroquine resistant (cr) plasmodium vivax infection has increased since emerging in 1989. the mechanism of resistance in cr p. vivax has not been defined. the resistance likely relates to the formation and disposition of hemozoin as chloroquine's primary mechanism of action involves disruption of hemozoin formation. cr p. berghei strains, like cr p. vivax strains, are confined to reticulocyte host cells and reportedly they do not accumulate appreciable ... | 2017 | 28279945 |
new derivatives of quinoline-4-carboxylic acid with antiplasmodial activity. | new analogues of the recently published compound ddd107498 were prepared. their activities were examined in vitro against the chloroquine-sensitive nf54 strain. the most active were also tested against the multiresistant k1 strain of plasmodium falciparum. a couple of the newly synthesized compounds showed promising antiplasmodial activity and selectivity. a single compound showed adequate reduction of parasitaemia (98.1%) in mice infected with plasmodium berghei. survival time was doubled compa ... | 2017 | 28279559 |
primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms. | primaquine is an anti-malarial used to prevent plasmodium vivax relapses and malaria transmission. however, pq metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (g6pd). fifteen pq-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes. | 2017 | 28279180 |
targeting angiotensin ii type-1 receptor (at1r) inhibits the harmful phenotype of plasmodium-specific cd8(+) t cells during blood-stage malaria. | cd8(+) t-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. our group and other have been shown that angiotensin ii (ang ii) and its receptor at1 (at1r), a key effector axis of renin-angiotensin system (ras), have immune regulatory effects on t cells. previously, we showed that inhibition of at1r signaling protects mice against the lethal disease induced by plasmodium berghei anka infection however, most of the ang ii/at1r actions were characterized by using on ... | 2017 | 28261571 |
vaccination with altered peptide ligands of a plasmodium berghei circumsporozoite protein cd8 t-cell epitope: a model to generate t cells resistant to immune interference by polymorphic epitopes. | many pathogens, including the malaria parasite plasmodium falciparum, display high levels of polymorphism within t-cell epitope regions of proteins associated with protective immunity. the t-cell epitope variants are often non-cross-reactive. herein, we show in a murine model, which modifies a protective cd8 t-cell epitope from the circumsporozoite protein (cs) of plasmodium berghei (syipsaeki), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive ... | 2017 | 28261200 |
in vivo efficacy of top five surveyed ghanaian herbal anti-malarial products. | anti-malarial herbal preparations (hps) continue to enjoy high patronage in ghana despite reports that the artemisinin-based combination therapy (act), the recommended first choice for treatment of uncomplicated malaria in the country, remains efficacious. a major issue with the use of these preparations is inadequate or unreliable data on their efficacy and quality. an assessment of the potency and quality of the most popular commercial anti-malarial hps in ghana was, therefore, carried out. th ... | 2017 | 28259160 |
antimalarials with benzothiophene moieties as aminoquinoline partners. | malaria is a severe and life-threatening disease caused by plasmodium parasites that are spread to humans through bites of infected anopheles mosquitoes. here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting plasmodium falciparum parasite growth. synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. benzothiophenes presented in this paper showed improved activities against a chloroquine su ... | 2017 | 28245583 |
gancidin w, a potential low-toxicity antimalarial agent isolated from an endophytic streptomyces suk10. | endophytic streptomyces strains are potential sources for novel bioactive molecules. in this study, the diketopiperazine gancidin w (gw) was isolated from the endophytic actinobacterial genus streptomyces, suk10, obtained from the bark of shorea ovalis tree, and it was tested in vivo against plasmodium berghei pzz1/100. gw exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg(-1) body weight on day four using the 4-day suppression test method on male icr strain mice. comparing gw at ... | 2017 | 28223778 |
palmitoylation of plasmodium alveolins promotes cytoskeletal function. | s-palmitoylation is a post-translational lipid modification that is widespread among plasmodium proteins and essential for parasite development. little is known about the contribution of palmitoylation to the function of individual parasite molecules and structures. alveolins are major components of the subpellicular network (spn), a cortical cytoskeleton primarily involved in providing mechanical strength to the cell. we show here that the alveolin imc1c is palmitoylated on a conserved cysteine ... | 2017 | 28223095 |
anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria. | the widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. in this study, chloroquine derivatives were evaluated for the improved anti-malarial activity. | 2017 | 28212631 |
erratum to: characterization of a plasmodium berghei sexual stage antigen pbph as a new candidate for malaria transmission-blocking vaccine. | | 2017 | 28209188 |
cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites. | apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. the identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. here we demonstrate that members of an apicomplexan-specific protein family-the novel putative transporters (npts)-play key roles in the uptake of cationic amino acids. we show that an npt from toxoplasma gondii (tgnpt1) is a selective arginine tran ... | 2017 | 28205520 |
the deubiquitinating enzyme cylindromatosis dampens cd8(+) t cell responses and is a critical factor for experimental cerebral malaria and blood-brain barrier damage. | cerebral malaria is a severe complication of human malaria and may lead to death of plasmodium falciparum-infected individuals. cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. although cd8(+) t cells have been implicated in the development of murine experimental cerebral malaria (ecm), several other studies have shown that cd8(+) t cells confer protection agai ... | 2017 | 28203236 |
plasmodium berghei plasmepsin viii is essential for sporozoite gliding motility. | plasmodium aspartic proteases, termed plasmepsins (pms) play many critical roles such as haemoglobin degradation, cleavage of pexel proteins and sporozoite development in the parasite life cycle. most of the plasmepsins are well characterized, however the role of pm viii in plasmodium remains unknown. here, we elucidate the functions of pm viii (pbanka_132910) in the rodent malaria parasite plasmodium berghei (pb). by targeted gene deletion, we show that pbpm viii is critical for sporozoite egre ... | 2017 | 28192122 |
antimalarial, antiplasmodial and analgesic activities of root extract of alchornea laxiflora. | alchornea laxiflora (benth.) pax. & hoffman (euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in nigeria. | 2017 | 28183236 |
the antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria. | according to the who, and despite reduction in mortality rates, there were an estimated 438 000 malaria deaths in 2015. therefore new antimalarials capable of limiting organ damage are still required. we show that systemic and lung adenovirus (ad)-mediated over-expression of trappin-2 (t-2) an antibacterial molecule with anti-inflammatory activity, increased mice survival following infection with the cerebral malaria-inducing plasmodium berghei anka (pbanka) strain. systemically, t-2 reduced pba ... | 2017 | 28181563 |
cellular stress associated with the differentiation of plasmodium berghei ookinetes. | for malaria transmission, plasmodium parasites must develop in the mosquito vector. oxidative stress in the insect midgut, triggered by environmental changes (e.g., ph and temperature), influences the cellular signaling involved in differentiation from gametocytes to mobile ookinetes for the purpose of parasite survival. oxidative stress activates the homeostatic response to stress characterized by the phosphorylation eif2α, the attenuation of protein synthesis, and the transcription of genes pa ... | 2017 | 28177775 |
the antimalarial effect of curcumin is mediated by the inhibition of glycogen synthase kinase-3β. | curcumin, a bioactive compound in curcuma longa, exhibits various pharmacological activities, including antimalarial effects. in silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (gsk3β)-inhibitory properties. the involvement of gsk3 in the antimalarial effects in vivo is yet to be demonstrated. in this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host gsk3β. intraperitoneal administration of curcu ... | 2017 | 28146408 |
plasmodium berghei exp-1 interacts with host apolipoprotein h during plasmodium liver-stage development. | the first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. hepatic plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (pv). here, we show that, during the parasite's hepatic replication, the c-terminal region of the parasitic pv membrane pro ... | 2017 | 28137845 |
increased cd11b and hypoxia-inducible factors-1alpha expressions in the lung tissue and surfactant protein-d levels in serum are related with acute lung injury in severe malaria of c57bl/6 mice. | we aimed to reveal the role of cd11b and hypoxia-inducible factors-1alpha (hif-1α) expressions on monocytes and alveolar macrophages of lung tissue, and the levels of serum surfactant protein-d (sp-d) in severe malaria-associated acute lung injury (ali). | 2017 | 28127335 |
sex-specific biology of the human malaria parasite revealed from the proteomes of mature male and female gametocytes. | the gametocytes of the malaria parasites are obligate for perpetuating the parasite's life cycle through mosquitoes, but the sex-specific biology of gametocytes is poorly understood. we generated a transgenic line in the human malaria parasite plasmodium falciparum, which allowed us to accurately separate male and female gametocytes by flow cytometry. in-depth analysis of the proteomes by liquid chromatography-tandem mass spectrometry identified 1244 and 1387 proteins in mature male and female g ... | 2017 | 28126901 |
sequestration of cholesterol within the host late endocytic pathway restricts liver-stage plasmodium development. | while lysosomes are degradative compartments and one of the defenses against invading pathogens, they are also hubs of metabolic activity. late endocytic compartments accumulate around plasmodium berghei liver-stage parasites during development, and whether this is a host defense strategy or active recruitment by the parasites is unknown. in support of the latter hypothesis, we observed that the recruitment of host late endosomes (les) and lysosomes is reduced in uis4(-) parasites, which lack a ... | 2017 | 28122820 |
grammomys surdaster, the natural host for plasmodium berghei parasites, as a model to study whole-organism vaccines against malaria. | inbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. to establish a more rigorous animal model, we acquired african woodland thicket rats of the genus grammomys, the natural hosts for plasmodium berghei thicket rats were acquired and identified as grammomys surdaster by skull and teeth measurements and mitochondrial dna genotyping. herein, we demonstrate that thicket rats are highly susceptible to infection by p berghei, an ... | 2017 | 28115674 |
motility precedes egress of malaria parasites from oocysts. | malaria is transmitted when an infected anopheles mosquito deposits plasmodium sporozoites in the skin during a bite. sporozoites are formed within oocysts at the mosquito midgut wall and are released into the hemolymph, from where they invade the salivary glands and are subsequently transmitted to the vertebrate host. we found that a thrombospondin-repeat containing sporozoite-specific protein named thrombospondin-releated protein 1 (trp1) is important for oocyst egress and salivary gland invas ... | 2017 | 28115054 |
pharmacomodulation of the antimalarial plasmodione: synthesis of biaryl- and n-arylalkylamine analogues, antimalarial activities and physicochemical properties. | with the aim of increasing the structural diversity on the early antimalarial drug plasmodione, an efficient and versatile procedure to prepare a series of biaryl- and n-arylalkylamines as plasmodione analogues is described. using the naturally occurring and commercially available menadione as starting material, a 2-step sequence using a kochi-anderson reaction and subsequent pd-catalyzed suzuki-miyaura coupling was developed to prepare three representative biphenyl derivatives in good yields fo ... | 2017 | 28106855 |
impact of extended duration of artesunate treatment on parasitological outcome in a cytocidal murine malaria model. | artemisinin-based combination therapies are a key pillar in global malaria control and are recommended as a first-line plasmodium falciparum treatment. they rely upon a rapid 4-log-unit reduction in parasitemia by artemisinin compounds with a short half-life and the killing of remaining parasites by a partner compound with a longer half-life. current treatment guidelines stipulate giving three 24-h-interval doses or six 12-h-interval doses over a 3-day period. due to the short half-life of artes ... | 2017 | 28096162 |
platelets activate a pathogenic response to blood-stage plasmodium infection but not a protective immune response. | clinical studies indicate that thrombocytopenia correlates with the development of severe falciparum malaria, suggesting that platelets either contribute to control of parasite replication, possibly as innate parasite killer cells or function in eliciting pathogenesis. removal of platelets by anti-cd41 mab treatment, platelet inhibition by aspirin, and adoptive transfer of wild-type (wt) platelets to cd40-ko mice, which do not control parasite replication, resulted in similar parasitemia compare ... | 2017 | 28096086 |
the threshold of protection from liver-stage malaria relies on a fine balance between the number of infected hepatocytes and effector cd8(+) t cells present in the liver. | since the demonstration of sterile protection afforded by injection of irradiated sporozoites, cd8(+) t cells have been shown to play a significant role in protection from liver-stage malaria. this is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. we used an adoptive transfer model to elucidate the kinetics of the effect ... | 2017 | 28087668 |
cloning, characterization and transmission blocking potential of midgut carboxypeptidase a in anopheles stephensi. | transmission-blocking vaccines (tbv) interrupt malaria parasite transmission and hence form an important component for malaria eradication. mosquito midgut exopeptidases such as aminopeptidase n & carboxypeptidase b have demonstrated tbv potential. in the present study, we cloned and characterized carboxypeptidase a (cpa) from the midgut of an important malarial vector, anopheles stephensi. clustalw amino acid alignment and in silico 3-dimensional structure analysis of cpa predicted the presence ... | 2017 | 28087198 |
in vivo antiplasmodial activity and toxicological assessment of hydroethanolic crude extract of ajuga remota. | malaria is one of the most life-threatening health problems worldwide and treatment has been compromised by drug resistance. identifying lead molecules from natural products might help to find better anti-malarial drugs, since those obtained from natural sources are still effective against malarial parasites. this study aimed at investigating the in vivo antiplasmodial activity of crude extract of the leaves of ajuga remota together with its safety in mice models. | 2017 | 28086782 |
a knockout screen of apiap2 genes reveals networks of interacting transcriptional regulators controlling the plasmodium life cycle. | a family of apicomplexa-specific proteins containing ap2 dna-binding domains (apiap2s) was identified in malaria parasites. this family includes sequence-specific transcription factors that are key regulators of development. however, functions for the majority of apiap2 genes remain unknown. here, a systematic knockout screen in plasmodium berghei identified ten apiap2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three wer ... | 2017 | 28081440 |
modulation of host cell sumoylation facilitates efficient development of plasmodium berghei and toxoplasma gondii. | sumoylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport, and protein-protein interactions. several viruses and bacteria modulate host sumoylation machinery for efficient infection. plasmodium sporozoites are infective forms of malaria parasite that invade mammalian hepatocytes and transforms into exoerythrocytic forms (eefs). here, we show that during eef development, the distribution of sumoylated proteins in host ... | 2017 | 28078755 |
a novel and conserved plasmodium sporozoite membrane protein speld is required for maturation of exo-erythrocytic forms. | plasmodium sporozoites are the infective forms of malaria parasite to vertebrate host and undergo dramatic changes in their transcriptional repertoire during maturation in mosquito salivary glands. we report here the role of a novel and conserved plasmodium berghei protein encoded by pbanka_091090 in maturation of exo-erythrocytic forms (eefs) and designate it as sporozoite surface protein essential for liver stage development (pbspeld). pbanka_091090 was previously annotated as pb402615.00.0 an ... | 2017 | 28067322 |
antimalarial activity of syzygium guineense during early and established plasmodium infection in rodent models. | in ethiopia, the leaves of syzygium guineense have been found useful for the prevention and cure of malaria, and demonstrated antiplasmodial activity in vitro. nevertheless, no scientific study has been conducted to confirm its antimalarial activity in vivo. therefore, the objective of the study was to evaluate the antimalarial effect of syzygium guineense leaf extract in mice. | 2017 | 28056963 |
in vivo antimalarial activity of crude extracts and solvent fractions of leaves of strychnos mitis in plasmodium berghei infected mice. | malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-saharan africa. today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. medicinal plants are the unquestionable source of effective antimalarials. the present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant strychnos mitis in plasmodium berghei infected mice. | 2017 | 28056932 |
inhibition of in vivo growth of plasmodium berghei by launaea taraxacifolia and amaranthus viridis in mice. | launaea taraxacifolia and amaranthus viridis used by people of western africa in the treatment of malaria and related symptoms were assessed for their antiplasmodial value against the chloroquine sensitive strain of plasmodium berghei. crude extracts (200 mg/kg) and chloroquine (5 mg/kg) were administered to different groups of swiss mice. the percentage of parasitemia, survival time, and haematological parameters were determined. both extracts significantly (p < 0.05) inhibited parasitemia and ... | 2016 | 28050307 |
antimalarial potential of carica papaya and vernonia amygdalina in mice infected with plasmodium berghei. | the study determined if administration of vernonia amygdalina and carica papaya plants provides synergistic effects in ameliorating plasmodium infection in mice. thirty mice (17.88-25.3 g) were divided into 6 groups of 5 mice each. group 1 was normal control, while groups 2-6 were intraperitoneally inoculated 2.5 × 10(7)plasmodium berghei parasitized red blood cell, followed by daily administration of 350 mg/kg aqueous leaf extracts after establishment of infection. group 2 was disease control, ... | 2016 | 28042299 |
antimalarial efficacy of low molecular weight chitosan against plasmodium berghei infection in mice. | despite continuous global attempts to fight parasitic infections, malaria still remains one of the major human life threatening diseases. difficulty of producing efficient antimalaria vaccines and increasing drug-resistant strains, highlight the urgent need to search for a new alternative antimalaria drug. the aim of this study was to find a new agent against malaria parasite with maximum efficacy and minimum range of side-effects. for this, the antiplasmodial activity of commercial chitosan, a ... | 2016 | 28035107 |
stage-specific changes in plasmodium metabolism required for differentiation and adaptation to different host and vector environments. | malaria parasites (plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (tca) metabolism in mosquito stages. here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage ... | 2016 | 28027318 |
preferentially expanding vγ1(+) γδ t cells are associated with protective immunity against plasmodium infection in mice. | γδ t cells play a crucial role in controlling malaria parasites. dendritic cell (dc) activation via cd40 ligand (cd40l)-cd40 signaling by γδ t cells induces protective immunity against the blood-stage plasmodium berghei xat (pbxat) parasites in mice. however, it is unknown which γδ t-cell subset has an effector role and is required to control the plasmodium infection. here, using antibodies to deplete tcr vγ1(+) cells, we saw that vγ1(+) γδ t cells were important for the control of pbxat infecti ... | 2017 | 28012161 |
transcriptomic profiling of microglia reveals signatures of cell activation and immune response, during experimental cerebral malaria. | cerebral malaria is a pathology involving inflammation in the brain. there are many immune cell types activated during this process, but there is little information on the response of microglia, in this severe complication. we examined microglia by genome wide transcriptomic analysis in a model of experimental cerebral malaria (ecm), in which c57bl/6 mice are infected with plasmodium berghei anka. thousands of transcripts were differentially expressed in microglia at two different time points du ... | 2016 | 27991544 |
evaluation of the antimalarial effect of ferulago angulata (schlecht.) boiss. extract and suberosin epoxide against plasmodium berghei in comparison with chloroquine using in-vivo test. | resistance to most antimalarial drugs has encouraged the development of novel drugs. an alternative source for discovering such drugs is natural products. some ferulago species are used in folk medicine for their sedative, tonic and anti-parasitic effects. besides, coumarins isolated from this genus found to have in vitro anti-leishmanicidal effect. the present study is aimed to evaluate the in-vivo antimalarial activity of ferulago angulata (schlecht.) boiss. extract and suberosin epoxide, usin ... | 2016 | 27980587 |
a malaria transmission-blocking (+)-usnic acid derivative prevents plasmodium zygote-to-ookinete maturation in the mosquito midgut. | the evolution of drug resistance is a recurrent problem that has plagued efforts to treat and control malaria. recent emergence of artemisinin resistance in southeast asia underscores the need to develop novel antimalarials and identify new targetable pathways in plasmodium parasites. transmission-blocking approaches, which typically target gametocytes in the host bloodstream or parasite stages in the mosquito gut, are recognized collectively as a strategy that when used in combination with anti ... | 2016 | 27978709 |
an apicomplexan actin-binding protein serves as a connector and lipid sensor to coordinate motility and invasion. | apicomplexa exhibit a unique form of substrate-dependent gliding motility central for host cell invasion and parasite dissemination. gliding is powered by rearward translocation of apically secreted transmembrane adhesins via their interaction with the parasite actomyosin system. we report a conserved armadillo and pleckstrin homology (ph) domain-containing protein, termed glideosome-associated connector (gac), that mediates apicomplexan gliding motility, invasion, and egress by connecting the m ... | 2016 | 27978434 |
association of heme oxygenase 1 with lung protection in malaria-associated ali/ards. | malaria is a serious disease, caused by the parasite of the genus plasmodium, which was responsible for 440,000 deaths in 2015. acute lung injury/acute respiratory distress syndrome (ali/ards) is one of the main clinical complications in severe malaria. the murine model dba/2 reproduces the clinical signs of ali/ards in humans, when infected with plasmodium berghei anka. high levels of ho-1 were reported in cases of severe malaria. our data indicated that the ho-1 mrna and protein expression are ... | 2016 | 27974865 |
asiatic acid-pectin hydrogel matrix patch transdermal delivery system influences parasitaemia suppression and inflammation reduction in p. berghei murine malaria infected sprague-dawley rats. | to report the influence of transdermal delivery of asiatic acid (aa) in plasmodium berghei-infected sprague dawley rats on physicochemical changes, %parasitaemia and associated pathophysiology. | 2016 | 27955745 |
sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance. | the present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (al) from a nanostructured lipid carrier (nlc) of lumefantrine (lum) and estimate the potential of al as an oral delivery system in malariogenic wistar mice. lum-nlcs were prepared by hot homogenization using precirol(®) ato 5/transcutol(®) hp and tallow fat/transcutol(®) hp optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. lum-nlc characteristics, ... | 2017 | 27932882 |
targeting neutrophils to prevent malaria-associated acute lung injury/acute respiratory distress syndrome in mice. | malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. when manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ali/ards). we have previously shown that a proportion of dba/2 mice infected with plasmodium berghei anka (pba) develop ali/ards and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. herein, we investig ... | 2016 | 27926944 |
decreased rate of plasma arginine appearance in murine malaria may explain hypoargininemia in children with cerebral malaria. | plasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion. | 2016 | 27923948 |
in vitro and ex vivo activity of an azadirachta indica a.juss. seed kernel extract on early sporogonic development of plasmodium in comparison with azadirachtin a, its most abundant constituent. | neemazal(®) (na) is a quantified extract from seed kernels of neem, azadirachta indica a.juss. (meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content. na contains several azadirachtins (a to l), azadirachtin a (azaa) being its main constituent. azaa has been shown to inhibit microgamete formation of the rodent malaria parasite plasmodium berghei, and na was found to completely inhibit the transmission of plasmodium berghei to anopheles stephensi ... | 2016 | 27912876 |
larval diet affects mosquito development and permissiveness to plasmodium infection. | the larval stages of malaria vector mosquitoes develop in water pools, feeding mostly on microorganisms and environmental detritus. richness in the nutrient supply to larvae influences the development and metabolism of larvae and adults. here, we investigated the effects of larval diet on the development, microbiota content and permissiveness to plasmodium of anopheles coluzzii. we tested three fish diets often used to rear mosquitoes in the laboratory, including two pelleted diets, dr. clarke's ... | 2016 | 27910908 |
in vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin. | the emergence of artemisinin-resistant plasmodium falciparum strains poses a serious challenge to the control of malaria. this necessitates the development of new anti-malarial drugs. previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the p. falciparum heat-shock protein 90 (pfhsp90). the aim of this study was to test the anti-malarial activity of harmine analogues. | 2016 | 27903279 |
the plasmodium falciparum cell-traversal protein for ookinetes and sporozoites as a candidate for preerythrocytic and transmission-blocking vaccines. | recent studies have shown that immune responses against the cell-traversal protein for plasmodium ookinetes and sporozoites (celtos) can inhibit parasite infection. while these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the plasmodium falciparum celtos in vivo using a newly developed rodent malaria chimeric parasite expressing the p. falciparum celtos (pfceltos), we evaluated the protective ... | 2017 | 27895131 |
progress in imaging methods: insights gained into plasmodium biology. | over the past decade, major advances in imaging techniques have enhanced our understanding of plasmodium spp. parasites and their interplay with mammalian hosts and mosquito vectors. cryoelectron tomography, cryo-x-ray tomography and super-resolution microscopy have shifted paradigms of sporozoite and gametocyte structure, the process of erythrocyte invasion by merozoites, and the architecture of maurer's clefts. intravital time-lapse imaging has been revolutionary for our understanding of pre-e ... | 2017 | 27890922 |
antiplasmodial activity of heinsia crinita (rubiaceae) and identification of new iridoids. | heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. its stem bark powder is found in some peripheral markets in the democratic republic of the congo (drc) as a remedy against malaria. investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties. | 2017 | 27890637 |
differences in the modulation of reactive species, lipid bodies, cyclooxygenase-2, 5-lipoxygenase and ppar-γ in cerebral malaria-susceptible and resistant mice. | proinflammatory responses are associated with the severity of cerebral malaria. no, h2o2, eicosanoid and ppar-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. this work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible cba and c57bl/6 and -resistant balb/c mice. mice were infected with plasmodium berghei anka, and the survival rates and parasitemia curves were assessed. on the sixth day post-infection, ... | 2017 | 27887739 |
antimalarial properties of aqueous crude extracts of gynostemma pentaphyllum and moringa oleifera leaves in combination with artesunate in plasmodium berghei-infected mice. | due to the emergence and spread of malaria parasite with resistance to antimalarial drugs, discovery and development of new, safe, and affordable antimalarial are urgently needed. in this respect, medicinal plant extracts are targets to optimize antimalarial actions and restore efficacy of standard antimalarial drugs. the present study was aimed at determining the antimalarial activities of gynostemma pentaphyllum and moringa oleifera leaf extracts in combination with artesunate against plasmodi ... | 2016 | 27872647 |
minocycline prevents cerebral malaria, confers neuroprotection and increases survivability of mice during plasmodium berghei anka infection. | cerebral malaria (cm) is a neurological complication arising due to plasmodium falciparum or plasmodium vivax infection. minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. in this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ecm). the currently accepted mouse model, c57bl/6 mice infected with plasmodium berghei anka, was used fo ... | 2017 | 27865203 |
antiplasmodial activity of the ethanolic root bark extract of icacina senegalensis in mice infected by plasmodium berghei. | the root of icacina senegalensis is used for the treatment of malaria and related conditions in southeastern nigeria. | 2017 | 27845882 |
mutation tendency of mutator plasmodium berghei with proofreading-deficient dna polymerase δ. | in this study, we investigated the mutation tendency of a mutator rodent malaria parasite, plasmodium berghei, with proofreading-deficient dna polymerase δ. wild-type and mutator parasites were maintained in mice for over 24 weeks, and the genome-wide accumulated mutations were determined by high-throughput sequencing. the mutator p. berghei had a significant preference for c/g to a/t substitutions; thus, its genome had a trend towards a higher at content. the mutation rate was influenced by the ... | 2016 | 27845384 |
novel metalloantimalarials: transmission blocking effects of water soluble cu(i), ag(i) and au(i) phosphane complexes on the murine malaria parasite plasmodium berghei. | the water soluble phosphane complexes [m(l)4]pf6 (m=cu(i), ag(i)) and [au(l)4]cl (l=thp (tris(hydroxymethyl)phosphane) or pta (1,3,5-triaza-7-phosphaadamantane)) showed notable in vitro activity against plasmodium early sporogonic stages, the sexual forms of the malaria parasite that are responsible for infection of the mosquito vector. effects varied according to both, the type of metal and phosphane ligands. [ag(thp)4]pf6 was the best performing complex exhibiting a half inhibitory concentrati ... | 2017 | 27815977 |
tacrolimus prevents murine cerebral malaria. | tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transplantation. tacrolimus is also reported to inhibit plasmodium falciparum growth in vitro. here, we report that tacrolimus prevented the death from cerebral malaria of plasmodium berghei anka-infected c57bl/6j mice, but not their death from malaria due to the high parasitaemia and severe anaemia. the mycophenolate mofetil-treated mice showed higher mortality from cerebral malaria and succumbed to malar ... | 2017 | 27546479 |
a neuroprotective effect of the glutamate receptor antagonist mk801 on long-term cognitive and behavioral outcomes secondary to experimental cerebral malaria. | cerebral malaria (cm) is a life-threatening complication of plasmodium falciparum infection, which can result in long-term cognitive and behavioral deficits despite successful anti-malarial therapy. due to the substantial social and economic burden of cm, the development of adjuvant therapies is a scientific goal of highest priority. apart from vascular and immune responses, changes in glutamate system have been reported in cm pathogenesis suggesting a potential therapeutic target. based on that ... | 2016 | 27796746 |
usp15 regulates type i interferon response and is required for pathogenesis of neuroinflammation. | genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. we identified a mutation in the gene encoding the deubiquitination enzyme usp15 (usp15(l749r)) that protected mice against both experimental cerebral malaria (ecm) induced by plasmodium berghei and experimental autoimmune encephalomyelitis (eae). c ... | 2017 | 27721430 |
endothelin-1 treatment induces an experimental cerebral malaria-like syndrome in c57bl/6 mice infected with plasmodium berghei nk65. | plasmodium berghei anka infection of c57bl/6 mice is a widely used model of experimental cerebral malaria (ecm). by contrast, the nonneurotropic p. berghei nk65 (pbn) causes severe malarial disease in c57bl/6 mice but does not cause ecm. previous studies suggest that endothelin-1 (et-1) contributes to the pathogenesis of ecm. in this study, we characterize the role of et-1 on ecm vascular dysfunction. mice infected with 10(6) pbn-parasitized red blood cells were treated with either et-1 or salin ... | 2016 | 27640146 |
t-cell immunoglobulin- and mucin-domain-containing molecule 3 signaling blockade improves cell-mediated immunity against malaria. | cell-mediated immune responses play important roles in immune protection against plasmodium infection. however, impaired immunity, such as lymphocyte exhaustion, is a common phenomenon in malaria. t-cell immunoglobulin- and mucin-domain-containing molecule 3 (tim-3) is an important regulatory molecule in cell-mediated immunity and has been implicated in malaria. in this study, it was found that tim-3 expression on key populations of lymphocytes was significantly increased in both plasmodium falc ... | 2016 | 27638944 |
spect/ct analysis of splenic function in genistein-treated malaria-infected mice. | spleen traps malaria-infected red blood cells, thereby leading to splenomegaly. splenomegaly induces impairment in splenic function, i.e., rupture. therefore, splenomegaly inhibition is required to protect the spleen. in our previous study, genistein was found to have an influence on malaria-induced splenomegaly. however, the effect of genistein in malaria-induced splenomegaly, especially on the function of spleen, has not been fully investigated. in this study, hematoxylin and eosin (h&e) stain ... | 2016 | 27585499 |
conjugation of n-acylhydrazone and 1,2,4-oxadiazole leads to the identification of active antimalarial agents. | malaria, caused by several plasmodium species, is the major life-threatening parasitic infection worldwide. due to the parasite resistance to quinoline based drugs, the search for antimalarial agents is necessary. here, we report the structural design, synthesis and antiparasitic evaluation of two novel series of 1,2,4-oxadiazoles in conjugation to n-acylhydrazones, both groups recognized as privileged structures, as well as the studies on the antimalarial activity of 16 previous described analo ... | 2016 | 27667552 |
nanostructured lipid carriers of artemether-lumefantrine combination for intravenous therapy of cerebral malaria. | patients with cerebral malaria (cm) are unable to take oral medication due to impaired consciousness and vomiting thus necessitating parenteral therapy. quinine, artemether, and artesunate which are currently used for parenteral malaria therapy have their own drawbacks. the world health organization (who) has now banned monotherapy and recommends artemisinin-based combination therapy for malaria treatment. however, presently there is no intravenous formulation available for combination therapy o ... | 2016 | 27596113 |
bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes. | the intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (hsa), into parasitized red blood cells (prbcs). we have designed hsa-based nanoparticles as a potential drug-delivery option for antimalarials. | 2016 | 27759489 |
antimalarial activity of the terpene nerolidol. | malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. the emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. we previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the us food an ... | 2016 | 27742206 |
uptake of parasite-derived vesicles by astrocytes and microglial phagocytosis of infected erythrocytes may drive neuroinflammation in cerebral malaria. | astrocytes and microglia are activated during cerebral malaria (cm) and contribute to the production and release of several mediators during neuroinflammatory processes. whether these changes are the consequence of a direct crosstalk between glial cells and the malarial parasite and how these cells participate in the pathogenesis of cm is not yet clear. we therefore examined the interaction of astrocytes and microglia with plasmodium berghei anka-infected red blood cells using primary cell cultu ... | 2017 | 27696532 |
the evolutionary divergence of stat transcription factor in different anopheles species. | anopheles mosquito transmits plasmodium, the malaria causing parasite. different species of anopheles mosquito dominate in a particular geographical location and are capable of transmitting specific strains of plasmodium. it is important to understand the biology of different anophelines to control the parasite transmission. stat is an evolutionary conserved transcription factor that regulates the parasite development in african malaria vector anopheles gambiae. unlike drosophila and aedes aegyp ... | 2017 | 27664587 |
natural products from zanthoxylum heitzii with potent activity against the malaria parasite. | zanthoxylum heitzii (rutaceae) (olon) is used in traditional medicine in central and west africa to treat malaria. to identify novel compounds with anti-parasitic activity and validate medicinal usage, extracts and compounds isolated from this tree were tested against the erythrocytic stages of the human malaria parasite plasmodium falciparum and for inhibition of transmission in rodent malaria parasite plasmodium berghei. | 2016 | 27649682 |
udp-galactose and acetyl-coa transporters as plasmodium multidrug resistance genes. | a molecular understanding of drug resistance mechanisms enables surveillance of the effectiveness of new antimicrobial therapies during development and deployment in the field. we used conventional drug resistance selection as well as a regime of limiting dilution at early stages of drug treatment to probe two antimalarial imidazolopiperazines, kaf156 and gnf179. the latter approach permits the isolation of low-fitness mutants that might otherwise be out-competed during selection. whole-genome s ... | 2016 | 27642791 |
transmission blocking effects of neem (azadirachta indica) seed kernel limonoids on plasmodium berghei early sporogonic development. | azadirachta indica, known as neem tree and traditionally called "nature's drug store" makes part of several african pharmacopeias and is widely used for the preparation of homemade remedies and commercial preparations against various illnesses, including malaria. employing a bio-guided fractionation approach, molecules obtained from a. indica ripe and green fruit kernels were tested for activity against early sporogonic stages of plasmodium berghei, the parasite stages that develop in the mosqui ... | 2016 | 27642038 |
tetrahydrobiopterin supplementation improves phenylalanine metabolism in a murine model of severe malaria. | tetrahydrobiopterin (bh4) is an essential cofactor for both phenylalanine hydroxylase and nitric oxide synthase. patients with severe malaria have low urinary bh4, elevated plasma phenylalanine, and impaired endothelium-dependent vasodilation, suggesting that bh4 depletion may limit phenylalanine metabolism and nitric oxide synthesis. we infected c57bl/6 mice with plasmodium berghei anka to characterize bh4 availability and to investigate the effects of bh4 supplementation. p. berghei anka infec ... | 2016 | 27641435 |
asiatic acid influences parasitaemia reduction and ameliorates malaria anaemia in p. berghei infected sprague-dawley male rats. | current malaria treatment is either "anti-parasitic", "anti-infectivity" or both without addressing the pathophysiological derangement (anti-disease aspect) associated with the disease. asiatic acid is a natural phytochemical with oxidant, antioxidant and anti-inflammatory properties whose effect on malarial and accompanying pathophysiology are yet to be investigated. asiatic acid influence in p. berghei-infected sprague dawley rats on %parasitaemia and malarial anaemia were investigated. | 2016 | 27618936 |
distinct prominent roles for enzymes of plasmodium berghei heme biosynthesis in sporozoite and liver stage maturation. | malarial parasites have evolved complex regulation of heme supply and disposal to adjust to heme-rich and -deprived host environments. in addition to its own pathway for heme biosynthesis, plasmodium likely harbors mechanisms for heme scavenging from host erythrocytes. elaborate compartmentalization of de novo heme synthesis into three subcellular locations, including the vestigial plastid organelle, indicates critical roles in life cycle progression. in this study, we systematically profile the ... | 2016 | 27600503 |
ex vivo maturation assay for testing antimalarial sensitivity of rodent malaria parasites. | ex vivo assay systems provide a powerful approach to studying human malaria parasite biology and to testing antimalarials. for rodent malaria parasites, short-term in vitro culture and ex vivo antimalarial susceptibility assays are relatively cumbersome, relying on in vivo passage for synchronization, since ring-stage parasites are an essential starting material. here, we describe a new approach based on the enrichment of ring-stage plasmodium berghei, p. yoelii, and p. vinckei vinckei using a s ... | 2016 | 27600050 |
establishment of a murine model of cerebral malaria in kunming mice infected with plasmodium berghei anka. | malaria remains one of the most devastating diseases. cerebral malaria (cm) is a severe complication of plasmodium falciparum infection resulting in high mortality and morbidity worldwide. analysis of precise mechanisms of cm in humans is difficult for ethical reasons and animal models of cm have been employed to study malaria pathogenesis. here, we describe a new experimental cerebral malaria (ecm) model with plasmodium berghei anka infection in kunming (km) mice. km mice developed ecm after bl ... | 2016 | 27574013 |
high resolution microscopy reveals an unusual architecture of the plasmodium berghei endoplasmic reticulum. | to fuel the tremendously fast replication of plasmodium liver stage parasites, the endoplasmic reticulum (er) must play a critical role as a major site of protein and lipid biosynthesis. in this study, we analysed the parasite's er morphology and function. previous studies exploring the parasite er have mainly focused on the blood stage. visualizing the plasmodium berghei er during liver stage development, we found that the er forms an interconnected network throughout the parasite with perinucl ... | 2016 | 27566438 |
blockage of galectin-receptor interactions by α-lactose exacerbates plasmodium berghei-induced pulmonary immunopathology. | malaria-associated acute lung injury (ali) is a frequent complication of severe malaria that is often caused by "excessive" immune responses. to better understand the mechanism of ali in malaria infection, here we investigated the roles of galectin (gal)-1, 3, 8, 9 and the receptors of gal-9 (tim-3, cd44, cd137, and pdi) in malaria-induced ali. we injected alpha (α)-lactose into mice-infected with plasmodium berghei anka (pbanka) to block galectins and found significantly elevated total proteins ... | 2016 | 27554340 |
glucagon-like peptide-1 analogue, liraglutide, in experimental cerebral malaria: implications for the role of oxidative stress in cerebral malaria. | cerebral malaria from plasmodium falciparum infection is major cause of death in the tropics. the pathogenesis of the disease is complex and the contribution of reactive oxygen and nitrogen species (ros/rns) in the brain is incompletely understood. insulinotropic glucagon-like peptide-1 (glp-1) mimetics have potent neuroprotective effects in animal models of neuropathology associated with ros/rns dysfunction. this study investigates the effect of the glp-1 analogue, liraglutide against the clini ... | 2016 | 27554094 |
cytochrome c and c1 heme lyases are essential in plasmodium berghei. | malaria parasites possess a de novo heme synthetic pathway. interestingly, this pathway is dispensable during the blood stages of development in mammalian hosts. the assembly of the two most important hemeproteins, cytochromes c and c1, is mediated by cytochrome heme lyase enzymes. plasmodium spp. possess two cytochrome heme lyases encoded by separate genes. given the redundancy of heme synthesis, we sought to determine if heme lyase function also exhibits redundancy. to answer this question, we ... | 2016 | 27520480 |
a suggested vital function for eif-5a and dhs genes during murine malaria blood-stage infection. | the biological function of the post-translational modification hypusine in the eukaryotic initiation factor 5a (eif-5a) in eukaryotes is still not understood. hypusine is formed by two sequential enzymatic steps at a specific lysine residue in the precursor protein eif-5a. one important biological function of eif-5a which was recently identified is the translation of polyproline-rich mrna, suggesting its biological relevance in a variety of biological processes. hypusinated eif-5a controls the p ... | 2016 | 27516964 |
4, 5-dihydrooxazole-pyrazoline hybrids: synthesis and their evaluation as potential antimalarial agents. | a new series of oxazoline-pyrazoline hybrids (4a-p) were synthesized by condensation reaction of substituted oxazoline based chalcones (3a-m) and substituted hydrazines in methanol. some of the compounds exhibited promising in vitro antimalarial activity for chloroquine sensitive cq(s) (3d7) strain and chloroquine resistant cq(r) (rkl9) strain. the most potent analogue 4i (ic50 0.322 μg/ml) exhibited significant in vivo antimalarial potential against plasmodium berghei mouse model. the stable co ... | 2016 | 27494165 |
antimalarial potential of leaves of chenopodium ambrosioides l. | in an effort to identify novel therapeutic alternatives for the treatment of malaria, the present study evaluated the antimalarial effect of the crude hydroalcoholic extract (hce) from the leaves of chenopodium ambrosioides l. for this purpose, the molecular affinity between the total proteins from erythrocytes infected with plasmodium falciparum and hce or chloroquine was evaluated by surface plasmon resonance (spr). subsequently, the plasmodicidal potential of hce was assessed in a p. falcipar ... | 2016 | 27492200 |
tissue-resident cd169(+) macrophages form a crucial front line against plasmodium infection. | tissue macrophages exhibit diverse functions, ranging from the maintenance of tissue homeostasis, including clearance of senescent erythrocytes and cell debris, to modulation of inflammation and immunity. their contribution to the control of blood-stage malaria remains unclear. here, we show that in the absence of tissue-resident cd169(+) macrophages, plasmodium berghei anka (pba) infection results in significantly increased parasite sequestration, leading to vascular occlusion and leakage and a ... | 2016 | 27477286 |
cannabinoid receptor 2 modulates susceptibility to experimental cerebral malaria through a ccl17-dependent mechanism. | cerebral malaria is a severe and often fatal complication of plasmodium falciparum infection. it is characterized by parasite sequestration, a breakdown of the blood-brain barrier, and a strong inflammation in the brain. we investigated the role of the cannabinoid receptor 2 (cb2), an important modulator of neuroinflammatory responses, in experimental cerebral malaria (ecm). strikingly, mice with a deletion of the cb2-encoding gene (cnr2(-/-)) inoculated with plasmodium berghei anka erythrocytes ... | 2016 | 27474745 |
integrin αdβ2 (cd11d/cd18) mediates experimental malaria-associated acute respiratory distress syndrome (ma-ards). | malaria-associated acute respiratory distress syndrome (ma-ards) is a potentially lethal complication of clinical malaria. acute lung injury in ma-ards shares features with ards triggered by other causes, including alveolar inflammation and increased alveolar-capillary permeability, leading to leak of protein-rich pulmonary oedema fluid. mechanisms and physiologic alterations in ma-ards can be examined in murine models of this syndrome. integrin αdβ2 is a member of the leukocyte, or β2 (cd18), s ... | 2016 | 27473068 |
potential cerebral malaria therapy: intramuscular arteether and vitamin d co-administration. | cerebral malaria (cm) shows lethality rate of 15-25% despite effective antimalarial chemotherapy. the effective adjunct treatment to counteract the cm pathogenesis is urgently required. in murine cm model, most interventions studied till date are administered before the onset of cm symptoms, which belittle its translational value to human. we studied intramuscular arteether-vitamin d (art-vd) combination treatment for cm outcome improvement after the onset of neurological symptoms. the intramusc ... | 2016 | 27440106 |
chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents. | we report the pharmacological activity of organoruthenium complexes containing chloroquine (cq) as a chelating ligand. the complexes displayed intraerythrocytic activity against cq-sensitive 3d7 and cq-resistant w2 strains of plasmodium falciparum, with potency and selectivity indexes similar to those of cq. complexes displayed activity against all intraerythrocytic stages, but moderate activity against plasmodium berghei liver stages. however, unlike cq, organoruthenium complexes impaired gamet ... | 2016 | 27439976 |
invasion of hepatocytes by plasmodium sporozoites requires cgmp-dependent protein kinase and calcium dependent protein kinase 4. | invasion of hepatocytes by sporozoites is essential for plasmodium to initiate infection of the mammalian host. the parasite's subsequent intracellular differentiation in the liver is the first developmental step of its mammalian cycle. despite their biological significance, surprisingly little is known of the signalling pathways required for sporozoite invasion. we report that sporozoite invasion of hepatocytes requires signalling through two second-messengers - cgmp mediated by the parasite's ... | 2016 | 27425827 |
artemether-lumefantrine nanostructured lipid carriers for oral malaria therapy: enhanced efficacy at reduced dose and dosing frequency. | artemether-lumefantrine (arm-lfn) is a world health organization (who) approved fixed-dose combination having low solubility and poor oral bioavailability. nanostructured lipid carriers (nlc) were developed to enhance the oral efficacy of this combination using the microemulsion template technique. they were characterized for drug content, entrapment efficiency, size distribution, in vitro release, antimalarial efficacy, and toxicity. the nlc showed sustained drug release. the recommended adult ... | 2016 | 27421912 |
evaluation of the combination of uvaria chamae (p. beauv.) and amodiaquine in murine malaria. | the leaf and fruit of uvaria chamae p. beauv (annonaceae) are used in antimalarial ethnomedical preparations. therefore, they were investigated for antimalarial activities as well as possible herb-drug interaction with amodiaquine (aq). | 2016 | 27416806 |
glut1-mediated glucose uptake plays a crucial role during plasmodium hepatic infection. | intracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite plasmodium berghei and that glucose uptake via the glut1 transporter is specifically enhanced in p. berghei-infected cells. we further show that atp levels of cells containing developing parasites are decreased, which is known to enhance membrane glut1 activity. in addition, glut1 mo ... | 2017 | 27404888 |