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heme uptake by leishmania amazonensis is mediated by the transmembrane protein lhr1.trypanosomatid protozoan parasites lack a functional heme biosynthetic pathway, so must acquire heme from the environment to survive. however, the molecular pathway responsible for heme acquisition by these organisms is unknown. here we show that l. amazonensis lhr1, a homolog of the c. elegans plasma membrane heme transporter hrg-4, functions in heme transport. tagged lhr1 localized to the plasma membrane and to endocytic compartments, in both l. amazonensis and mammalian cells. heme deprivatio ...201222807677
therapeutic efficacy induced by the oral administration of agaricus blazei murill against leishmania amazonensis.the development of therapeutic alternatives to treat leishmaniasis has received considerable attention. the present study aimed to investigate the efficacy of the agaricus blazei murill water extract (abm) to treat balb/c mice infected with leishmania amazonensis. first, a dose-titration curve was performed. the most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg(-1) day(-1). i ...201222797606
synthesis, cytotoxicity, and in vitro antileishmanial activity of mono-t-butyloxycarbonyl-protected diamines.leishmania amazonensis is the etiologic agent of the cutaneous and diffuse leishmaniasis. this species is often associated with drug resistance, and the conventional treatments exhibit high toxicity for patients. therefore, the search for new antileishmanial compounds is urgently needed since there is no vaccine available. in this study, using the in vitro traditional drug screening test, we have analyzed the effects of a series of diaminoalkanes monoprotected with t-butyloxycarbonyl (boc) again ...201121907525
intranasal immunization with lack-dna promotes protective immunity in hamsters challenged with leishmania chagasi.summarylack (leishmania analogue of the receptor kinase c) is a conserved protein in protozoans of the genus leishmania which is associated with the immunopathogenesis and susceptibility of balb/c mice to l. major infection. previously, we demonstrated that intranasal immunization with a plasmid carrying the lack gene of leishmania infantum (lack-dna) promotes protective immunity in balb/c mice against leishmania amazonensis and leishmania chagasi. in the present study, we investigated the prote ...201121867591
axenic leishmania amazonensis promastigotes sense both the external and internal arginine pool distinctly regulating the two transporter-coding genes.leishmania (l.) amazonensis uses arginine to synthesize polyamines to support its growth and survival. here we describe the presence of two gene copies, arranged in tandem, that code for the arginine transporter. both copies show similar open reading frames (orfs), which are 93% similar to the l. (l.) donovani aap3 gene, but their 5' and 3' utr's have distinct regions. according to quantitative rt-pcr, the 5.1 aap3 mrna amount was increased more than 3 times that of the 4.7 aap3 mrna along the p ...201122114701
potential utility of hyperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime.in this study we investigated the efficacy of hyperbaric oxygen (hbo) therapy, alone or combined with the pentavalent antimonial glucantime on leishmania amazonensis infection. in parallel, the effect of brazilian red propolis gel (propain) alone or combined with glucantime on l. amazonensis infection was evaluated. the inhibition of the infection in macrophages treated with glucantime in combination with hbo exposition was greater than that of macrophages treated with glucantime alone or hbo al ...201122183457
Effect of Bixa orellana against Leishmania amazonensis.Background: In the present study, an activity of Bixa orellana extract against Leishmania amazonensis was demonstrated. Result: Experimentally infected BALB/c mice were treated with B. orellana extract which showed a significant activity against promastigote and amastigote forms of L. amazonensis. Conclusion: This study supports the importance of natural sources as antileishmanial drugs.201122189367
Pterocarpanquinones, aza-pterocarpanquinone and derivatives: synthesis, antineoplasic activity on human malignant cell lines and antileishmanial activity on Leishmania amazonensis.Pterocarpanquinones (1a-e) and the aza-pterocarpanquinone (2) were synthesized through palladium catalyzed oxyarylation and azaarylation of conjugate olefins, and showed antineoplasic effect on leukemic cell lines (K562 and HL-60) as well as colon cancer (HCT-8), gliobastoma (SF-295) and melanoma (MDA-MB435) cell lines. Some derivatives were prepared (3-8) and evaluated, allowing establishing the structural requirements for the antineoplasic activity in each series. Compound 1a showed the best s ...201122000949
dermaseptin 01 as antimicrobial peptide with rich biotechnological potential: study of peptide interaction with membranes containing leishmania amazonensis lipid-rich extract and membrane models.this article addresses the interactions of the synthetic antimicrobial peptide dermaseptin 01 (glwstikqkgkeaaiaaa- kaagqaalgal-nh(2) , ds 01) with phospholipid (pl) monolayers comprising (i) a lipid-rich extract of leishmania amazonensis (lre-la), (ii) zwitterionic pl (dipalmitoylphosphatidylcholine, dppc), and (iii) negatively charged pl (dipalmitoylphosphatidylglycerol, dppg). the degree of interaction of ds 01 with the different biomembrane models was quantified from equilibrium and dynamic l ...201121805539
molecular determinants of ciliary membrane localization of trypanosoma cruzi flagellar calcium-binding protein.the flagellar calcium binding protein (fcabp)(4) of trypanosoma cruzi is localized to the flagellar membrane in all life cycle stages of the parasite. myristoylation and palmitoylation of the n-terminus of fcabp are necessary for flagellar membrane targeting. not all dually acylated proteins in t. cruzi are flagellar, however. other determinants of fcabp therefore likely contribute to flagellar specificity. we generated t. cruzi transfectants expressing the n-terminal 24 or 12 amino acids of fca ...201121784841
synthesis, evaluation against leishmania amazonensis and cytotoxicity assays in macrophages of sixteen new congeners morita-baylis-hillman adducts.we report the design, synthesis, in vitro evaluation against leishmania amazonensis (ic(50)), cytotoxicity assays in macrophages (cc(50)), and selectivity index (sicc(50)/ic(50)) of sixteen new congeners aromatic morita-baylis-hillman adducts 1-16. the 1-16 were prepared in good to excellent yields (58%-97%) from the "one pot" morita-baylis-hillman reaction between the aldehydes 29-36 and the acrylates 27 or 28 under dabco as promoter. the mbha 2-[hydroxy(2-nitrophenyl)propyl] propanoate (1, ic( ...201121775030
antileishmanial sesquiterpene lactones from pseudelephantopus spicatus, a traditional remedy from the chayahuita amerindians (peru). part iii.ethnopharmacological relevance: the study of traditional remedies used by the chayahuita, an ethnic group from the peruvian amazonia, has prompted us to investigate in detail the ethanolic extract of pseudelephantopus spicatus (juss. ex aubl.) c.f. baker, which has demonstrated strong biological activity towards leishmania amazonensis. our goal was to discover the active compound of this plant-based remedy. materials and methods: a bioguided fractionation of the crude extract was undertaken base ...201121771652
leishmania amazonensis: effects of oral treatment with copaiba oil in mice.leishmaniasis is a severe public-health problem, with high rates of morbidity and mortality. efforts to find new, effective and safe oral agents for the treatment of leishmaniasis have been ongoing for several decades, in order to avoid the problems with the currently used antimonials. in the present study, we found that a copaiba oil oral treatment (group iv) caused a significant reduction in the average lesion size (1.1±0.4mm) against leishmania amazonensis lesions compared with untreated mice ...201121771592
the in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant leishmania species of brazil.the in vitro leishmanicidal activity of miltefosine-« (zentaris gmbh) was assessed against four medically relevant leishmania species of brazil: leishmania (leishmania) amazonensis, leishmania (viannia) braziliensis, leishmania (viannia) guyanensis and leishmania (leishmania) chagasi. the activity of miltefosine against these new world species was compared to its activity against the old world strain, leishmania (leishmania) donovani, which is known to be sensitive to the effects of miltefosine. ...201121739037
miltefosine induces programmed cell death in leishmania amazonensis promastigotes.in the current study, we evaluated the mechanism of action of miltefosine, which is the first effective and safe oral treatment for visceral leishmaniasis, in leishmania amazonensis promastigotes. miltefosine induced a process of programmed cell death, which was determined by the externalization of phosphatidylserine, the incorporation of propidium iodide, cell-cycle arrest at the sub-g0/g1 phase and dna fragmentation into oligonucleosome-sized fragments. despite the intrinsic variation that is ...201121739043
design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: a molecular hybridization approach.the chalcone-like series 1a-1g was efficiently synthesized from morita-baylis-hillman reaction (52-74% yields). compounds 1a-1g were designed by molecular hybridization based on the anti-inflammatory drug methyl salicylate (3) and the antileishmanial moiety of the morita-baylis-hillman adducts 2a-2g. the 1a-1g compounds were much more actives than precursor series 2a-2g, for example, ic(50)=7.65 ++m on leishmania amazonensis and 10.14 ++m on leishmania chagasi (compound 1c) when compared to ic(5 ...201121684751
molecular factors governing inhibition of arylimidamides against leishmania: conservative computational modeling to improve chemotherapies.a dataset of 55 compounds with inhibitory activity against leishmania donovani axenic amastigotes and leishmania amazonensis intracellular parasites was examined through three-dimensional quantitative structure-activity relationship modeling employing molecular descriptors from both rigid and flexible compound alignments. for training and testing purposes, the compounds were divided into two datasets of 45 and 10 compounds, respectively. statistically significant models were constructed and vali ...201121741248
in silico predicted epitopes from the cooh-terminal extension of cysteine proteinase b inducing distinct immune responses during leishmania (leishmania) amazonensis experimental murine infection.abstract:201121824434
cratp interferes in the promastigote-macrophage interaction in leishmania amazonensis infection.recent have shown the relationship between ecto-nucleoside-triphosphate-diphosphohydrolases (ecto-ntpdases or ecto-nucleotidases) and virulence and infectivity in trypanosomatids. in this work, the inhibition of the ecto-atpase activities and promastigote growth of leishmania amazonensis by cratp was characterized. furthermore, this compound was used to investigate the role of ecto-nucleotidase in the interaction of l. amazonensis with resident peritoneal macrophages obtained from balb/c mice. c ...201121679488
leishmania amazonensis: characterization of an ecto-3'-nucleotidase activity and its possible role in virulence.ecto-3'-nucleotidase/nuclease (3'nt/nu) is a membrane-bound enzyme that plays a key role in the nutrition of leishmania sp. protozoan parasites. this enzyme generates nucleosides via hydrolyzes of 3'mononucleotides and nucleic acids, which enter the cell by specific transporters. in this work, we identify and characterize leishmania amazonensis ecto-3'-nucleotidase activity (la3'-nucleotidase), report ammonium tetrathiomolybdate (ttm) as a novel la3'-nucleotidase inhibitor and approach the possi ...201121827749
leishmanicidal activity of the agaricus blazei murill in different leishmania species.leishmaniasis is a major public health problem, and the alarming spread of parasite resistance underlines the importance of discovering new therapeutic products. the present study aims to investigate the in vitro leishmanicidal activity of an agaricus blazei murill mushroom extract as compared to different leishmania species and stages. the water extract proved to be effective against promastigote and amastigote-like stages of leishmania amazonensis, l. chagasi, and l. major, with ic(50) (50% in ...201121723957
new salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-n-oxide with antileishmanial and antimalarial activities.continuing with our efforts to identify new active compounds against malaria and leishmaniasis, 14 new 3-amino-1,4-di-n-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against plasmodium falciparum colombian fcr-3 strain and leishmania amazonensis strain mhom/br/76/ltb-012a. further computational studies were carried out in order to analyze graphic sar and adme properties. the results obtained indicate that ...201121724395
activity of cuban propolis extracts on leishmania amazonensis and trichomonas vaginalis.in this paper we analyzed the antiprotozoal effects of eighteen cuban propolis extracts (brown, red and yellow type) collected in different geographic areas, using leishmania amazonensis (as a model of intracellular protozoa) and trichomonas vaginalis (as a model of extracellular protozoa). all evaluated propolis extracts caused inhibitory effect on intracellular amastigotes of l. amazonensis. however, cytotoxicity on peritoneal macrophages from balb/c mice was observed. only five samples decrea ...201121834236
Sir2-Related Protein 1 from Leishmania amazonensis is a glycosylated NAD+-dependent deacetylase.SUMMARYSirtuin proteins form a family of NAD+-dependent protein deacetylases that are considered potential drug targets against parasites. Here, we present the first characterization of a sirtuin orthologue from Leishmania amazonensis, an aetiological agent of American tegumentary leishmaniasis that has been the subject of many studies focused in the development of therapeutic approaches. The protein has high sequence identity with other Kinetoplastid Silent information regulator 2 Related Prote ...201121819639
Infection with Leishmania amazonensis upregulates purinergic receptor expression and induces host-cell susceptibility to UTP-mediated apoptosis.Nucleotides are released into the extracellular milieu from infected cells and cells at inflammatory sites. The extracellular nucleotides bind to specific purinergic (P2) receptors and thereby induce a variety of cellular responses including anti-parasitic effects. Here we investigated whether extracellular nucleotides affect leishmanial infection in macrophages, and found that UTP reduces strongly the parasite load in peritoneal macrophages. Ultrastructural analysis of infected cells revealed t ...201121740498
in vitro activity of the clinical pulmonary surfactant surfacen® against leishmania amazonensis.surfacen® is an exogenous natural lung surfactant, composed by phospholipids and hydrophobic proteins, which is applied successfully in newborn respiratory distress syndrome. in this paper, in vitro activity of surfacen® against leishmania amazonensis is described. the product showed activity against the amastigote form found in peritoneal macrophages from balb/c mice, with an ic50 value of 17.9 ± 3.0 µg/ml; while no toxic effect on host cell was observed up to 200 µg/ml. this is the first repor ...201121915470
HPLC Analysis of Supercritical Carbon Dioxide and Compressed Propane Extracts from Piper amalago L. with Antileishmanial Activity.Piper amalago L. leaves were extracted with supercritical carbon dioxide and compressed propane under different conditions, and with chloroform by the conventional maceration method. These methods were compared for the pyrrolidine alkaloid content. Supercritical carbon dioxide (SFE-CO(2)) at 313 K and 12.55 MPa showed the highest selectivity for the main compound (600.53 mg/g of extract). A gradient high-performance liquid chromatography (HPLC) method was developed and validated to quantify the ...201122193211
Leishmanicidal effects of piperine, its derivatives, and analogues on Leishmania amazonensis.Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania which affects 12 million people worldwide. The discovery of drugs for the treatment of leishmaniasis is a pressing concern in global health programs. The aim of this study aim was to evaluate the leishmanicidal effect of piperine and its derivatives/analogues on Leishmania amazonensis. Our results showed that piperine and phenylamide are active against promastigotes and amastigotes in infected macrophages. ...201121885074
dot/icm type ivb secretion system requirements for coxiella burnetii growth in human macrophages.central to q fever pathogenesis is replication of the causative agent, coxiella burnetii, within a phagolysosome-like parasitophorous vacuole (pv) in mononuclear phagocytes. c. burnetii modulates pv biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a dot/icm type ivb secretion system (t4bss). in this study, we utilized a c. burnetii strain carrying icmd inactivated by the himar1 transposon to investigat ...201121862628
antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis.amiodarone (amio), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic chagas' disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, trypanosoma cruzi and leishmania. in this work, we characterized the effects of amio on proliferation, mitochondrial physiology, and ultrastructure of leishmania amazonensis promastigotes and intracellular amastigotes. the ic(50) values were 4.21 and 0.46 μm against promasti ...201122091415
the coxiella burnetii dot/icm system creates a comfortable home through lysosomal renovation.understanding the molecular pathogenesis of coxiella burnetii, the causative agent of human q fever, has historically been hindered by the technical difficulties of genetically manipulating obligate intracellular bacteria. the recent development of culture conditions suitable for axenic propagation of c. burnetii has paved the way for the application of a range of genetic techniques to address key questions within the field. recent studies using mutational analysis have revealed that the c. burn ...201122010216
human cutaneous leishmaniasis: interferon-dependent expression of double-stranded rna-dependent protein kinase (pkr) via tlr2.we investigated the type i interferon (ifn-1)/pkr axis in the outcome of the leishmania (leishmania) amazonensis infection, along with the underlying mechanisms that trigger and sustain this signaling pathway. reporter assays of cell extracts from raw-264.7 macrophages infected with l. (l.) amazonensis or hek-293t cells cotransfected with tlr2 and pkr promoter constructions were employed. primary macrophages of tlr2-knockout (ko) or ifnr-ko mice were infected, and the levels of pkr, ifn-1, and s ...201121846836
A new type of pterocarpanquinone that affects Toxoplasma gondii tachyzoites in vitro.Toxoplasma gondii, the agent of Toxoplasmosis, is an obligate intracellular protozoan able to infect a wide range of vertebrate cells, including nonprofessional and professional phagocytes. Therefore, drugs must have intracellular activities in order to control this parasite. The most common therapy for Toxoplasmosis is the combination of sulfadiazine and pyrimethamine. This treatment is associated with adverse reactions, thus, the development of new drugs is necessary. In previous studies, naph ...201122177332
lulo cell line derived from lutzomyia longipalpis (diptera: psychodidae): a novel model to assay leishmania spp. and vector interaction.leishmania (vianna) braziliensis, leishmania (leishmania) amazonensis and leishmania (leishmania) chagasi are important parasites in the scenario of leishmaniasis in brazil. during the life cycle of these parasites, the promastigote forms adhere to the midgut epithelial microvillii of phlebotomine insects to avoid being secreted along with digestive products. lulo cells are a potential model that will help to understand the features of this adhesion phenomenon. here, we analyze the interaction b ...201122082050
4-acetoxydolastane diterpene from the brazilian brown alga canistrocarpus cervicornis as antileishmanial agent.natural marine products have shown an interesting array of diverse and novel chemical structures with potent biological activities. our study reports the antiproliferative assays of crude extracts, fraction and pure compound (4r,9s,14s)-4α-acetoxy-9β,14α-dihydroxydolast-1(15),7-diene (1) obtained from brown alga canistrocarpus cervicornis showing the antileishmanial activity. we showed that 1 had a dose-dependent activity during 72 h of treatment, exhibiting ic(50) of 2.0 μg/ml, 12.0 μg/ml, and ...201122163190
immunological correlates of cure in the first american cutaneous leishmaniasis patient treated by immunotherapy in argentina. a case report.a patient with localized cutaneous leishmaniasis due to leishmania (leishmania) amazonensis infection was treated with an antigen containing heat-killed l. (l.) amazonensis promastigotes plus bcg. expression of t-cell differentiation, memory and senescence receptors markers were analyzed on t cell subpopulations, in order to establish the correlation between the percentages of expression of these receptors and his clinical status, at different stages of his follow up. the following case reports ...201122523846
use of in vivo and in vitro systems to select leishmania amazonensis expressing green fluorescent protein.various leishmania species were engineered with green fluorescent protein (gfp) using episomal vectors that encoded an antibiotic resistance gene, such as aminoglycoside geneticin sulphate (g418). most reports of gfp-leishmania have used the flagellated extracellular promastigote, the stage of parasite detected in the midgut of the sandfly vector; fewer studies have been performed with amastigotes, the stage of parasite detected in mammals. in this study, comparisons were made regarding the effi ...201122355202
Differential modulation of ATP-induced P2X7-associated permeabilities to cations and anions of macrophages by infection with Leishmania amazonensis.Leishmania and other parasites display several mechanisms to subvert host immune cell function in order to achieve successful infection. The ATP receptor P2X7, an agonist-gated cation channel widely expressed in macrophages and other cells of the immune system, is also coupled to inflammasome activation, IL-1 beta secretion, production of reactive oxygen species, cell death and the induction of the permeabilization of the plasma membrane to molecules of up to 900 Da. P2X7 receptors can function ...201121966508
morphological and physiological changes in leishmania promastigotes induced by yangambin, a lignan obtained from ocotea duckei.we have previously demonstrated that yangambin, a lignan obtained from ocotea duckei vattimo (lauraceae), shows antileishmanial activity against promastigote forms of leishmania chagasi and leishmania amazonensis. the aim of this study was to determine the in vitro effects of yangambin against these parasites using electron and confocal microscopy. l. chagasi and l. amazonensis promastigotes were incubated respectively with 50 μg/ml and 65 μg/ml of pure yangambin and stained with acridine orange ...201120691682
leishmania amazonensis: partial purification and study of the biochemical properties of the telomerase reverse transcriptase activity from promastigote-stage.telomeres are protein-dna complexes that protect chromosome ends from degradation and fusion. in leishmania spp., telomeric dna comprises a conserved ttaggg repeat and is maintained by telomerase. telomerase is a multisubunit enzymatic complex that ensures the complete dna replication by adding new telomeric repeats to the g-rich strand. in this report we aimed to purify and study the biochemical properties of leishmania amazonensis telomerase. in a first trial we used affinity chromatography wi ...201120692257
leishmania amazonensis meta2 protein confers protection against heat shock and oxidative stress.the meta cluster of leishmania amazonensis contains both meta1 and meta2 genes, which are upregulated in metacyclic promastigotes and encode proteins containing the meta domain. previous studies defined meta2 as a 48.0-kda protein, which is conserved in other leishmania species and in trypanosoma brucei. in this work, we demonstrate that meta2 protein expression is regulated during the leishmania life cycle but constitutive in t. brucei. meta2 protein is present in the cytoplasm and flagellum of ...201120713053
babassu aqueous extract (bae) as an adjuvant for t helper (th)1-dependent immune responses in mice of a th2 immune response-prone strain.the aqueous extract of a brazilian palm-tree fruit - the babassu - (bae) exerts a clear immunostimulative activity in vivo. in the present work, the possibility that bae can promote th1 immune responses in mice of a th2 immune response-prone strain - the balb/c was investigated. bae itself, and preparations consisting of leishmania amazonensis promastigote extract (le), adsorbed or not to al(oh)3, and in the presence or not of bae, were used as immunogens. le and al(oh)3 have been shown to prefe ...201121276258
effect of the synadenium carinatum latex lectin (scll) on leishmania (leishmania) amazonensis infection in murine macrophages.antiparasitic effect of a lectin isolated from synadenium carinatum latex (scll) was evaluated against leishmania (leishmania) amazonensis promastigotes/amastigotes. pretreatment of murine inflammatory peritoneal macrophages with scll reduced by 65.5% the association index of macrophages and l. (l) amazonensis promastigotes. expression of cytokines (il-12, il-1 and tnf-a) was detected in infected macrophages pretreated with scll (10µg/ml). scll also reduced the growth of l. (l) amazonensis amast ...201121320493
immune and inflammatory responses to leishmania amazonensis isolated from different clinical forms of human leishmaniasis in cba mice.leishmania amazonensis causes different diseases depending on the host and parasitic virulence factors. in this study, cba mice were infected with l. amazonensis isolates from patients with localized (ba125), diffuse cutaneous (ba276) or visceral leishmaniasis (ba109). mice infected with ba125 and ba276 progressed rapidly and lesions displayed an infiltrate rich in parasitized macrophages and were necrotic and ulcerated. ba109 induced smaller lesions and a mixed inflammatory infiltrate without n ...201121340351
[evidence of transmission of visceral leishmaniasis by lutzomyia cruzi in the municipality of jaciara, state of mato grosso, brazil].the municipality of jaciara was classified in 2003 as a transmission area for visceral leishmaniasis in outbreak situations. this study aimed to establish evidence of transmission of leishmania (leishmania) infantum chagasi by lutzomyia cruzi in the municipality of jaciara, state of mato grosso, brazil.201121340413
reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in leishmania amazonensis.leishmaniasis, a parasitic disease caused by protozoa of the genus leishmania, affects more than 12 million people worldwide. quercetin has generated considerable interest as a pharmaceutical compound with a wide range of therapeutic activities. one such activity is exhibited against the bloodstream parasite trypanosoma brucei and amastigotes of leishmania donovani. however, the mechanism of protozoan action of quercetin has not been studied.201121346801
in vitro antileishmanial activity and cytotoxicity of essential oil from lippia sidoides cham.leishmaniasis is a widespread tropical infection caused by different species of leishmania protozoa. there is no vaccine available for leishmania infections and conventional treatments are very toxic to the patients. therefore, antileishmanial drugs are urgently needed. in this study we have analyzed the effects of essential oils from lippia sidoides (lseo) and its major compound thymol on the growth, viability and ultrastructure of leishmania amazonensis. the essential oil and thymol showed sig ...201121421075
cytotoxic and anti-infective phenolic compounds isolated from mikania decora and cremastosperma microcarpum.an anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the peruvian rainforest, mikania decora and cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien-19-oic acid ( 1), three thymol derivatives, 10-acetoxy-8,9-dehydro-6-methoxythymol butyrate ( 2), 10-acetoxy-8,9-epoxy-6-methoxythymol isobutyrate ( 3), and acetylschizoginol ( 4), as well as one neolignan, (±)- trans-dehydrodiisoeugenol ( 5). only the ...201121472652
il-2 limits il-12 enhanced lymphocyte proliferation during leishmania amazonensis infection.c3h mice infected with leishmania amazonensis develop persistent, localized lesions with high parasite loads. during infection, memory/effector cd44(hi)cd4(+) t cells proliferate and produce il-2, but do not polarize to a known effector phenotype. previous studies have demonstrated il-12 is insufficient to skew these antigen-responsive t cells to a functional th1 response. to determine the mechanism of this il-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. memory/ ...201121481338
infection of retinal epithelial cells with l. amazonensis impacts in extracellular matrix proteins.one of the manifestations of leishmaniases is eye injuries which main characteristics are the injury of the anterior chamber of the eye and the resistance to specific treatments. the retinal pigment epithelial (rpe) cells participate in pathogen-induced intraocular inflammatory processes. we investigated leishmania amazonensis-rpe cells relationship and its impact in laminin and fibronectin production. using rpe cell (arpe-19), we demonstrated that l. amazonensis adhere to these cells in the fir ...201121494843
psilostachyin c: a natural compound with trypanocidal activity.in this study, the antiprotozoal activity of the sesquiterpene lactone psilostachyin c was investigated. this natural compound was isolated from ambrosia scabra by bioassay-guided fractionation and was identified by spectroscopic techniques. psilostachyin c exerted in vitro trypanocidal activity against trypanosoma cruzi epimastigotes, trypomastigotes and amastigotes, with 50% inhibitory concentration (ic(50)) values of 0.6, 3.5 and 0.9μg/ml, respectively, and displayed less cytotoxicity against ...201121497061
the influence of low oxygen on macrophage response to leishmania infection.hypoxia (low oxygen tension) is a common feature of inflamed and infected tissues. the influence of hypoxia on macrophage responses to microorganisms has only recently been studied. this study demonstrates that hypoxia induced macrophages to control leishmania amazonensis, an intracellular parasite which causes cutaneous and cutaneous metastatic lesions. the mechanisms which contribute to the control of macrophages against l. amazonensis infection under a hypoxic microenvironment are not known. ...201121517930
thiophene derivatives with antileishmanial activity isolated from aerial parts of porophyllum ruderale (jacq.) cass.porophyllum ruderale (jacq.) cass. is a plant native to brazil and in the northwest region of the state of paraná, brazil, aerial parts of p. ruderale have been used popularly in the treatment of lesions caused by leishmania sp.. in this study the antileishmanial and cytotoxic activities of the crude extract, fractions, and isolated compounds from aerial parts of p. ruderale was evaluated. the dichloromethane extract was submitted to chromatography to yield compounds active against leishmania am ...201121522080
effectiveness of the local or oral delivery of the novel naphthopterocarpanquinone lqb-118 against cutaneous leishmaniasis.objectives this paper describes the antileishmanial properties of lqb-118, a new compound designed by molecular hybridization, orally active in leishmania amazonensis-infected balb/c mice. methods in vitro antileishmanial activity was determined in l. amazonensis-infected macrophages. for in vivo studies, lqb-118 was administered intralesionally (15 μg/kg/day, five times a week), intraperitoneally (4.5 mg/kg/day, five times a week) or orally (4.5 mg/kg/day, five times a week) to l. amazonensis-i ...201121531758
protease expression by microorganisms and its relevance to crucial physiological/pathological events.the treatment of infections caused by fungi and trypanosomatids is difficult due to the eukaryotic nature of these microbial cells, which are similar in several biochemical and genetic aspects to host cells. aggravating this scenario, very few antifungal and anti-trypanosomatidal agents are in clinical use and, therefore, therapy is limited by drug safety considerations and their narrow spectrum of activity, efficacy and resistance. the search for new bioactive agents against fungi and trypanoso ...201121537490
correlation of meta 1 expression with culture stage, cell morphology and infectivity in leishmania (leishmania) amazonensis promastigotes.the parasitic protozoan leishmania (leishmania) amazonensis alternates between mammalian and insect hosts. in the insect host, the parasites proliferate as procyclic promastigotes andthen differentiate into metacyclic infective forms. the meta 1 gene is preferentially expressed during metacyclogenesis. meta 1 expression profile determination along parasite growth curves revealed that the meta 1 mrna level peaked at the early stationary phase then decreased to an intermediate level. no correlatio ...201121537679
the lfr1 ferric iron reductase of leishmania amazonensis is essential for the generation of infective parasite forms.the protozoan parasite leishmania is the causative agent of serious human infections worldwide. the parasites alternate between insect and vertebrate hosts, and cause disease by invading macrophages, where they replicate. parasites lacking the ferrous iron transporter lit1 cannot grow intracellularly, indicating that a plasma membrane-associated mechanism for iron uptake is essential for the establishment of infections. here we identify and functionally characterize a second member of the leishm ...201121558274
photodynamic therapy for american cutaneous leishmaniasis: the efficacy of methylene blue in hamsters experimentally infected with leishmania (leishmania) amazonensis.the aim of this study was to investigate the effectiveness of photodynamic therapy (pdt) using methylene blue (mb) as the photosensitizing compound and a light-emitting diode (led) in american cutaneous leishmaniasis (acl). hamsters were experimentally infected with leishmania (leishmania) amazonensis. after the development of the lesions in the footpad, the animals were treated with mb three times a week for 3months. ten minutes after each application of mb, the lesions were irradiated with led ...201121575635
evaluation of the microbicidal activity and cytokines/chemokines profile released by neutrophils from htlv-1 infected individuals.human t-cell lymphotropic virus-type 1 (htlv-1) induces activation and spontaneous proliferation of t cells with production of type-1 pro-inflammatory cytokines. it modifies the immune response to other antigens and increases susceptibility to infectious diseases. however, little is known about innate immunity in htlv-1 infection. htlv-1 infected individuals have higher spontaneous neutrophil activation than htlv-1 seronegative individuals, as shown by the nitroblue tetrazolium (nbt) assay. this ...201121595736
the pharmacological inhibition of sterol biosynthesis in leishmania is counteracted by enhancement of ldl endocytosis.leishmania parasites, despite being able to synthesize their own sterols, acquire and accumulate significant amounts of cholesterol through low density lipoprotein (ldl) particle endocytosis. the role of this system in leishmania amazonensis promastigotes under pharmacological pressure by sterol biosynthesis inhibitors (sbis) was investigated. first, thin layer chromatography demonstrated that l. amazonensis promastigotes, in response to ergosterol biosynthesis inhibition by treatment with 4.0 a ...201121601554
gene expression profiling and molecular characterization of antimony resistance in leishmania amazonensis.drug resistance is a major problem in leishmaniasis chemotherapy. rna expression profiling using dna microarrays is a suitable approach to study simultaneous events leading to a drug-resistance phenotype. genomic analysis has been performed primarily with old world leishmania species and here we investigate molecular alterations in antimony resistance in the new world species l. amazonensis.201121629719
new cassane diterpenes from caesalpinia echinata.an investigation of the ethanolic extract from stems of caesalpinia echinata lam (leguminosae-caesalpinioideae) led to the isolation of five new cassane diterpenes along with known lambertianic acid. their structures were determined based on spectroscopic methods. a preliminary study on leishmanicidal activity demonstrated that compounds 1, 2 and 6 were found to inhibit the growth of amastigote-like forms of leishmania amazonensis without affecting mononuclear cells obtained from human periphera ...201121641971
leishmania promotes its own virulence by inducing expression of the host immune inhibitory ligand cd200.leishmania parasites infect macrophages, cells normally involved in innate defense against pathogens. leishmania amazonensis and leishmania major cause severe or mild disease, respectively, consistent with each parasite's ability to survive within activated macrophages. the mechanisms underlying increased virulence of l. amazonensis are mostly unknown. we show that l. amazonensis promotes its own survival by inducing expression of cd200, an immunoregulatory molecule that inhibits macrophage ac ...201121669395
photodynamic therapy using methylene blue to treat cutaneous leishmaniasis.abstract objective: the purpose of this study was to show the efficiency and underlying mechanism of action of photodynamic therapy (pdt) using methylene blue (mb) and non-coherent light sources to treat cutaneous leishmaniasis (cl). background data: systemic treatment can cause severe side effects, and pdt using porphyrin precursors as sensitizers has been used as an alternative to treat cl. mb has been used under illumination or in the dark to treat a wide range of medical conditions, and it e ...201121671755
reductions in skin and systemic parasite burdens as a combined effect of topical paromomycin and oral miltefosine treatment of mice experimentally infected with leishmania (leishmania) amazonensis.this study aimed to investigate the activity of a combination of topical paromomycin gel and oral miltefosine for the treatment of experimental cutaneous leishmaniasis caused by leishmania (leishmania) amazonensis. the efficacy of the combination, evaluated by measuring lesion size and parasite burden in the skin and spleen, was assessed in balb/c mice infected by l. (l.) amazonensis. the miltefosine was administered orally at 10 mg/kg of body weight/day for 10 days, while 10% paromomycin gel wa ...201020713665
screening of medicinal plants against leishmania amazonensis.leishmaniasis is a widespread tropical infection caused by different species of leishmania protozoa. there is no immunoprophylaxis (vaccination) available for leishmania infections and conventional treatments are unsatisfactory; therefore antileishmanial drugs are urgently needed. natural products are attractive due to their structural diversity.201020731558
antileishmanial activity of a guaianolide from tanacetum parthenium (l.) schultz bip.leishmaniasis is one of the major infectious diseases affecting the poorest regions of the world. the present study evaluated the antileishmanial activity of a guaianolide purified from the hydroalcoholic extract of aerial parts of tanacetum parthenium (l.) schultz bip. the isolated compound showed activity against the promastigote form of leishmania amazonensis, with 50% inhibition (ic(50)) of cell growth at a concentration of 2.6 μg/ml. for the intracellular amastigote form, this guaianolide r ...201020732450
efficient synthesis of 16 aromatic morita-baylis-hillman adducts: biological evaluation on leishmania amazonensis and leishmania chagasi.sixteen aromatic morita-baylis-hillman adducts (mbha) 1-16 were efficiently synthesized in a one step morita-baylis-hillman reaction (mbhr) involving commercial aldehydes with methyl acrylate or acrylonitrile (81-100% yields) without the formation of side products on dabco catalysis and at low temperature (0°c). the toxicities of these compounds were assessed against promastigote form of leishmania amazonensis and leishmania chagasi. the low synthetic cost of these mbha, green synthetic protocol ...201020855101
antileishmanial activity of an essential oil from the leaves and flowers of achillea millefolium.an essential oil was recently extracted from the leaves and flowers of yarrow (achillea millefolium) and tested for in-vitro activity against leishmania amazonensis and murine macrophages (i.e. the j774g8 cell line). the median inhibitory concentration (ic(50)) against l. amazonensis promastigotes was 7.8 μg/ml whereas the survival of amastigotes of this pathogen, within peritoneal murine macrophages, was halved by treatment with the oil at 6.5 μg/ml. the mean value for the median cytotoxic conc ...201020863436
low and high-dose intradermal infection with leishmania major and leishmania amazonensis in c57bl/6 mice.a model of skin infection with leishmania amazonensis with low doses of parasites is compared to infection with high doses of l. amazonensis and low and high doses of leishmania major. c57bl/6 mice were infected with 10³ or 10(6) parasites in the ear and the outcome of infection was assessed. the appearance of lesions in mice infected with 10³ parasites was delayed compared to mice infected with 10(6) leishmania and parasites were detectable at the infection site before lesions became apparent. ...201020944986
antigenic extracts of leishmania braziliensis and leishmania amazonensis associated with saponin partially protects balb/c mice against leishmania chagasi infection by suppressing il-10 and il-4 production.this study evaluated two vaccine candidates for their effectiveness in protecting balb/c mice against leishmania chagasi infection. these immunogenic preparations were composed of leishmania amazonensis or leishmania braziliensis antigenic extracts in association with saponin adjuvant. mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of l. chagasi by intravenous injection. we observed that both v ...201020944999
antimicrobial and cytotoxic activities of medicinal plants of the brazilian cerrado, using brazilian cachaça as extractor liquid.ethnopharmacological importance: many species of plants in the brazilian cerrado (savanna) are widely used in ethnomedicine. however, the safety and effectiveness of medicinal plants used in communities with little or no access to manufactured drugs should be evaluated.201020951786
caffeic acid esters and lignans from piper sanguineispicum.three new caffeic acid esters (1-3), four new lignans (4-7), and the known compounds (7's)-parabenzlactone (8), dihydrocubebin (9), and justiflorinol (10) have been isolated from leaves of piper sanguineispicum. their structures were determined by spectroscopic methods, including 1d and 2d nmr, hrcims, cd experiments, and chemical methods. compounds 1-10 were assessed for their antileishmanial potential against axenic amastigote forms of leishmania amazonensis. caffeic acid esters 1 and 3 exhibi ...201020954722
biosensors for efficient diagnosis of leishmaniasis: innovations in bioanalytics for a neglected disease.the need for reliable, fast diagnostics is closely linked to the need for safe, effective treatment of the so-called "neglected" diseases. the list of diseases with no field-adapted diagnostic tools includes leishmaniasis, shigella, typhoid, and bacterial meningitis. leishmaniasis, in particular, is a parasitic disease caused by leishmania spp. transmitted by infected phlebotomine sandfly, which remains a public health concern in developing countries with ca. 12 million people infected and 350 m ...201021043437
antileishmanial sesquiterpenes from the brazilian red alga laurencia dendroidea.investigation of the bioactive crude extracts from two populations of the red alga laurencia dendroidea from the southeastern brazilian coast led to the identification of five sesquiterpenes: (+)-obtusane ( 1), a triquinane derivative ( 2), (-)-elatol ( 3), obtusol ( 4), and cartilagineol ( 5). an antileishmanial bioassay against leishmania amazonensis was conducted for crude lipophilic extracts and for sesquiterpenes 2, 3, and 4. compounds 3 and 4 displayed in vitro and in vivo leishmanicidal a ...201021058243
characterization of leishmania spp. causing cutaneous leishmaniasis in manaus, amazonas, brazil.in the state of amazonas, american tegumentary leishmaniasis is endemic and presents a wide spectrum of clinical variability due to the large diversity of circulating species in the region. isolates from patients in manaus and its metropolitan region were characterized using monoclonal antibodies and isoenzymes belonging to four species of the parasite: leishmania (viannia) guyanensis, 73% (153/209); leishmania (viannia) braziliensis, 14% (30/209); leishmania (leishmania) amazonensis, 8% (17/209 ...201021072540
neutrophils reduce the parasite burden in leishmania (leishmania) amazonensis-infected macrophages.studies on the role of neutrophils in leishmania infection were mainly performed with l. (l) major, whereas less information is available for l. (l) amazonensis. previous results from our laboratory showed a large infiltrate of neutrophils in the site of infection in a mouse strain resistant to l. (l.) amazonensis (c3h/hepas). in contrast, the susceptible strain (balb/c) displayed a predominance of macrophages harboring a high number of amastigotes and very few neutrophils. these findings led us ...201021082032
sand fly captures with disney traps in area of occurrence of leishmania (leishmania) amazonensis in the state of mato grosso do sul, mid-western brazil.the work was conducted to study phlebotomine fauna (diptera: psychodidae) and aspects of american cutaneous leishmaniasis transmission in a forested area where leishmania (leishmania) amazonensis occurs, situated in the municipality of bela vista, state of mato grosso do sul, brazil.201021085855
in vitro activity of hypnophilin from lentinus strigosus: a potential prototype for chagas disease and leishmaniasis chemotherapy.hypnophilin and panepoxydone, terpenoids isolated from lentinus strigosus, have significant inhibitory activity on trypanosoma cruzi trypanothione reductase (tr). although they have similar tr inhibitory activity at 10 μg/ml (40.3 μm and 47.6 μm for hypnophilin and panepoxydone, respectively; ~100%), hypnophilin has a slightly greater inhibitory activity (~71%) on t. cruzi amastigote (ama) growth in vitro as well as on in vitro phytohemagglutinin (pha)-induced peripheral blood mononuclear (pbmc) ...201021088803
δ²,³-ivermectin ethyl secoester, a conjugated ivermectin derivative with leishmanicidal activity but without inhibitory effect on mammalian p-type atpases.looking at a new putative target for the large spectrum antiparasitic drug ivermectin, we recently showed that avermectin-derived drugs are active against promastigote and amastigote forms of leishmania amazonensis at low micromolar concentrations. however, we then reported that at this concentration range ivermectin is also able to inhibit three important mammalian p-type atpases so that unacceptable adverse effects could occur if this drug were used at such high doses therapeutically. the pres ...201021088826
pcr-rflp of ribosomal internal transcribed spacers highlights inter and intra-species variation among leishmania strains native to la paz, bolivia.human leishmaniasis is highly endemic in bolivia and shows a growing incidence. this report reveals the genetic variability of 35 isolates mainly belonging to leishmania braziliensis and leishmania amazonensis species. among them, 31 were from human patients with different clinical presentations, 3 strains from lutzomya nuneztovari anglesi (the proven vector of l. amazonensis) and 1 strain of a mammal (conepatus chinga). the isolates were analyzed by isoenzyme electrophoresis (mlee) and pcr-rflp ...201021138774
effect of elatol, isolated from red seaweed laurencia dendroidea, on leishmania amazonensis.in the present study, we investigated the antileishmanial activity of sesquiterpene elatol, the major constituent of the brazilian red seaweed laurencia dendroidea (hudson) j.v. lamouroux, against l. amazonensis. elatol after 72 h of treatment, showed an ic(50) of 4.0 μm and 0.45 μm for promastigote and intracellular amastigote forms of l. amazonensis, respectively. by scanning and transmission electron microscopy, parasites treated with elatol revealed notable changes compared with control cell ...201021139841
leishmania spp. in didelphis albiventris and micoureus paraguayanus (didelphimorphia: didelphidae) of brazil.leishmaniasis is kept in nature by the participation of several animal species. this study evaluated the presence of leishmania spp. in skin samples of free-ranging marsupials micoureus paraguayanus (n=95) and didelphis albiventris (n=191), captured in morro do diabo state park and in sections of its surrounding forest, in the region of pontal do paranapanema, são paulo state, brazil. the samples were tested for the presence of kdna of leishmania spp. by polymerase chain reaction (pcr) and by re ...201021144664
eco-epidemiology of visceral leishmaniasis in the urban area of paracatu, state of minas gerais, brazil.the present study was developed in the urban area of paracatu, an endemic city for the american visceral leishmaniasis in brazil. a six-month canine survey was performed with 6295 domiciled dogs in 28 districts in that area and showed that 4.2% of those (267 dogs) were positive for vl by elisa and ifat serum assays. prevalence ratios for canine vl varied between 1.2% and 16.1%, depending on the district under investigation. fifteen dogs - 80% of which were clinically asymptomatic for vl - were s ...201021146311
fusion between leishmania amazonensis and leishmania major parasitophorous vacuoles: live imaging of coinfected macrophages.protozoan parasites of the genus leishmania alternate between flagellated, elongated extracellular promastigotes found in insect vectors, and round-shaped amastigotes enclosed in phagolysosome-like parasitophorous vacuoles (pvs) of infected mammalian host cells. leishmania amazonensis amastigotes occupy large pvs which may contain many parasites; in contrast, single amastigotes of leishmania major lodge in small, tight pvs, which undergo fission as parasites divide. to determine if pvs of these ...201021151877
leishmania sp. identification by pcr associated with sequencing of target ssu rdna in paraffin-embedded skin samples stored for more than 30 years.paraffin-embedded samples commonly stored at educational and research institutions constitute tissues banks for follow-up or epidemiological studies; however, the paraffin inclusion process involves the use of substances that can cause dna degradation. in this study, a pcr protocol was applied to identify leishmania strains in 33 paraffin-embedded skin samples of patients with american cutaneous leishmaniasis. dna was obtained by the phenol-chloroform protocol following paraffin removal and then ...201021161272
enhancement of experimental cutaneous leishmaniasis by leishmania molecules is dependent on interleukin-4, serine protease/esterase activity, and parasite and host genetic backgrounds.most inbred strains of mice, like the balb/c strain, are susceptible to leishmania amazonensis infections and resistant to leishmania braziliensis infections. this parasite-related difference could result from the activity of an l. amazonensis-specific virulence factor. in agreement with this hypothesis, it is shown here that the intravenous injection of balb/c mice with l. amazonensis amastigote extract (lae) but not the l. braziliensis extract confers susceptibility to l. braziliensis infectio ...201021173308
influence of long-term treatment with pravastatin on the survival, evolution of cutaneous lesion and weight of animals infected by leishmania amazonensis.the high toxicity of current drugs for treatment of leishmaniasis is a major hindrance for controlling the disease. pravastatin is a well-known drug with anti-inflammatory and immunomodulatory properties that may modulate host defense mechanisms against leishmania. we evaluated the influence of prolonged pravastatin treatment on the survival of leishmania amazonensis-infected animals (balb/c, c57bl6 mice and syrian hamsters), including weekly measurement of cutaneous lesions (footpad thickness) ...201021176775
differential microbicidal effects of human histone proteins h2a and h2b on leishmania promastigotes and amastigotes.recent studies have shown that histone proteins can act as antimicrobial peptides in host defense against extracellular bacteria, fungi, and leishmania promastigotes. in this study, we used human recombinant histone proteins to further study their leishmaniacidal effects and the underlying mechanisms. we found that the histones h2a and h2b (but not h1(0)) could directly and efficiently kill promastigotes of leishmania amazonensis, l. major, l. braziliensis, and l. mexicana in a treatment dose-de ...201021189319
detc induces leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in leishmaniasis.chemotherapy remains the primary tool for treatment and control of human leishmaniasis. however, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. affordable and less toxic drugs are urgently needed for leishmaniasis.201021200432
chemistry and biological activity of essential oils from piper claussenianum (piperaceae).analyses of essential oils obtained from fresh and dried leaves and inflorescences of piper clausenianum were performed using gc-fid, gc-ms and nmr techniques. forty compounds were detected for these four oils with the total of identified constituents ranging from 88.7% for the dried inflorescences to 97.7% for the dried leaves. sesquiterpenes were the main constituents in the volatile fraction from leaves with a high percentage of (e)-nerolidol (up to 83%). however, monoterpenes were identified ...201021213995
in vitro initial immune response against leishmania amazonensis infection is characterized by an increased production of il-10 and il-13.the initial encounter of leishmania with its host's immune system is important in the outcome of infection. previous studies have shown that pbmcs from healthy volunteers (hv) exposed to leishmania differ in ifn-γ production. we have expanded such observations evaluating the profile and kinetics of cytokines (ifn-γ, il-12p70, il-10, il-13), chemokines (ccl5, ccl3, ccl4, cxcl10), and chemokine receptors (ccr1,ccr5, cxcr3, ccr4) in vitro l. amazonensis-stimulated of hv's pbmcs. hvs were divided in ...201021221476
a deficiency in the b cell response of c57bl/6 mice correlates with loss of macrophage-mediated killing of leishmania amazonensis.infection of c3heb/fej and c57bl/6 mice with leishmania major stimulates a healing cell-mediated immune response, while leishmania amazonensis infection leads to chronic disease. here we show c3heb/fej mice co-infected with both species of leishmania heal, while co-infected c57bl/6 mice do not. using an in vitro killing assay we determined b cells from infected c57bl/6 mice are ineffective in promoting parasite killing compared with b cells from infected c3heb/fej mice. furthermore, infected c57 ...201020004204
functional characterization of lit1, the leishmania amazonensis ferrous iron transporter.leishmania amazonensis lit1 was identified based on homology with irt1, a ferrous iron transporter from arabidopsis thaliana. deltalit1l. amazonensis are defective in intracellular replication and lesion formation in vivo, a virulence phenotype attributed to defective intracellular iron acquisition. here we functionally characterize lit1, directly demonstrating that it functions as a ferrous iron membrane transporter from the zip family. conserved residues in the predicted transmembrane domains ...201020025906
synthesis and antileishmanial activity of lipidic amino alcohols.in this work, a number of lipidic amino alcohols wereas synthesized and evaluated in vitro on cultures of leishmania amazonensis and leishmania chagasi. nine amino alcohols showed inhibition of l. chagasi growth, and seven of them showed inhibition of l. amazonensis with ic(50) below 10 microm. compound 11f was more active than the reference drug amphotericin b against l. chagasi promastigote forms.201020028395
leishmania amazonensis: heme stimulates (na(+)+k(+))atpase activity via phosphatidylinositol-specific phospholipase c/protein kinase c-like (pi-plc/pkc) signaling pathways.in the present paper we studied the involvement of the phosphatidylinositol-specific plc (pi-plc)/protein kinase c (pkc) pathway in (na(+)+k(+))atpase stimulation by heme in leishmania amazonensis promastigotes. heme stimulated the pkc-like activity with a concentration of 50nm. interestingly, the maximal stimulation of the pkc-like activity promoted by phorbol ester was of the same magnitude promoted by heme. however, the stimulatory effect of heme is completely abolished by et-18-och(3) and u7 ...201020045694
evaluation of antileishmanial activity of eupomatenoid-5, a compound isolated from leaves of piper regnellii var. pallescens.infection with leishmania spp. causes a disease with multifaceted clinical manifestations in humans. the treatment for leishmaniasis is dependent on a limited range of drugs. here we investigated the antileishmanial activity of eupomatenoid-5, a neolignan isolated from leaves of piper regnellii var. pallescens. we showed that eupomatenoid-5 had a dose-dependent activity during 72h of treatment, exhibiting ic(50) of 9.0microg/ml and 13.0microg/ml for promastigote and axenic amastigote forms, resp ...201020064628
sialic acids in different leishmania sp., its correlation with nitric oxide resistance and host responses.the presence of different derivatives of sialic acids (sa) on leishmania donovani instigated us to investigate their status on different strains of leishmania sp. causing different forms of the disease. leishmania tropica (k27), leishmania major (jish118) and leishmania mexicana (lv4) responsible for cutaneous, leishmania braziliensis (l280) and leishmania amazonensis (lv81) causing diffuse and leishmania infantum (mon29) responsible for visceral leishmaniasis were included in this study. the st ...201020085901
leishmanicidal activity of himatanthus sucuuba latex against leishmania amazonensis.himatanthus sucuuba (hsl) latex exhibited a potent leishmanicidal activity against intracellular amastigotes of leishmania amazonensis, a causative agent of cutaneous leishmaniasis. hsl inhibited intracellular amastigote growth in a dose-dependent manner (ic(50)=15.7microg/ml). moreover, hsl increased nitric oxide (no) and tumor nuclear factor-alpha (tnf-alpha) and decreased transforming growth factor-beta (tgf-beta) production in macrophages. as assessed by plasma membrane integrity and mitocho ...201020096374
activation of leishmania (leishmania) amazonensis arginase at low temperature by binuclear mn2+ center formation of the immobilized enzyme on a ni2+ resin.in leishmania, arginase is responsible for the production of ornithine, a precursor of polyamines required for proliferation of the parasite. in this work, the activation kinetics of immobilized arginase enzyme from l. (l.) amazonensis were studied by varying the concentration of mn2+ applied to the nickel column at 23 degrees c. the intensity of the binding of the enzyme to the ni2+ resin was directly proportional to the concentration of mn2+. conformational changes of the enzyme may occur when ...201020109449
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