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mutation of val90 to his in the pseudoperoxidase from leishmania major enhances peroxidase activity.pseudoperoxidase from leishmania major (lmpp) catalyzes the breakdown of peroxynitrite though it can hardly react with h(2)o(2). our modeling structure predicts that a conserved his to val switch near the distal heme pocket of lmpp may determine the profile of its h(2)o(2) activity. to test this hypothesis, we have generated complementary mutations in the lmpp (v90h) and studied the formation of compounds i and ii. the rate of transition from high spin ferric state of v90h to compound i by h(2)o ...201223277197
transcriptomic signature of leishmania infected mice macrophages: a metabolic point of view.we analyzed the transcriptional signatures of mouse bone marrow-derived macrophages at different times after infection with promastigotes of the protozoan parasite leishmania major. ingenuity pathway analysis revealed that the macrophage metabolic pathways including carbohydrate and lipid metabolisms were among the most altered pathways at later time points of infection. indeed, l. major promastiogtes induced increased mrna levels of the glucose transporter and almost all of the genes associated ...201222928052
the crystal structure of the map kinase lmampk10 from leishmania major reveals parasite-specific features and regulatory mechanisms.mitogen-activated protein kinases (mapks) are involved in environmental signal sensing. they are thus expected to play key roles in the biology of trypanosomatid parasites, which display complex life cycles and use extracellular cues to modulate cell differentiation. despite their relevance, structural data of trypanosomatid mapks is lacking. we have now determined the crystal structure of leishmania major lmampk10, a stage-specifically activated mapk, both alone and in complex with sb203580. lm ...201222884419
mitigating an undesirable immune response of inherent susceptibility to cutaneous leishmaniosis in a mouse model: the role of the pathoantigenic hisa70 dna vaccine.leishmania major is the major cause of cutaneous leishmaniosis (cl) outside of the americas. in the present study we have cloned six leishmania genes (h2a, h2b, h3, h4, a2 and hsp70) into the eukaryotic expression vector pcmvβ-m2a, resulting in pcmv-hisa70m2a, which encodes all six pathoantigenic proteins as a single polyprotein. this expression plasmid has been evaluated as a novel vaccine candidate in the balb/c mouse model of cl. the dna vaccine shifted the immune response normally induced by ...201222876751
anti-leishmanial and toxicity activities of some selected iranian medicinal plants.leishmaniasis is caused by protozoan parasites belonging to the genus leishmania. cutaneous leishmaniasis is the most common form of leishmaniasis in iran. as there is not any vaccine for leishmaniasis, treatment is important to prevent the spreading of parasites. there is, therefore, a need to develop newer drugs from different sources. the aim of this study was to assess anti-leishmanial activity of the ethanolic extracts of 17 different medicinal plants against leishmania major promastigotes ...201222875395
effects of leishmania major clones showing different levels of virulence on infectivity, differentiation and maturation of human dendritic cells.leishmania parasites and dendritic cell interactions (dcs) play an essential role in initiating and directing t cell responses and influence disease evolution. these interactions may vary depending on leishmania species and strains. to evaluate the correlation between leishmania major (lm) virulence and in-vitro human dc response, we compared the ability of high (hv) and low virulent (lv) lm clones to invade, modulate cytokine production and interfere with differentiation of dcs. clones derived ...201222861367
leishmanicidal activities and cytotoxicities of bisnaphthoquinone analogues and naphthol derivatives from burman diospyros burmanica.a methanol extract of the wood of diospyros burmanica, collected in burma (myanmar), was found to exhibit significant activity against leishmania major. subsequent chromatographically resolved fractionation led to the isolation of three novel bisnaphthoquinone analogues, burmanin a, b, and c (1-3), together with nine known compounds (4-12). the structure of 1 was confirmed by x-ray crystallography, and those of 2 and 3 by spectroscopic techniques, including 1d and 2d nmr. the inhibitory activiti ...201222858297
leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response.leishmania (l.) species are the causative agent of leishmaniasis. due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. an appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo.201222848771
electroacupuncture at the st36 acupoint increases interleukin-4 responsiveness in macrophages, generation of alternatively activated macrophages and susceptibility to leishmania major infection.electroacupuncture (ea) has been used to treat inflammatory diseases. alternatively activated macrophages (aamo) stimulated by cytokines such as interleukin (il)-4, il-10 and il-13 are anti-inflammatory and mildly microbicidal. this study aimed to evaluate whether ea at the zusanli acupoint (st36) would change the profile of healthy murine macrophages, particularly the generation of aamo and susceptibility to leishmania major infection.201222838729
in silico analysis of trypanosomatids' helicases.trypanosomatids are unicellular protozoan parasites that cause many diseases in animals, including humans, and plants. these early divergent eukaryotes have many singular structures and processes, including the hyper-modified 'base j', a mitochondrial dna network, rna editing, and trans-splicing; all of these unique features involve a wide variety of specific dna/rna helicases. in this work, the genomes of trypanosomatids were analyzed by data mining, searching for genes coding for dna/rna helic ...201222835260
modeling and experimental analyses reveals signaling plasticity in a bi-modular assembly of cd40 receptor activated kinases.depending on the strength of signal dose, cd40 receptor (cd40) controls erk-1/2 and p38mapk activation. at low signal dose, erk-1/2 is maximally phosphorylated but p38mapk is minimally phosphorylated; as the signal dose increases, erk-1/2 phosphorylation is reduced whereas p38mapk phosphorylation is reciprocally enhanced. the mechanism of reciprocal activation of these two mapks remains un-elucidated. here, our computational model, coupled to experimental perturbations, shows that the observed r ...201222815717
dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after leishmania major infection of balb/c mice.prevention of tissue damages at the site of leishmania major inoculation can be achieved if the balb/c mice are systemically given l. major antigen (lmag)-loaded bone marrow-derived dendritic cells (dc) that had been exposed to cpg-containing oligodeoxynucleotides (cpg odn). as previous studies allowed establishing that interleukin-4 (il-4) is involved in the redirection of the immune response towards a type 1 profile, we were interested in further exploring the role of il-4. thus, wild-type (wt ...201222802978
leishmanicidal active withanolides from a pakistani medicinal plant, withania coagulans.in the course of screening for leishmanicidal constituents from asian and south american medicinal plants, a pakistani medicinal plant, withania coagulans, showed activity. we therefore studied the active components of the methanol extract of aerial parts of w. coagulans. from the ethyl acetate soluble fraction of the extract, four new withanolides (1-4) were isolated along with seven known withanolides (5-11). the new compounds were elucidated to be (14r,15r,17s,20s,22r)-14,15,17,20-tetrahydrox ...201222790824
structure of leishmania major cysteine synthase.cysteine biosynthesis is a potential target for drug development against parasitic leishmania species; these protozoa are responsible for a range of serious diseases. to improve understanding of this aspect of leishmania biology, a crystallographic and biochemical study of l. major cysteine synthase has been undertaken, seeking to understand its structure, enzyme activity and modes of inhibition. active enzyme was purified, assayed and crystallized in an orthorhombic form with a dimer in the asy ...201222750854
colloidal, in vitro and in vivo anti-leishmanial properties of transfersomes containing paromomycin sulfate in susceptible balb/c mice.the aim of this study was to develop transfersomal formulation with respect to dermal delivery of paromomycin sulfate (pm) for possible topical therapy of cutaneous leishmaniasis (cl). pm transfersomal formulations (pmtfs) with different percent of soy phosphatidylcholine, sodium cholate (na-ch) and ethanol were prepared and characterized for the size, zeta potential and encapsulation efficiency. the results showed that the most stable formulations with suitable colloidal properties were obtaine ...201222750480
metabolic characterization of leishmania major infection in activated and nonactivated macrophages.infection with leishmania spp. can lead to a range of symptoms in the affected individual, depending on underlying immune-metabolic processes. the macrophage activation state hereby plays a key role. whereas the l-arginine pathway has been described in detail as the main biochemical process responsible for either nitric oxide mediated parasite killing (classical activation) or amplification of parasite replication (alternative activation), we were interested in a wider characterization of metabo ...201222724526
kinetic and phylogenetic analysis of plant polyamine uptake transporters.the rice gene polyamine uptake transporter1 (put1) was originally identified based on its homology to the polyamine uptake transporters lmpot1 and tcpat12 in leishmania major and trypanosoma cruzi, respectively. here we show that five additional transporters from rice and arabidopsis that cluster in the same clade as put1 all function as high affinity spermidine uptake transporters. yeast expression assays of these genes confirmed that uptake of spermidine was minimally affected by 166 fold or g ...201222711282
probing the structure of leishmania major dhfr ts and structure based virtual screening of peptide library for the identification of anti-leishmanial leads.leishmaniasis, a multi-faceted ethereal disease is considered to be one of the world's major communicable diseases that demands exhaustive research and control measures. the substantial data on these protozoan parasites has not been utilized completely to develop potential therapeutic strategies against leishmaniasis. dihydrofolate reductase thymidylate synthase (dhfr-ts) plays a major role in the infective state of the parasite and hence the dhfr-ts based drugs remains of much interest to resea ...201222527276
characterization of anti-silencing factor 1 in leishmania major.anti-silencing factor 1 (asf1) is a histone chaperone that contributes to the histone deposition during nucleosome assembly in newly replicated dna. it is involved in chromatin disassembly, transcription activation and in the cellular response to dna damage. in leishmania major the asf1 gene (lmasf1) is located in chromosome 20 and codes for a protein showing 67% of identity with the trypanosoma brucei tbasf1a. compared to orthologous proteins, lmasf1 conserves the main residues relevant for its ...201222510834
does t helper differentiation correlate with resistance or susceptibility to infection with l. major? some insights from the murine model.the murine model of leishmania major infection has been an invaluable tool in understanding t helper differentiation in vivo. the initial evidence for a role of distinct cd4(+) t helper subsets in the outcome of infection was first obtained with this experimental model. the development of cd4(+) th1 cells was associated with resolution of the lesion, control of parasite replication, and resistance to re-infection in most of the mouse strains investigated (i.e., c57bl/6). in contrast, differentia ...201222566916
molecular diagnosis and species identification of mucosal leishmaniasis in iran and correlation with cytological findings.mucosal leishmaniasis (ml) is a rare destructive disease that mainly affects the mucous membranes of the mouth and nose. the etiologic agent(s) of ml are not well known in the middle east.201222555534
searching for new chemotherapies for tropical diseases: ruthenium-clotrimazole complexes display high in vitro activity against leishmania major and trypanosoma cruzi and low toxicity toward normal mammalian cells.eight new ruthenium complexes of clotrimazole (ctz) with high antiparasitic activity have been synthesized, cis,fac-[ru(ii)cl(2)(dmso)(3)(ctz)] (1), cis,cis,trans-[ru(ii)cl(2)(dmso)(2)(ctz)(2)] (2), na[ru(iii)cl(4)(dmso)(ctz)] (3), na[trans-ru(iii)cl(4)(ctz)(2)] (4), [ru(ii)(η(6)-p-cymene)cl(2)(ctz)] (5), [ru(ii)(η(6)-p-cymene)(bipy)(ctz)][bf(4)](2) (6), [ru(ii)(η(6)-p-cymene)(en)(ctz)][bf(4)](2) (7), and [ru(ii)(η(6)-p-cymene)(acac)(ctz)][bf(4)] (8) (bipy = bipyridine; en = ethlylenediamine; ac ...201222448965
transepidermal elimination in cutaneous leishmaniasis: a multiregional study.transepidermal elimination has been documented in a myriad of infectious diseases; however, its occurrence in cutaneous leishmaniasis has not been evaluated.201222443392
the diverse and dynamic nature of leishmania parasitophorous vacuoles studied by multidimensional imaging.an important area in the cell biology of intracellular parasitism is the customization of parasitophorous vacuoles (pvs) by prokaryotic or eukaryotic intracellular microorganisms. we were curious to compare pv biogenesis in primary mouse bone marrow-derived macrophages exposed to carefully prepared amastigotes of either leishmania major or l. amazonensis. while tight-fitting pvs are housing one or two l. major amastigotes, giant pvs are housing many l. amazonensis amastigotes. in this study, usi ...201222348167
multiple mutations in heterogeneous miltefosine-resistant leishmania major population as determined by whole genome sequencing.miltefosine (mf) is the first oral compound used in the chemotherapy against leishmaniasis. since the mechanism of action of this drug and the targets of mf in leishmania are unclear, we generated in a step-by-step manner leishmania major promastigote mutants highly resistant to mf. two of the mutants were submitted to a short-read whole genome sequencing for identifying potential genes associated with mf resistance.201222348164
acylation-dependent and-independent membrane targeting and distinct functions of small myristoylated proteins (smps) in leishmania major.trypanosomatid parasites express a number of mono- and diacylated proteins that are targeted to distinct regions of the plasma membrane including the cell body, the flagellum and the flagellar pocket. the extent to which the acylation status and other protein motifs regulate the targeting and/or retention of these proteins to the distinct membrane domains is poorly defined. we have previously described a family of small myristoylated proteins (smps) that are either monoacylated (myristoylated) o ...201222281304
backbone and side chain 1h, 15n & 13c chemical shift assignments of the holo-acyl carrier protein (acp) of leishmania major.acyl carrier protein (acp) is a small acidic protein, an important cofactor involved in fatty acid biosynthesis. its main function is to protect the growing acyl chain from the hydrophilic environment during fatty acid biosynthesis and simultaneously, present it to the active site of fatty acid pathway enzymes, liable for its elongation. the acp molecule is expressed as apo-acp (inactive) and is post-transitionally modified to the holo form (active) by the enzyme holo acp synthase (acps). here w ...201222278299
reciprocal regulation of protein kinase c isoforms results in differential cellular responsiveness.immunological homeostasis is often maintained by counteractive functions of two different cell types or two different receptors signaling through different intermediates in the same cell. one of these signaling intermediates is protein kinase c (pkc). ten differentially regulated pkc isoforms are integral to receptor-triggered responses in different cells. so far, eight pkc isoforms are reported to be expressed in macrophages. whether a single receptor differentially uses pkc isoforms to regulat ...201222271653
twenty-four new human cases of cutaneous leishmaniasis due to leishmania killicki in metlaoui, southwestern tunisia: probable role of phlebotomus sergenti in the transmission.metlaoui district in the south-west of tunisia is a classical focus of cutaneous leishmaniasis (cl) due to leishmania major. since 2005, a single case of cl due to l. killicki has been reported. we report twenty four human cases due to this parasite, affecting men and women from 2 to 70 years old. leishmania killicki have been typed using molecular techniques: polymerase chain reaction (pcr) followed by restriction fragment length polymorphism (rflp) and gene sequencing. four strains from patien ...201222306359
characterization of a compensatory mutant of leishmania major that lacks ether lipids but exhibits normal growth, and g418 and hygromycin resistance.ether glycerolipid biosynthesis in leishmania major initiates with the acylation of dihydroxyacetonephosphate by the glycosomal dihydroxyacetonephosphate acyltransferase lmdat. we previously reported that a null mutant of lmdat is severely affected in logarithmic growth, survival during stationary phase, and in virulence in mice. in addition, it lacks all ether glycerolipids, produces altered forms of the ether-lipid based virulence factors lipophosphoglycan and increased levels of gpi-anchored ...201222306069
clinical features and epidemiology of cutaneous leishmaniasis and leishmania major/hiv co-infection in cameroon: results of a large cross-sectional study.cutaneous leishmaniasis (cl) is endemic in central africa, including cameroon. however, data on its prevalence and co-infection with hiv are scarce. here we present the results of a large cross-sectional study reporting the prevalence, clinical features and species identification of cl and hiv co-infection in northern cameroon. a total of 32 466 subjects were clinically screened for cl during a door-to-door survey, followed by parasitological diagnosis in the field laboratory. amongst the subjec ...201222301076
developmentally regulated sphingolipid degradation in leishmania major.leishmania parasites alternate between extracellular promastigotes in sandflies and intracellular amastigotes in mammals. these protozoans acquire sphingolipids (sls) through de novo synthesis (to produce inositol phosphorylceramide) and salvage (to obtain sphingomyelin from the host). a single iscl (inositol phosphosphingolipid phospholipase c-like) enzyme is responsible for the degradation of both inositol phosphorylceramide (the ipc hydrolase or ipcase activity) and sphingomyelin (the smase a ...201222299050
[epidemiology of cutaneous leishmaniasis in five villages of dogon country, mali].the epidemiology of the cutaneous leishmaniasis (cl) with leishmania major is poorly documented in mali. following reports of cl in the tourist areas of the dogon country (bandiagara escarpment), a joint french and malian bio-clinical team conducted a field study from 16 to 27 january, 2010. the population of 5 villages has been examined by a dermato-infectiologist and cases were selected by visual inspection of skin lesions. smears and biopsies (from the lesions) and venous blood were obtained ...201222246557
synthesis and anti-leishmanial activity of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines containing n-[(1-benzyl-1h-1,2,3-triazol-4-yl)methyl] moieties.a novel series of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines were synthesized by introducing n-[(1-benzyl-1h-1,2,3-triazol-4-yl)methyl] moiety as a new functionality on the c-2 amine of thiadiazole ring via click chemistry. the title compounds namely, n-[(1-benzyl-1h-1,2,3-triazol-4-yl)methyl]-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines (3a-n) were characterized by ir, nmr and ms spectra. these compounds were evaluated for their in vitro anti-leishmanial activity against promostigote fo ...201222336386
gene expression induced by toll-like receptors in macrophages requires the transcription factor nfat5.toll-like receptors (tlrs) engage networks of transcriptional regulators to induce genes essential for antimicrobial immunity. we report that nfat5, previously characterized as an osmostress responsive factor, regulates the expression of multiple tlr-induced genes in macrophages independently of osmotic stress. nfat5 was essential for the induction of the key antimicrobial gene nos2 (inducible nitric oxide synthase [inos]) in response to low and high doses of tlr agonists but is required for tnf ...201222312110
genetic analysis of clinical isolates of leishmania major from isfahan, iran.leishmaniasis is a geographically widespread severe disease which includes visceral leishmaniasis (vl) and cutaneous leishmaniasis (cl). there are 350 million people at risk in over 80 countries. in the old world, cl is usually caused by leishmania major, l. tropica, and l. aetiopica complex of which 90% of cases occur in afghanistan, algeria, iran, iraq, saudi arabia, syria, brazil and peru. recently, eslami et al (2011) reported a novel tryp6 gene encoding tryparedoxin peroxidase from an irani ...201223135012
combination and monotherapy of leishmania major infection in balb/c mice using plant extracts and herbicides.leishmaniasis is a growing health problem in many parts of the world. efforts to find new chemotherapeutics for leishmaniasis remain a priority. this study was carried out to determine the effect of combination and monotherapies using plant extracts and herbicides on leishmania major infection in balb/c mice.201223135005
il-23 and il-27 levels in macrophages collected from peripheral blood of patients with healing vs non-healing form of cutaneous leishmaniasis.in this study the level of il-23 and il-27 produced by macrophages derived from peripheral blood mononuclear cell culture collected from patients with healing or non-healing form of cutaneous leishmaniasis lesion were compared before and after treatment with live leishmania to explore whether il-23 or il-27 plays any role in healing process of cutaneous lesions induced by l. major.201223133467
efficacy of microwave and infrared radiation in the treatment of the skin lesions caused by leishmania major in an animal model.cutaneous leishmaniasis caused by l. major is an important public health problem in endemic areas. the aim of this study was to explore the therapeutic effect of microwave and or infrared radiation in the treatment of lesion induced in balb/c mice by l. major inoculation.201223113229
interleukin-10 and transforming growth factor-β in early and late lesions of patients with leishmania major induced cutaneous leishmaniasis.cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. better understanding of host immune response to the parasite leads to helpful strategies for disease control. interleukin (il)-10 and transforming growth factor (tgf)-β are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. however, there is little information about the function of il-10 and tgf-β in old world ...201223109957
the multiple forms of leishmania major in balb/c mice lung in iran.cutaneous leishmaniasis is one of the most important parasitic diseases, which are endemic in different parts of iran. leishmania major and l. tropica are the primary causative agents of this disease. the aim of the present study was to detect the multiple forms of l. major in lung. ppromastigotes of l. major at stationary phase were injected to balb/c mice. after 60 days, the different forms of leishmania parasites were checked in lung tissue. promastigote and amastigote forms of leishmania par ...201223109953
role of exosome in infectious disease.exosome is the nano vesicle budded from the endosomal compartment that produces and releases by all kinds of mammalian cells. this vesicle contains the different proteins, lipid, mrna and mirna which are specific to the origin of cell derived from and contribute to the cell to cell communication. recently, it has been reported that a few single cell eukaryote, cryptoccoccus neoformance and leishmania major and donovani can secrete the exosome which influences on the immune system of the host. in ...201223228092
synthesis of n-(1-methyl-1h-indol-3-yl)methyleneamines and 3,3-diaryl-4-(1-methyl-1h-indol-3-yl)azetidin-2-ones as potential antileishmanial agents.a series of n-(1-methyl-1h-indol-3-yl)methyleneamines and eight new 3,3-diaryl-4-(1-methyl-1h-indol-3-yl)azetidin-2-ones have been synthesized and screened for their antileishmanial activity against leishmania major. 3,3-diaryl-4-(1-methyl-1h-indol-3-yl)azetidin-2-ones have been synthesized by the staudinger's ketene-imine cycloaddition employing two 2-diazo-1,2-diarylethanones as the precursors of diarylketenes. a marked improvement in anti-parasitic activity is observed by transformation of th ...201222832310
the role of liposome-protamine-dna nanoparticles containing cpg oligodeoxynucleotides in the course of infection induced by leishmania major in balb/c mice.an inoculation of virulent leishmania major is known as leishmanization (lz) which is proven to be the most effective control measure against cutaneous leishmaniasis (cl) and mimic natural infection. however, use of lz is restricted due to various reasons such as development of uncontrolled lesion. in the present study, the efficacy of coadminstration of live l. major with liposome-protamine-dna nanoparticles (lpd) containing immunostimulatory cpg oligodeoxynucleotides (cpg odn) which is an impr ...201222819791
glucosylated sesquiterpene alcohols from fraxinus griffithii.phytochemical investigation of the leaves of fraxinus griffithii has led to the isolation of two new glucosylated acyclic sesquiterpene alcohols, griffithosides d (1) and e (2), along with iridoid and secoiridoid glycosides. the molecular structures of these compounds were elucidated using nmr, ms and other spectroscopic techniques, as well as comparison with literature data. the isolated compounds were tested for radical-scavenging activity and cytotoxicity against a549 human lung adenocarcinom ...201222574443
improvement of n-glycan site occupancy of therapeutic glycoproteins produced in pichia pastoris.yeast is capable of performing posttranslational modifications, such as n- or o-glycosylation. it has been demonstrated that n-glycans play critical biological roles in therapeutic glycoproteins by modulating pharmacokinetics and pharmacodynamics. however, n-glycan sites on recombinant glycoproteins produced in yeast can be underglycosylated, and hence, not completely occupied. genomic homology analysis indicates that the pichia pastoris oligosaccharyltransferase (ost) complex consists of multip ...201222569635
fumarate hydratase isoforms of leishmania major: subcellular localization, structural and kinetic properties.fumarate hydratases (fhs; ec 4.2.1.2) are enzymes that catalyze the reversible hydration of fumarate to s-malate. parasitic protists that belong to the genus leishmania and are responsible for a complex of vector-borne diseases named leishmaniases possess two genes that encode distinct putative fh enzymes. genome sequence analysis of leishmania major friedlin reveals the existence of genes lmjf24.0320 and lmjf29.1960 encoding the putative enzymes lmfh-1 and lmfh-2, respectively. in the present w ...201222569531
environmental factors underlying spatial patterns of sand flies (diptera: psychodidae) associated with leishmaniasis in southern sinai, egypt.although leishmania major is endemic in parts of the sinai of egypt, the ecology and distribution of leishmania sand fly vectors in southern sinai has not been well characterized. accordingly, additional sand fly samples were obtained at 41 sites in the southern sinai region during 1996-1997, and analyzed to improve the characterization of risk of sand fly-borne pathogens. using a geographic information system (gis), species-specific spatial distributions that might suggest zoonotic cutaneous le ...201222410540
redundant notch1 and notch2 signaling is necessary for ifnγ secretion by t helper 1 cells during infection with leishmania major.the protective immune response to intracellular parasites involves in most cases the differentiation of ifnγ-secreting cd4(+) t helper (th) 1 cells. notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral cd4(+) t helper 1 cells is not well understood. of the four notch receptors, only notch1 (n1) and notch2 (n2) are expressed on activated cd4(+) t cells. to investigate the role of notch in th1 cell differentiation following parasi ...201222396647
transcription factor irf4 determines germinal center formation through follicular t-helper cell differentiation.follicular t-helper (t(fh)) cells cooperate with gl7(+)cd95(+) germinal center (gc) b cells to induce antibody maturation. herein, we identify the transcription factor irf4 as a t-cell intrinsic precondition for t(fh) cell differentiation and gc formation. after immunization with protein or infection with the protozoon leishmania major, draining lymph nodes (lns) of ifn-regulatory factor-4 (irf4(-/-)) mice lacked gcs and gc b cells despite developing normal initial hyperplasia. gcs were also abs ...201222552227
leishmania major peroxidase is a cytochrome c peroxidase.leishmania major peroxidase (lmp) exhibits both ascorbate and cytochrome c peroxidase activities. our previous results illustrated that lmp has a much higher activity against horse heart cytochrome c than ascorbate, suggesting that cytochrome c may be the biologically important substrate. to elucidate the biological function of lmp, we have recombinantly expressed, purified, and determined the 2.08 å crystal structure of l. major cytochrome c (lmcytc). like other types of cytochrome c, lmcytc ha ...201222372542
genetic polymorphism of leishmania major in two hyper endemic regions of iran revealed by ppip-pcr and its- rflp.zoonotic cutaneous leishmaniasis (zcl) is a polymorphic disease that may show various clinical manifestations. although it is suggested that the genetic variability of the parasite is one of the factors influencing clinical manifestations of leishmaniasis, no data exists regarding genetic polymorphism of leishmania major (l.major). this study investigates the determination of genetic variations within the species of l.major isolates from different cases of zcl in two hyper-endemic areas of iran.201222369303
efficient capture of infected neutrophils by dendritic cells in the skin inhibits the early anti-leishmania response.neutrophils and dendritic cells (dcs) converge at localized sites of acute inflammation in the skin following pathogen deposition by the bites of arthropod vectors or by needle injection. prior studies in mice have shown that neutrophils are the predominant recruited and infected cells during the earliest stage of leishmania major infection in the skin, and that neutrophil depletion promotes host resistance to sand fly transmitted infection. how the massive influx of neutrophils aimed at wound r ...201222359507
increase of leishmanicidal and tubercular activities using steroids linked to aminoquinoline. 201222551300
wing size and shape variation of phlebotomus papatasi (diptera: psychodidae) populations from the south and north slopes of the atlas mountains in morocco.the wing shape and size morphology of populations of the medically important phlebotomine sand fly, phlebotomus papatasi, were examined in two endemic (south of the atlas mountains) and nonendemic (north of the atlas mountains) foci of cutaneous leishmaniasis by using geometric morphometrics in morocco. although it is present in all of morocco, p. papatasi is the main vector of leishmania major in only southern part of the atlas mountains. there are four major mountain ranges that serve as geogr ...201222548547
first molecular detection of leishmania major within naturally infected phlebotomus salehi from a zoonotic cutaneous leishmaniasis focus in southern iran.human cutaneous leishmaniasis (cl) is a major notifiable public health problem in many parts of iran. it is often caused by the zooflagellate parasite leishmania major which is mainly transmitted by the bites of female phlebotomine sandflies belonging to the genus phlebotomus (diptera: psychodidae). the annual incidence of cl in fars province, southern iran, was about 108-144 in 2007. the leishmanial infections of wild sandflies that may act as vectors were thus investigated at an endemic focus ...201222543597
crystal structure of dihydroorotate dehydrogenase from leishmania major.dihydroorotate dehydrogenase (dhodh) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and has been exploited as the target for therapy against proliferative and parasitic diseases. in this study, we report the crystal structures of dhodh from leishmania major, the species of leishmania associated with zoonotic cutaneous leishmaniasis, in its apo form and in complex with orotate and fumarate molecules. both orotate and fumarate were found to bind to the same active site and exp ...201222542640
characterization of bifunctional sphingolipid δ4-desaturases/c4-hydroxylases of trypanosomatids by liquid chromatography-electrospray tandem mass spectrometry.six genes encoding putative sphingolipid desaturases have been identified in trypanosomatid genomes: one in trypanosoma brucei (tbsldes protein), one in trypanosoma cruzi (tcsldes) and four in leishmania major (lmsldes1-4), tandemly arrayed on chromosome 26. the six amino acid sequences showed the three characteristic histidine boxes, with a long spacer between the first and second box, as in fungal desaturases and bifunctional desaturases/hydroxylases, to which they are phylogenetically related ...201222542487
metabolic network analysis predicts efficacy of fda-approved drugs targeting the causative agent of a neglected tropical disease.systems biology holds promise as a new approach to drug target identification and drug discovery against neglected tropical diseases. genome-scale metabolic reconstructions, assembled from annotated genomes and a vast array of bioinformatics/biochemical resources, provide a framework for the interrogation of human pathogens and serve as a platform for generation of future experimental hypotheses. in this article, with the application of selection criteria for both leishmania major targets (e.g. ...201222540944
trypanosomatid comparative genomics: contributions to the study of parasite biology and different parasitic diseases.in 2005, draft sequences of the genomes of trypanosoma brucei, trypanosoma cruzi and leishmania major, also known as the tri-tryp genomes, were published. these protozoan parasites are the causative agents of three distinct insect-borne diseases, namely sleeping sickness, chagas disease and leishmaniasis, all with a worldwide distribution. despite the large estimated evolutionary distance among them, a conserved core of ~6,200 trypanosomatid genes was found among the tri-tryp genomes. extensive ...201222481868
a double-blind, randomized, clinical trial on the antileishmanial activity of a morinda citrifolia (noni) stem extract and its major constituents.a controlled study was conducted to determine the efficiency of a topical ointment prepared from the stem extract of morinda citrifolia against cutaneous leishmaniasis. similarly, the in vitro antileishmanial activity of morindicone and morinthone isolated from the extract were investigated against leishmania major. these compounds displayed good activity. out of 40 patients, 50% showed an excellent response and 30% exhibited good improvement.201222474954
molecular detection of leishmania major kdna from wild rodents in a new focus of zoonotic cutaneous leishmaniasis in an oriental region of iran.human cutaneous leishmaniasis is one of the most challenging public health issues in many tropical and subtropical countries of the world, including iran. more than half (54%) of the new zoonotic cutaneous leishmaniasis (zcl) cases among the eastern mediterranean countries were reported from iran in 2008. the detection of leishmania parasites in rodents is essential to incriminate them as probable reservoir hosts of zcl infection. as a result of the annual detection of about 200-250 clinical zcl ...201222651390
molecular detection of leishmania isolated from cutaneous leishmaniasis patients in jask county, hormozgan province, southern iran, 2008.to investigate on patients leishmanial infections in jask county.201222647811
leishcyc: a guide to building a metabolic pathway database and visualization of metabolomic data.the complexity of the metabolic networks in even the simplest organisms has raised new challenges in organizing metabolic information. to address this, specialized computer frameworks have been developed to capture, manage, and visualize metabolic knowledge. the leading databases of metabolic information are those organized under the umbrella of the biocyc project, which consists of the reference database metacyc, and a number of pathway/genome databases (pgdbs) each focussed on a specific organ ...201222639224
role of k(+) binding residues in stabilization of heme spin state of leishmania major peroxidase.the endogenous cation in peroxidases may contribute to the type of heme coordination. here a series of ferric and ferrous derivatives of wild-type leishmania major peroxidase (lmp) and of engineered k(+) site mutants of lmp, lacking potassium cation binding site, has been examined by electronic absorption spectroscopy at 25°c. using uv-visible spectrophotometry, we show that the removal of k(+) binding site causes substantial changes in spin states of both the ferric and ferrous forms. the spect ...201222617686
atg5 is essential for atg8-dependent autophagy and mitochondrial homeostasis in leishmania major.macroautophagy has been shown to be important for the cellular remodelling required for leishmania differentiation. we now demonstrate that l. major contains a functional atg12-atg5 conjugation system, which is required for atg8-dependent autophagosome formation. nascent autophagosomes were found commonly associated with the mitochondrion. l. major mutants lacking atg5 (δatg5) were viable as promastigotes but were unable to form autophagosomes, had morphological abnormalities including a much re ...201222615560
loss of tnf signaling facilitates the development of a novel ly-6c(low) macrophage population permissive for leishmania major infection.in the absence of tnf, the normally resistant c57bl/6 (b6.wt) strain develops a fatal, progressive form of leishmaniasis after infection with leishmania major. it is not yet understood which tnf activity or the lack thereof is responsible for the dramatic progression of leishmaniasis in tnf-negative (b6.tnf(-/-)) mice. to elucidate the underlying mechanisms resulting in the fatal outcome of l. major infection in this gene-deficient mouse strain, we analyzed the monocytic component of the inflamm ...201222615203
laboratory evaluation of oral treatment of rodents with systemic insecticides for control of bloodfeeding sand flies (diptera: psychodidae).the purpose of this study was to evaluate the efficacy of oral treatment of rodents with diets containing the systemic insecticides ivermectin, abamectin, imidacloprid, or spinosad, to control bloodfeeding sand flies. we found that diets containing concentrations higher than 10 mg/kg abamectin were not palatable to rodents, and that a diet containing 10 mg/kg abamectin (a palatable concentration) did not cause 100% mortality of bloodfeeding sand flies. treatment of rodents with imidacloprid was ...201222607066
molecular diagnosis of old world leishmaniasis: real-time pcr based on tryparedoxin peroxidase gene for the detection and identification of leishmania spp.rapid and accurate diagnosis and identification of leishmania sp causing cutaneous leishmaniasis is crucial in control and therapeutic programs. the problem of diagnosis with traditional methods is that they have a low sensitivity or time consuming but molecular techniques would be an alternative method for rapid and accurate diagnosis. in this work, tryparedoxine peroxidase gene-based real-time pcr was used for accurate identification of leishmania spp causing old-world cutaneous leishmaniasis.201222585237
evaluation of the anti-leishmania major activity of satureja bakhtiarica essential oil in vitro.leishmaniasis is a painless chronic skin disease that is caused by the protozoan parasite leishmania. due to the importance of this disease and the side effects of chemical drugs, use of drugs of plant origin to treat leishmaniasis is very important. in the present study, the chemical composition and the anti-leishmania major activity of the essential oils obtained from satureja bakhtiarica were evaluated in vitro. the oils were extracted using a clevenger apparatus and then the chemical composi ...201222428267
characteristics of "tip-dcs and mdscs" and their potential role in leishmaniasis.since the first description of dendritic cells (dcs) by steinman and cohn (1973), the myeloid lineage of leukocytes was investigated intensively. nowadays it is obvious that myeloid cells, especially dcs, are crucial for the adaptive and innate immune response against intracellular pathogens such as leishmania major parasites. based on the overlapping expression of molecules that were commonly used to classify myeloid cells, it becomes difficult to denominate those cell types precisely. of note, ...201222416241
in vitro activity of green tea extract against leishmania major promastigotes.systemic and topical treatment options against leishmaniasis are limited to a few drugs with inconsistent efficacy and unacceptable side effects and none of them is suitable for all forms of the disease.201222373836
t helper1/t helper2 cells and resistance/susceptibility to leishmania infection: is this paradigm still relevant?work in large part on leishmania major in the 1980s identified two distinct apparently counter-regulatory cd4(+) t cell populations, t helper (h)1 and th2, that controlled resistance/susceptibility to infection respectively. however, the generation of il-4(-/-) mice in the 1990s questioned the paramount role of this th2 archetypal cytokine in the non-healing response to leishmania infection. the more recent characterization of cd4(+) t cell regulatory populations and further effector cd4(+) t he ...201222566961
cell death features induced in leishmania major by 1,3,4-thiadiazole derivatives.under a variety of stress conditions, leishmania species display some morphological and biochemical features characteristic of mammalian programmed cell death or necrosis. nitroheteroaryl-1,3,4-thiadiazoles induce cell death in leishmania major (l. major). putative mechanisms of action of these compounds were investigated in vitro at cellular and molecular levels. we used colorimetric assay to measure acid phosphatase activity which is an indicator of cell viability in the promastigotes. the mod ...201222959410
leishmania parasites possess a platelet-activating factor acetylhydrolase important for virulence.leishmania parasites are intracellular protozoans capable of salvaging and remodeling lipids from the host. to understand the role of lipid metabolism in leishmania virulence, it is necessary to characterize the enzymes involved in the uptake and turnover of phospholipids. this study focuses on a putative phospholipase a2 (pla2)/platelet-activating factor acetylhydrolase (paf-ah) in leishmania major. in mammals, paf-ah is a subgroup of pla2 catalyzing the hydrolysis/inactivation of platelet-acti ...201222954769
molecular epidemiology of cutaneous leishmaniasis and heterogeneity of leishmania major strains in iran.to determine the geographical distribution of leishmania species causing cutaneous leishmaniasis (cl) and to study the genetic heterogeneity of leishmania major isolates from different endemic areas of iran.201222947226
an early reduction in treg cells correlates with enhanced local inflammation in cutaneous leishmaniasis in ccr6-deficient mice.resistance to leishmania major infection is dependent on the development of a cell-mediated th1 immune response in resistant c57bl/6 mice whereas th2-prone balb/c mice develop non-healing lesions after infection. the chemokine receptor ccr6 is shared by anti-inflammatory regulatory t cells and pro-inflammatory th17 cells. in a recent study we showed that c57bl/6 mice deficient in ccr6 exhibited enhanced footpad swelling and impaired t helper cell migration indicated by reduced recruitment of tot ...201223028548
antioxidants and proinflamatory cytokines in the sera of patients with cutaneous leishmaniasis.leishmania is a significant health problem in many parts of the world. tumor necrosis factor (tnf) plays an essential role in leishmania major infections.201223023385
euglena gracilis and trypanosomatids possess common patterns in predicted mitochondrial targeting presequences.euglena gracilis possessing chloroplasts of secondary green algal origin and parasitic trypanosomatids trypanosoma brucei, trypanosoma cruzi and leishmania major belong to the protist phylum euglenozoa. euglenozoa might be among the earliest eukaryotic branches bearing ancestral traits reminiscent of the last eukaryotic common ancestor (leca) or missing features present in other eukaryotes. leca most likely possessed mitochondria of endosymbiotic α-proteobacterial origin. in this study, we searc ...201223064754
[leishmania major yakimoff et schokhor, 1914 (kinetoplastida: trypanosomatidae) in meriones shawi duvernoy, 1842 (rodentia: gerbillidae): persistence of the infection in meriones and its infectivity for the sand fly vector (phlebotomus) papatasi scopoli, 1786 (diptera: psychodidae)].the ability of the sand fly phlebotomus papatasi to transmit leishmania major, the etiologic agent of zoonotic cutaneous leishmaniasis, to meriones shawi, the natural reservoir host of this parasite, was studied under laboratory conditions. sand flies became infected with l. major after feeding on a lesion of needle-inoculated m. shawi. moreover, p. papatasi, previously infected with l. major, transmitted the parasite to m. shawi by bite during a second bloodmeal. two months after the blood-meal ...201223055379
identification and frequency distribution of leishmania (l.) major infections in sand flies from a new endemic zcl focus in southeast iran.zoonotic cutaneous leishmaniasis (zcl) is an important public health challenge in iran. it is often caused by the protozoan parasite, leishmania major. this pathogen is principally transmitted by the infectious bites of adult female phlebotomine sand flies which belong to the subgenus phlebotomus (phlebotomus) rondani and berte (diptera: psychodidae). a recent outbreak of clinical zcl cases in the rural district of jask, hormozgan province, southern iran prompted the identification of sand flies ...201222782477
modulation of leishmania major aquaglyceroporin activity by a mitogen-activated protein kinase.leishmania major aquaglyceroporin (lmjaqp1) adventitiously facilitates the uptake of antimonite [sb(iii)], an active form of pentostam® or glucantime®, which are the first line of defence against all forms of leishmaniasis. the present paper shows that lmjaqp1 activity is modulated by the mitogen-activated protein kinase, lmjmpk2. leishmania parasites coexpressing lmjaqp1 and lmjmpk2 show increased sb(iii) uptake and increased sb(iii) sensitivity. when subjected to a hypo-osmotic stress, these c ...201222779703
rapid identification of leishmania spp. in formalin-fixed, paraffin-embedded tissue samples by fluorescence in situ hybridization.to describe and validate fluorescence in situ hybridization (fish), a new method of leishmania spp. identification. fish allows for a rapid detection of target organisms by specific binding of fluorescently labelled oligonucleotide probes to ribosomal rna.201222776353
protection against peroxynitrite by pseudoperoxidase from leishmania major.heme proteins share the ability to detoxify reactive nitrogen intermediates (no and peroxynitrite). but, to date, no heme-containing enzymatic defense against toxic reactive nitrogen intermediates has been discovered in leishmania species. we have cloned, expressed, and characterized a pseudoperoxidase from leishmania major (lmpp) that is capable of detoxifying peroxynitrite (onoo(-)). optical, epr, and resonance raman spectral studies demonstrate that onoo(-) can rapidly convert the six-coordin ...201222985938
dendritic cells in leishmania major infections: mechanisms of parasite uptake, cell activation and evidence for physiological relevance.leishmaniasis is one of the most important infectious diseases worldwide; a vaccine is still not available. infected dendritic cells (dc) are critical for the initiation of protective th1 immunity against leishmania major. phagocytosis of l. major by dc leads to cell activation, il-12 release and (cross-) presentation of leishmania antigens by dc. here, we review the role of fcγ receptor- and b cell-mediated processes for parasite internalization by dc. in addition, the early events after parasi ...201222983754
the role of liposome size on the type of immune response induced in balb/c mice against leishmaniasis: rgp63 as a model antigen.to develop an efficient liposomal vaccine delivery system, the size of liposomes is critical to their adjuvant activities. in the present study, liposomes with different sizes (100, 400, 1000 nm) containing recombinant major surface glycoprotein of leishmania (rgp63) were prepared, characterized, and inoculated subcutaneously into balb/c mice to evaluate the rate of protection and the type of immune response generated against leishmaniasis. the lowest footpad lesion size and splenic parasite bur ...201222982807
infectivity of macrophages and the histopathology of cutaneous lesions, liver and spleen is attenuated by leaf extract of vernonia amygdalina in leishmania major infected balb/c mice.preliminary investigation of the in vitro and in vivo efficacies of different extracts from the leaves of vernonia amygdalina (va), a plant widely used in nigeria was evaluated in balb/c mice infected with a laboratory strain of leishmania major (l. major). the ability of the methanol, hexane and aqueous extracts of the plant to suppress the infection rate and its cytotoxicity on macrophages and l929 cells were determined in the in vitro study. the in vivo study evaluated time course of infectio ...201222713278
cloning of a recombinant plasmid encoding thiol-specific antioxidant antigen (tsa) gene of leishmania majorand expression in the chinese hamster ovary cell line.tsa (thiol-specific antioxidant antigen) is the immune-dominant antigen of leishmania major and is considered to be the most promising candidate molecule for a recombinant or dna vaccine against leishmaniasis. the aim of the present work was to express a plasmid containing the tsa gene in eukaryotic cells.201222977370
mixed mucosal leishmaniasis infection caused by leishmania tropica and leishmania major.mixed infections with different leishmania species could explain differences in the clinical courses of these infections. on identification of leishmania parasites from iranian patients with mucosal leishmaniasis (ml), a patient with both oral and nasal lesions was found to be concomitantly infected with leishmania tropica and l. major. mixed infection was identified by pcr amplification of leishmania kinetoplast dna on scraping of cytological smears and histopathological sections. l. major and ...201222972819
[unusual clinical presentation of cutaneous leishmaniasis in three diabetic patients].cutaneous leishmaniasis (cl) is a parasitic infection characterized by significant clinical variability. unusual and atypical clinical aspects of infection have been reported in immunodeficient patients or associated with particular parasite species. we report three cases of cl from foci of leishmania major with a particular clinical presentation in diabetic patients.201222963963
western blot analysis as an aid for the diagnosis of cutaneous leishmaniasis due to leishmania major.cutaneous leishmaniasis (cl) due to leishmania major is endemic in the old world. to evaluate the diagnostic value of western blot (wb) compared with ifat, we tested serum samples from 45 patients with proven cl. twenty-one (47%) patients were positive by ifat and all patients were positive by wb with specific bands against 14kda and/or 18kda leishmania antigens. our results suggest that wb could be a useful non-invasive tool for the diagnosis of cl caused by l. major.201222657532
comparative genomics reveals two novel rnai factors in trypanosoma brucei and provides insight into the core machinery.the introduction ten years ago of rna interference (rnai) as a tool for molecular exploration in trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. in particular, a genome-wide rnai screen has recently been combined with next-generation illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. at present, this technology is restricted to rnai-positive protozoan parasites, whi ...201222654659
crystal structure of the leishmania major peroxidase-cytochrome c complex.the causative agent of leishmaniasis is the protozoan parasite leishmania major. part of the host protective mechanism is the production of reactive oxygen species including hydrogen peroxide. in response, l. major produces a peroxidase, l. major peroxidase (lmp), that helps to protect the parasite from oxidative stress. lmp is a heme peroxidase that catalyzes the peroxidation of mitochondrial cytochrome c. we have determined the crystal structure of lmp in a complex with its substrate, l. major ...201223100535
heat shock proteins enriched-promastigotes of leishmania major inducing th2 immune response in balb/c mice.heat shock proteins (hsp) are highly conserved molecules with many immunological functions. they are highly immunogenic with important role in cancer immunotherapy and in vaccine development against infectious diseases. as adjuvant, hsp can augment the immunogenicity of weak antigens and can stimulate antigen presenting cells. although vaccines have been successful for many infectious diseases, progress in leishmaniasis has not been achieved. in this report, the protective effect of hsp-enriched ...201223183620
synthesis and biological evaluation of 2,3-diarylimidazo[1,2-a]pyridines as antileishmanial agents.a novel series of 2,3-diarylimidazo[1,2-a]pyridines was synthesized and evaluated for their antileishmanial activities. four derivatives exhibited good activity against the promastigote and intracellular amastigote stages of leishmania major, coupled with a low cytotoxicity against the hela human cell line. the impact of compound lipophilicity on antiparasitic activities was investigated by log d comparison. although lmck1 could be the parasitic target for three compounds (13, 18, 21), the inhib ...201223164660
unusual domain architecture of aminoacyl trna synthetases and their paralogs from leishmania major.leishmania major, a protozoan parasite, is the causative agent of cutaneous leishmaniasis. due to the development of resistance against the currently available anti-leishmanial drugs, there is a growing need for specific inhibitors and novel drug targets. in this regards, aminoacyl trna synthetases, the linchpins of protein synthesis, have received recent attention among the kinetoplastid research community. this is the first comprehensive survey of the aminoacyl trna synthetases, their paralogs ...201223151081
interleukin-10 and transforming growth factor-β in early and late lesions of patients with leishmania major induced cutaneous leishmaniasis.cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. better understanding of host immune response to the parasite leads to helpful strategies for disease control. interleukin (il)-10 and transforming growth factor (tgf)-β are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. however, there is little information about the function of il-10 and tgf-β in old world ...201223109946
inhibition of murine systemic leishmaniasis by acetyl salicylic acid via nitric oxide immunomodulation.the purpose of this study was to evaluate antileishmanial effects of asa via no pathway in leishmania major infected balb/c mice. moreover, toxicity and pathological consequences of asa administration were investigated.201223109942
appraisal of a leishmania major strain stably expressing mcherry fluorescent protein for both in vitro and in vivo studies of potential drugs and vaccine against cutaneous leishmaniasis.leishmania major cutaneous leishmaniasis is an infectious zoonotic disease. it is produced by a digenetic parasite, which resides in the phagolysosomal compartment of different mammalian macrophage populations. there is an urgent need to develop new therapies (drugs) against this neglected disease that hits developing countries. the main goal of this work is to establish an easier and cheaper tool of choice for real-time monitoring of the establishment and progression of this pathology either in ...201223209866
[detection and species identification of two imported cases of cutaneous leishmaniasis].to diagnose and identify pathogen of two suspected cases of cutaneous leishmaniasis.201124822349
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