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functional transcriptomics of wild-caught lutzomyia intermedia salivary glands: identification of a protective salivary protein against leishmania braziliensis infection.leishmania parasites are transmitted in the presence of sand fly saliva. together with the parasite, the sand fly injects salivary components that change the environment at the feeding site. mice immunized with phlebotomus papatasi salivary gland (sg) homogenate are protected against leishmania major infection, while immunity to lutzomyia intermedia sg homogenate exacerbated experimental leishmania braziliensis infection. in humans, antibodies to lu. intermedia saliva are associated with risk of ...201323717705
molecular characterization of leishmania infection from naturally infected sand flies caught in a focus of cutaneous leishmaniasis (eastern iran).cutaneous leishmaniasis due to leishmania major is a serious and increasing problem affecting many rural areas of 17 out of 31 provinces in iran. little is known about sand fly fauna and leishmaniases in eastern iran and no study has been carried out in sarbisheh county. the aim of this study was to determine sand flies composition and probable leishmania infection to find the probable vectors of leishmaniasis in sarbisheh district.201324409437
protective role of the neuropeptide urocortin ii against experimental sepsis and leishmaniasis by direct killing of pathogens.we currently face an alarming resurgence in infectious diseases characterized by antimicrobial resistance and therapeutic failure. this has generated the urgent need of developing new therapeutic approaches that include agents with nontraditional modes of action. a recent interest focused on approaches based on our natural immune defenses, especially on peptides that combine innate antimicrobial activity against diverse pathogens and immunoregulatory functions. in this study, to our knowledge, w ...201324249730
the characterization of the phlebotomus papatasi transcriptome.as important vectors of human disease, phlebotomine sand flies are of global significance to human health, transmitting several emerging and re-emerging infectious diseases. the most devastating of the sand fly transmitted infections are the leishmaniases, causing significant mortality and morbidity in both the old and new world. here we present the first global transcriptome analysis of the old world vector of cutaneous leishmaniasis, phlebotomus papatasi (scopoli) and compare this transcriptom ...201323398403
predicting the proteins of angomonas deanei, strigomonas culicis and their respective endosymbionts reveals new aspects of the trypanosomatidae family.endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the trypanosomatidae family, thus classified as monoxenics. in an effort to better understand such symbiotic association ...201323560078
molecular detection and conventional identification of leishmania species in reservoir hosts of zoonotic cutaneous leishmaniasis in fars province, south of iran.the objectives of our research were to search for leishmania species in rodents in fars province, south of iran, and to compare molecular with conventional methods for detecting these parasites.201323914242
immunogenicity of hla-dr1 restricted peptides derived from leishmania major gp63 using fvb/n-dr1 transgenic mouse model.leishmaniasis is a worldwide disease prevalent in tropical and sub-tropical countries. in the present study the immunogenicity of three human hla-dr1 restricted peptides derived from l. major gp63 protein was evaluated using fvb/n-dr1 transgenic mouse model.201323914241
monarch-1 activation in murine macrophage cell line (j774 a.1) infected with iranian strain of leishmania major.leishmania major is an intracellular parasite transmitted through the bite of the female phlebotomine sand flies. leishmania major is able to escape the host immune defense and survive within macrophages. modulation of the nf-κb (nuclear factor-kappa b) activation and suppression of the pro-inflammatory cytokines by l. major are the main evasion mechanisms that remain to be explored. this study aims to examine the expression level of the monarch-1 in l. major-infected macrophages, as a negative ...201323914232
gene regulation of pteridine reductase 1 in leishmania promastigotes and amastigotes using a full-length antisense construct.pteridine metabolic pathway is unusual features of leishmania, which is necessary for the growth of parasite. leishmania has evolved a complex and versatile pteridine salvage network which has the ability of scavenging a wide area of the conjugated and unconjugated pteridines especially folate and biopterin. in this study, we focus on the inhibition of ptr1 gene expression.201323914230
linking climate to incidence of zoonotic cutaneous leishmaniasis (l. major) in pre-saharan north africa.shifts in surface climate may have changed the dynamic of zoonotic cutaneous leishmaniasis (zcl) in the pre-saharan zones of north africa. caused by leishmania major, this form multiplies in the body of rodents serving as reservoirs of the disease. the parasite is then transmitted to human hosts by the bite of a phlebotomine sand fly (diptera: psychodidae) that was previously fed by biting an infected reservoir. we examine the seasonal and interannual dynamics of the incidence of this zcl as a f ...201323912199
eukaryotic oligosaccharyltransferase generates free oligosaccharides during n-glycosylation.asparagine (n)-linked glycosylation regulates numerous cellular activities, such as glycoprotein quality control, intracellular trafficking, and cell-cell communications. in eukaryotes, the glycosylation reaction is catalyzed by oligosaccharyltransferase (ost), a multimembrane protein complex that is localized in the endoplasmic reticulum (er). during n-glycosylation in the er, the protein-unbound form of oligosaccharides (free oligosaccharides; foss), which is structurally related to n-glycan, ...201324062310
the immunomodulatory effect of plant lectins: a review with emphasis on artinm properties.advances in the glycobiology and immunology fields have provided many insights into the role of carbohydrate-protein interactions in the immune system. we aim to present a comprehensive review of the effects that some plant lectins exert as immunomodulatory agents, showing that they are able to positively modify the immune response to certain pathological conditions, such as cancer and infections. the present review comprises four main themes: (1) an overview of plant lectins that exert immunomo ...201323299509
iron overload favors the elimination of leishmania infantum from mouse tissues through interaction with reactive oxygen and nitrogen species.iron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. the host's iron overload is often associated with susceptibility to infection. however, it has been previously reported that iron overload prevented the growth of leishmania major, an agent of cutaneous leishmaniasis, in balb/c mice. in order to further clarify the impact of iron modulation on the growth of leishmania in vivo, we studie ...201323459556
il-4 attenuates th1-associated chemokine expression and th1 trafficking to inflamed tissues and limits pathogen clearance.interleukin 4 (il-4) plays a central role in the orchestration of type 2 immunity. during t cell activation in the lymph node, il-4 promotes th2 differentiation and inhibits th1 generation. in the inflamed tissue, il-4 signals promote innate and adaptive type-2 immune recruitment and effector function, positively amplifying the local th2 response. in this study, we identify an additional negative regulatory role for il-4 in limiting the recruitment of th1 cells to inflamed tissues. to test il-4 ...201323991011
the leishmania major bbsome subunit bbs1 is essential for parasite virulence in the mammalian host.bardet-biedl syndrome (bbs) is a human genetic disorder with a spectrum of symptoms caused by primary cilium dysfunction. the disease is caused by mutations in one of at least 17 identified genes, of which seven encode subunits of the bbsome, a protein complex required for specific trafficking events to and from the primary cilium. the molecular mechanisms associated with bbsome function remain to be fully elucidated. here, we generated null and complemented mutants of the bbsome subunit bbs1 in ...201323998526
first report on isolation and characterization of leishmania major from meriones hurrianae (rodentia: gerbillidae) of a rural cutaneous leishmaniasis focus in south-eastern iran.zoonotic cutaneous leishmaniasis (zcl) is an endemic health problem in many rural areas of iran, with doubled number of incidences over the last decade. different species of rodents serve as natural reservoir host for zcl. the disease is considered as a major health problem in rural areas of mirjaveh, chabahar, and konarak counties of sistan va baluchistan province.201324616787
the effect of avian blood on leishmania development in phlebotomus duboscqi.the development of pathogens transmitted by haematophagous invertebrate vectors is closely connected with the digestion of bloodmeals and is thus affected by midgut enzymatic activity. some studies have demonstrated that avian blood inhibits leishmania major infection in the old world vector phlebotomus papatasi; however, this effect has never been observed in the new world vectors of the genus lutzomyia infected by other leishmania species. therefore, our study was focused on the effect of chic ...201324059328
characterization of phlebotomus papatasi peritrophins, and the role of ppper1 in leishmania major survival in its natural vector.the peritrophic matrix (pm) plays a key role in compartmentalization of the blood meal and as barrier to pathogens in many disease vectors. to establish an infection in sand flies, leishmania must escape from the endoperitrophic space to prevent excretion with remnants of the blood meal digestion. in spite of the role played regarding leishmania survival, little is known about sand fly pm molecular components and structural organization. we characterized three peritrophins (ppper1, ppper2, and p ...201323516661
a newly emerged cutaneous leishmaniasis focus in northern israel and two new reservoir hosts of leishmania major.in 2006/7, 18 cases of cutaneous leishmaniasis (cl) were reported for the first time from sde eliyahu (pop. 650), a village in the beit she'an valley of israel. between 2007-2011, a further 88 cl cases were diagnosed bringing the total to 106 (16.3% of the population of sde eliyahu). the majority of cases resided in the south-western part of the village along the perimeter fence. the causative parasite was identified as leishmania major yakimoff & schokhor, 1914 (kinetoplastida: trypanosomatidae ...201323437408
the present status of cutaneous leishmaniasis in a recently emerged focus in south-west of kerman province, iran.the objective of this study was to assess the magnitude of the cutaneous leishmaniasis (cl) disease and identification of the causative agent by nested-pcr for current control strategy.201323515397
the mating competence of geographically diverse leishmania major strains in their natural and unnatural sand fly vectors.invertebrate stages of leishmania are capable of genetic exchange during their extracellular growth and development in the sand fly vector. here we explore two variables: the ability of diverse l. major strains from across its natural range to undergo mating in pairwise tests; and the timing of the appearance of hybrids and their developmental stage associations within both natural (phlebotomus duboscqi) and unnatural (lutzomyia longipalpis) sand fly vectors. following co-infection of flies with ...201323935521
validity and reliability of enzyme immunoassays using leishmania major or l. infantum antigens for the diagnosis of canine visceral leishmaniasis in brazil.american visceral leishmaniasis is caused by the protozoan leishmania infantum. dogs are the main reservoirs in the domestic transmission cycle. the limited accuracy of diagnostic tests for canine leishmaniasis may contribute to the lack of impact of control measures recommended by the brazilian ministry of health. the objective of this study was to estimate the accuracy of two enzyme-linked immunosorbent assays employing l. major or l. infantum antigens and their reliability between three labor ...201323922884
evaluation of pcr procedures for detecting and quantifying leishmania donovani dna in large numbers of dried human blood samples from a visceral leishmaniasis focus in northern ethiopia.visceral leishmaniasis (vl) is a disseminated protozoan infection caused by leishmania donovani parasites which affects almost half a million persons annually. most of these are from the indian sub-continent, east africa and brazil. our study was designed to elucidate the role of symptomatic and asymptomatic leishmania donovani infected persons in the epidemiology of vl in northern ethiopia.201323530965
actin expression in trypanosomatids (euglenozoa: kinetoplastea).heteroxenic and monoxenic trypanosomatids were screened for the presence of actin using a mouse polyclonal antibody produced against the entire sequence of the trypanosoma cruzi actin gene, encoding a 41.9 kda protein. western blot analysis showed that this antibody reacted with a polypeptide of approximately 42 kda in the whole-cell lysates of parasites targeting mammals (t. cruzi, trypanosoma brucei and leishmania major), insects (angomonas deanei, crithidia fasciculata, herpetomonas samuelpes ...201323903980
molecular epidemiological study of cutaneous leishmaniasis in the focus of bushehr city, southwestern iran.cutaneous leishmaniasis (cl) represents the most frequent vector borne parasitoses in iran. the objective of this study was to determine the epidemiological features of cl including human infection and the reservoir host in the city of bushehr, bushehr province, iran during 2010-2011.201324409436
systematic analysis of proteomes with emphasis on insertions in malaria parasite plasmodium falciparum.protein insertion sequences and their biological role in many organisms have been largely unknown. here we study proteomes of 12 organisms of diverse genomes for insertion length and amino acid preferences. a total of 871 common proteins were catalogued amongst the 12 organisms for structure based sequence alignment. this underscores the key observations: (i) at-richness seems to have no implication on the average protein length in an organism as only dictyostelium discoideum and plasmodium falc ...201323688187
mc3: a steady-state model and constraint consistency checker for biochemical networks.stoichiometric models provide a structural framework for analyzing steady-state cellular behavior. models are developed either through augmentations of existing models or more recently through automatic reconstruction tools. there is currently no standardized practice or method for validating the properties of a model before placing it in the public domain. considerable effort is often required to understand a model's inconsistencies before its reuse within new research efforts.201324261865
the role of surface glycoconjugates in leishmania midgut attachment examined by competitive binding assays and experimental development in sand flies.binding of promastigotes to the sand fly midgut epithelium is regarded as an essential part of the leishmania life cycle in the vector. among leishmania surface molecules putatively involved in attachment to the sand fly midgut, two gpi-anchored molecules are the most prominent: lipophosphoglycan (lpg) and promastigote surface protease gp63. in this work, we examined midgut attachment of leishmania lines mutated in gpi-anchored molecules and compared results from 2 different techniques: in vivo ...201323611086
three leishmania/l. species--l. infantum, l. major, l. tropica--as causative agents of mucosal leishmaniasis in iran.cases of human oro-mucosal leishmaniasis are mainly reported in areas where leishmania (viannia) braziliensis perpetuates and the damages are mainly located at the cartilaginous nasal septum and frontal portions of the nasal fossa. in iran, an area free of any l.(v) braziliensis, three leishmania species are known to perpetuate through distinct (i) blood-feeding sand flies and (ii) rodents or (iii) canidae. thus while establishing the diagnosis of any human oro-mucosal lesions, three leishmania ...201323916336
s-nitrosoglutathione (gsno) is cytotoxic to intracellular amastigotes and promotes healing of topically treated leishmania major or leishmania braziliensis skin lesions.this study was designed to verify the cytotoxic activity of s-nitrosoglutathione (gsno) against intracellular leishmania amastigotes and to test its efficacy as a topical treatment of localized cutaneous leishmaniasis (lcl) in leishmania major- or leishmania braziliensis-infected mice.201323788476
first molecular-based detection of mucocutaneous leishmaniasis caused by leishmania major in iran.mucocutaneous leishmaniasis, which mostly occurs in the new world, is mainly associated with leishmania braziliensis and to a lesser degree l. panamensis and l. amazonensis infections. primary mucosal leishmaniasis is very rare in iran in spite of high prevalence of cutaneous and visceral leishmanisis. a nine-year-old boy had cutaneous leishmaniaisis for five years involving the left side of his face; he then developed swelling and ulceration of the lip and left side buccal mucosa five months be ...201323669431
live attenuated leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in balb/c mice.leishmaniasis causes significant morbidity and mortality worldwide, and no vaccines against this disease are available. previously, we had shown that the amastigote-specific protein p27 (ldp27) is a component of an active cytochrome c oxidase complex in leishmania donovani and that upon deletion of its gene the parasite had reduced virulence in vivo. in this study, we have shown that ldp27(-/-) parasites do not survive beyond 20 wk in balb/c mice and hence are safe as an immunogen. upon virulent ...201323338240
nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of leishmania species, including strains obtained from hiv-positive patients.there is a general lack of effective and non-toxic chemotherapeutic agents for leishmaniasis and there is as yet no study about the effect of hiv peptidase inhibitors (hiv pis) on leishmania/hiv-coinfected patients. in the present work, we performed a comparative analysis of the spectrum of action of hiv pis on different leishmania spp., including strains obtained from hiv-positive patients receiving or not receiving antiretroviral treatment.201323109184
molecular detection of leishmania infection in sand flies in border line of iran-turkmenistan: restricted and permissive vectors.a molecular study was carried out to incriminate sand fly vectors of cutaneous leishmaniasis (cl) in rural areas of sarakhs district, khorassane-razavi province, northeastern iran, in 2011. sand flies of sergentomyia with three species and phlebotomus with six species respectively comprised 73.3% and 26.7% of the specimens. phlebotomus papatasi was the most common phlebotomine species in outdoor and indoor resting places. leishmania infection was found at least in 17 (22%) specimens including ph ...201323933280
noncovalent complexation of amphotericin-b with poly(α-glutamic acid).a noncovalent complex of amphotericin b (amb) and poly(α-glutamic acid) (pga) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. the loading of amb in the complex was in the range of ∼20-50%. amb was in a highly aggregated state with an aggregation ratio often above 2.0. this complex (amb-pga) was shown to be stable and to have reduced toxicity to human red blood cells and kb cells compared to the parent compound; cell viability was not affected at an amb c ...201323234235
different susceptibilities of leishmania spp. promastigotes to the annona muricata acetogenins annonacinone and corossolone, and the platymiscium floribundum coumarin scoparone.leishmaniasis is a zoonotic disease that can manifest itself in visceral and cutaneous form. the aim of this study was to search for new leishmanicidal compounds. preliminarily, artemia salina assay was applied to compounds from two plants found in northeastern brazil, platymiscium floribundum and annona muricata. then these compounds were tested against three leishmania species (leishmania donovani, leishmania mexicana and leishmania major). a screening assay using luciferase-expressing promast ...201323232251
identification of tunisian leishmania spp. by pcr amplification of cysteine proteinase b (cpb) genes and phylogenetic analysis.discrimination of the old world leishmania parasites is important for diagnosis and epidemiological studies of leishmaniasis. we have developed pcr assays that allow the discrimination between leishmania major, leishmania tropica and leishmania infantum tunisian species. the identification was performed by a simple pcr targeting cysteine protease b (cpb) gene copies. these pcr can be a routine molecular biology tools for discrimination of leishmania spp. from different geographical origins and d ...201323228525
detection and chronology of parasitic kinetoplast dna presence in hair of experimental leishmania major infected balb/c mice by real time pcr.hair can accumulate foreign chemical or biological substances. recently, it has been reported that parasite dna can also be detected in the hair of leishmania infantum infected dogs. the aim of this work has been to find out whether parasite dna incorporates in the hair of leishmania major experimentally infected animals. for this purpose, a group of 4 balb/c mice, intradermally inoculated in both ears with 1000 l. major v1 strain promastigote forms, was monitored for parameters associated to th ...201323916508
in silico and in vitro comparative activity of novel experimental derivatives against leishmania major and leishmania infantum promastigotes.this in silico and in vitro comparative study was designed to evaluate the effectiveness of some biurets (k1 to k8) and glucantime against leishmania major and leishmania infantum promastigotes. overall, eight experimental ligands and glucantime were docked using autodock 4.3 program into the active sites of leishmania major and leishmania infantum pteridine reductase 1, which were modeled using homology modeling programs. the colorimetric mtt assay was used to find l. major and l. infantum prom ...201323872452
cutaneous and post kala-azar dermal leishmaniasis caused by leishmania infantum in endemic areas of visceral leishmaniasis, northwestern iran 2002-2011: a case series.visceral leishmaniasis (vl) is endemic in northwest and southern iran. reports of cutaneous leishmaniasis (cl) in northwest areas are rare, and its etiological agents are unknown. in the current study, we report six cl and two post kala-azar dermal leishmaniasis (pkdl) cases caused by leishmania infantum from endemic areas of vl in the northwest. smears were made from skin lesions of 30 suspected patients in 2002-2011, and cl was determined by microscopy or culture. leishmania spp. were identifi ...201323816511
comparison between in vitro effects of aqueous extract of artemisia seiberi and artemisinin on leishmania major.it is necessary to develop novel, affordable, and accessible drugs with few side effects as alternatives of the currently available chemical agents for leishmaniasis.201324624191
a newly emerged cutaneous leishmaniasis focus in central iran.this study was performed to evaluate the epidemiological status of cutaneous leishmaniasis (cl) in the most important endemic foci of qom province, central iran. the city of qom is the largest center for shi'a scholarship in the world and is a significant pilgrimage destination.201324011629
[demonstration of the leishmanicidal activity of stachys guyoniana against leishmania major in eastern algeria].the authors report the results of the assessment of the leishmanicidal activity of a plant species of the lamiaceae family, stachys guyoniana. this in vitro study used the species endemic in algeria, leishmania major. both the butanolic and ethyl acetate extracts showed strong activity against this strain.201324001646
in vitro immunobiological studies of novel 5-(5-nitrofuran-2-yl)-1, 3, 4-thiadiazoles with piperazinyl-linked benzamidine substituents against leishmania major.it was recently demonstrated that 5-(5-nitrofuran-2-yl)-1, 3, 4-thiadiazoles with piperazinyl-linked benzamidine substituents are effective in vitro against leishmania major.following on this evidence, we used colorimetric assay of acid phosphatase activity in the promastigotes as an indicator for cell viability. also we studied the effect of these compounds on induction of nitric oxide (no) in macrophage and production of reactive oxygen species (ros) in lymphocyte that have important role in a ...201323996713
igg1 and igg2a profile of serum antibodies to leishmania major amastigote in balb/c and c57bl/6mice.it is well accepted that in experimental model of leishmania major infection, balb/c mice mount a th2 response and produce igg1 predominantly whereas c57bl/6mice enhance th1 response with the biased production of igg2a antibodies. therefore, screening for parasite antigens on the basis of reactivity with sera from infected susceptible or resistant mice might be used for the identification of th1- or th2-inducing antigens.in this study, the antigenic profile of leishmania major amastigote that in ...201323996712
tlr2 and tlr4 in cutaneous leishmaniasis caused by leishmania major.cutaneous leishmaniasis (cl) is a self-healing skin disease which rarely for unknown reason(s) the lesion develops to a non-healing form. it seems that the initial contact of leishmania parasites with the host innate immune system is an important step in the outcome of the disease. recent studies suggested that toll-like receptors (tlrs) play a role in leishmania recognition. in this study, the level of tlr2 and tlr4 was checked in patients with healing form of lesion and compared with that of p ...201323980810
combination therapy using pentostam and praziquantel improves lesion healing and parasite resolution in balb/c mice co-infected with leishmania major and schistosoma mansoni.most natural host populations are exposed to a diversity of parasite communities and co-infection of hosts by multiple parasites is commonplace across a diverse range of systems. co-infection with leishmania major and schistosoma mansoni may have important consequences for disease development, severity and transmission dynamics. pentavalent antimonials and praziquantel (pzq) have been relied upon as a first line of treatment for leishmania and schistosoma infections respectively. however, it is ...201323968249
effects of sheep and mouse urine on the growth pattern of leishmania major promastigotes.the protozoan parasites of the genus leishmania are the causative agents of different clinical diseases. fetal calf serum (fcs) is the main part and the most expensive ingredient of the leishmania culture media. here, the efficacies of different concentrations (1%, 2.5%, 5%, and 10%) of the filtered and autoclaved sheep and mouse urine were evaluated as a growth stimulator in leishmania culture procedure. the results indicated that culture media enriched with the filtered sheep and mouse urine s ...201323957003
molecular characterization of leishmania spp. in reservoir hosts in endemic foci of zoonotic cutaneous leishmaniasis in iran.zoonotic cutaneous leishmaniasis (zcl) is an expanding disease and a public health issue in iran. in the present study, rate of natural infection of rodent populations with leishmania was investigated in six endemic foci including 28 villages in golestan, esfahan, yazd, fars, khuzestan and ilam provinces. a total of 593 rodents were captured and identified as rhombomys opimus (n = 325), meriones libycus (n = 171), meriones persicus (n = 27), tatera indica (n = 37), nesokia indica (n = 12), rattu ...201323951928
an essential type i nitroreductase from leishmania major can be used to activate leishmanicidal prodrugs.nitroaromatic prodrugs are used to treat a range of microbial infections with selectivity achieved by specific activation reactions. for trypanosomatid parasites, this is mediated by type i nitroreductases. here, we demonstrate that the causative agent of leishmaniasis, leishmania major, expresses an fmn-containing nitroreductase (lmntr) that metabolizes a wide range of substrates, and based on electron donor and acceptor preferences, it may function as an nadh:quinone oxidoreductase. using gene ...201323946481
tridimensional ultrastructure and glycolipid pattern studies of trypanosoma dionisii.trypanosoma (schizotrypanum) dionisii is a non-pathogenic bat trypanosome closely related to trypanosoma cruzi, the etiological agent of chaga's disease. both kinetoplastids present similar morphological stages and are able to infect mammalian cells in culture. in the present study we examined 3d ultrastructure aspects of the two species by serial sectioning epimastigote and trypomastigote forms, and identified common carbohydrate epitopes expressed in t. dionisii, t. cruzi and leishmania major. ...201323933185
sheep blood-lb agar base medium (slm) as a simple and suitable medium for the cultivation of leishmania major promastigotes.several methods of cultivation of leishmania parasites are available, and among them, biphasic media like nicolle-novy-macneal medium are considered to be superior for the initial isolation of the parasites and their in vivo infectivity. in the present work, the efficacy of sheep blood-lb agar base medium (slm) was evaluated for the cultivation of leishmania major promastigotes. the slm supports the proliferation of the parasites and can be used for routine isolation and cultivation of leishmani ...201323925445
induction of protection against leishmaniasis in susceptible balb/c mice using simple dotap cationic nanoliposomes containing soluble leishmania antigen (sla).a suitable adjuvant and delivery system are needed to develop an effective vaccine against leishmaniasis. to induce a th1 type of response and protection in balb/c mice against leishmania major infection, 1,2-dioleoyl-3-trimethylammonium-propane (dotap) nanoliposomes bearing an intrinsic adjuvanticity, were used as an antigen delivery system and immunoadjuvant for soluble leishmania antigens (sla). dotap liposomes containing different concentrations of sla were prepared by using lipid film metho ...201323916506
crystallization and preliminary x-ray diffraction analysis of selenophosphate synthetases from trypanosoma brucei and leishmania major.selenophosphate synthetase (sps) plays an indispensable role in selenium metabolism, being responsible for catalyzing the activation of selenide with adenosine 5'-triphosphate (atp) to generate selenophosphate, the essential selenium donor for selenocysteine synthesis. recombinant full-length leishmania major sps (lmsps2) was recalcitrant to crystallization. therefore, a limited proteolysis technique was used and a stable n-terminal truncated construct (δn-lmsps2) yielded suitable crystals. the ...201323908029
calpains: potential targets for alternative chemotherapeutic intervention against human pathogenic trypanosomatids.the treatment for both leishmaniasis and trypanosomiasis, which are severe human infections caused by trypanosomatids belonging to leishmania and trypanosoma genera, respectively, is extremely limited because of concerns of toxicity and efficacy with the available anti-protozoan drugs, as well as the emergence of drug resistance. consequently, the urgency for the discovery of new trypanosomatid targets and novel bioactive compounds is particularly necessary. in this context, the investigation of ...201323899207
genetic diversity of leishmania major strains isolated from different clinical forms of cutaneous leishmaniasis in southern iran based on minicircle kdna.cutaneous leishmaniasis (cl) has been reported from 20 of 31 provinces of iran. it is a polymorphic disease, which may show various clinical manifestations. although genetic diversity of the parasite is suggested to be one of the factors influencing the clinical manifestations in cl, there is still no data regarding the genetic variation of leishmania major based on the sequencing of kdna .the amplification of the kinetoplast dna based on 21 isolates of l. major from different clinical forms of ...201323892374
neolignan licarin a presents effect against leishmania (leishmania) major associated with immunomodulation in vitro.leishmaniasis' treatment is based mostly on pentavalent antimonials or amphotericin b long-term administration, expensive drugs associated with severe side effects. considering these aforementioned, the search for alternative effective and safe leishmaniasis treatments is a necessity. this work evaluated a neolignan, licarin a anti-leishmanial activity chemically synthesized by our study group. it was observed that licarin a effectively inhibited leishmania (leishmania) major promastigotes (ic₅₀ ...201323891943
ibrutinib is an irreversible molecular inhibitor of itk driving a th1-selective pressure in t lymphocytes.given its critical role in t-cell signaling, interleukin-2-inducible kinase (itk) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and neoplastic diseases. ablation of itk subverts th2 immunity, thereby potentiating th1-based immune responses. while small-molecule itk inhibitors have been identified, none have demonstrated clinical utility. ibrutinib is a confirmed irreversible inhibitor of bruton tyrosine kinase (btk) with outstanding ...201323886836
metal-drug synergy: new ruthenium(ii) complexes of ketoconazole are highly active against leishmania major and trypanosoma cruzi and nontoxic to human or murine normal cells.in our ongoing search for new metal-based chemotherapeutic agents against leishmaniasis and chagas disease, six new ruthenium-ketoconazole (ktz) complexes have been synthesized and characterized, including two octahedral coordination complexes-cis,fac-[ru(ii)cl2(dmso)3(ktz)] (1) and cis-[ru(ii)cl2(bipy)(dmso)(ktz)] (2) (where dmso is dimethyl sulfoxide and bipy is 2,2'-bipyridine)-and four organometallic compounds-[ru(ii)(η(6)-p-cymene)cl2(ktz)] (3), [ru(ii)(η(6)-p-cymene)(en)(ktz)][bf4]2 (4), [ ...201323881220
molecular characterization of sandflies and leishmania detection in main vector of zoonotic cutaneous leishmaniasis in abarkouh district of yazd province, iran.to assess molecular characterization, distribution, seasonal activities of sandfly species and leishmania parasites infecting them for this zoonotic cutaneous leishmaniasis focus.201323870468
natural infection and phylogenetic classification of leishmania spp. infecting rhombomys opimus, a primary reservoir host of zoonotic cutaneous leishmaniasis in northeast iran.in the northeast and central parts of iran, rhombomys opimus (great gerbil) is the primary reservoir host of zoonotic cutaneous leishmaniasis (zcl). this study used both parasitological and molecular methods to identify leishmania spp. and their different haplotypes that were circulating in the great gerbil populations in zcl foci from northeastern iran.201323868742
targeting leishmania major antigens to dendritic cells in vivo induces protective immunity.efficient vaccination against the parasite leishmania major, the causative agent of human cutaneous leishmaniasis, requires development of type 1 t-helper (th1) cd4(+) t cell immunity. because of their unique capacity to initiate and modulate immune responses, dendritic cells (dcs) are attractive targets for development of novel vaccines. in this study, for the first time, we investigated the capacity of a dc-targeted vaccine to induce protective responses against l. major. to this end, we genet ...201323840706
leishmania major inhibits il-12 in macrophages by signalling through cr3 (cd11b/cd18) and down-regulation of ets-mediated transcription.leishmania major is an aetiological agent of cutaneous leishmaniasis. the parasite primarily infects immune sentinel cells, specifically macrophages and dendritic cells, in the mammalian host. infection is receptor mediated and is known to involve parasite binding to cell surface protein complement receptor 3 (cr3, mac-1, cd11b/cd18). engagement of cr3 by various ligands inhibits production of interleukin-12 (il-12), the cytokine that drives antileishmanial t helper 1-type immune responses. like ...201323834512
effect of distal his mutation on the peroxynitrite reactivity of leishmania major peroxidase.the conserved distal histidine in peroxidases has been considered to play a major role as a general acid-base catalyst for heterolytic cleavage of an oo bond in h2o2. however, heme peroxidases react with peroxynitrite to form transient intermediates but the role of the distal histidine in this reaction is still unknown. in order to investigate catalytic roles of the histidine at the distal cavity, two leishmania major peroxidase (lmp) mutants (h68e, h68v) were prepared. the rate of transition fr ...201323831153
first molecular identification of leishmania species in a new endemic area of cutaneous leishmaniasis in lorestan, iran.to identify leishmania using pcr.201323827149
dressings combined with injection of meglumine antimoniate in the treatment of cutaneous leishmaniasis: a randomized controlled clinical trial.cutaneous leishmaniasis (cl) is a neglected infectious disease and a major health problem in several developing countries. despite some reasonable explanation for their potential benefits, there is only trace evidence regarding the role of dressings in the treatment of cl.201323826087
t cell-derived il-10 determines leishmaniasis disease outcome and is suppressed by a dendritic cell based vaccine.in the murine model of leishmania major infection, resistance or susceptibility to the parasite has been associated with the development of a th1 or th2 type of immune response. recently, however, the immunosuppressive effects of il-10 have been ascribed a crucial role in the development of the different clinical correlates of leishmania infection in humans. since t cells and professional apc are important cellular sources of il-10, we compared leishmaniasis disease progression in t cell-specifi ...201323825956
mir-182 and mir-10a are key regulators of treg specialisation and stability during schistosome and leishmania-associated inflammation.a diverse suite of effector immune responses provide protection against various pathogens. however, the array of effector responses must be immunologically regulated to limit pathogen- and immune-associated damage. cd4(+)foxp3(+) regulatory t cells (treg) calibrate immune responses; however, how treg cells adapt to control different effector responses is unclear. to investigate the molecular mechanism of treg diversity we used whole genome expression profiling and next generation small rna seque ...201323825948
in vitro activity of alkanna frigida extracts in comparison with glucantime against leishmania major.current chemotherapies of cutaneous leihmaniasis have faced to some problems and limitations; development of new leishmanicidal drugs from different sources like herbal plants, are crucially important. the objective of the present study was evaluation of in vitro activity of alkanna frigida extracts in comparison with glucantime against leishmania major.201323825738
nano-based antileishmanial agents: a toxicological study on nanoparticles for future treatment of cutaneous leishmaniasis.cutaneous leishmaniasis (cl) is endemic in the tropical and subtropical countries. antileishmanial drugs that are traditionally used for treatment of cl are mainly toxic, ineffective for some parasite isolates, and mostly expensive. previous studies showed that some metal and metal oxide nanoparticles have antimicrobial activity. moreover, the use of nanoparticles together with ultra violet (uv) and infra red (ir) light increases toxic effects of nanoparticles by generation of reactive oxygen sp ...201323806227
deficiency of leishmania phosphoglycans influences the magnitude but does not affect the quality of secondary (memory) anti-leishmania immunity.despite inducing very low ifn-γ response and highly attenuated in vivo, infection of mice with phosphoglycan (pg) deficient leishmania major (lpg2-) induces protection against virulent l. major challenge. here, we show that mice infected with lpg2- l. major generate leishmania-specific memory t cells. however, in vitro and in vivo proliferation, il-10 and ifn-γ production by lpg2- induced memory cells were impaired in comparison to those induced by wild type (wt) parasites. interestingly, tnf re ...201323776605
membrane targeting of the small myristoylated protein 2 (smp-2) in leishmania major.leishmania parasites express three highly conserved small myristoylated proteins (smps) that are targeted to distinct membranes. smp-1 is exclusively found in the flagellum, depending on myristoylation and palmitoylation. in contrast, monoacylated smp-2 and smp-4 are localized to the flagellar pocket and plasma membrane, respectively. here, we demonstrate that unlike smp-4, smp-2 resides in detergent resistant membranes, but can be readily solubilized in the presence of high concentrations of sa ...201323727225
a new abc half-transporter in leishmania major is involved in resistance to antimony.the characterization of abci4, a new intracellular atp-binding cassette (abc) half-transporter in leishmania major, is described. we show that abci4 is involved in heavy metal export, thereby conferring resistance to pentostam, to sb(iii), and to as(iii) and cd(ii). parasites overexpressing abci4 showed a lower mitochondrial toxic effect of antimony by decreasing reactive oxygen species production and maintained higher values of both the mitochondrial electrochemical potential and total atp leve ...201323716044
leishmania major self-limited infection increases blood cholesterol and promotes atherosclerosis development.leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a th1 proinflammatory response. atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. in this study, we evaluated the influence of l. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein e-deficient (apoe ko) mice. after 6 weeks of infection, apoe ko mice exhibited reduced footpad swel ...201323710353
evaluation of the fat-tailed gerbil, pachyuromys duprasi (rodentia: gerbillidae), as a new animal model for studies of leishmania major infection and transmission.the fat-tailed gerbil pachyuromys duprasi is a common burrowing rodent found across the northern sahara desert from morocco to egypt. there is overlap in the geographical distribution and ecological habitats of p. duprasi, several old world leishmania species, and numerous sand fly vectors of leishmania, but there are no records that document the natural occurrence of this gerbil with any species of leishmania or phlebotomine sand fly. experiments were conducted to determine its potential as a n ...201323697770
geographical distribution of leishmania species of human cutaneous leishmaniasis in fars province, southern iran.the goal of this study was to know the identity of leishmania species responsible of cutaneous leishmaniasis (cl) in fars province, southern iran.201323682265
molecular characterization of calcineurin b from the non-virulent trypanosoma rangeli kinetoplastid indicates high gene conservation.calcineurin b, the regulatory subunit of calcineurin, a serine/threonine protein phosphatase, is highly conserved throughout the evolutionary scale including trypanosomatids such as trypanosoma cruzi, and leishmania major. thus, in these flagellates the protein is required for mammalian host cell invasion and virulence and stress responses. with the aim of determining the presence of calcineurin b in trypanosoma rangeli, a non-virulent trypanosome for mammals, the respective gene was amplified b ...201323677712
the interactions and essential effects of intrinsic insulin-like growth factor-i on leishmania (leishmania) major growth within macrophages.previously, we showed in leishmania infections that extrinsic insulin-like growth factor (igf)-i favored leishmania proliferation and leishmaniasis development. in this study, the interaction of intrinsically expressed igf-i and leishmania (leishmania) major in macrophages was addressed, and a key finding was the observation, using confocal microscopy, of the co-localization of igf-i and parasites within macrophages. following stimulation with interferon-γ (ifn-γ), which is known to inhibit igf- ...201323668415
genomic analysis of sequence-dependent dna curvature in leishmania.leishmania major is a flagellated protozoan parasite of medical importance. like other members of the trypanosomatidae family, it possesses unique mechanisms of gene expression such as constitutive polycistronic transcription of directional gene clusters, gene amplification, mrna trans-splicing, and extensive editing of mitochondrial transcripts. the molecular signals underlying most of these processes remain under investigation. in order to investigate the role of dna secondary structure signal ...201323646176
unusual presentation of disseminated cutaneous leishmaniasis due to leishmania major: case reports of four iranian patients.we report four disseminated cutaneous leishmaniasis(dcl) cases referred to leishmaniasis laboratory at the school of public health, tehran university of medical sciences with multiple nodular, ulcerative and crusted lesions extended on the face, trunk, and extremities. none of the patients had any complication and historical involvement in their immunological system conditions that suggest as the criteria for dcl. direct smears of ulcers were positive for leishmania parasite. the parasite was is ...201323608338
low diversity of leishmania parasites in sandflies and the absence of the great gerbil in foci of zoonotic cutaneous leishmaniasis in fars province, southern iran.fars province lies to the south of the main foci of zoonotic cutaneous leishmaniasis (zcl) caused by leishmania major in central and northern iran, and its zcl foci might have emerged more recently because of different transmission cycles. however, there have been limited studies of the parasites infecting the regional sandfly vectors.201323604865
galectin-3 negatively regulates the frequency and function of cd4(+) cd25(+) foxp3(+) regulatory t cells and influences the course of leishmania major infection.galectin-3, an endogenous glycan-binding protein, plays essential roles during microbial infection by modulating innate and adaptive immunity. however, the role of galectin-3 within the cd4(+) cd25(+) foxp3(+) t regulatory (treg ) cell compartment has not yet been explored. here, we found, in a model of leishmania major infection, that galectin-3 deficiency increases the frequency of peripheral treg cells both in draining lymph nodes (lns) and sites of infection. these observations correlated wi ...201323592449
a novel leishmania major amastigote assay in 96-well format for rapid drug screening and its use for discovery and evaluation of a new class of leishmanicidal quinolinium salts.in most laboratories, the screening for leishmanicidal compounds is carried out with leishmania promastigotes or axenic amastigotes. however, the best approach to identify leishmanicidal compounds is the use of amastigotes residing in macrophages. reporter gene-based assays are relatively new tools in the search for drugs against eucaryotic protozoa, permitting the development of faster, more automated assays. in this paper, we report on the establishment of a rapid screening assay in a 96-well ...201323587955
gene identification and comparative molecular modeling of a trypanosoma rangeli major surface protease.trypanosoma rangeli is a hemoflagellate parasite which is able to infect humans. distinct from trypanosoma cruzi, the causative agent of chagas disease, t. rangeli is non-pathogenic to the vertebrate host. the manner by which the t. rangeli interacts with the host is still unknown, but it certainly depends on the surface molecules. major surface proteins (msp) are gpi-anchored, zinc-dependent metalloproteases present in the surface of all trypanosomatids studied so far, which are implicated as v ...201323584556
isolation of new monoterpene coumarins from micromelum minutum leaves and their cytotoxic activity against leishmania major and cancer cells.on the basis of a leishmanicidal assay-guided isolation, two new monoterpene coumarins, minutin a and minutin b, were purified from micromelum minutum leaves together with four known coumarins, 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-2',3'-diol, 8-hydroxyisocapnolactone-2',3'-diol, 8-hydroxy-3″,4″-dihydrocapnolactone-2',3'-diol, and clauslactone e. among these compounds, minutin a, minutin b, 8-hydroxyisocapnolactone-2',3'-diol and clauslactone e showed a significant cytotoxic activity against ...201323561131
the transcriptome of leishmania major in the axenic promastigote stage: transcript annotation and relative expression levels by rna-seq.although the genome sequence of the protozoan parasite leishmania major was determined several years ago, the knowledge of its transcriptome was incomplete, both regarding the real number of genes and their primary structure.201323557257
a cell-surface phylome for african trypanosomes.the cell surface of trypanosoma brucei, like many protistan blood parasites, is crucial for mediating host-parasite interactions and is instrumental to the initiation, maintenance and severity of infection. previous comparisons with the related trypanosomatid parasites t. cruzi and leishmania major suggest that the cell-surface proteome of t. brucei is largely taxon-specific. here we compare genes predicted to encode cell surface proteins of t. brucei with those from two related african trypanos ...201323556014
il-17 mediates immunopathology in the absence of il-10 following leishmania major infection.leishmaniasis, resulting from infection with the protozoan parasite leishmania, consists of a wide spectrum of clinical manifestations, from healing cutaneous lesions to fatal visceral infections. a particularly severe form of cutaneous leishmaniasis, termed mucosal leishmaniasis, exhibits decreased il-10 levels and an exaggerated inflammatory response that perpetuates the disease. using a mouse model of leishmaniasis, we investigated what cytokines contribute to increased pathology when il-10-m ...201323555256
effect of il-22 on dna vaccine encoding lack gene of leishmania major in balb/c mice.in the present study, the effect of il-22 together with the plasmid encoding lack (leishmania homolog of receptors for activated c-kinase) gene of leishmania major on the trend of leishmaniasis in balb/c mice was evaluated. evaluation of the cellular and humoral immunity was performed by measurement of il-4 and ifn-γ, culture of splenocytes and mtt assay, and measurement of total igg, igg1, and igg2a in the control and immunized groups. clinical evaluations were also carried out by measurement o ...201323541883
evaluation of anti-leishmanial effects of killed leishmania vaccine with bcg adjuvant in balb/c mice infected with leishmania major mrho/ir/75/er.there are many strategies to control leishmaniasis, but majority of them are inadequate. killed leishmania vaccine (klv) has been applied for its immunogenicity in human and mouse model. bacillus calmette-guerin (bcg) as adjuvant is an immune-modulator inducing humoral and cellular immune responses during zoonotic cutaneous leishmaniasis (zcl). both klv and bcg have been applied for their immune responses in hosts for controlling leishmaniasis. in this study, klv and bcg were applied to inhibit ...201323539946
identification of leishmania species causing cutaneous leishmaniasis using random amplified polymorphic dna (rapd-pcr) in kharve, iran.leishmaniasis, especially cutaneous leishmaniasis, is considered an important health problem in many parts of iran including kharve, khorasan razavi province. cutaneous leishmaniasis is caused by various species of leishmania, each having a different secondary host. thus, identifying the parasites' specie is of paramount importance for containment strategy planning. the morphological differentiation of leishmania species is not possible, rendering the molecular methods as the sole means to this ...201326989711
comparison of th1 and th2 responses in non-healing and healing patients with cutaneous leishmaniasis.cutaneous leishmaniasis is an endemic disease in many regions of iran, including the city of mashhad. in recent years, some cases have not responded to glucantime, the usual treatment for this disease. the cellular immune response caused by t-helper type 1 (th1) cells has an important role in protection against leishmaniasis, and activation of the t-helper type 2 (th2) response causes progression of the disease. by analyzing these responses we hope to find a more effective treatment than that cu ...201326989708
in leishmania major-induced inflammation, interleukin-13 reduces hyperalgesia, down-regulates il-1β and up-regulates il-6 in an il-4 independent mechanism.infection with high dose leishmania major induces a sustained hyperalgesia in balb/c mice while low dose induces a short lived hyperalgesia both accompanied with the upregulation of il-1β and il-6. although il-13 was shown to reduce the high dose l. major hyperalgesia during the treatment period, this effect was accompanied by a significant decrease in the levels of il-1β and a significant increase in the levels of il-6 in the paws of mice even beyond this period. those results suggest that il-1 ...201323499883
attraction of phlebotomine sand flies to baited and non-baited horizontal surfaces.female phlebotomine sand flies (diptera: psychodidae) transmit leishmaniasis as they engorge on vertebrate blood required for egg production. phlebotomus (phlebotomus) papatasi (scopoli, 1786), the vector of leishmania major (yakimoff & schokhor, 1914), the causative agent of cutaneous leishmaniasis (cl) were not attracted to large horizontal sticky traps (lhsts) unless these were baited with co2 derived from dry ice or from fermenting sugar/yeast mixture (sym). attraction of p. papatasi males b ...201323499863
molecular characterization of leishmania infection in sand flies from al-madinah al-munawarah province, western saudi arabia.cutaneous leishmaniasis (cl) is caused by various species of the genus leishmania. the disease is considered a major health problem in different areas of saudi arabia including al-madinah al-munawarah province. we aimed to identify leishmania species isolated from sand fly vectors by molecular analysis. sand fly sampling was carried out from may 2010 to october 2010 in province of al-madinah al-munawarah from four different localities. female sand flies collected were subjected to dna extraction ...201323474205
in vitro analysis regarding the safety of components used in a film-based therapeutic system loaded with meglumine antimoniate and its activity toward leishmania major experimental infections: a preliminary study.owing to its biocompatibility properties and its ability to promote the scar healing process, chitosan is employed in tissue engineering for the manufacture of formulations. to control the characteristic skin ulcers of cutaneous leishmaniasis (cl), the use of a biopolymeric system that favors the scar healing process and releases an active agent such as meglumine antimoniate may be a better option. for these reasons, here we analyzed the cytotoxic capabilities of excipients [medium molecular wei ...201323473403
an epidemiological study of cutaneous leishmaniasis in al-jabal al-gharbi, libya.cutaneous leishmaniasis (cl) is an endemic parasitic infection in the mediterranean region, including libya and its al-jabal al-gharbi province. we aimed at studying the occupational relevance as well as other epidemiological aspects of cl. we investigated 140 cl cases who attended at gharyan outpatient polyclinic during a period of 6 months in 2009. cl infection was clinically diagnosed and confirmed by demonstration of leishmania parasites on smears from lesions. our findings showed that males ...201323467624
the route of leishmania tropica infection determines disease outcome and protection against leishmania major in balb/c mice.leishmania tropica is one of the causative agents of leishmaniasis in humans. routes of infection have been reported to be an important variable for some species of leishmania parasites. the role of this variable is not clear for l. tropica infection. the aim of this study was to explore the effects of route of l. tropica infection on the disease outcome and immunologic parameters in balb/c mice. two routes were used; subcutaneous in the footpad and intradermal in the ear. mice were challenged b ...201323467583
arginine transport is impaired in c57bl/6 mouse macrophages as a result of a deletion in the promoter of slc7a2 (cat2), and susceptibility to leishmania infection is reduced.host genetic factors play a crucial role in immune response. to determine whether the differences between c57bl/6 and balb-c mice are due only to the production of cytokines by t-helper 1 cells or t-helper 2 cells, we obtained bone marrow-derived macrophages from both strains and incubated them with these cytokines. although the induction of nos2 and arg1 was similar in the 2 strains, infectivity to leishmania major differed, as did macrophage uptake of arginine, which was higher in balb-c macro ...201323460752
molecular dynamics reveal binding mode of glutathionylspermidine by trypanothione synthetase.the trypanothione synthetase (trys) catalyses the two-step biosynthesis of trypanothione from spermidine and glutathione and is an attractive new drug target for the development of trypanocidal and antileishmanial drugs, especially since the structural information of trys from leishmania major has become available. unfortunately, the trys structure was solved without any of the substrates and lacks loop regions that are mechanistically important. this contribution describes docking and molecular ...201323451087
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