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the effect of aqueous garlic extract on interleukin-12 and 10 levels in leishmania major (mrho/ir/75/er) infected macrophages.the aim of the present study was to investigate the immunomodulation effects of aqueous garlic extract (age) in the cultured macrophages infected by leishmania major.201123113109
vectorial competence of phlebotomus papatasi (diptera: psychodidae) to transmit two old world leishmania species: leishmania major and l. tropica.the vectorial competence of phlebotomus papatasi for two old world leishmania species, l. major & l. tropica was investigated. phlebotomus papatasi originally collected from suez governorate, were membrane fed on homogenized hamster's lesion infected with l. major, mhom/eg/06/rtc-63, and l. tropica, mger/eg/06/rtc-74 identified from patients with suspected cl in northern sinai, egypt. fed flies were dissected at different time intervals and examined microscopically to determine the infection rat ...201122435150
the effect of garlic extract on expression of infγ and inos genes in macrophages infected with leishmania major.the study was aimed to show the effect of molecular mechanism of aqueous garlic extract (age) on expression of ifnγ and inos genes in leishmania major.201122347300
immunotherapy using autoclaved l. major antigens and m. vaccae with meglumine antimoniate, for the treatment of experimental canine visceral leishmaniasis.to evaluate immunotherapy against canine visceral leishmaniasis, leishmania major antigen and heat-killed mycobacterium vaccae (srl172) were used as stimulators of immune defense mechanisms and the results were compared with standard chemotherapy meglumine antimoniate.201122347294
in vitro and in vivo activities of peganum harmala extract against leishmania major.in vitro and in vivo antileishmanial activities of crude hydroalcoholic extract of peganum harmala seeds were investigated against leishmania major.201122279479
Leishmania major protein disulfide isomerase as a drug target : Enzymatic and functional characterization.Leishmaniasis is a major health problem worldwide and tools available for their control are limited. Effective vaccines are still lacking, drugs are toxic and expensive, and parasites develop resistance to chemotherapy. In this context, new antimicrobials are urgently needed to control the disease in both human and animal. Here, we report the enzymatic and functional characterization of a Leishmania virulence factor, Leishmania major Protein disulfide isomerase (LmPDI) that could constitute a po ...201122160278
leishmania major infection among psammomys obesus and meriones shawi: reservoirs of zoonotic cutaneous leishmaniasis in sidi bouzid(central tunisia).a study was undertaken between november 2008 and march 2010, in the focus of cutaneous leishmaniasis of central tunisia, to evaluate the role of psammomys obesus (n=472) and meriones shawi (n=167) as reservoir hosts for leishmania major infection. prevalence of l. major infection was 7% versus 5% for culture (p=not signifiant [ns]), 19% versus 16% for direct examination of smears (p=ns), and 20% versus 33% (p=ns) for indirect fluorescent antibody test among p. obesus and m. shawi, respectively. ...201121919726
Functional expression of parasite drug targets and their human orthologs in yeast.The exacting nutritional requirements and complicated life cycles of parasites mean that they are not always amenable to high-throughput drug screening using automated procedures. Therefore, we have engineered the yeast Saccharomyces cerevisiae to act as a surrogate for expressing anti-parasitic targets from a range of biomedically important pathogens, to facilitate the rapid identification of new therapeutic agents.201121991399
[Spread of Leishmania major to the north of Algeria.]Since a long time, Leishmania major and L. infantum foci in Algeria were geographically separated by the mountains of the Tell Atlas which represent a natural barrier. Recently, a new focus of cutaneous leishmaniasis (CL) has emerged in the village of El M'hir, located on the north side of the chain of the Tell Atlas, in the basin of the Soummam. During the period 2004-2010, 152 CL cases have been registered and 12 isolates were obtained from patients who declared never having been outside the v ...201122170408
cd40 and tumour necrosis factor-α co-operate to up-regulate inducuble nitric oxide synthase expression in macrophages.regulation of inducible nitric oxide synthase (nos2) expression is important given the role of this enzyme in inflammation, control of infections and immune regulation. in contrast to tumour necrosis factor-α (tnf-α) alone or cd40 stimulation alone, simultaneous stimulation of mouse macrophages through cd40 ligation and tnf-α led to up-regulation of nos2 and nitric oxide production. this response was of functional relevance because cd40/tnf-α-stimulated macrophages acquired nitric oxide-dependen ...201122044243
Isolation and detection of Leishmania species among naturally infected Rhombomis opimus, a reservoir host of zoonotic cutaneous leishmaniasis in Turkemen Sahara, North East of Iran.In Iran, three species of Leishmania have been incriminated as the causative agents of human leishmaniasis, Leishmania (L.) major, Leishmania tropica, and Leishmania infantum.Rhombomis opimus have been incriminated as a principal reservoirs of the parasitic protozoan Leishmania major, the causative agent of rural zoonotic cutaneous leishmaniasis (ZCL) in Iran. Rodents captured and examined to find Leishmania species using conventional methods including direct impression smear and microscopic obs ...201121945269
Morphological events during the cell cycle of Leishmania major.The morphological events involved in the Leishmania major promastigote cell cycle have been investigated in order to provide a detailed description of the chronological processes by which the parasite replicates its set of single-copy organelles and generates a daughter cell. Immunofluorescence labeling of ß-tubulin was used to follow the dynamics of the subcellular cytoskeleton and to monitor the division of the nucleus via visualization of the mitotic spindle, while RAB11 was found to be a use ...201121926331
New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities.Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain ...201122072992
First report of natural infection of least weasel (Mustela nivalis Linnaeus, 1776) with Leishmania major in Tunisia.Zoonotic cutaneous leishmaniasis, caused by Leishmania major (L. major), is endemic in Tunisia. Several rodents have been identified as reservoir hosts of parasites. This study reports, for the first time, the natural infection with L. major zymodeme MON-25 in a specimen of least weasel: Mustela nivalis Linnaeus, 1776 (M. nivalis) collected in Sidi Bouzid. This finding justifies further research on larger samples of this animal to verify its role as a potential reservoir host for cutaneous leish ...201121867414
interleukin-13 reduces hyperalgesia and the level of interleukin-1ß in balb/c mice infected with leishmania major with an up-regulation of interleukin-6.the anti-inflammatory cytokines interleukin-10 (il-10) and interleukin-13 (il-13) were shown to reduce hyperalgesia in some models such as rats exposed to uv rays. in addition, il-10 was also shown to reduce hyperalgesia in high dose of leishmania major-induced inflammation in balb/c mice accompanied by a significant decrease in the levels of interleukin-1ß (il-1ß) in the paws of infected mice, while no effect on the levels of il-6 was observed. in this study, we injected balb/c mice with a high ...201121402416
cysteine proteinase type i, encapsulated in solid lipid nanoparticles induces substantial protection against leishmania major infection in c57bl/6 mice.appropriate adjuvant, proper antigen(s) and a suitable formulation are required to develop stable, safe and immunogenic vaccines. leishmanial cysteine proteinase type i (cpb) is a promising vaccine candidate; nevertheless, it requires a delivery system to induce a potent immune response. herein, solid lipid nanoparticles (sln) have been applied for cpb [with and without c-terminal extension (cte)] formulation to utilize as a vaccine against leishmania major infection in c57bl/6 mice. therefore, ...201121410716
an overview of a diagnostic and epidemiologic reappraisal of cutaneous leishmaniasis in iran.cutaneous leishmaniasis (cl) is a widespread tropical infection which has a high incidence rate in iran. leishmania tropica, the causative agent of anthroponotic cutaneous leishmaniasis (acl), and leishmania major, which causes zoonotic cutaneous leishmaniasis (zcl), are endemic in various parts of iran with a high incidence rate. the aim of this study was to evaluate the reappraisal of the diagnosis and epidemiology of cl in iran, by different clinical, parasitological and molecular assays amon ...201121412584
genotypic characterization of cutaneous leishmaniasis at al baha and al qasim provinces (saudi arabia).fifty samples of skin ulcers were collected from the western region of saudi arabia kingdom (al baha and al qasim) to study genotypic characterization of cutaneous leishmaniasis in this area. thirty-six samples were recorded as leishmania isolates. the same isolates were subsequently tested with fingerprinting with single arbitrary primers. the primers used derived from the core sequence of the phage m13, and the repeat sequences (gtg)5 and (gaca)4. the 36 isolates were all identified as leishma ...201121417928
isolation and characterization of functional leishmania major virulence factor udp-galactopyranose mutase.human parasitic pathogens of the genus leishmania are the causative agents of cutaneous, mucocutaneous, and visceral leishmaniasis. currently, there are millions of people infected with these diseases and over 50,000 deaths occur annually. recently, it was shown that the flavin-dependent enzyme udp-galactopyranose mutase (ugm) is a virulence factor in leishmania major. ugm catalyzes the conversion of udp-galactopyranose to udp-galactofuranose. the product, udp-galactofuranose, is the only source ...201121419104
resolving the question of trypanosome monophyly: a comparative genomics approach using whole genome data sets with low taxon sampling.since the first attempts to classify the evolutionary history of trypanosomes, there have been conflicting reports regarding their true phylogenetic relationships and, in particular, their relationships with other vertebrate trypanosomatids, e.g. leishmania sp., as well as with the many insect parasitising trypanosomatids. perhaps the issue that has provided most debate is that concerning the monophyly (or otherwise) of genus trypanosoma and, even with the advent of molecular methods, the findin ...201121419879
the double-length tyrosyl-trna synthetase from the eukaryote leishmania major forms an intrinsically asymmetric pseudo-dimer.the single tyrosyl-trna synthetase (tyrrs) gene in trypanosomatid genomes codes for a protein that is twice the length of tyrrs from virtually all other organisms. each half of the double-length tyrrs contains a catalytic domain and an anticodon-binding domain; however, the two halves retain only 17% sequence identity to each other. the structural and functional consequences of this duplication and divergence are unclear. tyrrs normally forms a homodimer in which the active site of one monomer p ...201121420975
immunotherapy with imiquimod increases the efficacy of glucantime therapy of leishmania major infection.leishmaniasis is a complex disease which presents as visceral, cutaneous and mucocutaneous forms. the current treatment options for this infection are very limited and the immunological state of the host appears to play an important role in the efficacy of the treatment. immunostimulation through immune response activating agents such as imiquimod is another rational approach for this purpose.201121427495
a high-throughput turbidometric assay for screening inhibitors of leishmania major protein disulfide isomerase.the use of a high-throughput technique to perform a pilot screen for leishmania major protein disulfide isomerase (lmpdi) inhibitors identification is reported. in eukaryotic cells, protein disulfide isomerase (pdi) plays a crucial role in protein folding by catalyzing the rearrangement of disulfide bonds in substrate proteins following their synthesis. lmpdi displays similar domain structure organization and functional properties to other pdi family members and is involved in leishmania virulen ...201121441416
h-ras and n-ras are dispensable for t-cell development and activation but critical for protective th1 immunity.the small guanine nucleotide binding proteins of the ras family, including in mammals the highly homologous h-ras, n-ras, and k-ras isoforms, are rapidly activated on ligation of the t-cell antigen receptor (tcr), but whether each isoform plays specific roles in t cells is largely unknown. here, we show, with the use of mice specifically lacking h-ras or n-ras, that these isoforms are dispensable for thymocyte development and mature t-cell activation. by contrast, cd4? t cells from ras-deficient ...201121444916
the crystal structure of the leishmania major deoxyuridine triphosphate nucleotidohydrolase in complex with nucleotide analogues, dump, and deoxyuridine.members of the leishmania genus are the causative agents of the life-threatening disease leishmaniasis. new drugs are being sought due to increasing resistance and adverse side effects with current treatments. the knowledge that dutpase is an essential enzyme and that the all a-helical dimeric kinetoplastid dutpases have completely different structures compared with the trimeric ß-sheet type dutpase possessed by most organisms, including humans, make the dimeric enzymes attractive drug targets. ...201121454646
miltefosine-induced apoptotic cell death on leishmania major and l. tropica strains.the aim of this study was to assess the cytotoxic effects of various concentrations of miltefosine on leishmania major (mrho/ir/75/er) and l. tropica (mhom/ir/02/mash10) promastigotes and to observe the programmed cell death features. the colorimetric mtt assay was used to find l. major and l. tropica viability and the obtained results were expressed as 50% inhibitory concentration (ic50). also, 50% effective doses (ed50) for l. major and l. tropica amastigotes were also determined. annexin-v fl ...201121461264
crystal structure of the leishmania major mix protein: a scaffold protein that mediates protein-protein interactions.infection by leishmania and trypanosoma causes severe disease and can be fatal. the reduced effectiveness of current treatments is largely due to drug resistance, hence the urgent need to develop new drugs, preferably against novel targets. we have recently identified a mitochondrial membrane-anchored protein, designated mix, which occurs exclusively in these parasites and is essential for virulence. we have determined the crystal structure of leishmania major mix to a resolution of 2.4 å. mix f ...201121465610
c-rel promotes type 1 and type 17 immune responses during leishmania major infection.recent studies demonstrated the crucial role of c-rel in directing treg lineage commitment and its involvement in t helper 1 (th1) cell-mediated autoimmune inflammation. we thus wondered whether these opposite functions of c-rel influence the course of antiparasitic immune responses against leishmania major, an accepted model for the impact of t-cell subsets on disease outcome. here we show that c-rel-deficient (rel(-/-) ) mice infected with l. major displayed dramatically exacerbated leishmania ...201121469108
cd40-modulated dual-specificity phosphatases mapk phosphatase (mkp)-1 and mkp-3 reciprocally regulate leishmania major infection.the macrophage-expressed cd40 regulates immune responses to leishmania major infection by reciprocal signaling through p38 mapk and erk1/2. cd40-induced il-10 or il-12 plays crucial roles in the promotion or protection from l. major infection, respectively. because p38 mapk and erk1/2 are dephosphorylated by dual-specificity mapk phosphatases (mkps), we tested the role of cd40 in the regulation of mkps in l. major infection. mkp-1 expression and activity increased whereas mkp-3 expression and ac ...201121471446
il-2 limits il-12 enhanced lymphocyte proliferation during leishmania amazonensis infection.c3h mice infected with leishmania amazonensis develop persistent, localized lesions with high parasite loads. during infection, memory/effector cd44(hi)cd4(+) t cells proliferate and produce il-2, but do not polarize to a known effector phenotype. previous studies have demonstrated il-12 is insufficient to skew these antigen-responsive t cells to a functional th1 response. to determine the mechanism of this il-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. memory/ ...201121481338
high throughput screens yield small molecule inhibitors of leishmania crk3:cyc6 cyclin-dependent kinase.leishmania species are parasitic protozoa that have a tightly controlled cell cycle, regulated by cyclin-dependent kinases (cdks). cdc2-related kinase 3 (crk3), an essential cdk in leishmania and functional orthologue of human cdk1, can form an active protein kinase complex with leishmania cyclins cyca and cyc6. here we describe the identification and synthesis of specific small molecule inhibitors of bacterially expressed leishmania crk3:cyc6 using a high throughput screening assay and iterativ ...201121483720
mast cells promote th1 and th17 responses by modulating dendritic cell maturation and function.mast cells (mcs) play an important role in the regulation of protective adaptive immune responses against pathogens. however, it is still unclear whether mcs promote such host defense responses via direct effects on t cells or rather by modifying the functions of antigen-presenting cells. to identify the underlying mechanisms of the immunoregulatory capacity of mcs, we investigated the impact of mcs on dendritic cell (dc) maturation and function. we found that murine peritoneal mcs underwent dir ...201121491417
leishmania repression of host translation through mtor cleavage is required for parasite survival and infection.the protozoan parasite leishmania alters the activity of its host cell, the macrophage. however, little is known about the effect of leishmania infection on host protein synthesis. here, we show that the leishmania protease gp63 cleaves the mammalian/mechanistic target of rapamycin (mtor), a serine/threonine kinase that regulates the translational repressor 4e-bp1. mtor cleavage results in the inhibition of mtor complex 1 (mtorc1) and concomitant activation of 4e-bp1 to promote leishmania prolif ...201121501832
synthesis and antileishmanial activity of novel 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituents.in order to optimize the antileishmanial activity of piperazinyl-linked 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazoles, we synthesized a series of 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituent as scaffold found in pentamidine related antiprotozoals. the structure of target compounds was confirmed by ir, (1)h nmr, (13)c nmr and mass spectral data. all compounds were tested for in vitro activity against the promastigote and amastigote forms of leishmania major. ...201121501907
an evolutionary analysis of trypanosomatid gp63 proteases.the trypanosomatid gp63 proteases are known to be involved in parasite-host interaction and exhibit strong sequence and structural similarities to those of their hosts and insect vectors. based on genome sequences of the three trypanosomatids, trypanosoma brucei, trypanosoma cruzi, and leishmania spp., we annotated all their gp63 proteases and divided highly duplicated t. cruzi gp63 proteases into four novel groups according to sequence features. in leishmania spp., we studied the evolutionary d ...201121503641
a role for leukocyte-derived il-1ra in dc homeostasis revealed by increased susceptibility of il-1ra-deficient mice to cutaneous leishmaniasis.dendritic cell (dc)-derived il-1α/β plays a critical role in the induction of t helper type 1 (th1)-dependent immunity against leishmania. dcs from susceptible balb/c mice produce less il-1α/β when compared with resistant c57bl/6 mice, contributing to aberrant th2 development and ultimate death of infected mice. we have extended our studies of the role of il-1 in leishmaniasis using il-1ra(-/-) balb/c mice that are characterized by upregulated il-1 receptor signaling. unexpectedly, infection of ...201121525884
genetic exchange and emergence of novel strains in directly transmitted trypanosomatids.the breeding structure of protozoan infections, i.e. whether and how frequently parasites exchange genes ("sexual reproduction"), is a crucially important parameter for many important questions; it also matters for how new virulent strains might emerge. whether protozoan parasites are clonal or sexual is therefore a hotly debated issue. for trypanosomatids, few experimental tests of breeding structure exist to date and are limited to the vector-borne human diseases trypanosoma brucei, trypanosom ...201121252000
direct diagnosis of leishmania species on serosity materials punctured from cutaneous leishmaniasis patients using pcr-rflp.this study was aimed at identifying the leishmania species using serosity materials punctured from skin lesions of cutaneous leishmaniasis (cl) patients by using internal transcribed spacer1 (its1) polymerase chain reaction (pcr)-restriction fragment length polymorphism (rflp). we used the pcr-rflp on 60 parasitological confirmed cl patients who referred to leishmaniasis laboratory from the school of public health, tehran university of medical sciences. the pcr-rflp could correctly detect 51 lei ...201121254238
leishmanicidal activity of synthetic antimicrobial peptides in an infection model with human dendritic cells.different species of leishmania are responsible for cutaneous, mucocutaneous or visceral leishmaniasis infections in millions of people around the world [14]. the adverse reactions caused by antileishmanial drugs, emergence of resistance and lack of a vaccine have motivated the search for new therapeutic options to control this disease. different sources of antimicrobial molecules are under study as antileishmanial agents, including peptides with antimicrobial and/or immunomodulatory activity, w ...201121262294
distribution of leishmania major zymodemes in relation to populations of phlebotomus papatasi sand flies.phlebotomus papatasi (scopoli) (diptera: psychodidae) is the main vector of leishmania major yakimoff & schokhor (kinetoplastida: trypanosomatidae), the causative agent of zoonotic cutaneous leishmaniasis in the old world. multilocus enzyme electrophoresis (mlee) was extensively used to type different l. major stocks all over the world. multilocus microsatellite typing (mlmt) has been recently used to investigate p. papatasi sand flies at population and subpopulation levels. in this article, the ...201121266079
hiv proteinase inhibitors target the ddi1-like protein of leishmania parasites.hiv proteinase inhibitors reduce the levels of leishmania parasites in vivo and in vitro, but their biochemical target is unknown. we have identified an ortholog of the yeast ddi1 protein as the only member of the aspartic proteinase family in leishmania parasites, and in this study we investigate this protein as a potential target for the drugs. to date, no enzyme assay has been developed for the ddi1 proteins, but saccharomyces cerevisiae lacking the ddi1 gene secrete high levels of protein in ...201121266539
exploring leishmania major inositol phosphorylceramide synthase (lmjipcs): insights into the ceramide binding domain.the synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. these have been assayed against the parasitic protozoan enzyme lmjipcs. these studies showed that whilst the c-3 hydroxyl group was not essential for turnover it provided enhanced affinity. reflecting the membrane bound nature of the enzyme a long (c(13)) hydrocarbon ceramide tail was necessary for both high affinity and turnover. whilst the n-acyl chain ...201121267500
leishmania major: protective capacity of dna vaccine using amastin fused to hsv-1 vp22 and egfp in balb/c mice model.an intercellular spreading strategy using herpes simplex virus type 1 (hsv-1) vp22 protein is employed to enhance dna vaccine potency of leishmania major amastin antigen in balb/c mice model. we evaluated the immunogenicity and protective efficacy of plasmid dna vaccines encoding amastin-enhanced green fluorescent protein (egfp) and vp22-amastin-egfp. optimal cell-mediated immune responses were observed in balb/c mice immunized with vp22-amastin-egfp as assessed by cytokine gene expression analy ...201121276444
characterization of the colloidal properties, in vitro antifungal activity, antileishmanial activity and toxicity in mice of a di-stigma-steryl-hemi-succinoyl-glycero-phosphocholine liposome-intercalated amphotericin b.1,2-di-stigma-steryl-hemi-succinoyl-sn-glycero-3-phosphocholine (dshemspc) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. since amphotericin b (amb) interacts with sterols, we postulated that dshemspc could be used in amb liposome formulations. thirty-two dshemspc-amb formulations were prepared using various mole ratios of dshemspc, phosphatidylcholine and phosphatidylglycerol at different ph ...201121277963
leishmania major attenuates host immunity by stimulating local indoleamine 2,3-dioxygenase expression.inflammation stimulates immunity but can create immune privilege in some settings. here, we show that cutaneous leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (ido) in local lymph nodes. induced ido attenuated the t cell stimulatory functions of dendritic cells and suppressed local t cell responses to exogenous and nominal parasite antigens. ido ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition ...201121282196
pkcd regulates il-12p40/p70 production by macrophages and dendritic cells, driving a type 1 healer phenotype in cutaneous leishmaniasis.the protein kinase c (pkc) family is involved in the regulation of many intracellular signalling pathways. here, we report that the pkcd isoform regulates il-12p40/p70 production in macrophages and dc and that pkcd deficiency in mice transforms the 129/sv healer to a non-healer strain during cutaneous leishmaniasis. leishmania major-infected pkcd(-/-) 129/sv mice developed a rapid increase in footpad swelling and parasite burden with disease progression, leading to necrosis and ulceration simila ...201121287553
the hus1 homologue of leishmania major encodes a nuclear protein that participates in dna damage response.the protozoan parasite leishmania presents a dynamic and plastic genome in which gene amplification and chromosome translocations are common phenomena. such plasticity hints at the necessity of dependable genome maintenance pathways. eukaryotic cells have evolved checkpoint control systems that recognize altered dna structures and halt cell cycle progression allowing dna repair to take place. in these cells, the pcna-related heterotrimeric complex formed by the proteins hus1, rad9, and rad1 is k ...201121291918
cell cycle arrest evidence, parasiticidal and bactericidal properties induced by l-amino acid oxidase from bothrops atrox snake venom.the present article describes an l-amino acid oxidase from bothrops atrox snake venom as with antiprotozoal activities in trypanosoma cruzi and in different species of leishmania (leishmania braziliensis, leishmania donovani and leishmania major). leishmanicidal effects were inhibited by catalase, suggesting that they are mediated by h(2)o(2) production. leishmania spp. cause a spectrum of diseases, ranging from self-healing ulcers to disseminated and often fatal infections, depending on the spe ...201121300133
the magnitude of cd4(+) t-cell activation rather than tcr diversity determines the outcome of leishmania infection in mice.cd4(+) t cells play a critical role in determining the disease outcome in murine cutaneous leishmaniasis, and selective usage of t-cell receptor (tcr) is implied in promoting leishmania major infection. however, little information is available on tcr usage in leishmania-specific, ifn-?-producing cd4(+) t cells. in this study, we investigated the tcr diversity and activation of cd4(+) t cells in a nonhealing model associated with l. amazonensis (la) infection and a self-healing model associated w ...201121306400
the protective effect against leishmania infection conferred by sand fly bites is limited to short-term exposure.under laboratory conditions, hosts exposed twice to sand fly saliva are protected against severe leishmaniasis. however, people in endemic areas are exposed to the vector over a long term and may experience sand fly-free periods. therefore, we exposed mice long- or short-term to phlebotomus duboscqi bites, followed by leishmania major infection either immediately or after a sand fly-free period. we showed that protection against leishmaniasis is limited to short-term exposure to sand flies immed ...201121310158
potency, efficacy and durability of dna/dna, dna/protein and protein/protein based vaccination using gp63 against leishmania donovani in balb/c mice.visceral leishmaniasis (vl) caused by an intracellular protozoan parasite leishmania, is fatal in the absence of treatment. at present there are no effective vaccines against any form of leishmaniasis. here, we evaluate the potency, efficacy and durability of dna/dna, dna-prime/protein-boost, and protein/protein based vaccination against vl in a susceptible murine model.201121311597
superior efficacy of oral fluconazole 400 mg daily versus oral fluconazole 200 mg daily in the treatment of cutaneous leishmania major infection: a randomized clinical trial. 201121315963
genetic and biochemical analysis of protozoal polyamine transporters.polyamines are aliphatic polycations that function in key cellular processes such as growth, differentiation, and macromolecular biosynthesis. intracellular polyamines pools are maintained from de novo synthesis and from transport of polyamines from the extracellular milieu. this acquisition of exogenous polyamines is mediated by cell surface transporter proteins. protozoan parasites are the etiologic agents of a plethora of devastating and often fatal diseases in humans and their domestic anima ...201121318882
calcineurin is required for leishmania major stress response pathways and for virulence in the mammalian host.leishmania parasites must adapt to elevated temperatures and other environmental stresses during infection of their mammalian hosts. how these environmental cues are sensed is poorly understood. in this study we show that calcium uptake is required for parasite thermotolerance at 34-37°c. to identify potential downstream targets of calcium influx, a leishmania major mutant lacking the essential regulatory subunit (cnb) of the ca(2+) /calmodulin-dependent serine/threonine-specific phosphatase, ca ...201121320183
identification of the meiotic life cycle stage of trypanosoma brucei in the tsetse fly.elucidating the mechanism of genetic exchange is fundamental for understanding how genes for such traits as virulence, disease phenotype, and drug resistance are transferred between pathogen strains. genetic exchange occurs in the parasitic protists trypanosoma brucei, t. cruzi, and leishmania major, but the precise cellular mechanisms are unknown, because the process has not been observed directly. here we exploit the identification of homologs of meiotic genes in the t. brucei genome and demon ...201121321215
endoplasmic reticulum stress-induced apoptosis in leishmania through ca2+-dependent and caspase-independent mechanism.numerous reports have shown that mitochondrial dysfunctions play a major role in apoptosis of leishmania parasites, but the endoplasmic reticulum (er) stress-induced apoptosis in leishmania remains largely unknown. in this study, we investigate er stress-induced apoptotic pathways in leishmania major using tunicamycin as an er stress inducer. er stress activates the expression of er-localized chaperone protein bip/grp78 (binding protein/identical to the 78-kda glucose-regulated protein) with con ...201121330370
cell biology and immunology of leishmania.more than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan leishmania major was associated with the development of t-helper 1 (th1)- and th2-dominated immune responses, respectively. this infectious disease model was later used to identify and assess the role of key factors, such as interleukin-12 (il-12) and il-4, in th1 and th2 maturation. while infection by leishmania remains a popular model for immunologists ...201121349100
synthesis and antileishmanial activity of 5-(5-nitroaryl)-2-substituted-thio-1,3,4-thiadiazoles.a series of novel 2-substituted-thio-1,3,4-thiadiazoles bearing a 5-nitroaryl moiety including nitrofuran, nitrothiophene or nitroimidazole at the 5-position and a bulky residue attached to the 2-position of the thiadiazole ring were synthesised as potential antileishmanial agents. the target compounds were evaluated against the promastigote form of leishmania major using the tetrazolium bromide salt (mtt) colorimetric assay. all test compounds exhibited high activity against l. major promastigo ...201120578974
a combined luciferase imaging and reverse transcription polymerase chain reaction assay for the study of leishmania amastigote burden and correlated mouse tissue transcript fluctuations.laboratory mice display features of bona fide hosts for parasites such as leishmania major and leishmania donovani. characterizing the amastigote population size fluctuations and the mouse transcript abundance accounting for these fluctuations demands the capacity to record in real time and integrate quantitative multiparametric datasets from the host tissues where these processes occur. to this end, two technologies, luciferase-expressing leishmania imaging and a very sensitive quantitative ana ...201120846338
increased glycolytic atp synthesis is associated with tafenoquine resistance in leishmania major.tafenoquine (tfq), an 8-aminoquinoline used to treat and prevent plasmodium infections, could represent an alternative therapy for leishmaniasis. indeed, tfq has shown significant leishmanicidal activity both in vitro and in vivo, where it targets leishmania mitochondria and activates a final apoptosis-like process. in order not to jeopardize the life span of this potential antileishmania drug, it is important to determine the likelihood that leishmania will develop resistance to tfq and the mec ...201121199921
efficient control of leishmania and strongyloides despite partial suppression of nematode-induced th2 response in co-infected mice.endemic regions for the pathogenic nematode strongyloides and parasitic protist leishmania overlap and therefore co-infections with both parasites frequently occur. as the th2 and th1 immune responses necessary to efficiently control strongyloides and leishmania infections are known to counterregulate each other, we analysed the outcome of co-infection in the murine system. here, we show that leishmania major-specific th1 responses partially suppressed the nematode-induced th2 response in co-inf ...201121204851
immunomodulatory properties of borage (echium amoenum) on balb/c mice infected with leishmania major.leishmaniasis is caused by parasitic protozoa transmitted by the bite of a female sand fly and is currently endemic in 88 countries. balb/c mice are highly susceptible to the infection with the parasite leishmania major, and this susceptibility has been attributed, in part, to the expansion of th2 cells, production of their cytokines, and downregulation of th1 cytokine, interferon gamma (ifn-γ). in this report, we used both aqueous and alcoholic extracts of iranian borage (echium amoenum fisch & ...201121225450
dissecting the metabolic roles of pteridine reductase 1 in trypanosoma brucei and leishmania major.leishmania parasites are pteridine auxotrophs that use an nadph-dependent pteridine reductase 1 (ptr1) and nadh-dependent quinonoid dihydropteridine reductase (qdpr) to salvage and maintain intracellular pools of tetrahydrobiopterin (h(4)b). however, the african trypanosome lacks a credible candidate qdpr in its genome despite maintaining apparent qdpr activity. here we provide evidence that the nadh-dependent activity previously reported by others is an assay artifact. using an hplc-based enzym ...201121239486
biased cellular locations of tandem repeat antigens in african trypanosomes.trypanosoma brucei subspecies cause african trypanosomiasis in humans and animals. these parasites possess genes encoding proteins with large tandem repeat (tr) domains as do the other trypanosomatid parasites. we have previously demonstrated that tr protein of leishmania infantum and trypanosoma cruzi are often targets of b-cell responses. however, african trypanosomes are susceptible to antibody-mediated immunity, and it may be detrimental for the parasites to have such b-cell antigens on the ...201121241659
phlebotomus sergenti (parrot, 1917) identified as leishmania killicki host in gharda+»a, south algeria.since 2005, an outbreak of human cutaneous leishmaniasis (cl) in gharda+»a, south algeria, was studied and one output of these investigations was the identification of two leishmania species, leishmania major and leishmania killicki, as the cl causative agents. in the present study, we were curious to focus on sand fly fauna present in this area and detection of leishmania-positive sand fly females. sand flies (3717) were collected during two seasons using sticky papers and cdc light traps in ur ...201121382502
amine-reactive ova multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for gcp-2 in l. major infection.anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. we here describe a two-step procedure based on the use of ova multimers purified by size exclusion chromatography after incubation with glutaraldehyde at ph 6. when such polymers are incubated with a target protein at ph 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. the ...201121385949
vaccination with photodynamic therapy-treated macrophages induces highly suppressive t-regulatory cells.the present study explores whether photodynamic therapy (pdt)-induced apoptosis can increase the number of tolerogenic regulatory t cells (treg) and limit collateral tissue damage.201121392113
aberrant il-4 production by socs3-over-expressing t cells during infection with leishmania major exacerbates disease manifestations.suppressor of cytokine signaling (socs) 3 is a major negative feedback regulator of signal transducer and activator of transcription 3-activating cytokines. studies using t-cell-specific socs3-deficient mice indicate that the absence of socs3 in t cells results in exacerbation of disease progression after infection by leishmania major due to skewing of the t(h)3 cell phenotype accompanied by hyper-production of il-10 and transforming growth factor +¦ (tgf-+¦). here we show that transgenic mice o ...201121393635
expression of a leishmaniadonovani nucleotide sugar transporter in leishmaniamajor enhances survival in visceral organs.leishmania donovani and leishmaniainfantum infections cause fatal visceral leishmaniasis, and leishmaniamajor causes self healing cutaneous lesions. it is poorly understood what genetic differences between these leishmania species are responsible for the different pathologies of infection. to investigate whether l.donovani species-specific genes are involved in visceral leishmania infection, we have examined a l.donovani species-specific gene ld1590 (ortholog of linj15_v3.0900) that is a pseudog ...201121978449
therapeutic enhancement of protective immunity during experimental leishmaniasis.leishmaniasis remains a significant cause of morbidity and mortality in the tropics. available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory cd4(+) t cell responses, something mirrored in descriptive studies of human disease. recombinant il-2/diphtheria toxin fusion protein (ril-2/dtx), a drug that is fda-approved for ...201121909452
first microscopical and molecular-based characterization of leishmania major within naturally infected phlebotomus salehi (diptera; psychodidae) in fars province, southern iran.zoonotoc cutaneous leishmaniasis is endemic in several parts of iran. jahrom district is one of the most important endemic foci of leishmaniasis located in fars province, southern iran. to identify the vectors of leishmaniasis in this area, a total of 349 sandflies were collected during may to august 2009. they were caught from outdoors in five regions of jahrom district including villages of mousavieh, ghotb-abad, heydar-abad, fath-abad and jahrom county. eleven species of phlebotomine (three ...201122185942
Characterization of Trypanosoma cruzi telomerase.High telomerase activity is always associated with actively dividing cells, however the detection of this activity in dividing Leishmania and Trypanosoma cruzi cells has always been disappointingly low. Recently, we have found that Leishmania major telomerase activity can be activated by heat, which combined with dilutions of the nuclear extracts produced an increase in activity comparable to cancer cells. Here we examined whether T. cruzi telomerase shares the same physicochemical properties of ...201121893016
exposure to phlebotomus papatasi and/or leishmania major: possible etiologic link to tunisian pemphigus. 201122011908
functional genomics of trypanosomatids.the decoding of the tritryp reference genomes nearly seven years ago provided a first peek into the biology of pathogenic trypanosomatids and a blueprint that has paved the way for genome-wide studies. although 60-70% of the predicted protein coding genes in trypanosoma brucei, trypanosoma cruzi and leishmania major remain unannotated, the functional genomics landscape is rapidly changing. facilitated by the advent of next-generation sequencing technologies, improved structural and functional an ...201122132795
anti-leishmanial activity of homo- and heteroleptic bismuth(iii) carboxylates.bismuth(iii) complexes of nsaids (non-steroidal anti inflammatory drugs) and substituted benzoic acids (o-methoxybenzoic acid, m-methoxybenzoic acid, o-nitrobenzoic acid, 3,5-diacetamidobenzoic acid, and 5-[(r/s)-2,3-dihydroxypropyl carbamoyl]-2-pyridine carboxylic acid) have been synthesised and fully characterised. two new bis-carboxylato bismuth complexes have been characterised by single crystal x-ray diffraction, namely [phbi(o-meoc(6)h(4)co(2))(2)(bipy)]·0.5etoh (bipy=2,2'-bipyridine) and ...201120851471
cutaneous leishmaniasis in mali.while not as common as in other parts of the world, cutaneous leishmaniasis is endemic to countries in africa, particularly in the north, central, east, and south. sporadic case reports of cutaneous leishmaniasis in countries spanning west africa have allowed scientists to propose an endemic belt in sub-saharan africa ranging from senegal to cameroon. while the presence of cutaneous leishmaniasis in west africa is well established, there is a paucity of data regarding the parasite species, vecto ...201121095531
leishmania major map kinase 10 is protective against experimental l. major infection.leishmania, a protozoan parasite that resides and replicates obligatorily within macrophages, inflicts a complex of severe diseases known as leishmaniasis. the diseases have significant socio-economic impact through gross disfiguration, morbidity and mortality worldwide. despite these problems, an effective anti-leishmanial vaccine remains elusive. herein, we have analyzed the immunogenicity and protective efficacy of l. major map kinase 10 (lmjmapk10) against the challenge infection with the pa ...201121527301
molecular adaptability of nucleoside diphosphate kinase b from trypanosomatid parasites: stability, oligomerization and structural determinants of nucleotide binding.nucleoside diphosphate kinases play a crucial role in the purine-salvage pathway of trypanosomatid protozoa and have been found in the secretome of leishmania sp., suggesting a function related to host-cell integrity for the benefit of the parasite. due to their importance for housekeeping functions in the parasite and by prolonging the life of host cells in infection, they become an attractive target for drug discovery and design. in this work, we describe the first structural characterization ...201121528129
delivery of a cocktail dna vaccine encoding cysteine proteinases type i, ii and iii with solid lipid nanoparticles potentiate protective immunity against leishmania major infection.earlier generations of leishmania vaccines have reached the third-phase of clinical trials, however none of them have shown adequate efficacy due to lack of an appropriate adjuvant. in this study, cationic solid lipid nanoparticles (cslns) were used to formulate three pdnas encoding l. major cysteine proteinase type i (cpa), ii (cpb) and iii (cpc). balb/c mice were immunized twice with a 3-week interval, with sln-pcdna-cpa/b/c, pcdna-cpa/b/c, sln, sln-pcdna and pbs. footpad assessments, parasite ...201121530597
langerhans cells are negative regulators of the anti-leishmania response.migratory skin dendritic cells (dcs) are thought to play an important role in priming t cell immune responses against leishmania major, but dc subtypes responsible for the induction of protective immunity against this pathogen are still controversial. in this study, we analyzed the role of langerin(+) skin-derived dcs in the leishmania model using inducible in vivo cell ablation. after physiologically relevant low-dose infection with l. major (1,000 parasites), mice depleted of all langerin(+) d ...201121536741
characterization of the antibody response to the saliva of phlebotomus papatasi in people living in endemic areas of cutaneous leishmaniasis.abstract. important data obtained in mice raise the possibility that immunization against the saliva of sand flies could protect from leishmaniasis. sand fly saliva stimulates the production of specific antibodies in individuals living in endemic areas of parasite transmission. to characterize the humoral immune response against the saliva of phlebotomus papatasi in humans, we carried out a prospective study on 200 children living in areas of leishmania major transmission. we showed that 83% of ...201121540371
the protective th1 response in mice is induced in the t-cell zone only three weeks after infection with leishmania major and not during early t-cell activation.the protozoan parasite leishmania spp. causes clinical pictures ranging in severity from spontaneously healing skin ulcers to systemic disease. the immune response associated with healing involves the differentiation of ifnγ-producing th1 cells, whereas the non-healing phenotype is associated with il4-producing th2 cells. the widespread assumption has been that the t-cell differentiation that leads to a healing or non-healing phenotype is established at the time of t-cell activation early after ...201121547563
the crystal structure of leishmania major peroxidase and characterization of the compound i tryptophan radical.the parasitic protozoa, leishmania major, produces a peroxidase (abbreviated lmp) that exhibits activities characteristic of both yeast cytochrome c peroxidase (ccp) and plant cytosolic ascorbate peroxidase (apx). one common feature is a key trp residue, trp208 in lmp and trp191 in ccp, that is situated adjacent to the proximal his heme ligand in ccp, apx and lmp. in ccp trp191 forms a stable cationic radical after reaction with h2o2 to form compound i; in apx the radical is located on the porph ...201121566139
seasonality and prevalence of leishmania major infection in phlebotomus duboscqi neveu-lemaire from two neighboring villages in central mali.phlebotomus duboscqi is the principle vector of leishmania major, the causative agent of cutaneous leishmaniasis (cl), in west africa and is the suspected vector in mali. although found throughout the country the seasonality and infection prevalence of p. duboscqi has not been established in mali. we conducted a three year study in two neighboring villages, kemena and sougoula, in central mali, an area with a leishmanin skin test positivity of up to 45%. during the first year, we evaluated the o ...201121572984
sphingolipid degradation by leishmania is required for its resistance to acidic ph in the mammalian host.leishmania parasites alternate between flagellated promastigotes in sandflies and non-flagellated amastigotes in mammals, causing a spectrum of serious diseases. to survive, they must resist the harsh conditions in phagocytes (including acidic ph, elevated temperature, and increased oxidative/nitrosative stress) and evade the immune response. recent studies have highlighted the importance of sphingolipid (sl) metabolism in leishmania virulence. in particular, we have generated a l. major mutant ...201121576322
dynamics of immunosuppression in hamsters with experimental visceral leishmaniasis. 201121584442
a comparative study of the effects of venoms from five rear-fanged snake species on the growth of leishmania major: identification of a protein with inhibitory activity against the parasite.leishmania parasites of several species cause cutaneous and visceral disease to millions of people worldwide, and treatment for this vector-borne protozoan parasite typically involves administration of highly toxic antimonial drugs. snake venoms are one of the most concentrated enzyme sources in nature, displaying a broad range of biological effects, and several drugs now used in humans were derived from venoms. in this study, we compared the effects of the venoms of the south american rear-fang ...201121601589
habitats of the sandfly vectors of leishmania tropica and l. major in a mixed focus of cutaneous leishmaniasis in southeast tunisia.from 2009 to 2010, 3129 sandflies were caught in cdc light traps placed in various habitats in ghomrassen, tataouine governorate, southeast tunisia, a mixed focus of human cutaneous leishmaniasis caused by leishmania tropica and leishmania major. species diversity was quantified in anthropogenic, semi-anthropogenic and semi-natural locations. sandflies were identified according to morphological characters and also by the comparative sequence analysis of a fragment of the mitochondrial cytochrome ...201121605538
platelet activation attracts a subpopulation of effector monocytes to sites of leishmania major infection.leishmania species trigger a brisk inflammatory response and efficiently induce cell-mediated immunity. we examined the mechanisms whereby leukocytes were recruited into lesions after leishmania major infection of mice. we found that a subpopulation of effector monocytes expressing the granulocyte marker gr1 (ly6c) is rapidly recruited into lesions, and these monocytes efficiently kill l. major parasites. the recruitment of this subpopulation of monocytes depends on the chemokine receptor ccr2 a ...201121606505
leishmania aethiopica: development of specific and sensitive pcr diagnostic test.pcr has proved useful for rapid diagnosis and typing of leishmania. lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. previously developed primers either require pcr-rflp analysis for leishmania aethiopica discrimination or lack sensitivity to detect l. aethiopica from clinical samples. here we report the development and validation of l. aethiopica specific pcr primers (v5f/v10r) based on cysteine protease b (cpb), a ...201121616071
leishmania major: activity of tamoxifen against experimental cutaneous leishmaniasis.leishmaniasis is a family of diseases caused by protozoan parasites of the genus leishmania. various leishmania species can cause human infection, producing a spectrum of clinical manifestations. the current treatments are unsatisfactory, and in absence of a vaccine, there is an urgent need for effective drugs to replace/supplement those currently in use. recent studies have shown that the antineoplastic drug, tamoxifen, had direct leishmanicidal effect on several leishmania species in vitro. mo ...201121620834
detection of leishmania parasites in the blood of patients with isolated cutaneous leishmaniasis.background: the consequences of the spread of leishmania parasites to the blood from lesions in patients with cutaneous leishmaniasis are numerous. to assess the magnitude of this invasion we conducted the present study on patients referred to the american university of beirut medical center for cutaneous leishmaniasis. methods: patients referred for the management of cutaneous leishmaniasis were included in the study. skin and blood cultures for leishmania were taken from these patients. result ...201121621442
visualisation of leishmania donovani fluorescent hybrids during early stage development in the sand fly vector.the leishmania protozoan parasites cause devastating human diseases. leishmania have been considered to replicate clonally, without genetic exchange. however, an accumulation of evidence indicates that there are inter-specific and intra-specific hybrids among natural populations. the first and so far only experimental proof of genetic exchange was obtained in 2009 when double drug resistant leishmania major hybrids were produced by co-infecting sand flies with two strains carrying different drug ...201121637755
effect of bmap-28 antimicrobial peptides on leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival.protozoan parasites, such as leishmania, still pose an enormous public health problem in many countries throughout the world. current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. several innovative approaches are under investigation, including the utilization of host defence peptides (hdps) as emerging anti-parasitic therapies. hdps are characterised by their small size, amphipathic nature and cationicity, which induce permeabilizatio ...201121655347
behavioral evidence for the presence of a sex pheromone in male phlebotomus papatasi scopoli (diptera: psychodidae).phlebotomus papatasi (diptera: psychodidae) is the old world sand fly vector of zoonotic cutaneous leishmaniasis caused by leishmania major (trypanosomatidae: kinetoplastida), a debilitating and disfiguring protist parasitic disease prevalent throughout southern mediterranean countries, the middle east, as well as southern and eastern european countries, where it is regarded as a serious public health problem. little is known of the mating ecology of p. papatasi, and, in particular, the role (if ...201121661311
multilocus microsatellite typing shows three different genetic clusters of leishmania major in iran.ten polymorphic microsatellite markers were used to analyse 25 strains of leishmania major collected from cutaneous leishmaniasis cases in different endemic areas in iran. nine of the markers were polymorphic, revealing 21 different genotypes. the data displayed significant microsatellite polymorphism with rare allelic heterozygosity. bayesian statistic and distance based analyses identified three genetic clusters among the 25 strains analysed. cluster i represented mainly strains isolated in th ...201121664984
leishmania promotes its own virulence by inducing expression of the host immune inhibitory ligand cd200.leishmania parasites infect macrophages, cells normally involved in innate defense against pathogens. leishmania amazonensis and leishmania major cause severe or mild disease, respectively, consistent with each parasite's ability to survive within activated macrophages. the mechanisms underlying increased virulence of l. amazonensis are mostly unknown. we show that l. amazonensis promotes its own survival by inducing expression of cd200, an immunoregulatory molecule that inhibits macrophage ac ...201121669395
specific and nonhomologous isofunctional enzymes of the genetic information processing pathways as potential therapeutical targets for tritryps.leishmania major, trypanosoma brucei, and trypanosoma cruzi (tritryps) are unicellular protozoa that cause leishmaniasis, sleeping sickness and chagas' disease, respectively. most drugs against them were discovered through the screening of large numbers of compounds against whole parasites. nonhomologous isofunctional enzymes (nises) may present good opportunities for the identification of new putative drug targets because, though sharing the same enzymatic activity, they possess different three ...201121808726
accelerated healing of cutaneous leishmaniasis in non-healing balb/c mice using water soluble amphotericin b-polymethacrylic acid.cutaneous leishmaniasis (cl) is a neglected tropical disease that causes prominent skin scaring. no water soluble, non-toxic, short course and low cost treatment exists. we developed a new water soluble amphotericin b-polymethacrylic acid (amb-pma) using established and scalable chemistries. amb-pma was stable for 9 months during storage. in vitro, it was effective against leishmania spp. promastigotes and amastigote infected macrophages. it was also less toxic and more effective than deoxychola ...201121807409
post-earthquake outbreak of cutaneous leishmaniasis in a rural region of southern iran.human cutaneous leishmaniasis (cl) is of increasing public-health importance in iran. on 10 july 2003, two mild earthquakes struck the rural town of zarindasht in the southern iranian province of fars. the results of passive detection of cl cases in this town (in which patients with any skin lesions were evaluated) from april 2002 to april 2004 indicated that the earthquakes may have led to an outbreak of the disease; annual incidence increased from 58·6 detected cases/100,000 in the 12 months b ...201121801500
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