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leishmania donovani and leishmania tropica. 191220766083
"leishmania donovani" in the soudan. 190420761564
antiplasmodial, anti-trypanosomal, anti-leishmanial and cytotoxicity activity of selected tanzanian medicinal plants.the antiplasmodial, anti-trypanosomal and anti-leishmanial activity of 25 plant extracts obtained from seven tanzanian medicinal plants: annickia (enantia) kummeriae (annonaceae), artemisia annua (asteraceae), pseudospondias microcarpa (anacardiaceae), drypetes natalensis (euphorbiaceae), acridocarpus chloropterus (malpighiaceae), maytenus senegalensis (celastraceae) and neurautanenia mitis (papilonaceae), were evaluated in vitro against plasmodium falciparum k1, trypanosoma brucei rhodesiense s ...200920734703
echinacea and trypanasomatid parasite interactions: growth-inhibitory and anti-inflammatory effects of echinacea.herbal preparations derived from various species and parts of echinacea (asteraceae) have been advocated for various medical applications, as a result of the many antimicrobial and immunomodulatory activities attributed to them.201020731557
qsar and docking studies of novel antileishmanial diaryl sulfides and sulfonamides.leishmaniasis is a neglected disease transmitted in many tropical and sub-tropical countries, with few studies devoted to its treatment. in this work, the activities of two antileishmanial compound classes were modeled using dragon descriptors, and multiple linear (mlr) and support vector machines (svm) as linear and nonlinear regression methods, respectively. both models were highly predictive, with calibration, leave-one-out validation and external validation r(2) of 0.79, 0.72 and 0.78, respe ...201020728249
cloning, overexpression and characterization of leishmania donovani squalene synthase.squalene synthase (ssn, ec 2.5.1.21), a major enzyme in the sterol biosynthetic pathway, catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate (fpp) in a two-step reaction to form squalene. fpp serves as a metabolic intermediate in the formation of sterols, dolichols, ubiquinones and farnesylated proteins. here, we report cloning, expression and purification of a catalytically active recombinant squalene synthase of leishmania donovani (ldssn). the p ...201020722739
bromopyrrole alkaloids as lead compounds against protozoan parasites.in the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide b (3) and dispacamide d (4), stevensine (5) and spongiacidin b (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide b (8) and longamide a (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau'amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin a (13), and agelongine (14), obtained from marine sponges belonging to axinella and agelas ...201020714430
the effect of c-terminal domain deletion on the catalytic activity of leishmania donovani surface proteinase gp63: role of ser446 in proteolysis.the kinetoplastid protozoan leishmania encodes major surface glycoprotein gp63, a zinc metallo-peptidase (ec.3.4.24.36) expressed both in promastigote and amastigote life stages. in the present study, we explored for the first time the role of c-terminal domain (ctd) in proteinase activity by serial truncation of leishmania donovani gp63 (ldgp63) from carboxyl terminal end (ctend). deletion of 180-211 amino acids from ctend (δ420 and δ389) resulted in almost 50% loss of catalytic activity agains ...201020678540
amphotericin b inhibits entry of leishmania donovani into primary macrophages.visceral leishmaniasis is a vector-borne disease caused by an obligate intra-macrophage protozoan parasite leishmania donovani. the molecular mechanisms involved in internalization of leishmania are still poorly understood. amphotericin b and its formulations are considered as the best existing drugs against visceral leishmaniasis and are being increasingly used. the reason for its antileishmanial activity is believed to be its ability to bind ergosterol found in parasite membranes. in case of i ...201020678487
leishmania subtilisin is a maturase for the trypanothione reductase system and contributes to disease pathology.proteases are a ubiquitous group of enzymes that play key roles in the life cycle of parasites, in the host-parasite relationship, and in the pathogenesis of parasitic diseases. furthermore, proteases are druggable targets for the development of new anti-parasitic therapy. the subtilisin protease (sub; clan sb, family s8) of leishmania donovani was cloned and found to possess a unique catalytic triad. this gene was then deleted by gene knock-out, which resulted in reduced ability by the parasite ...201020675366
non-peptide macrocyclic histone deacetylase inhibitors derived from tricyclic ketolide skeleton.inhibition of histone deacetylase (hdac) function is a validated therapeutic strategy for cancer treatment. of the several structurally distinct small molecule histone deacetylase inhibitors (hdaci) reported, macrocyclic depsipeptides possess the most complex cap groups and have demonstrated excellent hdac inhibition potency and isoform selectivity. unfortunately, the development of macrocyclic depsipeptides has been hampered in part because of development problems characteristic of large peptid ...201020669972
a tyrosyl dna phosphodiesterase 1 from kinetoplastid parasite leishmania donovani (ldtdp1) capable of removing topo i-dna covalent complexes.tyrosyl dna phosphodiesterase 1 (tdp1) is a member of phospholipase d superfamily, which cleaves a broad range of 3'-dna adducts, the best characterized of which is the phosphodiester bond formed between dna and topoisomerase ib. this study describes cloning and functional characterization of the enzyme, termed as ldtdp1 in the kinetoplastid parasite leishmania donovani. sequence analysis confirmed conservation of the active site motifs typical for all tdp1 proteins. ldtdp1 activity was detected ...201020659295
dyserythropoiesis in visceral leishmaniasis. 201020652969
qsar, docking, and comfa studies of gsk3 inhibitors.gsk-3 inhibitors are interesting candidates to develop anti-alzheimer compounds. gsk-3β are also interesting as anti-parasitic compounds active against plasmodium falciparum, trypanosoma brucei, and leishmania donovani; the causative agents for malaria, african trypanosomiasis and leishmaniosis. the high number of possible candidates creates the necessity of quantitative structure-activity relationship models in order to guide the gsk3 (glycogen synthase kinase 3 inhibitor) synthesis. in this wo ...201020642432
in search of an ideal test for diagnosis and prognosis of kala-azar.the latex agglutination test (katex), direct agglutination test (dat), and the rk39 immuno-chromatographic strip test (dipstick test) were evaluated for their role in the diagnosis and prognosis of visceral leishmaniasis (kala-azar) in india. sera and urine samples from 455 subjects--150 confirmed visceral leishmaniasis cases, 160 endemic controls, 100 non-endemic controls, and 45 other febrile diseases--were included in the study. the sensitivity of the katex, dat, and rk39 strip test was 87% [ ...201020635639
detection of leptomonas sp. parasites in clinical isolates of kala-azar patients from india.we report here nine unusual cases of kala-azar, of which parasites were isolated and found by 18s rrna gene sequencing to be most similar to leptomonas species. one of these isolates was used to inoculate balb/c mice; organs were collected and directly submitted to a genus-specific rdna-its1 pcr analysis: this revealed the presence of both leptomonas sp. and leishmania donovani. therefore, we conclude that there was a mixed infection of leptomonas sp. and l. donovani in this isolate. we consider ...201020633704
synthesis, structural elucidation and in vitro antiparasitic activity against trypanosoma cruzi and leishmania chagasi parasites of novel tetrahydro-1-benzazepine derivatives.forty six new 1,4-epoxy-2-exo-aryl- and cis-2-aryl-4-hydroxytetrahydro-1-benzazepine derivatives were synthesized and fully characterized. all compounds were tested in vitro against both trypanosoma cruzi and leishmania chagasi parasites and also for cytotoxicity using vero and thp-1 mammalian cell lines. many of the evaluated compounds showed remarkable activity against the epimastigote and intracellular amastigote forms of t. cruzi, with ic₅₀ values comparable with that of control drug nifurti ...201020627590
solution structure and dynamics of adf/cofilin from leishmania donovani.leishmania donovani adf/cofilin (ldcof) is a novel member of adf/cofilin family. ldcof depolymerizes, but does not co-sediment with, rabbit muscle actin filaments. its f-actin depolymerizing activity is ph independent. further, it possesses weak f-actin severing activity. in order to better understand its characteristic properties, we have determined the solution nmr structure of ldcof and have analyzed protein backbone dynamics from (15)n-relaxation measurements. the structure of ldcof possesse ...201020627129
stromal cell-derived cxcl12 and ccl8 cooperate to support increased development of regulatory dendritic cells following leishmania infection.in the immune system, stromal cells provide specialized niches that control hematopoiesis by coordinating the production of chemokines, adhesion molecules, and growth factors. stromal cells also have anti-inflammatory effects, including support for the differentiation of hematopoietic progenitors into dendritic cells (dcs) with immune regulatory properties. together, these observations suggest that the alterations in hematopoiesis commonly seen in infectious disease models, such as experimental ...201020624948
antiprotozoal activity of melampyrum arvense and its metabolites.an activity guided isolation of the h(2)o subextract of the crude extract of melampyrum arvense l. afforded iridoid glucosides: aucubin (1), melampyroside (2), mussaenoside (3), mussaenosidic acid (4), 8-epi-loganin (5); flavonoids: apigenin (6), luteolin (7), luteolin 7-o-β-glucopyranoside (8); a lignan glycoside dehydrodiconiferyl alcohol 9-o-β-glucopyranoside (9); and benzoic acid (10). β-sitosterol (11) and a fatty acid mixture (12) were identified as the active principles of the chcl(3) sub ...201120623589
stage specific developmental changes in the mitochondrial and surface membrane associated redox systems of leishmania donovani promastigote and amastigote.energy metabolism of leishmania donovani parasite has been investigated under conditions imitating intralysosomal-like environment in the host organism. trans-plasma membrane electron transport and oxygen uptake were inhibited progressively when promastigote cells were exposed to ph 5.5 and 37 degrees c. a special feature of the respiratory chain in amastigote was the absence of complex i, ii, and iv. when l. donovani was grown at ph 5.5 and 37 degrees c, the acid excretory product succinate was ...201020618140
lysine n(epsilon)-trimethylation, a tool for improving the selectivity of antimicrobial peptides.the effects of lysine n(epsilon)-trimethylation at selected positions of the antimicrobial cecropin a-melittin hybrid peptide kwklfkkigavlkvl-amide have been studied. all five monotrimethylated, four bis-trimethylated plus the per-trimethylated analogues have been synthesized and tested for antimicrobial activity on leishmania parasites and on gram-positive and -negative bacteria, as well as for hemolysis of sheep erythrocytes as a measure of cytotoxicity. the impact of trimethylation on the sol ...201020617807
species discrimination and phylogenetic inference of 17 chinese leishmania isolates based on internal transcribed spacer 1 (its1) sequences.leishmaniasis is a geographically widespread disease, caused by protozoan flagellates of the genus leishmania. this disease still remains endemic in china, especially in the west and northwest frontier regions. to date, the phylogenetic relationships among chinese leishmania isolates are still unclear, and the possible taxonomic diversity remains to be established. in this study, the its1-5.8s fragments of ten isolates collected from different foci in china were determined. to infer the phylogen ...201020617444
antiprotozoal steroidal saponins from the marine sponge pandaros acanthifolium.the chemical composition of the caribbean sponge pandaros acanthifolium was reinvestigated and led to the isolation of 12 new steroidal glycosides, namely, pandarosides e-j (1-6) and their methyl esters (7-12). their structures were determined on the basis of extensive spectroscopic analyses, including two-dimensional nmr and hresims data. like the previously isolated pandarosides a-d (13-16), the new compounds 1-12 share an unusual oxidized d-ring and a cis c/d ring junction. the absolute confi ...201020614907
antimicrobial and antiparasitic abietane diterpenoids from the roots of clerodendrum eriophyllum.chromatographic separation of the roots of a kenyan medicinal plant, clerodendrum eriophyllum, led to the isolation of ten abietane diterpenoids (1-10), one of which (1) was isolated for the first time from a natural source. using spectroscopic data, the structure of 1 was determined to be 12-hydroxy-8,12-abietadiene-3,11,14-trione. circular dichroism (cd) spectra showed that the stereochemistry of compounds 1, 3, and 6-8 belongs to the normal series of abietane diterpenes, which confirmed the a ...201020614808
cyclosporin a treatment of leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability.cyclosporin a (csa) has important anti-microbial activity against parasites of the genus leishmania, suggesting csa-binding cyclophilins (cyps) as potential drug targets. however, no information is available on the genetic diversity of this important protein family, and the mechanisms underlying the cytotoxic effects of csa on intracellular amastigotes are only poorly understood. here, we performed a first genome-wide analysis of leishmania cyps and investigated the effects of csa on host-free l ...201020614016
immunolocalization and characterization of two novel proteases in leishmania donovani: putative roles in host invasion and parasite development.two novel intracellular proteases having identical molecular mass (58 kda) were purified from virulent indian strain of leishmania donovani by a combination of aprotinin-agarose affinity chromatography, ion exchange chromatography and finally continuous elution electrophoresis. both of these proteases migrate in sds-page as a single homogeneous bands suggesting monomeric nature of these proteases. the enzyme activity of one of the proteases was inhibited by serine protease inhibitor aprotinin an ...201020595064
probing the dynamic nature of signalling pathways by imac and seldi-tof ms.one major obstacle to the analysis of signalling pathways is the dynamic nature of signalling response to environmental stimuli. to overcome this limitation we applied immobilized metal affinity chromatography (imac) in combination with seldi-tof ms to investigate the temporal variation of protein phosphorylation. we analysed the phospho-proteome variations in our model organism, leishmania donovani, in response to changes in ph and temperature, which induce differentiation from promastigotes to ...201020590411
a novel achiral seco-cyclopropylpyrido[e]indolone (cpyi) analog of cc-1065 and the duocarmycins: synthesis, dna interactions, in vivo anticancer and anti-parasitic evaluation.the synthesis of an achiral seco-hydroxy-aza-cbi-tmi analog (8) of the duocarmycins is reported. its specificity for the dna minor groove of at-rich sequences and covalent bonding to adenine-n3 was ascertained by a thermal cleavage assay. compound 8 was found to be cytotoxic in the nanomolar range against murine and human cancer cells. it was further demonstrated that compound 8 was active against murine melanoma (b16-f0) grown in c57bl/6 mice. compound 8 was also shown to inhibit the growth of ...201020579889
regulatory role of nitric oxide in the reduced survival of erythrocytes in visceral leishmaniasis.nitric oxide (no) plays a vital role in maintaining the survivability of circulating erythrocytes. here we have investigated whether no depletion associated with visceral leishmaniasis (vl) is responsible for the reduced survival of erythrocytes observed during the disease.201020576500
comparison of bcg, mpl and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis.the development of an effective vaccine against visceral leishmaniasis (vl) caused by leishmania donovani is an essential aim for controlling the disease. use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. earlier we reported the protective efficacy of cationic liposome-associated l. donovani promastigote antigens (lag) against experimental vl. the aim of the present study was to compare the effectiveness of t ...201020576102
leishmania donovani amastigotes impair gamma interferon-induced stat1alpha nuclear translocation by blocking the interaction between stat1alpha and importin-alpha5.the protozoan parasite leishmania donovani, the etiological agent of visceral leishmaniasis, is renowned for its capacity to sabotage macrophage functions and signaling pathways stimulated by activators such as gamma interferon (ifn-gamma). our knowledge of the strategies utilized by l. donovani to impair macrophage responsiveness to ifn-gamma remains fragmentary. in the present study, we investigated the impact of an infection by the amastigote stage of l. donovani on ifn-gamma responses and si ...201020566692
antimycobacterial, antiprotozoal and cytotoxic potential of twenty-one brown algae (phaeophyceae) from british and irish waters.in the continuation of our research on seaweeds, crude extracts of 21 brown algae collected from the south coast of england and the west coast of ireland were screened for in vitro trypanocidal, leishmanicidal and antimycobacterial activities. mammalian stages of a small set of parasitic protozoa; i.e. trypanosoma brucei rhodesiense, t. cruzi and leishmania donovani, and the tubercle bacillus mycobacterium tuberculosis were used as test organisms. the extracts were also evaluated for selectivity ...201020564461
identification of old world leishmania species by pcr-rflp of the 7 spliced leader rna gene and reverse dot blot assay.the aim of the study was to assess the 7sl rna pcr followed by restriction fragment length polymorphism (rflp) and reverse dot blot (rdb) assays for use in identification of old world leishmania species. species-specific rflp patterns were obtained for leishmania major, leishmania tropica and the leishmania donovani complex when the 7sl rna pcr product was digested with the restriction enzyme bsuri, an isoschizomer of haeiii. for the rdb assay, biotin-labelled 7sl rna amplicons were hybridized t ...201020561310
elevated levels of tryparedoxin peroxidase in antimony unresponsive leishmania donovani field isolates.enhancement of the anti-oxidant metabolism of leishmania parasites, dependent upon the unique dithiol trypanothione, has been implicated in laboratory-generated antimony resistance. here, the role of the trypanothione-dependent anti-oxidant pathway is studied in antimony-resistant clinical isolates. elevated levels of tryparedoxin and tryparedoxin peroxidase, key enzymes in hydroperoxide detoxification, were observed in antimonial resistant parasites resulting in an increased metabolism of perox ...201020553768
profiling of lipids in leishmania donovani using hydrophilic interaction chromatography in combination with fourier transform mass spectrometry.there is evidence from our current research on resistance to stibigluconate and from some previous observations that lipid composition may be altered in resistant leishmania donovani and in order to explore this we required a comprehensive lipidomics method. phospholipids can be analysed by direct infusion into a mass spectrometer and such methods can work very well. however, chromatographic methods can also be very effective and are extensively used. they potentially avoid ion suppression effec ...201020552712
assignment of uv-vis spectrum of (3,3')-diindolylmethane, a leishmania donovani topoisomerase ib inhibitor and a candidate dna minor groove binder.the geometrical optimization of (3,3')-diindolylmethane (dim), an inhibitor of the bisubunit enzyme topoisomerase i from leishmania donovani, a pathogenic protozoan parasite, mostly diffused in developing countries, has been carried out through quantum mechanical calculation. using first-principle dft restrained geometrical optimization, a potential energy surface has been constructed to identify a set of local minimum energy conformations of dim. starting from these conformations, the experimen ...201020550156
synthesis and antileishmanial activity of piperoyl-amino acid conjugates.based on reported antileishmanial activity of naturally occurring alkaloid piperine and amino acid esters, their conjugates were synthesized by the hydrolysis of piperine to piperic acid followed by reaction with amino acid methyl esters. these conjugates were further converted to compounds with free carboxyl group and those with reduced double bonds. the synthesized compounds were evaluated for activity against promastigote and amastigote forms of l. donovani in vitro. all the compounds showed ...201020546981
amphotericin b regulates the host immune response in visceral leishmaniasis: reciprocal regulation of protein kinase c isoforms.treatment of visceral leishmaniasis (vl) is marked by the failure of pentavalent antimonials which has brought amphotericin b (ampb) to the forefront. in this study we have focused on signaling pathway regulating ampb triggered effector response.201020546775
screening leishmania donovani-specific genes required for visceral infection.comparison of the leishmania infantum genome with leishmania braziliensis and leishmania major genomes has identified 25 l. infantum species-specific genes that are absent or pseudogenes in l. major and l. braziliensis. to determine whether these l. infantum species-specific genes are involved in visceral leishmania infection, we cloned the orthologues of 14 l. infantum species-specific genes from the genetically closely related leishmania donovani and introduced them into l. major. two of these ...201020545850
drug targeting to macrophages using paromomycin-loaded albumin microspheres for treatment of visceral leishmaniasis: an in vitro evaluation.leishmania parasite is an obligate intracellular parasite of the mammalian host and lives inside resident macrophages of liver and spleen. a high dose of paromomycin (pm) is required for the treatment.201120545446
immunostimulatory properties of dendritic cells after leishmania donovani infection using an in vitro model of liver microenvironment.recent advances demonstrated that liver dendritic cells (dcs) promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. although there has been significant work on the phenotypic and functional roles of such dcs, the impact of liver microenvironment on the immune properties of infected dc is still poorly explored, probably because of the limitations of modelization.201020544029
co-infection of mucosal leishmaniasis and extra pulmonary tuberculosis in a patient with inherent immune deficiency.in sri lanka, cutaneous leishmaniasis is a well-established disease caused by leishmania donovani. only a few cases of visceral disease and mucosal localization have been reported to date.201020534090
use of miltefosine in the treatment of visceral leishmaniasis in children at a tertiary care hospital of karachi.existing standard treatment options for visceral leishmaniasis are less than optimal. we report here the use of oral miltefosine in the treatment of two paediatric cases of visceral leishmaniasis at a tertiary care hospital in karachi, pakistan. one patient came from balochistan while the second patient was from northern pakistan. both presented with a prolonged history of fever, massive hepatosplenomegaly, anaemia and thrombocytopenia. visceral leishmaniasis was diagnosed with bone marrow studi ...201020527651
sero-epidemiological study of visceral leishmaniasis in basrah, southern iraq.to study selected epidemiological aspects of visceral leishmaniasis, assess direct agglutination test (dat) as a diagnostic method and the sero-epidemiological prevalence of the disease among apparently healthy children in basrah, iraq.201020527645
cd40 expression levels modulate regulatory t cells in leishmania donovani infection.dendritic cell (dc)-expressed cd40 is shown to play crucial roles in eliciting effector t cell responses, primarily the proinflammatory cd4(+) th subsets and cytotoxic cd8(+) t cells that eliminate various infections and tumors, respectively. in contrast, dcs are also implied in the generation of regulatory t cells (tregs) that counteract the functions of the proinflammatory th subsets and exacerbate infections. however, the role of dc-expressed cd40 in the generation of tregs is unknown. in thi ...201020525887
molecular docking, structure-activity relationship and biological evaluation of the anticancer drug monastrol as a pteridine reductase inhibitor in a clinical isolate of leishmania donovani.using the pteridine reductase (ptr1) enzyme of leishmania as the target, the objective of our study was to find a drug candidate that can enter the clinical development process after being evaluated for safety and efficacy in animals.201020519355
clinical and epidemiological studies on the cutaneous leishmaniasis caused by leishmania (leishmania) donovani in sri lanka.sri lanka is the newest reported focus of human leishmaniasis within the indian subcontinent. over the last 8 years, more than 2000 cases of cutaneous leishmaniasis (cl), apparently caused by leishmania donovani (a species usually associated with the visceral form of the disease), have been passively identified in the country. the clinical profiles of 401 suspected cases of cl in sri lanka were recently explored and some of the cases' immunological responses were investigated, in antibody-detect ...201020507695
influence of topography on the endemicity of kala-azar: a study based on remote sensing and geographical information system.kala-azar, a fatal infectious disease in many indian states, particularly in bihar, west bengal, uttar pradesh, and jharkhand, is caused by the protozoan parasite leishmania donovani and transmitted by the sandfly vector phlebotomus argentipes. the vector is distributed all over the country but the disease is confined to particular zones since before the last century. in this study, parameters such as altitude, temperature, humidity, rainfall and the normalized difference vegetation index (ndvi) ...201020503185
histopathological and parasitological investigations of ear healthy skin of dogs naturally and experimentally infected with leishmania (leishmania) chagasi.although 90% of clinical cases of american visceral leishmaniasis (avl) occur in the northeastern region of brazil, the incidence of cases in recent years has increased in southeastern states such as minas gerais (mg), where the disease has been reported in several cities, including belo horizonte, the state capital. some studies have shown a strong correlation between the incidence of avl and canine visceral leishmaniasis (cvl) in belo horizonte. a study of 108 dogs with parasite leishmania cha ...201020503176
leishmania donovani isolates with antimony-resistant but not -sensitive phenotype inhibit sodium antimony gluconate-induced dendritic cell activation.the inability of sodium antimony gluconate (sag)-unresponsive kala-azar patients to clear leishmania donovani (ld) infection despite sag therapy is partly due to an ill-defined immune-dysfunction. since dendritic cells (dcs) typically initiate anti-leishmanial immunity, a role for dcs in aberrant ld clearance was investigated. accordingly, regulation of sag-induced activation of murine dcs following infection with ld isolates exhibiting two distinct phenotypes such as antimony-resistant (sb(r)ld ...201020502630
arabinosylated lipoarabinomannan-mediated protection in visceral leishmaniasis through up-regulation of toll-like receptor 2 signaling: an immunoprophylactic approach.visceral leishmaniasis is characterized by severe immunosuppression of the host cell, resulting in loss of the proinflammatory response. toll-like receptor 2 (tlr2) is involved in myriad disease forms, including visceral leishmaniasis. during leishmania donovani infection, the parasite modulates tlr2 to suppress interleukin 12 production, indicating the possible involvement of tlr2 in regulation of the immune response against l. donovani infection. arabinosylated lipoarabinomannan (ara-lam) poss ...201020500089
diagnosis of visceral leishmaniasis by polymerase chain reaction of dna extracted from giemsa's solution-stained slides.visceral leishmaniasis (vl) is caused by the protozoan parasite leishmania donovani and is a potentially fatal disease in endemic areas of the world. nepal is an endemic area in which vl causes major public health problems in the lowland areas of the southeast regions. the aim of the present study was to evaluate the sensitivity of polymerase chain reaction (pcr) amplification for the detection of leishmania dna from giemsa's solution-stained bone marrow slides. bone marrow samples were aspirate ...201020499093
localization and induction of the a2 virulence factor in leishmania: evidence that a2 is a stress response protein.leishmaniasis is a vector-borne infectious disease with a wide range of pathologies depending on the species of leishmania. leishmania parasites are transmitted by the sand fly vector as promastigotes; within the mammalian host, leishmania parasites differentiate into amastigotes and replicate in macrophages. the a2 protein from leishmania donovani is expressed predominantly in amastigotes and therefore likely plays a role in survival in the mammalian host. in the present study, we have determin ...201020497497
leishmania parasitophorous vacuoles interact continuously with the host cell's endoplasmic reticulum; parasitophorous vacuoles are hybrid compartments.macrophages that express representative endoplasmic reticulum (er) molecules tagged with green fluorescence protein were generated to assess the recruitment of er molecules to leishmania parasitophorous vacuoles (pvs). more than 90% of pvs harbouring leishmania pifanoi or leishmania donovani parasites recruited calnexin, to their pv membrane. an equivalent proportion of pvs also recruited the membrane-associated soluble n-ethylmaleimide-sensitive factor attachment protein receptors (snares), sec ...201020497181
in vitro and in vivo antileishmanial efficacy of nitazoxanide against leishmania donovani.control of leishmania infection relies primarily on chemotherapy, and the current drug available for treating leishmaniasis is limited. nitazoxanide (ntz) is a broad spectrum antiparasitic agent with activity against protozoa, nematodes, cestodes, and trematodes. in the present study, the in vitro antileishmanial efficacy of ntz was evaluated by incubation of leishmania donovani promastigotes with ntz, indicating that ntz can affect the ultrastructure of parasite promastigote and efficiently inh ...201020495931
cpg oligodeoxynucleotide augments the antileishmanial activity of miltefosine against experimental visceral leishmaniasis.to evaluate the combination of cpg oligodeoxynucleotide (cpg odn) and miltefosine for the treatment of experimental visceral leishmaniasis (vl).201020495208
accordance and concordance of pcr and nasba followed by oligochromatography for the molecular diagnosis of trypanosoma brucei and leishmania.to evaluate the repeatability and reproducibility of four simplified molecular assays for the diagnosis of trypanosoma brucei spp. or leishmania ssp. in a multicentre ring trial with seven participating laboratories.201020487429
sensitivity and specificity of the leishmania oligoc-test and nasba-oligochromatography for diagnosis of visceral leishmaniasis in kenya.to estimate the sensitivity and specificity of the oligoc-test and nucleic acid sequence-based amplification coupled to oligochromatography (nasba-oc) for molecular detection of leishmania in blood from patients with confirmed visceral leishmaniasis (vl) and healthy endemic controls from kenya.201020487428
epidemiology of leishmania donovani infection in high-transmission foci in nepal.nepal reports a visceral leishmaniasis (vl) incidence of 5 per 10 000 per year on the basis of notification by health facilities, but little community-based epidemiological information exists. we report data on prevalence rates of leishmania donovani infection in ten communities in east nepal.201020487421
the epidemiology of leishmania donovani infection in high transmission foci in india.visceral leishmaniasis (vl) is highly prevalent in bihar, india. india and its neighbours aim at eliminating vl, but several knowledge gaps in the epidemiology of vl may hamper that effort. the prevalence of asymptomatic infections with leishmania donovani and their role in transmission dynamics are not well understood. we report data from a sero-survey in bihar.201020487420
a chronic mutilating rhinopathy with a delayed diagnosis of mucocutaneous leishmaniasis.mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin and mucosal lesions. mucocutaneous leishmaniasis is very rare in india and to our knowledge, only two cases have been reported, and this is the first case of mucocutaneous leishmaniasis presenting with mutilating rhinopathy reported from the indian subcontinent.201020465699
spatial analysis of leishmania donovani exposure in humans and domestic animals in a recent kala azar focus in nepal.summary: visceral leishmaniasis (vl) is a major public health problem in the indian subcontinent where the leishmania donovani transmission cycle is described as anthroponotic. however, the role of animals (in particular domestic animals) in the persistence and expansion of vl is still a matter of debate. we combined direct agglutination test (dat) results in humans and domestic animals with geographic information system technology (i.e. extraction maps and scan statistic) to evaluate the exposu ...201020459877
synthesis of 2-(pyrimidin-2-yl)-1-phenyl-2,3,4,9-tetrahydro-1h-beta-carbolines as antileishmanial agents.a series of 2-(pyrimidin-2-yl)-1-phenyl-2,3,4,9-tetrahydro-1h-beta-carboline derivatives has been synthesized and evaluated for antileishmanial activity against leishmania donovani. compound 8 exhibited best antileishmanial activity with ic(50) value of 1.93 microg/ml against amastigotes, high selectivity index, and was more active than reference drugs sodium stilbogluconate and pentamidine.201020457476
almiramides a-c: discovery and development of a new class of leishmaniasis lead compounds.leishmaniasis is a debilitating disease caused by protozoan parasites of the genus leishmania, which affects an estimated 12 million people worldwide. the discovery of new lead compounds for leishmaniasis is therefore a pressing concern for global health programs. the organic extract of a panamanian collection of the marine cyanobacterium lyngbya majuscula showed strong in vitro activity in two complementary screens against the tropical parasite leishmania donovani, the causative agent of viscer ...201020441198
leishmania donovani complex (kinetoplastida, trypanosomatidae): comparison of deoxyribonucleic acid based techniques for typing of isolates from ethiopia.in ethiopia, visceral leishmaniasis (vl) is an increasing public health concern. recently, a new outbreak of vl claimed the lives of hundreds of ethiopians. mapping its distribution and the identification of the causative leishmania species is important for proper use of resources and for control planning. the choice of appropriate typing technique is the key for determining the infecting species. here we compared three deoxyribonucleic acid (dna) based markers. we used, for the first time, cpbe ...201020438727
randomized, double-blind, comparative clinical trial on the efficacy and safety of intralesional sodium stibogluconate and intralesional 7% hypertonic sodium chloride against cutaneous leishmaniasis caused by l. donovani.since cutaneous leishmaniasis (cl) is a self healing disease, an ideal therapy should be rapidly effective, easily administered, cheap, available at all times at all centers and should have no side effects.201020438389
an outbreak of the desert sub-type of zoonotic visceral leishmaniasis in jiashi, xinjiang uygur autonomous region, people's republic of china.few outbreaks of the desert sub-type of zoonotic visceral leishmaniasis (vl) have been described worldwide. in 2008, the incidence rate of vl in jiashi county, xinjiang uygur autonomous region in the western part of the people's republic of china, increased more than twenty-folds compared to the average annual incidence rate. the majority of the cases (96.6%) occurred among <2 year-old infants. for the first time in the desert area of xinjiang, the parasites were isolated from bone marrow aspira ...201020434585
immune restoration disease associated with leishmania donovani infection following antiretroviral therapy for hiv infection.immune restoration disease following antiretroviral therapy for human immunodeficiency virus infection can cause significant morbidity and mortality. we describe the dramatic clinical course of an human immunodeficiency virus-infected patient who developed severe immune restoration disease associated with leishmania donovani infection in a non-endemic area of the world. it highlights the need to consider previous travel history when screening for opportunistic infections before starting antiretr ...201020434127
differential alterations in the activity of matrix metalloproteinases within the nervous tissue of dogs in distinct manifestations of visceral leishmaniasis.canine visceral leishmaniasis is an important emerging disease with a multitude of clinical symptoms, including neurological alterations. matrix metalloproteinases (mmp) are proteases implicated with the extracellular matrix remodelling and, within the central nervous system, these enzymes are involved with blood-brain-barrier disruption and inflammation. to establish the involvement of mmp-2 and -9 within the nervous tissue of dogs with spontaneous visceral leishmaniasis, fragments of nervous t ...201020430448
chemistry, cytotoxicity and antileishmanial activity of the essential oil from piper auritum.leishmaniasis is one of the most important parasitic infections, but current treatments are unsatisfactory due to their toxicity, cost and resistance. therefore, the development of new antileishmanial compounds is imperative. many people who live in endemic areas use plants as an alternative to treat the disease. in this paper, we characterised the essential oil from piper auritum, evaluated its cytotoxicity and determined its antileishmanial activity. the chromatogram obtained by gas chromatogr ...201020428676
overexpression of histone h2a modulates drug susceptibility in leishmania parasites.resistance to antimonials has emerged as a major hurdle to the treatment and control of visceral leishmaniasis (vl), also know as kala-azar (ka), the disease caused by leishmania donovani, in india where >60% of ka patients are unresponsive to sodium antimony gluconate (sag) treatment. determinants of resistance in laboratory strains are partly known, however the mechanism operating in field isolates is not well understood. in microarray-based expression profiling with rna isolated from field is ...201020427152
phosphoproteome dynamics reveal heat-shock protein complexes specific to the leishmania donovani infectious stage.leishmania is exposed to a sudden increase in environmental temperature during the infectious cycle that triggers stage differentiation and adapts the parasite phenotype to intracellular survival in the mammalian host. the absence of classical promoter-dependent mechanisms of gene regulation and constitutive expression of most of the heat-shock proteins (hsps) in these human pathogens raise important unresolved questions as to regulation of the heat-shock response and stage-specific functions of ...201020404152
efficacy of artemisinin in experimental visceral leishmaniasis.visceral leishmaniasis (vl), caused by the protozoan leishmania sp., affects 500000 people annually, with the indian subcontinent contributing a significant proportion of these cases. emerging refractoriness to conventional antimony therapy has emphasised the need for safer yet effective antileishmanial drugs. artemisinin, a widely used antimalarial, demonstrated anti-promastigote activity and the 50% inhibitory concentration (ic(50)) ranged from 100 microm to 120 microm irrespective of leishman ...201020403680
visceral leishmaniasis due to leishmania donovani in a patient with advanced hiv infection.an eritrean-born man observed over an extended period had upper gastrointestinal symptoms, fever, hepatosplenomegaly and pancytopenia in the setting of advanced hiv infection and poor adherence to antiretroviral therapy. despite thorough investigation, it was not until a repeat gastroscopic examination and gastric biopsy were performed 18 months after initial presentation that leishmania infection was diagnosed. the species was identified by polymerase chain reaction assay as l. donovani. physic ...201020402615
cd40 signaling in cd8+cd40+ t cells turns on contra-t regulatory cell functions.cd4(+) regulatory t cells (treg cells) mediate immunosuppression, whereas cd8(+) t cells confer resistance in many diseases. it is unknown whether cd8(+) t cells confer protection by antagonizing the treg cells. using a model of stage-specific immune responses against leishmania donovani infection in susceptible balb/c mice, we report that cd3(+)cd8(+)cd40(+) t cells executed cd40-dependent cytotoxicity on cd3(+)cd4(+)cd127(dim)gitr(+)cd25(+) treg cells during the initial phase of the infection ...201020400702
antiprotozoal, schistosomicidal, and antimicrobial activities of the essential oil from the leaves of baccharis dracunculifolia.baccharis dracunculifolia dc. (asteraceae), popularly known as 'alecrim do campo', is a native plant from brazil used in folk medicine as febrifuge, anti-inflammatory, antiseptic, and to treat skin sores. also, b. dracunculifolia is the most important plant source of the brazilian green propolis, which is recognized for its antiseptic and antiprotozoal activities. this study aimed at investigating the in vitro antiprotozoal, schistosomicidal, and antimicrobial activities of the essential oil fro ...201020397234
essential-oil composition, antileishmanial, and toxicity study of artemisia abyssinica and satureja punctata ssp. punctata from ethiopia.essential oils of artemisia abyssinica and satureja punctata ssp. punctata from ethiopia were analyzed by gc and gc/ms, and screened for leishmanicidal activity against promastigote and axenic amastigotes of leishmania donovani and l. aethiopica, including toxicity studies on human monocytic leukemia cells (thp-1) and erythrocytes in vitro. gc/ms of a. abyssinica oil revealed 67 compounds (99.94%) with the major constituents yomogi alcohol (38.47%), artemisyl acetate (24.88%), and artemisia alco ...201020397218
phlebotomus argentipes seasonal patterns in india and nepal.the current control of phebotomus argentipes (annandale and brunetti), the vector of leishmania donovani (laveran and mesnil), on the indian subcontinent is base on indoor residual spraying. the efficacy of this method depends, among other factors, on the timing and number of spraying rounds, which depend on the p. argentipes seasonality. to describe p. argentipes' seasonal patterns, six visceral leishmaniasis (vl) endemic villages, three in muzaffarpur and three in sunsari districts in india an ...201020380311
synthesis and biological evaluation of new [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines against leishmania donovani.a series of [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines were synthesized and screened for their in vitro antileishmanial activity against leishmania donovani. among all, 8 compounds have shown more than 90% inhibition against promastigotes and ic50 in the range of 4.01-57.78 microm against amastigotes. compound 5, a triazino[5,6-b]indol-3-ylthio-1,3,5-triazine derivative was found to be the most active and least toxic with 20- & 10-fo ...201020371140
novel arylimidamides for treatment of visceral leishmaniasis.arylimidamides (aias) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [ic(50)], <1 microm) against both leishmania donovani axenic amastigotes and intracellular leishmania, the causative agent for human visceral leishmaniasis (vl). a systematic lead discovery program was employed to characterize in vitro and in vivo antileishmanial activities, pharmacokinetics, mutagenicities, and toxicities of two novel aias, db745 and db766. they we ...201020368397
amplification of adenine phosphoribosyltransferase suppresses the conditionally lethal growth and virulence phenotype of leishmania donovani mutants lacking both hypoxanthine-guanine and xanthine phosphoribosyltransferases.leishmania donovani cannot synthesize purines de novo and obligatorily scavenge purines from the host. previously, we described a conditional lethal deltahgprt/deltaxprt mutant of l. donovani (boitz, j. m., and ullman, b. (2006) j. biol. chem. 281, 16084-16089) that establishes that l. donovani salvages purines primarily through hypoxanthine-guanine phosphoribosyltransferase (hgprt) and xanthine phosphoribosyltransferase (xprt). unlike wild type l. donovani, the deltahgprt/deltaxprt knock-out ca ...201020363738
identification, characterization, and expression of a unique secretory lipase from the human pathogen leishmania donovani.lipases have been implicated to be of importance in the life cycle development, virulence, and transmission of a variety of parasitic organisms. potential functions include the acquisition of host resources for energy metabolism and as simple building blocks for the synthesis of complex parasite lipids important for membrane remodeling and structural purposes. using a molecular approach, we identified and characterized the structure of an ldlip3-lipase gene from the primitive trypanosomatid path ...201020349119
leishmania donovani: genetic diversity of isolates from sudan characterized by pcr-based rapd.drug unresponsiveness in patients with visceral leishmaniasis (vl) is a problem in many endemic areas. this study aimed to determine genetic diversity of leishmania donovani isolates from a vl endemic area in sudan as a possible explanation for drug unresponsiveness in some patients. thirty clinically stibogluconate (ssg)-sensitive isolates were made ssg-unresponsive in vitro by gradually increasing ssg concentrations. the sensitive isolates and their ssg-unresponsive counterparts were typed usi ...201020346944
[leishmania donovani delays phagolysosomal acidification]. 201020346266
water-soluble polymer-drug conjugates for combination chemotherapy against visceral leishmaniasis.there is a need for new safe, effective and short-course treatments for leishmaniasis; one strategy is to use combination chemotherapy. polymer-drug conjugates have shown promise for the delivery of anti-leishmanial agents such as amphotericin b. in this paper, we report on the preparation and biological evaluation of polymer-drug conjugates of n-(2-hydroxypropyl)methacrylamide (hpma), amphotericin b and alendronic acid. the combinatorial polymer-drug conjugates were effective anti-leishmanial a ...201020338769
a clinical isolate of leishmania donovani with its1 sequence polymorphism as a cause of para-kala-azar dermal leishmaniasis in an ethiopian human immunodeficiency virus-positive patient on highly active antiretroviral therapy.the diagnosis of para-kala-azar dermal leishmaniasis (pkdl/vl), either as an immune reconstitution inflammatory syndrome (iris)-associated syndrome or as a complication of visceral leishmaniasis (vl) during human immunodeficiency virus (hiv) co-infection in patients with or without highly active antiretroviral therapy, represents a challenge for prompt treatment. the aim of this study was to identify the causative leishmania species and to clarify whether the post-kala-azar dermal leishmaniasis ...201020331449
bone marrow aspiration findings in kala-azar.to describe the bone marrow aspiration cytologic findings in visceral leishmaniasis.201020306983
[prevalence of anti-leishmania spp antibodies in dogs from garanhuns, in the middle scrub zone (agreste) of pernambuco].considering the unknown situation regarding canine visceral leishmaniasis in garanhuns, this study had the aim of investigating occurrences of anti-leishmania spp antibodies in domesticated and partially domesticated dogs, and the possible risk factors involved.201020305967
leishmania donovani s.l.: evaluation of the proliferation potential of promastigotes using cfse staining and flow cytometry.leishmania infantum causes visceral leishmaniasis in all countries in the mediterranean basin. it uses phlebotomine sandflies as vectors where the promastigote stage develops, reproduces and becomes infective. therefore the reproductive power of the promastigotes determines the inoculum size of the isolate. ten leishmania strains from cyprus: two leishmania donovani and eight l. infantum were used to study the proliferation capacity of the promastigotes. population increase during a 6-day cultur ...201020303953
synthetic udp-furanoses inhibit the growth of the parasite leishmania.the chemical synthesis of udp-6-nhac-6-deoxy-galf was performed and it led to the isolation of both pure anomers. they were then evaluated together with the previously prepared udp-furanoses for their anti-parasitic properties against leishmania donovani promastigotes, one of the agents responsible for visceral leishmaniasis. amongst them, the unnatural 1,2-trans udp-6-nhac-galf demonstrated a high potency in inhibiting the growth of the parasite.201020303072
dynamic imaging of experimental leishmania donovani-induced hepatic granulomas detects kupffer cell-restricted antigen presentation to antigen-specific cd8 t cells.kupffer cells (kcs) represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. although kcs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific cd8(+) t cells. here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2- ...201020300603
innate killing of leishmania donovani by macrophages of the splenic marginal zone requires irf-7.highly phagocytic macrophages line the marginal zone (mz) of the spleen and the lymph node subcapsular sinus. although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. here, we have combined gene expression profiling and rnai using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal z ...201020300600
studies on haemoflagellates; a study of the growth rates of leishmania donovani, l. brasiliensis, l. tropica, and trypanosoma cruzi in culture. 194720292839
the behaviour of a sudan strain of leishmania donovani in phlebotomus papatasii; a comparison of strains of leishmania. 194720243885
molecular characterization of leishamania isolates from china by inter-simple sequence repeat polymerase chain reaction.leishmania has distinct epidemiological and biological characteristics and causes a variety of clinical symptoms. to understand the genetic diversity and the phylogenetic relationships among leishmania isolates from china, 29 leishmania isolates from different geographic origins, vectors, and hosts were analyzed using 21 inter-simple sequence repeat polymerase chain reaction (issr-pcr) primers. a total of 864 polymorphic bands were obtained. according to the results of the neighbor-joining phylo ...201020237800
re-evaluation of the euk516 probe for the domain eukarya results in a suitable probe for the detection of kinetoplastids, an important group of parasitic and free-living flagellates.two frequently used universal eukaryote probes, euk1209 and euk516, are not consistent with one branch of the eukaryotic phylogenetic tree, the kinetoplastida, which has undergone rapid evolution of their small subunit rrna gene. kinetoplastids include medically important parasitic organisms (e.g. trypanosoma, leishmania) and free-living flagellates that occur in all aquatic environments and in soils (e.g. bodo, neobodo, rhynchomonas). a modified probe presented here as kin516, now based on the ...201020236188
inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice.receptor tyrosine kinases are involved in multiple cellular processes, and drugs that inhibit their action are used in the clinic to treat several types of cancer. however, the value of receptor tyrosine kinase inhibitors (rtkis) for treating infectious disease has yet to be explored. here, we have shown in mice that administration of the broad-spectrum rtki sunitinib maleate (sm) blocked the vascular remodeling and progressive splenomegaly associated with experimental visceral leishmaniasis. fu ...201020234089
an enhanced method for the identification of leishmania spp. using real-time polymerase chain reaction and sequence analysis of the 7sl rna gene region.the accurate identification of leishmania spp. is important for the treatment of infected patients. molecular methods offer an alternative to time-consuming traditional laboratory techniques for species determination. we redesigned a 7sl rna gene-based polymerase chain reaction and sequence assay for increased species identification. dna extracted from 17 reference strains and 10 cultured clinical isolates was examined. sequence comparison was used successfully to identify organisms to the compl ...201020226334
the antiprotozoal activity of methylated flavonoids from ageratum conyzoides l.the dichloromethane extract prepared from aerial parts of ageratum conyzoides l. (asteraceae), a plant commonly used in folk medicine for a number of illnesses including sleeping sickness, was recently found to exhibit a prominent activity (ic(50)=0.78 microg/ml) against bloodstream forms of trypanosoma brucei rhodesiense, the etiologic agent of east african human trypanosomiasis (east african sleeping sickness). this extract also exhibited noticeable activities against leishmania donovani (kala ...201020219663
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