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serological evidence of leishmania donovani infection in apparently healthy dogs using direct agglutination test (dat) and rk39 dipstick tests in kafta humera, north-west ethiopia.leishmania (kinetoplastida: trypanosomatidae) are protozoan parasites of significant medical and veterinary importance. over the last decade, visceral leishmaniasis (vl) has emerged as a major opportunistic infection associated with hiv/aids in north western ethiopia. this paper reports on serological evidence of possible leishmania donovani (l. donovani) infection in dogs using two serological tests: direct agglutination test (dat) and kalazar detect rapid test (kdrt). two hundred and seventeen ...201121371289
biochemical characterization of dipeptidylcarboxypeptidase of leishmania donovani.the incidence of parasitic infection, leishmaniasis, has been steadily increasing worldwide. since, the existing chemotherapy of these diseases suffers from lack of safe and effective drugs and/or the presence of widespread drug resistance, there is an urgent need for development of potent, mechanism-based anti-parasitic agents. the peptidases of protozoan parasites are becoming increasingly important for their role in parasite survival and pathogenecity. leishmania donovani dipeptidylcarboxypep ...201121366963
distribution and ecological aspects of sand fly (diptera: psychodidae) species in sri lanka.human indigenous cutaneous leishmaniasis caused by leishmania donovani complex is endemic in sri lanka. we performed an entomological survey to determine the distribution of probable vector species. sand flies were collected in districts in the dry zone, in the wet zone highlands, and in the wet zone coastal belt of sri lanka using cdc light traps, sticky traps and cattle-baited net traps during july, 2005. the survey was reconducted in february, 2006. overall, 584 sand flies belonging to phlebo ...201121366784
ecology and control of the sand fly vectors of leishmania donovani in east africa, with special emphasis on phlebotomus orientalis.a literature review is provided on the state of knowledge of the ecology and control of the sand fly vectors of leishmania donovani in east africa, with a special emphasis on phlebotomus orientalis. visceral leishmaniasis caused by l. donovani is a major health problem in several areas in east africa. studies conducted in the past 70 years identified p. orientalis parrot and p. martini parrot as the principal vectors of l. donovani in sudan, ethiopia and kenya and p. celiae minter as the seconda ...201121366778
in vitro refolding of triosephosphate isomerase from l. donovani.the triosephosphate isomerase of leishmania donovani (ldtim) was expressed at high level in escherichia coli. the tim gene was cloned in expression vector pet-23(a) with c-terminal 6× his tag fused in frame, and expressed as a 27.6-kda protein in e. coli as inclusion bodies. the recombinant ldtim from e. coli lysate was solubilized in 6 m guanidine hydrochloride and purified by ni-nta chromatography. in the present study, the effect of bovine serum albumin on the reactivation of tim was investig ...201121365180
identification of small molecule lead compounds for visceral leishmaniasis using a novel ex vivo splenic explant model system.new drugs are needed to treat visceral leishmaniasis (vl) because the current therapies are toxic, expensive, and parasite resistance may weaken drug efficacy. we established a novel ex vivo splenic explant culture system from hamsters infected with luciferase-transfected leishmania donovani to screen chemical compounds for anti-leishmanial activity.201121358812
generating knock-in parasites: integration of an ornithine decarboxylase transgene into its chromosomal locus in leishmania donovani.leishmania null mutants created by targeted gene replacement are typically complemented with chimeric episomes harboring the replaced gene in order to validate that the observed phenotype is due to the specific gene deletion. however, the current inventory of available episomes for complementation of genetic lesions in leishmania is unstable in the absence of drug selection, and levels of gene expression cannot be controlled, especially in vivo. to circumvent this impediment, a strategy to re-in ...201121354142
bioinformatic analysis of glycogen synthase kinase 3: human versus parasite kinases.summaryobjective. glycogen synthase kinase 3 (gsk-3) is a promising target for the treatment of various human diseases such as type 2 diabetes, alzheimer's disease and inflammation. successful inhibition of the homologues of this kinase in plasmodium falciparum, trypanosoma brucei and leishmania donovani makes the kinase an attractive target for the treatment of malaria, trypanosomiasis and leishmaniasis, respectively. the aim of this work was to compare the binding sites of the gsk-3 kinases of ...201121349219
didemnidines a and b, indole spermidine alkaloids from the new zealand ascidian didemnum sp.two new indole spermidine alkaloids, didemnidines a (1) and b (2), have been isolated from the new zealand ascidian didemnum sp. the structures of the metabolites, determined by analysis of 2d nmr spectra and confirmed via synthesis, embody an indole-3-glyoxylamide moiety linked to the n(1) position of spermidine, the latter motif being particularly rare among marine natural products. didemnidine b and a synthetic precursor exhibited mild in vitro growth inhibition of plasmodium falciparum with ...201121348447
reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in leishmania amazonensis.leishmaniasis, a parasitic disease caused by protozoa of the genus leishmania, affects more than 12 million people worldwide. quercetin has generated considerable interest as a pharmaceutical compound with a wide range of therapeutic activities. one such activity is exhibited against the bloodstream parasite trypanosoma brucei and amastigotes of leishmania donovani. however, the mechanism of protozoan action of quercetin has not been studied.201121346801
visceral leishmaniasis: experimental models for drug discovery.visceral leishmaniasis (vl) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality. the causative agent is a haemoflagellate protozoan leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system. most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application. as an alternate strategy, vaccination is also under exper ...201121321417
ubiquitination of mrna cycling sequence binding protein from leishmania donovani (ldcsbp) modulates the rna endonuclease activity of its smr domain.in trypanosomatid parasites, an octanucleotide sequence (c/a)auagaa(g/a) in the utrs primarily determines the stability of s-phase specific mrnas. a multi-domain protein ldcsbp from leishmania donovani interacts with the utr of an s-phase rna containing the octanucleotide sequence through its unique ccch-type zn-finger motifs. interestingly, the rna binding protein contains a previously characterized dna endonuclease domain - smr. it has been demonstrated here that the ldcsbp smr domain independ ...201121315716
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
role of unique basic residues in cytotoxic, antibacterial and antiparasitic activities of human eosinophil cationic protein.eosinophil granule proteins, eosinophil cationic protein (ecp) and eosinophil-derived neurotoxin are members of the rnase a superfamily, which play a crucial role in host defense against various pathogens as they are endowed with several biological activities. some of the biological activities possessed by ecp have been attributed to its strong basic character. in the current study, we have investigated the role of five unique basic residues, arg22, arg34, arg61, arg77 and his64 of ecp in its ca ...201121303303
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
design and synthesis of novel tetrahydronaphthyl azoles and related cyclohexyl azoles as antileishmanial agents.a novel series of trans-2-aryloxy-1,2,3,4,-tetrahydronaphthyl azoles and related cyclohexyl azoles were synthesized and evaluated in vitro against leishmania donovani. compound 9 identified as most active analog with ic(50) value of 0.64 µg/ml and si value of 34.78 against amastigotes, and is several folds more potent than the reference drugs sodium stilbogluconate and paromomycin. it also exhibited significant in vivo inhibition of 83.33%, and provided a new structural scaffold for antileishman ...201121295472
antileishmania immunological tests for asymptomatic subjects living in a visceral leishmaniasis-endemic area in brazil.the objective of this study was to evaluate the behavior of different tests used for the diagnosis of visceral leishmaniasis (vl) in asymptomatic subjects living in an endemic area. no gold standard is available for the diagnosis of asymptomatic infection with leishmania. in continuation of a previous study, 1,017 subjects living in a vl-endemic area were clinically reevaluated. of these, 576 had at least one positive serological test in a first assessment. about 3 years after the first evaluati ...201121292896
recurrent leishmaniasis in kidney transplant recipients: report of 2 cases and systematic review of the literature.the characteristics of 8 episodes of leishmaniasis with atypical manifestations in 2 italian kidney transplant recipients are analyzed and contextualized among those of 52 other episodes of leishmaniasis observed in 19 transplant recipients found through a systematic review of the international literature. in all the patients, the initial episode was visceral leishmaniasis, which was associated with mucocutaneous involvement in 2 cases. with the exception of 1 case of post kala-azar dermal leish ...201121281418
andrographolide nanoparticles in leishmaniasis: characterization and in vitro evaluations.andrographolide (ag) is a diterpenoid lactone isolated from the leaves of andrographis paniculata. ag is a potent and low-toxicity antileishmanial agent. chemotherapy applications of ag are, however, seriously constrained because of poor bioavailability, short plasma half-life, and inappropriate tissue localization. nanoparticulation of ag was therefore envisaged as a possible solution. ag nanoparticles (agnp) loaded in 50:50 poly(dl-lactide-co-glycolic acid) were prepared for delivery into the ...201021270962
mitochondrial associated ubiquitin fold modifier-1 mediated protein conjugation in leishmania donovani.in this report, we demonstrate the existence of the ubiquitin fold modifier-1 (ufm1) and its conjugation pathway in trypanosomatid parasite leishmania donovani. ldufm1 is activated by e1-like enzyme lduba5. ldufc1 (e2) specifically interacted with ldufm1 and lduba5 to conjugate ldufm1 to proteinaceous targets. mass spectrometry analysis revealed that ldufm1 is conjugated to leishmania protein targets that are associated with mitochondria. immunofluorescence experiments showed that leishmania ufm ...201121264253
a new atp-binding cassette protein is involved in intracellular haem trafficking in leishmania.the characterization of labcg5, a new intracellular atp-binding cassette protein in leishmania donovani, is described. unlike other abcg half-transporters, labcg5 is not involved in either drug resistance or phospholipid efflux. however, we provide evidence suggesting that this protein is involved in intracellular haem trafficking. thus, downregulation of labcg5 function produced upon overexpression of an inactive version of the protein caused a dramatic growth arrest unless a haemin supplement ...201121255121
molecular detection and genetic diversity of leishmania donovani in naturally infected phlebotomus chinensi from southwestern china.zoonotic visceral leishmaniasis is an important vector-borne infectious disease in western china. in this study, an epidemiological study was carried out on the vector of zoonotic visceral leishmaniasis in rural areas from sichuan province, southwestern china. in the 1263 phlebotomine sandflies captured, 859 (68.01%) were females and 404 (31.99%) males, belonging to phlebotomus chinensis (83.37%), sergentomyia koloshanensis (6.57%), sergentomyia squamirostris (4.04%), and sergentomyia barraudi ( ...201121254870
critical role of irf-5 in the development of t helper 1 responses to leishmania donovani infection.the transcription factor interferon regulatory factor 5 (irf-5) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and tlr activation and to play an essential role in the innate inflammatory response. in this study, we used the experimental model of visceral leishmaniasis to investigate the role of irf-5 in the generation of th1 responses and in the formation of th1-type liver granulomas in leishmania donovani infected mice. we show that t ...201121253574
cocktail of gp63 and hsp70 induces protection against leishmania donovani in balb/c mice.the 63-kda antigen of leishmania donovani is a membrane-anchored matrix metalloprotease that has been shown to be involved in the infection process. we have shown that this antigen alone generates a th1 type of protective response that is partial but when the animals are primed with the antigen along with the hsp70, the level of protection is raised significantly, which is demonstrated by a considerable reduction in parasite load of immunized animals when compared to the infected controls. delay ...201121226722
species delimitation and phylogenetic relationships of chinese leishmania isolates reexamined using kinetoplast cytochrome oxidase ii gene sequences.leishmaniasis is a geographically widespread disease caused by protozoan parasites belonging to the genus leishmania and transmitted by certain species of sand fly. this disease still remains endemic in china, especially in the west and northwest frontier regions. a recent its1 phylogeny of chinese leishmania isolates has challenged some aspects for their traditional taxonomy and cladistic hypotheses of their phylogeny. however, disagreement with respect to relationships within chinese leishmani ...201121221640
combination therapy with paromomycin-associated stearylamine-bearing liposomes cures experimental visceral leishmaniasis through th1-biased immunomodulation.visceral leishmaniasis (vl) caused by the parasite leishmania donovani is a potentially fatal disease. available limited drugs are toxic, require prolonged treatment duration, and are costly. a low-cost parenteral formulation of paromomycin sulfate (pm) has recently been approved for the treatment of vl. monotherapy with pm runs the risk of development of resistance. hence, efforts are needed to develop a combination therapy of pm with other drugs to shorten the duration of treatment and prolong ...201121220536
in vitro activities of new 2-substituted quinolines against leishmania donovani.a series of 9 quinolines and 18 styrylquinolines was evaluated for the drugs' in vitro antileishmanial activities and cytotoxicities. the 7-aroylstyrylquinoline scaffold appeared to be the most promising one, with the most interesting compound, no. 35, exhibiting a 50% inhibitory concentration (ic(50)) of 1.2 μm and a selectivity index value of 121.5. compound 35 was 10-fold and 8-fold more active than miltefosine and sitamaquine, the reference compounds, with selectivity indexes 607-fold and 60 ...201121220526
the first total synthesis of the (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid and related analogs with antileishmanial activity.the first total synthesis of the marine cyclopropane fatty acid (±)-17-methyltrans- 4,5-methyleneoctadecanoic acid was accomplished in 8 steps and in 9.1% overall yield starting from 1-bromo-12-methyltridecane. the cis analog (±)-17- methyl-cis-4,5-methyleneoctadecanoic acid was also synthesized but in 7 steps and in 16.4% overall yield. with the two isomeric cyclopropane fatty acids at hand it was possible to unequivocally corroborate the trans relative configuration of the naturally occurring ...201021218160
antiprotozoal activity of sesquiterpenes from jasonia glutinosa.two sesquiterpene alcohols, [11 r]-eudesm-4(14)-en-5ß,11,12-triol ( 1 ) and [11r]-eudesm-4(14)-en-5a,11-12-triol ( 2 ), from jasonia glutinosa aerial parts (asteraceae), have been tested using an in vitro technique against leishmania donovani (promastigote forms) and plasmodium falciparum . sesquiterpene 1 was not effective at the assayed concentrations. sesquiterpene 2 was found to be active against leishmania donovani and plasmodium falciparum .200021214458
antileishmanial efficacy of fluconazole and miltefosine in combination with an immunomodulator--picroliv.the chemotherapy of visceral leishmaniasis (vl) has several limitations including resistance and toxicity of the existing drugs. downregulation of immune system further aggravates the problems. to combat this situation, leishmanicidal efficacy of already marketed standard antifungal drug, fluconazole under the approach of "therapeutic switching" in combination with standard antileishmanial drug, miltefosine, and a potent immunomodulator agent, picroliv, were evaluated in hamsters infected with l ...201121212980
post-transcriptional repair of a split heat shock protein 90 gene by mrna trans-splicing.heat shock protein 90 participates in diverse biological processes ranging from protein folding, cell cycle, signal transduction and development to evolution in all eukaryotes. it is also critically involved in regulating growth of protozoa such as dictyostelium discoideum, leishmania donovani, plasmodium falciparum, trypanosoma cruzi, and trypanosoma evansi. selective inhibition of hsp90 has also been explored as an intervention strategy against important human diseases such as cancer, malaria, ...201121209094
structure of recombinant leishmania donovani pteridine reductase reveals a disordered active site.pteridine reductase (ptr1) is a potential target for drug development against parasitic trypanosoma and leishmania species, protozoa that are responsible for a range of serious diseases found in tropical and subtropical parts of the world. as part of a structure-based approach to inhibitor development, specifically targeting leishmania species, well ordered crystals of l. donovani ptr1 were sought to support the characterization of complexes formed with inhibitors. an efficient system for recomb ...201021206018
longlasting insecticidal nets for prevention of leishmania donovani infection in india and nepal: paired cluster randomised trial.to test the effectiveness of large scale distribution of longlasting nets treated with insecticide in reducing the incidence of visceral leishmaniasis in india and nepal.201021190965
prevention of leishmania donovani infection. 201021190964
atp independent type ib topoisomerase of leishmania donovani is stimulated by atp: an insight into the functional mechanism.most type ib topoisomerases do not require atp and mg(2+) for activity. however, as shown previously for vaccinia topoisomerase i, we demonstrate that atp stimulates the relaxation activity of the unusual heterodimeric type ib topoisomerase from leishmania donovani (ldtop1l/s) in the absence of mg(2+). the stimulation is independent of atp hydrolysis but requires salt as a co-activator. atp binds to ldtop1l/s and increases its rate of strand rotation. docking studies indicate that the amino acid ...201021186185
oral putrescine restores virulence of ornithine decarboxylase-deficient leishmania donovani in mice.administration of putrescine as a 1% solution in the drinking water ameliorated the profound loss of virulence exhibited by ornithine decarboxylase (odc) deficient leishmania donovani in mice. furthermore, supplying α-difluoromethylornithine, an odc inhibitor, at 2% in the drinking water reduced but did not eliminate infection with wild type l. donovani in the mouse model. taken collectively, these findings: (1) demonstrate that oral putrescine can access the phagolysosome of macrophages in whic ...201021182873
monitoring of intracellular nitric oxide in leishmaniasis: its applicability in patients with visceral leishmaniasis.nitric oxide (no) has been demonstrated to be a principal effector molecule responsible for mediating intracellular killing of leishmania parasites, the causative organism of leishmaniasis. as measurement of intracellular no remains a challenge to biologists, we have developed a flow cytometric approach to perform real time biological detection of no within leishmania parasites and parasitized macrophages using a membrane permeable derivative of diaminofluorescein [4,5-diaminofluorescein diaceta ...201121182181
synthesis and antiprotozoal activity of n-alkoxy analogues of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine with improved human blood-brain barrier permeability.to improve the blood-brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five n-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and n-alkoxy-n-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). this involved: (a) formation of a thiourea intermediate, (b) removal of the amine protecting groups, and (c) intramolecular cyclization. the blood-brain ...201021175162
activity and turnover of eosinophil and neutrophil granulocytes are altered in visceral leishmaniasis.visceral leishmaniasis (vl) is a health issue in sudan. our aim was to investigate the involvement of eosinophils and neutrophils in vl by serum and plasma measurements of eosinophil cationic protein (ecp) and myeloperoxidase (mpo) and some key cytokines and chemokines. blood was collected from 125 vl patients and 181 healthy sudanese controls from the same rural area. results showed reduced eosinophil and neutrophil counts in the vl group (p=0.0001 and p=0.002, respectively). serum-ecp levels w ...201021172349
lysine transporters in human trypanosomatid pathogens.in previous studies we characterized arginine transporter genes from trypanosoma cruzi and leishmania donovani, the etiological agents of chagas disease and kala azar, respectively, both fatal diseases in humans. unlike arginine transporters in higher eukaryotes that transport also lysine, these parasite transporters translocate only arginine. this phenomenon prompted us to identify and characterize parasite lysine transporters. here we demonstrate that ldaap7 and tcaap7 encode lysine-specific p ...201021170560
persistence of leishmania donovani antibodies in past visceral leishmaniasis cases in india.the persistence of anti-leishmania donovani antibodies in past visceral leishmaniasis (vl) cases was retrospectively assessed by means of the direct agglutination test (dat) and the rk39 enzyme-linked immunosorbent assay (elisa). antibody titers remained high for an extended period of time in past cases of vl. these results highlight the need to carefully elicit the history of patients with vl symptoms.201021159922
complete structural assignment of serratol, a cembrane-type diterpene from boswellia serrata, and evaluation of its antiprotozoal activity.from the dichloromethane extract obtained from the gum resin of boswellia serrata roxb. (burseraceae), a well-known medicinal plant resin ("indian olibanum"), the cembrane-type diterpene serratol was isolated in high yield. its structure, previously reported without clear specification of double-bond geometry and without specification of stereochemistry, was reanalysed by means of spectroscopic measurements and unambiguously assigned as s(-)-cembra-3 e,7 e,11 e-triene-1-ol. full assignment of al ...201021157686
monitoring of intracellular nitric oxide in leishmaniasis: its applicability in patients with visceral leishmaniasis.nitric oxide (no) has been demonstrated to be a principal effector molecule responsible for mediating intracellular killing of leishmania parasites, the causative organism of leishmaniasis. as measurement of intracellular no remains a challenge to biologists, we have developed a flow cytometric approach to perform real time biological detection of no within leishmania parasites and parasitized macrophages using a membrane permeable derivative of diaminofluorescein [4,5-diaminofluorescein diaceta ...201021154977
metabolomics to unveil and understand phenotypic diversity between pathogen populations.leishmaniasis is a debilitating disease caused by the parasite leishmania. there is extensive clinical polymorphism, including variable responsiveness to treatment. we study leishmania donovani parasites isolated from visceral leishmaniasis patients in nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for l. donovani t ...201021152055
interferon regulatory factor 7 contributes to the control of leishmania donovani in the mouse liver.optimal hepatic resistance to leishmania donovani in mice requires the coordinated effort of a variety of leukocyte populations that together induce activation of local macrophages to a leishmanicidal state. although nitric oxide and reactive oxygen intermediates are potent leishmanicidal effector molecules operating in the acquired phase of immunity, there have long been suggestions that other mechanisms of leishmanicidal activity exist. we recently discovered that irf-7 regulates a novel innat ...201021149596
proteomic approaches for discovery of new targets for vaccine and therapeutics against visceral leishmaniasis.visceral leishmaniasis (vl) is the most devastating type caused by leishmania donovani, leishmania infantum, and leishmania chagasi. the therapeutic mainstay is still based on the antiquated pentavalent antimonial against which resistance is now increasing. unfortunately, due to the digenetic life cycle of parasite, there is significant antigenic diversity. there is an urgent need to develop novel drug/vaccine targets against vl for which the primary goal should be to identify and characterize t ...200821136840
in vitro and in vivo prophylactic and curative activity of the triterpene saponin px-6518 against cutaneous leishmania species.the oleanane triterpene saponin px-6518, with known potent in vitro and in vivo activity against leishmania donovani, was investigated for its spectrum against the cutaneous species leishmania mexicana, leishmania panamensis and leishmania major.201021131319
first total synthesis and antileishmanial activity of (z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge dragmaxia undata.the first total synthesis for the (z)-16-methyl-11-heptadecenoic acid, a novel fatty acid from the sponge dragmaxia undata, was accomplished in seven steps and in a 44% overall yield. the use of (trimethylsilyl)acetylene was key in the synthesis. based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 10-bromo-1-decanol followed by a second acetylide coupling ...201021129369
post-kala-azar dermal leishmaniasis--an overview.post-kala-azar dermal leishmaniasis (pkdl) is a dermal sequela of visceral leishmaniasis (vl), reported mainly from two regions - sudan in eastern africa and the indian subcontinent, with incidences of 50-60% and 5-10%, respectively. importantly, patients with pkdl are considered as reservoirs of vl, linking its eradication to effective control of pkdl. the etiopathogenesis of pkdl is presumably due to an immunological assault on latent dermal parasites. immunological markers include il-10, whos ...201021128917
in silico screening, structure-activity relationship, and biologic evaluation of selective pteridine reductase inhibitors targeting visceral leishmaniasis.in this study we utilized the concept of rational drug design to identify novel compounds with optimal selectivity, efficacy and safety, which would bind to the target enzyme pteridine reductase 1 (ptr1) in leishmania parasites. twelve compounds afforded from baylis-hillman chemistry were docked by using the quantum program into the active site of leishmania donovani ptr1 homology model. the biological activity for these compounds was estimated in green fluorescent protein-transfected l. donovan ...201021115787
inference of population structure of leishmania donovani strains isolated from different ethiopian visceral leishmaniasis endemic areas.parasites' evolution in response to parasite-targeted control strategies, such as vaccines and drugs, is known to be influenced by their population genetic structure. the aim of this study was to describe the population structure of ethiopian strains of leishmania donovani derived from different areas endemic for visceral leishmaniasis (vl) as a prerequisite for the design of effective control strategies against the disease.201021103373
valeriana wallichii root extracts and fractions with activity against leishmania spp.leishmanial diseases, posing a public health problem worldwide, are caused by leishmania parasites with a dimorphic life cycle alternating between the promastigote and amastigote forms. promastigotes transmitted by the vector are transformed into amastigotes residing in the host tissue macrophages. presently, new antiparasitic agents are needed against leishmania donovani and leishmania major, the respective organisms causing visceral and cutaneous leishmaniasis, since the available treatments a ...201021085992
leishmania major survival in selective phlebotomus papatasi sand fly vector requires a specific scg-encoded lipophosphoglycan galactosylation pattern.phlebotomine sand flies that transmit the protozoan parasite leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. in "selective" sand flies, leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (lpg), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (pg ...201021085609
adaptive immunity against leishmania nucleoside hydrolase maps its c-terminal domain as the target of the cd4+ t cell-driven protective response.nucleoside hydrolases (nhs) show homology among parasite protozoa, fungi and bacteria. they are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. immune protection against nhs would prevent disease at the early infection of several pathogens. we have identified the domain of the nh of l. donovani (nh36) responsible for its immunogenicity and protective efficacy against murine visceral lei ...201021085470
simple data-reduction method for high-resolution lc-ms data in metabolomics.metabolomics lc-ms experiments yield large numbers of peaks, few of which can be identified by database matching. many of the remaining peaks correspond to derivatives of identified peaks (e.g., isotope peaks, adducts, fragments and multiply charged molecules). in this article, we present a data-reduction approach that automatically identifies these derivative peaks.200921083103
antileishmanial activity of benzocycloalkyl azole oximino ethers: the conformationally constraint analogues of oxiconazole.antileishmanial activities of 16 synthetic oximino benzocycloalkyl azoles against leishmania donovani were evaluated in vitro against extracellular promastigotes and intracellular amastigotes. based on si (selectivity index), five compounds were tested further in vivo in hamster model. out of these, three compounds have shown medium activity (53-58%) and one has shown significant inhibition of parasite multiplication (70%). despite the fact that these compounds were better than the existing anti ...201021078278
leishmania donovani: assessment of leishmanicidal effects of herbal extracts obtained from plants in the visceral leishmaniasis endemic area of bihar, india.one obstacle faced in the effective control of visceral leishmaniasis (vl) is the limited number of available treatment options. furthermore, control efforts have been hindered further by the emergence of leishmania resistance to many of the available drugs. in this study, we investigated the anti-leishmanial properties of 30 medicinally important plants from the vl endemic area of bihar, india and compared them to two available anti-leishmanial drugs (sodium antimony gluconate and amphotericin ...201021070771
a rapid, efficient and economical method for generating leishmanial gene targeting constructs.targeted gene replacement is a powerful tool in leishmania genetics that can be time-consuming to implement. one tedious aspect that delays progress is the multi-step construction of gene targeting vectors. to accelerate this process, we developed a streamlined method that allows the assembly of a complete targeting vector from all its constituent parts in a single-step multi-fragment ligation. the individual components to be assembled are flanked by sites for the restriction endonuclease sfii t ...201021055426
paromomycin for the treatment of visceral leishmaniasis in sudan: a randomized, open-label, dose-finding study.a recent study has shown that treatment of visceral leishmaniasis (vl) with the standard dose of 15 mg/kg/day of paromomycin sulphate (pm) for 21 days was not efficacious in patients in sudan. we therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.201021049063
geographical variation in the response of visceral leishmaniasis to paromomycin in east africa: a multicentre, open-label, randomized trial.visceral leishmaniasis (vl) is a major health problem in developing countries. the untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. improved treatment options are needed. paromomycin was shown to be an efficacious first-line treatment with low toxicity in india.201021049059
insecticide susceptibility of phlebotomus argentipes in visceral leishmaniasis endemic districts in india and nepal.to investigate the ddt and deltamethrin susceptibility of phlebotomus argentipes, the vector of leishmania donovani, responsible for visceral leishmaniasis (vl), in two countries (india and nepal) with different histories of insecticide exposure.201021049013
antileishmanial phenylpropanoids from alpinia galanga (linn.) willd.hexane, chloroform and ethyl acetate extracts (100 microg/ml) of alpinia galanga rhizomes exhibited significant activity in vitro against promastigotes of l. donovani. twelve compounds namely, methyleugenol (1), p-coumaryl diacetate (2), 1'-acetoxychavicol acetate (3), 1'-acetoxyeugenol acetate (4), trans-p-acetoxycinnamyl alcohol (5), trans-3,4-dimethoxycinnamyl alcohol (6), p-hydroxybenzaldehyde (7), p-hydroxycinnamaldehyde (8), trans-p-coumaryl alcohol (9), galangin (10), trans-p-coumaric aci ...201021046987
[leishmaniasis isolated to the larynx as cause of chronic laryngitis].mucosal leishmaniasis is uncommon outside central and south america, where it is commonly caused by leishmania (l.) braziliensis. we present a case of isolated laryngeal leishmaniasis detected in a 78-year-old male, who presented with chronic hoarseness. histologic examination of biopsies taken from the larynx showed l. amastigotes. an l.-specific indirect fluorescent antibody test was positive. polymerase chain reaction showed infection with l. donovani, l. infantum or l. tropica, species which ...201021040662
antimicrobial, antimalarial, and antileishmanial activities of mono- and bis-quaternary pyridinium compounds.pyridinium-based oxime compounds have been utilized worldwide as antidotes following exposure to anticholinesterase agents. in the event of combined chemical and biological incident, it is of vital importance to know the ability of antidotes to provide additional protection against biological threats. this paper reports results of in vitro antimicrobial and antiprotozoal activities of a series of quaternary pyridinium oximes against a number of lower pathogenicity bsl-1 and 2 agents. in general, ...201021040494
visceral leishmaniasis mimicking lymphoproliferative disease. 201021037515
validation of a leishmania infantum elisa rapid test for serological diagnosis of leishmania chagasi in dogs.canine visceral leishmaniasis (cvl) is caused by leishmania donovani complex parasites including l. donovani, leishmania infantum and leishmania chagasi. as some studies suggest that l. chagasi and l. infantum may be very similar or even the same species, the aim of the present study was to evaluate a commercial rapid elisa test, originally designed for l. infantum, in the diagnosis of cvl in dogs naturally infected by l. chagasi. a total of 400 serum canine samples, including 283 positive dogs ...201021030153
two exogenous cases of visceral leishmaniasis (kalaazar) in the united states with notes on cultivation of leishmania donovani in vitro. 194521010820
difference in responses of leishmania canis and leishmania donovani toward ureastibamine. 194520997131
the effect of treatment on the spleen of the golden hamster (cricetus auratus) infected with leishmania donovani. 194620989194
the action in vitro of diamidines and other compounds on leishmania donovani. 194620984396
visceral leishmaniasis in a case of acute lymphoblastic leukemia at both remission and relapse, diagnosed by bone marrow aspiration. 201020968169
the oligopeptidase b of leishmania regulates parasite enolase and immune evasion.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 targets for the development of new anti-parasitic therapy. protozoan parasites like leishmania predominantly express clan ca cysteine proteases for key life cycle functions. it was therefore unexpected to find a high level of serine protease activity expressed by leishmania donovani. purificati ...201020961853
enhanced case detection and improved diagnosis of pkdl in a kala-azar-endemic area of bangladesh.to support the bangladesh national kala-azar elimination programme (nkep), we investigated the feasibility of using trained village volunteers for detecting post-kala-azar dermal leishmaniasis (pkdl) cases, using polymerase chain reaction (pcr) for confirmation of diagnosis and treatment compliance by pkdl patients in kanthal union of trishal sub-district, mymensingh, bangladesh.201020957193
mechanism of interaction of sitamaquine with leishmania donovani.this study focuses on the mechanism of interaction of sitamaquine with leishmania donovani membranes, and its accumulation within the parasites.201020956354
multiple levels of gene regulation mediate differentiation of the intracellular pathogen leishmania.for many years, mrna abundance has been used as the surrogate measure of gene expression in biological systems. however, recent genome-scale analyses in both bacteria and eukaryotes have revealed that mrna levels correlate with steady-state protein abundance for only 50-70% of genes, indicating that translation and post-translation processes also play important roles in determining gene expression. what is not yet clear is whether dynamic processes such as cell cycle progression, differentiation ...201020952481
vaccination with recombinant leishmania donovani gamma-glutamylcysteine synthetase fusion protein protects against l. donovani infection.visceral leishmaniasis presents a serious health threat in many parts of the world. there is, therefore, an urgent need for an approved vaccine for clinical use to protect against infection. in this study, the ability of recombinant leishmania donovani gamma-glutamyl cysteine synthetase protein (ldγgcs) alone or incorporated into a non-ionic surfactant vesicle (niv) delivery system to protect against l. donovani infection was evaluated in a balb/c mouse model. immunization with ldγgcs alone or l ...201020950100
yield, content, and composition of peppermint and spearmints as a function of harvesting time and drying.peppermint ( mentha × piperita l.) and spearmints ('scotch' spearmint, m. × gracilis sole, and 'native' spearmint, mentha spicata l.) are widely grown essential oil crops in more northern latitudes; however, there is limited information on how harvest time and drying influence peppermint and spearmint yield, oil composition, and bioactivity, when grown south of the 41st parallel. in this 2-year study, the effects of harvest time and drying on the yield, oil composition, and bioactivity of pepper ...201020942459
first computational chemistry multi-target model for anti-alzheimer, anti-parasitic, anti-fungi, and anti-bacterial activity of gsk-3 inhibitors in vitro, in vivo, and in different cellular lines.in the work described here, we developed the first multi-target quantitative structure-activity relationship (qsar) model able to predict the results of 42 different experimental tests for gsk-3 inhibitors with heterogeneous structural patterns. gsk-3β inhibitors are interesting candidates for developing anti-alzheimer compounds. gsk-3β are also of interest as anti-parasitic compounds active against plasmodium falciparum, trypanosoma brucei, and leishmania donovani; the causative agents for mala ...201020931280
adaptive responses to purine starvation in leishmania donovani.starvation of leishmania donovani parasites for purines leads to a rapid amplification in purine nucleobase and nucleoside transport. studies with nucleoside transport-deficient l. donovani indicate that this phenomenon is mediated by the nucleoside transporters ldnt1 and ldnt2, as well as by the purine nucleobase transporter ldnt3. the escalation in nucleoside transport cannot be ascribed to an increase in either ldnt1 or ldnt2 mrna. however, western analyses on parasites expressing epitope-tag ...201020923417
characterization of amplicons that suppress the conditional lethal growth phenotype of a leishmania donovani mutant lacking normal purine salvage mechanisms.a conditionally lethal mutant of leishmania donovani that lacks both hypoxanthine-guanine phosphoribosyltransferase and xanthine phosphoribosyltransferase exhibits a strikingly restricted growth phenotype, can only survive as the promastigote under pharmacological constraints, and is profoundly compromised in its ability to infect macrophages and mice. interestingly, the conditionally lethal growth phenotype displayed by these mutant parasites can be suppressed in vitro by selection of strains t ...201020888372
comparison of diagnostic methods in cutaneous leishmaniasis (histopathology compared to skin smears).present study is carried out to compare laboratory diagnostic methods of cutaneous leishmaniasis (cl) for the outdoor patients of bolan medical college complex hospital, quetta, balochistan. from november 2005 to december 2007, three hundred cases of cl patients were selected without restriction of age and sex. the lesions were divided into two groups. early with duration less than 2 months and late duration between 2 to 4 months and were noted as nodules, plaques, ulcers and scarring (in case o ...201020884447
leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells.we investigated the properties of leishmania exosomes with respect to influencing innate and adaptive immune responses. exosomes from leishmania donovani modulated human monocyte cytokine responses to ifn-γ in a bimodal fashion by promoting il-10 production and inhibiting that of tnf-α. moreover, these vesicles were inhibitory with respect to cytokine responses (il-12p70, tnf-α, and il-10) by human monocyte-derived dendritic cells. exosomes from wild-type (wt) l. donovani failed to prime monocyt ...201020881185
disruption of the lipid-transporting ldmt-ldros3 complex in leishmania donovani affects membrane lipid asymmetry but not host cell invasion.maintenance and regulation of the asymmetric lipid distribution across eukaryotic plasma membranes is governed by the concerted action of specific membrane proteins controlling lipid movement across the bilayer. here, we show that the miltefosine transporter (ldmt), a member of the p4-atpase subfamily in leishmania donovani, and the cdc50-like protein ldros3 form a stable complex that plays an essential role in maintaining phospholipid asymmetry in the parasite plasma membrane. loss of either ld ...201020865154
treatment of visceral leishmaniasis in 2010: direction from bihar state, india. 201020860475
tgf-β-regulated tyrosine phosphatases induce lymphocyte apoptosis in leishmania donovani-infected hamsters.visceral leishmaniasis, which is caused by leishmania donovani, is one of the major health problems of the indian subcontinent. infected hosts have been reported to have impaired lymphoproliferation. however, the fate of anergic cells is still elusive. in the present investigation, l. donovani-infected hamsters were used to study the mechanism of lymphocyte cell death. lymph node-derived lymphocytes were analysed for apoptotic death through mitochondrial abnormality, caspase activity and dna deg ...201120856262
2-hexadecynoic acid inhibits plasmodial fas-ii enzymes and arrests erythrocytic and liver stage plasmodium infections.acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. in this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (hdas) and evaluated their in vitro activity against erythrocytic (blood) stages of plasmodium falciparum and liver stages of plasmodium yoelii infections. since the type ii fatty acid biosynthesis pathway (pffas-ii) has recently been shown to be indispensable for liver stage malaria parasites, t ...201020855214
synthesis and biological evaluation of indolyl glyoxylamides as a new class of antileishmanial agents.a series of indolylglyoxylamide derivatives have been synthesized and evaluated in vitro against amastigote form of leishmania donovani. compound 8c has been identified as the most active analog of the series with ic(50) value of 5.17μm and si value of 31.48, and is several folds more potent than the standard drugs sodium stilbogluconate and pentamidine.201020850302
immunomodulatory effect of picroliv on the efficacy of paromomycin and miltefosine in combination in experimental visceral leishmaniasis.combination therapy for the treatment of visceral leishmaniasis has increasingly been advocated as a way to increase treatment efficacy and tolerance, to reduce treatment duration and cost, and to limit the emergence of drug resistance. in the present work, we have adopted a rational approach, which can modulate the immune response to overcome the negative control systems and to boost the positive killing responses. this study was designed to investigate the immunomodulatory effect of picroliv ( ...201120846525
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
proteome mapping of overexpressed membrane-enriched and cytosolic proteins in sodium antimony gluconate (sag) resistant clinical isolate of leishmania donovani.this study aimed to identify differentially overexpressed membrane-enriched as well as cytosolic proteins in sag sensitive and resistant clinical strains of l. donovani isolated from vl patients which are involved in the drug resistance mechanism.201020840452
antileishmanial and antitrypanosomal activities of the 8-aminoquinoline tafenoquine.the 8-aminoquinoline tafenoquine showed significant in vitro activity against leishmania species, including l. donovani amastigotes in macrophages, with 50% inhibitory concentrations (ic(50)s) between 0.1 and 4.0 μm for both pentavalent antimony (sbv)-sensitive and sbv-resistant strains and by oral administration in balb/c mice, with 50% effective dose (ed(50)) values of 1.2 to 3.5 mg/kg for 5 days. tafenoquine was less active against intracellular trypanosoma cruzi amastigotes, with an ic(50) o ...201020837750
experimental chemotherapy with allium sativum (liliaceae) methanolic extract in rodents infected with leishmania major and leishmania donovani.several plant products have been tested and found to possess antileishmanial activity. the present study was undertaken to establish whether methanolic extract of allium sativum linn has antileishmanial activity in comparison to standard drugs.201020834086
synthesis and evaluation of original amidoximes as antileishmanial agents.an original series of amidoxime derivatives was synthesized using manganese(iii) acetate, buchwald-hartwig and heck reactions. two amidoximes (39 and 52) showed interesting in vitro activities toward leishmania donovani promastigotes, exhibiting 8.3 and 8.8 μm ic(50) values. moreover, the cytotoxicity of these compounds was evaluated on human thp1 cells, giving access to the corresponding selectivity index. among the 25 tested compounds, amidoximes 38 and 39 and diamidoximes 50 and 52 exhibited ...201020833057
leishmania donovani promastigotes evade the antimicrobial activity of neutrophil extracellular traps.upon their recruitment to a site of infection and their subsequent activation, neutrophils release dna and a subset of their granule content to form filamentous structures, known as neutrophil extracellular traps, which capture and kill microorganisms. in this study, we show that leishmania promastigotes induced the rapid release of neutrophil extracellular traps from human neutrophils and were trapped by these structures. the use of leishmania mutants defective in the biosynthesis of either lip ...201020826753
cumulative cardiac toxicity of sodium stibogluconate and amphotericin b in treatment of kala-azar.kala-azar or visceral leishmaniasis is a disseminated protozoal infection caused by parasites of the genus leishmania (leishmania donovani in india). conventional therapy for visceral leishmaniasis continues to be pentavalent antimony (sodium antimony gluconate [sag]). amphotericin b is widely used for sag-unresponsive cases and sometimes even as a first-line drug, especially in endemic areas. with the conventional regimen of sag, cardiac toxicity has been reported in 8% to 17% of cases with 5% ...201120823781
antiprotozoal activities of some constituents of markhamia tomentosa (bignoniaceae).phytochemical investigation of an ethyl-acetate extract of the stem bark of markhamia tomentosa (bignoniaceae), which had good antimalarial activity in vitro, resulted in the isolation of eight known compounds: 2-acetylnaphtho[2,3-b]furan-4,9-dione (1), 2-acetyl-6-methoxynaphtho[2,3-b]furan-4,9-dione (2), oleanolic acid (3), pomolic acid (4), 3-acetylpomolic acid (5), tormentic acid (6), beta-sitosterol (7) and beta-sitosterol-3-o-beta-d-glucopyranoside (8). the structures of these compounds wer ...201020819307
liquid nitrogen cryotherapy on leishmania donovani cutaneous leishmaniasis.abstract objective: to evaluate the efficacy and the safety of liquid nitrogen cryotherapy (ln) on leishmania donovani cutaneous leishmaniasis and on type v skin. methods: ln was applied to 65 patients (121 lesions) using cotton swabs attached to ekels. cryosessions were performed for 15-20 seconds, two per site, weekly for 1-3 weeks, fortnightly for 4-5 weeks and then monthly until cure. patients were followed-up for 6 months after cure. results: a total of 91.7% of patients were cured within o ...201020818996
iron enhances generation of free radicals by artemisinin causing a caspase-independent, apoptotic death in leishmania donovani promastigotes.an increasing incidence of unresponsiveness to antimonials in leishmaniasis has led to identification of plant-derived anti-leishmanial compounds like artemisinin. since iron-mediated generation of free radicals sustains the anti-malarial activity of artemisinin, this study investigated whether similar mechanisms accounted for its activity in leishmania promastigotes. artemisinin effectively disrupted the redox potential via an increased generation of free radicals along with a decrease in level ...201020815780
linking in vitro and in vivo survival of clinical leishmania donovani strains.leishmania donovani is an intracellular protozoan parasite that causes a lethal systemic disease, visceral leishmaniasis (vl), and is transmitted between mammalian hosts by phlebotomine sandflies. leishmania expertly survives in these 'hostile' environments with a unique redox system protecting against oxidative damage, and host manipulation skills suppressing oxidative outbursts of the mammalian host. treating patients imposes an additional stress on the parasite and sodium stibogluconate (ssg) ...201020808916
selective fusion of azurophilic granules with leishmania-containing phagosomes in human neutrophils.leishmania parasites use polymorphonuclear neutrophils as intermediate hosts before their ultimate delivery to macrophages following engulfment of parasite-infected neutrophils. this leads to a silent and unrecognized entry of leishmania into the macrophage host cell. neutrophil function depends on its cytoplasmic granules, but their mobilization and role in how leishmania parasites evade intracellular killing in neutrophils remain undetermined. here, we have found by ultrastructural approaches ...201020801889
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