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leishmania donovani-specific 25- and 28-kda urinary proteins activate macrophage effector functions, lymphocyte proliferation and th1 cytokines production.growing incidence of drug resistance against leishmaniasis in endemic areas and limited drug options necessitates the need for a vaccine. notwithstanding significant leishmanial research in the past decades, a vaccine candidate is far from reality. in this study, we report the potential of two urinary leishmanial proteins to induce macrophage effector functions, inflammatory cytokines production and human lymphocytes proliferation. a total four proteins of molecular mass 25, 28, 54 and 60 kda we ...201323334693
identification and functional characterization of leishmania donovani secretory peroxidase: delineating its role in nramp1 regulation.leishmania silently evades host immune system and establish in the hostile environment of host macrophage phagolysosomes. for differentiation, growth and division parasite acquires divalent cations especially iron from the host nutritive pool. natural resistance associated with macrophage protein1 (nramp1), a cation transporter that effluxes out divalent cations specifically iron from phagosomal milieu to the cytosol, to create ions deprived status for pathogenic microorganisms. the mechanisms o ...201323326430
synthesis of perspicamide a and related diverse analogues: their bioevaluation as potent antileishmanial agents.the first protocol for the synthesis of perspicamide a and related diverse analogues has been developed from economical and readily available starting materials. furthermore, a few synthesized analogues, 24a, 24b, 24c, 24d, and 24l, exhibited potent activity against leishmania donovani with ic(50) values ranging from 3.75 to 10.37 μm and a selectivity index (si) ranging from 9.58 to 53.12, which is improved compared to the standard drug miltefosine (ic(50) 12.4 μm and si 4.1).201323289499
lc-ms metabolomics from study design to data-analysis - using a versatile pathogen as a test case.thanks to significant improvements in lc-ms technology, metabolomics is increasingly used as a tool to discriminate the responses of organisms to various stimuli or drugs. in this minireview we discuss all aspects of the lc-ms metabolomics pipeline, using a complex and versatile model organism, leishmania donovani, as an illustrative example. the benefits of a hyphenated mass spectrometry platform and a detailed overview of the entire experimental pipeline from sampling, sample storage and sampl ...201324688684
leishmaniasis: an update of current pharmacotherapy.leishmaniasis broadly manifests as visceral leishmaniasis (vl), cutaneous leishmaniasis (cl) and mucocutaneous leishmaniasis (mcl). the treatment of vl is challenging. the duration of treatment is long, and drugs are toxic thereby needing monitoring and hospitalization.201323256501
human hepatic stellate cells in primary culture are safe targets for leishmania donovani.leishmania parasites can escape the immune response by invading cell types lacking leishmanicidal mechanisms. silent persistence of leishmania parasites in the host organism is responsible for asymptomatic carriage and relapses after cured leishmaniasis. here, we studied the interaction between hepatic stellate cells (hsc) and leishmania. an original model of human hsc in primary culture infected with l. donovani was developed. the presence of intracellular parasites was studied and quantified u ...201323253952
unresponsiveness of mycobacterium w vaccine in managing acute and chronic leishmania donovani infections in mouse and hamster.the role of mycobacterium w (mw) vaccine as an immunomodulator and immunoprophylactant in the treatment of mycobacterial diseases (leprosy and pulmonary tuberculosis) is well established. the fact that it shares common antigens with leishmanial parasites prompted its assessment as an immunostimulant and as an adjunct to known anti-leishmanials that may help in stimulating the suppressed immune status of leishmania donovani-infected individuals. the efficacy of mw vaccine was assessed as an immun ...201323253783
visceral and post-kala-azar dermal leishmaniasis isolates show significant difference in their in vitro drug susceptibility pattern.visceral leishmaniasis (vl) remains a major health problem in old world, and india accounts for half of the world burden. the widespread emergence of resistance to standard drug in india poses a major obstacle in the control of leishmaniasis. post-kala-azar dermal leishmaniasis (pkdl) is considered as main source of drug resistance. experimental data indicate that resistance against newer drugs is also imminent. therefore, in vitro studies were carried out to test minimum parasiticidal concentra ...201323242321
validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of leishmania donovani.simple, cost-effective approach for routine surveillance of parasite susceptibility to antileishmanial drug miltefosine (mil) is highly desirable for controlling emergence of drug resistance in visceral leishmaniasis (vl). we validated a simple resazurin-based fluorimetric assay using promastigotes to track natural mil tolerance in leishmania donovani parasites from vl cases (n = 17) against standard amastigote assay, in two different labs in india. the inter-stage mil susceptibility correlated ...201323239091
noncovalent complexation of amphotericin-b with poly(α-glutamic acid).a noncovalent complex of amphotericin b (amb) and poly(α-glutamic acid) (pga) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. the loading of amb in the complex was in the range of ∼20-50%. amb was in a highly aggregated state with an aggregation ratio often above 2.0. this complex (amb-pga) was shown to be stable and to have reduced toxicity to human red blood cells and kb cells compared to the parent compound; cell viability was not affected at an amb c ...201323234235
different susceptibilities of leishmania spp. promastigotes to the annona muricata acetogenins annonacinone and corossolone, and the platymiscium floribundum coumarin scoparone.leishmaniasis is a zoonotic disease that can manifest itself in visceral and cutaneous form. the aim of this study was to search for new leishmanicidal compounds. preliminarily, artemia salina assay was applied to compounds from two plants found in northeastern brazil, platymiscium floribundum and annona muricata. then these compounds were tested against three leishmania species (leishmania donovani, leishmania mexicana and leishmania major). a screening assay using luciferase-expressing promast ...201323232251
identification of tunisian leishmania spp. by pcr amplification of cysteine proteinase b (cpb) genes and phylogenetic analysis.discrimination of the old world leishmania parasites is important for diagnosis and epidemiological studies of leishmaniasis. we have developed pcr assays that allow the discrimination between leishmania major, leishmania tropica and leishmania infantum tunisian species. the identification was performed by a simple pcr targeting cysteine protease b (cpb) gene copies. these pcr can be a routine molecular biology tools for discrimination of leishmania spp. from different geographical origins and d ...201323228525
leishmanization revisited: immunization with a naturally attenuated cutaneous leishmania donovani isolate from sri lanka protects against visceral leishmaniasis.leishmaniasis is a neglected tropical disease caused by leishmania protozoa and associated with three main clinical presentations: cutaneous, mucocutaneous and visceral leishmaniasis. visceral leishmaniasis is the second most lethal parasitic disease after malaria and there is so far no human vaccine. leishmania donovani is a causative agent of visceral leishmaniasis in south east asia and eastern africa. however, in sri lanka, l. donovani causes mainly cutaneous leishmaniasis, while visceral le ...201323219435
assessing the essentiality of leishmania donovani nitroreductase and its role in nitro drug activation.the nitroimidazole fexinidazole has potential as a safe and effective oral drug therapy for the treatment of visceral leishmaniasis. to date, nitroheterocyclics have not been used in the treatment of leishmaniasis, and relatively little is known about their mechanism of action. in african trypanosomes, nitro drugs are reductively activated by a type i nitroreductase (ntr), absent in mammalian cells. modulation of nitroreductase levels in trypanosoma brucei directly affected sensitivity to nitro ...201323208716
identification of r2tp complex of leishmania donovani and plasmodium falciparum using genome wide in-silico analysis.recently discovered r2tp complex is an important multiprotein complex involved in multiple cellular process like snornp biogenesis, pikk signaling, rna polymerase ii assembly and apoptosis. within r2tp complex, pih1 tightly interacts with rvb1/rvb2 and with tah1 to form r2tp macromolecular complex. r2tp complex further interacts with hsp90 to form r2tp-hsp90 complex, which has been found critical in many cellular process. the genome wide screening of leishmania donovani and plasmodium falciparum ...201324505500
survey of antibodies to leishmania spp. in wild canids from pennsylvania and tennessee.visceral leishmaniasis (vl) is a zoonosis with worldwide distribution. infections with the leishmania donovani complex, including leishmania infantum, cause the vl. domestic dogs are the most important reservoir host for human vl, and wild canids are also susceptible. in the united states, infections with l. infantum are common in the foxhound dog breed. little information is available regarding l. infantum in wild canids in the unites states. sera from 11 foxes and 256 coyotes originating in pe ...201324450086
protective immunity using mpl-a and autoclaved leishmania donovani as adjuvants along with a cocktail vaccine in murine model of visceral leishmaniasis.the current study is an extension of our previous study where we tested the protective efficacy of gp63 and hsp70 against murine visceral leishmaniasis. the cocktail vaccine was combined with mpl-a and ald adjuvants and the protection afforded by the three vaccines was compared. inbred balb/c mice were immunized twice at an interval of two weeks with the vaccine formulations. two weeks after the booster, they were challenged with 10(7) promastigotes of leishmania donovani and sacrificed on 30, 6 ...201324431576
elisa and western blotting for the detection of hsp70 and hsp83 antigens of leishmania donovani.visceral leishmaniasis (vl) is endemic in the tropical, sub-tropical regions of asia, africa, the mediterranean, southern europe and south and central america. approximately 500,000 new cases are reported annually. classically the diagnosis of vl is confirmed by the demonstration of the parasite in aspirates of spleen, bone marrow or liver which can yield false negative results, also these methods are invasive. in this study, we aimed to evaluate the serodiagnostic potential of two heat shock pr ...201324431544
ecology- and bioassay-guided drug discovery for treatments of tropical parasitic disease: 5alpha,8alpha-epidioxycholest-6-en-3beta-ol isolated from the mollusk dolabrifera dolabrifera shows significant activity against leishmania donovani.an ecology- and bioassay-guided search employed to discover compounds with activity against tropical parasitic diseases and cancer from the opisthobranch mollusk, dolabrifera dolabrifera, led to the discovery of antileishmanial properties in the known compound, 5alpha,8alpha-epidioxycholest-6-en-3beta-ol (1). compound 1 was identified through nuclear magnetic resonance spectroscopy (1h, 13c) and mass spectrometry. the compound was concentrated in the digestive gland of d. dolabrifera, but was no ...201324427935
in vitro susceptibilities of wild and drug resistant leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin e derivative tpgs for nanoparticle efficacy.visceral leishmaniasis (vl) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. there is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant vl. to address this need, andrographolide (ag) nanoparticles were designed with p-gp efflux inhibitor vitamin e tpgs (d-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant leishmania strains ...201324339938
post-kala-azar dermal leishmaniasis due to leishmania donovani in europe--case report. 201324261735
cathepsin b gene disruption induced leishmania donovani proteome remodeling implies cathepsin b role in secretome regulation.leishmania cysteine proteases are potential vaccine candidates and drug targets. to study the role of cathepsin b cysteine protease, we have generated and characterized cathepsin b null mutant l. donovani parasites. l. donovani cathepsin b null mutants grow normally in culture, but they show significantly attenuated virulence inside macrophages. quantitative proteome profiling of wild type and null mutant parasites indicates cathepsin b disruption induced remodeling of l. donovani proteome. we i ...201324244582
spinigerin induces apoptotic like cell death in a caspase independent manner in leishmania donovani.antimicrobial peptides (amps) are multifunctional components of the innate immune system. chemotherapeutic agents used for treatment of visceral leishmaniasis (vl) are now threatened due to the emergence of acquired drug resistance and toxicity. amps are attractive alternative to conventional pharmaceuticals. in this study, first time we explored the antileishmanial activity of spinigerin originally derived from pseudacanthotermes spiniger. leishmania donovani promastigotes present apoptosis-lik ...201324184774
chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.the indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. we have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stib ...201324167266
a petri net model of granulomatous inflammation: implications for il-10 mediated control of leishmania donovani infection.experimental visceral leishmaniasis, caused by infection of mice with the protozoan parasite leishmania donovani, is characterized by focal accumulation of inflammatory cells in the liver, forming discrete "granulomas" within which the parasite is eventually eliminated. to shed new light on fundamental aspects of granuloma formation and function, we have developed an in silico petri net model that simulates hepatic granuloma development throughout the course of infection. the model was extensive ...201324363630
the lignan glycosides lyoniside and saracoside poison the unusual type ib topoisomerase of leishmania donovani and kill the parasite both in vitro and in vivo.lignans are diphenyl propanoids with vast range of biological activities. the present study provides an important insight into the anti-leishmanial activities of two lignan glycosides, viz. lyoniside and saracoside. these compounds inhibit catalytic activities of topoisomerase ib (ldtopib) of leishmania donovani in non-competitive manner and stabilize the ldtopib mediated cleavage complex formation both in vitro and in leishmania promastigotes and subsequently inhibit the religation of cleaved s ...201324134912
115 kda serine protease confers sustained protection to visceral leishmaniasis caused by leishmania donovani via ifn-γ induced down-regulation of tnf-α mediated mmp-9 activity.visceral leishmaniasis caused by the intracellular parasite leishmania donovani is a major public health problem in the developing world. the emergence of increasing number of l. donovani strains resistance to antimonial drugs recommended worldwide requires the intervention of effective vaccine strategy for treatment of vl. in the present study l. donovani culture derived, soluble, secretory serine protease (psp) has been shown to be vaccine target of vl. protection from vl could be achieved by ...201322440312
analysis of sequence, structure of gapdh of leishmania donovani and its interactions.drug resistance acquired by leishmania donovani (ldv) is a major problem in the treatment and control of visceral leishmaniasis (vl). glyceraldehyde-3-phosphate dehydrogenase (gapdh), a major glycolytic enzyme has been targeted as is found in other protozoan which cause diseases like sleeping sickness. gapdh gene of ldv (ag83 strain) was amplified, sequenced, and modeled on the basis of crystal structure of leishmania mexicana. the model of the ldv gapdh exhibited nad-binding domain with rossman ...201322830998
lingual leishmaniasis presenting to maxillofacial surgery in uk with successful treatment with miltefosine.leishmaniasis is a disease that is caused by protozoa of the genus leishmania, which is prevalent in tropical and subtropical areas. clinical forms of leishmaniasis are particularly diverse representing a complex of diseases. we present a case of lingual leishmaniasis in an immunocompetent man. the lesions were caused by leishmania donovani/infantum species. the patient responded excellently to miltefosine treatment, with no reactivation during followup. to the authors' knowledge, it is the firs ...201324194765
genetic diversity of leishmania donovani/infantum complex in china through microsatellite analysis.the leishmania strains from different epidemic areas in china were assessed for their genetic relationship. twenty-nine strains of leishmania infantum isolated from 1950 to 2001 were subjected to multilocus microsatellite typing (mlmt) using 14 highly polymorphic microsatellite markers. twenty-two mlmt profiles were recognized among the 29 l. infantum strains, which differed from one another in 13 loci. bayesian model-based and distance-based analysis of the data inferred two main populations in ...201424480049
mass spectrometry-based proteomic analysis of leishmania donovani soluble proteins in indian clinical isolate.leishmania donovani, a causative organism of visceral leishmaniasis (vl), is responsible for high mortality throughout the world. due to the unsatisfactory treatment measures and increasing drug resistance, there has been an urgent need to develop novel drug/vaccine targets against vl. the aim of this study was to identify novel targets in soluble l. donovani (sld) protein. sld protein was isolated and resolved by two-dimensional gel electrophoresis and analyzed through maldi-tof/tof-based mass ...201424115687
an actin-like protein is involved in regulation of mitochondrial and flagellar functions as well as in intramacrophage survival of leishmania donovani.actin-related proteins are ubiquitous actin-like proteins that show high similarity with actin in terms of their amino acid sequence and three-dimensional structure. however, in lower eukaryotes, such as trypanosomatids, their functions have not yet been explored. here, we show that a novel actin-related protein (orf lmjf.13.0950) is localized mainly in the leishmania mitochondrion. we further reveal that depletion of the intracellular levels of this protein leads to an appreciable decrease in t ...201424354789
apoptosis-like death in leishmania donovani promastigotes induced by eugenol-rich oil of syzygium aromaticum.leishmaniasis consists of a complex spectrum of infectious diseases with worldwide distribution of which visceral leishmaniasis or kala-azar caused by leishmania donovani is the most devastating. in the absence of vaccines, chemotherapy remains the mainstay for the control of leishmaniasis. the drugs of choice are expensive and associated with multiple adverse side effects. because of these limitations, the development of new antileishmanial compounds is imperative and plants offer prospects in ...201424161990
performance of an indigenous β-mercaptoethanol-modified antigen in comparison with a commercial reference in direct agglutination test for detection of canine visceral leishmaniasis.we compared the performance of a locally produced β-mercaptoethanol-modified promastigote antigen (β-me-ag) of an indigenous leishmania infantum strain against that of a trypsinized leishmania donovani reference (ref-ag) in the direct agglutination test (dat) for detection of canine visceral leishmaniasis (cvl). one hundred and fifty-one serum samples collected from dogs belonging to four groups with different conditions were included. at a dat titre of 1 : 320, statistically determined as optim ...201424143006
stat4 is critical for immunity but not for antileishmanial activity of antimonials in experimental visceral leishmaniasis.we and others have previously shown that il-12 is indispensable for immunity and is required for the optimal antiparasitic activity of antimonials in experimental visceral leishmaniasis caused by leishmania donovani. here we investigated the role of stat4 in immunity against l. donovani using stat4 knockout mice and also determined the effect of stat4 deficiency in response to antimonial therapy. upon infection with l. donovani, stat4⁻/⁻ balb/c and c57bl/6 mice showed enhanced susceptibility to ...201424242758
exploring leishmania donovani 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) as a potential drug target by biochemical, biophysical and inhibition studies.3-hydroxy-3-methylglutaryl-coa (hmg-coa) reductase (hmgr), an nadph dependant enzyme catalyzes the synthesis of mevalonic acid from hmg-coa required for isoprenoid biosynthesis. the hmgr gene from leishmania donovani was cloned and expressed. genome analysis of l. donovani revealed that hmgr gene having an open reading frame of 1305 bp encodes a putative protein of 434 amino acids. ldhmgr showed optimal activity at ph 7.2 and temperature 37 °c. kinetic analysis of this enzyme revealed km values ...201424239940
biomarkers for intracellular pathogens: establishing tools as vaccine and therapeutic endpoints for visceral leishmaniasis.visceral leishmaniasis in south asia is a serious disease affecting children and adults. acute visceral leishmaniasis develops in only a fraction of those infected individuals, the majority being asymptomatic with the potential to transmit infection and develop disease. we followed 56 individuals characterized as being asymptomatic by seropositivity with rk39 rapid diagnostic test in a hyperendemic district of bangladesh to define the utility of leishmania-specific antibodies and dna in identify ...201424237596
click chemistry decoration of amino sterols as promising strategy to developed new leishmanicidal drugs.a series of 1,2,3-triazolylsterols was prepared from pregnenolone through reductive amination and copper(i)-catalyzed azide-alkyne cycloaddition (click chemistry). the newly generated stereocenter of the key propargylamino intermediate provided a mixture of diastereomers which were separated chromatographically, and the configuration of the r isomer was determined by x-ray crystallography. ten triazolyl sterols were prepared, and the products and intermediates were screened in vitro against diff ...201424200958
comparison of pcr-based diagnoses for visceral leishmaniasis in bangladesh.the diagnosis of visceral leishmaniasis (vl) is performed using multiple methods encompassing parasitological, serological and nucleic acid-based diagnostic tools, each method with its own unique advantages and disadvantages. conventional parasitological methods are risky for the patient and require skilled personnel to collect specimens from spleen or bone marrow, and hence they are not generally available in impoverished areas. polymerase chain reaction (pcr) has been validated as an excellent ...201424333754
post-kala-azar dermal leishmaniasis mimicking leprosy relapse: a diagnostic dilemma.post-kala-azar dermal leishmaniasis (pkdl) is well recognized in the indian subcontinent and is not infrequently confused with leprosy. the present report describes findings in an unusual case of pkdl.201424321013
sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen porphyromonas gingivalis.a carbonic anhydrase (ca, ec 4.2.1.1) denominated pgica, belonging to the γ-class, from the oral pathogenic bacteria porphyromonas gingivalis, the main causative agent of periodontitis, was investigated for its inhibition profile with sulfonamides and one sulfamate. dichlorophenamide, topiramate and many simple aromatic/heterocyclic sulfonamides were ineffective as pgica inhibitors whereas the best inhibition was observed with halogenosulfanilamides incorporating heavy halogens, 4-hydroxy- and 4 ...201424316122
triazino indole-quinoline hybrid: a novel approach to antileishmanial agents.a novel series of 1,2,4-triazino-[5,6b]indole-3-thione covalently linked to 7-chloro-4-aminoquinoline have been synthesized and evaluated for their in vitro activity against extracellular promastigote and intracellular amastigote form of leishmania donovani. among all tested compounds, compounds 7a and 7b were found to be the most active with ic50 values 1.11, 0.36μm and selectivity index (si) values 67, >1111, respectively, against amastigote form of l. donovani which is several folds more pote ...201424314395
leishmania donovani prevents oxidative burst-mediated apoptosis of host macrophages through selective induction of suppressors of cytokine signaling (socs) proteins.one of the mechanisms for establishment of infection employed by intra-macrophage pathogen-like leishmania is inhibition of oxidative burst-mediated macrophage apoptosis to protect their niche for survival and replication. we tried to elucidate the underlying mechanism for this by using h2o2 for induction of apoptosis. leishmania donovani-infected macrophages were much more resistant to h2o2-mediated apoptosis compared with control. although infected cells were capable of comparable reactive oxy ...201424275663
molecular mechanisms of in vitro betulin-induced apoptosis of leishmania donovani.although leishmanial infections of humans occur globally, the major health impact lies in developing nations, thus, leishmaniases remain "neglected" diseases for new drugs development. multidrug resistance has been documented in most countries where leishmaniases is endemic. betulin is a widely available and affordable natural product exerting leishmanicidal activity at micromolar concentration. in this study, the molecular mechanisms of death that contribute to the anti-leishmanial activity of ...201424420777
leishmania donovani activates uncoupling protein 2 transcription to suppress mitochondrial oxidative burst through differential modulation of srebp2, sp1 and usf1 transcription factors.in order to reside and multiply successfully within the host macrophages, leishmania parasites impair the generation of cellular as well as mitochondrial reactive oxygen species (ros), which is a major host defense mechanism against any invading pathogen. mitochondrial uncoupling protein 2 (ucp2) is strongly induced in leishmania infection, both at mrna and protein levels, to suppress the mitochondrial ros generation. in the present study we have demonstrated that leishmania donovani infection i ...201424417972
new fluoranthene flun-550 as a fluorescent probe for selective staining and quantification of intracellular lipid droplets.a new class of live cell permeant, nontoxic fluoranthene-based fluorescent probe (flun-550) having a high stokes shift in aqueous medium has been discovered. it showed selective staining of lipid droplets (lds, dynamic cytoplasmic organelles) at a low concentration without background noise in in vitro live cell imaging of 3t3-l1 preadipocytes, j774 macrophages, mcf7 breast cancer cells, and single-celled, parasitic protozoa leishmania donovani promastigotes and in vivo nonparasitic soil nematode ...201424410145
in vitro screening test using leishmania promastigotes stably expressing mcherry protein.transgenic leishmania major and leishmania donovani axenic promastigotes constitutively expressing mcherry were used for in vitro antileishmanial drug screening. this method requires minimal sample manipulation and can be easily adapted to automatic drug tests, allowing primary high-throughput screenings without the need for expensive and sophisticated instruments.201424395225
post kala-azar dermal leishmaniasis following treatment with 20 mg/kg liposomal amphotericin b (ambisome) for primary visceral leishmaniasis in bihar, india.the skin disorder post kala-azar dermal leishmaniasis (pkdl) occurs in up to 10% of patients treated for visceral leishmaniasis (vl) in india. the pathogenesis of pkdl is not yet fully understood. cases have been reported in india following therapy with most available treatments, but rarely in those treated with liposomal amphotericin b (ambisome). between july 2007 and august 2012 with the support of the rajendra memorial research institute (rmri), médecins sans frontières (msf) supported a vl ...201424392171
five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin b (ambisome) for visceral leishmaniasis in bihar, india.visceral leishmaniasis (vl; also known as kala-azar) is an ultimately fatal disease endemic in bihar. a 2007 observational cohort study in bihar of 251 patients with vl treated with 20 mg/kg intravenous liposomal amphotericin b (ambisome) demonstrated a 98% cure rate at 6-months. between july 2007 and august 2012, médecins sans frontières (msf) and the rajendra memorial research institute (rmri) implemented a vl treatment project in bihar, india-an area highly endemic for leishmania donovani-usi ...201424392168
leishmania donovani targets tumor necrosis factor receptor-associated factor (traf) 3 for impairing tlr4-mediated host response.intramacrophage pathogen leishmania donovani escapes host immune response by subverting toll-like receptor (tlr) signaling, which is critically regulated by protein ubiquitination. in the present study, we identified tumor necrosis factor receptor-associated factor (traf) 3, degradative ubiquitination of which is essential for tlr4 activation, as a target for leishmania to deactivate lps-mediated tlr4 signaling. we used lps-treated raw 264.7 cells and compared the tlr4-mediated immune response i ...201424391131
serological survey and associated risk factors of visceral leish-maniasis in qom province, central iran.visceral leishmaniasis (vl) or kala-azar is considered as a parasitic disease caused by the species of leishmania donovani complex which is intracellular parasites. this systemic disease is endemic in some parts of provinc-es of iran. the aim of this study was to determine the seroprevalence of vl in qom province, central iran using di-rect agglutination test (dat).201426060679
efficacy of leishmania donovani trypanothione reductase, identified as a potent th1 stimulatory protein, for its immunogenicity and prophylactic potential against experimental visceral leishmaniasis.in visceral leishmaniasis (vl), th1-type of immune responses play an important role which correlates with recovery from and resistance to disease resulting in lifelong immunity. based on this rationale, the soluble leishmanial antigens that elicit cellular responses in peripheral blood mononuclear cells (pbmcs) from cured leishmania patients were characterized through immunoproteomic approach which led to the identification of trypanothione reductase (tpr) (a cytosolic enzyme explored as a drug ...201424370734
tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis.effect of pure herb, tinospora cordifolia was studied for its hepatoprotective, nephroprotective and immunomodulatory activity against high dose cisplatin treatment in leishmania donovani infected balb/c mice. administration of cisplatin (5mg/kg b.wt. daily for 5 days, i.p.) reduced the parasite load in l. donovani infected balb/c mice but produced damage in liver and kidney as manifested biochemically by an increase in serum glutamate oxaloacetate transaminase (sgot), serum glutamate pyruvate t ...201424370645
in vitro synergistic effect of amphotericin b and allicin on leishmania donovani and l. infantum.current monotherapy against visceral leishmaniasis has serious side effects, and resistant leishmania strains have been identified. amphotericin b (amb) has shown an extraordinary antileishmanial efficacy without emergence of resistance; however, toxicity has limited its general use. results obtained showed, using a fixed-ratio analysis, that the combination of diallyl thiosulfinate (allicin) and amb ranged from moderately synergic to synergic at low concentrations (0.07 μm amb plus 35.45 μm all ...201424366748
il-4 contributes to failure, and colludes with il-10 to exacerbate leishmania donovani infection following administration of a subcutaneous leishmanial antigen vaccine.visceral leishmaniasis caused by the protozoan parasite leishmania donovani complex is a potentially fatal disease if left untreated. few treatment options exist and are toxic, costly and ineffective against resistant strains. thus a safe and efficacious vaccine to combat this disease is needed. previously, we reported that intraperitoneal administration of leishmanial antigens (lag) entrapped in liposomes conferred protection to balb/c mice against l. donovani challenge infection. however, this ...201424428931
a soluble phosphodiesterase in leishmania donovani negatively regulates camp signaling by inhibiting protein kinase a through a two way process involving catalytic as well as non-catalytic sites.intracellular camp level and camp mediated responses are elevated when leishmania are exposed to macrophage phagolysosome conditions (37 °c and ph 5.5). phosphodiesterases play major role in camp regulation and in the present study we have cloned and characterized a 2.1 kb cytosolic isoform of phosphodiesterase from leishmania donovani (ldpded) which plays important role in camp homeostasis when the promastigotes are exposed to macrophage phagolysome conditions for converting to axenic amastigot ...201425310904
comparative lc-ms-based metabolite profiling of the ancient tropical rainforest tree symphonia globulifera.in the last few years, several phytochemical studies have been undertaken on the tropical tree symphonia globulifera leading to the isolation and characterisation of several compounds exhibiting antiparasitic activities against plasmodium falciparum, trypanosoma brucei and leishmania donovani. the comparative lc-ms based metabolite profiling study conducted on the tree led to the identification of compounds originating from specific tissues. the results showed that renewable organs/tissues can b ...201425301665
the emergence of leishmania major and leishmania donovani in southern turkey.in southern turkey, leishmania tropica and l. infantum are both the causative agents of cutaneous leishmaniasis (cl) and visceral leishmaniasis (vl), respectively. however, l. major and l. donovani were known to exist after the influx of syrian refugees.201424449479
comparative transcript expression analysis of miltefosine-sensitive and miltefosine-resistant leishmania donovani.leishmania donovani is the causative agent of anthroponotic visceral leishmaniasis in the indian subcontinent. oral miltefosine therapy has recently replaced antimonials in endemic areas. however, the drug is at risk of emergence of resistance due to unrestricted use, and, already, there are indications towards decline in treatment efficacy. hence, understanding the mechanism of miltefosine resistance in the parasite is crucial. we employed genomic microarray analysis to compare the gene express ...201424449447
selective inhibition of leishmania donovani by active extracts of wild mushrooms used by the tribal population of india: an in vitro exploration for new leads against parasitic protozoans.the study was intended at evaluating the anti-proliferating effect of mushrooms used in traditional folklore of santal tribal population in india against leishmania donovani (mhom/in/83/ag83). a total of eighteen extracts, three estracts from each mushroom [(80% ethanol extracted; fa), (water-soluble polysaccharide fraction; fb), (polyphenolic fraction; fc)], from six wild mushrooms were obtained. these extracts were tested against the promastigotes and amastigotes for their antileishmanial capa ...201424440295
covalent functionalized self-assembled lipo-polymerosome bearing amphotericin b for better management of leishmaniasis and its toxicity evaluation.amphotericin b remains the preferred choice for leishmanial infection, but it has limited clinical applications due to substantial dose limiting toxicities. in the present work, amb has been formulated in lipo-polymerosome (l-psome) by spontaneous self-assembly of synthesized glycol chitosan-stearic acid copolymer. the optimized l-psome formulation with vesicle size of 243.5 ± 17.9 nm, pdi of 0.168 ± 0.08 and zeta potential of (+) 27.15 ± 0.46 mv with 25.59 ± 0.87% amb loading was obtained. the ...201424495144
liposomal cholesterol delivery activates the macrophage innate immune arm to facilitate intracellular leishmania donovani killing.leishmania donovani causes visceral leishmaniasis (vl) by infecting the monocyte/macrophage lineage and residing inside specialized structures known as parasitophorous vacuoles. the protozoan parasite has adopted several means of escaping the host immune response, with one of the major methods being deactivation of host macrophages. previous reports highlight dampened macrophage signaling, defective antigen presentation due to increased membrane fluidity, and the downregulation of several genes ...201424478076
characterization of glycolytic enzymes--raldolase and renolase of leishmania donovani, identified as th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis.th1 immune responses play an important role in controlling visceral leishmaniasis (vl) hence, leishmania proteins stimulating t-cell responses in host, are thought to be good vaccine targets. search of such antigens eliciting cellular responses in peripheral blood mononuclear cells (pbmcs) from cured/exposed/leishmania patients and hamsters led to the identification of two enzymes of glycolytic pathway in the soluble lysate of a clinical isolate of leishmania donovani--enolase (ldeno) and aldola ...201424475071
biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs.visceral leishmaniasis (vl) is caused by the intracellular protozoan leishmania donovani complex. vl may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. the nutritional status of the patients with vl is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. changes in lipoproteins and plasma proteins may have major impacts in the host durin ...201424474015
disuccinyl betulin triggers metacaspase-dependent endonuclease g-mediated cell death in unicellular protozoan parasite leishmania donovani.the unicellular organism leishmania undergoes apoptosis-like cell death in response to external stress or exposure to antileishmanial agents. here, we showed that 3-o,28-o-disuccinyl betulin (disb), a potent topoisomerase type ib inhibitor, induced parasitic cell death by generating oxidative stress. the characteristic feature of the death process resembled the programmed cell death (pcd) seen in higher eukaryotes. in the current study, the generation of reactive oxygen species (ros), followed b ...201424468787
alkyl galactofuranosides strongly interact with leishmania donovani membrane and provide antileishmanial activity.we investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e., octyl-β-d-galactofuranoside (compound 1), 6-amino-β-d-galactofuranoside (compound 2), 6-n-acetamido-β-d-galactofuranoside (compound 3), and 6-azido-β-d-galactofuranoside (compound 4), on leishmania donovani. their mechanism of action was explored using electron paramagnetic resonance spectroscopy (epr) and nuclear magnetic resonance (nmr), and ultrastructural alterations were analyzed by transmission electron ...201424468785
strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in india and nepal.asymptomatic persons infected with the parasites causing visceral leishmaniasis (vl) usually outnumber clinically apparent cases by a ratio of 4-10 to 1. we assessed the risk of progression from infection to disease as a function of dat and rk39 serological titers.201424466361
deletion of vitamin c biosynthesis enzyme, arabino-1, 4-lactone oxidase in leishmania donovani results in increased pro-inflammatory responses from host immune cells.recently, we reported molecular characterization, localization and functional importance of arabino-1, 4-lactone oxidase (alo) enzyme from leishmania donovani that catalyses the last step in ascorbate biosynthesis pathway. vitamin c (l-ascorbic acid) is implicated in several crucial physiological processes. to elucidate the biological role of d-arabinono-γ-lactone oxidase in leishmania, we made l. donovani alo null mutant (δalo) by double targeted gene replacement. this mutant lacked alo activit ...201424456202
aptamer based, non-pcr, non-serological detection of chagas disease biomarkers in trypanosoma cruzi infected mice.chagas disease affects about 5 million people across the world. the etiological agent, the intracellular parasite trypanosoma cruzi (t. cruzi), can be diagnosed using microscopy, serology or pcr based assays. however, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. it is well documented that several parasite proteins called t. cruzi excreted secreted antigens (tesa) ...201424454974
immunomodulation in human dendritic cells leads to induction of interferon-gamma production by leishmania donovani derived kmp-11 antigen via activation of nf-κb in indian kala-azar patients.dendritic cells (dcs) and macrophages (mφs) are well-known antigen presenting cells with an ability to produce il-12 which indicates that they have potential of directing acquired immunity toward a th1-biased response. the aim of this study was to examine the effect of leishmania specific kmp-11 antigen through comparison of immune responses after presentation by dcs and mφs to t cells in indian patients with vl. patients with dcs and mφs were directed against a purified leishmania donovani anti ...201424587999
deletion of ubiquitin fold modifier protein ufm1 processing peptidase ufsp in l. donovani abolishes ufm1 processing and alters pathogenesis.previously, we showed leishmania donovani ufm1 has a gly residue conserved at the c-terminal region with a unique 17 amino acid residue extension that must be processed prior to conjugation to target proteins. in this report, we describe for the first time the isolation and characterization of the leishmania ufm1-specific protease ufsp. biochemical analysis of l. donovani ufsp showed that this protein possesses the ufm1 processing activity using sensitive fret based activity probes. the ufm1 cle ...201424587462
metabolic reprogramming during purine stress in the protozoan pathogen leishmania donovani.the ability of leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. however, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. to elucidate nutrient stress response pathways in leishmania donovani, we have used purine starvation as the paradigm. the salvage of purines from the host milieu is obligatory for parasite replicati ...201424586154
whole blood assay and visceral leishmaniasis: challenges and promises.for years, the ability to study immune responses in patients with active visceral leishmaniasis (vl) has been hampered by the absence of detectable antigen-specific th1 responses using cells from peripheral blood mononuclear cells (pbmcs). employing whole blood assay (wba), we recently reported that whole blood cells of active vl patients maintain the capacity to secrete significant levels of antigen driven ifn-γ and il-10. furthermore, wba that uses soluble leishmania antigen (sla) have advanta ...201424571797
generation of adenosine tri-phosphate in leishmania donovani amastigote forms.leishmania, the causative agent of various forms of leishmaniasis, is the significant cause of morbidity and mortality. regarding energy metabolism, which is an essential factor for the survival, parasites adapt to the environment under low oxygen tension in the host using metabolic systems which are very different from that of the host mammals. we carried out the study of susceptibilities to different inhibitors of mitochondrial electron transport chain and studies on substrate level phosphoryl ...201424570045
the curative effect of fucoidan on visceral leishmaniasis is mediated by activation of map kinases through specific protein kinase c isoforms.fucoidan can cure both antimony-sensitive and antimony-resistant visceral leishmaniasis through immune activation. however, the signaling events underlying this cellular response remain uncharacterized. the present study reveals that fucoidan induces activation of p38 and erk1/2 and nf-κb dna binding in both normal and leishmania donovani-infected macrophages, as revealed by western blotting and electrophoretic mobility shift assay (emsa), respectively. pharmacological inhibition of p38, erk1/2 ...201424561457
elucidation of cellular mechanisms involved in experimental paromomycin resistance in leishmania donovani.leishmania donovani is the causative agent of the potentially fatal disease visceral leishmaniasis (vl). chemotherapeutic options available to treat vl are limited and often face parasite resistance, inconsistent efficacy, and toxic side effects. paromomycin (pmm) was recently introduced to treat vl as a monotherapy and in combination therapy. it is vital to understand the mechanisms of pmm resistance to safeguard the drug. in the present study, we utilized experimentally generated pmm-resistant ...201424550335
nonmigrant children with visceral leishmaniasis from the nonendemic area of uttarakhand.the emergence of visceral leishmaniasis (vl) in nonendemic areas is a matter of great concern. we conducted a study and present a brief description of six nonmigrant children with vl from the nonendemic area of uttarakhand, diagnosed in our tertiary teaching hospital from february 2012 to june 2013. we also present here a geographic distribution of these cases to assess the impact of global warming and climate change on the spread of the disease. patients were diagnosed as vl by clinical finding ...201424531375
synthesis, antileishmanial activity and docking study of n'-substitutedbenzylidene-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4h)-yl)acetohydrazides.a series of n'-substitutedbenzylidene-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4h)-yl)acetohydrazide derivatives is synthesized and evaluated for antileishmanial activity against leishmania donovani promastigotes. compounds 9a and 9i were shown significant antileishmanial when compared with standard sodium stilbogluconate. antimicrobial study revealed that compound 9b has potent as well as broad spectrum antibacterial activity when compared with ampicillin and compound 9e showed promising antifungal ...201424513045
characterization of cross-protection by genetically modified live-attenuated leishmania donovani parasites against leishmania mexicana.previously, we showed that genetically modified live-attenuated leishmania donovani parasite cell lines (ldcen(-/-) and ldp27(-/-)) induce a strong cellular immunity and provide protection against visceral leishmaniasis in mice. in this study, we explored the mechanism of cross-protection against cutaneous lesion-causing leishmania mexicana. upon challenge with wild-type l. mexicana, mice immunized either for short or long periods showed significant protection. immunohistochemical analysis of ea ...201425156362
combining cationic liposomal delivery with mpl-tdm for cysteine protease cocktail vaccination against leishmania donovani: evidence for antigen synergy and protection.with the paucity of new drugs and hiv co-infection, vaccination remains an unmet research priority to combat visceral leishmaniasis (vl) requiring strong cellular immunity. protein vaccination often suffers from low immunogenicity and poor generation of memory t cells for long-lasting protection. cysteine proteases (cps) are immunogenic proteins and key mediators of cellular functions in leishmania. here, we evaluated the vaccine efficacies of cps against vl, using cationic liposomes with toll l ...201425144181
in vitro anti-leishmanial efficacy of potato tuber extract (ptex): leishmanial serine protease(s) as putative target.leishmaniasis, a neglected tropical disease (ntd) causes major health problems in the tropical and subtropical world. most of the antileishmanial modern therapies with different formulations of pentavalent antimonials, miltefosine, amphotericin b etc. are not satisfactory in recent times due to high toxicity to the host and present rising strain resistance issues. so there is an urgent need to develop new, safe and cost-effective drugs against leishmaniasis. in this regard, bioactive phytocompon ...201425128800
ascorbate peroxidase, a key molecule regulating amphotericin b resistance in clinical isolates of leishmania donovani.amphotericin b (amb), a polyene macrolide, is now a first-line treatment of visceral leishmaniasis cases refractory to antimonials in india. amb relapse cases and the emergence of secondary resistance have now been reported. to understand the mechanism of amb, differentially expressed genes in amb resistance strains were identified by a dna microarray and real-time reverse transcriptase pcr (rt-pcr) approach. of the many genes functionally overexpressed in the presence of amb, the ascorbate pero ...201425114128
characterization of mitochondrial bioenergetic functions between two forms of leishmania donovani - a comparative analysis.leishmaniasis is a growing health problem in many parts of the world partly due to drug resistance of the parasite. this study reports on the fisibility of studying mitochondrial properties of two forms of wild-type l. donovani through the use of selective inhibitors. amastigote forms of l. donovani exhibited a wide range of sensitivities to these inhibitors. mitochondrial complex ii inhibitor thenoyltrifluoroacetone and fof1-atp synthase inhibitors oligomycin and dicyclohexylcarbodiimide were r ...201425107348
a screen-and-treat strategy targeting visceral leishmaniasis in hiv-infected individuals in endemic east african countries: the way forward?in the wake of the hiv epidemic, visceral leishmaniasis (vl), a disseminated protozoan infection caused by the leishmania donovani complex, has been re-emerging, particularly in north ethiopia where up to 40% of patients with vl are co-infected with hiv. management of vl in hiv co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. tackling l. donovani infection befor ...201425101627
a new approach for the delivery of artemisinin: formulation, characterization, and ex-vivo antileishmanial studies.artemisinin, a potential antileishmanial compound with poor bioavailability and stability has limited efficacy in visceral leishmaniasis. encapsulating artemisinin into poly lactic-co glycolic nanoparticles may improve its effectiveness and reduce toxicity.201425086720
carbon nanotube based betulin formulation shows better efficacy against leishmania parasite.we report a novel antileishmanial formulation of betulin (bet) attached to functionalized carbon nanotubes (f-cnts). we conjugated betulin, a pentacyclic triterpenoid secondary metabolite, to carboxylic acid chains on f-cnts to obtain bet attached functionalized carbon nanotubes (f-cnt-bet). the drug release profile demonstrated a fairly slow release of bet. the in-vitro cytotoxicities of bet, f-cnt and f-cnt-bet on j774a.1 macrophage cell line were 211.05±7.14μg/ml; 24.67±3.11μg/ml and 72.63±6. ...201425086374
protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from withania somnifera and asparagus racemosus.visceral leishmaniasis (vl) is a vector-borne parasitic disease targeting tissue macrophages. it is among the most neglected infectious diseases. as available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. one of the immunopathological consequences of active visceral leishmaniasis is suppression of protective t-helper (th)-1 cells and induction of disease-promoting th-2 cells, and thus the treatment of vl relies on immunomodulation. in ...201425082945
diverse modes of binding in structures of leishmania major n-myristoyltransferase with selective inhibitors.the leishmaniases are a spectrum of global diseases of poverty associated with immune dysfunction and are the cause of high morbidity. despite the long history of these diseases, no effective vaccine is available and the currently used drugs are variously compromised by moderate efficacy, complex side effects and the emergence of resistance. it is therefore widely accepted that new therapies are needed. n-myristoyltransferase (nmt) has been validated pre-clinically as a target for the treatment ...201425075346
induction of mitochondrial dysfunction and oxidative stress in leishmania donovani by orally active clerodane diterpene.this study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (k-09) in leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (vl). k-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in l. donovani promastigotes. mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the ...201425070112
reactive oxygen species regulates expression of iron-sulfur cluster assembly protein iscs of leishmania donovani.the cysteine desulfurase, iscs, is a highly conserved and essential component of the mitochondrial iron-sulfur cluster (isc) system that serves as a sulfur donor for fe-s clusters biogenesis. fe-s clusters are versatile and labile cofactors of proteins that orchestrate a wide array of essential metabolic processes, such as energy generation and ribosome biogenesis. however, no information regarding the role of iscs or its regulation is available in leishmania, an evolving pathogen model with rap ...201425062827
retraction. anti-citrullinated peptide antibodies and rheumatoid factor in sudanese patients with leishmania donovani infection. 201425054607
prostaglandin e2 negatively regulates the production of inflammatory cytokines/chemokines and il-17 in visceral leishmaniasis.persistence of intracellular infection depends on the exploitation of factors that negatively regulate the host immune response. in this study, we elucidated the role of macrophage pge2, an immunoregulatory lipid, in successful survival of leishmania donovani, causative agent of the fatal visceral leishmaniasis. pge2 production was induced during infection and resulted in increased camp level in peritoneal macrophages through g protein-coupled e-series prostanoid (ep) receptors. among four diffe ...201425049356
the isolation of antiprotozoal compounds from libyan propolis.propolis is increasingly being explored as a source of biologically active compounds. until now, there has been no study of libyan propolis. two samples were collected in north east libya and tested for their activity against trypanosoma brucei. extracts from both samples had quite high activity. one of the samples was fractionated and yielded a number of active fractions. three of the active fractions contained single compounds, which were found to be 13-epitorulosal, acetyl-13-epi-cupressic ac ...201425044090
synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against leishmania donovani and trypanosoma cruzi.a high-throughput (hts) and high-content screening (hcs) campaign of a commercial library identified 2,3-dihydroimidazo[1,2-a]benzimidazole analogues as a novel class of anti-parasitic agents. a series of synthetic derivatives were evaluated for their in vitro anti-leishmanial and anti-trypanosomal activities against leishmania donovani and trypanosoma cruzi, which have been known as the causative parasites for visceral leishmaniasis and chagas disease, respectively. in the case of leishmania, t ...201425036797
parasite load estimation by qpcr differentiates between asymptomatic and symptomatic infection in indian visceral leishmaniasis.using quantitative pcr (qpcr), we differentiated asymptomatic and symptomatic indian leishmania donovani infection. qpcr on blood of 40 visceral leishmaniasis, 130 endemic, and 40 non-endemic healthy controls showed 500 times less (p < .0001) parasitemia in asymptomatic compared to the symptomatic ones and threshold of 5 parasite genome/ml for the clinical disease.201425023070
genetic analysis of leishmania donovani tropism using a naturally attenuated cutaneous strain.a central question in leishmania research is why most species cause cutaneous infections but others cause fatal visceral disease. interestingly, l. donovani causes both visceral and cutaneous leishmaniasis in sri lanka. l. donovani clinical isolates were therefore obtained from cutaneous leishmaniasis (cl-sl) and visceral leishmaniasis (vl-sl) patients from sri lanka. the cl-sl isolate was severely attenuated compared to the vl-sl isolate for survival in visceral organs in balb/c mice. genomic a ...201424992200
synthesis, antileishmanial and antitrypanosomal activities of n-substituted tetrahydro-β-carbolines.a series of n-substituted tetrahydro-β-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of leishmania donovani, the causative agent for visceral leishmaniasis. the thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with ic50 values of 12.7, 9.1 and 22.1 μm, respectively. analogs 9b and 11h were also effective against axenic amastigo ...201424980054
growth factor and th2 cytokine signaling pathways converge at stat6 to promote arginase expression in progressive experimental visceral leishmaniasis.host arginase 1 (arg1) expression is a significant contributor to the pathogenesis of progressive visceral leishmaniasis (vl), a neglected tropical disease caused by the intracellular protozoan leishmania donovani. previously we found that parasite-induced arg1 expression in macrophages was dependent on stat6 activation. arg1 expression was amplified by, but did not require, il-4, and required de novo synthesis of unknown protein(s). to further explore the mechanisms involved in arg1 regulation ...201424967908
leishmania spp. proteome data sets: a comprehensive resource for vaccine development to target visceral leishmaniasis.visceral leishmaniasis is a neglected infectious disease caused primarily by leishmania donovani and leishmania infantum protozoan parasites. a significant number of infections take a fatal course. drug therapy is available but still costly and parasites resistant to first line drugs are observed. despite many years of trial no commercial vaccine is available to date. however, development of a cost effective, needle-independent vaccine remains a high priority. reverse vaccinology has attracted m ...201424959165
mianserin, an antidepressant kills leishmania donovani by depleting ergosterol levels.in the present study, we have investigated the antileishmanial potential of mianserin, an antidepressant. mianserin was found to inhibit both the promastigote and amastigote forms of the parasite in a dose dependant manner. the ic50 values for promastigotes and amastigotes were 21 μm and 46 μm respectively. interestingly, mianserin failed to inhibit thp-1 differentiated macrophages up to 100 μm concentration thus, exhibiting parasite selectivity. when mianserin was incubated with recombinant lei ...201424950381
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