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targeting the human parasite leishmania donovani: discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series.we report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. in vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of leishmania donovani, j774a.1 murine and hepg2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). new derivatives were then synthesized to allow structure-activity and -toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying ...201324080103
synthesis of marine α-methoxylated fatty acid analogs that effectively inhibit the topoisomerase ib from leishmania donovani with a mechanism different from that of camptothecin.sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties and in some cases they display enhanced anticancer activities. however, the antiprotozoal properties of the α-methoxylated fatty acids have been less studied. in this work, we describe the total synthesis of (5z,9z)-(±)-2-methoxy-5, 9-eicosadienoic acid (1) and its acetylenic analog (±)-2-methoxy-5,9-eicosadiynoic acid (2), and report that they inhibit (ec₅₀ values between 31 and 22 µm) the leishm ...201324084785
design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents.an analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. these molecules were tested for their in vitro and in vivo biological activity against leishmania donovani. metabolic stability of these compounds was also improved through the introduction of halogen substituents. compound (26g), found to be the most active; exhibited an ic₅₀ value of 0.2 μm and >180 fold selectivity. the hydrochloride sa ...201324095747
asparagus racemosus ameliorates cisplatin induced toxicities and augments its antileishmanial activity by immunomodulation in vivo.current drugs for the treatment of visceral leishmaniasis are inadequate and their efficacies are also compromised due to suppression of immune function associated during the course of infection. to overcome this problem, efforts are needed to develop therapies with effective immunomodulatory agents where decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. in this study we have evaluated a new therapeutic approach based on combination of asparagus race ...201424103199
increased parasite surface antigen-2 expression in clinical isolates of leishmania donovani augments antimony resistance.resistance to sodium antimony gluconate (sag) is a major cause of therapeutic failure in a large proportion of visceral leishmaniasis (vl) cases. determinants of sag resistance have been widely studied; however, the mechanism operating in clinical isolates is poorly understood. in the present study, expression of parasite surface antigen-2 (psa-2) gene was studied in clinical isolates of leishmania donovani comprising of antimony resistant (n=10) and sensitive (n=4) parasites. the expression of ...201324103752
relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting leishmania donovani strain.leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the indian subcontinent. this relapse ...201324105765
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
constitutive mosaic aneuploidy is a unique genetic feature widespread in the leishmania genus.using fluorescence in situ hybridization, we determined the ploidy of four species of leishmania: leishmania infantum, leishmania donovani, leishmania tropica and leishmania amazonensis. we found that each cell in a strain possesses a combination of mono-, di- and trisomies for all chromosomes; ploidy patterns were different among all strains/species. these results extend those we previously described in leishmania major, demonstrating that mosaic aneuploidy is a genetic feature widespread to th ...201424120456
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
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
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
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
therapeutic options for visceral leishmaniasis.visceral leishmaniasis (vl), also known as kala-azar, is a disseminated protozoal infection caused principally by leishmania donovani and leishmania infantum (known as leishmania chagasi in south america). the therapeutic options for vl are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, hiv co-infection, malnourishment and other concomitant infections. this article provides an exhaustive review of the lit ...201324170666
survey of infectious agents in the endangered darwin's fox (lycalopex fulvipes): high prevalence and diversity of hemotrophic mycoplasmas.very little is known about the diseases affecting the darwin's fox (lycalopex fulvipes), which is considered to be one of the most endangered carnivores worldwide. blood samples of 30 foxes captured on chiloé island (chile) were tested with a battery of pcr assays targeting the following pathogens: ehrlichia/anaplasma sp., rickettsia sp., bartonella sp., coxiella burnetti, borrelia sp., mycoplasma sp., babesia sp., hepatozoon canis, hepatozoon felis, leishmania donovani complex, and filariae. an ...201324176254
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
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
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
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
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
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
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
identification of a secreted casein kinase 1 in leishmania donovani: effect of protein over expression on parasite growth and virulence.casein kinase 1 (ck1) plays an important role in eukaryotic signaling pathways, and their substrates include key regulatory proteins involved in cell differentiation, proliferation and chromosome segregation. the leishmania genome encodes six potential ck1 isoforms, of which five have orthologs in other trypanosomatidae. leishmania donovani ck1 isoform 4 (ldck1.4, orthologous to lmjf27.1780) is unique to leishmania and contains a putative secretion signal peptide. the full-length gene and three ...201324260187
post-kala-azar dermal leishmaniasis due to leishmania donovani in europe--case report. 201324261735
a2 and other visceralizing proteins of leishmania: role in pathogenesis and application for vaccine development.visceral leishmaniasis is a re-emergent disease and a significant cause of morbidity worldwide. amongst the more than 20 leishmania species, leishmania donovani, leishmania infantum and more rarely leishmania amazonensis are associated with visceral leishmaniasis. a major question in leishmaniasis research is how these species migrate to and infect visceral organs whereas other species such as leishmania major and leishmania braziliensis remain in the skin, causing tegumentary leishmaniasis. her ...201424264241
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
attraction of ethiopian phlebotomine sand flies (diptera: psychodidae) to light and sugar-yeast mixtures (co(2)).visceral leishmaniasis (vl) known as kala-azar is a serious systemic disease caused by leishmania donovani parasites (trypanosomatidae: kinetoplastida). the disease is prevalent in the indian sub-continent, east africa and brazil. in africa, the worst affected regions are in sudan, with an estimated 15,000-20,000 cases annually and ethiopia with 5,000-7,000 cases a year. the main vector of vl in sudan and northern ethiopia is phlebotomus orientalis, a sand fly frequently found in association wit ...201324305038
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
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
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
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
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
over-expression of 60s ribosomal l23a is associated with cellular proliferation in sag resistant clinical isolates of leishmania donovani.sodium antimony gluconate (sag) unresponsiveness of leishmania donovani (ld) had effectively compromised the chemotherapeutic potential of sag. 60s ribosomal l23a (60srl23a), identified as one of the over-expressed protein in different resistant strains of l.donovani as observed with differential proteomics studies indicates towards its possible involvement in sag resistance in l.donovani. in the present study 60srl23a has been characterized for its probable association with sag resistance mecha ...201324340105
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
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
pharmacological assessment defines leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infection.protein kinase inhibitors have emerged as new drugs in various therapeutic areas, including leishmaniasis, an important parasitic disease. members of the leishmania casein kinase 1 (ck1) family represent promising therapeutic targets. leishmania casein kinase 1 isoform 2 (ck1.2) has been identified as an exokinase capable of phosphorylating host proteins, thus exerting a potential immune-suppressive action on infected host cells. moreover, its inhibition reduces promastigote growth. despite thes ...201324366737
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
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
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
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
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
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
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
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
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
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
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
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
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
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
sialic acids siglec interaction: a unique strategy to circumvent innate immune response by pathogens.sialic acids (sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. sialic acid binding immunoglobulins (ig)-like lectins (siglecs) are generally expressed on various immune cells. they selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. many pathogens either synthesize or acquire sialic acids from the host. sialylated pathogens generally use siglecs to manipulate the host immune response. the ...201324434319
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
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
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
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
genomic confirmation of hybridisation and recent inbreeding in a vector-isolated leishmania population.although asexual reproduction via clonal propagation has been proposed as the principal reproductive mechanism across parasitic protozoa of the leishmania genus, sexual recombination has long been suspected, based on hybrid marker profiles detected in field isolates from different geographical locations. the recent experimental demonstration of a sexual cycle in leishmania within sand flies has confirmed the occurrence of hybridisation, but knowledge of the parasite life cycle in the wild still ...201424453988
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
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
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
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
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
molecular and serological detection of tick-borne pathogens in dogs from an area endemic for leishmania infantum in mato grosso do sul, brazil.tick-borne pathogens affect a wide range of vertebrate hosts. to identify tick-borne pathogens among dogs from campo grande, ms, brazil testing seropositive for leishmania infantum (syn. l. chagasi), a serological and molecular study was conducted to detect ehrlichia canis, anaplasma platys and babesia vogeli in 60 serum and spleen samples. a confirmatory diagnosis of l. infantum based on serological and molecular assays was also performed, as was sequence alignment and phylogenetic analysis to ...201424473877
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
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
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
specific noninvasive detection of leishmania donovani in desquamated buccal cell swab samples from human visceral leishmaniasis-hiv coinfected patients.diagnosis of human immunodeficiency virus (hiv) infection with visceral leishmaniasis (vl) coinfection is challenging. specific diagnosis of vl in hiv-coinfected patients was evaluated by molecular methods in desquamated buccal swab samples, demonstrating 86.3% sensitivity and 98.3% specificity in controls. this test holds significant potential for development as a noninvasive diagnostic tool for vl in hiv-coinfected patients.201424478413
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
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
identification of the intracellular gate for a member of the equilibrative nucleoside transporter (ent) family.equilibrative nucleoside transporters of the slc29 family play important roles in many physiological and pharmacological processes, including import of drugs for treatment of cancer, aids, cardiovascular, and parasitic diseases. however, no crystal structure is available for any member of this family. in previous studies we generated a computational model of the leishmania donovani nucleoside transporter 1.1 (ldnt1.1) that captured this permease in the outward-closed conformation, and we identif ...201424497645
risk factors for visceral leishmaniasis and asymptomatic leishmania donovani infection in india and nepal.there is increasing interest in the role of asymptomatic infection in transmission of visceral leishmaniasis (vl). we studied the individual, household and environmental factors associated with asymptomatic leishmania donovani infected individuals and vl. 7,538 individuals living in vl endemic villages in india and nepal were divided into three mutually exclusive groups based on their vl history and direct agglutination test (dat) results in yearly serosurveys over a two-year period. the groups ...201424498159
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
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
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
di-cationic arylimidamides act against neospora caninum tachyzoites by interference in membrane structure and nucleolar integrity and are active against challenge infection in mice.neospora caninum is considered to be the main cause of bovine abortion in europe and the usa, leading to considerable financial impact. losses are caused directly by abortions or indirectly through breeding of calves with impaired viability. due to the lack of effective chemotherapy against bovine neosporosis, there is a need to develop new anti-protozoal compounds, which would either eliminate the parasite or avoid its transmission. in order to identify compounds of interest, the in vitro activ ...201224533272
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
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
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
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
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
significantly lower anti-leishmania igg responses in sudanese versus indian visceral leishmaniasis.visceral leishmaniasis (vl), a widely distributed systemic disease caused by infection with the leishmania donovani complex (l. donovani and l. infantum), is almost always fatal if symptomatic and untreated. a rapid point-of-care diagnostic test for anti-leishmania antibodies, the rk39-immunochromatographic test (rk39-ict), has high sensitivity and specificity in south asia but is less sensitive in east africa. one of the underlying reasons may be continent-specific molecular diversity in the rk ...201424587456
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
comparative analysis of salivary gland transcriptomes of phlebotomus orientalis sand flies from endemic and non-endemic foci of visceral leishmaniasis.in east africa, phlebotomus orientalis serves as the main vector of leishmania donovani, the causative agent of visceral leishmaniasis (vl). phlebotomus orientalis is present at two distant localities in ethiopia; addis zemen where vl is endemic and melka werer where transmission of vl does not occur. to find out whether the difference in epidemiology of vl is due to distant compositions of p. orientalis saliva we established colonies from addis zemen and melka werer, analyzed and compared the t ...201424587463
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
a study of haematological and bone marrow changes in symptomatic patients with human immune deficiency virus infection with special mention of functional iron deficiency, anaemia of critically ill and haemophagocytic lymphohistiocytosis.haematological abnormalities are among the most common complications of hiv. these involve all lineages of blood cells. bone marrow studies form integral part of complete workup of the hiv positive patients specially when they present as case of pyrexia of unknown origin (puo), refractory anaemia and pancytopenia.201324600136
study the effects of plga-peg encapsulated amphotericin b nanoparticle drug delivery system against leishmania donovani.drug delivery systems are a promising technology to increase poor solubility and bioavailability of compounds. therefore we have developed plga-peg encapsulated amphotericin b nanoparticles (nps) drug delivery technology to increase the solubility of amphotericin b and target the macrophage of infected tissues during visceral leishmaniasis. the structural characterization by transmission electron microscopy and dynamic light scattering revealed the nano-size of the particle (30-35 nanometers). f ...201524601828
development of targeted 1,2-diacyl-sn-glycero-3-phospho-l-serine-coated gelatin nanoparticles loaded with amphotericin b for improved in vitro and in vivo effect in leishmaniasis.the principle objective of this study was to develop 1,2-diacyl-sn-glycero-3-phospho-l-serine (ps)-coated gelatin nanoparticles (gnps) bearing amphotericin b (amb) for specific targeting to the macrophages involved in visceral leishmaniasis (vl).201424606222
leishmania donovani: dynamics of l. donovani evasion of innate immune cell attack due to malnutrition in visceral leishmaniasis.malnutrition may be significant in the modulation of immune responses in visceral leishmaniasis (vl). data on the relationship between malnutrition and innate immune response in vl are limited. the aim of this study was to examine the effect of malnutrition on the profile of innate immune functions of polymorphonuclear neutrophil granulocytes (pmns) and monocytes through comparison of well-nourished and malnourished indian patients with vl.201424607302
identification and functional characterization of a novel bacterial type asparagine synthetase a: a trna synthetase paralog from leishmania donovani.asparagine is formed by two structurally distinct asparagine synthetases in prokaryotes. one is the ammonia-utilizing asparagine synthetase a (asna), and the other is asparagine synthetase b (asnb) that uses glutamine or ammonia as a nitrogen source. in a previous investigation using sequence-based analysis, we had shown that leishmania spp. possess asparagine-trna synthetase paralog asparagine synthetase a (ldasna) that is ammonia-dependent. here, we report the cloning, expression, and kinetic ...201424610810
characterization of the proliferating cell nuclear antigen of leishmania donovani clinical isolates and its association with antimony resistance.previously, through a proteomic analysis, proliferating cell nuclear antigen (pcna) was found to be overexpressed in the sodium antimony gluconate (sag)-resistant clinical isolate compared to that in the sag-sensitive clinical isolate of leishmania donovani. the present study was designed to explore the potential role of the pcna protein in sag resistance in l. donovani. for this purpose, the protein was cloned, overexpressed, purified, and modeled. western blot (wb) and real-time pcr (rt-pcr) a ...201424614385
bone marrow parasite burden among patients with new world kala-azar is associated with disease severity.kala-azar or visceral leishmaniasis, found mostly throughout the indian subcontinent, east africa, and brazil, kills 20,000-40,000 persons annually. the agents, leishmania donovani and leishmania infantum, are obligatory intracellular protozoa of mononuclear phagocytes found principally in the spleen and bone marrow. protracted fever, anemia, wasting, hepatosplenomegaly, hemorrhages, and bacterial co-infections are typical features. one hundred and twenty-two (122) in-hospital patients were stud ...201424615127
experimental selection of paromomycin and miltefosine resistance in intracellular amastigotes of leishmania donovani and l. infantum.although widespread resistance of leishmania donovani and l. infantum against miltefosine (mil) and paromomycin (pmm) has not yet been demonstrated, both run the risk of resistance selection. unraveling the dynamics and mechanisms of resistance development is key to preserve drug efficacy in the field. in this study, resistance against pmm and mil was experimentally selected in vitro in intracellular amastigotes of several strains of both species with different antimony susceptibility background ...201424615359
toll like receptor 2 and cc chemokine receptor 5 cluster in the lipid raft enhances the susceptibility of leishmania donovani infection in macrophages.in experimental visceral leishmaniasis the causative obligate protozoan parasite, l. donovani invades and multiplies inside of macrophages, one of the sentries of the mammalian immune system. the initial host-parasite interaction between the leishmania promastigote and the macrophage takes place at the plasma membrane interface. to trace any possible interaction between toll-like receptor 2 (tlr2) and cc chemokine receptor 5 (ccr5) during early leishmania-macrophage interactions, it was observed ...201424617012
studies on the protective efficacy of second-generation vaccine along with standard antileishmanial drug in leishmania donovani infected balb/c mice.it is well established that visceral leishmaniasis (vl; also known as kala azar) causes immunosuppression, and a successful drug treatment is associated with the development of cell-mediated immunity. therefore combining a drug with an immune enhancer can provide a better approach for the treatment of the disease. keeping this in mind, the in vivo antileishmanial efficacy of immunochemotherapy was evaluated with the use of a 78 kda antigen with or without monophosphoryl lipid a (mpl-a) along wit ...201424618257
isolation, characterization and antimicrobial evaluation of a novel compound n-octacosan 7β ol, from fumaria parviflora lam.fumaria parviflora lam. (fumaraceae) is widely used in traditional as well as folkloric system of medicine from ancient. it is commonly known as 'pitpapra' or 'shahtrah' in indian traditional system of medicine and used for treating numerous ailments like diarrhea, fever, influenza, blood purifier and other complications. the object of the present study was to evaluate the antileishmanial, antibacterial, antifungal and cytotoxic potential of isolated compound.201424621260
absence of leishmania infantum in cave bats in an endemic area in spain.though dogs have been historically considered the main reservoir of leishmania infantum, the role of wildlife in its epidemiology is attracting increasing attention. rodents, wild carnivores and, recently, hares (lepus spp.) have been proposed as sylvatic reservoirs for this parasite. bats have never been tested for l. infantum infection in europe. nevertheless, bats have a widespread distribution, they live in abundant colonies, and some species inhabit caves, where constant temperatures and hu ...201424623348
a quantitative proteomic screen to identify potential drug resistance mechanism in α-difluoromethylornithine (dfmo) resistant leishmania donovani.visceral leishmaniasis (vl) caused by leishmania donovani is a systemic protozoan disease that is fatal if left untreated. the promastigote form of l. donovani is sensitive to growth inhibition by dl-α-difluoromethylornithine (dfmo), an inhibitor of ornithine decarboxylase (odc), the first enzyme of the polyamine biosynthetic pathway. exposure of a wild type (di700) cell population to gradually increasing concentrations of dfmo resulted in the selection of a strain of leishmania (dfmo-16), which ...201424631822
tissue requirements for establishing long-term cd4+ t cell-mediated immunity following leishmania donovani infection.organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by leishmania donovani. experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. cd4+ t cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. in this study, we show ...201424634490
analysis of the leishmania peroxin 7 interactions with peroxin 5, peroxin 14 and pts2 ligands.lpex7 (leishmania peroxin 7) is essential for targeting newly synthesized proteins with a pts2 (peroxisome-targeting signal type 2) import signal into the glycosome. in the present paper, we describe the biophysical characterization of a functional lpex7 isolated from escherichia coli inclusion bodies. pull-down assays showed that lpex7 binds the interacting partners ldpex5 (leishmania donovani peroxin 5) and ldpex14, but, more importantly, this receptor can specifically bind pts2 cargo proteins ...201424635481
synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents.antileishmanial activities of a library of synthetic chalcone analogues have been examined. among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of leishmania donovani. three promising compounds, 16, 17, and 22, were tested in a l. donovani/hamster model. oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, re ...201424635539
anti-l. donovani activity in macrophage/amastigote model of palmarumycin cp18 and its large scale production.palmarumycin cp18, isolated from an extract of the fermentation broth and mycelium of the panamanian endophytic fungus edenia sp., was previously reported with strong and specific activity against leishmania donovani. here we report that when the same strain was cultured on different solid media--harrold agar, leonian agar, potato dextrose agar (pda), corn meal agar, honey peptone agar, and eight vegetables (v8) agar--in order to determine the optimal conditions for isolation of palmarumycin cp1 ...201424660473
activity of olive leaf extracts against the promastigote stage of leishmania species and their correlation with the antioxidant activity.leishmaniasis is one of the neglected tropical diseases in terms of drug discovery and development. furthermore, the chemotherapy used to treat this disease has been proved to be highly toxic and to present resistance issues. as consequent, the need for novel leishmanicidal molecules has notably increased in the recent years. in the present work an attempt was made to evaluate the antioxidant and leishmanicidal activities besides presence of compounds in leaf extracts of 5 different tunisian oli ...201424662269
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