| methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in leishmania donovani. | we investigate the role of methionine aminopeptidase 2 (map2) in miltefosine induced programmed cell death (pcd) in promastigote form of l. donovani. we report that tnp-470, an inhibitor of map2, inhibits programmed cell death in miltefosine treated promastigotes. it inhibits the biochemical features of metazoan apoptosis, including caspase3/7 protease like activity, oligonucleosomal dna fragmentation, collapse of mitochondrial transmembrane potential, and increase in cytosolic pool of calcium i ... | 2017 | 28273904 |
| new developments in probing and targeting protein acylation in malaria, leishmaniasis and african sleeping sickness. | infections by protozoan parasites, such as plasmodium falciparum or leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. the increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. post-translational modifications (ptms) are important modulators of ... | 2017 | 28270257 |
| role of leishmanial acidocalcisomal pyrophosphatase in the camp homeostasis in phagolysosome conditions required for intra-macrophage survival. | exposure of leishmania donovani to macrophage phagolysosome conditions (pc) (37°c and ph 5.5) led to increased intracellular camp and camp-mediated responses, which help in intra-macrophage survival pre-requisite for infectivity. in the absence of typical orthologs for g-proteins and g-protein coupled receptors, we sought to study the precise mechanisms for positive modulation of camp production during exposure to pc. amongst two promastigote-stage specific membrane bound receptor adenylate cycl ... | 2017 | 28268199 |
| integrating genomics and proteomics permits identification of immunodominant antigens associated with drug resistance in human visceral leishmaniasis in india. | resistance of human pathogens like leishmania to drugs is a growing concern where the multidrug-resistant phenotype renders chemotherapy ineffective. the acquired resistance of leishmania to antimony has promoted intense research on the mechanisms involved but the question has not been resolved yet. in this study we have explored host-pathogen- drug interactions leading to identification of pharmacological determinants of host macrophages that resist the sodium antimony gluconate (sag) mediated ... | 2017 | 28263760 |
| single locus genotyping to track leishmania donovani in the indian subcontinent: application in nepal. | we designed a straightforward method for discriminating circulating leishmania populations in the indian subcontinent (isc). research on transmission dynamics of visceral leishmaniasis (vl, or kala-azar) was recently identified as one of the key research priorities for elimination of the disease in the isc. vl in bangladesh, india, and nepal is caused by genetically homogeneous populations of leishmania donovani parasites, transmitted by female sandflies. classical methods to study diversity of ... | 2017 | 28249021 |
| glycyrrhizic acid attenuates growth of leishmania donovani by depleting ergosterol levels. | in the present study, glycyrrhizic acid (ga) the main component of glycyrrhiza glabra was evaluated for its efficacy as antileishmanial agent and its mode of action explored. ga inhibits promastigotes and intracellular amastigotes in a dose dependent manner at an ic50 value of 34 ± 3.0 μm and 20 ± 4.2 μm respectively. ga was non-toxic against thp-1 macrophage host cell line. ga was found to inhibit recombinant leishmania donovani hmg-coa reductase (ldhmgr) enzyme at the half-maximum inhibitory c ... | 2017 | 28242356 |
| synthesis and antitrypanosomal activities of novel pyridylchalcones. | a library of novel pyridylchalcones were synthesised and screened against trypanosoma brucei rhodesiense. eight were shown to have good activity with the most potent 8 having an ic50 value of 0.29 μm. cytotoxicity testing with human kb cells showed a good selectivity profile for this compound with a selectivity index of 47. little activity was seen when the library was tested against leishmania donovani. in conclusion, pyridylchalcones are promising leads in the development of novel compounds fo ... | 2017 | 28189085 |
| cloning, characterization and subcellular localization of nuclear lim interactor interacting factor gene from leishmania donovani. | lim domains are zinc-binding motifs that mediate protein-protein interactions and are found in a wide variety of cytoplasmic and nuclear proteins. the nuclear lim domain family members have a number of different functions including transcription factors, gene regulation, cell fate determination, organization of the cytoskeleton and tumour formation exerting their function through various lim domain interacting protein partners/cofactors. nuclear lim domain interacting proteins/factors have not b ... | 2017 | 28188871 |
| putative drug and vaccine target identification in leishmania donovani membrane proteins using naïve bayes probabilistic classifier. | predicting the role of protein is one of the most challenging problems. there are few approaches available for the prediction of role of unknown protein in terms of drug target or vaccine candidate. we propose here naïve bayes probabilistic classifier, a promising method for reliable predictions. this method is tested on the proteins identified in our mass spectrometry based membrane protemics study of leishmania donovani parasite that causes a fatal disease (visceral leishmaniasis) in humans al ... | 2017 | 28182549 |
| glucose-6-phosphate dehydrogenase and trypanothione reductase interaction protects leishmania donovani from metalloid mediated oxidative stress. | exploration of metabolons as viable drug target is rare in kinetoplastid biology. here we present a novel protein-protein interaction among glucose-6-phosphate dehydrogenase (ldg6pdh) and trypanothione reductase (ldtryr) of leishmania donovani displaying interconnection between central glucose metabolism and thiol metabolism of this parasite. digitonin fractionation patterns observed through immunoblotting indicated localisation of both ldg6pdh and ldtryr in cytosol. in-silico and in-vitro inter ... | 2017 | 28179112 |
| copper salisylaldoxime (cusal) imparts protective efficacy against visceral leishmaniasis by targeting leishmania donovani topoisomerase ib. | in vitro and in vivo anti-leishmanial efficacy of copper salisylaldoxime (cusal), a transition metal complex, was evaluated and the underlying mechanism was studied. in vitro studies revealed that 30 μm of cusal causes 96% reduction in parasite burden in infected macrophages. cusal is least toxic in host cells. a dose of 5 mg/kg bodyweight per mice on alternate days (5 doses) gives ∼97% protection in both liver and spleen. moreover, cusal potentially inhibits the catalytic activity of ldtopils a ... | 2017 | 28174102 |
| evaluation of the antileishmanial potency, toxicity and phytochemical constituents of methanol bark extract of sterculia villosa. | visceral leishmaniasis is a protozoan disease caused by leishmania donovani parasite. the genus sterculia (malvaceae) possesses ethnobotanical potential against this protozoan infection. | 2017 | 28173714 |
| apoptosis-like cell death in leishmania donovani treated with kalsometm10, a new liposomal amphotericin b. | the present study aimed to elucidate the cell death mechanism in leishmania donovani upon treatment with kalsometm10, a new liposomal amphotericin b. | 2017 | 28170432 |
| efficacy of protease inhibitor from marine streptomyces sp. vitbvk2 against leishmania donovani - an in vitro study. | in the present study the leishmanicidal effect of potential protease inhibitor producing marine actinobacterial isolate has been investigated against leishmania donovani, the causative agent of visceral leishmaniasis. among 89 marine actinobacteria isolated from a salt pan in kanyakumari, only one isolate (bvk2) showed 97% of protease inhibition activity against trypsin. moderate to high protease inhibitor activity was shown by isolate bvk2 on proteinase (30%) and chymotrypsin (85%). in optimiza ... | 2017 | 28167209 |
| changes in lipid and fatty acid composition during intramacrophagic transformation of leishmania donovani complex promastigotes into amastigotes. | leishmania sp., are trypanosomatid parasites that are phagocytized by human and animal macrophages. transformation from the vector promastigote stage to the intracellular amastigote host cell stage is mandatory, since development in the host depends on the internalization of the parasite. we identified and analyzed the lipids involved in the promastigote to amastigote transformation process in the leishmania donovani complex. four lipid classes, phospholipids, free fatty acids, triglycerides and ... | 2017 | 28161835 |
| withania somnifera chemotype nmitli 101r significantly increases the efficacy of antileishmanial drugs by generating strong ifn-γ and il-12 mediated immune responses in leishmania donovani infected hamsters. | withania somnifera (l.) dunal (solanaceae), commonly known as ashwagandha, is one of the most important medicinal plant in the traditional indian medical systems. pharmacological studies have established that root extracts of w. somnifera contain several bioactive constituents called withanolides. the plant has long been used for its several beneficial properties and recently as an immunomodulator. | 2017 | 28160866 |
| synthesis of 16 new hybrids from tetrahydropyrans derivatives and morita-baylis-hillman adducts: in vitro screening against leishmania donovani. | leishmaniases are a group of neglected tropical diseases (ntds) caused by protozoan parasites from >20 leishmania species. visceral leishmaniasis (vl), also known as kala-aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. the morita-baylis-hillman adducts (mbhas) are being explored as drug candidates against several diseases, one of them being leishmaniasis. we present here the design, synthesis and in vitro screening against leishmania dono ... | 2017 | 28146095 |
| transcriptional profiling in experimental visceral leishmaniasis reveals a broad splenic inflammatory environment that conditions macrophages toward a disease-promoting phenotype. | visceral leishmaniasis (vl), caused by the intracellular protozoan leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. progressive disease is considered to be due to impaired effector t cell function and/or failure of macrophages to be activated to kill the intracellular parasite. in previous studies, we used the syrian hamster (mesocricetus auratus) as a model because it mimics the pro ... | 2017 | 28141856 |
| laboratory confirmed miltefosine resistant cases of visceral leishmaniasis from india. | miltefosine unresponsive and relapse cases of visceral leishmaniasis (vl) are increasingly being reported. however, there has been no laboratory confirmed reports of miltefosine resistance in vl. here, we report two laboratory confirmed cases of vl from india. | 2017 | 28137296 |
| genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite leishmania. | 5-hydroxymethyluracil (5hmu) is a thymine base modification found in the genomes of a diverse range of organisms. to explore the functional importance of 5hmu, we develop a method for the genome-wide mapping of 5hmu-modified loci based on a chemical tagging strategy for the hydroxymethyl group. | 2017 | 28137275 |
| comprehensive identification of mrna-binding proteins of leishmania donovani by interactome capture. | leishmania are unicellular eukaryotes responsible for leishmaniasis in humans. like other trypanosomatids, leishmania regulate protein coding gene expression almost exclusively at the post-transcriptional level with the help of rna binding proteins (rbps). due to the presence of polycystronic transcription units, leishmania do not regulate rna polymerase ii-dependent transcription initiation. recent evidence suggests that the main control points in gene expression are mrna degradation and transl ... | 2017 | 28135300 |
| antiprotozoal glutathione derivatives with flagellar membrane binding activity against t. brucei rhodesiense. | a new series of n-substituted s-(2,4-dinitrophenyl)glutathione dibutyl diesters were synthesized to improve in vitro anti-protozoal activity against the pathogenic parasites trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the results obtained indicate that n-substituents enhance the inhibitory properties of glutathione diesters whilst showing reduced toxicity against kb cells as in the cases of compounds 5, 9, 10, 16, 18 and 19. we suggest that the interaction of n-sub ... | 2017 | 28131508 |
| indian erythrodermic postkala-azar dermal leishmaniasis. | postkala-azar dermal leishmaniasis (pkdl) is a complication of kala-azar or visceral leishmaniasis and is caused by leishmania donovani. we describe an indian male patient with the rarer erythrodermic form of pkdl and multiple unusual skin lesions viz. verrucous, annular and mucosal ulceration. | 2017 | 28130283 |
| optimized crispr-cas9 genome editing for leishmania and its use to target a multigene family, induce chromosomal translocation, and study dna break repair mechanisms. | crispr-cas9-mediated genome editing has recently been adapted for leishmania spp. parasites, the causative agents of human leishmaniasis. we have optimized this genome-editing tool by selecting for cells with crispr-cas9 activity through cotargeting the miltefosine transporter gene; mutation of this gene leads to miltefosine resistance. this cotargeting strategy integrated into a triple guide rna (grna) expression vector was used to delete all 11 copies of the a2 multigene family; this was not p ... | 2017 | 28124028 |
| exploration of new and potent lead molecules against caax prenyl protease i of leishmania donovani through pharmacophore based virtual screening approach. | visceral leishmaniasis is a deadly disease left untreated in over 95% of cases. it is characterized by irregular bouts of fever, weight loss, enlargement of the spleen and liver, and anemia. it is highly endemic in the indian subcontinent. caax prenyl proteasei of leishmania donovani is one of the important targets regulating the post translational modification process. hence identifying potent drug candidate against the target is essential. this study mainly focuses on developing new and potent ... | 2017 | 28116998 |
| antiprotozoal activity-based profiling of a dichloromethane extract from anthemis nobilis flowers. | a dichlomethane extract of anthemis nobilis flower cones showed promising in vitro antiprotozoal activity against trypanosoma brucei rhodesiense and leishmania donovani, with ic50 values of 1.43 ± 0.50 and 1.40 ± 0.07 μg/ml, respectively. a comprehensive profiling of the most active fractions afforded 19 sesquiterpene lactones, including 15 germacranolides, two seco-sesquiterpenes, one guaianolide sesquiterpene lactone, and one cadinane acid. of these, 13 compounds were found to be new natural p ... | 2017 | 28116906 |
| elimination of kala-azar from the southeast asia region. | visceral leishmaniasis (vl), popularly known as kala-azar, is essentially a disease of poverty. kala-azar is caused by a parasite, leishmania donovani recent review indicates that worldwide 98 countries are endemic for kala-azar. approximately 0.2-0.4 million new vl cases occur each year worldwide. more than 90% of global vl cases occur in bangladesh, brazil, ethiopia, india, south sudan, and sudan. this trend is slowly changing due to the progress in kala-azar elimination in southeast asia, whe ... | 2017 | 28115678 |
| design, synthesis and antimalarial activity of novel bis{n-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives. | novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of w2 and 3d7 plasmodium falciparum strains. biological results showed good antimalarial activity with ic50 in the μm range. in attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward leishmania donovani were also investigated and revealed their selective antiplasmodial profil ... | 2017 | 28114821 |
| in situ immunopathological changes in cutaneous leishmaniasis due to leishmania donovani. | cutaneous leishmaniasis in sri lanka is a newly established parasitic disease caused by the usually visceralizing leishmania donovani. skin lesions manifest as non-itchy, non-tender papules, nodules or ulcers. in situ cytokine expression provides clues for immunopathogenesis of this localized form of disease. skin biopsies from 58 patients were analyzed for histological appearance and in situ cytokine expression of t-helper 1 (th1) and t-helper 2 (th2) cytokines, namely interferon (ifn)-γ, inter ... | 2017 | 28112425 |
| splenic cd4+ t cells in progressive visceral leishmaniasis show a mixed effector-regulatory phenotype and impair macrophage effector function through inhibitory receptor expression. | visceral leishmaniasis (vl), caused by infection with the intracellular protozoan leishmania donovani, is a chronic progressive disease with a relentlessly increasing parasite burden in the spleen, liver and bone marrow. the disease is characterized by fever, splenomegaly, cachexia, and pancytopenia, and progresses to death if not treated. control of leishmania infection is mediated by th1 (ifnγ-producing) cd4+ t cells, which activate macrophages to produce nitric oxide and kill intracellular pa ... | 2017 | 28103263 |
| snapshot profiling of the antileishmanial potency of lead compounds and drug candidates against intracellular leishmania donovani amastigotes, with a focus on human-derived host cells. | this study characterized the in vitro potencies of antileishmanial agents against intracellular leishmania donovani amastigotes in primary human macrophages, obtained with or without cd14-positive monocyte enrichment, phorbol 12-myristate 13-acetate (pma)-differentiated thp-1 cells, and mouse peritoneal exudate macrophages (pems). host cell-dependent potency was confirmed for pentavalent and trivalent antimony. fexinidazole was inactive against intracellular amastigotes across the host cell pane ... | 2017 | 28069646 |
| assessment of formulated amodiaquine microparticles in leishmania donovani infected rats. | the aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against leishmania donovani. microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. the microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. the size range of the microparticles formulated was between 1.9 and 10 μm with an average zeta potential of -25.5 mv. of t ... | 2017 | 28067090 |
| immunization with leishmania donovani protein disulfide isomerase dna construct induces th1 and th17 dependent immune response and protection against experimental visceral leishmaniasis in balb/c mice. | in the present study, the efficacy of leishmania donovani protein disulfide isomerase (ldpdi) as a dna vaccine was evaluated in balb/c mice. mice immunized with the ldpdi-dna construct were found to be the most immuno-reactive, as the construct induced higher t-cell proliferation. the increased t-cell proliferation was associated with a substantial rise in th1 and th17+ cd4 cell response and triggered a higher proportion of cd8+ t cells for the release of interferon-gamma along with a reduced sp ... | 2017 | 28064069 |
| antileishmanial activity of pyrazolopyridine derivatives and their potential as an adjunct therapy with miltefosine. | a series of pyrazolo(dihydro)pyridines was synthesized and evaluated for antileishmanial efficacy against experimental visceral leishmaniasis (vl). among all compounds, 6d and 6j exhibited better activity than miltefosine against intracellular amastigotes. compound 6j (50 mg/kg/day) was further studied against leishmania donovani/balb/c mice via the intraperitoneal route for 5 days and displayed >91 and >93% clearance of splenic and liver parasitic burden, respectively. combination treatment of ... | 2017 | 28059524 |
| naloxonazine, an amastigote-specific compound, affects leishmania parasites through modulation of host-encoded functions. | host-directed therapies (hdts) constitute promising alternatives to traditional therapy that directly targets the pathogen but is often hampered by pathogen resistance. hdt could represent a new treatment strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite leishmania. this protozoan develops exclusively within phagocytic cells, where infection relies on a complex molecular interplay potentially exploitable for drug targets. we previously identif ... | 2016 | 28036391 |
| subcellular localization studies of ldbpk_070020, a conserved protein of leishmania donovani. | | 2016 | 28035116 |
| the screening of novel inhibitors against leishmania donovani calcium ion channel to fight leishmaniasis. | leishmania is an intracellular protozoan parasite which causes leishmaniasis, a global health problem affecting millions of people throughout 89 different countries in the world. the current treatment which includes use of amphotericin b, antimonials, and others has major drawbacks due to toxicity, resistance, and extraordinary high cost. so there is an urgent need of development of new drug targets to fight against leishmaniasis. in this regard we have selected leishmania donovani ca2+ ion chan ... | 2016 | 28034363 |
| nanotized curcumin and miltefosine, a potential combination for treatment of experimental visceral leishmaniasis. | leishmaniasis chemotherapy remains very challenging due to high cost of the drug and its associated toxicity and drug resistance, which develops over a period of time. combination therapies (ct) are now in use to treat many diseases, such as cancer and malaria, since it is more effective and affordable than monotherapy. ct are believed to represent a new explorable strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite leishmania in the present stu ... | 2017 | 28031196 |
| novel β-carboline-quinazolinone hybrids disrupt leishmania donovani redox homeostasis and show promising antileishmanial activity. | visceral leishmaniasis is a deadly parasitic disease caused by leishmania donovani. paucity exists in the discovery of novel chemotherapeutics against leishmaniasis. in this study, we synthesized a natural product inspired diversity oriented synthesis library of l. donovani trypanothione reductase (ldtr) inhibitor β-carboline-quinazolinone hybrids, which are different in stereochemical architecture and diverse in the bioactive chemical space. it is noteworthy that chirality affects drug-to-prote ... | 2017 | 28017772 |
| mycobacterium indicus pranii (mw)-mediated protection against visceral leishmaniasis by reciprocal regulation of host dual-specificity phosphatases. | leishmania donovani resides within the host macrophages by dampening host defence mechanisms and thereby it modulates the host cell functions for its survival. multiple host cell factors compete during the interplay between the host and the parasite. roles for dual-specificity phosphatases (dusps) are implicated in various pathological conditions. however, the reciprocity of these dusps was unknown in l. donovani infection in a susceptible model. here, we show that mycobacterium indicus pranii ( ... | 2016 | 28013190 |
| pharmacological inhibition of p110δ subunit of pi3k confers protection against experimental leishmaniasis. | this study aimed to evaluate the immuno-prophylactic and -therapeutic effect of p110δ-specific pharmacological inhibitors (cal-101 and ic87114), either alone or in combination with amphotericin b, against experimental cutaneous leishmaniasis (cl) and visceral leishmaniasis (vl). | 2017 | 27999013 |
| leishmania recombinant antigen modulates macrophage effector function facilitating early clearance of intracellular parasites. | immunmodulation combined with chemotherapy has emerged as an alternative to treat infections. the study evaluates immunomodulatory properties of a leishmania recombinant protein (ra6) in activating macrophages and clearing intracellular parasites. | 2016 | 27941165 |
| a mitochondrial hsp70 (hspa9b) is linked to miltefosine resistance and stress response in leishmania donovani. | protozoan parasites of the genus leishmania are responsible for leishmaniasis, a neglected tropical disease affecting millions worldwide. visceral leishmaniasis (vl), caused by leishmania donovani, is the most severe form of leishmaniasis with high rates of mortality if left untreated. current treatments include pentavalent antimonials and amphotericin b. however, high toxicity and emergence of resistance hinder the success of these options. miltefosine (hepc) is the first oral treatment availab ... | 2016 | 27906059 |
| spatiotemporal uncoupling of microrna-mediated translational repression and target rna degradation controls micrornp recycling in mammalian cells. | microrna (mirna)-mediated repression controls expression of more than half of protein-coding genes in metazoan animals. translation repression is associated with target mrna degradation initiated by decapping and deadenylation of the repressed mrnas. earlier evidence suggests the endoplasmic reticulum (er) as the site where micrornps (mirnps) interact with their targets before translation repression sets in, but the subcellular location of subsequent degradation of mirna-repressed messages is la ... | 2017 | 27895152 |
| identification of b-cell epitope of leishmania donovani and its application in diagnosis of visceral leishmaniasis. | diagnosis of visceral leishmaniasis (vl) is often hindered by cross-reactions with antigens from other related parasite infections. this study aimed to develop an immunochromatographic test (ict) which can detect the antigen present in circulating immune complexes (cics) of vl patients using b-cell epitope-specific antibodies. ms analysis of six immunoreactive 2de spots revealed two epitopes i.e. rffvqgdgigqhslqealerr (p1) and rrvavlvlldrl (p2) (from a hypothetical protein [acc no: xp_003861458. ... | 2016 | 27892844 |
| in silico sequence analysis, homology modeling and function annotation of leishmanolysin from leishmania donovani. | leishmaniases are a complex of diseases that range from the deadly visceral disease and some self-curing lesions to gross disfigurations. about 12 million peoples from 88 different countries get infected by this protozoan parasite through the sand flies. visceral leishmaniasis is a potentially fatal disease endemic to large parts of asia and africa, primarily caused by the protozoan parasite leishmania donovani. l. donovani is a species of leishmania, a hemoflagellate parasite and causative agen ... | 2016 | 27876928 |
| diagnostic accuracy of rklo8 versus rk26 elisas for screening of canine visceral leishmaniasis. | canine visceral leishmaniasis (cvl) represents an important public health issue. despite numerous diagnostic tests available, cvl diagnosis still needs to be improved to achieve a more accurate detection rate. recently, rklo8, a new antigenic protein of sudanese leishmania donovani, was studied for the first time in diagnosis of human visceral leishmaniasis (hvl) and showed good performance. the present study aimed to evaluate serum reactivity to rkl08 and the reference antigen rk26, and to comp ... | 2017 | 27876645 |
| development of leishmania donovani stably expressing dsred for flow cytometry-based drug screening using chalcone thiazolyl-hydrazone as a new antileishmanial target. | green fluorescent protein produces significant fluorescence and is extremely stable, however its excitation maximum is close to the ultraviolet range and thus can damage living cells. hence, leishmania donovani stably expressing dsred were developed and their suitability for flow cytometry-based antileishmanial screening was assessed by evaluating the efficacies of standard drugs as well as newly synthesised chalcone thiazolyl-hydrazone compounds. the dsred gene was successfully integrated at th ... | 2016 | 27876275 |
| leishmania donovani development in phlebotomus argentipes: comparison of promastigote- and amastigote-initiated infections. | leishmania parasites alternate in their life cycle between promastigote stages that develop in the gut of phlebotomine sand flies and amastigotes residing inside phagocytic cells of vertebrate hosts. for experimental infections of sand flies, promastigotes are frequently used as this way of infection is technically easier although ingestion of promastigotes by sand flies is unnatural. here we aimed to answer a critical question, to what extent do promastigote-initiated experimental infections di ... | 2017 | 27876097 |
| detection and differentiation of leishmania spp. in clinical specimens by use of a sybr green-based real-time pcr assay. | leishmaniasis in humans is caused by leishmania spp. in the subgenera leishmania and viannia species identification often has clinical relevance. until recently, our laboratory relied on conventional pcr amplification of the internal transcribed spacer 2 (its2) region (its2-pcr) followed by sequencing analysis of the pcr product to differentiate leishmania spp. here we describe a novel real-time quantitative pcr (qpcr) approach based on the sybr green technology (lsg-qpcr), which uses genus-spec ... | 2017 | 27847378 |
| leishmania donovani-induced increase in macrophage bcl-2 favors parasite survival. | members of the bcl-2 family are major regulators of apoptosis in mammalian cells, and hence infection-induced perturbations in their expression could result into elimination of the parasites or creation of a niche favoring survival. in this investigation, we uncover a novel role of host bcl-2 in sustaining leishmania donovani infection. a rapid twofold increase in bcl-2 expression occurred in response to parasite challenge. downregulation of post infection bcl-2 increase using sirna or functiona ... | 2016 | 27826299 |
| functional analysis of an amp forming acetyl coa synthetase from leishmania donovani by gene overexpression and targeted gene disruption approaches. | leishmaniasis, a neglected tropical disease is endemic in 98 countries and >350 million people are at risk of getting the infection. the existing chemotherapy of leishmaniasis is limited due to adverse effects, resistance to existing drugs and increasing cases of hiv-leishmaniasis co-infection. hence, there is a need to identify novel metabolic pathways for design of new chemical entities. acetyl-coa synthetase (acecs) is an enzyme of acetate metabolic pathway whose functions are unknown in leis ... | 2017 | 27825908 |
| imaging visceral leishmaniasis in real time with golden hamster model: monitoring the parasite burden and hamster transcripts to further characterize the immunological responses of the host. | characterizing the clinical, immunological and parasitological features associated with visceral leishmaniasis is complex. it involves recording in real time and integrating quantitative multi-parametric data sets from parasite infected host tissues. although several models have been used, hamsters are considered the bona fide experimental model for leishmania donovani studies. to study visceral leishmaniasis in hamsters we generated virulent transgenic l. donovani that stably express a reporter ... | 2017 | 27794505 |
| oleanolic acid loaded poly lactic co- glycolic acid- vitamin e tpgs nanoparticles for the treatment of leishmania donovani infected visceral leishmaniasis. | oleanolic acid (oa) has low aqueous solubility and low permeability, which results poor bioavailability. to surmount the inadequacy, our aim was to fabricate oleanolic acid loaded poly lactic co- glycolic acid (plga)- d-α- tocopheryl polyethylene glycol 1000 succinate (tpgs) nanoparticles, which could be efficacious for the treatment of leishmania donovani mediated visceral leishmaniasis (vl). oa loaded plga- tpgs nanoparticles were prepared by emulsion solvent evaporation technique. cellular up ... | 2016 | 27645930 |
| pharmacovigilance of miltefosine in treatment of visceral leishmaniasis in endemic areas of bihar, india. | miltefosine, the only oral drug for visceral leishmaniasis (vl), is being used as the first-line drug under the vl elimination program in the indian subcontinent. miltefosine is an oral drug which was used as a topical application for skin metastasis of breast cancer. it was found to be effective against leishmania donovani the main adverse events (ae) reported previously with miltefosine use includes diarrhea, vomiting, and dehydration. other aes include, raised serum alanine transaminase/aspar ... | 2016 | 27645786 |
| coccinia grandis (l.) voigt leaf extract exhibits antileishmanial effect through pro-inflammatory response: an in vitro study. | the conventional drugs used for the treatment of human visceral leishmaniasis have concerns about the toxicity and most importantly parasite resistance. to overcome these troubles, more efforts are made for the development of innovative therapeutic agents having effective antileishmanial activity and simultaneously stimulate adaptive immune system of host cells. hence, search for new leishmanicidal from the natural origin like plants has shown its effectiveness for the treatment of this tropical ... | 2017 | 27796492 |
| gamma interferon-regulated chemokines in leishmania donovani infection in the liver. | in the livers of c57bl/6 mice, gamma interferon (ifn-γ) controls intracellular leishmania donovani infection and the efficacy of antimony (sb) chemotherapy. since both responses usually correlate with granulomatous inflammation, we tested six prominently expressed, ifn-γ-regulated chemokines-cxcl9, cxcl10, cxcl13, cxcl16, ccl2, and ccl5-for their roles in (i) mononuclear cell recruitment and granuloma assembly and maturation, (ii) initial control of infection and self-cure, and (iii) responsiven ... | 2017 | 27795366 |
| arginase is essential for survival of leishmania donovani promastigotes but not intracellular amastigotes. | studies of leishmania donovani have shown that both ornithine decarboxylase and spermidine synthase, two enzymes of the polyamine biosynthetic pathway, are critical for promastigote proliferation and required for maximum infection in mice. however, the importance of arginase (arg), the first enzyme of the polyamine pathway in leishmania, has not been analyzed in l. donovani to test arg function in intact parasites, we generated δarg null mutants in l. donovani and evaluated their ability to prol ... | 2017 | 27795357 |
| phosphorylation of translation initiation factor 2-alpha in leishmania donovani under stress is necessary for parasite survival. | the transformation of leishmania donovani from a promastigote to an amastigote during mammalian host infection displays the immense adaptability of the parasite to survival under stress. induction of translation initiation factor 2-alpha (eif2α) phosphorylation by stress-specific eif2α kinases is the basic stress-perceiving signal in eukaryotes to counter stress. here, we demonstrate that elevated temperature and acidic ph induce the phosphorylation of leishmania donovani eif2α (ldeif2α). in vit ... | 2017 | 27736773 |
| synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates. | thirteen new polyamine derivatives coupled to hydroxybenzotriazole have been synthesized and evaluated for their in vitro antikinetoplastid activity. trypanosoma trypanothione reductase (tryr) was envisioned as a potential target. among all tested molecules, only one compound, a n(3)-spermidine-benzotriazole derivative, displayed relevant inhibitory activity on this enzyme but was not active on parasites. the corresponding boc-protected spermidine-benzotriazole was however trypanocidal against t ... | 2017 | 27793448 |
| glucose deprivation induced upregulation of phosphoenolpyruvate carboxykinase modulates virulence in leishmania donovani. | various physiological stimuli trigger the conversion of noninfective leishmania donovani promastigotes to the infective form. here, we present the first evidence of the effect of glucose starvation, on virulence and survival of these parasites. glucose starvation resulted in a decrease in metabolically active parasites and their proliferation. however, this was reversed by supplementation of gluconeogenic amino acids. glucose starvation induced metacyclogenesis and enhanced virulence through pro ... | 2016 | 27664030 |
| ancistectorine d, a naphthylisoquinoline alkaloid with antiprotozoal and antileukemic activities, and further 5,8'- and 7,1'-linked metabolites from the chinese liana ancistrocladus tectorius. | from the twigs and stems of the chinese liana ancistrocladus tectorius (ancistrocladaceae), two new 5,8'-coupled naphthylisoquinolines, ancistectorine d (5) and its 6-o-demethyl derivative 6, were isolated, along with two new 7,1'-linked alkaloids, 6-o-methylancistectorine b1 (7) and ancistectorine b2 (8). two further compounds, ancistroealaine a (4) and 6-o-demethyl-8-o-methyl-7-epi-ancistrobrevine d (10), already known from related asian and african ancistrocladus species, were discovered for ... | 2016 | 27646602 |
| genetic markers for antimony resistant clinical isolates differentiation from indian kala-azar. | visceral leishmaniasis or kala-azar is caused by the protozoan parasites belonging to the genus leishmania. once thought eradicated from the indian subcontinent, the disease came back with drug resistance to almost all prevalent drugs. molecular epidemiological studies revealed the polymorphic nature of the population of the main player of the disease, leishmania donovani and involvement of other species (l. tropica) and other genus (leptomonas) with the disease. this makes control measures almo ... | 2016 | 27629023 |
| dna sequencing confirms pcr-rflp identification of wild caught larroussius sand flies from crete and cyprus. | many phlebotomine sand fly species (diptera, psychodidae) are vectors of the protozoan parasite leishmania causing a group of diseases called the leishmaniases. the subgenus larroussius includes sand fly vectors found in south east mediterranean basin responsible for visceral (vl) and cutaneous human leishmaniasis (cl). it is important to monitor these medically important insects in order to safely predict possible leishmania transmission cycles. leishmania infantum is endemic in the islands of ... | 2016 | 27609635 |
| recombinant leishmania rab6 (rldrab6) is recognized by sera from visceral leishmaniasis patients. | rab proteins form the largest branch of the ras superfamily. rab proteins are key regulators of intracellular vesicular transport and membrane trafficking. although rabgtpases are well-recognized targets in human diseases but are under-explored therapeutically in the leishmania parasite. using a quantitative cytofluorimetric assay, we analyzed the composition and organization of rab6gtpase protein which was found to be primarily localized on the parasite subpellicular membrane and flagellum due ... | 2016 | 27666959 |
| phenotypic characterization of a leishmania donovani cyclophilin 40 null mutant. | protozoan parasites of the genus leishmania adapt to their arthropod and vertebrate hosts through the development of defined life cycle stages. stage differentiation is triggered by environmental stress factors and has been linked to parasite chaperone activities. using a null mutant approach we previously revealed important, nonredundant functions of the cochaperone cyclophilin 40 in l. donovani-infected macrophages. here, we characterized in more detail the virulence defect of cyp40-/- null mu ... | 2016 | 27216143 |
| safety and efficacy of a combination of paromomycin and miltefosine for two versus three courses in patients with post kala-azar dermal leishmaniasis (pkdl) - an observational pilot study. | pkdl is a dermal form of leishmaniasis caused by protozoal parasite leishmania donovani. it is characterized by macular, popular and nodular lesions or a mixture of these(1) . it is mainly seen in sudan and india, where it follows treatment of visceral leishmaniasis (vl) in 50% and 5-10% of cases respectively(2) . a phase iii study on miltefosine-paromomycin combination for 10 days for treatment of indian visceral leishmaniasis (n=157) revealed high cure rate (98.7%) with minimal toxicity, good ... | 2016 | 27781268 |
| immunotherapeutic potential of eugenol emulsion in experimental visceral leishmaniasis. | the therapy of visceral leishmaniasis (vl) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in hiv-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (cmi). thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. several plant-derived compounds have been found to exert leishmanicidal act ... | 2016 | 27776125 |
| protective inflammatory response against visceral leishmaniasis with potato tuber extract: a new approach of successful therapy. | the increasing number of drug resistance issue of leishmania donovani strain to common drugs compels to develop new therapeutics against leishmaniasis with minimal toxicity. in this regard, bioactive phytocomponents may lead to the discovery of new medicines with appropriate efficiency. the important roles of leishmania proteases in the virulence of leishmania parasite make them very hopeful targets for the improvement of current remedial of leishmaniasis. as part of a hunt for new drugs, we hav ... | 2016 | 27567589 |
| integrated machine learning, molecular docking and 3d-qsar based approach for identification of potential inhibitors of trypanosomal n-myristoyltransferase. | n-myristoyltransferase (nmt) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. it is a studied and validated pre-clinical drug target for fungal and parasitic infections. in the present study, a machine learning approach, docking studies and comfa analysis have been integrated with the objective of translation o ... | 2016 | 27766319 |
| identification of internalin-a-like virulent proteins in leishmania donovani. | an active immune surveillance and a range of barriers to infection allow the host to effectively eliminate microbial pathogens. however, pathogens may use diverse strategies to subdue such host defences. for instance, one such mechanism is the use of leucine-rich repeat (lrr) proteins by pathogens (microbial) to cause infection. in this study, we aimed at identifying novel virulence factor(s) in leishmania donovani, based on the possibility of lateral gene transfers of bacterial virulence factor ... | 2016 | 27765050 |
| phagocytosis of hemozoin by raw 264.7 cells, but not thp-1 cells, promotes infection by leishmania donovani with a nitric oxide-independent mechanism. | during its intra-erythrocytic development, the malaria parasite plasmodium falciparum synthesizes insoluble hemozoin (hz) crystals that are released into the circulation upon rupture of parasitized red blood cells, and rapidly phagocytized by host mononuclear cells. here, hz persists undigested, causing functional impairment and possibly leading to increased host susceptibility to secondary infections. in patients with malaria and visceral leishmaniasis (vl) co-infections, hz-loaded macrophages ... | 2017 | 27623326 |
| pitfalls in the synthesis of fluorescent methotrexate oligopeptide conjugates. | methotrexate (mtx) conjugates with poly[lys(dl-alam)] based polymeric polypeptides are efficient against leishmania donovani parasite infection, but the mechanism of the effect is not known yet. we prepared therefore the 5(6)-carboxyfluorescein (cf) labeled oligopeptide [cf-k(aaaa)] (a: d-alanine, a: l-alanine) and the corresponding mtx conjugates [cf-k(mtx-aaaa)] as model compounds for structure-activity experiments. the conjugate aimed to be synthesized with solid phase methodology on mbha res ... | 2016 | 27357306 |
| visual assessment of parasitic burden in infected macrophage by plasmonic detection of leishmania specific marker rna. | visceral leishmaniasis is a neglected tropical disease and may prove fatal if not diagnosed and treated early. the amastigotes of leishmania donovani nest in the macrophage of human host and thus, determination of parasitic burden in the infected macrophages has been the most crucial step in diagnosis, dose determination and medical management of relapse cases of this fatal disease. microscopic count following giemsa staining and other morphological analysis are the classical ways vastly used in ... | 2016 | 27720714 |
| leishmania donovani inhibits macrophage apoptosis and pro-inflammatory response through akt-mediated regulation of β-catenin and foxo-1. | in order to establish infection, intra-macrophage parasite leishmania donovani needs to inhibit host defense parameters like inflammatory cytokine production and apoptosis. in the present study, we demonstrate that the parasite achieves both by exploiting a single host regulator akt for modulating its downstream transcription factors, β-catenin and foxo-1. l. donovani-infected raw264.7 and bone marrow-derived macrophages (bmdm) treated with akt inhibitor or dominant negative akt constructs showe ... | 2016 | 27662364 |
| noninvasive diagnosis of visceral leishmaniasis: development and evaluation of two urine-based immunoassays for detection of leishmania donovani infection in india. | visceral leishmaniasis (vl), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. post kala-azar dermal leishmaniasis (pkdl), a skin related outcome, is a potential reservoir for the spread of vl. diagnostic tests available for vl such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. serological tests although less invasive than tissue aspiration are incompetent to assess cure. parasitological examination o ... | 2016 | 27741241 |
| nonresponsiveness to standard treatment in cutaneous leishmaniasis: a case series from sri lanka. | leishmaniasis is caused by parasitic protozoa of the genus leishmania. cutaneous leishmaniasis (cl) is endemic in sri lanka with over 3000 cases during the last decade and numbers are increasing. treatment options available in sri lanka for cl include intralesional/intramuscular sodium stibogluconate and cryotherapy. eight cases of treatment failure with standard therapy are reported from the dermatology clinic, teaching hospital anuradhapura. therapeutic regimes aim for clinical healing, these ... | 2017 | 27722106 |
| in vitro 'time-to-kill' assay to assess the cidal activity dynamics of current reference drugs against leishmania donovani and leishmania infantum. | despite a continued search for novel antileishmanial drugs, treatment options remain restricted to a few standard drugs, e.g. antimonials, miltefosine, amphotericin b and paromomycin. although these drugs have now been used for several decades, their mechanism of action still remains partly hypothetical and their dynamics of cidal action and time-to-kill are still poorly documented. | 2017 | 27707992 |
| a comparison of the effectiveness of sodium stibogluconate monotherapy to sodium stibogluconate and paromomycin combination for the treatment of severe post kala azar dermal leishmaniasis in south sudan - a retrospective cohort study. | post-kala-azar dermal leishmaniasis (pkdl) is a common dermatological complication following successful treatment of visceral leishmaniasis (vl) caused by leishmania donovani. pkdl presents as macular, papular, nodular or mixed skin rash on sun-exposed body parts. patients are not ill unless there are complications due to mucosal involvement or ulceration. as pkdl in east africa is typically self-healing, and treatment is long and with significant adverse events, only severe and complicated case ... | 2017 | 27658288 |
| cd4+ recent thymic emigrants are recruited into granulomas during leishmania donovani infection but have limited capacity for cytokine production. | recent thymic emigrants (rtes) represent a source of antigen-naïve t cells that enter the periphery throughout life. however, whether rtes contribute to the control of chronic parasitic infection and how their potential might be harnessed by therapeutic intervention is currently unclear. here, we show that cd4+ recent thymic emigrants emerging into the periphery of mice with ongoing leishmania donovani infection undergo partial activation and are recruited to sites of granulomatous inflammation. ... | 2017 | 27658046 |
| ent-pimarane and ent-kaurane diterpenes from aldama discolor (asteraceae) and their antiprotozoal activity. | aldama discolor (syn.viguiera discolor) is an endemic asteraceae from the brazilian "cerrado", which has not previously been investigated for its chemical constituents and biological activity. diterpenes are common secondary metabolites found in aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. in this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2 ... | 2016 | 27649126 |
| interaction between cysteine synthase and serine o-acetyltransferase proteins and their stage specific expression in leishmania donovani. | leishmania possess a unique trypanothione redox metabolism with undebated roles in protection from oxidative damage and drug resistance. the biosynthesis of trypanothione depends on l-cysteine bioavailability which is regulated by cysteine biosynthesis pathway. the de novo cysteine biosynthesis pathway is comprised of serine o-acetyltransferase (sat) and cysteine synthase (cs) enzymes which sequentially mediate two consecutive steps of cysteine biosynthesis, and is absent in mammalian host. howe ... | 2016 | 27638321 |
| β-nitrostyrenes as potential anti-leishmanial agents. | development of new therapeutic approach to treat leishmaniasis has become a priority. in the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. a series of β-nitrostyrenes have been synthesized by using henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against leishmania donovani promastigotes by following standard guidelines. the most ... | 2016 | 27635124 |
| gene deleted live attenuated leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human pbmcs. | currently no effective vaccine is available for human visceral leishmaniasis(vl) caused by leishmania donovani. previously, we showed that centrin1 and p27gene deleted live attenuated leishmania parasites (ldcen1(-/-) and ldp27(-/-)) are safe, immunogenic and protective in animal models. here, to assess the correlates of protection, we evaluated immune responses induced by ldcen1(-/-) and ldp27(-/-) in human blood samples obtained from healthy, healed vl (hvl), post kala-azar dermal leishmaniasi ... | 2016 | 27624408 |
| a novel sterol isolated from a plant used by mayan traditional healers is effective in treatment of visceral leishmaniasis caused by leishmania donovani. | visceral leishmaniasis (vl), caused by the protozoan parasite leishmania donovani, is a global health problem affecting millions of people worldwide. treatment of vl largely depends on therapeutic drugs such as pentavalent antimonials, amphotericin b, and others, which have major drawbacks due to drug resistance, toxicity, and high cost. in this study, for the first time, we have successfully demonstrated the synthesis and antileishmanial activity of the novel sterol pentalinonsterol (pen), whic ... | 2015 | 27623316 |
| cd271+ mesenchymal stem cells as a possible infectious niche for leishmania infantum. | visceral leishmaniasis (vl) is a serious and fatal disease. therapeutic drugs are toxic and non-sterilizing. the etiological agents leishmania infantum and leishmania donovani cause active and asymptomatic diseases. effective drugs to treat vl exist but unfortunately, post-treatment relapses are common. little is known why drugs are non-sterilizing or how these intracellular pathogens can escape treatment. here, using a murine model of vl we found that cd271+/sca1+ bone marrow mesenchymal stem c ... | 2016 | 27622907 |
| transgenic t cell-specific expression of cxcr3 enhances splenic and hepatic t cell accumulation but does not affect the outcome of visceral leishmaniasis. | the outcome of visceral leishmaniasis, caused by parasite leishmania donovani, depends on the recruitment of leishmanicidal th1 cells. chemokine receptor cxcr3, preferentially expressed by th1 cells, is critical for migration of these t cells during infection. during chronic vl, there is a decrease in the presence of cxcr3-expressing cd4(+) t cells in the spleen, which is associated with high parasitic burden in this organ. we therefore examined whether t cell-specific expression of cxcr3 in mic ... | 2016 | 27614845 |
| molecular modeling and virtual screening approach to discover potential antileishmanial inhibitors against ornithine decarboxylase. | visceral leishmaniasis (vl) is a tropical neglected disease, which encounters poorest of poor people living in asia, africa and latin america; causes the mortality of more than 30,000 people worldwide. the armamentarium for the treatment of vl cases is limited and continuously facing decreasing of efficacy for existing drugs. ornithine decarboxylase (odc) is one of the interesting drug targets in leishmania donovani, due to its association with redox metabolism. | 2016 | 27604958 |
| antileishmanial mechanism of diamidines involves targeting kinetoplasts. | leishmaniasis is a disease caused by pathogenic leishmania parasites; current treatments are toxic and expensive, and drug resistance has emerged. while pentamidine, a diamidine-type compound, is one of the treatments, its antileishmanial mechanism of action has not been investigated in depth. here we tested several diamidines, including pentamidine and its analog db75, against leishmania donovani and elucidated their antileishmanial mechanisms. we identified three promising new antileishmanial ... | 2016 | 27600039 |
| antileishmanial ferrocenylquinoline derivatives: synthesis and biological evaluation against leishmania donovani. | the emergence of resistance against existing antileishmanial drugs necessitates the search for new classes of antileishmanial compounds. herein a series of structurally diverse ferrocenylquinolines have been synthesized and evaluated for in vitro antileishmanial activity against leishmania donovani using the mtt assay. thirteen (m2-m14) substituted ferrocenylquinoline congeners possessing triazole rings were generated by palladium mediated suzuki-miyaura coupling reaction of 5-iodoferrocenylquin ... | 2016 | 27598235 |
| magnesium-dependent ecto-atp diphosphohydrolase activity in leishmania donovani. | in this work, we have described the expression of ecto-atpdase on the external surface of leishmania donovani. this enzyme has the ability to hydrolyze extracellular atp. there is a low level of atp hydrolysis in the absence of divalent cation 2.5 ± 0.51 nm pi 10(7) cells/h which shows the divalent cation-dependent activity of this enzyme in the intact parasite. however, mgcl2 stimulated the atp hydrolysis to a greater extent compared with cacl2 and zncl2. this activity was also observed when re ... | 2016 | 27589852 |
| live attenuated leishmania donovani centrin knock out parasites generate non-inferior protective immune response in aged mice against visceral leishmaniasis. | visceral leishmaniasis (vl) caused by the protozoan parasite leishmania donovani causes severe disease. age appears to be critical in determining the clinical outcome of vl and at present there is no effective vaccine available against vl for any age group. previously, we showed that genetically modified live attenuated l. donovani parasites (ldcen-/-) induced a strong protective innate and adaptive immune response in young mice. in this study we analyzed ldcen-/- parasite mediated modulation of ... | 2016 | 27580076 |
| taxonomic and predicted metabolic profiles of the human gut microbiome in pre-columbian mummies. | characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. we characterized the gut microbiome of two pre-columbian andean mummies dating to the 10-15th centuries using 16s rrna gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century ad pre-columbian andean mummy. our previous study sh ... | 2016 | 27559027 |
| the immunology of post-kala-azar dermal leishmaniasis (pkdl). | post-kala-azar dermal leishmaniasis (pkdl) is a common complication of visceral leishmaniasis (vl) caused by leishmania donovani. because of its possible role in transmission it is considered a public health problem in vl endemic areas. the clinical features include a skin rash consisting of macules, papules or nodules in an otherwise healthy individual; this presentation is determined by the immune response towards parasites in the skin that probably persisted from the previous vl episode. the ... | 2016 | 27553063 |
| nitrotriazole-based acetamides and propanamides with broad spectrum antitrypanosomal activity. | 3-nitro-1h-1,2,4-triazole-based acetamides bearing a biphenyl- or a phenoxyphenyl moiety have shown remarkable antichagasic activity both in vitro and in an acute murine model, as well as substantial in vitro antileishmanial activity but lacked activity against human african trypanosomiasis. we have shown now that by inserting a methylene group in the linkage to obtain the corresponding propanamides, both antichagasic and in particular anti-human african trypanosomiasis potency was increased. th ... | 2016 | 27543881 |
| immunogenicity and protective efficacy of dna vaccine against visceral leishmaniasis in balb/c mice. | the current study was designed to examine the protective efficacy of dna vaccines based on gp63 and hsp70 against murine visceral leishmaniasis. inbred balb/c mice were immunized subcutaneously twice at an interval of three weeks with pcdna3.1(+) encoding t cell epitopes of gp63 and hsp70 individually and in combination. animals were challenged intracardially with 10(7) promastigotes of leishmania donovani 10 days post immunization and sacrificed 1, 2 and 3 months post challenge. the immunized a ... | 2016 | 27533939 |
| nkt cell activation by leishmania mexicana lpg: description of a novel pathway. | nkt cells have been associated with protection against leishmania donovani, yet their role in infections with leishmania mexicana has not been addressed, nor has the activation pathway been defined after stimulation with leishmania mexicana lipophosphoglycan (lpg). we analyzed the activation of nkt cells and their cytokine production in response to leishmania mexicana lpg. additionally we compared nkt-cell numbers and cytokine profile in lymph nodes of skin lesions induced by leishmania mexicana ... | 2017 | 27523746 |
| synthesis and activity of novel homodimers of morita-baylis-hillman adducts against leishmania donovani: a twin drug approach. | it is reported here the synthesis of novel homodimers 12-19 of morita-baylis-hillman adducts (mbha) from one-pot morita-baylis-hillman reaction (mbhr) between aromatic aldehydes as eletrophiles and ethylene glycol diacrylate as michael acceptor (35-94% yields) using cheap and green conditions. the bioactivities were evaluated against promastigote form of leishmania donovani. all homodimers showed to be more potent than corresponding monomers. it is worth highlighting that the halogenated homodim ... | 2016 | 27520941 |
| a novel spirooxindole derivative inhibits the growth of leishmania donovani parasites both in vitro and in vivo by targeting type ib topoisomerase. | visceral leishmaniasis is a fatal parasitic disease, and there is an emergent need for development of effective drugs against this neglected tropical disease. we report here the development of a novel spirooxindole derivative, n-benzyl-2,2'α-3,3',5',6',7',7α,α'-octahydro-2methoxycarbonyl-spiro[indole-3,3'-pyrrolizidine]-2-one (compound 4c), which inhibits leishmania donovani topoisomerase ib (ldtopib) and kills the wild type as well as drug-resistant parasite strains. this compound inhibits cata ... | 2016 | 27503653 |
| grind2-based 3d-qsar and prediction of activity spectra for symmetrical bis-pyridinium salts with promastigote antileishmanial activity. | leishmaniasis is a major group of neglected tropical diseases caused by the protozoan parasite leishmania. about 12 million people are affected in 98 countries and 350 million people worldwide are at risk of infection. current leishmaniasis treatments rely on a relatively small arsenal of drugs, including amphotericin b, pentamidine and others, which in general have some type of inconvenience. recently, we have synthesized antileishmanial bis-pyridinium derivatives and symmetrical bis-pyridinium ... | 2016 | 27495391 |