Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| leishmanial sphingolipid induces apoptosis in sarcoma 180 cancer cells through regulation of tumour growth via angiogenic switchover. | sphingolipids are membrane and intracellular lipids that typically modulate cellular processes to cause cell death. exogenous administration of sphingolipids may cause restriction of tumour growth and several alternative strategies are being used to control the cell growth. the microbes, their cellular component(s) or metabolites like dha, epa and also fty720 have been employed as new therapeutic entities to regulate the disease condition. the therapeutic efficacy of lipids from leishmania donov ... | 2015 | 25524576 |
| "squalenoylcurcumin" nanoassemblies as water-dispersible drug candidates with antileishmanial activity. | curcumin, a natural polyphenolic compound, showed antiparasitic potential, including trypanocidal and leishmanicidal activity, in several in vitro and in vivo models. the molecule is well tolerated in humans. however, it is insoluble in water and displays poor oral bioavailability as a result of low absorption. new derivatives of curcumin were prepared by esterification of one or two of its phenolic groups with 1,1',2-tris-norsqualenic acid. these "squalenoylcurcumins" were formulated as water-d ... | 2015 | 25523035 |
| randomized, double-blind, controlled, comparative study on intralesional 10% and 15% hypertonic saline versus intralesional sodium stibogluconate in leishmania donovani cutaneous leishmaniasis. | intralesional 7% hypertonic saline (hs) has been shown to be effective and safe against leishmania donovani and leishmania major cutaneous leishmaniasis (cl), with cure rates of 92% and 96%, respectively. this study was designed to assess the efficacy and safety of 10% and 15% hs in cl. | 2015 | 25600472 |
| leishmania infantum amastigotes trigger a subpopulation of human b cells with an immunoregulatory phenotype. | visceral leishmaniasis is caused by the protozoan parasites leishmania infantum and leishmania donovani. this infection is characterized by an uncontrolled parasitization of internal organs which, when left untreated, leads to death. disease progression is linked with the type of immune response generated and a strong correlation was found between disease progression and serum levels of the immunosuppressive cytokine il-10. other studies have suggested a role for b cells in the pathology of this ... | 2015 | 25710789 |
| the neurotrophic receptor ntrk2 directs lymphoid tissue neovascularization during leishmania donovani infection. | the neurotrophic tyrosine kinase receptor type 2 (ntrk2, also known as trkb) and its ligands brain derived neurotrophic factor (bdnf), neurotrophin-4 (nt-4/5), and neurotrophin-3 (nt-3) are known primarily for their multiple effects on neuronal differentiation and survival. here, we provide evidence that ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. we show that in leishmania donovani-infected mice, ntrk2 is aberrantly expressed on splenic endo ... | 2015 | 25710496 |
| differential immune response against recombinant leishmania donovani peroxidoxin 1 and peroxidoxin 2 proteins in balb/c mice. | we assessed the immune response against recombinant proteins of two related, albeit functionally different, peroxidoxins from leishmania donovani: peroxidoxin 1 (ldpxn1) and peroxidoxin 2 (ldpxn2) in balb/c mice. we also evaluated the effect of coadministration of tlr agonists (cpg odn and gla-se) on the antigen-specific immune response. immunization with recombinant ldpxn1 alone induced a predominantly th2 type immune response that is associated with the production of high level of igg1 and no ... | 2015 | 26380320 |
| 3-nitrotriazole-based piperazides as potent antitrypanosomal agents. | novel linear 3-nitro-1h-1,2,4-triazole-based piperazides were synthesized and evaluated as antitrypanosomal agents. in addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. most 3-nitrotriazole-based derivatives were potent and selective against trypanosoma cruzi parasites, but only one displayed these desired properties against trypanosoma brucei rhodesiense. moreover, two 3-nitrotriazole-based chlorophenylpiperazides were mod ... | 2015 | 26363868 |
| antimony-resistant leishmania donovani exploits mir-466i to deactivate host myd88 for regulating il-10/il-12 levels during early hours of infection. | infection with antimony-resistant leishmania donovani (sb(r)ld) induces aggressive pathology in the mammalian hosts as compared with ones with antimony-sensitive l. donovani (sb(s)ld) infection. sb(r)ld, but not sb(s)ld, interacts with tlr2/tlr6 to induce il-10 by exploiting p50/c-rel subunits of nf-κb in infected macrophages (mϕs). most of the tlrs exploit the universal adaptor protein myd88 to activate nf-κb. we now show that infection of mϕs from myd88(-/-) mice with sb(r)ld gave rise to sign ... | 2015 | 26283478 |
| immunological comparison of dna vaccination using two delivery systems against canine leishmaniasis. | visceral leishmaniasis (vl) is a fatal disease caused by the intracellular protozoan parasite leishmania infantum. dogs are the primary reservoirs of this parasite, and vaccination of dogs could be an effective method to reduce its transfer to humans. in order to develop a vaccine against vl (apart from the choice of immunogenic candidate antigens), it is necessary to use an appropriate delivery system to promote a proper antigen-specific immune response. in this study, we compared two vaccine d ... | 2015 | 26255093 |
| detection of leishmania donovani and l. tropica in ethiopian wild rodents. | human visceral (vl, also known as kala-azar) and cutaneous (cl) leishmaniasis are important infectious diseases affecting countries in east africa that remain endemic in several regions of ethiopia. the transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various leishmania spp., sand fly vectors, and reservoir animals besides human hosts. particularly in east africa, the role of animals as reservoirs for human vl remai ... | 2015 | 25700710 |
| leishmania donovani skews the cd56(+) natural killer t cell response during human visceral leishmaniasis. | the objective of this study was to understand the categorical function of cd4(+)cd56(+) and cd8(+)cd56(+) nkt cells in human visceral leishmaniasis. these cell populations were significantly deregulated in human peripheral blood during vl. the in vitro experiments showed that cd4(+)nkt cells, but not cd8(+)nkt cells, migrated towards the leishmania donovani infection site. additionally, cd4(+)nkt cells from vl subjects primarily expressed cd25(+)foxp3 and il-10 compared with healthy subjects. ho ... | 2015 | 25697139 |
| metabolic reconfiguration of the central glucose metabolism: a crucial strategy of leishmania donovani for its survival during oxidative stress. | understanding the mechanism that allows the intracellular protozoan parasite leishmania donovani (ld) to respond to reactive oxygen species (ros) is of increasing therapeutic importance because of the continuing resistance toward antileishmanial drugs and for determining the illusive survival strategy of these parasites. a shift in primary carbon metabolism is the fastest response to oxidative stress. a (14)co2 evolution study, expression of glucose transporters together with consumption assays, ... | 2015 | 25690656 |
| repurposing of the open access malaria box for kinetoplastid diseases identifies novel active scaffolds against trypanosomatids. | phenotypic screening had successfully been used for hit generation, especially in the field of neglected diseases, in which feeding the drug pipeline with new chemotypes remains a constant challenge. here, we catalyze drug discovery research using a publicly available screening tool to boost drug discovery. the malaria box, assembled by the medicines for malaria venture, is a structurally diverse set of 200 druglike and 200 probelike compounds distilled from more than 20,000 antimalarial hits fr ... | 2015 | 25690568 |
| proteomic-based approach to gain insight into reprogramming of thp-1 cells exposed to leishmania donovani over an early temporal window. | leishmania donovani, a protozoan parasite, is the causative agent of visceral leishmaniasis. it lives and multiplies within the harsh environment of macrophages. in order to investigate how intracellular parasite manipulate the host cell environment, we undertook a quantitative proteomic study of human monocyte-derived macrophages (thp-1) following infection with l. donovani. we used the isobaric tags for relative and absolute quantification (itraq) method and liquid chromatography-tandem mass s ... | 2015 | 25690103 |
| antigen presenting cells targeting and stimulation potential of lipoteichoic acid functionalized lipo-polymerosome: a chemo-immunotherapeutic approach against intracellular infectious disease. | antigen presenting cells (apc) are well-recognized therapeutic targets for intracellular infectious diseases, including visceral leishmaniasis. these targets have raised concerns regarding their potential for drug delivery due to overexpression of a variety of receptors for pathogen associated molecular pathways after infection. since, lipoteichoic acid (lta), a surface glycolipid of gram-positive bacteria responsible for recognition of bacteria by apc receptors that also regulate their activati ... | 2015 | 25671728 |
| up-regulation of silent information regulator 2 (sir2) is associated with amphotericin b resistance in clinical isolates of leishmania donovani. | silent information regulator 2 (sir2) is involved in parasite survival and apoptosis. here, we aimed to explore the involvement of sir2 in amphotericin b (amb) resistance mechanism in leishmania donovani. | 2015 | 25667407 |
| the host-protective effect of arabinosylated lipoarabinomannan against leishmania donovani infection is associated with restoration of ifn-γ responsiveness. | visceral leishmaniasis (vl), which is endemic as a major infectious disease in the tropical and subtropical countries, is caused by a protozoan parasite leishmania donovani. at present, restricted treatment options and lack of vaccines intensify the problem of controlling vl. therefore, finding a novel immunoprophylactic or therapeutic principle is a pressing need. here, we report that arabinosylated lipoarabinomannan (ara-lam), a tlr2-ligand isolated from mycobacterium smegmatis, exhibits a str ... | 2015 | 25658110 |
| protective effect of croton caudatus geisel leaf extract against experimental visceral leishmaniasis induces proinflammatory cytokines in vitro and in vivo. | in the present state of overwhelming emergence of drug-unresponsive phenotypes of leishmania donovani and persistent severe toxicity in conventional anti-leishmanial therapy, in search for novel leads, the aim of this study has been fixed to identify the active extract(s) of croton caudatus geisel. var. tomentosus hook effective against the parasitic protozoans in vitro and in vivo. c. caudatus geisel. is often used by chakma and hmar community, the local tribes of north-east india for medicinal ... | 2015 | 25655407 |
| surface-engineered dendrimeric nanoconjugates for macrophage-targeted delivery of amphotericin b: formulation development and in vitro and in vivo evaluation. | the present study aimed to develop an optimized dendrimeric delivery system for amphotericin b (amb). fifth-generation (5.0 g) poly(propylene imine) (ppi) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including fourier transform infrared spectroscopy (ftir), (1)h nuclear magnetic resonance ((1)h-nmr) spectroscopic analysis, and atomic force microscopy (afm). mannose-conjugated 5.0 g ppi (mppi) dendrimers were loaded with amb and ... | 2015 | 25645852 |
| experimental resistance to drug combinations in leishmania donovani: metabolic and phenotypic adaptations. | together with vector control, chemotherapy is an essential tool for the control of visceral leishmaniasis (vl), but its efficacy is jeopardized by growing resistance and treatment failure against first-line drugs. to delay the emergence of resistance, the use of drug combinations of existing antileishmanial agents has been tested systematically in clinical trials for the treatment of visceral leishmaniasis (vl). in vitro, leishmania donovani promastigotes are able to develop experimental resista ... | 2015 | 25645828 |
| antiprotozoal activity and dna binding of dicationic acridones. | dicationic acridone derivatives were synthesized and their antiparasitic activity was evaluated. acridones displayed in vitro nanomolar ic50 values against trypanosoma brucei rhodesiense stib900 with selectivity indices >1000. compounds 1b, 3a, and 3b were as potent as the reference drug melarsoprol in this assay. submicromolar-range activities were observed against wild-type (nf54) and resistant (k1) strains of plasmodium falciparum, whereas no significant activity was detected against trypanos ... | 2015 | 25642604 |
| northalrugosidine is a bisbenzyltetrahydroisoquinoline alkaloid from thalictrum alpinum with in vivo antileishmanial activity. | screening of a plant-derived natural product library led to the observation of in vitro antileishmanial activity by three bisbenzyltetrahydroisoquinoline alkaloids (1-3) that were purified previously from thalictrum alpinum. a spectroscopic study of the active compounds was conducted to confirm their identities. of the compounds tested, northalrugosidine (1) showed the most potent in vitro activity against leishmania donovani promastigotes (0.28 μm) and the highest selectivity (29.3-fold) versus ... | 2015 | 25629555 |
| synthesis and biological evaluation of ferrocenylquinoline as a potential antileishmanial agent. | the emergence of resistance against antileishmanial drugs in current use necessitates the search for new classes of antileishmanial compounds. herein we report the design, synthesis, and evaluation of a novel ferrocenylquinoline for activity against leishmania donovani. 7-chloro-n-[2-(1h-5-ferrocenyl-1,2,3-triazol-1-yl)ethyl]quinolin-4-amine (1) was generated by coupling an iron(ii) ethynylferrocene species with 4-(2-ethylazido)amino-7-chloroquinoline using click chemistry. the synthesized compo ... | 2015 | 25619822 |
| studies on cocktails of 31-kda, 36-kda and 51-kda antigens of leishmania donovani along with saponin against murine visceral leishmaniasis. | a substantial number of antigens of leishmania donovani have been described in the past. however, identifying candidate antigens is not enough. appropriate antigen delivery to induce the right type of immune response against leishmaniasis (i.e. induction of a strong antigen-specific th1 type of immune response) is another crucial component of an effective vaccine. therefore, 'cocktail' vaccines are proposed based on the assumption that such cocktails will show enhanced efficacy. studies have bee ... | 2015 | 25615543 |
| chemical proteomics versus leishmaniasis. | in this issue of chemistry & biology, wright et al. (2015) describe an elegant approach to evaluating substrates and the drug target potential of leishmania donovani n-myristoyltransferase (nmt) using a technically simple and straightforward chemical proteomics approach. | 2015 | 25794432 |
| targeting ergosterol biosynthesis in leishmania donovani: essentiality of sterol 14 alpha-demethylase. | leishmania protozoan parasites (trypanosomatidae family) are the causative agents of cutaneous, mucocutaneous and visceral leishmaniasis worldwide. while these diseases are associated with significant morbidity and mortality, there are few adequate treatments available. sterol 14alpha-demethylase (cyp51) in the parasite sterol biosynthesis pathway has been the focus of considerable interest as a novel drug target in leishmania. however, its essentiality in leishmania donovani has yet to be deter ... | 2015 | 25768284 |
| predicting antiprotozoal activity of benzyl phenyl ether diamine derivatives through qsar multi-target and molecular topology. | multi-target qsar is a novel approach that can predict simultaneously the activity of a given chemical compound on different pharmacological targets. in this work, we have used molecular topology and statistical tools such as multilinear regression analysis and artificial neural networks, to achieve a multi-target qsar model capable to predict the antiprotozoal activity of a group of benzyl phenyl ether diamine derivatives. the activity was related to three parasites with a high prevalence rate ... | 2015 | 25754076 |
| sar refinement of antileishmanial n(2),n(4)-disubstituted quinazoline-2,4-diamines. | visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. new drugs that are inexpensive, orally active, and effective could be useful tools in the fight against this disease. we previously showed that n(2),n(4)-disubstituted quinazoline-2,4-diamines displayed low- to sub-micromolar potency against intracellular leishmania, and lead compound n(4)-(furan-2-ylmethyl)-n(2)-isopropyl-7-methylquinazoline-2,4-diamine (4) exhibited modest efficac ... | 2015 | 25749014 |
| comprehensive proteomics analysis of glycosomes from leishmania donovani. | leishmania donovani is a kinetoplastid protozoan that causes a severe and fatal disease kala-azar, or visceral leishmaniasis. l. donovani infects human host after the phlebotomine sandfly takes a blood meal and resides within the phagolysosome of infected macrophages. previous studies on host-parasite interactions have not focused on leishmania organelles and the role that they play in the survival of this parasite within macrophages. leishmania possess glycosomes that are unique and specialized ... | 2015 | 25748437 |
| in vitro and in vivo evaluation of anti-leishmanial and immunomodulatory activity of neem leaf extract in leishmania donovani infection. | the toxicity and emergence of resistance to available chemical drugs against visceral leishmaniasis is evoking to explore herbal treatment. one such attempt with the neem is being reported here. the current study is primarily focused to evaluate the anti-leishmanial effects of neem leaf extracts. among which, ethyl acetate fraction (eaf) alone was found to exhibit leishmanicidal effect validated through cytotoxicity assay and estimated its ic₅₀ to be 52.4 µg/ml on the promastigote stage. propidi ... | 2015 | 25747203 |
| recombinant nad-dependent sir-2 protein of leishmania donovani: immunobiochemical characterization as a potential vaccine against visceral leishmaniasis. | the development of a vaccine conferring long-lasting immunity remains a challenge against visceral leishmaniasis (vl). immunoproteomic characterization of leishmania donovani proteins led to the identification of a novel protein nad+-dependent silent information regulatory-2 (sir2 family or sirtuin) protein (ldsir2rp) as one of the potent immunostimulatory proteins. proteins of the sir2 family are characterized by a conserved catalytic domain that exerts unique nad-dependent deacetylase activity ... | 2015 | 25745863 |
| new compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource. | using whole-cell phenotypic assays, the glaxosmithkline high-throughput screening (hts) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. leishmania donovani, trypanosoma cruzi and trypanosoma brucei. secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. hit compounds were chemically clustered and triaged for desirable physico ... | 2015 | 25740547 |
| cross talk between leishmania donovani cpg dna and toll-like receptor 9: an immunoinformatics approach. | the precise and potential contribution of toll-like receptors (tlrs) signaling pathways in fighting parasitic infections of leishmania spp., an intracellular protozoan parasite, has gained significant attention during the last decades. although it is well established that tlr9 recognizes cpg motifs in microbial genomes, the specificity of the cpg dna pattern of leishmania parasite interacting with endosomal tlr9 is still unknown. hence in our study to identify the cpg dna pattern of leishmania d ... | 2015 | 25735984 |
| global analysis of protein n-myristoylation and exploration of n-myristoyltransferase as a drug target in the neglected human pathogen leishmania donovani. | n-myristoyltransferase (nmt) modulates protein function through the attachment of the lipid myristate to the n terminus of target proteins, and is a promising drug target in eukaryotic parasites such as leishmania donovani. only a small number of nmt substrates have been characterized in leishmania, and a global picture of n-myristoylation is lacking. here, we use metabolic tagging with an alkyne-functionalized myristic acid mimetic in live parasites followed by downstream click chemistry and an ... | 2015 | 25728269 |
| glycyrrhizic acid-mediated subdual of myeloid-derived suppressor cells induces antileishmanial immune responses in a susceptible host. | cd11b(+) gr1(+) myeloid-derived suppressor cells (mdscs), a heterogeneous population of precursor cells, modulate protective immunity against visceral leishmaniasis by suppressing t cell functions. we observed that cd11b(+) gr1(+) mdscs, which initially expanded in soluble leishmanial antigen (sla)-immunized mice and later diminished, suppressed proliferation of t cells isolated from sla-immunized mice, but to a lesser extent than the case in naive mice. this lesser suppression of mdscs accompan ... | 2015 | 26351281 |
| characterisation of cutaneous leishmaniasis in matara district, southern sri lanka: evidence for case clustering. | leishmaniasis is a neglected tropical disease transmitted by phlebotomus spp. sand flies. cutaneous leishmaniasis (cl) in sri lanka is caused by leishmania donovani. transmission patterns are different in southern and northern sri lanka. current study examined the prevalence, risk factors and distribution of cl in matara district, southern sri lanka. total of 2260 individuals from four district secretariat divisions (dsds) were screened by house to house surveys using an interviewer administered ... | 2015 | 26345305 |
| discovery of potent nitrotriazole-based antitrypanosomal agents: in vitro and in vivo evaluation. | 3-nitro-1h-1,2,4-triazole- and 2-nitro-1h-imidazole-based amides with an aryloxy-phenyl core were synthesized and evaluated as antitrypanosomal agents. all 3-nitrotriazole-based derivatives were extremely potent anti-trypanosoma cruzi agents at sub nm concentrations and exhibited a high degree of selectivity for the parasite. the 2-nitroimidazole analogs were only moderately active against t. cruzi amastigotes and exhibited low selectivity. both types of compound were active against leishmania d ... | 2015 | 26344593 |
| aminothiazoles: hit to lead development to identify antileishmanial agents. | as part of drugs for neglected diseases initiative's lead optimization program for the development of new chemical entities to treat visceral leishmaniasis (vl), a series of aminothiazoles were synthesized and screened for in vitro efficacy, solubility and microsomal stability. the primary aim of identifying a lead structure with sub-micromolar activity was achieved. out of 43 compounds synthesized, 16 compounds showed in vitro activity at less than 1 μm against vl. compound 32 showed excellent ... | 2015 | 26318065 |
| a proteomic map of the unsequenced kala-azar vector phlebotomus papatasi using cell line. | the debilitating disease kala-azar or visceral leishmaniasis is caused by the kinetoplastid protozoan parasite leishmania donovani. the parasite is transmitted by the hematophagous sand fly vector of the genus phlebotomus in the old world and lutzomyia in the new world. the predominant phlebotomine species associated with the transmission of kala-azar are phlebotomus papatasi and phlebotomus argentipes. understanding the molecular interaction of the sand fly and leishmania, during the developmen ... | 2015 | 26307495 |
| developing imidazole analogues as potential inhibitor for leishmania donovani trypanothione reductase: virtual screening, molecular docking, dynamics and admet approach. | visceral leishmaniasis (vl) affects indian subcontinent, african and south american continent, and it covers 70 countries worldwide. visceral form of leishmaniasis is caused by leishmania donovani in indian subcontinent which is lethal if left untreated. extensive resistance to antileishmanial drugs such as sodium stibogluconate, pentamidine and miltefosine and their decreased efficacy has been reported in the endemic region. amphotericin b drug has shown good antileishmanial activity with signi ... | 2015 | 26305585 |
| case report: no response to liposomal daunorubicin in a patient with drug-resistant hiv-associated visceral leishmaniasis. | visceral leishmaniasis (vl) in patients with hiv co-infection presents a significant therapeutic challenge due to the lessened chance of achieving long-term cure. we report a case of vl in a 60-year-old man with hiv infection who became refractory to anti-leishmania treatment due to multi-drug resistance. in the face of a worsening clinical situation, and with no other options available, he was treated with an experimental regimen of liposomal daunorubicin, which has previously been shown to hav ... | 2015 | 26305562 |
| immunomodulation of host-protective immune response by regulating foxp3 expression and treg function in leishmania-infected balb/c mice: critical role of irf1. | visceral leishmaniasis (vl), caused by a protozoan parasite leishmania donovani, is still a threat to mankind due to treatment failure, drug resistance and coinfection with hiv. the limitations of first-line drugs have led to the development of new strategies to combat this dreaded disease. recently, we have shown the immunomodulatory property of ara-lam, a tlr2 ligand, against leishmanial pathogenesis. in this study, we have extended our study to the effect of ara-lam on regulatory t cells in a ... | 2015 | 26297915 |
| mannose-binding lectin (mbl) as a susceptible host factor influencing indian visceral leishmaniasis. | visceral leishmaniasis (vl), caused by leishmania donovani is endemic in the indian sub-continent. mannose-binding lectin (mbl) is a complement lectin protein that binds to the surface of leishmania promastigotes and results in activation of the complement lectin cascade. we utilized samples of 218 vl patients and 215 healthy controls from an indian population. mbl2 functional variants were genotyped and the circulating mbl serum levels were measured. mbl serum levels were elevated in patients c ... | 2015 | 26297290 |
| il-17a-producing γδ t cells suppress early control of parasite growth by monocytes in the liver. | intracellular infections, such as those caused by the protozoan parasite leishmania donovani, a causative agent of visceral leishmaniasis (vl), require a potent host proinflammatory response for control. il-17 has emerged as an important proinflammatory cytokine required for limiting growth of both extracellular and intracellular pathogens. however, there are conflicting reports on the exact roles for il-17 during parasitic infections and limited knowledge about cellular sources and the immune p ... | 2015 | 26538396 |
| toll-like receptor 2 targeted rectification of impaired cd8⁺ t cell functions in experimental leishmania donovani infection reinstates host protection. | leishmania donovani, a protozoan parasite, causes the disease visceral leishmanisis (vl), characterized by inappropriate cd8+ t-cell activation. therefore, we examined whether the toll-like receptor 2 (tlr2) ligand ara-lam, a cell wall glycolipid from non-pathogenic mycobacterium smegmatis, would restore cd8+ t-cell function during vl. we observed that by efficient upregulation of tlr2 signaling-mediated nf-κb translocation and mapk signaling in cd8+ t-cells (cd25+cd28+il-12r+ifn-γr+), ara-lam t ... | 2015 | 26559815 |
| cinnamic acid bornyl ester derivatives from valeriana wallichii exhibit antileishmanial in vivo activity in leishmania major-infected balb/c mice. | human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by leishmania major or leishmania donovani, respectively. some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileish ... | 2015 | 26554591 |
| synthesis and biological evaluation of polyalthic acid derivatives for the treatment of neglected diseases. | polyalthic acid is a naturally occurring diterpene found in copaiba oil, one of the most popular natural medicines in the amazon. based on the reported antileishmanial activity of copaiba oil, a series of amides and diols derivatives of polyalthic acid were synthesized and tested against leishmania donovani and trypanosoma brucei. polyalthic acid was active in both assays with ic50 ranging from 3.87 to 8.68 μg/ml. the compound with best antileishmanial activity was 2 h (ic50=3.84 μg/ml) and comp ... | 2015 | 26520665 |
| clinico-epidemiological analysis of post kala-azar dermal leishmaniasis (pkdl) cases in india over last two decades: a hospital based retrospective study. | patients with post kala-azar dermal leishmaniasis (pkdl) are considered a reservoir of leishmania donovani. it is imperative to identify and treat them early for control of visceral leishmaniasis (vl), a current priority in the indian subcontinent. we explored trends in clinico-epidemiological features of pkdl cases over last two decades, for improving management of the disease. | 2015 | 26503551 |
| implications of co-infection of leptomonas in visceral leishmaniasis in india. | protozoan parasites leishmania donovani (family: trypanosomatidae) cause fatal visceral leishmaniasis (vl) and the infection relapses in apparently cured population as post kala-azar dermal leishmaniasis (pkdl) in the indian subcontinent. in recent years co-infection of another trypanosomatid parasite leptomonas with l. donovani during vl/pkdl in this region has become prominent. the observation of clinically lesser-known insect parasite, leptomonas in leishmaniasis is intriguing to researchers. ... | 2015 | 26492813 |
| correction: combining cationic liposomal delivery with mpl-tdm for cysteine protease cocktail vaccination against leishmania donovani: evidence for antigen synergy and protection. | 2015 | 26485528 | |
| synthesis of unsymmetrical sulfides and their oxidation to sulfones to discover potent antileishmanial agents. | unsymmetrical sulfides were first synthesized using combinations of a 1,3-dicarbonyl, an aromatic aldehyde and a thiol in the presence of 10 mol % ethanolic piperidine. these sulfides derivatives were subsequently converted into corresponding sulfones via oxidation in the presence of m-chloroperoxybenzoic acid (m-cpba) at ice-bath to room temperature. the former reaction was achieved at room temperature through one-pot three-component. the later was obtained in good yields using mild reaction co ... | 2015 | 26441303 |
| phytochemical composition, antiparasitic and α-glucosidase inhibition activities from pelliciera rhizophorae. | panama has an extensive mangrove area and it is one of the countries with the highest biodiversity in america. mangroves are widely used in traditional medicine, nevertheless, there are very few studies that validates their medicinal properties in america. given the urgent need for therapeutic options to treat several diseases of public health importance, mangrove ecosystem could be an interesting source of new bioactive molecules. this study was designed to evaluate the potential of pelliciera ... | 2015 | 26435737 |
| counteractive functions are encrypted in the residues of cd154. | cd40, as a single receptor that binds cd154 (cd40-ligand or cd40l), regulates counteractive effector functions such as production of pro- and anti-inflammatory cytokines. therefore, we examined whether such dual messages are encrypted in cd40l. as such message encryption was never investigated, we hypothesized that mutation of certain amino acid residues should in principle enhance pro-inflammatory cytokine production whereas mutation of some others would enhance anti-inflammatory cytokine secre ... | 2015 | 26429321 |
| development and validation of a novel leishmania donovani screening cascade for high-throughput screening using a novel axenic assay with high predictivity of leishmanicidal intracellular activity. | visceral leishmaniasis is an important parasitic disease of the developing world with a limited arsenal of drugs available for treatment. the existing drugs have significant deficiencies so there is an urgent need for new and improved drugs. in the human host, leishmania are obligate intracellular parasites which poses particular challenges in terms of drug discovery. to achieve sufficient throughput and robustness, free-living parasites are often used in primary screening assays as a surrogate ... | 2015 | 26407168 |
| comparative fitness of a parent leishmania donovani clinical isolate and its experimentally derived paromomycin-resistant strain. | paromomycin has recently been introduced for the treatment of visceral leishmaniasis and emergence of drug resistance can only be appropriately judged upon its long term routine use in the field. understanding alterations in parasite behavior linked to paromomycin-resistance may be essential to assess the propensity for emergence and spread of resistant strains. a standardized and integrated laboratory approach was adopted to define and assess parasite fitness of both promastigotes and amastigot ... | 2015 | 26469696 |
| bioactive phloroglucinols from mallotus oppositifolius. | the two new acylphloroglucinol derivatives, methylene-bis-aspidinol ab (1) and mallopposinol (2), together with the nine known compounds, aspidinol b (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of mallotus oppositifolius. their structures were elucidated by spectral analysis including ms, 1d and 2d-nmr spectroscopy. in vitro trypanocidal and antileishmanial acti ... | 2015 | 26463755 |
| development and comparative evaluation of two antigen detection tests for visceral leishmaniasis. | visceral leishmaniasis (vl) can be fatal without timely diagnosis and treatment. treatment efficacies vary due to drug resistance, drug toxicity and co-morbidities. it is important to monitor treatment responsiveness to confirm cure and curtail relapse. currently, microscopy of spleen, bone marrow or lymph node biopsies is the only definitive method to evaluate cure. a less invasive test for treatment success is a high priority for vl management. | 2015 | 26395447 |
| novel agents against miltefosine-unresponsive leishmania donovani. | visceral leishmaniasis is a deadly endemic disease. unresponsiveness to the only available oral drug miltefosine poses a big challenge for the chemotherapy of the disease. we report a novel molecule, ps-203 {4-(4,4,8-trimethyl-7-oxo-3-oxabicyclo[3.3.1]non-2-yl)-benzoic acid methyl ester}, as effective against a miltefosine-unresponsive strain of the parasite. further, combinations of ps-203 with miltefosine were also evaluated and showed promising results against a miltefosine-unresponsive strai ... | 2015 | 26392497 |
| leishmanicidal activity of piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by th1 immunostimulatory potential in vivo. | visceral leishmaniasis (vl) is a life-threatening protozoal infection chiefly impinging the rural and poor population in the tropical and sub-tropical countries. the deadly affliction is rapidly expanding after its association with aids, swiftly defying its status of a neglected disease. despite successful formulation of vaccine against canine leishmaniasis, no licensed vaccine is yet available for human vl, chemotherapy is in appalling state, and the development of new candidate drugs has been pa ... | 2015 | 26696979 |
| polymerase chain reaction detection of leishmania dna in skin biopsy samples in sri lanka where the causative agent of cutaneous leishmaniasis is leishmania donovani. | leishmania donovani is the known causative agent of both cutaneous (cl) and visceral leishmaniasis in sri lanka. cl is considered to be under-reported partly due to relatively poor sensitivity and specificity of microscopic diagnosis. we compared robustness of three previously described polymerase chain reaction (pcr) based methods to detect leishmania dna in 38 punch biopsy samples from patients presented with suspected lesions in 2010. both, leishmania genus-specific jw11/jw12 kdna and litsr/l ... | 2015 | 26676321 |
| bioactivity guided fractionation of moringa oleifera lam. flower targeting leishmania donovani. | leishmaniases is a group of diseases caused by the protozoan parasite belonging to the genus leishmania. at least 20 species of leishmania are known to infect humans transmitted by female sandflies, phlebotomus spp. leishmania donovani causes visceral leishmaniasis, considered most lethal among the common three forms of leishmaniasis. lack of appropriate vaccines, emergence of drug resistance and side effects of currently used drugs stress the need for better alternative drugs, particularly from ... | 2015 | 26669018 |
| antiproteolytic and leishmanicidal activity of coccinia grandis (l.) voigt leaf extract against leishmania donovani promastigotes. | in visceral leishmaniasis (vl), development of alternative safe therapeutic strategy is gaining paramount wherein natural components of plant origin have prominence. we explored coccinia grandis (l.) voigt, a medicinal plant known in traditional folk medicine, for its antileishmanial efficacy. sds-page analysis of the c. grandis leaf extract (cg-ex) showed few protein bands about 14-66 kda among which three (64.8, 55.8 and 15.3 kda) were identified as serine protease inhibitors by reverse zymogr ... | 2015 | 26669017 |
| in vitro and in vivo antileishmanial properties of a 2-n-propylquinoline hydroxypropyl β-cyclodextrin formulation and pharmacokinetics via intravenous route. | 2-n-propylquinoline (2-n-pq) had shown interesting in vivo antileishmanial activities after administration by oral route on leishmaniasis animal models. however, the lipophilic properties of this compound avoid its use by intravenous route, this route being indicated in cases of severe visceral leishmaniasis with vomiting. thus, a 2-n-propylquinoline hydroxypropyl beta-cyclodextrin (2-n-pq-hpc) formulation was set up in this aim. the formulation was active in vitro both on leishmania donovani ax ... | 2015 | 26653559 |
| lack of correlation between the promastigote back-transformation assay and miltefosine treatment outcome. | widespread antimony resistance in the indian subcontinent has enforced a therapy shift in visceral leishmaniasis treatment primarily towards miltefosine and secondarily also towards paromomycin. in vitro selection of miltefosine resistance in leishmania donovani turned out to be quite challenging. although no increase in ic50 was detected in the standard intracellular amastigote susceptibility assay, promastigote back-transformation remained positive at high miltefosine concentrations, suggestin ... | 2015 | 26253089 |
| search for antiprotozoal activity in herbal medicinal preparations; new natural leads against neglected tropical diseases. | sleeping sickness, chagas disease, leishmaniasis, and malaria are infectious diseases caused by unicellular eukaryotic parasites ("protozoans"). the three first mentioned are classified as neglected tropical diseases (ntds) by the world health organization and together threaten more than one billion lives worldwide. due to the lack of research interest and the high increase of resistance against the existing treatments, the search for effective and safe new therapies is urgently required. in vie ... | 2015 | 26248069 |
| diagnostic accuracy of rk28-based immunochromatographic rapid diagnostic tests for visceral leishmaniasis: a prospective clinical cohort study in sudan. | rapid diagnostic tests (rdts) for visceral leishmaniasis (vl) based on rk39 antigen showed suboptimal sensitivity in east africa. a prospective clinical cohort study in sudan was designed to validate a novel rk28-based rdt for leishmania donovani vl. | 2015 | 26246251 |
| 2-phenoxy-1,4-naphthoquinones: from a multitarget antitrypanosomal to a potential antitumor profile. | a small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives was initially developed to optimize the antitrypanosomatid profile of the multitarget hit compound b6 (1). the whole series was evaluated against the three most important human trypanosomatid pathogens (trypanosoma brucei rhodesiense, trypanosoma cruzi, and leishmania donovani), and two compounds (14 and 21) showed good activity, despite a concomitant mammalian cytotoxicity. furthermore, a subset also inh ... | 2015 | 26237241 |
| the leishmania donovani peroxin 14 binding domain accommodates a high degeneracy in the pentapeptide motifs present on peroxin 5. | the glycosome is a unique organelle found in kinetoplastids known to compartmentalize vital metabolic pathways including glycolysis, β-fatty acid oxidation and purine salvage. organelle biogenesis depends on a network of proteins for trafficking and translocation of nascent protein into the glycosome. the interaction of the proteins ldpex14 and ldpex5 at the glycosome membrane is crucial for targeting proteins into this organelle. | 2015 | 26231924 |
| the proliferation potential of promastigotes of the main leishmania species of the old world in nnn culture medium prepared using blood of four different mammals. | the efficacy of the in vitro cultivation of promastigotes of four leishmania spp. was tested in the biphasic novy-macneal-nicolle (nnn) medium prepared using blood from different animals (horse, donkey, goat and sheep). the aim was to test which nnn preparation gave the best yield in the shortest time for different parasite species, in order to obtain a large crop of promastigotes for experimental work and for antigen preparation. promastigotes of leishmania infantum, leishmania donovani, leishm ... | 2015 | 26219203 |
| ifn-γ-induced macrophage antileishmanial mechanisms in mice: a role for immunity-related gtpases, irgm1 and irgm3, in leishmania donovani infection in the liver. | in c57bl/6 mice, leishmania donovani infection in the liver provoked ifn-γ-induced expression of the immunity-related gtpases (irg), irgm1 and irgm3. to gauge the antileishmanial effects of these macrophage factors in the liver, intracellular infection was analyzed in irg-deficient mice. in early- (but not late-) stage infection, irgm3(-/-) mice failed to properly control parasite replication, generated little tissue inflammation and were hyporesponsive to pentavalent antimony (sb) chemotherapy. ... | 2015 | 26208780 |
| use of a clinical tool for screening and diagnosis of cutaneous leishmaniasis in sri lanka. | cutaneous leishmaniasis (cl) was first detected in sri lanka in 1992.local disease is caused by a genetically different variant of leishmania donovani. early case detection and management is the mainstay of l. donovani control. high degree of clinical suspicion is critical but a clinical diagnostic tool is not available for leishmaniasis. current study described, for the first time, a two-staged clinical algorhythm that facilitates screening of cl in sri lanka by primary health care worker in st ... | 2015 | 26184581 |
| anti-protozoal activities of cembrane-type diterpenes from vietnamese soft corals. | based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as trypanosoma and plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the vietnamese sea to an in vitro screening for anti-protozoal activity against trypanosoma brucei rhodesiense (tbr), t. cruzi (tc), leishmania donovani (ld), and plasmodium falciparum (pf). twelve of the tested compounds displayed significant ... | 2015 | 26184133 |
| antileishmanial effect of mevastatin is due to interference with sterol metabolism. | visceral leishmaniasis (vl) is one of the most severe forms of leishmaniasis which is fatal if left untreated. sterol biosynthetic pathway in leishmania is currently being explored for its therapeutic potential. in the present study, we have evaluated the antileishmanial efficacy of mevastatin, a known inhibitor of 3-hydroxy-3-methyl glutaryl-coa reductase (hmgr) enzyme. mevastatin inhibited leishmania donovani promastigotes and intracellular amastigotes with an 50% inhibitory concentration (ic5 ... | 2015 | 26183607 |
| inadequacy of 12-week miltefosine treatment for indian post-kala-azar dermal leishmaniasis. | post-kala-azar dermal leishmaniasis (pkdl) is a chronic dermatosis that generally occurs after apparent cure of visceral leishmaniasis caused by leishmania donovani. in view of the prolonged treatment regimens necessary for pkdl, noncompliance is a major limitation; an optimal regimen is yet to be defined, but 12 weeks of therapy with miltefosine is generally recommended. we performed a single-arm open-label trial of miltefosine administered daily for 16 weeks in 27 patients in kolkata with pkdl ... | 2015 | 26175030 |
| leishmania donovani infection drives the priming of human monocyte-derived dendritic cells during plasmodium falciparum co-infections. | functional impairment of dendritic cells (dcs) is part of a survival strategy evolved by leishmania and plasmodium parasites to evade host immune responses. here, the effects of co-exposing human monocyte-derived dcs to leishmania donovani promastigotes and plasmodium falciparum-infected erythrocytes were investigated. co-stimulation resulted in a dual, dose-dependent effect on dc differentiation which ranged from semi-mature cells, secreting low interleukin(-12p70 levels to a complete lack of p ... | 2015 | 26173941 |
| [two cases of visceral leishmaniasis from kahramanmaraş, turkey]. | turkey is an endemic area for cutaneous leishmaniasis (cl) according to the data of world health organization. cl is more widely distributed in sanliurfa region (located at south-eastern part of anatolia) of turkey, while visceral leishmaniasis (vl) is reported sporadically from all parts of turkey, especially in pediatric cases. however vl has not been reported from our region yet. here we report two cases of vl from kahramanmaraş region (located at eastern part of south anatolia), one of which ... | 2015 | 26167831 |
| irak-m regulates the inhibition of tlr-mediated macrophage immune response during late in vitro leishmania donovani infection. | intramacrophage protozoan parasite leishmania donovani, causative agent of visceral leishmaniasis, escapes toll-like receptor (tlr) dependent early host immune response by inducing the deubiquitinating enzyme a20, which is sustained up to 6 h postinfection only. therefore, leishmania must apply other means to deactivate late host responses. here, we elucidated the role of il-1 receptor-associated kinase m (irak-m), a negative regulator of tlr signaling, in downregulating macrophage proinflammato ... | 2015 | 26140693 |
| development of an immunochromatographic test for diagnosis of visceral leishmaniasis based on detection of a circulating antigen. | visceral leishmaniasis (vl) is a life-threatening disease caused by protozoan parasites of the leishmania donovani complex. early case detection followed by adequate treatment is essential to the control of vl. however, the available diagnostic tests are either invasive and require considerable expertise (parasitological demonstration of the parasite in tissue smears) or unable to distinguish between past and active infection (serological methods). therefore, we aimed to develop a lateral flow a ... | 2015 | 26125560 |
| leptin augments protective immune responses in murine macrophages and enhances potential of miltefosine against experimental visceral leishmaniasis. | adverse side effects and drug resistance issues are the two most important drawbacks which influence the widespread use of existing antileishmanial drugs. use of immune stimulating agent with standard antileishmanial might be helpful to minimize the toxic effect of drug, shorten the dose regimen and delay the emergence of resistance. in the present study, we explored the in vitro immunomodulatory potential of an immunomodulator, leptin with lower concentration of standard drug, miltefosine. the ... | 2015 | 26119043 |
| elevated ergosterol protects leishmania parasites against antimony-generated stress. | parasite lipids can serve as signaling molecules, important membrane components, energy suppliers, and pathogenesis factors critical for survival. functional roles of lipid changes in response to drug-generated stress in parasite survival remains unclear. to investigate this, leishmania donovani parasites, the causative agents of kala-azar, were exposed to the antileishmanial agent potassium antimony tartrate (pat) (half-maximal inhibitory concentration ∼ 284 µg/ml). analysis of cell extracts us ... | 2015 | 26116701 |
| [development and application of rapid molecular method for detection of asymptomatic infection of leishmania]. | to develop a rapid molecular biological method for detection of the asymptomatic infection of leishmania. | 2015 | 26094413 |
| in vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis. | the present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against leishmania donovani. amphotericin b was used as a positive control drug. in vitro activity involved incubation of various drug concentrations with promastigotes or vero cells in culture before determination of parasite growth inhibition or cell death while in vivo evaluations involved infection of various mice groups with virulent l. donovani parasites and tr ... | 2015 | 26060445 |
| macyranones: structure, biosynthesis, and binding mode of an unprecedented epoxyketone that targets the 20s proteasome. | in our screening efforts to identify unique scaffolds from myxobacteria for the drug discovery process, we used lc-spe-nmr-ms techniques to isolate six linear peptides, termed macyranone a-f, from cystobacter fuscus mcy9118. the macyranones are characterized by a rare 2-methylmalonamide moiety and an α-amino ketone fragment including an α',β'-epoxyketone in macyranone a. gene disruption experiments confirmed the biosynthetic gene cluster of the macyranones as pks/nrps hybrid. detailed in silico ... | 2015 | 26050527 |
| irf-5-mediated inflammation limits cd8+ t cell expansion by inducing hif-1α and impairing dendritic cell functions during leishmania infection. | inflammation is known to be necessary for promoting, sustaining, and tuning cd8+ t cell responses. following experimental leishmania donovani infection, the inflammatory response is mainly induced by the transcription factor irf-5. irf-5 is responsible for the activation of several genes encoding key pro-inflammatory cytokines, such as il-6 and tnf. here, we investigate the role of irf-5-mediated inflammation in regulating antigen-specific cd8+ t cell responses during l. donovani infection. our ... | 2015 | 26046638 |
| effect of different serine protease inhibitors in validating the 115 kda leishmania donovani secretory serine protease as chemotherapeutic target. | proteases have been considered as an important group of targets for development of antiprotozoal drugs due to their essential roles in host-parasite interactions, parasite immune evasion, life cycle transition and pathogenesis of parasitic diseases. the development of potent and selective serine protease inhibitors targeting l. donovani secretory serine protease (psp) could pave the way to the discovery of potential antileishmanial drugs. here, we employed different classical serine protease inh ... | 2015 | 26040107 |
| pls-prediction and confirmation of hydrojuglone glucoside as the antitrypanosomal constituent of juglans spp. | naphthoquinones (nqs) occur naturally in a large variety of plants. several nqs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human african trypanosomiasis (sleeping sickness), chagas disease and leishmaniasis. prominent nq-producing plants can be found among juglans spp. (juglandaceae) with juglone derivatives as known constituents. in this study, 36 highly variable extracts were prepared from different plant parts of j. regia, ... | 2015 | 26035104 |
| genetically engineered ascorbic acid-deficient live mutants of leishmania donovani induce long lasting protective immunity against visceral leishmaniasis. | visceral leishmaniasis caused by leishmania donovani is the most severe systemic form of the disease. there are still no vaccines available for humans and there are limitations associated with the current therapeutic regimens for leishmaniasis. recently, we reported functional importance of arabino-1, 4-lactone oxidase (alo) enzyme from l. donovani involved in ascorbate biosynthesis pathway. in this study, we have shown that δalo parasites do not affect the ability of null mutants to invade visc ... | 2015 | 26035062 |
| green synthesis of silver and titanium dioxide nanoparticles using euphorbia prostrata extract shows shift from apoptosis to g0/g1 arrest followed by necrotic cell death in leishmania donovani. | the aim of the present study was to synthesize silver (ag) and titanium dioxide (tio2) nanoparticles (nps) using green synthesis from aqueous leaf extract of euphorbia prostrata as antileishmanial agents and to explore the underlying molecular mechanism of induced cell death. in vitro antileishmanial activity of synthesized nps was tested against promastigotes of leishmania donovani by alamarblue and propidium iodide uptake assays. antileishmanial activity of synthesized nps on intracellular ama ... | 2015 | 26033724 |
| interaction of frataxin, an iron binding protein, with iscu of fe-s clusters biogenesis pathway and its upregulation in ampb resistant leishmania donovani. | leishmania donovani is a unicellular protozoon parasite that causes visceral leishmaniasis (vl), which is a fatal disease if left untreated. certain fe-s proteins of the tca cycle and respiratory chain have been found in the leishmania parasite but the precise mechanisms for their biogenesis and the maturation of fe-s clusters remains unknown. fe-s clusters are ubiquitous cofactors of proteins that perform critical cellular functions. the clusters are biosynthesized by the mitochondrial iron-sul ... | 2015 | 26032732 |
| in vivo selection of paromomycin and miltefosine resistance in leishmania donovani and l. infantum in a syrian hamster model. | in 2002 and 2006, respectively, miltefosine (mil) and paromomycin (pmm) were licensed in the indian subcontinent for treatment of visceral leishmaniasis; however, their future routine use might become jeopardized by the development of drug resistance. although experimental selection of resistant strains in vitro has repeatedly been reported using the less relevant promastigote vector stage, the outcome of resistance selection on intracellular amastigotes was reported to be protocol and species d ... | 2015 | 26014955 |
| studies on the protective efficacy of freeze thawed promastigote antigen of leishmania donovani along with various adjuvants against visceral leishmaniasis infection in mice. | visceral leishmaniasis (vl) caused by leishmania donovani persists as a major public health issue in tropical and subtropical areas of the world. current treatment of this disease relies on use of drugs. it is doubtful that chemotherapy can alone eradicate the disease, so there is a need for an effective vaccine. killed antigen candidates remain a good prospect considering their ease of formulation, stability, low cost and safety. to enhance the efficacy of killed vaccines suitable adjuvant and ... | 2015 | 26001730 |
| a novel triterpene from astraeus hygrometricus induces reactive oxygen species leading to death in leishmania donovani. | the effect of astrakurkurone, a novel triterpene, isolated from indian mushroom astraeus hygrometricus has been investigated to elucidate the mechanisms involved in selective cell death of leishmania donovani. | 2015 | 26000650 |
| leishmania donovani influenced cytokines and toll-like receptors expression among sudanese visceral leishmaniasis patients. | leishmaniasis remains a serious health problem. the outcome of leishmania infection depends on the early innate response. in this study, whole blood samples of 40 patients with visceral leishmaniasis (vl), 10 leishmanin skin test-negative (lst-ve) controls and 10 leishmanin skin test-positive (lst+ve) controls were stimulated by live l. donovani promastigotes. also, thp1 human cell line was infected with l. donovani. the production of interleukin 10 (il-10), tumour necrosis factor alpha (tnf) an ... | 2015 | 25982946 |
| platelet-activating factor receptor contributes to antileishmanial function of miltefosine. | miltefosine [hexadecylphosphocholine (hpc)] is the only orally bioavailable drug for the disease visceral leishmaniasis, which is caused by the protozoan parasite leishmania donovani. although miltefosine has direct leishmanicidal effects, evidence is mounting for its immune system-dependent effects. the mechanism of such indirect antileishmanial effects of miltefosine remains to be discovered. as platelet-activating factor and hpc share structural semblances and both induce killing of intracell ... | 2015 | 25980013 |
| uncovering leishmania-macrophage interplay using imaging flow cytometry. | host-pathogen interaction is an area of considerable interest. intracellular parasites such as leishmania reside inside phagocytes such as macrophages, dendritic cells and neutrophils. macrophages can be activated by cytokines such as ifn-γ and toll like receptor (tlr) agonists resulting in enhanced microbicidal activity. leishmania parasites hijack the microbicidal function of macrophages, mainly by interfering with intracellular signaling initiated by ifn-γ and tlr ligands. here we used transg ... | 2015 | 25967951 |
| hat3-mediated acetylation of pcna precedes pcna monoubiquitination following exposure to uv radiation in leishmania donovani. | histone modifications impact various processes. in examining histone acetyltranferase hat3 of leishmania donovani, we find elimination of hat3 causes decreased cell viability due to defects in histone deposition, and aberrant cell cycle progression pattern. hat3 associates with proliferating cell nuclear antigen (pcna), helping load pcna onto chromatin in proliferating cells. hat3-nulls show heightened sensitivity to uv radiation. following uv exposure, pcna cycles off/on chromatin only in cells ... | 2015 | 25948582 |
| leishmania donovani p23 protects parasites against hsp90 inhibitor-mediated growth arrest. | in leishmania donovani, the hsp90 chaperone complex plays an essential role in the control of the parasite's life cycle, general viability and infectivity. several of the associated co-chaperones were also shown to be essential for viability and/or infectivity to mammalian cells. here, we identify and describe the co-chaperone p23 and distinguish its function from that of the structurally related small heat shock protein hsp23. p23 is expressed constitutively and associates itself with members o ... | 2015 | 25948161 |
| 2,6,9-trisubstituted purines as crk3 kinase inhibitors with antileishmanial activity in vitro. | here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with cdc2-related protein kinase 3 (crk3) and subsequently for activity against parasitic leishmania species. the most active compound inhibited recombinant crk3 with an ic50 value of 162 nm and was active against leishmania major and leishmania donovani at low micromolar concentrations in vitro. its mode of binding to crk3 was investigated by molecular docking using a h ... | 2015 | 25937014 |
| therapeutic efficacy of artemisinin-loaded nanoparticles in experimental visceral leishmaniasis. | visceral leishmaniasis (vl) is a fatal vector-borne parasitic syndrome attributable to the protozoa of the leishmania donovani complex. the available chemotherapeutic options are not ideal due to their potential toxicity, high cost and prolonged treatment schedule. in the present study, we conjectured the use of nano drug delivery systems for plant-derived secondary metabolite; artemisinin as an alternative strategy for the treatment of experimental vl. artemisinin-loaded poly lactic co-glycolic ... | 2015 | 25936561 |
| targeted chemotherapy of visceral leishmaniasis by lactoferrin-appended amphotericin b-loaded nanoreservoir: in vitro and in vivo studies. | exploitation of lactoferrin-appended amphotericin b bearing nanoreservoir (lcfpgnp-amb) for targeted eradication of leishmania donovani. | 2015 | 25929567 |