| host-mediated leishmania donovani treatment using ar-12 encapsulated in acetalated dextran microparticles. | leishmaniasis is a disease caused by parasites of leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. the current treatments for visceral leishmaniasis (vl), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. one way to limit emergence of resistant pathogens is th ... | 2016 | 26768723 |
| simple and efficient synthesis of 5'-aryl-5'-deoxyguanosine analogs by azide-alkyne click reaction and their antileishmanial activities. | a series of non-hydrolysable 5'-aryl substituted gdp analogs has been synthesized by reacting 5'-azido-5'-deoxyguanosine with different aryl- and benzyloxy-alkynes. cu(i) nanoparticles in water were found to be the most efficient catalyst, producing the desired 5'-arylguanosines with good yields. the synthesized compounds were screened for in vitro antileishmanial activity against leishmania donovani axenic amastigotes and intramacrophage amastigotes stages. the 4-(3-nitrobenzyl)-1,2,3-triazole ... | 2016 | 26754628 |
| intradermal immunization of leishmania donovani centrin knock-out parasites in combination with salivary protein ljm19 from sand fly vector induces a durable protective immune response in hamsters. | visceral leishmaniasis (vl) is a neglected tropical disease and is fatal if untreated. there is no vaccine available against leishmaniasis. the majority of patients with cutaneous leishmaniasis (cl) or vl develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. we have previously report ... | 2016 | 26752686 |
| up regulation of a2b adenosine receptor on monocytes are crucially required for immune pathogenicity in indian patients exposed to leishmania donovani. | adenosine, an endogenous purine nucleoside is one such extracellular signalling molecule whose role in regulation of anti-inflammatory cytokines and immune pathogenicity in visceral leishmaniasis is not fully understood. here, we investigated the relationship between leishmania donovani infection and expression of a2b receptor on monocytes in vl patients in their pre and post treatment stage. we also investigated the molecular mechanisms influencing the interaction between immunopathogenicity an ... | 2016 | 26748211 |
| up-regulation of cytosolic tryparedoxin in amp b resistant isolates of leishmania donovani and its interaction with cytosolic tryparedoxin peroxidase. | leishmania is a unicellular protozoan parasite which causes leishmaniasis, a neglected tropical disease. it possess a unique thiol metabolism comprising of several proteins among which, tryparedoxin (ctxn) and tryparedoxin peroxidase (ctxnpx), function in concert as oxidoreductases, utilizing trypanothione as a source of electrons to reduce the hydroperoxides produced by macrophages during infection. this detoxification pathway is unique and essential for the survival of leishmania. herein, we r ... | 2016 | 26743980 |
| evaluation of in vitro antiprotozoal activity of ajuga laxmannii and its secondary metabolites. | context some ajuga l. (lamiaceae) species are traditionally used for the treatment of malaria, as well as fever, which is a common symptom of many parasitic diseases. objective in the continuation of our studies on the identification of antiprotozoal secondary metabolites of turkish lamiaceae species, we have investigated the aerial parts of ajuga laxmannii. materials and methods the aerial parts of a. laxmannii were extracted with meoh. the h2o subextract was subjected to polyamide, c18-mplc an ... | 2016 | 26734766 |
| immunomodulation mediated through leishmania donovani protein disulfide isomerase by eliciting cd8+ t-cell in cured visceral leishmaniasis subjects and identification of its possible hla class-1 restricted t-cell epitopes. | protein disulphide isomerase (pdi) is one of the key enzymes essential for the survival of leishmania donovani in the host. our study suggested that pdi is associated with the generation of th1-type of cellular responses in treated visceral leishmaniasis (vl) subjects. the stimulation of peripheral blood mononuclear cells (pbmcs) with recombinant protein disulphide isomerase upregulated the reactive oxygen species generation, nitric oxide release, il12 and ifn-γ production indicating its pivotal ... | 2017 | 26727289 |
| in vitro selection of miltefosine resistance in promastigotes of leishmania donovani from nepal: genomic and metabolomic characterization. | in this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (mil) resistance in two clinically derived leishmania donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain sb-s; and antimony resistant sb-r). mil-r was easily induced in both strains using the promastigote-stage, but a significant increase in mil-r in the intracellular amastigote compared to the corresponding wild-type did not occur ... | 2016 | 26713880 |
| 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 |
| leptin induces the phagocytosis and protective immune response in leishmania donovani infected thp-1 cell line and human pbmcs. | visceral leishmaniasis (vl) is an infectious disease responsible for several deaths in malnourished children due to impaired cell-mediated immunity, which is accompanied by low circulating leptin levels. the cytokine function of leptin is implicated for several immune regulation activities such as hematopoiesis, angiogenesis, innate and adaptive immunity. its deficiency associated with polarization of th2 response, which coincides with vl pathogenesis. to determine the cytokine role of leptin in ... | 2016 | 26688099 |
| 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 |
| leishmania donovani exploits myeloid cell leukemia 1 (mcl-1) protein to prevent mitochondria-dependent host cell apoptosis. | apoptosis is one of the mechanisms used by host cells to remove unwanted intracellular organisms, and often found to be subverted by pathogens through use of host anti-apoptotic proteins. in the present study, with the help of in vitro and in vivo approaches, we documented that the macrophage anti-apoptotic protein myeloid cell leukemia 1 (mcl-1) is exploited by the intra-macrophage parasite leishmania donovani to protect their "home" from actinomycin d-induced mitochondria-dependent apoptosis. ... | 2016 | 26670606 |
| 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 |
| identification and characterization of a leishmania donovani serine protease inhibitor: possible role in regulation of host serine proteases. | this study aims to identify, purify, and characterize an endogenous serine protease inhibitor from an indian strain of leishmania donovani, which causes the fatal visceral leishmaniasis. | 2016 | 26656469 |
| 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 |
| development of plga-peg encapsulated miltefosine based drug delivery system against visceral leishmaniasis. | targeted drug delivery systems are ideal technology to increase the maximum mechanism of action with smaller dose, we have developed miltefosine encapsulated plga–peg nanoparticles (ppem) to target macrophage of infected tissues against leishmania donovani. the structural characterization of plga–peg by transmission electron microscopy (tem) has shown a size range of 10 to 15 nm. synthesis and drug encapsulation confirmed by dynamic light scattering (dls) and fourier transform infrared spectrosc ... | 2016 | 26652429 |
| induction of apoptosis by zerumbone isolated from zingiber zerumbet (l.) smith in protozoan parasite leishmania donovani due to oxidative stress. | in the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against leishmania infection. various ginger spices of the zingiberaceae family are widely used as spices, flavouring agents, and medicines in southeast asia because of their unique flavour as well as due to their medicinal properties. zerumbone, a natural component of zingiber zerumbet (l.) s ... | 2016 | 26643969 |
| pathogenicity of leishmania donovani is associated with the high expression of a group low molecular weight proteins. | with few exceptions, members of the leishmania donovani complex such as l. donovani, l. infantum and l. chagashi are the etiological agents of visceral leishmaniasis or kala-azar. promastigotes of leishmania spp. lose their pathogenicity; the ability to establish infection in a susceptible host, after prolonged culture. the molecular basis of this evolution of pathogenic to nonpathogenic culture has not been very well understood. it has been proposed that the loss of pathogenicity is associated ... | 2017 | 26629453 |
| a new bisbenzylisoquinoline alkaloid isolated from thalictrum foliolosum, as a potent inhibitor of dna topoisomerase ib of leishmania donovani. | chemical investigation of the stem of thalictrum foliolosum resulted in the isolation of two new bisbenzylisoquinoline alkaloids (1 and 2) along with known protoberberine group of isoquinoline alkaloids thalifendine (3) and berberine (4). the structures of the new compounds were established by detailed 2d nmr spectral analysis with their configurations determined from their optical rotation values and confirmed using circular dichroism. inhibitory activities of these four compounds against dna t ... | 2016 | 26625837 |
| establishment of correlation between in-silico and in-vitro test analysis against leishmania hgprt to inhibitors. | hypoxanthine phosphoribosyltransferase (hgprt; ec 2.4.2.8) is a central enzyme in the purine recycling pathway of all protozoan parasites. protozoan parasites cannot synthesize purine bases (dna/rna) which is essential for survival as lack of de-novo pathway. thus its good target for drug design and discovery as inhibition leads to cessation of replication. prtase (transferase enzyme) has common prtase type i folding pattern domain for its activities. genomic studies revealed the sequence patter ... | 2016 | 26616453 |
| impaired snx9 expression in immune cells during chronic inflammation: prognostic and diagnostic implications. | chronic inflammation is associated with immunosuppression and downregulated expression of the tcr cd247. in searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (snx9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. snx9 expression was affected earlier than cd247 by the generated harmful environment, suggesting that i ... | 2016 | 26608909 |
| il-17a promotes susceptibility during experimental visceral leishmaniasis caused by leishmania donovani. | leishmania donovani is an intracellular parasite that infects professional phagocytes and causes visceral leishmaniasis (vl). the immune response during vl has been extensively studied in the context of t-helper (th)1 and th2 responses. immunity against this parasite is dependent on ifn-γ production and subsequent macrophage activation, and the th2 response promotes granuloma formation. the cytokine il-17a is associated with neutrophilic inflammation. depletion of neutrophils during experimental ... | 2016 | 26581600 |
| comparative study of structural models of leishmania donovani and human gdp-mannose pyrophosphorylases. | leishmania is the parasite responsible for the neglected disease leishmaniasis. its virulence and survival require biosynthesis of glycoconjugates, whose guanosine diphospho-d-mannose pyrophosphorylase (gdp-mp) is a key player. however, experimentally resolved structures of this enzyme are still lacking. we herein propose structural models of the gdp-mp from human and leishmania donovani. based on a multiple sequences alignment, the models were built with modeller and then carefully refined with ... | 2016 | 26562546 |
| 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 |
| molecular docking and structure-based virtual screening studies of potential drug target, caax prenyl proteases, of leishmania donovani. | targeting caax prenyl proteases of leishmania donovani can be a good approach towards developing a drug molecule against leishmaniasis. we have modeled the structure of caax prenyl protease i and ii of l. donovani, using homology modeling approach. the structures were further validated using ramachandran plot and prosa. active site prediction has shown difference in the amino acid residues present at the active site of caax prenyl protease i and caax prenyl protease ii. the electrostatic potenti ... | 2016 | 26551589 |
| synthesis and antileishmanial evaluation of some 2,3-disubstituted-4(3h)-quinazolinone derivatives. | leishmaniasis is a neglected tropical parasitic diseases affecting millions of people around the globe. quinazolines are a group of compounds with diverse pharmacological activities. owing to their promising antileishmanial activities, some 3-aryl-2-(substitutedstyryl)-4(3h)-quinazolinones were synthesized in good yields (65.2% to 86.4%). | 2014 | 26548988 |
| 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 |
| short-course treatment regimen of indian visceral leishmaniasis with an indian liposomal amphotericin b preparation (fungisome™). | india bears the burden of about half of global visceral leishmaniasis (vl) cases with emerging problems of stibanate resistance. liposomal preparations have improved treatment outcome through shorter duration of therapy and lower toxicity compared with conventional amphotericin b. we report the efficacy of two short-course regimens of an indian preparation of liposomal amphotericin b (fungisome™) for vl caused by leishmania donovani in india. an open-label, randomized, single-center comparative ... | 2016 | 26526926 |
| 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 |
| leishmania donovani-specific ub-related modifier-1: an early endosome-associated ubiquitin-like conjugation in leishmania donovani. | protein modification by ubiquitin (ub) and ub-like molecules (ubls) is a diverse biological process that regulates the activity of the target proteins. systematic studies of ubls in trypanosomatids like leishmania, the causative organism of potentially fatal visceral leishmaniasis, would yield a better understanding of the disease pathogenesis and identify novel therapeutic targets. the present study is the first to characterize leishmania donovani-specific ub-related modifier-1 (ldurm1) and the ... | 2016 | 26481108 |
| 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 |
| protein kinase a signaling during bidirectional axenic differentiation in leishmania. | parasitic protozoa of the genus leishmania are obligatory intracellular parasites that cycle between the phagolysosome of mammalian macrophages, where they proliferate as intracellular amastigotes, and the midgut of female sand flies, where they proliferate as extracellular promastigotes. shifting between the two environments induces signaling pathway-mediated developmental processes that enable adaptation to both host and vector. developmentally regulated expression and phosphorylation of prote ... | 2016 | 26460237 |
| 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 |
| exploring the inhibitory activity of withaferin-a against pteridine reductase-1 of l. donovani. | withaferin a is an abundant withanolide present in withania somnifera leaves and to some extent in roots. it has been known for its profound anti-cancer properties, but its role in counteracting the leishmania donovani infection has to be explored. pteridine reductase 1 (ptr1) is involved in pteridine salvage and an important enzyme for the parasite growth, which could be targeted for the development of an efficient antileishmanial drug. we employed molecular docking studies to identify the bind ... | 2016 | 26406482 |
| 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 |
| first evidence of leishmania infection in european brown hare (lepus europaeus) in greece: gis analysis and phylogenetic position within the leishmania spp. | although the existence of a sylvatic transmission cycle of leishmania spp., independent from the domestic cycle, has been proposed, data are scarce on leishmania infection in wild mammals in greece. in this study, we aimed to investigate the presence of leishmania infection in the european brown hare in greece, to infer the phylogenetic position of the leishmania parasites detected in hares in greece, and to identify any possible correlation between leishmania infection in hares with environment ... | 2016 | 26386969 |
| 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 |
| novel inhibitors of ornithine decarboxylase of leishmania parasite (ldodc): the parasite resists ldodc inhibition by overexpression of spermidine synthase. | ornithine decarboxylase (ldodc), a key enzyme in polyamine biosynthesis in leishmania donovani, catalyzes the conversion of ornithine to putrescine that is finally used for synthesis of spermidine and other polyamines. inhibition of ornithine decarboxylase is likely to deplete the parasite trypanothione and may result in increased reactive oxygen species (ros). sequence as well as structure of ldodc and human odc shows significant difference; therefore, we have identified novel specific inhibito ... | 2016 | 26362015 |
| 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 |
| antimicrobial and antileishmanial activities of diterpenoids isolated from the roots of salvia deserta. | four diterpenes with biological activity were isolated from salvia deserta roots. taxodione was considered leishmanicidal with an ic50 value of 1.46 µm (0.46 mg/l) against leishmania donovani and also exhibited antifungal and antimicrobial activities. ferruginol displayed the greatest activity [24-h ic50 of 4.5 µm (1.29 mg/l)] against the fish pathogenic bacteria streptococcus iniae. the crude extract fraction that contained the isolated compounds 7-o-acetylhorminone and horminone showed stronge ... | 2016 | 26308356 |
| 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 |
| hepatic stellate cells regulate liver immunity to visceral leishmaniasis through p110δ-dependent induction and expansion of regulatory t cells in mice. | visceral leishmaniasis (vl) is associated with severe immune dysfunction and if untreated leads to death. because the liver is one of the primary target organs in vl, unraveling the mechanisms governing the local hepatic immune response is important for understanding the immunopathogenesis of vl. we previously reported that mice with inactivating knockin mutation in the p110δ gene (p110δ(d910a) ) are resistant to vl, due in part to impaired regulatory t-cell (treg) expansion. in this study, we i ... | 2016 | 26289140 |
| 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 |
| a network map of interleukin-10 signaling pathway. | interleukin-10 (il-10) is an anti-inflammatory cytokine with important immunoregulatory functions. it is primarily secreted by antigen-presenting cells such as activated t-cells, monocytes, b-cells and macrophages. in biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer il-10 receptor and induces downstream signaling. il-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as burkitt lymphoma, non-hodgkins lymp ... | 2016 | 26253919 |
| 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 |
| synthesis and in vitro screening of 29, 30-dibromo-28-oxoallobetulin against parasitic protozoans, leishmania donovani and leishmania major. | a simple synthesis and in vitro antileishmanial activity of 29,30-dibromo-28-oxoallobetulin against the parasitic protozoans, leishmania donovani and leishmania major is described. the structure of the compound is established on the basis of spectral data (ir, nmr, ms). both the antiproliferative effect and the cell cycle progression were studied. | 2017 | 26009654 |
| 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 |