Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| anthocephaline, a new indole alkaloid and cadambine, a potent inhibitor of dna topoisomerase ib of leishmania donovani (ldtop1ls), isolated from anthocephalus cadamba. | chemical investigation of the stem bark of anthocephalus cadamba has resulted in the isolation of anthocephaline (1), a new indole alkaloid, along with strictosamide (2), vincosamide (3) and cadambine (4). the structures of the isolated alkaloids (1-4) were established by detailed 2d nmr spectral analysis. cadambine (4) exhibited potent dna topoisomerase ib inhibitory activity. | 2015 | 25920266 |
| correction: recombinant nad-dependent sir-2 protein of leishmania donovani: immunobiochemical characterization as a potential vaccine against visceral leishmaniasis. | [this corrects the article doi: 10.1371/journal.pntd.0003557.]. | 2015 | 25901962 |
| chemical and bioassay techniques to authenticate quality of the anti-leishmanial drug miltefosine. | miltefosine, an effective oral treatment of visceral leishmaniasis (vl), was selected in may 2005, by the governments of india, nepal, and bangladesh for the elimination of vl. however, abnormally high treatment failure rates reported in patients in bangladesh, given a miltefosine generic product ("miltefos", popular pharmaceuticals ltd.) during 2008, led the world health organization (who) to procure this formulation for quality testing. proton ((1)h) and phosphorous ((31)p) nuclear magnetic re ... | 2015 | 25897058 |
| l-asparaginase as a new molecular target against leishmaniasis: insights into the mechanism of action and structure-based inhibitor design. | l-asparaginases belong to a family of amidohydrolases that catalyze the conversion of l-asparagine into l-aspartic acid and ammonia. although bacterial l-asparaginases have been used extensively as anti-leukemic agents, their possible role as potential drug targets for pathogenic organisms has not been explored. the presence of genes coding for putative l-asparaginase enzymes in the leishmania donovani genome hinted towards the specific role of these enzymes in extending survival benefit to the ... | 2015 | 25893895 |
| leishmania donovani bodies in neutrophils on a peripheral blood smear examination: report of an unusual incident in a clinically unsuspected case. | 2015 | 25885157 | |
| therapeutic and immunomodulatory activities of short-course treatment of murine visceral leishmaniasis with kalsome™10, a new liposomal amphotericin b. | visceral leishmaniasis (vl), a potentially fatal disease, is most prevalent in the indian subcontinent, east africa and south america. since the conventional antileishmanial drugs have many limitations we evaluated a new ergosterol rich liposomal amphotericin b formulation, kalsome™10 for its leishmanicidal efficacy, tolerability and immunomodulatory activity. | 2015 | 25884796 |
| mapk1 of leishmania donovani modulates antimony susceptibility by downregulating p-glycoprotein efflux pumps. | emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (vl) in the indian subcontinent. mitogen-activated protein kinases (mapks) are well-known mediators of signal transduction of eukaryotes, regulating important processes, like proliferation, differentiation, stress response, and apoptosis. in leishmania, mapk1 has been shown to be consistently downregulated in antimony-resistant field isolates, suggesting that it has a role i ... | 2015 | 25870075 |
| click inspired synthesis of antileishmanial triazolyl o-benzylquercetin glycoconjugates. | the 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with o-benzylquercetin alkynes (5-7) to afford regioselective triazole-linked o-benzylquercetin glycoconjugates (8-10) was investigated in the presence of cui/dipea in dichloromethane. all the developed glycoconjugates (8-10) were evaluated for anti-leishmanial activity against the promastigotes and amastigotes of leishmania donovani. graphical abstract click inspired synthesis of antileishmanial triazolyl o-benzylquercetin glycoconjugates. | 2015 | 25869315 |
| fitness of leishmania donovani parasites resistant to drug combinations. | drug resistance represents one of the main problems for the use of chemotherapy to treat leishmaniasis. additionally, it could provide some advantages to leishmania parasites, such as a higher capacity to survive in stress conditions. in this work, in mixed populations of leishmania donovani parasites, we have analyzed whether experimentally resistant lines to one or two combined anti-leishmanial drugs better support the stress conditions than a susceptible line expressing luciferase (luc line). ... | 2015 | 25849149 |
| antileishmanial pharmacomodulation in 8-nitroquinolin-2(1h)-one series. | an antileishmanial pharmacomodulation at position 4 of 8-nitroquinolin-2(1h)-one was conducted by using the sonogashira and suzuki-miyaura coupling reactions. a series of 25 derivatives was tested in vitro on the promastigote stage of leishmania donovani along with an in vitro cytotoxicity evaluation on the human hepg2 cell line. only the derivatives bearing a phenyl moiety at position 4 of the quinoline ring displayed interesting biologic profile, when the phenyl moiety was substituted at the p ... | 2015 | 25846065 |
| immunomodulatory and antileishmanial activity of phenylpropanoid dimers isolated from nectandra leucantha. | three phenylpropanoid dimers (1-3) including two new metabolites were isolated from the extract of the twigs of nectandra leucantha using antileishmanial bioassay-guided fractionation. the in vitro antiparasitic activity of the isolated compounds against leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. compounds 1-3 were effective against the intracellular amastigotes within macrophages, with ic50 values of 26.7, 17.8, and 101.9 μm, respective ... | 2015 | 25835647 |
| antineoplastic impact of leishmanial sphingolipid in tumour growth with regulation of angiogenic event and inflammatory response. | very often conventional therapy, i.e. chemotherapeutic treatment, develops resistance in cancer cells and fails to be effective against disease states. an alternative strategy or a new entity may resolve the problem. interestingly, the microbial world has begun to be explored in medicinal research as a potential new source to deliver bio-active molecules such as sphingolipids for efficacious cancer treatment. a sphingolipid of microbial origin, especially from leishmania donovani (lspl), is a no ... | 2015 | 25828883 |
| synthesis and biological evaluation of 2-arylbenzimidazoles targeting leishmania donovani. | a set of 56 2-arylbenzimidazoles was designed, synthesized and tested against leishmania donovani amastigotes. the left- and right-hand side rings of the molecule, as well as the amide linker were modified. structurally different derivatives were screened on l. donovani axenic amastigotes at concentrations of 5, 15 and 50 μm, and the ten most active derivatives were selected for further testing. 2-arylbenzimidazole derivative 24 was active against l. donovani-infected thp-1 cells showing 46% par ... | 2015 | 25827525 |
| immunostimulatory potential and proteome profiling of leishmania donovani soluble exogenous antigens. | isolation of the soluble exogenous antigens (seags), its immune response study and proteome profiling is an essential prerequisite for understanding the molecular pathogenesis of leishmania donovani. the immunostimulatory potential of l. donovani seags, purified from culture of l. donovani clinical isolate, was evaluated for their ability to induce cellular responses in treated/cured hamsters. seags induced significant proliferative responses in lymphocytes (si 5.6 ± 2.3; p < 0.01) isolated from ... | 2015 | 25824598 |
| chronic generalized fibrotic skin lesions from disseminated leishmaniasis caused by leishmania martiniquensis in two patients from northern thailand infected with hiv. | leishmaniasis is a newly emerging infection in thailand. most of the previous human cases have presented with the clinical features of visceral leishmaniasis and were mainly found in southern thailand. here we report the first two patients from northern thailand presenting with disseminated cutaneous leishmaniasis. | 2015 | 25823707 |
| a novel sterol isolated from a plant used by mayan traditional healers is effective in treatment of visceral leishmaniasis caused by leishmania donovani. | visceral leishmaniasis (vl), caused by the protozoan parasite leishmania donovani, is a global health problem affecting millions of people worldwide. treatment of vl largely depends on therapeutic drugs such as pentavalent antimonials, amphotericin b, and others, which have major drawbacks due to drug resistance, toxicity, and high cost. in this study, for the first time, we have successfully demonstrated the synthesis and antileishmanial activity of the novel sterol pentalinonsterol (pen), whic ... | 2015 | 27623316 |
| discovery of high affinity inhibitors of leishmania donovani n-myristoyltransferase. | n-myristoyltransferase (nmt) is a potential drug target in leishmania parasites. scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for leishmania donovani nmt; development led to high affinity inhibitors with excellent ligand efficiency. the binding mode was characterised by crystallography and provides a structural rationale for selectivity. | 2015 | 26962429 |
| characteristics of phlebotomine sandflies in selected areas of sri lanka. | cutaneous leishmaniasis (cl) is an endemic disease in sri lanka. studies on vector aspects, although important for better understanding of disease transmission dynamics, are still limited. the present study describes the species distribution and behavioral patterns of sandflies within selected disease-prevalent zones in the country. adult sandflies were collected from several field sites over a two-year duration in sri lanka using cattle-baited net traps, cdc light traps and manual methods. spec ... | 2015 | 26867357 |
| integrating ribosomal promoter vectors that offer a choice of constitutive expression profiles in leishmania donovani. | we have designed a novel series of integrating ribosomal rna promoter vectors with five incrementally different constitutive expression profiles, covering a 250-fold range. differential expression was achieved by placing different combinations of synthetic or leishmanial dna sequences upstream and downstream of the transgene coding sequence in order to modulate pre-mrna processing efficiency and mrna stability, respectively. all of the vectors have extensive multiple cloning sites, and versions ... | 2015 | 26844641 |
| efficient one-pot synthesis, molecular docking and in silico adme prediction of bis-(4-hydroxycoumarin-3-yl) methane derivatives as antileishmanial agents. | bis-(4-hydroxycoumarin-3-yl) methane derivatives 3(a-l) were synthesized from 4-hydroxycoumarin and substituted aromatic aldehydes using succinimide-n-sulfonic acid as catalyst and evaluated for their in vitro antileishmanial activity against promastigotes form of leishmania donovani. compounds 3a (ic50= 155 μg/ml), 3g (ic50= 157.5 μg/ml) and 3l (ic50= 150 μg/ml) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (ic50= 490 μg/ml). also, synthesized ... | 2015 | 26839526 |
| testing urine samples with rk39 strip as the simplest non-invasive field diagnosis for visceral leishmaniasis: an early report from eastern india. | diagnosis of visceral leishmaniasis (vl) is a major obstacle in the control of this disease. the rk39 strip-test using patient's blood is a breakthrough; however, it still requires a blood sample, which is a concern for safety in the field. we tried to simplify the test using the patient's urine instead of blood. | 2015 | 23023349 |
| study the effects of plga-peg encapsulated amphotericin b nanoparticle drug delivery system against leishmania donovani. | drug delivery systems are a promising technology to increase poor solubility and bioavailability of compounds. therefore we have developed plga-peg encapsulated amphotericin b nanoparticles (nps) drug delivery technology to increase the solubility of amphotericin b and target the macrophage of infected tissues during visceral leishmaniasis. the structural characterization by transmission electron microscopy and dynamic light scattering revealed the nano-size of the particle (30-35 nanometers). f ... | 2015 | 24601828 |
| reduction of leishmania donovani infectivity in whole blood using riboflavin and ultraviolet light. | leishmaniasis is a vector-borne disease caused by the protozoan parasite leishmania sp. that is transmitted by sandflies. travelers to endemic areas, and us military personnel stationed in the middle east, are at risk for contracting the disease. | 2015 | 25156473 |
| leishmania donovani phosphoproteins pp41 and pp29 re-establishes host protective immune response in visceral leishmaniasis. | as phospho proteins are reported to be involved in virulence and survival, the ability of leishmania to inhibit macrophage effector functions may result from a direct interference of leishmanial molecules with macrophage signal transduction pathways. several such proteins such as pp63, pp41 and pp29 have also been identified as a th1 stimulatory protein in the leishmania donovani. in the present study, the immunogenicity of a cocktail of pp63+pp41+pp29 was assessed by estimation of serum antibod ... | 2015 | 25224164 |
| probing the molecular mechanism of hypericin-induced parasite death provides insight into the role of spermidine beyond redox metabolism in leishmania donovani. | hypericin, a natural compound from hypericum perforatum (st. john's wort), has been identified as a specific inhibitor of leishmania donovani spermidine synthase (ldss) using integrated computational and biochemical approaches. hypericin showed in vitro inhibition of recombinant ldss enzyme activity. the in vivo estimation of spermidine levels in leishmania promastigotes after hypericin treatment showed significant decreases in the spermidine pools of the parasites, indicating target specificity ... | 2015 | 25313212 |
| design, synthesis and anti-leishmanial activity of novel symmetrical bispyridinium cyclophanes. | nine novel symmetrical bispyridinium cyclophanes have been synthesized. they are rigid derivatives with an upper spacer which joins the two exocyclic amino groups, and a lower spacer joining the two positively charged nitrogen atoms. at least one of the two spacers is an aliphatic linker, such as an alkane or oxyalkane fragment. the activity of these compounds has been evaluated against promastigotes and intracellular amastigotes of leishmania donovani and leishmania major. all the cyclophanes a ... | 2015 | 25462252 |
| evaluation of the immunoprophylactic potential of a killed vaccine candidate in combination with different adjuvants against murine visceral leishmaniasis. | despite a large number of field trials, till date no prophylactic antileishmanial vaccine exists for human use. killed antigen formulations offer the advantage of being safe but they have limited immunogenicity. recent research has documented that efforts to develop effective leishmania vaccine have been limited due to the lack of an appropriate adjuvant. addition of adjuvants to vaccines boosts and directs the immunogenicity of antigens. so, the present study was done to evaluate the effectiven ... | 2015 | 25316605 |
| specific antibody responses as indicators of treatment efficacy for visceral leishmaniasis. | acute visceral leishmaniasis (vl) is caused by infection with parasites of the leishmania donovani complex and may be fatal if not treated. early diagnosis and efficacious treatment are the keys to effective vl management and control. novel regimens are being developed to overcome limitations in vl treatment options, which are currently restricted by high costs, severe systemic side effects, and unresponsiveness. although simple and accurate serological tests are available to help confirm vl, no ... | 2015 | 25407374 |
| nitroimidazo-oxazole compound dndi-vl-2098: an orally effective preclinical drug candidate for the treatment of visceral leishmaniasis. | the objective of this study was to identify a nitroimidazo-oxazole lead molecule for the treatment of visceral leishmaniasis (vl). | 2015 | 25389223 |
| screening leishmania donovani complex-specific genes required for visceral disease. | leishmania protozoan parasites are the causing agent of leishmaniasis. depending on the infecting species, leishmania infection can causes a wide variety of diseases such as self-healing cutaneous lesions by l. major and fatal visceral leishmaniasis by l. donovani and l. infantum. comparison of the visceral disease causing l. infantum genome with cutaneous disease causing l. major and l. braziliensis genomes has identified 25 l. infantum (l. donovani complex) species-specific genes that are abse ... | 2015 | 25388124 |
| characterization of microrna expression profiles in leishmania-infected human phagocytes. | leishmania are intracellular protozoa that influence host immune responses eliciting parasite species-specific pathologies. micrornas (mirnas) are short single-stranded ribonucleic acids that complement gene transcripts to block protein translation and have been shown to regulate immune system molecular mechanisms. human monocyte-derived dendritic cells (dc) and macrophages (mp) were infected in vitro with leishmania major or leishmania donovani parasites. small rnas were isolated from total rna ... | 2015 | 25376316 |
| identification of leishmania donovani peroxin 14 residues required for binding the peroxin 5 receptor proteins. | trafficking of peroxisomal targeting signal 1 (pts1) proteins to the leishmania glycosome is dependent on the docking of the ldpex5 receptor to ldpex14 on the glycosomal membrane. a combination of deletion and random mutagenesis was used to identify residues in the ldpex14 n-terminal region that are critical for mediating the ldpex5-ldpex14 interaction. these studies highlighted residues 35-75 on ldpex14 as the core domain required for binding ldpex5. single point mutation within this core domai ... | 2015 | 25370715 |
| cationic liposomal sodium stibogluconate (ssg), a potent therapeutic tool for treatment of infection by ssg-sensitive and -resistant leishmania donovani. | pentavalent antimonials have been the first-line treatment for leishmaniasis for decades. however, the development of resistance to sodium stibogluconate (ssg) has limited its use, especially for treating visceral leishmaniasis (vl). the present work aims to optimize a cationic liposomal formulation of ssg for the treatment of both ssg-sensitive (ag83) and ssg-resistant (ge1f8r and ck1r) leishmania donovani infections. parasite killing was determined by the 3-(4,5-dimethylthiazol-2)-2,5-diphenyl ... | 2015 | 25367907 |
| ornithine decarboxylase of leishmania donovani: biochemical properties and possible role of n-terminal extension. | leishmaniasis is a wide spread tropical disease caused by protozoan parasite leishmania which belongs to order kinetoplastida and family trypanosomatidae. ornithine decarboxylase is key enzyme in polyamine biosynthesis in leishmania donovani. here, we report biochemical characterization of ornithine decarboxylase from l. donovani. furthermore, we have also investigated the role of n-terminal extension (250 amino acids) found in ornithine decarboxylase of l. donovani (ldodc). the removal of n-ter ... | 2015 | 24939662 |
| isolated cutaneous leishmaniasis by leishmania donovani in a soldier returning from afghanistan. | 2015 | 25062262 | |
| atypical manifestations of visceral leishmaniasis in patients with hiv in north ethiopia: a gap in guidelines for the management of opportunistic infections in resource poor settings. | in regions where it is endemic, visceral leishmaniasis is an important opportunistic infectious disease in people living with hiv. typically, clinical presentation of visceral leishmaniasis includes chronic fever, hepatosplenomegaly, and weight loss. in leishmania infantum endemic regions in europe, atypical visceral leishmaniasis presentations have been well documented, with almost every possible organ involved. however, such reports are rare in leishmania donovani endemic regions such as east ... | 2015 | 25300862 |
| recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids. | the 2-alkynoic fatty acids are an interesting group of synthetic compounds that display antimycobacterial, antifungal, anticancer, and pesticidal activities but their antiprotozoal activity has received little attention until recently. in this review we have summarized our present knowledge of the biomedical potential of the 2-hexadecynoic acid (2-hda) and 2-octadecynoic acid (2-oda) together with several mechanistic pieces of work attesting to the fact that these compounds, and their metabolite ... | 2016 | 23727443 |
| a case report of isolated lymphadenopathy revealing localized leishmanial lymphadenopathy in an asthenic 25-year-old man. | visceral leishmaniasis (vl) is endemic in large areas of the tropics, the subtropics, and the mediterranean basin. besides classical vl presentation, exceptional cases of a limited form of vl have been reported. here we describe the challenges of diagnosis and management of this intriguing entity. | 2016 | 27442631 |
| specific k39 antibody response and its persistence after treatment in patients with imported leishmaniasis. | the sensitivity of a k39 elisa (leishmania igg, virion/serion) for the detection of antibodies in patients with imported leishmaniasis was compared with an immunofluorescence assay (ifa), which was applied as "golden standard". the retrospective study comprised 93 ifa-positive or borderline sera from 42 patients with visceral (n = 16) or cutaneous (n = 26) leishmaniasis. patients had acquired infection predominately in the mediterranean area or the middle east. the leishmania species (leishmania ... | 2016 | 26508007 |
| expression and purification of an engineered, yeast-expressed leishmania donovani nucleoside hydrolase with immunogenic properties. | leishmania donovani is the major cause of visceral leishmaniasis (kala-azar), now recognized as the parasitic disease with the highest level of mortality second only to malaria. no human vaccine is currently available. a 36 kda l. donovani nucleoside hydrolase (ldnh36) surface protein has been previously identified as a potential vaccine candidate antigen. here we present data on the expression of ldnh36 in pichia pastoris and its purification at the 20 l scale to establish suitability for futur ... | 2016 | 26839079 |
| 15d-prostaglandin j2 induced reactive oxygen species-mediated apoptosis during experimental visceral leishmaniasis. | 15-deoxy-delta (12,14)-prostaglandin j2 (15d-pgj2) is a potent bioactive lipid mediator, known to possess several roles in cell regulation and differentiation along with antimicrobial efficacy against different bacterial and viral infections. in the present study, we investigated the therapeutic efficacy and mechanism of action of 15d-pgj2 in vitro in leishmania donovani promastigotes and infected j774 macrophages, and in vivo in balb/c mice/golden hamster model of experimental visceral leishman ... | 2016 | 26830627 |
| induction of il-10 and tgfβ from cd4+cd25+foxp3+ t cells correlates with parasite load in indian kala-azar patients infected with leishmania donovani. | visceral leishmaniasis (vl) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. however, the direct association between different immunological correlates and parasite numbers remains largely unknown. | 2016 | 26829554 |
| deprivation of l-arginine induces oxidative stress mediated apoptosis in leishmania donovani promastigotes: contribution of the polyamine pathway. | the growth and survival of intracellular parasites depends on the availability of extracellular nutrients. deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. to further understand the relationship, the mechanistic role of l-arginine in regulation of redox mediated survival of leishmania donovani promastigotes was investigated. l-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferat ... | 2016 | 26808657 |
| leucine-684: a conserved residue of an amp-acetyl coa synthetase (acecs) from leishmania donovani is involved in substrate recognition, catalysis and acetylation. | amp-acetyl coa synthetase (amp-acecs) is a key enzyme which catalyzes the activation of acetate to acetyl coa, an important intermediate at the cross roads of various anabolic and catabolic pathways. multiple sequence alignment of leishmania donovani acecs with other organisms revealed the presence of a highly conserved leucine residue at 684 position which is known to be crucial for acetylation by protein acetyl transferases in other organisms. in an attempt to understand the role of leucine re ... | 2016 | 26794803 |
| design, synthesis and biological evaluation of 1,3,6-trisubstituted β-carboline derivatives for cytotoxic and anti-leishmanial potential. | in the present study, 23 derivatives of 1,3,6-trisubstituted β-carboline were synthesized and evaluated for cytotoxic potential against four human cancer cells, namely a-549, hela, hep g2 and mcf-7 as well as anti-leishmanial activity against leishmania donovani (mhom/80/in/dd8) promastigotes. among the studied compounds, compounds 13c and 13q showed potent cytotoxic activity better than the parent compound 10. for instance, compound 13c was found to be the most cytotoxic with ic50 of 4.72, 3.59 ... | 2016 | 26791014 |
| highly improved antiparasitic activity after introduction of an n-benzylimidazole moiety on protein farnesyltransferase inhibitors. | in our search for new protein farnesyltransferase inhibitors with improved antiparasitic activities, we modified our previously developed 3-arylthiophene series of inhibitors by replacing the thioisopropyl group by different substituted imidazolylmethanamino moieties. twenty four new derivatives were synthesized and evaluated against human and parasite farnesyltransferases, and their anti-parasitic activity was determined against plasmodium falciparum, trypanosoma brucei, trypanosoma cruzi, and ... | 2016 | 26774924 |
| detection of natural infection of leishmania donovani (kinetoplastida: trypanosomatidae) in phlebotomus argentipes (diptera: psychodidae) from a forest ecosystem in the western ghats, india, endemic for cutaneous leishmaniasis. | a new focus of transmission of leishmania donovani causing cutaneous manifestations (cl) was reported by us earlier, in the western ghats region of thiruvananthapuram district, kerala, india. 12,253 sand fly specimens, comprising of three species belonging to the genus phlebotomus (24.7%) and 16 species belonging to the genus sergentomyia (57.3%) were collected from the region during 2012-2014. among phlebotomus species, phlebotomus argentipes was found predominant (77.3%), followed by phlebotom ... | 2016 | 26774685 |
| suppression of host pten gene expression for leishmania donovani survival in indian visceral leishmaniasis. | lipid phosphatase, pten is amongst the host gene actively involved in determining disease susceptibility. expression of pten and other genes in vicinity egr1 &4e-bp1 were evaluated in splenic tissue before and after treatment in visceral leishmaniasis patients. lower expression of egr1 in correlation with pten suppressed 4e-bp1 gene in active cases. the higher levels of pten mrna expression post treatment confirmed its role in effective clearance of leishmania. therefore, it is hypothesized that ... | 2016 | 26774334 |
| leishmania infantum asparagine synthetase a is dispensable for parasites survival and infectivity. | a growing interest in asparagine (asn) metabolism has currently been observed in cancer and infection fields. asparagine synthetase (as) is responsible for the conversion of aspartate into asn in an atp-dependent manner, using ammonia or glutamine as a nitrogen source. there are two structurally distinct as: the strictly ammonia dependent, type a, and the type b, which preferably uses glutamine. absent in humans and present in trypanosomatids, as-a was worthy of exploring as a potential drug tar ... | 2016 | 26771178 |
| 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 |
| accurate serodetection of asymptomatic leishmania donovani infection by use of defined antigens. | infection with leishmania donovaniis typically asymptomatic, but a significant number of individuals may progress to visceral leishmaniasis (vl), a deadly disease that threatens 200 million people in areas where it is endemic. while diagnosis of acute vl has been simplified by the use of cost-effective confirmatory serological tests, similar standardized tools are not widely available for detecting asymptomatic infection, which can be 4 to 20 times more prevalent than active disease. a simple an ... | 2016 | 26842701 |
| identification of a diverse indole-2-carboxamides as a potent antileishmanial chemotypes. | a novel series of highly diverse indole-2-carboxamides was synthesized utilizing the isocyanide based multicomponent reaction (imcr)-post modification approach and were identified as potential antileishmanial chemotype. among the synthesized 18 analogues, 12 analogues exhibited better antileishmanial activity against intracellular amastigotes form of leishmania donovani (ic50 values of 0.6-7.5 μm) as compared to standard drugs miltefosine and sodium stibogluconate. the compounds were also non-to ... | 2016 | 26840364 |
| dynein clusters into lipid microdomains on phagosomes to drive rapid transport toward lysosomes. | diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule ... | 2016 | 26853472 |
| abietane-type diterpenoid amides with highly potent and selective activity against leishmania donovani and trypanosoma cruzi. | dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, leishmania donovani and trypanosoma cruzi, were assayed. the most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an ic50 value of 0.37 μm against l. donovani axenic amastigotes and an outstanding ... | 2016 | 26849852 |
| ent-pimarane and ent-kaurane diterpenes from aldama discolor (asteraceae) and their antiprotozoal activity. | aldama discolor (syn.viguiera discolor) is an endemic asteraceae from the brazilian "cerrado", which has not previously been investigated for its chemical constituents and biological activity. diterpenes are common secondary metabolites found in aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. in this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2 ... | 2016 | 27649126 |
| interaction between cysteine synthase and serine o-acetyltransferase proteins and their stage specific expression in leishmania donovani. | leishmania possess a unique trypanothione redox metabolism with undebated roles in protection from oxidative damage and drug resistance. the biosynthesis of trypanothione depends on l-cysteine bioavailability which is regulated by cysteine biosynthesis pathway. the de novo cysteine biosynthesis pathway is comprised of serine o-acetyltransferase (sat) and cysteine synthase (cs) enzymes which sequentially mediate two consecutive steps of cysteine biosynthesis, and is absent in mammalian host. howe ... | 2016 | 27638321 |
| β-nitrostyrenes as potential anti-leishmanial agents. | development of new therapeutic approach to treat leishmaniasis has become a priority. in the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. a series of β-nitrostyrenes have been synthesized by using henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against leishmania donovani promastigotes by following standard guidelines. the most ... | 2016 | 27635124 |
| gene deleted live attenuated leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human pbmcs. | currently no effective vaccine is available for human visceral leishmaniasis(vl) caused by leishmania donovani. previously, we showed that centrin1 and p27gene deleted live attenuated leishmania parasites (ldcen1(-/-) and ldp27(-/-)) are safe, immunogenic and protective in animal models. here, to assess the correlates of protection, we evaluated immune responses induced by ldcen1(-/-) and ldp27(-/-) in human blood samples obtained from healthy, healed vl (hvl), post kala-azar dermal leishmaniasi ... | 2016 | 27624408 |
| a replicative in vitro assay for drug discovery against leishmania donovani. | the protozoan parasite leishmania donovani is the causative agent of visceral leishmaniasis, a disease potentially fatal if not treated. current available treatments have major limitations, and new and safer drugs are urgently needed. in recent years, advances in high-throughput screening technologies have enabled the screening of millions of compounds to identify new antileishmanial agents. however, most of the compounds identified in vitro did not translate their activities when tested in in v ... | 2016 | 27021313 |
| structure based medicinal chemistry-driven strategy to design substituted dihydropyrimidines as potential antileishmanial agents. | in an attempt to explore novel and more potent antileishmanial compounds to diversify the current inhibitors, we pursued a medicinal chemistry-driven strategy to synthesize novel scaffolds with common pharmacophoric features of dihydropyrimidine and chalcone as current investigational antileishmanial compounds. based on the reported x-ray structure of pteridine reductase 1 (ptr1) from leishmania major, we have designed a number of dihydropyrimidine-based derivatives to make specific interactions ... | 2016 | 27017551 |
| in vivo characterization of two additional leishmania donovani strains using the murine and hamster model. | leishmania donovani is a protozoan parasite causing the neglected tropical disease visceral leishmaniasis. one difficulty to study the immunopathology upon l. donovani infection is the limited adaptability of the strains to experimental mammalian hosts. our knowledge about l. donovani infections relies on a restricted number of east african strains (lv9, 1s). isolated from patients in the 1960s, these strains were described extensively in mice and syrian hamsters and have consequently become 're ... | 2016 | 27012562 |
| heat killed attenuated leishmania induces apoptosis of hepg2 cells through ros mediated p53 dependent mitochondrial pathway. | cytotoxic effect of attenuated leishmania on liver cancer cells by inducing ros generation. | 2016 | 27010918 |
| dna vaccine against visceral leishmaniasis: a promising approach for prevention and control. | the visceral leishmaniasis (vl) caused by leishmania donovani parasite severely affects large populations in tropical and subtropical regions of the world. the arsenal of drugs available is limited, and resistance is common in clinical field isolates. therefore, vaccines could be an important alternative for prevention against vl. recently, some investigators advocated the protective efficacy of dna vaccines, which induces the t cell-based immunity against vl. the vaccine antigens are selected a ... | 2016 | 27009772 |
| laboratory diagnosis of human visceral leishmaniasis. | visceral leishmaniasis (vl), caused by the leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. vl patients may be asymptomatic or they may present symptoms and findings of a systemic infection. the positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic disease ... | 2016 | 27004573 |
| evolutionary genomics of epidemic visceral leishmaniasis in the indian subcontinent. | leishmania donovani causes visceral leishmaniasis (vl), the second most deadly vector-borne parasitic disease. a recent epidemic in the indian subcontinent (isc) caused up to 80% of global vl and over 30,000 deaths per year. resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of l. donovani from the isc. we identify independent radiati ... | 2016 | 27003289 |
| one-pot synthesis and evaluation of antileishmanial activities of functionalized s-alkyl/aryl benzothiazole-2-carbothioate scaffold. | the synthesis of hitherto unreported s-alkyl/aryl benzothiazole-2-carbothioate is reported from thiols, oxalyl chloride, and 2-aminothiophenols using 10 mol % n-tetrabutylammonium iodide (tbai) as catalyst in acetonitrile through multicomponent reaction (mcr) strategy. the present protocol favored formation of benzothiazoles and thioesters via simultaneous formation of c-n and c-s bonds in good yields with a wide range of substrates. a few of the synthesized derivatives were evaluated for their ... | 2016 | 26999637 |
| an experimental challenge model of visceral leishmaniasis by leishmania donovani promastigotes in mice. | although visceral leishmaniasis is a fatal disease in humans and dogs, the use of mouse models is important for obtaining a better understanding of the pathogenesis, immunity, and host-parasite interactions of this disease. such models are also useful for the evaluation of vaccines and chemotherapies for treatment of visceral leishmaniasis. here, we present our method of experimental inoculation of mice with leishmania donovani promastigotes. nutrient-enriched undefined media may be beneficial f ... | 2016 | 26987675 |
| local production of a liquid direct agglutination test as a sustainable measure for control of visceral leishmaniasis in sudan. | a prerequisite for the control of visceral leishmaniasis (vl) is the accessibility to reference diagnostics. the high price of the freeze-dried direct agglutination test (fd-dat) and the short shelf-life time of the rk39 strip test (rk39) have limited the application of these tests in sudan. an original liquid dat (lq-dat) with high reproducibility compared with the fd-dat and rk39 has been routinely produced in our laboratory since 1999. in this study, a 3.4-year-old batch (of more than 90 test ... | 2016 | 26976890 |
| first molecular characterization of leishmania species causing visceral leishmaniasis among children in yemen. | visceral leishmaniasis (vl) is a debilitating, often fatal disease caused by leishmania donovani complex; however, it is a neglected tropical disease. l. donovani complex comprises two closely related species, l. donovani that is mostly anthroponotic and l. infantum that is zoonotic. differentiation between these two species is critical due to the differences in their epidemiology and pathology. however, they cannot be differentiated morphologically, and their speciation using isoenzyme-based me ... | 2016 | 26966902 |
| mutational and structural analysis of conserved residues in ribose-5-phosphate isomerase b from leishmania donovani: role in substrate recognition and conformational stability. | ribose-5-phosphate isomerase b from leishmania donovani (ldrpib) is one of the potential drug targets against visceral leishmaniasis. in the present study, we have targeted several conserved amino acids for mutational analysis (i.e. cys69, his11, his102, his138, asp45, tyr46, pro47 and glu149) to gain crucial insights into their role in substrate binding, catalysis and conformational stability of the enzyme. all the eight ldrpib variants were cloned, sequenced, expressed and purified. c69s, h102 ... | 2016 | 26953696 |
| hemoglobin guided nanocarrier for specific delivery of amphotericin b to leishmania infected macrophage. | leishmania donovani being an intracellular parasite poses many challenges against the attempted chemotherapy. after the resistance towards the first line of antileishmanial drug, amphotericin b has been the treatment of choice against visceral leishmaniasis, a fatal tropical disease. however, unfavorable toxicity profile, severe side effects, prolonged parenteral administration procedure limits the use of amphotericin b. lack of available specific delivery system also makes this drug unsafe for ... | 2016 | 26945483 |
| hemophagocytosis in experimental visceral leishmaniasis by leishmania donovani. | hemophagocytosis is a phenomenon in which macrophages phagocytose blood cells. there are reports on up-regulated hemophagocytosis in patients with infectious diseases including typhoid fever, tuberculosis, influenza and visceral leishmaniasis (vl). however, mechanisms of infection-associated hemophagocytosis remained elusive due to a lack of appropriate animal models. here, we have established a mouse model of vl with hemophagocytosis. at 24 weeks after infection with 1 x 10(7) leishmania donova ... | 2016 | 26942577 |
| differential expression of mirna regulates t cell differentiation and plasticity during visceral leishmaniasis infection. | visceral leishmaniasis (vl) is a tropical neglected disease caused by leishmania donovani, results in significant mortality in the indian subcontinent. the plasticity of t cell proliferation and differentiation depends on microrna mediated gene regulation which leads th1/th2 or th17/treg type of immune response during human vl. this study depicts the identification of target immune signaling molecule and transcription factors, which play a role in t-cell proliferation and differentiation followe ... | 2016 | 26941729 |
| structure of leishmania donovani coronin coiled coil domain reveals an antiparallel 4 helix bundle with inherent asymmetry. | coiled coils are ubiquitous structural motifs that serve as a platform for protein-protein interactions and play a central role in myriad physiological processes. though the formation of a coiled coil requires only the presence of suitably spaced hydrophobic residues, sequence specificities have also been associated with specific oligomeric states. rhxxhe is one such sequence motif, associated with parallel trimers, found in coronins and other proteins. coronin, present in all eukaryotes, is an ... | 2016 | 26940672 |
| in vitro susceptibilities of wild and drug resistant leishmania donovani amastigotes to piperolactam a loaded hydroxypropyl-β-cyclodextrin nanoparticles. | leishmaniasis is an epidemic in various countries, and the parasite leishmania donovani is developing resistance against available drugs. in the present study the antileishmanial action of piperolactam a (pl), isolated after bioactivity guided fractionation from root extracts of piper betle was accentuated in detail. activity potentiation was achieved via cyclodextrin complexation. crude hydro-ethanolic extract (pb) and three fractions obtained from pb and fabricated pl-hydroxypropyl-β-cyclodext ... | 2016 | 26940000 |
| genetic manipulation of leishmania donovani to explore the involvement of argininosuccinate synthase in oxidative stress management. | reactive oxygen and nitrogen species (ros and rns) produced by the phagocytic cells are the most common arsenals used to kill the intracellular pathogens. however, leishmania, an intracellular pathogen, has evolved mechanisms to survive by counterbalancing the toxic oxygen metabolites produced during infection. polyamines, the major contributor in this anti-oxidant machinery, are largely dependent on the availability of l-arginine in the intracellular milieu. argininosuccinate synthase (ass) pla ... | 2016 | 26939071 |
| host resistance to visceral leishmaniasis: prevalence and prevention. | visceral leishmaniasis (vl) is a chronic parasitic disease caused by the vector-borne leishmania donovani and leishmania (l.) infantum chagasi parasites. the disease affects about 12 million humans in more than 90 countries worldwide. if not treated, the visceral form of leishmania infection is potentially fatal, yielding about 50000 deaths per year. in the vertebrate host, the leishmania species causing vl spread systematically to propagate in macrophage reservoirs distributed in the tissues of ... | 2016 | 26934623 |
| attenuated leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 mapk dependent phagosome maturation in leishmania donovani co-infected macrophages. | promastigote form of leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. but till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict leishmania growth. attenuated leishmania strain exposed raw 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. the augmentation of pro-inflammatory activity is mostly attributed to p38 mapk and p44/42 mapk. in our study, these ac ... | 2016 | 26928472 |
| understanding the importance of conservative hypothetical protein ldbpk_070020 in leishmania donovani and its role in subsistence of the parasite. | the genome of leishmania donovani, the causative agent of visceral leishmaniasis, codes for approximately 65% of both conserved and non-conserved hypothetical proteins. studies on 'conserved hypothetical' proteins are expected to reveal not only new and crucial aspects of leishmania biochemistry, but it could also lead to discovery of novel drug candidates. conserved hypothetical protein, ldbpk_070020, is a 31.14 kda protein, encoded by an 810 bp gene. blast analysis of ldbpk_070020, performed a ... | 2016 | 26926257 |
| antileishmanial and cytotoxic activity of some highly oxidized abietane diterpenoids from the bald cypress, taxodium distichum. | two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of taxodium distichum, collected in central ohio. the active subfraction from which all compounds isolated in this study were purified was tested in vivo using leishmania donovani-infected mice and was found to dose-dependently reduce the para ... | 2016 | 26905523 |
| repositioning antitubercular 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for neglected tropical diseases: structure-activity studies on a preclinical candidate for visceral leishmaniasis. | 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives were initially studied for tuberculosis within a backup program for the clinical trial agent pretomanid (pa-824). phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of dndi-vl-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (vl). additional work was then conducted to delineate its essential structural features, aiming to improve solubility and ... | 2016 | 26901446 |
| visceral leishmaniasis: a forgotten epidemic. | visceral leishmaniasis (vl or kala-azar) is most endemic in asia and africa and commonly affects young children. it is usually caused by leishmania donovani or leishmania infantum that are transmitted by phlebotomine sand flies. transmission may be anthroponotic or zoonotic or both, depending on the endemic area. clinical features include fever, hepatosplenomegaly, weight loss and pancytopenia. younger age, malnutrition and immunosuppression (hiv infection, use of immunosuppressive drugs) are ri ... | 2016 | 26895806 |
| universal minicircle sequence binding protein of leishmania donovani regulates pathogenicity by controlling expression of cytochrome-b. | leishmania contains a concatenated mitochondrial dna, kdna. universal minicircle sequence binding protein (umsbp), a mitochondrial protein, initiates kdna replication by binding with a conserved universal minicircle sequence (ums) of kdna. here, we describe first time in l. donovani the regulation of dna binding activity of umsbp and the role of umsbp in virulence. | 2016 | 26889377 |
| successful therapy of murine visceral leishmaniasis with astrakurkurone, a triterpene isolated from the mushroom astraeus hygrometricus, involves the induction of protective cell-mediated immunity and tlr9. | in our previous report, we showed that astrakurkurone, a triterpene isolated from the indian mushroom astraeus hygrometricus (pers.) morgan, induced reactive oxygen species, leading to apoptosis in leishmania donovani promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 μg/ml. the aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to ... | 2016 | 26883702 |
| combined immune therapy for the treatment of visceral leishmaniasis. | chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. immunoregulatory networks are established to prevent tissue damage caused by inflammation. although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. immune checkpoint blockade has recently been successfully employed to treat cancer. this strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tu ... | 2016 | 26872334 |
| synthesis and activity of novel homodimers of morita-baylis-hillman adducts against leishmania donovani: a twin drug approach. | it is reported here the synthesis of novel homodimers 12-19 of morita-baylis-hillman adducts (mbha) from one-pot morita-baylis-hillman reaction (mbhr) between aromatic aldehydes as eletrophiles and ethylene glycol diacrylate as michael acceptor (35-94% yields) using cheap and green conditions. the bioactivities were evaluated against promastigote form of leishmania donovani. all homodimers showed to be more potent than corresponding monomers. it is worth highlighting that the halogenated homodim ... | 2016 | 27520941 |
| a novel spirooxindole derivative inhibits the growth of leishmania donovani parasites both in vitro and in vivo by targeting type ib topoisomerase. | visceral leishmaniasis is a fatal parasitic disease, and there is an emergent need for development of effective drugs against this neglected tropical disease. we report here the development of a novel spirooxindole derivative, n-benzyl-2,2'α-3,3',5',6',7',7α,α'-octahydro-2methoxycarbonyl-spiro[indole-3,3'-pyrrolizidine]-2-one (compound 4c), which inhibits leishmania donovani topoisomerase ib (ldtopib) and kills the wild type as well as drug-resistant parasite strains. this compound inhibits cata ... | 2016 | 27503653 |
| grind2-based 3d-qsar and prediction of activity spectra for symmetrical bis-pyridinium salts with promastigote antileishmanial activity. | leishmaniasis is a major group of neglected tropical diseases caused by the protozoan parasite leishmania. about 12 million people are affected in 98 countries and 350 million people worldwide are at risk of infection. current leishmaniasis treatments rely on a relatively small arsenal of drugs, including amphotericin b, pentamidine and others, which in general have some type of inconvenience. recently, we have synthesized antileishmanial bis-pyridinium derivatives and symmetrical bis-pyridinium ... | 2016 | 27495391 |
| direct evidence for role of anti-saliva antibodies against salivary gland homogenate of p. argentipes in modulation of protective th1-immune response against leishmania donovani. | currently the main concerns regarding control of visceral leishmaniasis (vl) caused by l. donovani are immunosuppression, relating toxicity of anti-leishmanial drug and little development in appropriate vaccine and vector (p. argentipes) control. reports available from ex-vivo studies reflect significance of vector salivary gland homogenate (sgh) in reverting immunosuppression of infected vl subjects and as such the immunogenic nature of sgh can be a strategy to modulate immune system and anti-l ... | 2016 | 27484246 |
| leishmania donovani-induced prostaglandin e2 generation is critically dependent on host toll-like receptor 2-cytosolic phospholipase a2 signaling. | visceral leishmaniasis (vl) is the second-largest parasitic killer disease after malaria. during vl, the protozoan leishmania donovani induces prostaglandin e2 (pge2) generation within host macrophages to aid parasite survival. pge2 significantly influences leishmanial pathogenesis, as l. donovani proliferation is known to be attenuated in pge2-inhibited macrophages. here, we report for the first time that signaling via macrophage toll-like receptor 2 (tlr2) plays an instrumental role in inducin ... | 2016 | 27481248 |
| arylthiosemicarbazones as antileishmanial agents. | based on a screening process, we targeted substituted thiosemicarbazone as potential antileishmanial agents. our objective was to identify the key structural elements contributing to the anti-parasite activity that might be used for development of effective drugs. a series of 32 compounds was synthesized and their efficacy was evaluated against the clinically relevant intracellular amastigotes of leishmania donovani. from these, 22 compounds showed ec50 values below 10 μm with the most active de ... | 2016 | 27475107 |
| optimizing immunization strategies for the induction of antigen-specific cd4 and cd8 t cell responses for protection against intracellular parasites. | immunization strategies that generate either cd4 or cd8 t cell responses are relatively well described, but less is known with regard to optimizing regimens to induce both cd4 and cd8 memory t cells. considering the importance of both cd4 and cd8 t cells in the control of intracellular pathogens such as leishmania donovani, we wanted to identify vaccines that could raise both cd4 and cd8 t cell responses and determine how to configure immunization strategies to generate the best combined protect ... | 2016 | 27466350 |
| microrna expression profiling of leishmania donovani-infected host cells uncovers the regulatory role of mir30a-3p in host autophagy. | leishmania is an obligate intracellular parasite that replicates inside phagolysosomes or parasitophorous vacuoles (pv) of the monocyte/macrophage lineage. it reprograms macrophages and produces a metabolic state conducive to successful infection and multiplication. micrornas (mirnas), a class of small 22 to 24 nucleotide noncoding regulatory rnas alter the gene expression and consequently proteome output by targeting mrnas, may play a regulatory role in modulating host cell functions. in the pr ... | 2016 | 27459332 |
| application of rapid in vitro co-culture system of macrophages and t-cell subsets to assess the immunogenicity of dogs vaccinated with live attenuated leishmania donovani centrin deleted parasites (ldcen-/-). | live attenuated leishmania donovani parasites as ldcen(-/-) were shown to confer protective immunity against leishmania infection in mice, hamsters, and dogs. strong immunogenicity in dogs vaccinated with ldcen(-/-) has been previously reported, including increased antibody response favoring th1 response lymphoproliferative responses, cd4(+) and cd8(+) t-cells activation, increased levels of th1 and reduction of th2 cytokines, in addition to a significant reduction in parasite burden after 18 an ... | 2016 | 27136900 |
| quantitative proteome analysis of leishmania donovani under spermidine starvation. | we have earlier reported antileishmanial activity of hypericin by spermidine starvation. in the current report, we have used label free proteome quantitation approach to identify differentially modulated proteins after hypericin treatment. a total of 141 proteins were found to be differentially regulated with anova p value less than 0.05 in hypericin treated leishmania promastigotes. differentially modulated proteins have been broadly classified under nine major categories. increase in ribosomal ... | 2016 | 27123864 |