Publications

experimental resistance to drug combinations in leishmania donovani: metabolic and phenotypic adaptations.	together with vector control, chemotherapy is an essential tool for the control of visceral leishmaniasis (vl), but its efficacy is jeopardized by growing resistance and treatment failure against first-line drugs. to delay the emergence of resistance, the use of drug combinations of existing antileishmanial agents has been tested systematically in clinical trials for the treatment of visceral leishmaniasis (vl). in vitro, leishmania donovani promastigotes are able to develop experimental resista ...	2015	25645828
antiprotozoal activity and dna binding of dicationic acridones.	dicationic acridone derivatives were synthesized and their antiparasitic activity was evaluated. acridones displayed in vitro nanomolar ic50 values against trypanosoma brucei rhodesiense stib900 with selectivity indices >1000. compounds 1b, 3a, and 3b were as potent as the reference drug melarsoprol in this assay. submicromolar-range activities were observed against wild-type (nf54) and resistant (k1) strains of plasmodium falciparum, whereas no significant activity was detected against trypanos ...	2015	25642604
northalrugosidine is a bisbenzyltetrahydroisoquinoline alkaloid from thalictrum alpinum with in vivo antileishmanial activity.	screening of a plant-derived natural product library led to the observation of in vitro antileishmanial activity by three bisbenzyltetrahydroisoquinoline alkaloids (1-3) that were purified previously from thalictrum alpinum. a spectroscopic study of the active compounds was conducted to confirm their identities. of the compounds tested, northalrugosidine (1) showed the most potent in vitro activity against leishmania donovani promastigotes (0.28 μm) and the highest selectivity (29.3-fold) versus ...	2015	25629555
synthesis and biological evaluation of ferrocenylquinoline as a potential antileishmanial agent.	the emergence of resistance against antileishmanial drugs in current use necessitates the search for new classes of antileishmanial compounds. herein we report the design, synthesis, and evaluation of a novel ferrocenylquinoline for activity against leishmania donovani. 7-chloro-n-[2-(1h-5-ferrocenyl-1,2,3-triazol-1-yl)ethyl]quinolin-4-amine (1) was generated by coupling an iron(ii) ethynylferrocene species with 4-(2-ethylazido)amino-7-chloroquinoline using click chemistry. the synthesized compo ...	2015	25619822
studies on cocktails of 31-kda, 36-kda and 51-kda antigens of leishmania donovani along with saponin against murine visceral leishmaniasis.	a substantial number of antigens of leishmania donovani have been described in the past. however, identifying candidate antigens is not enough. appropriate antigen delivery to induce the right type of immune response against leishmaniasis (i.e. induction of a strong antigen-specific th1 type of immune response) is another crucial component of an effective vaccine. therefore, 'cocktail' vaccines are proposed based on the assumption that such cocktails will show enhanced efficacy. studies have bee ...	2015	25615543
chemical proteomics versus leishmaniasis.	in this issue of chemistry & biology, wright et al. (2015) describe an elegant approach to evaluating substrates and the drug target potential of leishmania donovani n-myristoyltransferase (nmt) using a technically simple and straightforward chemical proteomics approach.	2015	25794432
targeting ergosterol biosynthesis in leishmania donovani: essentiality of sterol 14 alpha-demethylase.	leishmania protozoan parasites (trypanosomatidae family) are the causative agents of cutaneous, mucocutaneous and visceral leishmaniasis worldwide. while these diseases are associated with significant morbidity and mortality, there are few adequate treatments available. sterol 14alpha-demethylase (cyp51) in the parasite sterol biosynthesis pathway has been the focus of considerable interest as a novel drug target in leishmania. however, its essentiality in leishmania donovani has yet to be deter ...	2015	25768284
predicting antiprotozoal activity of benzyl phenyl ether diamine derivatives through qsar multi-target and molecular topology.	multi-target qsar is a novel approach that can predict simultaneously the activity of a given chemical compound on different pharmacological targets. in this work, we have used molecular topology and statistical tools such as multilinear regression analysis and artificial neural networks, to achieve a multi-target qsar model capable to predict the antiprotozoal activity of a group of benzyl phenyl ether diamine derivatives. the activity was related to three parasites with a high prevalence rate ...	2015	25754076
sar refinement of antileishmanial n(2),n(4)-disubstituted quinazoline-2,4-diamines.	visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. new drugs that are inexpensive, orally active, and effective could be useful tools in the fight against this disease. we previously showed that n(2),n(4)-disubstituted quinazoline-2,4-diamines displayed low- to sub-micromolar potency against intracellular leishmania, and lead compound n(4)-(furan-2-ylmethyl)-n(2)-isopropyl-7-methylquinazoline-2,4-diamine (4) exhibited modest efficac ...	2015	25749014
comprehensive proteomics analysis of glycosomes from leishmania donovani.	leishmania donovani is a kinetoplastid protozoan that causes a severe and fatal disease kala-azar, or visceral leishmaniasis. l. donovani infects human host after the phlebotomine sandfly takes a blood meal and resides within the phagolysosome of infected macrophages. previous studies on host-parasite interactions have not focused on leishmania organelles and the role that they play in the survival of this parasite within macrophages. leishmania possess glycosomes that are unique and specialized ...	2015	25748437
in vitro and in vivo evaluation of anti-leishmanial and immunomodulatory activity of neem leaf extract in leishmania donovani infection.	the toxicity and emergence of resistance to available chemical drugs against visceral leishmaniasis is evoking to explore herbal treatment. one such attempt with the neem is being reported here. the current study is primarily focused to evaluate the anti-leishmanial effects of neem leaf extracts. among which, ethyl acetate fraction (eaf) alone was found to exhibit leishmanicidal effect validated through cytotoxicity assay and estimated its ic₅₀ to be 52.4 µg/ml on the promastigote stage. propidi ...	2015	25747203
recombinant nad-dependent sir-2 protein of leishmania donovani: immunobiochemical characterization as a potential vaccine against visceral leishmaniasis.	the development of a vaccine conferring long-lasting immunity remains a challenge against visceral leishmaniasis (vl). immunoproteomic characterization of leishmania donovani proteins led to the identification of a novel protein nad+-dependent silent information regulatory-2 (sir2 family or sirtuin) protein (ldsir2rp) as one of the potent immunostimulatory proteins. proteins of the sir2 family are characterized by a conserved catalytic domain that exerts unique nad-dependent deacetylase activity ...	2015	25745863
new compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource.	using whole-cell phenotypic assays, the glaxosmithkline high-throughput screening (hts) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. leishmania donovani, trypanosoma cruzi and trypanosoma brucei. secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. hit compounds were chemically clustered and triaged for desirable physico ...	2015	25740547
cross talk between leishmania donovani cpg dna and toll-like receptor 9: an immunoinformatics approach.	the precise and potential contribution of toll-like receptors (tlrs) signaling pathways in fighting parasitic infections of leishmania spp., an intracellular protozoan parasite, has gained significant attention during the last decades. although it is well established that tlr9 recognizes cpg motifs in microbial genomes, the specificity of the cpg dna pattern of leishmania parasite interacting with endosomal tlr9 is still unknown. hence in our study to identify the cpg dna pattern of leishmania d ...	2015	25735984
global analysis of protein n-myristoylation and exploration of n-myristoyltransferase as a drug target in the neglected human pathogen leishmania donovani.	n-myristoyltransferase (nmt) modulates protein function through the attachment of the lipid myristate to the n terminus of target proteins, and is a promising drug target in eukaryotic parasites such as leishmania donovani. only a small number of nmt substrates have been characterized in leishmania, and a global picture of n-myristoylation is lacking. here, we use metabolic tagging with an alkyne-functionalized myristic acid mimetic in live parasites followed by downstream click chemistry and an ...	2015	25728269
selective elimination of leptomonas from the in vitro co-culture with leishmania.	leishmania and leptomonas are protozoan parasites of the family trypanosomatidae. leishmania donovani causes the fatal visceral leishmaniasis (vl; kala-azar) in mammals and is transmitted by sand fly vector. certain vl-cured human populations in india and sudan develop post kala-azar dermal leishmaniasis (pkdl) due to the same parasite. although leptomonas is parasitic mainly in insects, several recent reports on the clinical isolates of l. donovani from vl and pkdl patients in india confirm co- ...	2015	25582929
th1-biased immunomodulation and therapeutic potential of artemisia annua in murine visceral leishmaniasis.	in the absence of vaccines and limitations of currently available chemotherapy, development of safe and efficacious drugs is urgently needed for visceral leishmaniasis (vl) that is fatal, if left untreated. earlier we reported in vitro apoptotic antileishmanial activity of n-hexane fractions of artemisia annua leaves (aal) and seeds (aas) against leishmania donovani. in the present study, we investigated the immunostimulatory and therapeutic efficacy of aal and aas.	2015	25568967
anti-citrullinated peptide antibodies in sudanese patients with leishmania donovani infection exhibit reactivity not dependent on citrullination.	african patients with leishmania donovani infections have signs of strong systemic inflammation and high levels of circulating immune complexes (ic) and rheumatoid factor (rf), all serologic markers of rheumatic disease. as inflammation in general is associated with citrullination, we sought to investigate acpa responses in sudanese leishmania patients. serum samples were collected from sudanese patients with visceral leishmaniasis (vl) and post-kala-azar dermal leishmaniasis (pkdl) as well as f ...	2015	25565324
looking for new antileishmanial derivatives in 8-nitroquinolin-2(1h)-one series.	from a recently identified antileishmanial pharmacophore, a structure-activity relationship study was conducted by introducing various aminated, phenoxy or thiophenoxy moieties at position 4 of the 8-nitroquinolin-2(1h)-one scaffold, using snar reactions. thus a series of 47 derivatives was synthesized and evaluated in vitro on the promastigote stage of leishmania donovani. in parallel, the cytotoxicity of the active molecules was tested on the human hepg2 cell line. the results we obtained show ...	2015	25559208
mucocutaneous leishmaniasis caused by leishmania donovani infection in an indian man.	leishmaniasis is a protozoal disease caused by species of leishmania. mucocutaneous leishmaniasis (mcl) involves the skin and mucosa. india is endemic for species such as leishmania donovani and leishmania major, which are responsible for visceral and cutaneous leishmaniasis, respectively. although mcl has been reported from india previously, the implicated pathogen was identified as l. donovani in only one case.	2015	25557311
adaptation of leishmania donovani to cutaneous and visceral environments: in vivo selection and proteomic analysis.	leishmaniasis is a neglected tropical disease caused by leishmania protozoa. two main forms are found in the old world, self-limited cutaneous leishmaniasis and potentially fatal visceral leishmaniasis, with parasite dissemination to liver, bone marrow, and spleen. the leishmania donovani species complex is the causative agent of visceral leishmaniasis worldwide, but atypical l. donovani strains can cause cutaneous leishmaniasis. we hypothesized that l. donovani can adapt to survive in response ...	2015	25536015
therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced t cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules.	visceral leishmaniasis (vl) or kala-azar (ka) is one of the most deadly forms of disease among all neglected tropical diseases. there are no satisfactory drugs or vaccine candidates available for this dreaded disease. our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (i.m.) and intraperitoneal (i.p.) route in balb/c mice model.	2015	25532783
leishmanial sphingolipid induces apoptosis in sarcoma 180 cancer cells through regulation of tumour growth via angiogenic switchover.	sphingolipids are membrane and intracellular lipids that typically modulate cellular processes to cause cell death. exogenous administration of sphingolipids may cause restriction of tumour growth and several alternative strategies are being used to control the cell growth. the microbes, their cellular component(s) or metabolites like dha, epa and also fty720 have been employed as new therapeutic entities to regulate the disease condition. the therapeutic efficacy of lipids from leishmania donov ...	2015	25524576
"squalenoylcurcumin" nanoassemblies as water-dispersible drug candidates with antileishmanial activity.	curcumin, a natural polyphenolic compound, showed antiparasitic potential, including trypanocidal and leishmanicidal activity, in several in vitro and in vivo models. the molecule is well tolerated in humans. however, it is insoluble in water and displays poor oral bioavailability as a result of low absorption. new derivatives of curcumin were prepared by esterification of one or two of its phenolic groups with 1,1',2-tris-norsqualenic acid. these "squalenoylcurcumins" were formulated as water-d ...	2015	25523035
leishmania infantum amastigotes trigger a subpopulation of human b cells with an immunoregulatory phenotype.	visceral leishmaniasis is caused by the protozoan parasites leishmania infantum and leishmania donovani. this infection is characterized by an uncontrolled parasitization of internal organs which, when left untreated, leads to death. disease progression is linked with the type of immune response generated and a strong correlation was found between disease progression and serum levels of the immunosuppressive cytokine il-10. other studies have suggested a role for b cells in the pathology of this ...	2015	25710789
the neurotrophic receptor ntrk2 directs lymphoid tissue neovascularization during leishmania donovani infection.	the neurotrophic tyrosine kinase receptor type 2 (ntrk2, also known as trkb) and its ligands brain derived neurotrophic factor (bdnf), neurotrophin-4 (nt-4/5), and neurotrophin-3 (nt-3) are known primarily for their multiple effects on neuronal differentiation and survival. here, we provide evidence that ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. we show that in leishmania donovani-infected mice, ntrk2 is aberrantly expressed on splenic endo ...	2015	25710496
novel protein-protein interaction between spermidine synthase and s-adenosylmethionine decarboxylase from leishmania donovani.	polyamine biosynthesis pathway has long been considered an essential drug target for trypanosomatids including leishmania. s-adenosylmethionine decarboxylase (adometdc) and spermidine synthase (spdsyn) are enzymes of this pathway that catalyze successive steps, with the product of the former, decarboxylated s-adenosylmethionine (dcsam), acting as an aminopropyl donor for the latter enzyme. here we have explored the possibility of and identified the protein-protein interaction between spdsyn and ...	2015	25511700
arg-265: a critical residue of l.donovani cytosolic shmt in maintaining the binding of thf and catalysis.	serine hydroxymethyltransferase belongs to the class of pyridoxal-5-phosphate enzymes along with aspartate aminotransferase. to explore the function of residue(s) involved in binding of the carboxylate group of tetrahydrofolic acid (thf) to l. donovani cytosolic serine hydroxymethyltransferase (ldcshmt), the gene was cloned in pet-28(a) vector, overexpressed and purified to homogeneity. with the help of docking results of thf to the active site of protein, the key residues involved in interactio ...	2015	25499510
design, synthesis and in vitro antikinetoplastid evaluation of n-acylated putrescine, spermidine and spermine derivatives.	a structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. among them, a spermidine derivative (compound 13) was specifically active in vitro against leishmania donovani axenic amastigotes (ic50 at 5.4μm; selectivity index >18.5) and a spermine derivative (compound 28) specifically active against trypanosoma brucei gambiense (ic50 at 1.9μm; selectivity index >52).	2015	25499437
immunological consequences of stress-related proteins--cytosolic tryparedoxin peroxidase and chaperonin tcp20--identified in splenic amastigotes of leishmania donovani as th1 stimulatory, in experimental visceral leishmaniasis.	in earlier studies, proteomic characterization of splenic amastigote fractions from clinical isolates of leishmania donovani, exhibiting significant cellular responses in cured leishmania subjects, led to the identification of cytosolic tryparedoxin peroxidase (ldctryp) and chaperonin-tcp20 (ldtcp20) as th1-stimulatory proteins. both the proteins, particularly ldtcp20 for the first time, were successfully cloned, overexpressed, purified and were found to be localized in the cytosol of purified s ...	2015	25498563
mechanisms of action of substituted β-amino alkanols on leishmania donovani.	leishmaniasis is the protozoan disease second in importance for human health, superseded only by malaria; however, the options for chemotherapeutic treatment are increasingly limited due to drug resistance and toxicity. under this perspective, a quest for new chemical compounds is urgently needed. an n-substituted 2-aminoalkan-1-ol scaffold has been shown to be a versatile scaffold for antiparasitic activity. knowledge about its mechanism of action is still rather limited. in this work, we endea ...	2015	25487805
cutaneous leishmaniasis caused by leishmania donovani in the tribal population of the agasthyamala biosphere reserve forest, western ghats, kerala, india.	cutaneous leishmaniasis (cl), a neglected tropical disease, is reported to be prevalent in tribal villages located in the agasthyamala biosphere reserve forests of western ghats, kerala state, india. we carried out an investigation to characterize the species of leishmania parasites involved in these infections prevalent among one of the oldest human tribal populations in india. skin aspirates collected from 13 clinically diagnosed cases were subjected to histopathological investigations, serolo ...	2015	25480880
a defective oxidative burst and impaired antigen presentation are hallmarks of human visceral leishmaniasis.	survival of the leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (vl).	2015	25479930
vaccination using live attenuated leishmania donovani centrin deleted parasites induces protection in dogs against leishmania infantum.	live attenuated leishmania donovani parasites such as ldcen(-/-) have been shown elicit protective immunity against leishmanial infection in mice and hamster models. previously, we have reported on the induction of strong immunogenicity in dogs upon vaccination with ldcen(-/-) including an increase in immunoglobulin isotypes, higher lymphoproliferative response, higher frequencies of activated cd4(+) and cd8(+) t cells, ifn-γ production by cd8(+) t cells, increased secretion of tnf-α and il-12/i ...	2015	25475955
chemotherapy of leishmaniasis part xiii: design and synthesis of novel heteroretinoid-bisbenzylidine ketone hybrids as antileishmanial agents.	some novel heteroretinoid-bisbenzylidine ketone hybrids have been synthesized and evaluated for their in vitro antileishmanial activity against intramacrophagic amastigotes of leishmania donovani. among all the nine synthetic compounds, five compounds (7c, 7d and 7f-h) have shown significant (less than 7μm) activity against intramacrophagic amastigotes. the ic50 values of these compounds were found better than the reference drugs sodium stibogluconate (ssg) and miltefosine. this study helped us ...	2015	25475205
unmethylated cpg motifs in the l. donovani dna regulate tlr9-dependent delay of programmed cell death in macrophages.	regulation of macrophage pcd plays an important role in pathogenesis of leishmaniasis. however, the precise involvement of any parasite molecule in this process remains uncertain. in the current study, in silico wide analysis demonstrated that genes in the leishmania donovani genome are highly enriched for cpg motifs, with sequence frequency of 8.7%. here, we show that unmethylated species-specific cpg motifs in lddna significantly (p = 0.01) delay macrophage pcd by endosomal interaction with tl ...	2015	25473100
characterization of a ricin-resistant mutant of leishmania donovani that expresses lipophosphoglycan.	the abundant cell-surface lipophosphoglycan (lpg) of leishmania parasites plays a central role throughout the eukaryote's life cycle. a number of lpg-defective mutants and their complementing genes have been isolated and have proven invaluable in assessing the importance of lpg and related glycoconjugates in parasite virulence. while ricin agglutination selection protocols frequently result in lpg- mutants, one leishmania donovani variant we isolated, named jabba, was found to be lpg+. procycli ...	2015	25472443
randomized, double-blind, controlled, comparative study on intralesional 10% and 15% hypertonic saline versus intralesional sodium stibogluconate in leishmania donovani cutaneous leishmaniasis.	intralesional 7% hypertonic saline (hs) has been shown to be effective and safe against leishmania donovani and leishmania major cutaneous leishmaniasis (cl), with cure rates of 92% and 96%, respectively. this study was designed to assess the efficacy and safety of 10% and 15% hs in cl.	2015	25600472
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
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
granzyme-mediated regulation of host defense in the liver in experimental leishmania donovani infection.	in the livers of susceptible c57bl/6 (b6) mice infected with leishmania donovani, cd8(+) t cell mechanisms are required for granuloma assembly, macrophage activation, intracellular parasite killing, and self-cure. since gene expression of perforin and granzymes a and b (gzma and gzmb), cytolytic proteins linked to cd8(+) cell effector function, was enhanced in infected liver tissue, b6 mice deficient in these granular proteins were used to gauge host defense roles. neither perforin nor gzma was ...	2015	25452549
leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of leishmania in visceral leishmaniasis.	ornithine decarboxylase, the rate limiting enzyme of the polyamine biosynthesis pathway, is significant in the synthesis of trypanothione, t(sh)2, the major reduced thiol which is responsible for the modulation of the immune response and pathogenesis in visceral leishmaniasis. data on the relationship between ornithine decarboxylase and the cellular immune response in vl patients are limited. therefore, we purified a recombinant ornithine decarboxylase from leishmania donovani (r-ldodc) of appro ...	2015	25449949
evaluation of the immunogenicity and protective efficacy of killed leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis.	visceral leishmaniasis (vl) caused by leishmania donovani is a life-threatening disease involving uncontrolled parasitization of vital organs. drugs to treat leishmaniasis have one or more limitations or insufficiencies in the long run. a safe and efficacious vaccine to control this disease is needed. killed antigens that could be safer as vaccines have shown limited efficacy in clinical trials. immunogenic enhancement with appropriate adjuvants may thus be required to elicit protective immunity ...	2015	25432859
anti-leishmanial, anti-inflammatory and antimicrobial activities of phenolic derivatives from tibouchina paratropica.	a new phenolic derivative, 2,8-dihydroxy-7h-furo[2,3-f]chromen-7-one (1), together with isoquercitrin (2), was isolated from the aerial parts of tibouchina paratropica. compound structures were elucidated by spectroscopic methods. both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti-parasitic activity against leishmania donovani (ic50 = 0.809 µg/ml). in addition, an 85% reduction in the secretion of the pro-inflammato ...	2015	25417600
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
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
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
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
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
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
isolated cutaneous leishmaniasis by leishmania donovani in a soldier returning from afghanistan.		2015	25062262
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
immunomodulation in human dendritic cells leads to induction of interferon-gamma production by leishmania donovani derived kmp-11 antigen via activation of nf-κb in indian kala-azar patients.	dendritic cells (dcs) and macrophages (mφs) are well-known antigen presenting cells with an ability to produce il-12 which indicates that they have potential of directing acquired immunity toward a th1-biased response. the aim of this study was to examine the effect of leishmania specific kmp-11 antigen through comparison of immune responses after presentation by dcs and mφs to t cells in indian patients with vl. patients with dcs and mφs were directed against a purified leishmania donovani anti ...	2014	24587999
deletion of ubiquitin fold modifier protein ufm1 processing peptidase ufsp in l. donovani abolishes ufm1 processing and alters pathogenesis.	previously, we showed leishmania donovani ufm1 has a gly residue conserved at the c-terminal region with a unique 17 amino acid residue extension that must be processed prior to conjugation to target proteins. in this report, we describe for the first time the isolation and characterization of the leishmania ufm1-specific protease ufsp. biochemical analysis of l. donovani ufsp showed that this protein possesses the ufm1 processing activity using sensitive fret based activity probes. the ufm1 cle ...	2014	24587462
metabolic reprogramming during purine stress in the protozoan pathogen leishmania donovani.	the ability of leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. however, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. to elucidate nutrient stress response pathways in leishmania donovani, we have used purine starvation as the paradigm. the salvage of purines from the host milieu is obligatory for parasite replicati ...	2014	24586154
whole blood assay and visceral leishmaniasis: challenges and promises.	for years, the ability to study immune responses in patients with active visceral leishmaniasis (vl) has been hampered by the absence of detectable antigen-specific th1 responses using cells from peripheral blood mononuclear cells (pbmcs). employing whole blood assay (wba), we recently reported that whole blood cells of active vl patients maintain the capacity to secrete significant levels of antigen driven ifn-γ and il-10. furthermore, wba that uses soluble leishmania antigen (sla) have advanta ...	2014	24571797
generation of adenosine tri-phosphate in leishmania donovani amastigote forms.	leishmania, the causative agent of various forms of leishmaniasis, is the significant cause of morbidity and mortality. regarding energy metabolism, which is an essential factor for the survival, parasites adapt to the environment under low oxygen tension in the host using metabolic systems which are very different from that of the host mammals. we carried out the study of susceptibilities to different inhibitors of mitochondrial electron transport chain and studies on substrate level phosphoryl ...	2014	24570045
the curative effect of fucoidan on visceral leishmaniasis is mediated by activation of map kinases through specific protein kinase c isoforms.	fucoidan can cure both antimony-sensitive and antimony-resistant visceral leishmaniasis through immune activation. however, the signaling events underlying this cellular response remain uncharacterized. the present study reveals that fucoidan induces activation of p38 and erk1/2 and nf-κb dna binding in both normal and leishmania donovani-infected macrophages, as revealed by western blotting and electrophoretic mobility shift assay (emsa), respectively. pharmacological inhibition of p38, erk1/2 ...	2014	24561457
elucidation of cellular mechanisms involved in experimental paromomycin resistance in leishmania donovani.	leishmania donovani is the causative agent of the potentially fatal disease visceral leishmaniasis (vl). chemotherapeutic options available to treat vl are limited and often face parasite resistance, inconsistent efficacy, and toxic side effects. paromomycin (pmm) was recently introduced to treat vl as a monotherapy and in combination therapy. it is vital to understand the mechanisms of pmm resistance to safeguard the drug. in the present study, we utilized experimentally generated pmm-resistant ...	2014	24550335
nonmigrant children with visceral leishmaniasis from the nonendemic area of uttarakhand.	the emergence of visceral leishmaniasis (vl) in nonendemic areas is a matter of great concern. we conducted a study and present a brief description of six nonmigrant children with vl from the nonendemic area of uttarakhand, diagnosed in our tertiary teaching hospital from february 2012 to june 2013. we also present here a geographic distribution of these cases to assess the impact of global warming and climate change on the spread of the disease. patients were diagnosed as vl by clinical finding ...	2014	24531375
synthesis, antileishmanial activity and docking study of n'-substitutedbenzylidene-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4h)-yl)acetohydrazides.	a series of n'-substitutedbenzylidene-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4h)-yl)acetohydrazide derivatives is synthesized and evaluated for antileishmanial activity against leishmania donovani promastigotes. compounds 9a and 9i were shown significant antileishmanial when compared with standard sodium stilbogluconate. antimicrobial study revealed that compound 9b has potent as well as broad spectrum antibacterial activity when compared with ampicillin and compound 9e showed promising antifungal ...	2014	24513045
retraction. anti-citrullinated peptide antibodies and rheumatoid factor in sudanese patients with leishmania donovani infection.		2014	25054607
prostaglandin e2 negatively regulates the production of inflammatory cytokines/chemokines and il-17 in visceral leishmaniasis.	persistence of intracellular infection depends on the exploitation of factors that negatively regulate the host immune response. in this study, we elucidated the role of macrophage pge2, an immunoregulatory lipid, in successful survival of leishmania donovani, causative agent of the fatal visceral leishmaniasis. pge2 production was induced during infection and resulted in increased camp level in peritoneal macrophages through g protein-coupled e-series prostanoid (ep) receptors. among four diffe ...	2014	25049356
the isolation of antiprotozoal compounds from libyan propolis.	propolis is increasingly being explored as a source of biologically active compounds. until now, there has been no study of libyan propolis. two samples were collected in north east libya and tested for their activity against trypanosoma brucei. extracts from both samples had quite high activity. one of the samples was fractionated and yielded a number of active fractions. three of the active fractions contained single compounds, which were found to be 13-epitorulosal, acetyl-13-epi-cupressic ac ...	2014	25044090
synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against leishmania donovani and trypanosoma cruzi.	a high-throughput (hts) and high-content screening (hcs) campaign of a commercial library identified 2,3-dihydroimidazo[1,2-a]benzimidazole analogues as a novel class of anti-parasitic agents. a series of synthetic derivatives were evaluated for their in vitro anti-leishmanial and anti-trypanosomal activities against leishmania donovani and trypanosoma cruzi, which have been known as the causative parasites for visceral leishmaniasis and chagas disease, respectively. in the case of leishmania, t ...	2014	25036797
parasite load estimation by qpcr differentiates between asymptomatic and symptomatic infection in indian visceral leishmaniasis.	using quantitative pcr (qpcr), we differentiated asymptomatic and symptomatic indian leishmania donovani infection. qpcr on blood of 40 visceral leishmaniasis, 130 endemic, and 40 non-endemic healthy controls showed 500 times less (p < .0001) parasitemia in asymptomatic compared to the symptomatic ones and threshold of 5 parasite genome/ml for the clinical disease.	2014	25023070
genetic analysis of leishmania donovani tropism using a naturally attenuated cutaneous strain.	a central question in leishmania research is why most species cause cutaneous infections but others cause fatal visceral disease. interestingly, l. donovani causes both visceral and cutaneous leishmaniasis in sri lanka. l. donovani clinical isolates were therefore obtained from cutaneous leishmaniasis (cl-sl) and visceral leishmaniasis (vl-sl) patients from sri lanka. the cl-sl isolate was severely attenuated compared to the vl-sl isolate for survival in visceral organs in balb/c mice. genomic a ...	2014	24992200
synthesis, antileishmanial and antitrypanosomal activities of n-substituted tetrahydro-β-carbolines.	a series of n-substituted tetrahydro-β-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of leishmania donovani, the causative agent for visceral leishmaniasis. the thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with ic50 values of 12.7, 9.1 and 22.1 μm, respectively. analogs 9b and 11h were also effective against axenic amastigo ...	2014	24980054
growth factor and th2 cytokine signaling pathways converge at stat6 to promote arginase expression in progressive experimental visceral leishmaniasis.	host arginase 1 (arg1) expression is a significant contributor to the pathogenesis of progressive visceral leishmaniasis (vl), a neglected tropical disease caused by the intracellular protozoan leishmania donovani. previously we found that parasite-induced arg1 expression in macrophages was dependent on stat6 activation. arg1 expression was amplified by, but did not require, il-4, and required de novo synthesis of unknown protein(s). to further explore the mechanisms involved in arg1 regulation ...	2014	24967908
leishmania spp. proteome data sets: a comprehensive resource for vaccine development to target visceral leishmaniasis.	visceral leishmaniasis is a neglected infectious disease caused primarily by leishmania donovani and leishmania infantum protozoan parasites. a significant number of infections take a fatal course. drug therapy is available but still costly and parasites resistant to first line drugs are observed. despite many years of trial no commercial vaccine is available to date. however, development of a cost effective, needle-independent vaccine remains a high priority. reverse vaccinology has attracted m ...	2014	24959165
mianserin, an antidepressant kills leishmania donovani by depleting ergosterol levels.	in the present study, we have investigated the antileishmanial potential of mianserin, an antidepressant. mianserin was found to inhibit both the promastigote and amastigote forms of the parasite in a dose dependant manner. the ic50 values for promastigotes and amastigotes were 21 μm and 46 μm respectively. interestingly, mianserin failed to inhibit thp-1 differentiated macrophages up to 100 μm concentration thus, exhibiting parasite selectivity. when mianserin was incubated with recombinant lei ...	2014	24950381
deficiency of p110δ isoform of the phosphoinositide 3 kinase leads to enhanced resistance to leishmania donovani.	visceral leishmaniasis is the most clinically relevant and dangerous form of human leishmaniasis. most traditional drugs for treatment of leishmaniasis are toxic, possess many adverse reactions and drug resistance is emerging. therefore, there is urgent need for identification of new therapeutic targets. recently, we found that mice with an inactivating knock-in mutation in the p110δ isoform of pi3k, (p110δ(d910a)) are hyper resistant to l. major, develop minimal cutaneous lesion and rapidly cle ...	2014	24945303
clinical and parasitological protection in a leishmania infantum-macaque model vaccinated with adenovirus and the recombinant a2 antigen.	visceral leishmaniasis (vl) is a severe vector-born disease of humans and dogs caused by leishmania donovani complex parasites. approximately 0.2 to 0.4 million new human vl cases occur annually worldwide. in the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. thus, a prophylactic vaccine appears to be essential for vl control. the current efforts to develop an efficacious vaccine include the use o ...	2014	24945284
characterization of cross-protection by genetically modified live-attenuated leishmania donovani parasites against leishmania mexicana.	previously, we showed that genetically modified live-attenuated leishmania donovani parasite cell lines (ldcen(-/-) and ldp27(-/-)) induce a strong cellular immunity and provide protection against visceral leishmaniasis in mice. in this study, we explored the mechanism of cross-protection against cutaneous lesion-causing leishmania mexicana. upon challenge with wild-type l. mexicana, mice immunized either for short or long periods showed significant protection. immunohistochemical analysis of ea ...	2014	25156362
combining cationic liposomal delivery with mpl-tdm for cysteine protease cocktail vaccination against leishmania donovani: evidence for antigen synergy and protection.	with the paucity of new drugs and hiv co-infection, vaccination remains an unmet research priority to combat visceral leishmaniasis (vl) requiring strong cellular immunity. protein vaccination often suffers from low immunogenicity and poor generation of memory t cells for long-lasting protection. cysteine proteases (cps) are immunogenic proteins and key mediators of cellular functions in leishmania. here, we evaluated the vaccine efficacies of cps against vl, using cationic liposomes with toll l ...	2014	25144181
in vitro anti-leishmanial efficacy of potato tuber extract (ptex): leishmanial serine protease(s) as putative target.	leishmaniasis, a neglected tropical disease (ntd) causes major health problems in the tropical and subtropical world. most of the antileishmanial modern therapies with different formulations of pentavalent antimonials, miltefosine, amphotericin b etc. are not satisfactory in recent times due to high toxicity to the host and present rising strain resistance issues. so there is an urgent need to develop new, safe and cost-effective drugs against leishmaniasis. in this regard, bioactive phytocompon ...	2014	25128800
ascorbate peroxidase, a key molecule regulating amphotericin b resistance in clinical isolates of leishmania donovani.	amphotericin b (amb), a polyene macrolide, is now a first-line treatment of visceral leishmaniasis cases refractory to antimonials in india. amb relapse cases and the emergence of secondary resistance have now been reported. to understand the mechanism of amb, differentially expressed genes in amb resistance strains were identified by a dna microarray and real-time reverse transcriptase pcr (rt-pcr) approach. of the many genes functionally overexpressed in the presence of amb, the ascorbate pero ...	2014	25114128
characterization of mitochondrial bioenergetic functions between two forms of leishmania donovani - a comparative analysis.	leishmaniasis is a growing health problem in many parts of the world partly due to drug resistance of the parasite. this study reports on the fisibility of studying mitochondrial properties of two forms of wild-type l. donovani through the use of selective inhibitors. amastigote forms of l. donovani exhibited a wide range of sensitivities to these inhibitors. mitochondrial complex ii inhibitor thenoyltrifluoroacetone and fof1-atp synthase inhibitors oligomycin and dicyclohexylcarbodiimide were r ...	2014	25107348
a screen-and-treat strategy targeting visceral leishmaniasis in hiv-infected individuals in endemic east african countries: the way forward?	in the wake of the hiv epidemic, visceral leishmaniasis (vl), a disseminated protozoan infection caused by the leishmania donovani complex, has been re-emerging, particularly in north ethiopia where up to 40% of patients with vl are co-infected with hiv. management of vl in hiv co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. tackling l. donovani infection befor ...	2014	25101627
a new approach for the delivery of artemisinin: formulation, characterization, and ex-vivo antileishmanial studies.	artemisinin, a potential antileishmanial compound with poor bioavailability and stability has limited efficacy in visceral leishmaniasis. encapsulating artemisinin into poly lactic-co glycolic nanoparticles may improve its effectiveness and reduce toxicity.	2014	25086720
carbon nanotube based betulin formulation shows better efficacy against leishmania parasite.	we report a novel antileishmanial formulation of betulin (bet) attached to functionalized carbon nanotubes (f-cnts). we conjugated betulin, a pentacyclic triterpenoid secondary metabolite, to carboxylic acid chains on f-cnts to obtain bet attached functionalized carbon nanotubes (f-cnt-bet). the drug release profile demonstrated a fairly slow release of bet. the in-vitro cytotoxicities of bet, f-cnt and f-cnt-bet on j774a.1 macrophage cell line were 211.05±7.14μg/ml; 24.67±3.11μg/ml and 72.63±6. ...	2014	25086374
protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from withania somnifera and asparagus racemosus.	visceral leishmaniasis (vl) is a vector-borne parasitic disease targeting tissue macrophages. it is among the most neglected infectious diseases. as available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. one of the immunopathological consequences of active visceral leishmaniasis is suppression of protective t-helper (th)-1 cells and induction of disease-promoting th-2 cells, and thus the treatment of vl relies on immunomodulation. in ...	2014	25082945
diverse modes of binding in structures of leishmania major n-myristoyltransferase with selective inhibitors.	the leishmaniases are a spectrum of global diseases of poverty associated with immune dysfunction and are the cause of high morbidity. despite the long history of these diseases, no effective vaccine is available and the currently used drugs are variously compromised by moderate efficacy, complex side effects and the emergence of resistance. it is therefore widely accepted that new therapies are needed. n-myristoyltransferase (nmt) has been validated pre-clinically as a target for the treatment ...	2014	25075346
induction of mitochondrial dysfunction and oxidative stress in leishmania donovani by orally active clerodane diterpene.	this study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (k-09) in leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (vl). k-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in l. donovani promastigotes. mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the ...	2014	25070112
reactive oxygen species regulates expression of iron-sulfur cluster assembly protein iscs of leishmania donovani.	the cysteine desulfurase, iscs, is a highly conserved and essential component of the mitochondrial iron-sulfur cluster (isc) system that serves as a sulfur donor for fe-s clusters biogenesis. fe-s clusters are versatile and labile cofactors of proteins that orchestrate a wide array of essential metabolic processes, such as energy generation and ribosome biogenesis. however, no information regarding the role of iscs or its regulation is available in leishmania, an evolving pathogen model with rap ...	2014	25062827
tlr mediated gsk3β activation suppresses creb mediated il-10 production to induce a protective immune response against murine visceral leishmaniasis.	during leishmania donovani (ld) infection interleukin (il)-10 favors parasite replication and plays a central role as a target for immune-based therapy. glycogen synthase kinase 3 (gsk3)β differentially regulates tlr-mediated cytokine production. creb, an important transcription factor that induces il-10 production is negatively regulated by gsk3β. however, down regulation of il-10 via creb suppression has not been well explored in controlling ld infection. here we demonstrate that, the tlr4 ago ...	2014	25223889
leishmania donovani activates srebp2 to modulate macrophage membrane cholesterol and mitochondrial oxidants for establishment of infection.	establishment of infection by an intracellular pathogen depends on successful internalization with a concomitant neutralization of host defense machinery. leishmania donovani, an intramacrophage pathogen, targets host srebp2, a critical transcription factor, to regulate macrophage plasma membrane cholesterol and mitochondrial reactive oxygen species generation, favoring parasite invasion and persistence. leishmania infection triggered membrane-raft reorientation-dependent lyn-pi3k/akt pathway ac ...	2014	25218172
imipramine exploits histone deacetylase 11 to increase the il-12/il-10 ratio in macrophages infected with antimony-resistant leishmania donovani and clears organ parasites in experimental infection.	the efflux of antimony through multidrug resistance protein (mdr)-1 is the key factor in the failure of metalloid treatment in kala-azar patients infected with antimony-resistant leishmania donovani (sb(r)ld). previously we showed that mdr-1 upregulation in sb(r)ld infection is il-10-dependent. imipramine, a drug in use for the treatment of depression and nocturnal enuresis in children, inhibits il-10 production from sb(r)ld-infected macrophages (sb(r)ld-mϕs) and favors accumulation of surrogate ...	2014	25217162
insilico analysis of hypothetical proteins unveils putative metabolic pathways and essential genes in leishmania donovani.	leishmaniasis is a parasitic disease caused by the protozoan leishmania, which is active in two broad forms namely, visceral leishmaniasis (vl or kala azar) and cutaneous leishmaniasis (cl). the disease is most prevalent in the tropical regions and poses a threat to over 70 countries across the globe. about 200 million people are estimated to be at risk of developing vl in the indian subcontinent, and this refers to around 67% of the global vl disease burden. the indian state of bihar alone acco ...	2014	25206363
sitamaquine-resistance in leishmania donovani affects drug accumulation and lipid metabolism.	this study focuses on the mechanism of sitamaquine-resistance in leishmania donovani. sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (wt) and of sitamaquine-resistant (sita-r160) l. donovani promastigotes, respectively. the sitamaquine accumulation was a concentration-dependent process in wt whereas a saturation occurred in sita-r160 suggesting a reduced uptake or an increase of the sitamaquine efflux. membrane negative phospholipids being the main target ...	2014	25201056
immunotherapy and targeted therapies in treatment of visceral leishmaniasis: current status and future prospects.	visceral leishmaniasis (vl) is a vector-borne chronic infectious disease caused by the protozoan parasite leishmania donovani or leishmania infantum. vl is a serious public health problem, causing high morbidity and mortality in the developing world with an estimated 0.2-0.4 million new cases each year. in the absence of a vaccine, chemotherapy remains the favored option for disease control, but is limited by a narrow therapeutic index, significant toxicities, and frequently acquired resistance. ...	2014	25183962
a small heat shock protein is essential for thermotolerance and intracellular survival of leishmania donovani.	leishmania parasites must survive and proliferate in two vastly different environments - the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. the change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. although the functions of the main heat shock protein fami ...	2014	25179594
comparison of pcr with stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis.	visceral leishmaniasis (vl), also known as kala-azar, is a disseminated protozoan infection caused by leishmania donovani complex. traditionally the definite diagnosis is made by amastigote detection in the tissue. the aim this study was to evaluate the pcr technique in stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis. slides were selected totaling 62 suspect cases (33 bone marrow samples and 29 lymph node samples) and 17 positive cases (8 bone mar ...	2014	25159534
covalent functionalized self-assembled lipo-polymerosome bearing amphotericin b for better management of leishmaniasis and its toxicity evaluation.	amphotericin b remains the preferred choice for leishmanial infection, but it has limited clinical applications due to substantial dose limiting toxicities. in the present work, amb has been formulated in lipo-polymerosome (l-psome) by spontaneous self-assembly of synthesized glycol chitosan-stearic acid copolymer. the optimized l-psome formulation with vesicle size of 243.5 ± 17.9 nm, pdi of 0.168 ± 0.08 and zeta potential of (+) 27.15 ± 0.46 mv with 25.59 ± 0.87% amb loading was obtained. the ...	2014	24495144
liposomal cholesterol delivery activates the macrophage innate immune arm to facilitate intracellular leishmania donovani killing.	leishmania donovani causes visceral leishmaniasis (vl) by infecting the monocyte/macrophage lineage and residing inside specialized structures known as parasitophorous vacuoles. the protozoan parasite has adopted several means of escaping the host immune response, with one of the major methods being deactivation of host macrophages. previous reports highlight dampened macrophage signaling, defective antigen presentation due to increased membrane fluidity, and the downregulation of several genes ...	2014	24478076