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exploring the biological activities of echeveria leucotricha.echeveria leucotricha j. a. purpus (crassulaceae) was evaluated for its potential antibacterial, antifungal, antiparasitic, cytotoxic and anti-inflammatory bioactivities. aerial parts were extracted with hexane, methanol and chloroform, and fractionated accordingly. biological activity was assessed in vitro against five gram-positive and four gram-negative bacteria, four human pathogenic fungi and the protozoan leishmania donovani. extracts and fractions showing bioactivities were further invest ...201322845689
real-time pcr to quantify leishmania donovani in hamsters.visceral leishmaniasis, a vector-borne disease caused by leishmania donovani and leishmania infantum , currently affects 12 million individuals in 88 countries. in the present study, a real-time pcr (rt-pcr) assay has been optimized and validated against 2 other routine methods, i.e., microscopy and limiting dilution culture assay, to estimate parasite load in the liver of infected syrian hamsters (mesocricetus auratus). a set of specific primers amplified a 116-bp target template of the kinetop ...201322924923
pcr-based detection of leishmania donovani dna in a stray dog from a visceral leishmaniasis endemic focus in bangladesh.although phlebotomus argentipes as the only known vector of visceral leishmaniasis (vl) is zoophilic in nature, vl is considered to be anthroponotic in the indian subcontinent. peripheral blood samples from 85 stray dogs were examined for any molecular evidence of leishmania infection in vl endemic areas of bangladesh. parasite dna was detected in a blood sample from 1 of 85 (1.2%) stray dogs using its1-pcr, and pcr sequencing of the rrna-its and cytochrome b gene confirmed that the parasitic dn ...201322878541
drug-resistant microorganisms with a higher fitness--can medicines boost pathogens?drug-resistant microorganisms (drms) are generally thought to suffer from a fitness cost associated with their drug-resistant trait, inflicting them a disadvantage when the drug pressure reduces. however, leishmania resistant to pentavalent antimonies shows traits of a higher fitness compared to its sensitive counterparts. this is likely due the combination of an intracellular pathogen and a drug that targets the parasite's general defense mechanisms while at the same time stimulating the host's ...201322950457
laryngeal leishmaniasis: case report of a rare infection.we report a case of laryngeal leishmaniasis in a united kingdom (uk) resident who lived in spain for 5 years.201322972594
antineoplastic drug, carboplatin, protects mice against visceral leishmaniasis.in the present study, the leishmanicidal effect of two doses (5 and 10 mg/kg body weight) of the carboplatin was studied in leishmania donovani-infected balb/c mice. mice were infected intracardially with promastigotes of l. donovani, and a month after infection, they were treated intraperitoneally with the two doses of the drug (5 and 10 mg/kg body weight) for five continuous days. animals were sacrificed on 1 and 15 posttreatment days. hepatic parasite load was assessed on geimsa-stained impri ...201322961311
the hsp90-sti1 interaction is critical for leishmania donovani proliferation in both life cycle stages.the heat shock protein 90 plays a pivotal role in the life cycle control of leishmania donovani promoting the fast-growing insect stage of this parasite. equally important for insect stage growth is the co-chaperone sti1. we show that replacement of sti1 is only feasible in the presence of additional sti1 transgenes indicating an essential role. to better understand the impact of sti1 and its interaction with hsp90, we performed a mutational analysis of hsp90. we established that a single amino ...201323107115
a versatile proline/alanine transporter in the unicellular pathogen leishmania donovani regulates amino acid homoeostasis and osmotic stress responses.unlike all other organisms, parasitic protozoa of the family trypanosomatidae maintain a large cellular pool of proline that, together with the alanine pool, serve as alternative carbon sources as well as reservoirs of organic osmolytes. these reflect adaptation to their insect vectors whose haemolymphs are exceptionally rich in the two amino acids. in the present study we identify and characterize a new neutral amino acid transporter, ldaap24, that translocates proline and alanine across the le ...201322994895
role of cytosolic glyceraldehyde-3-phosphate dehydrogenase in visceral organ infection by leishmania donovani.the initial 7 steps of the glycolytic pathway from glucose to 3-phosphoglycerate are localized in the glycosomes in leishmania, including step 6, catalyzed by the enzyme glyceraldehyde-3-phosphate dehydrogenase (gapdh). in l. donovani and l. mexicana, there exists a second gapdh enzyme present in the cytosol that is absent in l. braziliensis and that has become a pseudogene in l. major. to investigate the role of the cytosolic gapdh (cgapdh), an l. donovani cgapdh-null mutant was generated, and ...201323125352
geographical distribution and epidemiological features of old world leishmania infantum and leishmania donovani foci, based on the isoenzyme analysis of 2277 strains.a series of 2277 leishmania strains from old world visceral leishmaniasis foci, isolated between 1973 and 2008, were studied by isoenzyme analysis. the strains were obtained from humans, domestic and wild carnivores, rodents and phlebotomine sandflies, and came from 36 countries. in all, 60 different zymodemes were identified and clustered by a phenetic analysis into 3 different groups corresponding to the typically visceralizing species l. donovani (20 zymodemes, 169 strains), l. archibaldi (3 ...201323146283
chemotherapy of leishmaniasis part x: synthesis and bioevaluation of novel terpenyl heterocycles.some novel α and β ionone based chalcones and their dihydropyrazolidines/pyrazolidines have been synthesized and evaluated for their in vitro and in vivo antileishmanial activities against leishmania donovani. amongest all, one compound (4d) exhibited significant in vitro activity against intracellular amastigotes of leishmania donovani with ic(50) values of 7.49 μm and was found promising as compared to reference drug, miltefosine. on the basis of good selectivity index (s.i.), the compound was ...201323177254
8,8-dialkyldihydroberberines with potent antiprotozoal activity.semisynthetic 8,8-dialkyldihydroberberines (8,8-ddbs) were found to possess mid- to low-nanomolar potency against plasmodium falciparum blood-stage parasites, leishmania donovani intracellular amastigotes, and trypanosoma brucei brucei bloodstream forms. for example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro ic50 values of 77, 100, and 5.3 nm against these three parasites, respectively. in turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-ddbs, wer ...201323167812
relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting leishmania donovani strain.leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the indian subcontinent. this relapse ...201324105765
increased parasite surface antigen-2 expression in clinical isolates of leishmania donovani augments antimony resistance.resistance to sodium antimony gluconate (sag) is a major cause of therapeutic failure in a large proportion of visceral leishmaniasis (vl) cases. determinants of sag resistance have been widely studied; however, the mechanism operating in clinical isolates is poorly understood. in the present study, expression of parasite surface antigen-2 (psa-2) gene was studied in clinical isolates of leishmania donovani comprising of antimony resistant (n=10) and sensitive (n=4) parasites. the expression of ...201324103752
novel approaches for the identification of inhibitors of leishmanial dipeptidylcarboxypeptidase.leishmaniasis imposes a substantial burden of mortality and morbidity affecting 12 million globally and continues to be a neglected tropical disease. control of the disease is mainly based on chemotherapy, which relies on a handful of drugs with serious limitations. over the last decade, target-based drug discovery is also being employed in addition to the random screening of compounds. leishmanial dipeptidylcarboxypeptidase (ldcp), an angiotensin converting enzyme (ace) related metallopeptidase ...201323745836
inhibition of leishmania infantum trypanothione reductase by azole-based compounds: a comparative analysis with its physiological substrate by x-ray crystallography.herein we report a study aimed at discovering a new class of compounds that are able to inhibit leishmania donovani cell growth. evaluation of an in-house library of compounds in a whole-cell screening assay highlighted 4-((1-(4-ethylphenyl)-2-methyl-5-(4-(methylthio)phenyl)-1h-pyrrol-3-yl)methyl)thiomorpholine (compound 1) as the most active. enzymatic assays on leishmania infantum trypanothione reductase (litr, belonging to the leishmania donovani complex) shed light on both the interaction wi ...201323733388
effectiveness of miltefosine treatment in targeting anti-leishmanial ho-1/nrf-2-mediated oxidative responses in visceral leishmaniasis patients.miltefosine, an alkylphosphocholine anti-cancer drug, exhibits direct activity against leishmania donovani and also promotes anti-leishmanial host immunomodulatory functions. nuclear factor-erythroid 2-related factor 2 (nrf-2), a redox-sensitive transcription factor, regulates the host stress responses leading to effective microbial clearance by a positive effect on haem oxygenase-1 (ho-1) enzyme expression/activity. we aimed to investigate the role of miltefosine in regulating ho-1/nrf-2-mediat ...201323729024
synthesis of novel guttiferone a derivatives: in-vitro evaluation toward plasmodium falciparum, trypanosoma brucei and leishmania donovani.the catechol pharmacomodulation of the natural product guttiferone a, isolated from the symphonia globulifera tree, led to the semisynthesis of a collection of twenty derivatives. the ester and ether derivatives of guttiferone a were evaluated for their anti-plasmodial, trypanocidal and anti-leishmanial activities. some compounds described below have shown potent antiparasitic activity against plasmodium falciparum, trypanosoma brucei and leishmania donovani in a range from 1 to 5 μm. the evalua ...201323727538
evaluation of toxicity & therapeutic efficacy of a new liposomal formulation of amphotericin b in a mouse model.current therapy for leishmaniasis is limited and unsatisfactory. amphotericin b, a second-line treatment is gradually replacing antimonials, the first-line treatment and is used as the preferred treatments in some regions. though, presently it is the only drug with highest cure rate, its use is severely restricted by its acute toxicity. in the present study novel lipid-amphotericin b formulations with lower toxicity than the parent drug were evaluated for the treatment of visceral leishmaniasis ...201323703346
cloning, overexpression, purification and crystallization of the crn12 coiled-coil domain from leishmania donovani.leishmania donovani coronin crn12 is an actin-binding protein which consists of two domains: an n-terminal wd repeat domain and a c-terminal coiled-coil domain. the coiled-coil domain is 53 residues in length. helix-helix interactions in general and coiled coils in particular are ubiquitous in the structure of proteins and play a significant role in the association among proteins, including supramolecular assemblies and transmembrane receptors that mediate cellular signalling, transport and acti ...201323695571
enrichment of leishmania donovani atp-binding proteins using a staurosporine capture compound.trypanosomatid parasites of the genus leishmania cause severe human diseases collectively termed leishmaniasis. parasite atp-binding proteins have emerged as potent targets for chemotherapeutic intervention. however, many parasite-specific atp-binding proteins may escape current efforts in drug target identification, validation and deconvolution due to the lack of sequence conservation and functional annotation of these proteins in early branching eukaryotic trypanosomatids. here, we selectively ...201323684787
bone marrow negative visceral leishmaniasis in an adolescent male.visceral leishmaniasis or kala azar is endemic in certain regions of india. in endemic areas, the constellation of fever, progressive weight loss, weakness, pronounced splenomegaly, anemia, leukopenia, and hypergammaglobulinemia is highly suggestive of visceral leishmaniasis. demonstration of the parasite in liver, splenic or bone marrow aspirates is confirmatory. we present a case in which leishmania donovani (ld) bodies were demonstrated on splenic aspirate. we were unable to demonstrate ld bo ...201323682278
synthesis and biological evaluation of a novel series of aryl s,n-ketene acetals as antileishmanial agents.a series of aryl s,n-ketene acetals 7(a-f) was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against leishmania donovani. all the 6 compounds exhibited significant in vitro activity against intracellular amastigotes of l. donovani with ic50 values ranging from 1.2 to 3.5 μm and were found promising as compared with reference drugs, sodium stibogluconate (ssg) and paromomycin. on the basis of good selectivity indices (si), they were further tested for their in ...201323673014
successful substitution of fetal calf serum by human plasma for bulk cultivation of leishmania donovani promastigotes.the potential of human plasma (hp) or serum (hs) as a replacement for fetal calf serum (fcs) was evaluated in a liver infusion tryptose (lit) medium for bulk cultivation of leishmania donovani promastigotes. the promastigote yield with the lit-fcs standard medium was 0.4-1.8×10(7) ml(-1), and yields of 0.5-3.4×10(7) (p = 0.527) and 0.4-2.4×10(7) (p = 0.062) were recorded for two lit medium variants containing hp or hs as supplement instead of fcs. significantly, higher promastigote yields of 1.3 ...201323657530
the loss of virulence of histone h1 overexpressing leishmania donovani parasites is directly associated with a reduction of hsp83 rate of translation.overexpression of leishmania histone h1 (leishh1) was previously found to cause a promastigote-to-amastigote differentiation handicap, deregulation of cell-cycle progression, and loss of parasite infectivity. the aim of this study was to identify changes in the proteome of leishh1 overexpressing parasites associated with the avirulent phenotype observed. 2d-gel electrophoresis analysis revealed only a small protein subset of differentially expressed proteins in the leishh1 overexpressing promast ...201323647017
discovery of a new class of natural product-inspired quinazolinone hybrid as potent antileishmanial agents.the high potential of quinazolinone containing natural products and their derivatives in medicinal chemistry led us to discover four novel series of 53 compounds of quinazolinone based on the concept of molecular hybridization. most of the synthesized analogues exhibited potent leishmanicidal activity against intracellular amastigotes (ic50 from 0.65 ± 0.2 to 7.76 ± 2.1 μm) as compared to miltefosine (ic50 = 8.4 ± 2.1 μm) and nontoxic toward the j-774a.1 cell line and vero cells. moreover, activ ...201323611626
bone marrow aspirate showing leishmania donovani in polymorphs. 201323589788
chemotherapy of leishmaniasis. part xii: design, synthesis and bioevaluation of novel triazole integrated phenyl heteroterpenoids as antileishmanial agents.a novel series of triazole integrated phenyl heteroterpenoids have been synthesized and screened for their in vitro activity against intracellular amastigote form of leishmania donovani. among all tested compounds, compound 3a was found to be the most active with ic50 6.4μm and better selectivity index (si) 18 as compared to reference drugs, miltefosine and miconazole. when evaluated in vivo in l. donovani/hamster model, 3a has exhibited 79±11% inhibition of parasite multiplication at 50mgkg(-1) ...201323582274
comparison of a high-throughput high-content intracellular leishmania donovani assay with an axenic amastigote assay.visceral leishmaniasis is a neglected tropical disease with significant health impact. the current treatments are poor, and there is an urgent need to develop new drugs. primary screening assays used for drug discovery campaigns have typically used free-living forms of the leishmania parasite to allow for high-throughput screening. such screens do not necessarily reflect the physiological situation, as the disease-causing stage of the parasite resides inside human host cells. assessing the drug ...201323571538
[what is your diagnosis? leishmania donovani visceral leishmaniasis]. 201323570920
in vitro leishmanicidal activity of some cameroonian medicinal plants.eleven plants used in the cameroonian traditional medicine for the treatment of some parasitic infections were tested for their activity on the promastigote form of leishmania donovani. after incubation with different plant extracts at doses of 1600, 800, 400 and 200 microgram/ml, the evaluation of the cell viability was done by the trypan blue exclusion technique and by flow cytometry. this study shows that 48 h after incubation of promastigotes with plant extract, solanocia mannii and solanum ...201323562881
phylogenetic analysis of lack gene sequences for 22 chinese leishmania isolates.the phylogenetic relationships between chinese leishmania strains were investigated using lack (leishmania homolog of receptors for activated protein kinase c) gene sequences, and the power of this gene was assessed for understanding the epidemiology and population genetics of leishmania.201323541410
design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents.an analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. these molecules were tested for their in vitro and in vivo biological activity against leishmania donovani. metabolic stability of these compounds was also improved through the introduction of halogen substituents. compound (26g), found to be the most active; exhibited an ic₅₀ value of 0.2 μm and >180 fold selectivity. the hydrochloride sa ...201324095747
synthesis of marine α-methoxylated fatty acid analogs that effectively inhibit the topoisomerase ib from leishmania donovani with a mechanism different from that of camptothecin.sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties and in some cases they display enhanced anticancer activities. however, the antiprotozoal properties of the α-methoxylated fatty acids have been less studied. in this work, we describe the total synthesis of (5z,9z)-(±)-2-methoxy-5, 9-eicosadienoic acid (1) and its acetylenic analog (±)-2-methoxy-5,9-eicosadiynoic acid (2), and report that they inhibit (ec₅₀ values between 31 and 22 µm) the leishm ...201324084785
targeting the human parasite leishmania donovani: discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series.we report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. in vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of leishmania donovani, j774a.1 murine and hepg2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). new derivatives were then synthesized to allow structure-activity and -toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying ...201324080103
degree of anemia correlates with increased utilization of heme by leishmania donovani parasites in visceral leishmaniasis.anemia in kala-azar patients is a serious problem. the present study has addressed this problem with the hypothesis that as the leishmania parasite is completely devoid of heme biosynthetic pathway, therefore the excessive use of heme by the parasites in the human patients can be one of the possible reason of anemia. we investigated that whether, the inability of leishmania donovani to synthesize heme, can enforce leishmania parasite to utilize heme derived from host sources in indian ka patient ...201324076432
role of efflux pumps and intracellular thiols in natural antimony resistant isolates of leishmania donovani.in view of the recent upsurge in the phenomenon of therapeutic failure, drug resistance in leishmania, developed under natural field conditions, has become a great concern yet little understood. accordingly, the study of determinants of antimony resistance is urgently warranted. efflux transporters have been reported in leishmania but their role in clinical resistance is still unknown. the present study was designed to elucidate the mechanism of natural antimony resistance in l. donovani field i ...201324069359
the il-33/st2 axis is associated with human visceral leishmaniasis and suppresses th1 responses in the livers of balb/c mice infected with leishmania donovani.during visceral leishmaniasis, the control of hepatic parasite burden is mainly due to granuloma assembly in a microenvironment consisting of both th1 and th2 components. using enzyme-linked immunosorbent assay (elisa) dosages, quantitative pcr (qpcr), immunohistochemistry, and flow cytometry, we studied the role of interleukin-33 (il-33), a recently described cytokine signaling through the st2 receptor, during visceral leishmaniasis. we showed that a higher level of il-33 was detected in the se ...201324045639
novel role of calmodulin in regulating protein transport to mitochondria in a unicellular eukaryote.lower eukaryotes like the kinetoplastid parasites are good models to study evolution of cellular pathways during steps to eukaryogenesis. in this study, a kinetoplastid parasite, leishmania donovani, was used to understand the process of mitochondrial translocation of a nucleus-encoded mitochondrial protein, the mitochondrial tryparedoxin peroxidase (mtxnpx). we report the presence of an n-terminal cleavable mitochondrial targeting signal (mts) validated through deletion and grafting experiments ...201324043313
a transcriptomic network identified in uninfected macrophages responding to inflammation controls intracellular pathogen survival.intracellular pathogens modulate host cell function to promote their survival. however, in vitro infection studies do not account for the impact of host-derived inflammatory signals. examining the response of liver-resident macrophages (kupffer cells) in mice infected with the parasite leishmania donovani, we identified a transcriptomic network operating in uninfected kupffer cells exposed to inflammation but absent from kupffer cells from the same animal that contained intracellular leishmania. ...201324034621
vaccination with leishmania hemoglobin receptor-encoding dna protects against visceral leishmaniasis.leishmaniasis is a severe infectious disease. drugs used for leishmaniasis are very toxic, and no vaccine is available. we found that the hemoglobin receptor (hbr) of leishmania was conserved across various strains of leishmania, and anti-hbr antibody could be detected in kala-azar patients' sera. our results showed that immunization with hbr-dna induces complete protection against virulent leishmania donovani infection in both balb/c mice and hamsters. moreover, hbr-dna immunization stimulated ...201324027025
identification and characterization of the regions involved in the nuclear translocation of the heterodimeric leishmanial dna topoisomerase ib.leishmania donovani, the causative organism for visceral leishmaniasis, contains a unique heterodimeric dna-topoisomerase ib (ldtopib). ldtopib is a heterodimer made up of a large subunit and a small subunit that must interact with each other to build an active enzyme able to solve the topological tensions on the dna. as ldtopib is located within the nucleus, one or more nuclear localization signals (nls) should exist to ensure its nuclear translocation. in this report three novel nls have been ...201324023887
metabolic adaptations of leishmania donovani in relation to differentiation, drug resistance, and drug pressure.antimonial (sodium stibogluconate, ssg) resistance and differentiation have been shown to be closely linked in leishmania donovani, with ssg-resistant strains showing an increased capacity to generate infectious (metacyclic) forms. this is the first untargeted lc-ms metabolomics study which integrated both phenomena in one experimental design and provided insights into metabolic differences between three clinical l. donovani strains with a similar genetic background but different ssg-susceptibil ...201324020363
novel 3-nitro-1h-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents.we have previously shown that 3-nitro-1h-1,2,4-triazole-based amines demonstrate significant trypanocidal activity, in particular against trypanosoma cruzi, the causative parasite of chagas disease. in the present work we further expanded our research by evaluating in vitro the trypanocidal activity of nitrotriazole-based piperazines and nitrotriazole-based 2-amino-1,3-benzothiazoles to establish additional sars. all nitrotriazole-based derivatives were active or moderately active against t. cru ...201324012457
on the catalytic mechanism of dimeric dutpases.the tritryps trypanosoma brucei, trypanosoma cruzi and leishmania donovani are responsible for great morbidity and mortality in developing countries. their dimeric dutpases are members of the all-α ntp pyrophosphohydrolase family and represent promising drug targets due to their essential nature and markedly different structural and biochemical properties compared with the trimeric human enzyme. in the present paper we describe the structure of the t. brucei enzyme in open and closed conformatio ...201324001052
computational elucidation of structural basis for ligand binding with leishmania donovani adenosine kinase.enzyme adenosine kinase is responsible for phosphorylation of adenosine to amp and is crucial for parasites which are purine auxotrophs. the present study describes development of robust homology model of leishmania donovani adenosine kinase to forecast interaction phenomenon with inhibitory molecules using structure-based drug designing strategy. docking calculation using reported organic small molecules and natural products revealed key active site residues such as arg131 and asp16 for ligand ...201323984386
in vitro susceptibility of leishmania donovani to miltefosine in indian visceral leishmaniasis.promastigote miltefosine (mil) susceptibility was performed on leishmania donovani isolates from indian patients with visceral leishmaniasis treated with mil. isolates that were obtained before the onset of mil treatment, after completion of treatment (29th day), or at the time of treatment failure, were screened using in vitro promastigote assay. the mil susceptibility of the pre-treatment isolates (n = 24, mean ic50 ± sem = 3.74 ± 0.38 μm) was significantly higher than that of the post-treatme ...201323980130
leishmania donovani: influence of anti-leishmanial therapy on expression of lymphocyte function-associated antigen-3 and its relevance to pathogenisis in visceral leishmaniasis.lymphocyte function associated antigen 3 (lfa-3) is known as adhesion molecule with its role in t-cell activation signaling as well as in foxp3 expression. its influences on il-10 production is also available, whose role in pathogenesis is well documented. however, this molecule is not yet directly addressed for its association with visceral leishmaniasis (vl). we investigated the relationship between leishmania donovani infection and expression of lfa-3 in vl patients in their pre and post trea ...201323974052
evaluation of a diospyrin derivative as antileishmanial agent and potential modulator of ornithine decarboxylase of leishmania donovani.world health organization has called for academic research and development of new chemotherapeutic strategies to overcome the emerging resistance and side effects exhibited by the drugs currently used against leishmaniasis. diospyrin, a bis-naphthoquinone isolated from diospyros montana roxb., and its semi-synthetic derivatives, were reported for inhibitory activity against protozoan parasites including leishmania. presently, we have investigated the antileishmanial effect of a di-epoxide deriva ...201323973194
miltefosine resistance in leishmania donovani involves suppression of oxidative stress-induced programmed cell death.miltefosine (mil), an alkylphospholipid, is the first orally administrable anti-leishmanial drug. but due to its long half-life, miltefosine is highly vulnerable for resistance. hence it is important to understand the mechanism of resistance and to elucidate its action on leishmania. here we investigate the miltefosine induced process of programmed cell death in wild type (miltefosine sensitive) and in laboratory generated resistant strains of leishmania donovani. results indicate that miltefosi ...201323968687
the malnutrition-related increase in early visceralization of leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow.in a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4-5-fold increase in early visceralization of l. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). to begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. there was no difference in th ...201323967356
two case reports on visceral leishmaniasis diagnosed in romania.two cases of visceral leishmaniasis with a species from leishmania donovani complex were detected in the fundeni clinical institute. in one case, two infection sources were possible: one from italy, where the patient worked three years, the other from the southwest of romania (dolj county), where he was resident and where few human and canine leishmaniasis cases were registered in the past. in the second case, the patient lived in the northeast of romania (iaşi county), but worked in the same so ...201323947013
molecular detection of leishmania infection in sand flies in border line of iran-turkmenistan: restricted and permissive vectors.a molecular study was carried out to incriminate sand fly vectors of cutaneous leishmaniasis (cl) in rural areas of sarakhs district, khorassane-razavi province, northeastern iran, in 2011. sand flies of sergentomyia with three species and phlebotomus with six species respectively comprised 73.3% and 26.7% of the specimens. phlebotomus papatasi was the most common phlebotomine species in outdoor and indoor resting places. leishmania infection was found at least in 17 (22%) specimens including ph ...201323933280
post-kala-azar dermal leishmaniasis with mucosal involvement: an unusual case presentation including successful treatment with miltefosine.post-kala-azar dermal leishmaniasis (pkdl) is a dermatologic manifestation that usually occurs after visceral leishmaniasis (vl) caused by leishmania donovani. it is characterized by hypopigmented patches, a macular or maculopapular rash and nodular skin lesions on the body surface. involvement of the mucosae is very rare and unusual in pkdl. we report a case of pkdl that presented with polymorphic skin lesions, along with involvement of peri-oral mucosa and tongue from an endemic area for kala- ...201323930349
antiprotozoal screening of 60 south african plants, and the identification of the antitrypanosomal germacranolides schkuhrin i and ii.two hundred and seven extracts were prepared from sixty plants from south africa and screened for in vitro activity against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum. for the 21 extracts which inhibited the growth of one or more parasites with more than 95 % at 10 µg/ml, the ic50 values against all four protozoal parasites and cytotoxic ic50 values against l6 myoblasts were determined. amongst the most notable results are the activities of ...201323929246
design, synthesis and biological evaluation of aryl pyrimidine derivatives as potential leishmanicidal agents.a series of substituted aryl pyrimidine derivatives was synthesized and evaluated in vitro for their antileishmanial potential against intracellular amastigotes of leishmania donovani using reporter gene luciferase assay. among all, 8 compounds showed promising ic50 values ranging from 0.5 to 12.9 μm. selectivity indices (s.i.) of all these compounds are far better than reference drugs, sodium stibogluconate (ssg) and miltefosine. on the basis of good s.i., compounds were further screened for th ...201323910597
miltefosine-unresponsive leishmania donovani has a greater ability than miltefosine-responsive l. donovani to resist reactive oxygen species.resistance of leishmania parasites to miltefosine, which is only available oral drug, is a great concern. we have analyzed global gene expression profiles of miltefosine-unresponsive and miltefosine-responsive leishmania donovani in order to understand the various metabolic processes involved in miltefosine drug resistance. the microarray data clearly indicated a role of oxidative metabolism in miltefosine resistance. furthermore, fluorescence microscopy experiments suggested that miltefosine-un ...201323890327
[severe oral mucositis in a patient with hiv infection].a 50-year-old man with hiv infection (first diagnosed > 20 years ago) presented at our hospital with fulminant oral mucositis. antiretroviral therapy (tenofovir, emtricitabine, raltegravir) had been started 2 months ago. previously he had no opportunistic infections and no other pre-existing illnesses. he had not travelled outside europe but stayed in spain for several weeks during summer.201323884748
rklo8, a novel leishmania donovani - derived recombinant immunodominant protein for sensitive detection of visceral leishmaniasis in sudan.for effective control of visceral leishmaniasis (vl) in east africa, new rapid diagnostic tests are required to replace current tests with low sensitivity. the aim of this study is to improve diagnosis of vl in east africa by testing a new antigen from an autochthonous l. donovani strain in sudan.201323875052
synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives.sixty-two cationic benzyl phenyl ether derivatives (36 amidines and 26 prodrugs) were prepared and assayed for activities in vitro and in vivo against trypanosoma brucei rhodesiense (stib900), and in vitro against plasmodium falciparum (k1) and leishmania donovani axenic amastigotes. 3-amidinobenzyl 4-amidino-2-iodo-6-methoxyphenyl ether dihydrochloride (55, ic50 = 3.0 nm) and seven other compounds exhibited ic50 values below 10 nm against t. b. rhodesiense in vitro. the 2-bromo-4,4'-diamidino a ...201323871911
microalbuminuria and glomerular filtration rate in paediatric visceral leishmaniasis.visceral leishmaniasis, caused by leishmania donovani, is a serious form of leishmaniasis and fatal if untreated. nearly half of the vl cases are children. there are very few studies of renal function in pediatric visceral leishmaniasis. the aim of this study was to evaluate renal dysfunction by studying glomerular filtration rate (gfr), microalbuminuria, and microscopic examination of urine. laboratory analysis was performed on blood and urine samples of 40 parasitologically confirmed pediatric ...201323865054
the r enantiomer of the antitubercular drug pa-824 as a potential oral treatment for visceral leishmaniasis.the novel nitroimidazopyran agent (s)-pa-824 has potent antibacterial activity against mycobacterium tuberculosis in vitro and in vivo and is currently in phase ii clinical trials for tuberculosis (tb). in contrast to m. tuberculosis, where (r)-pa-824 is inactive, we report here that both enantiomers of pa-824 show potent parasiticidal activity against leishmania donovani, the causative agent of visceral leishmaniasis (vl). in leishmania-infected macrophages, (r)-pa-824 is 6-fold more active tha ...201323856774
synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.importance of heme in african trypanosomes, leishmania sp. and plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. consequently, twenty-four porphyrin precursors and derivatives were evaluated against leishmania donovani, trypanosoma brucei and plasmodium sp. the best active compound against trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, wit ...201323851117
adenine and adenosine salvage in leishmania donovani.6-aminopurine metabolism in leishmania is unique among trypanosomatid pathogens since this genus expresses two distinct routes for adenine salvage: adenine phosphoribosyltransferase (aprt) and adenine deaminase (aah). to evaluate the relative contributions of aprt and aah, adenine salvage was evaluated in δaprt, δaah, and δaprt/δaah null mutants of l. donovani. the data confirm that aah plays the dominant role in adenine metabolism in l. donovani, although either enzyme alone is sufficient for s ...201323845934
characterization of a novel putative s-adenosylmethionine decarboxylase-like protein from leishmania donovani.in addition to the s-adenosylmethionine decarboxylase (ad) present in all organisms, trypanosomatids including leishmania spp. possess an additional copy, annotated as the putative s-adenosylmethionine decarboxylase-like proenzyme (adl). phylogenetic analysis confirms that adl is unique to trypanosomatids and has several unique features such as lack of autocatalytic cleavage and a distinct evolutionary lineage, even from trypanosomatid ads. in trypanosoma adl was found to be enzymaticaly dead bu ...201323840377
3-(oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid trypanosoma brucei, the causative agent for human african trypanosomiasis.a whole organism high-throughput screen of approximately 87,000 compounds against trypanosoma brucei brucei led to the recent discovery of several novel compound classes with low micromolar activity against this organism and without appreciable cytotoxicity to mammalian cells. herein we report a structure-activity relationship (sar) investigation around one of these hit classes, the 3-(oxazolo[4,5-b]pyridin-2-yl)anilides. sharp sar is revealed, with our most active compound (5) exhibiting an ic₅ ...201323831695
cyclophilin-mediated reactivation pathway of inactive adenosine kinase aggregates.monomeric adenosine kinase (adk), a pivotal salvage enzyme of the purine auxotrophic parasite, leishmania donovani, tends to aggregate naturally or selectively in presence of adp, leading to inactivation. a cyclophilin (ldcyp) from the parasite reactivated the enzyme by disaggregating it. we studied the aggregation pathway of adk with or without adp. transmission electron microscopy revealed that adp-induced aggregates, as opposed to annular or torus-shaped natural aggregates, were mostly amorph ...201323831509
in vivo and in vitro antileishmanial activity of bungarus caeruleus snake venom through alteration of immunomodulatory activity.leishmaniasis threatens more than 350 million people worldwide specially in tropical and subtropical region. antileishmanial drugs that are currently available have various limitations. the search of new drugs from natural products (plants, animals) possessing antileishmanial activity is ventured throughout the world. the present study deals with the antileishmanial activity of bungarus caeruleus snake venom (bcv) on in vitro promastigotes and amastigotes of leishmania donovani parasite and leis ...201323830987
the triterpenoid fraction from trichosanthes dioica root exhibits in vitro antileishmanial effect against leishmania donovani promastigotes.trichosanthes dioica roxb. (cucurbitaceae), called pointed gourd in english is a dioecious climber found wild throughout the plains of the indian subcontinent and traditionally used in india for several medicinal purposes.201323798885
antileishmanial activity, uptake, and biodistribution of an amphotericin b and poly(α-glutamic acid) complex.a noncovalent, water-soluble complex of amphotericin b (amb) and poly(α-glutamic acid) (pga), with amb loadings ranging from 25 to 55% (wt/wt) using pga with a molecular weight range of 50,000 to 70,000, was prepared as a potential new treatment for visceral leishmaniasis (vl). the amb-pga complex was shown to be as active as fungizone (amb deoxycholate) against intracellular leishmania donovani amastigotes in differentiated thp-1 cells. the in vitro uptake of the amb-pga complex by differentiat ...201323796924
gene expression modulation and the molecular mechanisms involved in nelfinavir resistance in leishmania donovani axenic amastigotes.drug resistance is a major public health challenge in leishmaniasis chemotherapy, particularly in the case of emerging leishmania/hiv-1 co-infections. we have delineated the mechanism of cell death induced by the hiv-1 protease inhibitor, nelfinavir, in the leishmania parasite. in order to further study nelfinavir-leishmania interactions, we selected nelfinavir-resistant axenic amastigotes in vitro and characterized them. rna expression profiling analyses and comparative genomic hybridizations o ...201323782314
comparative study of microscopy and polymerase chain reaction for the diagnosis of suspected visceral leishmaniasis patients in nepal.visceral leishmaniasis is potentially fatal protozoan diseases caused by leishmania donovani. nepal is an endemic region in which visceral leishmaniasis causes a major public health problem in the lowland areas that border the endemic areas of bihar state in india. accurate diagnosis to inform treatment is a first step in achieving the goal of visceral leishmaniasis elimination from south east asian regions by 2020.201323774406
in vitro drug susceptibility of leishmania infantum isolated from humans and dogs.visceral leishmaniasis (vl) caused by parasites of leishmania donovani complex is a severe human disease which often leads to death if left untreated. domestic dogs are the main reservoir hosts for zoonotic human visceral infection caused by leishmania infantum. in the absence of effective human and dog vaccines, the only feasible way to treat and control leishmaniasis is through the use of suitable medications. to know the drug susceptibility of human and canine leishmania strains from lisbon-p ...201323747751
development of doxorubicin loaded novel core shell structured nanocapsules for the intervention of visceral leishmaniasis.the aim of this study was to develop novel nanoemuslion core loaded nanocapsules (ncs) with high payload of doxorubicin (dox) and to assess its efficacy against leishmania donovani. the low energy emulsification method was used to obtained nanoemulsion core as template, followed by stepwise addition of additional layer components protamine sulphate and sodium alginate. zeta potential studies revealed that there was reversal in charge after each layering. ncs were characterized on the basis of si ...201323534494
synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine k for antimalarial, antileishmanial, antibacterial, antifungal, and anti-hiv activities.fifty analogues of batzelladine k were synthesized and evaluated for in vitro antimalarial (plasmodium falciparum), antileishmanial (leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (hiv-1) activities. analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive d6 strain with ic(50) 1.25 and 0.88 μm and chloroquine-resistant w2 strain with ic(50) 1.64 and 1.07 μm, respectively. analogues 12c and 14c having nonyl substitution showed th ...201323534411
leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. severe anemia and leucopenia is associated with the disease. although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how l. donovani alters hematopoiesis. in this study, we used syrian golden hamsters to investigate effects of l. donovani infection on erythropoiesis. infection resulted in seve ...201323533629
studies on the protective and immunomodulatory efficacy of withania somnifera along with cisplatin against experimental visceral leishmaniasis.visceral leishmaniasis (vl) or kala-azar continues to persist as one of the major public health problems in many tropical countries. however, no effective treatment for cure of the disease is yet available. the present study was designed to investigate the nephroprotective and immunomodulatory effect of withania somnifera in cisplatin-treated leishmania donovani-infected balb/c mice. administration of cisplatin (5 mg/kg body weight (b.wt.) daily for 5 days, i.p.) reduced the parasite load in l. ...201323519426
the race to discover the insect vector of kala-azar: a great saga of tropical medicine 1903-1942.in the 19(th) century, a devastating epidemic of visceral leishmaniasis (kala-azar) swept through northeast india. after identification of the pathogenic agent, leishmania donovani, in 1903, the question of its transmission remained to be resolved. in 1904, thanks to work by l. rogers on cultures of this parasite it became probable that a haematophagous arthropod was responsible for transmission. j.a. sinton suggested, in 1925, the distribution of the sand fly phlebotomus argentipes was similar ...201323516011
antiprotozoal isoflavan quinones from abrus precatorius ssp. africanus.a library of 206 extracts from selected south african plants was screened in vitro against a panel of protozoan parasites, plasmodium falciparum, trypanosoma brucei rhodesiense, and leishmania donovani. a ch2cl2/meoh (1 : 1) extract of abrus precatorius l. ssp. africanus strongly inhibited p. falciparum (98 %), t. b. rhodesiense (100 %), and l. donovani (76 %) when tested at a concentration of 10.0 µg/ml. the active constituents were tracked by hplc-based activity profiling and isolated by prepa ...201323512498
antiprotozoal activity of khaya anthotheca, (welv.) c.d.c. a plant used by chimpanzees for self-medication.khaya species, endemic to africa and madagascar, continues to be valuable in indigenous traditional medicine. their bitter tasting barks are decocted to treat fevers, several febrile conditions, microbial infections and worm infestations. in the budongo rain forest of western uganda, non-human primates, especially chimpanzees and baboons, have been observed to eat the bitter non-nutritious bark and occasionally the seed.201323501156
chromone linked nitrone derivative induces the expression of inos2 and th1 cytokines but reduces the th2 response in experimental visceral leishmaniasis.in our previous work we have shown that the novel synthetic chromone derivative could effectively inhibit the leishmania donovani replication in vitro and in vivo with less cytotoxicity on murine splenocytes. the aim of the present study is to explore the possible mechanism of anti-leishmanial effect of c-(6-methyl-4-oxo-4h-1-benzopyran-3-yl)-n-(p-tolyl) nitrone (designated as np1) in vitro and in vivo in experimental visceral leishmaniasis caused by l. donovani. the cytotoxic effect of this der ...201323499679
heterologous priming-boosting with dna and vaccinia virus expressing kinetoplastid membrane protein-11 induces potent cellular immune response and confers protection against infection with antimony resistant and sensitive strains of leishmania (leishmania) donovani.emergence of resistance against commonly available drugs poses a major threat in the treatment of visceral leishmaniasis (vl), particularly in the indian subcontinent. absence of any licensed vaccine against vl emphasizes the urgent need to develop an effective alternative vaccination strategy.201323499564
leishmania donovani targets dicer1 to downregulate mir-122, lower serum cholesterol, and facilitate murine liver infection.leishmania donovani causes visceral leishmaniasis (vl) where the parasite infects and resides inside liver and spleen tissue macrophages. given the abnormal lipid profile observed in vl patients, we examined the status of serum lipids in an experimental murine model of vl. the murine vl liver displayed altered expression of lipid metabolic genes, many of which are direct or indirect targets of the liver-specific microrna-122. concomitant reduction of mir-122 expression was observed in vl liver. ...201323498953
leishmania dices away cholesterol for survival.host lipid alterations are centrally involved in leishmania donovani infection, and infected patients exhibit hypocholesterolemia. in this issue of cell host & microbe, ghosh et al. (2013) show that the metalloprotease gp63 released by l. donovani in the liver cleaves dicer1, inhibiting mir-122 maturation, which regulates cholesterol metabolism. these events decrease serum cholesterol and promote parasite growth.201323498949
comparison of visceral leishmaniasis diagnostic antigens in african and asian leishmania donovani reveals extensive diversity and region-specific polymorphisms.visceral leishmaniasis (vl), caused by infection with leishmania donovani complex, remains a major public health problem in endemic regions of south asia, east africa, and brazil. if untreated, symptomatic vl is usually fatal. rapid field diagnosis relies principally on demonstration of anti-leishmania antibodies in clinically suspect cases. the rk39 immunochromatographic rapid diagnostic test (rdt) is based on rk39, encoded by a fragment of a kinesin-related gene derived from a brazilian l. cha ...201323469296
molecular and serological markers of leishmania donovani infection in healthy individuals from endemic areas of bihar, india.recent epidemiological reports indicate that asymptomatic human infections with leishmania donovani, the causative agent of visceral leishmaniasis or kala-azar (ka), occur frequently in india. we explored markers of infection.201323464581
latent infection with leishmania donovani in highly endemic villages in bihar, india.asymptomatic persons infected with the parasites causing visceral leishmaniasis (vl) usually outnumber clinically apparent cases by a ratio of 4-10 to 1. we describe patterns of markers of leishmania donovani infection and clinical vl in relation to age in bihar, india.201323459501
parenteral formulation of an antileishmanial drug candidate--tackling poor solubility, chemical instability, and polymorphism.the paullon chalcone derivative kurei300 is active against leishmania donovani, the protozoans causing visceral leishmaniasis. the aim of this study was the development of a parenteral formulation of the virtually water insoluble compound in order to enable future studies in mice. mixed lecithin/bile salt micelles, liposomes, supercooled smectic cholesterol myristate nanoparticles, cubic phase nanoparticles and a triglyceride emulsion were screened for their solubilizing properties. due to the l ...201323454203
anti-protozoal activity of aporphine and protoberberine alkaloids from annickia kummeriae (engl. & diels) setten & maas (annonaceae).malaria, trypanosomiasis and leishmaniasis have an overwhelming impact in the poorest countries in the world due to their prevalence, virulence and drug resistance ability. currently, there is inadequate armory of drugs for the treatment of malaria, trypanosomiasis and leishmaniasis. this underscores the continuing need for the discovery and development of new anti-protozoal drugs. consequently, there is an urgent need for research aimed at the discovery and development of new effective and safe ...201323445637
examination of the mode of action of the almiramide family of natural products against the kinetoplastid parasite trypanosoma brucei.almiramide c is a marine natural product with low micromolar activity against leishmania donovani, the causative agent of leishmaniasis. we have now shown that almiramide c is also active against the related parasite trypanosoma brucei, the causative agent of human african trypanosomiasis. a series of activity-based probes have been synthesized to explore both the molecular target of this compound series in t. brucei lysates and site localization through epifluorescence microscopy. these target ...201323445522
eleganolone, a diterpene from the french marine alga bifurcaria bifurcata inhibits growth of the human pathogens trypanosoma brucei and plasmodium falciparum.organic extracts of 20 species of french seaweed have been screened against trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. these extracts have previously shown potent antiprotozoal activities in vitro against plasmodium falciparum and leishmania donovani. the selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian l6 cell line. the ethyl acetate extract of the brown seaweed, bifurcaria bifurcata, showed strong trypano ...201323442789
application of loop-mediated isothermal amplification assay for the sensitive and rapid diagnosis of visceral leishmaniasis and post-kala-azar dermal leishmaniasis.loop-mediated isothermal amplification (lamp) is at the forefront in the search for innovative diagnostics for rapid and specific amplification of target dna under isothermal conditions. we have applied lamp assay using sybr green for clear-cut naked eye detection of leishmania (leishmania) donovani in 200 clinical samples of visceral leishmaniasis (vl) and post-kala-azar dermal leishmaniasis (pkdl). the assay was positive in 53/55 vl blood samples (sensitivity, 96.4%; 95% confidence interval [c ...201323433714
first report of the visceral leishmaniasis vector phlebotomus martini (diptera: psychodidae) in tanzania.phlebotomus martini is a known vector of visceral leishmaniasis caused by leishmania donovani in sub-saharan africa. the disease is known to be endemic in areas of north and south sudan, kenya, ethiopia, uganda, and somalia but has not been reported from tanzania. in this report we present the first documented collection of p. martini and p. vansomerenae in tanzania. sand flies were collected using standard dry-ice baited cdc light traps (john w. hock company, gainesville, fl) from five sampling ...201323427673
functional complexity of the leishmania granuloma and the potential of in silico modeling.in human and canine visceral leishmaniasis and in various experimental models of this disease, host resistance is strongly linked to efficient granuloma development. however, it is unknown exactly how the granuloma microenvironment executes an effective antileishmanial response. recent studies, including using advanced imaging techniques, have improved our understanding of granuloma biology at the cellular level, highlighting heterogeneity in granuloma development and function, and hinting at co ...201323423646
identifying salivary antigens of phlebotomus argentipes by a 2de approach.in the indian subcontinent visceral leishmaniasis, also known as kala-azar, is caused by the protozoa leishmania donovani and is transmitted to humans by the bite of infected female sand flies phlebotomus argentipes in an anthroponotic cycle. sand fly saliva is known to play an important role in host infection outcome after an infective bite. immunogenicity of p. argentipes saliva has already been described. however, specific antigens that can contribute to these immunogenic properties are unkno ...201323422341
an in vitro study of apoptotic like death in leishmania donovani promastigotes by withanolides.the aim of this study was to isolate and evaluate the withanolides in inducing apoptotic like death in leishmania donovani in vitro. withanolides were fractionated and isolated from the leaves of withania somnifera and lc-ms/ms analysis of two fractions namely, f5 and f6 of ethanolic extracts, obtained through column chromatography with silica gel, was performed. the antileishmanial effect of withanolides on l. donovani promastigotes was assessed in vitro using pi dye exclusion test. the effect ...201323416156
induction of immunogenicity by live attenuated leishmania donovani centrin deleted parasites in dogs.zoonotic visceral leishmaniasis, caused by the intracellular protozoan parasite leishmania infantum, is a neglected tropical disease that is often fatal when untreated. dogs are considered the main reservoir of l. infantum in zoonotic vl as the presence of infected dogs may increase the risk for human infection. canine visceral leishmaniasis (cvl) is a major veterinary and public health problem in southern europe, middle east and south america. control of animal reservoirs relies on elimination ...201323398933
proteome changes associated with leishmania donovani promastigote adaptation to oxidative and nitrosative stresses.phagocytic cells produce reactive oxygen and nitrogen species (ros & rns) as the most common arsenal to kill intracellular pathogens. leishmania, an obligate intracellular pathogen also confronts this antimicrobial assault during the early phase of infection but nevertheless is able to survive these attacks and proliferate in macrophage. adaptation of leishmania to the toxic effects of ros and rns, involves a rapid change in the parasite proteome to combat the host defense response that macropha ...201323376486
immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using amphotericin b-encapsulated nanoemulsion template-based chitosan nanocapsules.the accessible treatment options for life-threatening neglected visceral leishmaniasis (vl) disease have problems with efficacy, stability, adverse effects, and cost, making treatment a complex issue. here we formulated nanometric amphotericin b (amb)-encapsulated chitosan nanocapsules (cnc-amb) using a polymer deposition technique mediated by nanoemulsion template fabrication. cnc-amb exhibited good steric stability in vitro, where the chitosan content was found to be efficient at preventing de ...201323357762
antimony-resistant but not antimony-sensitive leishmania donovani up-regulates host il-10 to overexpress multidrug-resistant protein 1.the molecular mechanism of antimony-resistant leishmania donovani (sb(r)ld)-driven up-regulation of il-10 and multidrug-resistant protein 1 (mdr1) in infected macrophages (ms) has been investigated. this study showed that both promastigote and amastigote forms of sb(r)ld, but not the antimony-sensitive form of ld, express a unique glycan with n-acetylgalactosamine as a terminal sugar. removal of it either by enzyme treatment or by knocking down the relevant enzyme, galactosyltransferase in sb(r) ...201323341611
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