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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
structure prediction of gbp21 protein of l. donovani and its molecular interaction.visceral leishmaniasis (kala-azar) is a fatal disease caused by the obligate intracellular parasite leishmania donovani and the available drugs for the treatment are few, and are frequently associated with side effects and toxicity. rna editing is one of the essential metabolic processes in the kinetoplastids, where the pre-mrnas are edited post-transcriptionally by the guide rnas with the addition or deletion of uridine residues. the aim is to block the gbp21 protein involved in rna editing pro ...201423746168
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
recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids.the 2-alkynoic fatty acids are an interesting group of synthetic compounds that display antimycobacterial, antifungal, anticancer, and pesticidal activities but their antiprotozoal activity has received little attention until recently. in this review we have summarized our present knowledge of the biomedical potential of the 2-hexadecynoic acid (2-hda) and 2-octadecynoic acid (2-oda) together with several mechanistic pieces of work attesting to the fact that these compounds, and their metabolite ...201623727443
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
antileishmanial activity evaluation of bis-lawsone analogs and dna topoisomerase-i inhibition studies.for the development of potent novel antileishmanial agents, 3,3'-(arylmethylene)bis(2-hydroxynaphthalene-1,4 dione) derivatives were synthesized from lawsone and evaluated for cytotoxicity on leishmania donovani promastigotes as well as on leishmanial dna topoisomerase-i. enzyme inhibition studies were conducted with simultaneous and preincubation conditions. total inhibition is compared to camptothecin (cpt), which was taken as positive control on both the systems of enzyme inhibition. the rang ...201423534930
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
leishmania donovani-specific 25- and 28-kda urinary proteins activate macrophage effector functions, lymphocyte proliferation and th1 cytokines production.growing incidence of drug resistance against leishmaniasis in endemic areas and limited drug options necessitates the need for a vaccine. notwithstanding significant leishmanial research in the past decades, a vaccine candidate is far from reality. in this study, we report the potential of two urinary leishmanial proteins to induce macrophage effector functions, inflammatory cytokines production and human lymphocytes proliferation. a total four proteins of molecular mass 25, 28, 54 and 60 kda we ...201323334693
identification and functional characterization of leishmania donovani secretory peroxidase: delineating its role in nramp1 regulation.leishmania silently evades host immune system and establish in the hostile environment of host macrophage phagolysosomes. for differentiation, growth and division parasite acquires divalent cations especially iron from the host nutritive pool. natural resistance associated with macrophage protein1 (nramp1), a cation transporter that effluxes out divalent cations specifically iron from phagosomal milieu to the cytosol, to create ions deprived status for pathogenic microorganisms. the mechanisms o ...201323326430
synthesis of perspicamide a and related diverse analogues: their bioevaluation as potent antileishmanial agents.the first protocol for the synthesis of perspicamide a and related diverse analogues has been developed from economical and readily available starting materials. furthermore, a few synthesized analogues, 24a, 24b, 24c, 24d, and 24l, exhibited potent activity against leishmania donovani with ic(50) values ranging from 3.75 to 10.37 μm and a selectivity index (si) ranging from 9.58 to 53.12, which is improved compared to the standard drug miltefosine (ic(50) 12.4 μm and si 4.1).201323289499
lc-ms metabolomics from study design to data-analysis - using a versatile pathogen as a test case.thanks to significant improvements in lc-ms technology, metabolomics is increasingly used as a tool to discriminate the responses of organisms to various stimuli or drugs. in this minireview we discuss all aspects of the lc-ms metabolomics pipeline, using a complex and versatile model organism, leishmania donovani, as an illustrative example. the benefits of a hyphenated mass spectrometry platform and a detailed overview of the entire experimental pipeline from sampling, sample storage and sampl ...201324688684
leishmaniasis: an update of current pharmacotherapy.leishmaniasis broadly manifests as visceral leishmaniasis (vl), cutaneous leishmaniasis (cl) and mucocutaneous leishmaniasis (mcl). the treatment of vl is challenging. the duration of treatment is long, and drugs are toxic thereby needing monitoring and hospitalization.201323256501
human hepatic stellate cells in primary culture are safe targets for leishmania donovani.leishmania parasites can escape the immune response by invading cell types lacking leishmanicidal mechanisms. silent persistence of leishmania parasites in the host organism is responsible for asymptomatic carriage and relapses after cured leishmaniasis. here, we studied the interaction between hepatic stellate cells (hsc) and leishmania. an original model of human hsc in primary culture infected with l. donovani was developed. the presence of intracellular parasites was studied and quantified u ...201323253952
unresponsiveness of mycobacterium w vaccine in managing acute and chronic leishmania donovani infections in mouse and hamster.the role of mycobacterium w (mw) vaccine as an immunomodulator and immunoprophylactant in the treatment of mycobacterial diseases (leprosy and pulmonary tuberculosis) is well established. the fact that it shares common antigens with leishmanial parasites prompted its assessment as an immunostimulant and as an adjunct to known anti-leishmanials that may help in stimulating the suppressed immune status of leishmania donovani-infected individuals. the efficacy of mw vaccine was assessed as an immun ...201323253783
visceral and post-kala-azar dermal leishmaniasis isolates show significant difference in their in vitro drug susceptibility pattern.visceral leishmaniasis (vl) remains a major health problem in old world, and india accounts for half of the world burden. the widespread emergence of resistance to standard drug in india poses a major obstacle in the control of leishmaniasis. post-kala-azar dermal leishmaniasis (pkdl) is considered as main source of drug resistance. experimental data indicate that resistance against newer drugs is also imminent. therefore, in vitro studies were carried out to test minimum parasiticidal concentra ...201323242321
validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of leishmania donovani.simple, cost-effective approach for routine surveillance of parasite susceptibility to antileishmanial drug miltefosine (mil) is highly desirable for controlling emergence of drug resistance in visceral leishmaniasis (vl). we validated a simple resazurin-based fluorimetric assay using promastigotes to track natural mil tolerance in leishmania donovani parasites from vl cases (n = 17) against standard amastigote assay, in two different labs in india. the inter-stage mil susceptibility correlated ...201323239091
noncovalent complexation of amphotericin-b with poly(α-glutamic acid).a noncovalent complex of amphotericin b (amb) and poly(α-glutamic acid) (pga) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. the loading of amb in the complex was in the range of ∼20-50%. amb was in a highly aggregated state with an aggregation ratio often above 2.0. this complex (amb-pga) was shown to be stable and to have reduced toxicity to human red blood cells and kb cells compared to the parent compound; cell viability was not affected at an amb c ...201323234235
different susceptibilities of leishmania spp. promastigotes to the annona muricata acetogenins annonacinone and corossolone, and the platymiscium floribundum coumarin scoparone.leishmaniasis is a zoonotic disease that can manifest itself in visceral and cutaneous form. the aim of this study was to search for new leishmanicidal compounds. preliminarily, artemia salina assay was applied to compounds from two plants found in northeastern brazil, platymiscium floribundum and annona muricata. then these compounds were tested against three leishmania species (leishmania donovani, leishmania mexicana and leishmania major). a screening assay using luciferase-expressing promast ...201323232251
identification of tunisian leishmania spp. by pcr amplification of cysteine proteinase b (cpb) genes and phylogenetic analysis.discrimination of the old world leishmania parasites is important for diagnosis and epidemiological studies of leishmaniasis. we have developed pcr assays that allow the discrimination between leishmania major, leishmania tropica and leishmania infantum tunisian species. the identification was performed by a simple pcr targeting cysteine protease b (cpb) gene copies. these pcr can be a routine molecular biology tools for discrimination of leishmania spp. from different geographical origins and d ...201323228525
leishmanization revisited: immunization with a naturally attenuated cutaneous leishmania donovani isolate from sri lanka protects against visceral leishmaniasis.leishmaniasis is a neglected tropical disease caused by leishmania protozoa and associated with three main clinical presentations: cutaneous, mucocutaneous and visceral leishmaniasis. visceral leishmaniasis is the second most lethal parasitic disease after malaria and there is so far no human vaccine. leishmania donovani is a causative agent of visceral leishmaniasis in south east asia and eastern africa. however, in sri lanka, l. donovani causes mainly cutaneous leishmaniasis, while visceral le ...201323219435
assessing the essentiality of leishmania donovani nitroreductase and its role in nitro drug activation.the nitroimidazole fexinidazole has potential as a safe and effective oral drug therapy for the treatment of visceral leishmaniasis. to date, nitroheterocyclics have not been used in the treatment of leishmaniasis, and relatively little is known about their mechanism of action. in african trypanosomes, nitro drugs are reductively activated by a type i nitroreductase (ntr), absent in mammalian cells. modulation of nitroreductase levels in trypanosoma brucei directly affected sensitivity to nitro ...201323208716
di-cationic arylimidamides act against neospora caninum tachyzoites by interference in membrane structure and nucleolar integrity and are active against challenge infection in mice.neospora caninum is considered to be the main cause of bovine abortion in europe and the usa, leading to considerable financial impact. losses are caused directly by abortions or indirectly through breeding of calves with impaired viability. due to the lack of effective chemotherapy against bovine neosporosis, there is a need to develop new anti-protozoal compounds, which would either eliminate the parasite or avoid its transmission. in order to identify compounds of interest, the in vitro activ ...201224533272
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
conjugation of quinones with natural polyamines: toward an expanded antitrypanosomatid profile.a combinatorial library of quinone-polyamine conjugates designed to optimize the antitrypanosomatid profile of hit compounds 1 and 2 has been prepared by a solid-phase approach. the conjugates were evaluated against the three most important human trypanosomatid pathogens (trypanosoma brucei rhodesiense, trypanosoma cruzi, and leishmania donovani), and several showed promising activity. a subset also inhibited trypanothione reductase in vitro and induced oxidase activity of the enzyme. a highly p ...201223153330
cysteine cross-linking defines the extracellular gate for the leishmania donovani nucleoside transporter 1.1 (ldnt1.1).equilibrative nucleoside transporters are a unique family of proteins that enable uptake of nucleosides/nucleobases into a wide range of eukaryotes and internalize a myriad of drugs used in the treatment of cancer, heart disease, aids, and parasitic infections. in previous work we generated a structural model for such a transporter, the ldnt1.1 nucleoside permease from the parasitic protozoan leishmania donovani, using ab initio computation. the model suggested that aromatic residues present in ...201223150661
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
cxcl10 is critical for the generation of protective cd8 t cell response induced by antigen pulsed cpg-odn activated dendritic cells.the visceral form of leishmaniasis is the most severe form of the disease and of particular concern due to the emerging problem of hiv/visceral leishmaniasis (vl) co-infection in the tropics. till date miltefosine, amphotericin b and pentavalent antimony compounds remain the main treatment regimens for leishmaniasis. however, because of severe side effects, there is an urgent need for alternative improved therapies to combat this dreaded disease. in the present study, we have used the murine mod ...201223144947
cloning, characterization and sub-cellular localization of gamma subunit of t-complex protein-1 (chaperonin) from leishmania donovani.t-complex protein-1 (tcp1) complex, a chaperonin class of protein, ubiquitous in all genera of life, is involved in intracellular assembly and folding of various proteins. the gamma subunit of tcp1 complex (tcp1γ), plays a pivotal role in the folding and assembly of cytoskeleton protein(s) as an individual or complexed with other subunits. here, we report for the first time cloning, characterization and expression of the tcp1γ of leishmania donovani (ldtcp1γ), the causative agent of indian kala- ...201223137535
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
first total synthesis of the (±)-2-methoxy-6-heptadecynoic acid and related 2-methoxylated analogs as effective inhibitors of the leishmania topoisomerase ib enzyme.the fatty acids (±)-2-methoxy-6z-heptadecenoic acid (1), (±)-2-methoxy-6-heptadecynoic acid (2) and (±)-2-methoxyheptadecanoic acid (3) were synthesized and their inhibitory activity against the leishmania dna topoisomerase ib enzyme (ldtopib) determined. acids 1 and 2 were synthesized from 4-bromo-1-pentanol, the former in ten steps and in 7% overall yield, while the latter in seven steps and in 14% overall yield. acid 3 was prepared in six steps and in 42% yield from 1-hexadecanol. acids 1-3 i ...201223118491
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
expression of concern: ahlin e et al.,"anti-citrullinated peptide antibodies and rheumatoid factor in sudanese patients with leishmania donovani infection", rev bras reumatol 2011; 51(6):572-86. 201223090367
molecular and parasitological detection of leishmania spp. in dogs caught in palmas, to, brazil.this study evaluated occurrences of leishmania infantum in dogs in the municipality of palmas, tocantins, comparing diagnostic data obtained using the polymerase chain reaction (pcr) and parasitological diagnosis. blood samples and lymph node aspirates were collected from 63 dogs of males and females and various ages and races, with or without owners, between august 2009 and june 2010. slides containing smears of lymph node aspirates were stained with giemsa stained. in pcr, the 145 bp target se ...201223070439
hyperlipidemia offers protection against leishmania donovani infection: role of membrane cholesterol.leishmania donovani (ld), the causative agent of visceral leishmaniasis (vl), extracts membrane cholesterol from macrophages and disrupts lipid rafts, leading to their inability to stimulate t cells. restoration of membrane cholesterol by liposomal delivery corrects the above defects and offers protection in infected hamsters. to reinforce further the protective role of cholesterol in vl, mice were either provided a high-cholesterol (atherogenic) diet or underwent statin treatment. subsequent ld ...201223060454
leishmania donovani triose phosphate isomerase: a potential vaccine target against visceral leishmaniasis.visceral leishmaniasis (vl) is one of the most important parasitic diseases with approximately 350 million people at risk. due to the non availability of an ideal drug, development of a safe, effective, and affordable vaccine could be a solution for control and prevention of this disease. in this study, a potential th1 stimulatory protein- triose phosphate isomerase (tpi), a glycolytic enzyme, identified through proteomics from a fraction of leishmania donovani soluble antigen ranging from 89.9- ...201223049855
leishmanicidal activity of two naphthoquinones against leishmania donovani.here we studied ability of two naphthoquinones to inhibit leishmania growth (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (tr 001) and 2,3-dibromo-1,4-naphthoquinone (tr 002). tr 001 was more efficient than tr 002 in inducing killing of promastigotes and intracellular amastigotes. these values compare well to those obtained with the standard first-line antileishmanial agent sodium stibogluconate (ssg). tr 001 also induced significantly more nitric oxide (no) production than tr 002 or ssg. taken ...201223037165
chemotherapy of leishmaniasis. part xi: synthesis and bioevaluation of novel isoxazole containing heteroretinoid and its amide derivatives.novel isoxazole containing heteroretinoid (4) and its amide derivatives (5a-j) have been synthesized and evaluated for their in vivo antileishmanial activity against leishmania donovani in hamsters. compounds 3, 5a, 5d, 5k and 5l inhibited 70-76% parasite growth at 50 mg kg(-1) ×5 days. the present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent.201223031597
chemotherapy of leishmaniasis. part ix: synthesis and bioevaluation of aryl substituted ketene dithioacetals as antileishmanial agents.a new series of aryl substituted ketene dithioacetals 6a-h was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against leishmania donovani. two compounds exhibited significant in vitro activity against intracellular amastigotes of l. donovani with ic(50) values 3.56 and 5.12 μm and were found promising as compared with reference drug, miltefosine. on the basis of good selectivity indices (s.i.), they were further tested for their in vivo response against l. dono ...201223031588
the lignan niranthin poisons leishmania donovani topoisomerase ib and favours a th1 immune response in mice.niranthin, a lignan isolated from the aerial parts of the plant phyllanthus amarus, exhibits a wide spectrum of pharmacological activities. in the present study, we have shown for the first time that niranthin is a potent anti-leishmanial agent. the compound induces topoisomerase i-mediated dna-protein adduct formation inside leishmania cells and triggers apoptosis by activation of cellular nucleases. we also show that niranthin inhibits the relaxation activity of heterodimeric type ib topoisome ...201223027614
testing urine samples with rk39 strip as the simplest non-invasive field diagnosis for visceral leishmaniasis: an early report from eastern india.diagnosis of visceral leishmaniasis (vl) is a major obstacle in the control of this disease. the rk39 strip-test using patient's blood is a breakthrough; however, it still requires a blood sample, which is a concern for safety in the field. we tried to simplify the test using the patient's urine instead of blood.201523023349
a rapid method to assess the stage differentiation in leishmania donovani by flow cytometry.in this study we describe a rapid and novel method to assess the morphological stage differentiation in leishmania donovani by flow cytometry (fcm). fcm is fast, accurate, and inexpensive to study the stage differentiation of promastigote into l. donovani axenic amastigote (ldaxam). the non-flourimetric fcm method is easy to perform; with requirement of little expertise, and provides unambiguous results. it is an advanced tool, requires minimal time, and no fluorescent dyes. the gradual increase ...201223022521
a pentapeptide signature motif plays a pivotal role in leishmania dna topoisomerase ib activity and camptothecin sensitivity.leishmania donovani - the causative agent of visceral leishmaniasis - has several evolutionary characteristics that make the disease difficult to combat. among these differences, a rare heterodimeric dna topoisomerase ib has been reported thus opening a new promising field in the therapy of leishmaniasis. several studies of the human enzyme have pointed to the importance of the linker domain in respect to camptothecin sensitivity. at present, it has been impossible to pinpoint the regions that m ...201223000572
effect of allicin on promastigotes and intracellular amastigotes of leishmania donovani and l. infantum.anti-leishmanial activity of allicin (=diallyl thiosulphinate) has been tested in vitro against promastigotes and intracellular amastigotes of leishmania donovani and leishmania infantum. macrophage infections have been carried out in vitro in the murine cell line j774 and ex vivo with peritoneal macrophages from balb/c mice with a modified method to isolate metacyclic promastigotes. the compound has shown a significant in vitro effect on the multiplication of promastigotes of l. donovani and l. ...201222995646
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
synthesis and structure-activity relationships of lansine analogues as antileishmanial agents.clear and rational thinking: a series of rationally designed, lansine-derived carbazoles was synthesized and evaluated for activity against promastigotes and amastigotes of leishmania donovani, the causative agent of leishmaniasis. some structural modifications gave rise to compounds with enhanced activity and selectivity over lansine, allowing structure-activity relationships to be elucidated and providing a foundation for the further development of this pharmacophore.201222987791
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
rflps of its, its1 and hsp70 amplicons and sequencing of its1 of recent clinical isolates of kala-azar from india and bangladesh confirms the association of l. tropica with the disease.visceral leishmaniasis or kala-azar (ka) is a serious health concern in india. in the present study, restriction fragment length polymorphism (rflp) of three genetic markers viz., internal transcribed spacer (its), its1 and heat shock protein 70 (hsp70) have been employed for typing the clinical isolates [n=15] of ka and post kala-azar dermal leishmaniosis (pkdl) collected from india and bangladesh in the period of 2006-2010. experimentally, its, its1 and hsp70 regions of genomes of all the clin ...201222960646
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