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serological evidence of leishmania donovani infection in apparently healthy dogs using direct agglutination test (dat) and rk39 dipstick tests in kafta humera, north-west ethiopia.leishmania (kinetoplastida: trypanosomatidae) are protozoan parasites of significant medical and veterinary importance. over the last decade, visceral leishmaniasis (vl) has emerged as a major opportunistic infection associated with hiv/aids in north western ethiopia. this paper reports on serological evidence of possible leishmania donovani (l. donovani) infection in dogs using two serological tests: direct agglutination test (dat) and kalazar detect rapid test (kdrt). two hundred and seventeen ...201121371289
multilocus microsatellite typing revealed high genetic variability of leishmania donovani strains isolated during and after a kala-azar epidemic in libo kemkem district, northwest ethiopia.in 2004, an outbreak of kala-azar (ka) occurred for the first time in libo kemkem district, in the highland area of northwest ethiopia. in order to track the possible origins of the outbreak parasites, we have investigated 19 strains of leishmania donovani that were collected during (n = 6) and after (n = 13) the outbreak by using 14 highly polymorphic microsatellite markers. unique microsatellite profiles were obtained for all strains from libo kemkem. when compared to those of l. donovani stra ...201121382503
antiparasitic and antimicrobial indolizidines from the leaves of prosopis glandulosa var. glandulosa*a new indolizidine alkaloid, named +ö(1,6)-juliprosopine ( 1), together with previously known indolizidine analogs ( 2- 6), was isolated from the leaves of prosopis glandulosa var. glandulosa, collected from nevada, usa; while two other known indolizidines, juliprosopine ( 6) and juliprosine ( 7), were isolated from p. glandulosa leaves collected in texas, usa. the structures of compound 1 and 7 were determined using a combination of nmr and ms techniques. compound 7 exhibited potent antiplasmod ...201121384317
synthesis and evaluation of new furanyl and thiophenyl azoles as antileishmanial agents.a series of benzyloxy furanyl and benzyloxy thiophenyl azoles were synthesized and screened for their in vitro antileishmanial activity against leishmania donovani. among all, 16 compounds have shown more than 90% inhibition against promastigotes at 20 ++m while 11 compounds exhibited ic50 in the range of 3.04-9.39 ++m against amastigotes. compound 4, a 3-chlorobenzyloxy furanyl imidazole emerged as the most active compound in the series with ic50 value of 3.04 ++m and si value of 19.80, and was ...201121385661
noninvasive molecular diagnosis of human visceral leishmaniasis.previously developed methods for noninvasive pcr diagnosis of visceral leishmaniasis (vl) have significant limitations. diagnosis of vl using pcr and buccal swabs was evaluated in 307 subjects, including 148 patients confirmed to have vl. this method is simple and well tolerated and has good potential for development, showing 83% sensitivity with 90.56% specificity in control groups.201121389158
in vitro interactions between sitamaquine and amphotericin b, sodium stibogluconate, miltefosine, paromomycin and pentamidine against leishmania donovani.to evaluate in vitro interactions between sitamaquine and the current antileishmanial drugs amphotericin b, sodium stibogluconate, miltefosine, paromomycin and pentamidine against intracellular leishmania donovani amastigotes in peritoneal mouse macrophages. a second objective was to evaluate the susceptibility of antimony-resistant l. donovani isolates to sitamaquine.201121393188
targeted killing of leishmania donovani in vivo and in vitro with amphotericin b attached to functionalized carbon nanotubes.this study describes the antileishmanial efficacy of the novel drug formulation of amphotericin b (amb) attached to functionalized carbon nanotubes (f-cnts) and compares it with amb.201121393222
fucoidan cures infection with both antimony-susceptible and -resistant strains of leishmania donovani through th1 response and macrophage-derived oxidants.the aim of this study was to evaluate and characterize the antileishmanial efficacy of fucoidan, a polyanionic sulphated polysaccharide from brown algae, in experimental infections of balb/c mice with antimony-susceptible (ag83) and -resistant (ge18er) leishmania donovani.201121393231
antileishmanial activity of drug infused mini-agar plates on leishmania donovani promastigotes.drug infused mini agar plates were found to be a better alternative of broth dilution method in the determination of antileishmanial susceptibility of two commonly used drugs, sodium antimony gluconate and amphotericin b against leishmania donovani promastigotes. these two drugs were used here as models for antileishmanial compounds. the stability of the drugs in the stored agar plates was also tested for six months and found that they were same as fresh plates. determination of antileishmanial ...201021399608
kinetoplast morphology and segregation pattern as a marker for cell cycle progression in leishmania donovani.trypanosomatids are typified by uniquely configured mitochondrial dna--the kinetoplast. the replication timing of kinetoplast dna (kdna) is closely linked to nuclear s phase, but nuclear and kinetoplast compartments display staggered timing of segregation, post-replication. kinetoplast division is completed before nuclear division in trypanosoma species while nuclear division is completed first in crithidia species. leishmania donovani is the causative agent of visceral leishmaniasis, a form of ...201121401783
identification and characterization of a novel, 37-kilodalton leishmania donovani antigen for diagnosis of indian visceral leishmaniasis.the biggest challenge in the serological diagnosis of visceral leishmaniasis (vl) is to find a biomarker with a high specificity. this study was undertaken to identify novel leishmania donovani antigens to solve the existing problem. the soluble l. donovani promastigote antigen was separated by sds-page, and a western blot was probed with pooled sera of five subjects with confirmed vl before (n = 9 pools) and after (n = 9 pools) treatment and at the 6-month follow-up visit (n = 9 pools), healthy ...201121411602
in vitro screening of traditional south african malaria remedies against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum.three hundred extracts were prepared from plants traditionally used in south africa to treat malaria and screened in vitro for activity against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum. for the 43 extracts which inhibited the growth of one or more parasites to more than 95 % at 9.7 µg/ml, the ic (50) values against all four protozoal parasites and cytotoxic ic (50)s against rat myoblast l6 cells were determined. amongst the most notable re ...201121412695
expression of il-10-triggered stat3-dependent il-4ra is required for induction of arginase 1 in visceral leishmaniasis.although enhanced macrophage-specific arginase activity is directly related to increased parasite burden in cutaneous leishmaniasis (cl), the regulation and precise role of arginase in the disease outcome of visceral leishmaniasis (vl) has yet to be explored. as in cl, balb/c mice infected with leishmania donovani showed increased levels of arginase in acute infection. arginase 1 is the major isoform associated with infection and while the il-4-induced arginase pathway is operative in cl, il-10 ...201121413004
a clinical trial to evaluate the safety and immunogenicity of the leish-f1+mpl-se vaccine for use in the prevention of visceral leishmaniasis.healthy indian adult volunteers, with or without a history of leishmaniasis, were evaluated for evidence of previous infection with leishmania donovani based on the direct agglutination test (dat). three cohorts of 6 dat-negative and 6 dat-positive subjects were enrolled in an open-label, dose-escalating, uncontrolled clinical trial and received three injections of the leish-f1+mpl-se vaccine (consisting of 5µg, 10µg, or 20µg recombinant leishmania polyprotein leish-f1 antigen+25µg mpl®-se adjuv ...201121414377
therapy with sodium stibogluconate in stearylamine-bearing liposomes confers cure against ssg-resistant leishmania donovani in balb/c mice.resistance of leishmania donovani to pentavalent antimonials, the first-line treatment of visceral leishmaniasis (vl), has become a critical issue worldwide. second-line and new drugs are also not devoid of limitations. suitable drug-delivery systems can improve the mode of administration and action of the existing antimonials, thus increasing their clinical life.201121423750
leishmania donovani glycosphingolipid facilitates antigen presentation by inducing relocation of cd1d into lipid rafts in infected macrophages.nkt cells respond to presentation of specific glycolipids with release of both th1- and th2-type cytokines. leishmania donovani (ld)-infected splenic macrophages (sm?(i)) and bone marrow-derived dendritic cells (bmdc(i)) failed to activate nkt cells in response to a-galactosyl ceramide (a-galcer). the defective antigen presentation could be corrected by treating the cells with the immunostimulating glycosphingophospholipid (gspl) of ld parasites. in vitro pulsing of bmdc(i) or sm?(i) with gspl, ...201121425159
novel compounds to combat trypanosomatid infections: a medicinal chemical perspective.introduction: the current therapeutic arsenal against the kinetoplastids trypanosoma brucei, trypanosoma cruzi and leishmania spp. is clearly inadequate and underscores the urgent need to develop new effective, safe and cost-effective drugs. areas covered: accordingly, this review of patented products and processes using anti-kinetoplastid agents provides insight into the identification of novel or more refined drugs. in this review, we describe products developed in recent years for the treatme ...201121428846
anti-tumor and anti-leishmanial evaluations of 1,3,4-oxadiazine, pyran derivatives derived from cross-coupling reactions of +¦-bromo-6h-1,3,4-oxadiazine derivatives.cyanoacetylhydrazine reacted with the ¤ë-bromoacetophenones 2a,b to give hydrazide-hydrazone derivatives 3a,b. the latter products were cyclized to the 1,3,4-oxadiazine derivatives 4a,b. bromination of the latter products gave the 6-bromo-6h-1,3,4-oxadiazine derivatives 5a,b which underwent a series of cross-coupling reactions. the antitumor evaluation of the newly synthesized products against the three cancer cells namely breast adenocarcinoma (mcf-7), non-small cell lung cancer (nci-h460) and ...201121435889
the use of conjunctival swab samples for pcr screening for visceral leishmaniasis in vaccinated dogs.the polymerase chain reaction (pcr) has been shown to provide a rapid and sensitive technique for leishmania detection. the aim of this study was to evaluate the technique of noninvasive conjunctival swabs (cs) as a sampling method for molecular screening for visceral leishmaniasis (vl) in a group of 42 police dogs, all of them vaccinated against vl, and to compare the results with those obtained by serological tests. the serological assays were performed independently by three laboratories. lab ...201121439230
a novel a2 allele found in leishmania (leishmania) infantum chagasi.visceral leishmaniasis (vl) is a widely spread zoonotic disease. in brazil the disease is caused by leishmania (leishmania)infantum chagasi. peridomestic sandflies acquire the etiological agent by feeding on blood of infected reservoir animals, such as dogs or wildlife. the disease is endemic in brazil and epidemic foci have been reported in densely populated cities all over the country. many clinical features of leishmania infection are related to the host-parasite relationship, and many candid ...201121439231
leishmania aflp: paving the way towards improved molecular assays and markers of diversity.diversity, phylogenetic, and population genetic studies of the genus leishmania, causative agent of leishmaniasis, nowadays generally involve multilocus microsatellite and multilocus sequence typing. even though these are well established and useful applications, amplified fragment length polymorphisms (aflp) can provide complementary information. in addition, as the technique essentially probes the entire genome at random, without prior sequence knowledge, it is ideally suited as a screening to ...201121439405
a high-throughput turbidometric assay for screening inhibitors of leishmania major protein disulfide isomerase.the use of a high-throughput technique to perform a pilot screen for leishmania major protein disulfide isomerase (lmpdi) inhibitors identification is reported. in eukaryotic cells, protein disulfide isomerase (pdi) plays a crucial role in protein folding by catalyzing the rearrangement of disulfide bonds in substrate proteins following their synthesis. lmpdi displays similar domain structure organization and functional properties to other pdi family members and is involved in leishmania virulen ...201121441416
effect of a2 gene on infectivity of the nonpathogenic parasite leishmania tarentolae.several species of protozoan parasites of the genus leishmania are pathogenic to mammals and cause a wide spectrum of pathologies in human. however, the genus includes some species which infect reptiles. leishmania tarentolae is a lizard pathogen absolutely nonpathogenic to mammals. recent studies have shown that among some major virulence factors, a2 is absent in this species. first identified as an amastigote-specific gene in leishmania donovani, a2 has been proved to play a major role in para ...201121442256
adaptation of a 2d in-gel kinase assay to trace phosphotransferase activities in the human pathogen leishmania donovani.the protozoan parasite leishmania donovani undergoes various developmental transitions during its infectious cycle that are triggered by environmental signals encountered inside insect and vertebrate hosts. intracellular differentiation of the pathogenic amastigote stage is induced by ph and temperature shifts that affect protein kinase activities and downstream protein phosphorylation. identification of parasite proteins with phosphotransferase activity during intracellular infection may reveal ...201121443974
biophysical and folding parameters of trypanothione reductase from leishmania infantum.out of various tropical diseases caused by trypanosomatids, leishmaniasis is a life-threatening disease caused by the leishmania parasite. we are targeting the thiol metabolic pathway of the parasite for drug development, and trypanothione reductase (tryr) is a key enzyme of this pathway. it is important to gather significant knowledge about biophysical and intrinsic properties of this enzyme which will be helpful in better understanding of this drug-target enzyme. we report here the modulation ...201121445596
structure-activity relationship investigations of leishmanicidal n-benzylcytisine derivatives.in vitro leishmanicidal activity of 16 n-benzylcytisine derivatives has been evaluated using leishmania donovani axenic amastigotes. in general, halogen (bromo-, chloro-) derivatives appeared to be more toxic against parasites than their parent compounds. quantum-chemical calculations helped to recognize certain patterns in the structure of frontier orbitals related to bioactivity of compounds. thus, the presence of halogen atom is shown to have a significant effect on both distribution and the ...201121457471
leishmania express a functional cdc20 homologue.our knowledge concerning the mechanisms of cell cycle regulation in organisms belonging to the trypanosometidae family is limited. leishmania donovani are parasitic protozoa that cause kala azar, a fatal form of visceral leishmaniasis in humans. here we provide evidence that the l. donovani genome contains a cdc20 homologue. cdc20 is a regulator of the anaphase promoting complex/cyclosome (apc/c) that mediates ubiquitin-dependent proteasomal degradation of key cell cycle regulators in eukaryotes ...201121458414
cutaneous leishmaniasis after travel to cyprus and successful treatment with miltefosine.a patient presenting with an atypical manifestation of cutaneous leishmaniasis after travel to cyprus was successfully treated with miltefosine. the k26 typing revealed a hitherto undescribed strain of the leishmania donovani/infantum complex as the causing agent.201121460010
antimony-resistant clinical isolates of leishmania donovani are susceptible to paromomycin and sitamaquine.widespread antimonial resistance in anthroponotic visceral leishmaniasis (vl) makes it critical to monitor the susceptibility of prevailing field isolates to upcoming antileishmanials in order to frame the right treatment policies to protect these drugs against development of resistance. we aimed to generate the baseline data on natural in vitro susceptibility to paromomycin and sitamaquine in leishmania donovani field isolates from vl patients (n = 20) coming from zones of varying sodium antimo ...201121464251
berberine chloride mediates its anti-leishmanial activity via differential regulation of the mitogen activated protein kinase pathway in macrophages.a complex interplay between leishmania and macrophages influences parasite survival and necessitates disruption of signaling molecules, eventually resulting in impairment of macrophage function. in this study, we demonstrate the immunomodulatory activity of berberine chloride in leishmania infected macrophages.201121483684
[acquisition and analysis of lipophosphoglycan 1 gene and the noncoding region of leishmania donovani isolates from hilly foci of china].a fragment about 2.2 kb located at upstream of lipophosphoglycan 1 (lpg1) gene of leishmania donovani isolate from hilly foci of china was obtained by pcr. the nucleotide sequence of the fragment was determined by sequencing. the sequence of the lpg1 gene and its downstream fragment (about 2 kb) was determined by using genome walking method. the above two fragment splicing result showed that the nucleotide sequence of the lpg1 gene with the noncoding region was 4 121 bp (genbank accession number ...201021500538
quantitative proteome profiling informs on phenotypic traits that adapt leishmania donovani for axenic and intracellular proliferation.protozoan parasites of the genus leishmania are important human pathogens that differentiate inside host macrophages into an amastigote life cycle stage. although this stage causes the pathogenesis of leishmaniasis, only few proteins have been implicated in amastigote intracellular survival. here we compare morphology, infectivity and protein expression of l. donovani ld1s grown in host free (axenic) culture, or exclusively propagated in infected hamsters, with the aim to reveal parasite traits ...201121501362
imaging host cell-leishmania interaction dynamics implicates parasite motility, lysosome recruitment, and host cell wounding in the infection process.leishmania donovani causes human visceral leishmaniasis. the parasite infectious cycle comprises extracellular flagellated promastigotes that proliferate inside the insect vector, and intracellular nonmotile amastigotes that multiply within infected host cells. using primary macrophages infected with virulent metacyclic promastigotes and high spatiotemporal resolution microscopy, we dissect the dynamics of the early infection process. we find that motile promastigotes enter macrophages in a pola ...201121501831
characterization of plasma membrane bound inorganic pyrophosphatase from leishmania donovani promastigotes and amastigotes.currently, a major problem in the management of visceral leishmaniasis or kala-azar, especially in the indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy. membrane bound pyrophophatase (ppases) do not exist in plasma membrane from mammals. thus, h(+)-ppases from leishmania plasma membrane might be potential target in rational chemotherapy of the disease caused by leishmania parasites.200921503171
the leishmania donovani ump synthase is essential for promastigote viability and has an unusual tetrameric structure that exhibits substrate-controlled oligomerization.the final two steps of de novo uridine 5'-monophosphate (ump) biosynthesis are catalyzed by orotate phosphoribosyltransferase (oprt) and orotidine 5'-monophosphate decarboxylase (ompdc). in most prokaryotes and simple eukaryotes these two enzymes are encoded by separate genes, whereas in mammals they are expressed as a bifunctional gene product called ump synthase (umps), with oprt at the n terminus and ompdc at the c terminus. leishmania and some closely related organisms also express a bifunct ...201121507942
guns, germs and dogs: on the origin of leishmania chagasi.the evolutionary history of leishmania chagasi, the aetiological agent of visceral leishmaniasis in south america has been widely debated. this study addresses the problem of the origin of l. chagasi, its timing and demography with fast evolving genetic markers, a suite of bayesian clustering algorithms and coalescent modelling. here, using 14 microsatellite markers, 450 strains from the leishmania donovani complex, we show that the vast majority of the central and south american l. chagasi were ...201121511057
a novel sucrose/h(+) symport system and an intracellular sucrase in leishmania donovani.the flagellated form of pathogenic parasitic protozoa leishmania, resides in the alimentary tract of its sandfly vector, where sucrose serves as a major nutrient source. in this study we report the presence of a sucrose transport system in leishmania donovani promastigotes. the kinetics of sucrose uptake in promastigotes are biphasic in nature with both high affinity k(m) (k(m) of ∼75μm) and low affinity k(m) (k(m)∼1.38mm) components. by contrast the virulent amastigotes take up sucrose via a lo ...201121515279
evaluation of turkish seaweeds for antiprotozoal, antimycobacterial and cytotoxic activities.as part of our continuing research on seaweeds, crude meoh extracts of two green, three brown and six red algae collected from marmara, black, aegean and mediterranean seas were screened. four parasitic protozoa, i.e. plasmodium falciparum, trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani and the tubercle bacillus mycobacterium tuberculosis were used as test organisms for the in vitro assays. the selective toxicity of the extracts was also determined against mammalian l6 cells. all ...201121520472
toxicity of betulin derivatives and in vitro effect on promastigotes and amastigotes of leishmania infantum and l. donovani.the toxicity and antileishmanial activity of 20 betulin derivatives were studied. the toxicity of betulin and synthesized compounds was determined using a bacterial test (microtox) and two mammalian cell lines (cho-k1 and j774). the antileishmanial activity of compounds (50 μm) was examined in both the promastigote and intracellular amastigote stages of leishmania infantum and l. donovani. no correlation was found among the toxicity tests. all the compounds showed significant antipromastigote ac ...201121522160
interferon-gamma release assay (modified quantiferon) as a potential marker of infection for leishmania donovani, a proof of concept study.in areas endemic for visceral leishmaniasis (vl), a large number of infected individuals mount a protective cellular immune response and remain asymptomatic carriers. we propose an interferon-gamma release assay (ifn-γra) as a novel marker for latent l. donovani infection.201121526219
antiprotozoal activities of traditional medicinal plants from the garhwal region of north west himalaya, india.in a search for new plant-derived biologically active compounds against protozoan parasites, an ethnopharmacological study was carried out to evaluate extracts from selected 17 traditional medicinal plants which were used by healers from the garhwal region of north west himalaya for the treatment of protozoal infections and fever including malaria.201121527328
generation and evaluation of a2-expressing lactococcus lactis live vaccines against leishmania donovani in balb/c mice.leishmaniasis is a parasitic disease affecting over 12 million individuals worldwide. since current treatments are insufficient, the development of an effective vaccine is a priority. we generated and assessed the efficacy of leishmania vaccines engineered from the non-colonizing, non-pathogenic gram-positive bacterium lactococcus lactis. a truncated, codon-optimized version of the a2 antigen from leishmania donovani was engineered for expression in l. lactis at three different subcellular compa ...201121527547
studies on the protective efficacy and immunogenicity of hsp70 and hsp83 based vaccine formulations in leishmania donovani infected balb/c mice.visceral leishmaniasis, a chronic systemic infection, is the major cause of morbidity and mortality in many parts of world. the current drugs for the treatment of leishmaniasis are toxic, expensive, difficult to administer and becoming ineffective due to the emergence of drug resistance. in the absence of effective treatment, vaccination remains the only hope for control of the disease. we have evaluated the protective efficacy of two heat shock proteins (hsp70 and hsp83) in combination with two ...201121530477
role of endothelial dysfunction in modulating the plasma redox homeostasis in visceral leishmaniasis.evidence in the literature suggests that down-regulation of nitric oxide (no) is associated with the pathophysiological conditions during visceral leishmaniasis (vl). here we have investigated the mechanism that leads to the down regulation of systemic no in the infected condition. moreover, we have determined whether down regulation of no is associated with increased generation of reactive oxygen species (ros) during this disease. therapeutic strategy targeting signaling molecules of these even ...201121530614
treatment with ip-10 induces host-protective immune response by regulating the t regulatory cell functioning in leishmania donovani-infected mice.visceral leishmaniasis (vl), caused by the protozoan parasite, leishmania donovani, is characterized by an infection in the liver and spleen. the failure of the first-line drugs has led to the development of new strategies for combating vl. recently, our group has shown that interferon-γ-inducible protein (ip)-10, a cxc chemokine, renders protection against vl. in the present study, we have elucidated the mechanism by which ip-10 renders protection in in vivo l. donovani infection. we observed t ...201121533785
spermidine synthase is required for virulence of leishmania donovani.genetic lesions in the polyamine biosynthetic pathway of leishmania donovani, the causal agent of visceral leishmaniasis, are conditionally lethal mutations that render the insect vector form of the parasite auxotrophic for polyamines. recently, we have demonstrated that a δodc l. donovani null mutant lacking ornithine decarboxylase (odc), the rate limiting enzyme in polyamine biosynthesis, was profoundly compromised in its ability to infect mice indicating that odc is essential for the infectio ...201121536795
cpg-oligodeoxynucleotide (2006) and miltefosine: a potential combination for treatment of experimental vl.in view of the severe immunosuppression in vl, a rational approach to effectively combat the parasitic scourge would be to enhance the immune status of the host. use of cpg-oligodeoxynucleotide (odn) has previously been reported against leishmaniasis especially as immunomodulators and adjuvant with various immunogens. the experiments were carried out in balb/c mice and hamsters, infected with leishmania donovani. immunostimulating class b bacterial cpg odn namely, odn-2006 was administered at va ...201121537026
isolated leishmanial lymphadenopathy - a rare type of leishmaniasis in india: a case report.a patient presented with isolated, soft to firm, inguinal swelling since childhood clinically thought to be a benign lipomatous lesion. fine-needle aspiration of the swelling revealed amastigote form of leishmania donovani in a background of reactive lymphoid hyperplasia. excision of the swelling resulted in reversal of positive aldehyde test. isolated leishmanial lymphadenopathy in an immunocompetent person, is a rare manifestation of leishmaniasis in india. the possible role of transplacental ...201121538958
synthesis and evaluation of monoamidoxime derivatives: toward new antileishmanial compounds.a new series of monoamidoxime derivatives was synthesized using manganese(iii) acetate by microwave irradiation. several amidoximes (27-31, 33, 38) showed valuable in vitro activities toward leishmania donovani promastigotes, exhibiting ic(50) values between 5.21 and 7.89 μm. in parallel, the cytotoxicity of these compounds was evaluated on murine j774a.1 cells, revealing the corresponding selectivity index (si). among the 13 tested compounds, 4 monoamidoximes (27-30) exhibited an si more than 2 ...201121555166
natural leishmania donovani/leishmania aethiopica hybrids identified from ethiopia.natural hybridization events have been demonstrated between closely and distantly related leishmania groups despite a predominantly clonal and endogamically sexual mode of reproduction. here we report the first natural hybrid between leishmania aethiopica and leishmania donovani, as evidenced from the analysis of several clones from strain mhom/et/94/abauy. targeted species-identification pcrs revealed the presence of both genotypes, and amplified fragment length polymorphisms indicated that the ...201121558020
intracellular eukaryotic parasites have a distinct unfolded protein response.insult to the endoplasmic reticulum (er) activates the unfolded protein response (upr), a set of signaling pathways that protect the cell from the potential damage caused by improperly folded proteins. accumulation of misfolded proteins in the er lumen initiates a series of signal transduction events via activation of three transmembrane er proteins: ire1, atf6 and perk. activation of these proteins results in the transcriptional up-regulation of the components of the folding, trafficking and de ...201121559456
mtor signaling pathway regulates the il-12/il-10 axis in leishmania donovani infection.leishmania-induced interleukin-12 (il-12) expression is negatively regulated by the phosphatidylinositol 3-kinase (pi3k) and extracellular signal regulated kinase (erk) 1/2 pathways in human monocyte derived macrophages (mdms). to extend these studies, we examined the pathways downstream from pi3k in l. donovani-induced reciprocal regulation of il-12/il-10 axis in thp-1-derived macrophages. we show for the first time that in thp-1-derived macrophages and human monocytes, mtor inhibition by rapam ...201121567173
antimicrobial, anti-inflammatory, antiparasitic, and cytotoxic activities of galium mexicanum.ethnopharmacological relevance: to study the potential benefit of the traditional mexican medicinal plant galium mexicanum kunth (rubiaceae). hexane, chloroform, and methanol extracts as well as various fractions from these extracts were tested to determine antibacterial, antifungal, antiparasitic or anti-inflammatory activities in vitro. materials and methods: aerial parts of the plant were extracted with various solvents and fractionated accordingly. their antibacterial and antifungal activiti ...201121586319
incidence of visceral leishmaniasis in the vaishali district of bihar, india: spatial patterns and role of inland water bodies.the role of the distribution of inland water bodies with respect to the transmission of visceral leishmaniasis (vl) and its dominant vector, phlebotomous argentipes, has been studied at the regional scale in bihar, eastern india. the landsat tm sensor multispectral scanning radiometer, with a spatial resolution of 30 m in the visible, reflective-infrared and shortwave-infrared (swir) bands, was used to identify water bodies using the normalized differential pond index (ndpi) calculated as follow ...201121590671
the paratransgenic sand fly: a platform for control of leishmania transmission.abstract: background: leishmania donovani is transmitted by the bite of the sand fly, phlebotomus argentipes. this parasite is the agent of visceral leishmaniasis (vl), an endemic disease in bihar, india, where prevention has relied mainly on ddt spraying. pesticide resistance in sand fly populations, environmental toxicity, and limited resources confound this approach. a novel paratransgenic strategy aimed at control of vectorial transmission of l. donovani is presented using bacillus subtilis, ...201121595907
study of parasite kinetics with antileishmanial drugs using real-time quantitative pcr in indian visceral leishmaniasis.objectives this study describes parasite kinetics in the blood of visceral leishmaniasis patients treated with liposomal amphotericin b (l-amb) or a preformed fat emulsion of amphotericin b (apl) using real-time quantitative pcr (qpcr). methods forty-six patients were treated with a single dose (15 mg/kg of body weight) of either l-amb (n = 13) or apl (n = 33). qpcr was used to estimate parasite kinetics by detection of leishmania donovani dna using kinetoplast dna-specific primers in peripheral ...201121609983
nano-structured nickel oxide based dna biosensor for detection of visceral leishmaniasis (kala-azar).sol-gel synthesized nickel oxide (nio) film deposited onto indium tin oxide (ito) coated glass plate has been utilized for the development of sensitive and stable dna biosensor and demonstrated for diagnosis of visceral leishmaniasis also known as kala-azar. leishmania specific sensor is developed by immobilizing 23mer dna sequence (oligonucleotide) identified from 18s rrna gene sequences from leishmania donovani. characterization studies like x-ray diffraction and scanning electron microscopy r ...201121611668
mannosylated liposomes bearing amphotericin b for effective management of visceral leishmaniasis.the cationic and mannosylated liposomes were prepared using the cast film method and compared for their antileishmaniasis activity. the surface of the amphotericin b (amp b)-bearing cationic multilamellar liposomes was covalently coupled with p-aminophenyl-α-d-mannoside using glutaraldehyde as a coupling agent, which was confirmed by agglutination of the vesicles with concanavalin a. the prepared liposomes were characterized for shape, size, percent drug entrapment, vesicle count, zeta potential ...201121612342
an unusual case of amphotericin b refractoriness in visceral leishmaniasis from a non-endemic region of india.a patient with visceral leishmaniasis showing inadequate response to amphotericin-b belonging to non-endemic region is reported, with l. donovani showing increased tolerance to amphotericin-b in vivo. four snps, detected in the cysteine proteinase b gene, resulted in changes to the deduced amino acid sequence: valine→alanine, arginine→leucine. over and under expression of protein/s was observed in 65-80 kda range and 20 kda, respectively.201121613432
antiprotozoal, antitubercular and cytotoxic potential of cyanobacterial (blue-green algal) extracts from ireland.cyanobacteria (= blue-green algae) are prolific producers of structurally distinct and biologically active metabolites. in the continuation of our search for new sources of anti-infective natural products, we have assessed the in vitro antiprotozoal (plasmodium falciparum, trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani) and antitubercular (mycobacterium tuberculosis) potential of samples of two terrestrial cyanobacteria, nostoc commune (collected when desiccated and wet) and rivul ...201121615033
leishmania aethiopica: development of specific and sensitive pcr diagnostic test.pcr has proved useful for rapid diagnosis and typing of leishmania. lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. previously developed primers either require pcr-rflp analysis for leishmania aethiopica discrimination or lack sensitivity to detect l. aethiopica from clinical samples. here we report the development and validation of l. aethiopica specific pcr primers (v5f/v10r) based on cysteine protease b (cpb), a ...201121616071
endogenous il-13 plays a crucial role in liver granuloma maturation during leishmania donovani infection, independent of il-4r{alpha}-responsive macrophages and neutrophils.previous studies comparing interleukin 4 receptor α (il-4rα)(-/-) and interleukin 4 (il-4)(-/-) balb/c mice have indicated that interleukin 13 (il-13), whose receptor shares the il-4rα subunit with il-4, plays a protective role during visceral leishmaniasis. we demonstrate that il-13(-/-) balb/c mice were less able to control hepatic growth of leishmania donovani compared with wild-type mice. this correlated with significantly retarded granuloma maturation in il-13(-/-) mice, defective interfero ...201121628656
disseminated cutaneous leishmaniasis resembling post-kala-azar dermal leishmaniasis caused by leishmania donovani in three patients co-infected with visceral leishmaniasis and human immunodeficiency virus/acquired immunodeficiency syndrome in ethiopia.abstract. we report paired strains of leishmania parasites, one from the viscera and the other from skin lesions that were isolated from three patients with visceral leishmaniasis and disseminated cutaneous leishmaniasis that were co-infected with human immunodeficiency virus. the causative parasites were characterized by polymerase chain reaction-restriction length polymorphism of the ribosomal dna internal transcribed spacer 1 and by a panel of multilocus microsatellite markers. we demonstrate ...201121633027
identification of a functional type ia topoisomerase, ldtopiiiβ, from kinetoplastid parasite leishmania donovani.dna topoisomerases of kinetoplastids represent a family of dna processing enzymes that essentially solve the topological problems not only in nuclear dna but also in kinetoplast dna. we have, for the first time, identified a leishmania donovani homologue of bacterial and eukaryotic ia type of topoisomerase iii protein and termed as ldtopiiiβ. complementation study of wild-type and mutant ldtopiiiβ with slow-growing topoisomerase iii mutant yeast s. cerevisiae revealed the functional conservation ...201121637326
visualisation of leishmania donovani fluorescent hybrids during early stage development in the sand fly vector.the leishmania protozoan parasites cause devastating human diseases. leishmania have been considered to replicate clonally, without genetic exchange. however, an accumulation of evidence indicates that there are inter-specific and intra-specific hybrids among natural populations. the first and so far only experimental proof of genetic exchange was obtained in 2009 when double drug resistant leishmania major hybrids were produced by co-infecting sand flies with two strains carrying different drug ...201121637755
efficacy of leishmania donovani ribosomal p1 gene as dna vaccine in experimental visceral leishmaniasis.the acidic ribosomal proteins of the protozoan parasites have been described as prominent antigens during human disease. we present here data showing the molecular cloning and protective efficacy of p1 gene of leishmaniadonovani as dna vaccine. the pcr amplified complete orf cloned in either pqe or pvax vector was used either as peptide or dna vaccine against experimentally induced visceral leishmaniasis in hamsters. the recombinant protein rldp1 was given along with freund's adjuvant and the pl ...201121640106
survey of domestic cattle for anti-leishmania antibodies and leishmania dna in a visceral leishmaniasis endemic area of bangladesh.visceral leishmaniasis (vl), caused by an intracellular parasite leishmania donovani in the indian subcontinent, is considered to be anthroponotic. the role of domestic animals in its transmission is still unclear. although cattle are the preferred blood host for phlebotomus argentipes, the sandfly vector of vl in the indian subcontinent, very little information is available for their role in the disease transmission. in this study, we examined domestic cattle for serological and molecular evide ...201121651757
foxp3 and il-10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (pkdl) patients.post kala-azar dermal leishmaniasis (pkdl), a sequel to visceral leishamaniasis (vl) in 5-15% cases, constitutes a parasite reservoir important in disease transmission. the precise immunological cause of pkdl outcome remains obscure. however, overlapping counter regulatory responses with elevated ifn-γ and il-10 are reported.201121655313
quantitative structure-activity relationship study of phloroglucinol-terpene adducts as anti-leishmanial agents.phloroglucinol class of natural products occur widely in myrtaceae family and possess variety of biological activities viz. antimicrobial, antimalarial, cancer chemopreventive, anti-hiv and anti-leishmanial. in the present article, quantitative structure-activity relationship (qsar) study was carried out for a series of phloroglucinol-terpene adducts exhibiting anti-leishmanial activity to find out the structural features which are crucial for the biological activity. the qsar study was carried ...201121665468
comparative microsatellite typing of new world leishmania infantum reveals low heterogeneity among populations and its recent old world origin.leishmania infantum (syn. l. chagasi) is the causative agent of visceral leishmaniasis (vl) in the new world (nw) with endemic regions extending from southern usa to northern argentina. the two hypotheses about the origin of vl in the nw suggest (1) recent importation of l. infantum from the old world (ow), or (2) an indigenous origin and a distinct taxonomic rank for the nw parasite. multilocus microsatellite typing was applied in a survey of 98 l. infantum isolates from different nw foci. the ...201121666787
the 8-aminoquinoline analogue sitamaquine causes oxidative stress in leishmania donovani promastigotes by targeting succinate dehydrogenase.the 8-aminoquinoline analogue sitamaquine (sq) is an oral antileishmanial drug currently undergoing phase 2b clinical trials for the treatment of visceral leishmaniasis. in the present study, we investigated the mechanism of action of this drug in leishmania donovani promastigotes. sq causes a dose-dependent inhibition of complex ii (succinate dehydrogenase) of the respiratory chain in digitonin-permeabilized promastigotes, together with a drop in intracellular atp levels and a decrease of the m ...201121670183
role of fine-needle aspiration cytology in the prompt diagnosis of recurrence of visceral leishmaniasis presented as isolated cervical leishmanial lymphadenopathy.we report a case of isolated cervical leishmanial lymphadenopathy diagnosed by fine-needle aspiration cytology (fnac) in apparently cured case of visceral leishmaniasis. a 28-year-old female presented with cervical lymphnode enlargement to surgery outpatient department and was subjected for fnac. smear showed numerous leishmania donovani bodies in the cytoplasm of macrophages and giant cells, and extracellular spaces. she was treated by amphotericin b for alternate 14 days and the size of the ly ...201121671412
improved treatment of visceral leishmaniasis (kala-azar) by using combination of ketoconazole, miltefosine with an immunomodulator-picroliv.visceral leishmaniasis (vl) caused by the parasite leishmania donovani, is a potentially fatal disease. it is characterized by prolonged fever, enlarged spleen and liver, substantial weight loss and progressive anemia. available drugs are toxic, costly and require prolonged treatment duration viz; 28 days of oral treatment with miltefosine, 30 days infusion with amphotericin b and 21 days intramascular with paromomycin sulfate. drug combination for vl clinically proved to shorten the duration of ...201121679679
exclusion of synaptotagmin v at the phagocytic cup by leishmania donovani lipophosphoglycan results in decreased promastigote internalization.regulators of membrane fusion play an important role in phagocytosis, as they regulate the focal delivery of endomembrane that is required for optimal internalization of large particles. during internalization of leishmania promastigotes, the surface glycolipid lipophosphoglycan (lpg) is transferred to the macrophage membrane and modifies its fusogenic properties. in this study, we investigated the impact of lpg on the recruitment of the exocytosis regulator synaptotagmin v (syt v) at the area o ...201121680635
anti-leishmanial activity of disubstituted purines and related pyrazolo[4,3-d]pyrimidines.we report here results of screening directed to finding new anti-leishmanial drugs among 2,6-disubstituted purines and corresponding 3,7-disubstituted pyrazolo[4,3-d]pyrimidines. these compounds have previously been shown to moderately inhibit human cyclin-dependent kinases. since some compounds reduced viability of axenic amastigotes of leishmania donovani, we screened them for interaction with recombinant leishmanial cdc-2 related protein kinase (crk3/cyc6), an important cell cycle regulator o ...201121683592
ca(2+)-activated transbilayer movement of plasma membrane phospholipids in leishmania donovani during ionomycin or thapsigargin stimulation.the protozoan parasite leishmania causes serious infections in humans all over the world. after being inoculated into the skin through the bite of an infected sandfly, leishmania promastigotes must gain entry into macrophages to initiate a successful infection. specific, surface exposed phospholipids have been implicated in leishmania-macrophage interaction but the mechanisms controlling and regulating the plasma membrane lipid distribution remains to be elucidated. here, we provide evidence for ...201121684309
visceral leishmaniasis: adult population of abbottabad at risk now.leishmaniasis is a disease complex caused by the parasite of genus leishmania. visceral leishmaniasis is caused by leishmania donovani transmitted to human by sand fly. some wild animals and human reservoir is the major reservoir in most of the cases. the disease is prevalent in different parts of the world including india, nepal, bangladesh, sudan and brazil. it has also been reported from northern half of pakistan. in hazara division, it has been reported from galiat, battagram, kaladhaka, koh ...201021702307
compartment-specific remodeling of splenic micro-architecture during experimental visceral leishmaniasis.progressive splenomegaly is a hallmark of visceral leishmaniasis in humans, canids, and rodents. in experimental murine visceral leishmaniasis, splenomegaly is accompanied by pronounced changes in microarchitecture, including expansion of the red pulp vascular system, neovascularization of the white pulp, and remodeling of the stromal cell populations that define the b-cell and t-cell compartments. here, we show that ly6c/g(+) (gr-1(+)) cells, including neutrophils and inflammatory monocytes, ac ...201121703391
uncoupling protein 2 negatively regulates mitochondrial reactive oxygen species generation and induces phosphatase-mediated anti-inflammatory response in experimental visceral leishmaniasis.to reside and multiply successfully within the host macrophages, leishmania parasites impair the generation of reactive oxygen species (ros), which are a major host defense mechanism against any invading pathogen. mitochondrial uncoupling proteins are associated with mitochondrial ros generation, which is the major contributor of total cellular ros generation. in the present study we have demonstrated that leishmania donovani infection is associated with strong upregulation of uncoupling protein ...201121705615
identification of substrates of an s-phase cell cycle kinase from leishmania donovani.despite the importance of cyclin-cdk related kinases (crk) in regulation of cell and life cycle of kinetoplastida parasites, only limited knowledge about their substrates are presently available. here, the potential substrates were searched for an s-phase ldcyc1-crk3 complex from leishmania donovani based on the presence of cdk target phosphorylation site together with the cyclin interacting cy-motif in genome-derived putative protein sequences. three substrates could be identified with one of t ...201121708149
encecalol angelate, an unstable chromene from ageratum conyzoides l.: total synthesis and investigation of its antiprotozoal activity.in agreement with ethnomedicinal reports, the dichloromethane extract of ageratum conyzoides l. (asteraceae) was recently shown to be of considerable activity against trypanosoma brucei rhodesiense, the etiologic agent of east african human trypanosomiasis (east african sleeping sickness). isolated compounds, namely, methoxylated flavonoids as well as the chromene derivative encecalol methyl ether, were less active than the crude extract. the activity of the extract was found to decrease conside ...201121708240
atypical lesions as a sign of cutaneous dissemination of visceral leishmaniasis in a human immunodeficiency virus-positive patient simultaneously infected by two viscerotropic leishmania species.leishmaniasis is considered an emerging opportunistic disease in human immunodeficiency virus (hiv)-infected patients who have considerably variable clinical presentation. we report a patient with visceral leishmaniasis who had unexpected clinical aspects (atypical cutaneous lesions appearing after long-term evidence of visceral parasites). the patient had hepatoesplenomegaly in the absence of fever, but was otherwise generally healthy. the hiv viral load was low despite severe immunossupression ...201121734124
differential expression of proteins in antimony-susceptible and -resistant isolates of leishmania donovani.visceral leishmaniasis (vl) is a parasitic disease caused by the protozoan parasite leishmania donovani. resistance to pentavalent antimonials (sbv), the mainstay therapy for leishmaniasis is now a major concern, due to emergence of drug resistance. hence, understanding the underlying mechanism of resistance to antimonials is required. here we used quantitative mass spectrometery to identify global proteome differences between antimony-susceptible/-resistant isolates. we detected modification of ...201121736901
the in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant leishmania species of brazil.the in vitro leishmanicidal activity of miltefosine-« (zentaris gmbh) was assessed against four medically relevant leishmania species of brazil: leishmania (leishmania) amazonensis, leishmania (viannia) braziliensis, leishmania (viannia) guyanensis and leishmania (leishmania) chagasi. the activity of miltefosine against these new world species was compared to its activity against the old world strain, leishmania (leishmania) donovani, which is known to be sensitive to the effects of miltefosine. ...201121739037
miltefosine induces programmed cell death in leishmania amazonensis promastigotes.in the current study, we evaluated the mechanism of action of miltefosine, which is the first effective and safe oral treatment for visceral leishmaniasis, in leishmania amazonensis promastigotes. miltefosine induced a process of programmed cell death, which was determined by the externalization of phosphatidylserine, the incorporation of propidium iodide, cell-cycle arrest at the sub-g0/g1 phase and dna fragmentation into oligonucleosome-sized fragments. despite the intrinsic variation that is ...201121739043
molecular factors governing inhibition of arylimidamides against leishmania: conservative computational modeling to improve chemotherapies.a dataset of 55 compounds with inhibitory activity against leishmania donovani axenic amastigotes and leishmania amazonensis intracellular parasites was examined through three-dimensional quantitative structure-activity relationship modeling employing molecular descriptors from both rigid and flexible compound alignments. for training and testing purposes, the compounds were divided into two datasets of 45 and 10 compounds, respectively. statistically significant models were constructed and vali ...201121741248
genetic and functional evidence implicating dll1 as the gene that influences susceptibility to visceral leishmaniasis at chromosome 6q27.visceral leishmaniasis (vl) is caused by leishmania donovani and leishmania infantum chagasi. genome-wide linkage studies from sudan and brazil identified a putative susceptibility locus on chromosome 6q27.201121742847
antiprotozoal activities of organic extracts from french marine seaweeds.marine macrophytes contain a variety of biologically active compounds, some reported to have antiprotozoal activity in vitro. as a part of a screening program to search for new natural antiprotozoals, we screened hydroalcoholic and ethyl acetate extracts of 20 species of seaweeds from three phyla (rhodophyta, heterokontophyta and chlorophyta), sampled along the normandy (france) coast. we tested them in vitro against the protozoa responsible for three major endemic parasitic diseases: plasmodium ...201121747738
novel betulin derivatives as antileishmanial agents with mode of action targeting type ib dna topoisomerase.towards developing antileishmanial agents with mode of action targeted to dna topoisomerases of leishmania donovani, we have synthesized a large number of derivatives of betulin. the compound, a natural triterpene isolated from the cork layer of betula plants exhibits several pharmacological properties. three compounds viz. disuccinyl betulin, diglutaryl dihydrobetulin and disuccinyl dihydrobetulin inhibit growth of the parasite as well as relaxation activity of the enzyme type ib topoisomerase ...201121750153
in vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against leishmania donovani in balb/c mice.the in vitro and in vivo activity of diminazene (dim), artesunate (art) and combination of dim and art (dim-art) against leishmania donovani was compared to reference drug; amphotericin b. ic50 of dim-art was found to be 2.28 ± 0.24 µg/ml while those of dim and art were 9.16 ± 0.3 µg/ml and 4.64 ± 0.48 µg/ml respectively. the ic50 for amphot b was 0.16 ± 0.32 µg/ml against stationary-phase promastigotes. in vivo evaluation in the l. donovani balb/c mice model indicated that treatments with the c ...201121755234
easy test for visceral leishmaniasis and post-kala-azar dermal leishmaniasis.to the editor: diagnosis of visceral leishmaniasis (vl), fatal if untreated, is complex because the symptoms are the same for many fever-associated ailments. despite limitations, diagnosis remains based on finding leishmania amastigotes in spleen and/or bone marrow aspirates (1). sophisticated laboratory methods, although sensitive, are costly. the immunochromatographic strip test that uses recombinant k39 antigen (rk39), although satisfactory in india, is less sensitive in africa, latin america ...201121762596
aircraft and risk of importing a new vector of visceral leishmaniasis.to the editor: kala-azar, or visceral leishmaniasis, is a parasitic disease that leads to fever, anemia, and hepatosplenomegaly. death is the usual outcome when infection is not treated. the majority of infections are caused by the protozoan leishmania donovani, restricted to india and eastern africa, but the most widespread are caused by l. infantum, found from people's republic of china to the new world, where it infects humans, dogs, and wild canids. all mediterranean countries are affected b ...201121762613
cytomegalovirus and leishmania donovani coinfection in a renal allograft recipient.infection is a leading cause of death in renal allograft recipients. apart from the immunosuppressive drugs, immunomodulatory viral infections also predispose the recipient to many opportunistic infections. kala-azar in renal allograft recipients is infrequently reported even in endemic areas. in majority of cases, there was delay in diagnosis and treatment. we report a case of renal allograft recipient, where we faced a diagnostic dilemma because of coinfection of cytomegalovirus and visceral l ...201121769179
detection of urinary antigens and their seroreactivity with serum of patients in leishmania donovani infection.to detect leishmanial antigens in pre and post treated urine of visceral leishmaniasis (vl) patients.201121771678
early activated th-1 type and dominantly diverse natural killer t (cd3(+)cd161(+)va24(-)) cells in bone marrow among visceral leishmaniasis patients.lipid antigens of leishmania donovani-like lipophosphoglycans (lpg) are demonstrated to be a potent ligand for natural killer t (nkt) cell activation. little is known about the phenotype or function of these cells and their trafficking pattern to the bone marrow (bm) of visceral leishmaniasis (vl) patients. their precise role in humans still requires pathological validation. the study included 42 parasitologically confirmed patients (mean age 24.80±16.26years; range 3-70years; 25 males and 17 fe ...201121787777
antiparasitic activity of c-geranyl flavonoids from mimulus bigelovii.bioactivity-directed fractionation of the meoh fraction of the extract of mimulus bigelovii by means of an axenic leishmania amastigote assay and chromatographic techniques resulted in the isolation of four c-geranyl flavanones, diplacone (1), 3'-o-methyldiplacone (2), 4'-o-methyldiplacone (3), 3'-o-methyldiplacol (4), together with a geranylated flavone, cannflavin a (5). these compounds were separated from m. bigelovii for the first time. all compounds showed moderate antileishmanial activity ...201121796699
human visceral leishmaniasis: decrease in serum cholesterol as a function of splenic parasite load. 201121801506
formylated phloroglucinols from eucalyptus loxophleba foliage.two new naturally occurring formylated phloroglucinol compounds (fpcs), a dimer, loxophlebal b (10) and a cyclized fpc, loxophlebene (8) together with eight other formylated phloroglucinols (1-7 and 9) were isolated from the chloroform-methanol (8:2) extract of the leaves of eucalyptus loxophleba ssp. lissophloia. the structures of new compounds were established by comprehensive spectral analysis and by comparison of their nmr data with those of related compounds in the literature. all the isola ...201121803129
knockdown of ldmc1 and hsp70 by antisense oligonucleotides causes cell-cycle defects and programmed cell death in leishmania donovani.programmed cell death (pcd) has important implications in the biology of unicellular parasites, especially in devising control strategies against them. in this study, we examined the role of metacaspase ldmc1 and heat shock protein hsp70 in leishmania donovani through transient gene knockdown using antisense oligonucleotides (asos), during mg132-induced pcd. proteasome inhibitor mg132 was used for inducing pcd in the in vitro culture of leishmania donovani, which was confirmed by morphological a ...201121805355
differential regulation of the immune response in the spleen and liver of mice infected with leishmania donovani.immunity to pathogens requires generation of effective innate and adaptive immune responses. leishmania donovani evades these host defense mechanisms to survive and persist in the host. a better understanding and identification of mechanisms that l. donovani employs for its survival is critical for developing novel therapeutic interventions that specifically target the parasite. this paper will highlight some of the mechanisms that the parasite utilizes for its persistence and also discuss how t ...201221811511
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