Publications

cutaneous pseudolymphoma in association with leishmania donovani.		2007	17714564
in vivo studies on the antileishmanial activity of buparvaquone and its prodrugs.	the efficacy of different formulations of the naphthoquinone buparvaquone and two phosphate prodrugs in in vivo models of both visceral and cutaneous leishmaniasis is described.	2007	17715126
characterization of metacaspases with trypsin-like activity and their putative role in programmed cell death in the protozoan parasite leishmania.	in this report, we have characterized two metacaspases of leishmania donovani, l. donovani metacaspase-1 (ldmc1) and ldmc2. these two proteins show 98% homology with each other, and both contain a characteristic c-terminal proline-rich domain. both genes are transcribed in promastigotes and axenic amastigotes of l. donovani; however, ldmc1 shows increased mrna levels in axenic amastigotes. an anti-ldmc antibody was obtained and showed reactivity with a single approximately 42-kda protein band in ...	2007	17715367
in vitro activity of an essential oil against leishmania donovani.	the in vitro antileishmanial effect of the essential oil from chenopodium ambrosioides against leishmania donovani was investigated. the product showed significant activity against promastigotes and amastigotes, with a 50% effective concentration of 4.45 and 5.1 microg/ml, respectively. the essential oil caused an irreversible inhibition of the growth of promastigotes after a treatment with 100 or 10 microg/ml for 1 or 24 h, respectively. the phagocytic activity of the macrophages was preserved ...	2007	17724767
first detection and genetic typing of leishmania infantum mon-24 in a dog from the moroccan mediterranean coast: genetic diversity of mon-24.	as in the countries edging the mediterranean basin, leishmania infantum zymodeme mon-1 is the main causative agent of visceral leishmaniasis in morocco, where visceral leishmaniasis is most active in the north-eastern slopes of the rif mountains. the dog was confirmed to be the main reservoir of l. infantum mon-1, while the reservoir of l. infantum mon-24 causative agent of both infantile visceral leishmaniasis and cutaneous leishmaniasis has not yet been identified. here we report the first det ...	2007	17603990
visceral leishmaniasis: a threat to immunocompromised patients in non-endemic areas?	visceral leishmaniasis is rare in western europe, but may be life-threatening in immunocompromised patients. it is therefore important to understand the incidence of the disease in a non-endemic area and its relationship with immunosuppressive conditions. between 1990 and 2005, 12 patients were diagnosed with leishmaniasis at basel university hospital, switzerland. eleven presented with visceral symptoms and ten had an underlying immunosuppressive condition. since increasing numbers of immunosup ...	2007	17610597
increased levels of thiols protect antimony unresponsive leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony.	the current trend of antimony (sb) unresponsiveness in the indian subcontinent is a major impediment to effective chemotherapy of visceral leishmaniasis (vl). although contributory mechanisms studied in laboratory-raised sb-r parasites include an up-regulation of drug efflux pumps and increased thiols, their role in clinical isolates is not yet substantiated. accordingly, our objectives were to study the contributory role of thiols in the generation of sb unresponsiveness in clinical isolates. p ...	2007	17612420
antileishmanial efficacy of amphotericin b bearing emulsomes against experimental visceral leishmaniasis.	amphotericin b (amb) was formulated in trilaurin-based emulsomes (nanosize lipid particles) stabilized by soya phosphatidylcholine (pc), as a new delivery system for macrophage targeting for the treatment of visceral leishmaniasis (vl). emulsomes were modified by coating them with macrophage-specific ligand (o-palmitoyl mannan, opm). the antileishmanial activity of amb-deoxycholate (amb-doc) and emulsome entrapped amb was tested in vitro in leishmania donovani infected macrophage-amastigote syst ...	2007	17613662
synthesis, biological evaluation, and molecular modeling of 3,5-substituted-n1-phenyl-n4,n4-di-n-butylsulfanilamides as antikinetoplastid antimicrotubule agents.	dinitroanilines are of interest as antiprotozoal lead compounds because of their selective activity against the tubulin of these organisms, but concern has been raised due to the potentially mutagenic nitro groups. analogues of n(1)-phenyl-3,5-dinitro-n(4),n(4)-di-n-butylsulfanilamide (gb-ii-150, compound 2b), a selective antimitotic agent against african trypanosomes and leishmania, have been prepared where the nitro groups are replaced with amino, chloro, cyano, carboxylate, methyl ester, amid ...	2007	17618122
first case of indigenous visceral leishmaniasis from central india.	visceral leishmaniasis is endemic in the eastern states of india, but central india remains free of leishmaniais. this report describes the first indigenous case of visceral leishmaniasis in a seven-year-old girl from central india. the child presented with fever for 10 days and was diagnosed by bone marrow examination, serology using rke16 and rk39 antigens, and a polymerase chain reaction specific for the kinesin gene. sequencing of the immunodominant region of the kinesin gene of the parasite ...	2007	17620636
comparison of conventional methods for diagnosis of visceral leishmaniasis in children of the center-west region of brazil.	in brazil, sophisticated techniques currently employed for diagnosis of visceral leishmaniasis, such as polymerase chain reaction-based assays, are only available in major research centers, whereas conventional methods are still used in many areas where the disease occurs. in the state of mato grosso do sul, in the country's center-west region, visceral leishmaniasis has recently emerged in many cities, and duration of the disease, from the onset of symptoms to diagnosis, has been short. conside ...	2007	17625737
visceral leishmaniasis diagnosed on duodenal biopsy.		2007	17628327
inactivation of the miltefosine transporter, ldmt, causes miltefosine resistance that is conferred to the amastigote stage of leishmania donovani and persists in vivo.	miltefosine (hexadecylphosphocholine) is the first oral antileishmanial drug. in this study, we addressed the question whether miltefosine-resistant leishmania donovani promastigotes transform to miltefosine-resistant amastigotes. a promastigote line, m-mutr, showed defective internalisation of miltefosine owing to mutations in ldmt, similar to previously described resistant lines. m-mutr parasites were infective to macrophages in vitro as well as in balb/c mice in vivo. there was good correlati ...	2007	17628445
evolutionary and geographical history of the leishmania donovani complex with a revision of current taxonomy.	leishmaniasis is a geographically widespread severe disease, with an increasing incidence of two million cases per year and 350 million people from 88 countries at risk. the causative agents are species of leishmania, a protozoan flagellate. visceral leishmaniasis, the most severe form of the disease, lethal if untreated, is caused by species of the leishmania donovani complex. these species are morphologically indistinguishable but have been identified by molecular methods, predominantly multil ...	2007	17517634
the utility of exoantigens for detection of leishmania infections.	exoantigens released by leishmania promastigotes were the subject of a workshop held in mombasa, kenya. investigators from the walter reed army institute of research (silver spring, maryland) met with scientists from government and academic institutes and industry to review the current global status of leishmaniasis and to explore the potential role of exoantigens in the detection of leishmania in the vertebrate host and arthropod vector. some encouraging data, particularly in the immunodiagnosi ...	2007	17521094
leishmania donovani iron superoxide dismutase a is targeted to the mitochondria by its n-terminal positively charged amino acids.	many reports have shown that leishmania species are susceptible to reactive oxygen species (ros) and reactive nitrogen species (rns)-mediated killing. the superoxide dismutase (sod) is one of the antioxidant defense enzymes important for parasite survival through its detoxification of superoxide into hydrogen peroxide and oxygen. the mitochondria produce numerous superoxide radicals as a by-product of cellular respiration and hence targeting of sods to the mitochondria is critical in maintaining ...	2007	17524502
synthesis and in vitro protozoocidal activity of diazabicyclic benzotropolone derivatives.	we describe the synthesis and protozoocidal evaluation of a series of diazabicycles based on benzotropolone ethers. several of the compounds, which can be obtained through a high-yielding hetero diels-alder reaction using simple and readily available starting materials, have in vitro activities against trypanosoma cruzi and leishmania donovani that are comparable to, and in some cases better than, those of currently used chemotherapies.	2007	17532634
autochthonous visceral leishmaniasis: a report of a second case in thailand.	visceral leishmaniasis (vl) is a rare disease in thailand. only one previous case has been reported in which transmission was likely autochthonous. we conducted an investigation of a case of vl, which included serological and symptom surveys of people who lived near the case in nan province and bangkok, serological surveys of domestic animals in his home village and sand fly surveys in his home village and in bangkok. no humans interviewed met our case definition for possible vl. one hundred thi ...	2007	17539239
leishmania donovani and cutaneous leishmaniasis, sri lanka.	to investigate the relationship of cutaneous leishmaniasis isolates from sri lanka to known species, we performed dna sequencing and microsatellite analyses. we identified leishmania donovani as the agent of sri lanka cutaneous leishmaniasis and showed that these parasites are closely related to those causing visceral leishmaniasis in the indian subcontinent.	2007	17552105
kala-azar control, uganda.		2007	17552117
amino acid residues of leishmania donovani cyclophilin key to interaction with its adenosine kinase: biological implications.	cyclophilins (cyps), by interacting with a variety of proteins, often modulate their biological activities and thus have been implicated in several cellular functions. however, mechanisms that determine such interactions are poorly understood. we earlier reported that an endoplasmic reticulum (er)-located cyclophilin (ldcyp) from the purine auxotrophic parasitic protozoan leishmania donovani reactivated its adenosine kinase (adk). the adk-reactivating property of ldcyp was however abolished at h ...	2007	17552497
transcriptome analysis during the process of in vitro differentiation of leishmania donovani using genomic microarrays.	leishmania donovani causes visceral disease (kala-azar), a major health problem throughout the tropics with 500 000 new cases every year. leishmania differentiates from the promastigote to the amastigote form to establish infection in a mammalian host. to understand the process of differentiation, we assessed the global variation in gene expression in promastigotes, an intermediate stage of differentiation (pa24) and axenic amastigotes in culture using an l. donovani genomic microarray with 4224 ...	2007	17553180
mrna cycling sequence binding protein from leishmania donovani (ldcsbp) is covalently modified by ubiquitination.	the lack of transcriptional regulation in trypanosomatids suggests the presence of distinct posttranscriptional mechanisms to control differential gene expression. in fact, the stability of s-phase specific mrnas in these parasites is determined primarily by the presence of the octanucleotide sequence (c/a)auagaa(g/a) in the utrs of the transcripts. here, the characterization of ldcsbp is reported, which specifically binds to the octanucleotide containing rna. the ldcsbp protein contains multipl ...	2007	17559572
a computational docking study for prediction of binding mode of diospyrin and derivatives: inhibitors of human and leishmanial dna topoisomerase-i.	a computational approach was utilized to study the relative binding modes of diospyrin (bisnaphthoquinonoid) with the crystal structure of human dna-topoi and the recently reported leishmania donavani dna-topoi. additionally, the binding site interactions of amino derivatives of diospyrin with human topoi were studied extensively. based on the docking results, binding modes of diospyrin with the human and leishmanial topoi catalytic core were predicted. the parallel use of two efficient and pred ...	2007	17562360
visceral leishmaniasis after allogeneic hematopoietic stem cell transplantation.		2007	17572716
injectable paromomycin for visceral leishmaniasis in india.	visceral leishmaniasis (kala-azar) affects large, rural, resource-poor populations in south asia, africa, and brazil. safe, effective, and affordable new therapies are needed. we conducted a randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin b, the present standard of care in bihar, india.	2007	17582067
tamoxifen is effective against leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring leishmania (leishmania) amazonensis amastigotes.	this study was performed to investigate the activity of tamoxifen, an antioestrogen widely used in the treatment of breast cancer, against leishmania.	2007	17584801
locally acquired visceral leishmaniasis in sri lanka.		2007	17585579
ornithine decarboxylase and s-adenosylmethionine decarboxylase in trypanosomatids.	the production of polyamines has been shown to be an effective target for a drug against the west african form of sleeping sickness caused by trypanosoma brucei gambiense. t. brucei belongs to the group of protozoan parasites classed as trypanosomatids. parasitic species of this group are the causative agents of various tropical diseases besides african sleeping sickness, e.g. chagas' disease (trypanosoma cruzi), cutaneous (lesihmania spp.) and visceral (leishmania donovani) leishmaniasis. the m ...	2007	17371268
amphotericin b-gum arabic conjugates: synthesis, toxicity, bioavailability, and activities against leishmania and fungi.	gum arabic, a branched polysaccharide consisting of more than 90% arabinogalactan having a molecular weight around 250,000 da is the oldest and best known of all natural gums. the objective of the present investigation was to examine whether amphotericin b (amb), the polyene antibiotic when conjugated to periodate oxidized gum arabic still retained its anti-fungal and anti-leishmanial activity and to evaluate its toxicity and bioavailability.	2007	17372682
sodium stibogluconate-sensitive visceral leishmaniasis in the non-endemic hilly region of uttarakhand, india.	although visceral leishmaniasis (vl) is endemic in various parts of india, mainly bihar, west bengal and orissa, and neighbouring countries such as nepal and bangladesh, it is rarely reported from the hilly areas of india. we report on nine male vl cases from the non-endemic garhwal region of uttarakhand who were treated successfully with sodium stibogluconate. we conclude that sodium stibogluconate-sensitive vl is emerging in this region and that urgent and effective vector control measures may ...	2007	17382981
the hunt for an elusive source of pyrexia in a foreign worker.	we report a 23-year-old bangladeshi man who presented with fever and hepatosplenomegaly. the initial laboratory findings were bicytopenia with elevated serum globulins. the diagnosis of visceral leishmaniasis (kala azar) was suspected. the parasite leishmania donovani was found on bone marrow aspiration. he was treated with liposomal amphotericin b and had a good response to treatment. the case highlights the need to be aware of this disease occurring in a foreign national from an endemic region ...	2007	17384865
splenic accumulation of il-10 mrna in t cells distinct from cd4+cd25+ (foxp3) regulatory t cells in human visceral leishmaniasis.	visceral leishmaniasis (vl) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. interleukin (il)-10 has been implicated in the suppression of host immunity in human vl based on the elevated levels of il-10 observed in plasma and lesional tissue, and its role in preventing clearance of leishmania donovani in murine models of vl. the aim of this study was to identify the cellular source of il-10 in human vl and determine if cd4(+)cd25(+ ...	2007	17389235
nk cell activation in visceral leishmaniasis requires tlr9, myeloid dcs, and il-12, but is independent of plasmacytoid dcs.	natural killer (nk) cells are sentinel components of the innate response to pathogens, but the cell types, pathogen recognition receptors, and cytokines required for their activation in vivo are poorly defined. here, we investigated the role of plasmacytoid dendritic cells (pdcs), myeloid dcs (mdcs), toll-like receptors (tlrs), and of nk cell stimulatory cytokines for the induction of an nk cell response to the protozoan parasite leishmania infantum. in vitro, pdcs did not endocytose leishmania ...	2007	17389237
hla class i-restricted t cell epitopes of the kinetoplastid membrane protein-11 presented by leishmania donovani-infected human macrophages.	visceral leishmaniasis is a protozoal disease caused by the intracellular parasites leishmania donovani and l. chagasi/infantum, and it is usually deadly if not treated. to date, no vaccine exists for prophylaxis or immunotherapy, nor has it been established which effector mechanisms of the immune system are most instrumental against the parasites. recent reports have suggested that cd8(+) t cells, in addition to cd4(+) t cells, might play major roles in the defense against infection and in the ...	2007	17397010
molecular architecture of leishmania ef-1alpha reveals a novel site that may modulate protein translation: a possible target for drug development.	elongation factor-1alpha plays an essential role in eukaryotic protein biosynthesis. recently, we have shown by protein structure modeling the presence of a hairpin-loop of 12 amino acids in mammalian ef-1alpha that is absent in the leishmania homologue [d. nandan, a. cherkasov, r. sabouti, t. yi, n.e. reiner, molecular cloning, biochemical and structural analysis of elongation factor-1 alpha from leishmania donovani: comparison with the mammalian homologue, biochem. biophys. res. commun. 302 (2 ...	2007	17397800
synthesis of isoquinuclidine analogs of chloroquine: antimalarial and antileishmanial activity.	the isoquinuclidine (2-azabicyclo[2.2.2]octane) ring system may be viewed as a semi-rigid boat form of the piperidine ring and, when properly substituted, a scaffold for rigid analogs of biologically active ethanolamines and propanolamines. it is present in natural products (such as ibogaine and dioscorine) that display interesting pharmacological properties. in this study, we have expanded our continuing efforts to incorporate this ring system in numerous pharmacophores, by designing and synthe ...	2007	17400457
circulating immune complexes (ic) and ic-induced levels of gm-csf are increased in sudanese patients with acute visceral leishmania donovani infection undergoing sodium stibogluconate treatment: implications for disease pathogenesis.	infection with leishmania donovani is associated with il-10 as well as with gm-csf. immune complexes (ic) exert important functions by stimulation of monocytes/macrophage-mediated production of pro- and anti-inflammatory cytokines in rheumatic diseases. in this investigation, we have explored ic-induced cytokine production during leishmania infection. sera from 43 patients with visceral leishmaniasis (vl), 17 patients with post-kala-azar dermal leishmaniasis, and 20 healthy sudanese controls wer ...	2007	17404324
[laryngeal leishmaniasis].	leishmaniasis consists in a zoonotic infection, that means affect animals. due to the puncture of the female sand fly type phlebotomus (ancient world) or lutzomya (new world) the human being can be also affected. the clinical manifestations are very varied, depending to factors related with host, vector and the proper parasit. in this present work, we expose the three unic cases of leishmaniasis affecting the larynx, diagnosticated in the sanitary area of toledo. due to the specific characterist ...	2007	17405455
a structural insight into the inhibition of human and leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane.	the critical role of polyamines in key processes such as cell growth, differentiation and macromolecular synthesis makes the enzymes involved in their synthesis potential targets in the treatment of certain types of cancer and parasitic diseases. here we present a study on the inhibition of human and leishmania donovani odc (ornithine decarboxylase), the first committed enzyme in the polyamine biosynthesis pathway, by apa (1-amino-oxy-3-aminopropane). the present study shows apa to be a potent i ...	2007	17407445
nuclear localization of an actin-related protein (orf lmjf21.0230) in leishmania+.		2007	17408765
how to diagnose and manage common parasitic pneumonias.	parasitic pneumonia is being increasingly reported from many parts of the world due to globalization and travel across the continents. this review outlines the recent developments in the diagnosis and management of parasitic pneumonias.	2007	17414130
dna vaccination against the parasite enzyme gamma-glutamylcysteine synthetase confers protection against leishmania donovani infection.	in this study the potential of using leishmania donovani gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, gamma-gcs) as a rational target for vaccine development was determined. mice, immunised with plasmid containing the full gene sequence for gamma-gcs (pvaxgammagcs) or plasmid alone (pvax control), were challenged with a high dose of l. donovani amastigotes to give a stringent test of the ability of the vaccine to protect against infection. vaccination with pvaxgammagcs resulted ...	2007	17418459
characterization of natural antimony resistance in leishmania donovani isolates.	clinical resistance to pentavalent antimonial compounds has long been recognized as a major problem in the treatment of visceral leishmaniasis in india. however, mechanisms of natural resistance are unclear. in this study, we observed that leishmania donovani clinical isolates not responsive to sodium stibogluconate showed resistance to antimony treatment in both in vitro and in vivo laboratory conditions. the resistant isolates have increased levels of intracellular thiols. this increase in thi ...	2007	17426170
synthesis, dna binding, and leishmania topoisomerase inhibition activities of a novel series of anthra[1,2-d]imidazole-6,11-dione derivatives.	nine novel anthra[1,2-d]imidazole-6,11-diones, differing in their side chain, were synthesized. uv-vis spectroscopy and viscometric titrations of these molecules with duplex dna were used to assess their binding with dna. five of the nine compounds showed high inhibition activity against topoisomerase i of leishmania donovani, with the one bearing the tetrazole side chain exhibiting an ic50 approximately 1 microm. the inhibition activities were not related with their dna binding affinity and dep ...	2007	17444624
aloe vera leaf exudate induces a caspase-independent cell death in leishmania donovani promastigotes.	leishmaniasis constitutes a complex of diseases with clinical and epidemiological diversity and includes visceral leishmaniasis, a disease that is fatal when left untreated. in earlier studies, the authors reported that aloe vera leaf exudate (avl) is a potent antileishmanial agent effective in promastigotes of leishmania braziliensis, leishmania mexicana, leishmania tropica, leishmania major and leishmania infantum and also in axenic amastigotes of leishmania donovani. in the present study, it ...	2007	17446285
antileishmanial 2-substituted quinolines: in vitro behaviour towards biological components.	quinolines substituted on their carbon 2 have in vivo antileishmanial activity but some of them could not be detected in plasma when assayed for pharmacokinetic studies, suggesting a sequestration of the drugs by components of the blood compartment. the present study, performed on three quinolines (1, 2 and 3), showed strong affinity for two of them (2 and 3) with red blood cells (rbcs), whereas quinoline 1 did not react with them. this process was saturable, temperature dependant and positively ...	2007	17459651
lack of cxcr3 delays the development of hepatic inflammation but does not impair resistance to leishmania donovani.	cxc chemokine receptor 3 (cxcr3) ligands cxcl9 and cxcl10 are produced at high levels in mice and humans infected with leishmania donovani, but their contribution to host resistance against l. donovani is not clear. here, using cxcr3(-/-) mice, we demonstrate that, although cxcr3 regulates early immune cell trafficking and hepatic inflammation during l. donovani infection, it is not essential for immunity against l. donovani, unlike l. major. cxcr3(-/-) c57bl/6 mice show a delayed onset of hepat ...	2007	17471442
chemotherapy of leishmaniasis part vi: synthesis and bioevaluation of some novel terpenyl s,n- and n,n-acetals.	some novel terpene based oxoketene s,n-acetals 2(a-g) and n,n-acetals 3(a-c) have been synthesized from oxoketene dithioacetal 1. the compounds were screened for their in vivo antileishmanial activity. some of the compounds showed 50-70% inhibition in the hamster model.	2007	17178176
safety trial using the leishmune vaccine against canine visceral leishmaniasis in brazil.	a group of 600 healthy and asymptomatic dogs from brazilian canine visceral leishmaniasis endemic areas was vaccinated with three sc doses of leishmune which is the industrialized formulation of the fml-saponin, recently licensed for commercialization in brazil, which previously showed 76-80% vaccine efficacy against canine visceral leishmaniasis. safety evaluation was performed for 14 days after each vaccine injection and disclosed transient reactions of local pain (40.87%), anorexia (20.48%), ...	2007	17239495
miltefosine affects lipid metabolism in leishmania donovani promastigotes.	miltefosine (hexadecylphosphocholine [hepc]) is the first orally active antileishmanial drug. transient hepc treatment of leishmania donovani promastigotes at 10 microm significantly reduced the phosphatidylcholine content and enhanced the phosphatidylethanolamine (pe) content in parasite membranes, suggesting a partial inactivation of pe-n-methyltransferase. phospholipase d activity did not seem to be affected by hepc. in addition, the enhancement of the lysophosphatidylcholine content could be ...	2007	17242145
indel-based targeting of essential proteins in human pathogens that have close host orthologue(s): discovery of selective inhibitors for leishmania donovani elongation factor-1alpha.	we propose a novel strategy for selective targeting of essential pathogen proteins that contain sizable indels (insertions/deletions) in their sequences compared with their host orthologues. this approach has been tested on elongation factor-1alpha (ef-1alpha) from the protozoan pathogen leishmania donovani. leishmania ef-1alpha is 82% identical to the corresponding human orthologue, but possesses a 12 aminoacid sequence deletion compared with human ef-1alpha. we used this indel-differentiated r ...	2007	17243179
limonoid orthoacetates and antiprotozoal compounds from the roots of pseudocedrela kotschyi.	the dicholoromethane extract of pseudocedrela kotschyi root demonstrated marked antileishmanial properties in preliminary screening of extracts from 21 species commonly used in malian traditional medicine. phytochemical investigation of the active extract yielded three novel phragmalin-type limonoid orthoacetates (1-3), named kotschyins a-c, and the known compounds 7-deacetylgedunin (4) and 7-deacetyl-7-oxogedunin (5). the structures of 1-3 were elucidated by analytical methods including 1d- and ...	2007	17253841
molecular dissection and expression of the ldk39 kinesin in the human pathogen, leishmania donovani.	in this study we show for the first time the intracellular distribution of a k39 kinesin homologue in leishmania donovani, a medically important parasite of humans. further, we demonstrated that this motor protein is expressed in both the insect and mammalian developmental forms (i.e. promastigote and amastigotes) of this organism. moreover, in both of these parasite developmental stages, immunofluorescence indicated that the ldk39 kinesin accumulated at anterior and posterior cell poles and tha ...	2007	17257310
the role of mannose receptor during experimental leishmaniasis.	the primary host cells for leishmania replication are macrophages (mp). several molecules on the surface of professional phagocytic cells have been implicated in the initial process of parasite internalization and initiation of signaling pathways. these pattern recognition receptors distinguish molecular patterns on pathogen surfaces. mannose receptor (mr), specifically, recognizes mannose residues on the surface of leishmania parasites. we studied the role of mr in the pathogenesis of experimen ...	2007	17261547
over-expression of leishmania major map kinases reveals stage-specific induction of phosphotransferase activity.	during the infectious cycle, protozoan parasites undergo various developmental transitions and switch virulence factors in response to extracellular signals in insect vectors and human hosts. despite the importance of environmental sensing in parasite pathogenicity, little is known about the pathways that transduce extracellular signals into stage-specific gene expression. here, we used a transgenic approach to gain insight into localisation and activity of three green fluorescence protein (gfp) ...	2007	17481635
age-influenced population kinetics and immunological responses of leishmania donovani in hamsters.	susceptibility of animals to infections depends upon various factors including sex and age of the host, which plays a pivotal role. in this communication, we have investigated the "intake" of leishmania donovani infection in young (3-4 weeks old) and adult (15-16 weeks old) golden hamsters. the splenic parasite load in young hamsters on day 15 post infection (p.i.) was 54 +/- 4 amastigotes/100 macrophage nuclei and increased to 106.3 +/- 3.5 on day 30 p.i. however, adult group showed 2.2-(p < 0. ...	2007	17484071
cutaneous leishmaniasis caused by leishmania tropica in bikaner, india: parasite identification and characterization using molecular and immunologic tools.	identification of new foci of cutaneous leishmaniasis (cl), along with reports of leishmania donovani causing the disease, is an issue of concern. clinico-epidemiologic analysis of 98 cases in the endemic regions of rajasthan state, india, suggested the preponderance of infection in men (62.24%) compared with women (37.75%). species characterization by internal transcribed spacer 1 (its1) polymerase chain reaction (pcr)-restriction fragment length polymorphism (rflp), kdna-pcr, and immunofluores ...	2007	17488912
short report: production of recombinant kinesin-related protein of leishmania donovani and its application in the serodiagnosis of visceral leishmaniasis.	to detect igg antibody in the serodiagnosis of visceral leishmaniasis (vl), a recombinant antigen rk39, which is part of a leishmania chagasi kinesin-related protein, has been used successfully and showed high sensitivity and specificity. we report production of a recombinant protein rkrp42, which is part of an l. donovani kinesin-related protein and a homolog of rk39, and its application in an enzyme-linked immunosorbent assay (elisa) for the diagnosis of vl. when rkrp42 and rk39 were compared, ...	2007	17488913
y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in sudan.	familial clustering and ethnic differences suggest that visceral leishmaniasis caused by leishmania donovani is under genetic control. a recent genome scan provided evidence for a major susceptibility gene on chromosome 22q12 in the aringa ethnic group in sudan. we now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related masalit ethnic group. a primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at ...	2007	17500593
[treatment of visceral leishmaniasis in children].	visceral leishmania infantum leishmaniasis is endemic in the south of france. for many years the mainstay for treatment of infected children was pentavalent antimony: meglumine antimoniate (glucantime) or sodium stibogluconate (pentostam). however these drugs are poorly tolerated and resistance similar to that observed in the treatment of indian visceral leishmania donovani leishmaniasis has been reported. currently liposomal amphotericin b is being used instead of antimony for treatment of visc ...	2007	17506279
leishmania donovani: inhibition of phagosomal maturation is rescued by nitric oxide in macrophages.	leishmania donovani promastigotes, the causative agent of visceral leishmaniasis, survive inside macrophages by inhibiting phagosomal maturation. the main surface glycoconjugate on promastigotes, lipophosphoglycan (lpg), is crucial for parasite survival. lpg has several detrimental effects on macrophage function, including inhibition of periphagosomal filamentous actin (f-actin) breakdown during phagosomal maturation. however, in raw 264.7 macrophages pre-stimulated with lipopolysaccharide (lps) ...	2007	17511987
analysis of the leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation.	leishmania donovani is an intracellular protozoan parasite that causes kala-azar in humans. during infection the extracellular insect forms (promastigotes) undergo rapid differentiation to intracellular amastigotes that proliferates in phagolysosomes of mammalian macrophages. we used microarray-based expression profiling to investigate the time-course of changes in rna abundance during promastigote-to-amastigote differentiation in a host-free system that mimics this process. these studies reveal ...	2007	17204342
role of abc transporter mrpa, gamma-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of leishmania donovani.	the resistance of clinical isolates of leishmania donovani to sodium antimony gluconate (sag), the mainstay of treatment in indian visceral leishmaniasis, has become a critical issue in india. the present work investigates the mechanism of resistance to sag in parasites isolated from patients who are unresponsive to sag.	2007	17213267
circulating nitric oxide and c-reactive protein levels in indian kala azar patients: correlation with clinical outcome.	interferon gamma (ifn-gamma) and nitric oxide (no) are the major players of the host defense against leishmania. in the present study circulating levels of ifn-gamma, no, interleukin (il)-6 and c-reactive protein (crp) were compared in kala azar (ka), post-kala azar dermal leishmaniasis (pkdl) and healthy controls. a significantly elevated level of these parameters was evident in ka compared to pkdl or control. further, significantly elevated levels of ifn-gamma, no and crp were observed in sodi ...	2007	17218153
leishmania donovani-induced ceramide as the key mediator of akt dephosphorylation in murine macrophages: role of protein kinase czeta and phosphatase.	leishmania donovani is an intracellular protozoan parasite that impairs the host macrophage immune response to render it suitable for its survival and establishment. l. donovani-induced immunosuppression and alteration of host cell signaling is mediated by ceramide, a pleiotropic second messenger playing an important role in regulation of several kinases, including mitogen-activated protein kinase and phosphatases. we observed that the endogenous ceramide generated during leishmanial infection l ...	2007	17220321
leishmania donovani bisubunit topoisomerase i gene fusion leads to an active enzyme with conserved type ib enzyme function.	all eukaryotic topoisomerase i enzymes are monomeric enzymes, whereas the kinetoplastid family (trypanosoma and leishmania) possess an unusual bisubunit topoisomerase i. to determine what happens to the enzyme architecture and catalytic property if the two subunits are fused, and to explore the functional relationship between the two subunits, we describe here in vitro gene fusion of leishmania bisubunit topoisomerase i into a single orf encoding a new monomeric topoisomerase i (ldtopil-fus-s). ...	2007	17222179
a s-adenosylmethionine synthetase gene from the pathogenic piscine hemoflagellate, cryptobia salmositica.	we report on the identification of a cryptobia genomic dna gene, predict it to encode a s-adenosylmethionine synthetase signature 1 motif and propose to name it s-adenosylmethionine synthetase (mat). the open reading frame of mat is 1,046 bp with 341 deduced amino acids. the mat gene was identified using universal genome walking and southern blot analysis revealed it to be a multi-copy gene. the s-adenosylmethionine synthetase of cryptobia salmositica amino acid sequence is similar to those of o ...	2007	17226041
possibility of membrane modification as a mechanism of antimony resistance in leishmania donovani.	resistance to antimonials has become a clinical threat in the treatment of visceral leishmaniasis (vl). unravelling the resistance mechanism needs attention to circumvent the problem of drug resistance. in one of the resistant isolates, we earlier identified a gene (pg1) implicated in antimony resistance whose localization in the present study was confirmed on the pellicular plasma membrane of the parasite thereby indicating towards membrane modification as a mechanism of resistance in this resi ...	2007	17169604
kinetic characterization of inosine monophosphate dehydrogenase of leishmania donovani.	trypanosomatid protozoan pathogens are purine auxotrophs that are highly dependent on the enzyme inosine monophosphate dehydrogenase (impdh) for the synthesis of guanylate nucleotides. enzymatic characterization of the leishmania donovani impdh (ldimpdh) overexpressed in e. coli revealed that this enzyme was highly specific for the substrates imp and nad(+) with k(m)(app) values of 33 and 390 microm, respectively. in contrast to other impdhs, ldimpdh exhibits no substrate inhibition in high conc ...	2007	17173987
miltefosine induces apoptosis in arsenite-resistant leishmania donovani promastigotes through mitochondrial dysfunction.	the control of leishmaniasis in absence of vaccine solely depends on the choice of chemotherapy. the major hurdle in successful leishmanial chemotherapy is emergence of drug resistance. miltefosine, the first orally administrable anti-leishmanial drug, has shown the potential against drug-resistant strains of leishmania. however, there are discrepancies regarding the involvement of p-glycoprotein (pgp) and sensitivity of miltefosine in multiple drug-resistant (mdr) cell lines that overexpress pg ...	2007	17161839
development and validation of rp-hplc-uv method for simultaneous determination of buparvaquone, atenolol, propranolol, quinidine and verapamil: a tool for the standardization of rat in situ intestinal permeability studies.	a simple, sensitive and specific reversed phase high performance liquid chromatographic (rp-hplc) method with uv detection at 251 nm was developed for simultaneous quantitation of buparvaquone (bpq), atenolol, propranolol, quinidine and verapamil. the method was applicable in rat in situ intestinal permeability study to assess intestinal permeability of bpq, a promising lead compound for leishmania donovani infections. the method was validated on a c-4 column with mobile phase comprising ammoniu ...	2007	17157469
3d-quantitative structure-activity relationships of synthetic antileishmanial ring-substituted ether phospholipids.	the application of 2d-nmr spectroscopy and molecular modeling in determining the active conformation of flexible molecules in 3d-qsar was demonstrated in the present study. in particular, a series of 33 flexible synthetic phospholipids, either 2-(4-alkylidene-cyclohexyloxy)ethyl- or omega-cycloalkylidene-substituted ether phospholipids were systematically evaluated for their in vitro antileishmanial activity against the promastigote forms of leishmania infantum and leishmania donovani by comfa a ...	2007	17158053
bioinformatic identification of tandem repeat antigens of the leishmania donovani complex.	with large amounts of parasite gene sequence available, additional bioinformatic tools to screen these sequences for identifying genes encoding antigens are needed. proteins containing tandem repeat (tr) domains are often b-cell antigens, and antibody responses toward tr domains of the proteins are dominant in human infected with certain parasites. we hypothesized that antigens of serological significance could be identified with a search for tr domains. here we show the result of bioinformatic ...	2007	17088350
glycoprotein 63 (gp63) genes show gene conversion and reveal the evolution of old world leishmania.	species of the subgenus leishmania (leishmania) cause the debilitating disease leishmaniasis on four continents. species grouped within the leishmania donovani complex cause visceral leishmaniasis, a life-threatening disease, often associated with poverty, and affecting some 0.5 million people each year. the leishmania glycoprotein gp63, or major surface protease, is a metalloprotease involved in parasite survival, infectivity and virulence. here, we show that evolution of the gp63 multigene fam ...	2007	17280675
miltefosine (hexadecylphosphocholine) inhibits cytochrome c oxidase in leishmania donovani promastigotes.	miltefosine (hexadecylphosphocholine [hepc]) is currently on trial as a first-choice, orally active drug for the treatment of visceral leishmaniasis when resistance to organic pentavalent antimonials becomes epidemic. however, data on the targets involved in its leishmanicidal mechanism have, until now, been only fragmentary. we have carried out a systematic study of the alterations induced on the bioenergetic metabolism of leishmania donovani promastigotes by hepc. overnight incubation with hep ...	2007	17283192
milk of cow (bos taurus), buffalo (bubalus bubalis), and goat (capra hircus): a better alternative than fetal bovine serum in media for primary isolation, in vitro cultivation, and maintenance of leishmania donovani promastigotes.	tyndalized milk of goat, cow, and buffalo was found to be a potential substitute for fetal bovine serum (fbs) in the medium for the cultivation of leishmania donovani promastigotes. the numbers (means) of promastigotes reached 2.6 x 10(7), 2.3 x 10(7), and 2.1 x 10(7)/ml, respectively, in the medium supplemented with 10% milk of goat, cow, and buffalo, in comparison to 1.9 x 10(7)/ml in the control with 10% fbs. in primary isolation, the milk-supplemented medium showed that 22 out of 26 samples ...	2007	17287321
antileishmanial potential of a marine sponge, haliclona exigua (kirkpatrick) against experimental visceral leishmaniasis.	in this study, we are reporting antileishmanial activity of a marine sponge haliclona exigua, belonging to phylum porifera. the crude methanol extract and its three fractions were tested both in vitro and in vivo. the crude extract exerted almost complete inhibition of promastigotes at 50 microg/ml and 76.4 +/- 6.5% inhibition of intracellular amastigotes at 100 microg/ml concentration with ic50 values of 18.6 microg/ml and 47.2 microg/ml, respectively. when administered to leishmania donovani i ...	2007	17294216
proteomic approach for identification and characterization of novel immunostimulatory proteins from soluble antigens of leishmania donovani promastigotes.	visceral leishmaniasis (vl) caused by leishmania donovani is a major parasitic disease prevalent in endemic regions of bihar in india. in the absence of good chemotherapeutic options, there is a need to develop an effective vaccine against vl which should be dependent on the generation of a t helper type 1 (th1) immune response. we have shown that soluble proteins from promastigote of a new clinical isolate of l. donovani (2001) ranging from 68 to 97.4 kda (f2 fraction), induce th1 responses in ...	2007	17295358
differential gene expression analysis in antimony-unresponsive indian kala azar (visceral leishmaniasis) clinical isolates by dna microarray.	in this study, cdna microarray analysis of a closely related species, leishmania major, was used as a screening tool to compare antimonial-resistant and susceptible clinical isolates of leishmania donovani in order to to identify candidate genes on the basis of antimony resistance. clinically confirmed resistant isolate 39 and sensitive isolate 2001 were used in this study. many differentially regulated genes were identified whose expression levels differ in sodium antimony gluconate (sag)-treat ...	2007	17306059
multilocus microsatellite typing (mlmt) reveals genetically isolated populations between and within the main endemic regions of visceral leishmaniasis.	multilocus enzyme electrophoresis (mlee) is the gold standard for taxonomy and strain typing of leishmania, but has some limitations. an alternative reliable and fast genotyping method for addressing population genetic and key epidemiological questions, is multilocus microsatellite typing (mlmt). mlmt using 15 markers was applied to 91 strains of l. donovani, l. archibaldi, l. infantum and l. chagasi from major endemic regions of visceral leishmaniasis. population structures were inferred by com ...	2007	17307010
characterization of leishmania isolates from nepalese patients with visceral leishmaniasis.	in nepal, visceral leishmaniasis (vl) is endemic in 13 districts of the central and eastern regions. a total of 166 bone-marrow aspirates were obtained from patients with suspected vl. ninety-seven were identified as positive by microscopy, and 29 of those were successfully isolated and cultured. we characterized these isolates by molecular analysis and by their ability to infect mice. pcr-restriction fragment length polymorphism analysis of the mini-exon and the cysteine proteinase b gene showe ...	2007	17310397
comparative evaluation of enzyme-linked immunosorbent assays based on crude and recombinant leishmanial antigens for serodiagnosis of symptomatic and asymptomatic leishmania infantum visceral infections in dogs.	the diagnosis of visceral leishmaniasis remains difficult in rural areas where the disease is endemic, and serologic methods still need assessment, as they are not very sensitive for the detection of asymptomatic infectious dogs. here we present data on the development of enzyme-linked immunosorbent assay (elisa)-based methods for the detection of antibodies against recombinant leishmanial antigens (namely, the recombinant k26 [rk26] and rk39 antigens from leishmania infantum and the ra2 protein ...	2007	17314229
venturamides a and b: antimalarial constituents of the panamanian marine cyanobacterium oscillatoria sp.	two new modified cyclic hexapeptides, venturamides a (1) and b (2), were isolated from the marine cyanobacterium oscillatoria sp. by antimalarial bioassay-guided fractionation. the isolation of 1 and 2 represents the first example of the identification of cyanobacterial peptides with selective antimalarial activity. the planar structures of 1 and 2 were determined by 1d and 2d nmr analyses and, in the case of venturamide a (1), comparison with the literature data for a previously reported synthe ...	2007	17328572
antiparasitic activity of some new caledonian medicinal plants.	twenty-nine extracts of 18 medicinal plants used in new caledonia by traditional healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro against several parasites (leishmania donovani, trypanosoma brucei brucei, trichomonas vaginalis and caenorhabditis elegans). among the selected plants, scaevola balansae and premna serratifolia l. were the most active against leishmania donovani with ic(50) values between 5 and 10microg/ml. the almond and aril extracts from myr ...	2007	17329051
antipromastigote activity of the malabaricones of myristica malabarica (rampatri).	a major problem in the management of visceral leishmaniasis, especially in the indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy, indicating the urgent need to identify new antileishmanial compounds. this study was undertaken to evaluate the antileishmanial activity of the fruit rind of myristica malabarica that is used as a spice and is also credited with medicinal properties. the antipromastigote activity of different extracts/fractions of m. malabarica an ...	2007	17335115
[construction and expression of recombinant eucaryotic expression plasmid of amastin gene of leishmania donovani].	to construct recombinant eukaryotic expression plasmid of amastin gene of leishmania donovani and detect expression of the gene in nih3t3 cells.	2007	17343786
alteration of serum copper in kala-azar patients during sag therapy.	we conducted an analytic case-control study in kala-azar patients during sodium antimony gluconate (sag) therapy to assess the changes in serum copper. a total of 89 subjects were included in the study. diagnosed patients of kala-azar with parasitological evidence of leishmania donovani (ld) bodies in bone marrow, were selected as cases (n=54). they were selected from medicine and paediatric wards of mymensingh medical college hospital, mymensingh and nearby fulbaria upazila of mymensingh distri ...	2007	17344788
antileishmanial and antimalarial chalcones: synthesis, efficacy and cytotoxicity of pyridinyl and naphthalenyl analogs.	the antileishmanial and antimalarial activity of methoxy-substituted chalcones (1,3-diphenyl-2-propen-1-ones) is well established. the few analogs prepared to date where the 3-phenyl group is replaced by either a pyridine or naphthalene suggest these modifications are potency enhancing. to explore this hypothesis, sixteen 3-naphthalenyl-1-phenyl-2-prop-1-enones and ten 1-phenyl-3-pyridinyl-2-prop-1-enones were synthesized and their in vitro efficacies against leishmania donovani and plasmodium f ...	2007	17348849
antimonial treatment of visceral leishmaniasis: are current in vitro susceptibility assays adequate for prognosis of in vivo therapy outcome?	in most of the indian subcontinent, the first line treatment for visceral leishmaniasis (vl) is sodium stibogluconate (ssg), an antimonial drug, but the efficacy of the drug varies according to region. we aimed to characterize the in vitro antimony susceptibility of clinical isolates of nepalese vl patients, and to correlate this in vitro parasite phenotype to clinical therapy outcome. thirty-three clinical isolates of l. donovani were taken from patients with known disease history. these isolat ...	2007	17350306
in vitro and in vivo antileishmanial efficacy of a new nitrilquinoline against leishmania donovani.	the in vitro activity of a new analogue of 2-alkenylquinoline (2-nitrilquinoline or nq) against leishmania donovani was compared to oral reference drug miltefosine (hepc). ic(50) of nq was found at 38.6 microm against promastigotes and 2.4 microm against intramacrophage amastigotes. in vivo evaluation in the l. donovani balb/c mice model indicated that oral treatments at 12.5 and 25 mg/kg for 10 consecutive days significantly reduced the parasite burden in the liver by 68.9 and 68.5%, respective ...	2007	17360145
cross-protection against leishmania donovani but not l. braziliensis caused by vaccination with l. major soluble promastigote exogenous antigens in balb/c mice.	vaccinating with soluble leishmania major promastigote exogenous antigens (lmseags) protects mice against challenge with l. major. to explore the potential of lmseags to cross-protect against infection with other species of leishmania, balb/c mice were immunized with lmseags prior to challenge with either l. donovani or l. braziliensis promastigotes. such mice were protected against l. donovani but not l. braziliensis infection. leishmania braziliensis-infected mice developed lesions that were n ...	2007	17360887
proteophosphoglycan is differentially expressed in sodium stibogluconate-sensitive and resistant indian clinical isolates of leishmania donovani.	leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (ppgs) some of which are secreted while others are found on the surface of promastigotes and amastigotes. these proteins are thought to be important in the transmission, invasion and subsequent intracellular survival of parasites. the structure and function of ppgs are species and stage-specific in the case of l. major and l. mexicana, but no such information has hitherto been available for l. donovani. this ...	2007	17362540
visceral leishmaniasis with aplastic bonemarrow: coincidental or causal.	acquired aplastic anaemia (aaa) is caused by aetiologies ranging from infectious agents, chemical toxins, drugs, and autoimmune disorders. few reports exist which establish a causal association of parasites in aaa. causal association of leishmania donavani infection in aaa has not been reported to date.	2007	17366060
confocal microscopic investigation of tubulin distribution and effect of paclitaxel on posttranslationally modified tubulins in sodium arsenite resistant leishmania donovani.	the affinity of arsenic towards the cytoskeleton leading to disturbance of tubulin polymerization is well known. tubulin undergoes extensive posttranslational modifications which effect stability and dynamics of microtubules but little is known about the effect of antimicrotubule drugs on their distribution and function in kinetoplastid parasites such as leishmania. the current study was undertaken to investigate the effect of continuous sodium arsenite exposure on the tubulin distribution profi ...	2007	17367783
sequence elements essential for the rapid turnover of crithidia fasciculata ornithine decarboxylase.	ornithine decarboxylase (odc) has a very fast turnover in mammalian cells, but is a stable enzyme in t. brucei and other trypanosmatid parasites like leishmania donovani. however, crithidia fasciculata, which is a phylogenetically closely related trypanosomatid to l. donovani, has an odc with a rapid turnover. interestingly, c. fasciculata odc, but not l. donovani odc, is rapidly degraded also in mammalian systems. in order to obtain information on what sequences are important for the rapid degr ...	2008	17514492
synthesis and antiprotozoal activities of simplified analogs of naphthylisoquinoline alkaloids.	the naphthylisoquinoline alkaloids (niqs) represent a class of natural products with manifold activities against various tropical diseases. they are isolated from rare and difficult-to-cultivate tropical plants. in order to find novel, more easily accessible analogs and to study structure-activity relationships, a variety of simplified analogs were produced, which bear the functional groups typical of the niqs, but avoid the synthetically difficult elements of chirality, stereogenic centers and ...	2008	17475370
genetic fingerprinting and identification of differentially expressed genes in isolates of leishmania donovani from indian patients of post-kala-azar dermal leishmaniasis.	post-kala-azar dermal leishmaniasis (pkdl) is an unusual dermatosis that develops as a sequel in 5-15% of cured cases of kala-azar (ka) after months or years of treatment in india. molecular differences are reported to exist between the ka and pkdl isolates which may underlie the diversity in clinical manifestations of the disease. here, arbitrary primed-pcr (ap-pcr) has been used for genetic fingerprinting of parasite isolates from dermal lesions of pkdl patients (n=14) and compared with bone-m ...	2008	17761024
evaluation of antiprotozoal and antimycobacterial activities of the resin glycosides and the other metabolites of scrophularia cryptophila.	resin glycosides are secondary metabolites exclusive to the convolvulaceous plants. in this study, crypthophilic acids a-c (1-3), the first resin glycosides occurring in another family (scrophulariaceae), and the other constituents of scrophularia cryptophila were examined for in vitro antiprotozoal and antimycobacterial potentials. except for crypthophilic acid b (2), all tested compounds exhibited growth-inhibitory effect against trypanosoma brucei rhodesiense, with l-tryptophan (6) and buddle ...	2008	17761408
gastric and cutaneous dissemination of visceral leishmaniasis in a patient with advanced hiv.		2008	17643333