Publications

mitochondrial associated ubiquitin fold modifier-1 mediated protein conjugation in leishmania donovani.	in this report, we demonstrate the existence of the ubiquitin fold modifier-1 (ufm1) and its conjugation pathway in trypanosomatid parasite leishmania donovani. ldufm1 is activated by e1-like enzyme lduba5. ldufc1 (e2) specifically interacted with ldufm1 and lduba5 to conjugate ldufm1 to proteinaceous targets. mass spectrometry analysis revealed that ldufm1 is conjugated to leishmania protein targets that are associated with mitochondria. immunofluorescence experiments showed that leishmania ufm ...	2011	21264253
monitoring of intracellular nitric oxide in leishmaniasis: its applicability in patients with visceral leishmaniasis.	nitric oxide (no) has been demonstrated to be a principal effector molecule responsible for mediating intracellular killing of leishmania parasites, the causative organism of leishmaniasis. as measurement of intracellular no remains a challenge to biologists, we have developed a flow cytometric approach to perform real time biological detection of no within leishmania parasites and parasitized macrophages using a membrane permeable derivative of diaminofluorescein [4,5-diaminofluorescein diaceta ...	2011	21182181
characterization of leishmania donovani mcm4: expression patterns and interaction with pcna.	events leading to origin firing and fork elongation in eukaryotes involve several proteins which are mostly conserved across the various eukaryotic species. nuclear dna replication in trypanosomatids has thus far remained a largely uninvestigated area. while several eukaryotic replication protein orthologs have been annotated, many are missing, suggesting that novel replication mechanisms may apply in this group of organisms. here, we characterize the expression of leishmania donovani mcm4, and ...	2011	21829589
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 ...	2011	21741248
antimonial resistance in leishmania donovani is associated with increased in vivo parasite burden.	leishmania donovani is an intracellular protozoan parasite that causes visceral leishmaniasis (vl). antimonials (ssg) have long been the first-line treatment against vl, but have now been replaced by miltefosine (mil) in the indian subcontinent due to the emergence of ssg-resistance. our previous study hypothesised that ssg-resistant l. donovani might have increased in vivo survival skills which could affect the efficacy of other treatments such as mil. the present study attempts to validate the ...	2011	21829701
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 ...	2011	21734124
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 ...	2011	21684309
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 ...	2011	21736901
solution structure and dynamics of adf from toxoplasma gondii.	toxoplasma gondii adf (tgadf) belongs to a functional subtype characterized by strong g-actin sequestering activity and low f-actin severing activity. among the characterized adf/cofilin proteins, tgadf has the shortest length and is missing a c-terminal helix implicated in f-actin binding. in order to understand its characteristic properties, we have determined the solution structure of tgadf and studied its backbone dynamics from (15)n-relaxation measurements. tgadf has conserved adf/cofilin f ...	2011	21820516
chemical constituents of the new endophytic fungus mycosphaerella sp. nov. and their anti-parasitic activity.	chemical investigation of a new endophytic fungus, mycosphaerella sp. nov. strain f2140, associated with the foliage of the plant psychotria horizontalis (rubiaceae) in panama, resulted in the isolation of cercosporin (1) and a new cercosporin analog (3) as the major components. the structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-6-ethyl-3-hydroxy-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-5-hydroxy-2-methoxy-6-methyl- ...	2011	21815421
immunogenicity of leishmania donovani iron superoxide dismutase b1 and peroxidoxin 4 in balb/c mice: the contribution of toll-like receptor agonists as adjuvant.	in this study, we assessed the immune response of two leishmania donovani recombinant proteins: iron superoxide dismutase b1 (sodb1) and peroxidoxin 4 (pxn4) in balb/c mice. assessment of the immunogenicity of these proteins alone or combined with toll-like receptor 9 (tlr-9) agonist (cpg odn) or tlr-4 agonist (gla-se) showed that they elicit specific antibody as well as cytokine production in response to the respective antigen in vitro. the use of adjuvants augmented immunogenicity of these ant ...	2011	21835175
[immunogenicity of the recombinant plasmid of leishmania donovani amastin gene].	to investigate the immunogenicity of recombinant plasmid pcdna3.1-amastin with leishmania donovani amastin gene.	2011	21826897
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 ...	2011	21683592
tgf-β(1) re-programs tlr4 signaling in l. donovani infection: enhancement of shp-1 and ubiquitin-editing enzyme a20.	visceral leishmaniasis (vl), caused by leishmania donovani, is a major health concern in india. it represents t-helper type 2 (th2) bias of cytokines in active state and th1 bias at cure. however, the role of the parasite in regulating toll-like receptor (tlr)-mediated macrophage activation in vl patients remains elusive. in this report, we demonstrated that later stages of l. donovani infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokin ...	2011	21968712
Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection.	Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its ...	2011	22206029
Redox-active antiparasitic drugs.	Significance: Parasitic diseases affect hundreds of millions of people worldwide and represent major health problems. Treatment is becoming extremely difficult due to the emergence of drug-resistance, the absence of effective vaccines and the spread of insecticide-resistant vectors. Thus, identification of affordable and readily available drugs against resistant parasites is of global demand. Recent Advances: Susceptibility of many parasites to oxidative stress is a well-known phenomenon. There ...	2011	22122517
A novel 12.6-kDa protein of Leishmania donovani for the diagnosis of Indian visceral leishmaniasis.	For the diagnosis of visceral leishmaniasis (VL), rK39 antigen-based rapid test is widely used. Unfortunately, up to 32% healthy individuals from endemic region test positive with this antigen. There is an urgent need to search for a more specific antigen with sensitivity similar to rK39.	2011	21923256
Vaccination with Liposomal Leishmanial Antigens Adjuvanted with Monophosphoryl Lipid-Trehalose Dicorynomycolate (MPL-TDM) Confers Long-Term Protection against Visceral Leishmaniasis through a Human Administrable Route.	The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human adm ...	2011	22133194
Multifaceted Population Structure and Reproductive Strategy in Leishmania donovani Complex in One Sudanese Village.	Leishmania species of the subgenus Leishmania and especially L. donovani are responsible for a large proportion of visceral leishmaniasis cases. The debate on the mode of reproduction and population structure of Leishmania parasites remains opened. It has been suggested that Leishmania parasites could alternate different modes of reproduction, more particularly clonality and frequent recombinations either between related individuals (endogamy) or between unrelated individuals (outcrossing) withi ...	2011	22206035
Cloning, expression, characterization and inhibition studies on trypanothione synthetase, a drug target enzyme, from Leishmania donovani.	Trypanothione synthetase, a validated drug target, synthesizes trypanothione from glutathione and spermidine. Here we report the gene cloning, expression, characterization and inhibition studies of trypanothione synthetase from Leishmania donovani (LdTryS). The purified recombinant LdTryS enzyme obeyed Michaelis-Menten kinetics. High substrate inhibition was observed with glutathione (K(m)=33.24 µm, k(cat)=1.3 s(-1), K(i)=866 µm). The enzyme shows simple hyperbolic kinetics with fixed glutathion ...	2011	22050226
post-kala-azar dermal leishmaniasis: recent developments.	a substantial number of patients who recover from kala-azar will develop dermatosis [commonly known as post-kala-azar dermal leishmaniasis (pkdl)]. it usually occurs in the indian subcontinent and east africa. as many as 10-20% of indian cases and 50-60% of sudanese cases develop pkdl after successful treatment of visceral leishmaniasis. most cases occur after infection with leishmania donovani and less commonly after leishmania infantum. however, the pkdl is extremely rare in patients infected ...	2011	22126871
Incidence of symptomatic and asymptomatic Leishmania donovani infections in high-endemic foci in India and Nepal: a prospective study.	Incidence of Leishmania donovani infection and Visceral Leishmaniasis (VL) was assessed in a prospective study in Indian and Nepalese high-endemic villages. DAT-seroconversion was used as marker of incident infection in 3 yearly surveys. The study population was followed up to month 30 to identify incident clinical cases. In a cohort of 9034 DAT-negative individuals with neither active signs nor history of VL at baseline, 42 VL cases and 375 asymptomatic seroconversions were recorded in the firs ...	2011	21991397
screening natural products database for identification of potential antileishmanial chemotherapeutic agents.	leishmaniasis is a parasitic infection caused by unicellular protozoan organism belonging to the family trypanosomatidae. among various forms of the disease, visceral leishmaniasis is the most lethal and caused by leishmania infantum or leishmania donovani. the redox metabolism of parasite requires a key enzyme, trypanothione reductase which is a validated drug target. in the past decade, it was observed that these protozoan parasites had developed resistance against many of available drugs. imp ...	2011	21956744
[visceral leishmaniasis associated hemophagocytic lymphohistiocytosis: report of four childhood cases].	the clinical features of four cases of visceral leishmaniasis (vl)-associated hemophagocytic lymphohistiocytosis (vl-hlh) were retrospectively analyzed for the purpose of helping the diagnosis of secondary hlh.	2011	22088188
Restoration of IFN?R subunit assembly, IFN? signaling and parasite clearance in Leishmania donovani infected macrophages: role of membrane cholesterol.	Despite the presence of significant levels of systemic Interferon gamma (IFN?), the host protective cytokine, Kala-azar patients display high parasite load with downregulated IFN? signaling in Leishmania donovani (LD) infected macrophages (LD-MØs); the cause of such aberrant phenomenon is unknown. Here we reveal for the first time the mechanistic basis of impaired IFN? signaling in parasitized murine macrophages. Our study clearly shows that in LD-MØs IFN? receptor (IFN?R) expression and their l ...	2011	21931549
development of derivatives of 3, 3'-diindolylmethane as potent leishmania donovani bi-subunit topoisomerase ib poisons.	the development of 3, 3'-diindolyl methane (dim) resistant parasite leishmania donovani (lddr50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric dna topoisomerase i of leishmania (ldtop1ls). mutation of large subunit of ldtop1ls at f270l is responsible for resistance to dim up to 50 µm concentration.	2011	22174820
Bis(oxyphenylene)benzimidazoles: A novel class of anti-Plasmodium falciparum agents.	A small library of 26 2,2'-[alkane-a,?-diylbis(oxyphenylene)]bis-1H-benzimidazoles has been prepared and evaluated against Giardia intestinalis, Entamoeba histolytica, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. Among the tested compounds, eight derivatives (17, 19, 20, 24, 27, 30, 32 and 35) exhibited an anti-Plasmodium falciparum activity characterized by IC(50) values in the range of 180-410nM (0.11-0.21µg/mL) and selectivity indexes (IC( ...	2011	22061825
Arabinosylated lipoarabinomannan skews Th2 phenotype towards Th1 during Leishmania infection by chromatin modification: involvement of MAPK signaling.	The parasitic protozoan Leishmania donovani is the causative organism for visceral leishmaniasis (VL) which persists in the host macrophages by deactivating its signaling machinery resulting in a critical shift from proinflammatory (Th1) to an anti-inflammatory (Th2) response. The severity of this disease is mainly determined by the production of IL-12 and IL-10 which could be reversed by use of effective immunoprophylactics. In this study we have evaluated the potential of Arabinosylated Lipoar ...	2011	21935379
Leishmania donovani encodes a functional enzyme involved in vitamin C biosynthesis: arabino-1,4-lactone oxidase.	Plants and most animals can synthesize ascorbate (vitamin C) for their own requirements, but humans have lost this ability during evolution. The last step in the biosynthesis of L-ascorbic acid involves the conversion of an aldonolactone substrate to ascorbate (or analogues), reactions catalyzed by a family of flavoprotein aldonolactone oxidase/dehydrogenases. We report cloning, molecular characterization, localization and functional importance of arabinonolactone oxidase (LdALO), an enzyme from ...	2011	21907739
Screening and evaluation of antiparasitic and in vitro anticancer activities of Panamanian endophytic fungi.	Many compounds produced by fungi have relevant pharmaceutical applications. The purpose of this study was to collect and isolate endophytic fungi from different regions of Panama and then to test their potential therapeutic activities against Leishmania donovani, Plasmodium falciparum, and Trypanosoma cruzi as well as their anticancer activities in MCF-7 cells. Of the 25 fungal isolates obtained, ten of them had good anti-parasitic potential, showing selective activity against L. donovani; four ...	2011	22069153
il-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis.	the mechanisms underlying the failure to contain the growth of leishmania parasites in human visceral leishmaniasis (vl) are not understood. l donovani amastigotes were quantified in cultured splenic aspirate cells to assess the function of il-10 in lesional tissue ex vivo. in 67 patients with active vl, il-10 neutralization promoted parasite killing in 73% and complete clearance in 30%, while 18% had more parasites and 9% did not change. the splenic cells secreted increased levels of both tumor ...	2011	21881130
Recent advances in post-kala-azar dermal leishmaniasis.	Post-kala-azar dermal leishmaniasis (PKDL) is a challenge for clinicians and researchers, because its burden is poorly investigated and pathogenesis is disputable. However, recent studies contributed to understanding of the pathogenesis of PKDL especially its association with host immunological factors, and also how to improve its diagnosis and treatment. This review focuses on recent advances in diagnosis, new insights into pathogenesis and case management.	2011	21885919
leishmania donovani: proteasome-mediated down-regulation of methionine adenosyltransferase.	summarymethionine adenosyltransferase (mat) is an important enzyme for metabolic processes, to the extent that its product, s-adenosylmethionine (adomet), plays a key role in trans-methylation, trans-sulphuration and polyamine synthesis. previous studies have shown that a mat-overexpressing strain of leishmania donovani controls adomet production, keeping the intracellular adomet concentration at levels that are compatible with cell survival. this unexpected result, together with the fact that m ...	2011	21813028
a screen against leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit.	the ability to screen compounds in a high-throughput manner is essential in the process of small molecule drug discovery. critical to the success of screening strategies is the proper design of the assay, often implying a compromise between ease/speed and a biologically relevant setting. leishmaniasis is a major neglected disease with limited therapeutic options. in order to streamline efforts for the design of productive drug screens against leishmania, we compared the efficiency of two screeni ...	2011	21811648
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 ...	2011	21805355
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 ...	2011	21803129
human visceral leishmaniasis: decrease in serum cholesterol as a function of splenic parasite load.		2011	21801506
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 ...	2011	21796699
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 ...	2011	21787777
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.	2011	21771678
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 ...	2011	21769179
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 ...	2011	21762613
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 ...	2011	21762596
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 ...	2011	21755234
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 ...	2011	21750153
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 ...	2011	21747738
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. ...	2011	21739037
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.	2011	21742847
increased metacyclogenesis of antimony-resistant leishmania donovani clinical lines.	summarymathematical models predict that the future of epidemics of drug-resistant pathogens depends in part on the competitive fitness of drug-resistant strains. considering metacyclogenesis (differentiation process essential for infectivity) as a major contributor to the fitness of leishmania donovani, we tested its relationship with pentavalent antimony (sbv) resistance in clinical lines. different methods for the assessment of metacyclogenesis were cross-validated: gene expression profiling ( ...	2011	21819638
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 ...	2011	21705615
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 ...	2011	21708240
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 ...	2011	21703391
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 ...	2011	21739043
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 ...	2011	21680635
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 ...	2011	21679679
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 ...	2011	21708149
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 ...	2011	21507942
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 ...	2011	21511057
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 ...	2011	21515279
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 ...	2011	21520472
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 ...	2011	21522160
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.	2011	21526219
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.	2011	21527328
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 ...	2011	21527547
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 ...	2011	21530477
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 ...	2011	21530614
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 ...	2011	21533785
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 ...	2011	21536795
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 ...	2011	21537026
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 ...	2011	21538958
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 ...	2011	21555166
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 ...	2011	21558020
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 ...	2011	21559456
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 ...	2011	21567173
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 ...	2011	21586319
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 ...	2011	21590671
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, ...	2011	21595907
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 ...	2011	21609983
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 ...	2011	21611668
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 ...	2011	21612342
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.	2011	21613432
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 ...	2011	21615033
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 ...	2011	21616071
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 ...	2011	21628656
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 ...	2011	21633027
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 ...	2011	21637326
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 ...	2011	21637755
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 ...	2011	21640106
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 ...	2011	21651757
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.	2011	21655313
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 ...	2011	21665468
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 ...	2011	21666787
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 ...	2011	21670183
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 ...	2011	21671412
drug targeting to macrophages using paromomycin-loaded albumin microspheres for treatment of visceral leishmaniasis: an in vitro evaluation.	leishmania parasite is an obligate intracellular parasite of the mammalian host and lives inside resident macrophages of liver and spleen. a high dose of paromomycin (pm) is required for the treatment.	2011	20545446
antiprotozoal activity of melampyrum arvense and its metabolites.	an activity guided isolation of the h(2)o subextract of the crude extract of melampyrum arvense l. afforded iridoid glucosides: aucubin (1), melampyroside (2), mussaenoside (3), mussaenosidic acid (4), 8-epi-loganin (5); flavonoids: apigenin (6), luteolin (7), luteolin 7-o-β-glucopyranoside (8); a lignan glycoside dehydrodiconiferyl alcohol 9-o-β-glucopyranoside (9); and benzoic acid (10). β-sitosterol (11) and a fatty acid mixture (12) were identified as the active principles of the chcl(3) sub ...	2011	20623589
a combined luciferase imaging and reverse transcription polymerase chain reaction assay for the study of leishmania amastigote burden and correlated mouse tissue transcript fluctuations.	laboratory mice display features of bona fide hosts for parasites such as leishmania major and leishmania donovani. characterizing the amastigote population size fluctuations and the mouse transcript abundance accounting for these fluctuations demands the capacity to record in real time and integrate quantitative multiparametric datasets from the host tissues where these processes occur. to this end, two technologies, luciferase-expressing leishmania imaging and a very sensitive quantitative ana ...	2011	20846338
immunomodulatory effect of picroliv on the efficacy of paromomycin and miltefosine in combination in experimental visceral leishmaniasis.	combination therapy for the treatment of visceral leishmaniasis has increasingly been advocated as a way to increase treatment efficacy and tolerance, to reduce treatment duration and cost, and to limit the emergence of drug resistance. in the present work, we have adopted a rational approach, which can modulate the immune response to overcome the negative control systems and to boost the positive killing responses. this study was designed to investigate the immunomodulatory effect of picroliv ( ...	2011	20846525
tgf-β-regulated tyrosine phosphatases induce lymphocyte apoptosis in leishmania donovani-infected hamsters.	visceral leishmaniasis, which is caused by leishmania donovani, is one of the major health problems of the indian subcontinent. infected hosts have been reported to have impaired lymphoproliferation. however, the fate of anergic cells is still elusive. in the present investigation, l. donovani-infected hamsters were used to study the mechanism of lymphocyte cell death. lymph node-derived lymphocytes were analysed for apoptotic death through mitochondrial abnormality, caspase activity and dna deg ...	2011	20856262
cumulative cardiac toxicity of sodium stibogluconate and amphotericin b in treatment of kala-azar.	kala-azar or visceral leishmaniasis is a disseminated protozoal infection caused by parasites of the genus leishmania (leishmania donovani in india). conventional therapy for visceral leishmaniasis continues to be pentavalent antimony (sodium antimony gluconate [sag]). amphotericin b is widely used for sag-unresponsive cases and sometimes even as a first-line drug, especially in endemic areas. with the conventional regimen of sag, cardiac toxicity has been reported in 8% to 17% of cases with 5% ...	2011	20823781