Publications

sub-optimal dose of sodium antimony gluconate (sag)-diperoxovanadate combination clears organ parasites from balb/c mice infected with antimony resistant leishmania donovani by expanding antileishmanial t-cell repertoire and increasing ifn-gamma to il-10 ratio.	we demonstrate that the combination of sub-optimal doses of sodium antimony gluconate (sag) and the diperoxovanadate compound k[vo(o2)2(h2o)], also designated as pv6, is highly effective in combating experimental infection of balb/c mice with antimony resistant (sb(r)) leishmania donovani (ld) as evident from the significant reduction in organ parasite burden where sag is essentially ineffective. interestingly, such treatment also allowed clonal expansion of antileishmanial t-cells coupled with ...	2009	19422069
the antiprotozoal activity of sixteen asteraceae species native to sudan and bioactivity-guided isolation of xanthanolides from xanthium brasilicum.	in vitro screening of the dichloromethane extracts of 16 asteraceae species native to sudan for activity against major protozoan pathogens revealed that a xanthium brasilicum vell. [syn. x. strumarium var. brasilicum (vell.) baker in mart.] extract was the most active against trypanosoma brucei rhodesiense, the etiological agent of east african human trypanosomiasis (ic(50) = 0.1 microg/ml). this plant extract also exhibited noticeable activities against t. cruzi (chagas disease), leishmania don ...	2009	19431098
immunogenicity of candidate chimeric dna vaccine against tuberculosis and leishmaniasis.	mycobacterium tuberculosis and leishmania donovani are important intracellular pathogens, especially in indian context. in india and other south east asian countries, both these infections are highly endemic and in about 20% cases co-infection of these pathogens is reported. for both these pathogens cell mediated immunity plays most important role. the available treatment of these infections is either prolonged or cumbersome or it is ineffective in controlling the outbreaks and spread. therefore ...	2009	19559111
b7-h1 blockade increases survival of dysfunctional cd8(+) t cells and confers protection against leishmania donovani infections.	experimental visceral leishmaniasis (vl) represents an exquisite model to study cd8(+) t cell responses in a context of chronic inflammation and antigen persistence, since it is characterized by chronic infection in the spleen and cd8(+) t cells are required for the development of protective immunity. however, antigen-specific cd8(+) t cell responses in vl have so far not been studied, due to the absence of any defined leishmania-specific cd8(+) t cell epitopes. in this study, transgenic leishma ...	2009	19436710
antiprotozoal activity of 1-phenethyl-4-aminopiperidine derivatives.	a series of 44 4-aminopiperidine derivatives was screened in vitro against four protozoan parasites (trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum). this screening identified 29 molecules selectively active against bloodstream-form t. b. rhodesiense trypomastigotes, with 50% inhibitory concentrations (ic50) ranging from 0.12 to 10 microm, and 33 compounds active against the chloroquine- and pyrimethamine-resistant k1 strain of p. falciparum (ic ...	2009	19564359
6-br-5methylindirubin-3'oxime (5-me-6-bio) targeting the leishmanial glycogen synthase kinase-3 (gsk-3) short form affects cell-cycle progression and induces apoptosis-like death: exploitation of gsk-3 for treating leishmaniasis.	indirubins known to target mammalian cyclin-dependent kinases (cdks) and glycogen synthase kinase (gsk-3) were tested for their antileishmanial activity. 6-br-indirubin-3'-oxime (6-bio), 6-br-indirubin-3'acetoxime and 6-br-5methylindirubin-3'oxime (5-me-6-bio) were the most potent inhibitors of leishmania donovani promastigote and amastigote growth (half maximal inhibitory concentration (ic(50)) values < or =1.2 microm). since the 6-br substitution on the indirubin backbone greatly enhances the ...	2009	19445946
improvement of direct agglutination test (dat) for laboratory diagnosis of visceral leishmaniasis in brazil.	we previously standardized the direct agglutination test (dat) to detect anti-leishmania chagasi promastigote antibodies (dat-lpc) with good sensitivity and specificity for diagnosing visceral leishmaniasis (vl). in this paper, we present a technical upgrade by introducing some modifications into the antigen preparation. this antigen was evaluated in dat (dat-mod) using 61 sera samples from vl patients and 96 samples from patients with other diseases. the dat-mod presented a cut-off of 1:100, sa ...	2009	19457530
greater abundance of extracellular leishmania donovani bodies: possible clue from comparison of bone marrow aspirate and imprint findings.		2009	19474363
mucosal leishmaniasis in a sudanese patient.	mucosal leishmaniasis (ml) is an oral disease caused by the parasite leishmania donovani. the disease has been proven to be pandemic in many areas of the world. it affects young men living in leishmaniasis-endemic areas. ml might be accompanied or proceeded by visceral leishmaniasis (vl), although in most of the cases seen in sudan, ml occurs as a primary lesion. ml can mimic oral cancer or fungal infections, with ulceration as the most common finding in ml lesions. in this report, the patient c ...	2009	19478252
a novel 1-indanone isolated from uvaria afzelii roots.	bioactivity-guided fractionations of chloromethylenic extract of the roots of u. afzelii (annonaceae), using leishmania donovani and trypanosoma brucei brucei bioassay, resulted in the isolation of the two known compounds, emorydone (1) and demethoxymatteucinol (2), previously isolated from the stems, which were characterised from this source. in addition, the novel 1-indanone, afzeliindanone (3), was also isolated. the structure determination of afzeliindanone (3) was elucidated on the basis of ...	2009	19521904
an ab initio structural model of a nucleoside permease predicts functionally important residues.	permeases belonging to the equilibrative nucleoside transporter family promote uptake of nucleosides and/or nucleobases into a wide range of eukaryotes and mediate the uptake of a variety of drugs used in the treatment of cancer, heart disease, aids, and parasitic infections. no experimental three-dimensional structure exists for any of these permeases, and they are not present in prokaryotes, the source of many membrane proteins used in crystal structure determination. to generate a structural ...	2009	19429678
arginine homeostasis and transport in the human pathogen leishmania donovani.	arginine is an essential amino acid for the human pathogen leishmania but not to its host. thus, the mechanism by which this protozoan parasite regulates cellular homeostasis of arginine is critical for its survival and virulence. in a previous study, we cloned and functionally characterized a high affinity arginine-specific transporter, ldaap3, from leishmania donovani. in this investigation, we have characterized the relationship between arginine transport via ldaap3 and amino acid availabilit ...	2009	19439418
miltefosine promotes ifn-gamma-dominated anti-leishmanial immune response.	leishmania donovani, a protozoan parasite, resides and replicates as amastigotes within macrophages. the parasite inflicts the disease visceral leishmaniasis by suppressing host cell function. neither a therapeutic vaccine nor an effective anti-leishmanial drug to reverse the immunosuppression is available. although miltefosine (hexadecylphosphocholine or hpc) is a promising orally bioavailable anti-leishmanial drug, its efficacy is seriously compromised by contra-indications in pregnant women. ...	2009	19454711
unusual presentations of visceral leishmaniasis.	we report 3 cases of visceral leishmaniasis, who presented with unusual clinical manifestations. one child was diagnosed as hemophagocytic syndrome; another masqueraded with features of leukemoid changes alongwith hemophagocytosis and trilineage myelodysplasia; the third case presented with pyothorax. all the three patients showed amastigote forms of leishmania donovani and positive serology (rk39 antigen). they showed complete clinical, hematological and parasitological resolution with amphoter ...	2009	19475352
synthesis and in vitro antiplasmodial evaluation of 4-anilino-2-trichloromethylquinazolines.	to identify a new safe antiplasmodial molecular scaffold, an original series of 2-trichloromethylquinazolines, functionalized in position 4 by an alkyl- or arylamino substituent, was synthesized from 4-chloro-2-trichloromethylquinazoline 1, via a cheap, fast and efficient solvent-free operating procedure. among the 40 molecules prepared, several exhibit a good profile with both a significant antiplasmodial activity on the w2 plasmodium falciparum strain (ic(50) values: 0.4-2.2 microm) and a prom ...	2009	19482476
down regulation of kmp-11 in leishmania infantum axenic antimony resistant amastigotes as revealed by a proteomic screen.	the therapeutic mainstay against the protozoan parasite leishmania is still based on the antiquated pentavalent antimonials, but resistance is increasing in several parts of the world. resistance is now partly understood in laboratory promastigote isolates, but the mechanism leading to drug resistance in amastigote isolates is lagging behind. here we describe a comparative proteomic analysis of a genetically related pair of antimonial-sensitive and -resistant leishmania infantum axenic amastigot ...	2009	19500579
identification of novel leishmania donovani antigens that help define correlates of vaccine-mediated protection in visceral leishmaniasis.	visceral leishmaniasis (vl), caused by the intracellular parasite leishmania donovani is a major public health problem in the developing world. but there is no effective and safe vaccine approved for clinical use against any form of leishmaniasis. through reactivity with kala-azar patient and cured sera, polypeptides ranging from 91 to 31-kda from l. donovani promastigotes were previously identified as potential protective vaccine candidates. in this study four polypeptides 91(ld91), 72 (ld72), ...	2009	19503834
quantitative structure--antiprotozoal activity relationships of sesquiterpene lactones.	prompted by results of our previous studies where we found high activity of some sesquiterpene lactones (stls) against trypanosoma brucei rhodesiense (which causes east african sleeping sickness), we have now conducted a structure-(in-vitro)-activity study on a set of 40 stls against t. brucei rhodesiense, t. cruzi, leishmania donovani and plasmodium falciparum. furthermore, cytotoxic activity against l6 rat skeletal myoblast cells was assessed. some of the compounds possess high activity, espec ...	2009	19513006
high-throughput screening of amastigotes of leishmania donovani clinical isolates against drugs using a colorimetric beta-lactamase assay.	a simple colorimetric beta-lactamase assay for quantifying leishmania amastigotes in macrophages grown in microtiter plates has been reported. the beta-lactamase gene was integrated into the rrna region of the genome, thereby allowing for high-level stable expression of the enzyme. both visceral leishmaniasis (vl) and post-kala azar dermal leishmaniasis (pkdl) isolates were transfected with beta-lactamase gene. these beta-lactamase-expressing promastigotes were used for infecting intracellular j ...	2009	19634714
anti-il-10 mab protection against experimental visceral leishmaniasis via induction of th1 cytokines and nitric oxide.	visceral leishmaniasis is characterized by severe immune suppression of the host. this suppression of the host immune system is primarily mediated by the immunosuppressive cytokine interleukin-10 (il-10), whose levels are significantly upregulated during leishmaniasis. this immune suppression is reflected at the level of t-cell dysfunction and abrogation of leishmaniacidal molecules along with a dampened th1 cytokine response. in the present study, we showed in vivo neutralization of il-10 by ad ...	2009	19634715
transgenic leishmania donovani clinical isolates expressing green fluorescent protein constitutively for rapid and reliable ex vivo drug screening.	several leishmania strains with episomal expression of green fluorescent protein (gfp) require constant drug pressure for its continuous expression and hence limit its use in ex vivo or in vivo systems. the aim of this study was to alleviate this problem by stably integrating the gfp gene into the parasite genome, so as to use these transfectants for ex vivo and in vivo drug screening.	2009	19525291
first total synthesis and antiprotozoal activity of (z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge polymastia penicillus.	the first total synthesis for the (z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. the use of (trimethylsilyl)acetylene was key in the synthesis. based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 12-bromo-1-dodecanol followed by a second acetylide coupling to the short-chain 3-methyl-1-bromobutane, which res ...	2009	19527698
pro-apoptotic effect of the landrace bangla mahoba of piper betle on leishmania donovani may be due to the high content of eugenol.	in the absence of effective and safe treatment for visceral leishmaniasis or kala-azar - a devastating parasitic disease caused by leishmania donovani - the search for anti-leishmanial agents from natural resources in common use is imperative. recently, the comparative in vitro anti-leishmanial activity of methanolic extracts from two landraces of piper betle - p. betle landrace bangla mahoba (pb-bm) and p. betle landrace kapoori vellaikodi (pb-kv) - has been reported. here, the putative pathway ...	2009	19528177
role of the domestic dog as a reservoir host of leishmania donovani in eastern sudan.	abstract:	2009	19534802
immunization with the dna-encoding n-terminal domain of proteophosphoglycan of leishmania donovani generates th1-type immunoprotective response against experimental visceral leishmaniasis.	leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (ppgs) which exist as secretory as well as surface-bound forms in both promastigotes and amastigotes. the structure and function of ppgs have been reported to be species and stage specific as in the case of leishmania major and leishmania mexicana; there has been no such information available for leishmania donovani. we have recently demonstrated that ppg is differentially expressed in sodium stibogluconate- ...	2009	19542458
in vitro antileishmanial, antiplasmodial and cytotoxic activities of phenolics and triterpenoids from baccharis dracunculifolia d. c. (asteraceae).	baccharis dracunculifolia (asteraceae), the most important plant source of the brazilian green propolis (gpe), displayed in vitro activity against leishmania donovani, with an ic(50) value of 45 microg/ml, while gpe presented an ic(50) value of 49 microg/ml. among the isolated compounds of b. dracunculifolia, ursolic acid, and hautriwaic acid lactone showed ic(50) values of 3.7 microg/ml and 7.0 microg/ml, respectively. uvaol, acacetin, and ermanin displayed moderate antileishmanial activity. re ...	2009	19540316
n-chlorotaurine shows high in vitro activity against promastigotes and amastigotes of leishmania species.	protozoan parasites of the genus leishmania are the causative agents of life-threatening visceral as well as cutaneous and mucocutaneous leishmaniasis. first-line drugs are antimonials, but toxicity and resistance in some endemic areas cause serious problems. in the current study, the antileishmanial activity of the weak oxidant n-chlorotaurine (nct) was investigated. nct is a derivative of the amino acid taurine produced by granulocytes and monocytes during oxidative burst, but can also be synt ...	2009	19541788
sub-optimal dose of sodium antimony gluconate (sag)-diperoxovanadate combination clears organ parasites from balb/c mice infected with antimony resistant leishmania donovani by expanding antileishmanial t-cell repertoire and increasing ifn-gamma to il-10 ratio.	we demonstrate that the combination of sub-optimal doses of sodium antimony gluconate (sag) and the diperoxovanadate compound k[vo(o(2))(2)(h(2)o)], also designated as pv6, is highly effective in combating experimental infection of balb/c mice with antimony resistant (sb(r)) leishmania donovani (ld) as evident from the significant reduction in organ parasite burden where sag is essentially ineffective. interestingly, such treatment also allowed clonal expansion of antileishmanial t-cells coupled ...	2009	19545517
development of species-specific pcr and pcr-restriction fragment length polymorphism assays for l.infantum/l.donovani discrimination.	discrimination of leishmania infantum and l. donovani, the members of the l. (l.) donovani complex, is important for diagnosis and epidemiological studies of visceral leishmaniasis (vl). we have developed two molecular tools including a restriction fragment length polymorphisms of amplified dna (pcr-rflp) and a pcr that are capable to discriminate l. donovani from l. infantum. typing of the complex was performed by a simple pcr of cysteine protease b (cpb) gene followed by digestion with draiii. ...	2009	19545519
in vitro susceptibilities of leishmania donovani promastigote and amastigote stages to antileishmanial reference drugs: practical relevance of stage-specific differences.	the in vitro susceptibilities of the reference strain leishmania donovani mhom/et/67/l82 to sodium stibogluconate, amphotericin b, miltefosine, and the experimental compound px-6518 were determined for extracellular log-phase promastigotes, established axenic amastigotes, fresh spleen-derived amastigotes, and intracellular amastigotes in primary mouse peritoneal macrophages. susceptibility to amphotericin b did not differ across the various axenic models (50% inhibitory concentrations [ic50], 0. ...	2009	19546361
leishmania donovani trypanothione reductase: role of urea and guanidine hydrochloride in modulation of functional and structural properties.	trypanothione reductase [tr], an nadph-dependent disulfide oxidoreductase, unique to kinetoplastid parasites including trypanosoma and leishmania, is a validated target for the design of improved drugs. tr is a stable homodimer with a fad molecule tightly bound to each subunit. in this paper, structure, function, stability properties and cofactor protein interactions of recombinant tr from leishmania donovani were investigated under equilibrium unfolding/denaturing conditions. urea induced unfol ...	2009	19563920
leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts.	lipophosphoglycan (lpg), the major surface glycoconjugate on leishmania donovani promastigotes, is crucial for the establishment of infection inside macrophages. lpg comprises a polymer of repeating galbeta1,4manalpha-po(4) attached to a lysophosphatidylinositol membrane anchor. lpg is transferred from the parasite to the host macrophage membrane during phagocytosis and induces periphagosomal f-actin accumulation correlating with an inhibition of phagosomal maturation. the biophysical properties ...	2009	19070677
immunochromatographic rk39 strip test in the serodiagnosis of visceral leishmaniasis in tunisia.	the performance of the rk39 strip test in the diagnosis of tunisian visceral leishmaniasis (vl) was evaluated and compared with that of immunofluorescent antibody test (ifat). a total of 929 sera, including 574 from vl patients, 54 from cutaneous leishmaniasis (cl) patients, 42 from patients with other protozoan diseases, 152 from patients with non-parasitic diseases and 107 from healthy controls, were used in the study. the sensitivity and specificity of the rk39 strip test were 87.1 and 94.4%, ...	2009	19070876
cutaneous leishmaniasis with lymphadenopathy due to leishmania donovani.	we describe a case of cutaneous leishmaniasis with lymphadenopathy due to leishmania donovani, which was successfully treated with oral miltefosine. given the increased prevalence of travelling, patients presenting with lymph-node enlargement should have leishmaniasis included in the differential diagnosis even in the absence of typical ulceration.	2009	19077092
9- o-acetylated sialic acids enhance entry of virulent leishmania donovani promastigotes into macrophages.	summary: distribution of 9-o-acetylated sialic acids (9-o-acsa) on leishmania donovani has been previously reported. considering their role in recognition, the differential distribution of sialic acids especially 9-o-acetylated sialic acids in avirulent (ur6) versus virulent (ag83 and ge1) promastigotes of leishmania donovani and its role in entry into macrophages was explored. fluorimetric-hplc, fluorimetric determination and elisa revealed 14-, 8- and 5-fold lower sialic acids in ur6 as compar ...	2009	19079847
antileishmanial activity, pharmacokinetics and tissue distribution studies of mannose-grafted amphotericin b lipid nanospheres.	leishmania parasite resides mainly in the liver and the spleen and multiplies. effective therapy of leishmaniasis could be achieved by delivering antileishmanial drugs to these sites. present investigations were aimed at developing lipid nanospheres of amphotericin b (ln-a) anchored with mannose to achieve targeted delivery to the liver. mannose is specifically involved in the recognition of parasite or appropriate ligands on the macrophage surface ln-a, and mannose-anchored lipid nanospheres (l ...	2009	19089691
molecular epidemiology of leishmaniasis in asia (focus on cutaneous infections).	leishmaniasis has a wider geographical distribution than before. this review focuses on molecular epidemiological studies of new foci of cutaneous leishmaniasis in south and southeast asia.	2009	19276879
synthesis and evaluation of 2-pyridyl pyrimidines with in vitro antiplasmodial and antileishmanial activity.	a series of 2-pyridyl pyrimidines, reported inhibitors of plasmodium falciparum methionine aminopeptidase 1b were synthesized and evaluated for their antiplasmodial activities. an analysis of physicochemical properties demonstrated a link between lipophilicity and antiparasitic activity. cross screening of the library against cultured leishmania donovani parasites revealed this class of compounds as potent inhibitors of parasite development in vitro.	2009	19091562
aryloxy cyclohexyl imidazoles: a novel class of antileishmanial agents.	thirteen novel aryloxy cyclohexane-based mono and bis imidazoles were synthesized and evaluated in vitro as antileishmanials against leishmania donovani and cytotoxicity assessed. these compounds were better than the existing drugs, sodium stibogluconate and pentamidine in respect to ic(50) and si values. promising compounds were tested further in vivo. among all, the bis methylimidazole with 2-fluoro, 4-nitro aryloxy group (9) exhibited significant in vivo inhibition of 77.9%, thus providing ne ...	2009	19091566
n-(2-hydroxypropyl)methacrylamide-amphotericin b (hpma-amb) copolymer conjugates as antileishmanial agents.	leishmaniasis is a major health problem in many parts of the world, caused by various species of leishmania. amastigotes are the clinically relevant form of the parasite in the human host and reside in the parasitophorous vacuole within macrophages. polymer-drug conjugates have been used for lysosomotropic drug delivery and have already shown potential in anticancer and antileishmanial chemotherapy. we synthesised n-(2-hydroxypropyl)methacrylamide-amphotericin b (hpma-amb) copolymer conjugates i ...	2009	19097763
identification of old world leishmania spp. by specific polymerase chain reaction amplification of cysteine proteinase b genes and rapid dipstick detection.	we used the cysteine proteinase b (cpb) gene family of the trypanosomatid genus leishmania as a target to develop rapid, specific, and easy-to-use polymerase chain reaction (pcr) tests to discriminate leishmania infantum, leishmania donovani, leishmania tropica, leishmania aethiopica, and leishmania major. identification of all 5 old world species and validation of intraspecies variability are features lacking in other species-specific pcrs. amplicon analysis was done on agarose gels and was fur ...	2009	19097841
synthesis and antiparasitic and antifungal evaluation of 2'-arylsubstituted-1h,1'h-[2,5']bisbenzimidazolyl-5-carboxamidines.	a series of 2'-arylsubstituted-1h,1'h-[2,5']-bisbenzimidazolyl-5-carboxamidines were prepared in a six-step process starting from 4-amino-3-nitrobenzonitrile. the antiparasitic activity against trypanosoma brucei rhodesiense (t.b.r.), plasmodium falciparum (p.f.), leishmania donovani (l.d.) and trypanosoma cruzi (t.c.) and antifungal activity against candida albicans and candida krusei were evaluated in vitro. several compounds showed promising in vitro activity against t.b.r., p.f. and c. albic ...	2009	19010569
in vitro susceptibility of field isolates of leishmania donovani to miltefosine and amphotericin b: correlation with sodium antimony gluconate susceptibility and implications for treatment in areas of endemicity.	indian leishmania donovani isolates (n = 19) from regional zones representing various levels of antimony resistance displayed significantly (p < 0.01) correlated results with respect to in vitro susceptibility to the antileishmanial drugs sodium antimony gluconate, amphotericin b, and miltefosine, raising the possibility of cross-resistance mechanisms operating in the field isolates. the results of gene expression analysis of ldmt and ldros3 were suggestive of alternate mechanisms of miltefosine ...	2009	19015344
one-step generation of double-allele gene replacement mutants in leishmania donovani.	due to the apparent lack of sexual recombination in leishmania spp., gene replacement strategies in this diploid organism necessitate the subsequent targeting of two gene alleles by using two constructs, bearing different antibiotic resistance markers. this approach is time consuming and often gives rise to spontaneous amplification of the targeted gene, nullifying efforts to create functional null mutants. here, we show that by using two homologous recombination constructs in a co-transfection ...	2009	19028498
quassin alters the immunological patterns of murine macrophages through generation of nitric oxide to exert antileishmanial activity.	the aim of this study was to characterize the in vitro antileishmanial activity of quassin, a traditional chinese herbal medicine.	2009	19036753
expression of vflip in a lentiviral vaccine vector activates nf-{kappa}b, matures dendritic cells, and increases cd8+ t-cell responses.	lentiviral vectors deliver antigens to dendritic cells (dcs) in vivo, but they do not trigger dc maturation. we therefore expressed a viral protein that constitutively activates nf-kappab, vflip from kaposi's sarcoma-associated herpesvirus (kshv), in a lentivector to mature dcs. vflip activated nf-kappab in mouse bone marrow-derived dcs in vitro and matured these dcs to a similar extent as lipopolysaccharide; costimulatory markers cd80, cd86, cd40, and icam-1 were upregulated and tumor necrosis ...	2009	19036811
killing of trypanosomatid parasites by a modified bovine host defense peptide, bmap-18.	tropical diseases caused by parasites continue to cause socioeconomic devastation that reverberates worldwide. there is a growing need for new control measures for many of these diseases due to increasing drug resistance exhibited by the parasites and problems with drug toxicity. one new approach is to apply host defense peptides (hdp; formerly called antimicrobial peptides) to disease control, either to treat infected hosts, or to prevent disease transmission by interfering with parasites in th ...	2009	19190729
phlebotomus (euphlebotomus) barguesae n. sp. from thailand (diptera - psychodidae).	abstract:	2009	19128518
udp-gal: n-acetylglucosamine beta 1-4 galactosyltransferase expressing live attenuated parasites as vaccine for visceral leishmaniasis.	as compared to cutaneous leishmaniasis, vaccination against visceral leishmaniasis (vl) has received limited attention. in this study, we demonstrate for the first time that an udp-galactose: n-acetylglucosamine beta 1-4 galactosyltransferase (genbank accession no. ef159943) expressing attenuated ld clonal population (a-ld) is able to confer protection against the experimental challenge with the virulent ld ag83 parasite. a-ld was also effective in established leishmania infection. the vaccinate ...	2009	19005752
structure and topology of slc11a1(164-191) with g169d mutation in membrane-mimetic environments.	solute carrier family 11 member 1 (slc11a1) is a proton-mediated divalent metal cation transporter with 12 putative transmembrane domains. variation in it reveals alterations in host resistance against intracellular pathogens. a naturally occurring glycine to aspartic acid mutation at position 169 (g169d) in the putative transmembrane domain 4 (tm4) makes mice susceptible to salmonella typhimurim, leishmania donovani, and mycobacterium bovis. in this work, a 28-residue peptide corresponding to s ...	2009	18929666
leishmania donovani vs immunity: t-cells sensitized from leishmania of one donor may modulate their cytokines pattern on re-stimulation with leishmania from different donor in visceral leishmaniasis.	antimony resistance is frequently encountered during treatment of visceral leishmaniasis (vl) and the differences are well characterized by inadequate ifn-gamma dominant type-1 protection mechanisms. the part played by leishmania parasites derived from antimony treated patients in the outcome of an immune response largely remains to be investigated. in the present study we observed that macrophages of balb/c mice infected with antimony non-responder (sag-nr) isolates had a greater amastigote bur ...	2009	18948098
multilocus microsatellite typing (mlmt) reveals genetic homogeneity of leishmania donovani strains in the indian subcontinent.	in this population genetic study of leishmania donovani parasites in the indian subcontinent, 132 isolates obtained from patients in bangladesh, india, nepal and sri lanka suffering from kala-azar (100), post-kala-azar dermal leishmaniasis (pkdl) (25) and cutaneous leishmaniasis (cl) (2), and from 5 patients whose clinical patterns were not defined, were analysed by using 15 hyper-variable microsatellite loci. multilocus microsatellite typing (mlmt) data were analysed by using a bayesian model-b ...	2009	18957333
vaccination with a novel recombinant leishmania antigen plus mpl provides partial protection against l. donovani challenge in experimental model of visceral leishmaniasis.	the acquisition of immunity following subclinical or resolved infection with the intracellular parasite leishmania donovani suggests that vaccination could prevent visceral leishmaniasis. the characteristics and in vitro stimulating capability of the recombinant proteins expressed by previously identified clones on the basis of their capacity to stimulate an indigenously established leishmania-specific cell line leading to high level of ifn-gamma suggested these to be potential candidates for im ...	2009	18983842
cutaneous leishmaniasis in sri lanka: a study of possible animal reservoirs.	cutaneous leishmaniasis (cl) has been detected with increasing frequency in sri lanka in recent years. leishmania donovani has been identified as the causative agent, but no information is available on vector(s) or reservoir(s). in this paper we present data on the screening of possible reservoirs for evidence of infection.	2009	19095480
a glutathione-specific aldose reductase of leishmania donovani and its potential implications for methylglyoxal detoxification pathway.	methylglyoxal is mainly catabolized by two major enzymatic pathways. the first is the ubiquitous detoxification pathway, the glyoxalase pathway. in addition to the glyoxalase pathway, aldose reductase pathway also plays a crucial role in lowering the levels of methylglyoxal. the gene encoding aldose reductase (alr) has been cloned from leishmania donovani, a protozoan parasite causing visceral leishmaniasis. dna sequence analysis revealed an open reading frame (orf) of approximately 855 bp encod ...	2009	18983902
identification, purification, and characterization of a secretory serine protease in an indian strain of leishmania donovani.	an aprotinin sensitive serine protease was identified in the culture supernatant of the indian strain of leishmania donovani (mhom/in/1983/ag83). the protease was subsequently purified and characterized. the apparent molecular mass of the enzyme was 115 kda in sds-page under non-reducing condition, while on reduction it showed a 56 kda protein band indicating that the protease is a dimeric protein. the purified enzyme was optimally active at the ph and temperature of 7.5 and 28 degrees c, respec ...	2009	18587671
the development of a real-time pcr assay for the quantification of leishmania infantum dna in canine blood.	recent research has demonstrated the high sensitivity of real time pcr (qpcr) in the diagnosis of leishmania infantum infection. the goal of this study was to develop and evaluate a qpcr detection system for the diagnosis of visceral leishmaniosis (vl) in dogs. specific primer sets were developed for the leishmania donovani complex, in which a fragment of 132 bp of kdna from l. infantum was amplified. the reaction was performed using the abi prism 7000 system with abi prism software used to carr ...	2009	18603455
evidence for the presence of r250g mutation at the atpase domain of topoisomerase ii in an arsenite-resistant leishmania donovani exhibiting a differential drug inhibition profile.	resistance to operational drugs is a major barrier to successful antileishmanial chemotherapy that demands development of novel drug intervention strategies based on rational approaches. model drug resistance phenotypes, such as arsenite resistance used in the current study, facilitate our understanding of the mechanism of drug resistance and assist in identifying new drug target(s). the current study was undertaken to investigate the sensitivity of topoisomerase ii (topo ii) of arsenite-sensiti ...	2009	18805675
leishmania donovani depletes labile iron pool to exploit iron uptake capacity of macrophage for its intracellular growth.	intracellular pathogens employ several strategies for iron acquisition from host macrophages for survival and growth, whereas macrophage resists infection by actively sequestering iron. here, we show that instead of allowing macrophage to sequester iron, protozoan parasite leishmania donovani (ld) uses a novel strategy to manipulate iron uptake mechanisms of the host and utilizes the taken up iron for its intracellular growth. to do so, intracellular ld directly scavenges iron from labile iron p ...	2009	18823384
leishmania donovani ornithine decarboxylase is indispensable for parasite survival in the mammalian host.	mutations within the polyamine biosynthetic pathway of leishmania donovani, the etiological agent of visceral leishmaniasis, confer polyamine auxotrophy to the insect vector or promastigote form of the parasite. however, whether the infectious or amastigote form of the parasite requires an intact polyamine pathway has remained an open question. to address this issue, conditionally lethal deltaodc mutants lacking ornithine decarboxylase (odc), the rate-limiting enzyme in polyamine biosynthesis, w ...	2009	19064633
trifluralin liposomal formulations active against leishmania donovani infections.	the purpose of this study was to increase the therapeutic index of the antiparasitic drug, trifluralin (tfl), to allow its parenteral administration without the need of toxic solvents. this was achieved by incorporating tfl in liposomes with high loading capacity. these formulations were stable in freeze-dried form during at least one year and in frozen form during at least three months. therapeutic activity, assessed on a visceral model of infection, showed that tfl liposomes reduced the number ...	2009	18761404
phase transfer catalyzed synthesis of bis-quinolines: antileishmanial activity in experimental visceral leishmaniasis and in vitro antibacterial evaluation.	a one-pot synthesis of some novel bis-quinolines has been achieved under phase transfer catalyzed conditions using 8-hydroxy quinoline derivatives as substrates. the synthesized analogues were evaluated for antileishmanial activity against leishmania donovani promastigotes and amastigotes. the entire bis-quinolines showed efficacy in both in vitro and in vivo studies. compound 5 (1,1-bis-[(5-chloro-8-quinolyl)oxy]methane) exhibited the most significant activity. compounds 4 (1,1-bis-[(8-quinolyl ...	2009	18538452
enhanced lesional foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory t cells in indian post-kala-azar dermal leishmaniasis.	indian post-kala-azar dermal leishmaniasis (pkdl) is a low-frequency (5-10%) dermal sequela of visceral leishmaniasis (vl) caused by leishmania donovani; importantly, affected individuals are speculated to be parasite reservoirs. insight into its immunopathogenesis could translate into rational immunomodulatory therapeutic approaches against leishmaniases. in patients with pkdl (n=21), peripheral lymphocytes were analyzed for surface markers, intracellular cytokines, and lymphoproliferative resp ...	2010	20032994
n-myristoyltransferase from leishmania donovani: structural and functional characterisation of a potential drug target for visceral leishmaniasis.	n-myristoyltransferase (nmt) catalyses the attachment of the 14-carbon saturated fatty acid, myristate, to the amino-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction. in these pathways, n-myristoylation facilitates association of substrate proteins with membranes or the hydrophobic domains of other partner peptides. nmt function is essential for viability in all cell types tes ...	2010	20036251
characterization of dipeptidylcarboxypeptidase of leishmania donovani: a molecular model for structure based design of antileishmanials.	leishmania donovani dipeptidylcarboxypeptidsae (lddcp), an angiotensin converting enzyme (ace) related metallopeptidase has been identified and characterized as a putative drug target for antileishmanial chemotherapy. the kinetic parameters for lddcp with substrate, hip-his-leu were determined as, km, 4 mm and vmax, 1.173 micromole/ml/min. inhibition studies revealed that known ace inhibitors (captopril and bradykinin potentiating peptide; bpp1) were weak inhibitors for lddcp as compared to huma ...	2010	20039100
comparative in vivo expression of amastigote up regulated leishmania genes in three different forms of leishmaniasis.	in old world leishmania infections in india, leishmania donovani is responsible for visceral leishmaniasis (vl) and post kala-azar dermal leishmaniasis (pkdl) while l. tropica is responsible for cutaneous leishmaniasis (cl) in humans. the molecular differences between the two species of leishmania and within the same species causing distinct pathologies that govern the outcome of infection and pathogenesis in the human host are unknown. quantitative expression of selected genes was evaluated dir ...	2010	19963076
antimalarial and antitubercular nostocarboline and eudistomin derivatives: synthesis, in vitro and in vivo biological evaluation.	the synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin n and o is reported. these compounds were evaluated in vitro against four parasites (trypanosoma brucei rhodesiense stib 900, trypanosoma cruzi tulahuen c2c4, leishmania donovani mhom-et-67/l82 axenic amastigotes, and plasmod ...	2010	20133138
expression of a pts2-truncated hexokinase produces glucose toxicity in leishmania donovani.	compartmentalization of glycolytic enzymes in glycosomes is vital in trypanosomatid parasites. retention of these enzymes in the cytosol induces sugar toxicity and accumulation of intermediate metabolites, notably the hexokinase product glucose-6-phosphate. however, the role of hexokinase in sugar mediated toxicity remains unexplored. we have generated leishmania donovani transfectants expressing a catalytically active cytosolic mutant of hexokinase. in the presence of glucose, these transfectan ...	2010	19925831
development and evaluation of different pcr-based typing methods for discrimination of leishmania donovani isolates from nepal.	leishmania donovani, the causative agent of visceral leishmaniasis in the indian subcontinent, has been reported to be genetically homogeneous. in order to support ongoing initiatives to eliminate the disease, highly discriminative tools are required for documenting the parasite population and dynamics.	2010	20109247
original quinazoline derivatives displaying antiplasmodial properties.	the multistep synthesis of new quinazoline-derived molecules and their in vitro antiplasmodial evaluation on the w2 chloroquino-resistant plasmodium falciparum strain is described herein. these molecules have also been studied concerning their in vitro cytotoxicity toward two human cell lines (k652 and hepg2) in order to calculate their respective selectivity indexes (s.i.). among the fourteen tested molecules, two exhibited both significant antiplasmodial activity (ic(50)=0.95 and 1.3 microm) a ...	2010	19926173
synthesis and biological evaluation of trifluralin analogues as antileishmanial agents.	a series of new analogues of trifluralin (tfl) were synthesized and characterized in view of changing the unfavorable properties that limits its use as antileishmanial agent. some of the tfl analogues display more activity than a standard drug (miltefosine) against the promastigote forms of leishmania infantum and leishmania donovani and the intracellular form (thp-1 infected with l. infantum). all analogues showed a clear advantage over miltefosine, as they are not hemolytic. some analogues can ...	2010	19926293
synthesis and antiprotozoal activity of cationic 1,4-diphenyl-1h-1,2,3-triazoles.	novel dicationic triazoles 1-60 were synthesized by the pinner method from the corresponding dinitriles, prepared via the copper(i)-catalyzed azide-alkyne cycloaddition (cuaac). the type and the placement of cationic moieties as well as the nature of aromatic substituents influenced in vitro antiprotozoal activities of compounds 1-60 against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani and their cytotoxicity for mammalian cells. eight congeners displayed antitry ...	2010	19928900
identification of transport-critical residues in a folate transporter from the folate-biopterin transporter (fbt) family.	the synechocystis slr0642 protein and its plastidial arabidopsis (arabidopsis thaliana) ortholog at2g32040 belong to the folate-biopterin transporter (fbt) family within the major facilitator superfamily. both proteins transport folates when expressed in escherichia coli. because the structural requirements for transport activity are not known for any fbt protein, we applied mutational analysis to identify residues that are critical to transport and interpreted the results using a comparative st ...	2010	19923217
novel convenient synthesis of biologically active esters of hydroxylamine.	alkylation of ethyl n-hydroxyacetimidate with readily available methanesulfonates of functionally substituted alcohols and subsequent deprotection of aminooxy group is a novel and convenient method to prepare functionally substituted esters of hydroxylamine with high overall yield. this approach is a good alternative to well-known reaction of n-hydroxyphthalimide with alcohols under the mitsunobu conditions. the properties of ethoxyethylidene protection of aminooxy group on the contrary to that ...	2010	19997759
acidic residues in the purine binding site govern the 6-oxopurine specificity of the leishmania donovani xanthine phosphoribosyltransferase.	leishmania possess distinct xanthine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase enzymes that mediate purine salvage, an obligatory nutritional function for these pathogenic parasites. the xanthine phosphoribosyltransferase preferentially uses xanthine as a substrate, while the hypoxanthine-guanine phosphoribosyltransferase phosphoribosylates only hypoxanthine and guanine. these related phosphoribosyltransferases were used as model system to investigate the molec ...	2010	19861168
synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents.	a series of aryloxy alkyl/aryl alkyl imidazoles were synthesized and evaluated in vitro as antileishmanials against leishmania donovani. all the 19 compounds exhibited 94-100% inhibition at 10microg/ml against promastigotes and 12 compounds exhibited high inhibition with an ic(50) in the range of 0.47-4.85microg/ml against amastigotes. promising compounds were tested further in vivo. among all, compounds 4 and 23 with 4-cf(3) aryloxy moiety exhibited medium in vivo inhibition of 58-60%, thus pro ...	2010	19913413
antimalarial and antileishmanial activities of histone deacetylase inhibitors with triazole-linked cap group.	histone deacetylase inhibitors (hdaci) are endowed with plethora of biological functions including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. parsing the structure-activity relationship (sar) for each disease condition is vital for long-term therapeutic applications of hdaci. we report in the present study specific cap group substitution patterns and spacer-group chain lengths that enhance the antimalarial and antileishmanial activity of aryltriazo ...	2010	19914074
antiprotozoal, antimycobacterial and cytotoxic potential of twenty-three british and irish red algae.	as part of our continuing research on seaweeds, we have screened the crude extracts of 23 red marine algae collected from england and ireland. the clinically important blood-stage life forms of trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani and mycobacterium tuberculosis were used as test organisms in the in vitro assays. the selectivity of the extracts was determined by using mammalian skeletal myoblast (l6) cells. all algal extracts showed activity against t. brucei rhodesiense, ...	2010	20077438
synthesis and antiprotozoal activity of 4-arylcoumarins.	a large series of 4-arylcoumarins was synthesized by suzuki-miyaura cross-coupling reaction and evaluated for antiprotozoal activity against plasmodium falciparum and leishmania donovani. several compounds were found to strongly inhibit the proliferation of human cell line and/or parasites. the 4-(3,4-dimethoxyphenyl)-6,7-dimethoxycoumarin exhibit a potent activity on l. donovani amastigotes with a selectivity index (si=265) twice than amphotericin b (si=140).	2010	19914747
fluorinated rhodacyanine (sjl-01) possessing high efficacy for visceral leishmaniasis (vl).	anti-leishmania in vitro and in vivo activities of various rhodacyanine derivatives have been examined. among them, the fluorinatied variant sjl-01 (8) showed ic(50) of 0.011 microm against leishmania donovani strain mhom/et/67/l82 (selective index of >15000) and 95-97% inhibition against l. donovani strain mhom/et/67/hu in female balb/c mice by 1.3-12.5 mg/kg x 5 iv administrations. negative results on chromosomal aberration test and in vitro micronucleus test suggest that compound 8 is a hopef ...	2010	19894726
antiprotozoal, antimycobacterial and cytotoxic potential of some british green algae.	in the continuation of our search for natural sources for antiprotozoal and antitubercular molecules, we have screened the crude extracts of four green marine algae (cladophora rupestris, codium fragile ssp. tomentosoides, ulva intestinalis and ulva lactuca) collected from the dorset area of england. trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani and mycobacterium tuberculosis were used as test organisms in the in vitro assays. the selective toxicity of the extracts was a ...	2010	19960429
antileishmanial effect of cisplatin against murine visceral leishmaniasis.	drug development in visceral leishmaniasis is extremely vital as the existing therapeutic modalities are plagued by the unwanted twosome of toxicity and drug resistance. antineoplastic drugs have in the past been effective against the parasitic infections, for example, miltefosine. cisplatin is a first-generation platinum-containing drug, used in the treatment of various solid tumors. its in vitro antileishmanial effect has already been demonstrated. in the present study, the leishmanicidal pote ...	2010	19853668
amplified fragment length polymorphism (aflp) analysis is useful for distinguishing leishmania species of visceral and cutaneous forms.	the leishmania strains belonging to cutaneous leishmaniasis (cl) and visceral leishmaniasis (vl) have been reported to possess close homology in genome profiles. to confirm this on genetic basis an attempt was made to differentiate leishmania major; leishmania tropica and leishmania donovani genetically for the first time using amplified fragment length polymorphism (aflp)--a high throughput dna fingerprinting technique. the objective of this research work was to identify dna markers of cl and v ...	2010	19854144
innate immune defense in visceral leishmaniasis: cytokine mediated protective role by allogeneic effector cell.	antileishmanial role of mouse splenic natural killer (nk) cell was studied in allogeneic condition. in vitro data indicates that nk cells of allogeneic (c57bl/6, h2(b)) non-leishmania exposed mouse have strong antileishmanial effect against leishmania donovani infected balb/c (h2(d)) macrophages. physical contact between the effector (nk cell) and the target cells (infected macrophages) is essential in this system since; cell free supernatant generated after coculturing of effector cells with in ...	2010	19879234
identification and characterization of a novel deoxyhypusine synthase in leishmania donovani.	deoxyhypusine synthase, an nad(+)-dependent enzyme, catalyzes the first step in the post-translational synthesis of an unusual amino acid, hypusine (n(epsilon)-(4-amino-2-hydroxybutyl)lysine), in the eukaryotic initiation factor 5a precursor protein. two putative deoxyhypusine synthase (dhs) sequences have been identified in the leishmania donovani genome, which are present on chromosomes 20: dhsl20 (dhs-like gene from chromosome 20) and dhs34 (dhs from chromosome 34). although both sequences ex ...	2010	19880510
leishmania cell surface prohibitin: role in host-parasite interaction.	proteins selectively upregulated in infective parasitic forms could be critical for disease pathogenesis. a mammalian prohibitin orthologue is upregulated in infective metacyclic promastigotes of leishmania donovani, a parasite that causes visceral leishmaniasis. leishmania donovani prohibitin shares 41% similarity with mammalian prohibitin and 95-100% within the genus. prohibitin is concentrated at the surface of the flagellar and the aflagellar pole, the aflagellar pole being a region through ...	2010	19888987
innate killing of leishmania donovani by macrophages of the splenic marginal zone requires irf-7.	highly phagocytic macrophages line the marginal zone (mz) of the spleen and the lymph node subcapsular sinus. although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. here, we have combined gene expression profiling and rnai using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal z ...	2010	20300600
dynamic imaging of experimental leishmania donovani-induced hepatic granulomas detects kupffer cell-restricted antigen presentation to antigen-specific cd8 t cells.	kupffer cells (kcs) represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. although kcs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific cd8(+) t cells. here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2- ...	2010	20300603
synthetic udp-furanoses inhibit the growth of the parasite leishmania.	the chemical synthesis of udp-6-nhac-6-deoxy-galf was performed and it led to the isolation of both pure anomers. they were then evaluated together with the previously prepared udp-furanoses for their anti-parasitic properties against leishmania donovani promastigotes, one of the agents responsible for visceral leishmaniasis. amongst them, the unnatural 1,2-trans udp-6-nhac-galf demonstrated a high potency in inhibiting the growth of the parasite.	2010	20303072
leishmania donovani s.l.: evaluation of the proliferation potential of promastigotes using cfse staining and flow cytometry.	leishmania infantum causes visceral leishmaniasis in all countries in the mediterranean basin. it uses phlebotomine sandflies as vectors where the promastigote stage develops, reproduces and becomes infective. therefore the reproductive power of the promastigotes determines the inoculum size of the isolate. ten leishmania strains from cyprus: two leishmania donovani and eight l. infantum were used to study the proliferation capacity of the promastigotes. population increase during a 6-day cultur ...	2010	20303953
a chronic mutilating rhinopathy with a delayed diagnosis of mucocutaneous leishmaniasis.	mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin and mucosal lesions. mucocutaneous leishmaniasis is very rare in india and to our knowledge, only two cases have been reported, and this is the first case of mucocutaneous leishmaniasis presenting with mutilating rhinopathy reported from the indian subcontinent.	2010	20465699
a clinical isolate of leishmania donovani with its1 sequence polymorphism as a cause of para-kala-azar dermal leishmaniasis in an ethiopian human immunodeficiency virus-positive patient on highly active antiretroviral therapy.	the diagnosis of para-kala-azar dermal leishmaniasis (pkdl/vl), either as an immune reconstitution inflammatory syndrome (iris)-associated syndrome or as a complication of visceral leishmaniasis (vl) during human immunodeficiency virus (hiv) co-infection in patients with or without highly active antiretroviral therapy, represents a challenge for prompt treatment. the aim of this study was to identify the causative leishmania species and to clarify whether the post-kala-azar dermal leishmaniasis ...	2010	20331449
water-soluble polymer-drug conjugates for combination chemotherapy against visceral leishmaniasis.	there is a need for new safe, effective and short-course treatments for leishmaniasis; one strategy is to use combination chemotherapy. polymer-drug conjugates have shown promise for the delivery of anti-leishmanial agents such as amphotericin b. in this paper, we report on the preparation and biological evaluation of polymer-drug conjugates of n-(2-hydroxypropyl)methacrylamide (hpma), amphotericin b and alendronic acid. the combinatorial polymer-drug conjugates were effective anti-leishmanial a ...	2010	20338769
[leishmania donovani delays phagolysosomal acidification].		2010	20346266
leishmania donovani: genetic diversity of isolates from sudan characterized by pcr-based rapd.	drug unresponsiveness in patients with visceral leishmaniasis (vl) is a problem in many endemic areas. this study aimed to determine genetic diversity of leishmania donovani isolates from a vl endemic area in sudan as a possible explanation for drug unresponsiveness in some patients. thirty clinically stibogluconate (ssg)-sensitive isolates were made ssg-unresponsive in vitro by gradually increasing ssg concentrations. the sensitive isolates and their ssg-unresponsive counterparts were typed usi ...	2010	20346944
cpg oligodeoxynucleotide augments the antileishmanial activity of miltefosine against experimental visceral leishmaniasis.	to evaluate the combination of cpg oligodeoxynucleotide (cpg odn) and miltefosine for the treatment of experimental visceral leishmaniasis (vl).	2010	20495208
identification, characterization, and expression of a unique secretory lipase from the human pathogen leishmania donovani.	lipases have been implicated to be of importance in the life cycle development, virulence, and transmission of a variety of parasitic organisms. potential functions include the acquisition of host resources for energy metabolism and as simple building blocks for the synthesis of complex parasite lipids important for membrane remodeling and structural purposes. using a molecular approach, we identified and characterized the structure of an ldlip3-lipase gene from the primitive trypanosomatid path ...	2010	20349119
leishmania parasitophorous vacuoles interact continuously with the host cell's endoplasmic reticulum; parasitophorous vacuoles are hybrid compartments.	macrophages that express representative endoplasmic reticulum (er) molecules tagged with green fluorescence protein were generated to assess the recruitment of er molecules to leishmania parasitophorous vacuoles (pvs). more than 90% of pvs harbouring leishmania pifanoi or leishmania donovani parasites recruited calnexin, to their pv membrane. an equivalent proportion of pvs also recruited the membrane-associated soluble n-ethylmaleimide-sensitive factor attachment protein receptors (snares), sec ...	2010	20497181
localization and induction of the a2 virulence factor in leishmania: evidence that a2 is a stress response protein.	leishmaniasis is a vector-borne infectious disease with a wide range of pathologies depending on the species of leishmania. leishmania parasites are transmitted by the sand fly vector as promastigotes; within the mammalian host, leishmania parasites differentiate into amastigotes and replicate in macrophages. the a2 protein from leishmania donovani is expressed predominantly in amastigotes and therefore likely plays a role in survival in the mammalian host. in the present study, we have determin ...	2010	20497497
amplification of adenine phosphoribosyltransferase suppresses the conditionally lethal growth and virulence phenotype of leishmania donovani mutants lacking both hypoxanthine-guanine and xanthine phosphoribosyltransferases.	leishmania donovani cannot synthesize purines de novo and obligatorily scavenge purines from the host. previously, we described a conditional lethal deltahgprt/deltaxprt mutant of l. donovani (boitz, j. m., and ullman, b. (2006) j. biol. chem. 281, 16084-16089) that establishes that l. donovani salvages purines primarily through hypoxanthine-guanine phosphoribosyltransferase (hgprt) and xanthine phosphoribosyltransferase (xprt). unlike wild type l. donovani, the deltahgprt/deltaxprt knock-out ca ...	2010	20363738