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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 ...200918983842
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 ...200918983902
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 ...200918805675
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 ...200919005752
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 ...200919010569
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 ...200919015344
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 ...200919028498
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.200919036753
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 ...200919036811
redox-active dinitrodiphenylthioethers against leishmania: synthesis, structure-activity relationships and mechanism of action studies.btb 06237 (2-[(2,4-dichloro-5-methylphenyl)sulfanyl]-1,3-dinitro-5-(trifluoromethyl) benzene), a compound previously identified through qsar pharmacophore development and a virtual screen of the maybridge database, possesses potent and selective activity against leishmania parasites. in the present study, several analogs of btb 06237 were synthesized and analyzed for activity against leishmania axenic amastigotes, their ability to reduce the level of parasitemia in peritoneal macrophages, and th ...200919058972
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 ...200919064633
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 ...200919070677
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%, ...200919070876
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.200919077092
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 ...200919079847
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 ...200919089691
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.200919091562
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 ...200919091566
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.200919095480
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 ...200919097763
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 ...200919097841
molecular basis of antimony treatment in leishmaniasis.leishmaniasis is a disease that affects 2 million people and kills 70000 persons every year. it is caused by leishmania species, which are human protozoan parasites of the trypanosomatidae family. trypanosomatidae differ from the other eukaryotes in their specific redox metabolism because the glutathione/glutathione reductase system is replaced by the unique trypanothione/trypanothione reductase system. the current treatment of leishmaniasis relies mainly on antimonial drugs. the crystal structu ...200919317451
is leishmaniasis in sri lanka benign and be ignored?cutaneous leishmaniasis is now an endemic disease in sri lanka. many studies have focussed on various aspects of this disease but the knowledge, particularly on epidemiological and vector aspects is still poor and the awareness among the general public and even medical/paramedical personnel regarding this disease remains grossly inadequate. the steady increase in the numbers and spread of cutaneous leishmaniasis cases in sri lanka and the very close similarity (genotypic and phenotypic) between ...200919326703
synthesis and biological evaluation of novel 4-(hetero) aryl-2-piperazino quinazolines as anti-leishmanial and anti-proliferative agents.a series of new class of 4-(hetero)aryl-2-piperazino quinazolines were synthesized and assessed for in vitro activity against extracellular promastigotes and intracellular amastigotes of leishmania donovani. among the compounds evaluated, compound 4bb and 4cb showed the selectivity index (si) value>8.03 and 4.21, respectively, which is promising as compared with sodium stilbogluconate (ssg) and pentamidine with the si of 6.38 and 2.07, respectively. the synthesized compounds were also tested for ...200919328690
leishmania donovani lacking the golgi gdp-man transporter lpg2 exhibit attenuated virulence in mammalian hosts.surface phosophoglycans such as lipophosphoglycan (lpg) or proteophosphoglycan (ppg) and glycosylinositol phospholipids (gipls) modulate essential interactions between leishmania and mammalian macrophages. phosphoglycan synthesis depends on the golgi gdp-mannose transporter encoded by lpg2. lpg2-null (lpg2(-)) leishmania major cannot establish macrophage infections or induce acute pathology, whereas lpg2(-)leishmania mexicana retain virulence. lpg2(-)leishmania donovani has been reported to surv ...200919328787
topoisomerase i gene mutations at f270 in the large subunit and n184 in the small subunit contribute to the resistance mechanism of the unicellular parasite leishmania donovani towards 3,3'-diindolylmethane.3,3'-diindolylmethane (dim), a novel poison targeting leishmania donovani topoisomerase i (ldtop1ls), induces programmed cell death in leishmania parasites. the development of resistant parasites by adaptation with increasing concentrations of dim generates random mutations in ldtop1ls. single-nucleotide mutations result in the amino acid substitutions f270l and k430n in the large subunit and n184s in the small subunit of the enzyme. dim failed to inhibit the catalytic activity of the recombinan ...200919332675
peganine hydrochloride dihydrate an orally active antileishmanial agent.protozoic infections caused by genus leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2d-nmr spectral data and single crystal x-ray crystallography data indicated ...200919339182
biologically active cannabinoids from high-potency cannabis sativa.nine new cannabinoids (1-9) were isolated from a high-potency variety of cannabis sativa. their structures were identified as (+/-)-4-acetoxycannabichromene (1), (+/-)-3''-hydroxy-delta((4'',5''))-cannabichromene (2), (-)-7-hydroxycannabichromane (3), (-)-7r-cannabicoumarononic acid a (4), 5-acetyl-4-hydroxycannabigerol (5), 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol (6), 8-hydroxycannabinol (7), 8-hydroxycannabinolic acid a (8), and 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone (9) throug ...200919344127
relapse of visceral leishmaniasis after miltefosine treatment in a nepalese patient.we report the first case of visceral leishmaniasis (vl) relapse in a healthy individual after complete miltefosine treatment. the patient attended hospital with a history of fever for 2 months, splenomegaly, hepatomegaly, and weight loss. the case was confirmed as vl by microscopical detection of leishmania parasites in a bone marrow specimen and by a positive result for the immunochromatography-based test targeting the leishmania donovani rk39 antibody. a polymerase chain reaction (pcr) specifi ...200919346379
targeting histone deacetylase inhibitors for anti-malarial therapy.it is now clear that histone acetylation plays key roles in regulating gene transcription in both eukaryotes and prokaryotes, the acetylated form inducing gene expression while deacetylation silences genes. recent studies have identified roles for histone acetyltransferases (hats) and/or histone deacetylases (hdacs) in a number of parasites including entamoeba histolytica, toxoplasma gondii, schistosoma mansoni, cryptosporidium sp., leishmania donovani, neospora caninum, and plasmodium falciparu ...200919355992
leishmania donovani: thionins, plant antimicrobial peptides with leishmanicidal activity.the leishmanicidal activity of plant antibiotic peptides (paps) from the principal families, such wheat thionins, a barley lipid transfer protein and potato defensins and snakins were tested in vitro against leishmania donovani. only thionins and defensins were active against this human pathogen at a low micromolar range of concentrations. thionins resulted as the most active peptides tested until now. they collapsed ionic and ph gradients across the parasite plasma membrane together with a rapi ...200919361504
parasitological diagnosis of canine visceral leishmaniasis: is intact skin a good target?the objective of this study was to evaluate intact skin of seroreactive dogs as a possible target for the parasitological confirmation of canine visceral leishmaniasis (cvl). for this purpose, 394 dogs identified in serological surveys carried out in the metropolitan region of belo horizonte were studied. blood was collected from all animals for serology and a tissue sample was obtained from two sites for parasitological diagnosis. skin obtained from the ear and scapular region was simultaneousl ...200919364614
bioactive (+)-manzamine a and (+)-8-hydroxymanzamine a tertiary bases and salts from acanthostrongylophora ingens and their preparations.the genus acanthostrongylophora is famous for producing a wide array of manzamine alkaloids as natural hydrochloride salts. an examination of a. ingens has now yielded two tertiary bases, (+)-8-hydroxymanzamine a (1) and (+)-manzamine a (2), by chromatography over alumina using chcl3-meoh-nh3.h2o as solvent. in addition, (+)-8-hydroxymanzamine a hydrochloride (3) and (+)-manzamine a hydrochloride (4) were isolated under the same conditions from the same source by silica gel chromatography. the s ...200919370920
functionality of drug efflux pumps in antimonial resistant leishmania donovani field isolates.the recent upsurge of antimony (sb) resistance is a major impediment to successful chemotherapy of visceral leishmaniasis (vl). mechanisms involved in antimony resistance have demonstrated an upregulation of drug efflux pumps; however, the biological role drug efflux pumps in clinical isolates remains to be substantiated. thus, in this study, the functionality of drug efflux pumps was measured in promastigotes and axenic amastigotes isolated from vl patients, who were either sb-sensitive (ag83, ...200919374259
the paraphyletic composition of leishmania donovani zymodeme mon-37 revealed by multilocus microsatellite typing.multilocus microsatellite typing (mlmt) was employed to compare strains of leishmania donovani belonging to the mon-37 zymodeme (mon-37 strains) from cyprus and israel to mon-37 strains from the indian subcontinent, the middle east, china and east africa as well as strains of other zymodemes. the mlmt data were processed with a distance-based method for construction of phylogenetic trees, factorial correspondence analysis and a bayesian model-based clustering algorithm. all three approaches assi ...200919376262
quinacrine and a novel apigenin dimer can synergistically increase the pentamidine susceptibility of the protozoan parasite leishmania.the aim of this study was to investigate the synergistic effect of quinacrine and a novel apigenin dimer (compound 9d) on reversing pentamidine resistance of leishmania parasites.200919377065
genetics and visceral leishmaniasis: of mice and man.ninety per cent of the 500,000 annual new cases of visceral leishmaniasis (vl) occur in india/bangladesh/nepal, sudan and brazil. importantly, 80-90% of human infections are sub-clinical or asymptomatic, usually associated with strong cell-mediated immunity. understanding the environmental and genetic risk factors that determine why two people with the same exposure to infection differ in susceptibility could provide important leads for improved therapies. recent research using candidate gene as ...200919388946
mutational studies reveal lysine 352 on the large subunit is indispensable for catalytic activity of bi-subunit topoisomerase i from leishmania donovani.from the vanadate complex crystal structure of leishmania donovani topoisomerase i, several amino acid residues have been implicated to be involved in the catalytic reaction. although several predictions and propositions have been made, the exact role of these amino acids has not yet been clearly demonstrated in vitro. among these residues, lysine 352 and arginine 314 stand as potential candidates for playing the role of a general acid during the cleavage step. in this study, we have characteriz ...200919393162
flow cytometric determination of intracellular non-protein thiols in leishmania promastigotes using 5-chloromethyl fluorescein diacetate.leishmania parasites lack catalase and therefore, their anti-oxidant system hinges primarily upon non-protein thiols; accordingly, depletion of thiols could potentially serve as an effective drug target. we have developed a flow cytometry based assay using 5-chloromethyl fluorescein diacetate based upon its selective staining of non-protein thiols. its specificity was confirmed using buthionine sulphoximine (a gamma-glutamyl cysteine synthetase inhibitor), diamide (an oxidizing agent of intracel ...200919393240
ancient leishmania coronin (crn12) is involved in microtubule remodeling during cytokinesis.in general, coronins play an important role in actin-based processes, and are expressed in a variety of eukaryotic cells, including leishmania. here, we show that leishmania coronin preferentially distributes to the distal tip during cytokinesis, and interacts with microtubules through a microtubule-based motor, kinesin k39. we further show that reduction in coronin levels by 40-50% in heterozygous coronin mutants results in generation of bipolar cells (25-30%), specifically in the log phase, ow ...200919401334
synthesis and antiprotozoal activities of dicationic bis(phenoxymethyl)benzenes, bis(phenoxymethyl)naphthalenes, and bis(benzyloxy)naphthalenes.a series of 37 dicationically substituted bis(phenoxymethyl)benzene bis(phenoxymethyl)naphthalene, and bis(benzyloxy)naphthalene analogues of pentamidine was prepared and evaluated for antiprotozoal activities and cytotoxicity in in vitro. 1,3-bis(4-amidinophenoxymethyl)benzene (1) was the most active against trypanosoma brucei rhodesiense (ic(50)=2.1 nm). 1,3-bis[4-(n-isopropylamidino)phenoxymethyl]benzene (2) was most active against plasmodium falciparum (ic(50)=3.6 nm) and displayed a selecti ...200919409677
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 ...200919422069
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 ...200919429678
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 ...200919431098
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 ...200919436710
presentation of leishmaniasis (leishmania infantum) in the skin of a patient with severe atopic dermatitis. 200919438451
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 ...200919439418
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 ...200919445946
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. ...200919454711
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 ...200919457530
greater abundance of extracellular leishmania donovani bodies: possible clue from comparison of bone marrow aspirate and imprint findings. 200919474363
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 ...200919475352
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 ...200919478252
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 ...200919482476
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 ...200919500579
the sandflies of the satluj river valley, himachal pradesh (india): some possible vectors of the parasite causing human cutaneous and visceral leishmaniases in this endemic focus.the recently recognized endemic focus of leishmaniasis in satluj river valley in himachal pradesh (india) lies in north-western himalayas (30 degrees n, 70 degrees e). this endemic focus of leishmaniasis appears peculiar where localized cutaneous leishmaniasis (lcl) co-exists with visceral leishmaniasis (vl), and leishmania donovani is predominant pathogen for lcl whereas only a few cases have been due to leishmania tropica. this study was carried out to collect sandflies, identify and delineate ...200919502693
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), ...200919503834
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 ...200919513006
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 ...200919521904
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.200919525291
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 ...200919527698
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 ...200919528177
role of the domestic dog as a reservoir host of leishmania donovani in eastern sudan.abstract:200919534802
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 ...200919540316
malnutrition promotes prostaglandin over leukotriene production and dysregulates eicosanoid-cytokine crosstalk in activated resident macrophages.we previously described a murine model of malnutrition that mimicked features of moderate human malnutrition, and led to increased dissemination of leishmania donovani. in this study, we investigated the effect of malnutrition on macrophage production of cytokines, prostaglandins (pgs), and leukotrienes (lts). using either lps or calcium ionophore a23187 as a stimulus, macrophages from the malnourished mice produced a 3-fold higher pg/lt ((pge(2)+6-keto-pgf(1alpha))/(ltb(4)+cysteinyl leukotriene ...200919541468
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 ...200919541788
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- ...200919542458
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 ...200919545517
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. ...200919545519
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. ...200919546361
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 ...200919559111
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 ...200919563920
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 ...200919564359
phlebotomus (euphlebotomus) barguesae n. sp. from thailand (diptera - psychodidae).abstract:200919128518
primary laryngeal leishmaniasis: a rare case report.laryngeal leishmaniasis is extremely rare. we report a case of primary laryngeal leishmaniasis in a 70-year-old male who was admitted with complaints of gradual progressive hoarseness of the voice, dyspnea, cough for the past 3 months and noisy breathing for the past 5 days. an x-ray of the soft tissue of the neck showed a prevertebral soft tissue mass causing narrowing of the airway at the c6-c7 vertebral level. a computerized tomography (ct) scan showed a soft tissue mass in the subglottic reg ...200919136784
screening of agelasine d and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral leishmaniasis and chagas disease.there is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. the marine sponge (agelas sp.) metabolite agelasine d, as well as other agelasine analogs and related structures were screened for inhibitory activity against plasmodium falciparum, leishmania infantum, trypanosoma brucei and t. cruzi, as well as for toxicity against mrc-5 fibroblast cells. many compounds displayed high general toxicity towards both the protozoa and mrc-5 cells. however, tw ...200919136916
paromomycin: uptake and resistance in leishmania donovani.paromomycin is currently in phase iv clinical trials against leishmaniasis. in the present work we elucidate the effect and mechanism of uptake of paromomycin in leishmania donovani. the in vitro sensitivities of both promastigotes and amastigotes were determined to this aminoglycoside. association of paromomycin with l. donovani involved a rapid initial phase that was non-saturable up to 1mm of the drug. this initial phase was largely independent of temperature and not affected by metabolic inh ...200919146886
cutaneous leishmaniasis due to leishmania chagasi/le. infantum in an endemic area of guarico state, venezuela.this study reports cutaneous leishmaniasis (cl) caused by leishmania chagasi/le. infantum in venezuela, with some atypical characteristics. out of 63 cases of cl in the suburbs of altagracia de orituco, guarico state, venezuela, 30 presented clinical, parasitological, immunological and epidemiological features different from those of the classical cl known in the country. the initial lesion was small and nodular, which, if not treated, might progress to a superficial ulcer. no secondary infectio ...200919150102
kmp-11 dna immunization significantly protects against l. donovani infection but requires exogenous il-12 as an adjuvant for comparable protection against l. major.as vaccine potential of cross-species protection by a candidate antigen is less explored, in this study we compared cross-specific protective efficacy of kinetoplastid membrane protein-11 (kmp-11) as a dna vaccine alone and in conjunction with exogenous il-12 administration in experimental balb/c model against two most widely prevalent forms of clinical diseases caused by leishmania major (lm) and leishmania donovani (ld). whereas, kmp-11 dna vaccination alone showed significant potential in ter ...200919162111
vaccination route that induces transforming growth factor beta production fails to elicit protective immunity against leishmania donovani infection.balb/c mice immunized intraperitoneally (i.p.) and intravenously (i.v.) with leishmania donovani promastigote membrane antigens (lag), either free or encapsulated in liposomes, were protected against challenge infection with l. donovani, whereas mice immunized by the subcutaneous (s.c.) and intramuscular routes were not protected. protected mice showed strong parasite resistance in both the liver and spleen, along with enhanced immunoglobulin g2a and delayed-type hypersensitivity responses. agai ...200919168736
the rk39 immunochromatic dipstick testing: a study for k39 seroprevalence in dogs and human leishmaniasis patients for possible animal reservoir of cutaneous and visceral leishmaniasis in endemic focus of satluj river valley of himachal pradesh (india).the newly recognized endemic focus of leishmaniasis in satluj river valley of himachal pradesh (india) has both localized cutaneous leishmaniasis (lcl) and visceral leishmaniasis (vl) predominantly caused by leishmania donovani. rapid rk39 immunochromatographic dipstick test detects circulating antibodies to recombinant k39 antigen of l. donovani-infantum complex and is highly specific/sensitive in diagnosing symptomatic or asymptomatic infection in humans and dogs.200919172032
leishmania donovani leishmaniasis in cyprus. 200919179221
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 ...200919190729
trypanocidal, leishmanicidal and cytotoxic effects of anthecotulide-type linear sesquiterpene lactones from anthemis auriculata.trypanosomiasis and leishmaniasis pose major public health threats for many countries, particularly those in sub-saharan africa and south america. in the present study, we evaluated the in vitro antiprotozoal activity of three irregular, linear sesquiterpene lactones recently isolated from greek anthemis auriculata, namely anthecotulide (1), 4-hydroxyanthecotulide (2) and 4-acetoxyanthecotulide (3). trypomastigote forms of trypanosoma brucei rhodesiense and t. cruzi as well as axenic amastigotes ...200919200703
rna editing and mitochondrial activity in promastigotes and amastigotes of leishmania donovani.kinetoplast maxicircle dna sequence organisation was investigated in leishmania donovani, strain 1s ldbob. gene arrangement in the coding (conserved) region of the maxicircle is collinear with that of most trypanosomatids, with individual genes showing 80-90% nucleotide identity to leishmania tarentolae, strain uc. the notable exception was an integration of a full-size minicircle sequence in the nd1 gene coding region found in l. donovani. editing patterns of the mitochondrial mrnas investigate ...200919109964
potentiation by cigarette smoke of macrophage function against leishmania donovani infection.cigarette smoke is able to induce the generation of reactive oxygen species and pro-inflammatory cytokines, which are mediators of macrophage function and therefore, we have investigated the ability of cigarette smoke to activate leishmania donovani infected peritoneal macrophage.200919115041
synthesis and antileishmanial activity of novel 2,4,6-trisubstituted pyrimidines and 1,3,5-triazines.a series of 2,4,6-trisubstituted pyrimidines and 1,3,5-triazines have been synthesized and screened for their in vitro and in vivo antileishmanial activity against leishmania donovani. among all, 14 compounds have shown promising inhibition of 80-100% at 10 microg/ml against promastigotes and ic(50) in the range of 0.89-9.68 microg/ml against amastigotes. three compounds 13, 32 and 33 with good selectivity index (s.i.) were screened for their in vivo activity in golden hamsters (mesocricetus aur ...200919217698
pcr and direct agglutination as leishmania infection markers among healthy nepalese subjects living in areas endemic for kala-azar.to compare a pcr assay and direct agglutination test (dat) for the detection of potential markers of leishmania infection in 231 healthy subjects living in a kala-azar endemic focus of nepal.200919228350
presence of antibodies against leishmania chagasi in haemodialysed patients.in the last decades there has been an increase in cases of visceral leishmaniasis complicating the post-transplant phase, mainly following kidney transplantation. the aim of this study was to evaluate the reactivity of haemodialysed patients using ifat. blood samples of 310 individuals from natal, rn, brazil, were collected and analysed. data regarding blood transfusion, cause of end-stage renal disease and duration of haemodialysis were also analysed. in total, 69 patients (22.3%) were positive ...200919237180
use of multilocus microsatellite typing (mlmt) for the genetic analysis of indian isolates of leishmania donovani. 200919583916
in vivo induction of the autophagic machinery in human bone marrow cells during leishmania donovani complex infection.autophagy is a homeostatic process promoting cell survival in periods of stress. the induction of the autophagic machinery has also been implicated in both innate and adaptive immunity. leishmania donovani, which is the causative pathogen of visceral leishmaniasis, is an intracellular parasite that invades and multiplies in bone marrow macrophages. we describe the induction of host cell autophagic machinery during acute natural bone marrow infection by l. donovani complex, detected by lc3b immun ...200919591960
intracellular replication-deficient leishmania donovani induces long lasting protective immunity against visceral leishmaniasis.no vaccine is currently available for visceral leishmaniasis (vl) caused by leishmania donovani. this study addresses whether a live attenuated centrin gene-deleted l. donovani (ldcen1(-/-)) parasite can persist and be both safe and protective in animals. ldcen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. safety was shown by the lack of parasites in spleen and liver in susceptible balb/c mice, immune compromised scid mice, and human vl model hamste ...200919592661
evaluation of anti-leishmanial activity of selected indian plants known to have antimicrobial properties.the severe toxicity, exorbitant cost and the emerging resistance of leishmania spp. against most of the currently used drugs led to the urgent need for exploiting our traditional ayurvedic knowledge to treat visceral leishmaniasis. the aim of this study was to evaluate the in vitro anti-leishmanial activity of various extracts from ten traditionally used indian medicinal plants. the methanolic extract from only two plants, withania somnifera dunal (ashwagandha) and allium sativum linn. (garlic), ...200919593584
holiday souvenirs from the mediterranean: three instructive cases of visceral leishmaniasis.with expanding travel activities, visceral leishmaniasis increasingly occurs in non-endemic areas and affects immunocompetent individuals with no other risk factor than holidays at the mediterranean coast. we report 3 instructive swiss cases of visceral leishmaniasis presenting with fever of unknown origin and pancytopenia and review current diagnostic and therapeutic concepts.200919593691
complete protection against experimental visceral leishmaniasis with complete soluble antigen from attenuated leishmania donovani promastigotes involves th1-immunity and down-regulation of il-10.compared with cutaneous leishmaniasis, vaccination against visceral leishmaniasis has received limited attention. most available drugs are toxic, and relapse after cure remains a chronic problem. growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine strategy against visceral leishmaniasis deepens the crisis. complete soluble antigen (csa), from a beta1-4 galactosyltransferase expressing attenuated leishmania donovani paras ...200919593771
visceral leishmaniasis and anti-tnf-alpha therapy: case report and review of the literature.visceral leishmaniasis (vl) is an extremely rare example of opportunistic infection in patients treated with tnf-alpha antagonists and only a few cases have been described. in this paper risk factors, clinical features, diagnostic work-up and outcome of patients developing vl under biologic therapy are described.200919604446
synthesis and antiprotozoal activity of pyridyl analogues of pentamidine.a series of novel pyridyl analogues 1-18 of antiprotozoal drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) has been synthesized and tested for in vitro activities against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani, and for cytotoxicity against mammalian cells. antiprotozoal properties of compounds 1-18 depended on the placement of cationic moieties on the pyridine rings as well as the nature of substituents on the amidine groups. diamidine 6 with cationic m ...200919606902
il-17 and il-22 are associated with protection against human kala azar caused by leishmania donovani.il-17 and il-22 have been shown to increase protection against certain bacteria and fungal pathogens in experimental models. however, no human studies have demonstrated a crucial role of il-17 and il-22 in protection against infections. we show here that leishmania donovani, which can cause the lethal visceral disease kala azar (ka), stimulates the differentiation of th17 cells, which produce il-17, il-22, and ifn-gamma. analysis of th1, th2, and th17 cytokine responses by cultured pbmcs from in ...200919620772
an orally effective dihydropyrimidone (dhpm) analogue induces apoptosis-like cell death in clinical isolates of leishmania donovani overexpressing pteridine reductase 1.the protozoan parasite leishmania donovani is the causative agent of visceral leishmaniasis. the enzyme pteridine reductase 1 (ptr1) of l. donovani acts as a metabolic bypass for drugs targeting dihydrofolate reductase (dhfr); therefore, for successful antifolate chemotherapy to be developed against leishmania, it must target both enzyme activities. leishmania cells overexpressing ptr1 tagged at the n-terminal with green fluorescent protein were established to screen for proprietary dihydropyrim ...200919621245
improvement of the newly developed latex agglutination test (katex) for diagnosis of visceral lieshmaniasis.different methods are available for diagnosis of visceral leishmaniasis (vl), among them the urine-based antigen detection assay, latex agglutination test (katex), is a recently developed one. the main drawback of the test is false-positive reactivity in some of healthy individuals. the false positivity of the test can be removed by boiling the urine sample for 5 min before testing. in this study an attempt was made to improve katex by removing unpleasant boiling process, which also decreases fi ...200919623643
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