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antileishmanial ring-substituted ether phospholipids.three series of ring-substituted ether phospholipids were synthesized carrying n,n,n-trimethylammonium, n-methylpiperidino, or n-methylmorpholino headgroups. the first series is substituted by 2-cyclohexyloxyethyl or 2-(4-alkylidenecyclohexyloxy)ethyl groups, the second series by cyclohexylidenealkyl or adamantylidenealkyl moieties, and the third series by 2-aryloxyethyl or 6-aryloxyhexyl groups in the alkyl portion of the molecule. the antileishmanial activity of the new compounds was evaluated ...200312593656
characterization of the immune response to leishmania infantum recombinant antigens.leishmaniases have a high prevalence in tropical countries. in order to improve existing diagnostic systems based on total leishmania proteins, and to identify antigen candidates for vaccine development, an intensive search for the identification of antigens was performed using molecular biology techniques. in this study, the immune response to three l. infantum recombinant antigens was evaluated. upon stimulation with kmp11, mononuclear cells from leishmaniasis patients produced high levels of ...200312593967
overexpression and increased dna topoisomerase ii-like enzyme activity in arsenite resistant leishmania donovani.western immunoblot analyses of whole cell lysates probed with a human specific monoclonal anti-topoisomerase iialpha antibody identified a 190 kda protein over expressed in the arsenite resistant leishmania donovani strain. the crude nuclear extract of the resistant strain showed higher topoisomerase ii-like enzyme activity. suggesting a possible regulatory role of putative topoisomerase ii in arsenite resistant leishmania.200312608580
induction of autophagic cell death in leishmania donovani by antimicrobial peptides.we demonstrate that antimicrobial peptides induce an autophagic cell death in the protozoan pathogen, leishmania donovani. in our study, three antimicrobial peptides, indolicidin, and two peptides derived from seminalplasmin exhibit antileishmanial activity with a 50% lethal dose of 3.5 x 10(-5), 3.8 x 10(-4) and 1.7 x 10(-8) microm, respectively. the action of these antimicrobial peptides on the leishmania cell involves ionic interactions, which are modulated by lipophosphoglycan on the parasit ...200312615333
genetic control of visceral leishmaniasis in a sudanese population: candidate gene testing indicates a linkage to the nramp1 region.there is some evidence showing that genetic factors are involved in human susceptibility to parasitic diseases such as schistosomiasis and malaria. studies have shown that the nramp1 and h-2 genes are implicated in the control of leishmania donovani infection in mice. we sought genetic loci involved in the control of susceptibility to visceral disease caused by l. donovani in humans. we studied 37 families with at least two affected sibs living in a village in eastern sudan, where an outbreak of ...200312618857
habropetaline a, an antimalarial naphthylisoquinoline alkaloid from triphyophyllum peltatum.the isolation, structural elucidation, and antiprotozoal activities of habropetaline a, a novel naphthylisoquinoline alkaloid from triphyophyllum peltatum, are described. this alkaloid had previously only been identified on line, by the lc-ms/ms-nmr-cd triad, in the crude extract of the rare and difficult-to-provide related plant species habropetalum dawei, whose small quantities available had not permitted to isolate the compound. as predicted by quantitative structure-activity relationship (qs ...200312620347
identification and characterization of adsorbed serum sialoglycans on leishmania donovani promastigotes.sialic acids as terminal residues of oligosaccharide chains play a crucial role in several cellular recognition events. the presence of sialic acid on promastigotes of leishmania donovani, the causative organism of indian visceral leishmaniasis, was demonstrated by fluorimetric high-performance liquid chromatography showing neu5ac and, to a minor extent, neu5,9ac2. the presence of neu5ac was confirmed by gc/ms analysis. furthermore, binding with sialic acid-binding lectins sambucus nigra aggluti ...200312626423
dendritic cell (dc)-based protection against an intracellular pathogen is dependent upon dc-derived il-12 and can be induced by molecularly defined antigens.upon loading with microbial ag and adoptive transfer, dendritic cells (dc) are able to induce immunity to infections. this offers encouragement for the development of dc-based vaccination strategies. however, the mechanisms underlying the adjuvant effect of dc are not fully understood, and there is a need to identify ag with which to arm dc. in the present study, we analyzed the role of dc-derived il-12 in the induction of resistance to leishmania major, and we evaluated the protective efficacy ...200312626575
prostaglandin production from arachidonic acid and evidence for a 9,11-endoperoxide prostaglandin h2 reductase in leishmania.lysates of leishmania promastigotes can metabolise arachidonic acid to prostaglandins. prostaglandin production was heat sensitive and not inhibited by aspirin or indomethacin. we cloned and sequenced the cdna of leishmania major, leishmania donovani, and leishmania tropica prostaglandin f(2alpha) synthase, and overexpressed their respective 34-kda recombinant proteins that catalyse the reduction of 9,11-endoperoxide pgh(2) to pgf(2alpha). database search and sequence alignment showed that l. ma ...200312633659
infection pattern and immune response in the spleen and liver of balb/c mice intracardially infected with leishmania donovani amastigotes.intracardial inoculation of balb/c mice with leishmania donovani amastigotes induced progressive visceral leishmaniasis (vl) with increasing splenic parasite load when followed upto 4-month postinfection period. in contrast, the liver parasite load reached maximum around 2-month postinfection period following which it started declining. the infection pattern differed somewhat from the earlier reports on mouse model of vl induced by intravenous inoculation of parasites with respect to the duratio ...200312644314
proteome mapping of the protozoan parasite leishmania and application to the study of drug targets and resistance mechanisms.leishmania is a protozoan parasite responsible for significant morbidity and mortality worldwide. few parasites have been subjected to proteomic analysis to date, but a genome sequencing project for leishmania major is currently underway, making these studies possible. here we present a high resolution proteome for l. major comprising almost 3700 spots, making it the most complete two-dimensional gel representation of a parasite proteome generated to date. we have identified a number of landmark ...200312644573
molecular cloning, biochemical and structural analysis of elongation factor-1 alpha from leishmania donovani: comparison with the mammalian homologue.the src-homology 2 domain containing protein tyrosine phosphatase-1 (shp-1) is involved in the pathogenesis of infection with leishmania. recently, we identified elongation factor-1 alpha (ef-1 alpha) from leishmania donovani as a shp-1 binding and activating protein [j. biol. chem. 277 (2002) 50190]. to characterize this apparent leishmania virulence factor further, the cdna encoding l. donovani ef-1 alpha was cloned and sequenced. whereas nearly complete sequence conservation was observed amon ...200312646217
role of protein kinase c alpha for uptake of unopsonized prey and phagosomal maturation in macrophages.protein kinase c alpha (pkc alpha) participates in f-actin remodeling during phagocytosis and phagosomal maturation in macrophages. leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal f-actin instead of the disassembly observed around other prey [cell. microbiol. 7 (2001) 439]. this accumulation is induced by promastigote lipophosphoglycan (lpg), which has several effects on macrophages including inhibition of pkc alpha. to investigate a p ...200312646218
turnover of trypanosomal ornithine decarboxylases.interestingly, there is a major difference in turnover rate between ornithine decarboxylases (odcs) from various trypanosomatids. odcs from trypanosoma brucei and leishmania donovani are both stable proteins, whereas odc from crithidia fasciculata is a metabolically unstable protein in the parasite. c. fasciculata odc is also rapidly degraded in mammalian systems, whereas the closely related l. donovani odc is not. the degradation of c. fasciculata odc in the mammalian systems is shown to be dep ...200312653649
specific recognition of leishmania major poly-beta-galactosyl epitopes by galectin-9: possible implication of galectin-9 in interaction between l. major and host cells.leishmania parasites are the causative agents of leishmaniasis, manifesting itself in a species-specific manner. the glycan epitopes on the parasite are suggested to be involved in the leishmania pathogenesis. one of such established species-unique glycan structures is the poly-beta-galactosyl epitope (galbeta1-3)n found on l. major, which can develop cutaneous infections with strong inflammatory responses. interestingly, the polygalactosyl epitope is also suggested to be involved in the develop ...200312684513
molecular diagnosis of leishmaniosis in dogs. comparative application of traditional diagnostic methods and the proposed assay on clinical samples.leishmaniosis is a zoonotic, parasitic disease caused by members of the genus leishmania. the disadvantages of the traditional methods have currently rendered the polymerase chain reaction (pcr), the most reliable alternative for the laboratory diagnosis of this disease. several relevant protocols have been described in the past but their application is in most cases limited to research use. the latter combined with the diagnostic problems that can be caused by the genetic variability of the dif ...200312695035
anti-leishmania antibodies in cerebrospinal fluid from dogs with visceral leishmaniasis.visceral leishmaniasis in brazil is caused by leishmania (leishmania) chagasi and the dog is its most important reservoir. the clinical features in dogs include loss of weight, lymphadenopathy, renal failure, skin lesions, fever, hypergammaglobulinemia, hepatosplenomegaly, anemia, and, rarely, neurological symptoms. most infected animals develop active disease, characterized by high anti-leishmania antibody titers and depressed lymphoproliferative ability. antibody production is not primarily im ...200312700826
immunosuppression in hamsters with progressive visceral leishmaniasis is associated with an impairment of protein kinase c activity in their lymphocytes that can be partially reversed by okadaic acid or anti-transforming growth factor beta antibody.progressive visceral infection of golden hamsters by leishmania donovani amastigotes led to gradual impairment of the proliferative responses of their splenic or peripheral blood mononuclear cells (spmc or pbmc, respectively) to in vitro stimulation with phorbol 12-myristate 13-acetate (pma) and ionomycin (io). removal of macrophage-like adherent cells from spmc or pbmc of infected animals (i-spmc or i-pbmc) was earlier shown to restore almost completely their lymphoproliferative responses to pm ...200312704114
antimonial-induced increase in intracellular ca2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular leishmania donovani amastigotes.the capability of the obligate intracellular parasites like leishmania donovani to survive within the host cell parasitophorous vacuoles as nonmotile amastigotes determines disease pathogenesis, but the mechanism of elimination of the parasites from these vacuoles are not well understood. by using the anti-leishmanial drug potassium antimony tartrate, we demonstrate that, upon drug exposure, intracellular l. donovani amastigotes undergo apoptotic death characterized by nuclear dna fragmentation ...200312707265
members of a unique histidine acid phosphatase family are conserved amongst a group of primitive eukaryotic human pathogens.recently, we identified and characterized the genes encoding several distinct members of the histidine-acid phosphatase enzyme family from leishmania donovani, a primitive protozoan pathogen of humans. these included genes encoding the heavily phosphorylated/glycosylated, tartrate-sensitive, secretory acid phosphatases (ld sacp-1 and ld sacp-2) and the unique, tartrate-resistant, externally-oriented, surface membrane-bound acid phosphatase (ld macp) of this parasite. it had been previously sugge ...200312708742
the in vivo susceptibility of leishmania donovani to sodium stibogluconate is drug specific and can be reversed by inhibiting glutathione biosynthesis.resistance to pentavalent antimonial (sb(v)) agents such as sodium stibogluconate (ssg) is creating a major problem in the treatment of visceral leishmaniasis. in the present study the in vivo susceptibilities of leishmania donovani strains, typed as ssg resistant (strain 200011) or ssg sensitive (strain 200016) on the basis of their responses to a single ssg dose of 300 mg of sb(v)/kg of body weight, to other antileishmanial drugs were determined. in addition, the role of glutathione in ssg res ...200312709318
peroxisomal function is altered during leishmania infection.the aim of this study was to investigate host peroxisomal properties after leishmania infection and provide clues to protect peroxisomes during the search for new chemotherapeutic strategies against leishmaniasis.200312709663
antileishmanial activity of two gamma-pyrones from podolepsis hieracioides (asteraceae).two gamma-pyrones isolated from the seeds of podolepsis hieracioides (asteraceae) have been tested for their in vitro leishmanicidal activity against the promastigote form of leishmania donovani, l. major, l. infantum and l. enriettii (ic(50)=3.76-5.43 microg/ml), and against the amastigote form of l. donovani residing within raw 264.7 macrophage-like host cells (ic(50)=8.29-8.59 microg/ml). general toxicity of the gamma-pyrones was investigated in parallel against three mammalian cell lines (ra ...200312711109
synthesis and antiprotozoal activity of naphthofuranquinones and naphthothiophenequinones containing a fused thiazole ring.the synthesis of tetracyclic quinones 10a,b, 14a,b, 19a,b and 20a,b is described. the preparations involve regioselective diels-alder reactions via trapping the thiazole o-quinodimethane 9 with several benzofuranquinones and benzothiophenequinones. the structure of the regioisomers was assigned through 2d nmr 1h-13c hmbc experiments performed on 10a and 14a. compounds 10a,b, 14a as well as phenol 1 and the starting quinones 2, 5, 7 and 15 are evaluated against leishmania sp., toxoplasma gondii a ...200312713827
a preliminary report on culture of leishmania donovani in mymensingh medical college and evaluation of new immuno-chromatography test (ict).a total of 51 inpatients having prolonged low grade irregular fever with anaemia, hepatosplenomegaly, emaciation and other allied features were evaluated by findings of haematologic, seroimmunologic, microscopic examination for ld body and culture for l. donovani. the study was done during the period from september' 1999 to january' 2000. bone marrow or splenic aspirates were examined for ld bodies and those samples were cultured in modified nnn media following a standard method. out of 51 sampl ...200312715645
leishmania mexicana and leishmania major: attenuation of wild-type parasites and vaccination with the attenuated lines.a method for attenuation of leishmania species by culturing in vitro under gentamicin pressure has been used successfully with leishmania mexicana, l. major, l. infantum, and l. donovani. the attenuated lines invaded but were unable to survive within bone marrow-derived macrophages in vitro, whereas wild-type parasites survived and multiplied. the attenuated lines of l. mexicana and l. major both failed to induce cutaneous lesions in the majority of balb/c mice over a minimum 12-week observation ...200312721947
visceral leishmaniasis presenting as subcutaneous nodules in a hiv-positive patient. 200312736797
variation of leishmanicidal activity in four populations of urechites andrieuxii.urechites andrieuxii muell.-arg. (apocynaceae) is widely used in the yucatan peninsula for the treatment of cutaneous leishmaniasis. the influence of the environment in the variability of the leishmanicidal activity of the plant was evaluated using crude methanol extracts of roots from individuals belonging to four natural populations growing in the yucatan peninsula. the results of the growth inhibition test using three leishmania spp. promastigotes showed a stronger leishmanicidal activity in ...200312738094
effect of itraconazole and terbinafine on leishmania promastigotes.the antiproliferative effect induced in vitro by two antifungal compounds, the azole itraconazole and the allylamine terbinafine on leishmania major, l. donovani and l. mexicana promastigotes are reported. treatment of promastigotes cultures with itraconazole or with terbinafine induced growth arrest with l. major but neither with l. donovani nor with l. mexicana. concentrations of 0.75 microl/l or more of itraconazole induced cell lysis after 72 hours with l. major. however, even relatively lar ...200312739804
improvements in transfection efficiency and tests of rna interference (rnai) approaches in the protozoan parasite leishmania.approaches which eliminate mrna expression directly are ideally suited for reverse genetics applications in eukaryotic microbes which are asexual diploids, such as the protozoan parasite leishmania. rna interference (rnai) approaches have been successful in many species, including the related parasite trypanosoma brucei. for rnai tests in leishmania, we developed improved protocols for transient and stable dna transfection, attaining efficiencies of up to 25 and 3%, respectively. this facilitate ...200312742588
igg1/igg2 antibody dichotomy in sera of vaccinated or naturally infected dogs with visceral leishmaniosis.canine antibody igg, igg1 and igg2 anti-fml responses were investigated in dogs vaccinated with the fucose-mannose ligand (fml)-vaccine of leishmania donovani and in dogs with naturally acquired visceral leishmaniosis. while similar levels of total igg antibodies were seen in the seropositive naturally infected dogs and in vaccinees, significant differences between the groups were found regarding their igg1/igg2 anti-fml antibody composition (p<0.005). higher igg1 absorbencies were seen in infec ...200312744895
dendritic cell-based immunotherapy combined with antimony-based chemotherapy cures established murine visceral leishmaniasis.dendritic cells (dcs) have been proposed to play a critical role as adjuvants in vaccination and immunotherapy. in this study we evaluated the combined effect of soluble leishmania donovani ag (slda)-pulsed syngeneic bone marrow-derived dc-based immunotherapy and antimony-based chemotherapy for the treatment of established murine visceral leishmaniasis. three weekly injections of slda-pulsed dcs into l. donovani-infected mice reduced liver and splenic parasite burden significantly, but could not ...200312759442
antileishmanial drugs cause up-regulation of interferon-gamma receptor 1, not only in the monocytes of visceral leishmaniasis cases but also in cultured thp1 cells.apparently for the first time, the peripheral blood monocytes of individuals with active visceral leishmaniasis (vl) have been found to show reduced expression of interferon gamma receptor-1 (ifngr1). since interferon gamma is the main cytokine responsible for defence against leishmanial parasites, it was thought possible that effective antileishmanial drugs may up-regulate ifngr1. confocal microscopy confirmed that monocytes from vl patients who had been treated, with sodium antimony gluconate ...200312803856
[involvement of the renal function in patients with visceral leishmaniasis (kala-azar)].evaluation of the renal involvement of visceral leishmaniasis (kala-azar) aiming at verifying clinical and laboratorial repercussions of the renal implication on vl. laboratory analysis was performed of blood and urine samples collected immediately after confirming diagnosis through the finding of leishmania in bone marrow. two (18.1%) patient presented complications associated with kala-azar. five patients (45.4%) presented macroscopic hematuria and one case (n 9) clinical manifestations compa ...200312806457
functional analysis of an inosine-guanosine transporter from leishmania donovani. the role of conserved residues, aspartate 389 and arginine 393.equilibrative nucleoside transporters encompass two conserved, charged residues that occur within predicted transmembrane domain 8. to assess the role of these "signature" residues in transporter function, the asp389 and arg393 residues within the ldnt2 nucleoside transporter from leishmania donovani were mutated and the resultant phenotypes evaluated after transfection into delta ldnt2 parasites. whereas an r393k mutant retained transporter activity similar to that of wild type ldnt2, the r393l ...200312807872
decrease of intestinal p-glycoprotein activity by 2n-propylquinoline, a new oral treatment for visceral leishmaniasis.drugs currently available for visceral leishmaniasis treatment are potentially toxic, have to be administered by parenteral route and frequently give rise to drug resistance, due to the involvement of p-glycoproteins (p-gp) in leishmania. the purpose of this study was to investigate a possible inhibitory effect of 2n-propylquinoline (2npq) on p-gp activity. 2npq is a new oral anti-leishmanial drug that has demonstrated its efficacy in balb/c infected mice with leishmania donovani [antimicrob. ag ...200312810046
synthesis and biological evaluation of substrate-based inhibitors of 6-phosphogluconate dehydrogenase as potential drugs against african trypanosomiasis.the synthesis and biological evaluation of three series of 6-phosphogluconate (6pg) analogues is described. (2r)-2-methyl-4,5-dideoxy, (2r)-2-methyl-4-deoxy and 2,4-dideoxy analogues of 6pg were tested as inhibitors of 6-phosphogluconate dehydrogenase (6pgdh) from sheep liver and also trypanosoma brucei where the enzyme is a validated drug target. among the three series of analogues, seven compounds were found to competitively inhibit 6pgdh from t. brucei and sheep liver enzymes at micromolar co ...200312818683
immune responses induced by the leishmania (leishmania) donovani a2 antigen, but not by the lack antigen, are protective against experimental leishmania (leishmania) amazonensis infection.leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the americas, which overlaps with the areas of transmission of many other leishmania species. the lack and a2 antigens are shared by various leishmania species. a2 was previously shown to induce a potent th1 immune response and protection against l. donovani infection in balb/c mice. lack is effective against l. major infection, but no sig ...200312819086
antimicrobial and antiparasitic (+)-trans-hexahydrodibenzopyrans and analogues from machaerium multiflorum.machaerium multiflorum yielded two additional new (+)-trans-hexahydrodibenzopyrans (hhdbp's), machaeriol c (1) and machaeriol d (2), and three new 5,6-seco-hhdbp's, machaeridiol a (3), machaeridiol b (4), and machaeridiol c (5). their structures and stereochemistries were determined by 1d and 2d nmr data, including hmbc, noesy, and circular dichroism experiments. machaeriol c (1) demonstrated in vitro antibacterial activity against staphylococcus aureus (ic(50) 0.65 microg/ml) and methicillin-re ...200312828466
new manzamine alkaloids with activity against infectious and tropical parasitic diseases from an indonesian sponge.eleven manzamine type alkaloids, two beta-carbolines, and five nucleosides have been isolated from an indonesian sponge. among these are the previously characterized 12,34-oxamanzamine a, 12,34-oxamanzamine e, manzamine a (1), 8-hydroxymanzamine a, 6-deoxymanzamine x, manzamine e (2), manzamine x, manzamine f (4), norharman, thymine, 2',3'-didehydro-2',3'-dideoxyuridine, uracil, thymidine, and 2'-deoxyuridine. the structures for the five new compounds have been assigned as 32,33-dihydro-31-hydro ...200312828469
comparison of the a2 gene locus in leishmania donovani and leishmania major and its control over cutaneous infection.in old world leishmania infections, leishmania donovani is responsible for fatal visceral leishmaniasis, and l. major is responsible for non-fatal cutaneous leishmaniasis in humans. the genetic differences between these species which govern the pathology or site of infection are not known. we have therefore carried out detailed analysis of the a2 loci in l. major and l. donovani because a2 is expressed in l. donovani but not l. major, and a2 is required for survival in visceral organs by l. dono ...200312829719
in-vitro antileishmanial and trypanocidal activities of arsonoliposomes and preliminary in-vivo distribution in balb/c mice.we have studied the antiprotozoal activity of some recently prepared and characterized arsonoliposome formulations. plain arsonoliposomes and phosphatidylcholine arsonoliposomes prepared with palmitoyl- (c16) or lauroyl-(c12) acyl side chain arsonolipids showed in-vitro antileishmanial activity after a 72-h incubation period against wild-type promastigote forms of leishmania donovani. the ic50 values ranged from 0.40 to 11.6 microm arsonolipid. interestingly, all preparations tested were found t ...200312831507
identification of surface-membrane p-type atpases resembling fungal k(+)- and na(+)-atpases, in trypanosoma brucei, trypanosoma cruzi and leishmania donovani.genomic dna fragments encoding nine, novel, p-type atpases in trypanosomatid organisms were amplified in pcr, using degenerate oligonucleotide primers that recognize the atp-binding and -phosphorylation sites present in all p-type atpases. subsequent phylogenetic analysis, based on the presence of conserved motifs in predicted peptide sequences for six trypanosoma brucei, t. cruzi or leishmania donovani pcr fragments, identified calcium-, proton- and phospholipid-translocating atpases. dna fragm ...200312831521
equilibrative nucleoside transporter family members from leishmania donovani are electrogenic proton symporters.leishmania donovani express two members of the equilibrative nucleoside transporter family; ldnt1 encoded by two closely related and linked genes, ldnt1.1 and ldnt1.2, that transport adenosine and pyrimidine nucleosides and ldnt2 that transports inosine and guanosine exclusively. ldnt1.1, ldnt1.2, and ldnt2 have been expressed in xenopus laevis oocytes and found to be electrogenic in the presence of nucleoside ligands for which they mediate transport. further analysis revealed that ligand uptake ...200312835315
genetic susceptibility to visceral leishmaniasis in the sudan: linkage and association with il4 and ifngr1.longitudinal studies in sudan show ethnic differences in incidence and clinical phenotypes associated with leishmania donovani. immunologically, bias in type 1 vs type 2 cytokine responses is important. to determine whether polymorphisms at il4/il9 or ifngr1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (vl) with/without post kala-azar dermal leishmaniasis (pkdl). multipoint nonparametric analysis (allegro) linked il4/il9 to vl per se (p=0.002). transm ...200312847550
the domestic dog, a potential reservoir for leishmania in the peten region of guatemala.in the present study, domestic dogs in a leishmania endemic area in the peten region of guatemala were sampled to determine if they are a potential reservoir for leishmania parasites. blood from 100 dogs from six villages was tested with two different antibody-capture assays for leishmania-specific antibodies and a 28% seroprevalence was determined. tissue scrapings from six dogs presenting with chronic lesions characteristic of leishmania infection were sampled and four dogs were positive by a ...200312860062
identification of new leishmanicidal peptide lead structures by automated real-time monitoring of changes in intracellular atp.leishmanicidal drugs interacting stoichiometrically with parasite plasma membrane lipids, thus promoting permeability, have raised significant expectations for leishmania chemotherapy due to their nil or very low induction of resistance. inherent in this process is a decrease in intracellular atp, either wasted by ionic pumps to restore membrane potential or directly leaked through larger membrane lesions caused by the drug. we have adapted a luminescence method for fast automated real-time moni ...200312864731
an overview of paediatric leishmaniasis.leishmaniasis, a parasitic disease transmitted by the bite of some species of sandflies affects various age groups depending on the infecting leishmania species, geographic location, disease reservoir, and host immunocompetence. visceral leishmaniasis is the most severe form of the disease affecting children. the extent and presentation of the disease depend on several factors, including the humoral and cell-mediated immune response of the host, the virulence of the infecting species, and the pa ...200312865569
antiparasitic activity of marine pyridoacridone alkaloids related to the ascididemins.a series of pyridoacridone alkaloids, including the marine alkaloid ascididemin were tested in vitro for antiparasitic activity against p. falciparum (k1, nf54), l. donovani, t. cruzi, t. b. rhodesiense and two mammalian cell lines (l6, raw 264.7). most compounds showed high antiplasmodial activity, moderate antileishmanial activity against both extra- and intracellular forms, and significant trypanocidal effects against t. cruzi and t. b. brucei. however, when tested against mammalian cell line ...200312865971
determinants of response to interleukin-10 receptor blockade immunotherapy in experimental visceral leishmaniasis.in established leishmania donovani visceral infection in normal mice, anti-interleukin (il)-10 receptor (il-10r) monoclonal antibody (mab) treatment induced intracellular parasite killing within liver macrophages. il-10r blockade maintained il-12 protein 40, markedly increased interferon (ifn)-gamma serum levels, and enhanced tissue inducible nitric oxide synthase (inos) expression and granuloma assembly. optimal mab-induced killing, including synergism with antimony chemotherapy, required endog ...200312870129
both interleukin-4 (il-4) and il-4 receptor alpha signaling contribute to the development of hepatic granulomas with optimal antileishmanial activity.the roles of interleukin-4 (il-4) and il-13 in the regulation of immunity to leishmania donovani infection are still poorly understood. here we show that the increased parasite load observed in il-4(-/-) and il-4 receptor alpha(-/-) mice correlates with retarded granuloma maturation and antileishmanial activity and that the increased parasite load observed in il-4 receptor alpha(-/-) mice correlates with increased nos2 expression and decreased serum gamma interferon levels. il-4 and il-13 appear ...200312874364
old world cutaneous leishmaniasis in los angeles: a case report, overview of the current literature, and guide for the treating dermatopathologist.we describe a case of cutaneous leishmaniasis in a spanish patient visiting los angeles. leishmania species cause both cutaneous and visceral disease; the majority of infections with leishmania are of the cutaneous form. although leishmaniasis is a relatively rare occurrence in the united states, travel by united states' citizens to endemic regions and increased united states military operations in the middle east raise the chances of encountering cutaneous leishmaniasis. the following case repo ...200312876489
leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug.miltefosine (hexadecylphosphocholine [hepc]) is the first drug approved for the oral treatment of visceral leishmaniasis. as part of a study on the mechanisms of action of this drug and on the rates of resistance to this drug, we have been working in vitro with an leishmania donovani line that was previously shown to be 15-fold more resistant to hepc. we have studied the accumulation of [(14)c]hepc by l. donovani promastigotes and have found a drastic reduction (>95%) in the ability of the resis ...200312878496
immunoenhancement combined with amphotericin b as treatment for experimental visceral leishmaniasis.to determine if stimulation of th1-cell-associated immune responses, mediated by interleukin 12 (il-12) and gamma interferon (ifn-gamma), enhance the antileishmanial effect of amphotericin b (amb), leishmania donovani-infected balb/c mice were first treated with (i) exogenous il-12 to induce ifn-gamma, (ii) agonist anti-cd40 monoclonal antibody (mab) to maintain il-12 and induce ifn-gamma, or (iii) anti-il-10 receptor (il-10r) mab to blockade suppression of il-12 and ifn-gamma. in animals with e ...200312878513
antiparasitic alkaloids from psychotria klugii.psychotria klugii yielded two new benzoquinolizidine alkaloids, klugine (1) and 7'-o-demethylisocephaeline (2), together with the previously known cephaeline (3), isocephaeline (4), and 7-o-methylipecoside (5). the structures and stereochemistry of 1 and 2 were determined by 1d and 2d nmr data and circular dichroism experiments. cephaeline (3) demonstrated potent in vitro antileishmanial activity against leishmania donavani (ic(50) 0.03 microg/ml) and was >20- and >5-fold more potent than pentam ...200312880315
phospholipid microspheres: a novel delivery mode for targeting antileishmanial agent in experimental leishmaniasis.novel phospholipid microspheres were prepared from polylactic-co-glycolic acid (plga) and phosphatidyl ethanol amine in the molar ratio 1:71, to deliver drugs to macrophages in experimental leishmaniasis. liposomes, well known as drug carrier systems, made from phosphatidylethanolamine, cholesterol and dicetyl phosphate in the molar ratio 7:2:1, were used as control, in order to compare the efficacies of the two carriers. as such, the membrane fluidity of the two carriers was kept at comparable ...200312881199
immunochromatographic (rk39) strip test in the diagnosis of visceral leishmaniasis in bangladesh.immunochromatographic strip test (ict strip test) for the diagnosis of visceral leishmaniasis was evaluated in this study in the context of a case-control study. a total sixty consecutive cases of kala-azar admitted in all four medicine units of mymensingh medical college hospital during the period of may 2002 to february 2003 was included here. parasitological confirmation was done by demonstration of leishmania donovani bodies in bone marrow or splenic aspiration in all cases. a total 120 cont ...200312894040
novel mechanism of drug resistance in kala azar field isolates.clinical resistance to pentavalent antimonial drugs in the form of sodium antimony gluconate (sag) has become a major problem in the treatment of kala azar (visceral leishmaniasis) in india. the mechanism of resistance is unclear in these clinical isolates, although work has been conducted with leishmania species mutants selected in vitro by stepwise increase of drug concentration, using antimony-related metal arsenic and, more recently, sag. in the present study, we investigated the molecular a ...200312898450
selection of aptamers against kmp-11 using colloidal gold during the selex process.selex procedure is a methodology in which single stranded oligonucleotides are selected from a wide variety of sequences based on their interaction with a target molecule. we have designed a novel selex methodology using colloidal gold to select high affinity single stranded dna aptamers against leishmania infantum kmp-11. kinetoplastid membrane protein-11 (kmp-11) is a major component of the cell membrane of kinetoplastid parasites. although its function is not known, the fact that kmp-11 is a ...200312901856
extracellular release of the surface metalloprotease, gp63, from leishmania and insect trypanosomatids.protease activity was found in spent culture medium collected from leishmania donovani, l. mexicana, l. major, as well as the insect trypanosomatids, crithidia luciliae and leptomonas seymouri. released protease activity increased linearly over time and was correlated to promastigote density. in sds-page, zymogram gels showed that the protease's molecular weight ranged from 43-100 kda. spent culture medium proteases were blocked by the metallo-protease inhibitors, 1,10-phenanthroline and z-tyr-l ...200312923634
naphthoquinone derivatives and lignans from the paraguayan crude drug "tayï pytá" (tabebuia heptaphylla, bignoniaceae).the paraguayan crude drug "tayï pytá" is used to treat cancer, wounds and inflammation. it consist of the bark and trunkwood of tabebuia heptaphylla (bignoniaceae). a phytochemical study of the crude drug gave, in addition to previously described naphthoquinones and the known lignans cycloolivil and secoisolariciresinol, three new lapachenol (lapachonone)-, two naphthofuran-, a chromone and a naphthalene derivative. the structures were elucidated by means of high field nmr spectroscopy. the biol ...200312939034
membrane orientation of laminin binding protein.earlier we presented several lines of evidence that a 67-kda laminin binding protein (lbp) in leishmania donovani, that is different from the putative mammalian 67-kda laminin receptor, may play an important role in the onset of leishmaniasis, as these parasites invade macrophages in various organs after migrating through the extracellular matrix. here we describe the membrane orientation of this leishmania laminin receptor. flow cytometric analysis using anti-lbp ig revealed its surface localiz ...200312950264
case 2. cutaneous leishmaniasis, leishmania amastigotes. 200312950363
prophylactic potential of autoclaved leishmania donovani with bcg against experimental visceral leishmaniasis.the prophylactic efficacy of autoclaved leishmania donovani (ald) and autoclaved l. major (alm)--a heterologous vaccine developed against cutaneous leishmaniasis (used as a reference vaccine), along with bcg--was evaluated against l. donovani in hamsters (mesocricetus auratus). animals were immunized with triple doses (21 days apart) of either ald or alm (1.0 mg) with or without bcg (0.1 mg) and challenged 21 days later with 1 x 10(6) l. donovani amastigotes intracardially. animals immunized wit ...200312954011
functional dissection of the c-terminal domain of type ii dna topoisomerase from the kinetoplastid hemoflagellate leishmania donovani.the amino acid sequences of the c-terminal domain (ctd) of the type ii dna topoisomerases are divergent and species specific as compared with the highly conserved n-terminal and central domains. a set of c-terminal deletion mutants of leishmania donovani topoisomerase ii was constructed. removal of more than 178 amino acids out of 1236 amino acid residues from the c-terminus inactivates the enzyme, whereas removal of 118 amino acids or less has no apparent effect on the ability of the parasite e ...200312954766
multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-kappab activation, and nitric oxide production.we have described previously a murine model of multinutrient undernutrition that reproduced the features of moderate human malnutrition and led to increased early dissemination of leishmania donovani. peritoneal cells from these malnourished mice produced decreased no after stimulation with ifn-gamma/lps. we hypothesized that malnutrition may cause a deficit in nf-kappab activation, a principal transcription pathway for inducible no synthase and proinflammatory cytokines. macrophages from malnou ...200312960263
bioactive alkyl phenols and embelin from oxalis erythrorhiza.the benzoquinone embelin and four alkyl phenols were isolated from an argentinean collection of oxalis erythrorhiza. 3-heptadecyl-5-methoxy-phenol is reported for the first time. the structures were determined by spectroscopic methods. embelin presented inhibitory effect on methicillin-resistant staphylococcus aureus, escherichia coli and the dermatophytic fungi epidermophyton floccosum, microsporum canis, microsporum gypseum, trichophyton mentagrophytes and trichophyton rubrum with mics ranging ...200312963150
abortive infection of lutzomyia longipalpis insect vectors by aflagellated ldarl-3a-q70l overexpressing leishmania amazonensis parasites.leishmania donovani adp-ribosylation factor-like protein 3a (ldarl-3a) is a small g protein isolated from the protozoan parasite l. donovani with no defined physiological function. previously [cuvillier, a., redon, f., antoine, j.-c., chardin, p., devos, t., and merlin, g. (2000) j cell sci 113: 2065-2074] we have shown that overexpression in l. amazonensis promastigotes of the mutated protein ldarl-3a-q70l, which remains constitutively associated with gtp, leads to the disappearance of the flag ...200312969377
post-kala-azar dermal leishmaniasis (pkdl): the first case report from nepal.post-kala-azar dermal leishmaniasis (pkdl) is condition characterized by non-ulcerative lesions of the skin caused by leishmania donovani that is usually seen after the completion of treatment of kala-azar (visceral leishmaniasis). we document the first case report of pkdl in nepal.200312971510
developmentally induced changes of the proteome in the protozoan parasite leishmania donovani.in order to proceed through their life cycle, protozoan parasites of the genus leishmania cycle between sandflies and mammals. this change of environment correlates with the differentiation from the promastigote stage (insect form) to the amastigote stage (intracellular mammalian form). the molecular basis underlying this major transformation is poorly understood so far; however, heat shock protein 90 (hsp90) appears to play a pivotal role. to further elucidate this process we identified protein ...200312973740
human mixed infections of leishmania spp. and leishmania-trypanosoma cruzi in a sub andean bolivian area: identification by polymerase chain reaction/hybridization and isoenzyme.parasites belonging to leishmania braziliensis, leishmania donovani, leishmania mexicana complexes and trypanosoma cruzi (clones 20 and 39) were searched in blood, lesions and strains collected from 28 patients with active cutaneous leishmaniasis and one patient with visceral leishmaniasis. pcr-hybridization with specific probes of leishmania complexes (l. braziliensis, l. donovani and l. mexicana) and t. cruzi clones was applied to the different dna samples. over 29 patients, 8 (27.6%) presente ...200312764443
dihydrobetulinic acid induces apoptosis in leishmania donovani by targeting dna topoisomerase i and ii: implications in antileishmanial therapy.leishmaniasis is the second-most dreaded parasitic disease in the modern world, behind malaria. the lack of effective vaccines demand improved chemotherapy along with the development of lead compounds and newer targets. we report here that the pentacyclic triterpenoid, dihydrobetulinic acid (dhba), is a novel lead compound for antileishmanial therapy. it acts by targeting dna topoisomerases. dna topoisomerase i and ii activity was studied using relaxation and decatenation assays. mechanistic stu ...200312765337
targeting of immunostimulatory dna cures experimental visceral leishmaniasis through nitric oxide up-regulation and t cell activation.active targeting of cpg-containing oligodeoxynucleotide (cpg-odn) to macrophages was studied by incorporating it in mannose-coated liposomes, using visceral leishmaniasis as the model macrophage disease. mannosylated liposomal cpg-odn was more effective than liposomal or free cpg-odn in inhibiting amastigote multiplication within macrophages. moreover, in a 60-day mouse model of visceral leishmaniasis, complete elimination of spleen parasite burden was achieved by mannosylated liposomal cpg-odn, ...200312778468
the activity of diguanidino and 'reversed' diamidino 2,5-diarylfurans versus trypanosoma cruzi and leishmania donovani.the in vitro activity of 20 dicationic molecules containing either diguanidino or reversed amidine cationic groups were evaluated versus trypanosoma cruzi and leishmania donovani. the most active compounds were in the reversed amidine series and six exhibited ic(50) values of less than 1 micro mol versus t. cruzi and five gave similar values versus l. donovani.200312781196
structure-activity relationships of antileishmanial and antimalarial chalcones.a series of oxygenated chalcones which have been evaluated earlier for antimalarial activity (plasmodium falciparum k1) were tested for antileishmanial activity against leishmania donovani amastigotes. a comparison of structure-activity relationships reveal that different physicochemical and structural requirements exist for these two activities. antileishmanial activity is associated with less lipophilic chalcones, in particular those with 4'-hydroxyl-substituted b rings and hetero/polyaromatic ...200312788347
prognostic factors for death from visceral leishmaniasis in teresina, brazil.a possible strategy to reduce fatality rates of visceral leishmaniasis is to identify prognostic factors that can be easily assessed and used as an aid to clinical decision-making.200312789476
fever, hepatosplenomegaly, and pancytopenia in a renal transplant recipient. 200312791075
antiprotozoal activities of symmetrical bishydroxamic acids.symmetrical bishydroxamic acids along with their sodium salts containing an alkyl spacer between two aromatic rings were synthesized, and their antiparasitic activities were evaluated. bishydroxamic acids were conveniently prepared from the alkylation of methyl 4-hydroxybenzoate with various dihalo-alkane, -alkene, and -ether followed by reaction with hydroxylamine. surprisingly, the bishydroxamic acids and their sodium salts possess strong inhibitory activities against plasmodium falciparum par ...200313129572
leishmania donovani-induced expression of suppressor of cytokine signaling 3 in human macrophages: a novel mechanism for intracellular parasite suppression of activation.leishmania donovani protozoan parasites, the causative agent of visceral leishmaniasis, establish an infection partly by interfering with cytokine signaling in the host macrophages. therefore, we investigated the expression of the suppressor of cytokine signaling (socs) genes in human macrophages infected with l. donovani. the expression of socs3 mrna was induced transiently after exposure to live or heat-killed parasites, but not purified lipophosphoglycan, while that of other socs genes remain ...200312654831
infection of human mononuclear phagocytes and macrophage-like thp1 cells with leishmania donovani results in modulation of expression of a subset of chemokines and a chemokine receptor.the expression of chemokines and chemokine receptors was studied in leishmania donovani (ld)-infected human mononuclear phagocytes and the human monocytic cell line thp1. our studies showed that ld infection caused the upregulation of three beta chemokines (macrophage inflammatory protein-1 alpha (mip-1alpha), mip-1beta and rantes (regulated on activation normal t cell expressed and secreted)), one alpha chemokine (interleukin-8 (il-8)) and the cc chemokine receptor 5 (ccr5) but not ccr1, as evi ...200312662300
unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites.monocyte-derived dendritic cells (dcs) and macrophages (ms) generated in vitro from the same individual blood donors were exposed to 5 different pathogens, and gene expression profiles were assessed by microarray analysis. responses to mycobacterium tuberculosis and to phylogenetically distinct protozoan (leishmania major, leishmania donovani, toxoplasma gondii) and helminth (brugia malayi) parasites were examined, each of which produces chronic infections in humans yet vary considerably in the ...200312663451
detection, differentiation, and quantitation of pathogenic leishmania organisms by a fluorescence resonance energy transfer-based real-time pcr assay.real-time technology eliminates many of the pitfalls of diagnostic pcr, but this method has not been applied to differentiation of leishmania organisms so far. we have developed a real-time pcr that simultaneously detects, quantitates, and categorizes leishmania organisms into three relevant groups causing distinct clinical pictures. the analytical sensitivity (detection rate of >or=95% at 94.1 parasites/ml of blood) was within a range that has been determined previously to facilitate the confir ...200312682141
structure-activity relationships of the antimalarial agent artemisinin. 8. design, synthesis, and comfa studies toward the development of artemisinin-based drugs against leishmaniasis and malaria.artemisinin (1) and its analogues have been well studied for their antimalarial activity. here we present the antimalarial activity of some novel c-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. further, antileishmanial activity of more than 70 artemisinin derivatives against leishmania donovani promastigotes is described for the first time. a comprehensive structure-activity relationship study using comfa is discussed. these analogues exhibited leishman ...200313678403
in vitro antileishmanial activity of amphotericin b loaded in poly(epsilon-caprolactone) nanospheres.the activity of formulations for amphotericin b (amb) associated with poly(epsilon-caprolactone) nanospheres and coated with variable amounts of a non ionic surfactant poloxamer 188, was evaluated against amb-susceptible (wt) and amb-resistant (amb(r)) strains of leishmania donovani amastigotes in thioglycolate-elicited peritoneal macrophages. amb-nanospheres were more actives than free amb only against amastigotes of wild strain. the activity was not influenced by the concentration of poloxamer ...200212683663
synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase.dihydrofolate reductase is a drug target that has not been thoroughly investigated in leishmania and trypanosomes. work has previously shown that 5-benzyl-2,4-diaminopyrimidines are selective inhibitors of the leishmanial and trypanosome enzymes. modelling predicted that alkyl/aryl substitution on the 6-position of the pyrimidine ring should increase enzyme activity of 5-benzyl-2,4-diaminopyrimidines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. various compounds were pr ...200212683746
visceral leishmaniasis: clinical features, pathology, diagnosis and chemotherapeutic developments.visceral leishmaniasis, or kala-azar, is a chronic disease caused by leishmania donovani, leishmania chagasi or leishmania infantum. the disease is transmitted through the bite of a species of sandfly of the genus phlebotomus, releasing amastigote parasites that invade various organs of the body and eventually result in such conditions as anemia, splenomegaly and hepatomegaly. although no vaccine exists for the disease, diagnostic techniques based not only on pathological tests, but more sophist ...200212677177
neuroimmunomodulatory effects of morphine in leishmania donovani-infected hamsters.the effect of morphine on host defense during leishmania donovani infection in golden hamsters was studied.200212759563
kala-azar in uttar pradesh--a study of 66 patients.sixty-six laboratory confirmed cases of kala-azar from uttar pradesh attending various hospitals of delhi over a period of 10 years (1989-1999) have been analysed. the geographical distribution showed that the disease involved widespread areas varying from a height of 10,000 ft. extending up-to the plains. male, female ratio was 2:1 and maximum patients were in the age group of 5-15 years. l.d. bodies could be demonstrated in 59 patients in bone marrow aspirate smears while in 7 in splenic aspir ...200212718341
c-reactive protein-mediated phagocytosis of leishmania donovani promastigotes does not alter parasite survival or macrophage responses.c-reactive protein (crp) is an acute phase protein that binds to surface structures of a number of different organisms. leishmania donovani express crp ligand when first entering the mammalian host and crp has been shown to alter macrophage function. the aim of this study was to investigate the functional significance of crp-mediated uptake of l. donovani on survival of the parasite within human macrophages and macrophage cell responses to the infection. crp opsonized l. donovani uptake was inhi ...200212654086
phagocytosis and phagosome maturation are regulated by calcium in j774 macrophages interacting with unopsonized prey.phagocytosis by neutrophils, macrophages, and other professional phagocytes requires rapid remodeling of actin. early phagosomes are surrounded by a rim of f-actin that is disassembled during phagosomoal maturation. breakdown of periphagosomal f-actin and phagolysosome fusion are calcium dependent processes in neutrophils interacting with serum-opsonized prey, but appears to be calcium independent in macrophages interacting with serum- or igg-opsonized prey. in the present study, we found that c ...200212635850
establishment of asymptomatic leishmania donovani infection in indian langurs (presbytis entellus) through intradermal route.indian langurs, which were previously reported to be highly susceptible, were infected intradermally using variable numbers of promastigotes along with different doses, 1/2 pair, 5 pairs and 10 pairs respectively of salivary gland lysate (sgl). although, all the monkeys developed mild infection and remained subclinically infected throughout the observation period, which later resolved, none of them could develop the classical disease. no marked antigen specific antibody or lymphoproliferative re ...200212622211
the role of calpain and calpastatin in the catabolism of erythrocyte-membrane proteins during anaemia in hamsters (mesocricetus auretus) infected with leishmania donovani.the anaemia associated with visceral leishmaniasis is accompanied by altered ca(2+) homeostasis and degradation of the cytoskeletal and integral proteins of the erythrocytic membrane. in the present study, such changes were followed in hamsters that were anaemic as the result of their experimental infection with leishmania donovani. at each stage of the infection, the blood concentration of haemoglobin was found to be negatively correlated with the concentration of ca(2+) (r(2) = 0.91), the perc ...200212625933
identification of a gene linked to drug resistance in field isolates of leishmania donovani. 200212625940
[cloning and sequence analysis of lack gene of leishmania donovani isolates from plain and desert foci of china].to determine the nucleotide sequence of the lack (leishmania homologue of receptors for activated protein kinase c) gene of leishmania donovani isolates from plain foci (l. d sd1) and desert foci (l. d xj771) of china, and to find out the difference of the sequence of lack gene with other leishimania spp. and also the isolate from hill foci of china.200212568016
monoclonal antibody affinity purification of a 78 kda membrane protein of leishmania donovani of indian origin and its role in host-parasite interaction.monoclonal antibodies were raised against pathogenic promastigotes of leishmania donovani of indian origin. among these, one was used for immuno-affinity purification of a 78 kda membrane protein present in both the amastigote and promastigote forms of the parasite. results of immunoblot experiments with the anti-78 kda antibody revealed that the protein was present only in parasites belonging to the l. donovani complex. the expression of the protein was observed to be the same during different ...200212571371
diagnosis of visceral leishmaniasis: comparative potential of amastigote antigen, recombinant antigen and pcr.development of simple, economical and non-invasive tests for the early diagnosis of visceral leishmaniasis (vl) or kala-azar (ka) remains a challenge, and serological studies based on antigen prepared from the amastigote stage of leishmania donovani, the stage that causes infection, are lacking. in the present study, circulating antibodies to total antigen isolated from the promastigote and amastigote stages of the parasite, as well as to recombinant k39 (rk39) antigen, are measured by enzyme-li ...200212572956
involvement of protein tyrosine kinases and phosphatases in uptake and intracellular replication of virulent and avirulent leishmania donovani promastigotes in mouse macrophage cells.in this study we show that protein tyrosine kinases (ptks) and also protein tyrosine phosphatases are involved in the uptake of virulent and avirulent leishmania donovani promastigotes by macrophage cells. protein tyrosine kinase inhibitors such as genistein or tyrphostin 25 decrease parasite uptake in a dose-dependent manner. addition of sodium orthovanadate, a protein tyrosine phosphatase inhibitor, prior to infection significantly increases parasite internalization. a similar uptake profile w ...200212516781
sequence analysis of the nramp1 genes from different bovine and buffalo breeds.the natural resistance associated macrophage protein 1 (nramp1) has been reported to confer resistance or susceptibility to mycobacterium bovis, salmonella typhimurium, and leishmania donovani in the mouse, mus musculus. a gly and asp substitution at position 169 of the mouse nramp protein is invariably associated with the resistant and susceptible phenotypes, respectively. the present study aimed to detect polymorphisms in the nramp1 gene from different cattle and buffalo breeds. genomic dnas f ...200212499702
nadh-oxidase, nadph-oxidase and myeloperoxidase activity of visceral leishmaniasis patients.it is believed that the enhanced capability of activated macrophages to resist infection is related to the remarkable increase in the production of oxygen metabolites in response to phagocytosis. both the production of h2o2 and the oxidation of nad(p)h are directly dependent upon nad(p)h-oxidase. it has been established that the respiratory burst is due to activation of nad(p)h-oxidase localised in the plasmalemma. myeloperoxidase is believed to be involved in augmenting the cytotoxic activity o ...200212435061
defective ccr7 expression on dendritic cells contributes to the development of visceral leishmaniasis.interaction between dendritic cells (dcs) and t cells is essential for the generation of cell-mediated immunity. here we show that dcs from mice with chronic leishmania donovani infection fail to migrate from the marginal zone to the periarteriolar region of the spleen. stromal cells were fewer, which was associated with loss of ccl21 and ccl19 expression. the residual stromal cells and endothelium produced sufficient ccl21 to direct the migration of dcs transferred from naïve mice. however, dcs ...200212436111
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