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symplocamide a, a potent cytotoxin and chymotrypsin inhibitor from the marine cyanobacterium symploca sp.investigation of a symploca sp. from papua new guinea has led to the isolation of symplocamide a (1), a potent cancer cell cytotoxin, which also inhibits serine proteases with a 200-fold greater inhibition of chymotrypsin over trypsin. the complete stereostructure of symplocamide a was determined by detailed nmr and ms analysis as well as chiral hplc analysis of the component amino acid residues. the presence of several unusual structural features in symplocamide a provides new insights into the ...200818163584
effect of alkyl-lysophospholipids on some aspects of the metabolism of leishmania donovani.alkyl-lysophospholipids (alps), developed initially to be antitumor agents, have proved highly effective in the treatment of visceral leishmaniasis, a disease caused by the species making up the protozoan complex leishmania donovani. although their effectiveness is known, the mode of action against this parasite is not completely understood. in the present work, we have studied the effect of 3 derivatives, edelfosine, miltefosine, and ilmofosine. using nuclear magnetic resonance spectroscopy ('h ...200718163358
a new strategy for elimination of kala-azar from rural bihar.bihar state of india has been an endemic state for kala-azar. there has been many phases of ddt sprays for vector control. an outbreak of kala-azar occurred in goanpura, 6 km from patna, bihar, in 2003. we undertook this study with a new approach of kala-azar elimination in this village with priority to treatment of cases followed by supplementation with supervised ddt spray for vector control.200718160749
leishmania donovani leishmaniasis in cyprus. 200818156082
content, composition, and bioactivity of the essential oils of three basil genotypes as a function of harvesting.a study was conducted to evaluate the effect of cut on biomass productivity, oil content, composition, and bioactivity of ocimum basilicum l. (cvs. german and mesten) and ocimum sanctum l. (syn. o. tenuiflorum l.) (cv. local) in mississippi. yields of basil herbage and essential oil were high and comparable to those reported in the literature. essential oil content of o. basilicum cv. german varied from 0.40 to 0.75%, the oil content of cv. mesten varied from 0.50 to 0.72%, and the oil content o ...200818095647
comparison of the effects of leishmania major or leishmania donovani infection on macrophage gene expression.the intracellular parasite leishmania causes a wide spectrum of human disease, ranging from self-resolving cutaneous lesions to fatal visceral disease, depending on the species of leishmania involved. the mechanisms by which different leishmania species cause different pathologies are largely unknown. we have addressed this question by comparing the gene expression profiles of bone marrow-derived macrophages infected with either leishmania donovani or l. major promastigotes. we found that the tw ...200818086813
evaluation of antileishmanial potential of tinospora sinensis against experimental visceral leishmaniasis.the chemotherapeutic interventions against visceral leishmaniasis (vl) are limited and facing serious concerns of toxicity, high cost, and emerging drug resistance. there is a greater interest in new drug developments from traditionally used medicinal plants which offers unprecedented diversity in structures and bioactivity. with this rationale, ethanolic extract of tinospora sinensis linn and its four fractions were tested in vitro against promastigotes and intracellular amastigotes and in vivo ...200818080140
role of intracellular camp in differentiation-coupled induction of resistance against oxidative damage in leishmania donovani.even though the human parasite leishmania donovani encounters tremendous oxidative burst during macrophage invasion, a set of parasites survives and proliferates intracellularly, leading to transformation from promastigote to amastigote form and disease manifestation. the striking shifts in temperature (from 22 degrees c in the insect gut to 37 degrees c in the mammalian host) and ph (7.2 in the insect gut to 5.5 in the parasitophorous vacuole of macrophages) are the key environmental triggers f ...200818078824
conservation of the pro-apoptotic nuclease activity of endonuclease g in unicellular trypanosomatid parasites.endonuclease g is a mitochondrial protein implicated in dna fragmentation during apoptosis in cell types ranging from fungi to mammals. features of programmed cell death have been reported in a number of single-celled organisms, including the human trypanosomatid parasites leishmania and trypanosoma. however, the protozoan cell death pathways and the effector molecules involved in such processes remain to be identified. in this report, we describe the pro-apoptotic function of endonuclease g in ...200818073240
modulation of gene expression in human macrophages treated with the anti-leishmania pentavalent antimonial drug sodium stibogluconate.within the mammalian host, leishmania donovani is an obligatory intracellular protozoan parasite that resides and multiplies exclusively in the phagolysosomes of macrophages. leishmania control relies primarily on chemotherapy, with the mainstay being pentavalent antimony (sbv) complexed to carbohydrates in the form of sodium stibogluconate (pentostam) or meglumine antimoniate (glucantime). the mode of action of sbv is still not known precisely. to explore the effect of sbv on macrophage gene ex ...200818070969
neutrophils contribute to development of a protective immune response during onset of infection with leishmania donovani.neutrophils are key components of the inflammatory response and as such contribute to the killing of microorganisms. in addition, recent evidence suggests their involvement in the development of the immune response. the role of neutrophils during the first weeks post-infection with leishmania donovani was investigated in this study. when l. donovani-infected mice were selectively depleted of neutrophils with the nimp-r14 monoclonal antibody, a significant increase in parasite numbers was observe ...200818056477
inhibition of abc transporters abolishes antimony resistance in leishmania infection.the emergence of antimony (sb) resistance has jeopardized the treatment of visceral leishmaniasis in various countries. previous studies have considered the part played by leishmanial parasites in antimony resistance, but the involvement of host factors in the clinical scenario remained to be investigated. here we show that unlike infection with sb-sensitive (sbs) leishmania donovani, infection with sb-resistant (sb r) l. donovani induces the upregulation of multidrug resistance-associated prote ...200818056276
six naphthylisoquinoline alkaloids and a related benzopyranone from a congolese ancistrocladus species related to ancistrocladus congolensis.from the roots of a recently discovered ancistrocladus taxon, with close affinities to ancistrocladus congolensis regarding molecular its sequence data, six naphthylisoquinoline alkaloids, 5'-o-demethylhamatine (2), 5'-o-demethylhamatinine (3), 6-o-demethylancistroealaine a (4), 6,5'-o,o-didemethylancistroealaine a (5), 5-epi-6-o-methylancistrobertsonine a (6), and 5-epi-4'-o-demethylancistrobertsonine c (7), have been isolated, along with a likewise benzopyranone carboxylic acid, 8. the structu ...200818054973
isolation, purification, characterization and antigenic evaluation of gpi-anchored membrane proteins from leishmania (viannia) braziliensis.gpi-anchored proteins from the plasma membrane of leishmania (viannia) braziliensis promastigotes were isolated, characterized and their migration pattern compared with those from other leishmania species. in all cases the sds-page migration patterns were obtained under reducing and non-reducing conditions, using dl-dithiothreitol (dtt) as a reducer agent. our results reveal that under reducing conditions the sds-page migration pattern is modified as a consequence of the disruption of disulphur- ...200818054342
morphine-induced neuroimmunomodulation in murine visceral leishmaniasis: the role(s) of cytokines and nitric oxide.opioid modulation of host resistance to infectious diseases is well documented; however, not much is known during visceral leishmaniasis (vl). low doses of morphine, administered subcutaneously in leishmania donovani-infected balb/c mice, on days 0 and +15, significantly (p < 0.05) suppressed (1 mg/kg/day) or even sterile-cleared (2 mg/kg/day) the infection; paradoxically, high doses (10 and 30 mg/kg/day) exacerbated the infection. in vitro, low concentration (1 x 10(-9) and 1 x 10(-11) m) morph ...200718040852
[a case of antimony resistant kala-azar cured with amphotericin b]. 200718038767
identification of leishmania donovani as a cause of cutaneous leishmaniasis in sudan.eight patients with cutaneous ulcers were referred to the institute of endemic diseases, khartoum, sudan, from june 2000 to march 2002 for the diagnosis of suspected cutaneous leishmaniasis (cl). diagnosis was confirmed parasitologically by both positive giemsa-stained smears and successful culture of leishmania promastigotes in nnn medium. the eight parasite isolates were shown to belong to the leishmania donovani complex by kdna pcr. isoenzyme typing of three isolates revealed that they were i ...200818037149
the large subunit of leishmania topoisomerase i functions as the 'molecular steer' in type ib topoisomerase.kinetoplastid topoisomerase ib is an unusual bisubunit enzyme where reconstitution of the large (ldtopil or l) and small (ldtopis or s) subunits shows functional activity. it is yet to be deciphered whether one subunit or both navigate the heterodimer to its cellular dna targets. tethering a specific dna-binding protein to topoisomerase i alters its site specificity. the chimeric constructs umsbp-ldtopil/s or u-l/s (fusion of umsbp to the n-terminus of l and reconstituted with s) and ldtopil/ums ...200818036140
non-coding pdna bearing immunostimulatory sequences co-entrapped with leishmanial antigens in cationic liposomes elicits almost complete protection against experimental visceral leishmaniasis in balb/c mice.the difficulty in making successful vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. non-coding plasmid dna (pdna) bearing immunostimulatory sequences (iss) is a potent activator of innate immunity, and can thus act as an adjuvant with vaccine antigen. we therefore evaluated the efficacy of pdna and soluble leishmanial antigens (sla) to protect against challenge with leishmania donovani infection. we demonstrate that immunomodulatory activity of pdna, which potent ...200718031874
identification of leishmania fructose-1,6-bisphosphate aldolase as a novel activator of host macrophage src homology 2 domain containing protein tyrosine phosphatase shp-1.the macrophage protein tyrosine phosphatase-1 shp-1 has been implicated in the pathogenesis of infection with leishmania. to identify the factors that may interact with shp-1, leishmania donovani promastigote lysates were added to a gst-shp-1 affinity matrix. a 44kda specifically bound protein was identified as leishmania fructose-1,6-bisphosphate aldolase (aldolase). purified leishmania aldolase bound to shp-1 indicating that the interaction was direct. in contrast, purified mammalian aldolase ...200718028878
innovative serum-free medium for in vitro cultivation of promastigote forms of leishmania species.we described a comparatively simple medium formula (cml) using common, available and reasonably priced ingredients that could be used in place of medium that requires calf serum enhancement for cultivation of leishmania promastigote forms. this medium equivalently supported the growth of parasites at rates comparable with those obtained with serum supplemented rpmi-1640 medium. leishmania promastigotes reproduced in cml exhibited moderate to high infectivity capacities when tested against j774 m ...200818024187
adenosine deaminase activity in sera of patients with visceral leishmaniasis in india.serum adenosine deaminase (ada) activity increases in diseases where cellular immunity is involved. since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ada activity in different pathological conditions.200818023276
induction of host protective th1 immune response by chemokines in leishmania donovani-infected balb/c mice.the resolution from leishmanial infection is dependent on the coordinated interactions between the components of the cell mediated immune system and the activation of t-cell population into appropriate cytokine production and the activation of macrophages. earlier reports established that c-c chemokines particularly macrophage inflammatory protein (mip)-1alpha and macrophage chemoattractant protein (mcp)-1 restrict the parasitic burden via the regulation of impaired protein kinase c (pkc) signal ...200718021365
azaterphenyl diamidines as antileishmanial agents.eighteen diamidino azaterphenyls and analogues were evaluated as anti-leishmanials; nine of the compounds gave ic50 values less than 1 microm, five exhibited values less than 0.40 microm, and two gave values less than 0.10 microm in a leishmania donovani axenic amastigote assay. the activity of the diamidines strongly depends on the ring n-atom location relative to the amidine groups and correlates with dna affinity. transmission electron microscopy studies showed a dramatic dilation of the mito ...200818006310
deletion study of dna topoisomerase ib from leishmania donovani: searching for a minimal functional heterodimer.the substantial differences between trypanosomal and leishmanial dna topoisomerase ib concerning to their homologues in mammals have provided a new lead in the study of the structural determinants that can be effectively targeted. leishmania donovani, the causative agent of visceral leishmaniasis, contains an unusual heterodimeric dna topoisomerase ib. the catalytically active enzyme consists of a large subunit (ldtopil), which contains the non-conserved n-terminal end and the phylogenetically c ...200718000548
temporal regulation of interleukin-12p70 (il-12p70) and il-12-related cytokines in splenic dendritic cell subsets during leishmania donovani infection.dendritic cells (dc) play an essential role in initiating and directing t-cell responses, in part by production of interleukin-12p70 (il-12p70), il-23, and il-27. however, comparative studies on the capacity for cytokine production of dc subsets are rare. here, we compare splenic cd8alpha+, cd4+, and double-negative (dn) dc, isolated 5 h to 28 days after leishmania donovani infection, for (i) production of il-12p70, (ii) accumulation of il-12/23p40, il-12p35, il-23p19, and il-27p28 mrnas, and (i ...200817998312
polymorphisms of cpb multicopy genes in the leishmania (leishmania) donovani complex.in leishmaniasis, cysteine protease b (cpb) multicopy genes have been extensively studied because of their implication in host-parasite interactions. in the leishmania donovani complex, responsible for visceral leishmaniasis, a set of interesting polymorphisms has been revealed, such as copy sequence or expression according to the parasite's life stage. the single nucleotide polymorphisms observed among these copies could be related to clinical characteristics such as dermotropic versus viscerot ...200817996911
s-euglobals: biomimetic synthesis, antileishmanial, antimalarial, and antimicrobial activities.several new euglobal analogues (named as s-euglobals) were synthesized from phloroglucinol via a biomimetic three-component reaction involving knoevenagel condensation followed by [4+2]-diels-alder cycloaddition with monoterpene. newly synthesized euglobal analogues involve monoterpenes that have not yet been encountered in natural euglobals. s-euglobals along with previously synthesized robustadial a and b were evaluated for in vitro antileishmanial, antimalarial, antimicrobial, and cytotoxic a ...200817976995
participation of chlorobiumquinone in the transplasma membrane electron transport system of leishmania donovani promastigote: effect of near-ultraviolet light on the redox reaction of plasma membrane.the respiratory quinone composition of the parasitic protozoa leishmania donovani promastigote was investigated. 1'-oxomenaquinone-7, a chlorobiumquinone was found to be the major isoprenoid quinone. substantial level of ubiquinone-9 was also present. isolation and identification of the quinone from the purified plasma membrane yielded mainly 1'-oxomenaquinone-7 and ubiquinone-9; menaquinone was not detected. membrane bound 1'-oxomenaquinone-7 could be destroyed by near-ultraviolet irradiation, ...200817976919
synthesis and biological evaluation of fluorescent leishmanicidal analogues of hexadecylphosphocholine (miltefosine) as probes of antiparasite mechanisms.the leishmanicidal mechanism of miltefosine (hexadecylphosphocholine, mt) is not clearly understood. valuable insights into its mode of action could be obtained by fluorescence techniques, given suitably emitting analogues. in this regard, the synthesis and biological characterization of two fully competent mt fluorescent analogues is reported here: all-(e)-13-phenyltrideca-6,8,10,12-tetraenylphosphocholine (pte-mt) and all-(e)-13-phenyltrideca-8,10,12-trien-6-ynylphosphocholine (ptri-mt). both ...200717973359
stearylamine-bearing cationic liposomes kill leishmania parasites through surface exposed negatively charged phosphatidylserine.lipid-associated formulations of antileishmanial agents have proved to be more effective therapies with reduced toxicities. previous studies from our group and others revealed that liposomes bearing phosphatidylcholine and stearylamine (sa) themselves kill leishmania and other protozoan parasites in vitro and in vivo, without causing any adverse effect on host. in the present study, we offer detailed insights into the mechanism of action of these liposomes.200817965031
oral therapy with amlodipine and lacidipine, 1,4-dihydropyridine derivatives showing activity against experimental visceral leishmaniasis.amlodipine and lacidipine, conventional antihypertensive drugs, inhibited leishmania donovani infection in vitro and in balb/c mice when administered orally. these 1,4-dihydropyridine derivatives functioned through dose-dependent inhibition of oxygen consumption, triggering caspase 3-like activation-mediated programmed cell death of the parasites.200817954702
synthesis and evaluation of antiparasitic activities of new 4-[5-(4-phenoxyphenyl)-2h-pyrazol-3-yl]morpholine derivatives.a series of new 4-[5-(4-phenoxyphenyl)-2h-pyrazol-3-yl]morpholine derivatives, prepared by two synthetic routes, were in vitro assayed against three trypanosoma strains, leishmania donovani, and plasmodium falciparum k1. seven out of 17 compounds showed moderate to very good activity against blood stage t. b. rhodesiense, with 10 and 17 exhibiting highest potency (ic50 of 1.0 and 1.1 microm, respectively). interestingly, the beta-diketone precursors 1-3 had good antitrypanosomal activity toward ...200717949068
synthesis and in vitro antiprotozoal activity of bisbenzofuran cations.forty three cationic bisbenzofurans were synthesized either by interaction of o-hydroxyaldehydes with alpha-halogenated ketones followed by intramolecular ring closure or by a copper- or palladium-mediated heteroannulation of substituted o-iodophenols with terminal acetylenes. in vitro antiprotozoal activities of compounds 1-43 against trypanosoma brucei rhodesiense, plasmodium falciparum, and leishmania donovani and cytotoxicity against mammalian cells were influenced by the position and the ty ...200717948982
use of a newly developed beta-mercaptoethanol enzyme-linked immunosorbent assay to diagnose visceral leishmaniasis in patients in eastern sudan.corroboration of serology results is essential for restricting the risk of inappropriate antileishmanial prescription. a direct agglutination test (dat) and a recently developed beta-mercaptoethanol-modified enzyme-linked immunosorbent assay (beta-me elisa) based on the use of antigen prepared as described for the dat were applied to 416 sera from two sudanese populations with and without clinical evidence of visceral leishmaniasis (vl). of 285 sera with the lowest antileishmanial dat titers (</ ...200717942614
nramp-1 expression modulates protein-tyrosine phosphatase activity in macrophages: impact on host cell signaling and functions.nramp-1 (natural resistance-associated macrophage protein-1) has been associated with innate resistance to unrelated intracellular pathogen infections, up-regulation of proinflammatory phagocyte functions, and susceptibility to autoimmune diseases. it is still unclear how the divalent cation transport function of nramp-1 accounts for the associated pleiotropic effects. in this study, we evaluated the impact of murine macrophage nramp-1 expression on the activity of protein-tyrosine phosphatases ...200717942403
visceral leishmaniasis: what are the needs for diagnosis, treatment and control?visceral leishmaniasis (vl) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. poor and neglected populations in east africa and the indian sub-continent are particularly affected. early and accurate diagnosis and treatment remain key components of vl control. in addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. miltefosine, paromomycin and liposomal amphotericin b are gradually replacing pentavalent antimonial ...200717938629
a urine-based polymerase chain reaction method for the diagnosis of visceral leishmaniasis in immunocompetent patients.in the mediterranean basin and middle east, including iran, visceral leishmaniasis (vl), also known as kala-azar, is caused by leishmania donovani infantum. for the first time, the use of urine samples for the diagnosis of vl in immunocompetent patients has been used in this study. based on its high sensitivity and specificity, as well as simplicity, this approach can serve as a valuable tool in the diagnosis of vl. we studied 60 urine samples from 60 individuals, 30 of which were patients with ...200817931819
gene expression profiling of leishmania (leishmania) donovani: overcoming technical variation and exploiting biological variation.gene expression profiling is increasingly used in the field of infectious diseases for characterization of host, pathogen and the nature of their interaction. the purpose of this study was to develop a robust, standardized method for comparative expression profiling and molecular characterization of leishmania donovani clinical isolates. the limitations and possibilities associated with expression profiling in intracellular amastigotes and promastigotes were assessed through a series of comparat ...200817931458
synthesis and in vitro protozoocidal evaluation of novel diazabicyclic tropolone derivatives.the synthesis and in vitro antiparasitic activity of twenty-seven novel diazabicycles based on tropolone ethers is presented. the compounds can be readily prepared by means of a high-yielding hetero diels-alder reaction using simple and readily available starting materials. several of the new diazabicycles have in vitro activities against trypanosoma cruzi, leishmania donovani, trypanosoma brucei rhodesiense, and chloroquine-resistant plasmodium falciparum that are comparable or superior to thos ...200717924365
an insight into the mechanism of inhibition of unusual bi-subunit topoisomerase i from leishmania donovani by 3,3'-di-indolylmethane, a novel dna topoisomerase i poison with a strong binding affinity to the enzyme.dim (3,3'-di-indolylmethane), an abundant dietary component of cruciferous vegetables, exhibits a wide spectrum of pharmacological properties. in the present study, we show that dim is a potent inhibitor of leishmania donovani topoisomerase i with an ic50 of 1.2 microm. equilibrium dialysis shows that dim binds strongly to the free enzyme with a binding constant of 9.73x10(-9) m. the binding affinity of dim to the small subunit is 8.6-fold more than that of the large subunit of unusual ldtop1ls ...200817922678
antiprotozoal polyacetylenes from the tanzanian medicinal plant cussonia zimmermannii.from the petroleum ether extract of the root bark of cussonia zimmermannii four polyacetylenes, 1- 4, were isolated, three of which ( 1- 3) were active against trypanosoma brucei rhodesiense, trypanosoma cruzi, plasmodium falciparum, and leishmania donovani.200717922552
synthetic modification of manzamine a via grubbs metathesis. novel structures with enhanced antibacterial and antiprotozoal properties.a strategy for the structural modification of biologically important alkene-containing natural products via ring-opening olefin metathesis is described. exposure of manzamine a 1 to the second-generation grubbs catalyst in the presence of ethylene leads to the formation of 2 and 4. the antibacterial activity of the novel manzamine analogue 2 (ic50=0.10 nm) against mycobacterium intracellulare is ca. 2-fold more potent than that of ciprofloxacin (ic50=0.18 nm), a drug that is frequently used agai ...200717918854
il-10- and tgf-beta-mediated susceptibility in kala-azar and post-kala-azar dermal leishmaniasis: the significance of amphotericin b in the control of leishmania donovani infection in india.visceral leishmaniasis (vl) or kala-azar is known to be associated with a mixed th1-th2 response, and effective host defense requires the induction of ifn-gamma and il-12. we address the role of the differential decline of il-10 and tgf-beta in response to sodium antimony gluconate (sag) and amphotericin b (amb), the therapeutic success of sag and amb in indian vl, and the significance of il-10 and tgf-beta in the development and progression of post-kazla-azar dermal leishmaniasis (pkdl). in the ...200717911647
antileishmanial structure-activity relationships of synthetic phospholipids: in vitro and in vivo activities of selected derivatives.antileishmanial activities of 91 synthetic phospholipids against leishmania donovani were evaluated in vitro and cytotoxicity assessed against two mammalian cell lines. promising compounds were tested further in vivo. in vitro structure-activity relationships showed a positive contribution of head groups bearing ring systems (n-methylpiperidino and n-methylmorpholino) to antileishmanial activity.200717908944
hybrid cell vaccination resolves leishmania donovani infection by eliciting a strong cd8+ cytotoxic t-lymphocyte response with concomitant suppression of interleukin-10 (il-10) but not il-4 or il-13.there is an acute dearth of therapeutic interventions against visceral leishmaniasis that is required to restore an established defective cell-mediated immune response. hence, formulation of effective immunotherapy requires the use of dominant antigen(s) targeted to elicit a specific antiparasitic cellular immune response. we implemented hybrid cell vaccination therapy in leishmania donovani-infected balb/c mice by electrofusing dominant leishmania antigen kinetoplastid membrane protein 11 (kmp- ...200717908806
leishmania donovani: role of cd2 on cd4+ t-cell function in visceral leishmaniasis.in this study, we investigated whether alteration in the cd2 mediated coordination of an immune response was associated with down regulation of cd4 associated th1 cell response during visceral leishmaniasis (vl). leishmania donovani (ld) infection in vl patients markedly reduced expression of cd2 cell surface antigen on cd4+ cells. t-cells of vl patients were mostly in g0/g1 stage of the cell cycle (98.20%) with little or no activity of protein kinase c-alpha (pkc-alpha) isoform. however, pre-in ...200817904553
structural insights on the small subunit of dna topoisomerase i from the unicellular parasite leishmania donovani.leishmania donovani, the causative organism of visceral leishmaniasis, contains a unique heterodimeric dna topoisomerase ib (ldtop1). the catalytically active enzyme consists of a large subunit (ldtop1l), which contains the non-conserved n-terminal end and a phylogenetically conserved core domain, and of a small subunit (ldtop1s) which harbours the c-terminal region with a characteristic tyrosine residue in the active site. heterologous co-expression of ldtop1l and ldtop1s in a topoisomerase i d ...200717900785
[leishmaniasis in rheumatoid arthritis].leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. visceral leishmaniasis is of higher priority than cutaneous leishmaniasis as it is a fatal disease in the absence of treatment. the clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. the role of cellular immune responses of the th1 type in the protection against disease in experimental and human leishmaniasis is well established. ...200717898884
profile of fatal visceral leishmaniasis at an indian tertiary care center.visceral leishmaniasis is a highly morbid and incapacitating infection, which usually presents with prolonged fever, weight loss and hepato-splenomegaly. despite the availability of effective treatment, the disease can have a high mortality even at referral centers. a case series of fatal visceral leishmaniasis, encountered during a prospective, two year period is presented. all the patients died due to multisystem organ failure. however, delayed diagnosis due to atypical manifestations was an i ...200717896607
development of a molecular assay specific for the leishmania donovani complex that discriminates l. donovani/leishmania infantum zymodemes: a useful tool for typing mon-1.we have developed a simple, rapid, sensitive, and cost-effective typing method, based on the amplicon size of the k26 gene, capable of species/strain discrimination of leishmania donovani complex strains causing visceral leishmaniasis (vl). it was evaluated on 112 strains and compared with multilocus enzyme electrophoresis (mlee) typing. the k26 polymerase chain reaction (pcr) applied on 26 representative l. donovani complex strains gave 14 different amplicon sizes. the assay was specific to the ...200817889482
structure-activity relationship of antileishmanials neolignan analogues.twenty-two synthetic analogues of neolignans comprising beta-ketoethers and beta-ketosulfides were obtained from condensation reactions among beta-bromoketones and phenols or thiophenols, respectively, in basic solutions, and assayed in vitro for activity against intracellular leishmania amazonensis and leishmania donovani amastigotes, the causative agents of cutaneous and visceral leishmaniasis. the highest selective activity was found for compounds with sulfur bridges, whereas beta-ketosulphox ...200717888668
an epitope-specific pcr test for diagnosis of leishmania donovani infections.the carboxy-terminal region of recombinant heat shock protein 70 of leishmania donovani has been shown to have an immunodominant epitope. we designed a pcr assay using a new set of primers encompassing the gene sequence from 457bp to 927bp, which amplified a segment of the l. donovani genome in a species-specific manner. the assay was sensitive enough to detect 0.5pg of parasite dna, which increased 10-fold (0.05pg) when an internal probe (583-609bp) was used in the southern blot. the assay was ...200817888473
antileishmanial, antiplasmodial and cytotoxic activities of 12,16-dideoxy aegyptinone b from zhumeria majdae rech.f. & wendelbo.the ethanol extract of zhumeria majdae showed potent antileishmanial and antiplasmodial activity in vitro. bioactivity guided fractionation of the extract led to the isolation of 12,16-dideoxy aegyptinone b. this compound exhibited potent in vitro antileishmanial activity with an ic(50) of 0.75 microg/ml and a strong antiplasmodial activity with ic(50) values of 1.3 and 1.4 microg/ml against chloroquine sensitive and resistant strains, respectively. this compound was further found to have mild c ...200817886231
retooling leishmania metabolism: from sand fly gut to human macrophage.to survive extremely different environments, intracellular parasites require highly adaptable physiological and metabolic systems. leishmania donovani extracellular promastigotes reside in a glucose-rich, slightly alkaline environment in the sand fly vector alimentary tract. on entry into human macrophage phagolysosomes, promastigotes differentiate into intracellular amastigotes. these cope with an acidic milieu, where glucose is scarce while amino acids are abundant. here, we use an axenic diff ...200817884972
inhibition of groups 1 and 2 cd1 molecules on human dendritic cells by leishmania species.dendritic cells are potent immune-activating cells, which traditionally are thought of as presenters of protein antigen to lymphocytes to initiate an immune response. recently, another mechanism of immune surveillance, the detection of lipid antigens, has been found to be mediated by the nonpolymorphic family of cd1 molecules. there are two different cd1 families, group 1 consisting of cd1a, cd1b and cd1c, and group 2 consisting only of cd1d. leishmania donovani-infected dendritic cells have pre ...200717883454
epidemiological, clinical and therapeutic features of pediatric kala-azar.kala-azar (visceral leishmaniasis) is endemic in southern iran. we retrospectively evaluated 367 infants and children with visceral leishmaniasis at hospitals affiliated to shiraz university of medical sciences in fars province (located in the southwestern part of iran). seasonal variation was observed with more cases presenting in late winter, spring and a few in summer. the predominant clinical features in these patients were chronic fever, pallor, weight loss, abdominal distention, and hepato ...200717882998
use of rk39 for diagnosis of post kala-azar dermal leishmaniasis in nepal.a recently developed nitrocellulose-based dipstick test, rk39, has been widely used for the diagnosis of kala-azar. in this study, we evaluated its use for the diagnosis of post kala-azar dermal leishmaniasis (pkdl). we also investigated the time taken by patients to develop pkdl after apparent cure of kala-azar (visceral leishmaniasis, vl) and the time taken by patients to come to the hospital after the appearance of symptoms of pkdl. a majority of patients developed the disease within three ye ...200717882997
trypanocidal and antileishmanial dihydrochelerythrine derivatives from garcinia lucida.three benzo[ c]phenanthridine alkaloids have been isolated from the stem bark of garcinia lucida: dihydrochelerythrine ( 1), 6-acetonyldihydrochelerythrine ( 2), and its new derivative, ( s)1''-(9,10-dihydro-2',3'-dihydroxy-7,8-dimethoxy-10-methyl-1,2-benzophenanthridin-9-yl)propan-2''-one (lucidamine a) ( 3). the new diisoprenylated derivative of lucidamine b ( 4) was obtained by semisynthesis. these dihydrochelerythrine derivatives as well as the crude extract displayed attractive antiprotozoa ...200717880175
[comparative validation study between the elisa and rifi techniques for diagnosing leishmania sp in stray dogs caught in the municipality of campos de goytacazes, state of rio de janeiro].a survey was carried out aiming to verify the elisa test effectiveness for detecting antibodies against leishmania sp in dogs, comparing with rifi human pattern and for investigating sorological zoonosis situation in the microregion. an accordance about 97.6% considered strong was reported.200717876477
long term failure of miltefosine in the treatment of refractory visceral leishmaniasis in aids patients.we carried out a retrospective and descriptive study of 4 hiv infected patients with relapsing visceral leishmaniasis (vl) seen at 2 tertiary-care hospitals in spain during the last 6 y, in whom miltefosine was used as a compassionate use treatment at a dosage of 50 mg b.i.d. patients had a medium cd4 lymphocyte count of 69 cells/microl and were c stage. all patients received at least 2 different anti-leishmanial drugs and had at least 3 relapses before miltefosine treatment (range 3-7). three p ...200817852921
wilson disease with visceral leishmaniasis: an extremely uncommon presentation.visceral leishmaniasis (vl), which is caused by the protozoa leishmania donovani and transmitted by the bite of the female sand fly phlebotomus argentipes, is common in bihar, india. wilson disease is an autosomal recessive disorder of copper metabolism in which copper is deposited in the brain and liver. we report a case of an extremely uncommon combination of these diseases in a patient. treatment options for such a combination of diseases are limited and difficult.200717827379
chemical transformation and biological studies of marine sesquiterpene (s)-(+)-curcuphenol and its analogs.chemical transformation studies of the marine sesquiterpene phenol (s)-(+)-curcuphenol (1), isolated from the jamaican sponges myrmekioderma styx, were accomplished. in order to optimize the activity and better understand the sar of (s)-(+)-curcuphenol, nineteen semisynthetic analogs were prepared and evaluated for activity against infectious diseases. a number of analogs showed significant activity against mtb and leishmania donovani, while showed good to moderate activities in antibacterial an ...200717804167
artemisinin triggers induction of cell-cycle arrest and apoptosis in leishmania donovani promastigotes.a major impediment to effective anti-leishmanial chemotherapy is the emergence of drug resistance, especially to sodium antimony gluconate, the first-line treatment for leishmaniasis. artemisinin, a sesquiterpene lactone isolated from artemisia annua, is an established anti-malarial compound that showed anti-leishmanial activity in both promastigotes and amastigotes, with ic(50) values of 160 and 22 microm, respectively, and, importantly, was accompanied by a high safety index (>22-fold). the le ...200717761485
racemoside a, an anti-leishmanial, water-soluble, natural steroidal saponin, induces programmed cell death in leishmania donovani.leishmaniasis remains a major health problem of the tropical and subtropical world. the visceral form causes the most fatalities if left untreated. dramatic increases in the rates of infection and drug resistance and the non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents. this study reports that racemoside a, a water-soluble steroidal saponin purified from the fruits of asparagus racemosus, is a potent anti-leishmanial ...200717761483
evaluation of antiprotozoal and antimycobacterial activities of the resin glycosides and the other metabolites of scrophularia cryptophila.resin glycosides are secondary metabolites exclusive to the convolvulaceous plants. in this study, crypthophilic acids a-c (1-3), the first resin glycosides occurring in another family (scrophulariaceae), and the other constituents of scrophularia cryptophila were examined for in vitro antiprotozoal and antimycobacterial potentials. except for crypthophilic acid b (2), all tested compounds exhibited growth-inhibitory effect against trypanosoma brucei rhodesiense, with l-tryptophan (6) and buddle ...200817761408
genetic fingerprinting and identification of differentially expressed genes in isolates of leishmania donovani from indian patients of post-kala-azar dermal leishmaniasis.post-kala-azar dermal leishmaniasis (pkdl) is an unusual dermatosis that develops as a sequel in 5-15% of cured cases of kala-azar (ka) after months or years of treatment in india. molecular differences are reported to exist between the ka and pkdl isolates which may underlie the diversity in clinical manifestations of the disease. here, arbitrary primed-pcr (ap-pcr) has been used for genetic fingerprinting of parasite isolates from dermal lesions of pkdl patients (n=14) and compared with bone-m ...200817761024
in vitro activity of an essential oil against leishmania donovani.the in vitro antileishmanial effect of the essential oil from chenopodium ambrosioides against leishmania donovani was investigated. the product showed significant activity against promastigotes and amastigotes, with a 50% effective concentration of 4.45 and 5.1 microg/ml, respectively. the essential oil caused an irreversible inhibition of the growth of promastigotes after a treatment with 100 or 10 microg/ml for 1 or 24 h, respectively. the phagocytic activity of the macrophages was preserved ...200717724767
characterization of metacaspases with trypsin-like activity and their putative role in programmed cell death in the protozoan parasite leishmania.in this report, we have characterized two metacaspases of leishmania donovani, l. donovani metacaspase-1 (ldmc1) and ldmc2. these two proteins show 98% homology with each other, and both contain a characteristic c-terminal proline-rich domain. both genes are transcribed in promastigotes and axenic amastigotes of l. donovani; however, ldmc1 shows increased mrna levels in axenic amastigotes. an anti-ldmc antibody was obtained and showed reactivity with a single approximately 42-kda protein band in ...200717715367
in vivo studies on the antileishmanial activity of buparvaquone and its prodrugs.the efficacy of different formulations of the naphthoquinone buparvaquone and two phosphate prodrugs in in vivo models of both visceral and cutaneous leishmaniasis is described.200717715126
cutaneous pseudolymphoma in association with leishmania donovani. 200717714564
phlebotomus (euphlebotomus) mascomai n. sp. (diptera-psychodidae).a new species of sandfly is described from limestone caves in thailand. the inclusion of this species in the subgenus euphlebotomus is justified on the basis of characters of the male genitalia (paramere, basal lobe). the male-female gathering in the same taxon is based on ecological (cavernicolous species), morphological (length of male genital filaments and female spermathecal ducts) and molecular (homology of cytochrome b mt dna sequences) criteria. a differential diagnosis between phlebotomu ...200717710436
2,n6-disubstituted adenosine analogs with antitrypanosomal and antimalarial activities.a library of 2,n(6)-disubstituted adenosine analogs was synthesized and the analogs were tested for their antiprotozoal activities. it was found that 2-methoxy and 2-histamino and n(6)-m-iodobenzyl substitutions generally produced analogs with low levels of antiprotozoal activity. the best antiplasmodial activity was achieved with large aromatic substitutions, such as n(6)-2,2-diphenylethyl and naphthylmethyl, which could indicate a mechanism of action through aromatic stacking with heme in the ...200717698622
in vitro activity of 10-deacetylbaccatin iii against leishmania donovani promastigotes and intracellular amastigotes.current treatments for leishmaniasis are unsatisfactory due to their route of administration, toxicity and expense but, most importantly, to the developed resistance of leishmania to first-line drugs. therefore, the identification of new effective targeted drugs is an urgent need. since many studies have shown that medicinal plants contain compounds active against protozoa we have undertaken a study aiming to determine the antileishmanial activity of the taxoid 10-deacetylbaccatin iii, isolated ...200717691059
interleukin-10 and the pathogenesis of human visceral leishmaniasis.the mechanisms underlying the failure to control the growth and systemic spread of leishmania parasites in human visceral leishmaniasis (vl) are not well understood. although the absence of antigen-specific th1 responses in the peripheral blood mononuclear cells from vl patients is thought to be causally related to disease progression, the finding that these patients also express elevated interferon-gamma mrna in lesional tissue, as well as elevated serum levels of proinflammatory cytokines, sug ...200717689290
amphotericin b treatment for indian visceral leishmaniasis: response to 15 daily versus alternate-day infusions.for patients with indian visceral leishmaniasis, amphotericin b deoxycholate is usually given as 15 alternate-day infusions of 1 mg/kg over 30 days (total dose, 15 mg/kg); daily treatment with 1 mg/kg for 20 days (total dose, 20 mg/kg) is also used. this study was done to address the unsettled therapeutic questions of administration schedule (alternate-day vs. daily administration) and dose (1 vs. 0.75 mg/kg) and to determine whether the duration of amphotericin b treatment in bihar, india, can ...200717682988
leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized th1 response.leishmaniasis affects 12 million people, and it is generally agreed that vaccination provides the best long-term strategy for its control. an ideal vaccine should be effective in both preventing and treating leishmaniasis. however, immunological correlates to predict vaccine efficacy and success of treatment in visceral leishmaniasis (vl) remain ill defined. here, we correlated the vaccine efficacy of soluble leishmanial antigens (sla) from leishmania donovani promastigote membrane, entrapped in ...200717655984
induction of apoptosis-like cell death by pentamidine and doxorubicin through differential inhibition of topoisomerase ii in arsenite-resistant l. donovani.the current study has been undertaken to investigate the sensitivity of the topoisomerase ii (topo ii) of wild type (ld-wt) and arsenite-resistant (ld-as20) l. donovani to an anti-leishmanial agent pentamidine and an anti-cancer drug doxorubicin. we demonstrate that the cross resistance to pentamidine and doxorubicin in ld-as20, was in part implicated through differential inhibition of topo ii in ld-wt and ld-as20. further, the treatment of promastigotes at drug concentrations inhibiting 50% of ...200717655815
trafficking of leishmania donovani promastigotes in non-lytic compartments in neutrophils enables the subsequent transfer of parasites to macrophages.inoculation of leishmania (l.) spp. promastigotes in the dermis of mammals by blood-feeding sand flies can be accompanied by the rapid recruitment of neutrophils, inflammatory monocytes and dendritic cells. despite the presence of these lytic leucocytes, parasitism is efficiently established. we show here that leishmania donovani promastigotes are targeted to two different compartments in neutrophils. the compartments harbouring either damaged or non-damaged parasites were characterized at the e ...200817651446
evaluation of immune responses and protection induced by a2 and nucleoside hydrolase (nh) dna vaccines against leishmania chagasi and leishmania amazonensis experimental infections.several antigens have been tested as vaccine candidates against leishmania infections but controversial results have been reported when different antigens are co-administered in combined vaccination protocols. immunization with a2 or nucleoside hydrolase (nh) antigens was previously shown to induce th1 immune responses and protection in balb/c mice against leishmania donovani and l. amazonensis (a2) or l. donovani and l. mexicana (nh) infections. in this work, we investigated the protective effi ...200717644455
albumin-quercetin combination offers a therapeutic advantage in the prevention of reduced survival of erythrocytes in visceral leishmaniasis.visceral leishmaniasis is associated with the reduced survival of erythrocytes, the cause of which remains to be fully explored. here, we described the mechanism underlying the shortened lifespan of erythrocytes in visceral leishmaniasis and proposed a combination therapy with quercetin and hamster serum albumin towards its rectification. decreased redox potential in erythrocytes followed by oxidative denaturation of hemoglobin and pathologic association of iron with the cell membrane facilitate ...200717644434
gastric and cutaneous dissemination of visceral leishmaniasis in a patient with advanced hiv. 200817643333
biochemical characterization of leishmania major aquaglyceroporin lmaqp1: possible role in volume regulation and osmotaxis.the leishmania major aquaglyceroporin, lmaqp1, is responsible for the transport of trivalent metalloids, arsenite and antimonite. we have earlier shown that downregulation of lmaqp1 provides resistance to trivalent antimony compounds whereas increased expression of lmaqp1 in drug-resistant parasites can reverse the resistance. in this paper we describe the biochemical characterization of lmaqp1. expression of lmaqp1 in xenopus oocytes rendered them permeable to water, glycerol, methylglyoxal, di ...200717640270
[differential diagnosis of visceral leishmaniasis, progressive disseminated histoplasmosis and penicilliosis marneffei].visceral leishmaniasis, progressive disseminated histoplasmosis and penicilliosis marneffei are infections found in both human and animals. their clinical manifestations, morphology of the pathogens under microscope are similar. misdiagnosis was common and prognosis was poor when wrong therapy was given. this article is to introduce the epidemiology, clinical manifestation, laboratory findings and the treatment of these infections.200717639707
[cloning of avastin gene of leishmania donovani isolates from sichuan province and its expression in eucaryotic system].to clone and express the avastin gene of two leishmania donovani isolates from sichuan province of china.200717633823
[antileishmanial activity of five 2- or 3- quinolines by enyne group].leishmaniasis is an emergent orphan disease because of its co-infection with hiv aids. we report herein the in vitro biological evalution of five news quinolines, 2- or 3-substituted by an enyne group against leishmania donovani (mhom/et/l82/lv9).200517633005
inactivation of the miltefosine transporter, ldmt, causes miltefosine resistance that is conferred to the amastigote stage of leishmania donovani and persists in vivo.miltefosine (hexadecylphosphocholine) is the first oral antileishmanial drug. in this study, we addressed the question whether miltefosine-resistant leishmania donovani promastigotes transform to miltefosine-resistant amastigotes. a promastigote line, m-mutr, showed defective internalisation of miltefosine owing to mutations in ldmt, similar to previously described resistant lines. m-mutr parasites were infective to macrophages in vitro as well as in balb/c mice in vivo. there was good correlati ...200717628445
visceral leishmaniasis diagnosed on duodenal biopsy. 200717628327
comparison of conventional methods for diagnosis of visceral leishmaniasis in children of the center-west region of brazil.in brazil, sophisticated techniques currently employed for diagnosis of visceral leishmaniasis, such as polymerase chain reaction-based assays, are only available in major research centers, whereas conventional methods are still used in many areas where the disease occurs. in the state of mato grosso do sul, in the country's center-west region, visceral leishmaniasis has recently emerged in many cities, and duration of the disease, from the onset of symptoms to diagnosis, has been short. conside ...200717625737
first case of indigenous visceral leishmaniasis from central india.visceral leishmaniasis is endemic in the eastern states of india, but central india remains free of leishmaniais. this report describes the first indigenous case of visceral leishmaniasis in a seven-year-old girl from central india. the child presented with fever for 10 days and was diagnosed by bone marrow examination, serology using rke16 and rk39 antigens, and a polymerase chain reaction specific for the kinesin gene. sequencing of the immunodominant region of the kinesin gene of the parasite ...200717620636
synthesis, biological evaluation, and molecular modeling of 3,5-substituted-n1-phenyl-n4,n4-di-n-butylsulfanilamides as antikinetoplastid antimicrotubule agents.dinitroanilines are of interest as antiprotozoal lead compounds because of their selective activity against the tubulin of these organisms, but concern has been raised due to the potentially mutagenic nitro groups. analogues of n(1)-phenyl-3,5-dinitro-n(4),n(4)-di-n-butylsulfanilamide (gb-ii-150, compound 2b), a selective antimitotic agent against african trypanosomes and leishmania, have been prepared where the nitro groups are replaced with amino, chloro, cyano, carboxylate, methyl ester, amid ...200717618122
antileishmanial efficacy of amphotericin b bearing emulsomes against experimental visceral leishmaniasis.amphotericin b (amb) was formulated in trilaurin-based emulsomes (nanosize lipid particles) stabilized by soya phosphatidylcholine (pc), as a new delivery system for macrophage targeting for the treatment of visceral leishmaniasis (vl). emulsomes were modified by coating them with macrophage-specific ligand (o-palmitoyl mannan, opm). the antileishmanial activity of amb-deoxycholate (amb-doc) and emulsome entrapped amb was tested in vitro in leishmania donovani infected macrophage-amastigote syst ...200717613662
increased levels of thiols protect antimony unresponsive leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony.the current trend of antimony (sb) unresponsiveness in the indian subcontinent is a major impediment to effective chemotherapy of visceral leishmaniasis (vl). although contributory mechanisms studied in laboratory-raised sb-r parasites include an up-regulation of drug efflux pumps and increased thiols, their role in clinical isolates is not yet substantiated. accordingly, our objectives were to study the contributory role of thiols in the generation of sb unresponsiveness in clinical isolates. p ...200717612420
visceral leishmaniasis: a threat to immunocompromised patients in non-endemic areas?visceral leishmaniasis is rare in western europe, but may be life-threatening in immunocompromised patients. it is therefore important to understand the incidence of the disease in a non-endemic area and its relationship with immunosuppressive conditions. between 1990 and 2005, 12 patients were diagnosed with leishmaniasis at basel university hospital, switzerland. eleven presented with visceral symptoms and ten had an underlying immunosuppressive condition. since increasing numbers of immunosup ...200717610597
first detection and genetic typing of leishmania infantum mon-24 in a dog from the moroccan mediterranean coast: genetic diversity of mon-24.as in the countries edging the mediterranean basin, leishmania infantum zymodeme mon-1 is the main causative agent of visceral leishmaniasis in morocco, where visceral leishmaniasis is most active in the north-eastern slopes of the rif mountains. the dog was confirmed to be the main reservoir of l. infantum mon-1, while the reservoir of l. infantum mon-24 causative agent of both infantile visceral leishmaniasis and cutaneous leishmaniasis has not yet been identified. here we report the first det ...200717603990
visceral leishmaniasis in gizan, saudi arabia.visceral leishmaniasis is endemic in southern saudi arabia. we prospectively evaluated 121 patients with visceral leishmaniasis at king fahad hospital in gizan. all patients were infants and children. seasonal variation was observed with more cases presenting in late spring and summer and few in winter. the predominant clinical features in these patients were chronic fever, abdominal distention, weight loss and hepatosplenomegaly. lymphadenopathy was rare in contrast to african kala-azar. common ...199417586953
locally acquired visceral leishmaniasis in sri lanka. 200717585579
tamoxifen is effective against leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring leishmania (leishmania) amazonensis amastigotes.this study was performed to investigate the activity of tamoxifen, an antioestrogen widely used in the treatment of breast cancer, against leishmania.200717584801
injectable paromomycin for visceral leishmaniasis in india.visceral leishmaniasis (kala-azar) affects large, rural, resource-poor populations in south asia, africa, and brazil. safe, effective, and affordable new therapies are needed. we conducted a randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin b, the present standard of care in bihar, india.200717582067
visceral leishmaniasis after allogeneic hematopoietic stem cell transplantation. 200717572716
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