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[spontaneous rupture of the spleen in a patient with visceral leishmaniasis]. 200515899186
characterization of the atpase activity of topoisomerase ii from leishmania donovani and identification of residues conferring resistance to etoposide.we have cloned and expressed the 43 kda n-terminal domain of leishmania donovani topoisomerase ii. this protein has an intrinsic atpase activity and obeys michaelis-menten kinetics. cross-linking studies indicate that the n-terminal domain exists as a dimer both in the presence and absence of nucleotides. etoposide, an effective antitumour drug, traps eukaryotic dna topoisomerase ii in a covalent complex with dna. in the present study, we report for the first time that etoposide inhibits the atp ...200515901238
kinetoplastid membrane protein-11 dna vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of leishmania donovani that correlates with inducible nitric oxide synthase activity and il-4 generation: evidence for mixed th1- and th2-like responses in visceral leishmaniasis.the emergence of an increasing number of leishmania donovani strains resistant to pentavalent antimonials (sbv), the first line of treatment for visceral leishmaniasis worldwide, accounts for decreasing efficacy of chemotherapeutic interventions. a kinetoplastid membrane protein-11 (kmp-11)-encoding construct protected extremely susceptible golden hamsters from both pentavalent antimony responsive (ag83) and antimony resistant (ge1f8r) virulent l. donovani challenge. all the kmp-11 dna vaccinate ...200515905560
chemotherapy of leishmaniasis part ii: synthesis and bioevaluation of substituted arylketene dithioacetals as antileishmanial agents.some novel aryl substituted ketene dithioacetals have been synthesized using novel synthetic methods. the compounds were screened against leishmania donovani in hamsters for their activity profile. some of the compounds inhibited 50-65% parasite growth at 50 mg kg(-1) x 5 days.200515907348
leishmanicidal cycloartane-type triterpene glycosides from astragalus oleifolius.two new cycloartane-type glycosides oleifoliosides a (1) and b (2) were isolated from the lower stem parts of astragalus oleifolius. their structures were identified as 3-o-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-o-beta-xylopyranosyl-3beta,6alpha,16beta,24(s),25-pentahydroxycycloartane and 3-o-[beta-xylopyranosyl-(1 --> 2)-alpha-arabinopyranosyl]-6-o-beta-glucopyranosyl-3beta,6alpha,16beta,24(s),25-pentahydroxycycloartane, respectively, by means of spectroscopic methods (ir, 1d a ...200515922377
leishmania donovani amastigotes mobilize organic and inorganic osmolytes during regulatory volume decrease.the protozoan parasite leishmania donovani encounters large fluctuations in osmolality as it cycles between its insect vector and human host. the flagellated promastigote exhibits regulatory volume responses involving organic and inorganic osmolytes, but little is known about volume regulation in the clinically relevant amastigote that multiplies within the parasitophorous vacuoles of mammalian host cells. using a combination of morphological, x-ray microanalytical, and biochemical approaches we ...200515927005
peroxin 5-peroxin 14 association in the protozoan leishmania donovani involves a novel protein-protein interaction motif.import of proteins with a pts1 (peroxisomal targeting signal 1) into the leishmania glycosomal organelle involves docking of a pts1-laden ldpex5 [leishmania donovani pex5 (peroxin 5)] receptor to ldpex14 on the surface of the glycosomal membrane. in higher eukaryotes, the pex5-pex14 interaction is mediated by a conserved diaromatic wxxxy/f motif. site-directed and deletion mutageneses of the three wxxxy/f repeats in ldpex5 did not abolish the ldpex5-ldpex14 association. analysis of the equilibri ...200515929724
evaluation of a dot-immunoblot assay for detecting leishmanial antigen in naturally infected phlebotomus argentipes (diptera: psychodidae).a simple and highly reproducible dot-immunoblot assay was developed to detect leishmanial antigen in phlebotomus argentipes that were naturally infected with leishmania donovani. the test was sensitive to as little as 10 ng of antigenic protein (equivalent to the gut content of one laboratory-infected sandfly) and also appeared to be specific, in that it gave a positive result with some p. argentipes (the primary vector of l. donovani in india) and l. donovani but not with p. papatasi or other p ...200515949184
modulation of leishmania donovani infection and cell viability by testosterone in bone marrow-derived macrophages: signaling via surface binding sites.androgens can increase susceptibility toward numerous parasitic infections as well as modulate apoptosis of immune cells. according to the current view, androgens mediate immune cell activities not only through classical intracellular androgen receptors (ar), but also through membrane receptors on the cell surface. here, using murine bone marrow-derived macrophages (bmms), we examined the influence of testosterone on leishmania donovani infection and cell viability in vitro as well as the possib ...200515964042
localized cutaneous leishmaniasis due to leishmania donovani and leishmania tropica: preliminary findings of the study of 161 new cases from a new endemic focus in himachal pradesh, india.localized cutaneous leishmaniasis (lcl) in india is due mostly to leishmania tropica. it is mainly endemic in the deserts of rajasthan. recently, himachal pradesh has been identified as a new endemic focus for the disease. in the last few years, the number of new cases has been increasing almost to epidemic proportions. this report presents the preliminary findings of clinico-epidemiologic and investigative results of 161 new localized cases of lcl seen between may 2001 and december 2003. the st ...200515964970
antagonizing deactivating cytokines to enhance host defense and chemotherapy in experimental visceral leishmaniasis.in experimental visceral leishmaniasis, inhibition of interleukin 10 (il-10) signaling enhances th1-cell-associated responses, promoting gamma interferon (ifn-gamma) secretion, granuloma assembly, macrophage activation with substantial liver parasite killing, and synergy with pentavalent antimony (sb) chemotherapy. to determine if inhibiting other suppressive cytokines has similar therapeutic potential, leishmania donovani-infected balb/c mice were injected with anti-il-4 monoclonal antibody or ...200515972476
a type ii ribonuclease h from leishmania mitochondria: an enzyme essential for the growth of the parasite.replication of kdna in the mitochondrion of the kinetoplastid protozoan is an essential process. one of the proteins that may be required for the kdna replication is the ribonuclease h (rnase h; ec 3.1.26.4). we have identified four distinct ribonuclease h genes in leishmania, one type i (lrnase hi) and three type ii (lrnase hiia, lrnase hiib and lrnase hiic). we detail here molecular characterization of lrnase hiic. the coding sequence of lrnase hiic is 1425 bp in length encoding a 474-amino ac ...200515978682
alteration of fatty acid and sterol metabolism in miltefosine-resistant leishmania donovani promastigotes and consequences for drug-membrane interactions.miltefosine (hexadecylphosphocholine [hepc]) is the first orally active drug approved for the treatment of visceral leishmaniasis. in order to investigate the biochemical modifications occurring in hepc-resistant (hepc-r) leishmania donovani promastigotes, taking into account the lipid nature of hepc, we investigated their fatty acid and sterol metabolisms. we found that the content of unsaturated phospholipid alkyl chains was lower in hepc-r parasite plasma membranes than in those of the wild t ...200515980336
proteasome-mediated degradation of stat1alpha following infection of macrophages with leishmania donovani.activation of the janus-activated kinase 2 (jak2)/stat1alpha signaling pathway is repressed in leishmania-infected macrophages. this represents an important mechanism by which this parasite subverts the microbicidal functions of the cell to promote its own survival and propagation. we recently provided evidence that the protein tyrosine phosphatase (ptp) shp-1 was responsible for jak2 inactivation. however, stat1 translocation to the nucleus was not restored in the absence of shp-1. in the prese ...200515983048
influence of phospholipid composition on the adjuvanticity and protective efficacy of liposome-encapsulated leishmania donovani antigens.in this study, we evaluate the effect of phospholipid on the adjuvanicity and protective efficacy of liposome vaccine carriers against visceral leishmaniasis (vl) in a hamster model. liposomes prepared with distearyol derivative of l-alpha-phosphatidyl choline (dspc) having liquid crystalline transition temperature (tc) 54 c were as efficient as dipalmitoyl (dppc) (tc 41 c) and dimyristoyl (dmpc) (tc 23 c) derivatives in their ability to entrap leishmania donovani membrane antigens (lag) and to ...200515986599
the molecular characterization of clinical isolates from indian kala-azar patients by mlee and rapd-pcr.kala-azar is a serious health problem in india. the situation has worsened further due to the occurrence of cases unresponsive to antimonials. about 30-50% patients do not respond to the prevailing regimen of antimonials. the etiological agent for indian kala-azar has long been known to be leishmania donovani. recently, in a somewhat startling report, it was claimed that l. tropica causes nearly 25% of current kala-azar cases in india. it was also suggested that this might be in some way related ...200515990683
curcumin overcomes the inhibitory effect of nitric oxide on leishmania.upon leishmania infection, macrophages are activated to produce nitrogen and oxygen radicals simultaneously. it is well established that the infected host cells rely on nitric oxide (no) as the major weapon against the intracellular parasite. in india where leishmaniasis is endemic, the spice turmeric is used prolifically in food and for insect bites. curcumin, the active principle of turmeric, is a scavenger of no. this report shows that curcumin protects promastigotes and amastigotes of the vi ...200515772867
topoisomerase i amino acid substitutions, gly185arg and asp325glu, confer camptothecin resistance in leishmania donovani.the antitumor compound camptothecin (cpt) is also recognized for its specific activity against leishmania donovani topoisomerase i (topo-i). in consequence, defining cpt resistance mechanisms represents an important strategic tool in the acquisition of a better understanding of its mode of action. in the present study, we selected a single highly resistant l. donovani strain termed ldrcpt.160 by stepwise exposure to cpt. gene sequencing revealed two single nucleotide mutations in the ldrcpt.160 ...200515793124
a2 gene of old world cutaneous leishmania is a single highly conserved functional gene.leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. the various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. among the candidate factors of parasite virulence are the a2 genes, a family of multiple genes that are developmentally expressed in species of the leishmania donovani group responsible for visceral diseases (vl) ...200515794817
flow cytometric assessment of leishmania spp metacyclic differentiation: validation by morphological features and specific markers.characterization of infective metacyclic promastigotes of leishmania spp can be an essential step in several experimental protocols. metacyclic forms of all leishmania species display a typical morphology with short, narrow cell body, and an elongated flagellum. this feature suggests that metacyclics can be distinguished from procyclic forms by non-fluorimetric flow cytometric parameters thus enabling the follow-up of their appearance and acquisition of specific properties, during metacyclogenes ...200515804377
dichotomy of protective cellular immune responses to human visceral leishmaniasis.healing/protective responses in human visceral leishmaniasis (vl) are associated with stimulation/production of th1 cytokines, such as interferon ifn-gamma, and conversion in the leishmanin skin test (lst). such responses were studied for 90 days in 44 adult healthy volunteers from vl non-endemic areas, with no past history of vl/cutaneous leishmaniasis (cl) and lst non-reactivity following injection with one of four doses of alum-precipitated autoclaved leishmania major (alum/alm) +/- bacille c ...200515807861
therapeutic use of quercetin in the control of infection and anemia associated with visceral leishmaniasis.flavonoids are a broad class of plant phenolics that are known to possess a well-established protective effect against membrane lipoperoxidative damages. oxidative damage of erythrocytes has been implicated in the reduced survival of erythrocytes during leishmanial infection. this study reveals the efficacy of five naturally occurring flavonoids in arresting the development of anemia during the postinfection period. among the compounds studied, quercetin was most successful in inhibiting the oxi ...200515808423
novobiocin induces apoptosis-like cell death in topoisomerase ii over-expressing arsenite resistant leishmania donovani.leishmaniasis affects millions of people worldwide every year. lack of effective vaccination, co-infection with other dreaded diseases like aids and generation of drug resistant strains demand immediate attention into this neglected area of research. the sodium m-arsenite (naaso2) resistant leishmania donovani used in this study is resistant to 20 microm naaso2, which shows a 13-fold increase in resistance compared with wild type. here we report that the arsenite resistant strain of l. donovani ...200515811527
differentiation of leishmania donovani in host-free system: analysis of signal perception and response.leishmania donovani are the causative agents of kala-azar in humans. they undergo a developmental program following changes in the environment, resulting in the reversible transformation between the extracellular promastigote form in the sand fly vector and the obligatory intracellular amastigote form in phagolysosomes of macrophages. a host-free differentiation system for l. donovani was used to investigate the initial process of promastigote to amastigote differentiation. within an hour after ...200515811531
prevention of relapse after chemotherapy in a chronic intracellular infection: mechanisms in experimental visceral leishmaniasis.in visceral leishmaniasis, chemotherapy probably seldom eradicates all parasites in tissue macrophages; nevertheless, most t cell-intact patients show long-lasting clinical cure after treatment despite residual intracellular infection. to characterize prevention of posttreatment relapse, amphotericin b was used to kill approximately 90-95% of leishmania donovani in livers of mice deficient in mechanisms of acquired antileishmanial resistance. recrudescence subsequently developed 1) in animals de ...200515814719
osteolytic osteomyelitis associated with visceral leishmaniasis in a dog.a dog was examined with a history of weight loss and lameness of the left hind limb. a painful response to examination of the left hip joint, and lymphadenopathy were noted. amastigote forms of leishmania sp. were observed by cytology in samples from the popliteus lymph node, and anti-leishmania sp. antibodies at a titer of 1:640 were detected in serum by indirect immunofluorescence. radiological changes included osteolysis and a periosteal proliferative reaction in the left femoral greater troc ...200515817202
immunomodulatory activity of analog of muramyl dipeptide and their use as adjunct to chemotherapy of leishmania donovani in hamster.in search of a potent immunomodulator to be used as an immunoprophylactic agent and as adjunct to chemotherapy against leishmania infection, two analogs of muramyl dipeptide, viz. n.ac-normur-meval-d-isogln (86/448) and n.acmur-acc-d-isogln (89/729) were evaluated for desired activity. effect of these peptides on cell mediated and humoral immunity was studied by immunizing the peptide treated mouse with sheep red blood cells (srbc) and determining ha-titer, plaque forming cells assay and delayed ...200515829410
leishmania promastigote membrane antigen-based enzyme-linked immunosorbent assay and immunoblotting for differential diagnosis of indian post-kala-azar dermal leishmaniasis.diagnosis of post-kala-azar dermal leishmaniasis (pkdl), caused by leishmania donovani, is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. since the disease generally appears very late after the clinical cure of kala-azar in india, it is also difficult to correlate pkdl with a previous exposure to l. donovani. very few attempts have been made so far to diagnose pkdl serologically, and the diagnostic methods vary in their ...200515750095
role of sulfhydryl groups in band 3 in the inhibition of phosphate transport across erythrocyte membrane in visceral leishmaniasis.membrane destabilization in erythrocytes plays an important role in the premature hemolysis and development of anemia during visceral leishmaniasis (vl). marked degradation of the anion channel protein band 3 is likely to allow modulation of anion flux across the red cell membrane in infected animals. the present study describes the effect of structural modification of band 3 on phosphate transport in vl using (31)p nmr. the result showed progressive decrease in the rate and extent of phosphate ...200515752716
design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors of trypanosomal and leishmanial dihydrofolate reductase.this paper describes the design, synthesis and evaluation of a series of 2,4-diaminoquinazolines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. compounds were designed by a generating virtual library of compounds and docking them into the enzyme active site. following their synthesis, they were found to be potent and selective inhibitors of leishmanial dihydrofolate reductase. the compounds were also found to have potent activity against trypanosoma brucei rhodesiense, a ...200515755663
immunostimulatory cellular responses of cured leishmania-infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of leishmania donovani.development of an effective immunoprophylactic agent for visceral leishmaniasis (vl) has become imperative due to the increasing number of cases of drug resistance and relapse. live and killed whole parasites as well as fractionated and recombinant preparations have been evaluated for vaccine potential. however, a successful vaccine against the disease has been elusive. because protective immunity in human and experimental leishmaniasis is predominantly of the th1 type, immunogens with th1 stimu ...200515762886
efficacy of desmodium gangeticum extract and its fractions against experimental visceral leishmaniasis.crude ethanolic extract of indian medicinal plant, desmodium gangeticum (a001) and its three fractions-hexane (f002), n-butanol (f003) and aqueous (f004) were evaluated chemoprophylactically and chemotherapeutically against experimental visceral leishmaniasis in hamsters. ethanolic extract showed 41.2+/-5.3% inhibition of parasite multiplication when administered at a dose of 250 mg/kgx2 on day -7 and +7 of leishmania donovani challenge. its n-butanol fraction exhibited better efficacy than the ...200515763367
leishmania (viannia) subgenus kdna amplification for the diagnosis of mucosal leishmaniasis.the utility of 2 polymerase chain reaction (pcr)-based assays amplifying genus or viannia subgenus leishmania minicircle kdna for the diagnostics of ml was assessed. the viannia subgenus product was yielded after pcr from isolates of l. (viannia) braziliensis, l. (viannia) colombiensis, and l. (viannia) guyanensis, whereas no product was obtained with the non-viannia-pertaining species: l. (leishmania) amazonensis, l. (leishmania) donovani, and l. (leishmania) chagasi. with both assays, 11 of 13 ...200515766604
expression, purification, and characterization of leishmania donovani trypanothione reductase in escherichia coli.trypanothione reductase (tr) is an nadph-dependent flavoprotein oxidoreductase central to thiol metabolism in all the trypanosomatids including leishmania. the unique presence of this enzyme in trypanosomatids and absence in mammalian host make this enzyme an attractive target for the development of the antileishmanials. complete open reading frame encoding trypanothione reductase from leishmania donovani (dd8 strain, causative agent of indian visceral leishmaniasis) was cloned, sequenced, and e ...200515766869
therapeutic potential of new pt(ii) and ru(iii) triazole-pyrimidine complexes against leishmania donovani.we have already established an in vitro culture system using murine macrophages infected with leishmania donovani in which the time course of parasite growth is determined quantitatively. we adopted this system for the screening of three triazole-pyrimidine derivatives that would ideally prove to be effective against l. donovani with no toxicity to the host cell. amphotericin b deoxycholate was used as the standard drug and gave a ic50 value of 3.89 microg/ml. the three triazole-pyrimidine compo ...200515452362
second-site suppression of a nonfunctional mutation within the leishmania donovani inosine-guanosine transporter.ldnt2 is a member of the equilibrative nucleoside transporter family, which possesses several conserved residues located mainly within transmembrane domains. one of these residues, asp(389) within ldnt2, was shown previously to be critical for transporter function without affecting ligand affinity or plasma membrane targeting. to further delineate the role of asp(389) in ldnt2 function, second-site suppressors of the ldnt2-d389n null mutation were selected in yeast deficient in purine nucleoside ...200515501825
reconstitution of gdp-mannose transport activity with purified leishmania lpg2 protein in liposomes.activated nucleotide sugars required for the synthesis of glycoconjugates within the secretory pathway of eukaryotes are provided by the action of nucleotide sugar transporters (nsts). typically, nsts are studied in microsomal preparations from wild-type or mutant lines; however, in this setting it can be difficult to assess nst properties because of the presence of glycosyltransferases and other interfering activities. here we have engineered leishmania donovani to express high levels of an act ...200515542612
a new pcr-elisa for diagnosis of visceral leishmaniasis in blood of hiv-negative subjects.the pcr-elisa represents a promising advance for diagnosis of visceral leishmaniasis (vl) in blood samples. however, the method has been validated mostly with hiv-positive patients who are known to have high levels of parasitaemia. we developed a new pcr-elisa assay for specific detection of leishmania in patients' blood and validated it in nepalese subjects with clinically suspected vl, almost all of whom were hiv-negative. for blood samples, pcr-elisa was more sensitive (83.9%) than convention ...200515550258
[the differential features of bone marrow morphology of several rare infectious disorders].to facilitate the diagnosis of histoplasmosis, kala-azar, penicilliosis marneffei, toxoplasmosis and cryptococcosis with the help of bone marrow morphology.200516409725
antileishmanial and trypanocidal activity of brazilian cerrado plants.the side effects and the emerging resistance to the available drugs against leishmaniasis and trypanosomiasis led to the urgent need for new therapeutic agents against these diseases. thirty one extracts of thirteen medicinal plants from the brazilian cerrado were therefore evaluated in vitro for their antiprotozoal activity against promastigotes of leishmania donovani, and amastigotes of trypanosoma cruzi. among the selected plants, casearia sylvestris var. lingua was the most active against bo ...200516419337
genetics of murine leishmaniasis.leishmaniasis encompasses a number of disease syndromes, caused by several species of the digenetic protozoan leishmania, and is transmitted by sandflies. the mouse model of the disease has been used to identify genes involved in disease susceptibility--for example, the slc11a1 gene, important in resistance to leishmania donovani--and to map loci important in leishmania major infection. the genetics of the host response to l. major has been shown to be complex and to involve much more than the t ...200516420752
first report on the presence of morphospecies a and b of phlebotomus argentipes sensu lato (diptera: psychodidae) in sri lanka--implications for leishmaniasis transmission. 200516457386
value of culture and nested polymerase chain reaction of blood in the prediction of relapses in patients co-infected with leishmania and human immunodeficiency virus.the use of culture and a nested polymerase chain reaction (pcr) of blood in predicting the probability of relapse was evaluated in 20 patients co-infected with leishmania and human immunodeficiency virus (hiv). fourteen of 20 patients relapsed, with 24 clinical relapses diagnosed. during clinical relapse, the parasite was detected by culture in 21 of 24 blood samples and by nested pcr in 23 of 24 blood samples. after treatment and during asymptomatic periods, the parasite was detected by culture ...200516354803
antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class of trypanothione reductase inhibitor, and of n-acyl derivatives of 2-amino-4-chlorophenyl phenyl sulfide.quaternization of the nitrogen atom of 2-amino-4-chlorophenyl phenyl sulfide analogues of chlorpromazine improved inhibition approximately 40-fold (3',4'-dichlorobenzyl-[5-chloro-2-phenylsulfanyl-phenylamino)-propyl]-dimethylammonium chloride inhibited trypanothione reductase from trypanosoma cruzi with a linear competitive ki value of 1.7 +/- 0.2 microm). molecular modelling explained docking orientations and energies by: (i) involvement of the z-site hydrophobic pocket (roughly bounded by f396 ...200516335933
sodium stibogluconate resistance in leishmania donovani correlates with greater tolerance to macrophage antileishmanial responses and trivalent antimony therapy.co-treatment of mice infected with different strains of leishmania donovani with a non-ionic surfactant vesicle formulation of buthionine sulfoximine (bso-niv), and sodium stibogluconate (ssg), did not alter indicators of th1 or th2 responses but did result in a significant strain-independent up-regulation of il6 and nitrite levels by stimulated splenocytes from treated mice compared to controls. the efficacy of bso-niv/ssg treatment was dependent on the host being able to mount a respiratory bu ...200516336728
application of an improved method for the recombinant k 39 enzyme-linked immunosorbent assay to detect visceral leishmaniasis disease and infection in bangladesh.several serology-based immunoassays are used to diagnose visceral leishmaniasis (vl), a chronic protozoan parasitic disease caused by the leishmania donovani complex. these tests are primarily designed to diagnose the most severe clinical form of vl, known as kala-azar. however, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. we modified a previously described enzyme-linked immunosorbent assay (elisa) that ...200516339064
treatment of visceral leishmaniasis.the leishmania donovani complex includes l. chagasi and l. infantum, and causes visceral leishmaniasis (vl), a disseminated and potentially fatal form of leishmaniasis. the treatment options for vl are limited. pentavalent antimonials (sbv) are the first-line treatment options worldwide except for in europe and sbv-unresponsive regions of india. amphotericin b deoxycholate is the drug of choice in india, as are its lipid formulations in europe. however, liposomal amphotericin b (ambisome, gilead ...200516318433
antileishmanial and trypanocidal activities of new miltefosine liposomal formulations.liposomes composed of hexadecylphosphocholine/egg phosphatidylcholine/stearylamine (hepc/epc/sa) 10:10:0.1, 10:10:0.5 and 10:10:1 (molar ratio) (1-3) were prepared and lyophilized. the liposomes were physicochemically characterized (size and zeta-potential) and they were found stable at 4 degrees c over a period of 4 weeks. in vitro, liposomes 1 and 2 were about twice more active than hepc against leishmania donovani wt whereas liposomes 3 were about three times more active than hepc on hepc-res ...200516325367
post-kala-azar dermal leishmaniasis: a histopathological study.post-kala-azar dermal leishmaniasis follows an attack of visceral leishmaniasis and is caused by the same organism, i.e. leishmania donovani.200516394433
clinical presentation and management of visceral leishmaniasis.febrile illnesses like malaria, typhoid, and tuberculosis are the commonest problems in our area, but visceral leishmaniasis (vl) is also one of the diseases presenting with fever in this part of the country. this study was conducted to evaluate its clinical spectrum and way of management.200516599036
[management of cutaneous leishmaniasis in adults and children].cutaneous leishmaniasis can present a variety of clinical features and courses. the causative leishmania species is an important prognostic factor in immunocompetent patients. local treatment modalities including topical paromomycin, cryotherapy, localized controlled heat, carbon dioxide laser therapy, or intralesional meglumine antimoniate can be effective against leishmania major or leishmania tropica. oral fluconazole may be a second-line treatment. parenteral antimonials are useful for persi ...200516465821
molecular characterization of a human brca2 homolog in leishmania donovani.the breast cancer susceptibility protein brca2 is implicated in the dna double-strand break (dsb) repair pathway through its association with rad51. it is almost a ubiquitous eukaryotic protein; homologs of the brca2 gene (brh2) have been identified in many mammals, as well as nonmammals. as a part of our quest to understand the dna damage, repair, and recombination process in the parasitic protozoan, leishmania sp., we have cloned and characterized a brca2 homolog from leishmania sp. (lbrh2). l ...200516539040
rapid & reliable diagnostic tests for visceral leishmaniasis. 200516517995
preservation of leishmania donovani promastigotes in blood agar slants.long-term cultivation of leishmania promastigotes by weekly passage to fresh medium was reported to be disadvantageous because needs labor, risk of contamination, lowering in infectivity and virulence pattern. cryopreservation and lyophilization require expensive facilities which could be a burden and unaffordable to most laboratories of developing countries where the disease is endemic. these problems could be minimized by simple preservation of leishmania donovani promastigotes in blood agar s ...200517080702
[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
epidemiology of a new focus of localized cutaneous leishmaniasis in himachal pradesh.a new focus of localised cutaneous leishmaniasis has emerged along the satluj river valley in the mountainous region of north west himachal pradesh. the main endemic region extends from pooh subdivision of kinnaur district to kumarsain subdivision of shimla district with adjoining nirmand subdivision of kullu district comprising 86 villages. the climate of the affected areas varies from temperate to subtropical. a total of 285 cases were recorded from 1988 to january, 2005. the age of these pati ...200517278657
in vitro antiprotozoal activity of the lipophilic extracts of different parts of turkish pistacia vera l.thirteen lipophilic extracts prepared with n-hexane from various parts of pistacia vera l. tree (anacardiaceae) growing in turkey were screened for their in vitro activity against four parasitic protozoa, trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani and plasmodium falciparum. melarsoprol, benznidazole, miltefosine, artemisinin and chloroquine were used as reference drugs. the cytotoxic potentials of the extracts on rat skeletal myoblast (l6) cells were also assessed and ...200617085297
aspects of the cytological activity of edelfosine, miltefosine, and ilmofosine in leishmania donovani.to discover the mode of action of alkyl-lysophospholipids in leishmania donovani, we studied the effects of edelfosine, miltefosine, and ilmofosine on intracellular ph, the parasite's cell cycle, and the induction of apoptosis. the effect of the alkyl-lysophospholipids was combined with that of inhibitors of some pumps and exchange regulators of intracellular ph (na+/ h+; cl-/co- 3; and the na+/k+ atpase). the effect of the 3 alkyl-lysophospholipids on intracellular ph was indirect; the primary ...200617152926
diagnosing human asymptomatic visceral leishmaniasis in an urban area of the state of minas gerais, using serological and molecular biology techniques.a population-based cross-sectional study was set up in sabará country, southeastern brazil, to identify asymptomatic human visceral leishmaniasis in an urban area of low disease prevalence. blood was collected on filter paper (n=1,604 inhabitants) and examined by indirect immunofluorescent test, enzyme-linked immunosorbent assay and immunochromatographic strip test. the prevalence rates of infection ranged from 2.4 to 5.6% depending on the test used. one year later, venous blood was collected in ...200617160317
a new library of c-16 modified artemisinin analogs and evaluation of their anti-parasitic activities.a library of c-16 modified artemisinin analogs was prepared and their antimalarial as well as antileishmanial activities were evaluated. synthesis of these compounds involved the conversion of artemisinin to its phenol derivatives 7 and 12, and subsequent parallel derivatization by introducing new chemical groups through ester, carbamate, sulfate, phosphate and isourea linkages. comparison of in vitro antimalarial activities showed that c9-beta artemisinin analogs (8a-f) are more potent than the ...200617168678
antituberculotic and antiprotozoal activities of primin, a natural benzoquinone: in vitro and in vivo studies.primin (=2-methoxy-6-pentylcyclohexa-2,5-diene-1,4-dione), a natural benzoquinone synthesized in our laboratory, was investigated for its in vitro antiprotozoal, antimycobacterial, and cytotoxic potential. primin showed very potent activity against trypanosoma brucei rhodesiense (ic50 0.144 microm) and leishmania donovani (ic50 0.711 microm), and revealed low cytotoxicity (ic50 15.4 microm) on mammalian cells. only moderate inhibitory activity was observed against mycobacterium tuberculosis, try ...200617193236
first case of cutanous leishmaniasis in nepalese patient.visceral leishmaniasis (vl) is a serious disease caused by leishmania donovani (ld) complex and prevalent in the temperate and tropical zones of the earth. vl, endemic in the southern plains of the 14 districts in the terai region of nepal, is considered a major public health problem. cutanous leishmaniasis (cl) is prevalent mainly in the tropics and subtropics, affects nearly 1.5 million people worldwide. no reported cases of cl have been identified in nepal until now. we report the first case ...200617203834
comparative evaluation of freeze-dried and liquid antigens in the direct agglutination test for serodiagnosis of visceral leishmaniasis (itma-dat/vl).the direct agglutination test (dat) for visceral leishmaniasis (vl) with liquid (lq) antigen is known to be only moderately reproducible because of inter-observer and batch-to-batch variability as well as its sensitivity to temperature and shaking during transport. we evaluated a dat with freeze-dried (fd) antigen and compared it with the lq antigen version.200617176341
visceral leishmaniasis in southeastern nepal: a cross-sectional survey on leishmania donovani infection and its risk factors.to document the frequency of leishmania donovani infection at community level in a highly endemic region in southeastern nepal, and to assess socioeconomic and environmental risk factors.200617176343
leishmaniasis in ancient egypt and upper nubia. 200617176592
visceral leishmaniasis in nepal during 1980-2006.visceral leishmaniasis (vl) or kala-azar is a potentially fatal vector-borne zoonotic disease caused by a protozoan parasite, leishmania donovani. nepal, together with india, bangladesh, brazil and sudan constitutes the five countries of the world where more than 90% of vl occurs. in nepal, the disease affects eastern terai region which lies adjacent to the bihar state of india. although leishmaniasis is regarded as a significant health problem in nepal by the ministry of health, there is no act ...200617370676
chronic diarrhea and malabsorption caused by leishmania donovani.chronic diarrhea and malabsorption are uncommon in immunocompetent patients with visceral leishmaniasis. we report two immunocompetent patients with visceral leishmaniasis where the predominant presentation was chronic diarrhea. one of them had clinically overt malabsorption and duodenal mucosa was loaded with leishmania donovani bodies. the other patient had diffuse colonic aphthous and discrete ulcerations and leishmania donovani bodies were seen in the crush smears of the colonic mucosa. with ...200617264434
mapping the antigenicity of the parasites in leishmania donovani infection by proteome serology.leishmaniasis defines a cluster of protozoal diseases with diverse clinical manifestations. the visceral form caused by leishmania donovani is the most severe. so far, no vaccines exist for visceral leishmaniasis despite indications of naturally developing immunity, and sensitive immunodiagnostics are still at early stages of development.200617183669
role of host protein tyrosine phosphatase shp-1 in leishmania donovani-induced inhibition of nitric oxide production.in order to survive within the macrophages of its host organism, the protozoan parasite leishmania inhibits a number of critical, gamma interferon (ifn-gamma)-inducible, macrophage functions, including the generation of nitric oxide. we have previously shown that the protein tyrosine phosphatase shp-1 (src-homology 2 domain containing phosphatase-1) is activated during leishmania infection and plays an important role in both the survival of leishmania within cultured macrophages and disease prog ...200617057094
genes and environment in susceptibility to visceral leishmaniasis.kala azar (ka) is a lethal disease caused by leishmania parasites (leishmania donovani s.l.) that multiply in large numbers in deep organs such as spleen and liver. the host immunological response to these organisms is complex and experimental studies in animals have detected a large number of genetic loci involved in the control of infection and disease. we report here on a study in a human population of sudan carried out during an outbreak of ka. the following conclusions are presented: (1) en ...200617067929
evaluation of azasterols as anti-parasitics.in this article, the design and synthesis of some novel azasterols is described, followed by their evaluation against trypanosoma brucei rhodesiense, t. cruzi, leishmania donovani, and plasmodium falciparum, the causative agents of human african trypanosomiasis, chagas disease, leishmaniasis, and malaria, respectively. some of the compounds showed anti-parasitic activity. in particular, a number of compounds appeared to very potently inhibit the growth of the blood stream form t. b. rhodesiense, ...200617004723
evaluation of a glycerol-preserved antigen in the direct agglutination test for diagnosis of visceral leishmaniasis at rural level in eastern sudan.three-hundred and eight patients with suspected visceral leishmaniasis (vl) were received at doka hospital (eastern sudan) during the period september 2004 to october 2005. the sensitivity and specificity of a glycerol-preserved (gp) antigen for vl diagnosis was assessed against the results of repeated lymph node aspiration and readings from a direct agglutination test (dat) employing standard formaldehyde-fixed (ff) or freeze-dried (fd) antigen. despite 13 months of storage at ambient temperatu ...200617005782
functional characterization of nucleoside transporter gene replacements in leishmania donovani.leishmania donovani express two nucleoside transporters of non-overlapping ligand selectivity. to evaluate the physiological role of nucleoside transporters in l. donovani, homozygous null mutants of the genes encoding the ldnt1 adenosine-pyrimidine nucleoside transporter and the ldnt2 inosine-guanosine transporter were created singly and in combination by single targeted gene replacement followed by selection for loss-of-heterozygosity. the mutant alleles were verified by southern blotting, and ...200617050001
'leishman' topoisomerase i: an ideal chimera for unraveling the role of the small subunit of unusual bi-subunit topoisomerase i from leishmania donovani.the active site tyrosine residue of all monomeric type ib topoisomerases resides in the c-terminal domain of the enzyme. leishmania donovani, possesses unusual heterodimeric type ib topoisomerase. the small subunit harbors the catalytic tyrosine within the skxxy motif. to explore the functional relationship between the two subunits, we have replaced the small subunit of l.donovani topoisomerase i with a c-terminal fragment of human topoisomerase i (htop14). the purified ldtop1l (large subunit of ...200617098934
studies on the cpa cysteine peptidase in the leishmania infantum genome strain jpcm5.visceral leishmaniasis caused by members of the leishmania donovani complex is often fatal in the absence of treatment. research has been hampered by the lack of good laboratory models and tools for genetic manipulation. in this study, we have characterised a l. infantum line (jpcm5) that was isolated from a naturally infected dog and then cloned. we found that jpcm5 has attributes that make it an excellent laboratory model; different stages of the parasite life cycle can be studied in vitro, it ...200617101050
species-specific pcr assay for l. infantum/l. donovani discrimination.leishmania infantum and leishmania donovani both pertain to the l. (l.) donovani complex. the status of certain strains is questioned in the literature and there are no reliable discriminative markers to identify them. molecular tools are needed to (i) identify diagnostic markers and (ii) to allow a better understanding of phylogenetic relationships. we have developed a pcr based on cysteine protease b (cpb). this pcr discriminates between l. infantum and l. donovani with 50-100pg of dna. these ...200617141723
transfusion medicine illustrated. electron micrographic study of the removal of leishmania from blood products by leukodepletion filters. 200616533268
nucleotide-sugar transporters: structure, function and roles in vivo.the glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. a large proportion of these enzymes are located within the lumen of the golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. thus, nucleotide-sugars are translocated from the cytosol to the lumen of the golgi apparatus and endoplasmic reticulum by multiple spanning domain pr ...200616981043
inhibition of il-2 induced il-10 production as a principle of phase-specific immunotherapy.leishmania donovani, a protozoan parasite, inflicts a fatal disease, visceral leishmaniasis. the suppression of antileishmanial t cell responses that characterizes the disease was proposed to be due to deficiency of a t cell growth factor, il-2. we demonstrate that during the first week after l. donovani infection, il-2 induces il-10 that suppresses the host-protective functions of t cells 14 days after infection. the observed suppression is concurrent with increased cd4+ glucocorticoid-induced ...200616982902
synthesis of oxysterols and nitrogenous sterols with antileishmanial and trypanocidal activities.two sterol families have been synthesized: the first one is nitrogenous sterols containing amino, n-hydroxyimino or cyano group and the second one is oxysterols such as ketosterol and hydroxysterols. these compounds were then evaluated in vitro against leishmania donovani promastigotes and trypanosoma brucei brucei trypomastigotes. the most active compounds against l. donovani promastigotes were 7beta-aminomethylcholesterol and 7alpha,beta-aminocholesterol (ic50 in a range from 1 to 3 microm, pe ...200616949702
phagocytosis of leishmania donovani amastigotes is rac1 dependent and occurs in the absence of nadph oxidase activation.macrophages produce little superoxide during phagocytosis of leishmania donovani amastigotes. in this study, we characterized molecular events associated with l. donovani amastigotes uptake by mouse macrophages, to further define the mechanisms by which they are internalized without triggering superoxide production. using transient transfections, we first showed that internalization of l. donovani amastigotes is mediated by the gtpases rac1 and arf6, of which rac1 is recruited and retained on pa ...200616955522
interaction between miltefosine and amphotericin b: consequences for their activities towards intestinal epithelial cells and leishmania donovani promastigotes in vitro.the aim of this study was to evaluate the potential of a combination of two antileishmanial drugs, miltefosine (hepc) and amphotericin b (amb), when administered by the oral route. caco-2 cell monolayers were used as a validated in vitro model of the intestinal barrier and leishmania donovani promastigotes as a model for evaluating the effect of the drug combination. spectroscopic measurements demonstrated that hepc and amb associate, leading to the formation of mixed aggregates in which amb is ...200616966395
the thiol-based redox networks of pathogens: unexploited targets in the search for new drugs.hydroperoxide metabolism in diverse pathogens is reviewed under consideration of involved enzymes as potential drug targets. the common denominator of the peroxidase systems of trypanosoma, leishmania, plasmodium, and mycobacterium species is the use of nad(p)h to reduce hydroperoxides including peroxynitrite via a flavin-containing disulfide reductase, a thioredoxin (trx)-related protein and a peroxidase that operates with thiol catalysis. in plasmodium falciparum, thioredoxin- and glutathione ...200617012768
lymph node cells from balb/c mice with chronic visceral leishmaniasis exhibiting cellular anergy and apoptosis: involvement of ser/thr phosphatase.visceral leishmaniasis (vl) produced in balb/c mice through intracardial administration of leishmania donovani amastigotes was accompanied by hepatosplenomegaly with high organ parasite load and lymphadenopathy when followed up to 4-months or so. to elucidate the mechanism of immunosuppression associated with vl, we report here progressive impairment of the proliferative response of lymph node cells (lymphocytes) from infected animals (i-lnc) to in vitro stimulation with the combination of phorb ...200617013755
evaluation of rk39 strip test for the diagnosis of visceral leishmaniasis in infants.this study estimated the sensitivity and specificity of the rk39 strip test compared with the immunofluorescent antibody test and microscopy of bone marrow aspirate smears (the gold standard) in 47 children with suspected visceral leishmaniasis. a control group of children with other diagnoses (tuberculosis, toxoplasmosis, systemic lupus erythematosus, malaria or cutaneous leishmaniasis) were also tested to check false positive results. the sensitivity and specificity of the strip test were 82.4 ...200617037697
topoisomerases of kinetoplastid parasites: why so fascinating?dna topoisomerases are the key enzymes involved in carrying out high precision dna transactions inside the cells. however, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the dna. the discovery of unusual heterodimeric topoisomerase i in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to ...200617042788
[visceral leishmaniasis with cardiac affectation in an immunocompetent patient]. 200617043012
modification at the c9 position of the marine natural product isoaaptamine and the impact on hiv-1, mycobacterial, and tumor cell activity.as part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the c9 position of isoaaptamine (2) isolated from the aaptos sponge. this library of new semisynthetic products was evaluated for biological activity against hiv-1, mtb, aids-oi, tropical parasitic diseases, and cancer. compound 4 showed potent activity against hiv- ...200617045480
testosterone attenuates p38 mapk pathway during leishmania donovani infection of macrophages.leishmania donovani (l. donovani) is an obligatory intracellular pathogen that resides and multiplies in the macrophages and has been found to alter the signaling parameters of the host. testosterone plays a key role as signaling molecules in the regulation of parasite infections and could increase l. donovani infection of macrophages. the mitogen-activated protein kinases (mapks) pathway participates in the regulation of functions involved in parasite infection and host defense. in this work, t ...200616547729
visceral leishmania donovani infection in interleukin-13-/- mice.leishmania donovani-infected interleukin-13-/- balb/c mice showed impaired initial gamma interferon secretion and incomplete granuloma assembly at parasitized liver foci. nonetheless, control of early parasite replication, resolution of liver infection, and responsiveness to antileishmanial chemotherapy were intact. by itself, interleukin-13 does not appear to materially influence acquired resistance in this intracellular infection.200616552085
a novel high-affinity arginine transporter from the human parasitic protozoan leishmania donovani.we describe the first functional and molecular characterization of an amino acid permease (ldaap3) from the human parasitic protozoan leishmania donovani, the causative agent of visceral leishmaniasis in humans. this permease contains 480 amino acids with 11 predicted trans-membrane domains. expressing ldaap3 in saccharomyces cerevisiae mutants revealed that ldaap3 codes for a high-affinity arginine transporter (km 1.9 microm). ldaap3 is highly specific for arginine as its transport was not inhi ...200616556218
acylated and deacylated saponins of quillaja saponaria mixture as adjuvants for the fml-vaccine against visceral leishmaniasis.the adjuvant of the fml-vaccine against murine and canine visceral leishmaniasis, the riedel de haen saponin mixture, was fractionated by ion exchange chromatography on deae-cellulose to afford one tlc homogeneous quillaja saponaria molina qs21 saponin fraction (18.0%), a mixture of two deacylsaponins (19.4%), sucrose (39.9%), sucrose and glucose (19.7%), rutin (0.8%) and quercetin (2.2%), that were identified by comparison of 1h and 13c nmr spectroscopy. the qs21 shows the typical aldehyde grou ...200616556475
effect of natural l- to d-amino acid conversion on the organization, membrane binding, and biological function of the antimicrobial peptides bombinins h.antimicrobial peptides (amps) are evolutionarily old components of innate immunity found in all living pluricellular organisms. interestingly, some organisms express families of amps with only a slight variation among their members, possibly to increase their spectrum of activity. despite the growing body of knowledge about their biological activity and mode of action on bacteria, only a few of them have been tested on leishmania, a worldwide spread protozoan pathogen, and the parameters contrib ...200616566601
antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies.trypanosomiasis and leishmaniasis are important parasitic diseases affecting millions of people in africa, asia, and south america. in a previous study, we identified several flavonoid glycosides as antiprotozoal principles from a turkish plant. here we surveyed a large set of flavonoid aglycones and glycosides, as well as a panel of other related compounds of phenolic and phenylpropanoid nature, for their in vitro activities against trypanosoma brucei rhodesiense, trypanosoma cruzi, and leishma ...200616569852
treatment options for visceral leishmaniasis.this review summarizes the current developments in therapy for visceral leishmaniasis. with the recent introduction of new drugs, the main limits in reducing deaths from visceral leishmaniasis are difficulty in diagnosis in the field and health inequality--patients lack of access to treatment. no new drugs are currently in the early stages of development. there are good reasons for the use of combination therapy; to prevent further development of resistance against the limited therapeutic option ...200616597201
leishmania donovani singly deficient in hgprt, aprt or xprt are viable in vitro and within mammalian macrophages.leishmania species express three phosphoribosyltransferase enzymes, hypoxanthine-guanine phosphoribosyltransferase (hgprt), adenine phosphoribosyltransferase (aprt), and xanthine phosphoribosyltransferase (xprt), which enable this genus to acquire purine nutrients from their hosts. to test whether any of these enzymes is essential for viability, transformation into amastigotes, and infectivity and proliferation within mammalian macrophages, deltahgprt, deltaaprt, and deltaxprt null mutants were ...200616597468
upregulation of surface proteins in leishmania donovani isolated from patients of post kala-azar dermal leishmaniasis.five to fifteen percent of visceral leishmaniasis (vl) patients in india develop post kala-azar dermal leishmaniasis (pkdl), usually 1-2 years after apparent clinical cure. there is evidence pointing to a role played by the host immune responses in the disease pathogenesis, however, the contribution of changes in parasite gene expression has not been explored. highly sensitive gene expression microarray technology was employed to identify genes that are differentially expressed in leishmania par ...200616469521
leishmania tropica-isolated patient with visceral leishmaniasis in southern iran.visceral leishmaniasis (vl) is caused by various strains of leishmania donovani, leishmania infantum, and leishmania chagasi with different geographical distribution. the aim of this study was to identify the strains of leishmania that can cause vl in southern iran. dna of leishmania were extracted from the slides of bone marrow aspirates (#42) and spleen punctures (#22), which were positive for leishman body from the patients who were referred to the hospitals affiliated with shiraz university ...200616474088
spatial clustering and epidemiological aspects of visceral leishmaniasis in two endemic villages, baringo district, kenya.visceral leishmaniasis (vl) seroprevalence in kenya is unknown because of the lack of a practical and accurate diagnostic test or surveillance system. a novel serological assay was used to estimate the seroprevalence of leishmania-specific antibodies, and global information system and spatial clustering techniques were applied to study the presence of spatial clusters in parkarin and loboi villages in baringo district in 2001. vl seroprevalences were 52.5% in parkarin and 16.9% in loboi. signifi ...200616474089
hfip-induced structures and assemblies of the peptides from the transmembrane domain 4 of membrane protein nramp1.membrane protein nramp1 (natural resistance-associated macrophage protein 1) is a ph-dependent divalent metal cation transporter that regulates macrophage activation in infectious and autoimmune diseases. a naturally occurring glycine to aspartic acid substitution at position 169 (g169d) within the transmembrane domain 4 (tm4) of nramp1 makes mice susceptible to leishmania donovani, salmonella typhimurium, and mycobacterium bovis. here we present a structural and self-assembling study on two syn ...200616479587
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