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in vitro antiprotozoal activities and cytotoxicity of some selected cameroonian medicinal plants.eight extracts from seven selected cameroonian medicinal plants, traditionally used to treat malaria and other protozoal diseases, were tested in vitro for their antiprotozoal activities against plasmodium falciparum k1 chloroquine-resistant strain, leishmania donovani, trypanosoma cruzi and trypanosoma brucei rhodesiense, protozoa responsible for malaria, visceral leishmaniasis, chagas disease and african trypanosomiasis, respectively. the most active extract against plasmodium falciparum k1 st ...200717141994
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
synthesis and evaluation of isosteres of n-methyl indolo[3,2-b]-quinoline (cryptolepine) as new antiinfective agents.isosteres of cryptolepine (1) were synthesized and evaluated for their antiinfective activities. overall, the sulfur isostere, 5-methyl benzothieno[3,2-b]quinolinium salt (5b), was equipotent to 1 and has shown no cytotoxicity at 23.8 microg/ml. compound 5b was also found to have a broad spectrum of activity. both the carbon and oxygen isosteres were less potent than cryptolepine. a limited library of 2-substituted analogs of 5b has been synthesized and evaluated in antifungal screens but did no ...200717134906
specific cpb copies within the leishmania donovani complex: evolutionary interpretations and potential clinical implications in humans.leishmania infantum and leishmania donovani both pertain to the l. (l.) donovani complex and are responsible for visceral leishmaniasis. to explore the l. donovani complex, we focused our study on cysteine protease b (cpb) and especially on 2 cpb copies: cpbe and cpbf. we selected cpb genes because of their phylogenetic interest and host-parasite interaction involvement. sequencing these 2 copies revealed (i) that cpbe is specific to l. infantum and cpbf is specific to l. donovani and (ii) that ...200717129395
leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.a number of anticancer and antiparasitic drugs are postulated to target the polyamine biosynthetic pathway and polyamine function, but the exact mode of action of these compounds is still being elucidated. to establish whether polyamine analogs specifically target enzymes of the polyamine pathway, a model was developed using strains of the protozoan parasite leishmania donovani that overproduce each of the polyamine biosynthetic enzymes. promastigotes overexpressing episomal constructs encoding ...200717116678
identification of the benzodiazepines as a new class of antileishmanial agent.the continual increase in drug resistance; the lack of new chemotherapeutic agents; the toxicity of existing agents and the increasing morbidity with hiv co-infection mean the search for new antileishmanial agents has never been more urgent. we have identified the benzodiazepines as a structural class for antileishmanial hit optimisation, and demonstrated that their in vitro activity is comparable with the clinically used drug, sodium stibogluconate, and that the compounds are not toxic to macro ...200717113290
antileishmanial effect of 3-aminooxy-1-aminopropane is due to polyamine depletion.the polyamines putrescine, spermidine, and spermine are organic cations that are required for cell growth and differentiation. ornithine decarboxylase (odc), the first and rate-limiting enzyme in the polyamine biosynthetic pathway, catalyzes the conversion of ornithine to putrescine. as the polyamine biosynthetic pathway is essential for the growth and survival of leishmania donovani, the causative agent of visceral leishmaniasis, inhibition of the pathway is an important leishmaniacidal strateg ...200717101681
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
'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
bioinformatic identification of tandem repeat antigens of the leishmania donovani complex.with large amounts of parasite gene sequence available, additional bioinformatic tools to screen these sequences for identifying genes encoding antigens are needed. proteins containing tandem repeat (tr) domains are often b-cell antigens, and antibody responses toward tr domains of the proteins are dominant in human infected with certain parasites. we hypothesized that antigens of serological significance could be identified with a search for tr domains. here we show the result of bioinformatic ...200717088350
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
synthesis, antimalarial, antileishmanial, antimicrobial, cytotoxicity, and methemoglobin (methb) formation activities of new 8-quinolinamines.we report the synthesis, in vitro antiprotozoal (against plasmodium and leishmania), antimicrobial, cytotoxicity (vero and methb-producing properties), and in vivo antimalarial activities of two series of 8-quinolinamines. n1-{4-[2-(tert-butyl)-6-methoxy-8-quinolylamino]pentyl}-(2s/2r)-2-aminosubstitutedamides (21-33) and n1-[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-(2s/2r)-2-aminosubstitutedamides (51-63) were synthesized in six steps from 6-methoxy-8-nitroquinoline and 4-methox ...200717084633
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
congenital visceral leishmaniasis. 200617080586
antiprotozoal and antimicrobial activities of o-alkylated and formylated acylphloroglucinols.in the present article, we examined the antileishmanial, antimalarial, antibacterial, and antifungal activities of several newly synthesized o-alkylated phloroglucinol compounds (11-19) which are analogues of the naturally occurring antimalarial compound 1. analogues 12 and 16 exhibited antileishmanial activity against, leishmania donovani promastigotes with ic(50)s of 5.3 and 4.2microg/ml, respectively. naturally occurring monomeric formylated acylphloroglucinol compounds, grandinol (2), jensen ...200717070063
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
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
a proteomics screen implicates hsp83 and a small kinetoplastid calpain-related protein in drug resistance in leishmania donovani clinical field isolates by modulating drug-induced programmed cell death.the therapeutic mainstay against the protozoan parasite leishmania is still based on the antiquated pentavalent antimonials (sb(v)), but resistance is increasing in several parts of the world. resistance is now partly understood in laboratory isolates, but our understanding of resistance in field isolates is lagging behind. we describe here a comparative analysis of a genetically related pair of sb(v)-sensitive and -resistant leishmania donovani strains isolated from kala-azar patients. the resi ...200717050524
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
translation of open reading frame in kinetoplast dna minicircles of clinical isolates of l. donovani.till today, it remains an enigma whether the open reading frames said to be transcribed in minicircle sequences are indeed translated into protein products or not. we establish a protein-coding gene in minicircle variable region of kinetoplast dna from clinical isolates of leishmania donovani. the protein was expressed as an n-tagged green fluorescent protein (gfp) fusion protein in leishmanial expression system. fluorescence microscopy of the transfectants carrying recombinant gfp construct sho ...200717047999
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
[visceral leishmaniasis with cardiac affectation in an immunocompetent patient]. 200617043012
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
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
the leishmania donovani complex: genotypes of five metabolic enzymes (icd, me, mpi, g6pdh, and fh), new targets for multilocus sequence typing.flagellates of the leishmania donovani complex are causative agents of human cutaneous and visceral leishmaniasis. the complex is comprised of l. donovani, leishmania infantum and leishmania archibaldi, although the latter is not now considered to be a valid species. morphological distinction of leishmania species is impractical, so biochemical, immunological and dna-based criteria were introduced. multilocus enzyme electrophoresis (mlee) is the present gold standard. we have sequenced the genes ...200717027989
leishmania donovani: dyskinetoplastid cells survive and proliferate in the presence of pyruvate and uridine but do not undergo apoptosis after treatment with camptothecin.we have shown that treatment with luteolin in leishmanial cells causes loss of mt-dna and induces apoptosis through mitochondria dependent pathway [sen, n., das, b.b., ganguly, a., banerjee, b., sen, t., majumder, h.k., 2006. leishmania donovani: intracellular atp level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells. experimental parasitology, in press]. here, we report that mitochondrial dna depleted leishmanial cells require exogenous sources of pyruvate and uridine ...200717027973
genetic heterogeneity among visceral and post-kala-azar dermal leishmaniasis strains from eastern india.in india and sudan, some patients of visceral leishmaniasis develop post-kala-azar dermal leishmaniasis (pkdl) while majority will not. similarly, the clinical manifestations and treatment outcome are reported to vary from district to district and state to state in india. present study is focused on to find out the genetic variations between vl & pkdl causing strains. nuclear dna from 24 strains of leishmania donovani, isolated from patients of visceral leishmaniasis (18) and pkdl (6) was extrac ...200717027344
assessment of the monoterpene, glycidic and triterpene-moieties' contributions to the adjuvant function of the cp05 saponin of calliandra pulcherrima benth during vaccination against experimental visceral leishmaniasis.the cp05 saponin from calliandra pulcherrima benth, shows remarkable similarities to the qs21 saponin of quillaja saponaria molina. both shared a monoterpene hydrophobic moiety, a glycidic chain attached to the triterpene c28, and three sugars attached to c3. different from qs21, the cp05 does not show the aldehyde group in triterpene c4 involved in th1 response. balb/c mice were immunized either intact saponin (cp05), the monoterpene-deprived (bs), the c28 carbohydrate-deprived (hs) or the sapo ...200717014936
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
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
epidemiological dynamics of antimonial resistance in leishmania donovani: genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from nepal.pentavalent antimonials (sbv) are the first line drug against leishmaniasis worldwide, but drug resistance is increasingly reported, particularly in the indian sub-continent, where it represents a major threat for the control of anthroponotic visceral leishmaniasis (vl). in order to understand the epidemiological dynamics of antimonial resistance in anthroponotic vl, we analysed here the population structure of 24 leishmania donovani stocks isolated from anthroponotic vl-patients from eastern ne ...200717010679
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
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
the ugi reaction in the generation of new nucleosides as potential antiviral and antileishmanial agents.5-formyl-2'-deoxyuridine-3',5'-diacetate was converted to a small library of 5-substituted pyrimidine nucleoside n-acylamino acid amides by means of a ugi multicomponent reaction. the reaction allowed introduction of various substituents at the acyl moiety, at the amino acid alpha-amide group, and at the amino acid carboxyl function. evaluation of these novel 5-substituted nucleosides against vaccinia virus and cowpox virus provided one compound with discernable activity against cowpox virus but ...200716996561
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
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
spatial analysis of american visceral leishmaniasis in mato grosso do sul state, central brazil.to map american visceral leishmaniasis (avl) in mato grosso do sul state (central brazil).200716979241
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
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
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
interaction of sitamaquine with membrane lipids of leishmania donovani promastigotes.sitamaquine is an 8-aminoquinoline which is active by the oral route for the treatment of life-threatening visceral leishmaniasis caused by leishmania donovani, with an ic50 of 29.2 microm against the promastigote form in vitro. at high concentration (100 microm), sitamaquine affected parasite motility, morphology and growth in a way that was only partially reversible. as a first approach to determine its mechanism of action, we describe the interaction of sitamaquine with parasite membrane comp ...200716945323
the schistosoma mansoni hepatic egg granuloma provides a favorable microenvironment for sustained growth of leishmania donovani.parasitic co-infections are prevalent in many parts of the world. however, relatively little is known about how an underlying infection may impact on the host's ability to control a newly acquired parasite, especially if both infect the same organ. we have studied this using an experimental co-infection model in c57bl/6 mice involving schistosoma mansoni and leishmania donovani, two important human pathogens affecting the liver. we show that mice with established s. mansoni infections fail to co ...200616936268
single-step duplex kdna-pcr for detection of leishmania donovani complex in human peripheral blood samples.a duplex polymerase chain reaction (pcr) assay was performed using a sense leishmania genus-specific oligonucleotides to amplify the conserved region of 120 bp of minicircle kdna and an additional antisense leishmania donovani oligonucleotide that amplifies a complex-specific fragment of 90 bp. all 12 tested reference isolates of the l. donovani complex yielded a complex-specific amplification product of 90 bp concurrently with a genus-specific 120-bp product. all 17 tested reference isolates pe ...200616935456
[visceral leishmaniasis--surgical aspects].visceral leishmaniasis is a multi-organic parasitic disease caused by an intracellular protozoon named leishmania donovani; the mean signs are: weight loss, cough, fever, hepatosplenomegaly, adenopathy and cutaneous lesions; death without treatment is the rule. the main treatment is a conservative one. surgical treatment is necessary for complications, especially for those intra-abdominally. we wish to present a young female patient who underwent two subsequent interventions due to an unclear di ...200616927925
[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).200616924841
beta-mercaptoethanol-modified elisa for diagnosis of visceral leishmaniasis.following antigen preparation procedures similar to those of the direct agglutination test (dat), an igg elisa employing intact beta-mercaptoethanol (beta-me)-treated leishmania donovani promastigotes was developed. the performance of the beta-me elisa thus developed was assessed in patients with confirmed visceral leishmaniasis (vl), revealing slightly lower sensitivity (39/40=97.5%) than that of the dat (40/40=100%). when challenged with sera of individuals with non-vl conditions, including le ...200616914648
transfusion transmitted leishmaniasis: a case report and review of literature.leishmaniasis is caused by the infection of haemoparasite leishmania . the disease is a major public health problem in at least 88 countries, including india. various species of leishmania are involved in causing this disease. in india, leishmania donovani species causes visceral leishmaniasis or kala-azar. the parasite is mainly transmitted from infected to uninfected person through the bites of female sandfly. rarely the parasite can transmit through placenta from mother to child, through sexu ...200616912434
photoinactivation of leishmania donovani infantum in red cell suspensions by a flexible thiopyrylium sensitizer.leishmaniasis is a disease caused by protozoan parasites of the genus leishmania, which are intracellular parasites of monocytes and macrophages. transmission of the organism has been observed by transfusion of infected blood from asymptomatic donors to immunocompromised recipients, leading to clinically apparent disease. there is no licensed leishmania screening test currently available.200616907880
antiprotozoal and cytotoxic naphthalene derivatives from diospyros assimilis.chemical investigation of the roots of diospyros assimilis had led to the isolation and characterization of six naphthalene derivatives, two 2-naphthaldehyes, namely 4-hydroxy-3,5-dimethoxy-2-naphthaldehyde 1, 4-hydroxy-5-methoxy-2-naphthaldehye 2, its related isomer 5-hydroxy-4-methoxy-2-naphthaldehyde 3 and three commonly occurring naphthoquinones, diospyrin 4, 8'-hydroxyisodiospyrin 5 and the simple monomer, plumbagin 6. their chemical structures were established by detailed nmr investigation ...200616890968
antileishmanial activity of natural diterpenes from cistus sp. and semisynthetic derivatives thereof.eleven cis-clerodane diterpenes, seven labdane type diterpenes and one triterpene isolated from cistus monspeliensis and the resin "ladano" of cistus creticus subsp. creticus were evaluated against leishmania donovani promastigotes, the causative agent for visceral leishmaniasis. in addition, eleven semisynthetic manoyl oxide, seventeen labdane type derivatives and a triterpene were also evaluated for their antileishmanial activity. 18-acetoxy-cis-clerod-3-en-15-ol, 15,18-diacetoxy-cis-clerod-3- ...200616880643
structurally diverse 5-substituted pyrimidine nucleosides as inhibitors of leishmania donovani promastigotes in vitro.the following structurally diverse 5-substituted-2'-deoxyuridine nucleosides displayed potent in vitro antileishmanial activity: 5-formyl, 5-(2,2,-dicyanovinyl)-, 5-(2-cyano-2-ethoxycarbonylvinyl), 5-(2-cyano-2-methoxycarbonylvinyl)-, 5-(2-amino-3-cyano-5-oxo-5,6,7,8-tetrahydro-4h-chromen-4-yl)- and related congeners, and the 5-(3-methyl-5-oxo-1-phenyl-4,5-dihydro-4h-pyrazol-4-ylidene) group.200616879965
endogenous interleukin-18 is involved in immunity to leishmania donovani but its absence does not adversely influence the therapeutic activity of sodium stibogluconate.immunity to leishmania donovani is associated with an interleukin (il)-12 driven t helper 1 (th1) response. in addition, the ability to respond to chemotherapy with sodium stibogluconate (ssg) requires a fully competent immune response and both th1 and th2 responses have been shown to positively influence the outcome of drug treatment. in the present study, the influence of il-18, which can modulate both interferon (ifn)-gamma and il-4 production, on the outcome of primary l. donovani infection ...200616879623
anti-plasmodial and anti-leishmanial activity of conformationally restricted pentamidine congeners.a library of 52 pentamidine congeners in which the flexible pentyldioxy linker in pentamidine was replaced with various restricted linkers was tested for in-vitro activity against two plasmodium falciparum strains and leishmania donovani. the tested compounds were generally more effective against p. falciparum than l. donovani. the most active compounds against the chloroquine-sensitive (d6, sierra leone) and -resistant (w2, indochina) strains of p. falciparum were bisbenzamidines linked with a ...200616872549
manzamine b and e and ircinal a related alkaloids from an indonesian acanthostrongylophora sponge and their activity against infectious, tropical parasitic, and alzheimer's diseases.four new manzamine-type alkaloids, 12,28-oxamanzamine e (2), 12,34-oxa-6-hydroxymanzamine e (3), 8-hydroxymanzamine b (5), and 12,28-oxaircinal a (11), were isolated from three collections of an indonesian sponge of the genus acanthostrongylophora together with 13 known manzamine alkaloids, ircinal a, ircinol a, xestomanzamine a, manzamines a, e, f, j, and y, manadomanzamines a and b, neo-kauluamine, 8-hydroxymanzamine a, and manzamine a n-oxide. the structures of the new compounds were elucidat ...200616872140
synthesis of 16-mercaptohexadecylphosphocholine, a miltefosine analog with leishmanicidal activity.the alkylphosphocholine miltefosine (n-hexadecylphosphocholine, mt) has been introduced recently as a very effective drug for the oral treatment of human leishmaniasis. however, the parasiticidal mechanism of mt at a molecular level is far from being understood. here we report the synthesis and biological characterization of 16-mercaptohexadecylphosphocholine, a thiol analog of mt which was designed to facilitate the search of mt interacting targets within the parasite by a variety of analytical ...200616870434
leishmania donovani lipophosphoglycan blocks nadph oxidase assembly at the phagosome membrane.phagocytosis of leishmania donovani promastigotes is characterized by an inhibition of phagolysosome biogenesis mediated by the surface glycolipid lipophosphoglycan (lpg). however, the consequences of this inhibition on macrophage function remain to be determined. in this study, we investigated the impact of lpg-mediated phagosome remodelling on the assembly and function of the nadph oxidase complex. phagocytosis of both wild-type and lpg-defective l. donovani promastigotes triggered the release ...200616848789
apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin a and is facilitated by apoptotic topoisomerase i-dna complex.protein kinase c (pkc) is an important constituent of the signaling pathways involved in apoptosis. we report here that like staurosporine, withaferin a is a potent inhibitor of pkc. in leishmania donovani, the inhibition of pkc by withaferin a causes depolarization of deltapsim and generates ros inside cells. loss of deltapsim leads to the release of cytochrome c into the cytosol and subsequently activates caspase-like proteases and oligonucleosomal dna cleavage. moreover, in treated cells, oxi ...200716841091
visceral leishmaniasis, or kala azar (ka): high incidence of refractoriness to antimony is contributed by anthroponotic transmission via post-ka dermal leishmaniasis.individuals with visceral leishmaniasis, or kala azar (ka) and individuals with post-ka dermal leishmaniasis (pkdl) are considered to be reservoirs of transmission of leishmania donovani in india. when intracellular amastigotes were used to assess the natural susceptibility that pkdl isolates and ka isolates have to sodium antimony gluconate (sag), the mean ed(50) was found to be 12.0+/-2.49 and 11.0+/-1.38 microg/ml, respectively; and there was a significant correlation with the clinical respon ...200616826477
leishmania donovani infection of human myeloid dendritic cells leads to a th1 response in cd4+ t cells from healthy donors and patients with kala-azar.the role played by dendritic cells (dcs) in leishmania donovani infection is poorly understood. here, we report that l. donovani amastigotes efficiently infect human peripheral-blood monocyte-derived dcs. opsonization with normal human serum enhanced the infectivity of amastigotes and promastigotes only marginally. surface attachment versus internalization was distinguished by incubation of dcs with live, fluorescein isothiocyanate-labeled parasites, followed by quenching with crystal violet. in ...200616826476
activity of and initial mechanistic studies on a novel antileishmanial agent identified through in silico pharmacophore development and database searching.a 3d pharmacophore was generated to describe the antileishmanial activity of dinitroaniline sulfonamides by catalyst 3d-qsar methodology, and this pharmacophore was used to search the maybridge database. two compounds identified in this search, btb 06237 and btb 06256, were highly active with ic(50) values against l. donovani amastigotes of 0.5 +/- 0.2 and 2.3 +/- 0.8 microm, respectively. btb 06237 also reduced parasite burdens in l. mexicana-infected j774 macrophages at low micromolar concentr ...200616821779
selective targeting of indel-inferred differences in spatial structures of homologous proteins.the eukaryotic pathogen leishmania donovani possesses a housekeeping protein elongation-factor-1alpha (ef-1alpha) which has been found to be unexpectedly involved in the pathogen's virulence. because it is associated with virulence and essential for cell survival, this protein is an attractive choice for drug targeting; however, its sequence is highly similar (> 80% sequence identity) to that of its human homolog, rendering it a risky choice for a drug target. the chief difference between these ...200616819791
leishmania histone h1 overexpression delays parasite cell-cycle progression, parasite differentiation and reduces leishmania infectivity in vivo.episomal expression of leishmania histone h1 sense mrnas in leishmania major promastigotes was found previously to result in overexpression of this molecule and to reduce parasite infectivity in vitro. herein, we evaluated the in vivo infectivity of these transfectants, in balb/c mice, and showed that it is dramatically reduced. no lesions were observed in this group of mice and this was associated with an extremely low number of parasites both in the footpad and in the draining lymph nodes. int ...200616796681
distinct roles for il-6 and il-12p40 in mediating protection against leishmania donovani and the expansion of il-10+ cd4+ t cells.adoptive dendritic cell (dc) immunotherapy provides a useful experimental tool to evaluate immunoregulation in vivo and has previously been successfully used to enhance host resistance in a variety of experimental models of leishmaniasis. here, we used this approach to identify il-6 and il-12p40 as critical cytokines that cooperate to mediate host protection to leishmania donovani but which act independently to regulate expansion of il-10(+) cd4(+) t cells, shown here for the first time to be as ...200616791879
responses to leishmania donovani in mice deficient in interleukin-12 (il-12), il-12/il-23, or il-18.interleukin-12 (il-12) orchestrates acquired resistance in intracellular leishmania donovani infection in the liver, inducing gamma interferon and, in turn, macrophage activation and parasite killing. nevertheless, testing in il-18(-/-) mice compared to wild-type mice and in il-12p40(-/-) compared to il-12p35(-/-) mice also suggested both early-acting (il-18) and late-acting (il-23) antileishmanial effects independent of il-12.200616790814
cutting edge: stat1 and t-bet play distinct roles in determining outcome of visceral leishmaniasis caused by leishmania donovani.t-bet and stat1 regulate ifn-gamma gene transcription in cd4+ t cells, which mediate protection against leishmania. here we show that t-bet and stat1 are required for the induction of an efficient th1 response during leishmania donovani infection, but they play distinct roles in determining disease outcome. both stat1(-/-) and t-bet(-/-) mice failed to mount a th1 response, but stat1(-/-) mice were highly resistant to l. donovani and developed less immunopathology, whereas t-bet(-/-) mice were h ...200616785492
phospholipid translocation and miltefosine potency require both l. donovani miltefosine transporter and the new protein ldros3 in leishmania parasites.the antitumor drug miltefosine has been recently approved as the first oral drug active against visceral leishmaniasis. we have previously identified the l. donovani miltefosine transporter (ldmt) as a p-type atpase involved in phospholipid translocation at the plasma membrane of leishmania parasites. here we show that this protein is essential but not sufficient for the phospholipid translocation activity and, thus, for the potency of the drug. based on recent findings in yeast, we have identif ...200616785229
drug resistance mechanisms in clinical isolates of leishmania donovani.leishmania are protozoan parasites distributed worldwide. about 1.5-2.0 million cases are reported in the world annually from this disease and the death toll is estimated to be 57,000. along with brazil, sudan and bangladesh, india contributes to 90 per cent of the global burden of visceral leishmaniasis (vl). the absence of effective vaccines and vector control programmes, makes chemotherapy the most widely used tool against leishmaniasis. chemotherapy based on pentavalent antimonials has been ...200616778320
drug unresponsiveness & combination therapy for kala-azar.pentavalent antimonials (sbv) have been successfully used for treatment of kala-azar since last six decades. since 1970s its conventional dosages have failed to achieve with 60 per cent unresponsiveness reported with who regimen in bihar (india). pentamidine initially used as a second line of drug, acquired resistance (25%) even with prolonged dosage. newer oral drug miltefosine is a potent antileishmanial drug with longer half-life, a property likely to acquire resistance. paromomycin has under ...200616778318
childhood visceral leishmaniasis.visceral leishmaniasis (vl) is caused by the protozoan parasite leishmania donovani and transmitted by the bite of infected sandfly phlebotomus argentipes. nearly half of the vl cases occur in children (childhood or paediatric vl). the clinical manifestations of childhood vl are more or less same as in the adults. prolonged fever with anorexia and loss of appetite are the major presenting features. marked enlargement of the spleen and liver (spleen larger than liver) with moderate to severe anae ...200616778316
visceral leishmaniasis (kala-azar): challenges ahead.indian visceral leishmaniasis (vl) is a parasitic disease caused by a haemoflagellete leishmania donovani and transmitted by the bite of sand fly phlebotomus argentipes. it affects various age groups. in india about 1,00,000 cases of vl are estimated to occur annually; of these, the state of bihar accounts for over than 90 per cent of the cases. diagnosis of vl typically relies on microscopic examination of tissue smears but serology and molecular methods are better alternatives currently. notwi ...200616778314
challenges in the diagnosis of post kala-azar dermal leishmaniasis.post kala-azar dermal leishmaniasis (pkdl) is a dermatosis that occurs as a sequel of visceral leishmaniasis (vl). elimination of vl requires detection and treatment of pkdl, necessarily because of its capacity to serve as a reservoir for the causative parasite, leishmania donovani. diagnosis of pkdl presents a challenge due to low parasite burden in the lesions. in this article we have reviewed the recent advances in the development of immunological and molecular methods for diagnosis of pkdl.200616778312
visceral leishmaniasis in the new world & africa.visceral leishmaniasis in the new world, primarily found in northeastern brazil, is caused by leishmania chagasi. compared to india, unusual features of brazilian disease are the large number of asymptomatic infections versus symptomatic infections, and the apparent change from a zoonotic disease to a partially anthroponotic one. visceral disease in africa is caused by l. donovani as in india, but disease differs from that in india in being zoonotic rather than anthroponotic, and in the large nu ...200616778311
topoisomerase research of kinetoplastid parasite leishmania, with special reference to development of therapeutics.protozoan parasites of the order kinetoplastida cause severe diseases primarily in the tropical and subtropical areas. the enormous development of molecular and cellular biology in recent times have provided opportunities for discovering newer molecular targets for drug designing, which now form a rational basis for the development of improved anti-parasitic therapy. dna topoisomerases play a key role in cellular processes affecting the topology and organization of intracellular dna. recently, e ...200616778306
glycobiology of leishmania donovani.leishmania donovani, the causative organism of visceral leishmaniasis (vl) is one of the deadliest of the entire known leishmania species. this protozoan parasite displays immense adaptability to survive under extremely harsh conditions. cell surface glycoconjugates play a pivotal role in parasite virulence and infectivity. this review mainly highlights on the importance of these molecules and their reported roles with special emphasis on l. donovani sialobiology. the recently evolved informatio ...200616778305
critical evaluation of the therapeutic potential of bassic acid incorporated in oil-in-water microemulsions and poly-d,l-lactide nanoparticles against experimental leishmaniasis.bassic acid, an unsaturated triterpene acid isolated from mimusops elangii, was tested for its antileishmanial properties both in vitro and in vivo. the in vitro antileishmanial activity of bassic acid being encouraging, its activity in vivo was evaluated in hamster models of visceral leishmaniasis, both in free form, as well as incorporated in two different delivery systems, viz microemulsions and polylactide nanoparticles. the delivery systems were prepared by published protocols. the percenta ...200616777677
comprehensive examination of charged intramembrane residues in a nucleoside transporter.permeases of the equilibrative nucleoside transporter family mediate the uptake of nucleosides and/or nucleobases in a diverse array of eukaryotes and transport a host of drugs used for treatment of cancer, heart disease, aids, and parasitic infections. to identify residues that play central roles in transport function, we have systematically substituted by site-directed mutagenesis all the charged residues located within predicted transmembrane domains of the leishmania donovani nucleoside tran ...200616769726
leishmania in sle mimicking an exacerbation.systemic lupus erythematosus is a protean disease which may present manifestations that resemble other diseases posing serious problems of differential diagnosis. visceral leishmaniasis is a parasitic infection, endemic in 88 countries, whose hallmarks may mimic a lupus flare. fever, pancytopenia, splenomegaly, hypergammaglobulinemia, production of autoantibodies and complement consumption are some of the overlapping features between the two diseases. thus, extra attention must be paid to patien ...200616762157
responses to leishmania donovani in mice deficient in both phagocyte oxidase and inducible nitric oxide synthase.mice deficient in phagocyte oxidase (phox) and inducible nitric oxide synthase (inos), which are primary macrophage killing mechanisms, generated tissue granulomas but showed unrestrained leishmania donovani visceral replication and suboptimal initial responsiveness to antimony treatment. nevertheless, visceral infection was controlled post-treatment and did not recur. a phox/inos-independent macrophage mechanism, which was not triggered by l. donovani, emerges after chemotherapy.200616760512
rab5b localization to early endosomes in the protozoan human pathogen leishmania donovani.leishmania donovani is a primitive trypanosomatid pathogen of humans. this protozoan is apically polarized such that the flagellar reservoir, the exclusive site of endocytosis and exocytosis, is situated at the anterior end. recent evidence for the existence of an endocytic pathway in leishmania has prompted us to investigate candidate temporal markers for endocytosis. in this study we identify the l. donovani rab5b gene, and demonstrate the localization of a rab5b chimera to early endosomes. a ...200616752082
hemophagocytic syndrome associated with visceral leishmaniasis.the present paper reports a case of 6-year-old male child, suffering from pallor, fever and hepatosplenomegaly. a clinical diagnosis of enteric fever with a second possibility of malaria was considered. laboratory findings included bicytopenia, hyperbilirubinemia and raised liver enzymes. bone marrow examination revealed active hemophagocytosis. on extensive search few amastigote forms of leishmania donovani were seen. patient was negative for other viral, bacterial and malaria infections. the f ...200616741336
towards multilocus sequence typing of the leishmania donovani complex: resolving genotypes and haplotypes for five polymorphic metabolic enzymes (asat, gpi, nh1, nh2, pgd).multilocus enzyme electrophoresis is the gold standard for identification of leishmania species and strains. drawbacks include: only amino acid polymorphisms affecting electrophoretic mobility are detected; distinct allozymes can have coincident mobilities; few characters are available; and parasites must be cultured in bulk. so far, thousands of leishmania strains have been phenotyped by multilocus enzyme electrophoresis. here, we sequence enzyme-coding genes to provide a pcr-based higher resol ...200616725143
burkitt lymphoma and leishmaniasis in the same tissue sample in an aids patient. 200616722944
chronic heat-shock treatment driven differentiation induces apoptosis in leishmania donovani.the present study investigates the role of apoptosis in the regulation of cell numbers of leishmania donovani during the in vitro differentiation of promastigote stage to amastigote stage in axenic conditions. we report that apoptosis is induced in leishmania donovani due to chronic heat-shock treatment of 37 ( degrees )c that also mediates the differentiation of promastigotes to amastigotes. this is characterized by the fragmentation of dna, blebbing in the parasite cell membrane, nuclear conde ...200616718376
a sphingolipid rich lipid fraction isolated from attenuated leishmania donovani promastigote induces apoptosis in mouse and human melanoma cells in vitro.lipids, especially sphingolipids, are emerging as inducer of apoptosis in a wide range of immortal cells, potentiating their therapeutic application in cancer. in the present study, a sphingolipid rich lipid fraction (denoted here as all), isolated from an attenuated strain of leishmania donovani promastigote, was tested for its tumoricidal activity taking melanoma, the dreaded form of skin cancer cells, as model. all was found to induce chromatin condensation, internucleosomal dna fragmentation ...200616718368
leishmania donovani: an in vitro study of antimony-resistant amphotericin b-sensitive isolates.drug sensitivity of clinically antimony-unresponsive leishmania donovani isolates from eastern sudan was evaluated in an in vitro culture system against sodium stibogluconate (pentostam) and amphotericin b. eight isolates, six from antimony-resistant and two from clinically responsive patients were included in the study. parasites were tested as promastigotes and four of them were selected to be tested as amastigotes using a murine macrophage-like cell line. the results indicated that the conven ...200616716301
peroxisome is a reservoir of intracellular calcium.we have examined fura 2-loaded purified peroxisomes under confocal microscope to prove that this mammalian organelle is a store of intracellular calcium pool. presence of calcium channel and vanadate sensitive ca(2+)-atpase in the purified peroxisomal membrane has been demonstrated. we have further observed that machineries to maintain calcium pool in this mammalian organelle are impaired during infection caused by leishmania donovani. results reveal that peroxisomes have a merit to play a signi ...200616713100
leishmania donovani: intracellular atp level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells.leishmaniasis presents a spectrum of diseases ranging from benign cutaneous lesions to the often-fatal visceralizing form. luteolin, a dietary flavone induces apoptosis-like death in both promastigote and amastigote forms of leishmania, the causative agent of the diseases. here, we have elucidated the mechanism of action of luteolin by analyzing the mitochondrial and cytosolic changes associated with apoptosis-like death of leishmanial cells. in leishmania donovani, treatment with luteolin induc ...200616707127
canine visceral leishmaniasis, united states and canada, 2000-2003.visceral leishmaniasis, caused by protozoa of the genus leishmania donovani complex, is a vectorborne zoonotic infection that infects humans, dogs, and other mammals. in 2000, this infection was implicated as causing high rates of illness and death among foxhounds in a kennel in new york. a serosurvey of >12,000 foxhounds and other canids and 185 persons in 35 states and 4 canadian provinces was performed to determine geographic extent, prevalence, host range, and modes of transmission within fo ...200616704782
parasite glycoconjugates. part 16: synthesis of a disaccharide and phosphorylated di- and tri-saccharides from leishmania lipophosphoglycan.a neutral disaccharide beta-d-galp-(1-->4)-alpha-d-manp and phosphorylated di- and tri-saccharides beta-d-galp-(1-->3)-[h(2)po(3)-6]-beta-d-galp-o[ch(2)](8)chch(2) and beta-d-galp-(1-->3)-[h(2)po(3)-6]-beta-d-galp-(1-->4)-alpha-d-manp, which are fragments of the phosphoglycan portion of the surface lipophosphoglycan from leishmania donovani (the disaccharide) or leishmania major (all three compounds), were prepared and used as tlc standards to help the identification and differentiation of the e ...200616697981
turkish freshwater and marine macrophyte extracts show in vitro antiprotozoal activity and inhibit fabi, a key enzyme of plasmodium falciparum fatty acid biosynthesis.the ethanolic extracts of a number of turkish freshwater macrophytes (potamogeton perfoliatus, ranunculus tricophyllus and cladophora glomerata) and marine macroalgae (dictyota dichotoma, halopteris scoparia, posidonia oceanica, scinaia furcellata, sargassum natans and ulva lactuca) were assayed for their in vitro antiprotozoal activity. trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani and plasmodium falciparum were used as test organisms. the cytotoxicity of the extracts w ...200616697632
chemotherapy of leishmaniasis part iii: synthesis and bioevaluation of novel aryl substituted terpenyl pyrimidines as antileishmanial agents.some aryl substituted terpenyl pyrimidines 4 (a-p) have been synthesized using novel synthetic methods. the compounds were screened for in vitro antileishmanial activity against promastigotes. compounds 4c, 4i and 4l showed ic(50) values as 35, 35 and 25 microg ml(-1).200616697490
leishmania-hiv co-infection: an emerging problem in india. 200616691082
expression of a mitochondrial peroxiredoxin prevents programmed cell death in leishmania donovani.leishmania promastigote cells transmitted by the insect vector get phagocytosed by macrophages and convert into the amastigote form. during development and transformation, the parasites are exposed to various concentrations of reactive oxygen species, which can induce programmed cell death (pcd). we show that a mitochondrial peroxiredoxin (ldmprx) protects leishmania donovani from pcd. whereas this peroxiredoxin is restricted to the kinetoplast area in promastigotes, it covers the entire mitocho ...200616682463
use of pcr-rflp to identify leishmania species in naturally-infected dogs.tissue imprints on giemsa stained slides from dogs were used to investigate the presence of leishmania amastigotes by either optical microscopy (om) or polymerase chain reaction (pcr) detection of dna. samples from skin, spleen, lymph node, liver and bone marrow from a leishmaniasis endemic area dogs where leishmania (leishmania) chagasi and leishmania (viannia) braziliensis are sympatric were studied. dogs were initially diagnosed by indirect immunofluorescence (iif), as which 39 were iif posit ...200616682124
antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides.n(1)-phenyl-3,5-dinitro-n(4),n(4)-di-n-propylsulfanilamide (1) and n(1)-phenyl-3,5-dinitro-n(4),n(4)-di-n-butylsulfanilamide (2) show potent in vitro antimitotic activity against kinetoplastid parasites but display poor in vivo activity. seventeen new dinitroaniline sulfonamide and eleven new benzamide analogs of these leads are reported here. nine of the sulfonamides display in vitro ic(50) values under 500 nm against african trypanosomes, and the most active antikinetoplastid compounds also in ...200616675220
pre-systemic metabolism prevents in vivo antikinetoplastid activity of n1,n4-substituted 3,5-dinitro sulfanilamide, gb-ii-150.we previously showed that n1-phenyl-3,5-dinitro-n4,n4-di-n-butylsulfanilamide (denoted gb-ii-150) possesses selective antimicrotubule activity against leishmania donovani and trypanosoma brucei in vitro [bhattacharya, g., herman, j., delfin, d., salem, m.m., barszcz, t., mollet, m., riccio, g., brun, r., werbovetz, k.a., 2004. synthesis and antitubulin activity of n(1)- and n(4)-substituted 3,5-dinitro sulfanilamides against african trypanosomes and leishmania. journal of medicinal chemistry 47, ...200616643960
sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in leishmania donovani-infected macrophages.pentavalent antimony complexes, such as sodium stibogluconate and sodium antimony gluconate (sag), are still the first choice for chemotherapy against various forms of leishmaniasis, including visceral leishmaniasis, or kala-azar. although the requirement of a somewhat functional immune system for the antileishmanial action of antimony was reported previously, the cellular and molecular mechanism of action of sag was not clear. herein, we show that sag induces extracellular signal-regulated kina ...200616641451
immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-dna vaccine of leishmania donovani.the nucleoside hydrolase (nh36) of leishmania (l.) donovani is a vital enzyme which releases purines or pyrimidines of foreign dna to be used in the synthesis of parasite dna. as a bivalent dna vaccine, the vr1012-nh36 was immunoprotective against visceral and cutaneous murine leishmaniasis. in this work we tested the immunotherapy against leishmania (l.) chagasi infection, using two doses of 100 or 20 microg vr1012-nh36 vaccine (i.m. route), and, as a possible immunomodulator, aqueous garlic ex ...200616635538
leishmania donovani requires functional cdc42 and rac1 to prevent phagosomal maturation.leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. the main surface glycoconjugate on promastigotes, lipophosphoglycan (lpg), is crucial for survival and mediates the formation of a protective shell of f-actin around the phagosome. previous studies have demonstrated that this effect involves inhibition of protein kinase c alpha. the present study shows that functional cdc42 and rac1 are required for the formation of f-actin around l. donov ...200616622197
reduced nitric oxide synthase 2 (nos2) promoter activity in the syrian hamster renders the animal functionally deficient in nos2 activity and unable to control an intracellular pathogen.progressive disease in the hamster model of visceral leishmaniasis, caused by leishmania donovani, in contrast to infection in mice, mimics the progressive disease observed in untreated humans. during progressive infection in hamsters, there was a vigorous type 1 cellular immune response, which is typically associated with control of infection, suggesting that there was ineffective ifn-gamma-mediated macrophage activation. indeed, at the site of infection, hamsters did not express no synthase 2 ...200616622021
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