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2-alkynoic fatty acids inhibit topoisomerase ib from leishmania donovani.2-alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. in this work we synthesized the 2-octadecynoic acid (2-oda), 2-hexadecynoic acid (2-hda), and 2-tetradecynoic acid (2-tda) and show that 2-oda is the best inhibitor of the leishmania donovani dna topoisomerase ib enzyme (ldtopib) with an ec(50)=5.3±0.7μm. the potency of ldtopib inhibition follows the trend 2-oda>2-hda>2-tda, indicating that the e ...201222932312
involvement of cd4⁺ foxp3⁺ regulatory t cells in persistence of leishmania donovani in the liver of alymphoplastic aly/aly mice.visceral leishmaniasis (vl) is a chronic and fatal disease in humans and dogs caused by the intracellular protozoan parasites, leishmania donovani and l. infantum (l. chagasi). relapse of disease is frequent in immunocompromised patients, in which the number of vl cases has been increasing recently. the present study is aimed to improve the understanding of mechanisms of l. donovani persistence in immunocompromised conditions using alymphoplastic aly/aly mice. hepatic parasite burden, granuloma ...201222928057
in vitro antileishmanial drug susceptibility of clinical isolates from patients with indian visceral leishmaniasis--status of newly introduced drugs.regional variations in susceptibility of leishmania donovani clinical isolates have been reported to antimonials but not other antileishmanial drugs. therefore, we evaluated the susceptibility of four antileishmanial drugs in clinical use in 28 clinical isolates from endemic and non-endemic regions in the j774a.1 macrophage cell line, and we found increased tolerance of miltefosine and paromomycin in isolates from a patient from a high endemic region. effective dose for 90% killing (ed(90)) valu ...201222927497
development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis.the purpose of this study was to explore the applicability, targeting potential and drug delivery to specialized phagocytes via phosphatidylserine (ps)-specific ligand-anchored nanocapsules (ncs) bearing doxorubicin.201222872448
immunization with leishmania vaccine-alum-bcg and montanide isa 720 adjuvants induces low-grade type 2 cytokines and high levels of igg2 subclass antibodies in the vervet monkey (chlorocebus aethiops) model.the availability of hundreds of adjuvants has prompted a need for identifying rational standards for the selection of adjuvant formulation based on sound immunological principles for human vaccines. as cytokines elaborated by activated t cells are required for the regulation of isotype switch during b-cell development, a study of th2 cytokines and subclass distribution of the antibodies may shed new light on the processes involved in the polarization of the immune responses during vaccination st ...201222862788
sialoglycosylation of rbc in visceral leishmaniasis leads to enhanced oxidative stress, calpain-induced fragmentation of spectrin and hemolysis.visceral leishmaniasis (vl) caused by the intracellular parasite leishmania donovani accounts for an estimated 12 million cases of human infection. it is almost always associated with anemia, which severely complicates the disease course. however, the pathological processes leading to anemia in vl have thus far not been adequately characterized to date. in studying the glycosylation patterns of peripheral blood cells we found that the red blood cells (rbc) of vl patients (rbc(vl)) express eight ...201222860118
manadoperoxides, a new class of potent antitrypanosomal agents of marine origin.chemical investigation of the marine sponge plakortis cfr. lita afforded a library of endoperoxyketal polyketides, manadoperoxides b-k (3-5 and 7-13) and peroxyplakoric esters b(3) (6) and c (14). eight of these metabolites are new compounds and some contain an unprecedented chlorine-bearing thf-type ring in the side chain. the library of endoperoxide derivatives was evaluated for in vitro activity against trypanosoma brucei rhodesiense and leishmania donovani. some compounds, such as manadopero ...201222859016
quantitative proteomic profiling of the promastigotes and the intracellular amastigotes of leishmania donovani isolates identifies novel proteins having a role in leishmania differentiation and intracellular survival.protozoan parasites of the genus leishmania are important human pathogens that cycle between an extracellular promastigote stage residing in the sandflies and an intracellular amastigote stage colonizing the phagolysosomal compartment of the mammalian macrophages. here, we used the isobaric tagging method to quantify the global proteomic differences between the promastigotes and the intracellular amastigotes of three different leishmania donovani clones derived from the thp-1 human macrophage ce ...201222850196
pcr-based detection of leishmania dna in skin samples of post kala-azar dermal leishmaniasis patients from an endemic area of bangladesh.post kala-azar dermal leishmaniasis (pkdl) is a sequel of visceral leishmaniasis (vl) and pkdl patients are an important reservoir for anthroponotic transmission of vl. therefore, diagnosis and treatment of pkdl is important for the kala-azar elimination program in south asia, including bangladesh. while definitive diagnosis of pkdl is still based on microscopy, despite the low sensitivity of this method of diagnosis, pcr for identification of kinetoplast dna (kdna) from leishmania parasites is ...201222814154
phylogenic analysis of chinese leishmania isolates based on small subunit ribosomal rna (ssu rrna) and 7 spliced leader rna (7sl rna).the leishmaniases are zoonotic diseases caused by protozoan parasites of the genus leishmania. leishmaniases are still endemic in china, especially in the west and northwest froniter regions. to revalue the preliminary phylogenetic results of chinese leishmania isolates, we amplified partial fragment of small subunit ribosomal rna (ssu rrna) and 7 spliced leader rna (7sl rna), then tested the phylogenetic relationships among chinese leishmania isolates and their relatives by analyzing ssu rrna g ...201222807046
mycobacterium indicus pranii (mw) re-establishes host protective immune response in leishmania donovani infected macrophages: critical role of il-12.leishmania donovani, a protozoan parasite, causes a strong immunosuppression in a susceptible host and inflicts the fatal disease visceral leishmaniasis. relatively high toxicity, low therapeutic index, and failure in reinstating host-protective anti-leishmanial immune responses have made anti-leishmanial drugs patient non-compliant and an immuno-modulatory treatment a necessity. therefore, we have tested the anti-leishmanial efficacy of a combination of a novel immunomodulator, mycobacterium in ...201222792256
role of oxidative stress and apoptosis in the cellular response of murine macrophages upon leishmania infection.leishmania parasites are able to survive in the macrophage, one of the most hostile environments of the vertebrate host. the present study investigated how leishmania infection influences these host cell defence mechanisms. macrophages were infected with antimony-susceptible and -resistant leishmania strains. free radical production in leishmania-infected macrophages was measured by electron paramagnetic resonance. apoptosis was detected with fluorescence microscopy using annexin-v fitc labellin ...201222776404
evaluation of antileishmanial activity of south indian medicinal plants against leishmania donovani.infections due to protozoa of the genus leishmania are a major worldwide health problem, with high endemicity in developing countries. the aim of this study was to evaluate the in vitro antileishmanial activity of the acetone and methanol leaf extracts of anisomeles malabarica, flower of gloriosa superba, leaf of ocimum basilicum, leaf and seed of ricinus communis against promastigotes form of leishmania donovani. antiparasitic evaluations of different plant crude extracts were performed on 96 w ...201222771864
combination of paromomycin and miltefosine promotes tlr4-dependent induction of antileishmanial immune response in vitro.to evaluate the in vitro activity of antileishmanial drugs, paromomycin and miltefosine, to generate th-1-biased immunomodulation in hosts against intracellular leishmania donovani.201222761329
genetic markers for ssg resistance in leishmania donovani and ssg treatment failure in visceral leishmaniasis patients of the indian subcontinent.the current standard to assess pentavalent antimonial (ssg) susceptibility of leishmania is a laborious in vitro assay of which the result has little clinical value because ssg-resistant parasites are also found in ssg-cured patients. candidate genetic markers for clinically relevant ssg-resistant parasites identified by full genome sequencing were here validated on a larger set of clinical strains. we show that 3 genomic locations suffice to specifically detect the ssg-resistant parasites found ...201222753945
genetic typing reveals monomorphism between antimony sensitive and resistant leishmania donovani isolates from visceral leishmaniasis or post kala-azar dermal leishmaniasis cases in india.resistance to pentavalent antimonials has emerged as a major hurdle to the treatment and control of visceral leishmaniasis (vl), also known as kala-azar (ka), caused by leishmania donovani. in india, over 60% of ka patients are unresponsive to the first-line drug sodium antimony gluconate (sag). resistance determinants in laboratory strains are partly known; however, the mechanism operating in field isolates is not well understood. in this study, we attempted to analyze the genetic polymorphism ...201222752721
leishmania donovani pteridine reductase 1: comparative protein modeling and protein-ligand interaction studies of the leishmanicidal constituents isolated from the fruits of piper longum.visceral leishmaniasis or kala-azar is caused by the dimorphic parasite leishmania donovani in the indian subcontinent. treatment options for kala-azar are currently inadequate due to various limitations. currently, drug discovery for leishmaniases is oriented towards rational drug design; the aim is to identify specific inhibitors that target particular metabolic activities as a possible means of controlling the parasites without affecting the host. leishmania salvages pteridin from its host an ...201222752544
evidence for involvement of th17 type responses in post kala azar dermal leishmaniasis (pkdl).post kala-azar dermal leishmaniasis (pkdl), a dermal sequel of visceral leishmaniasis, caused by leishmania donovani, constitutes an important reservoir for the parasite. parallel functioning of counter acting immune responses (th1/th2) reflects a complex immunological scenario, suggesting the involvement of additional regulatory molecules in the disease pathogenesis.201222724038
an image-based high-content screening assay for compounds targeting intracellular leishmania donovani amastigotes in human macrophages.leishmaniasis is a tropical disease threatening 350 million people from endemic regions. the available drugs for treatment are inadequate, with limitations such as serious side effects, parasite resistance or high cost. driven by this need for new drugs, we developed a high-content, high-throughput image-based screening assay targeting the intracellular amastigote stage of different species of leishmania in infected human macrophages. the in vitro infection protocol was adapted to a 384-well-pla ...201222720099
potential antileishmanial effect of three medicinal plants.the antileishmanial activity of three organic solvent extracts and water residue of the plants: acacia nilotica (mimosaceae) (husk), ambrosia miratima (astraceae) (aerial shoot) and azadarichta indica (meliaceae) (leaves) were tested in vitro against leishmania donovani promastigotes. the study revealed that the extracts of a. nilotica and a. miratima have effectious antileishmanial activity at concentrations (ic(50)) less than 8 μg/ml, while the extracts of a. indica lack antileishmanial activi ...201223326001
human visceral leishmaniasis in kermanshah province, western iran, during 2011-2012.visceral leishmaniasis (vl) or kala-azar is a parasitic disease caused by the species of leishmania donovani complex. it is endemic in some parts of provinces of iran. according to the reported cases of vl in kermanshah province in recent years, this study was conducted to determine the seroprevalence of vl in high risk villages of the province.201223323091
asymmetric synthesis and anti-protozoal activity of the 8,4'-oxyneolignans virolin, surinamensin and analogues.the asymmetric synthesis of 8,4'-oxyneolignans (-)-virolin, (-)-surinamensin and a number of analogues has been achieved. a divergent synthesis was used, with all compounds being elaborated from a single chiral aldehyde derived from ethyl lactate. in the 15 compounds that were tested, the level of substitution on the a-ring was found to directly influence the activity against leishmania donovani whilst the activity against plasmodium falciparum was influenced by numerous substitution and stereoc ...201223313632
imipramine is an orally active drug against both antimony sensitive and resistant leishmania donovani clinical isolates in experimental infection.in an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. the only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. thus there is a genuine need for an orally active antileishmanial drug. previously it was shown that imipramine, a tricyclic antidepressant alters the proton ...201223301108
a parasite rescue and transformation assay for antileishmanial screening against intracellular leishmania donovani amastigotes in thp1 human acute monocytic leukemia cell line.leishmaniasis is one of the world's most neglected diseases, largely affecting the poorest of the poor, mainly in developing countries. over 350 million people are considered at risk of contracting leishmaniasis, and approximately 2 million new cases occur yearly(1). leishmania donovani is the causative agent for visceral leishmaniasis (vl), the most fatal form of the disease. the choice of drugs available to treat leishmaniasis is limited (2);current treatments provide limited efficacy and many ...201223299097
leishmania donovani develops resistance to drug combinations.drug combinations for the treatment of leishmaniasis represent a promising and challenging chemotherapeutic strategy that has recently been implemented in different endemic areas. however, the vast majority of studies undertaken to date have ignored the potential risk that leishmania parasites could develop resistance to the different drugs used in such combinations. as a result, this study was designed to elucidate the ability of leishmania donovani to develop experimental resistance to anti-le ...201223285310
identification of drosophila gene products required for phagocytosis of leishmania donovani.the identity and function of host factors required for efficient phagocytosis and intracellular maintenance of the protozoan parasite leishmania donovani are poorly understood. utilising the phagocytic capability of drosophila s2 cells, together with available tools for modulating gene expression by rnai, we have developed an experimental system in which to identify host proteins of this type on a genome-wide scale. we have shown that l. donovani amastigotes can be phagocytosed by s2 cells, in w ...201223272175
leishmania donovani zymodeme mon-37 isolated from an autochthonous visceral leishmaniasis patient in sri lanka.although the strain causing cutaneous leishmaniasis (cl) in sri lanka was first identified in 2003, the strain causing visceral leishmaniasis (vl) has not yet been identified. we report the first isoenzyme typing of a strain causing vl in sri lanka at an early stage of emergence of vl in the country. the parasite was isolated from a 57-year-old civil soldier who had been in the jungle in the vavuniya district in the northern province of sri lanka for a period of nearly 6 months immediately befor ...201223265615
apoptotic marker expression in the absence of cell death in staurosporine-treated leishmania donovani.the protozoan parasite leishmania donovani undergoes several developmental transitions in its insect and vertebrate hosts that are induced by environmental changes. the roles of protein kinases in these adaptive differentiation steps and their potential as targets for antiparasitic intervention are only poorly characterized. here, we used the generic protein kinase inhibitor staurosporine to gain insight into how interference with phosphotransferase activities affects the viability, growth, and ...201223263009
vaccine development against leishmania donovani.visceral leishmaniasis (vl) caused by leishmania donovani and leishmania infantum/chagasi represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. zoonotic vl caused by l. infantum is a re-emergent canid zoonoses which represents a complex epidemiological cycle in the new world where domestic dogs serve as a reservoir host responsible for potentially fatal human infection and where dog culling is the only measure for res ...201222615707
leishmania donovani argininosuccinate synthase is an active enzyme associated with parasite pathogenesis.gene expression analysis in leishmania donovani (ld) identified an orthologue of the urea cycle enzyme, argininosuccinate synthase (ldass), that was more abundantly expressed in amastigotes than in promastigotes. in order to characterize in detail this newly identified protein in leishmania, we determined its enzymatic activity, subcellular localization in the parasite and affect on virulence in vivo.201223094117
manipulation of costimulatory molecules by intracellular pathogens: veni, vidi, vici!!some of the most successful pathogens of human, such as mycobacterium tuberculosis (mtb), hiv, and leishmania donovani not only establish chronic infections but also remain a grave global threat. these pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. costimulatory molecul ...201222719245
leishmania promastigotes: building a safe niche within macrophages.upon their internalization by macrophages, leishmania promastigotes inhibit phagolysosome biogenesis. the main factor responsible for this inhibition is the promastigote surface glycolipid lipophosphoglycan (lpg). this glycolipid has a profound impact on the phagosome, causing periphagosomal accumulation of f-actin and disruption of phagosomal lipid microdomains. functionally, this lpg-mediated inhibition of phagosome maturation is characterized by an impaired assembly of the nadph oxidase and t ...201223050244
identification of leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates.visceral leishmaniasis (vl) is a serious lethal parasitic disease caused by leishmania donovani in asia and by leishmania infantum chagasi in southern europe and south america. vl is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. this high incidence is due in part to the lack of an efficacious vaccine. here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with vl. we combi ...201222443237
antimicrobial, anti-inflammatory, antiparasitic, and cytotoxic activities of laennecia confusa.the current paper investigated the potential benefit of the traditional mexican medicinal plant laennecia confusa (cronquist) g. l. nesom (asteraceae). fractions from the hexane, chloroform, methanol, and aqueous extracts were analyzed for antibacterial, antifungal, anti-inflammatory, and antiparasitic activities. the antimicrobial activity of the extracts and fractions was assessed on bacterial and fungal strains, in addition to the protozoa leishmania donovani, using a microdilution assay. the ...201222623891
multilocus microsatellite typing (mlmt) of strains from turkey and cyprus reveals a novel monophyletic l. donovani sensu lato group.new foci of human cl caused by strains of the leishmania donovani (l. donovani) complex have been recently described in cyprus and the çukurova region in turkey (l. infantum) situated 150 km north of cyprus. cypriot strains were typed by multilocus enzyme electrophoresis (mlee) using the montpellier (mon) system as l. donovani zymodeme mon-37. however, multilocus microsatellite typing (mlmt) has shown that this zymodeme is paraphyletic; composed of distantly related genetic subgroups of differen ...201222348162
reassessment of immune correlates in human visceral leishmaniasis as defined by cytokine release in whole blood.depressed cell-mediated immunity in human visceral leishmaniasis (vl) (also known as kala-azar), revealed as the inability of peripheral blood mononuclear cells (pbmcs) to respond to leishmania antigen, remains a hallmark of and is thought to underlie the progressive nature of this disease. we recently reported the ability of a whole-blood, gamma interferon (ifn-γ) release assay to detect subclinical infections among healthy individuals living in an area where kala-azar is endemic (bihar, india) ...201222539471
kdna genetic signatures obtained by lssp-pcr analysis of leishmania (leishmania) infantum isolated from the new and the old world.visceral leishmaniasis (vl) caused by species from the leishmania donovani complex is the most severe form of the disease, lethal if untreated. vl caused by leishmania infantum is a zoonosis with an increasing number of human cases and millions of dogs infected in the old and the new world. in this study, l. infantum (syn. l.chagasi) strains were isolated from human and canine vl cases. the strains were obtained from endemic areas from brazil and portugal and their genetic polymorphism was ascer ...201222912862
antiparasitic antioxidant phenylpropanoids and iridoid glycosides from tecoma mollis.a radical scavenging guided phytochemical study on the stem bark of tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). the structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. compounds (1-7) displayed promising antioxidant activity (dpph assay) in relation to ascorbic acid (positive control). the antimicrobial activity for compounds (1-8) was evaluated ag ...201222245081
adenine aminohydrolase from leishmania donovani: a unique enzyme in parasite purine metabolism.adenine aminohydrolase (aah) is an enzyme that is not present in mammalian cells and is found exclusively in leishmania among the protozoan parasites that infect humans. aah plays a paramount role in purine metabolism in this genus by steering 6-aminopurines into 6-oxypurines. l. donovani aah is 38% and 23% identical to the saccharomyces cerevisiae aah and human adenosine deaminase enzymes, respectively, catalyzes adenine deamination to hypoxanthine with an apparent k(m) of 15.4 μm, and does n ...201222238346
epidemiology of imported cutaneous leishmaniasis at the hospital for tropical diseases, london, united kingdom: use of polymerase chain reaction to identify the species.abstract. this study reviewed all patients diagnosed with imported cutaneous leishmaniasis (cl) at the hospital for tropical diseases in london, united kingdom, over an 11-year period. diagnostic and epidemiologic information was collected prospectively for all patients with imported cl to this hospital during 1998-2009. a total of 223 patients were given a diagnosis of cl. ninety patients were diagnosed with old world cl, which was caused most commonly by leishmania donovani complex (n = 20). a ...201222232460
Identification of phospholipid species affected by miltefosine action in Leishmania donovani cultures using LC-ELSD, LC-ESI/MS, and multivariate data analysis.Leishmaniasis is a widespread parasitic disease principally treated by intravenous drugs. Hexadecylphosphocholine (miltefosine) has recently proved its efficacy by oral route. Although its mechanism of action has been investigated, and principally relies on perturbations of the metabolism of lipids and especially phospholipids, further studies need to be conducted to detect precisely which metabolic pathways are impacted. For this purpose, the present work proposes a complete lipidomic study foc ...201222065347
Downregulation of Mitogen-Activated Protein Kinase 1 of Leishmania donovani Field Isolates Is Associated with Antimony Resistance.Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) on the Indian subcontinent. The mechanisms operating in laboratory-generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding mitogen-activated protein kinase 1 (MAPK1) for the kinetoplast protozoan Leishmania donovani (LdMA ...201222064540
Development of Vaccines against Visceral Leishmaniasis.Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral), visceral leishmaniasis (VL) accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection with Leishmania donovani or L. infantum, VL represents a serious public health problem in endemic regions a ...201221912561
Identification of TLR inducing Th1-responsive Leishmania donovani amastigote-specific antigens.Leishmania is known to elicit Th2 response that causes leishmaniasis progression; on the other hand, Th1 cytokines restricts amastigote growth and disease progression. In this study, we report the potential of two leishmanial antigens (65 and 98 kDa, in combination) which enhance strong macrophage effector functions, viz., production of respiratory burst enzymes, nitric oxide, and Th1 cytokines. The identification of antigens were done by resolving the crude soluble antigens on SDS-PAGE and elut ...201221858498
Myeloid cell IL-10 production in response to leishmania involves inactivation of glycogen synthase kinase-3ß downstream of phosphatidylinositol-3 kinase.Leishmania disease expression has been linked to IL-10. In this study, we investigated the regulation of IL-10 production by macrophages infected with Leishmania donovani. Infection of either murine or human macrophages brought about selective phosphorylation of Akt-2 in a PI3K-dependent manner. These events were linked to phosphorylation and inactivation of glycogen synthase kinase-3ß (GSK-3ß) at serine 9, as the latter was abrogated by inhibition of either PI3K or Akt. One of the transcription ...201222140263
Discovery of Safe and Orally Effective 4-Aminoquinaldine Analogues as Apoptotic Inducers with Activity against Experimental Visceral Leishmaniasis.Novel antileishmanials are urgently required to overcome emergence of drug resistance, cytotoxic effects, and difficulties in oral delivery. Toward this, we investigated a series of novel 4-aminoquinaldine derivatives, a new class of molecules, as potential antileishmanials. 4-Aminoquinaldine derivatives presented inhibitory effects on L. donovani promastigotes and amastigotes (50% inhibitory concentration range, 0.94 to 127 µM). Of these, PP-9 and PP-10 were the most effective in vitro and demo ...201222024817
Genome-wide SNP and microsatellite variation illuminate population-level epidemiology in the Leishmania donovani species complex.The species of the Leishmania donovani species complex cause visceral leishmaniasis, a debilitating infectious disease transmitted by sandflies. Understanding molecular changes associated with population structure in these parasites can help unravel their epidemiology and spread in humans. In this study, we used a panel of standard microsatellite loci and genome-wide SNPs to investigate population-level diversity in L. donovani strains recently isolated from a small geographic area spanning Indi ...201222119748
Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis.The present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (?)-irradiated Leishmania donovani. A second immunization was given after 15days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measur ...201222019416
diverse viscerotropic isolates of leishmania all express a highly conserved secretory nuclease during human infections.previously, we characterized a gene encoding the unique nuclease (ldnuc(s)) from a sudanese isolate of the human pathogen leishmania donovani. this parasite secretory enzyme is involved in the salvage of host-derived purines and is constitutively expressed by both developmental forms of the parasite. currently, we assessed whether an ldnuc(s)-like nuclease was conserved among other geographically disparate isolates of l. donovani and whether this enzyme was produced by intracellular amastigotes ...201222020747
Immunity to visceral leishmaniasis using genetically defined live-attenuated parasites.Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). Drug treatments are expensive and often result in the development of drug resistance. No vaccine is available against leishmaniasis. Subunit Leishmania vaccine immunization in animal models has shown some efficacy but little or none in humans. How ...201221912560
immunobiology of visceral leishmaniasis.visceral leishmaniasis (vl), commonly known as kala-azar, is caused by leishmania donovani and leishmania infantum (leishmania chagasi in the americas). these leishmania species infect macrophages throughout the viscera, and parasites are typically found in the spleen, liver, and bone marrow. patients with active disease typically exhibit marked immunosuppression, lack reactivity to the leishmania skin test (lst), a delayed type hypersensitivity test, and their peripheral blood mononuclear cells ...201222912637
prevalence of sand flies and leishmania donovani infection in a natural population of female phlebotomus argentipes in bihar state, india.leishmaniasis is a vector-borne disease, and in the indian subcontinent the female phlebotomus argentipes is the vector for leishmania donovani. however, data on the extent of sand fly infection rates in natural settings using molecular methods have not been extensively reported in india. in this study a pcr technique was applied targeting the 18s rrna encoding region to determine the prevalence of leishmania infection in female p. argentipes captured in the field. for this study, sand flies wer ...201222217179
a unique modification of the eukaryotic initiation factor 5a shows the presence of the complete hypusine pathway in leishmania donovani.deoxyhypusine hydroxylase (dohh) catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (n(€)-(4-amino-2-hydroxybutyl) lysine), which is present on only one cellular protein, eukaryotic initiation factor 5a (eif5a). we present here the molecular and structural basis of the function of dohh from the protozoan parasite, leishmania donovani, which causes visceral leishmaniasis. the l. donovani dohh gene is 981 bp and encodes a putative polypeptide of 326 amin ...201222438895
the narrow active-site cleft of o-acetylserine sulfhydrylase from leishmania donovani allows complex formation with serine acetyltransferases with a range of c-terminal sequences.cysteine is a crucial substrate for the synthesis of glutathione and trypanothione, which in turn maintain intracellular redox homeostasis and defend against oxidative stress in the pathogen leishmania donovani. here, the identification, sequencing, characterization and crystal structure at 1.79 å resolution of o-acetylserine sulfhydrylase (oass), a cysteine-biosynthetic pathway enzyme from l. donovani (ldoass), are reported. it shows binding to the serine acetyltransferase (sat) c-terminal pept ...201222868756
antitrypanosomal alkaloids from the marine bacterium bacillus pumilus.fractionation of the ethyl acetate extract of the marine bacterium bacillus pumilus isolated from the black coral antipathes sp. led to the isolation of five compounds: cyclo-(l-leu-l-pro) (1), 3-hydroxyacetylindole (2), n-acetyl-β-oxotryptamine (3), cyclo-(l-phe-l-pro) (4), and 3-formylindole (5). the structures of compounds 1-5 were established by spectroscopic analyses, including hresitof-ms and nmr (1h, 13c, hsqc, hmbc and cosy). compounds 2, 3 and 5 caused the inhibition on the growth of tr ...201222990456
leishmanicidal and anticandidal activity of constituents of indian edible mushroom astraeus hygrometricus.two new lanostane-type triterpenes, 1 and 2, were isolated from astraeus hygrometricus. the structures were established by ir, (1)h- and (13)c-nmr, ms, and x-ray crystallographic experiments. the triterpenes exhibited excellent in vitro toxicities against candida albicans, comparable to standard antifungal antibiotics. the triterpene 2 significantly inhibited the growth of leishmania donovani promastigotes in vitro. the triterpene skeleton may be considered a template structure in search for new ...201222899612
antimicrobial metabolites from the paracel islands sponge agelas mauritiana.four new alkaloids, (-)-8'-oxo-agelasine d (2), ageloxime b (3), (+)-2-oxo-agelasidine c (4), and 4-bromo-n-(butoxymethyl)-1h-pyrrole-2-carboxamide (5), and the known compound (-)-ageloxime d (1) were isolated from the marine sponge agelas mauritiana. their chemical structures were established on the basis of spectroscopic analysis. compounds 1 and 3 both showed antifungal activity against cryptococcus neoformans and antileishmanial activity against leishmania donovani in vitro. compound 3 also ...201222360686
kinetics and docking studies of two potential new inhibitors of the nucleoside hydrolase from leishmania donovani.in this study the recombinant enzyme nucleoside hydrolase of leishmania donovani (rldnh) was expressed in escherichia coli in connection with maltose binding protein (mbp). the rldnh-mbp showed efficient a significant in vitro activity with inosine as substrate. from the coupled reaction with xanthine oxidase (xo) it was possible to determine the kinetic constants of rldnh-mbp as k(m) (434 ± 109 μm) and v(max) (0.20 ± 0.02 μm). in addition, two nucleoside analogs (compounds 1 and 2) were tested ...201222947894
identification and characterization of a novel ribose 5-phosphate isomerase b from leishmania donovani.leishmaniasis is a group of tropical diseases caused by protozoan parasites of the genus leishmania. due to the emergence of resistance to the available antileishmanial drugs there is an immediate need to identify molecular targets on which to base future treatment strategies. ribose 5-phosphate isomerase (rpi; ec 5.3.1.6) is a key enzyme of the pentose phosphate pathway (ppp) which catalyses the reversible aldose-ketose isomerization between ribose 5-phosphate (r5p) and ribulose 5-phosphate (ru ...201222483752
leishmania donovani hslv does not interact stably with hslu proteins.genes for hslvu-type peptidases are found in bacteria and in a few select eukaryota, among those such important pathogens as plasmodium spp. and leishmania spp. in this study, we performed replacements of all three hslv/hslu gene homologues and found one of those, hslv, to be essential for leishmania donovani viability. the leishmania hslv gene can also partially relieve the thermosensitive phenotype of a combined hslvu/lon/clpxp knockout mutant of escherichia coli, indicating a conserved functi ...201222370310
subclinical leishmaniasis associated with infertility and chronic prostatitis in a dog.a stud dog was presented for acquired infertility. haematospermia and teratozoospermia were found on two ejaculates 2 weeks apart. a presumptive diagnosis of prostatitis was made follo-wing ultrasound examination. an ultrasound-guided needle core biopsy was performed under general anaesthesia, revealing a mild chronic macrophagic and plasma cell prostatitis with intracytoplasmic amastigotes consistent with leishmania spp. infection. presence of leishmania infantum, leishmania donovani or leishma ...201222690941
immunopathogenesis of non-healing american cutaneous leishmaniasis and progressive visceral leishmaniasis.the outcomes of leishmania infection are determined by host immune and nutrition status, parasite species, and co-infection with other pathogens. while subclinical infection and self-healing cutaneous leishmaniasis (cl) are common, uncontrolled parasite replication can lead to non-healing local lesions or visceral leishmaniasis (vl). it is known that infection control requires th1-differentiation cytokines (il-12, il-18, and il-27) and th1 cell and macrophage activation. however, there is no gen ...201223053396
synthesis, dna binding and antileishmanial activity of low molecular weight bis-arylimidamides.the effects of reducing the molecular weight of the antileishmanial compound db766 on dna binding affinity, antileishmanial activity and cytotoxicity are reported. the bis-arylimidamides were prepared by the coupling of aryl s-(2-naphthylmethyl)thioimidates with the corresponding amines. specifically, we have prepared new series of bis-arylimidamides which include 3a, 3b, 6, 9a, 9b, 9c, 13, and 18. three compounds 9a, 9c, and 18 bind to dna with similar or moderately lower affinity to that of db ...201222840696
efficacy and tolerability of oleylphosphocholine (olpc) in a laboratory model of visceral leishmaniasis.the alkylphospholipid oleylphosphocholine (olpc) is a structural analogue of miltefosine and may represent a potential therapeutic backup for the treatment of visceral leishmaniasis (vl). this laboratory study compared the in vitro and in vivo activity profile of both olpc and miltefosine.201222782488
seroprevalence and asymptomatic carriage of leishmania spp. in austria, a non-endemic european country.leishmaniasis is a rare disease in central europe and is diagnosed almost exclusively in travellers or migrants coming from tropical or subtropical countries. we conducted an explorative cross-sectional serological study, using a commercial elisa, in 1048 healthy austrian individuals to assess the distribution of specific antibodies against leishmania spp. in humans in austria. overall, 47 individuals (4.5%) tested positive, and an additional 32 (3.1%) showed borderline results. after 12 months, ...201322764887
cloning, characterization, and inhibition studies of a β-carbonic anhydrase from leishmania donovani chagasi, the protozoan parasite responsible for leishmaniasis.leishmaniasis is an infection provoked by protozoans belonging to the genus leishmania. among the many species and subsepecies of such protozoa, leishmania donovani chagasi causes visceral leishmaniasis. a β-carbonic anhydrase (ca, ec 4.2.1.1) was cloned and characterized from this organism, denominated here ldcca. ldcca possesses effective catalytic activity for the co2 hydration reaction, with kcat of 9.35 × 10(5) s(-1) and kcat/km of 5.9 × 10(7) m(-1) s(-1). a large number of aromatic/heteroc ...201323977960
live attenuated leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in balb/c mice.leishmaniasis causes significant morbidity and mortality worldwide, and no vaccines against this disease are available. previously, we had shown that the amastigote-specific protein p27 (ldp27) is a component of an active cytochrome c oxidase complex in leishmania donovani and that upon deletion of its gene the parasite had reduced virulence in vivo. in this study, we have shown that ldp27(-/-) parasites do not survive beyond 20 wk in balb/c mice and hence are safe as an immunogen. upon virulent ...201323338240
atypical mucocutaneous involvement with leishmania donovani.mucocutaneous leishmaniasis has rarely been reported from india. the usual causative organisms of this infection are leishmania braziliensis and l. tropica. another species, l. donovani, which usually causes visceral leishmaniasis, has recently been reported to cause mucocutaneous disease in a few patients from sri lanka. we report two patients who had undiagnosed chronic skin lesions for several years. skin biopsies revealed leishmania and the species was characterized as l. donovani in both pa ...201322963292
survey of infectious agents in the endangered darwin's fox (lycalopex fulvipes): high prevalence and diversity of hemotrophic mycoplasmas.very little is known about the diseases affecting the darwin's fox (lycalopex fulvipes), which is considered to be one of the most endangered carnivores worldwide. blood samples of 30 foxes captured on chiloé island (chile) were tested with a battery of pcr assays targeting the following pathogens: ehrlichia/anaplasma sp., rickettsia sp., bartonella sp., coxiella burnetti, borrelia sp., mycoplasma sp., babesia sp., hepatozoon canis, hepatozoon felis, leishmania donovani complex, and filariae. an ...201324176254
leishmania in hlh: a rare finding with significant treatment implications.hemophagocytic lymphohistiocytosis (hlh) associated with visceral leishmaniasis (vl) is a very rare phenomenon. we report the first known north american case in a 21 month old boy. he was initially diagnosed with epstein barr virus (ebv) triggered hlh and treated with the international treatment protocol, hlh-2004. stem cell transplant was planned due to repeated reactivations of disease, but his pretransplant bone marrow revealed an unexpected protozoan-leishmania donovani. treatment with lipos ...201323511497
a study of haematological and bone marrow changes in symptomatic patients with human immune deficiency virus infection with special mention of functional iron deficiency, anaemia of critically ill and haemophagocytic lymphohistiocytosis.haematological abnormalities are among the most common complications of hiv. these involve all lineages of blood cells. bone marrow studies form integral part of complete workup of the hiv positive patients specially when they present as case of pyrexia of unknown origin (puo), refractory anaemia and pancytopenia.201324600136
human immunodeficiency virus/leishmania infantum in the first foci of urban american visceral leishmaniasis: clinical presentation from 1994 to 2010.human immunodeficiency virus (hiv) coinfection with leishmania infantum or leishmania donovani, the agents of visceral leishmaniasis (or kala-azar), has become a fatal public health problem in the tropics where kala-azar is endemic.201323666663
discovery of 3,3'-diindolylmethanes as potent antileishmanial agents.an efficient protocol for synthesis of 3,3'-diindolylmethanes using recyclable fe-pillared interlayered clay (fe-pilc) catalyst under aqueous medium has been developed. all synthesized 3,3'-diindolylmethanes showed promising antileishmanial activity against leishmania donovani promastigotes as well as axenic amastigotes. structure-activity relationship analysis revealed that nitroaryl substituted diindolylmethanes showed potent antileishmanial activity. the 4-nitrophenyl linked 3,3'-diindolylmet ...201323517732
chemo-informatic design of antibiotic geldenamycin analogs to target stress proteins hsp90 of pathogenic protozoan parasites.stress proteins hsp90 (heat shock proteins) are essential molecular chaperones involved in signal transduction, cell cycle control, stress management, folding and degradation of proteins. hsp90 have been found in a variety of organisms including pathogens suggesting that they are ancient and conserved proteins. here, using molecular modeling and docking protocols, antibiotic geldenamycin and its analog are targeted to the hsp90 homolog proteins of pathogenic protozoans plasmodium falciparum, lei ...201323750075
over-expression of 60s ribosomal l23a is associated with cellular proliferation in sag resistant clinical isolates of leishmania donovani.sodium antimony gluconate (sag) unresponsiveness of leishmania donovani (ld) had effectively compromised the chemotherapeutic potential of sag. 60s ribosomal l23a (60srl23a), identified as one of the over-expressed protein in different resistant strains of l.donovani as observed with differential proteomics studies indicates towards its possible involvement in sag resistance in l.donovani. in the present study 60srl23a has been characterized for its probable association with sag resistance mecha ...201324340105
identification of a secreted casein kinase 1 in leishmania donovani: effect of protein over expression on parasite growth and virulence.casein kinase 1 (ck1) plays an important role in eukaryotic signaling pathways, and their substrates include key regulatory proteins involved in cell differentiation, proliferation and chromosome segregation. the leishmania genome encodes six potential ck1 isoforms, of which five have orthologs in other trypanosomatidae. leishmania donovani ck1 isoform 4 (ldck1.4, orthologous to lmjf27.1780) is unique to leishmania and contains a putative secretion signal peptide. the full-length gene and three ...201324260187
substrate inhibition of uracil phosphoribosyltransferase by uracil can account for the uracil growth sensitivity of leishmania donovani pyrimidine auxotrophs.the pathogenic protozoan parasite leishmania donovani is capable of both de novo pyrimidine biosynthesis and salvage of pyrimidines from the host milieu. genetic analysis has authenticated l. donovani uracil phosphoribosyltransferase (lduprt), an enzyme not found in mammalian cells, as the focal enzyme of pyrimidine salvage because all exogenous pyrimidines that can satisfy the requirement of the parasite for pyrimidine nucleotides are funneled to uracil and then phosphoribosylated to ump in the ...201323986453
adenylosuccinate synthetase and adenylosuccinate lyase deficiencies trigger growth and infectivity deficits in leishmania donovani.leishmania are auxotrophic for purines, and consequently purine acquisition from the host is a requisite nutritional function for the parasite. both adenylosuccinate synthetase (adss) and adenylosuccinate lyase (asl) have been identified as vital components of purine salvage in leishmania donovani, and therefore δadss and δasl null mutants were constructed to test this hypothesis. unlike wild type l. donovani, δadss and δasl parasites in culture exhibited a profoundly restricted growth phenotype ...201323404497
drug resistance in natural isolates of leishmania donovani s.l. promastigotes is dependent of pgp170 expression.resistance of pathogens to drugs is a growing concern regarding many diseases. parasites like leishmania, plasmodium and entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. the acquired resistance of leishmania to antimony has generated intense research on the mechanisms involved but the question has not yet been resolved. to test the hypothesis that drug efflux in leishmania, as measured by flow cytometry using the fluoresce ...201323776486
highlights on molecular identification of closely related species.the term "complex" emerged in the literature at the beginning of the genomic era associated to taxonomy and grouping organisms that belong to different species but exhibited similar patterns according to their morphological, physiological and/or other phenotypic features. dna-dna hybridization values ~70% and high identity on 16s rrna gene sequences were recommended for species delineation. electrophoretic methods showed in some cases to be useful for species identification and population struct ...201322982158
polymorphism in the haspb repeat region of east african leishmania donovani strains.visceral leishmaniasis (vl) caused by leishmania donovani is a major health problem in ethiopia. parasites in disparate regions are transmitted by different vectors, and cluster in distinctive genotypes. recently isolated strains from vl and hiv-vl co-infected patients in north and south ethiopia were characterized as part of a longitudinal study on vl transmission.201323358849
pharmacological assessment defines leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infection.protein kinase inhibitors have emerged as new drugs in various therapeutic areas, including leishmaniasis, an important parasitic disease. members of the leishmania casein kinase 1 (ck1) family represent promising therapeutic targets. leishmania casein kinase 1 isoform 2 (ck1.2) has been identified as an exokinase capable of phosphorylating host proteins, thus exerting a potential immune-suppressive action on infected host cells. moreover, its inhibition reduces promastigote growth. despite thes ...201324366737
cross-sectional study to assess risk factors for leishmaniasis in an endemic region in sri lanka.sri lanka reports significantly more cutaneous leishmaniasis (cl) cases than visceral leishmaniasis (vl) cases, both of which are caused by leishmania donovani mon-37. a cross-sectional study conducted in an area with a high prevalence of cl prevalent included 954 participants of an estimated population of 61,674 to estimate the number of cl cases, ascertain whether there is a pool of asymptomatic vl cases, and identify risk factors for transmission. a total of 31 cases of cl were identified, of ...201323918217
seasonal variation in the prevalence of sand flies infected with leishmania donovani.visceral leishmaniasis (vl) is a life threatening neglected infectious disease in the indian subcontinent, transmitted by the bite of female sand flies. estimation of the infectivity in the vector population, collected in different seasons, may be useful to better understanding the transmission dynamics of vl as well as to plan vector control measures.201323585896
solid™ sequencing of genomes of clinical isolates of leishmania donovani from india confirm leptomonas co-infection and raise some key questions.known as 'neglected disease' because relatively little effort has been applied to finding cures, leishmaniasis kills more than 150,000 people every year and debilitates millions more. visceral leishmaniasis (vl), also called kala azar (ka) or black fever in india, claims around 20,000 lives every year. whole genome analysis presents an excellent means to identify new targets for drugs, vaccine and diagnostics development, and also provide an avenue into the biological basis of parasite virulence ...201323418454
low prevalence of leishmania donovani infection among the blood donors in kala-azar endemic areas of bangladesh.visceral leishmaniasis (vl) is a major public health problem in bangladesh with the highest disease burden in the mymensingh district. the disease is transmitted by sand fly bites, but it may also be transmitted through blood transfusions. no information is available about the prevalence of leishmania infection among blood donors in bangladesh; therefore we aimed to investigate this question.201323375008
an outbreak investigation of visceral leishmaniasis among residents of dharan town, eastern nepal, evidence for urban transmission of leishmania donovani.visceral leishmaniasis (vl) is a predominantly rural disease, common in the low lands of eastern nepal. since 1997 vl cases have also been reported among residents of the city of dharan. our main research objective was to find out whether there had been local transmission of vl inside the city.201323327548
analysis of kinetoplast cytochrome b gene of 16 leishmania isolates from different foci of china: different species of leishmania in china and their phylogenetic inference.leishmania species belong to the family trypanosomatidae and cause leishmaniasis, a geographically widespread disease that infects humans and other vertebrates. this disease remains endemic in china. due to the large geographic area and complex ecological environment, the taxonomic position and phylogenetic relationship of chinese leishmania isolates remain uncertain. a recent internal transcribed spacer 1 and cytochrome oxidase ii phylogeny of chinese leishmania isolates has challenged some asp ...201323383990
phlebotomus orientalis sand flies from two geographically distant ethiopian localities: biology, genetic analyses and susceptibility to leishmania donovani.phlebotomus orientalis parrot (diptera: psychodidae) is the main vector of visceral leishmaniasis (vl) caused by leishmania donovani in east africa. here we report on life cycle parameters and susceptibility to l. donovani of two p. orientalis colonies originating from different sites in ethiopia: a non-endemic site in the lowlands - melka werer (mw), and an endemic focus of human vl in the highlands - addis zemen (az).201323638207
attraction of ethiopian phlebotomine sand flies (diptera: psychodidae) to light and sugar-yeast mixtures (co(2)).visceral leishmaniasis (vl) known as kala-azar is a serious systemic disease caused by leishmania donovani parasites (trypanosomatidae: kinetoplastida). the disease is prevalent in the indian sub-continent, east africa and brazil. in africa, the worst affected regions are in sudan, with an estimated 15,000-20,000 cases annually and ethiopia with 5,000-7,000 cases a year. the main vector of vl in sudan and northern ethiopia is phlebotomus orientalis, a sand fly frequently found in association wit ...201324305038
sergentomyia schwetzi is not a competent vector for leishmania donovani and other leishmania species pathogenic to humans.sand fly species of the genus sergentomyia are proven vectors of reptilian leishmania that are non-pathogenic to humans. however, a consideration of the role of sergentomyia spp. in the circulation of mammalian leishmaniasis appears repeatedly in the literature and the possibility of leishmania transmission to humans remains unclear. here we studied the susceptibility of colonized sergentomyia schwetzi to leishmania donovani and two other leishmania species pathogenic to humans: l. infantum and ...201323786805
a new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies.visceral leishmaniasis (vl) is transmitted by sand flies. protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for vl.201323288926
evaluation of pcr procedures for detecting and quantifying leishmania donovani dna in large numbers of dried human blood samples from a visceral leishmaniasis focus in northern ethiopia.visceral leishmaniasis (vl) is a disseminated protozoan infection caused by leishmania donovani parasites which affects almost half a million persons annually. most of these are from the indian sub-continent, east africa and brazil. our study was designed to elucidate the role of symptomatic and asymptomatic leishmania donovani infected persons in the epidemiology of vl in northern ethiopia.201323530965
moving from unsequenced to sequenced genome: reanalysis of the proteome of leishmania donovani.the kinetoplastid protozoan parasite, leishmania donovani, is the causative agent of kala azar or visceral leishmaniasis. kala azar is a severe form of leishmaniasis that is fatal in the majority of untreated cases. studies on proteomic analysis of l. donovani thus far have been carried out using homology-based identification based on related leishmania species (l. infantum, l. major and l. braziliensis) whose genomes have been sequenced. recently, the genome of l. donovani was fully sequenced a ...201323665000
antimicrobial, antiparasitic, anti-inflammatory, and cytotoxic activities of lopezia racemosa.the present study investigates the potential benefits of the mexican medicinal plant lopezia racemosa (onagraceae). extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. aerial parts of the plant were extracted with various solvents and fractionated accordingly. extracts and fractions were tested against a panel of nine bacterial and four fungal species. the antiparasi ...201323843731
regulatory actions of toll-like receptor 2 (tlr2) and tlr4 in leishmania donovani infection in the liver.in livers of susceptible but self-curing c57bl/6 mice, intracellular leishmania donovani infection enhanced toll-like receptor 4 (tlr4) and tlr2 gene expression. in the liver, infected tlr4(-/-) mice showed reduced gamma interferon (ifn-γ), tumor necrosis factor (tnf), and inducible nitric oxide synthase (inos) mrna expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of ifn-γ to interleukin 10 (il ...201323589575
sialic acids siglec interaction: a unique strategy to circumvent innate immune response by pathogens.sialic acids (sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. sialic acid binding immunoglobulins (ig)-like lectins (siglecs) are generally expressed on various immune cells. they selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. many pathogens either synthesize or acquire sialic acids from the host. sialylated pathogens generally use siglecs to manipulate the host immune response. the ...201324434319
therapeutic options for visceral leishmaniasis.visceral leishmaniasis (vl), also known as kala-azar, is a disseminated protozoal infection caused principally by leishmania donovani and leishmania infantum (known as leishmania chagasi in south america). the therapeutic options for vl are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, hiv co-infection, malnourishment and other concomitant infections. this article provides an exhaustive review of the lit ...201324170666
an antileishmanial prenyloxy-naphthoquinone from roots of plumbago zeylanica.leishmania donovani, an obligate intracellular parasite of genus leishmania causes visceral leishmaniasis that affects millions of people worldwide, especially in the indian subcontinent and east africa. generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness but the growing incidence of their resistance has seriously hampered their use. this study discloses strong in vitro antileishmanial activity of 2-methyl-5 -(3'-methyl ...201322708724
animal reservoirs of visceral leishmaniasis in india.visceral leishmaniasis (vl) is a disease that has both zoonotic and anthroponotic etiologies. in india, vl is endemic, considered to be anthroponotic, and caused by leishmania donovani . anthroponotic diseases are maintained by transmission from human to human and to a lesser extent from human to animals. serum samples from 1,220 animals from 7 human vl endemic districts of bihar, india, were tested for antibodies to a recombinant kinetoplast antigen (rk39 antigen) present in amastigotes of visc ...201322765517
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