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identification, characterization, and expression of a unique secretory lipase from the human pathogen leishmania donovani.lipases have been implicated to be of importance in the life cycle development, virulence, and transmission of a variety of parasitic organisms. potential functions include the acquisition of host resources for energy metabolism and as simple building blocks for the synthesis of complex parasite lipids important for membrane remodeling and structural purposes. using a molecular approach, we identified and characterized the structure of an ldlip3-lipase gene from the primitive trypanosomatid path ...201020349119
amplification of adenine phosphoribosyltransferase suppresses the conditionally lethal growth and virulence phenotype of leishmania donovani mutants lacking both hypoxanthine-guanine and xanthine phosphoribosyltransferases.leishmania donovani cannot synthesize purines de novo and obligatorily scavenge purines from the host. previously, we described a conditional lethal deltahgprt/deltaxprt mutant of l. donovani (boitz, j. m., and ullman, b. (2006) j. biol. chem. 281, 16084-16089) that establishes that l. donovani salvages purines primarily through hypoxanthine-guanine phosphoribosyltransferase (hgprt) and xanthine phosphoribosyltransferase (xprt). unlike wild type l. donovani, the deltahgprt/deltaxprt knock-out ca ...201020363738
novel arylimidamides for treatment of visceral leishmaniasis.arylimidamides (aias) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [ic(50)], <1 microm) against both leishmania donovani axenic amastigotes and intracellular leishmania, the causative agent for human visceral leishmaniasis (vl). a systematic lead discovery program was employed to characterize in vitro and in vivo antileishmanial activities, pharmacokinetics, mutagenicities, and toxicities of two novel aias, db745 and db766. they we ...201020368397
synthesis and biological evaluation of new [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines against leishmania donovani.a series of [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines were synthesized and screened for their in vitro antileishmanial activity against leishmania donovani. among all, 8 compounds have shown more than 90% inhibition against promastigotes and ic50 in the range of 4.01-57.78 microm against amastigotes. compound 5, a triazino[5,6-b]indol-3-ylthio-1,3,5-triazine derivative was found to be the most active and least toxic with 20- & 10-fo ...201020371140
phlebotomus argentipes seasonal patterns in india and nepal.the current control of phebotomus argentipes (annandale and brunetti), the vector of leishmania donovani (laveran and mesnil), on the indian subcontinent is base on indoor residual spraying. the efficacy of this method depends, among other factors, on the timing and number of spraying rounds, which depend on the p. argentipes seasonality. to describe p. argentipes' seasonal patterns, six visceral leishmaniasis (vl) endemic villages, three in muzaffarpur and three in sunsari districts in india an ...201020380311
essential-oil composition, antileishmanial, and toxicity study of artemisia abyssinica and satureja punctata ssp. punctata from ethiopia.essential oils of artemisia abyssinica and satureja punctata ssp. punctata from ethiopia were analyzed by gc and gc/ms, and screened for leishmanicidal activity against promastigote and axenic amastigotes of leishmania donovani and l. aethiopica, including toxicity studies on human monocytic leukemia cells (thp-1) and erythrocytes in vitro. gc/ms of a. abyssinica oil revealed 67 compounds (99.94%) with the major constituents yomogi alcohol (38.47%), artemisyl acetate (24.88%), and artemisia alco ...201020397218
antiprotozoal, schistosomicidal, and antimicrobial activities of the essential oil from the leaves of baccharis dracunculifolia.baccharis dracunculifolia dc. (asteraceae), popularly known as 'alecrim do campo', is a native plant from brazil used in folk medicine as febrifuge, anti-inflammatory, antiseptic, and to treat skin sores. also, b. dracunculifolia is the most important plant source of the brazilian green propolis, which is recognized for its antiseptic and antiprotozoal activities. this study aimed at investigating the in vitro antiprotozoal, schistosomicidal, and antimicrobial activities of the essential oil fro ...201020397234
cd40 signaling in cd8+cd40+ t cells turns on contra-t regulatory cell functions.cd4(+) regulatory t cells (treg cells) mediate immunosuppression, whereas cd8(+) t cells confer resistance in many diseases. it is unknown whether cd8(+) t cells confer protection by antagonizing the treg cells. using a model of stage-specific immune responses against leishmania donovani infection in susceptible balb/c mice, we report that cd3(+)cd8(+)cd40(+) t cells executed cd40-dependent cytotoxicity on cd3(+)cd4(+)cd127(dim)gitr(+)cd25(+) treg cells during the initial phase of the infection ...201020400702
visceral leishmaniasis due to leishmania donovani in a patient with advanced hiv infection.an eritrean-born man observed over an extended period had upper gastrointestinal symptoms, fever, hepatosplenomegaly and pancytopenia in the setting of advanced hiv infection and poor adherence to antiretroviral therapy. despite thorough investigation, it was not until a repeat gastroscopic examination and gastric biopsy were performed 18 months after initial presentation that leishmania infection was diagnosed. the species was identified by polymerase chain reaction assay as l. donovani. physic ...201020402615
efficacy of artemisinin in experimental visceral leishmaniasis.visceral leishmaniasis (vl), caused by the protozoan leishmania sp., affects 500000 people annually, with the indian subcontinent contributing a significant proportion of these cases. emerging refractoriness to conventional antimony therapy has emphasised the need for safer yet effective antileishmanial drugs. artemisinin, a widely used antimalarial, demonstrated anti-promastigote activity and the 50% inhibitory concentration (ic(50)) ranged from 100 microm to 120 microm irrespective of leishman ...201020403680
phosphoproteome dynamics reveal heat-shock protein complexes specific to the leishmania donovani infectious stage.leishmania is exposed to a sudden increase in environmental temperature during the infectious cycle that triggers stage differentiation and adapts the parasite phenotype to intracellular survival in the mammalian host. the absence of classical promoter-dependent mechanisms of gene regulation and constitutive expression of most of the heat-shock proteins (hsps) in these human pathogens raise important unresolved questions as to regulation of the heat-shock response and stage-specific functions of ...201020404152
overexpression of histone h2a modulates drug susceptibility in leishmania parasites.resistance to antimonials has emerged as a major hurdle to the treatment and control of visceral leishmaniasis (vl), also know as kala-azar (ka), the disease caused by leishmania donovani, in india where >60% of ka patients are unresponsive to sodium antimony gluconate (sag) treatment. determinants of resistance in laboratory strains are partly known, however the mechanism operating in field isolates is not well understood. in microarray-based expression profiling with rna isolated from field is ...201020427152
chemistry, cytotoxicity and antileishmanial activity of the essential oil from piper auritum.leishmaniasis is one of the most important parasitic infections, but current treatments are unsatisfactory due to their toxicity, cost and resistance. therefore, the development of new antileishmanial compounds is imperative. many people who live in endemic areas use plants as an alternative to treat the disease. in this paper, we characterised the essential oil from piper auritum, evaluated its cytotoxicity and determined its antileishmanial activity. the chromatogram obtained by gas chromatogr ...201020428676
differential alterations in the activity of matrix metalloproteinases within the nervous tissue of dogs in distinct manifestations of visceral leishmaniasis.canine visceral leishmaniasis is an important emerging disease with a multitude of clinical symptoms, including neurological alterations. matrix metalloproteinases (mmp) are proteases implicated with the extracellular matrix remodelling and, within the central nervous system, these enzymes are involved with blood-brain-barrier disruption and inflammation. to establish the involvement of mmp-2 and -9 within the nervous tissue of dogs with spontaneous visceral leishmaniasis, fragments of nervous t ...201020430448
immune restoration disease associated with leishmania donovani infection following antiretroviral therapy for hiv infection.immune restoration disease following antiretroviral therapy for human immunodeficiency virus infection can cause significant morbidity and mortality. we describe the dramatic clinical course of an human immunodeficiency virus-infected patient who developed severe immune restoration disease associated with leishmania donovani infection in a non-endemic area of the world. it highlights the need to consider previous travel history when screening for opportunistic infections before starting antiretr ...201020434127
an outbreak of the desert sub-type of zoonotic visceral leishmaniasis in jiashi, xinjiang uygur autonomous region, people's republic of china.few outbreaks of the desert sub-type of zoonotic visceral leishmaniasis (vl) have been described worldwide. in 2008, the incidence rate of vl in jiashi county, xinjiang uygur autonomous region in the western part of the people's republic of china, increased more than twenty-folds compared to the average annual incidence rate. the majority of the cases (96.6%) occurred among <2 year-old infants. for the first time in the desert area of xinjiang, the parasites were isolated from bone marrow aspira ...201020434585
randomized, double-blind, comparative clinical trial on the efficacy and safety of intralesional sodium stibogluconate and intralesional 7% hypertonic sodium chloride against cutaneous leishmaniasis caused by l. donovani.since cutaneous leishmaniasis (cl) is a self healing disease, an ideal therapy should be rapidly effective, easily administered, cheap, available at all times at all centers and should have no side effects.201020438389
leishmania donovani complex (kinetoplastida, trypanosomatidae): comparison of deoxyribonucleic acid based techniques for typing of isolates from ethiopia.in ethiopia, visceral leishmaniasis (vl) is an increasing public health concern. recently, a new outbreak of vl claimed the lives of hundreds of ethiopians. mapping its distribution and the identification of the causative leishmania species is important for proper use of resources and for control planning. the choice of appropriate typing technique is the key for determining the infecting species. here we compared three deoxyribonucleic acid (dna) based markers. we used, for the first time, cpbe ...201020438727
almiramides a-c: discovery and development of a new class of leishmaniasis lead compounds.leishmaniasis is a debilitating disease caused by protozoan parasites of the genus leishmania, which affects an estimated 12 million people worldwide. the discovery of new lead compounds for leishmaniasis is therefore a pressing concern for global health programs. the organic extract of a panamanian collection of the marine cyanobacterium lyngbya majuscula showed strong in vitro activity in two complementary screens against the tropical parasite leishmania donovani, the causative agent of viscer ...201020441198
synthesis of 2-(pyrimidin-2-yl)-1-phenyl-2,3,4,9-tetrahydro-1h-beta-carbolines as antileishmanial agents.a series of 2-(pyrimidin-2-yl)-1-phenyl-2,3,4,9-tetrahydro-1h-beta-carboline derivatives has been synthesized and evaluated for antileishmanial activity against leishmania donovani. compound 8 exhibited best antileishmanial activity with ic(50) value of 1.93 microg/ml against amastigotes, high selectivity index, and was more active than reference drugs sodium stilbogluconate and pentamidine.201020457476
spatial analysis of leishmania donovani exposure in humans and domestic animals in a recent kala azar focus in nepal.summary: visceral leishmaniasis (vl) is a major public health problem in the indian subcontinent where the leishmania donovani transmission cycle is described as anthroponotic. however, the role of animals (in particular domestic animals) in the persistence and expansion of vl is still a matter of debate. we combined direct agglutination test (dat) results in humans and domestic animals with geographic information system technology (i.e. extraction maps and scan statistic) to evaluate the exposu ...201020459877
a chronic mutilating rhinopathy with a delayed diagnosis of mucocutaneous leishmaniasis.mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin and mucosal lesions. mucocutaneous leishmaniasis is very rare in india and to our knowledge, only two cases have been reported, and this is the first case of mucocutaneous leishmaniasis presenting with mutilating rhinopathy reported from the indian subcontinent.201020465699
the epidemiology of leishmania donovani infection in high transmission foci in india.visceral leishmaniasis (vl) is highly prevalent in bihar, india. india and its neighbours aim at eliminating vl, but several knowledge gaps in the epidemiology of vl may hamper that effort. the prevalence of asymptomatic infections with leishmania donovani and their role in transmission dynamics are not well understood. we report data from a sero-survey in bihar.201020487420
epidemiology of leishmania donovani infection in high-transmission foci in nepal.nepal reports a visceral leishmaniasis (vl) incidence of 5 per 10 000 per year on the basis of notification by health facilities, but little community-based epidemiological information exists. we report data on prevalence rates of leishmania donovani infection in ten communities in east nepal.201020487421
sensitivity and specificity of the leishmania oligoc-test and nasba-oligochromatography for diagnosis of visceral leishmaniasis in kenya.to estimate the sensitivity and specificity of the oligoc-test and nucleic acid sequence-based amplification coupled to oligochromatography (nasba-oc) for molecular detection of leishmania in blood from patients with confirmed visceral leishmaniasis (vl) and healthy endemic controls from kenya.201020487428
accordance and concordance of pcr and nasba followed by oligochromatography for the molecular diagnosis of trypanosoma brucei and leishmania.to evaluate the repeatability and reproducibility of four simplified molecular assays for the diagnosis of trypanosoma brucei spp. or leishmania ssp. in a multicentre ring trial with seven participating laboratories.201020487429
cpg oligodeoxynucleotide augments the antileishmanial activity of miltefosine against experimental visceral leishmaniasis.to evaluate the combination of cpg oligodeoxynucleotide (cpg odn) and miltefosine for the treatment of experimental visceral leishmaniasis (vl).201020495208
in vitro and in vivo antileishmanial efficacy of nitazoxanide against leishmania donovani.control of leishmania infection relies primarily on chemotherapy, and the current drug available for treating leishmaniasis is limited. nitazoxanide (ntz) is a broad spectrum antiparasitic agent with activity against protozoa, nematodes, cestodes, and trematodes. in the present study, the in vitro antileishmanial efficacy of ntz was evaluated by incubation of leishmania donovani promastigotes with ntz, indicating that ntz can affect the ultrastructure of parasite promastigote and efficiently inh ...201020495931
leishmania parasitophorous vacuoles interact continuously with the host cell's endoplasmic reticulum; parasitophorous vacuoles are hybrid compartments.macrophages that express representative endoplasmic reticulum (er) molecules tagged with green fluorescence protein were generated to assess the recruitment of er molecules to leishmania parasitophorous vacuoles (pvs). more than 90% of pvs harbouring leishmania pifanoi or leishmania donovani parasites recruited calnexin, to their pv membrane. an equivalent proportion of pvs also recruited the membrane-associated soluble n-ethylmaleimide-sensitive factor attachment protein receptors (snares), sec ...201020497181
localization and induction of the a2 virulence factor in leishmania: evidence that a2 is a stress response protein.leishmaniasis is a vector-borne infectious disease with a wide range of pathologies depending on the species of leishmania. leishmania parasites are transmitted by the sand fly vector as promastigotes; within the mammalian host, leishmania parasites differentiate into amastigotes and replicate in macrophages. the a2 protein from leishmania donovani is expressed predominantly in amastigotes and therefore likely plays a role in survival in the mammalian host. in the present study, we have determin ...201020497497
diagnosis of visceral leishmaniasis by polymerase chain reaction of dna extracted from giemsa's solution-stained slides.visceral leishmaniasis (vl) is caused by the protozoan parasite leishmania donovani and is a potentially fatal disease in endemic areas of the world. nepal is an endemic area in which vl causes major public health problems in the lowland areas of the southeast regions. the aim of the present study was to evaluate the sensitivity of polymerase chain reaction (pcr) amplification for the detection of leishmania dna from giemsa's solution-stained bone marrow slides. bone marrow samples were aspirate ...201020499093
arabinosylated lipoarabinomannan-mediated protection in visceral leishmaniasis through up-regulation of toll-like receptor 2 signaling: an immunoprophylactic approach.visceral leishmaniasis is characterized by severe immunosuppression of the host cell, resulting in loss of the proinflammatory response. toll-like receptor 2 (tlr2) is involved in myriad disease forms, including visceral leishmaniasis. during leishmania donovani infection, the parasite modulates tlr2 to suppress interleukin 12 production, indicating the possible involvement of tlr2 in regulation of the immune response against l. donovani infection. arabinosylated lipoarabinomannan (ara-lam) poss ...201020500089
leishmania donovani isolates with antimony-resistant but not -sensitive phenotype inhibit sodium antimony gluconate-induced dendritic cell activation.the inability of sodium antimony gluconate (sag)-unresponsive kala-azar patients to clear leishmania donovani (ld) infection despite sag therapy is partly due to an ill-defined immune-dysfunction. since dendritic cells (dcs) typically initiate anti-leishmanial immunity, a role for dcs in aberrant ld clearance was investigated. accordingly, regulation of sag-induced activation of murine dcs following infection with ld isolates exhibiting two distinct phenotypes such as antimony-resistant (sb(r)ld ...201020502630
histopathological and parasitological investigations of ear healthy skin of dogs naturally and experimentally infected with leishmania (leishmania) chagasi.although 90% of clinical cases of american visceral leishmaniasis (avl) occur in the northeastern region of brazil, the incidence of cases in recent years has increased in southeastern states such as minas gerais (mg), where the disease has been reported in several cities, including belo horizonte, the state capital. some studies have shown a strong correlation between the incidence of avl and canine visceral leishmaniasis (cvl) in belo horizonte. a study of 108 dogs with parasite leishmania cha ...201020503176
influence of topography on the endemicity of kala-azar: a study based on remote sensing and geographical information system.kala-azar, a fatal infectious disease in many indian states, particularly in bihar, west bengal, uttar pradesh, and jharkhand, is caused by the protozoan parasite leishmania donovani and transmitted by the sandfly vector phlebotomus argentipes. the vector is distributed all over the country but the disease is confined to particular zones since before the last century. in this study, parameters such as altitude, temperature, humidity, rainfall and the normalized difference vegetation index (ndvi) ...201020503185
clinical and epidemiological studies on the cutaneous leishmaniasis caused by leishmania (leishmania) donovani in sri lanka.sri lanka is the newest reported focus of human leishmaniasis within the indian subcontinent. over the last 8 years, more than 2000 cases of cutaneous leishmaniasis (cl), apparently caused by leishmania donovani (a species usually associated with the visceral form of the disease), have been passively identified in the country. the clinical profiles of 401 suspected cases of cl in sri lanka were recently explored and some of the cases' immunological responses were investigated, in antibody-detect ...201020507695
molecular docking, structure-activity relationship and biological evaluation of the anticancer drug monastrol as a pteridine reductase inhibitor in a clinical isolate of leishmania donovani.using the pteridine reductase (ptr1) enzyme of leishmania as the target, the objective of our study was to find a drug candidate that can enter the clinical development process after being evaluated for safety and efficacy in animals.201020519355
cd40 expression levels modulate regulatory t cells in leishmania donovani infection.dendritic cell (dc)-expressed cd40 is shown to play crucial roles in eliciting effector t cell responses, primarily the proinflammatory cd4(+) th subsets and cytotoxic cd8(+) t cells that eliminate various infections and tumors, respectively. in contrast, dcs are also implied in the generation of regulatory t cells (tregs) that counteract the functions of the proinflammatory th subsets and exacerbate infections. however, the role of dc-expressed cd40 in the generation of tregs is unknown. in thi ...201020525887
sero-epidemiological study of visceral leishmaniasis in basrah, southern iraq.to study selected epidemiological aspects of visceral leishmaniasis, assess direct agglutination test (dat) as a diagnostic method and the sero-epidemiological prevalence of the disease among apparently healthy children in basrah, iraq.201020527645
use of miltefosine in the treatment of visceral leishmaniasis in children at a tertiary care hospital of karachi.existing standard treatment options for visceral leishmaniasis are less than optimal. we report here the use of oral miltefosine in the treatment of two paediatric cases of visceral leishmaniasis at a tertiary care hospital in karachi, pakistan. one patient came from balochistan while the second patient was from northern pakistan. both presented with a prolonged history of fever, massive hepatosplenomegaly, anaemia and thrombocytopenia. visceral leishmaniasis was diagnosed with bone marrow studi ...201020527651
co-infection of mucosal leishmaniasis and extra pulmonary tuberculosis in a patient with inherent immune deficiency.in sri lanka, cutaneous leishmaniasis is a well-established disease caused by leishmania donovani. only a few cases of visceral disease and mucosal localization have been reported to date.201020534090
immunostimulatory properties of dendritic cells after leishmania donovani infection using an in vitro model of liver microenvironment.recent advances demonstrated that liver dendritic cells (dcs) promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. although there has been significant work on the phenotypic and functional roles of such dcs, the impact of liver microenvironment on the immune properties of infected dc is still poorly explored, probably because of the limitations of modelization.201020544029
visceral leishmaniasis: adult population of abbottabad at risk now.leishmaniasis is a disease complex caused by the parasite of genus leishmania. visceral leishmaniasis is caused by leishmania donovani transmitted to human by sand fly. some wild animals and human reservoir is the major reservoir in most of the cases. the disease is prevalent in different parts of the world including india, nepal, bangladesh, sudan and brazil. it has also been reported from northern half of pakistan. in hazara division, it has been reported from galiat, battagram, kaladhaka, koh ...201021702307
adaptive immunity against leishmania nucleoside hydrolase maps its c-terminal domain as the target of the cd4+ t cell-driven protective response.nucleoside hydrolases (nhs) show homology among parasite protozoa, fungi and bacteria. they are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. immune protection against nhs would prevent disease at the early infection of several pathogens. we have identified the domain of the nh of l. donovani (nh36) responsible for its immunogenicity and protective efficacy against murine visceral lei ...201021085470
leishmania major survival in selective phlebotomus papatasi sand fly vector requires a specific scg-encoded lipophosphoglycan galactosylation pattern.phlebotomine sand flies that transmit the protozoan parasite leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. in "selective" sand flies, leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (lpg), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (pg ...201021085609
valeriana wallichii root extracts and fractions with activity against leishmania spp.leishmanial diseases, posing a public health problem worldwide, are caused by leishmania parasites with a dimorphic life cycle alternating between the promastigote and amastigote forms. promastigotes transmitted by the vector are transformed into amastigotes residing in the host tissue macrophages. presently, new antiparasitic agents are needed against leishmania donovani and leishmania major, the respective organisms causing visceral and cutaneous leishmaniasis, since the available treatments a ...201021085992
inference of population structure of leishmania donovani strains isolated from different ethiopian visceral leishmaniasis endemic areas.parasites' evolution in response to parasite-targeted control strategies, such as vaccines and drugs, is known to be influenced by their population genetic structure. the aim of this study was to describe the population structure of ethiopian strains of leishmania donovani derived from different areas endemic for visceral leishmaniasis (vl) as a prerequisite for the design of effective control strategies against the disease.201021103373
in silico screening, structure-activity relationship, and biologic evaluation of selective pteridine reductase inhibitors targeting visceral leishmaniasis.in this study we utilized the concept of rational drug design to identify novel compounds with optimal selectivity, efficacy and safety, which would bind to the target enzyme pteridine reductase 1 (ptr1) in leishmania parasites. twelve compounds afforded from baylis-hillman chemistry were docked by using the quantum program into the active site of leishmania donovani ptr1 homology model. the biological activity for these compounds was estimated in green fluorescent protein-transfected l. donovan ...201021115787
post-kala-azar dermal leishmaniasis--an overview.post-kala-azar dermal leishmaniasis (pkdl) is a dermal sequela of visceral leishmaniasis (vl), reported mainly from two regions - sudan in eastern africa and the indian subcontinent, with incidences of 50-60% and 5-10%, respectively. importantly, patients with pkdl are considered as reservoirs of vl, linking its eradication to effective control of pkdl. the etiopathogenesis of pkdl is presumably due to an immunological assault on latent dermal parasites. immunological markers include il-10, whos ...201021128917
first total synthesis and antileishmanial activity of (z)-16-methyl-11-heptadecenoic acid, a new marine fatty acid from the sponge dragmaxia undata.the first total synthesis for the (z)-16-methyl-11-heptadecenoic acid, a novel fatty acid from the sponge dragmaxia undata, was accomplished in seven steps and in a 44% overall yield. the use of (trimethylsilyl)acetylene was key in the synthesis. based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 10-bromo-1-decanol followed by a second acetylide coupling ...201021129369
in vitro and in vivo prophylactic and curative activity of the triterpene saponin px-6518 against cutaneous leishmania species.the oleanane triterpene saponin px-6518, with known potent in vitro and in vivo activity against leishmania donovani, was investigated for its spectrum against the cutaneous species leishmania mexicana, leishmania panamensis and leishmania major.201021131319
validation of a leishmania infantum elisa rapid test for serological diagnosis of leishmania chagasi in dogs.canine visceral leishmaniasis (cvl) is caused by leishmania donovani complex parasites including l. donovani, leishmania infantum and leishmania chagasi. as some studies suggest that l. chagasi and l. infantum may be very similar or even the same species, the aim of the present study was to evaluate a commercial rapid elisa test, originally designed for l. infantum, in the diagnosis of cvl in dogs naturally infected by l. chagasi. a total of 400 serum canine samples, including 283 positive dogs ...201021030153
visceral leishmaniasis mimicking lymphoproliferative disease. 201021037515
antimicrobial, antimalarial, and antileishmanial activities of mono- and bis-quaternary pyridinium compounds.pyridinium-based oxime compounds have been utilized worldwide as antidotes following exposure to anticholinesterase agents. in the event of combined chemical and biological incident, it is of vital importance to know the ability of antidotes to provide additional protection against biological threats. this paper reports results of in vitro antimicrobial and antiprotozoal activities of a series of quaternary pyridinium oximes against a number of lower pathogenicity bsl-1 and 2 agents. in general, ...201021040494
[leishmaniasis isolated to the larynx as cause of chronic laryngitis].mucosal leishmaniasis is uncommon outside central and south america, where it is commonly caused by leishmania (l.) braziliensis. we present a case of isolated laryngeal leishmaniasis detected in a 78-year-old male, who presented with chronic hoarseness. histologic examination of biopsies taken from the larynx showed l. amastigotes. an l.-specific indirect fluorescent antibody test was positive. polymerase chain reaction showed infection with l. donovani, l. infantum or l. tropica, species which ...201021040662
antileishmanial phenylpropanoids from alpinia galanga (linn.) willd.hexane, chloroform and ethyl acetate extracts (100 microg/ml) of alpinia galanga rhizomes exhibited significant activity in vitro against promastigotes of l. donovani. twelve compounds namely, methyleugenol (1), p-coumaryl diacetate (2), 1'-acetoxychavicol acetate (3), 1'-acetoxyeugenol acetate (4), trans-p-acetoxycinnamyl alcohol (5), trans-3,4-dimethoxycinnamyl alcohol (6), p-hydroxybenzaldehyde (7), p-hydroxycinnamaldehyde (8), trans-p-coumaryl alcohol (9), galangin (10), trans-p-coumaric aci ...201021046987
insecticide susceptibility of phlebotomus argentipes in visceral leishmaniasis endemic districts in india and nepal.to investigate the ddt and deltamethrin susceptibility of phlebotomus argentipes, the vector of leishmania donovani, responsible for visceral leishmaniasis (vl), in two countries (india and nepal) with different histories of insecticide exposure.201021049013
geographical variation in the response of visceral leishmaniasis to paromomycin in east africa: a multicentre, open-label, randomized trial.visceral leishmaniasis (vl) is a major health problem in developing countries. the untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. improved treatment options are needed. paromomycin was shown to be an efficacious first-line treatment with low toxicity in india.201021049059
paromomycin for the treatment of visceral leishmaniasis in sudan: a randomized, open-label, dose-finding study.a recent study has shown that treatment of visceral leishmaniasis (vl) with the standard dose of 15 mg/kg/day of paromomycin sulphate (pm) for 21 days was not efficacious in patients in sudan. we therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.201021049063
a rapid, efficient and economical method for generating leishmanial gene targeting constructs.targeted gene replacement is a powerful tool in leishmania genetics that can be time-consuming to implement. one tedious aspect that delays progress is the multi-step construction of gene targeting vectors. to accelerate this process, we developed a streamlined method that allows the assembly of a complete targeting vector from all its constituent parts in a single-step multi-fragment ligation. the individual components to be assembled are flanked by sites for the restriction endonuclease sfii t ...201021055426
leishmania donovani: assessment of leishmanicidal effects of herbal extracts obtained from plants in the visceral leishmaniasis endemic area of bihar, india.one obstacle faced in the effective control of visceral leishmaniasis (vl) is the limited number of available treatment options. furthermore, control efforts have been hindered further by the emergence of leishmania resistance to many of the available drugs. in this study, we investigated the anti-leishmanial properties of 30 medicinally important plants from the vl endemic area of bihar, india and compared them to two available anti-leishmanial drugs (sodium antimony gluconate and amphotericin ...201021070771
antileishmanial activity of benzocycloalkyl azole oximino ethers: the conformationally constraint analogues of oxiconazole.antileishmanial activities of 16 synthetic oximino benzocycloalkyl azoles against leishmania donovani were evaluated in vitro against extracellular promastigotes and intracellular amastigotes. based on si (selectivity index), five compounds were tested further in vivo in hamster model. out of these, three compounds have shown medium activity (53-58%) and one has shown significant inhibition of parasite multiplication (70%). despite the fact that these compounds were better than the existing anti ...201021078278
interferon regulatory factor 7 contributes to the control of leishmania donovani in the mouse liver.optimal hepatic resistance to leishmania donovani in mice requires the coordinated effort of a variety of leukocyte populations that together induce activation of local macrophages to a leishmanicidal state. although nitric oxide and reactive oxygen intermediates are potent leishmanicidal effector molecules operating in the acquired phase of immunity, there have long been suggestions that other mechanisms of leishmanicidal activity exist. we recently discovered that irf-7 regulates a novel innat ...201021149596
metabolomics to unveil and understand phenotypic diversity between pathogen populations.leishmaniasis is a debilitating disease caused by the parasite leishmania. there is extensive clinical polymorphism, including variable responsiveness to treatment. we study leishmania donovani parasites isolated from visceral leishmaniasis patients in nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for l. donovani t ...201021152055
monitoring of intracellular nitric oxide in leishmaniasis: its applicability in patients with visceral leishmaniasis.nitric oxide (no) has been demonstrated to be a principal effector molecule responsible for mediating intracellular killing of leishmania parasites, the causative organism of leishmaniasis. as measurement of intracellular no remains a challenge to biologists, we have developed a flow cytometric approach to perform real time biological detection of no within leishmania parasites and parasitized macrophages using a membrane permeable derivative of diaminofluorescein [4,5-diaminofluorescein diaceta ...201021154977
complete structural assignment of serratol, a cembrane-type diterpene from boswellia serrata, and evaluation of its antiprotozoal activity.from the dichloromethane extract obtained from the gum resin of boswellia serrata roxb. (burseraceae), a well-known medicinal plant resin ("indian olibanum"), the cembrane-type diterpene serratol was isolated in high yield. its structure, previously reported without clear specification of double-bond geometry and without specification of stereochemistry, was reanalysed by means of spectroscopic measurements and unambiguously assigned as s(-)-cembra-3 e,7 e,11 e-triene-1-ol. full assignment of al ...201021157686
persistence of leishmania donovani antibodies in past visceral leishmaniasis cases in india.the persistence of anti-leishmania donovani antibodies in past visceral leishmaniasis (vl) cases was retrospectively assessed by means of the direct agglutination test (dat) and the rk39 enzyme-linked immunosorbent assay (elisa). antibody titers remained high for an extended period of time in past cases of vl. these results highlight the need to carefully elicit the history of patients with vl symptoms.201021159922
lysine transporters in human trypanosomatid pathogens.in previous studies we characterized arginine transporter genes from trypanosoma cruzi and leishmania donovani, the etiological agents of chagas disease and kala azar, respectively, both fatal diseases in humans. unlike arginine transporters in higher eukaryotes that transport also lysine, these parasite transporters translocate only arginine. this phenomenon prompted us to identify and characterize parasite lysine transporters. here we demonstrate that ldaap7 and tcaap7 encode lysine-specific p ...201021170560
activity and turnover of eosinophil and neutrophil granulocytes are altered in visceral leishmaniasis.visceral leishmaniasis (vl) is a health issue in sudan. our aim was to investigate the involvement of eosinophils and neutrophils in vl by serum and plasma measurements of eosinophil cationic protein (ecp) and myeloperoxidase (mpo) and some key cytokines and chemokines. blood was collected from 125 vl patients and 181 healthy sudanese controls from the same rural area. results showed reduced eosinophil and neutrophil counts in the vl group (p=0.0001 and p=0.002, respectively). serum-ecp levels w ...201021172349
synthesis and antiprotozoal activity of n-alkoxy analogues of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine with improved human blood-brain barrier permeability.to improve the blood-brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five n-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and n-alkoxy-n-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). this involved: (a) formation of a thiourea intermediate, (b) removal of the amine protecting groups, and (c) intramolecular cyclization. the blood-brain ...201021175162
the first total synthesis of the (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid and related analogs with antileishmanial activity.the first total synthesis of the marine cyclopropane fatty acid (±)-17-methyltrans- 4,5-methyleneoctadecanoic acid was accomplished in 8 steps and in 9.1% overall yield starting from 1-bromo-12-methyltridecane. the cis analog (±)-17- methyl-cis-4,5-methyleneoctadecanoic acid was also synthesized but in 7 steps and in 16.4% overall yield. with the two isomeric cyclopropane fatty acids at hand it was possible to unequivocally corroborate the trans relative configuration of the naturally occurring ...201021218160
andrographolide nanoparticles in leishmaniasis: characterization and in vitro evaluations.andrographolide (ag) is a diterpenoid lactone isolated from the leaves of andrographis paniculata. ag is a potent and low-toxicity antileishmanial agent. chemotherapy applications of ag are, however, seriously constrained because of poor bioavailability, short plasma half-life, and inappropriate tissue localization. nanoparticulation of ag was therefore envisaged as a possible solution. ag nanoparticles (agnp) loaded in 50:50 poly(dl-lactide-co-glycolic acid) were prepared for delivery into the ...201021270962
antileishmanial activity of drug infused mini-agar plates on leishmania donovani promastigotes.drug infused mini agar plates were found to be a better alternative of broth dilution method in the determination of antileishmanial susceptibility of two commonly used drugs, sodium antimony gluconate and amphotericin b against leishmania donovani promastigotes. these two drugs were used here as models for antileishmanial compounds. the stability of the drugs in the stored agar plates was also tested for six months and found that they were same as fresh plates. determination of antileishmanial ...201021399608
serological markers for leishmania donovani infection in nepal: agreement between direct agglutination test and rk39 elisa.visceral leishmaniasis (vl) is an important vector-borne disease caused by leishmania donovani in the indian subcontinent. the actual incidence and role of asymptomatic infections in the region are not wellknown. we used the direct agglutination test (dat) and the rk39 elisa as l. donovani infection markers in 10 vl endemic villages in nepal. dat titre distribution showed two subgroups in the population (infected and non-infected individuals), while rk39 did not. the agreement between both tests ...201021998875
hematologic changes in visceral leishmaniasis/kala azar.visceral leishmaniasis (vl) or kala azar is a chronic infectious disease caused by parasites of the leishmania donovani complex that can cause various hematologic manifestations. it is characterized by fever, enlargement of liver and spleen, weight loss, pancytopenia and hypergammaglobinemia. it is endemic in the indian subcontinent, mainly seen in the states of bihar and west bengal. patients with vl can present to the haematologist for various haematological problems prior to receiving the dia ...201021886387
[acquisition and analysis of lipophosphoglycan 1 gene and the noncoding region of leishmania donovani isolates from hilly foci of china].a fragment about 2.2 kb located at upstream of lipophosphoglycan 1 (lpg1) gene of leishmania donovani isolate from hilly foci of china was obtained by pcr. the nucleotide sequence of the fragment was determined by sequencing. the sequence of the lpg1 gene and its downstream fragment (about 2 kb) was determined by using genome walking method. the above two fragment splicing result showed that the nucleotide sequence of the lpg1 gene with the noncoding region was 4 121 bp (genbank accession number ...201021500538
oral putrescine restores virulence of ornithine decarboxylase-deficient leishmania donovani in mice.administration of putrescine as a 1% solution in the drinking water ameliorated the profound loss of virulence exhibited by ornithine decarboxylase (odc) deficient leishmania donovani in mice. furthermore, supplying α-difluoromethylornithine, an odc inhibitor, at 2% in the drinking water reduced but did not eliminate infection with wild type l. donovani in the mouse model. taken collectively, these findings: (1) demonstrate that oral putrescine can access the phagolysosome of macrophages in whic ...201021182873
atp independent type ib topoisomerase of leishmania donovani is stimulated by atp: an insight into the functional mechanism.most type ib topoisomerases do not require atp and mg(2+) for activity. however, as shown previously for vaccinia topoisomerase i, we demonstrate that atp stimulates the relaxation activity of the unusual heterodimeric type ib topoisomerase from leishmania donovani (ldtop1l/s) in the absence of mg(2+). the stimulation is independent of atp hydrolysis but requires salt as a co-activator. atp binds to ldtop1l/s and increases its rate of strand rotation. docking studies indicate that the amino acid ...201021186185
prevention of leishmania donovani infection. 201021190964
longlasting insecticidal nets for prevention of leishmania donovani infection in india and nepal: paired cluster randomised trial.to test the effectiveness of large scale distribution of longlasting nets treated with insecticide in reducing the incidence of visceral leishmaniasis in india and nepal.201021190965
structure of recombinant leishmania donovani pteridine reductase reveals a disordered active site.pteridine reductase (ptr1) is a potential target for drug development against parasitic trypanosoma and leishmania species, protozoa that are responsible for a range of serious diseases found in tropical and subtropical parts of the world. as part of a structure-based approach to inhibitor development, specifically targeting leishmania species, well ordered crystals of l. donovani ptr1 were sought to support the characterization of complexes formed with inhibitors. an efficient system for recomb ...201021206018
post-transcriptional repair of a split heat shock protein 90 gene by mrna trans-splicing.heat shock protein 90 participates in diverse biological processes ranging from protein folding, cell cycle, signal transduction and development to evolution in all eukaryotes. it is also critically involved in regulating growth of protozoa such as dictyostelium discoideum, leishmania donovani, plasmodium falciparum, trypanosoma cruzi, and trypanosoma evansi. selective inhibition of hsp90 has also been explored as an intervention strategy against important human diseases such as cancer, malaria, ...201121209094
antileishmanial efficacy of fluconazole and miltefosine in combination with an immunomodulator--picroliv.the chemotherapy of visceral leishmaniasis (vl) has several limitations including resistance and toxicity of the existing drugs. downregulation of immune system further aggravates the problems. to combat this situation, leishmanicidal efficacy of already marketed standard antifungal drug, fluconazole under the approach of "therapeutic switching" in combination with standard antileishmanial drug, miltefosine, and a potent immunomodulator agent, picroliv, were evaluated in hamsters infected with l ...201121212980
quantitative proteome profiling informs on phenotypic traits that adapt leishmania donovani for axenic and intracellular proliferation.protozoan parasites of the genus leishmania are important human pathogens that differentiate inside host macrophages into an amastigote life cycle stage. although this stage causes the pathogenesis of leishmaniasis, only few proteins have been implicated in amastigote intracellular survival. here we compare morphology, infectivity and protein expression of l. donovani ld1s grown in host free (axenic) culture, or exclusively propagated in infected hamsters, with the aim to reveal parasite traits ...201121501362
imaging host cell-leishmania interaction dynamics implicates parasite motility, lysosome recruitment, and host cell wounding in the infection process.leishmania donovani causes human visceral leishmaniasis. the parasite infectious cycle comprises extracellular flagellated promastigotes that proliferate inside the insect vector, and intracellular nonmotile amastigotes that multiply within infected host cells. using primary macrophages infected with virulent metacyclic promastigotes and high spatiotemporal resolution microscopy, we dissect the dynamics of the early infection process. we find that motile promastigotes enter macrophages in a pola ...201121501831
identification and characterization of genes involved in leishmania pathogenesis: the potential for drug target selection.identifying and characterizing leishmania donovani genes and the proteins they encode for their role in pathogenesis can reveal the value of this approach for finding new drug targets. effective drug targets are likely to be proteins differentially expressed or required in the amastigote life cycle stage found in the patient. several examples and their potential for chemotherapeutic disruption are presented. a pathway nearly ubiquitous in living cells targeted by anticancer drugs, the ubiquitin ...201122091403
cyp5122a1, a novel cytochrome p450 is essential for survival of leishmania donovani.cytochrome p450s (cyp450s) are hemoproteins catalysing diverse biochemical reactions important for metabolism of xenobiotics and synthesis of physiologically important compounds such as sterols. therefore, they are functionally important for survival of invading pathogens. one such opportunistic pathogen leishmania donovani causes visceral leishmaniasis worldwide, which is an important public health problem due to significant disease burden. the parasite genome database, gene db, annotates 3 cyp ...201121966477
structure and in vitro antiparasitic activity of constituents of citropsis articulata root bark.from the results of an ethnomedicinal investigation of plants from uganda with antimalarial activity, citropsis articulata was selected because of the antiplasmodial effect of an ethyl acetate extract of its root bark. thus, from the cyclohexane, ethyl acetate, and methanol extracts, two new heterocyclic compounds, omubioside (1) and katimborine (2), were isolated in addition to five known coumarins (rutarin (3), seselin (4), suberosin (5), demethylsuberosin (6), and haploperoside (7)), two know ...201121985060
diagnosis of visceral leishmaniasis: developments over the last decade.diagnostic parameters for visceral leishmaniasis (vl), a potentially fatal parasitic disease caused by leishmania donovani, have been redefined in the last decade with the development of serological and molecular tests, though a definitive diagnosis still banks on the century-old parasitological methods in many areas. recombinant antigens have improved performance of serodiagnostic methods. serology-based tests, rk39 antigen dipstick, and direct agglutination test commonly employed in the field ...201122065060
the histone h4 lysine 14 acetylation in leishmania donovani is mediated by the myst family protein hat4.post-translational modifications (ptms) of histones regulate almost all facets of dna metabolism in eukaryotes, such as replication, repair, transcription and chromatin condensation. while histone ptms have been exhaustively examined in yeast and higher eukaryotes, less is known of their functional consequences in trypanosomatids. trypanosome histones are highly divergent from other eukaryotes, and specific ptms have been identified in histones of trypanosoma species. the characterization of thr ...201122016570
effect of pam3cys induced protection on the therapeutic efficacy of miltefosine against experimental visceral leishmaniasis.prophylactic potential of synthetic bacterial lipopeptide and a tlr2 agonist, pam3cys was first evaluated against experimental visceral leishmaniasis in rodent model. after establishing the potential its effect on therapeutic efficacy of miltefosine was also studied. pam3cys showed 74.64% inhibition in parasitic establishment when administered by ip route at a dose of 100 μg/animal spaced at two weeks, i.e. on day -7 and +7 of challenge with leishmania donovani amastigotes. however, when aforesa ...201121959258
multilocus genotyping reveals a polyphyletic pattern among naturally antimony-resistant leishmania braziliensis isolates from peru.in order to understand the epidemiological dynamics of antimonial (sb(v)) resistance in zoonotic tegumentary leishmaniasis and its link with treatment outcome, we analyzed the population structure of 24 peruvian leishmania braziliensis clinical isolates with known in vitro antimony susceptibility and clinical phenotype by multilocus microsatellite typing (14 microsatellite loci). the genetic variability in the peruvian isolates was high and the multilocus genotypes were strongly differentiated f ...201121871584
identification of novel inhibitors of dipeptidylcarboxypeptidase of leishmania donovani via ligand-based virtual screening and biological evaluation.current treatment of leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations, such as high cost, toxicity, and lack of efficacy in endemic regions. therefore, development of new, effective, and affordable anti-leishmanial drugs is a global health priority. dipeptidylcarboxypeptidase has been characterized and established as a drug target for antileishmanial drug discovery. we virtually screened a large chemical library of 15 452 compounds against a 3d ...201122014034
acute renal injury as a result of liposomal amphotericin b treatment in sodium stibogluconate unresponsive visceral leishmaniasis.abstract. we report an unusual case of visceral leishmaniasis occurring in a patient from sichuan china. the patient presented with a remitting fever, anemia, and pancytopenia. the case was confirmed as visceral leishmaniasis by microscopical detection of the leishmania species amastigote in bone marrow aspirate. the patient was treated with 10 mg/kg/day of sodium stibogluconate for 5 days, with no therapeutic response. as a result, the patient was treated with liposomal amphotericin b (lab) at ...201122144439
bone marrow leishmaniasis: a review of situation in thailand.leishmaniasis is an important tropical vector-borne disease. this infection can be seen in tropical area and it is considered to be one of the most important vector-borne infections at present. the general situation of the leishmaniasis in thailand is hereby reviewed. although thailand is a tropical country, the leishmaniasis is not endemic but sporadic. the imported cases are documented in some literatures. the serious form of leishmaniasis, the visceral leishmaniasis is also detectable in thai ...201122014727
a possible role for phlebotmus (anaphlebotmous) rodhaini (parrot 1930) in transmission of leishmania donovani.abstract: background: visceral leishmaniasis (vl, kala azar), caused by leishmania donovani is a major health problem in sudan and other east african countries. in this region the only proven vectors of l. donovani are phlebotomus orientalis in eastern sudan, ethiopia and upper nile areas of southern sudan and phlebotomus martini in ethiopia, kenya and southern sudan. in this report, we present the first evidence that phlebotomus rodhaini may also play a role in maintaining transmission of l. d ...201122188864
in vitro antileishmanial and antitrypanosomal activities of five medicinal plants from burkina faso.after ethnobotanical surveys in central and western regions of burkina faso, five plants namely lantana ukambensis (verbenaceae), xeoderris sthulmannii (fabaceae), parinari curatellifollia (chrysobalanaceae), ozoroa insignis (anacardiaceae), and ficus platyphylla (moraceae) were selected for their traditional use in the treatment of parasitic diseases and cancer. our previous studies have focused on the phytochemical, genotoxicity, antioxidant, and antiproliferative activities of these plants. i ...201122037827
enrichment of invariant natural killer t cells in the bone marrow of visceral leishmaniasis patients.lipid antigens of leishmania donovani like lipophosphoglycans are shown as a potent ligand for the activation of invariant natural killer t (inkt) cells. it is reported that activation of inkt cells augments the disease pathology in experimental visceral leishmaniasis (vl). in this study, we demonstrate the enrichment of inkt cells in the bone marrow, one of the disease sites among patients with vl.201121851364
visceral leishmaniasis in the indian subcontinent: modelling epidemiology and control.in the indian subcontinent, about 200 million people are at risk of developing visceral leishmaniasis (vl). in 2005, the governments of india, nepal and bangladesh started the first regional vl elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. a mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. this model was used to predict the effects of different ...201122140589
asymptomatic infection of visceral leishmaniasis in hyperendemic areas of vaishali district, bihar, india: a challenge to kala-azar elimination programmes.a cohort of 91 asymptomatic individuals with visceral leishmaniasis (vl) were identified during base line screening using recombinant 39-aminoacid antigen (rk-39) and polymerase chain reaction (pcr) conducted from december 2005 to june 2006 involving 997 individuals of two highly endemic villages of vaishali district, bihar. the point prevalence of asymptomatic infection was 98 per 1000 persons at baseline. there was no statistically significant difference between rk-39 and pcr positivity rate ( ...201121945327
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