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recombinant salivary proteins of phlebotomus orientalis are suitable antigens to measure exposure of domestic animals to sand fly bites.certain salivary proteins of phlebotomine sand flies injected into the host skin during blood-feeding are highly antigenic and elicit strong antibody-mediated immune responses in repeatedly-exposed hosts. these antibodies can be measured by enzyme-linked immuno sorbent assays (elisas) using salivary gland homogenates (sghs) as the source of antigens and serve as a markers for exposure to biting sand flies. large-scale screening for anti-sand fly saliva antibodies requires replacement of sgh with ...201626986566
an experimental challenge model of visceral leishmaniasis by leishmania donovani promastigotes in mice.although visceral leishmaniasis is a fatal disease in humans and dogs, the use of mouse models is important for obtaining a better understanding of the pathogenesis, immunity, and host-parasite interactions of this disease. such models are also useful for the evaluation of vaccines and chemotherapies for treatment of visceral leishmaniasis. here, we present our method of experimental inoculation of mice with leishmania donovani promastigotes. nutrient-enriched undefined media may be beneficial f ...201626987675
one-pot synthesis and evaluation of antileishmanial activities of functionalized s-alkyl/aryl benzothiazole-2-carbothioate scaffold.the synthesis of hitherto unreported s-alkyl/aryl benzothiazole-2-carbothioate is reported from thiols, oxalyl chloride, and 2-aminothiophenols using 10 mol % n-tetrabutylammonium iodide (tbai) as catalyst in acetonitrile through multicomponent reaction (mcr) strategy. the present protocol favored formation of benzothiazoles and thioesters via simultaneous formation of c-n and c-s bonds in good yields with a wide range of substrates. a few of the synthesized derivatives were evaluated for their ...201626999637
evolutionary genomics of epidemic visceral leishmaniasis in the indian subcontinent.leishmania donovani causes visceral leishmaniasis (vl), the second most deadly vector-borne parasitic disease. a recent epidemic in the indian subcontinent (isc) caused up to 80% of global vl and over 30,000 deaths per year. resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of l. donovani from the isc. we identify independent radiati ...201627003289
laboratory diagnosis of human visceral leishmaniasis.visceral leishmaniasis (vl), caused by the leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. vl patients may be asymptomatic or they may present symptoms and findings of a systemic infection. the positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic disease ...201627004573
dna vaccine against visceral leishmaniasis: a promising approach for prevention and control.the visceral leishmaniasis (vl) caused by leishmania donovani parasite severely affects large populations in tropical and subtropical regions of the world. the arsenal of drugs available is limited, and resistance is common in clinical field isolates. therefore, vaccines could be an important alternative for prevention against vl. recently, some investigators advocated the protective efficacy of dna vaccines, which induces the t cell-based immunity against vl. the vaccine antigens are selected a ...201627009772
heat killed attenuated leishmania induces apoptosis of hepg2 cells through ros mediated p53 dependent mitochondrial pathway.cytotoxic effect of attenuated leishmania on liver cancer cells by inducing ros generation.201627010918
in vivo characterization of two additional leishmania donovani strains using the murine and hamster model.leishmania donovani is a protozoan parasite causing the neglected tropical disease visceral leishmaniasis. one difficulty to study the immunopathology upon l. donovani infection is the limited adaptability of the strains to experimental mammalian hosts. our knowledge about l. donovani infections relies on a restricted number of east african strains (lv9, 1s). isolated from patients in the 1960s, these strains were described extensively in mice and syrian hamsters and have consequently become 're ...201627012562
structure based medicinal chemistry-driven strategy to design substituted dihydropyrimidines as potential antileishmanial agents.in an attempt to explore novel and more potent antileishmanial compounds to diversify the current inhibitors, we pursued a medicinal chemistry-driven strategy to synthesize novel scaffolds with common pharmacophoric features of dihydropyrimidine and chalcone as current investigational antileishmanial compounds. based on the reported x-ray structure of pteridine reductase 1 (ptr1) from leishmania major, we have designed a number of dihydropyrimidine-based derivatives to make specific interactions ...201627017551
a replicative in vitro assay for drug discovery against leishmania donovani.the protozoan parasite leishmania donovani is the causative agent of visceral leishmaniasis, a disease potentially fatal if not treated. current available treatments have major limitations, and new and safer drugs are urgently needed. in recent years, advances in high-throughput screening technologies have enabled the screening of millions of compounds to identify new antileishmanial agents. however, most of the compounds identified in vitro did not translate their activities when tested in in v ...201627021313
febrifugine analogues as leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, admet and molecular dynamics simulation.visceral leishmaniasis affects people from 70 countries worldwide, mostly from indian, african and south american continent. the increasing resistance to antimonial, miltefosine and frequent toxicity of amphotericin b drives an urgent need to develop an antileishmanial drug with excellent efficacy and safety profile. in this study we have docked series of febrifugine analogues (n = 8813) against trypanothione reductase in three sequential docking modes. extra precision docking resulted into 108 ...201727043972
comparative analysis of cellular immune responses in treated leishmania patients and hamsters against recombinant th1 stimulatory proteins of leishmania donovani.our prior studies demonstrated that cellular response of t helper 1 (th1) type was generated by a soluble antigenic fraction (ranging from 89.9 to 97.1 kda) of leishmania donovani promastigote, in treated leishmania patients as well as hamsters and showed significant prophylactic potential against experimental visceral leishmaniasis (vl). eighteen th1 stimulatory proteins were identified through proteomic analysis of this subfraction, out of which 15 were developed as recombinant proteins. in th ...201627047452
synthesis and pharmacological evaluation of mono-arylimidamides as antileishmanial agents.arylimidamide (aia) compounds containing two pyridylimidamide terminal groups (bis-aias) possess outstanding in vitro antileishmanial activity, and the frontrunner bis-aia db766 (2,5-bis[2-(2-isopropoxy)-4-(2-pyridylimino)aminophenyl]furan) is active in visceral leishmaniasis models when given orally. eighteen compounds containing a single pyridylimidamide terminal group (mono-aias) were synthesized and evaluated for their antileishmanial potential. six of these compounds exhibited sub-micromola ...201627048943
apoptotic protein profile in leishmania donovani after treatment with hexaazatrinaphthylenes derivatives.two hexaazatrinaphthylene derivatives, dgv-b and dgv-c previously known to induce an apoptotic-like process in leishmania donovani parasites were used in this study. for this purpose, two different human protein commercial arrays were used to determine the proteomic profile of the treated parasites compared to non-treated ones. one of the commercial arrays is able to detect the relative expression of 35 human apoptosis-related proteins and the other one is able to identify 9 different human kina ...201627060614
a role for adenine nucleotides in the sensing mechanism to purine starvation in leishmania donovani.purine salvage by leishmania is an obligatory nutritional process that impacts both cell viability and growth. previously, we have demonstrated that the removal of purines in culture provokes significant metabolic changes that enable leishmania to survive prolonged periods of purine starvation. in order to understand how leishmania sense and respond to changes in their purine environment, we have exploited several purine pathway mutants, some in which adenine and guanine nucleotide metabolism is ...201627062185
correction: leishmania donovani infection enhances lateral mobility of macrophage membrane protein which is reversed by liposomal cholesterol. 201627073882
repeated training of accredited social health activists (ashas) for improved detection of visceral leishmaniasis cases in bihar, india.accredited social health activists (ashas) are incentive-based, female health workers responsible for a village of 1000 population and living in the same community and render valuable services towards maternal and child health care, polio elimination program and other health care-related activities including visceral leishmaniasis (vl). one of the major health concerns is that cases remain in the endemic villages for weeks without treatment causing increased likelihood to treatment failure and d ...201627077313
in vitro permissiveness of bovine neutrophils and monocyte derived macrophages to leishmania donovani of ethiopian isolate.epidemiological studies in ethiopia have documented that the risk of visceral leishmaniasis (vl, kala-azar) is higher among people living with domestic animals. the recent report on isolation of leishmania donovani complex dna and the detected high prevalence of anti-leishmanial antibodies in the blood of domestic animals further strengthen the potential role of domestic animals in the epidemiology of vl in ethiopia. in mammalian hosts polymorphonuclear cells (pmn) and macrophages are the key im ...201627090082
antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds.a small series of 5-nitro-2-aminothiazole-based amides containing arylpiperazine-, biphenyl- or aryloxyphenyl groups in their core were synthesized and evaluated as antitrypanosomatid agents. all tested compounds were active or moderately active against trypanosoma cruzi amastigotes in infected l6 cells and trypanosoma brucei brucei, four of eleven compounds were moderately active against leishmania donovani axenic parasites while none were deemed active against t. brucei rhodesiense. for the mo ...201627092415
verbascoside inhibits promastigote growth and arginase activity of leishmania amazonensis.verbascoside (1) is a phenylethanoid glycoside that has antileishmanial activity against leishmania infantum and leishmania donovani. in this study, we verified the activity of 1 on leishmania amazonensis and arginase inhibition. compound 1 showed an ec50 of 19 μm against l. amazonensis promastigotes and is a competitive arginase inhibitor (ki = 0.7 μm). docking studies were performed to assess the interaction of 1 with arginase at the molecular level. arginase is an enzyme of the polyamine bios ...201627096224
mechanistic insight into the reactivation of bcaii enzyme from denatured and molten globule states by eukaryotic ribosomes and domain v rrnas.in all life forms, decoding of messenger-rna into polypeptide chain is accomplished by the ribosome. several protein chaperones are known to bind at the exit of ribosomal tunnel to ensure proper folding of the nascent chain by inhibiting their premature folding in the densely crowded environment of the cell. however, accumulating evidence suggests that ribosome may play a chaperone role in protein folding events in vitro. ribosome-mediated folding of denatured proteins by prokaryotic ribosomes h ...201627099964
alkanediamide-linked bisbenzamidines are promising antiparasitic agents.a series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two trypanosoma brucei (t.b.) subspecies: t.b. brucei and t.b. rhodesiense, trypanosoma cruzi, leishmania donovani and two plasmodium falciparum subspecies: a chloroquine-sensitive strain (nf54) and a chloroquine-resistant strain (k1). the in vitro cytotoxicity was determined against rat myoblast cells (l6). seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against bot ...201627104545
genomic appraisal of the multifactorial basis for in vitro acquisition of miltefosine resistance in leishmania donovani.protozoan parasites of the leishmania donovani complex are the causative agents of visceral leishmaniasis (vl), the most severe form of leishmaniasis, with high rates of mortality if left untreated. leishmania parasites are transmitted to humans through the bite of infected female sandflies (diptera: phlebotominae), and approximately 500,000 new cases of vl are reported each year. in the absence of a safe human vaccine, chemotherapy, along with vector control, is the sole tool with which to figh ...201627114280
differential role of leptin as an immunomodulator in controlling visceral leishmaniasis in normal and leptin-deficient mice.visceral leishmaniasis (vl) is caused by the protozoan parasite leishmania donovani there are no vaccines and available drugs against leishmaniasis are toxic. immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. therefore, finding novel immunomodulators for vl therapy is a pressing need. this study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the imm ...201627114296
quantitative proteome analysis of leishmania donovani under spermidine starvation.we have earlier reported antileishmanial activity of hypericin by spermidine starvation. in the current report, we have used label free proteome quantitation approach to identify differentially modulated proteins after hypericin treatment. a total of 141 proteins were found to be differentially regulated with anova p value less than 0.05 in hypericin treated leishmania promastigotes. differentially modulated proteins have been broadly classified under nine major categories. increase in ribosomal ...201627123864
application of rapid in vitro co-culture system of macrophages and t-cell subsets to assess the immunogenicity of dogs vaccinated with live attenuated leishmania donovani centrin deleted parasites (ldcen-/-).live attenuated leishmania donovani parasites as ldcen(-/-) were shown to confer protective immunity against leishmania infection in mice, hamsters, and dogs. strong immunogenicity in dogs vaccinated with ldcen(-/-) has been previously reported, including increased antibody response favoring th1 response lymphoproliferative responses, cd4(+) and cd8(+) t-cells activation, increased levels of th1 and reduction of th2 cytokines, in addition to a significant reduction in parasite burden after 18 an ...201627136900
bioprospecting sponge-associated microbes for antimicrobial compounds.sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. however, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. this review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. we discuss the current state-of-the-art by grouping the bioact ...201627144573
structure-based virtual screening, molecular docking, admet and molecular simulations to develop benzoxaborole analogs as potential inhibitor against leishmania donovani trypanothione reductase.visceral leishmaniasis (vl) is the most fatal form of leishmaniasis and it affects 70 countries worldwide. increasing drug resistant for antileishmanial drugs such as miltefosine, sodium stibogluconate and pentamidine has been reported in the vl endemic region. amphotericin b has shown potential antileishmanial activity in different formulations but its cost of treatment and associated nephrotoxicity have limited its use by affected people living in the endemic zone. to control the vl infection ...201727147242
the contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis.leishmania is a genus of protozoan parasites that give rise to a range of diseases called leishmaniasis that affects annually an estimated 1.3 million people from 88 countries. leishmania donovani and leishmania (l.) infantum chagasi are responsible to cause the visceral leishmaniasis. the parasite can use assorted strategies to interfere with the host homeostasis to establish persistent infections that without treatment can be lethal. in this review, we highlight the mechanisms involved in the ...201627148272
sla-pgn-primed dendritic cell-based vaccination induces th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of pkcβ.emergence of drug resistance during visceral leishmaniasis (vl) is a major obstacle imposed during successful therapy. an effective vaccine strategy against this disease is therefore necessary. our present study exploited the sla (soluble leishmanial antigen) and pgn (peptidoglycan) stimulated bone marrow-derived dendritic cells (dcs) as a suitable vaccine candidate during experimental vl. sla-pgn-stimulated dcs showed a significant decrease in hepatic and splenic parasite burden, which were ass ...201627150838
structure- and ligand-based approaches to evaluate aporphynic alkaloids from annonaceae as multi-target agent against leishmania donovani.leishmaniasis is a neglected disease that affects 15 million people around the world. many limitations are associated to the treatment as high cost and toxicity. several classes of natural substances with proven leishmanicidal activity were reported in the literature. phytochemsitry study of anaxagorea dolichocarpa (annonacea) reported the isolation of aporphine alkaloids.201627174814
seroepidemiology and molecular diversity of leishmania donovani complex in georgia.leishmaniasis includes multiple clinical syndromes, most notably visceral, cutaneous, and mucosal forms. visceral leishmaniasis (vl), also known as kala-azar, is a potentially fatal disease endemic to large parts of africa and asia, and in south-eastern europe (greece, turkey, georgia). visceral leishmaniasis is a parasitic zoonosis caused by species of the l. donovani complex. in the classical epidemiological model the main reservoir for vl are canines.201627177688
mobile suitcase laboratory for rapid detection of leishmania donovani using recombinase polymerase amplification assay.leishmania donovani (ld) is a protozoan parasite transmitted to humans from sand flies, which causes visceral leishmaniasis (vl). currently, the diagnosis is based on presence of the anti-ld antibodies and clinical symptoms. molecular diagnosis would require real-time pcr, which is not easy to implement at field settings. in this study, we report on the development and testing of a recombinase polymerase amplification (rpa) assay for the detection of ld.201627177926
supplementation of host response by targeting nitric oxide to the macrophage cytosol is efficacious in the hamster model of visceral leishmaniasis and adds to efficacy of amphotericin b.we investigated efficacy of nitric oxide (no) against leishmania donovani. no is a mediator of host response to infection, with direct parasiticidal activity in addition to its role in signalling to evoke innate macrophage responses. however, it is short-lived and volatile, and is therefore difficult to introduce into infected cells and maintain inracellular concentrations for meaningful periods of time. we incorporated diethylenetriamine no adduct (deta/no), a prodrug, into poly(lactide-co-glyc ...201627183429
elevated serum ada activity as a marker for diagnosis and prognosis of visceral leishmaniasis and post kala-azar dermal leishmaniasis in indian patients.serum adenosine deaminase (ada) activity increases in diseases where cellular immunity is involved. since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ada activity in different pathological conditions. adenosine deaminase was determined in sera of active visceral leishmaniasis (vl) patients (n = 39), active postkala-azar dermal leishmaniasis (pkdl) cases (n = 3 ...201627186641
purification and characterization of a novel intracellular sucrase enzyme of leishmania donovani promastigotes.the promastigote stage of leishmania resides in the sand fly gut, enriched with sugar molecules. recently we reported that leishmania donovani possesses a sucrose uptake system and a stable pool of intracellular sucrose metabolizing enzyme. in the present study, we purified the intracellular sucrase nearly to its homogeneity and compared it with the purified extracellular sucrase. the estimated size of intracellular sucrase is ~112 kda by gel filtration chromatography, native page, and substrate ...201627190649
the potential use of forensic dna methods applied to sand fly blood meal analysis to identify the infection reservoirs of anthroponotic visceral leishmaniasis.in the indian sub-continent, visceral leishmaniasis (vl), also known as kala azar, is a fatal form of leishmaniasis caused by the kinetoplastid parasite leishmania donovani and transmitted by the sand fly phlebotomus argentipes. vl is prevalent in northeast india where it is believed to have an exclusive anthroponotic transmission cycle. there are four distinct cohorts of l. donovani exposed individuals who can potentially serve as infection reservoirs: patients with active disease, cured vl cas ...201627192489
chemical and antimicrobial profiling of propolis from different regions within libya.extracts from twelve samples of propolis collected from different regions of libya were tested for their activity against trypanosoma brucei, leishmania donovani, plasmodium falciparum, crithidia fasciculata and mycobacterium marinum and the cytotoxicity of the extracts was tested against mammalian cells. all the extracts were active to some degree against all of the protozoa and the mycobacterium, exhibiting a range of ec50 values between 1.65 and 53.6 μg/ml. the toxicity against mammalian cell ...201627195790
detection of leishmania donovani in peripheral blood of asymptomatic individuals in contact with patients with visceral leishmaniasis.the majority of individuals infected with leishmania donovani complex remain asymptomatic. they may act as transmission reservoirs for visceral leishmaniasis (vl). we investigated sero-prevalence of l. donovani complex amongst those closely associated with patients with vl and whether these sero-reactive individuals had leishmania parasites in their peripheral blood. other risk factors were also investigated.201627198212
cholesterol corrects altered conformation of mhc-ii protein in leishmania donovani infected macrophages: implication in therapy.previously we reported that kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. splenic macrophages (mφ) of leishmania donovani (ld) infected mice show decrease in membrane cholesterol, while ld infected macrophages (i-mφ) show defective t cell stimulating ability that could be corrected by liposomal delivery of cholesterol. t helper cells recognize peptide antigen in the context of class ii mhc molecule. it is known that the conformation o ...201627214205
the anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis.there is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (vl). we report that delamanid (opc-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of leishmania donovani both in vitro and in vivo. twice-daily oral dosing of delamanid at 30 mg kg(-1) for 5 days resulted in sterile cures in a mouse model of vl. treatment with lower doses revealed a u-shaped (hormetic) dose-response curve with greater parasite ...201627215734
phenotypic characterization of a leishmania donovani cyclophilin 40 null mutant.protozoan parasites of the genus leishmania adapt to their arthropod and vertebrate hosts through the development of defined life cycle stages. stage differentiation is triggered by environmental stress factors and has been linked to parasite chaperone activities. using a null mutant approach we previously revealed important, nonredundant functions of the cochaperone cyclophilin 40 in l. donovani-infected macrophages. here, we characterized in more detail the virulence defect of cyp40-/- null mu ...201627216143
identification of leishmania donovani topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known top 1 inhibitors.a library of arylidenefuropyridinediones was discovered as potent inhibitors of leishmania donovani topoisomerase 1 (ldtop1) where the active molecules displayed considerable inhibition with single digit micromolar ec50 values. this molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. the design was rationalized by molecular docking analysis of the compound prototype with human to ...201627221589
phylogenetic position of leishmania isolates from khyber pakhtunkhwa province of pakistan.several species of the genus leishmania are causative agents of cutaneous leishmaniasis in pakistan. this study aimed to determine phylogenetic placement of leishmania species causing cutaneous leishmaniasis in khyber pakhtunkhwa province, pakistan (34 leishmania tropica, 3 leishmania infantum), in-relation to species from other geographical areas using gene sequences encoding cytochrome b (cytb) and internal transcribed spacer 2 (its2). based on cytochrome b sequence analysis, l. tropica strain ...201627233810
a gcn2-like eif2α kinase (ldek1) of leishmania donovani and its possible role in stress response.translation regulation in leishmania parasites assumes significance particularly because they encounter myriad of stresses during their life cycle. the eukaryotic initiation factor 2α (eif2α) kinases, the well-known regulators of translation initiation in higher eukaryotes have now been found to control various processes in these protozoan parasites as well. here, we report on cloning and characterization of a gcn2-like eif2α kinase from l. donovani and also on its modulation during nutrient sta ...201627248816
bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.kupffer cells (kcs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. recent studies have identified kcs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, ...201627262757
innate immune b cell activation by leishmania donovani exacerbates disease and mediates hypergammaglobulinemia.participation of b cells in the immune response by various antibody-independent mechanisms has recently been uncovered. b cells producing cytokines have been described for several infections and appear to regulate the adaptive immune response. b cell activation by leishmania donovani results in disease exacerbation. how leishmania activates b cells is still unknown. we show that l. donovani amastigotes activate b cells by triggering endosomal tlrs; this activation leads to the induction of vario ...201627264176
histone acetyltransferase hat4 modulates navigation across g2/m and re-entry into g1 in leishmania donovani.histone acetyltransferases impact multiple processes. this study investigates the role of histone acetyltransferase hat4 in leishmania donovani. though hat4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with hat4-nulls experiencing an unusually long g2/m. survival of hat4-nulls in macrophages was also substantially compromised. dna microarray analysis revealed that hat4 modestly regulated the expression of only a select number of genes, thu ...201627272906
integracides h-j: new tetracyclic triterpenoids from the endophytic fungus fusarium sp.three new tetracyclic triterpenoids namely, integracides h (1), i (4), and j (5), along with integracides b (3) and f (2) have been isolated from the endophytic fungus fusarium sp. isolated from the roots of mentha longifolia l. (labiatae) growing in saudi arabia. the structure elucidation of the isolated compounds was achieved by spectroscopic analysis including uv, ir, 1d ((1)h and (13)c) and 2d ((1)h(1)h cosy, tocsy, hsqc, hmbc, and noesy) nmr as well as hresims and comparison with literature ...201627282207
leishmania donovani aurora kinase: a promising therapeutic target against visceral leishmaniasis.aurora kinases are key mitotic kinases executing multiple aspects of eukaryotic cell-division. the apicomplexan homologs being essential for survival, suggest that the leishmania homolog, annotated ldairk, may be equally important.201627288586
optimization of loop-mediated isothermal amplification (lamp) assays for the detection of leishmania dna in human blood samples.visceral leishmaniasis (vl), one of the most important neglected tropical diseases, is caused by leishmania donovani eukaryotic protozoan parasite of the genus leishmania, the disease is prevalent mainly in the indian sub-continent, east africa and brazil. vl can be diagnosed by pcr amplifying its1 and/or kdna genes. the current study involved the optimization of loop-mediated isothermal amplification (lamp) for the detection of leishmania dna in human blood or tissue samples. three lamp systems ...201627288706
pi inhibits intracellular accumulation of methylglyoxal in promastigote form of l. donovani.similar to their mammalian counterpart, protozoan parasites including leishmania donovani detoxify methylglyoxal (mg),(1) a toxic ubiquitous product generated in glycolysis pathway. however, it differs in one or more way(s) from the humans. it is known that mg is eliminated either through glyoxalase (glo)(2) pathway and/or excreted across the cell membrane. this toxic metabolic by-product is known to be detoxified predominantly by the glo pathway and excretion across the cell membrane is never c ...201627297182
association of hla class i and ii genes with cutaneous leishmaniasis: a case control study from sri lanka and a systematic review.the outcome of leishmaniasis is an interplay between leishamania and the host. identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. leishmaniasis is caused exclusively by l. donovani in sri lanka with localized cutaneous leishmaniasis (lcl) being the predominant form. we report here an association study of human leucocyte antigen (hla) class i and ii genes with lcl in sri lanka, the first on hla associations in cutaneous le ...201627301744
prevalence of zoonotic and vector-borne infections among afghan national army recruits in afghanistan.to measure prevalence of prior/current plasmodium vivax and plasmodium falciparum (pv and pf), brucella spp. (br), dengue virus (denv), leishmania donovani (visceral leishmaniasis; vl), and crimean-congo hemorrhagic fever (cchf) virus exposure among afghan national army (ana) recruits.201627304051
activity of a novel sulfonamide compound 2-nitro-n-(pyridin-2-ylmethyl)benzenesulfonamide against leishmania donovani.new treatments for visceral leishmaniasis, caused by leishmania donovani, are needed to overcome sustained toxicity, cost, and drug resistance. the aim of this study was to evaluate the therapeutic effects of 2-nitro-n-(pyridin-2-ylmethyl)benzenesulfonamide (2nb) against promastigote and amastigote forms of l. donovani and examine its effect in combination with amphotericin b (amb) against amb-resistant clinical isolates. effects were assessed against extracellular promastigotes in vitro and int ...201627307706
measures to control phlebotomus argentipes and visceral leishmaniasis in india.visceral leishmaniasis is a deadly parasitic disease that is transmitted via the bite of a female sand fly, phlebotomus argentipes. the highest burden of this disease is in northern india. in 2005, india embarked on an initiative with nepal, bangladesh, and the world health organization to eliminate visceral leishmaniasis by 2015. with the goal of 1 case in 10,000 people still unmet, it is prudent to evaluate the tools that have been used thus far to reduce vector numbers and cases of the diseas ...201627308270
plumbagin, a plant-derived naphthoquinone metabolite induces mitochondria mediated apoptosis-like cell death in leishmania donovani: an ultrastructural and physiological study.naphthoquinones are known to exhibit a broad range of biological activities against microbes, cancer and parasitic diseases and have been widely used in indian traditional medicine. plumbagin is a plant-derived naphthoquinone metabolite (5-hydroxy-2-methyl-1,4-naphthoquinone) reported to inhibit trypanothione reductase, the principal enzyme and a validated drug target involved in detoxification of oxidative stress in leishmania. here, we report the mechanistic aspects of cell death induced by pl ...201627315817
synthesis and antileishmanial activity of c7- and c12-functionalized dehydroabietylamine derivatives.abietane-type diterpenoids, either naturally occurring or synthetic, have shown a wide range of pharmacological actions, including antiprotozoal properties. in this study, we report on the antileishmanial evaluation of a series of (+)-dehydroabietylamine derivatives functionalized at c7 and/or c12. thus, the activity in vitro against leishmania infantum, leishmania donovani, leishmania amazonensis and leishmania guyanensis, was studied. most of the benzamide derivatives showed activities at low ...201627318121
statin-induced chronic cholesterol depletion inhibits leishmania donovani infection: relevance of optimum host membrane cholesterol.leishmania are obligate intracellular protozoan parasites that invade and survive within host macrophages leading to leishmaniasis, a major cause of mortality and morbidity worldwide, particularly among economically weaker sections in tropical and subtropical regions. visceral leishmaniasis is a potent disease caused by leishmania donovani. the detailed mechanism of internalization of leishmania is poorly understood. a basic step in the entry of leishmania involves interaction of the parasite wi ...201627319380
corrigendum: identification of leishmania donovani topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known top 1 inhibitors. 201627323004
molecular detection, identification and phylogenetic inference of leishmania spp. in some desert lizards from northwest china by using internal transcribed spacer 1 (its1) sequences.leishmaniasis caused by leishmania is still endemic in northwest china. it has been thought that reptiles could be a reservoir for mammalian leishmaniasis. however, data are still scarce on natural infection of lizards with leishmania spp. in china. the present study deals with detection, identification and phylogenetic inference of leishmania parasites at species and intraspecies levels isolated from six desert lizard species from 10 geographical locations in northwest china using amplification ...201627338182
gmp reductase and genetic uncoupling of adenylate and guanylate metabolism in leishmania donovani parasites.purine acquisition is an essential nutritional process for leishmania. although purine salvage into adenylate nucleotides has been investigated in detail, little attention has been focused on the guanylate branch of the purine pathway. to characterize guanylate nucleotide metabolism in leishmania and create a cell culture model in which the pathways for adenylate and guanylate nucleotide synthesis can be genetically uncoupled for functional studies in intact cells, we created and characterized n ...201627343371
pitfalls in the synthesis of fluorescent methotrexate oligopeptide conjugates.methotrexate (mtx) conjugates with poly[lys(dl-alam)] based polymeric polypeptides are efficient against leishmania donovani parasite infection, but the mechanism of the effect is not known yet. we prepared therefore the 5(6)-carboxyfluorescein (cf) labeled oligopeptide [cf-k(aaaa)] (a: d-alanine, a: l-alanine) and the corresponding mtx conjugates [cf-k(mtx-aaaa)] as model compounds for structure-activity experiments. the conjugate aimed to be synthesized with solid phase methodology on mbha res ...201627357306
tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired ifn-γ production by spleen cells from human visceral leishmaniasis patients.the pro-inflammatory cytokine tumor necrosis factor (tnf)-α has an important role in control of experimental leishmania donovani infection. less is known about the role of tnf-α in human visceral leishmaniasis (vl). evidence for a protective role is primarily based on case reports of vl development in individuals treated with tnf-α neutralizing antibody. in this study, we have evaluated how tnf-α neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (sa ...201627372917
2.8-å cryo-em structure of the large ribosomal subunit from the eukaryotic parasite leishmania.leishmania is a single-cell eukaryotic parasite of the trypanosomatidae family, whose members cause an array of tropical diseases. the often fatal outcome of infections, lack of effective vaccines, limited selection of therapeutic drugs, and emerging resistant strains, underline the need to develop strategies to combat these pathogens. the trypanosomatid ribosome has recently been highlighted as a promising therapeutic target due to structural features that are distinct from other eukaryotes. he ...201627373148
implication of vector characteristics of phlebotomus argentipes in the kala-azar elimination programme in the indian sub-continent.visceral leishmaniasis (vl), also known as kala-azar in the indian sub-continent (isc), is a major public health concern in bangladesh, india, and nepal, where it is caused by leishmania donovani transmitted by the sand fly phlebotomus argentipes. various ecological parameters including air temperature, rainfall, wind speed, relative humidity, soil moisture, ph, and organic carbon are known to influence the oviposition of female sand flies, as well as the survival and development of larvae. howe ...027376500
corrigendum: leishmanicidal activity of piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by th1 immunostimulatory potential in vivo.[this corrects the article on p. 1368 in vol. 6, pmid: 26696979.].201627379073
twin attributes of tyrosyl-trna synthetase of leishmania donovani: a housekeeping protein translation enzyme and a mimic of host chemokine.aminoacyl-trna synthetases (aarss) are housekeeping enzymes essential for protein synthesis. apart from their parent aminoacylation activity, several aarss perform non-canonical functions in diverse biological processes. the present study explores the twin attributes of leishmania tyrosyl-trna synthetase (ldtyrrs) namely, aminoacylation, and as a mimic of host cxc chemokine. leishmania donovani is a protozoan parasite. its genome encodes a single copy of tyrosyl-trna synthetase. we first tested ...201627382051
molecular and serological evidence of leishmania infection in stray dogs from visceral leishmaniasis-endemic areas of bangladesh.visceral leishmaniasis (vl), or kala-azar, is mainly caused by two closely related leishmania species, leishmania infantum and leishmania donovani leishmania infantum is responsible for zoonotic vl, with dogs as the main reservoir host in the mediterranean, the middle east, asia, and south america. in the indian subcontinent, vl is caused by l. donovani and is considered anthroponotic, although the only known vector, the sand fly, is zoophilic in nature. the role of domestic and stray dogs in vl ...201627382083
immunoprotective effect of lentinan in combination with miltefosine on leishmania-infected j-774a.1 macrophages.rejuvenation of deteriorated host immune functions is imperative for successful annihilation of leishmania parasites. the use of immunomodulatory agents may have several advantages as they conquer immunosuppression and, when given in combination, improve current therapeutic regimens. we herein investigated the immunostimulatory potency of a β-glucan, lentinan either alone or in combination with short dose of standard drug, miltefosine on leishmania-infected j-774a.1 macrophages. our study shows ...201627387601
molecular detection of infection homogeneity and impact of miltefosine treatment in a syrian golden hamster model of leishmania donovani and l. infantum visceral leishmaniasis.control of visceral leishmaniasis caused by leishmania infantum and leishmania donovani primarily relies on chemotherapy using an increasingly compromised repertoire of antileishmanial compounds. for evaluation of novel drugs, the syrian golden hamster is considered as a clinically relevant laboratory model. in this study, two molecular parasite detection assays were developed targeting cathepsin-like cysteine protease b (cpb) dna and 18s rrna to achieve absolute amastigote quantification in the ...201627412759
evaluation of s.c. route of immunization by homologous radio attenuated live vaccine in experimental murine model of visceral leishmaniasis.our previous studies in balb/c mice showed substantial protection against the experimental murine visceral leishmaniasis (mvl) when the animals were immunized with γ-irradiated live leishmania donovani parasites through intra peritoneal (i.p.) and intra muscular (i.m.) routes respectively. the observations encouraged us to check the prophylactic efficacy of subcutaneous (s.c.) route as it is better alternative for human trial. the mice immunized with two subsequent doses of the radio attenuated ...201627413317
ongoing outbreak of cutaneous leishmaniasis in northwestern yemen: clinicoepidemiologic, geographic, and taxonomic study.cutaneous leishmaniasis (cl) is widespread in yemen but has not been fully documented.201627419356
loop-mediated isothermal amplification assay as a sensitive diagnostic tool for leishmania donovani infections in sri lanka.cutaneous leishmaniasis (cl) in sri lanka is caused by leishmania donovani mon 37. confirmation of diagnosis is done through microscopy, either directly or after in vitro culture. molecular diagnostic methods are sensitive, but require well established laboratories. loop mediated isothermal amplification assay (lamp) is rapid, specific for parasite speciesspecific dna amplification, and requires only basic laboratory equipment. the aim of the study was to determine the potential utility of lamp ...201627423747
a case report of isolated lymphadenopathy revealing localized leishmanial lymphadenopathy in an asthenic 25-year-old man.visceral leishmaniasis (vl) is endemic in large areas of the tropics, the subtropics, and the mediterranean basin. besides classical vl presentation, exceptional cases of a limited form of vl have been reported. here we describe the challenges of diagnosis and management of this intriguing entity.201627442631
volatile oil profile of some lamiaceous plants growing in saudi arabia and their biological activities.a comparative investigation of hydro-distilled essential oils from aerial parts of mentha longifolia l. (ml), mentha microphylla k.koch (mm), mentha australis r.br. (ma), and teucrium polium l. (tp) growing in al madinah al munawwarah, saudi arabia, was carried out. the total numbers of identified constituents were 22, 23, 14, and 20 in ml, mm, ma, and tp oils, representing 93.0, 99.3, 78.1, and 81.1% of the total oil composition, respectively. pulegone (40.7%) and cineole (33.4%) were the major ...201727458662
microrna expression profiling of leishmania donovani-infected host cells uncovers the regulatory role of mir30a-3p in host autophagy.leishmania is an obligate intracellular parasite that replicates inside phagolysosomes or parasitophorous vacuoles (pv) of the monocyte/macrophage lineage. it reprograms macrophages and produces a metabolic state conducive to successful infection and multiplication. micrornas (mirnas), a class of small 22 to 24 nucleotide noncoding regulatory rnas alter the gene expression and consequently proteome output by targeting mrnas, may play a regulatory role in modulating host cell functions. in the pr ...201627459332
optimizing immunization strategies for the induction of antigen-specific cd4 and cd8 t cell responses for protection against intracellular parasites.immunization strategies that generate either cd4 or cd8 t cell responses are relatively well described, but less is known with regard to optimizing regimens to induce both cd4 and cd8 memory t cells. considering the importance of both cd4 and cd8 t cells in the control of intracellular pathogens such as leishmania donovani, we wanted to identify vaccines that could raise both cd4 and cd8 t cell responses and determine how to configure immunization strategies to generate the best combined protect ...201627466350
arylthiosemicarbazones as antileishmanial agents.based on a screening process, we targeted substituted thiosemicarbazone as potential antileishmanial agents. our objective was to identify the key structural elements contributing to the anti-parasite activity that might be used for development of effective drugs. a series of 32 compounds was synthesized and their efficacy was evaluated against the clinically relevant intracellular amastigotes of leishmania donovani. from these, 22 compounds showed ec50 values below 10 μm with the most active de ...201627475107
effective anti-leishmanial activity of minimalist squaramide-based compounds.in order to evaluate the in vitro leishmanicidal activity of n,n'-squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against leishmania infantum, leishmania braziliensis and leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. infectivity and cytotoxicity tests were performed on j774.2 macrophage cells using meglumine anti ...201627480054
leishmania donovani-induced prostaglandin e2 generation is critically dependent on host toll-like receptor 2-cytosolic phospholipase a2 signaling.visceral leishmaniasis (vl) is the second-largest parasitic killer disease after malaria. during vl, the protozoan leishmania donovani induces prostaglandin e2 (pge2) generation within host macrophages to aid parasite survival. pge2 significantly influences leishmanial pathogenesis, as l. donovani proliferation is known to be attenuated in pge2-inhibited macrophages. here, we report for the first time that signaling via macrophage toll-like receptor 2 (tlr2) plays an instrumental role in inducin ...201627481248
direct evidence for role of anti-saliva antibodies against salivary gland homogenate of p. argentipes in modulation of protective th1-immune response against leishmania donovani.currently the main concerns regarding control of visceral leishmaniasis (vl) caused by l. donovani are immunosuppression, relating toxicity of anti-leishmanial drug and little development in appropriate vaccine and vector (p. argentipes) control. reports available from ex-vivo studies reflect significance of vector salivary gland homogenate (sgh) in reverting immunosuppression of infected vl subjects and as such the immunogenic nature of sgh can be a strategy to modulate immune system and anti-l ...201627484246
leishmania donovani utilize sialic acids for binding and phagocytosis in the macrophages through selective utilization of siglecs and impair the innate immune arm.leishmania donovani, belonging to a unicellular protozoan parasite, display the differential level of linkage-specific sialic acids on their surface. sialic acids binding immunoglobulin-like lectins (siglecs) are a class of membrane-bound receptors present in the haematopoetic cell lineages interact with the linkage-specific sialic acids. here we aimed to explore the utilization of sialic acids by leishmania donovani for siglec-mediated binding, phagocytosis, modulation of innate immune response ...201627494323
grind2-based 3d-qsar and prediction of activity spectra for symmetrical bis-pyridinium salts with promastigote antileishmanial activity.leishmaniasis is a major group of neglected tropical diseases caused by the protozoan parasite leishmania. about 12 million people are affected in 98 countries and 350 million people worldwide are at risk of infection. current leishmaniasis treatments rely on a relatively small arsenal of drugs, including amphotericin b, pentamidine and others, which in general have some type of inconvenience. recently, we have synthesized antileishmanial bis-pyridinium derivatives and symmetrical bis-pyridinium ...201627495391
a novel spirooxindole derivative inhibits the growth of leishmania donovani parasites both in vitro and in vivo by targeting type ib topoisomerase.visceral leishmaniasis is a fatal parasitic disease, and there is an emergent need for development of effective drugs against this neglected tropical disease. we report here the development of a novel spirooxindole derivative, n-benzyl-2,2'α-3,3',5',6',7',7α,α'-octahydro-2methoxycarbonyl-spiro[indole-3,3'-pyrrolizidine]-2-one (compound 4c), which inhibits leishmania donovani topoisomerase ib (ldtopib) and kills the wild type as well as drug-resistant parasite strains. this compound inhibits cata ...201627503653
synthesis and activity of novel homodimers of morita-baylis-hillman adducts against leishmania donovani: a twin drug approach.it is reported here the synthesis of novel homodimers 12-19 of morita-baylis-hillman adducts (mbha) from one-pot morita-baylis-hillman reaction (mbhr) between aromatic aldehydes as eletrophiles and ethylene glycol diacrylate as michael acceptor (35-94% yields) using cheap and green conditions. the bioactivities were evaluated against promastigote form of leishmania donovani. all homodimers showed to be more potent than corresponding monomers. it is worth highlighting that the halogenated homodim ...201627520941
nkt cell activation by leishmania mexicana lpg: description of a novel pathway.nkt cells have been associated with protection against leishmania donovani, yet their role in infections with leishmania mexicana has not been addressed, nor has the activation pathway been defined after stimulation with leishmania mexicana lipophosphoglycan (lpg). we analyzed the activation of nkt cells and their cytokine production in response to leishmania mexicana lpg. additionally we compared nkt-cell numbers and cytokine profile in lymph nodes of skin lesions induced by leishmania mexicana ...201727523746
immunogenicity and protective efficacy of dna vaccine against visceral leishmaniasis in balb/c mice.the current study was designed to examine the protective efficacy of dna vaccines based on gp63 and hsp70 against murine visceral leishmaniasis. inbred balb/c mice were immunized subcutaneously twice at an interval of three weeks with pcdna3.1(+) encoding t cell epitopes of gp63 and hsp70 individually and in combination. animals were challenged intracardially with 10(7) promastigotes of leishmania donovani 10 days post immunization and sacrificed 1, 2 and 3 months post challenge. the immunized a ...201627533939
visceral leishmaniasis on the indian subcontinent: modelling the dynamic relationship between vector control schemes and vector life cycles.visceral leishmaniasis (vl) is a disease caused by two known vector-borne parasite species (leishmania donovani, l. infantum), transmitted to man by phlebotomine sand flies (species: phlebotomus and lutzomyia), resulting in ≈50,000 human fatalities annually, ≈67% occurring on the indian subcontinent. indoor residual spraying is the current method of sand fly control in india, but alternative means of vector control, such as the treatment of livestock with systemic insecticide-based drugs, are be ...201627537774
nitrotriazole-based acetamides and propanamides with broad spectrum antitrypanosomal activity.3-nitro-1h-1,2,4-triazole-based acetamides bearing a biphenyl- or a phenoxyphenyl moiety have shown remarkable antichagasic activity both in vitro and in an acute murine model, as well as substantial in vitro antileishmanial activity but lacked activity against human african trypanosomiasis. we have shown now that by inserting a methylene group in the linkage to obtain the corresponding propanamides, both antichagasic and in particular anti-human african trypanosomiasis potency was increased. th ...201627543881
a review of visceral leishmaniasis during the conflict in south sudan and the consequences for east african countries.visceral leishmaniasis (vl), caused predominantly by leishmania donovani and transmitted by both phlebotomus orientalis and phlebotomus martini, is highly endemic in east africa where approximately 30 thousands vl cases are reported annually. the largest numbers of cases are found in sudan - where phlebotomus orientalis proliferate in acacia forests especially on sudan's eastern border with ethiopia, followed by south sudan, ethiopia, somalia, kenya and uganda. long-standing civil war and unrest ...201627549162
the immunology of post-kala-azar dermal leishmaniasis (pkdl).post-kala-azar dermal leishmaniasis (pkdl) is a common complication of visceral leishmaniasis (vl) caused by leishmania donovani. because of its possible role in transmission it is considered a public health problem in vl endemic areas. the clinical features include a skin rash consisting of macules, papules or nodules in an otherwise healthy individual; this presentation is determined by the immune response towards parasites in the skin that probably persisted from the previous vl episode. the ...201627553063
taxonomic and predicted metabolic profiles of the human gut microbiome in pre-columbian mummies.characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. we characterized the gut microbiome of two pre-columbian andean mummies dating to the 10-15th centuries using 16s rrna gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century ad pre-columbian andean mummy. our previous study sh ...201627559027
protective inflammatory response against visceral leishmaniasis with potato tuber extract: a new approach of successful therapy.the increasing number of drug resistance issue of leishmania donovani strain to common drugs compels to develop new therapeutics against leishmaniasis with minimal toxicity. in this regard, bioactive phytocomponents may lead to the discovery of new medicines with appropriate efficiency. the important roles of leishmania proteases in the virulence of leishmania parasite make them very hopeful targets for the improvement of current remedial of leishmaniasis. as part of a hunt for new drugs, we hav ...201627567589
live attenuated leishmania donovani centrin knock out parasites generate non-inferior protective immune response in aged mice against visceral leishmaniasis.visceral leishmaniasis (vl) caused by the protozoan parasite leishmania donovani causes severe disease. age appears to be critical in determining the clinical outcome of vl and at present there is no effective vaccine available against vl for any age group. previously, we showed that genetically modified live attenuated l. donovani parasites (ldcen-/-) induced a strong protective innate and adaptive immune response in young mice. in this study we analyzed ldcen-/- parasite mediated modulation of ...201627580076
magnesium-dependent ecto-atp diphosphohydrolase activity in leishmania donovani.in this work, we have described the expression of ecto-atpdase on the external surface of leishmania donovani. this enzyme has the ability to hydrolyze extracellular atp. there is a low level of atp hydrolysis in the absence of divalent cation 2.5 ± 0.51 nm pi 10(7) cells/h which shows the divalent cation-dependent activity of this enzyme in the intact parasite. however, mgcl2 stimulated the atp hydrolysis to a greater extent compared with cacl2 and zncl2. this activity was also observed when re ...201627589852
antileishmanial ferrocenylquinoline derivatives: synthesis and biological evaluation against leishmania donovani.the emergence of resistance against existing antileishmanial drugs necessitates the search for new classes of antileishmanial compounds. herein a series of structurally diverse ferrocenylquinolines have been synthesized and evaluated for in vitro antileishmanial activity against leishmania donovani using the mtt assay. thirteen (m2-m14) substituted ferrocenylquinoline congeners possessing triazole rings were generated by palladium mediated suzuki-miyaura coupling reaction of 5-iodoferrocenylquin ...201627598235
antileishmanial mechanism of diamidines involves targeting kinetoplasts.leishmaniasis is a disease caused by pathogenic leishmania parasites; current treatments are toxic and expensive, and drug resistance has emerged. while pentamidine, a diamidine-type compound, is one of the treatments, its antileishmanial mechanism of action has not been investigated in depth. here we tested several diamidines, including pentamidine and its analog db75, against leishmania donovani and elucidated their antileishmanial mechanisms. we identified three promising new antileishmanial ...201627600039
molecular modeling and virtual screening approach to discover potential antileishmanial inhibitors against ornithine decarboxylase.visceral leishmaniasis (vl) is a tropical neglected disease, which encounters poorest of poor people living in asia, africa and latin america; causes the mortality of more than 30,000 people worldwide. the armamentarium for the treatment of vl cases is limited and continuously facing decreasing of efficacy for existing drugs. ornithine decarboxylase (odc) is one of the interesting drug targets in leishmania donovani, due to its association with redox metabolism.201627604958
dna sequencing confirms pcr-rflp identification of wild caught larroussius sand flies from crete and cyprus.many phlebotomine sand fly species (diptera, psychodidae) are vectors of the protozoan parasite leishmania causing a group of diseases called the leishmaniases. the subgenus larroussius includes sand fly vectors found in south east mediterranean basin responsible for visceral (vl) and cutaneous human leishmaniasis (cl). it is important to monitor these medically important insects in order to safely predict possible leishmania transmission cycles. leishmania infantum is endemic in the islands of ...201627609635
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