Publications

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phagocytosis of hemozoin by raw 264.7 cells, but not thp-1 cells, promotes infection by leishmania donovani with a nitric oxide-independent mechanism.during its intra-erythrocytic development, the malaria parasite plasmodium falciparum synthesizes insoluble hemozoin (hz) crystals that are released into the circulation upon rupture of parasitized red blood cells, and rapidly phagocytized by host mononuclear cells. here, hz persists undigested, causing functional impairment and possibly leading to increased host susceptibility to secondary infections. in patients with malaria and visceral leishmaniasis (vl) co-infections, hz-loaded macrophages ...201727623326
coccinia grandis (l.) voigt leaf extract exhibits antileishmanial effect through pro-inflammatory response: an in vitro study.the conventional drugs used for the treatment of human visceral leishmaniasis have concerns about the toxicity and most importantly parasite resistance. to overcome these troubles, more efforts are made for the development of innovative therapeutic agents having effective antileishmanial activity and simultaneously stimulate adaptive immune system of host cells. hence, search for new leishmanicidal from the natural origin like plants has shown its effectiveness for the treatment of this tropical ...201727796492
gamma interferon-regulated chemokines in leishmania donovani infection in the liver.in the livers of c57bl/6 mice, gamma interferon (ifn-γ) controls intracellular leishmania donovani infection and the efficacy of antimony (sb) chemotherapy. since both responses usually correlate with granulomatous inflammation, we tested six prominently expressed, ifn-γ-regulated chemokines-cxcl9, cxcl10, cxcl13, cxcl16, ccl2, and ccl5-for their roles in (i) mononuclear cell recruitment and granuloma assembly and maturation, (ii) initial control of infection and self-cure, and (iii) responsiven ...201727795366
arginase is essential for survival of leishmania donovani promastigotes but not intracellular amastigotes.studies of leishmania donovani have shown that both ornithine decarboxylase and spermidine synthase, two enzymes of the polyamine biosynthetic pathway, are critical for promastigote proliferation and required for maximum infection in mice. however, the importance of arginase (arg), the first enzyme of the polyamine pathway in leishmania, has not been analyzed in l. donovani to test arg function in intact parasites, we generated δarg null mutants in l. donovani and evaluated their ability to prol ...201727795357
phosphorylation of translation initiation factor 2-alpha in leishmania donovani under stress is necessary for parasite survival.the transformation of leishmania donovani from a promastigote to an amastigote during mammalian host infection displays the immense adaptability of the parasite to survival under stress. induction of translation initiation factor 2-alpha (eif2α) phosphorylation by stress-specific eif2α kinases is the basic stress-perceiving signal in eukaryotes to counter stress. here, we demonstrate that elevated temperature and acidic ph induce the phosphorylation of leishmania donovani eif2α (ldeif2α). in vit ...201727736773
synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates.thirteen new polyamine derivatives coupled to hydroxybenzotriazole have been synthesized and evaluated for their in vitro antikinetoplastid activity. trypanosoma trypanothione reductase (tryr) was envisioned as a potential target. among all tested molecules, only one compound, a n(3)-spermidine-benzotriazole derivative, displayed relevant inhibitory activity on this enzyme but was not active on parasites. the corresponding boc-protected spermidine-benzotriazole was however trypanocidal against t ...201727793448
functional analysis of an amp forming acetyl coa synthetase from leishmania donovani by gene overexpression and targeted gene disruption approaches.leishmaniasis, a neglected tropical disease is endemic in 98 countries and >350 million people are at risk of getting the infection. the existing chemotherapy of leishmaniasis is limited due to adverse effects, resistance to existing drugs and increasing cases of hiv-leishmaniasis co-infection. hence, there is a need to identify novel metabolic pathways for design of new chemical entities. acetyl-coa synthetase (acecs) is an enzyme of acetate metabolic pathway whose functions are unknown in leis ...201727825908
imaging visceral leishmaniasis in real time with golden hamster model: monitoring the parasite burden and hamster transcripts to further characterize the immunological responses of the host.characterizing the clinical, immunological and parasitological features associated with visceral leishmaniasis is complex. it involves recording in real time and integrating quantitative multi-parametric data sets from parasite infected host tissues. although several models have been used, hamsters are considered the bona fide experimental model for leishmania donovani studies. to study visceral leishmaniasis in hamsters we generated virulent transgenic l. donovani that stably express a reporter ...201727794505
leishmania donovani development in phlebotomus argentipes: comparison of promastigote- and amastigote-initiated infections.leishmania parasites alternate in their life cycle between promastigote stages that develop in the gut of phlebotomine sand flies and amastigotes residing inside phagocytic cells of vertebrate hosts. for experimental infections of sand flies, promastigotes are frequently used as this way of infection is technically easier although ingestion of promastigotes by sand flies is unnatural. here we aimed to answer a critical question, to what extent do promastigote-initiated experimental infections di ...201727876097
detection and differentiation of leishmania spp. in clinical specimens by use of a sybr green-based real-time pcr assay.leishmaniasis in humans is caused by leishmania spp. in the subgenera leishmania and viannia species identification often has clinical relevance. until recently, our laboratory relied on conventional pcr amplification of the internal transcribed spacer 2 (its2) region (its2-pcr) followed by sequencing analysis of the pcr product to differentiate leishmania spp. here we describe a novel real-time quantitative pcr (qpcr) approach based on the sybr green technology (lsg-qpcr), which uses genus-spec ...201727847378
nonresponsiveness to standard treatment in cutaneous leishmaniasis: a case series from sri lanka.leishmaniasis is caused by parasitic protozoa of the genus leishmania. cutaneous leishmaniasis (cl) is endemic in sri lanka with over 3000 cases during the last decade and numbers are increasing. treatment options available in sri lanka for cl include intralesional/intramuscular sodium stibogluconate and cryotherapy. eight cases of treatment failure with standard therapy are reported from the dermatology clinic, teaching hospital anuradhapura. therapeutic regimes aim for clinical healing, these ...201727722106
in vitro 'time-to-kill' assay to assess the cidal activity dynamics of current reference drugs against leishmania donovani and leishmania infantum.despite a continued search for novel antileishmanial drugs, treatment options remain restricted to a few standard drugs, e.g. antimonials, miltefosine, amphotericin b and paromomycin. although these drugs have now been used for several decades, their mechanism of action still remains partly hypothetical and their dynamics of cidal action and time-to-kill are still poorly documented.201727707992
a comparison of the effectiveness of sodium stibogluconate monotherapy to sodium stibogluconate and paromomycin combination for the treatment of severe post kala azar dermal leishmaniasis in south sudan - a retrospective cohort study.post-kala-azar dermal leishmaniasis (pkdl) is a common dermatological complication following successful treatment of visceral leishmaniasis (vl) caused by leishmania donovani. pkdl presents as macular, papular, nodular or mixed skin rash on sun-exposed body parts. patients are not ill unless there are complications due to mucosal involvement or ulceration. as pkdl in east africa is typically self-healing, and treatment is long and with significant adverse events, only severe and complicated case ...201727658288
cd4+ recent thymic emigrants are recruited into granulomas during leishmania donovani infection but have limited capacity for cytokine production.recent thymic emigrants (rtes) represent a source of antigen-naïve t cells that enter the periphery throughout life. however, whether rtes contribute to the control of chronic parasitic infection and how their potential might be harnessed by therapeutic intervention is currently unclear. here, we show that cd4+ recent thymic emigrants emerging into the periphery of mice with ongoing leishmania donovani infection undergo partial activation and are recruited to sites of granulomatous inflammation. ...201727658046
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
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
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
immunomodulation mediated through leishmania donovani protein disulfide isomerase by eliciting cd8+ t-cell in cured visceral leishmaniasis subjects and identification of its possible hla class-1 restricted t-cell epitopes.protein disulphide isomerase (pdi) is one of the key enzymes essential for the survival of leishmania donovani in the host. our study suggested that pdi is associated with the generation of th1-type of cellular responses in treated visceral leishmaniasis (vl) subjects. the stimulation of peripheral blood mononuclear cells (pbmcs) with recombinant protein disulphide isomerase upregulated the reactive oxygen species generation, nitric oxide release, il12 and ifn-γ production indicating its pivotal ...201726727289
comparison of three blood transfusion guidelines applied to 31 feline donors to minimise the risk of transfusion-transmissible infections.objectives the increased demand for animal blood transfusions creates the need for an adequate number of donors. at the same time, a high level of blood safety must be guaranteed and different guidelines (gls) deal with this topic. the aim of this study was to evaluate the appropriateness of different gls in preventing transfusion-transmissible infections (tti) in italian feline blood donors. methods blood samples were collected from 31 cats enrolled as blood donors by the owners' voluntary choi ...201728840782
corrigendum to "cross reactive molecules of human lymphatic filaria brugia malayi inhibit leishmania donovani infection in hamsters" [acta trop. 152 (2015) 103-111]. 201728456277
a new antifungal and antiprotozoal bibenzyl derivative from gavilea lutea.a new bibenzyl derivative (4), together with two glycosylated flavonoids (1 and 2), batatasin iii (3) and the phenanthrene isohircinol (5) were isolated from the aerial parts of gavilea lutea. their structures were elucidated on the basis of spectroscopic studies including 1d and 2d nmr, uv, ir and hresims. all isolated compounds were evaluated for their antifungal activity towards candida albicans. the new compound 4 showed inhibitory activity with a miq of 50 μg. in addition, compound 4 exhibi ...201728595455
hydrophilic acylated surface protein a (haspa) of leishmania donovani: expression, purification and biophysico-chemical characterization.hydrophilic acylated surface proteins (hasps) are acidic surface proteins which get localized on the surface of leishmania parasite during infective stages through a "non-classical" pathway. in this study, we report the heterologous expression and purification of leishmania donovani haspa (r-ldhaspa) in e. coli system and its partial characterization. the structural aspects of the purified protein were analyzed using cd spectroscopy and modeling studies which indicate that r-ldhaspa consists of ...201728634775
the mitochondrial sir2 related protein 2 (sir2rp2) impacts leishmania donovani growth and infectivity.leishmania donovani, a protozoan parasite is the major causative agent of visceral leishmaniasis. increased toxicity and resistance to the existing repertoire of drugs has been reported. hence, an urgent need exists for identifying newer drugs and drug targets. previous reports have shown sirtuins (silent information regulator) from kinetoplastids as promising drug targets. leishmania species code for three sir2 (silent information regulator) related proteins. here, we for the first time report ...201728493888
efficacy of a binuclear cyclopalladated compound therapy for cutaneous leishmaniasis in the murine model of infection with leishmania amazonensis and its inhibitory effect on topoisomerase 1b.leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the leishmania genus. despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. the high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. we report here the evaluation of a binuclear cyclopalladated complex containing pd(ii) and ...201728507113
voacamine alters leishmania ultrastructure and kills parasite by poisoning unusual bi-subunit topoisomerase ib.indole alkaloids possess a large spectrum of biological activities including anti-protozoal action. here we report for the first time that voacamine, isolated from the plant tabernaemontana coronaria, is an antiprotozoal agent effective against a large array of trypanosomatid parasites including indian strain of leishmania donovani and brazilian strains of leishmania amazonensis and trypanosoma cruzi. it inhibits the relaxation activity of topoisomerase ib of l. donovani (ldtop1b) and stabilizes ...201728483460
in vitro antileishmanial activity and iron superoxide dismutase inhibition of arylamine mannich base derivatives.leishmaniasis is one of the world's most neglected diseases, and it has a worldwide prevalence of 12 million. there are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. therefore, research aiming at the development of new therapeutic tools to fight leishmaniasis remains a crucial goal today. with this purpose in mind, we present 20 arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against trypanosoma cruzi that have now ...201728789716
alkaloid constituents of the amaryllidaceae plant amaryllis belladonna l.the plant family amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. its representative, amaryllis belladonna, has a geographical distribution covering mainly southern africa, where it has significant usage in the traditional medicine of the native people. in this study, a. belladonna samples collected in brazil were examined for alkaloid content. alkaloid profiles of a. belladonna bulbs were generated by a combination of chroma ...201728858260
solute carrier protein family 11 member 1 (slc11a1) activation efficiently inhibits leishmania donovani survival in host macrophages.visceral leishmaniasis (kala-azar), a life threatening disease caused by l. donovani, is a latent threat to more than 147 million people living in disease endemic south east asia region of the indian subcontinent. the therapeutic option to control leishmanial infections are very limited, and at present comprise only two drugs, an antifungal amphotericin b and an antitumor miltefosine, which are also highly vulnerable for parasitic resistance. therefore, identification and development of alternat ...201728848257
structure and binding studies of proliferating cell nuclear antigen from leishmania donovani.proliferating cell nuclear antigen (pcna) acts as a sliding clamp to support dna replication and repair. the structure of pcna from leishmania donovani (ldpcna) has been determined at 2.73å resolution. structure consists of six crystallographically independent molecules which form two trimeric rings. the pore diameter of the individual trimeric ring is of the order of 37å. the two rings are stacked through their front to front faces. in order to gain a stable packing, the rings are rotated by 42 ...201728844736
synthesis and activity of a new series of antileishmanial agents.we have determined that tetrahydroindazoles such as 1 show potent activity against leishmania donovani, the causative agent of leishmaniasis. while the hsp90 activity and anticancer properties of 1 have previously been explored, we present here our efforts to optimize their activity against l. donovani via the synthesis of novel analogues designed to probe the hydrophobic pocket of the protozoan hsp90 orthologue, specifically through the auspices of functionalization of an amine embedded into th ...201728835791
comparative study on the nocturnal activity of phlebotomine sand flies in a highland and lowland foci of visceral leishmaniasis in north-western ethiopia with special reference to phlebotomus orientalis.leishmania donovani, the causative agent of visceral leishmaniasis (vl), is most probably vectored by phlebotomus orientalis in north-western ethiopia. the aim of this study was to determine and compare the nocturnal activity patterns of ph. orientalis in vl endemic foci of libo-kemkem (highland) and metema (lowland) districts of north-western ethiopia.201728830569
eugenol derived immunomodulatory molecules against visceral leishmaniasis.visceral leishmaniasis (vl) is a life threatening infectious disease caused by leishmania donovani. it leads to the severe immune suppression in the host defense system. higher cytotoxicity, rigorous side effects and lower therapeutic indexes (ti) of current antileishmanial drugs have created a necessity to develop new molecules with better antileishmanial activity and high ti value. in this study, we have synthesized 36 derivatives of eugenol and screened them for their activity against promast ...201728826085
identification of leishmania donovani antigen in circulating immune complexes of visceral leishmaniasis subjects for diagnosis.the unreliability of most of the existing antibody-based diagnostic kits to discriminate between active and treated vl cases, relapse situation and reinfection are a major hurdle in controlling the cases of kala-azar in an endemic area. an antigen targeted diagnostic approaches can be an attractive strategy to overcome these problems. hence, this study was focused on identifying the leishmania antigens, lies in circulating immune complex (cics), can be used for diagnostic as well as prognostic p ...201728820895
efficacy, safety and cost-effectiveness of thermotherapy in the treatment of leishmania donovani-induced cutaneous leishmaniasis: a randomized controlled clinical trial.leishmania donovani causes cutaneous leishmaniasis (cl) in sri lanka. standard treatment is multiple, painful doses of intralesional sodium stibogluconate (il-ssg). treatment failures are increasingly reported, hence the need to investigate alternatives. efficacy, safety, and cost-effectiveness of thermotherapy were assessed for the first time for l. donovani cl. a single blinded noninferiority randomized controlled trial was conducted on new laboratory-confirmed cl patients with single lesions ...201728820681
emergence of visceral leishmaniasis in sri lanka: a newly established health threat.sri lanka is a new focus of human cutaneous leishmaniasis caused by a genetic variant of usually visceralizing parasite leishmania donovani. over 3000 cases have been reported to our institution alone, during the past two decades. recent emergence of visceral leishmaniasis is of concern.201728820339
unveiling cerebral leishmaniasis: parasites and brain inflammation in leishmania donovani infected mice.visceral leishmaniasis (vl) is a systemic disease with multifaceted clinical manifestations, including neurological signs, however, the involvement of the nervous system during vl is underestimated. accordingly, we investigated both brain infection and inflammation in a mouse model of vl. using bioluminescent leishmania donovani and real-time 2d-3d imaging tools, we strikingly detected live parasites in the brain, where we observed a compartmentalized dual-phased inflammation pattern: an early p ...201728814754
3m-052 as an adjuvant for a plga microparticle-based leishmania donovani recombinant protein vaccine.it is believed that an effective vaccine against leishmaniasis will require a t helper type 1 (th 1) immune response. in this study, we investigated the adjuvanticity of the toll-like receptor (tlr) 7/8 agonist 3m-052 in combination with the leishmania donovani 36-kda nucleoside hydrolase recombinant protein antigen (nh36). nh36 and 3m-052 were encapsulated in separate batches of poly(lactic-co-glycolic acid) (plga) microparticles (mps). the loading efficiency for nh36 was 83% and for 3m-052 was ...201728804955
l-arginine uptake by cationic amino acid transporter promotes intra-macrophage survival of leishmania donovani by enhancing arginase-mediated polyamine synthesis.the survival of intracellular protozoan parasite, leishmania donovani, the causative agent of indian visceral leishmaniasis (vl), depends on the activation status of macrophages. l-arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. however, the role of l-arginine transport in vl still remains elusive. in this study, we demonstrated that intra-macrophage survival of l. donovani depends on the availability of extracellular l-arginine. infection of ...201728798743
identification of two natural compound inhibitors of leishmania donovani spermidine synthase (spds) through molecular docking and dynamic studies.visceral leishmaniasis caused by the protozoan leishmania donovani is the most severe form of leishmaniasis and it is potentially lethal if untreated. despite the availability of drugs for treating the disease, the current drug regime suffers from drawbacks like antibiotic resistance and toxicity. new drugs have to be discovered in order to overcome these limitations. our aim is to identify natural compounds from plant sources as putative inhibitors considering the occurrence of structural diver ...201728797195
lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles.a library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties was assayed for in vitro antiparasitic activity and the results were added to our previously reported derivatives for a comprehensive sar evaluation. four compounds showed an ic50 between 0.25 and 3μm against leishmania donovani and low cytotoxicity. compound g{16} (1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline), was particularly interesting with an ic50 similar to the reference drug miltefos ...201728789893
infection-adapted emergency hematopoiesis promotes visceral leishmaniasis.cells of the immune system are derived from hematopoietic stem cells (hscs) residing in the bone marrow. hscs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. however, the impact of infection-adapted hsc activation and differentiation on the persistence of chronic infections is poorly understood. we have examined here the bone marrow outcome of chronic visceral leishmaniasis and show that the parasite leishm ...201728787450
chitosan coated pluronicf127 micelles for effective delivery of amphotericin b in experimental visceral leishmaniasis.the goal of study was to develop micellar formulation of amphotericin b (amb) to improve its antileishmanial efficacy. amb loaded pluronic f127 (pf 127) micelles were developed and coated with chitosan (cs-pf-amb-m) to accord immunoadjuvant and macrophage targeting properties. hemolysis and cytotoxicity studies demonstrated that cs-pf-amb-m was 7.93 fold (at 20μg/ml amb concentration) and 9.35 fold less hemolytic and cytotoxic, respectively in comparison to amb suspension. flow cytometry studies ...201728780414
bifurcatriol, a new antiprotozoal acyclic diterpene from the brown alga bifurcaria bifurcata.linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. this study reports bifurcatriol (1), a new linear diterpene featuring two stereogenic centers isolated from the irish brown alga bifurcariabifurcata. the gross structure of this new natural product was elucidated based on its spectroscopic data (ir, 1d and 2d-nmr, hrms). its absolute configuration was identified by experimental and computational vibrational circular dichroism (vcd) spec ...201728767061
leishmania donovani inhibits inflammasome-dependent macrophage activation by exploiting the negative regulatory proteins a20 and ucp2.in visceral leishmaniasis, we found that the antileishmanial drug amp b produces a higher level of il-1β over the infected control. moreover, administering anti-il-1β antibody to infected amp b-treated mice showed significantly less parasite clearance. investigation revealed that leishmania inhibits stimuli-induced expression of a multiprotein signaling platform, nlrp3 inflammasome, which in turn inhibits caspase-1 activation mediated maturation of il-1β from its pro form. attenuation of nlrp3 a ...201728765172
evaluation of antimycobacterial, leishmanicidal and antibacterial activity of three medicinal orchids of arunachal pradesh, india.the ethnic population of arunachal pradesh uses a number of orchids as such, or in decoction for various ailments. three untapped orchids namely, rhynchostylis retusa, tropidia curculioides and satyrium nepalense, traditionally used in tuberculosis, asthma and cold stage of malaria in folk medicine, were selected for the present study.201728764749
f1 domain of the leishmania (leishmania) donovani nucleoside hydrolase promotes a th1 response in leishmania (leishmania) infantum cured patients and in asymptomatic individuals living in an endemic area of leishmaniasis.the leishmania (leishmania) donovani nucleoside hydrolase nh36 is the main antigen of the leishmune(®) vaccine and one of the promising candidates for vaccination against visceral leishmaniasis. the antigenicity of the n-terminal (f1), the central (f2), or the c-terminal recombinant domain (f3) of nh36 was evaluated using peripheral blood mononuclear cells (pbmc) from individuals infected with l. (l.) infantum from an endemic area of visceral leishmaniasis of spain. both nh36 and f1 domains sign ...201728747911
assessment of quality of life in patients with post kalaazar dermal leishmaniasis.post kala-azar dermal leishmaniasis (pkdl) is a dermatological disorder caused by protozoal parasite leishmania donovani. pkdl cases are thought to be a reservoir of parasites and may increase cases of visceral leishmaniasis. the disease is not life threatening but cosmetic disfigurement associated with it may impair the patients' quality of life. this study aimed to assess the health related quality of life in patients with post kalaazar dermal leishmanasis for the first time.201728738881
serological and molecular analysis of leishmania infection in healthy individuals from two districts of west bengal, india, endemic for visceral leishmaniasis.abstractseveral epidemiological studies have indicated the presence of asymptomatic infections with leishmania donovani in the indian subcontinent, where parasite transmission is considered anthroponotic. in india, such asymptomatic leishmania cases have been identified in the state of bihar. we explored here, the presence of asymptomatic leishmania infection among healthy individuals living in two districts in the state of west bengal, india, using serological and molecular tests. blood samples ...201728719266
homology modeling of leishmania donovani enolase and its molecular interaction with novel inhibitors.the treatment of indian tropical disease such as kala-azar is likely to be troublesome to the clinicians as ampb- and miltefosine-resistant leishmania donovani has been reported. the rationale behind designed a novel inhibitors of model of l. donovani enolase and performing a binding study with its inhibitors to gain details of the interaction between protein residues and ligand molecules.201728717332
hexadecylphosphocholine (miltefosine) stabilized chitosan modified ampholipospheres as prototype co-delivery vehicle for enhanced killing of l. donovani.lipid nanoparticles are stable, biodegradable and biocompatible carriers offering excellent therapeutic efficacy. here, a novel effort has been made to develop miltefosine (hepc- hexadecylphosphocholine) stabilized chitosan anchored nanostructured lipid carriers (nlc) of amphotericin b (amb) as co-delivery vehicle to enhance killing of l. donovani. the entrapment efficiency of amb was achieved upto 85.3% for hepc-amb-cnlcs with mean particle size of 150.8±8.4nm, and zeta potential value of +28.2 ...201728716750
synthesis of a glycosylphosphatidylinositol anchor derived from leishmania donovani that can be functionalized by cu-catalyzed azide-alkyne cycloadditions.a flexible assembly strategy has been developed for the synthesis of leishmania donovani gpi anchors that bear a clickable alkyne tag. this strategy is based on the use of the 2-naphthylmethyl (nap) ethers and levulinoyl (lev) ester for permanent protection of hydroxyls. removal of seven nap ethers by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone made it possible to prepare gpis having an alkyne functionality that could be modified by cu(i)-catalyzed [3 + 2] cycloadditions to install tags for imagin ...201728696125
molecular, biochemical characterization and assessment of immunogenic potential of cofactor-independent phosphoglycerate mutase against leishmania donovani: a step towards exploring novel vaccine candidate.despite immense efforts, vaccine against visceral leishmaniasis has yet not been developed. earlier our proteomic study revealed a novel protein, cofactor-independent phoshoglycerate mutase (ldipgam), an important enzyme in glucose metabolism, in t helper cells type 1 (th1) stimulatory region of soluble leishmania donovani antigen. in this study, ldipgam was biochemically and molecularly characterized and evaluated for its immunogenicity and prophylactic efficacy against l. donovani. immunogenic ...201728691653
the role of pd-1 in regulation of macrophage apoptosis and its subversion by leishmania donovani.programmed death-1 receptor (pd-1) expressed in many immune cells is known to trigger t-cell exhaustion but the significance of macrophage-associated pd-1 in relevance to macrophage apoptosis is not known. this study is aimed to delineate whether pd-1 pathway has any role in eliciting macrophage apoptosis and, if so, then how the intra-macrophage parasite, leishmania donovani modulates pd-1 pathway for protecting its niche. resting macrophages when treated with h2o2 showed increased pd-1 express ...201728690843
in vitro effects of purine and pyrimidine analogues on leishmania donovani and leishmania infantum promastigotes and intracellular amastigotes.inhibition of parasite metabolic pathways is a rationale for new chemotherapeutic strategies. the pyrimidine and purine salvage pathways are thus targets against leishmania donovani and l. infantum, causative agents of visceral human leishmaniasis and canine leishmaniosis. the antiproliferative effect of the pyrimidine analogues cytarabine and 5-fluorouracil and of the purine analogues azathioprine and 6-mercaptopurine was evaluated in vitro on the promastigote and the intracellular amastigote s ...201728682767
skin parasite landscape determines host infectiousness in visceral leishmaniasis.increasing evidence suggests that the infectiousness of patients for the sand fly vector of visceral leishmaniasis is linked to parasites found in the skin. using a murine model that supports extensive skin infection with leishmania donovani, spatial analyses at macro-(quantitative pcr) and micro-(confocal microscopy) scales indicate that parasite distribution is markedly skewed. mathematical models accounting for this heterogeneity demonstrate that while a patchy distribution reduces the expect ...201728680146
whole genome sequencing of live attenuated leishmania donovani parasites reveals novel biomarkers of attenuation and enables product characterization.no licensed human vaccines are currently available against leishmaniasis. several anti-leishmanial vaccines are currently undergoing testing, including genetically modified live-attenuated parasite vaccines. studies with live attenuated leishmania vaccines such as centrin deleted leishmania donovani parasites (ldcen (-/-)) showed protective immunity in animal models. such studies typically examined the biomarkers of protective immunity however the biomarkers of attenuation in the parasite prepar ...201728680050
tnf signalling drives expansion of bone marrow cd4+ t cells responsible for hsc exhaustion in experimental visceral leishmaniasis.visceral leishmaniasis is associated with significant changes in hematological function but the mechanisms underlying these changes are largely unknown. in contrast to naïve mice, where most long-term hematopoietic stem cells (lt-hscs; lsk cd150+ cd34- cd48- cells) in bone marrow (bm) are quiescent, we found that during leishmania donovani infection most lt-hscs had entered cell cycle. loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by se ...201728671989
antileishmanial and immunomodulatory activities of lupeol, a triterpene compound isolated from sterculia villosa.visceral leishmaniasis (vl) is one of the most severe forms of leishmaniasis, caused by the protozoan parasite leishmania donovani. nowadays there is a growing interest in the therapeutic use of natural products to treat parasitic diseases. sterculia villosa is an ethnomedicinally important plant. a triterpenoid was isolated from this plant and was screened for its antileishmanial and immunomodulatory activities in vitro and in vivo. biochemical colour test and spectroscopic data confirmed that ...201728669838
corrigendum: identification and characterization of mirnas in response to leishmania donovani infection: delineation of their roles in macrophage dysfunction.[this corrects the article on p. 314 in vol. 8, pmid: 28303124.].201728659911
wnt5a signaling promotes host defense against leishmania donovani infection.leishmania donovani infects macrophages, disrupting immune homeostasis. the underlying mechanism that sustains infection remains unresolved. in view of the potential of wnt5a signaling to support immune homeostasis, we evaluated the interrelationship of wnt5a signaling and leishmania donovani infection. upon infecting macrophages separately with antimony drug-sensitive and -resistant l. donovani, we noted disruption in the steady-state level of wnt5a. moreover, inhibition of wnt5a signaling by s ...201728659356
cisplatin along with herbal drug treatment reduces the percentage of regulatory t cells and decreased the severity of experimental visceral leishmaniasis.visceral leishmaniasis is the most alarming and devastating amongst the various forms of leishmaniases. it is caused by leishmania donovani, an obligate intracellular parasite of macrophages that survives through immunosuppression. absence of t regulatory cells provides complete clearance of the parasite. a few immunoprophylactics have been sought to battle instinctive leishmaniasis, with fluctuating achievement. our previous studies have shown that treatment of l. donovani infected mice with ci ...201728655574
leishmania donovani resides in modified early endosomes by upregulating rab5a expression via the downregulation of mir-494.several intracellular pathogens arrest the phagosome maturation in the host cells to avoid transport to lysosomes. in contrast, the leishmania containing parasitophorous vacuole (pv) is shown to recruit lysosomal markers and thus leishmania is postulated to be residing in the phagolysosomes in macrophages. here, we report that leishmania donovani specifically upregulates the expression of rab5a by degrading c-jun via their metalloprotease gp63 to downregulate the expression of mir-494 in thp-1 d ...201728650977
mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis.earlier we have established a carbazole alkaloid (mahanine) isolated from an indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. here we report for the first time that mahanine-treated drug resistant and sensitive virulent leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, dna fragmentation and cell cycle arrest. an early induction of reactive oxygen species (ros) suggests that the mahanine-induced apoptosis was ...201728646156
role of inhibitors of serine peptidases in protecting leishmania donovani against the hydrolytic peptidases of sand fly midgut.in vector-borne diseases such as leishmaniasis, the sand fly midgut is considered to be an important site for vector-parasite interaction. digestive enzymes including serine peptidases such as trypsin and chymotrypsin, which are secreted in the midgut are one of the obstacles for leishmania in establishing a successful infection. the presence of some natural inhibitors of serine peptidases (isps) has recently been reported in leishmania. in the present study, we deciphered the role of these isps ...201728645315
pharmacodynamics and biodistribution of single-dose liposomal amphotericin b at different stages of experimental visceral leishmaniasis.visceral leishmaniasis is a neglected tropical disease that causes significant morbidity and mortality worldwide. characterization of the pharmacokinetics and pharmacodynamics of antileishmanial drugs in preclinical models is important for drug development and use. here we investigated the pharmacodynamics and drug distribution of liposomal amphotericin b (ambisome) in leishmania donovani-infected balb/c mice at three different dose levels and two different time points after infection. we additi ...201728630200
multiplexed spliced-leader sequencing: a high-throughput, selective method for rna-seq in trypanosomatids.high throughput sequencing techniques are poorly adapted for in vivo studies of parasites, which require prior in vitro culturing and purification. trypanosomatids, a group of kinetoplastid protozoans, possess a distinctive feature in their transcriptional mechanism whereby a specific spliced leader (sl) sequence is added to the 5'end of each mrna by trans-splicing. this allows to discriminate trypansomatid rna from mammalian rna and forms the basis of our new multiplexed protocol for high-throu ...201728623350
ifn-γ, il-2, ip-10, and mig as biomarkers of exposure to leishmania spp., and of cure in human visceral leishmaniasis.new biomarkers are needed for monitoring the effectiveness of treatment for visceral leishmaniasis (vl). they might also improve the detection of the asymptomatic population in leishmania-endemic areas. this paper examines the il-2, ifn-γ, ifn-γ-induced protein 10 (ip-10), and monokine-induced-by-ifn-γ (mig) levels in whole blood-stimulated in vitro with soluble leishmania antigen (sla)-taken from asymptomatic individuals and patients treated for vl living in a post-outbreak (leishmania infantum ...201728620584
leishmania donovani infection activates tlr 2, 4 expressions and tgf-β mediated apoptosis in renal tissues.the present study was aimed to identify the underlying mechanisms of improper renal function in leishmania donovani infection that causes vl. mice (balb/c) were infected with l. donovani and different parameters for proteinuria were assessed. the levels of superoxide anion (o2(-)), hydrogen peroxide (h2o2), lipid peroxidation (mda), inflammatory cytokines, and toll-like receptor (tlr) 2 and 4 expression were found significantly elevated at 60th day in these animals and declined at 90th day post ...201728606413
alkaloids and leishmania donovani udp-galactopyarnose mutase: anovel approach in drug designing against visceral leishmaniasis.the unsatisfactory treatment options for visceral leishmaniasis (vl), needs identification of new drug targets. among natural products, alkaloids have been proved to be highly effective against number of diseases. in leishmania udp-galactopyranose mutase (ugm) is a critical enzyme required for cell wall synthesis and thus a drug target for structure based drug designing against l. donovani.201728595543
leishmaniasis in turkey: visceral and cutaneous leishmaniasis caused by leishmania donovani in turkey.in turkey, the main causative agents are leishmania tropica (l. tropica) and leishmania infantum (l. infantum) for cutaneous leishmaniasis (cl) and l. infantum for visceral leishmaniasis (vl). in this study, we investigated leishmaniasis cases caused by l. donovani and established animal models for understanding its tropism in in vivo conditions. clinical samples (lesion aspirations and bone marrow) obtained from cl/vl patients were investigated using parasitological (smear/nnn) and dna-based te ...201728587839
intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in leishmania donovani.leishmaniasis caused by leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. leishmania is an obligate intracellular parasite that alternates between sand fly and human host. to survive and establish infections, leishmania parasites scavenge and internalize nutrients from the host. nevertheless, host cells presents mechanism like nutrie ...201728586364
mining the proteome of leishmania donovani for the development of novel mhc class i restricted epitope for the control of visceral leishmaniasis.although, the precise host defence mechanism(s) is not completely understood, t cell-mediated immune responses is believed to play a pivotal role in controlling parasite infection. here we target the stage dependent over expressed gene. here, the consensus based computational approach was adopted for the screening of potential major histocompatibility complex class i restricted epitopes. based on the computational analysis and previously published report, a set 19 antigenic proteins derived from ...201728585770
b-cell activating factor deficiency suppresses splenomegaly during leishmania donovani infection.b-cell activating factor (baff) is a critical regulator for b-cell development and differentiation. we previously reported elevation of serum baff levels in patients with visceral leishmaniasis (vl). in this study, we examined if baff is involved in pathologies during infection of leishmania donovani. balb/ca mice infected with l. donovani showed significant elevation in serum baff and igg levels as seen in vl patients. in contrast, elevation of serum igg by l. donovani infection was significant ...201728583852
molecular signatures of neutrophil extracellular traps in human visceral leishmaniasis.infections with parasites of the leishmania donovani complex result in clinical outcomes that range from asymptomatic infection to severe and fatal visceral leishmaniasis (vl). neutrophils are major players of the immune response against leishmania, but their contribution to distinct states of infection is unknown. gene expression data suggest the activation of the netosis pathway during human visceral leishmaniasis. thus, we conducted an exploratory study to evaluate net-related molecules in re ...201728583201
gtpase sar1 regulates the trafficking and secretion of the virulence factor gp63 in leishmania.metalloprotease gp63 (leishmania donovani gp63 (ldgp63)) is a critical virulence factor secreted by leishmania however, how newly synthesized ldgp63 exits the endoplasmic reticulum (er) and is secreted by this parasite is unknown. here, we cloned, expressed, and characterized the gtpase ldsar1 and other copii components like ldsec23, ldsec24, ldsec13, and ldsec31 from leishmania to understand their role in er exit of ldgp63. using dominant-positive (ldsar1:h74l) and dominant-negative (ldsar1:t34 ...201728576830
increased miltefosine tolerance in clinical isolates of leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress.miltefosine (mil) is an oral antileishmanial drug used for treatment of visceral leishmaniasis (vl) in the indian subcontinent. recent reports indicate a significant decline in its efficacy with a high rate of relapse in vl as well as post kala-azar dermal leishmaniasis (pkdl). we investigated the parasitic factors apparently involved in miltefosine unresponsiveness in clinical isolates of leishmania donovani.201728575060
epitope mapping of recombinant leishmania donovani virulence factor a2 (recldvfa2) and canine leishmaniasis diagnosis using a derived synthetic bi-epitope.leishmaniasis is one of the most important zoonotic diseases spread in latin america. since many species are involved in dog infection with different clinical manifestations, the development of specific diagnostic tests is mandatory for more accurate disease control and vaccine strategies.201728557986
alcoholic fractions f5 and f6 from withania somnifera leaves show a potent antileishmanial and immunomodulatory activities to control experimental visceral leishmaniasis.visceral leishmaniasis (vl) causes fatal life-threatening disease, if left untreated. the current drugs have various limitations; hence, natural products from medicinal plants are being focused in search of new drugs to treat leishmaniasis. the aim of the present study was to evaluate the antileishmanial and immunomodulatory activities of f5 and f6 alcoholic fractions from withania somnifera leaves and purified withaferin-a in leishmania donovani-infected peritoneal macrophages and balb/c mice. ...201728553635
preliminary study on investigation of zoonotic visceral leishmaniasis in endemic foci of ethiopia by detecting leishmania infections in rodents.to investigate the zoonotic visceral leishmaniasis (zvl) by identification of the most probable reservoir hosts using parasite isolation and analysis of a possible transmission dynamics of the disease in extra-domestic agricultural fields and rural villages.201728552113
prediction and analysis of promiscuous t cell-epitopes derived from the vaccine candidate antigens of leishmania donovani binding to mhc class-ii alleles using in silico approach.visceral leishmaniasis is a dreadful infectious disease and caused by the intracellular protozoan parasites, leishmania donovani and leishmania infantum. despite extensive efforts for developing effective prophylactic vaccine, still no vaccine is available against leishmaniasis. however, advancement in immunoinformatics methods generated new dimension in peptide based vaccine development. the present study was aimed to identify t-cell epitopes from the vaccine candidate antigens like lipophospho ...201728549876
unravelling the rate of action of hits in the leishmania donovani box using standard drugs amphotericin b and miltefosine.in recent years, the neglected diseases drug discovery community has elected phenotypic screening as the key approach for the identification of novel hit compounds. however, when this approach is applied, important questions related to the mode of action for these compounds remain unanswered. one of such questions is related to the rate of action, a useful piece of information when facing the challenge of prioritising the most promising hit compounds. in the present work, compounds of the "leish ...201728542202
leishmania donovani restricts mitochondrial dynamics to enhance mirnp stability and target rna repression in host macrophages.micrornas (mirnas), the tiny regulatory rnas, form complexes with argonaute (ago) proteins and inhibit gene expression in metazoan cells. while studying parasite-invaded macrophages, we identify a unique mode of gene regulation in which the parasite leishmania donovani (ld) causes mitochondrial depolarization, reduces mitochondrial dynamics, and restricts turnover of cellular microrna ribonucleoprotein (mirnp) complexes in infected host cells. this leads to increased stability of mirnps along wi ...201728539410
modulation of aneuploidy in leishmania donovani during adaptation to different in vitro and in vivo environments and its impact on gene expression.aneuploidy is usually deleterious in multicellular organisms but appears to be tolerated and potentially beneficial in unicellular organisms, including pathogens. leishmania, a major protozoan parasite, is emerging as a new model for aneuploidy, since in vitro-cultivated strains are highly aneuploid, with interstrain diversity and intrastrain mosaicism. the alternation of two life stages in different environments (extracellular promastigotes and intracellular amastigotes) offers a unique opportu ...201728536289
establishing, expanding, and certifying a closed colony of phlebotomus argentipes (diptera: psychodidae) for xenodiagnostic studies at the kala azar medical research center, muzaffarpur, bihar, india.this pilot project was preliminary and essential to a larger effort to define the ability of certain human-subject groups across the infection spectrum to serve as reservoirs of leishmania donovani infection to sand flies in areas of anthroponotic transmission such as in bihar state, india. this is possible only via xenodiagnosis of well-defined subject groups using live vector sand flies. the objective was to establish at the kala azar medical research center (kamrc), muzaffarpur, bihar, india, ...201728525618
environmental factors associated with the distribution of visceral leishmaniasis in endemic areas of bangladesh: modeling the ecological niche.visceral leishmaniasis (vl) is a parasitic infection (also called kala-azar in south asia) caused by leishmania donovani that is a considerable threat to public health in the indian subcontinent, including densely populated bangladesh. the disease seriously affects the poorest subset of the population in the subcontinent. despite the fact that the incidence of vl results in significant morbidity and mortality, its environmental determinants are relatively poorly understood, especially in banglad ...201728515660
molecular events leading to death of leishmania donovani under spermidine starvation after hypericin treatment.we have previously reported that the hypericin treatment caused spermidine starvation and death of leishmania parasite. here, we report different molecular events under spermidine starvation and potential role of spermidine in processes other than redox homeostasis of the parasite. we have analyzed changes in expression of several genes by using quantitative gene expression analysis. further, these changes at molecular level were also confirmed by using biochemical and cellular studies. altered ...201728509385
combined treatment of miltefosine and paromomycin delays the onset of experimental drug resistance in leishmania infantum.since miltefosine monotherapy against visceral leishmaniasis (vl) caused by leishmania donovani has been discontinued in the indian subcontinent due to an increase in the number of treatment failures, single dose liposomal amphotericin b is now advocated as a treatment option of choice. paromomycin-miltefosine combination therapy can be used as substitute first-line treatment in regions without cold-chain potential. previous laboratory studies in the closely related species leishmania infantum h ...201728505185
alkamides from anacyclus pyrethrum l. and their in vitro antiprotozoal activity.in our ongoing study to evaluate the antiprotozoal activity of alkamides from asteraceae, a dichloromethane extract from the roots of anacycluspyrethrum l. showed a moderate in vitro activity against the nf54 strain of plasmodium falciparum and against leishmaniadonovani (amastigotes, mhom/et/67/l82 strain). seven pure alkamides and a mixture of two further alkamides were isolated by column chromatography followed by preparative high performance liquid chromatography. the alkamides were identifi ...201728498323
hat2 mediates histone h4k4 acetylation and affects micrococcal nuclease sensitivity of chromatin in leishmania donovani.histone post-translational modifications (ptms) such as acetylation and methylation are known to affect chromatin higher order structures. primary targets of these modifications include basic residues present at n-terminus tail region of core histones. four histone acetyltransferase (hat) genes have been identified in trypanosomatids. hat1, hat3 and hat4 of leishmania donovani have been partially characterized. however, there is no report about hat2 of leishmania donovani. lysine residues presen ...201728486547
oral delivery of ursolic acid-loaded nanostructured lipid carrier coated with chitosan oligosaccharides: development, characterization, in vitro and in vivo assessment for the therapy of leishmaniasis.visceral leishmaniasis (vl) is a life-threatening disease caused by leishmania donovani due to uncontrolled parasitisation of liver, spleen, and bone marrow. ursolic acid (ua), a promising anti-inflammatory, anti-bacterial and anti-diabetic drug used successfully for treatment of ailments. development of new delivery system is extremely urgent for ua with better efficacy and fewer side effects. the aim of present research work was to formulate and evaluate the potential anti-leishmanial activity ...201728465178
in vitro evaluation of antileishmanial activity of computationally screened compounds against ascorbate peroxidase to combat amphotericin b drug resistance.in visceral leishmaniasis (vl), the host macrophages generate oxidative stress to destroy the pathogen, while leishmania combats the harmful effect of radicals by redox homeostasis through its unique trypanothione cascade. leishmania donovani ascorbate peroxidase (ldapx) is a redox enzyme that regulates the trypanothione cascade and detoxifies the effect of h2o2 the absence of an ldapx homologue in humans makes it an excellent drug target. in this study, the homology model of ldapx was built, in ...201728461317
7-substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines: novel antitubercular agents lead to a new preclinical candidate for visceral leishmaniasis.within a backup program for the clinical investigational agent pretomanid (pa-824), scaffold hopping from delamanid inspired the discovery of a novel class of potent antitubercular agents that unexpectedly possessed notable utility against the kinetoplastid disease visceral leishmaniasis (vl). following the identification of delamanid analogue dndi-vl-2098 as a vl preclinical candidate, this structurally related 7-substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazine class was further explor ...201728459575
hsp90 inhibitors radicicol and geldanamycin have opposing effects on leishmania aha1-dependent proliferation.hsp90 and its co-chaperones are essential for the medically important parasite leishmania donovani, facilitating life cycle control and intracellular survival. activity of hsp90 is regulated by co-chaperones of the aha1 and p23 families. in this paper, we studied the expression of l. donovani aha1 in two life cycle stages, its interaction with hsp90 and the phenotype of aha1 null mutants during the insect stage and inside infected macrophages. this study provides a detailed in vitro analysis of ...201728455612
minimally invasive microbiopsies: a novel sampling method for identifying asymptomatic, potentially infectious carriers of leishmania donovani.visceral leishmaniasis (vl) is a potentially lethal, sand fly-borne disease caused by protozoan parasites belonging to the leishmania donovani species complex. there are several adequate methods for diagnosing vl, but the majority of infected individuals remain asymptomatic, comprising potential parasite reservoirs for transmission of the disease. the gold standard for assessing host infectiousness to biting vector insects is xenodiagnosis (i.e. scoring infection rates among insectary-reared ins ...201728455239
leishmania donovani tyrosyl-trna synthetase structure in complex with a tyrosyl adenylate analog and comparisons with human and protozoan counterparts.the crystal structure of leishmania donovani tyrosyl-trna synthetase (ldtyrrs) in complex with a nanobody and the tyrosyl adenylate analog tyrsa was determined at 2.75 å resolution. nanobodies are the variable domains of camelid heavy chain-only antibodies. the nanobody makes numerous crystal contacts and in addition reduces the flexibility of a loop of ldtyrrs. tyrsa is engaged in many interactions with active site residues occupying the tyrosine and adenine binding pockets. the ldtyrrs polypep ...201728427904
what pre-columbian mummies could teach us about south american leishmaniases?a recent report on the taxonomic profile of the human gut microbiome in pre-columbian mummies (santiago-rodriguez et al. 2016) gives for the first time evidence of the presence of leishmania dna (sequences similar to leishmania donovani according to the authors) that can be reminiscent of visceral leishmaniasis during the pre-columbian era. it is commonly assumed that leishmania infantum, the etiological agent of american visceral leishmaniasis (avl) was introduced into the new world by the iber ...201728423167
antiparasitic sesquiterpenes from the cameroonian spice scleria striatinux and preliminary in vitro and in silico dmpk assessment.the antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (dmpk) assessment of six isomeric sesquiterpenes (1-6), isolated from the cameroonian spice scleria striatinux de wild (cyperaceae) is reported. the study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on plasmodium falciparum, trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the in silico method em ...201728421410
development of high efficacy peptide coated iron oxide nanoparticles encapsulated amphotericin b drug delivery system against visceral leishmaniasis.visceral leishmaniasis, a protozoan disease transmitted by phlebotomine sandflies which affect mostly in indian sub-continent. the treatment for visceral leishmaniasis (vl) caused by leishmania donovani are limited and unsatisfactory. currently available drug against such as miltefosine and polymer based drugs ambisome has high efficacy against vl but found serious side effects and poor absorbance. to overcome this, we developed peptide (glycine) coated iron oxide (fe3o4) nanoparticles (ginps) e ...201728415438
development and evaluation of a cedrol-loaded nanostructured lipid carrier system for in vitro and in vivo susceptibilities of wild and drug resistant leishmania donovani amastigotes.leishmaniasis is an epidemic in various countries, and the parasite leishmania donovani is developing resistance against available drugs. in the present study the antileishmanial action of cedrol was evaluated in vitro and in vivo. activity potentiation was achieved via nanostructured lipid carrier (nlc) complexation of cedrol. cedrol-loaded nlc was prepared through the hot-melting emulsification-ultrasonication method. the cedrol- nlc prepared did not require the use of any organic solvents. th ...201728400285
anti-trypanosomatid elemanolide sesquiterpene lactones from vernonia lasiopus o. hoffm.sleeping sickness or human african trypanosomiasis (hat) is a neglected tropical disease (ntd) threatening millions of peoples' lives with thousands infected. the disease is endemic in poorly developed regions of sub-saharan africa and is caused by the kinetoplastid "protozoan" parasite trypanosoma brucei. the parasites are transmitted to humans through bites of infected tsetse flies of the genus glossina. the few available drugs for treatment of this disease are highly toxic, difficult to admin ...201728397756
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