| bacterial, fungal and protozoan carbonic anhydrases as drug targets. | the carbonic anhydrases (cas, ec 4.2.1.1), a group of ubiquitously expressed metalloenzymes, are involved in numerous physiological and pathological processes, as well as in the growth and virulence of pathogens belonging to bacteria, fungi and protozoa. | 2015 | 26235676 |
| inhibition studies of bacterial, fungal and protozoan β-class carbonic anhydrases with schiff bases incorporating sulfonamide moieties. | a series of new schiff bases derived from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide containing either a hydrophobic or a hydrophilic tail, have been investigated as inhibitors of three β-carbonic anhydrases (ca, ec 4.2.1.1) from three different microorganisms. their antifungal, antibacterial and antiprotozoan activities have been determined against the pathogenic fungus cryptococcus neoformans, the bacterial pathogen brucella suis and the protozoan parasite leis ... | 2015 | 26145821 |
| cross reactive molecules of human lymphatic filaria brugia malayi inhibit leishmania donovani infection in hamsters. | coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. earlier we showed that immunization with bmafii (sephadex g-200 eluted) fraction of human lymphatic filaria brugia malayi inhibited progression of leishmania donovani infection in golden hamsters. in the present study we identified cross reactive molecules of b. malayi, and investigated their effect on l. donovani infection and associated imm ... | 2015 | 26341753 |
| anti-infective assessment of senecio smithioides (asteraceae) and isolation of 9-oxoeuryopsin, a furanoeremophilane-type sesquiterpene with antiplasmodial activity. | the search for anti-infective activity in the antipyretic plant senecio smithioides was conducted. petroleum ether (pe), dichloromethane (ch2cl2), ethyl acetate (etoac) and hydroethanolic (96% etoh) extracts, and compounds 9-oxoeuryopsin (1), epoxydecompostin (2) and senecionine (3) were obtained from the aerial parts. all extracts and 1 were tested against chloroquine-resistant strain of plasmodium falciparum (ref. chloroquine), trypanosoma cruzi (ref. nifurtimox), leishmania braziliensis, leis ... | 2015 | 26606687 |
| leishmanicidal and anticandidal activity of constituents of indian edible mushroom astraeus hygrometricus. | two new lanostane-type triterpenes, 1 and 2, were isolated from astraeus hygrometricus. the structures were established by ir, (1)h- and (13)c-nmr, ms, and x-ray crystallographic experiments. the triterpenes exhibited excellent in vitro toxicities against candida albicans, comparable to standard antifungal antibiotics. the triterpene 2 significantly inhibited the growth of leishmania donovani promastigotes in vitro. the triterpene skeleton may be considered a template structure in search for new ... | 2012 | 22899612 |
| poly(amidoamine) dendrimers show carbonic anhydrase inhibitory activity against α-, β-, γ- and η-class enzymes. | four generations of poly(amidoamine) (pamam) dendrimers incorporating benzenesulfonamide moieties were investigated as inhibitors of carbonic anhydrases (cas, ec 4.2.1.1) belonging to the α-, β-, γ- and η-classes which are present in pathogenic bacteria, fungi or protozoa. the following bacterial, fungal and protozoan organisms were included in the study: vibrio cholerae, trypanosoma cruzi, leishmania donovani chagasi, porphyromonas gingivalis, cryptococcus neoformans, candida glabrata, and plas ... | 2015 | 26476668 |
| discovery of 3,3'-diindolylmethanes as potent antileishmanial agents. | an efficient protocol for synthesis of 3,3'-diindolylmethanes using recyclable fe-pillared interlayered clay (fe-pilc) catalyst under aqueous medium has been developed. all synthesized 3,3'-diindolylmethanes showed promising antileishmanial activity against leishmania donovani promastigotes as well as axenic amastigotes. structure-activity relationship analysis revealed that nitroaryl substituted diindolylmethanes showed potent antileishmanial activity. the 4-nitrophenyl linked 3,3'-diindolylmet ... | 2013 | 23517732 |
| antimicrobial metabolites from the paracel islands sponge agelas mauritiana. | four new alkaloids, (-)-8'-oxo-agelasine d (2), ageloxime b (3), (+)-2-oxo-agelasidine c (4), and 4-bromo-n-(butoxymethyl)-1h-pyrrole-2-carboxamide (5), and the known compound (-)-ageloxime d (1) were isolated from the marine sponge agelas mauritiana. their chemical structures were established on the basis of spectroscopic analysis. compounds 1 and 3 both showed antifungal activity against cryptococcus neoformans and antileishmanial activity against leishmania donovani in vitro. compound 3 also ... | 2012 | 22360686 |
| drug repurposing: mining protozoan proteomes for targets of known bioactive compounds. | to identify potential opportunities for drug repurposing by developing an automated approach to pre-screen the predicted proteomes of any organism against databases of known drug targets using only freely available resources. | 2016 | 23757409 |
| 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. | 2016 | 27304051 |
| structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties. | calreticulin (crt) is a multifaceted protein, initially discovered as an endoplasmic reticulum (er) chaperone protein, that is essential in calcium metabolism. various implications in cancer, early development and immunology have been discovered more recently for crt, as well as its role as a dominant 'eat-me' prophagocytic signal. intriguingly, cell-surface exposure/secretion of crt is among the infective strategies used by parasites such as trypanosoma cruzi, entamoeba histolytica, taenia soli ... | 2016 | 27840680 |
| structure-based design of inhibitors of the crucial cysteine biosynthetic pathway enzyme o-acetyl serine sulfhydrylase. | the cysteine biosynthetic pathway is of fundamental importance for the growth, survival, and pathogenicity of the many pathogens. this pathway is present in many species but is absent in mammals. the ability of pathogens to counteract the oxidative defences of a host is critical for the survival of these pathogens during their long latent phases, especially in anaerobic pathogens such as entamoeba histolytica, leishmania donovani, trichomonas vaginalis, and salmonella typhimurium. all of these o ... | 2016 | 26303427 |
| serological surveillance development for tropical infectious diseases using simultaneous microsphere-based multiplex assays and finite mixture models. | a strategy to combat infectious diseases, including neglected tropical diseases (ntds), will depend on the development of reliable epidemiological surveillance methods. to establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in kenya. | 2014 | 25078404 |
| chemo-informatic design of antibiotic geldenamycin analogs to target stress proteins hsp90 of pathogenic protozoan parasites. | stress proteins hsp90 (heat shock proteins) are essential molecular chaperones involved in signal transduction, cell cycle control, stress management, folding and degradation of proteins. hsp90 have been found in a variety of organisms including pathogens suggesting that they are ancient and conserved proteins. here, using molecular modeling and docking protocols, antibiotic geldenamycin and its analog are targeted to the hsp90 homolog proteins of pathogenic protozoans plasmodium falciparum, lei ... | 2013 | 23750075 |
| biochemical and inhibition studies of glutamine synthetase from leishmania donovani. | leishmaniasis is a group of tropical diseases caused by protozoan parasites of the genus leishmania. leishmania donovani is a protozoan parasite that causes visceral leishmaniasis, a fatal disease if left untreated. chemotherapy for leishmaniasis is problematic as the available drugs are toxic, costly and shows drug resistance, hence, there is a necessity to look out for the novel drug targets, chemical entities and vaccine. glutamine synthetase (gs) catalyzes the synthesis of glutamine from glu ... | 2017 | 28351708 |
| expression, purification, immunogenicity and protective efficacy of a recombinant nucleoside hydrolase from leishmania donovani, a vaccine candidate for preventing cutaneous leishmaniasis. | the nucleoside hydrolase gene from leishmania donovani was cloned and expressed in escherichia coli as a full length 36-kda protein (ldnh36). following lysis and extraction, the protein was purified by anion exchange and gel filtration chromatography. the purified protein had a molecular mass of approximately 36-kda and was confirmed to be >99% pure. using a nucleoside hydrolase assay, the protein was found to exhibit a km of 741 ± 246 μm. protein integrity was confirmed by lithium dodecyl sulfa ... | 2017 | 27773761 |
| biochemical characterization of dihydroorotase of leishmania donovani: understanding pyrimidine metabolism through its inhibition. | de novo pyrimidine biosynthesis pathway is well developed and functional in protozoan parasite leishmania donovani. the dihydroorotase (lddhoase) is third enzyme of the pathway. the enzyme was cloned, expressed in e. coli bl21 (de3), purified to homogeneity and biochemically characterized. the estimated kcat for the forward reaction and reverse reactions were 2.1 ± 0.1 s(-1) and 1.1 ± 0.15 s(-1), respectively. homology modeling and docking studies were done to find out potential inhibitors for l ... | 2016 | 27650727 |
| 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 ... | 2016 | 27319380 |
| leishmania donovani encodes a functional selenocysteinyl-trna synthase. | the synthesis of selenocysteine, the 21st amino acid, occurs on its transfer rna (trna), trna(sec). trna(sec) is initially aminoacylated with serine by seryl-trna synthetase and the resulting seryl moiety is converted to phosphoserine by o-phosphoseryl-trna kinase (pstk) in eukaryotes. the selenium donor, selenophosphate is synthesized from selenide and atp by selenophosphate synthetase. selenocysteinyl-trna synthase (sepsecs) then uses the o-phosphoseryl-trna(sec) and selenophosphate to form se ... | 2016 | 26586914 |
| heterologous expression, purification and characterization of l-type lectin homologue from leishmania donovani. | leishmaniasis, a disease of the developing world affects about 12 million people and has limited therapeutic interventions available. l-type lectins, endoplasmic reticulum golgi intermediate compartment/vesicular integral proteins (ergic-53/vip36) are involved in protein sorting in luminal compartments of animal cells and are important for parasite biology. a lectin homologue was identified through a bioinformatics analysis of leishmania genome and it was found to have n-terminal conserved carbo ... | 2015 | 28352576 |
| the tcp1γ subunit of leishmania donovani forms a biologically active homo-oligomeric complex. | chaperonins are a class of molecular chaperons that encapsulate nascent or stress-denatured proteins and assist their intracellular assembly and folding in an atp-dependent manner. the ubiquitous eukaryotic chaperonin, tcp1 ring complex is a hetero-oligomeric complex comprising two rings, each formed of eight subunits that may have distinct substrate recognition and atp hydrolysis properties. in leishmania, only the tcp1γ subunit has been cloned and characterized. it exhibited differential expre ... | 2015 | 26395202 |
| over-expression of cysteine leucine rich protein is related to sag resistance in clinical isolates of leishmania donovani. | resistance emergence against antileishmanial drugs, particularly sodium antimony gluconate (sag) has severely hampered the therapeutic strategy against visceral leishmaniasis, the mechanism of resistance being indistinguishable. cysteine leucine rich protein (clrp), was recognized as one of the overexpressed proteins in resistant isolates, as observed in differential proteomics between sensitive and resistant isolates of l. donovani. the present study deals with the characterization of clrp and ... | 2015 | 26295340 |
| immunogenicity and efficacy of recombinant 78 kda antigen of leishmania donovani formulated in various adjuvants against murine visceral leishmaniasis. | to analyze the protective efficacy of recombinant 78 kda antigen of leishmania donovani in combination with two adjuvants, that is, cationic liposomes or mpl-a against visceral leishmaniasis in balb/c mice. | 2015 | 26276280 |
| amp-acetyl coa synthetase from leishmania donovani: identification and functional analysis of 'px4gk' motif. | an adenosine monophosphate forming acetyl coa synthetase (acecs) which is the key enzyme involved in the conversion of acetate to acetyl coa has been identified from leishmania donovani for the first time. sequence analysis of l. donovani acecs (ldacecs) revealed the presence of a 'px4gk' motif which is highly conserved throughout organisms with higher sequence identity (96%) to lower sequence identity (38%). a ∼ 77 kda heterologous protein with c-terminal 6x his-tag was expressed in escherichia ... | 2015 | 25660655 |
| lipid isolated from a leishmania donovani strain reduces escherichia coli induced sepsis in mice through inhibition of inflammatory responses. | sepsis is the reflection of systemic immune response that manifests in the sequential inflammatory process in presence of infection. this may occur as a result of gram-negative bacterial sepsis including escherichia coli infection that gives rise to excessive production of inflammatory mediators and causes severe tissue injuries. we have reported earlier that the lipid of attenuated leishmania donovani suppresses the inflammatory responses in arthritis patients. using heat killed e. coli stimula ... | 2014 | 25120287 |
| integrity of the actin cytoskeleton of host macrophages is essential for leishmania donovani infection. | visceral leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoan parasite leishmania donovani. the molecular mechanism involved in internalization of leishmania is poorly understood. the entry of leishmania involves interaction with the plasma membrane of host cells. we have previously demonstrated the requirement of host membrane cholesterol in the binding and internalization of l. donovani into macrophages. in the present work, we explored the role of the host act ... | 2014 | 24780377 |
| analysis of the leishmania peroxin 7 interactions with peroxin 5, peroxin 14 and pts2 ligands. | lpex7 (leishmania peroxin 7) is essential for targeting newly synthesized proteins with a pts2 (peroxisome-targeting signal type 2) import signal into the glycosome. in the present paper, we describe the biophysical characterization of a functional lpex7 isolated from escherichia coli inclusion bodies. pull-down assays showed that lpex7 binds the interacting partners ldpex5 (leishmania donovani peroxin 5) and ldpex14, but, more importantly, this receptor can specifically bind pts2 cargo proteins ... | 2014 | 24635481 |
| identification and functional characterization of a novel bacterial type asparagine synthetase a: a trna synthetase paralog from leishmania donovani. | asparagine is formed by two structurally distinct asparagine synthetases in prokaryotes. one is the ammonia-utilizing asparagine synthetase a (asna), and the other is asparagine synthetase b (asnb) that uses glutamine or ammonia as a nitrogen source. in a previous investigation using sequence-based analysis, we had shown that leishmania spp. possess asparagine-trna synthetase paralog asparagine synthetase a (ldasna) that is ammonia-dependent. here, we report the cloning, expression, and kinetic ... | 2014 | 24610810 |
| identification of the intracellular gate for a member of the equilibrative nucleoside transporter (ent) family. | equilibrative nucleoside transporters of the slc29 family play important roles in many physiological and pharmacological processes, including import of drugs for treatment of cancer, aids, cardiovascular, and parasitic diseases. however, no crystal structure is available for any member of this family. in previous studies we generated a computational model of the leishmania donovani nucleoside transporter 1.1 (ldnt1.1) that captured this permease in the outward-closed conformation, and we identif ... | 2014 | 24497645 |
| over-expression of 60s ribosomal l23a is associated with cellular proliferation in sag resistant clinical isolates of leishmania donovani. | sodium antimony gluconate (sag) unresponsiveness of leishmania donovani (ld) had effectively compromised the chemotherapeutic potential of sag. 60s ribosomal l23a (60srl23a), identified as one of the over-expressed protein in different resistant strains of l.donovani as observed with differential proteomics studies indicates towards its possible involvement in sag resistance in l.donovani. in the present study 60srl23a has been characterized for its probable association with sag resistance mecha ... | 2013 | 24340105 |
| identification of a secreted casein kinase 1 in leishmania donovani: effect of protein over expression on parasite growth and virulence. | casein kinase 1 (ck1) plays an important role in eukaryotic signaling pathways, and their substrates include key regulatory proteins involved in cell differentiation, proliferation and chromosome segregation. the leishmania genome encodes six potential ck1 isoforms, of which five have orthologs in other trypanosomatidae. leishmania donovani ck1 isoform 4 (ldck1.4, orthologous to lmjf27.1780) is unique to leishmania and contains a putative secretion signal peptide. the full-length gene and three ... | 2013 | 24260187 |
| substrate inhibition of uracil phosphoribosyltransferase by uracil can account for the uracil growth sensitivity of leishmania donovani pyrimidine auxotrophs. | the pathogenic protozoan parasite leishmania donovani is capable of both de novo pyrimidine biosynthesis and salvage of pyrimidines from the host milieu. genetic analysis has authenticated l. donovani uracil phosphoribosyltransferase (lduprt), an enzyme not found in mammalian cells, as the focal enzyme of pyrimidine salvage because all exogenous pyrimidines that can satisfy the requirement of the parasite for pyrimidine nucleotides are funneled to uracil and then phosphoribosylated to ump in the ... | 2013 | 23986453 |
| adenylosuccinate synthetase and adenylosuccinate lyase deficiencies trigger growth and infectivity deficits in leishmania donovani. | leishmania are auxotrophic for purines, and consequently purine acquisition from the host is a requisite nutritional function for the parasite. both adenylosuccinate synthetase (adss) and adenylosuccinate lyase (asl) have been identified as vital components of purine salvage in leishmania donovani, and therefore δadss and δasl null mutants were constructed to test this hypothesis. unlike wild type l. donovani, δadss and δasl parasites in culture exhibited a profoundly restricted growth phenotype ... | 2013 | 23404497 |
| kinetics and docking studies of two potential new inhibitors of the nucleoside hydrolase from leishmania donovani. | in this study the recombinant enzyme nucleoside hydrolase of leishmania donovani (rldnh) was expressed in escherichia coli in connection with maltose binding protein (mbp). the rldnh-mbp showed efficient a significant in vitro activity with inosine as substrate. from the coupled reaction with xanthine oxidase (xo) it was possible to determine the kinetic constants of rldnh-mbp as k(m) (434 ± 109 μm) and v(max) (0.20 ± 0.02 μm). in addition, two nucleoside analogs (compounds 1 and 2) were tested ... | 2012 | 22947894 |
| identification and characterization of a novel ribose 5-phosphate isomerase b from leishmania donovani. | leishmaniasis is a group of tropical diseases caused by protozoan parasites of the genus leishmania. due to the emergence of resistance to the available antileishmanial drugs there is an immediate need to identify molecular targets on which to base future treatment strategies. ribose 5-phosphate isomerase (rpi; ec 5.3.1.6) is a key enzyme of the pentose phosphate pathway (ppp) which catalyses the reversible aldose-ketose isomerization between ribose 5-phosphate (r5p) and ribulose 5-phosphate (ru ... | 2012 | 22483752 |
| leishmania donovani hslv does not interact stably with hslu proteins. | genes for hslvu-type peptidases are found in bacteria and in a few select eukaryota, among those such important pathogens as plasmodium spp. and leishmania spp. in this study, we performed replacements of all three hslv/hslu gene homologues and found one of those, hslv, to be essential for leishmania donovani viability. the leishmania hslv gene can also partially relieve the thermosensitive phenotype of a combined hslvu/lon/clpxp knockout mutant of escherichia coli, indicating a conserved functi ... | 2012 | 22370310 |
| antileishmanial metabolites from geosmithia langdonii. | antileishmanial bioassay guided fractionation of geosmithia langdonii has resulted in the isolation and identification of two new compounds (1 and 2) together with 10 known compounds (3-12). the structures of the isolated metabolites were elucidated based on comprehensive 1d and 2d nmr spectroscopic data as well as mass spectrometry. the absolute configuration at c4, c5, and c6 of 2 was determined as r using a modified mosher esterification method and noesy correlations. the extracts and the iso ... | 2014 | 25084548 |
| mir-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as mirna mimic and antimir. | mir-122, a completely conserved liver-specific mirna in vertebrates, is essential for the maintenance of liver homeostasis. this 22 nucleotide rna regulates diverse functions such as cholesterol, glucose and iron homeostasis, lipid metabolism and infection of hepatitis c virus (hcv) and of the parasitic protozoa, leishmania donovani. it is the first mirna that underwent successful clinical trials in hcv infected patients. in contrast, mir-122 expression is reduced in nonalcoholic steatohepatitis ... | 2015 | 25537773 |
| serological assessment for leishmania donovani infection in blood donors of sunsari district, dharan, nepal. | visceral leishmaniasis (vl) is a major vector-borne disease caused by leishmania donovani, after replication of the parasites in macrophages, mononuclear phagocytic system. vl is endemic in 12 districts of central and eastern terai lowlands of nepal bordering north bihar, india with an estimated 8 million population at risk. in addition, vl endemicity is also extending to new endemic regions like dharan from its classical rural foci. hence, we aimed to detect the evidence of leishmania donovani ... | 2016 | 26855514 |
| crispr-cas9-mediated genome editing in leishmania donovani. | the prokaryotic crispr (clustered regularly interspaced short palindromic repeat)-cas9, an rna-guided endonuclease, has been shown to mediate efficient genome editing in a wide variety of organisms. in the present study, the crispr-cas9 system has been adapted to leishmania donovani, a protozoan parasite that causes fatal human visceral leishmaniasis. we introduced the cas9 nuclease into l. donovani and generated guide rna (grna) expression vectors by using the l. donovani rrna promoter and the ... | 2015 | 26199327 |
| survey of infectious agents in the endangered darwin's fox (lycalopex fulvipes): high prevalence and diversity of hemotrophic mycoplasmas. | very little is known about the diseases affecting the darwin's fox (lycalopex fulvipes), which is considered to be one of the most endangered carnivores worldwide. blood samples of 30 foxes captured on chiloé island (chile) were tested with a battery of pcr assays targeting the following pathogens: ehrlichia/anaplasma sp., rickettsia sp., bartonella sp., coxiella burnetti, borrelia sp., mycoplasma sp., babesia sp., hepatozoon canis, hepatozoon felis, leishmania donovani complex, and filariae. an ... | 2013 | 24176254 |
| a novel method of combining periodic acid schiff staining with wright-giemsa staining to identify the pathogens penicillium marneffei, histoplasma capsulatum, mucor and leishmania donovani in bone marrow smears. | penicillium marneffei, histoplasma capsulatum, mucor and leishmania donovani can lead to penicilliosis marneffei, histoplasmosis, mucormycosis and leishmaniasis, respectively, which, to a certain extent, share similar clinical manifestations. these pathogens are approximately the same size, therefore it is relatively difficult to rapidly diagnose the diseases. the aim of the present study was to explore a novel method that attempts to rapidly identify the pathogens of these diseases. in the wrig ... | 2015 | 26136921 |
| leishmania in hlh: a rare finding with significant treatment implications. | hemophagocytic lymphohistiocytosis (hlh) associated with visceral leishmaniasis (vl) is a very rare phenomenon. we report the first known north american case in a 21 month old boy. he was initially diagnosed with epstein barr virus (ebv) triggered hlh and treated with the international treatment protocol, hlh-2004. stem cell transplant was planned due to repeated reactivations of disease, but his pretransplant bone marrow revealed an unexpected protozoan-leishmania donovani. treatment with lipos ... | 2013 | 23511497 |
| an unusual presentation of leishmaniasis in a human immunodeficiency virus-positive individual. | leishmaniasis is a neglected tropical disease caused by vector-borne protozoa of the genus leishmania. cutaneous and mucocutaneous forms result in disfiguration or mutilation, whilst visceral leishmaniasis (vl) affects multiple organs and is fatal if untreated. notably, leishmania are capable of establishing a chronic infection, which may reactivate years after initial infection when the host becomes immune-suppressed. | 2016 | 28348746 |
| diagnosis of visceral leishmaniasis using peripheral blood microscopy in ethiopia: a prospective phase-iii study of the diagnostic performance of different concentration techniques compared to tissue aspiration. | visceral leishmaniasis (vl) is a fatal parasitic disease. unfortunately, diagnosis of vl in east africa currently relies on aspiration of tissue from the spleen or bone marrow, which is painful and potentially dangerous. we sought to determine whether peripheral blood could be used instead of invasive tissue aspirates to diagnose vl, using three parasite concentration techniques. three hundred and one consecutive people suspected of having vl were recruited. compared with microscopy of tissue as ... | 2017 | 27799651 |
| a study of haematological and bone marrow changes in symptomatic patients with human immune deficiency virus infection with special mention of functional iron deficiency, anaemia of critically ill and haemophagocytic lymphohistiocytosis. | haematological abnormalities are among the most common complications of hiv. these involve all lineages of blood cells. bone marrow studies form integral part of complete workup of the hiv positive patients specially when they present as case of pyrexia of unknown origin (puo), refractory anaemia and pancytopenia. | 2013 | 24600136 |
| specific noninvasive detection of leishmania donovani in desquamated buccal cell swab samples from human visceral leishmaniasis-hiv coinfected patients. | diagnosis of human immunodeficiency virus (hiv) infection with visceral leishmaniasis (vl) coinfection is challenging. specific diagnosis of vl in hiv-coinfected patients was evaluated by molecular methods in desquamated buccal swab samples, demonstrating 86.3% sensitivity and 98.3% specificity in controls. this test holds significant potential for development as a noninvasive diagnostic tool for vl in hiv-coinfected patients. | 2014 | 24478413 |
| human immunodeficiency virus/leishmania infantum in the first foci of urban american visceral leishmaniasis: clinical presentation from 1994 to 2010. | human immunodeficiency virus (hiv) coinfection with leishmania infantum or leishmania donovani, the agents of visceral leishmaniasis (or kala-azar), has become a fatal public health problem in the tropics where kala-azar is endemic. | 2013 | 23666663 |
| a chimera containing cd4+ and cd8+ t-cell epitopes of the leishmania donovani nucleoside hydrolase (nh36) optimizes cross-protection against leishmania amazonesis infection. | the leishmania donovani nucleoside hydrolase (nh36) and nh a34480 of leishmania amazonensis share 93% of sequence identity. in mice, the nh36 induced protection against visceral leishmaniasis is mediated by a cd4+ t cell response against its c-terminal domain (f3). besides this cd4+ th1 response, prevention and cure of l. amazonensis infection require also additional cd8+ and regulatory t-cell responses to the nh36 n-terminal (f1 domain). we investigated if mice vaccination with f1 and f3 domain ... | 2017 | 28280494 |
| perifosine mechanisms of action in leishmania species. | here the mechanism by which perifosine induced cell death in leishmania donovani and leishmania amazonensis is described. the drug reduced leishmania mitochondrial membrane potential and decreased cellular atp levels while increasing phosphatidylserine externalization. perifosine did not increase membrane permeabilization. we also found that the drug inhibited the phosphorylation of akt in the parasites. these results highlight the potential use of perifosine as an alternative to miltefosine aga ... | 2017 | 28096161 |
| 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 ... | 2016 | 27318121 |
| 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 ... | 2016 | 27096224 |
| 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 ... | 2016 | 27048943 |
| in vitro and in vivo miltefosine susceptibility of a leishmania amazonensis isolate from a patient with diffuse cutaneous leishmaniasis. | miltefosine was the first oral compound approved for visceral leishmaniasis chemotherapy, and its efficacy against leishmania donovani has been well documented. leishmania amazonensis is the second most prevalent species causing cutaneous leishmaniasis and the main etiological agent of diffuse cutaneous leishmaniasis in brazil. driven by the necessity of finding alternative therapeutic strategies for a chronic diffuse cutaneous leishmaniasis patient, we evaluated the susceptibility to miltefosin ... | 2014 | 25033218 |
| leishmania donovani nucleoside hydrolase terminal domains in cross-protective immunotherapy against leishmania amazonensis murine infection. | nucleoside hydrolases of the leishmania genus are vital enzymes for the replication of the dna and conserved phylogenetic markers of the parasites. leishmania donovani nucleoside hydrolase (nh36) induced a main cd4(+) t cell driven protective response against l. chagasi infection in mice which is directed against its c-terminal domain. in this study, we used the three recombinant domains of nh36: n-terminal domain (f1, amino acids 1-103), central domain (f2 aminoacids 104-198), and c-terminal do ... | 2014 | 24966857 |
| cross-protective immunity to leishmania amazonensis is mediated by cd4+ and cd8+ epitopes of leishmania donovani nucleoside hydrolase terminal domains. | the nucleoside hydrolase (nh) of leishmania donovani (nh36) is a phylogenetic marker of high homology among leishmania parasites. in mice and dog vaccination, nh36 induces a cd4+ t cell-driven protective response against leishmania chagasi infection directed against its c-terminal domain (f3). the c-terminal and n-terminal domain vaccines also decreased the footpad lesion caused by leishmania amazonensis. we studied the basis of the crossed immune response using recombinant generated peptides co ... | 2014 | 24822054 |
| in vitro and in vivo efficacy of novel flavonoid dimers against cutaneous leishmaniasis. | treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. we previously reported that synthetic flavonoid dimers have potent antipromastigote and antiamastigote activity against leishmania donovani, the causative agent of visceral leishmaniasis. here, we further investigate their leishmanicidal activities against cutaneous leishmania species. one of the flavonoid dimers (compound 39) has marked antipromastigote (50% inhib ... | 2014 | 24687505 |
| activity of anti-cancer protein kinase inhibitors against leishmania spp. | there is an urgent need to develop new and effective treatments for poverty-related neglected diseases. in light of the time required to bring a new drug to market and the cost involved (10-15 years, >1 billion us$), one approach to identifying new treatments for diseases like leishmaniasis is to evaluate drugs that are already registered for the treatment of other diseases. this paper describes the anti-leishmanial activities of 10 fda-approved protein kinase inhibitors already available for th ... | 2014 | 24668412 |
| a2 and other visceralizing proteins of leishmania: role in pathogenesis and application for vaccine development. | visceral leishmaniasis is a re-emergent disease and a significant cause of morbidity worldwide. amongst the more than 20 leishmania species, leishmania donovani, leishmania infantum and more rarely leishmania amazonensis are associated with visceral leishmaniasis. a major question in leishmaniasis research is how these species migrate to and infect visceral organs whereas other species such as leishmania major and leishmania braziliensis remain in the skin, causing tegumentary leishmaniasis. her ... | 2014 | 24264241 |
| constitutive mosaic aneuploidy is a unique genetic feature widespread in the leishmania genus. | using fluorescence in situ hybridization, we determined the ploidy of four species of leishmania: leishmania infantum, leishmania donovani, leishmania tropica and leishmania amazonensis. we found that each cell in a strain possesses a combination of mono-, di- and trisomies for all chromosomes; ploidy patterns were different among all strains/species. these results extend those we previously described in leishmania major, demonstrating that mosaic aneuploidy is a genetic feature widespread to th ... | 2014 | 24120456 |
| cloning, characterization, and inhibition studies of a β-carbonic anhydrase from leishmania donovani chagasi, the protozoan parasite responsible for leishmaniasis. | leishmaniasis is an infection provoked by protozoans belonging to the genus leishmania. among the many species and subsepecies of such protozoa, leishmania donovani chagasi causes visceral leishmaniasis. a β-carbonic anhydrase (ca, ec 4.2.1.1) was cloned and characterized from this organism, denominated here ldcca. ldcca possesses effective catalytic activity for the co2 hydration reaction, with kcat of 9.35 × 10(5) s(-1) and kcat/km of 5.9 × 10(7) m(-1) s(-1). a large number of aromatic/heteroc ... | 2013 | 23977960 |
| immunopathogenesis of non-healing american cutaneous leishmaniasis and progressive visceral leishmaniasis. | the outcomes of leishmania infection are determined by host immune and nutrition status, parasite species, and co-infection with other pathogens. while subclinical infection and self-healing cutaneous leishmaniasis (cl) are common, uncontrolled parasite replication can lead to non-healing local lesions or visceral leishmaniasis (vl). it is known that infection control requires th1-differentiation cytokines (il-12, il-18, and il-27) and th1 cell and macrophage activation. however, there is no gen ... | 2012 | 23053396 |
| synthesis, dna binding and antileishmanial activity of low molecular weight bis-arylimidamides. | the effects of reducing the molecular weight of the antileishmanial compound db766 on dna binding affinity, antileishmanial activity and cytotoxicity are reported. the bis-arylimidamides were prepared by the coupling of aryl s-(2-naphthylmethyl)thioimidates with the corresponding amines. specifically, we have prepared new series of bis-arylimidamides which include 3a, 3b, 6, 9a, 9b, 9c, 13, and 18. three compounds 9a, 9c, and 18 bind to dna with similar or moderately lower affinity to that of db ... | 2012 | 22840696 |
| 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 ... | 2016 | 27480054 |
| leishmania spp. in didelphis spp. from northeastern brazil. | the synanthropic behavior of marsupials of the genus didelphis in endemic areas of leishmaniasis suggests that these animals may play an important role in the epidemiology of this infection. the aim of the present study was to detect leishmania spp. dna in didelphis albiventris (white-eared opossum) and didelphis aurita (big-eared opossum) living in forested and peridomestic areas of northeastern brazil. blood samples were collected from 25 animals (23 d. albiventris and 2 d. aurita ) by cardiac ... | 2016 | 27691942 |
| imidazole-containing phthalazine derivatives inhibit fe-sod performance in leishmania species and are active in vitro against visceral and mucosal leishmaniasis. | the in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on leishmania infantum, leishmania braziliensis and leishmania donovani parasites, and their cytotoxicity on j774·2 macrophage cells was also measured. all compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their ... | 2015 | 25823476 |
| il2ra genetic variants reduce il-2-dependent responses and aggravate human cutaneous leishmaniasis. | the outcome of leishmania infections varies substantially, depending on the host and the parasite strain; infection may be asymptomatic or cause mild or severe skin ulcers (cutaneous leishmaniasis [cl]), limited or disseminated lesions, or lethal visceral disease. we previously reported an association between il-2r mutations and susceptibility to visceral leishmaniasis in children infected with leishmania donovani. in the present study, we evaluated the possible role of il-2 signaling in human c ... | 2015 | 25672756 |
| comparative in-silico genome analysis of leishmania (leishmania) donovani: a step towards its species specificity. | comparative genome analysis of recently sequenced leishmania (l.) donovani was unexplored so far. the present study deals with the complete scanning of l. (l.) donovani genome revealing its interspecies variations. 60 distinctly present genes in l. (l.) donovani were identified when the whole genome was compared with leishmania (l.) infantum. similarly 72, 159, and 265 species specific genes were identified in l. (l.) donovani when compared to leishmania (l.) major, leishmania (l.) mexicana and ... | 2014 | 25606461 |
| proteomic analyses of membrane enriched proteins of leishmania donovani indian clinical isolate by mass spectrometry. | visceral leishmaniasis (vl) is a major fatal disease prevalent in north-east india, caused by a protozoan parasite leishmania donovani. the parasite multiplies and thrives inside mammalian macrophages and is transmitted by the bite of the sandfly. due to the unsatisfactory treatment measures, increasing drug resistance and the advent of hiv-leishmania co-infection there has been an urgent need to develop novel drug/vaccine targets against vl. target identification is the key step in drug discove ... | 2015 | 25597695 |
| a case of mucocutaneous leishmaniasis diagnosed by serology. | a 43-year-old japanese bolivian male had been suffering from a right leg ulcer after an insect bite during his residence in bolivia. the ulcer healed after herbal medicine treatment. ten years later, the patient had symptoms of nasal obstruction, nasal bleeding, and pharyngodynia, which were accompanied by a destructive ulcer with surrounding erythema involving the right nostril apex and columella. papillary, irregular mucosal lesions were seen on the soft palate. giemsa staining and polymerase ... | 2014 | 25041360 |
| live attenuated leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in balb/c mice. | leishmaniasis causes significant morbidity and mortality worldwide, and no vaccines against this disease are available. previously, we had shown that the amastigote-specific protein p27 (ldp27) is a component of an active cytochrome c oxidase complex in leishmania donovani and that upon deletion of its gene the parasite had reduced virulence in vivo. in this study, we have shown that ldp27(-/-) parasites do not survive beyond 20 wk in balb/c mice and hence are safe as an immunogen. upon virulent ... | 2013 | 23338240 |
| atypical mucocutaneous involvement with leishmania donovani. | mucocutaneous leishmaniasis has rarely been reported from india. the usual causative organisms of this infection are leishmania braziliensis and l. tropica. another species, l. donovani, which usually causes visceral leishmaniasis, has recently been reported to cause mucocutaneous disease in a few patients from sri lanka. we report two patients who had undiagnosed chronic skin lesions for several years. skin biopsies revealed leishmania and the species was characterized as l. donovani in both pa ... | 2013 | 22963292 |
| efficacy and tolerability of oleylphosphocholine (olpc) in a laboratory model of visceral leishmaniasis. | the alkylphospholipid oleylphosphocholine (olpc) is a structural analogue of miltefosine and may represent a potential therapeutic backup for the treatment of visceral leishmaniasis (vl). this laboratory study compared the in vitro and in vivo activity profile of both olpc and miltefosine. | 2012 | 22782488 |
| seroprevalence and asymptomatic carriage of leishmania spp. in austria, a non-endemic european country. | leishmaniasis is a rare disease in central europe and is diagnosed almost exclusively in travellers or migrants coming from tropical or subtropical countries. we conducted an explorative cross-sectional serological study, using a commercial elisa, in 1048 healthy austrian individuals to assess the distribution of specific antibodies against leishmania spp. in humans in austria. overall, 47 individuals (4.5%) tested positive, and an additional 32 (3.1%) showed borderline results. after 12 months, ... | 2013 | 22764887 |
| leishmania donovani nucleoside hydrolase (nh36) domains induce t-cell cytokine responses in human visceral leishmaniasis. | development of immunoprotection against visceral leishmaniasis (vl) focused on the identification of antigens capable of inducing a th1 immune response. alternatively, antigens targeting the cd8 and t-regulatory responses are also relevant in vl pathogenesis and worthy of being included in a preventive human vaccine. we assessed in active and cured patients and vl asymptomatic subjects the clinical signs and cytokine responses to the leishmania donovani nucleoside hydrolase nh36 antigen and its ... | 2017 | 28321221 |
| 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 ... | 2016 | 27233810 |
| immunity to visceral leishmaniasis: implications for immunotherapy. | visceral leishmaniasis, caused by leishmania donovani, l. infantum (syn. leishmania chagasi), is a globally widespread disease with a burden of about 400,000 new infections reported annually. it is the most dangerous form of human leishmaniasis in terms of mortality and morbidity and is spreading to several nonendemic areas because of migration, global traveling and military conflicts. the emergence of leishmania-hiv co-infection and increased prevalence of drug-resistant strains have worsened t ... | 2014 | 25156379 |
| cutaneous leishmaniasis in north dakota. | in the united states, autochthonous cutaneous leishmaniasis caused by infection with leishmania mexicana has been reported from texas and oklahoma. here, we describe a child with 2 new features: cutaneous infection acquired outside of the south-central united states (in north dakota) and infection caused by leishmania donovani species complex. | 2014 | 24850800 |
| therapeutic options for visceral leishmaniasis. | visceral leishmaniasis (vl), also known as kala-azar, is a disseminated protozoal infection caused principally by leishmania donovani and leishmania infantum (known as leishmania chagasi in south america). the therapeutic options for vl are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, hiv co-infection, malnourishment and other concomitant infections. this article provides an exhaustive review of the lit ... | 2013 | 24170666 |
| subclinical leishmaniasis associated with infertility and chronic prostatitis in a dog. | a stud dog was presented for acquired infertility. haematospermia and teratozoospermia were found on two ejaculates 2 weeks apart. a presumptive diagnosis of prostatitis was made follo-wing ultrasound examination. an ultrasound-guided needle core biopsy was performed under general anaesthesia, revealing a mild chronic macrophagic and plasma cell prostatitis with intracytoplasmic amastigotes consistent with leishmania spp. infection. presence of leishmania infantum, leishmania donovani or leishma ... | 2012 | 22690941 |
| characterization of ciliobrevin a mediated dynein atpase inhibition on flagellar motility of leishmania donovani. | axonemal dyneins are members of aaa+ proteins involved in force generation and are responsible for flagellar motility in eukaryotes. in this study, we characterized the effects of ciliobrevin a (cba), a dynein atpase inhibitor, on flagella driven motility of the protozoan parasite leishmania donovani. using fast-capture video microscopy, we observed that cba decreased flagellar beat frequency of swimming parasites in a concentration-dependent manner. beat frequency of live and reactivated l. don ... | 2017 | 28389272 |
| immuno-informatics based approaches to identify cd8+ t cell epitopes within the leishmania donovani 3-ectonucleotidase in cured visceral leishmaniasis subjects. | leishmaniases are vector-borne diseases for which no vaccine exists. these diseases are caused by the leishmania species complex. activation of the cd8(+) t cell is crucial for protection against intracellular pathogens, and peptide antigens are attractive strategies for the precise activation of cd8(+) t in vaccine development against intracellular infections. the traditional approach to mine the epitopes is an arduous task. however, with the advent of immunoinformatics, in silico epitope predi ... | 2017 | 28373107 |
| structure and biosynthesis of isatropolones, bioactive amine-scavenging fluorescent natural products from streptomyces gö66. | the natural products isatropolone a-c (1-3) were reisolated from streptomyces gö66, with 1 and 3 showing potent activity against leishmania donovani. they contain a rare tropolone ring derived from a type ii polyketide biosynthesis pathway. their biosynthesis was elucidated by labeling experiments, analysis of the biosynthesis gene cluster, its partial heterologous expression, and structural characterization of various intermediates. owing to their 1,5-diketone moiety, they can react with ammoni ... | 2017 | 28371116 |
| expression profiling of sudanese visceral leishmaniasis patients pre- and post-treatment with sodium stibogluconate. | visceral leishmaniasis (vl) in sudan caused by leishmania donovani is fatal in susceptible individuals if untreated. treatment with sodium stibogluconate (ssg) leads to post kala azar dermal leishmaniasis (pkdl) in 58% of patients. here affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (n=9 paired samples) pre- and post-treatment with ssg. using the bioconductor package limma, 438 genes from 28,869 post quality-control probe-sets were differentially expre ... | 2017 | 28370072 |
| a systematic reconstruction and constraint-based analysis of leishmania donovani metabolic network: identification of potential antileishmanial drug targets. | visceral leishmaniasis, a lethal parasitic disease, is caused by the protozoan parasite leishmania donovani. the absence of an effective vaccine, drug toxicity and parasite resistance necessitates the identification of novel drug targets. reconstruction of genome-scale metabolic models and their simulation has been established as an important tool for systems-level understanding of a microorganism's metabolism. in this work, amalgamating the tools and techniques of computational systems biology ... | 2017 | 28367572 |
| anti-leishmanial and cytotoxic activities of amino acid-triazole hybrids: synthesis, biological evaluation, molecular docking and in silico physico-chemical properties. | according to who, leishmaniasis is a major tropical disease, ranking second after malaria. significant efforts have been therefore invested into finding potent inhibitors for the treatment. in this work, eighteen novel 1,2,3-triazoles appended with l-amino acid (phe/pro/trp) tail were synthesized via azide-alkyne click chemistry with moderate to good yield, and evaluated for their anti-leishmanial activity against promastigote form of leishmania donovani (dd8 strain). among all, compounds 40, 43 ... | 2017 | 28359789 |
| nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis. | visceral leishmaniasis (vl) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus leishmania. most of the therapeutics for vl are toxic, expensive, or ineffective. sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. association of artemisinin with liposome is a desirable str ... | 2017 | 28356736 |
| biologically-guided isolation of leishmanicidal secondary metabolites from euphorbia peplus l. | leishmaniasis is a worldwide health problem, highly endemic in developing countries. moreover, the severe side effects and the reported drug resistance make it an urgent need to search for effective drugs that can replace or supplement those currently used. in a research program designed to investigate the antileishmanial activity of plants collected from the egyptian flora, twenty extracts from fifteen plants growing in egypt have been investigated for in vitro leishmanicidal activity against l ... | 2017 | 28344474 |
| development of a rapid loop-mediated isothermal amplification assay for diagnosis and assessment of cure of leishmania infection. | leishmaniasis is a spectrum of diseases with great relevance to public health. conventional diagnostic methods are time consuming, needing trained personnel. a robust, rapid and cost effective diagnostic test is warranted for on-time diagnosis and field application. | 2017 | 28335752 |
| increased transmissibility of leishmania donovani from the mammalian host to vector sand flies after multiple exposures to sand fly bites. | patients with active visceral leishmaniasis are important reservoirs in the anthroponotic transmission cycle of leishmania donovani. the role of the blood or skin as a source of infection to sand flies remains unclear, and the possible effect of multiple exposures to fly bites on transmissibility has not been addressed. | 2017 | 28329329 |
| domestic dogs as reservoir hosts for leishmania donovani in the southernmost western ghats in india. | the peripheral blood samples from domestic dogs (n=47) and wild rats (n=25) in the kani tribe settlements, located southernmost part of the western ghats, thiruvananthapuram district, kerala, india were examined for leishmania infection. this area is known for cases of leishmaniasis with cutaneous manifestations and sandfly abundance. the tribes domesticate dogs to protect them from untoward activities of wild animals. leishmania donovani parasite dna was detected only from 6.4% (n=3) of the blo ... | 2017 | 28327413 |
| leishmania donovani resistant to ambisome or miltefosine exacerbates cd58 expression on nk cells and promotes trans-membrane migration in association with cd2. | visceral leishmaniasis (vl) is a disease that is associated with compromised immunity and drug un-responsiveness as well as with the emergence of drug resistance in leishmania donovani (ld). ld down-modulates cellular immunity by manipulating signaling agents, including a higher expression of the adhesion molecule cd58. the expression of cd58 and cd2 on natural killer (nk) cells facilitates intercellular adhesion and signaling. the influence of drug-resistant ld on the expression of cd58 and cd2 ... | 2017 | 28324803 |
| identification of novel inhibitors of leishmania donovani γ-glutamylcysteine synthetase using structure-based virtual screening, docking, molecular dynamics simulation, and in vitro studies. | trypansomatids maintain their redox balance by the trypanothione-based redox system, enzymes of which exhibit differences from mammalian homologues. γ-glutamylcysteine synthetase (gcs) is an essential enzyme in this pathway that performs the first and rate-limiting step. l-buthionine-(s,r)-sulfoximine (bso), a specific inhibitor of gcs, induces toxicity in hosts infected with trypanosoma brucei, underlining the need for novel gcs inhibitors. the present study reports identification of leishmania ... | 2017 | 28322559 |
| antileishmanial and immunomodulatory potential of ocimumsanctum linn. and cocosnucifera linn. in murine visceral leishmaniasis. | the role of immunomodulation in the therapeutic treatment of visceral leishmaniasis has gained eminence in view of moderate to severe drawbacks of the currently available drugs like toxicity, drug resistance and prohibitive costs. the potential for modulation of the immune system of many herbal plants can be tapped to address these problems. we conducted the present research study to investigate the antileishmanial and immunomodulatory effects of ocimum sanctum linn. and cocos nucifera linn. dur ... | 2017 | 28316391 |
| identification and characterization of mirnas in response to leishmania donovani infection: delineation of their roles in macrophage dysfunction. | the outcome of leishmania infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. micro rnas (mirnas) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding rna gene products, described to participate in the regulation of almost every cellular process investig ... | 2017 | 28303124 |
| deciphering the interplay between cysteine synthase and thiol cascade proteins in modulating amphotericin b resistance and survival of leishmania donovani under oxidative stress. | leishmania donovani is the causative organism of the neglected human disease known as visceral leishmaniasis which is often fatal, if left untreated. the cysteine biosynthesis pathway of leishmania may serve as a potential drug target because it is different from human host and regulates downstream components of redox metabolism of the parasites; essential for their survival, pathogenicity and drug resistance. however, despite the apparent dependency of redox metabolism of cysteine biosynthesis ... | 2017 | 28288415 |
| clinico-epidemiological patterns of cutaneous leishmaniasis patients attending the anuradhapura teaching hospital, sri lanka. | cutaneous leishmaniasis (cl) caused by leishmania donovani is an endemic vector-borne disease in sri lanka. over 2,500 cases have been reported since 2000 and the number of cl cases has dramatically increased annually. total 57 clinically suspected cl patients attending the dermatology clinic in anuradhapura teaching hospital were recruited from january to june 2015. slit skin smears and skin biopsies were taken from each of the subjects. clinical and epidemiological data were obtained using int ... | 2017 | 28285499 |
| leishmania donovani chaperonin 10 regulates parasite internalization and intracellular survival in human macrophages. | protozoa of the genus leishmania infect macrophages in their mammalian hosts causing a spectrum of diseases known as the leishmaniases. the search for leishmania effectors that support macrophage infection is a focus of significant interest. one such candidate is leishmania chaperonin 10 (cpn10) which is secreted in exosomes and may have immunosuppressive properties. here, we report for the first time that leishmania cpn10 localizes to the cytosol of infected macrophages. next, we generated two ... | 2017 | 28283754 |
| revisiting previously investigated plants: a molecular networking-based study of geissospermum laeve. | three new monoterpene indole alkaloids (1-3) have been isolated from the bark of geissospermum laeve, together with the known alkaloids (-)-leuconolam (4), geissolosimine (5), and geissospermine (6). the structures of 1-3 were elucidated by analysis of their hrms and nmr spectroscopic data. the absolute configuration of geissolaevine (1) was deduced from the comparison of experimental and theoretically calculated ecd spectra. the isolation workflow was guided by a molecular networking-based dere ... | 2017 | 28282127 |
| evaluation of caax prenyl protease ii of leishmania donovani as potential drug target: infectivity and growth of the parasite is significantly lowered after the gene knockout. | prenylation pathway is responsible for post translational modification of various signal proteins, including proteins of ras superfamily. caax prenyl proteases are known to be key players in prenylation pathway. in the current study, we have evaluated caax prenyl protease ii as a possible drug target against leishmania donovani parasite, the causative agent of visceral leishmaniasis. gene knockout strategy was employed to target caax prenyl protease ii and subsequent effects were studied. caax p ... | 2017 | 28279761 |