| experimental selection of paromomycin and miltefosine resistance in intracellular amastigotes of leishmania donovani and l. infantum. | although widespread resistance of leishmania donovani and l. infantum against miltefosine (mil) and paromomycin (pmm) has not yet been demonstrated, both run the risk of resistance selection. unraveling the dynamics and mechanisms of resistance development is key to preserve drug efficacy in the field. in this study, resistance against pmm and mil was experimentally selected in vitro in intracellular amastigotes of several strains of both species with different antimony susceptibility background ... | 2014 | 24615359 |
| bone marrow parasite burden among patients with new world kala-azar is associated with disease severity. | kala-azar or visceral leishmaniasis, found mostly throughout the indian subcontinent, east africa, and brazil, kills 20,000-40,000 persons annually. the agents, leishmania donovani and leishmania infantum, are obligatory intracellular protozoa of mononuclear phagocytes found principally in the spleen and bone marrow. protracted fever, anemia, wasting, hepatosplenomegaly, hemorrhages, and bacterial co-infections are typical features. one hundred and twenty-two (122) in-hospital patients were stud ... | 2014 | 24615127 |
| characterization of the proliferating cell nuclear antigen of leishmania donovani clinical isolates and its association with antimony resistance. | previously, through a proteomic analysis, proliferating cell nuclear antigen (pcna) was found to be overexpressed in the sodium antimony gluconate (sag)-resistant clinical isolate compared to that in the sag-sensitive clinical isolate of leishmania donovani. the present study was designed to explore the potential role of the pcna protein in sag resistance in l. donovani. for this purpose, the protein was cloned, overexpressed, purified, and modeled. western blot (wb) and real-time pcr (rt-pcr) a ... | 2014 | 24614385 |
| leishmania donovani: dynamics of l. donovani evasion of innate immune cell attack due to malnutrition in visceral leishmaniasis. | malnutrition may be significant in the modulation of immune responses in visceral leishmaniasis (vl). data on the relationship between malnutrition and innate immune response in vl are limited. the aim of this study was to examine the effect of malnutrition on the profile of innate immune functions of polymorphonuclear neutrophil granulocytes (pmns) and monocytes through comparison of well-nourished and malnourished indian patients with vl. | 2014 | 24607302 |
| development of targeted 1,2-diacyl-sn-glycero-3-phospho-l-serine-coated gelatin nanoparticles loaded with amphotericin b for improved in vitro and in vivo effect in leishmaniasis. | the principle objective of this study was to develop 1,2-diacyl-sn-glycero-3-phospho-l-serine (ps)-coated gelatin nanoparticles (gnps) bearing amphotericin b (amb) for specific targeting to the macrophages involved in visceral leishmaniasis (vl). | 2014 | 24606222 |
| study the effects of plga-peg encapsulated amphotericin b nanoparticle drug delivery system against leishmania donovani. | drug delivery systems are a promising technology to increase poor solubility and bioavailability of compounds. therefore we have developed plga-peg encapsulated amphotericin b nanoparticles (nps) drug delivery technology to increase the solubility of amphotericin b and target the macrophage of infected tissues during visceral leishmaniasis. the structural characterization by transmission electron microscopy and dynamic light scattering revealed the nano-size of the particle (30-35 nanometers). f ... | 2015 | 24601828 |
| immunomodulation in human dendritic cells leads to induction of interferon-gamma production by leishmania donovani derived kmp-11 antigen via activation of nf-κb in indian kala-azar patients. | dendritic cells (dcs) and macrophages (mφs) are well-known antigen presenting cells with an ability to produce il-12 which indicates that they have potential of directing acquired immunity toward a th1-biased response. the aim of this study was to examine the effect of leishmania specific kmp-11 antigen through comparison of immune responses after presentation by dcs and mφs to t cells in indian patients with vl. patients with dcs and mφs were directed against a purified leishmania donovani anti ... | 2014 | 24587999 |
| deletion of ubiquitin fold modifier protein ufm1 processing peptidase ufsp in l. donovani abolishes ufm1 processing and alters pathogenesis. | previously, we showed leishmania donovani ufm1 has a gly residue conserved at the c-terminal region with a unique 17 amino acid residue extension that must be processed prior to conjugation to target proteins. in this report, we describe for the first time the isolation and characterization of the leishmania ufm1-specific protease ufsp. biochemical analysis of l. donovani ufsp showed that this protein possesses the ufm1 processing activity using sensitive fret based activity probes. the ufm1 cle ... | 2014 | 24587462 |
| metabolic reprogramming during purine stress in the protozoan pathogen leishmania donovani. | the ability of leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. however, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. to elucidate nutrient stress response pathways in leishmania donovani, we have used purine starvation as the paradigm. the salvage of purines from the host milieu is obligatory for parasite replicati ... | 2014 | 24586154 |
| whole blood assay and visceral leishmaniasis: challenges and promises. | for years, the ability to study immune responses in patients with active visceral leishmaniasis (vl) has been hampered by the absence of detectable antigen-specific th1 responses using cells from peripheral blood mononuclear cells (pbmcs). employing whole blood assay (wba), we recently reported that whole blood cells of active vl patients maintain the capacity to secrete significant levels of antigen driven ifn-γ and il-10. furthermore, wba that uses soluble leishmania antigen (sla) have advanta ... | 2014 | 24571797 |
| generation of adenosine tri-phosphate in leishmania donovani amastigote forms. | leishmania, the causative agent of various forms of leishmaniasis, is the significant cause of morbidity and mortality. regarding energy metabolism, which is an essential factor for the survival, parasites adapt to the environment under low oxygen tension in the host using metabolic systems which are very different from that of the host mammals. we carried out the study of susceptibilities to different inhibitors of mitochondrial electron transport chain and studies on substrate level phosphoryl ... | 2014 | 24570045 |
| the curative effect of fucoidan on visceral leishmaniasis is mediated by activation of map kinases through specific protein kinase c isoforms. | fucoidan can cure both antimony-sensitive and antimony-resistant visceral leishmaniasis through immune activation. however, the signaling events underlying this cellular response remain uncharacterized. the present study reveals that fucoidan induces activation of p38 and erk1/2 and nf-κb dna binding in both normal and leishmania donovani-infected macrophages, as revealed by western blotting and electrophoretic mobility shift assay (emsa), respectively. pharmacological inhibition of p38, erk1/2 ... | 2014 | 24561457 |
| elucidation of cellular mechanisms involved in experimental paromomycin resistance in leishmania donovani. | leishmania donovani is the causative agent of the potentially fatal disease visceral leishmaniasis (vl). chemotherapeutic options available to treat vl are limited and often face parasite resistance, inconsistent efficacy, and toxic side effects. paromomycin (pmm) was recently introduced to treat vl as a monotherapy and in combination therapy. it is vital to understand the mechanisms of pmm resistance to safeguard the drug. in the present study, we utilized experimentally generated pmm-resistant ... | 2014 | 24550335 |
| nonmigrant children with visceral leishmaniasis from the nonendemic area of uttarakhand. | the emergence of visceral leishmaniasis (vl) in nonendemic areas is a matter of great concern. we conducted a study and present a brief description of six nonmigrant children with vl from the nonendemic area of uttarakhand, diagnosed in our tertiary teaching hospital from february 2012 to june 2013. we also present here a geographic distribution of these cases to assess the impact of global warming and climate change on the spread of the disease. patients were diagnosed as vl by clinical finding ... | 2014 | 24531375 |
| synthesis, antileishmanial activity and docking study of n'-substitutedbenzylidene-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4h)-yl)acetohydrazides. | a series of n'-substitutedbenzylidene-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4h)-yl)acetohydrazide derivatives is synthesized and evaluated for antileishmanial activity against leishmania donovani promastigotes. compounds 9a and 9i were shown significant antileishmanial when compared with standard sodium stilbogluconate. antimicrobial study revealed that compound 9b has potent as well as broad spectrum antibacterial activity when compared with ampicillin and compound 9e showed promising antifungal ... | 2014 | 24513045 |
| identification of r2tp complex of leishmania donovani and plasmodium falciparum using genome wide in-silico analysis. | recently discovered r2tp complex is an important multiprotein complex involved in multiple cellular process like snornp biogenesis, pikk signaling, rna polymerase ii assembly and apoptosis. within r2tp complex, pih1 tightly interacts with rvb1/rvb2 and with tah1 to form r2tp macromolecular complex. r2tp complex further interacts with hsp90 to form r2tp-hsp90 complex, which has been found critical in many cellular process. the genome wide screening of leishmania donovani and plasmodium falciparum ... | 2013 | 24505500 |
| covalent functionalized self-assembled lipo-polymerosome bearing amphotericin b for better management of leishmaniasis and its toxicity evaluation. | amphotericin b remains the preferred choice for leishmanial infection, but it has limited clinical applications due to substantial dose limiting toxicities. in the present work, amb has been formulated in lipo-polymerosome (l-psome) by spontaneous self-assembly of synthesized glycol chitosan-stearic acid copolymer. the optimized l-psome formulation with vesicle size of 243.5 ± 17.9 nm, pdi of 0.168 ± 0.08 and zeta potential of (+) 27.15 ± 0.46 mv with 25.59 ± 0.87% amb loading was obtained. the ... | 2014 | 24495144 |
| liposomal cholesterol delivery activates the macrophage innate immune arm to facilitate intracellular leishmania donovani killing. | leishmania donovani causes visceral leishmaniasis (vl) by infecting the monocyte/macrophage lineage and residing inside specialized structures known as parasitophorous vacuoles. the protozoan parasite has adopted several means of escaping the host immune response, with one of the major methods being deactivation of host macrophages. previous reports highlight dampened macrophage signaling, defective antigen presentation due to increased membrane fluidity, and the downregulation of several genes ... | 2014 | 24478076 |
| characterization of glycolytic enzymes--raldolase and renolase of leishmania donovani, identified as th1 stimulatory proteins, for their immunogenicity and immunoprophylactic efficacies against experimental visceral leishmaniasis. | th1 immune responses play an important role in controlling visceral leishmaniasis (vl) hence, leishmania proteins stimulating t-cell responses in host, are thought to be good vaccine targets. search of such antigens eliciting cellular responses in peripheral blood mononuclear cells (pbmcs) from cured/exposed/leishmania patients and hamsters led to the identification of two enzymes of glycolytic pathway in the soluble lysate of a clinical isolate of leishmania donovani--enolase (ldeno) and aldola ... | 2014 | 24475071 |
| biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs. | visceral leishmaniasis (vl) is caused by the intracellular protozoan leishmania donovani complex. vl may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. the nutritional status of the patients with vl is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. changes in lipoproteins and plasma proteins may have major impacts in the host durin ... | 2014 | 24474015 |
| disuccinyl betulin triggers metacaspase-dependent endonuclease g-mediated cell death in unicellular protozoan parasite leishmania donovani. | the unicellular organism leishmania undergoes apoptosis-like cell death in response to external stress or exposure to antileishmanial agents. here, we showed that 3-o,28-o-disuccinyl betulin (disb), a potent topoisomerase type ib inhibitor, induced parasitic cell death by generating oxidative stress. the characteristic feature of the death process resembled the programmed cell death (pcd) seen in higher eukaryotes. in the current study, the generation of reactive oxygen species (ros), followed b ... | 2014 | 24468787 |
| alkyl galactofuranosides strongly interact with leishmania donovani membrane and provide antileishmanial activity. | we investigated the in vitro effects of four alkyl-galactofuranoside derivatives, i.e., octyl-β-d-galactofuranoside (compound 1), 6-amino-β-d-galactofuranoside (compound 2), 6-n-acetamido-β-d-galactofuranoside (compound 3), and 6-azido-β-d-galactofuranoside (compound 4), on leishmania donovani. their mechanism of action was explored using electron paramagnetic resonance spectroscopy (epr) and nuclear magnetic resonance (nmr), and ultrastructural alterations were analyzed by transmission electron ... | 2014 | 24468785 |
| strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in india and nepal. | asymptomatic persons infected with the parasites causing visceral leishmaniasis (vl) usually outnumber clinically apparent cases by a ratio of 4-10 to 1. we assessed the risk of progression from infection to disease as a function of dat and rk39 serological titers. | 2014 | 24466361 |
| deletion of vitamin c biosynthesis enzyme, arabino-1, 4-lactone oxidase in leishmania donovani results in increased pro-inflammatory responses from host immune cells. | recently, we reported molecular characterization, localization and functional importance of arabino-1, 4-lactone oxidase (alo) enzyme from leishmania donovani that catalyses the last step in ascorbate biosynthesis pathway. vitamin c (l-ascorbic acid) is implicated in several crucial physiological processes. to elucidate the biological role of d-arabinono-γ-lactone oxidase in leishmania, we made l. donovani alo null mutant (δalo) by double targeted gene replacement. this mutant lacked alo activit ... | 2014 | 24456202 |
| aptamer based, non-pcr, non-serological detection of chagas disease biomarkers in trypanosoma cruzi infected mice. | chagas disease affects about 5 million people across the world. the etiological agent, the intracellular parasite trypanosoma cruzi (t. cruzi), can be diagnosed using microscopy, serology or pcr based assays. however, each of these methods has their limitations regarding sensitivity and specificity, and thus to complement these existing diagnostic methods, alternate assays need to be developed. it is well documented that several parasite proteins called t. cruzi excreted secreted antigens (tesa) ... | 2014 | 24454974 |
| survey of antibodies to leishmania spp. in wild canids from pennsylvania and tennessee. | visceral leishmaniasis (vl) is a zoonosis with worldwide distribution. infections with the leishmania donovani complex, including leishmania infantum, cause the vl. domestic dogs are the most important reservoir host for human vl, and wild canids are also susceptible. in the united states, infections with l. infantum are common in the foxhound dog breed. little information is available regarding l. infantum in wild canids in the unites states. sera from 11 foxes and 256 coyotes originating in pe ... | 2013 | 24450086 |
| the emergence of leishmania major and leishmania donovani in southern turkey. | in southern turkey, leishmania tropica and l. infantum are both the causative agents of cutaneous leishmaniasis (cl) and visceral leishmaniasis (vl), respectively. however, l. major and l. donovani were known to exist after the influx of syrian refugees. | 2014 | 24449479 |
| comparative transcript expression analysis of miltefosine-sensitive and miltefosine-resistant leishmania donovani. | leishmania donovani is the causative agent of anthroponotic visceral leishmaniasis in the indian subcontinent. oral miltefosine therapy has recently replaced antimonials in endemic areas. however, the drug is at risk of emergence of resistance due to unrestricted use, and, already, there are indications towards decline in treatment efficacy. hence, understanding the mechanism of miltefosine resistance in the parasite is crucial. we employed genomic microarray analysis to compare the gene express ... | 2014 | 24449447 |
| selective inhibition of leishmania donovani by active extracts of wild mushrooms used by the tribal population of india: an in vitro exploration for new leads against parasitic protozoans. | the study was intended at evaluating the anti-proliferating effect of mushrooms used in traditional folklore of santal tribal population in india against leishmania donovani (mhom/in/83/ag83). a total of eighteen extracts, three estracts from each mushroom [(80% ethanol extracted; fa), (water-soluble polysaccharide fraction; fb), (polyphenolic fraction; fc)], from six wild mushrooms were obtained. these extracts were tested against the promastigotes and amastigotes for their antileishmanial capa ... | 2014 | 24440295 |
| protective immunity using mpl-a and autoclaved leishmania donovani as adjuvants along with a cocktail vaccine in murine model of visceral leishmaniasis. | the current study is an extension of our previous study where we tested the protective efficacy of gp63 and hsp70 against murine visceral leishmaniasis. the cocktail vaccine was combined with mpl-a and ald adjuvants and the protection afforded by the three vaccines was compared. inbred balb/c mice were immunized twice at an interval of two weeks with the vaccine formulations. two weeks after the booster, they were challenged with 10(7) promastigotes of leishmania donovani and sacrificed on 30, 6 ... | 2013 | 24431576 |
| elisa and western blotting for the detection of hsp70 and hsp83 antigens of leishmania donovani. | visceral leishmaniasis (vl) is endemic in the tropical, sub-tropical regions of asia, africa, the mediterranean, southern europe and south and central america. approximately 500,000 new cases are reported annually. classically the diagnosis of vl is confirmed by the demonstration of the parasite in aspirates of spleen, bone marrow or liver which can yield false negative results, also these methods are invasive. in this study, we aimed to evaluate the serodiagnostic potential of two heat shock pr ... | 2013 | 24431544 |
| il-4 contributes to failure, and colludes with il-10 to exacerbate leishmania donovani infection following administration of a subcutaneous leishmanial antigen vaccine. | visceral leishmaniasis caused by the protozoan parasite leishmania donovani complex is a potentially fatal disease if left untreated. few treatment options exist and are toxic, costly and ineffective against resistant strains. thus a safe and efficacious vaccine to combat this disease is needed. previously, we reported that intraperitoneal administration of leishmanial antigens (lag) entrapped in liposomes conferred protection to balb/c mice against l. donovani challenge infection. however, this ... | 2014 | 24428931 |
| ecology- and bioassay-guided drug discovery for treatments of tropical parasitic disease: 5alpha,8alpha-epidioxycholest-6-en-3beta-ol isolated from the mollusk dolabrifera dolabrifera shows significant activity against leishmania donovani. | an ecology- and bioassay-guided search employed to discover compounds with activity against tropical parasitic diseases and cancer from the opisthobranch mollusk, dolabrifera dolabrifera, led to the discovery of antileishmanial properties in the known compound, 5alpha,8alpha-epidioxycholest-6-en-3beta-ol (1). compound 1 was identified through nuclear magnetic resonance spectroscopy (1h, 13c) and mass spectrometry. the compound was concentrated in the digestive gland of d. dolabrifera, but was no ... | 2013 | 24427935 |
| molecular mechanisms of in vitro betulin-induced apoptosis of leishmania donovani. | although leishmanial infections of humans occur globally, the major health impact lies in developing nations, thus, leishmaniases remain "neglected" diseases for new drugs development. multidrug resistance has been documented in most countries where leishmaniases is endemic. betulin is a widely available and affordable natural product exerting leishmanicidal activity at micromolar concentration. in this study, the molecular mechanisms of death that contribute to the anti-leishmanial activity of ... | 2014 | 24420777 |
| leishmania donovani activates uncoupling protein 2 transcription to suppress mitochondrial oxidative burst through differential modulation of srebp2, sp1 and usf1 transcription factors. | in order to reside and multiply successfully within the host macrophages, leishmania parasites impair the generation of cellular as well as mitochondrial reactive oxygen species (ros), which is a major host defense mechanism against any invading pathogen. mitochondrial uncoupling protein 2 (ucp2) is strongly induced in leishmania infection, both at mrna and protein levels, to suppress the mitochondrial ros generation. in the present study we have demonstrated that leishmania donovani infection i ... | 2014 | 24417972 |
| new fluoranthene flun-550 as a fluorescent probe for selective staining and quantification of intracellular lipid droplets. | a new class of live cell permeant, nontoxic fluoranthene-based fluorescent probe (flun-550) having a high stokes shift in aqueous medium has been discovered. it showed selective staining of lipid droplets (lds, dynamic cytoplasmic organelles) at a low concentration without background noise in in vitro live cell imaging of 3t3-l1 preadipocytes, j774 macrophages, mcf7 breast cancer cells, and single-celled, parasitic protozoa leishmania donovani promastigotes and in vivo nonparasitic soil nematode ... | 2014 | 24410145 |
| in vitro screening test using leishmania promastigotes stably expressing mcherry protein. | transgenic leishmania major and leishmania donovani axenic promastigotes constitutively expressing mcherry were used for in vitro antileishmanial drug screening. this method requires minimal sample manipulation and can be easily adapted to automatic drug tests, allowing primary high-throughput screenings without the need for expensive and sophisticated instruments. | 2014 | 24395225 |
| post kala-azar dermal leishmaniasis following treatment with 20 mg/kg liposomal amphotericin b (ambisome) for primary visceral leishmaniasis in bihar, india. | the skin disorder post kala-azar dermal leishmaniasis (pkdl) occurs in up to 10% of patients treated for visceral leishmaniasis (vl) in india. the pathogenesis of pkdl is not yet fully understood. cases have been reported in india following therapy with most available treatments, but rarely in those treated with liposomal amphotericin b (ambisome). between july 2007 and august 2012 with the support of the rajendra memorial research institute (rmri), médecins sans frontières (msf) supported a vl ... | 2014 | 24392171 |
| five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin b (ambisome) for visceral leishmaniasis in bihar, india. | visceral leishmaniasis (vl; also known as kala-azar) is an ultimately fatal disease endemic in bihar. a 2007 observational cohort study in bihar of 251 patients with vl treated with 20 mg/kg intravenous liposomal amphotericin b (ambisome) demonstrated a 98% cure rate at 6-months. between july 2007 and august 2012, médecins sans frontières (msf) and the rajendra memorial research institute (rmri) implemented a vl treatment project in bihar, india-an area highly endemic for leishmania donovani-usi ... | 2014 | 24392168 |
| leishmania donovani targets tumor necrosis factor receptor-associated factor (traf) 3 for impairing tlr4-mediated host response. | intramacrophage pathogen leishmania donovani escapes host immune response by subverting toll-like receptor (tlr) signaling, which is critically regulated by protein ubiquitination. in the present study, we identified tumor necrosis factor receptor-associated factor (traf) 3, degradative ubiquitination of which is essential for tlr4 activation, as a target for leishmania to deactivate lps-mediated tlr4 signaling. we used lps-treated raw 264.7 cells and compared the tlr4-mediated immune response i ... | 2014 | 24391131 |
| serological survey and associated risk factors of visceral leish-maniasis in qom province, central iran. | visceral leishmaniasis (vl) or kala-azar is considered as a parasitic disease caused by the species of leishmania donovani complex which is intracellular parasites. this systemic disease is endemic in some parts of provinc-es of iran. the aim of this study was to determine the seroprevalence of vl in qom province, central iran using di-rect agglutination test (dat). | 2014 | 26060679 |
| efficacy of leishmania donovani trypanothione reductase, identified as a potent th1 stimulatory protein, for its immunogenicity and prophylactic potential against experimental visceral leishmaniasis. | in visceral leishmaniasis (vl), th1-type of immune responses play an important role which correlates with recovery from and resistance to disease resulting in lifelong immunity. based on this rationale, the soluble leishmanial antigens that elicit cellular responses in peripheral blood mononuclear cells (pbmcs) from cured leishmania patients were characterized through immunoproteomic approach which led to the identification of trypanothione reductase (tpr) (a cytosolic enzyme explored as a drug ... | 2014 | 24370734 |
| tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis. | effect of pure herb, tinospora cordifolia was studied for its hepatoprotective, nephroprotective and immunomodulatory activity against high dose cisplatin treatment in leishmania donovani infected balb/c mice. administration of cisplatin (5mg/kg b.wt. daily for 5 days, i.p.) reduced the parasite load in l. donovani infected balb/c mice but produced damage in liver and kidney as manifested biochemically by an increase in serum glutamate oxaloacetate transaminase (sgot), serum glutamate pyruvate t ... | 2014 | 24370645 |
| in vitro synergistic effect of amphotericin b and allicin on leishmania donovani and l. infantum. | current monotherapy against visceral leishmaniasis has serious side effects, and resistant leishmania strains have been identified. amphotericin b (amb) has shown an extraordinary antileishmanial efficacy without emergence of resistance; however, toxicity has limited its general use. results obtained showed, using a fixed-ratio analysis, that the combination of diallyl thiosulfinate (allicin) and amb ranged from moderately synergic to synergic at low concentrations (0.07 μm amb plus 35.45 μm all ... | 2014 | 24366748 |
| a petri net model of granulomatous inflammation: implications for il-10 mediated control of leishmania donovani infection. | experimental visceral leishmaniasis, caused by infection of mice with the protozoan parasite leishmania donovani, is characterized by focal accumulation of inflammatory cells in the liver, forming discrete "granulomas" within which the parasite is eventually eliminated. to shed new light on fundamental aspects of granuloma formation and function, we have developed an in silico petri net model that simulates hepatic granuloma development throughout the course of infection. the model was extensive ... | 2013 | 24363630 |
| an actin-like protein is involved in regulation of mitochondrial and flagellar functions as well as in intramacrophage survival of leishmania donovani. | actin-related proteins are ubiquitous actin-like proteins that show high similarity with actin in terms of their amino acid sequence and three-dimensional structure. however, in lower eukaryotes, such as trypanosomatids, their functions have not yet been explored. here, we show that a novel actin-related protein (orf lmjf.13.0950) is localized mainly in the leishmania mitochondrion. we further reveal that depletion of the intracellular levels of this protein leads to an appreciable decrease in t ... | 2014 | 24354789 |
| in vitro susceptibilities of wild and drug resistant leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin e derivative tpgs for nanoparticle efficacy. | visceral leishmaniasis (vl) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. there is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant vl. to address this need, andrographolide (ag) nanoparticles were designed with p-gp efflux inhibitor vitamin e tpgs (d-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant leishmania strains ... | 2013 | 24339938 |
| comparison of pcr-based diagnoses for visceral leishmaniasis in bangladesh. | the diagnosis of visceral leishmaniasis (vl) is performed using multiple methods encompassing parasitological, serological and nucleic acid-based diagnostic tools, each method with its own unique advantages and disadvantages. conventional parasitological methods are risky for the patient and require skilled personnel to collect specimens from spleen or bone marrow, and hence they are not generally available in impoverished areas. polymerase chain reaction (pcr) has been validated as an excellent ... | 2014 | 24333754 |
| post-kala-azar dermal leishmaniasis mimicking leprosy relapse: a diagnostic dilemma. | post-kala-azar dermal leishmaniasis (pkdl) is well recognized in the indian subcontinent and is not infrequently confused with leprosy. the present report describes findings in an unusual case of pkdl. | 2014 | 24321013 |
| sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen porphyromonas gingivalis. | a carbonic anhydrase (ca, ec 4.2.1.1) denominated pgica, belonging to the γ-class, from the oral pathogenic bacteria porphyromonas gingivalis, the main causative agent of periodontitis, was investigated for its inhibition profile with sulfonamides and one sulfamate. dichlorophenamide, topiramate and many simple aromatic/heterocyclic sulfonamides were ineffective as pgica inhibitors whereas the best inhibition was observed with halogenosulfanilamides incorporating heavy halogens, 4-hydroxy- and 4 ... | 2014 | 24316122 |
| triazino indole-quinoline hybrid: a novel approach to antileishmanial agents. | a novel series of 1,2,4-triazino-[5,6b]indole-3-thione covalently linked to 7-chloro-4-aminoquinoline have been synthesized and evaluated for their in vitro activity against extracellular promastigote and intracellular amastigote form of leishmania donovani. among all tested compounds, compounds 7a and 7b were found to be the most active with ic50 values 1.11, 0.36μm and selectivity index (si) values 67, >1111, respectively, against amastigote form of l. donovani which is several folds more pote ... | 2014 | 24314395 |
| leishmania donovani prevents oxidative burst-mediated apoptosis of host macrophages through selective induction of suppressors of cytokine signaling (socs) proteins. | one of the mechanisms for establishment of infection employed by intra-macrophage pathogen-like leishmania is inhibition of oxidative burst-mediated macrophage apoptosis to protect their niche for survival and replication. we tried to elucidate the underlying mechanism for this by using h2o2 for induction of apoptosis. leishmania donovani-infected macrophages were much more resistant to h2o2-mediated apoptosis compared with control. although infected cells were capable of comparable reactive oxy ... | 2014 | 24275663 |
| post-kala-azar dermal leishmaniasis due to leishmania donovani in europe--case report. | | 2013 | 24261735 |
| cathepsin b gene disruption induced leishmania donovani proteome remodeling implies cathepsin b role in secretome regulation. | leishmania cysteine proteases are potential vaccine candidates and drug targets. to study the role of cathepsin b cysteine protease, we have generated and characterized cathepsin b null mutant l. donovani parasites. l. donovani cathepsin b null mutants grow normally in culture, but they show significantly attenuated virulence inside macrophages. quantitative proteome profiling of wild type and null mutant parasites indicates cathepsin b disruption induced remodeling of l. donovani proteome. we i ... | 2013 | 24244582 |
| stat4 is critical for immunity but not for antileishmanial activity of antimonials in experimental visceral leishmaniasis. | we and others have previously shown that il-12 is indispensable for immunity and is required for the optimal antiparasitic activity of antimonials in experimental visceral leishmaniasis caused by leishmania donovani. here we investigated the role of stat4 in immunity against l. donovani using stat4 knockout mice and also determined the effect of stat4 deficiency in response to antimonial therapy. upon infection with l. donovani, stat4⁻/⁻ balb/c and c57bl/6 mice showed enhanced susceptibility to ... | 2014 | 24242758 |
| exploring leishmania donovani 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) as a potential drug target by biochemical, biophysical and inhibition studies. | 3-hydroxy-3-methylglutaryl-coa (hmg-coa) reductase (hmgr), an nadph dependant enzyme catalyzes the synthesis of mevalonic acid from hmg-coa required for isoprenoid biosynthesis. the hmgr gene from leishmania donovani was cloned and expressed. genome analysis of l. donovani revealed that hmgr gene having an open reading frame of 1305 bp encodes a putative protein of 434 amino acids. ldhmgr showed optimal activity at ph 7.2 and temperature 37 °c. kinetic analysis of this enzyme revealed km values ... | 2014 | 24239940 |
| biomarkers for intracellular pathogens: establishing tools as vaccine and therapeutic endpoints for visceral leishmaniasis. | visceral leishmaniasis in south asia is a serious disease affecting children and adults. acute visceral leishmaniasis develops in only a fraction of those infected individuals, the majority being asymptomatic with the potential to transmit infection and develop disease. we followed 56 individuals characterized as being asymptomatic by seropositivity with rk39 rapid diagnostic test in a hyperendemic district of bangladesh to define the utility of leishmania-specific antibodies and dna in identify ... | 2014 | 24237596 |
| click chemistry decoration of amino sterols as promising strategy to developed new leishmanicidal drugs. | a series of 1,2,3-triazolylsterols was prepared from pregnenolone through reductive amination and copper(i)-catalyzed azide-alkyne cycloaddition (click chemistry). the newly generated stereocenter of the key propargylamino intermediate provided a mixture of diastereomers which were separated chromatographically, and the configuration of the r isomer was determined by x-ray crystallography. ten triazolyl sterols were prepared, and the products and intermediates were screened in vitro against diff ... | 2014 | 24200958 |
| spinigerin induces apoptotic like cell death in a caspase independent manner in leishmania donovani. | antimicrobial peptides (amps) are multifunctional components of the innate immune system. chemotherapeutic agents used for treatment of visceral leishmaniasis (vl) are now threatened due to the emergence of acquired drug resistance and toxicity. amps are attractive alternative to conventional pharmaceuticals. in this study, first time we explored the antileishmanial activity of spinigerin originally derived from pseudacanthotermes spiniger. leishmania donovani promastigotes present apoptosis-lik ... | 2013 | 24184774 |
| chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis. | the indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. we have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stib ... | 2013 | 24167266 |
| apoptosis-like death in leishmania donovani promastigotes induced by eugenol-rich oil of syzygium aromaticum. | leishmaniasis consists of a complex spectrum of infectious diseases with worldwide distribution of which visceral leishmaniasis or kala-azar caused by leishmania donovani is the most devastating. in the absence of vaccines, chemotherapy remains the mainstay for the control of leishmaniasis. the drugs of choice are expensive and associated with multiple adverse side effects. because of these limitations, the development of new antileishmanial compounds is imperative and plants offer prospects in ... | 2014 | 24161990 |
| performance of an indigenous β-mercaptoethanol-modified antigen in comparison with a commercial reference in direct agglutination test for detection of canine visceral leishmaniasis. | we compared the performance of a locally produced β-mercaptoethanol-modified promastigote antigen (β-me-ag) of an indigenous leishmania infantum strain against that of a trypsinized leishmania donovani reference (ref-ag) in the direct agglutination test (dat) for detection of canine visceral leishmaniasis (cvl). one hundred and fifty-one serum samples collected from dogs belonging to four groups with different conditions were included. at a dat titre of 1 : 320, statistically determined as optim ... | 2014 | 24143006 |
| the lignan glycosides lyoniside and saracoside poison the unusual type ib topoisomerase of leishmania donovani and kill the parasite both in vitro and in vivo. | lignans are diphenyl propanoids with vast range of biological activities. the present study provides an important insight into the anti-leishmanial activities of two lignan glycosides, viz. lyoniside and saracoside. these compounds inhibit catalytic activities of topoisomerase ib (ldtopib) of leishmania donovani in non-competitive manner and stabilize the ldtopib mediated cleavage complex formation both in vitro and in leishmania promastigotes and subsequently inhibit the religation of cleaved s ... | 2013 | 24134912 |
| mass spectrometry-based proteomic analysis of leishmania donovani soluble proteins in indian clinical isolate. | leishmania donovani, a causative organism of visceral leishmaniasis (vl), is responsible for high mortality throughout the world. due to the unsatisfactory treatment measures and increasing drug resistance, there has been an urgent need to develop novel drug/vaccine targets against vl. the aim of this study was to identify novel targets in soluble l. donovani (sld) protein. sld protein was isolated and resolved by two-dimensional gel electrophoresis and analyzed through maldi-tof/tof-based mass ... | 2014 | 24115687 |
| relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting leishmania donovani strain. | leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the indian subcontinent. this relapse ... | 2013 | 24105765 |
| increased parasite surface antigen-2 expression in clinical isolates of leishmania donovani augments antimony resistance. | resistance to sodium antimony gluconate (sag) is a major cause of therapeutic failure in a large proportion of visceral leishmaniasis (vl) cases. determinants of sag resistance have been widely studied; however, the mechanism operating in clinical isolates is poorly understood. in the present study, expression of parasite surface antigen-2 (psa-2) gene was studied in clinical isolates of leishmania donovani comprising of antimony resistant (n=10) and sensitive (n=4) parasites. the expression of ... | 2013 | 24103752 |
| asparagus racemosus ameliorates cisplatin induced toxicities and augments its antileishmanial activity by immunomodulation in vivo. | current drugs for the treatment of visceral leishmaniasis are inadequate and their efficacies are also compromised due to suppression of immune function associated during the course of infection. to overcome this problem, efforts are needed to develop therapies with effective immunomodulatory agents where decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. in this study we have evaluated a new therapeutic approach based on combination of asparagus race ... | 2014 | 24103199 |
| design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents. | an analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. these molecules were tested for their in vitro and in vivo biological activity against leishmania donovani. metabolic stability of these compounds was also improved through the introduction of halogen substituents. compound (26g), found to be the most active; exhibited an ic₅₀ value of 0.2 μm and >180 fold selectivity. the hydrochloride sa ... | 2013 | 24095747 |
| synthesis of marine α-methoxylated fatty acid analogs that effectively inhibit the topoisomerase ib from leishmania donovani with a mechanism different from that of camptothecin. | sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties and in some cases they display enhanced anticancer activities. however, the antiprotozoal properties of the α-methoxylated fatty acids have been less studied. in this work, we describe the total synthesis of (5z,9z)-(±)-2-methoxy-5, 9-eicosadienoic acid (1) and its acetylenic analog (±)-2-methoxy-5,9-eicosadiynoic acid (2), and report that they inhibit (ec₅₀ values between 31 and 22 µm) the leishm ... | 2013 | 24084785 |
| targeting the human parasite leishmania donovani: discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series. | we report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. in vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of leishmania donovani, j774a.1 murine and hepg2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). new derivatives were then synthesized to allow structure-activity and -toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying ... | 2013 | 24080103 |
| degree of anemia correlates with increased utilization of heme by leishmania donovani parasites in visceral leishmaniasis. | anemia in kala-azar patients is a serious problem. the present study has addressed this problem with the hypothesis that as the leishmania parasite is completely devoid of heme biosynthetic pathway, therefore the excessive use of heme by the parasites in the human patients can be one of the possible reason of anemia. we investigated that whether, the inability of leishmania donovani to synthesize heme, can enforce leishmania parasite to utilize heme derived from host sources in indian ka patient ... | 2013 | 24076432 |
| role of efflux pumps and intracellular thiols in natural antimony resistant isolates of leishmania donovani. | in view of the recent upsurge in the phenomenon of therapeutic failure, drug resistance in leishmania, developed under natural field conditions, has become a great concern yet little understood. accordingly, the study of determinants of antimony resistance is urgently warranted. efflux transporters have been reported in leishmania but their role in clinical resistance is still unknown. the present study was designed to elucidate the mechanism of natural antimony resistance in l. donovani field i ... | 2013 | 24069359 |
| the il-33/st2 axis is associated with human visceral leishmaniasis and suppresses th1 responses in the livers of balb/c mice infected with leishmania donovani. | during visceral leishmaniasis, the control of hepatic parasite burden is mainly due to granuloma assembly in a microenvironment consisting of both th1 and th2 components. using enzyme-linked immunosorbent assay (elisa) dosages, quantitative pcr (qpcr), immunohistochemistry, and flow cytometry, we studied the role of interleukin-33 (il-33), a recently described cytokine signaling through the st2 receptor, during visceral leishmaniasis. we showed that a higher level of il-33 was detected in the se ... | 2013 | 24045639 |
| novel role of calmodulin in regulating protein transport to mitochondria in a unicellular eukaryote. | lower eukaryotes like the kinetoplastid parasites are good models to study evolution of cellular pathways during steps to eukaryogenesis. in this study, a kinetoplastid parasite, leishmania donovani, was used to understand the process of mitochondrial translocation of a nucleus-encoded mitochondrial protein, the mitochondrial tryparedoxin peroxidase (mtxnpx). we report the presence of an n-terminal cleavable mitochondrial targeting signal (mts) validated through deletion and grafting experiments ... | 2013 | 24043313 |
| a transcriptomic network identified in uninfected macrophages responding to inflammation controls intracellular pathogen survival. | intracellular pathogens modulate host cell function to promote their survival. however, in vitro infection studies do not account for the impact of host-derived inflammatory signals. examining the response of liver-resident macrophages (kupffer cells) in mice infected with the parasite leishmania donovani, we identified a transcriptomic network operating in uninfected kupffer cells exposed to inflammation but absent from kupffer cells from the same animal that contained intracellular leishmania. ... | 2013 | 24034621 |
| vaccination with leishmania hemoglobin receptor-encoding dna protects against visceral leishmaniasis. | leishmaniasis is a severe infectious disease. drugs used for leishmaniasis are very toxic, and no vaccine is available. we found that the hemoglobin receptor (hbr) of leishmania was conserved across various strains of leishmania, and anti-hbr antibody could be detected in kala-azar patients' sera. our results showed that immunization with hbr-dna induces complete protection against virulent leishmania donovani infection in both balb/c mice and hamsters. moreover, hbr-dna immunization stimulated ... | 2013 | 24027025 |
| identification and characterization of the regions involved in the nuclear translocation of the heterodimeric leishmanial dna topoisomerase ib. | leishmania donovani, the causative organism for visceral leishmaniasis, contains a unique heterodimeric dna-topoisomerase ib (ldtopib). ldtopib is a heterodimer made up of a large subunit and a small subunit that must interact with each other to build an active enzyme able to solve the topological tensions on the dna. as ldtopib is located within the nucleus, one or more nuclear localization signals (nls) should exist to ensure its nuclear translocation. in this report three novel nls have been ... | 2013 | 24023887 |
| metabolic adaptations of leishmania donovani in relation to differentiation, drug resistance, and drug pressure. | antimonial (sodium stibogluconate, ssg) resistance and differentiation have been shown to be closely linked in leishmania donovani, with ssg-resistant strains showing an increased capacity to generate infectious (metacyclic) forms. this is the first untargeted lc-ms metabolomics study which integrated both phenomena in one experimental design and provided insights into metabolic differences between three clinical l. donovani strains with a similar genetic background but different ssg-susceptibil ... | 2013 | 24020363 |
| novel 3-nitro-1h-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents. | we have previously shown that 3-nitro-1h-1,2,4-triazole-based amines demonstrate significant trypanocidal activity, in particular against trypanosoma cruzi, the causative parasite of chagas disease. in the present work we further expanded our research by evaluating in vitro the trypanocidal activity of nitrotriazole-based piperazines and nitrotriazole-based 2-amino-1,3-benzothiazoles to establish additional sars. all nitrotriazole-based derivatives were active or moderately active against t. cru ... | 2013 | 24012457 |
| on the catalytic mechanism of dimeric dutpases. | the tritryps trypanosoma brucei, trypanosoma cruzi and leishmania donovani are responsible for great morbidity and mortality in developing countries. their dimeric dutpases are members of the all-α ntp pyrophosphohydrolase family and represent promising drug targets due to their essential nature and markedly different structural and biochemical properties compared with the trimeric human enzyme. in the present paper we describe the structure of the t. brucei enzyme in open and closed conformatio ... | 2013 | 24001052 |
| computational elucidation of structural basis for ligand binding with leishmania donovani adenosine kinase. | enzyme adenosine kinase is responsible for phosphorylation of adenosine to amp and is crucial for parasites which are purine auxotrophs. the present study describes development of robust homology model of leishmania donovani adenosine kinase to forecast interaction phenomenon with inhibitory molecules using structure-based drug designing strategy. docking calculation using reported organic small molecules and natural products revealed key active site residues such as arg131 and asp16 for ligand ... | 2013 | 23984386 |
| in vitro susceptibility of leishmania donovani to miltefosine in indian visceral leishmaniasis. | promastigote miltefosine (mil) susceptibility was performed on leishmania donovani isolates from indian patients with visceral leishmaniasis treated with mil. isolates that were obtained before the onset of mil treatment, after completion of treatment (29th day), or at the time of treatment failure, were screened using in vitro promastigote assay. the mil susceptibility of the pre-treatment isolates (n = 24, mean ic50 ± sem = 3.74 ± 0.38 μm) was significantly higher than that of the post-treatme ... | 2013 | 23980130 |
| leishmania donovani: influence of anti-leishmanial therapy on expression of lymphocyte function-associated antigen-3 and its relevance to pathogenisis in visceral leishmaniasis. | lymphocyte function associated antigen 3 (lfa-3) is known as adhesion molecule with its role in t-cell activation signaling as well as in foxp3 expression. its influences on il-10 production is also available, whose role in pathogenesis is well documented. however, this molecule is not yet directly addressed for its association with visceral leishmaniasis (vl). we investigated the relationship between leishmania donovani infection and expression of lfa-3 in vl patients in their pre and post trea ... | 2013 | 23974052 |
| evaluation of a diospyrin derivative as antileishmanial agent and potential modulator of ornithine decarboxylase of leishmania donovani. | world health organization has called for academic research and development of new chemotherapeutic strategies to overcome the emerging resistance and side effects exhibited by the drugs currently used against leishmaniasis. diospyrin, a bis-naphthoquinone isolated from diospyros montana roxb., and its semi-synthetic derivatives, were reported for inhibitory activity against protozoan parasites including leishmania. presently, we have investigated the antileishmanial effect of a di-epoxide deriva ... | 2013 | 23973194 |
| miltefosine resistance in leishmania donovani involves suppression of oxidative stress-induced programmed cell death. | miltefosine (mil), an alkylphospholipid, is the first orally administrable anti-leishmanial drug. but due to its long half-life, miltefosine is highly vulnerable for resistance. hence it is important to understand the mechanism of resistance and to elucidate its action on leishmania. here we investigate the miltefosine induced process of programmed cell death in wild type (miltefosine sensitive) and in laboratory generated resistant strains of leishmania donovani. results indicate that miltefosi ... | 2013 | 23968687 |
| the malnutrition-related increase in early visceralization of leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. | in a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4-5-fold increase in early visceralization of l. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). to begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. there was no difference in th ... | 2013 | 23967356 |
| to investigate the therapeutic potential of immunochemotherapy with cisplatin + 78 kda + mpl-a against leishmania donovani in balb/c mice. | leishmaniasis has recently garnered attention as one of the diseases 'most neglected' by drug research and development, as the current therapeutic modalities available for the patients are ridden with unacceptable toxicity due to high dosage of the drug, prolonged treatment schedules, resistance and prohibitive costs. a successful chemotherapy requires a restoration of immune response; therefore, we combined leishmania-specific 78 kda antigen (with or without adjuvant mpl-a) along with a novel d ... | 2014 | 23964700 |
| liposomal resiquimod for the treatment of leishmania donovani infection. | the imidazoquinoline family of drugs are toll-like receptor 7/8 agonists that have previously been used in the treatment of cutaneous leishmaniasis. because of the hydrophobic nature of imidazoquinolines, they are traditionally not administered systemically for the treatment of visceral leishmaniasis. we formulated liposomal resiquimod, an imidazoquinoline, for the systemic treatment of visceral leishmaniasis. | 2014 | 23956375 |
| two case reports on visceral leishmaniasis diagnosed in romania. | two cases of visceral leishmaniasis with a species from leishmania donovani complex were detected in the fundeni clinical institute. in one case, two infection sources were possible: one from italy, where the patient worked three years, the other from the southwest of romania (dolj county), where he was resident and where few human and canine leishmaniasis cases were registered in the past. in the second case, the patient lived in the northeast of romania (iaşi county), but worked in the same so ... | 2013 | 23947013 |
| molecular detection of leishmania infection in sand flies in border line of iran-turkmenistan: restricted and permissive vectors. | a molecular study was carried out to incriminate sand fly vectors of cutaneous leishmaniasis (cl) in rural areas of sarakhs district, khorassane-razavi province, northeastern iran, in 2011. sand flies of sergentomyia with three species and phlebotomus with six species respectively comprised 73.3% and 26.7% of the specimens. phlebotomus papatasi was the most common phlebotomine species in outdoor and indoor resting places. leishmania infection was found at least in 17 (22%) specimens including ph ... | 2013 | 23933280 |
| post-kala-azar dermal leishmaniasis with mucosal involvement: an unusual case presentation including successful treatment with miltefosine. | post-kala-azar dermal leishmaniasis (pkdl) is a dermatologic manifestation that usually occurs after visceral leishmaniasis (vl) caused by leishmania donovani. it is characterized by hypopigmented patches, a macular or maculopapular rash and nodular skin lesions on the body surface. involvement of the mucosae is very rare and unusual in pkdl. we report a case of pkdl that presented with polymorphic skin lesions, along with involvement of peri-oral mucosa and tongue from an endemic area for kala- ... | 2013 | 23930349 |
| antiprotozoal screening of 60 south african plants, and the identification of the antitrypanosomal germacranolides schkuhrin i and ii. | two hundred and seven extracts were prepared from sixty plants from south africa and screened for in vitro activity against trypanosoma brucei rhodesiense, trypanosoma cruzi, leishmania donovani, and plasmodium falciparum. for the 21 extracts which inhibited the growth of one or more parasites with more than 95 % at 10 µg/ml, the ic50 values against all four protozoal parasites and cytotoxic ic50 values against l6 myoblasts were determined. amongst the most notable results are the activities of ... | 2013 | 23929246 |
| design, synthesis and biological evaluation of aryl pyrimidine derivatives as potential leishmanicidal agents. | a series of substituted aryl pyrimidine derivatives was synthesized and evaluated in vitro for their antileishmanial potential against intracellular amastigotes of leishmania donovani using reporter gene luciferase assay. among all, 8 compounds showed promising ic50 values ranging from 0.5 to 12.9 μm. selectivity indices (s.i.) of all these compounds are far better than reference drugs, sodium stibogluconate (ssg) and miltefosine. on the basis of good s.i., compounds were further screened for th ... | 2013 | 23910597 |
| miltefosine-unresponsive leishmania donovani has a greater ability than miltefosine-responsive l. donovani to resist reactive oxygen species. | resistance of leishmania parasites to miltefosine, which is only available oral drug, is a great concern. we have analyzed global gene expression profiles of miltefosine-unresponsive and miltefosine-responsive leishmania donovani in order to understand the various metabolic processes involved in miltefosine drug resistance. the microarray data clearly indicated a role of oxidative metabolism in miltefosine resistance. furthermore, fluorescence microscopy experiments suggested that miltefosine-un ... | 2013 | 23890327 |
| [severe oral mucositis in a patient with hiv infection]. | a 50-year-old man with hiv infection (first diagnosed > 20 years ago) presented at our hospital with fulminant oral mucositis. antiretroviral therapy (tenofovir, emtricitabine, raltegravir) had been started 2 months ago. previously he had no opportunistic infections and no other pre-existing illnesses. he had not travelled outside europe but stayed in spain for several weeks during summer. | 2013 | 23884748 |
| rklo8, a novel leishmania donovani - derived recombinant immunodominant protein for sensitive detection of visceral leishmaniasis in sudan. | for effective control of visceral leishmaniasis (vl) in east africa, new rapid diagnostic tests are required to replace current tests with low sensitivity. the aim of this study is to improve diagnosis of vl in east africa by testing a new antigen from an autochthonous l. donovani strain in sudan. | 2013 | 23875052 |
| synthesis and antiprotozoal activities of benzyl phenyl ether diamidine derivatives. | sixty-two cationic benzyl phenyl ether derivatives (36 amidines and 26 prodrugs) were prepared and assayed for activities in vitro and in vivo against trypanosoma brucei rhodesiense (stib900), and in vitro against plasmodium falciparum (k1) and leishmania donovani axenic amastigotes. 3-amidinobenzyl 4-amidino-2-iodo-6-methoxyphenyl ether dihydrochloride (55, ic50 = 3.0 nm) and seven other compounds exhibited ic50 values below 10 nm against t. b. rhodesiense in vitro. the 2-bromo-4,4'-diamidino a ... | 2013 | 23871911 |
| microalbuminuria and glomerular filtration rate in paediatric visceral leishmaniasis. | visceral leishmaniasis, caused by leishmania donovani, is a serious form of leishmaniasis and fatal if untreated. nearly half of the vl cases are children. there are very few studies of renal function in pediatric visceral leishmaniasis. the aim of this study was to evaluate renal dysfunction by studying glomerular filtration rate (gfr), microalbuminuria, and microscopic examination of urine. laboratory analysis was performed on blood and urine samples of 40 parasitologically confirmed pediatric ... | 2013 | 23865054 |
| the r enantiomer of the antitubercular drug pa-824 as a potential oral treatment for visceral leishmaniasis. | the novel nitroimidazopyran agent (s)-pa-824 has potent antibacterial activity against mycobacterium tuberculosis in vitro and in vivo and is currently in phase ii clinical trials for tuberculosis (tb). in contrast to m. tuberculosis, where (r)-pa-824 is inactive, we report here that both enantiomers of pa-824 show potent parasiticidal activity against leishmania donovani, the causative agent of visceral leishmaniasis (vl). in leishmania-infected macrophages, (r)-pa-824 is 6-fold more active tha ... | 2013 | 23856774 |
| synthesis and antiprotozoal activity of original porphyrin precursors and derivatives. | importance of heme in african trypanosomes, leishmania sp. and plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. consequently, twenty-four porphyrin precursors and derivatives were evaluated against leishmania donovani, trypanosoma brucei and plasmodium sp. the best active compound against trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, wit ... | 2013 | 23851117 |