Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
deficiency of p110δ isoform of the phosphoinositide 3 kinase leads to enhanced resistance to leishmania donovani.visceral leishmaniasis is the most clinically relevant and dangerous form of human leishmaniasis. most traditional drugs for treatment of leishmaniasis are toxic, possess many adverse reactions and drug resistance is emerging. therefore, there is urgent need for identification of new therapeutic targets. recently, we found that mice with an inactivating knock-in mutation in the p110δ isoform of pi3k, (p110δ(d910a)) are hyper resistant to l. major, develop minimal cutaneous lesion and rapidly cle ...201424945303
clinical and parasitological protection in a leishmania infantum-macaque model vaccinated with adenovirus and the recombinant a2 antigen.visceral leishmaniasis (vl) is a severe vector-born disease of humans and dogs caused by leishmania donovani complex parasites. approximately 0.2 to 0.4 million new human vl cases occur annually worldwide. in the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. thus, a prophylactic vaccine appears to be essential for vl control. the current efforts to develop an efficacious vaccine include the use o ...201424945284
pkdl and other dermal lesions in hiv co-infected patients with leishmaniasis: review of clinical presentation in relation to immune responses.co-infection of leishmaniasis and hiv is increasingly reported. the clinical presentation of leishmaniasis is determined by the host immune response to the parasite; as a consequence, this presentation will be influenced by hiv-induced immunosuppression. as leishmaniasis commonly affects the skin, increasing immunosuppression changes the clinical presentation, such as in post-kala-azar dermal leishmaniasis (pkdl) and cutaneous leishmaniasis (cl); dermal lesions are also commonly reported in visc ...201425412435
leishmania donovani populations in eastern sudan: temporal structuring and a link between human and canine transmission.visceral leishmaniasis (vl), caused by the members of the leishmania donovani complex, has been responsible for devastating vl epidemics in the sudan. multilocus microsatellite and sequence typing studies can provide valuable insights into the molecular epidemiology of leishmaniasis, when applied at local scales. here we present population genetic data for a large panel of strains and clones collected in endemic sudan between 1993 and 2001.201425410888
bioactive derivatives of isopropylstilbene from mutasynthesis and chemical synthesis.isopropylstilbene is a natural product from photorhabdus luminescens tt01, with multiple biological activities. a mutant deficient in the production of both anthraquinones and cinnamic acid was constructed, thus giving a clean background according to uv detection. this anthraquinone and stilbene deficient (asd) mutant was used in mutasynthesis experiments to obtain new stilbene derivatives, which were detected by gc-ms. the structures of the new derivatives were confirmed by detailed ms analysis ...201425346446
a cluster of four cases of cutaneous leishmaniasis by leishmania donovani in cyprus: a case series.leishmaniasis is endemic in more than 95 countries and is the only tropical/subtropical vector-borne disease that has been endemic in southern europe for decades. to the best of our knowledge, this is the first case of cutaneous leishmaniasis by leishmania donovani in a child and the first cluster with adult cases reported in europe.201425343876
igg1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test.visceral leishmaniasis (vl), caused by protozoa of the leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic vl is usually fatal. distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care.201425340782
pharmacological activities of cilantro's aliphatic aldehydes against leishmania donovani.leishmaniasis is a chronic infectious disease caused by different leishmania species. global occurrences of this disease are primarily limited to tropical and subtropical regions. treatments are available; however, patients complain of side effects. different species of plants have been screened as a potential source of new drugs against leishmaniasis. in this study, we investigated the antileishmanial activity of cilantro (coriandrum sativum) essential oil and its main components: (e)-2-undecen ...201425340465
regulation of pkc mediated signaling by calcium during visceral leishmaniasis.calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various ca2+ pumps and channels. two such fundamental calcium pumps are plasma membrane calcium atpase (pmca) and sarco/endoplasmic reticulum calcium atpase (serca) which play a pivotal role in maintaining intracellular calcium homeostasis. this intracellular ca2+ homeostasis is often disturbed by the protozoan parasite ...201425329062
the treatment of visceral leishmaniasis: safety and efficacy.visceral leishmaniasis is the disease of poor; however availability of only expensive treatment of this disease impinges the socioeconomic condition of those affected. if untreated, almost all cases of visceral leishmaniasis are fatal. the demonstration of the leishmania donovani bodies from the tissue aspirates or serological tests confirms the diagnosis of the disease. pentavalent antimony, amphotericin b, paromomycin, diamine pentamidine, miltefosine, sitamaquine and some new combinations are ...201425327244
role of cd8(+) t cells in protection against leishmania donovani infection in healed visceral leishmaniasis individuals.majority of individuals with history of visceral leishmaniasis (vl) exhibit strong immunity to re-infection, however, the mechanism of resistance is poorly understood. it is unclear whether cd8(+) t cells contribute to protection against leishmania donovani infection through cytotoxic activity. the present study aims to evaluate immunological mechanism associated with resistance to the disease in healed vl (hvl) individuals and further, the contribution of cd8(+) t cells in the protective immuni ...201425471494
genes that encodes nagt, mif1 and mif2 are not virulence factors for kala-azar caused by leishmania infantum.kala-azar is a disease resulting from infection by leishmania donovani and leishmania infantum. most patients with the disease exhibit prolonged fever, wasting, anemia and hepatosplenomegaly without complications. however, some patients develop severe disease with hemorrhagic manifestations, bacterial infections, jaundice, and edema dyspnea, among other symptoms, followed by death. among the parasite molecules that might influence the disease severity are the macrophage migration inhibitory fact ...201425467261
screening and characterization of rapd markers in viscerotropic leishmania parasites.visceral leishmaniasis (vl) is mainly due to the leishmania donovani complex. vl is endemic in many countries worldwide including east africa and the mediterranean region where the epidemiology is complex. taxonomy of these pathogens is under controversy but there is a correlation between their genetic diversity and geographical origin. with steady increase in genome knowledge, rapd is still a useful approach to identify and characterize novel dna markers. our aim was to identify and characteriz ...201425313833
leishmania donovani infection causes distinct epigenetic dna methylation changes in host macrophages.infection of macrophages by the intracellular protozoan leishmania leads to down-regulation of a number of macrophage innate host defense mechanisms, thereby allowing parasite survival and replication. the underlying molecular mechanisms involved remain largely unknown. in this study, we assessed epigenetic changes in macrophage dna methylation in response to infection with l. donovani as a possible mechanism for leishmania driven deactivation of host defense. we quantified and detected genome-w ...201425299267
new series of monoamidoxime derivatives displaying versatile antiparasitic activity.following the promising antileishmanial results previously obtained in monoamidoxime series, a new series of derivatives was synthesized using manganese(iii) acetate, wittig reactions and suzuki-miyaura cross coupling reactions. pharmacomodulation in r(1), r(2) or r(3) substituents on the amidoxime structure is shown to influence antiprotozoan activity in vitro: a monosubstituted phenyl group in r1 (32-35) led to an activity against leishmania donovani promastigotes (32, ic50 = 9.16 μm), whereas ...201425282267
comparative proteomics and glycoproteomics of plasma proteins in indian visceral leishmaniasis.visceral leishmaniasis (vl) is a deadly parasitic diseases caused by leishmania donovani; it is a major health problem in many countries. a lack of proper understanding of the disease biology, poor diagnostic methods and increasing drug resistance are the main reasons for the growing burden of vl infection. comparative plasma proteomics are a relatively useful technique that can be used to investigate disease-associated alterations that can help in understanding host responses against pathogens, ...201425276097
th1 stimulatory proteins of leishmania donovani: comparative cellular and protective responses of rtriose phosphate isomerase, rprotein disulfide isomerase and relongation factor-2 in combination with rhsp70 against visceral leishmaniasis.in visceral leishmaniasis, the recovery from the disease is always associated with the generation of th1-type of cellular responses. based on this, we have previously identified several th1-stimulatory proteins of leishmania donovani -triose phosphate isomerase (tpi), protein disulfide isomerase (pdi) and elongation factor-2 (el-2) etc. including heat shock protein 70 (hsp70) which induced th1-type of cellular responses in both cured leishmania patients/hamsters. since, hsps, being the logical t ...201425268700
a bioinformatics approach to reanalyze the genome annotation of kinetoplastid protozoan parasite leishmania donovani.leishmania donovani is a kinetoplastid protozoan parasite which causes the fatal disease visceral leishmaniasis in humans. genome sequencing of l. donovani revealed information about the arrangement of genes and genome architecture. after curation of the genome sequence, many genes in l. donovani were assigned as truncated or "partial" genes by the genome sequencing group. in the present study, we have carried out an extensive analysis and attempted to improve the gene models of these partial ge ...201425265881
new flavonol methyl ether from the leaves of vitex peduncularis exhibits potential inhibitory activity against leishmania donovani through activation of inos expression.one new flavonol methyl ether (1), along with four known compounds from the leaves of methanol extract of vitex peduncularis wall and three known compounds from the leaves of methanol extract of vitex pinnata linn (verbenaceae) were isolated. the chemical structure of the new compound was established by detailed spectroscopic studies. the in vitro antileishmanial activities of 1 against both leishmania donovani promastigote and amastigote forms were evaluated. to characterize the effector mechan ...201425264585
quinone-amino acid conjugates targeting leishmania amino acid transporters.the aim of the present study was to investigate the feasibility of targeting leishmania transporters via appropriately designed chemical probes. leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (ldaap3 and ldaap7) to import these nutrients. probes 1-15 were originated by conjugating cytotoxic quinone fragments (ii and iii) with amino acids (i.e. arginine and lysine) by means of an amide linkage. the toxicit ...201425254495
the antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors.histone deacetylase inhibitors (hdaci) pleiotropy is largely due to their nonselective inhibition of various cellular hdac isoforms. connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting hdaci pleiotropy. the contribution of classes i and ii hdacs to the antileishmanial activity of hdaci was investigated using the amastigote and promastigote forms of leishmania donovani. we observed that the antileishmanial activities of hdaci are ...201425240614
novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents.we have previously shown that 3-nitro-1h-1,2,4-triazole-based arylamides and arylsulfonamides demonstrate significant activity in vitro against trypanosoma cruzi, the causative parasite of chagas disease. more importantly, several such analogs displayed significant antichagasic activity in vivo, superior to that of benznidazole, the current clinical standard. we now report the synthesis and in vitro evaluation of a small series of novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamid ...201425240098
structure-based design of potent and selective leishmania n-myristoyltransferase inhibitors.inhibitors of leishmania n-myristoyltransferase (nmt), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. crystal structures bound to leishmania major nmt were obtained, and the active diastereoisomer of one of the inhibitors was identified. on the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent leishmani ...201425238611
an imported case of cutaneous leishmaniasis caused by leishmania (leishmania) donovani in japan.leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. there have been few reports of leishmaniasis in japan and all were of foreign origin; therefore diagnosis is difficult for japanese physicians. there are 21 different pathogenic leishmania species, and identification is obtained by polymerase chain reaction (pcr). here we report an imported case of leishmaniasis by leishmania (leishmania) donovani infection from sri lanka. l. (l.) d ...201425228325
tlr mediated gsk3β activation suppresses creb mediated il-10 production to induce a protective immune response against murine visceral leishmaniasis.during leishmania donovani (ld) infection interleukin (il)-10 favors parasite replication and plays a central role as a target for immune-based therapy. glycogen synthase kinase 3 (gsk3)β differentially regulates tlr-mediated cytokine production. creb, an important transcription factor that induces il-10 production is negatively regulated by gsk3β. however, down regulation of il-10 via creb suppression has not been well explored in controlling ld infection. here we demonstrate that, the tlr4 ago ...201425223889
leishmania donovani activates srebp2 to modulate macrophage membrane cholesterol and mitochondrial oxidants for establishment of infection.establishment of infection by an intracellular pathogen depends on successful internalization with a concomitant neutralization of host defense machinery. leishmania donovani, an intramacrophage pathogen, targets host srebp2, a critical transcription factor, to regulate macrophage plasma membrane cholesterol and mitochondrial reactive oxygen species generation, favoring parasite invasion and persistence. leishmania infection triggered membrane-raft reorientation-dependent lyn-pi3k/akt pathway ac ...201425218172
imipramine exploits histone deacetylase 11 to increase the il-12/il-10 ratio in macrophages infected with antimony-resistant leishmania donovani and clears organ parasites in experimental infection.the efflux of antimony through multidrug resistance protein (mdr)-1 is the key factor in the failure of metalloid treatment in kala-azar patients infected with antimony-resistant leishmania donovani (sb(r)ld). previously we showed that mdr-1 upregulation in sb(r)ld infection is il-10-dependent. imipramine, a drug in use for the treatment of depression and nocturnal enuresis in children, inhibits il-10 production from sb(r)ld-infected macrophages (sb(r)ld-mϕs) and favors accumulation of surrogate ...201425217162
insilico analysis of hypothetical proteins unveils putative metabolic pathways and essential genes in leishmania donovani.leishmaniasis is a parasitic disease caused by the protozoan leishmania, which is active in two broad forms namely, visceral leishmaniasis (vl or kala azar) and cutaneous leishmaniasis (cl). the disease is most prevalent in the tropical regions and poses a threat to over 70 countries across the globe. about 200 million people are estimated to be at risk of developing vl in the indian subcontinent, and this refers to around 67% of the global vl disease burden. the indian state of bihar alone acco ...201425206363
sitamaquine-resistance in leishmania donovani affects drug accumulation and lipid metabolism.this study focuses on the mechanism of sitamaquine-resistance in leishmania donovani. sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (wt) and of sitamaquine-resistant (sita-r160) l. donovani promastigotes, respectively. the sitamaquine accumulation was a concentration-dependent process in wt whereas a saturation occurred in sita-r160 suggesting a reduced uptake or an increase of the sitamaquine efflux. membrane negative phospholipids being the main target ...201425201056
immunotherapy and targeted therapies in treatment of visceral leishmaniasis: current status and future prospects.visceral leishmaniasis (vl) is a vector-borne chronic infectious disease caused by the protozoan parasite leishmania donovani or leishmania infantum. vl is a serious public health problem, causing high morbidity and mortality in the developing world with an estimated 0.2-0.4 million new cases each year. in the absence of a vaccine, chemotherapy remains the favored option for disease control, but is limited by a narrow therapeutic index, significant toxicities, and frequently acquired resistance. ...201425183962
a small heat shock protein is essential for thermotolerance and intracellular survival of leishmania donovani.leishmania parasites must survive and proliferate in two vastly different environments - the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. the change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. although the functions of the main heat shock protein fami ...201425179594
comparison of pcr with stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis.visceral leishmaniasis (vl), also known as kala-azar, is a disseminated protozoan infection caused by leishmania donovani complex. traditionally the definite diagnosis is made by amastigote detection in the tissue. the aim this study was to evaluate the pcr technique in stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis. slides were selected totaling 62 suspect cases (33 bone marrow samples and 29 lymph node samples) and 17 positive cases (8 bone mar ...201425159534
nerve growth factor promotes killing of leishmania donovani by macrophages through the induction of hydrogen peroxide.visceral leishmaniasis is protozoonosis that occurs worldwide and still requires effective therapies with less toxicity. in this study, we examined the antileishmanial effect of nerve growth factor (ngf) using a murine infection model. ngf blocked the infection of macrophages by leishmania donovani, which was completely cancelled by a hydrogen peroxide inhibitor. in vivo, not only did ngf show antileishmanial effects, but combination therapy of ngf and sodium stibogluconate synergistically exhib ...201424937592
antigen-pulsed cpg-odn-activated dendritic cells induce host-protective immune response by regulating the t regulatory cell functioning in leishmania donovani-infected mice: critical role of cxcl10.visceral leishmaniasis (vl), caused by leishmania donovani, is a systemic infection of reticulo-endothelial system. there is currently no protective vaccine against vl and chemotherapy is increasingly limited due to appearance of drug resistance to first line drugs such as antimonials and amphotericin b. in the present study, by using a murine model of leishmaniasis we evaluated the function played by soluble leishmanial antigen (sla)-pulsed cpg-odn-stimulated dendritic cells (sla-cpg-dcs) in re ...201424926293
atypical cutaneous leishmaniasis in the immunosuppressed.a 45-year-old woman, known case of seronegative arthritis and on immunosuppressive therapy, presented with a 2-week history of a macular lesion on the left calf that became papular and eventually ulcerated. the rest of the history was otherwise unremarkable and systemic examination did not reveal any abnormalities. the lesion was repeatedly biopsied but failed to reveal leishmania donovani bodies. concurrent leishmania igg was positive but igm was negative. leishmania igg confirmatory testing by ...201424916985
leishmania donovani eukaryotic initiation factor 5a: molecular characterization, localization and homology modelling studies.eukaryotic translation initiation factor 5a (eif5a) is a small acidic protein highly conserved from archaea to mammals. eif5a is the only protein which undergoes a unique lysine residue modification to hypusine. hypusinylation is important for the function of eif5a which is reported to be essential for cell viability. eif5a promotes formation of the first peptide bond at the onset of protein synthesis. however, its function in leishmania donovani is unclear. the present study focuses on the char ...201424909104
ubiquitination-mediated interaction among domains is responsible for inhibition of rna endonuclease activity of mrna cycling sequence binding protein from l. donovani (ldcsbp).in nearly complete absence of transcriptional regulation, messenger rna (mrna) turnover mediated through specific cis-elements plays a predominant role in the control of differential gene expression for the disease causing trypanosomatid parasites. in these organisms, the periodic accumulation of s-phase messages during cell cycle is determined by the presence of one or more copies of a conserved cauagaag octanucleotide motif in the untranslated regions of mrnas. in our previous studies, a multi ...201424908431
chemical- and thermal-induced unfolding of leishmania donovani ribose-5-phosphate isomerase b: a single-tryptophan protein.ribose-5-phosphate isomerase b (rpib), a crucial enzyme of pentose phosphate pathway, was proposed to be a potential drug target for visceral leishmaniasis. in this study, we have analyzed the biophysical properties of leishmania donovani rpib (ldrpib) enzyme to gain insight into its unfolding pathway under various chemical and thermal denaturation conditions by using fluorescence and cd spectroscopy. ldrpib inactivation precedes the structural transition at lower concentrations of both urea and ...201424907042
biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. a major shortcoming in the vaccine development against blood-borne parasitic agents such as leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extr ...201424904589
stage-dependent expression and up-regulation of trypanothione synthetase in amphotericin b resistant leishmania donovani.kinetoplastids differ from other organisms in their ability to conjugate glutathione and spermidine to form trypanothione which is involved in maintaining redox homeostasis and removal of toxic metabolites. it is also involved in drug resistance, antioxidant mechanism, and defense against cellular oxidants. trypanothione synthetase (trys) of thiol metabolic pathway is the sole enzyme responsible for the biosynthesis of trypanothione in leishmania donovani. in this study, trys gene of l. donovani ...201424901644
hplc-based activity profiling for antiplasmodial compounds in the traditional indonesian medicinal plant carica papaya l.leaf decoctions of carica papaya have been traditionally used in some parts of indonesia to treat and prevent malaria. leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo.201424892830
studies on the antileishmanial mechanism of action of the arylimidamide db766: azole interactions and role of cyp5122a1.arylimidamides (aias) are inspired by diamidine antimicrobials but show superior activity against intracellular parasites. the aia db766 {2,5-bis[2-(2-i-propoxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride} displays outstanding potency against intracellular leishmania parasites and is effective in murine and hamster models of visceral leishmaniasis when given orally, but its mechanism of action is unknown. in this study, through the use of continuous db766 pressure, we raised leishmania do ...201424890590
equilibrium unfolding of cyclophilin from leishmania donovani: characterization of intermediate states.cyclophilin from leishmania donovani (ldcyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase involved in a host of important cellular activities, such as signaling, heat shock response, chaperone activity, mitochondrial pore maintenance and regulation of hiv-1 infectivity. it also acts as the prime cellular target for the auto-immune drug cyclosporine a (csa). ldcyp is composed of a beta barrel encompassing the unique hydrophobic core of the molecule and is flanked by two helices (h1, h2) on ...201424887548
cytokine profiles amongst sudanese patients with visceral leishmaniasis and malaria co-infections.the immune system plays a critical role in the development of co-infections, promoting or preventing establishment of multiple infections and shaping the outcome of pathogen-host interactions. its ability to mediate the interplay between visceral leishmaniasis (vl) and malaria has been suggested, but poorly documented. the present study investigated whether concomitant infection with leishmania donovani complex and plasmodium falciparum in naturally co-infected patients altered the immunological ...201424886212
an inhibitor-driven study for enhancing the selectivity of indirubin derivatives towards leishmanial glycogen synthase kinase-3 over leishmanial cdc2-related protein kinase 3.in search of new antiparasitic agents for overcoming the limitations of current leishmaniasis chemotherapy, we have previously shown that 6-bromoindirubin-3'-oxime (6bio) and several other 6-substituted analogues of indirubin, a naturally occurring bis-indole present in mollusks and plants, displayed reverse selectivity from the respective mammalian kinases, targeting more potently the leishmanial cyclin-dependent kinase-1 (cdk1) homologue [cdc2-related protein kinase 3 (lcrk3)] over leishmanial ...201424886176
a dual luciferase system for analysis of post-transcriptional regulation of gene expression in leishmania.gene expression in kinetoplastid parasites is regulated via post-transcriptional mechanisms that modulate mrna turnover, translation rate, and/or post-translational protein stability. to facilitate the analysis of post-transcriptional regulation, a dual luciferase system was developed in which firefly and renilla luciferase reporters genetically fused to compatible drug resistance genes are integrated in place of one allele of the gene of interest and of an internal control gene, respectively, i ...201424878002
antileishmanial activity of a series of n²,n⁴-disubstituted quinazoline-2,4-diamines.a series of n(2),n(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against leishmania donovani and l. amazonensis intracellular amastigotes. a structure-activity and structure-property relationship study was conducted in part using the topliss operational scheme to identify new lead compounds. this study led to the identification of quinazolines with ec50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. q ...201424874647
synthesis and biological evaluation of chalcones as potential antileishmanial agents.antileishmanial activities of thirty-five synthetic chalcones have been examined. among them, ten compounds (4, 6, 16, 22, 23, 24, 25, 29, 35 and 37) exhibited potent in vitro activity (ic50 range from 1.70 to 8 μm) against extracellular promastigotes and intracellular amastigotes form of leishmania donovani. two promising compounds 22 and 37 were tested in vivo in l. donovani/hamster model. chalcone 37 showed 83.32% parasite inhibition at a dose of 50 mg/kg for 10 days whereas, 75.89% parasite ...201424858541
class ii mhc/peptide interaction in leishmania donovani infection: implications in vaccine design.we show that leishmania donovani-infected macrophages (mφs) are capable of stimulating mhc class ii (mhc-ii)-restricted t cells at 6 h of infection. at 48 h, infected mφs (i-mφs) failed to stimulate mhc-ii-restricted t cells but not mhc class i-restricted ones, in contrast to normal mφs. such i-mφs could stimulate t cells at a higher ag concentration, indicating that general ag processing and trafficking of peptide-mhc-ii complexes are not defective. analysis of the kinetic parameters, like "kon ...201424850723
coating doxorubicin-loaded nanocapsules with alginate enhances therapeutic efficacy against leishmania in hamsters by inducing th1-type immune responses.the aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(sa) coated nanocapsule (ncs) loaded with doxorubicin (sa-ncs-dox) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (ne-dox).201424837879
generation of growth arrested leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.visceral leishmaniasis (vl) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. vl is caused by the protozoan parasite leishmania donovani or leishmania infantum. although several second generation vaccines have been licensed to protect dogs against vl, there are no effective vaccines against human vl [1]. since people cured of leishmaniasis develop lifelong protection, development of live attenuated leishmania parasites as vaccines, which can have ...201424837513
efficacy of withania somnifera chemotypes nmitli - 101r, 118r and withaferin a against experimental visceral leishmaniasis.the immunoprophylactic and therapeutic potentials of root extracts of withania somnifera chemotypes (nmitli-118, nmitli-101) and pure withanolide-withaferin a was investigated against leishmania donovani infection in hamsters. the naive animals, fed orally with immunostimulatory doses of chemotypes 101r, 118r (10 and 3 mg/kg) and withaferin a (9 and 3 mg/kg) for five consecutive days and challenged with leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of p ...201424830833
deficiency of lymph node-resident dendritic cells (dcs) and dysregulation of dc chemoattractants in a malnourished mouse model of leishmania donovani infection.malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan leishmania donovani. we previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination of l. donovani. in t ...201424818662
leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.leishmaniasis is a neglected tropical disease caused by leishmania species. it is a major health concern affecting 88 countries and threatening 350 million people globally. unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. the emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. the genome sequence of leishmania, provides access to novel genes that hold pot ...201424814525
the leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status.during its life cycle, the protozoan pathogen leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, to which the parasite must adapt for extra- and intracellular survival. combining null mutant analysis with phosphorylation site-specific mutagenesis and functional complementation we genetically tested the requirement of the l. donovani chaperone cyclophilin 40 (ldcyp40) for infection. targeted replacement of ldcyp40 had no effect on parasite viabili ...201424811325
4-amino bis-pyridinium derivatives as novel antileishmanial agents.the antileishmanial activity of a series of bis-pyridinium derivatives that are analogues of pentamidine have been investigated, and all compounds assayed were found to display activity against promastigotes and intracellular amastigotes of leishmania donovani and leishmania major, with 50% effective concentrations (ec50s) lower than 1 μm in most cases. the majority of compounds showed similar behavior in both leishmania species, being slightly more active against l. major amastigotes. however, ...201424798287
trend analysis of visceral leishmaniasis at addis zemen health center, northwest ethiopia.visceral leishmaniasis (vl) is a systemic disease caused by the leishmania donovani complex. it is one of the fatal diseases if left untreated. in ethiopia, there are many vl endemic foci. the aim of this study was to determine the trends of vl in the study area.201424783211
shagenes a and b, new tricyclic sesquiterpenes produced by an undescribed antarctic octocoral.the isolation and characterization of two new tricyclic sesquiterpenoids, shagenes a (1) and b (2) are presented. these compounds were isolated from an undescribed soft coral collected from the scotia arc in the southern ocean. one- and two-dimensional nmr spectroscopy and mass spectrometry provided the data necessary to characterize the compounds and their relative stereochemical configurations. exploration of the bioactivity of shagenes a and b found 1 active against the visceral leishmaniasis ...201424779517
a comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study.visceral leishmaniasis (vl) represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. ninety per cent of vl cases occur in five countries namely bangladesh, india, nepal, sudan and brazil. no licensed vaccine is available till date against any form of leishmaniasis. high toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in vl endemic regions of the world. to ...201424747611
regulation dynamics of leishmania differentiation: deconvoluting signals and identifying phosphorylation trends.leishmania are obligatory intracellular parasitic protozoa that cause a wide range of diseases in humans, cycling between extracellular promastigotes in the mid-gut of sand flies and intracellular amastigotes in the phagolysosomes of mammalian macrophages. although many of the molecular mechanisms of development inside macrophages remain a mystery, the development of a host-free system that simulates phagolysosome conditions (37 °c and ph 5.5) has provided new insights into these processes. the ...201424741111
evaluation of leishmania donovani disulfide isomerase as a potential target of cellular immunity against visceral leishmaniasis.in leishmania species, protein disulfide isomerase (pdi) - a redox chaperone is primarily associated with virulence and survival. the precise mechanism, especially in relation to redox changes and its effects on immunological responses in visceral leishmaniasis (vl) is not completely understood as yet. therefore, we purified a recombinant pdi from leishmania donovani (r-ldpdi) which was of ∼15 kda molecular size and examined its effects on immunological responses in peripheral blood (pbmc) of hu ...201424732062
combination of liposomal cpg oligodeoxynucleotide 2006 and miltefosine induces strong cell-mediated immunity during experimental visceral leishmaniasis.immuno-modulators in combination with antileishmanial drug miltefosine is a better therapeutic approach for treatment of visceral leishmaniasis (vl) as it not only reduces the dose of miltefosine but also shortens the treatment regimen. however, immunological mechanisms behind the perceived benefits of this combination therapy have not been investigated in detail. in the present study, we hypothesized that potential use of drugs that target the host in addition to the parasite might represent an ...201424732039
ketanserin, an antidepressant, exerts its antileishmanial action via inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) enzyme of leishmania donovani.leishmaniasis is one of the major health problems existing globally. the current chemotherapy for leishmaniasis presents several drawbacks like toxicity and increased resistance to existing drugs, and hence, there is a necessity to look out for the novel drug targets and new chemical entities. current trend in drug discovery arena is the "repurposing" of old drugs for the treatment of diseases. in the present study, an antidepressant, ketanserin, was found lethal to both leishmania donovani prom ...201424728519
design, synthesis, adme characterization and antileishmanial evaluation of novel substituted quinoline analogs.in vitro adme characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. compound 1 was highly permeable in intestinal pampa model (31 × 10(-6)cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. compound 1 was found to have no cyp450 liability with cyp2c9, 2 ...201424726804
[from unexplained fever to visceral leishmaniasis--a case report].visceral leishmaniasis or kala-azar is a systemic infectious vector-borne disease caused by protozoa leishmania donovani and leishmania infantum that are transmitted to mammalian hosts by sand flies. it occurrs sporadically in endemic areas, including mediterranean basin. southern coastal territories of croatia have been recognized as the foci of the disease. dogs are the main reservoir of human infection. clinical features include prolonged fever, malaise, hepatosplenomegaly, pancytopenia and i ...201424720151
flavone-resistant leishmania donovani overexpresses ldmrp2 transporter in the parasite and activates host mrp2 on macrophages to circumvent the flavone-mediated cell death.in parasites, atp-binding cassette (abc) transporters represent an important family of proteins related to drug resistance and other biological activities. resistance of leishmanial parasites to therapeutic drugs continues to escalate in developing countries, and in many instances, it is due to overexpressed abc efflux pumps. progressively adapted baicalein (bln)-resistant parasites (pb(25)r) show overexpression of a novel abc transporter, which was classified as abcc2 or leishmania donovani mul ...201424706751
antiprotozoal activities of millettia richardiana (fabaceae) from madagascar.with at least 60% of the millettia species (fabaceae) being in medicinal use, we found it relevant to assess the potential antiprotozoal and antifungal activities of millettia richardiana. water and methanol crude extracts of the stem barks from m. richardiana and the six fractions resulting from the fractionation of the methanol extract were tested. the dichloromethane extracted fraction showed the best in vitro antiprotozoal activities (ic50=5.8 μg/ml against plasmodium falciparum, 11.8 μg/ml ...201424705564
no stress--hsp90 and signal transduction in leishmania.summary hsp90 (a.k.a. hsp83) plays a significant role in the life cycle control of the protozoan parasite leishmania donovani. rather than protecting leishmania spp. against adverse and stressful environs, hsp90 is required for the maintenance of the motile, highly proliferative insect stage, the promastigote. however, hsp90 is also essential for survival and proliferation of the intracellular mammalian stage, the amastigote. moreover, recent evidence shows hsp90 and other components of large mu ...201424703183
leishmanial lipid suppresses the bacterial endotoxin-induced inflammatory response with attenuation of tissue injury in sepsis.the use of live, attenuated, or genetically modified microbes or their cellular component(s) or metabolites has begun to emerge as a potential new approach in medicinal research to deliver biologically active entities. thus, advancing our knowledge of such microbe-mediated therapy may suggest new avenues for therapeutic intervention in many diseases. we had earlier reported that the total lipid of attenuated leishmania donovani suppressed the inflammatory responses in rheumatoid arthritis patien ...201424696356
activity of olive leaf extracts against the promastigote stage of leishmania species and their correlation with the antioxidant activity.leishmaniasis is one of the neglected tropical diseases in terms of drug discovery and development. furthermore, the chemotherapy used to treat this disease has been proved to be highly toxic and to present resistance issues. as consequent, the need for novel leishmanicidal molecules has notably increased in the recent years. in the present work an attempt was made to evaluate the antioxidant and leishmanicidal activities besides presence of compounds in leaf extracts of 5 different tunisian oli ...201424662269
anti-l. donovani activity in macrophage/amastigote model of palmarumycin cp18 and its large scale production.palmarumycin cp18, isolated from an extract of the fermentation broth and mycelium of the panamanian endophytic fungus edenia sp., was previously reported with strong and specific activity against leishmania donovani. here we report that when the same strain was cultured on different solid media--harrold agar, leonian agar, potato dextrose agar (pda), corn meal agar, honey peptone agar, and eight vegetables (v8) agar--in order to determine the optimal conditions for isolation of palmarumycin cp1 ...201424660473
synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents.antileishmanial activities of a library of synthetic chalcone analogues have been examined. among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of leishmania donovani. three promising compounds, 16, 17, and 22, were tested in a l. donovani/hamster model. oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, re ...201424635539
tissue requirements for establishing long-term cd4+ t cell-mediated immunity following leishmania donovani infection.organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by leishmania donovani. experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. cd4+ t cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. in this study, we show ...201424634490
a quantitative proteomic screen to identify potential drug resistance mechanism in α-difluoromethylornithine (dfmo) resistant leishmania donovani.visceral leishmaniasis (vl) caused by leishmania donovani is a systemic protozoan disease that is fatal if left untreated. the promastigote form of l. donovani is sensitive to growth inhibition by dl-α-difluoromethylornithine (dfmo), an inhibitor of ornithine decarboxylase (odc), the first enzyme of the polyamine biosynthetic pathway. exposure of a wild type (di700) cell population to gradually increasing concentrations of dfmo resulted in the selection of a strain of leishmania (dfmo-16), which ...201424631822
absence of leishmania infantum in cave bats in an endemic area in spain.though dogs have been historically considered the main reservoir of leishmania infantum, the role of wildlife in its epidemiology is attracting increasing attention. rodents, wild carnivores and, recently, hares (lepus spp.) have been proposed as sylvatic reservoirs for this parasite. bats have never been tested for l. infantum infection in europe. nevertheless, bats have a widespread distribution, they live in abundant colonies, and some species inhabit caves, where constant temperatures and hu ...201424623348
studies on the protective efficacy of second-generation vaccine along with standard antileishmanial drug in leishmania donovani infected balb/c mice.it is well established that visceral leishmaniasis (vl; also known as kala azar) causes immunosuppression, and a successful drug treatment is associated with the development of cell-mediated immunity. therefore combining a drug with an immune enhancer can provide a better approach for the treatment of the disease. keeping this in mind, the in vivo antileishmanial efficacy of immunochemotherapy was evaluated with the use of a 78 kda antigen with or without monophosphoryl lipid a (mpl-a) along wit ...201424618257
toll like receptor 2 and cc chemokine receptor 5 cluster in the lipid raft enhances the susceptibility of leishmania donovani infection in macrophages.in experimental visceral leishmaniasis the causative obligate protozoan parasite, l. donovani invades and multiplies inside of macrophages, one of the sentries of the mammalian immune system. the initial host-parasite interaction between the leishmania promastigote and the macrophage takes place at the plasma membrane interface. to trace any possible interaction between toll-like receptor 2 (tlr2) and cc chemokine receptor 5 (ccr5) during early leishmania-macrophage interactions, it was observed ...201424617012
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 ...201424615359
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 ...201424615127
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 ...201424614385
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.201424607302
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).201424606222
structure prediction of gbp21 protein of l. donovani and its molecular interaction.visceral leishmaniasis (kala-azar) is a fatal disease caused by the obligate intracellular parasite leishmania donovani and the available drugs for the treatment are few, and are frequently associated with side effects and toxicity. rna editing is one of the essential metabolic processes in the kinetoplastids, where the pre-mrnas are edited post-transcriptionally by the guide rnas with the addition or deletion of uridine residues. the aim is to block the gbp21 protein involved in rna editing pro ...201423746168
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 ...201423964700
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.201423956375
antileishmanial activity evaluation of bis-lawsone analogs and dna topoisomerase-i inhibition studies.for the development of potent novel antileishmanial agents, 3,3'-(arylmethylene)bis(2-hydroxynaphthalene-1,4 dione) derivatives were synthesized from lawsone and evaluated for cytotoxicity on leishmania donovani promastigotes as well as on leishmanial dna topoisomerase-i. enzyme inhibition studies were conducted with simultaneous and preincubation conditions. total inhibition is compared to camptothecin (cpt), which was taken as positive control on both the systems of enzyme inhibition. the rang ...201423534930
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 ...201424103199
synthesis and antileishmanial evaluation of some 2,3-disubstituted-4(3h)-quinazolinone derivatives.leishmaniasis is a neglected tropical parasitic diseases affecting millions of people around the globe. quinazolines are a group of compounds with diverse pharmacological activities. owing to their promising antileishmanial activities, some 3-aryl-2-(substitutedstyryl)-4(3h)-quinazolinones were synthesized in good yields (65.2% to 86.4%).201426548988
lys-413 of s-phase mrna cycling sequence binding protein from leishmania donovani (ldcsbp) is modified through monoubiquitination that is responsible for inhibition of its riboendonuclease activity.in addition to well-known process of proteasome-mediated degradation of polyubiquitinated proteins, monoubiquitination of proteins is also an important post-translational modification that regulates various non-degradative cellular processes like protein trafficking, cellular signalling, dna replication and dna repair. we have previously characterized a multi-domain cycling sequence binding protein ldcsbp from leishmania donovani, which binds specifically to a conserved cauagaag octamer containi ...201425823230
leishmania donovani secretory serine protease alters macrophage inflammatory response via cox-2 mediated pge-2 production.leishmania parasites determine the outcome of the infection by inducing inflammatory response that suppresses macrophage's activation. defense against leishmania is dependent on th1 inflammatory response by turning off macrophages' microbicidal property by upregulation of cox-2, as well as immunosuppressive pge-2 production. to understand the role of l. donovani secretory serine protease (psp) in these phenomena, psp was inhibited by its antibody and serine protease inhibitor, aprotinin. western ...201425823228
tlr4-mediated activation of myd88 signaling induces protective immune response and il-10 down-regulation in leishmania donovani infection.in visceral leishmaniasis, a fragmentary il-12 driven type 1 immune response along with the expansion of il-10 producing t-cells correlates with parasite burden and pathogenesis. successful immunotherapy involves both suppression of il-10 production and enhancement of il-12 and nitric oxide (no) production. as custodians of the innate immunity, the toll-like receptors (tlrs) constitute the first line of defense against invading pathogens. the tlr-signaling cascade initiated following innate reco ...201425823227
immunosuppression during leishmania donovani infection: a potential target for the development of therapy.dysfunction of t-helper 1 mediated immune responses is a hallmark of the progression of visceral leishmaniosis (vl). several factors such as altered antigen presentation, and abnormalities in mhc/hla, antigen processing, and t cell receptor recognition regulate the onset of immunosuppression. recent investigations on vl patients suggest that susceptibility to visceral leishmaniosis is genetically determined and varies between populations in different geographical locations. emerging evidence als ...201425706420
parasites and fungi as a threat for prenatal and postnatal human development.recent literature data reveals the most common etiological agents of congenital parasitoses to be toxoplasma gondii, trypanosoma cruzi, leishmania donovani and plasmodium falciparum. an analysis of clinical data indicates that parasitic congenital infections are often asymptomatic, whereas symptomatic newborns usually display nonspecific symptoms, which greatly hinders correct diagnosis. the long-term consequences of prenatal infections are serious clinical problems. this article presents the po ...201425706418
[molecular cloning and localization of leishmania donovani expression site associated genes-like protein].to clone the novel gene that specifically expressed in the amastigotes of leishmania donovani, and observe subcellular localization of the gene encoding protein.201425726590
novel arsenic nanoparticles are more effective and less toxic than as (iii) to inhibit extracellular and intracellular proliferation of leishmania donovani.visceral leishmaniasis, a vector-borne tropical disease that is threatening about 350 million people worldwide, is caused by the protozoan parasite leishmania donovani. metalloids like arsenic and antimony have been used to treat diseases like leishmaniasis caused by the kinetoplastid parasites. arsenic (iii) at a relatively higher concentration (30 μg/ml) has been shown to have antileishmanial activity, but this concentration is reported to be toxic in several experimental mammalian systems. na ...201425614827
leishmania donovani bodies in bone marrow.we report a case of a 5-year-old female, resident of afghanistan, who presented with fever and massive splenomegaly. bone marrow revealed leishmania donovani bodies (ld bodies) in macrophages characterized by a kinetoplast and characteristic double dot appearance. she was diagnosed as visceral leishmaniasis which is transmitted by sandflies (phlebotomus).201425614819
procerenone: a fatty acid triterpenoid from the fruit pericarp of omphalocarpum procerum (sapotaceae).phytochemical investigation of a dichloromethane-methanol (1:1) extract of the fruit pericarp of omphalocarpum procerum which exhibited antiplasmodial activity during preliminary screening led to the isolation of the new fatty ester triterpenoid 3β-hexadecanoyloxy-28-hydroxyolean-12-en-11-one (1), together with five known compounds 2-6. the structure of the new compound as well as those of the known compounds was established by means of spectroscopic methods and by comparison with previously rep ...201425587333
isobenzofuranone derivatives exhibit antileishmanial effect by inhibiting type ii dna topoisomerase and inducing host response.leishmania, a protozoan parasite, causes a wide range of human diseases ranging from the localized self-healing cutaneous lesions to fatal visceral leishmaniasis. toxicity of traditional first line drugs and emergence of drug-resistant strains have worsened the situation. dna topoisomerase ii in kinetoplastid protozoan parasites are of immense interest as drug target because they take part in replication of unusual kinetoplast dna network. in this study, we have taken target-based therapeutic ap ...201425505614
leishmanicidal activities of artemisia annua leaf essential oil against visceral leishmaniasis.visceral leishmaniasis (vl), the second-most dreaded parasitic disease after malaria, is currently endemic in 88 countries. dramatic increases in the rates of infection, drug resistance, and non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents from natural sources. in this study, we showed the leishmanicidal effect of essential oil from artemisia annua leaves (aaleo) against leishmania donovani in vitro and in vivo. aaleo ...201425505453
quantitative pcr in epidemiology for early detection of visceral leishmaniasis cases in india.studies employing serological, dth or conventional pcr techniques suggest a vast proportion of leishmania infected individuals living in regions endemic for visceral leishmaniasis (vl) remain asymptomatic. this study was designed to assess whether quantitative pcr (qpcr) can be used for detection of asymptomatic or early leishmania donovani infection and as a predictor of progression to symptomatic disease.201425503103
Refresh
firstprev
...41424344454647484950...
nextlast
Displaying items 4601 - 4700 of 5301