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Sent on Tuesday, 2011 Jul 12Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| 1. | Eukaryot Cell. 2011 Jul 8. [Epub ahead of print]Poly(A)-specific Ribonuclease (PARN-1) function in stage-specific mRNA turnover in Trypanosoma brucei.Utter CJ, Garcia SA, Milone J, Bellofatto V.SourceDepartment of Microbiology and Molecular Genetics, University of Medicine and Dentistry-New Jersey Medical School, Newark, New Jersey 07103, USA. AbstractDeadenylation is often the rate-limiting event in regulating the turnover of cellular mRNAs in eukaryotes. Removal of the poly(A) tail initiates mRNA degradation by one of several decay pathways, including deadenylation-dependent decapping followed by 5' to 3' exonuclease decay or 3' to 5' exosome-mediated decay. In trypanosomatids, mRNA degradation is important in controlling the expression of differentially expressed genes. Genomic annotation studies have revealed several potential deadenylases. Poly(A)-specific ribonuclease (PARN) is a key deadenylase involved in regulating gene expression in mammals, Xenopus oocytes, and higher plants. Trypanosomatids possess three different PARN genes, PARN-1, -2 and -3, each of which is expressed at the mRNA level in two life cycle stages of the human parasite, Trypanosoma brucei. Here we show that T. brucei PARN-1 is an active deadenylase. To determine the role of PARN-1 on mRNA stability in vivo, we overexpressed this protein and analyzed perturbations in mRNA steady state levels as well as mRNA half-life. Interestingly, a subset of mRNAs was affected, including a family of mRNAs that encode for stage-specific coat proteins. These data suggest that PARN-1 functions in stage-specific protein production. |
| 2. | J Infect Dis. 2011 Aug;204(3):488-9. Epub 2011 Jul 8.A Potential Role of Indoleamine 2,3-Dioxygenase-Specific T cells in Leishmania Vaccination.Straten PT, Andersen MH.SourceCenter for Cancer Immune Therapy (CCIT), Department of Hematology, 54P4, Copenhagen University Hospital, Herlev, Denmark. |
| 3. | J Infect Dis. 2011 Aug;204(3):467-77.Genetic and Functional Evidence Implicating DLL1 as the Gene That Influences Susceptibility to Visceral Leishmaniasis at Chromosome 6q27.Fakiola M, Miller EN, Fadl M, Mohamed HS, Jamieson SE, Francis RW, Cordell HJ, Peacock CS, Raju M, Khalil EA, Elhassan A, Musa AM, Silveira F, Shaw JJ, Sundar S, Jeronimo SM, Ibrahim ME, Blackwell JM.SourceCambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, UK. AbstractBackground. Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum chagasi. Genome-wide linkage studies from Sudan and Brazil identified a putative susceptibility locus on chromosome 6q27. Methods. Twenty-two single-nucleotide polymorphisms (SNPs) at genes PHF10, C6orf70, DLL1, FAM120B, PSMB1, and TBP were genotyped in 193 VL cases from 85 Sudanese families, and 8 SNPs at genes PHF10, C6orf70, DLL1, PSMB1, and TBP were genotyped in 194 VL cases from 80 Brazilian families. Family-based association, haplotype, and linkage disequilibrium analyses were performed. Multispecies comparative sequence analysis was used to identify conserved noncoding sequences carrying putative regulatory elements. Quantitative reverse-transcription polymerase chain reaction measured expression of candidate genes in splenic aspirates from Indian patients with VL compared with that in the control spleen sample. Results. Positive associations were observed at PHF10, C6orf70, DLL1, PSMB1, and TBP in Sudan, but only at DLL1 in Brazil (combined P = 3 × 10(-4) at DLL1 across Sudan and Brazil). No functional coding region variants were observed in resequencing of 22 Sudanese VL cases. DLL1 expression was significantly (P = 2 × 10(-7)) reduced (mean fold change, 3.5 [SEM, 0.7]) in splenic aspirates from patients with VL, whereas other 6q27 genes showed higher levels (1.27 × 10(-6) < P < .01) than did the control spleen sample. A cluster of conserved noncoding sequences with putative regulatory variants was identified in the distal promoter of DLL1. Conclusions. DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated as the chromosome 6q27 VL susceptibility gene. |
| 4. | Acta Histochem. 2011 Jul 9. [Epub ahead of print]Immunocytochemical and immunohistochemical methods as auxiliary techniques for histopathological diagnosis of cutaneous leishmaniasis.Lunedo SN, Thomaz-Soccol V, de Castro EA, Telles JE.SourcePrograma de Pós-graduação em Processos Biotecnológicos, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. AbstractA significant increase in cutaneous leishmaniasis (CL) and its geographic expansion has motivated the development of techniques to help with diagnosis of the disease. Here we describe immunocytochemical (ICC) and immunohistochemical (IHC) techniques for the diagnosis of CL in the laboratory. Polyclonal antibodies and a modified avidin-biotin complex (Ultra Streptavidin(®)) for Leishmania (V.) braziliensis or Leishmania (L.) amazonensis were developed for the present study. In vitro culture and histological sections from experimentally infected tissues were submitted to ICC/IHC techniques. The polyclonal antibody specificity, stability and immunostaining were evaluated. The polyclonal antibodies purified by chromatography (Sephadex(®)) and obtained from L. (V.) braziliensis and L. (L.) amazonensis insoluble antigens presented 83.3% sensitivity, when the presence of antigens was evaluated, i.e., higher than histopathology or any equivalent method (in vitro culture). The polyclonal antibody presented 100% specificity when used against species frequently found in CL lesions. The ICC/IHC techniques developed in the current study were able to recognize amastigotes and antigens from in vivo and in vitro cultures and from biopsies, offering additional help in the diagnosis of CL. This methodology could be beneficially adopted in public health laboratories. Copyright © 2011 Elsevier GmbH. All rights reserved. |
| 5. | J Ethnopharmacol. 2011 Jun 28. [Epub ahead of print]Evaluation of an ethnopharmacologically selected Bhutanese medicinal plants for their major classes of marker compounds and biological activities.Wangchuk P, Keller PA, Pyne SG, Taweechotipatr M, Tonsomboon A, Rattanajak R, Kamchonwongpaisan S.SourceSchool of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia. AbstractETHNOPHARMACOLOGICAL RELEVANCE:As many as 229 medicinal plants have been currently used in the Bhutanese Traditional Medicine (BTM) as a chief ingredient of polyherbal formulations and these plants have been individually indicated for treating various types of infections including malaria, tumor, and microbial. We have focused our study only on seven species of these plants. AIM OF THE STUDY:We aim to evaluate the antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities of the seven medicinal plants of Bhutan selected using an ethno-directed bio-rational approach. This study creates a scientific basis for their use in the BTM and gives foundation for further phytochemical and biological evaluations which can result in the discovery of new drug lead compounds. MATERIALS AND METHODS:A three stage process was conducted which consisted of: (1) an assessment of a pharmacopoeia and a formulary book of the BTM for their mode of plant uses; (2) selecting 25 anti-infective medicinal plants based on the five established criteria, collecting them, and screening for their major classes of phytochemicals using appropriate test protocols; and (3) finally analyzing the crude extracts of the seven medicinal plants, using the standard test protocols, for their antiplasmodial, antimicrobial, anti-Trypanosoma brucei rhodesiense and cytotoxicity activities as directed by the ethnopharmacological uses of each plant. RESULTS:Out of 25 medicinal plants screened for their major classes of phytochemicals, the majority contained tannins, alkaloids and flavonoids. Out of the seven plant species investigated for their biological activities, all seven of them exhibited mild antimicrobial properties, five plants gave significant in vitro antiplasmodial activities, two plants gave moderate anti-Trypanosoma brucei rhodesiense activity, and one plant showed mild cytotoxicity. Meconopsis simplicifolia showed the highest antiplasmodial activity with IC50 values of 0.40μg/ml against TM4/8.2 strain (a wild type chloroquine and antifolate sensitive strain) and 6.39μg/ml against K1CB1 (multidrug resistant strain) strain. Significantly the extracts from this plant did not show any cytotoxicity. CONCLUSIONS:These findings provide the scientific basis for the use of seven medicinal plants in the BTM for the treatment of malaria, microbial infections, infectious fevers, and the Trypanosoma brucei rhodesiense infection. The results also form a good preliminary basis for the prioritization of candidate plant species for further in-depth phytochemical and pharmacological investigations toward our quest to unearth lead antiparasitic and antimicrobial compounds. Copyright © 2011. Published by Elsevier Ireland Ltd. |
| 6. | Acta Trop. 2011 Jul 2. [Epub ahead of print]Seroepidemiological survey of Leishmania infantum infection in dogs from northeastern Portugal.Sousa S, Lopes AP, Cardoso L, Silvestre R, Schallig H, Reed SG, Cordeiro da Silva A.SourceParasite Disease Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal. AbstractNortheastern Portugal is a region where canine leishmaniasis (CanL) is endemic. In this study, a sero-epidemiological survey was conducted in 654 dogs from that geographical area. Serum samples were evaluated by the direct agglutination test (DAT) and also by enzyme-linked immunosorbent assay (ELISA) using five different defined antigens. Seroprevalence of infection was 21.3% based on the assumption that seropositive animals were positive for at least three tests. A high degree of agreement was found between DAT and LAM-ELISA (89%; kappa value [κ]=0.67). A statistically significant difference (p<0.05) of seropositivity was found between adult (23.4%) and juvenile dogs (12.2%), apparently healthy (14.8%) and sick dogs (40.2%), vaccinated (19.7%) and non-vaccinated (41.2%) animals, seropositive (26.9%) and seronegative (18.0%) for Toxoplasma gondii, living in rural (18.5%) or urban (32.6%) areas, and between animals living exclusively outdoors (18.2%) and those living in a mixed habitat (27.5%). Risk factors for canine Leishmania infection, as defined by multiple logistic regression analysis, were of clinical status (odds ratio [OR]=3.1) and Toxoplasma infection (OR=1.5). Copyright © 2011 Elsevier B.V. All rights reserved. |
| 7. | Bioorg Med Chem. 2011 Jun 16. [Epub ahead of print]Molecular factors governing inhibition of arylimidamides against Leishmania: Conservative computational modeling to improve chemotherapies.Collar CJ, Zhu X, Werbovetz K, Boykin DW, Wilson WD.SourceDepartment of Chemistry, Georgia State University, Atlanta, GA 30303, United States. AbstractA dataset of 55 compounds with inhibitory activity against Leishmania donovani axenic amastigotes and Leishmania amazonensis intracellular parasites was examined through three-dimensional quantitative structure-activity relationship modeling employing molecular descriptors from both rigid and flexible compound alignments. For training and testing purposes, the compounds were divided into two datasets of 45 and 10 compounds, respectively. Statistically significant models were constructed and validated via the internal and external predictions. For all models employing steric, electrostatic, hydrophobic, H-donor and H-acceptor molecular descriptors, the R(2) values were greater than 0.90 and the SEE values were less than 0.22. The models obtained from rigid and flexible compounds were employed together to obtain a conservative method for predictions. This method minimized under predictions. Molecular descriptors from the models were then extrapolated, for the overall predictive devices and the individual compounds, and examined with regard to inhibitory activity. Information gained from the molecular descriptors is useful in the design of novel compounds. The models obtained can be employed to predict activities of the compounds designed and/or form predictions for compounds that exist and have not yet been examined with biological inhibitory assays. Copyright © 2011 Elsevier Ltd. All rights reserved. |
| 8. | Cell Microbiol. 2011 Jul 11. doi: 10.1111/j.1462-5822.2011.01630.x. [Epub ahead of print]Infection with Leishmania amazonen sis upregulates purinergic receptor expression and induces host-cell susceptibility to UTP-mediated apoptosis.Marques-da-Silva C, Chaves MM, Chaves SP, Figliuolo VR, Meyer-Fernandes JR, Corte-Real S, Lameu C, Ulrich H, Ojcius DM, Rossi-Bergmann B, Coutinho-Silva R.SourceLaboratory of Immunophysiology Laboratory of Imunopharmacology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro RJ, 21941-902, Brazil Laboratory of Structural Biology of Oswaldo Cruz Institute - FIOCRUZ, Rio de Janeiro, 21045-900, Brazil Center for Applied Toxinology CAT-CEPID, Instituto Butantan, São Paulo, Brazil Department of Biochemistry, Chemistry Institute, São Paulo University, São Paulo, Brazil Health Sciences Research Institute and School of Natural Sciences, University of California, Merced, CA 95343, USA Department of Medical Biochemistry, Federal University of Rio de Janeiro, RJ, Brazil. AbstractNucleotides are released into the extracellular milieu from infected cells and cells at inflammatory sites. The extracellular nucleotides bind to specific purinergic (P2) receptors and thereby induce a variety of cellular responses including anti-parasitic effects. Here we investigated whether extracellular nucleotides affect leishmanial infection in macrophages, and found that UTP reduces strongly the parasite load in peritoneal macrophages. Ultrastructural analysis of infected cells revealed that UTP induced morphological damage in the intracellular parasites. Uridine nucleotides also induced dose-dependent apoptosis of macrophages and production of ROI and RNI only in infected macrophages. The intracellular calcium measurements of infected cells showed that the response to UTP, but not UDP, increased the sensitivity and amplitude of cytosolic Ca(2+) changes. Infection of macrophages with Leishmania upregulated the expression of P2Y(2) and P2Y(4) receptor mRNA. The data suggest indirectly that Leishmania amazonensis infection induces modulation and heteromerization of P2Y receptors on macrophages. Thus UTP modulates the host response against L. amazonensis infection. UTP and UTP homologues should therefore be considered as novel components of therapeutic strategies against cutaneous leishmaniasis. © 2011 Blackwell Publishing Ltd. |
| 9. | Nat Prod Res. 2011 Jul;25(12):1195-201.Evaluation of antileishmanial, cytotoxic and antioxidant activities of essential oils extracted from plants issued from the leishmaniasis-endemic region of Sned (Tunisia).Ahmed SB, Sghaier RM, Guesmi F, Kaabi B, Mejri M, Attia H, Laouini D, Smaali I.Sourcea D?partement de Biologie, Facult? des Sciences de Gafsa, Campus Universitaire Zarroug-Gafsa 2112 , Gafsa , Tunisia. AbstractIn this study, we tested 10 essential oils (EOs) extracted from 10 plants issued from Sned region (Tunisia) to evaluate both their leishmanicidal effects against Leishmania major and L. infantum, and their cytotoxicity against murine macrophage cell line RAW 264.7 (ATCC, TIB-71). The antioxidant activity was also monitored by the DDPH method, while the chemical composition of active EO was assessed by GC?MS analysis. The results showed that the EOs obtained from Thymus hirtus sp. algeriensis (rich on monoterpenoids, especially linalool at 17.62% and camphor at 13.82%) is significantly active against both L. major and L. infantum, whereas Ruta chalepensis EO (rich on 2-undecanone at 84.28%) is only active against L. infantum. Both oil extracts showed low cytotoxicity towards murine macrophages. The characteristic ratios (IC(80) Raw264.7 cells/IC(50) L. infantum and IC(80) Raw264.7 cells/IC(50) L. major) were, respectively, 2.7 and 1.57 for T. hirtus sp. algeriensis, and 1.34 and 0.19 for R. chalepensis. However, when measuring the antioxidant effects (DDPH method), the two latter EOs presented a moderate 2,2-diphenyl-2-picrylhydrazyl hydrate scavenging effects compared to EOs from Eucaliptus globulus, Pinus halepensis, Pituranthos tortuosus, Rosmarinus officinalis, Tetraclinis articulata or to BHT. |
| 10. | J Liposome Res. 2011 Jul 8. [Epub ahead of print]Development and evaluation of tripalmitin emulsomes for the treatment of experimental visceral leishmaniasis.Pal A, Gupta S, Jaiswal A, Dube A, Vyas SP.SourceNanomedicine Research Center, Department Of Pharmaceutics, I.S.F. College Of Pharmacy , Moga 142 001 (PB) , INDIA. AbstractThe antifungal and antileishmanial agent amphotericin B (AmB) was formulated in tripalmitin based nanosize lipid partices (emulsomes) for macrophage targeting for the treatment of visceral leishmaniasis (VL). Emulsomes were modified by coating them with macrophage-specific ligand (O-palmitoyl mannan, OPM). The antileishmanial activity of AmB (0.5 and 1 mg/kg) was investigated in-vivo against VL by the inhibition of parasitic load in the spleen of L. donovani infected hamsters after intraperitoneal injections of AmB-Doc (Mycol), plain emulsomes (TPEs) and OPM coated emulsomes (TPEs-OPM). The formulations were found to be less effective at the dose of 0.5 mg/kg. At the dose of 1 mg/kg, formulation TPEs-OPM eliminated intracellular amastigotes of L. donovani within splenic macrophages more efficiently (62.76 ± 3.54 % parasite inhibition) than the formulation TPEs (42.68 ± 2.36 % parasite inhibition) (P < 0.01) or AmB-Doc (25.87 ± 3.87 % parasite inhibition) (P < 0.001). Our results suggest that these formulations (plain and ligand grafted emulsomes) are a promising substitute to the conventional AmB-Doc formulation for the treatment of VL. |
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