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Sent on Tuesday, 2012 March 27Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
1. | PPAR Res. 2012;2012:796235. Epub 2012 Feb 1.Peroxisome Proliferator-Activated Receptor-γ-Mediated Polarization of Macrophages in Leishmania Infection.Chan MM, Adapala N, Chen C.SourceDepartment of Microbiology and Immunology, Temple University School of Medicine, Room 534 OMS, 3400 North Broad Street, Philadelphia, PA 19140, USA. AbstractInfection is the outcome of a contest between a pathogen and its host. In the disease leishmaniasis, the causative protozoan parasites are harbored inside the macrophages. Leishmania species adapt strategies to make the infection chronic, keeping a balance between their own and the host's defense so as to establish an environment that is favorable for survival and propagation. Activation of peroxisome proliferator-activated receptor (PPAR) is one of the tactics used. This ligand-activated nuclear factor curbs inflammation to protect the host from excessive injuries by setting a limit to its destructive force. In this paper, we report the interaction of host PPARs and the pathogen for visceral leishmaniasis, Leishmania donovani, in vivo and in vitro. PPAR expression is induced by parasitic infection. Leishmanial activation of PPARγ promotes survival, whereas blockade of PPARγ facilitates removal of the parasite. Thus, Leishmania parasites harness PPARγ to increase infectivity. |
PMID: 22448168 [PubMed - in process] | |
2. | Drug Test Anal. 2012 Mar 22. doi: 10.1002/dta.339. [Epub ahead of print]Bioanalytical method development, pharmacokinetics, and toxicity studies of paromomycin and paromomycin loaded in albumin microspheres.Khan W, Sharma SS, Kumar N.SourceDepartment of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), S.A.S., Nagar, India. AbstractIntracellular location of leishmania parasite in macrophages protects them from both hosts defence system as well as from antibiotics like paromomycin (PM) acting against them, thus there is a need of a formulation targeting intracellular parasites. Considering this, PM-loaded albumin microspheres (PM-MS) were prepared to target PM to macrophages where leishmania parasites resides and evaluated for their safety profile. A new bioanalytical method for quantitative determination of PM in rat plasma was developed by pre-column derivatization with 9-fluorenylmethyl chloroformate. The developed bioanalytical method was validated and applied for pharmacokinetic studies of PM administered by intramuscular and intravenous routes as well as for developed PM-MS which were administered by intravenous route. Comparative acute and subacute toxicity studies were also carried out for these formulations. The developed method was found to be very sensitive with a quantification limit of 40 ng/ml. Pharmacokinetic studies demonstrated nearly 80% reduction in C(max) of PM when administered as PM-MS, compared to other formulations at equivalent dose. Toxicity studies indicated increased level of blood urea and blood urea nitrogen in PM intramuscular injection at 90 mg/kg dose, whereas at the same dose level PM-MS showed no symptoms of toxicity. Results obtained suggest that developed PM-MS formulation is a promising alternative to the presently marketed PM intramuscular injection for the treatment of visceral leishmaniasis. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd. |
PMID: 22447374 [PubMed - as supplied by publisher] | |
3. | Acta Trop. 2012 Mar 16. [Epub ahead of print]An insight into the Phlebotomus perniciosus saliva by a proteomic approach.Martín-Martín I, Molina R, Jiménez M.SourceServicio de Parasitología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo s/n, 28220, Majadahonda, Madrid, Spain. AbstractSand fly saliva is known to play an important role in the establishment of Leishmania spp. infection. As a consequence, identifying antigenic salivary proteins of different leishmaniasis vectors has currently become a major task in the field of anti-Leishmania vaccine development. The purpose of this work was to improve the knowledge of Phlebotomus perniciosus salivary proteins by combining two-dimensional gel electrophoresis (2DE) methodology, mass spectrometry and Western blotting (WB). Salivary protein profiles of three P. perniciosus colonies from different geographic origins in Spain were compared through SDS-PAGE, leading to a similar pattern with no qualitatively noticeable differences. A gradual increase of the protein content was significantly detected with the age of sand flies, reaching the complete salivary protein profiles at day four. The 2DE revealed a reproducible protein profile that matched the classic monodimensional SDS-PAGE pattern (1DE). More spots rather than protein bands (19 versus 11) were visualized by 2DE and 1DE, respectively, suggesting the presence of either protein isoforms or posttranslational modifications. Sera of mice and hamsters immunized through exposure to sand fly bites following different immunization schedules showed elevated anti-saliva IgG levels. These sera allowed the detection of 5 bands and 16 immunogenic spots in 1DE and 2DE, respectively, followed by WB. These antigens were identified by MALDITOF/TOF as SP03, SP03B, SP08, SP01, SP01B, SP04, SP04B, SP02, Phlebotomus ariasi SP16, and Phlebotomus argentipes SP13. This work is assumed to be the first attempt to establish 2DE proteomic maps of P. perniciosus saliva. All spots were identified as salivary proteins, confirming this technology as an interesting tool to improve sand fly salivary knowledge. Copyright © 2012. Published by Elsevier B.V. |
PMID: 22445778 [PubMed - as supplied by publisher] | |
4. | J Cutan Pathol. 2012 Apr;39(4):406-12. doi: 10.1111/j.1600-0560.2012.01890.x.Transepidermal elimination in cutaneous leishmaniasis: a multiregional study.Karram S, Loya A, Hamam H, Habib RH, Khalifeh I.SourceDepartment of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon Department of Pathology, Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore, Pakistan Department of Dermatology, Hammoud Hospital University Medical Center, Saida, Lebanon Department of Internal Medicine, Outcomes Research Unit, American University of Beirut Medical Center, Beirut, Lebanon. AbstractBackground: Transepidermal elimination has been documented in a myriad of infectious diseases; however, its occurrence in cutaneous leishmaniasis has not been evaluated. Methods: Skin biopsies (n = 212) with cutaneous leishmaniasis in Lebanon (n = 46), Syria (n = 53), Saudi Arabia (n = 45) and Pakistan (n = 68) were evaluated. Clinical data collected included age, gender, eruption type (papule, nodule, verrucous or scar), duration and anatomic location. Histopathologically, multiple parameters were recorded including Ridley's parasitic index and pattern, transepidermal elimination, interface changes, ulceration and necrosis. Transepidermal elimination was defined as the presence of amastigotes in the epidermis in all layers, limited to the basal layer or present in a perforating plug. All cases were confirmed by polymerase chain reaction (PCR) analysis followed by restriction fragment length polymorphism analysis for molecular subspeciation. Results: Leishmania tropica was identified in 88.2% and Leishmania major in 11.8% of all cases. Transepidermal elimination was observed in 28.3% of cases (29 perforating plug, 19 all layers and 12 basal layer) with a significant prevalence of L. major in this group (35 vs. 2%, p < 0.001). Cases with transepidermal elimination were associated with interface changes and higher parasitic index (p < 0.001) but not with an increased ulceration rate (p > 0.05). Multivariate analysis showed that transepidermal elimination was independently predicted by L. major [OR (95% confidence interval) = 80 (9-712); p < 0.001], parasitic index [OR = 3.4 (2.1-5.3); p < 0.001], interface changes [OR = 6.24 (2.2-17.8); p < 0.001] and necrosis [OR = 0.2 (0.1-0.8);p = 0.026]. Conclusions: We report the largest multiregional cutaneous leishmaniasis series with a 28.3% documented transepidermal elimination incidence of which 48% were perforating plug; a significant prevalence of L. major was also identified in the transepidermal elimination group. The association of transepidermal elimination with interface changes and a higher parasitic index, without an increased ulceration rate, may reflect a unique biologic alteration in the epidermis, serving to facilitate the extrusion of the parasites through the skin. Karram S, Loya A, Hamam H, Habib RH, Khalifeh I. Transepidermal elimination in cutaneous leishmaniasis: a multiregional study. Copyright © 2012 John Wiley & Sons A/S. |
PMID: 22443392 [PubMed - in process] | |
5. | New Phytol. 2012 Mar 23. doi: 10.1111/j.1469-8137.2012.04119.x. [Epub ahead of print]The hemibiotrophic cacao pathogen Moniliophthora perniciosa depends on a mitochondrial alternative oxidase for biotrophic development.Thomazella DP, Teixeira PJ, Oliveira HC, Saviani EE, Rincones J, Toni IM, Reis O, Garcia O, Meinhardt LW, Salgado I, Pereira GA.SourceLaboratório de Genômica e Expressão, Departamento de Genética, Evolução e Bioagentes, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, Campinas, SP 13083-970, Brazil Departamento de Biologia Vegetal, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, Campinas, SP 13083-970, Brazil Sustainable Perennial Crops Laboratory, USDA-ARS, 10300 Baltimore Ave., Bldg. 001, Beltsville, MD 20705-2350, USA. Abstract• The tropical pathogen Moniliophthora perniciosa causes witches' broom disease in cacao. As a hemibiotrophic fungus, it initially colonizes the living host tissues (biotrophic phase), and later grows over the dead plant (necrotrophic phase). Little is known about the mechanisms that promote these distinct fungal phases or mediate the transition between them. • An alternative oxidase gene (Mp-aox) was identified in the M. perniciosa genome and its expression was analyzed througout the fungal life cycle. In addition, the effects of inhibitors of the cytochrome-dependent respiratory chain (CRC) and alternative oxidase (AOX) were evaluated on the in vitro development of M. perniciosa. • Larger numbers of Mp-aox transcripts were observed in the biotrophic hyphae, which accordingly showed elevated sensitivity to AOX inhibitors. More importantly, the inhibition of CRC prevented the transition from the biotrophic to the necrotrophic phase, and the combined use of a CRC and AOX inhibitor completely halted fungal growth. • On the basis of these results, a novel mechanism is presented in which AOX plays a role in the biotrophic development of M. perniciosa and regulates the transition to its necrotrophic stage. Strikingly, this model correlates well with the infection strategy of animal pathogens, particularly Trypanosoma brucei, which uses AOX as a strategy for pathogenicity. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust. |
PMID: 22443281 [PubMed - as supplied by publisher] | |
6. | Parasite Immunol. 2012 Mar 24. doi: 10.1111/j.1365-3024.2012.01365.x. [Epub ahead of print]Identification of L. infantum chagasi proteins in VL patients' urine: a promising antigen discovery approach of vaccine candidates.Kashino SS, Abeijon C, Qin L, Kanunfre KA, Kubrusly FS, Silva FO, Costa DL, Campos DJ, Costa CH, Raw I, Campos-Neto A.SourceThe Forsyth Institute, Cambridge, MA DetectoGen Inc., Grafton, MA Institute of Tropical Medicine, University of São Paulo, São Paulo, SP, Brazil BioIndustrial Division, Butantan Institute/Foundation, São Paulo, SP, Brazil Laboratory of Leishmaniasis, Natan Portela Institute of Tropical Medicine, Federal University of Piauí, Teresina, PI, Brazil Department of Pediatrics, University of Brasilia, Brasília, DF, Brazil. AbstractVisceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in Southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver, and bone marrow lesions and excreted in the patients' urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1), and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in E. coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2 + BpMPLA-SE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to kala-azar and opens novel possibilities for vaccine development to other serious infectious diseases. © 2012 Blackwell Publishing Ltd. Copyright © 2012 Blackwell Publishing Ltd. |
PMID: 22443237 [PubMed - as supplied by publisher] | |
7. | J Immunol. 2012 Feb 15;188(4):1942-52. Epub 2012 Jan 18.Trypanosoma cruzi immune evasion mediated by host cell-derived microvesicles.Cestari I, Ansa-Addo E, Deolindo P, Inal JM, Ramirez MI.SourceLaboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil. AbstractThe innate immune system is the first mechanism of vertebrate defense against pathogen infection. In this study, we present evidence for a novel immune evasion mechanism of Trypanosoma cruzi, mediated by host cell plasma membrane-derived vesicles. We found that T. cruzi metacyclic trypomastigotes induced microvesicle release from blood cells early in infection. Upon their release, microvesicles formed a complex on the T. cruzi surface with the complement C3 convertase, leading to its stabilization and inhibition, and ultimately resulting in increased parasite survival. Furthermore, we found that TGF-β-bearing microvesicles released from monocytes and lymphocytes promoted rapid cell invasion by T. cruzi, which also contributed to parasites escaping the complement attack. In addition, in vivo infection with T. cruzi showed a rapid increase of microvesicle levels in mouse plasma, and infection with exogenous microvesicles resulted in increased T. cruzi parasitemia. Altogether, these data support a role for microvesicles contributing to T. cruzi evasion of innate immunity. |
PMID: 22262654 [PubMed - indexed for MEDLINE] | |
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8. | Molecules. 2011 Nov 23;16(11):9714-20.Trypanocidal activity of oxoaporphine and pyrimidine-β-carboline alkaloids from the branches of Annona foetida Mart. (Annonaceae).Costa EV, Pinheiro ML, de Souza AD, Barison A, Campos FR, Valdez RH, Ueda-Nakamura T, Filho BP, Nakamura CV.SourceLABORGANICS, Department of Chemistry, Federal University of Sergipe, 49100-000, São Cristóvão, SE, Brazil. emmanoelvilaca@yahoo.com.br AbstractPhytochemical investigation of the branches of Annona foetida Mart. led to isolation from the CH(2)Cl(2) extract of four alkaloids: Atherospermidine (1), described for the first time in this species, liriodenine (2), O-methylmoschatoline (3), and annomontine (4). Their chemical structures were established on the basis of spectroscopic data from IR, MS, NMR (1D and 2D), and comparison with the literature. Compounds 2-4 showed potent trypanocidal effect when evaluated against epimastigote and trypomastigote forms of Trypanosoma cruzi. © 2011 by the authors; licensee MDPI, Basel, Switzerland. |
PMID: 22113579 [PubMed - indexed for MEDLINE] | |
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9. | Infect Genet Evol. 2011 Dec;11(8):1891-8. Epub 2011 Aug 12.The infra-red (IR) landscape of Triatoma infestans. An hypothesis about the role of IR radiation as a cue for Triatominae dispersal.Catalá SS.SourceCRILAR-CONICET, Anillaco, 5301 La Rioja, Argentina. silviascatala@hotmail.com AbstractThis paper presents the infrared (IR) emission spectrum of hosts and habitats of Triatoma infestans in the chaco region of NW Argentina, representing the first attempt to correlate the natural infrared stimulus with the known behaviour of these blood-sucking insect, vectors of Trypanosoma cruzi--causative agent of Chagas disease. The study was carried out in two rural villages of La Rioja Province (Argentina). A FLYR i40 camera was used to obtain IR pictures which were analyzed to determine the thermal range for humans, domestic animals, building materials, and general background emissions. From sunset to the first hours of night, the thermal contrast between hosts and their landscape rises, increasing the likelihood that hosts could be differentiated by the vector. However, some building materials, can retain high temperatures during the night, which might add attractiveness to the presence of hosts. The results suggest that the most attractive habitats for dispersing bugs would be those at short distance, with high CO2 emission and strong IR radiation indicative of host presence. Goats corrals may be the most attractive habitat to disperse, within the domestic habitat. Dispersal would be favoured in periods of low atmospheric water saturation when IR perception is highest. In the IR band, the potential host and habitat discrimination available for the insects fits well with their known sensory capacities and observed dispersive behavior. Research in this area could be of considerable interest in relation to vector surveillance, epidemiology of Chagas disease transmission, and to develop new methods to minimise triatomine colonisation of new habitats. Copyright © 2011 Elsevier B.V. All rights reserved. |
PMID: 21856443 [PubMed - indexed for MEDLINE] | |
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