What's new for 'Trypanosomatids' in PubMed

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Sent on Friday, 2010 Nov 26
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 10 of 23

1.	J Biol Chem. 2010 Nov 24. [Epub ahead of print] Structural basis of molecular recognition the Leishmania small hydrophillic endoplasmic reticulum-associated protein, SHERP, at membrane surfaces. Moore B, Miles AJ, Guerra-Giraldez C, Simpson PJ, Iwata M, Wallace BA, Matthews SJ, Smith DF, Brown KA. Imperial College London, United Kingdom; Abstract The 57-residue small hydrophilic endoplasmic reticulum-associated protein (SHERP) shows highly specific, stage-regulated expression in the non-replicative vector-transmitted stages of the kinetoplastid parasite, Leishmania major, the causative agent of human cutaneous leishmaniasis. Previous studies have demonstrated that SHERP localises as a peripheral membrane protein on the cytosolic face of the endoplasmic reticulum and on outer mitochondrial membranes while its high copy number suggests a critical function in vivo. However, the absence of defined domains or identifiable orthologues, together with lack of a clear phenotype in transgenic parasites lacking SHERP, has limited functional understanding of this protein. Here, we use a combination of biophysical and biochemical methods to demonstrate that SHERP can be induced to adopt a globular fold in the presence of anionic lipids or sodium dodecyl sulfate. Crosslinking and binding studies suggest that SHERP has the potential to form a complex with the vacuolar type H+-ATPase. Taken together, these results suggest that SHERP may function in modulating cellular processes related to membrane organization and/or acidification during vector transmission of infective Leishmania.
	PMID: 21106528 [PubMed - as supplied by publisher]

2.	Presse Med. 2010 Nov 22. [Epub ahead of print] [Therapy of leishmaniasis in France: Consensus on proposed guidelines.] [Article in French] Buffet PA, Rosenthal E, Gangneux JP, Lightburne E, Couppié P, Morizot G, Lachaud L, Marty P, Dedet JP. Université Paris 6, UMR945 47, hôpital Pitié-Salpêtrière, service de parasitologie-mycologie, boulevard de l'hôpital, 75651 Paris cedex 13, France; Institut Pasteur, département de parasitologie, 75015 Paris, France. Abstract Because it relies on potentially toxic, difficult-to-handle, or expensive compounds the therapy of leishmaniasis is still a complex issue in 2010, especially for visceral leishmaniasis in immuno-suppressed subjects, or in patients with cutaneous and mucosal involvement. This induces a wide diversity of observed therapeutic practices, some being sub-optimal. TheSociété de Pathologie Exotiqueorganised a meeting dedicated to the therapy of leishmaniasis in France that led to the first consensus on therapeutic guidelines. Liposomal amphotericin B is the first-line option for visceral leishmaniasis both in immunocompetent, and immunosuppressed patients (cumulated doses of 20mg/kg and 30-40mg/kg, respectively). Secondary prophylaxis with either liposomal amphotericin B, pentamidine or meglumine antimoniate is proposed to patients with heavy immunosuppression until immunity has been restored for at least 6 months. While the efficacy of new topical formulations of paromomycin is being tested, patients with Old World cutaneous leishmaniasis may be left untreated, or be administered a combination of superficial cryotherapy plus intralesional antimony, or even - in complex situations - receive systemic therapy. The efficacy of a short course of pentamidine (L. guyanensis/L. panamensis) and a 20-day schedule of meglumine antimoniate (L. braziliensis) is solidly established. However, in well-defined situations, local therapy of New World cutaneous leishmaniasis is now considered acceptable. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
	PMID: 21106333 [PubMed - as supplied by publisher]

3.	FEMS Microbiol Lett. 2010 Oct 20. doi: 10.1111/j.1574-6968.2010.02142.x. [Epub ahead of print] Comparative studies on the biochemical properties of  the malic enzymes from Trypanosoma cruzi and Trypanosoma brucei. Leroux AE, Maugeri DA, Opperdoes FR, Cazzulo JJ, Nowicki C. Instituto de Química y Fisicoquímica Biológica IQUIFIB-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina IIB-INTECH, Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín-CONICET, Buenos Aires, Argentina Laboratory of Biochemistry, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium. Abstract Comparative studies showed that, like Trypanosoma cruzi, Trypanosoma brucei exhibits functional cytosolic and mitochondrial malic enzymes (MEs), which are specifically linked to NADP. Kinetic studies provided evidence that T. cruzi and T. brucei MEs display similarly high affinities towards NADP(+) and are also almost equally efficient in catalyzing the production of NADPH. Nevertheless, in contrast to the cytosolic ME from T. cruzi, which is highly activated by l-aspartate (over 10-fold), the T. brucei homologue is slightly more active (50%) in the presence of this amino acid. In T. brucei, both isozymes appear to be clearly more abundant in the insect stage, although they can be immunodetected in the bloodstream forms. By contrast, in T. cruzi the expression of the mitochondrial ME seems to be clearly upregulated in amastigotes, whereas the cytosolic isoform appears to be more abundant in the insect stages of the parasite. It might be hypothesized that in those environments where glucose is very low or absent, these pathogens depend on NADP-linked dehydrogenases such as the MEs for NADPH production, as in those conditions the pentose phosphate pathway cannot serve as a source of essential reducing power. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
	PMID: 21105905 [PubMed - as supplied by publisher]

4.	Planta Med. 2010 Nov 23. [Epub ahead of print] Anti-infective Activities of Pelargonium sidoides (EPS® 7630): Effects of Induced NO Production on Leishmania major in Infected Macrophages and Antiviral Effects as Assessed in a Fibroblast-Virus Protection Assay. Thäle C, Kiderlen AF, Kolodziej H. Freie Universität Berlin, Institut für Pharmazie, Pharmazeutische Biologie, Berlin, Germany. Abstract EPs® 7630 is an aqueous-ethanolic extract of the roots of PELARGONIUM SIDOIDES, employed in the treatment of upper respiratory tract infections. Its anti-infective activity is supposed to be associated with the activation of the nonspecific immune system. Using LEISHMANIA MAJOR GFP-infected murine BMMΦ, the NO production of EPs® 7630-activated macrophages was correlated with the reduction of the GFP signal measured at single cell levels using flow cytometry. The anti-infectious effect of EPs® 7630 (3-10 µg/mL) on its own (NO production: 4-13 µM; signal reduction: 25-73 %) was less prominent than that in combination with IFN- γ (100 U/mL) (NO production: 20-27 µM; signal reduction: 35-78 %). Furthermore, supernatants of EPs® 7630-stimulated BMMΦ (10 µg/mL) significantly reduced the cytopathic effect of EMCV on L929 fibroblasts (antiviral activity 80 U/mL) when compared with an IFN- γ standard (100 U/mL). Direct addition of EPs® 7630 to L929 did not mediate cytoprotective effects. The antiviral components induced in BMMΦ by EPs® 7630 remain to be identified. Detection of any IFNs by ELISA was unsuccessful, which may be due to their very low concentrations in cell supernatants. The current data provide convincing support for the induction of anti-infectious responses by EPs® 7630. © Georg Thieme Verlag KG Stuttgart · New York.
	PMID: 21104606 [PubMed - as supplied by publisher]

5.	Planta Med. 2010 Nov 23. [Epub ahead of print] Curcuma as a Parasiticidal Agent: A Review. Haddad M, Sauvain M, Deharo E. Laboratoire de pharmacochimie des substances naturelles et pharmacophores redox, UMR 152, UPS, Université de Toulouse, Toulouse, France. Abstract Members of the CURCUMA plant species (Zingiberaceae) have been used for centuries in cooking, cosmetics, staining and in traditional medicine as "omnipotent" remedies. Herbal preparations made with, and molecules extracted from, CURCUMA have been shown to possess a wide variety of pharmacological properties against malignant proliferation, hormonal disorders, inflammation, and parasitosis among other conditions. This review evaluates CURCUMA and its associated bioactive compounds, particularly focusing on studies examining the parasiticidal activity of these components against the tropical parasites PLASMODIUM, LEISHMANIA, TRYPANOSOMA, SCHISTOSOMA and more generally against other cosmopolitan parasites (nematodes, BABESIA, CANDIDA, GIARDIA, COCCIDIA and SARCOPTES). © Georg Thieme Verlag KG Stuttgart · New York.
	PMID: 21104602 [PubMed - as supplied by publisher]

6.	Braz J Med Biol Res. 2010 Nov 26. pii: S0100-879X2010007500134. [Epub ahead of print] Anti-Leishmania titers and positive skin tests in patients cured of kala-azar. Viana GM, Nascimento MD, Diniz Neto JA, Rabelo EM, Binda Júnior JR, Santos Júnior OM, Santos AC, Galvão CS, Guimarães RS. Departamento de Patologia, Universidade Federal do Maranhão, São Luís, MA, Brasil.
	PMID: 21103789 [PubMed - as supplied by publisher]

7.	PLoS Negl Trop Dis. 2010 Nov 16;4(11):e889. Inference of Population Structure of Leishmania donovani Strains Isolated from Different Ethiopian Visceral Leishmaniasis Endemic Areas. Gelanew T, Kuhls K, Hurissa Z, Weldegebreal T, Hailu W, Kassahun A, Abebe T, Hailu A, Schönian G. Institut für Mikrobiologie und Hygiene, Charité Universitätsmedizin Berlin, Berlin, Germany. Abstract BACKGROUND: Parasites' evolution in response to parasite-targeted control strategies, such as vaccines and drugs, is known to be influenced by their population genetic structure. The aim of this study was to describe the population structure of Ethiopian strains of Leishmania donovani derived from different areas endemic for visceral leishmaniasis (VL) as a prerequisite for the design of effective control strategies against the disease. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-three strains of L. donovani newly isolated from VL cases in the two main Ethiopian foci, in the north Ethiopia (NE) and south Ethiopia (SE) of the country were investigated by using 14 highly polymorphic microsatellite markers. The microsatellite profiles of 60 previously analysed L. donovani strains from Sudan, Kenya and India were included for comparison. Multilocus microsatellite typing placed strains from SE and Kenya (n = 30) in one population and strains from NE and Sudan (n = 65) in another. These two East African populations corresponded to the areas of distribution of two different sand fly vectors. In NE and Sudan Phlebotomus orientalis has been implicated to transmit the parasites and in SE and Kenya P. martini. The genetic differences between parasites from NE and SE are also congruent with some phenotypic differences. Each of these populations was further divided into two subpopulations. Interestingly, in one of the subpopulations of the population NE we observed predominance of strains isolated from HIV-VL co-infected patients and of strains with putative hybrid genotypes. Furthermore, high inbreeding irreconcilable from strict clonal reproduction was found for strains from SE and Kenya indicating a mixed-mating system. CONCLUSIONS/SIGNIFICANCE: This study identified a hierarchical population structure of L. donovani in East Africa. The existence of two main, genetically and geographically separated, populations could reflect different parasite-vector associations, different ecologies and varying host backgrounds and should be further investigated.
	PMID: 21103373 [PubMed - in process]

8.	PLoS Negl Trop Dis. 2010 Nov 16;4(11):e886. LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice. Bruhn KW, Marathe C, Maretti-Mira AC, Nguyen H, Haskell J, Tran TA, Vanchinathan V, Gaur U, Wilson ME, Tontonoz P, Craft N. Department of Medicine, Division of Dermatology and Infectious Diseases, Harbor-University of California Los Angeles Medical Center and Los Angeles Biomedical Research Institute, Torrance, California, United States of America. Abstract BACKGROUND: The liver X receptors (LXRs) are a family of nuclear receptor transcription factors that are activated by oxysterols and have defined roles in both lipid metabolism and cholesterol regulation. LXRs also affect antimicrobial responses and have anti-inflammatory effects in macrophages. As mice lacking LXRs are more susceptible to infection by intracellular bacteria Listeria monocytogenes and Mycobacterium tuberculosis, we hypothesized that LXR might also influence macrophage responses to the intracellular protozoan parasite Leishmania chagasi/infantum, a causative agent of visceral leishmaniasis. METHODS AND FINDINGS: Surprisingly, both LXRα knock-out and LXRα/LXRβ double-knock-out (DKO) mice were markedly resistant to systemic L. chagasi/infantum infection compared to wild-type mice. Parasite loads in the livers and spleens of these animals were significantly lower than in wild-type mice 28 days after challenge. Bone marrow-derived macrophages from LXR-DKO mice infected with L. chagasi/infantum in vitro in the presence of IFN-γ were able to kill parasites more efficiently than wild-type macrophages. This enhanced killing by LXR-deficient macrophages correlated with higher levels of nitric oxide produced, as well as increased gene expression of IL-1β. Additionally, LXR ligands abrogated nitric oxide production in wild-type macrophages in response to infection. CONCLUSIONS: These observations suggest that LXR-deficient mice and macrophages mount antimicrobial responses to Leishmania infection that are distinct from those mounted by wild-type mice and macrophages. Furthermore, comparison of these findings to other intracellular infection models suggests that LXR signaling pathways modulate host antimicrobial responses in a complex and pathogen-specific manner. The LXR pathway thus represents a potential therapeutic target for modulating immunity against Leishmania or other intracellular parasites.
	PMID: 21103366 [PubMed - in process]

9.	Nanotechnology. 2010 Nov 22;21(50):505102. [Epub ahead of print] Development of a nanoparticulate formulation of diminazene to treat African trypanosomiasis. Kroubi M, Daulouede S, Karembe H, Jallouli Y, Howsam M, Mossalayi D, Vincendeau P, Betbeder D. EA 4483, IFR 114 IMPRT, Faculté de Médecine, Pôle recherche, Département de Physiologie, 1 place de Verdun, 59045 Lille Cedex, France. Abstract There is a real need to develop new therapeutic strategies for African trypanosomiasis infections. In our study, we developed a new drug delivery system of diminazene (DMZ), a trypanocidal drug registered for veterinary use. This drug candidate presents a limited efficacy, a poor affinity for brain tissue and instability. The development of colloidal formulations based on a porous cationic nanoparticle with an oily core ((70)DGNP( + )), has potentially two advantages: stabilization of the drug and potential targeting of the parasite. We analyzed two processes of drug loading: in process (DMZ was added during the preparation of (70)DGNP( + ) at 80 °C) and post-loading (DMZ was mixed with a (70)DGNP( + ) solution at room temperature). Poor stability of the drug was observed using the in process technique. When using the post-loading technique over 80% drug entrapment efficiency was obtained at a ratio of DMZ:phospholipids (wt:wt) < 5%. Moreover, DMZ loaded into (70)DGNP( + ) was found to be protected against oxidation and was stable for at least six months at 4 °C. Finally, in vitro tests on T.b. brucei showed an increased efficacy of DMZ loaded in (70)DGNP( + ).
	PMID: 21098928 [PubMed - as supplied by publisher]

10.	J Immunol. 2010 Nov 22. [Epub ahead of print] Leishmania Inhibitor of Serine Peptidase 2 Prevents TLR4 Activation by Neutrophil Elastase Promoting Parasite Survival in Murine Macrophages. Faria MS, Reis FC, Azevedo-Pereira RL, Morrison LS, Mottram JC, Lima AP. Instituto de Biofisica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Brazil. Abstract Leishmania major is a protozoan parasite that causes skin ulcerations in cutaneous leishmaniasis. In the mammalian host, the parasite resides in professional phagocytes and has evolved to avoid killing by macrophages. We identified L. major genes encoding inhibitors of serine peptidases (ISPs), which are orthologs of bacterial ecotins, and found that ISP2 inhibits trypsin-fold S1A family peptidases. In this study, we show that L. major mutants deficient in ISP2 and ISP3 (Δisp2/3) trigger higher phagocytosis by macrophages through a combined action of the complement type 3 receptor, TLR4, and unregulated activity of neutrophil elastase (NE), leading to parasite killing. Whereas all three components are required to mediate enhanced parasite uptake, only TLR4 and NE are necessary to promote parasite killing postinfection. We found that the production of superoxide by macrophages in the absence of ISP2 is the main mechanism controlling the intracellular infection. Furthermore, we show that NE modulates macrophage infection in vivo, and that the lack of ISP leads to reduced parasite burdens at later stages of the infection. Our findings support the hypothesis that ISPs function to prevent the activation of TLR4 by NE during the Leishmania-macrophage interaction to promote parasite survival and growth.
	PMID: 21098233 [PubMed - as supplied by publisher]