What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2012 June 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 - 9 of 9

1.	Int J Biochem Cell Biol. 2012 Jun 20. [Epub ahead of print] Trypanosomes lacking uracil-DNA glycosylase are hypersensitive to antifolates and present a mutator phenotype. Castillo-Acosta VM, Aguilar-Pereyra F, Vidal AE, Navarro M, Ruiz-Pérez LM, González-Pacanowska D. Source Instituto de Parasitología y Biomedicina "López-Neyra". Consejo Superior de Investigaciones Científicas. Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, s/n 18100-Armilla (Granada), Spain. Abstract Cells contain low amounts of uracil in DNA which can be the result of dUTP misincorporation during replication or cytosine deamination. Elimination of uracil in the base excision repair pathway yields an abasic site, which is potentially mutagenic unless repaired. The Trypanosoma brucei genome presents a single uracil-DNA glycosylase responsible for removal of uracil from DNA. Here we establish that no excision activity is detected on U:G, U:A pairs or single-strand uracil-containing DNA in uracil-DNA glycosylase null mutant cell extracts, indicating the absence of back-up uracil excision activities. While procyclic forms can survive with moderate amounts of uracil in DNA, an analysis of the mutation rate and spectra in mutant cells revealed a hypermutator phenotype where the predominant events were GC to AT transitions and insertions. Defective elimination of uracil via the base excision repair pathway gives rise to hypersensitivity to antifolates and oxidative stress and an increased number of DNA strand breaks, suggesting the activation of alternative DNA repair pathways. Finally, we show that uracil-DNA glycosylase defective cells exhibit reduced infectivity in vivo demonstrating that efficient uracil elimination is important for survival within the mammalian host. Copyright © 2012. Published by Elsevier Ltd.
	PMID: 22728162 [PubMed - as supplied by publisher]

2.	Exp Parasitol. 2012 Jun 21. [Epub ahead of print] Improvements in obtaining New World Leishmania sp from mucosal lesions: notes on isolating and stocking parasites. Dorta ML, Oliveira MA, Fleuri AK, Duarte FB, Pinto SA, Pereira LI, Ribeiro-Dias F. Source Institute of Tropical Pathology and Public Health, Universidade Federal de Goiás, Rua 235 S/N - Setor Universitário, 74605-050, Goiânia, Goiás, Brazil. Abstract Tegumentary leishmaniasis is an endemic protozoan disease that, in Brazil, is caused by parasites from Viannia or Leishmania complex. The clinical forms of cutaneous disease comprise localized, disseminated, mucosal or mucocutaneous, and diffuse leishmaniasis. Viannia complex parasites are not easy to isolate from patient lesions, especially from mucosal lesions, and they are difficult to culture. The aim of the present study was to compare the efficiency of ex vivo (culture) and in vivo (IFNγ-deficient mice) parasite isolation methods to improve the isolation rate and storage of stocks of New World Leishmania species that cause cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML). Biopsy fragments from cutaneous or mucosal lesions were inoculated into culture medium or mouse footpads. We evaluated 114 samples (86 CL, 28 ML) using both methods independently. Samples from CL patients had a higher isolation rate in ex vivo cultures than in mice (34.1% vs. 18.7%, P < 0.05). Nevertheless, almost twice the number of isolates from ML lesions was isolated using the mouse model compared to ex vivo cultures (mouse, 6/25; culture, 3/27). The overall rates of isolation were 40.2% for CL samples and 29.6% for ML samples. Of the 43 isolations, we successfully stocked 35 isolates (81.4%; 27 CL, 8 ML). Contaminations were more frequently detected in cultures of ML than CL lesions. For comparison, the use of both methods simultaneously was performed in 74 samples of CL and 25 samples of ML, and similar results were obtained. Of the eight ML isolates, five were isolated only in mice, indicating the advantage of using the in vivo method to obtain ML parasites. All parasites obtained from in vivo isolation were cryopreserved, whereas only 68% of ex vivo isolations from CL lesions were stocked. In conclusion, the use of genetically modified mice can improve the isolation of parasites from ML. Isolation and stocking of New World Leishmania parasites, especially those from ML that are almost absent in laboratory stocks, are critical for evaluating parasite genetic diversity as well as studying host-parasite interactions to identify biological markers of Leishmania. In this paper, we also discuss some of the difficulties associated with isolating and stocking parasites. Copyright © 2012. Published by Elsevier Inc.
	PMID: 22728105 [PubMed - as supplied by publisher]

3.	Aten Primaria. 2012 Jun 20. [Epub ahead of print] [Community outbreak of leishmaniasis in the southern area of the community of Madrid.] [Article in Spanish] Noguerol Álvarez M, San Martín López JV, Aguado Lobo M, Aparicio Azcárraga P . Source Medicina de Familia y Comunitaria, Centro de Salud Cuzco, Fuenlabrada, Madrid, España.
	PMID: 22727435 [PubMed - as supplied by publisher]

4.	Trends Parasitol. 2012 Jun 20. [Epub ahead of print] Receptor-mediated phagocytosis of Leishmania: implications for intracellular survival. Ueno N, Wilson ME. Source Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. Abstract The extracellular promastigote stage of Leishmania spp. is transmitted to mammals by a sand fly vector. Leishmania promastigotes ligate host macrophage receptors, triggering phagocytosis and subsequent internalization, a crucial step for survival. Parasites transform intracellularly to the amastigote stage. Many studies document different receptors detecting promastigotes and amastigotes, but the relative importance of each interaction is ill-defined. Recent studies suggest that the macrophage receptors utilized during phagocytosis impact the intracellular fate of the parasite. This review summarizes the receptors implicated in Leishmania phagocytosis over the past 30 years. It then proceeds to weigh the evidence for or against their potential roles in intracellular parasite trafficking. Published by Elsevier Ltd.
	PMID: 22726697 [PubMed - as supplied by publisher]

5.	Trends Parasitol. 2012 Jun 20. [Epub ahead of print] Purine salvage in Leishmania: complex or simple by design? Boitz JM, Ullman B, Jardim A, Carter NS. Source Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, USA. Abstract Purine nucleotides function in a variety of vital cellular and metabolic processes including energy production, cell signaling, synthesis of vitamin-derived cofactors and nucleic acids, and as determinants of cell fate. Unlike their mammalian and insect hosts, Leishmania cannot synthesize the purine ring de novo and are absolutely dependent upon them to meet their purine requirements. The obligatory nature of purine salvage in these parasites, therefore, offers an attractive paradigm for drug targeting and, consequently, the delineation of the pathway has been under scientific investigation for over 30 years. Here, we review recent developments that reveal how purines flux in Leishmania and offer a potential 'Achilles' heel' for future validation. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22726696 [PubMed - as supplied by publisher]

6.	Adv Parasitol. 2012;79:299-337. Priorities for the elimination of sleeping sickness. Welburn SC, Maudlin I. Abstract Sleeping sickness describes two diseases, both fatal if left untreated: (i) Gambian sleeping sickness caused by Trypanosoma brucei gambiense, a chronic disease with average infection lasting around 3 years, and (ii) Rhodesian sleeping sickness caused by T. b. rhodesiense, an acute disease with death occurring within weeks of infection. Control of Gambian sleeping sickness is based on case detection and treatment involving serological screening, followed by diagnostic confirmation and staging. In stage I, patients can remain asymptomatic as trypanosomes multiply in tissues and body fluids; in stage II, trypanosomes cross the blood-brain barrier, enter the central nervous system and, if left untreated, death follows. Staging is crucial as it defines the treatment that is prescribed; for both forms of disease, stage II involves the use of the highly toxic drug melarsoprol or, in the case of Gambian sleeping sickness, the use of complex and very expensive drug regimes. Case detection of T. b. gambiense sleeping sickness is known to be inefficient but could be improved by the identification of parasites using molecular tools that are, as yet, rarely used in the field. Diagnostics are not such a problem in relation to T. b. rhodesiense sleeping sickness, but the high level of under-reporting of this disease suggests that current strategies, reliant on self-reporting, are inefficient. Sleeping sickness is one of the 'neglected tropical diseases' that attracts little attention from donors or policymakers. Proper quantification of the burden of sleeping sickness matters, as the primary reason for its 'neglect' is that the true impact of the disease is unknown, largely as a result of under-reporting. Certainly, elimination will not be achieved without vast improvements in field diagnostics for both forms of sleeping sickness especially if there is a hidden reservoir of 'chronic carriers'. Mass screening would be a desirable aim for Gambian sleeping sickness and could be handled on a national scale in the endemic countries - perhaps by piggybacking on programmes committed to other diseases. As well as improved diagnostics, the search for non-toxic drugs for stage II treatment should remain a research priority. There is good evidence that thorough active case finding is sufficient to control T. b. gambiense sleeping sickness, as there is no significant animal reservoir. Trypanosoma brucei rhodesiense sleeping sickness is a zoonosis and control involves interrupting the fly-animal-human cycle, so some form of tsetse control and chemotherapy of the animal reservoir must be involved. The restricted application of insecticide to cattle is the most promising, affordable and sustainable technique to have emerged for tsetse control. Animal health providers can aid disease control by treating cattle and, when allied with innovative methods of funding (e.g. public-private partnerships) not reliant on the public purse, this approach may prove more sustainable. Sleeping sickness incidence for the 36 endemic countries has shown a steady decline in recent years and we should take advantage of the apparent lull in incidence and aim for elimination. This is feasible in some sleeping sickness foci but must be planned and paid for increasingly by the endemic countries themselves. The control and elimination of T. b. gambiense sleeping sickness may be seen as a public good, as appropriate strategies depend on local health services for surveillance and treatment, but public-private funding mechanisms should not be excluded. It is timely to take up the tools available and invest in new tools - including novel financial instruments - to eliminate this disease from Africa. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22726645 [PubMed - in process]

7.	An Pediatr (Barc). 2012 Jun 20. [Epub ahead of print] [Pericardial effusion in a case of hemophagocytic lymphohistiocytosis secondary to leishmaniasis.] [Article in Spanish] Cerdán Vera MT, Bernal Ferrer AM, Sequi Canet JM, Sifre Aranda M. Source Servicio de Pediatría, Hospital Francesc de Borja, Gandía, Valencia, España.
	PMID: 22726300 [PubMed - as supplied by publisher]

8.	Expert Opin Drug Deliv. 2012 Jun 24. [Epub ahead of print] Drug delivery systems for the topical treatment of cutaneous leishmaniasis. Carneiro G, Aguiar MG, Fernandes AP, Ferreira LA. Source Federal University of Minas Gerais, Faculty of Pharmacy , Belo Horizonte, Minas Gerais , Brazil. Abstract Introduction: The parenteral administration of pentavalent antimonials for the treatment of all forms of leishmaniasis, including cutaneous leishamniasis (CL), has several limitations. Therapy is long, requiring repeated doses and the adverse reactions are frequent. Topical treatment is an attractive alternative for CL, offering significant advantages over systemic therapy: fewer adverse effects, ease of administration, and lower costs. Areas covered: This review covers, from 1984 to the present, the progress achieved for the development of topical treatment for CL, using different drugs such as paromomycin (PA), imiquimod, amphotericin B (AmB), miltefosine, and buparvaquone. PA is the most commonly studied drug, followed by AmB and Imiquimod. These drugs were incorporated in conventional dosage forms or loaded in lipid nanocarries, which have been used mainly for improved skin delivery and antileishmanial activity. Expert opinion: Developing an effective topical treatment for CL using these antileishmanial drugs still remains a great challenge. Insights into the most promising delivery strategies to improve treatment of CL with PA and AmB using conventional dosage forms, lipid nanocarriers, and combined therapy are presented and discussed. The results obtained with combined therapy and alternative delivery systems are promising perspectives for improving topical treatment of CL.
	PMID: 22724539 [PubMed - as supplied by publisher]

9.	J Proteome Res. 2012 Jun 22. [Epub ahead of print] Metabolic characterization of Leishmania major infection in activated and non-activated macrophages. Lamour SD, Choi BS, Keun HC, Muller I, Saric J. Abstract Infection with Leishmania spp. can lead to a range of symptoms in the affected individual, depending on underlying immune-metabolic processes. The macrophage activation state plays a key role hereby. Whereas the L-arginine pathway has been described in detail as the main biochemical process responsible for either nitric oxide mediated parasite killing (classical activation) or amplification of parasite replication (alternative activation), we were interested in a wider characterisation of metabolic events in vitro. We therefore assessed cell growth medium, parasite extract, and intra- and extracellular metabolome of activated and non-activated macrophages, in presence and absence of Leishmania major. A metabolic profiling approach was applied combining (1)H NMR spectroscopy with multi- and univariate data treatment. Metabolic changes were observed along both conditional axes i.e. infection state and macrophage activation, whereby significantly higher levels of potential parasite end products were found in parasite exposed samples including succinate, acetate and alanine, compared to uninfected macrophages. The different macrophage activation states were mainly discriminated by varying glucose consumption. The presented profiling approach allowed us to obtain a metabolic snapshot of the individual biological compartments in the assessed macrophage culture experiments and will be a valuable read out system for further multiple component in vitro studies.
	PMID: 22724526 [PubMed - as supplied by publisher]