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Sent on Sunday, 2011 Apr 03Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | ILAR J. 2011 Feb 8;52(1):e8-15.The brazilian legal framework on the scientific use of animals.Filipecki AT, Machado CJ, Valle S, Teixeira Mde O.Escola Politécnica de Saúde Joaquim Venâncio (EPSJV/LIC-Provoc), Fundação Oswaldo Cruz (Fiocruz), Av. Brasil, 4365, Manguinhos, Rio de Janeiro, Brazil, CEP 21040-360 or email afilipecki@fiocruz.br. AbstractBrazil has an exceptionally dynamic research sector in Latin America in health, biotechnology, and pharmacology, backed by defined government policies on science and technology and a health research agenda focusing on important neglected diseases: malaria, leishmaniasis, Chagas disease, turberculosis, leprosy, and dengue. The Brazilian health research policy promotes partnerships and networks among scientists in academic institutions in both wealthy industrialized and disease-endemic countries, and in these efforts the government's guidelines for animal use in biomedical research are considered fundamental to guarantee both animal welfare and the quality of research. Given international discussions of animal experimentation regulations and guidelines, in this article we describe current Brazilian legislation governing the use of animals in scientific investigations. We conclude that, despite advances in the implementation of the 3Rs (reduction, refinement, replacement), the new regulatory framework does not sufficiently incorporate ethical considerations, lacking explicit reference to the 3Rs as well as measures for their full application. The more humane use of animals in research will depend on the approach adopted by Brazil's National Council for the Control of Animal Experimentation to promote the 3Rs and to improve internal regulations as well as data collection and analysis in research institutions. In Brazil as elsewhere, one of the greatest challenges to policymakers is to harmonize the myriad and intertwined legal provisions without hindering biomedical research. |
PMID: 21454922 [PubMed - in process] | |
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2. | J Biol Chem. 2011 Mar 15. [Epub ahead of print]The crystal structure of the Leishmania major deoxyuridine triphosphate nucleotidohydrolase in complex with nucleotide analogues, dUMP and deoxyuridine.Hemsworth GR, Moroz OV, Fogg MJ, Scott B, Bosch-Navarrete C, Gonzalez-Pacanowska D, Wilson KS.University of York, United Kingdom; AbstractMembers of the Leishmania genus are the causative agents of the life-threatening disease leishmaniasis. New drugs are sought after due to increasing resistance and the adverse side effects with current treatments. The knowledge that dUTPase is an essential enzyme and that the all α-helical dimeric kinetoplastid dUTPases have totally different structures compared to the trimeric β-sheet type dUTPase possessed by most organisms, including humans, make the dimeric enzymes attractive drug targets. Here we present crystal structures of the Leishmania major dUTPase in complex with substrate analogues, the product dUMP and a substrate fragment, and of the homologous C. jejuni dUTPase in complex with a triphosphate substrate analogue. The metal binding properties of both enzymes are shown to be dependent upon the ligand identity, a previously unseen characteristic of this family. Furthermore, structures of the Leishmania enzyme in the presence of dUMP and deoxyuridine coupled with tryptophan fluorescence quenching indicate that occupation of the phosphate binding region is essential for induction of the closed conformation and hence for substrate binding. These findings will aid in the development of dUTPase inhibitors as potential new lead anti-trypanosomal compounds. |
PMID: 21454646 [PubMed - as supplied by publisher] | |
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3. | Heart Lung. 2011 Mar 29. [Epub ahead of print]Recurrent fever of unknown origin (FUO): Aseptic meningitis, hepatosplenomegaly, pericarditis and a double quotidian fever due to juvenile rheumatoid arthritis (JRA).Cunha BA, Hage JE, Nouri Y.Infectious Disease Division, Winthrop-University Hospital, Mineola, New York, and State University of New York School of Medicine, Stony Brook, New York. AbstractBACKGROUND: Fever of unknown origin (FUO) has been defined as a fever of ≥101°F that persists for 3 weeks or more. It is not readily diagnosed after 1 week of intensive in-hospital testing or after intensive outpatient or inpatient testing. Fevers of unknown origin may be caused by infectious diseases, malignancies, collagen vascular diseases, or a variety of miscellaneous disorders. The relative distribution of causes of FUOs is partly age-related. In the elderly, the preponderance of FUOs is attributable to neoplastic and infectious etiologies, whereas in children, collagen vascular diseases, neoplasms, and viral infectious disease predominate. The diagnostic approach to FUOs depends on a careful analysis of the history, physical findings, and laboratory tests. Most patients with FUOs exhibit localizing findings that should direct the diagnostic workup and limit diagnostic possibilities. The most perplexing causes of FUOs involve those without specific diagnostic tests, e.g., juvenile rheumatoid arthritis (JRA) or adult Still's disease. In a young adult with FUO, if all of the cardinal symptoms are present, JRA may present either a straightforward or an elusive diagnosis, if key findings are absent or if the diagnosis goes unsuspected. METHODS: We present a 19-year-old man with a recurrent FUO. His illness began 3 years before admission and has recurred twice since. In the past, he did not manifest arthralgias, arthritis, or a truncal rash. On admission, he presented with an FUO with hepatosplenomegaly, aseptic meningitis, and pericarditis. An extensive diagnostic workup ruled out lymphoma and leukemia. Moreover, a further extensive workup eliminated infectious causes of FUO appropriate to his clinical presentation, ie, tuberculosis, histoplasmosis, brucellosis, Q fever, typhoid fever, Epstein-Barr virus, infectious mononucleosis, cytomegalovirus, human herpes virus (HHV)-6, babesiosis, ehrlichiosis, viral hepatitis, and Whipple's disease. RESULTS: The diagnosis of JRA was based on the exclusion of infectious and neoplastic disorders in a young adult with hepatosplenomegaly, aseptic meningitis, pericarditis, and a double quotidian fever. With JRA, tests for rheumatic diseases are negative, as they were in this case. The only laboratory abnormalities in this patient included elevated serum transaminases, a mildly elevated erythrocyte sedimentation rate, and a moderately elevated level of serum ferritin. CONCLUSION: Diagnostic fever curves are most helpful in cases where the diagnosis is most elusive, as was the case here. Relatively few disorders are associated with a double quotidian fever, ie, visceral leishmaniasis, mixed malarial infections, right-sided gonococcal acute bacterial endocarditis, and JRA. Because the patient received antipyretics during the first week of admission, fever was not present. After infectious disease consultation during week 2 of hospitalization, antipyretics were discontinued, and a double quotidian fever was present, which provided the key diagnostic clue in this case. Copyright © 2011 Elsevier Inc. All rights reserved. |
PMID: 21453973 [PubMed - as supplied by publisher] | |
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4. | Lancet Infect Dis. 2011 Apr;11(4):322-5.Visceral leishmaniasis: elimination with existing interventions.Matlashewski G , Arana B, Kroeger A, Battacharya S, Sundar S, Das P, Sinha PK, Rijal S, Mondal D, Zilberstein D, Alvar J.Special Programme for Research and Training in Tropical Diseases, WHO, Geneva, Switzerland; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada. AbstractThe world's burden of infectious diseases can be substantially reduced by more-effective use of existing interventions. Advances in case detection, diagnosis, and treatment strategies have made it possible to consider the elimination of visceral leishmaniasis in the Indian subcontinent. The priority must now be to effectively implement existing interventions at the community level by actively finding cases in endemic villages and treating them with single-dose liposomal amphotericin B at primary-health-care centres. Once the elimination target of one case per 10 000 population has been reached, combination therapies involving miltefosine and paromomycin can be introduced to ensure long-term availability of several drugs for visceral leishmaniasis and to protect against resistance. Copyright © 2011 Elsevier Ltd. All rights reserved. |
PMID: 21453873 [PubMed - in process] | |
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