What's new for 'Trypanosomatids' in PubMed

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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 12

1.	Int J Microbiol. 2010;2010. pii: 819060. Epub 2010 Jul 12. Frequency of drug resistance gene amplification in clinical leishmania strains. Mary C, Faraut F, Deniau M, Dereure J, Aoun K, Ranque S, Piarroux R. Laboratoire de Parasitologie-Mycologie, Hôpital de la Timone, 264 Rue Saint Pierre, 13385 Marseille cedex 5, France. Abstract Experimental studies about Leishmania resistance to metal and antifolates have pointed out that gene amplification is one of the main mechanisms of drug detoxification. Amplified genes code for adenosine triphosphate-dependent transporters (multidrug resistance and P-glycoproteins P), enzymes involved in trypanothione pathway, particularly gamma glutamyl cysteine synthase, and others involved in folates metabolism, such as dihydrofolate reductase and pterine reductase. The aim of this study was to detect and quantify the amplification of these genes in clinical strains of visceral leishmaniasis agents: Leishmania infantum, L. donovani, and L. archibaldi. Relative quantification experiments by means of real-time polymerase chain reaction showed that multidrug resistance gene amplification is the more frequent event. For P-glycoproteins P and dihydrofolate reductase genes, level of amplification was comparable to the level observed after in vitro selection of resistant clones. Gene amplification is therefore a common phenomenon in wild strains concurring to Leishmania genomic plasticity. This finding, which corroborates results of experimental studies, supports a better understanding of metal resistance selection and spreading in endemic areas.
	PMID: 20706666 [PubMed - in process]
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2.	PLoS Negl Trop Dis. 2010 Aug 10;4(8). pii: e792. Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. I. Parasitological, Hematological and Pathological Parameters. Chamond N, Cosson A, Blom-Potar MC, Jouvion G, D'Archivio S, Medina M, Droin-Bergère S, Huerre M, Goyard S, Minoprio P. Laboratoire d'Immunobiologie des Infections à Trypanosoma, Département d'Immunologie, Institut Pasteur, Paris, France. Abstract African trypanosomiasis is a severe parasitic disease that affects both humans and livestock. Several different species may cause animal trypanosomosis and although Trypanosoma vivax (sub-genus Duttonella) is currently responsible for the vast majority of debilitating cases causing great economic hardship in West Africa and South America, little is known about its biology and interaction with its hosts. Relatively speaking, T. vivax has been more than neglected despite an urgent need to develop efficient control strategies. Some pioneering rodent models were developed to circumvent the difficulties of working with livestock, but disappointedly were for the most part discontinued decades ago. To gain more insight into the biology of T. vivax, its interactions with the host and consequently its pathogenesis, we have developed a number of reproducible murine models using a parasite isolate that is infectious for rodents. Firstly, we analyzed the parasitical characteristics of the infection using inbred and outbred mouse strains to compare the impact of host genetic background on the infection and on survival rates. Hematological studies showed that the infection gave rise to severe anemia, and histopathological investigations in various organs showed multifocal inflammatory infiltrates associated with extramedullary hematopoiesis in the liver, and cerebral edema. The models developed are consistent with field observations and pave the way for subsequent in-depth studies into the pathogenesis of T. vivax - trypanosomosis.
	PMID: 20706595 [PubMed - in process]
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3.	Int J Antimicrob Agents. 2010 Jul;36(1):79-83. Epub 2010 May 7. A comparative study of posaconazole and benznidazole in the prevention of heart damage and promot ion of trypanocidal immune response in a murine model of Chagas disease. Olivieri BP, Molina JT, de Castro SL, Pereira MC, Calvet CM, Urbina JA, Araújo-Jorge TC. Laboratory for Innovations in Therapy, Education and Bioproducts, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil. olivieri@ioc.fiocruz.br Abstract A comparative study was performed between the trypanocidal efficacy of and associated immune response to benznidazole and posaconazole in a murine model of Chagas disease. Both drugs led to 100% survival, suppression of parasitaemia and reduction of specific anti-Trypanosoma cruzi antibodies following chronic infection. All posaconazole-treated animals had negative haemocultures at 54 days post infection, whilst 50% of those treated with benznidazole had positive results. Although both drugs were effective in reducing parasitism and inflammation in the heart, posaconazole-treated animals had plasma enzymatic levels of cardiac lesion that were indistinguishable from those of uninfected mice, whilst for benznidazole the enzyme levels were significantly higher than those of uninfected controls 31 days after the start of treatment. Posaconazole was more effective than benznidazole in controlling spleen enlargement and unspecific splenocyte proliferation in the early acute phase, but allowed higher levels of activation of CD4(+) and CD8(+) T-cells in the late acute phase when the adaptive immune response takes control of the infection. These results support the notion that posaconazole could be superior to benznidazole for the treatment of T. cruzi infection in humans. (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
	PMID: 20452188 [PubMed - indexed for MEDLINE]
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4.	Acta Trop. 2010 Jul-Aug;115(1-2):5-13. Epub 2010 Apr 9. Chagas disease: 100 years after its discovery. A systemic review. Coura JR, Borges-Pereira J. Laboratório de Doenças Parasitárias, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brazil. coura@ioc.fiocruz.br Abstract Although Chagas disease was only discovered in 1909, it began millions of years ago as an enzootic disease among wild animals. Its transmission to man began accidentally as an anthropozoonosis when mankind invaded wild ecotopes. Endemic Chagas disease became established as a zoonosis over the last 200-300 years through deforestation for agriculture and livestock rearing and adaptation of triatomines to dwellings and to humans and domestic animals as food sources. When T. cruzi is transmitted to man, it invades the bloodstream and lymphatic system and lodges in muscle and heart tissue, the digestive system and phagocytic cells. Through this, it causes inflammatory lesions and an immune response, particularly mediated by CD4(+), CD8(+), IL2 and IL4, with cell and neuron destruction and fibrosis. These processes lead to blockage of the heart's conductive system, arrhythmias, heart failure, aperistalsis and dilatation of hollow viscera, especially the esophagus and colons. Chagas disease is characterized by an acute phase with or without symptoms, with (or more often without) T. cruzi penetration signs (inoculation chagoma or Romaña's sign), fever, adenomegaly, hepatosplenomegaly and patent parasitemia; and a chronic phase: indeterminate (asymptomatic, with normal electrocardiogram and heart, esophagus and colon X-rays) or cardiac, digestive or cardiac/digestive forms. There is great regional variation in the morbidity caused by Chagas disease: severe cardiac or digestive forms may occur in 10-50%, and indeterminate forms in the remaining, asymptomatic cases. The epidemiological and control characteristics of Chagas disease vary according to each country's ecological conditions and health policies. 2010. Published by Elsevier B.V.
	PMID: 20382097 [PubMed - indexed for MEDLINE]
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5.	Mol Biochem Parasitol. 2010 Aug;172(2):90-8. Epub 2010 Apr 2. Knockout of the gene encoding the kinetoplast-associated protein 3 (KAP3) in Trypanosoma cruzi: effect on kinetoplast organization, cell proliferation and differentiation. de Souza FS, Rampazzo Rde C, Manhaes L, Soares MJ, Cavalcanti DP, Krieger MA, Goldenberg S, Fragoso SP. Instituto Carlos Chagas, Fundação Oswaldo Cruz, Paraná, Brazil. Abstract Kinetoplast DNA (kDNA) of trypanosomatid protozoa consists of an unusual arrangement of two types of circular molecules catenated into a single network: (1) a few maxicircles that encode various mitochondrial enzyme subunits and rRNA in a cryptic pattern and (2) thousands of minicircles that encode guide RNAs (gRNAs). kDNA is associated with proteins, known as kinetoplast-associated proteins (KAPs), which condense the kDNA network. However, little is known about the KAPs of Trypanosoma cruzi, a parasite that displays different kDNA condensation patterns during its complex morphogenetic development. We cloned the T. cruzi gene encoding TcKAP3 (kinetoplast-associated protein 3). TcKAP3 is a single-copy gene that is transcribed into a 1.8-kb mRNA molecule and expressed in all stages of the parasite. Mouse antiserum raised against recombinant TcKPA3 recognized a 21.8kDa protein, which was found, by indirect immunofluorescence and immunoelectron microscopy, to be associated with the T. cruzi kinetoplast. Several features of TcKAP3, such as its small size, basic nature and similarity with KAP3 from the insect trypanosomatid Crithidia fasciculata, are consistent with a role in DNA charge neutralization and condensation. This suggests that this protein is involved in organizing the kDNA network. Gene deletion was used to investigate TcKAP3 function. Here we investigated the T. cruzi KAP3 null mutant, analyzing its fitness during proliferation, differentiation and infectivity.
	PMID: 20363262 [PubMed - indexed for MEDLINE]
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6.	Int J Parasitol. 2010 Jul;40(8):921-8. Epub 2010 Jan 22. Analysis of molecular diversity of the Trypanosoma cruzi trypomastigote small surface antigen reveals novel epitopes, evidence of positive selection and potential implications for lineage-specific serology. Bhattacharyya T, Brooks J, Yeo M, Carrasco HJ, Lewis MD, Llewellyn MS, Miles MA. Pathogen Molecular Biology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK. Tapan.Bhattacharyya@lshtm.ac.uk Abstract Chagas disease, marked by life-long chronic infection with Trypanosoma cruzi, remains a major parasitic disease in Latin America. Genetically heterogeneous, T. cruzi is divided into six discrete typing units (DTUs), most recently grouped as TcI-VI. The trypomastigote small surface antigen (TSSA) of T. cruzi has been described as the only known serological marker to identify infection by TcII-VI, as distinct from TcI. Here, by comparative analysis of a cohort of 25 reference strains representing all the known DTUs, we show that TSSA intra-specific diversity is greater than previously reported. Furthermore, TcIII and IV TSSA PCR products are, contrary to expectation, both digested by PvuII, revealing a more nuanced genotyping pattern. Amino acid sequence diversity reveals that the TSSA epitope considered to be serologically characteristic of TcII-VI is restricted to TcII, V and VI, but not of III or IV, and that the diagnostic peptide described as TcI-specific shares key features with TcIII and IV. Notably, TSSA sequences inferred greater phylogenetic affinities of TcIII and IV to TcI than to TcII, V or VI. A high ratio of non-synonymous to synonymous nucleotide substitutions (omega=1.233) indicates that the TSSA gene has been under positive selection pressure. The demonstration of lineage-specific epitopes within TcII-VI has implications for sero-epidemiological studies of Chagas disease based on this antigen. 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
	PMID: 20097201 [PubMed - indexed for MEDLINE]
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7.	J Vet Med Sci. 2010 Apr;72(4):417-24. Epub 2009 Dec 10. Isolation of Trypanosoma (Megatrypanum) theileri from dairy cattle in Taiwan. Lee YF, Cheng CC, Lin NN, Liu SA, Tung KC, Chiu YT. Department of Medical Research and Education, Taichung Veterans General Hospital, Taiwan. Abstract Although Trypanosoma (Megatrypanum) theileri, a blood parasite of bovid species, is spread widely throughout the world, it has never been reported in Taiwan. When an anti-coagulated blood sample from febrile dairy cattle was directly smeared, no parasite was observed. However, a highly distinctive morphological feature of trypanosome appeared in baby hamster kidney (BHK) cell culture inoculated with non-thrown blood buffy coat. The different stages and typical ultrastructures of trypanosome were observed in our isolate. The isolate was subsequently identified as T. theileri by species-specific PCR assay (Tth625), 18S rDNA sequencing alignment and internal transcribed spacer of ribosomal genes (ITS) as a marker for molecular phylogenetic analysis. The first T. theileri isolate in Taiwan (TWTth1) could be periodically passaged in BHK cell culture for more than one year and retained good re-cryopreservation viability. The BHK culture method would be excellent for diagnostic isolation and maintenance long-term development of this parasite. Free Article
	PMID: 20009352 [PubMed - indexed for MEDLINE]
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8.	Acta Trop. 2010 Jul-Aug;115(1-2):55-68. Epub 2009 Nov 10. Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Urbina JA. Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela. jurbina@mac.com Abstract A critical review of the development of specific chemotherapeutic approaches for the management of American Trypanosomiasis or Chagas disease is presented, including controversies on the pathogenesis of the disease, the initial efforts that led to the development of currently available drugs (nifurtimox and benznidazole), limitations of these therapies and novel approaches for the development of anti-Trypanosoma cruzi drugs, based on our growing understanding of the biology of this parasite. Among the later, the most promising approaches are ergosterol biosynthesis inhibitors such as posaconazole and ravuconazole, poised to enter clinical trials for chronic Chagas disease in the short term; inhibitors of cruzipain, the main cysteine protease of T. cruzi, essential for its survival and proliferation in vitro and in vivo; bisphosphonates, metabolic stable pyrophosphate analogs that have trypanocidal activity through the inhibition of the parasite's farnesyl-pyrophosphate synthase or hexokinase; inhibitors of trypanothione synthesis and redox metabolism and inhibitors of hypoxanthine-guanine phosphoribosyl-transferase, an essential enzyme for purine salvage in T. cruzi and related organisms. Finally, the economic and political challenges faced by development of drugs for the treatment of neglected tropical diseases, which afflict almost exclusively poor populations in developing countries, are analyzed and recent potential solutions for this conundrum are discussed. 2009 Elsevier B.V. All rights reserved.
	PMID: 19900395 [PubMed - indexed for MEDLINE]
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9.	Acta Trop. 2010 Jul-Aug;115(1-2):1-4. Epub 2009 Nov 4. Carlos Chagas: biographical sketch. Moncayo A. National Academy of Medicine, Carrera 7 No. 69-11, Bogotá DC, Colombia. amoncayo@uniandes.edu.co Abstract Carlos Chagas was born on 9 July 1878 in the farm "Bon Retiro" located close to the City of Oliveira in the interior of the State of Minas Gerais, Brazil. He started his medical studies in 1897 at the School of Medicine of Rio de Janeiro. In the late XIX century, the works by Louis Pasteur and Robert Koch induced a change in the medical paradigm with emphasis in experimental demonstrations of the causal link between microbes and disease. During the same years in Germany appeared the pathological concept of disease, linking organic lesions with symptoms. All these innovations were adopted by the reforms of the medical schools in Brazil and influenced the scientific formation of Chagas. Chagas completed his medical studies between 1897 and 1903 and his examinations during these years were always ranked with high grades. Oswaldo Cruz accepted Chagas as a doctoral candidate and directed his thesis on "Hematological studies of Malaria" which was received with honors by the examiners. In 1903 the director appointed Chagas as research assistant at the Institute. In those years, the Institute of Manguinhos, under the direction of Oswaldo Cruz, initiated a process of institutional growth and gathered a distinguished group of Brazilian and foreign scientists. In 1907, he was requested to investigate and control a malaria outbreak in Lassance, Minas Gerais. In this moment Chagas could not have imagined that this field research was the beginning of one of the most notable medical discoveries. Chagas was, at the age of 28, a Research Assistant at the Institute of Manguinhos and was studying a new flagellate parasite isolated from triatomine insects captured in the State of Minas Gerais. Chagas made his discoveries in this order: first the causal agent, then the vector and finally the human cases. These notable discoveries were carried out by Chagas in twenty months. At the age of 33 Chagas had completed his discoveries and published the scientific articles that gave him world recognition and a deserved high place in medical history. After the publication of his classic article the world paid homage to Chagas who was elected member of the National Academy of Medicine of Brazil on 26 October 1910, and at the age of 31, of other National Academies of the continent. The Committee of Hygiene of the Society of Nations, precursor of the World Health Organization, was created in 1929. Chagas was elected member of this Committee from its inception until 1933. The example of Chagas' life can be summarized in his interest that medical research should be translated into concrete benefits for human beings because he was convinced that disease had not only biological but social determinants as well. Carlos Chagas was a laboratory researcher, a clinician and a health administrator. For all these accomplishments he deserves our respect and admiration. 2009 Elsevier B.V. All rights reserved.
	PMID: 19895782 [PubMed - indexed for MEDLINE]
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10.	Acta Trop. 2010 Jul-Aug;115(1-2):35-43. Epub 2009 Aug 18. Alternative lifestyles: the population structure of Trypanosoma cruzi.Sturm NR, Campbell DA. Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. nsturm@ucla.edu Abstract The genetic palette from which the spectrum of variability in Trypanosoma cruzi has been drawn is astonishingly limited. In this review we address the roots of this unusual pedigree and the usefulness of various taxonomic markers in relation to the manifestation of clinical disease and the geographic distribution of the parasite. The circumstances leading to the population structure of the extant strains were dictated by the unusual and apparently exceedingly rare mode of genetic exchange employed in this species, that being the non-meiotic fusion of two diploid cells. Two-hybridization events have been postulated in the whole of the T. cruzi pedigree, the first of which yielded the four predominant nuclear genotypes. Hybridization may be a common occurrence among closely related strains of T. cruzi, but either infrequent or inefficient when two diverse strains attempt the process. Two of the genotypes define the parental lineages, while the other two are mosaics of the parental contributions distinguished from one another by polymorphisms accumulated after the separation of a common, homozygous hybrid progeny line. The greatest genetic complexity is seen in the result of the second fusion event between one of the original parental strains and a progeny strain. The second generation of progeny reveals the proximal consequences of fusion, maintaining widespread nuclear heterozygosity and the first examples of recombination between the genotypes involved in the second hybridization. If the genesis of the heterozygous progeny follows the same path as their predecessors, these lines will move toward homozygosity after having had the opportunity for recombination. Thus, the total number of alleles may increase to five in another few million years. 2009 Elsevier B.V. All rights reserved.
	PMID: 19695212 [PubMed - indexed for MEDLINE]
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