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Sent on Wednesday, 2010 Jan 06Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | J Parasitol. 2009 Aug;95(4):1029-33.Trypanosoma cf. varani in an imported ball python (Python reginus) from Ghana.Sato H, Takano A, Kawabata H, Une Y, Watanabe H, Mukhtar MM.Laboratory of Veterinary Parasitology, Faculty of Agriculture, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. sato7dp4@yamaguchi-u.ac.jp Peripheral blood from a ball python (Python reginus) imported from Ghana was cultured in Barbour-Stoenner-Kelly (BSK) medium for Borrelia spp. isolation, resulting in the prominent appearance of free, and clusters of, trypanosomes in a variety of morphological forms. The molecular phylogenetic characterization of these cultured trypanosomes, using the small subunit rDNA, indicated that this python was infected with a species closely related to Trypanosoma varani Wenyon, 1908, originally described in the Nile monitor lizard (Varanus niloticus) from Sudan. Furthermore, nucleotide sequences of glycosomal glyceraldehyde-3-phosphate dehydrogenase gene of both isolates showed few differences. Giemsa-stained blood smears, prepared from the infected python 8 mo after the initial observation of trypanosomes in hemoculture, contained trypomastigotes with a broad body and a short, free flagellum; these most closely resembled the original description of T. varani, or T. voltariae Macfie, 1919 recorded in a black-necked spitting cobra (Naja nigricollis) from Ghana. It is highly possible that lizards and snakes could naturally share an identical trypanosome species. Alternatively, lizards and snakes in the same region might have closely related, but distinct, Trypanosoma species as a result of sympatric speciation. From multiple viewpoints, including molecular phylogenetic analyses, reappraisal of trypanosome species from a wide range of reptiles in Africa is needed to clarify the relationship of recorded species, or to unmask unrecorded species. |
| PMID: 20050011 [PubMed - indexed for MEDLINE] | |
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| 2. | J Parasitol. 2009 Aug;95(4):781-6.Effect of polyamine-deficient chow on Trypanosoma brucei brucei infection in rats.Nishimura K, Yanase T, Nakagawa H, Matsuo S, Ohnishi Y, Yamasaki S.Laboratory of Infectious Diseases Control, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan. nisimura@vet.osakafu-u.ac.jp Polyamines are essential for proliferation of Trypanosoma brucei brucei, and feeding rats polyamine-deficient chow (PDC) decreases their blood polyamine concentrations. Proliferation of T. b. brucei (IL-tat 1.4 strain) (IL) is not restrained within PDC-fed rats. However, symptoms of IL-infected rats such as anemia decrease by PDC feeding. We reported cytokine and nitric oxide (NO) production of T. b. gambiense (Wellcome strain [WS])-infected rats were affected by PDC feeding, and WS proliferation was restrained. Therefore, we investigated whether the change in production of cytokines and NO by PDC feeding affects IL proliferation and decreases symptoms in vivo. In IL-infected PDC-fed rats, NO, interleukin (IL)-12, and tumor necrosis factor-alpha production increased while interferon-gamma and IL-10 decreased compared to normal chow-fed rats. IL proliferation was restrained by NO production when it was co-cultured with spleen cells harvested from uninfected rats. In contrast, IL proliferation in infected rats was not changed by PDC feeding, although NO production was increased. The results suggest that changes in cytokines and NO production in IL-infected rats by PDC feeding have little influence on IL proliferation. However, they may serve to decrease symptoms. |
| PMID: 20049984 [PubMed - indexed for MEDLINE] | |
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| 3. | PLoS One. 2010 Jan 1;5(1):e8538.Diacylglycerol-stimulated endocytosis of transferrin in trypanosomatids is dependent on tyrosine kinase activity.Subramanya S, Mensa-Wilmot K.Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America. Small molecule regulation of cell function is an understudied area of trypanosomatid biology. In Trypanosoma brucei diacylglycerol (DAG) stimulates endocytosis of transferrin (Tf). However, it is not known whether other trypanosomatidae respond similarly to the lipid. Further, the biochemical pathways involved in DAG signaling to the endocytic system in T. brucei are unknown, as the parasite genome does not encode canonical DAG receptors (e.g. C1-domains). We established that DAG stimulates endocytosis of Tf in Leishmania major, and we evaluated possible effector enzymes in the pathway with multiple approaches. First, a heterologously expressed glycosylphosphatidylinositol phospholipase C (GPI-PLC) activated endocytosis of Tf 300% in L. major. Second, exogenous phorbol ester and DAGs promoted Tf endocytosis in L. major. In search of possible effectors of DAG signaling, we discovered a novel C1-like domain (i.e. C1_5) in trypanosomatids, and we identified protein Tyr kinases (PTKs) linked with C1_5 domains in T. brucei, T. cruzi, and L. major. Consequently, we hypothesized that trypanosome PTKs might be effector enzymes for DAG signaling. General uptake of Tf was reduced by inhibitors of either Ser/Thr or Tyr kinases. However, DAG-stimulated endocytosis of Tf was blocked only by an inhibitor of PTKs, in both T. brucei and L. major. We conclude that (i) DAG activates Tf endocytosis in L. major, and that (ii) PTKs are effectors of DAG-stimulated endocytosis of Tf in trypanosomatids. DAG-stimulated endocytosis of Tf may be a T. brucei adaptation to compete effectively with host cells for vertebrate Tf in blood, since DAG does not enhance endocytosis of Tf in human cells. |
| PMID: 20049089 [PubMed - in process] | |
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| 4. | J Infect Dis. 2010 Jan 4. [Epub ahead of print]How to Shorten Patient Follow-Up after Treatment for Trypanosoma brucei gambiense Sleeping Sickness.Mumba Ngoyi D, Lejon V, Pyana P, Boelaert M, Ilunga M, Menten J, Mulunda JP, Van Nieuwenhove S, Muyembe Tamfum JJ, Büscher P.Department of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, and 2Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Mbuji Mayi, East Kasaï, Democratic Republic of the Congo; 3World Health Organization, Regional Office for Africa, Brazzaville, Republic of the Congo; Departments of 4Parasitology and 5Public Health, Institute of Tropical Medicine, Antwerp, Belgium. Background. Clinical management of human African trypanosomiasis requires patient follow-up of 2 years' duration. At each follow-up visit, cerebrospinal fluid (CSF) is examined for trypanosomes and white blood cells (WBCs). Shortening follow-up would improve patient comfort and facilitate control of human African trypanosomiasis. Methods. A prospective study of 360 patients was performed in the Democratic Republic of the Congo. The primary outcomes of the study were cure, relapse, and death. The WBC count, immunoglobulin M level, and specific antibody levels in CSF samples were evaluated to detect treatment failure. The sensitivity and specificity of shortened follow-up algorithms were calculated. Results. The treatment failure rate was 37%. Trypanosomes, a WBC count of 100 cells/muL, and a LATEX/immunoglobulin M titer of 1:16 in CSF before treatment were risk factors for treatment failure, whereas human immunodeficiency virus infection status was not a risk factor. The following algorithm, which had 97.8% specificity and 94.4% sensitivity, is proposed for shortening the duration of follow-up: at 6 months, patients with trypanosomes or a WBC count of 50 cells/muL in CSF are considered to have treatment failure, whereas patients with a CSF WBC count of 5 cells/muL are considered to be cured and can discontinue follow-up. At 12 months, the remaining patients (those with a WBC count of 6-49 cells/muL) need a test of cure, based on trypanosome presence and WBC count, applying a cutoff value of 20 cells/muL. Conclusion. Combining criteria for failure and cure allows follow-up of patients with second-stage human African trypanosomiasis to be shortened to a maximum duration of 12 months. |
| PMID: 20047500 [PubMed - as supplied by publisher] | |
| 5. | J Med Chem. 2010 Jan 4. [Epub ahead of print]Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives.Fotie J, Kaiser M, Delfín DA, Manley J, Reid CS, Paris JM, Wenzler T, Maes L, Mahasenan KV, Li C, Werbovetz KA.Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210. The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC(50) values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to >18000. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed an IC(50) value of 0.014 muM against these parasites and a selectivity index of 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (>14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives. |
| PMID: 20047276 [PubMed - as supplied by publisher] | |
| 6. | Am J Trop Med Hyg. 2009 Dec;81(6):1041-9.Genotyping of Trypanosoma cruzi: systematic selection of assays allowing rapid and accurate discrimination of all known lineages.Lewis MD, Ma J, Yeo M, Carrasco HJ, Llewellyn MS, Miles MA.Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. michael.lewis@lshtm.ac.uk Trypanosoma cruzi, the agent of Chagas disease, can be subdivided into six discrete typing units (DTUs), TcI, TcIIa, TcIIb, TcIIc, TcIId or TcIIe, each having distinct epidemiologically important features. Dozens of genetic markers are available to determine the DTU to which a T. cruzi isolate belongs, but there is no consensus on which should be used. We selected five assays: three polymerase chain reaction (PCR)-restriction fragment length polymorphisms based on single nucleotide polymorphisms (SNPs) in the HSP60, Histone H1, and GPI loci, and PCR product size polymorphism of the LSU rDNA and mini-exon loci. Each assay was tested for its capacity to differentiate between DTUs using a panel of 48 genetically diverse T. cruzi clones. Some markers allowed unequivocal identification of individual DTUs, however, only by using a combination of multiple markers could all six DTUs be resolved. Based upon the results we recommend a triple-assay comprising the LSU rDNA, HSP60 and GPI markers for reliable, rapid, low-cost DTU assignment. |
| PMID: 19996435 [PubMed - indexed for MEDLINE] | |
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| 7. | Am J Trop Med Hyg. 2009 Dec;81(6):1035-40.Seroprevalence of Trypanosoma cruzi in rural Ecuador and clustering of seropositivity within households.Black CL, Ocaña-Mayorga S, Riner DK, Costales JA, Lascano MS, Arcos-Terán L, Preisser JS, Seed JR, Grijalva MJ.Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. blackc@uga.edu We performed a cross-sectional study of Trypanosoma cruzi seroprevalence in 14 communities in three provinces of Ecuador and estimated the magnitude of the association of seropositive individuals within households. A total of 3,286 subjects from 997 households were included. Seroprevalence was 5.7%, 1.0%, and 3.6% in subjects in the Manabí, Guayas, and Loja provinces, respectively. Seroprevalence increased with increasing age in Manabí and Guayas, whereas in Loja, the highest prevalence occurred in children <or= 10 years of age. In the coastal provinces, clustering of seropositives within households was not observed after adjustment for other household factors. However, in the Andean province of Loja, the odds of seropositivity were more than two times greater for an individual living in a household with another seropositive person. Our results indicate that transmission of T. cruzi is ongoing in Ecuador, although intensity of transmission and mechanisms of interaction between humans and the insect vectors of disease vary between geographic regions. |
| PMID: 19996434 [PubMed - indexed for MEDLINE] | |
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| 8. | Parasite Immunol. 2009 Nov;31(11):673-85.The role of parasite persistence in pathogenesis of Chagas heart disease.Gutierrez FR, Guedes PM, Gazzinelli RT, Silva JS.Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil. Chagas disease (CD) is caused by the infection with the protozoan haemoflagellate Trypanosoma cruzi. This disease is still a great menace to public health, and is largely neglected as it affects mostly the poorest populations of Latin America. Nonetheless, there are neither effective diagnostic markers nor therapeutic options to accurately detect and efficiently cure this chronic infection. In spite of the great advances in the knowledge of the biology of natural transmission, as well as the immunobiology of the host-parasite interaction, the understanding of the pathogenesis of CD remains largely elusive. In the recent decades, a controversy in the research community has developed about the relevance of parasite persistence or autoimmune phenomena in the development of chronic cardiac pathology. One of the most notable aspects of chronic CD is the progressive deterioration of cardiac function, derived mostly from structural derangement, as a consequence of the intense inflammatory process. Here we review the evidence supporting the multifactorial nature of Chagas heart disease comprising pathogen persistence and altered host immunoregulatory mechanisms. |
| PMID: 19825107 [PubMed - indexed for MEDLINE] | |
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| 9. | Bioorg Med Chem. 2009 Nov 1;17(21):7500-9. Epub 2009 Sep 15.5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene.Gerpe A, Alvarez G, Benítez D, Boiani L, Quiroga M, Hernández P, Sortino M, Zacchino S, González M, Cerecetto H.Departamento de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases. |
| PMID: 19811923 [PubMed - indexed for MEDLINE] | |
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| 10. | Bioorg Med Chem Lett. 2009 Oct 15;19(20):5936-9. Epub 2009 Aug 20.Selective inactivation of triosephosphate isomerase from Trypanosoma cruzi by brevifolin carboxylate derivatives isolated from Geranium bellum Rose.Gayosso-De-Lucio J, Torres-Valencia M, Rojo-Domínguez A, Nájera-Peña H, Aguirre-López B, Salas-Pacheco J, Avitia-Domínguez C, Téllez-Valencia A.Area Académica de Farmacia, Universidad Autónoma del Estado de Hidalgo, Exhacienda La Concepción, Tilcuautla, Hidalgo 42160, Mexico. In the search of molecules that can serve as leads in the design of a new drug for the treatment of Chagas' disease, we found that some brevifolin carboxylate derivatives isolated from Geranium bellum Rose, inactivate triosephosphate isomerase from Trypanosoma cruzi (TcTIM) in a species-specific manner. After spectroscopic characterization, these compounds were identified as methylbrevifolin carboxylate (1), ethylbrevifolin carboxylate (2), butylbrevifolin carboxylate (3) and the methylated derivate methyl tri-O-methylbrevifolin carboxylate (4). The concentrations required to inactivate fifty percent the activity of TcTIM were 6.5, 8 and 14 microM of 1, 2 and 3, respectively, while compound 4 had no inhibitory effect. Molecular docking simulations of 1 on the structure of TcTIM showed that residues of both monomers interact with the compound. These compounds are very selective with respect to the parasite enzyme, since they showed no effect on the activity of human TIM at concentrations as high as 1mM. In conclusion, the brevifolin carboxylate derivatives described here are excellent leads in the search of a new chemotherapy for the treatment of this disease. |
| PMID: 19733070 [PubMed - indexed for MEDLINE] | |
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