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Sent on Sunday, 2009 Feb 22Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
- 1: RNA. 2009 Feb 18. [Epub ahead of print]
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Kinetoplastid guide RNA biogenesis is dependent on subunits of the mitochondrial RNA binding complex 1 and mitochondrial RNA polymerase.
Biology Centre, Institute of Parasitology, Czech Academy of Sciences and Faculty of Natural Sciences, University of South Bohemia, Ceské Budejovice (Budweis), Czech Republic.
The mitochondrial RNA binding complex 1 (MRB1) is a recently discovered complex of proteins associated with the TbRGG1 and TbRGG2 proteins in Trypanosoma brucei. Based on the phenotype caused by down-regulation of these two proteins, it was proposed to play an unspecified role in RNA editing. RNAi silencing of three newly characterized protein subunits, guide RNA associated proteins (GAPs) 1 and 2 as well as a predicted DExD/H-box RNA helicase, show they are essential for cell growth in the procyclic stage. Furthermore, their down-regulation leads to inhibition of editing in only those mRNAs for which minicircle-encoded guide (g) RNAs are required. However, editing remains unaffected when the maxicircle-encoded cis-acting gRNA is employed. Interestingly, all three proteins are necessary for the expression of the minicircle-encoded gRNAs. Moreover, down-regulation of a fourth assayed putative MRB1 subunit, Nudix hydrolase, does not appear to destabilize gRNAs, and down-regulation of this protein has a general impact on the stability of maxicircle-encoded RNAs. GAP1 and 2 are also essential for the survival of the bloodstream stage, in which the gRNAs become eliminated upon depletion of either protein. Immunolocalization revealed that GAP1 and 2 are concentrated into discrete spots along the mitochondrion, usually localized in the proximity of the kinetoplast. Finally, we demonstrate that the same mtRNA polymerase known to transcribe the maxicircle mRNAs may also have a role in expression of the minicircle-encoded gRNAs.
PMID: 19228586 [PubMed - as supplied by publisher]
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Related Articles
- TbRGG2, an essential RNA editing accessory factor in two Trypanosoma brucei life cycle stages. [J Biol Chem. 2008]
- Dyskinetoplastic Trypanosoma brucei contains functional editing complexes. [Eukaryot Cell. 2003]
- A population study of the minicircles in Trypanosoma cruzi: predicting guide RNAs in the absence of empirical RNA editing. [BMC Genomics. 2007]
- ReviewInsertional and deletional RNA editing in trypanosome mitochondria. [Nucleic Acids Symp Ser. 1997]
- ReviewRNA editing in trypanosomes. The us(e) of guide RNAs. [Mol Biol Rep. 1992]
- Patient Drug Information
- Allopurinol (Aloprim® , Zyloprim® ) Allopurinol is used to treat gout, high levels of uric acid in the body caused by certain cancer medications, and kidney stones. Allopurinol is in a class of medications called xanthine oxidase inhibitors. It works by re...
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- 2: Trop Med Int Health. 2009 Feb 17. [Epub ahead of print]
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PCR and direct agglutination as Leishmania infection markers among healthy Nepalese subjects living in areas endemic for Kala-Azar.
Unit of Molecular Parasitology, Institute of Tropical Medicine, Antwerpen, Belgium.
Summary Objective To compare a PCR assay and direct agglutination test (DAT) for the detection of potential markers of Leishmania infection in 231 healthy subjects living in a kala-azar endemic focus of Nepal. Methods The sample was composed of 184 (80%) persons without any known history of KA and not living in the same house as known kala-azar cases (HNK), 24 (10%) Healthy Household Contacts (HHC) and 23 (10%) past kala-azar cases which had been successfully treated (HPK). Results PCR and DAT positivity scores were, respectively: HNK, 17.6% and 5.6%; HHC, 12.5% and 20.8%; HPK, 26.1% and 95.7%. The ratio PCR-positives/DAT-positives was significantly higher in HNK (ratio = 3.1) than in HHC (ratio = 0.6, P = 0.036) and in HPK (ratio = 0.2, P = 0.012). The ratio PCR-positives/DAT-positives did not significantly differ between HHC (ratio = 0.6) and HPK (ratio = 0.2, P = 0.473). The positive agreement index between PCR and DAT in HNK was 5%; in HHC, 0%; in HPK, 43%. Conclusions Our study highlights the specific character of PCR and DAT for the exploration of Leishmania asymptomatic infections. PCR is probably more informative for very recent infections among HNK, while DAT provides more information among HHC and HPK, a feature likely related to the power of serology to track less recent infections.
PMID: 19228350 [PubMed - as supplied by publisher]
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- Superiority of dat over elisa as a diagnostic and seroepidemiological tool for the diagnosis of Indian kala-azar. [Indian J Med Microbiol. 2004]
- Epidemiological study of kala-azar by direct agglutination test in two rural communities of eastern Nepal. [Trop Med Int Health. 2004]
- Direct agglutination test for diagnosis and sero-epidemiological survey of kala-azar in the Sudan. [Trans R Soc Trop Med Hyg. 1991]
- Review[Feline leishmaniasis: what's the epidemiological role of the cat?] [Parassitologia. 2004]
- ReviewKala-azar as an AIDS-related opportunistic infection. [AIDS Patient Care STDS. 1999]
- 3: Trop Med Int Health. 2009 Feb 17. [Epub ahead of print]
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Comparison of operational criteria for treatment outcome in gambiense human African trypanosomiasis.
Institut National de Recherche Biomédicale, Avenue de la Démocratie, Kinshasa, Democratic Republic of the Congo.
Summary Objective To develop a simple and standard operational decision tool for the diagnosis of relapse after treatment for human African trypanosomiasis (HAT), by evaluating the performance of several criteria currently used by HAT control programs and research projects. Methods We identified 10 different criteria for relapse, based on trypanosome presence and/or white blood cell count in cerebrospinal fluid, and compared their specificity, sensitivity and time to diagnosis on a data set containing 63 relapsed and 247 cured T.b. gambiense patients. Results At any time point, the criterion 'Trypanosomes present and/or a cerebrospinal white blood cell count >/=50/mul' allowed accurate and timely detection of HAT relapse, irrespective of disease stage. This criterion was 13-25% more sensitive (P </= 0.013) than trypanosome detection alone and was >97% specific. Lumbar punctures at the end of treatment and at 3-month post-treatment provided limited clinical information. Conclusions Adequate detection of relapse was possible with a simple criterion but these findings should be validated in a prospective study before adoption in clinical practice.
PMID: 19228348 [PubMed - as supplied by publisher]
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Related Articles
- Novel markers for treatment outcome in late-stage Trypanosoma brucei gambiense trypanosomiasis. [Clin Infect Dis. 2008]
- Treatment outcomes and risk factors for relapse in patients with early-stage human African trypanosomiasis (HAT) in the Republic of the Congo. [Bull World Health Organ. 2006]
- Stage determination and therapeutic decision in human African trypanosomiasis: value of polymerase chain reaction and immunoglobulin M quantification on the cerebrospinal fluid of sleeping sickness patients in Côte d'Ivoire. [Trop Med Int Health. 2003]
- Review[Human African trypanosomiasis] [C R Seances Soc Biol Fil. 1996]
- Review[Criteria for diagnosis of the neurological stage of human African trypanosomiasis: update and perspectives] [Med Trop (Mars). 2008]
- 4: Acta Trop. 2009 Mar;109(3):219-25. Epub 2008 Nov 25.
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Antiproliferative effect of sera from chagasic patients on Trypanosoma cruzi epimastigotes. Involvement of xanthine oxidase.
School of Medicine, CAECIS, Universidad Abierta Interamericana, Montes de Oca 745, 1270 Buenos Aires, Argentina.
Serum from asymptomatic or symptomatic (with cardiovascular manifestations) chagasic patients depleted of the complement system displayed an antiproliferative effect on Trypanosoma cruzi epimastigotes, RA strain, when added to the growth medium. This effect was also observed when patient's serum was depleted of specific antibodies. The antiproliferative effect was both time and concentration dependent. It was confined to the non-dialyzable, high molecular weight, fraction of the serum. This effect was abrogated by allopurinol and catalase, and enhanced by N-ethylmaleimide. Xanthine oxidoreductase and xanthine oxidase activities were increased in the chagasic sera, while catalase activity remained unchanged. Parasites exposed to chagasic sera showed a decrease in Fe/superoxide dismutase activity as well as an increase in membrane lipoperoxidation. Our data provides evidence to support the idea that the antiproliferative activity observed in sera from chagasic patients may be due, at least partially, to a direct effect of hydrogen peroxide on the epimastigotes of T. cruzi. The increase of hydrogen peroxide to antiproliferative levels might result from an increase in xanthine oxidase activity in the serum of patients infected with the parasite.
PMID: 19073131 [PubMed - indexed for MEDLINE]
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Related Articles
- Epitopes common to Trypanosoma cruzi and mammalian tissues are recognized by sera from Chagas' disease patients: prognosis value in Chagas disease. [Acta Trop. 1996]
- Presence of autoantibodies against HeLa small nuclear ribonucleoproteins in chagasic and non-chagasic cardiac patients. [Braz J Med Biol Res. 2004]
- Reactivity of chagasic sera with crude and highly purified glycosphingolipid fractions from Trypanosoma cruzi epimastigotes. [J Clin Lab Anal. 1994]
- ReviewAnti-alpha-galactosyl antibodies in chagasic patients. Possible biological significance. [Braz J Med Biol Res. 1988]
- ReviewViews on the autoimmunity hypothesis for Chagas disease pathogenesis. [FEMS Immunol Med Microbiol. 2003]
- 5: Acta Trop. 2009 Mar;109(3):199-207. Epub 2008 Nov 20.
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Trypanosoma rangeli isolates of bats from Central Brazil: genotyping and phylogenetic analysis enable description of a new lineage using spliced-leader gene sequences.
Departamento de Parasitologia, Universidade de São Paulo, São Paulo, SP, Brazil.
Trypanosoma rangeli infects several mammalian orders but has never confidently been described in Chiroptera, which are commonly parasitized by many trypanosome species. Here, we described trypanosomes from bats captured in Central Brazil identified as T. rangeli, T. dionisii, T. cruzimarinkellei and T. cruzi. Two isolates, Tra643 from Platyrrhinus lineatus and Tra1719 from Artibeus planirostris were identified as T. rangeli by morphological, biological and molecular methods, and confirmed by phylogenetic analyses. Analysis using SSU rDNA sequences clustered these bat trypanosomes together with T. rangeli from other hosts, and separated them from other trypanosomes from bats. Genotyping based on length and sequence polymorphism of PCR-amplified intergenic spliced-leader gene sequences assigned Tra1719 to the lineage A whereas Tra643 was shown to be a new genotype and was assigned to the new lineage E. To our knowledge, these two isolates are the earliest T. rangeli from bats and the first isolates from Central Brazil molecularly characterized. Rhodnius stali captured for this study was found infected by T. rangeli and T. cruzi.
PMID: 19063857 [PubMed - indexed for MEDLINE]
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Related Articles
- A new species of trypanosome, Trypanosoma desterrensis sp. n., isolated from South American bats. [Parasitology. 2003]
- Comparative phylogeography of Trypanosoma rangeli and Rhodnius (Hemiptera: Reduviidae) supports a long coexistence of parasite lineages and their sympatric vectors. [Mol Ecol. 2007]
- Phylogenetic diversity of bat trypanosomes of subgenus Schizotrypanum based on multilocus enzyme electrophoresis, random amplified polymorphic DNA, and cytochrome b nucleotide sequence analyses. [Infect Genet Evol. 2003]
- ReviewCharacterization of Trypanosoma rangeli strains isolated in Central and South America: an overview. [Mem Inst Oswaldo Cruz. 1999]
- Review[Review of the biologic and diagnostic aspects of Trypanosoma (Herpetosoma) rangeli] [Rev Soc Bras Med Trop. 1998]
- 6: Acta Trop. 2009 Mar;109(3):187-93. Epub 2008 Nov 20.
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Differential distribution of Trypanosoma cruzi clones in human chronic chagasic cardiopathic and non-cardiopathic individuals.
Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile. jvenega@med.uchile.cl
PCR and Southern blot hybridization were used to determine the distribution of Trypanosoma cruzi clones in 37 chronic chagasic cardiopathic and non-cardiopathic patients. Parasite DNA amplified from peripheral blood or dejections of Triatoma infestans fed on patient blood was hybridized with probes containing hypervariable minicircle nucleotide sequences capable of detecting three sublineages of T. cruzi. Probes Z-I and Z-IIb detect unique sequences in lineages TcI and TcIIb, respectively. Probe Z-hybrid detects sequences of lineages TcIId and TcIIe. T. cruzi clones of the Z-I sublineage were detected in 62.2% of T. infestans dejections and 5.4% of peripheral blood samples. Clones of Z-IIb and Z-hybrid sublineages had similar distribution in blood and dejection samples. Interestingly, clones of the Z-IIb sublineage were significantly lower in cardiopathic than in non-cardiopathic patients (23.5% versus 75%; P=0.0006). Clones of the Z-hybrid sublineage were found in 29.4% of cardiopathic and 75% of non-cardiopathic patients, respectively (P=0.0051). By contrast, clones of sublineage Z-I were similarly distributed in both groups of patients. The low frequency of Z-IIb and Z-hybrid sublineage clones detected in cardiopathic patients suggests that the immunological mechanisms involved in controlling and eliminating these T. cruzi parasites may be detrimental to the host, leading to the development of chagasic cardiomyopathy.
PMID: 19059372 [PubMed - indexed for MEDLINE]
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Related Articles
- Dissimilar distribution of Trypanosoma cruzi clones in humans after chemotherapy with allopurinol and itraconazole. [J Antimicrob Chemother. 2006]
- Comparison of Trypanosoma cruzi detection by PCR in blood and dejections of Triatoma infestans fed on patients with chronic Chagas disease. [Acta Trop. 2006]
- Variation in Trypanosoma cruzi clonal composition detected in blood patients and xenodiagnosis triatomines: implications in the molecular epidemiology of Chile. [Am J Trop Med Hyg. 2006]
- ReviewDetection of Trypanosoma cruzi with the polymerase chain reaction and in situ hybridization in infected murine cardiac tissue. [Am J Trop Med Hyg. 1997]
- ReviewMolecular mimicry between Trypanosoma cruzi and host nervous tissues. [Acta Cient Venez. 1992]
- 7: Microbes Infect. 2008 Nov-Dec;10(14-15):1558-66. Epub 2008 Oct 8.
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Nitric oxide synthase-2 modulates chemokine production by Trypanosoma cruzi-infected cardiac myocytes.
Departments of Biochemistry and Immunology and Pathology, School of Medicine of Ribeirão Preto-USP, Ribeirão Preto, SP, Brazil. machadofs@icb.ufmg.br
An intense inflammatory process is associated with Trypanosoma cruzi infection. We investigated the mediators that trigger leukocyte activation and migration to the heart of infected mice. It is known that nitric oxide (NO) modulates the inflammatory response. During T. cruzi infection, increased concentrations of NO are produced by cardiac myocytes (CMs) in response to IFN-gamma and TNF. Here, we investigated whether NO, IFN-gamma and TNF regulate chemokine production by T. cruzi-infected CMs. In addition, we examined the effects of the NOS2 deficiency on chemokine expression both in cultured CMs and in hearts obtained from infected mice. After infection of cultured WT CMs with T. cruzi, the addition of IFN-gamma and TNF increased both mRNA and protein levels of the chemokines CXCL1, CXCL2, CCL2, CCL3, CCL4 and CCL5. Interestingly, T. cruzi-infected NOS2-deficient CMs produced significantly higher levels of CCL2, CCL4, CCL5 and CXL2 in the presence of IFN-gamma and TNF. Infection of NOS2-null mice resulted in a significant increase in the expression of both chemokine mRNA and protein levels in the heart of, compared with hearts obtained from, infected WT mice. Our data indicate that NOS2 is a potent modulator of chemokine expression which is critical to triggering the generation of the inflammatory infiltrate in the heart during T. cruzi infection.
PMID: 18951994 [PubMed - indexed for MEDLINE]
PMCID: PMC2643379 [Available on 2009/11/01]
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Related Articles
- Intracellular growth of Trypanosoma cruzi in cardiac myocytes is inhibited by cytokine-induced nitric oxide release. [Infect Immun. 2004]
- Trypanosoma cruzi-infected cardiomyocytes produce chemokines and cytokines that trigger potent nitric oxide-dependent trypanocidal activity. [Circulation. 2000]
- beta-Chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi. [Infect Immun. 1999]
- Leukotriene B(4) induces nitric oxide synthesis in Trypanosoma cruzi-infected murine macrophages and mediates resistance to infection. [Infect Immun. 2002]
- Experimental Trypanosoma cruzi infection in platelet-activating factor receptor-deficient mice. [Microbes Infect. 2003]
- 8: J Med Primatol. 2008 Dec;37(6):318-28. Epub 2008 Jul 30.
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Trypanosoma cruzi in non-human primates with a history of stillbirths: a retrospective study (Papio hamadryas spp.) and case report (Macaca fascicularis).
Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227, USA.
BACKGROUND: Congenital transmission of Trypanosoma cruzi has been described in humans and experimental work has been conducted with mice, but not with non-human primates (NHPs). METHODS: We conducted a retrospective study of female baboons (Papio hamadryas spp.) naturally seropositive or seronegative for T. cruzi with history of fetal loss, and we report a stillbirth in a cynomolgus macaque (Macaca fascicularis) with placental T. cruzi amastigotes. RESULTS: There were no differences in menstrual cycle parameters and the number of fetal losses between seropositive and seronegative baboons with history of fetal loss. The amount of parasite DNA detected using quantitative polymerase chain reaction (Q-PCR) in M. fascicularis placenta was within the range detected in infected baboon tissues. CONCLUSIONS: There is no evidence that chronic maternal T. cruzi infection causes fetal loss in baboons. Q-PCR is a useful diagnostic tool to study archived NHP placentas.
PMID: 18671769 [PubMed - indexed for MEDLINE]
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Related Articles
- The baboon model (Papio hamadryas) of fetal loss: maternal weight, age, reproductive history and pregnancy outcome. [J Med Primatol. 2008]
- Amplification of Trypanosoma cruzi-specific DNA sequences in formalin-fixed raccoon tissues using polymerase chain reaction. [J Parasitol. 2002]
- Trypanosoma cruzi detection in blood by xenodiagnosis and polymerase chain reaction in the wild rodent Octodon degus. [Am J Trop Med Hyg. 2007]
- Use of the placental perfusion model to evaluate transplacental passage of Trypanosoma cruzi. [Am J Obstet Gynecol. 2005]
- ReviewDetection of Trypanosoma cruzi with the polymerase chain reaction and in situ hybridization in infected murine cardiac tissue. [Am J Trop Med Hyg. 1997]
- 9: Immunobiology. 2006;211(1-2):117-25. Epub 2005 Dec 27.
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Parasite cysteine proteinase interactions with alpha 2-macroglobulin or kininogens: differential pathways modulating inflammation and innate immunity in infection by pathogenic trypanosomatids.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, C.C.S., Ilha do Fundão, Rio de Janeiro 21949-900, RJ, Brazil. scharf@biof.ufrj.br
Plasma extravasation is a common endothelium response to tissue injury provoked by pathogens. Herein I will review studies showing that host proteinase inhibitors (e.g., alpha2-macroglobulin (alpha2M) or kininogens) interact with protozoan cysteine proteinases (CPs) in extravascular infection sites, linking inflammation to innate immunity by different mechanisms. Using human monocytes as antigen presenting cells, we first demonstrated that alpha2M entrapment of cruzipain, a Trypanosoma cruzi CP, reduced the activation threshold of cruzipain-specific CD4 T cells due to facilitated uptake of alpha2M-cruzipain complexes by the multiscavenger receptor (CD91). More recently, studies of the mechanisms underlying inflammation elicited by T. cruzi revealed that kininogens, once bound to glycosaminoglycans, are not able to efficiently inactivate cruzipain via their inhibitory cystatin-like domains. Instead, we found that cruzipain readily processes surface-bound kininogens, liberating bioactive kinins. Acting as paracrine hormones, kinins vigorously activate host cells through bradykinin (BK) receptors, thus stimulating endocytic uptake of the pathogen. Rather than unilaterally enhancing parasite infectivity, the liberated kinins activate innate immunity by potently stimulating dendritic cell maturation via the BK B2 receptor. The discovery of chagasin, a novel family of endogenous inhibitors expressed by trypanosomatids, is likely another regulatory player involved in the dynamics of the inflammatory response.
PMID: 16446176 [PubMed - indexed for MEDLINE]
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Related Articles
- ReviewRoles of naturally occurring protease inhibitors in the modulation of host cell signaling and cellular invasion by Trypanosoma cruzi. [Subcell Biochem. 2008]
- ReviewKininogens coordinate adaptive immunity through the proteolytic release of bradykinin, an endogenous danger signal driving dendritic cell maturation. [Scand J Immunol. 2007]
- Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type 1 immunity in a mouse model of subcutaneous infection by Trypanosoma cruzi. [J Immunol. 2006]
- Human T cell responses against the major cysteine proteinase (cruzipain) of Trypanosoma cruzi: role of the multifunctional alpha 2-macroglobulin receptor in antigen presentation by monocytes. [Int Immunol. 1997]
- Chagasin, the endogenous cysteine-protease inhibitor of Trypanosoma cruzi, modulates parasite differentiation and invasion of mammalian cells. [J Cell Sci. 2005]
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