Friday, July 17, 2009

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 -7 of 7

1: Clin Vaccine Immunol. 2009 Jul 15. [Epub ahead of print]Click here to read

Development and validation of a fluorescent microsphere immunoassay for soluble CD30 testing.

Pavlov I, Martins TB, Delgado JC.

ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah; Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah.

Testing for soluble CD30 (sCD30), an indicator of Th2 immune response, is a useful prognostic marker in solid organ transplantation, lymphoproliferative disorders, autoimmunity, and various parasitic diseases. In this study we report the development and validation of a fluorescent microsphere immunoassay for determination of sCD30 in serum, plasma, and culture supernatants. The dynamic range of this assay is 1 to 400 ng/mL, with recovery for various concentrations of recombinant sCD30 from 97 to 116% (average recovery of 105%). The test showed a high degree of precision in both intra-assay and inter-assay studies (CV up to 7% and 8%, respectively), with a sensitivity of 1 ng/mL. The normal reference range calculated in cohort of 151 healthy individuals was 1 to 29 ng/mL. The clinical usefulness of the sCD30 fluorescent microsphere immunoassay was demonstrated by showing that levels of sCD30 have a positive correlation with specimens containing high titers of anti-double stranded DNA antibodies and high IgG anti-leishmania titers. Given the multiplexing potential of the sCD30 fluorescent microsphere immunoassay reported in this study, it is expected that testing of sCD30 concentrations along with other cytokines will become an important diagnostic tool in selected immunological and inflammatory diseases where Th2-type cytokine response have been reported.

PMID: 19605595 [PubMed - as supplied by publisher]

2: Eur J Med Chem. 2009 Jun 17. [Epub ahead of print]Click here to read

Scoring function for DNA-drug docking of anticancer and antiparasitic compounds based on spectral moments of 2D lattice graphsfor molecular dynamics trajectories.

Pérez-Montoto LG, Santana L, González-Díaz H.

Department of Microbiology & Parasitology, and Department of Organic Chemistry; Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.

We introduce here a new class of invariants for MD trajectories based on the spectral moments pi(k)(L) of the Markov matrix associated to lattice network-like (LN) graph representations of Molecular Dynamics (MD) trajectories. The procedure embeds the MD energy profiles on a 2D Cartesian coordinates system using simple heuristic rules. At the same time, we associate the LN with a Markov matrix that describes the probabilities of passing from one state to other in the new 2D space. We construct this type of LNs for 422 MD trajectories obtained in DNA-drug docking experiments of 57 furocoumarins. The combined use of psoralens+ultraviolet light (UVA) radiation is known as PUVA therapy. PUVA is effective in the treatment of skin diseases such as psoriasis and mycosis fungoides. PUVA is also useful to treat human platelet (PTL) concentrates in order to eliminate Leishmania spp. and Trypanosoma cruzi. Both are parasites that cause Leishmaniosis (a dangerous skin and visceral disease) and Chagas disease, respectively; and may circulate in blood products collected from infected donors. We included in this study both lineal (psoralens) and angular (angelicins) furocoumarins. In the study, we grouped the LNs on two sets; set1: DNA-drug complex MD trajectories for active compounds and set2: MD trajectories of non-active compounds or no-optimal MD trajectories of active compounds. We calculated the respective pi(k)(L) values for all these LNs and used them as inputs to train a new classifier that discriminate set1 from set2 cases. In training series the model correctly classifies 79 out of 80 (specificity=98.75%) set1 and 226 out of 238 (Sensitivity=94.96%) set2 trajectories. In independent validation series the model correctly classifies 26 out of 26 (specificity=100%) set1 and 75 out of 78 (sensitivity=96.15%) set2 trajectories. We propose this new model as a scoring function to guide DNA-docking studies in the drug design of new coumarins for anticancer or antiparasitic PUVA therapy.

PMID: 19604606 [PubMed - as supplied by publisher]

3: Clin Exp Rheumatol. 2009 May-Jun;27(3):503-6.

Visceral leishmaniasis and anti-TNF-alpha therapy:case report and review of the literature.

De Leonardis F, Govoni M, Lo Monaco A, Trotta F.

Section of Rheumatology, Department of Clinical and Experimental Medicine, University of Ferrara, Italy.

OBJECTIVES:Visceral leishmaniasis (VL) is an extremely rare example of opportunistic infection in patients treated with TNF-alpha antagonists and only a few cases have been described. In this paper risk factors, clinical features, diagnostic work-up and outcome of patients developing VL under biologic therapy are described.METHODS:Case report and review of the published cases of VL in patients under biologic treatment.RESULTS:We retrieved six patients, including ours, all of whom presented anarchic fever and pancytopenia. In 5 cases, splenomegaly was detected. The same number of patients came from endemic areas for VL. In the majority of the cases a bone marrow examination was not diagnostic, requiring the performance of a second one and/or the execution of other diagnostic tests. One fatal outcome was observed.CONCLUSION:Even if VL represents a sporadic complication of biologic treatments, its presence should always be suspected in patients developing a triad of signs and symptoms constituted by fluctuant fever, pancytopenia and splenomegaly, especially if coming from endemic areas. In these cases an extensive diagnostic work-up must be warranted. Atypical and confusing features may resemble autoimmune diseases at presentation and during the course of the illness.

PMID: 19604446 [PubMed - in process]

4: J Proteome Res. 2009 Jul 15. [Epub ahead of print]Click here to read

Prediction of Enzyme Classes from 3D Structure: General Model and Examples of Experimental-Theoretic Scoring of Peptide Mass Fingerprints of Leishmania Proteins.

Concu R, Dea-Ayuela MA, Pérez-Montoto LG, Bolas-Fernández F, Prado-Prado FJ, Podda G, Uriarte E, Ubeira FM, Gonzalez-Diaz H.

The number of protein and peptide structures included in Protein Data Bank (PDB) and Gen Bank without functional annotation has increased. Consequently, there is a high demand for theoretical models to predict these functions. Here we trained and validated, with an external set, a Markov Chain Model (MCM) that classifies proteins by their possible mechanism of action according to Enzyme Classification (EC) number. The methodology proposed is essentially new, and enables prediction of all EC classes with a single equation without the need for an equation for each class or non-linear models with multiple outputs. In addition, the model may be used to predict whether one peptide presents a positive or negative contribution of the activity of the same EC class. The model predicts the first EC number for 106 out of 151 (70.2%) oxidoreductases, 178/178 (100%) transferases, 223/223 (100%) hydrolases, 64/85 (75.3%) lyases, 74/74 (100%) isomerases and 100/100 (100%) ligases, as well as 745/811 (91.9%) non-enzymes. It is important to underline that this method may help us predict new enzyme proteins or select peptide candidates that improve enzyme activity, which may be of interest for the prediction of new drugs or drug targets. In order to illustrate the model's application, we report the 2D-Electrophoresis (2DE) isolation from Leishmania infantum as well as MADLI TOF Mass Spectra characterization and theoretical study of the Peptide Mass Fingerprints (PMFs) of a new protein sequence. The theoretical study focused on MASCOT, BLAST alignment, and alignment-free QSAR prediction of the contribution of 29 peptides found in the PMF of the new protein to specific enzyme action. This combined strategy may be used to identify and predict peptides of prokaryote and eukaryote parasites and their hosts as well as other superior organisms; which may be of interest in drug development or target identification.

PMID: 19603824 [PubMed - as supplied by publisher]

5: Infez Med. 2009 Mar;17(1):5-13.Click here to read LinkOut

[Chagas disease: an emerging public health problem in Italy?]

[Article in Italian]

Guerri-Guttenberg RA, Ciannameo A, Di Girolamo C, Milei JJ.

Instituto de Investigaciones Cardiologicas, Buenos Aires, Argentina.

Chagas' disease is an endemic parasitic illness in the American continent, affecting around 16 to 18 million people. Given that 9.5% of immigrants to Italy are from Latin America and that the infection can be transmitted in non-endemic countries congenitally by organ donations and blood transfusions, Chagas disease should be regarded as an emerging public health problem in Italy. Clinical guidelines as well as health protocols are needed to deal with this rarely recognized disease.

PMID: 19359818 [PubMed - indexed for MEDLINE]

6: J Clin Microbiol. 2009 Jun;47(6):1718-25. Epub 2009 Apr 8.Click here to read LinkOut

Probing population dynamics of Trypanosoma cruzi during progression of the chronic phase in chagasic patients.

D'Avila DA, Macedo AM, Valadares HM, Gontijo ED, de Castro AM, Machado CR, Chiari E, Galvão LM.

Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 Caixa Postal 486, 31270-901, Belo Horizonte, Minas Gerais, Brazil.

Our research aimed to characterize the genetic profiles of 102 Trypanosoma cruzi isolates recently obtained from 44 chronic chagasic patients from different regions of the states of Minas Gerais and Goiás in Brazil. At least two isolates were obtained from each patient at different times in order to study the parasite population dynamics during disease progression in the chronic phase. The isolates were characterized molecularly by genotyping the 3' region of the 24S alpha rRNA, the mitochondrial cytochrome oxidase subunit 2 (COII) gene, and the intergenic region of the spliced leader intergenic region (SL-IR) gene. Seventy-seven isolates were analyzed for nine microsatellite loci. The data presented here show a strong correlation between the T. cruzi lineage II (T. cruzi II) and human infection in these regions of Brazil. Interestingly, isolates from two patients were initially characterized (by rRNA genotyping) as T. cruzi I and hybrid strains, but subsequent analyses of the COII and SL-IR genes confirmed that those isolates belonged to T. cruzi III and a hybrid group, respectively. Our results confirm the risk of misclassifying T. cruzi isolates on the basis of analysis of a single molecular marker. The microsatellite profiles showed that different isolates obtained from the same patient were genetically identical and monoclonal. Exceptions were observed for T. cruzi isolates from two patients who presented differences for the SCLE11 locus and also from two other patients who showed amplification of three peaks for a microsatellite locus (TcAAAT6), implying that they were multiclonal. On the basis of the findings of the studies described here, we were not able to establish a correlation between the clinical forms of Chagas' disease and the genetic profiles of the T. cruzi isolates.

PMID: 19357212 [PubMed - indexed for MEDLINE]

PMCID: PMC2691080 [Available on 2009/12/01]

7: Microbes Infect. 2008 Aug-Sep;10(10-11):1201-9. Epub 2008 Jul 16.Click here to read Cited in PMC, LinkOut

Tissue-specific oxidative imbalance and mitochondrial dysfunction during Trypanosoma cruzi infection in mice.

Wen JJ, Dhiman M, Whorton EB, Garg NJ.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.

In this study, we examined the tissue specificity of inflammatory and oxidative responses and mitochondrial dysfunction in mice infected by Trypanosoma cruzi. In acute mice, parasite burden and associated inflammatory infiltrate was detected in all tissues (skeletal muscle>heart>stomach>colon). The extent of oxidative damage and mitochondrial decay was in the order of heart>stomach>skeletal muscle>colon. In chronic mice, a low level of parasite burden and inflammation continued in all tissues; however, oxidant overload and mitochondrial inefficiency mainly persisted in the heart tissue (also detectable in stomach). Further, we noted an unvaryingly high degree of oxidative stress, compromised antioxidant status, and decreased mitochondrial respiratory complex activities in peripheral blood of infected mice. A pair-wise log analysis showed a strong positive correlation in the heart-versus-blood (but not other tissues) levels of oxidative stress markers (malonyldialdehyde, glutathione disulfide), antioxidants (superoxide dismutase, MnSOD, catalase), and mitochondrial inhibition of respiratory complexes (CI/CIII) in infected mice. T. cruzi-induced acute inflammatory and oxidative responses are widespread in different muscle tissues. Antioxidant/oxidant status and mitochondrial function are consistently attenuated in the heart, and reflected in the peripheral-blood of T. cruzi-infected mice. Our results provide an impetus to investigate the peripheral-blood oxidative responses in relation to clinical severity of heart disease in chagasic human patients.

PMID: 18675934 [PubMed - indexed for MEDLINE]

PMCID: PMC2613841 [Available on 2009/08/01]

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