Thursday, July 2, 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 -10 of 12

1: Parasitol Int. 2009 Jun 27. [Epub ahead of print]

Endotoxin-like effects in acute-phase response to Trypanosoma brucei brucei infection are not due to gastrointestinal leakage.

Department of Biochemistry and Molecular Biology, Egerton University, PO. Box 536 Egerton, Kenya.

Trypanosomosis is mainly an immunological and inflammatory response mediated by increased levels of pro-inflammatory cytokines. Evidence suggests that pathological changes produced during infection with trypanosomes could be initiated by nonspecific endotoxin-like substances in trypanosomes and/or gram negative secondary bacterial infection. Studies in trypanosome infected rats indicate damage to the gastrointestinal tract (GIT) accompanied by increased leakage of the GIT mucosa. The current study was carried out to determine the in vivo response to endotoxin-like substances of T. brucei brucei. To this purpose we neutralized the entrance of endotoxin through the GIT using polymyxin B treatment and by monitoreding the plasma concentration of the acute phase proteins SAP and Hp and hence the in vivo effects of cytokines. The results in this study, where infection was performed in the presence of oral antibiotic that is not absorbed from GIT and which binds to and inactivates endotoxin, show that the elevated plasma levels of endotoxin-like activity and the resulting acute phase response indicated by an increase in levels of Hp and SAP, is due to trypanosome infection. Results obtained in the present study indicate that GIT is not the major source of elevated plasma endotoxin-like activity levels and the observed acute phase response was due to an increase in the levels of acute phase proteins SAP and haptoglobin. Therefore trypanosomes are responsible for the elevated plasma endotoxin-like activity levels and the subsequent systemic acute phase response in the host.

PMID: 19567273 [PubMed - as supplied by publisher]

2: Parasitol Int. 2009 Feb 4. [Epub ahead of print]

Characterization in vivo and in vitro of a strain of Leishmania (Viannia) shawi from the Amazon Region.

Instituto Evandro Chagas, Unidade de Microscopia Eletrônica, Av. Almirante Barroso 492, Bairro Marco, 66090-000, Belém, Pará, Brazil.

The present study analyses complement resistance, cell surface carbohydrates expression, lipidic composition and morphology in vivo and in vitro, of Leishmania (Viannia) shawi, a parasite identified in the Amazon region, Pará state, in 1989. We demonstrated that promastigotes in the stationary (STAT) growth phase are more resistant to complement lysis than in the logaritimic (LOG) growth phase. Ultrastructural analyses and imidazol technique showed accumulation of lipids in STAT growth phase promastigotes, which was confirmed by biochemical approach. Light and electron microscopy of skin lesion in hamster footpads caused by promastigotes in STAT growth phase, 90 days post inoculation, showed amastigotes inside of macrophage and free in the tissue surrounded by collagen fibers as well as extensive inflammatory reaction with tissue destruction. We also demonstrated, using lectins by agglutination assays and flow cytometry, the presence of fucose, mannose and/or glucose carbohydrate residues on the surface of LOG and STAT promastigotes. The results constitute the first characterization essay combining biochemical and morphological approaches dedicated to LOG and STAT growth phase promastigotes of L. (V) shawi contributing for a better knowledge of this poorly studied species of the New World.

PMID: 19567230 [PubMed - as supplied by publisher]

3: Arch Iran Med. 2009 Jul;12(4):371-6.

Immunophenotypic pattern and cytokine profiles of dry type cutaneous leishmaniasis.

Department of Dermatology, Kerman Medical School, Kerman Leishmaniasis Research Center, Kerman, Iran, meymandi_s@hotmail.com.

BACKGROUND: Dry type localized cutaneous leishmaniasis, one of the most prevalent cutaneous parasitic infections in Kerman Province, is presented as a polarized disease in which cytokine profiles secreted by immune cells play a major role in its presentation. In order to clarify the idea, immunohistochemical study of skin biopsies were performed to elucidate the cytokine release capabilities of immune cells. METHODS: Skin biopsies of acute, chronic nonlupoid, and chronic lupoid recidivans lesions of dry type localized cutaneous leishmaniasis were studied by immunohistochemical staining methods for immunophenotypic patterns (CD4, CD8, CD14, CD19, CD56, CD11a, CD18, CD1a, HLA-DR, CD54) and cytokines (INF-gamma, IL-12, IL-4, TNF-alpha) released by immune inflammatory cells. RESULTS: The descriptive analysis of data showed that the mean percentage of positive immunostained cells of CD4, CD8, and CD14; antigen-presenting cells (CD1a, HLA-DR); and markers of the extravasated positive memory T cells (CD11a, CD18, CD54) are more frequent in lupoid recidivans than in acute active and chronic nonlupoid lesions, in order of frequency. CONCLUSION: Based on the results, it seems that Th1-like response is predominant in acute active form and lupoid recidivans while Th2-like response is predominant in chronic nonlupoid lesions. It seems that lupoid recidivans is a type IV hypersensitivity reaction to the reactivation of hidden antigens.

PMID: 19566354 [PubMed - in process]

4: Zhonghua Liu Xing Bing Xue Za Zhi. 2009 Jan;30(1):6-9.

[Study on time-space clustering regarding the distribution of visceral leishmaniasis in Kashgar Region, Xinjiang]

[Article in Chinese]

The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai 200025, China.

OBJECTIVE: To probe time-space clustering on the distribution of visceral leishmaniasis (VL) in Kashgar Region. METHODS: Based on the geographic information system, a Poisson model of time-space statistical software was applied to analyze data over the past 11 years in the Kashgar Region. Zones with clustering phenomenon were conformed by geographic location and remote sensing images. RESULTS: There existed three high risk clustering zones and corresponding time frames of VL in Kashgar Region. The center location of zone A was located in E 76.08 degrees, N 39.52 degrees, with radius as 6.58 km. The high risk time frame was from January 1st of 1999 to December 31st of 2003. Within the zone and time frame, the relative risk (RR) of VL incidence was 45.98 times higher than those outside the scope (P < 0.0001). Zone B' s center location was at E 79.20 degrees, N 39.91 degrees, with the radius as 4.93 km. Its high risk time frame was from January 1st of 2002 to December 31st of 2006. Within the zone and time frame, the RR of VL incidence was 9.58 times higher than those outside of the scope (P < 0.0001). Zone C' s center location was in E 76.23 degrees, N 39.40 degrees, and the radius was 7.63 km, with the high risk time frame from January 1st of 2000 to December 31st of 2004. Within the zone and time frame, the RR of VL incidence was 5.18 times higher than the one from outside of the scope (P < 0.0001). CONCLUSION: The incidence of VL in Kashgar Region was non-randomly distributed while there existed obvious time-space clustering, with all of three high risk clustering zones located in oasis area where appeared the focus area for control and surveillance of VL.

PMID: 19565838 [PubMed - in process]

5: Nucleic Acids Res. 2009 Jun;37(10):3407-17. Epub 2009 Mar 31.Click here to read Nucleotide, LinkOut

Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi.

Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. daniella@icb.ufmg.br

A novel large multigene family was recently identified in the human pathogen Trypanosoma cruzi, causative agent of Chagas disease, and corresponds to approximately 6% of the parasite diploid genome. The predicted gene products, mucin-associated surface proteins (MASPs), are characterized by highly conserved N- and C-terminal domains and a strikingly variable and repetitive central region. We report here an analysis of the genomic organization and expression profile of masp genes. Masps are not randomly distributed throughout the genome but instead are clustered with genes encoding mucin and other surface protein families. Masp transcripts vary in size, are preferentially expressed during the trypomastigote stage and contain highly conserved 5' and 3' untranslated regions. A sequence analysis of a trypomastigote cDNA library reveals the expression of multiple masp variants with a bias towards a particular masp subgroup. Immunofluorescence assays using antibodies generated against a MASP peptide reveals that the expression of particular MASPs at the cell membrane is limited to subsets of the parasite population. Western blots of phosphatidylinositol-specific phospholipase C (PI-PLC)-treated parasites suggest that MASP may be GPI-anchored and shed into the medium culture, thus contributing to the large repertoire of parasite polypeptides that are exposed to the host immune system.

PMID: 19336417 [PubMed - indexed for MEDLINE]

6: Enferm Infecc Microbiol Clin. 2008 Dec;26(10):667-8.Click here to read LinkOut

[Increased liver enzymes and fever]

[Article in Spanish]

Servicio de Medicina Interna, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain. vpomar@santpau.cat

PMID: 19100197 [PubMed - indexed for MEDLINE]

7: Enferm Infecc Microbiol Clin. 2008 Dec;26(10):609-13.Click here to read LinkOut
Comment in:
Enferm Infecc Microbiol Clin. 2008 Dec;26(10):607-8.

[Epidemiological surveillance of vertically-transmitted Chagas disease at three maternity hospitals in the Valencian Community]

[Article in Spanish]

Servicio de Pediatría, Hospital Marina Alta, Denia, Alicante, Spain. paricio_jma@gva.es

INTRODUCTION AND AIM: Immigration to Spain of Latin Americans with Chagas disease in its indeterminate phase could result in vertical transmission of the disease or transmission by transfusion or organ transplantation. To ascertain the magnitude of this problem, we investigated the prevalence of bearers among women who gave birth in 3 state maternity hospitals in the Valencian Community and the incidence of vertical transmission. PATIENTS AND METHODS: An immunoprecipitation test to detect anti-Trypanosoma cruzi antibodies was carried out on 624 pregnant Latin American women. In positive cases, indirect immunofluorescence and PCR analysis were performed on mothers. In addition, a microhematocrit and PCR analysis were performed on the newborns of these mothers, and immune precipitation was carried out from age 7 months. Chagas-positive mothers were referred for outpatient care at the hospital internal medicine departments. Percentage of positive serology was calculated for the total number of patients and by country of origin. RESULTS: A total of 29 women (4.8%; 95% CI, 3.1-6.3) were Chagas-positive; all were asymptomatic and PCR-negative. None of their children were positive to the tests performed. Bolivian women were the most frequently affected: 24 out of 137 (17.5%; 95% CI, 11.2-23.9) DISCUSSION: The high prevalence of Chagas disease in the Latin American immigrant population has raised awareness of this disease among professionals involved in the study and treatment of this illness. Further epidemiological studies are needed to establish the feasibility of universal detection programs in this population.

PMID: 19100190 [PubMed - indexed for MEDLINE]

8: Enferm Infecc Microbiol Clin. 2008 Dec;26(10):607-8.Click here to read LinkOut
Comment on:
Enferm Infecc Microbiol Clin. 2008 Dec;26(10):609-13.

[Controlling vertical transmission of Trypanosoma cruzi: the biggest challenge for imported disease in Spain]

[Article in Spanish]

PMID: 19100189 [PubMed - indexed for MEDLINE]

9: J Inorg Biochem. 2009 Apr;103(4):609-16. Epub 2008 Nov 7.Click here to read LinkOut

Design of vanadium mixed-ligand complexes as potential anti-protozoa agents.

Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, C. C. 1157, Montevideo, Uruguay.

In the search for new therapeutic tools against Chagas' disease (American Trypanosomiasis) four novel mixed-ligand vanadyl complexes, [V(IV)O(L(2)-2H)(L(1))], including a bidentate polypyridyl DNA intercalator (L(1)) and a tridentate salycylaldehyde semicarbazone derivative (L(2)) as ligands were synthesized, characterized by a combination of techniques, and in vitro evaluated. EPR suggest a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and the polypyridyl ligand coordinated in an equatorial/axial mode. Both complexes including dipyrido[3,2-a: 2',3'-c]phenazine (dppz) as polypyridyl coligand showed IC(50) values in the muM range against Dm28c strain (epimastigotes) of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal reference drug Nifurtimox. To get an insight into the trypanocidal mechanism of action of these compounds, DNA was evaluated as a potential parasite target and EPR, and (51)V NMR experiments were also carried out upon aging aerated solutions of the complexes. Data obtained by electrophoretic analysis suggest that the mechanism of action of these complexes could include DNA interactions.

PMID: 19091422 [PubMed - indexed for MEDLINE]

10: Eur J Med Chem. 2009 Apr;44(4):1545-53. Epub 2008 Jul 23.Click here to read LinkOut

Study of 5-nitroindazoles' anti-Trypanosoma cruzi mode of action: electrochemical behaviour and ESR spectroscopic studies.

Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

New indazole derivatives have been developed to know about structural requirements for adequate anti-Trypanosoma cruzi activity. In relation to position 1 of indazole ring, we have observed that a butylaminopentyl substituent (14) affords good activity, but N-oxidation of omega-tertiary amino moiety yields completely inactive compounds (17, 18); the substituent at position 3 of indazole ring affects drastically the in vitro activity, 3-OH derivative 13 being completely inactive. On the other hand, since compound 22, denitro-analogue of active compound 4, does not show activity, the 5-nitro substituent of indazole ring seems to be essential. Intramolecular cyclization of side chain at position 1 also affords inactive compounds (19, 20). The electrochemical studies showed that the trypanocidal 5-nitroindazole derivatives yielded nitro-anion radical via one-electron process at physiological pH. This electrochemical behaviour occurs in the parasite according to ESR experiment with the T. cruzi microsomal fraction showing that 5-nitroindazole derivatives suffer bio-reduction without reactive oxygen species generation.

PMID: 18762357 [PubMed - indexed for MEDLINE]

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