Thursday, January 28, 2010

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 -6 of 6

1. J Rehabil Res Dev. 2009;46(6):673-84.

Infectious complications in OIF/OEF veterans with traumatic brain injury.

Dau B, Oda G, Holodniy M.

Department of Veterans Affairs (VA) Palo Alto Health Care System, Palo Alto, CA.

Of veterans from the U.S. Global War on Terrorism who have sought care in the Department of Veterans Affairs, approximately 12% have an infectious disease diagnosis. Infections in those veterans with traumatic brain injury (TBI) include infections associated with blast injuries and burns, such as skin and soft tissue infections; infections as a result of retained bullet or shrapnel fragments; pulmonary infections resulting from lung injury, intubation, or resultant tracheostomy; hospital-acquired infections, such as those associated with methicillin-resistant Staphylococcus aureus and other antimicrobial resistant organisms such as Acinetobacter baumannii; and infections from implanted prosthetic devices, such as metal hardware or skull flaps. Longer-term cognitive impairment may result in behaviors that place veterans with TBI at risk for human immunodeficiency virus or hepatitis C virus infections. Finally, chronic infections acquired abroad, such as cutaneous leishmaniasis or Q-fever, may be diagnosed after veterans return to the United States. These infections present challenges in terms of added morbidity and costs associated with complex antimicrobial management; isolation requirements; and surgical procedures, such as those to remove infected retained fragments or prosthetic devices. In this review, providers will become more familiar with the scope and complexity of infectious disease management in veterans with TBI.

PMID: 20104397 [PubMed - in process]
2. BMC Microbiol. 2010 Jan 26;10(1):20. [Epub ahead of print]

Exocytosis and protein secretion in Trypanosoma.

Geiger A, Hirtz C, Becue T, Bellard E, Centeno D, Gargani D, Rossignol M, Cuny G, Peltier JB.

ABSTRACT: BACKGROUND: Human African trypanosomiasis is a lethal disease caused by the extracellular parasite Trypanosoma brucei. The proteins secreted by T. brucei inhibit the maturation of dendritic cells and their ability to induce lymphocytic allogenic responses. To better understand the pathogenic process, we combined different approaches to characterize these secreted proteins. RESULTS: Overall, 444 proteins were identified using mass spectrometry, the largest parasite secretome described to date. Functional analysis of these proteins revealed a strong bias toward folding and degradation processes and to a lesser extent toward nucleotide metabolism. These features were shared by different strains of T. brucei, but distinguished the secretome from published T. brucei whole proteome or glycosome. In addition, several proteins had not been previously described in Trypanosoma and some constitute novel potential therapeutic targets or diagnostic markers. Interestingly, a high proportion of these secreted proteins are known to have alternative roles once secreted. Furthermore, bioinformatic analysis showed that a significant proportion of proteins in the secretome lack transit peptide and are probably not secreted through the classical sorting pathway. Membrane vesicles from secretion buffer and infested rat serum were purified on sucrose gradient and electron microscopy pictures have shown 50- to 100-nm vesicles budding from the coated plasma membrane. Mass spectrometry confirmed the presence of Trypanosoma proteins in these microvesicles, showing that an active exocytosis might occur beyond the flagellar pocket. CONCLUSIONS: This study brings out several unexpected features of the secreted proteins and opens novel perspectives concerning the survival strategy of Trypanosoma as well as possible ways to control the disease. In addition, concordant lines of evidence support the original hypothesis of the involvement of microvesicle-like bodies in the survival strategy allowing Trypanosoma to exchange proteins at least between parasites and/or to manipulate the host immune system.

PMID: 20102621 [PubMed - as supplied by publisher]
3. Immunology. 2010 Jan 22. [Epub ahead of print]

Evaluation of localized and systemic immune responses in cutaneous leishmaniasis caused by Leishmania tropica: interleukin-8, monocyte chemotactic protein-1 and nitric oxide are major regulatory factors.

Kumar R, Bumb RA, Salotra P.

Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India.

Summary We have established Leishmania tropica as the causative agent of cutaneous leishmaniasis (CL) in the region of India where the disease is endemic. The association between localized and circulating levels of immune-determinants in CL patients was evaluated. Reverse transcription-polymerase chain reaction analysis revealed up-regulation of interferon-gamma (IFN-gamma), interleukin (IL)-1beta, IL-8, tumour necrosis factor-alpha (TNF-alpha), IL-10 and IL-4 in dermal lesions at the pretreatment stage (n = 31) compared with healthy controls (P < 0.001) and a significant down-regulation after treatment (n = 14, P < 0.05). The results indicated that an unfavourable clinical outcome in CL was not related to an inadequate T helper 1 (Th1) cell response, but rather to impairment in multiple immune functions. Comparative assessment of treatment regimes with rifampicin (RFM) or sodium antimony gluconate (SAG) revealed tissue cytokine levels to be significantly reduced after treatment with RFM (P < 0.005), while no significant decrease was evident in the levels of IFN-gamma, TNF-alpha and IL-10 (P > 0.05) as a result of treatment with SAG. Increased transcripts of monocyte chemoattractant protein-1 (MCP-1) (P < 0.001) and inducible nitric oxide synthase (iNOS) (P < 0.05) were evident before treatment in tissue lesions and remained high after treatment. Immunohistochemistry demonstrated strong expression of myeloperoxidase (MPO) and IL-8, and moderate expression of iNOS in dermal lesions. The expression levels of IL-8, MCP-1 and nitric oxide (NO) were high in patient sera before treatment, as determined using cytokine bead array and enzyme-linked immunosorbent assay (ELISA). At the post-treatment stage, the serum IL-8 levels had decreased; however, the levels of MCP-1 and NO remained high. These data suggest that IL-8 is an effector immune-determinant in the progression of CL, whereas NO facilitates the parasite killing by macrophages via MCP-1-mediated stimulation.

PMID: 20102417 [PubMed - as supplied by publisher]
4. J Nat Prod. 2010 Jan 26. [Epub ahead of print]

Additional Insights on the Bastadins: Isolation of Analogues from the Sponge Ianthella cf. reticulata and Exploration of the Oxime Configurations (dagger).

Calcul L, Inman WD, Morris AA, Tenney K, Ratnam J, McKerrow JH, Valeriote FA, Crews P.

Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, Sandler Center for Basic Research in Parasitic Disease, University of California, San Francisco, San Francisco, California 94143, and Josephine Ford Cancer Center, Henry Ford Hospital, Detroit, Michigan 48202.

The focus of this study is on the bastadin class of bromotyrosine derivatives, commonly isolated from Ianthella marine sponges, and is the first report on the secondary metabolites from Ianthella cf. reticulata. Two new bastadins were isolated, (E,Z)-bastadin 19 (1b), a diastereoisomer of the known (E,E)-bastadin 19 (1a), and dioxepine bastadin 3 (2), an unusual dibenzo-1,3-dioxepine. A bastadin NMR database was created and assisted in the structure determination of 1b and 2 and the rapid dereplication of 10 other known compounds including bastadins 2-9 (3-10), 13 (11), and 19 (1a). The geometry of the 2-(hydroxyimino)-N-alkylamide chains, a chemical feature present in all bastadins, was further probed, and new insights regarding the natural oxime configuration are discussed. Bastadins possessing (E,Z)-, (Z,E)-, or (E,E)-dioxime configurations could be artifacts of isolation or storage in solution. Therefore, this point was explored by photochemical and thermal isomerization studies, as well as molecular mechanics calculations. Bastadins 13 (11) and 19 (1a) exhibited moderate inhibition against Trypanosoma brucei, and bastadin 4 (5) was cytotoxic to HCT-116 colon cancer cells.

PMID: 20102170 [PubMed - as supplied by publisher]
5. Phytomedicine. 2009 Nov;16(11):1059-63. Epub 2009 May 7.

The antitumoral, trypanocidal and antileishmanial activities of extract and alkaloids isolated from Duguetia furfuracea.

da Silva DB, Tulli EC, Militão GC, Costa-Lotufo LV, Pessoa C, de Moraes MO, Albuquerque S, de Siqueira JM.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil. debrentan@fcfrp.usp.br

The alkaloid extract and five alkaloids isolated from subterranean stem bark of Duguetia furfuracea (Annonaceae) were investigated for the following activities: antitumoral, trypanocidal and leishmanicidal. Dicentrinone showed weak cytotoxicity, but it had the strongest leishmanicidal activity (IC(50) 0.01 microM). Duguetine and duguetine beta-N-oxide caused considerable antitumoral activity in every cell lines evaluated, although duguetine was more active against trypomastigote forms (IC(50) 9.32 microM) than other alkaloids tested.

PMID: 19423311 [PubMed - indexed for MEDLINE]
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Publication Types:

  • Research Support, Non-U.S. Gov't

MeSH Terms:

  • Alkaloids/isolation & purification
  • Alkaloids/pharmacology*
  • Annonaceae/chemistry*
  • Antineoplastic Agents, Phytogenic/isolation & purification*
  • Aporphines/isolation & purification
  • Aporphines/pharmacology
  • Cell Line, Tumor
  • Humans
  • Leishmania braziliensis/drug effects*
  • Molecular Structure
  • Plant Extracts/pharmacology
  • Trypanocidal Agents/isolation & purification*
  • Trypanosoma cruzi/drug effects

Substances:

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Aporphines
  • Plant Extracts
  • Trypanocidal Agents
  • dicentrinone
  • duguetine
  • duguetine beta-N-oxide
6. Int J Infect Dis. 2009 Nov;13(6):e527-8. Epub 2009 May 2.

Reactivation of Chagas disease with central nervous system involvement: peripheral blood smear evidence.

Verdú J, De Paz F, Castaño V, Torrús D, Reus S.

Department of Hematology, General University Hospital, Alicante, Spain. pepever2@mixmail.com

PMID: 19414276 [PubMed - indexed for MEDLINE]
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Publication Types:

  • Case Reports

MeSH Terms:

  • AIDS-Related Opportunistic Infections/complications
  • AIDS-Related Opportunistic Infections/parasitology
  • Abscess*/parasitology
  • Abscess*/radiography
  • Adult
  • Brain*/parasitology
  • Brain*/radiography
  • Central Nervous System Protozoal Infections*/complications
  • Central Nervous System Protozoal Infections*/parasitology
  • Chagas Disease/complications*
  • Chagas Disease/parasitology
  • HIV Infections/complications*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Tomography Scanners, X-Ray Computed
  • Trypanosoma cruzi*/isolation & purification

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