Saturday, February 13, 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 -7 of 7

1. J Am Coll Nutr. 2009 Jun;28(3):257-65.

Impact of the discovery of human zinc deficiency on health.

Prasad AS.

Wayne State University School of Medicine, 1122 Elliman Bldg., 421 East Canfield, Detroit, MI 48201, prasada@karmanos.org.

The essentiality of zinc was recognized 46 years ago. Zinc deficiency resulting in growth retardation, hypogonadism, immune dysfunction and cognitive impairment affects nearly 2 billion subjects in the developing world. High phytate content of the cereal proteins consumed in the developing world, results in decreased availability of zinc for absorption. Zinc therapy has been very successful and life saving measure in patients with acrodermatitis enteropathica and Wilson's disease. Beneficial therapeutic responses of zinc supplementation have been ovserved in acute diarrhea in children, chronic hepatitis C, shigellosis, leprosy, leishmaniasis, and common cold. Zinc supplementation was effective in decreasing incidences of infection in elderly and patients with sickle cell disease. Zinc supplementation was effective in preventing blindness in 25% of the elderly with dry type of age related macular degeneration. Zinc supplementation in the elderly decreased oxidative stress and decreased generation of inflammatory cytokines. Zinc is an intracellular signaling molecule in monocytes, dendritic cells and macrophages and it plays an important role in cell-mediated immune functions and oxidative stress. Zinc is also an anti-inflammatory agent. These unique properties of zinc may have significant therapeutic benefits in several diseases in humans. In many diseases concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress and increase generation of inflammatory cytokines. Oxidative stress and chronic inflammation may play important causative roles in many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, and auto-immune diseases. It is therefore, important that status of zinc is assessed and zinc deficiency corrected in these chronic diseases. A controlled clinical trial of zinc supplementation in these disorders in order to document the preventive and therapeutic effects of zinc is warranted.

PMID: 20150599 [PubMed - in process]
2. CSH Protoc. 2010 Jan 1;2010(1):pdb.prot5369.

Dual-Color ELISPOT Assay for the Simultaneous Detection of IL-2 and/or IFN-{gamma} Secreting T Cells.

Boulet S, Ndongala ML, Bernard NF.

Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada.

INTRODUCTION The enzyme-linked immunospot (ELISPOT) assay measures the secretion intensity of effector molecules released by immune cells in response to ex vivo antigenic stimulation, as well as the frequency of these responding cells. This assay is highly sensitive, quantitative, easy to use, and amenable to high-throughput screening. For these reasons, the ELISPOT assay is considered by many as a gold standard for monitoring cellular immune responses. Until recently, ELISPOT assays using chromophores to detect the T cell secretion of cytokines were limited to the characterization of a single effector molecule. Notably, studies evaluating the immune response to chronic viral infections often measured IFN-gamma secretion by ELISPOT because of the known antiviral effects of this cytokine as well as its correlation to the cytotoxic capacity of T cells. However, maintenance of both IFN-gamma and IL-2 secretion by pathogen-specific T cells has been linked to a more favorable clinical outcome in human immunodeficiency virus (HIV) and Leishmania infections. Therefore, an ELISPOT assay able to simultaneously characterize T cell responses in terms of IL-2 and IFN-gamma secretion is potentially relevant for the monitoring of immune responses to certain infectious agents. In this protocol, we describe an ELISPOT assay for the simultaneous detection of IL-2 and IFN-gamma upon stimulation with viral peptides.

PMID: 20150128 [PubMed - in process]
3. Vet Parasitol. 2010 Jan 25. [Epub ahead of print]

In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi.

Gillingwater K, Kumar A, Ismail MA, Arafa RK, Stephens CE, Boykin DW, Tidwell RR, Brun R.

Parasite Chemotherapy, Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, 4002 Basel, Switzerland.

Trypanosoma evansi is an animal pathogenic protozoan, causing a wasting disease called Surra, which is broadly distributed in a wide range of mammalian hosts. Chemotherapy is the most efficient control method, which depends on four drugs. Unfortunately, with the appearance of resistance to these drugs, their effective use is threatened, emphasising a need to find new drugs. Diamidines bind to the minor groove of DNA at AT-rich sites and exert their anti-trypanosomal activity by inhibiting one or more DNA dependent enzymes or by directly impeding the transcription process. In total, 67 novel diamidine compounds were tested in vitro to determine activity against an animal pathogenic Chinese kinetoplastic T. evansi strain. In comparison, a human pathogenic Trypanosoma brucei rhodesiense strain and a P2 transporter knock out of a Trypanosoma brucei brucei strain were also tested. All diamidine compounds tested in this study against T. evansi produced inhibitory concentration (IC(50)) values below 50nM. The results demonstrate that these compounds are highly active against T. evansi in vitro. In addition, preliminary in vivo toxicity tests were performed on all 67 diamidines with 69% of the compounds showing no acute toxicity at an intra-peritoneal dose of 100mg/kg. Copyright © 2010 Elsevier B.V. All rights reserved.

PMID: 20149544 [PubMed - as supplied by publisher]
4. Ann Trop Med Parasitol. 2010 Jan;104(1):35-53.

The use of remote sensing in the identification of the eco-environmental factors associated with the risk of human visceral leishmaniasis (kala-azar) on the Gangetic plain, in north-eastern India.

Bhunia GS, Kumar V, Kumar AJ, Das P, Kesari S.

Department of Vector Biology and Control, Rajendra Memorial Research Institute of Medical Sciences (ICMR), Agamkuan, Patna - 800 007, Bihar, India.

Human visceral leishmaniasis (VL) or kala-azar remains a major cause of mortality, particularly in the developing world. The disease is common in the internal regions of north-eastern India, which have a tropical or sub-tropical climate. In a recent study on VL in this region, the relationship between the incidence of VL and certain physio-environmental factors was explored, using a combination of a geographical information system (GIS), satellite imagery and data collected 'on the ground'. Some eco-environmental parameters were then used to map and describe the spatial heterogeneity seen in the transmission of the parasite (Leishmania donovani) that causes VL in India, and to identify those habitats, on the Gangetic plain, where the sandfly vectors might thrive. It was found that the presence of waterbodies, woodland and urban, built-up areas, soil of the fluvisol type, air temperatures of 25.0-27.5 degrees C, relative humidities of 66%-75%, and an annual rainfall of 100-<160 cm were all positively associated with the incidence of VL. A VL map was created and stratified into areas of 'risk' and 'non-risk' for the disease, based on calculations of risk indices.

PMID: 20149291 [PubMed - in process]
5. Expert Rev Anti Infect Ther. 2009 Dec;7(10):1223-34.

Recognizing and meeting the challenge of Chagas disease in the USA.

Bowling J, Walter EA.

Infectious Diseases Fellow University of Texas Health Science Center San Antonio, Mail Code 7881, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. bowling@uthscsa.edu

It is estimated that over 300,000 people with Chagas disease are living in the USA, with more than 30,000 cases of Chagas cardiomyopathy expected per year. The epidemiology of Chagas disease in Central and South America differs from that of the USA, where particular attention must focus on blood bank screening, organ donation and vertical transmission. It is essential that healthcare practitioners have heightened awareness of Chagas disease in the differential diagnosis of certain patients and are aware of recommendations for the management of these patients in the USA. Ongoing attention must focus on trials that determine whether all patients will benefit from treatment as well as studies of new agents for therapy.

PMID: 19968514 [PubMed - indexed for MEDLINE]
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Publication Types:

  • Review

MeSH Terms:

  • Chagas Disease/diagnosis
  • Chagas Disease/drug therapy
  • Chagas Disease/epidemiology*
  • Chagas Disease/transmission
  • Guidelines as Topic
  • Humans
  • Nifurtimox/therapeutic use
  • Nitroimidazoles/therapeutic use
  • Trypanocidal Agents/therapeutic use
  • Trypanosoma cruzi/drug effects
  • United States

Substances:

  • Nitroimidazoles
  • Trypanocidal Agents
  • benzonidazole
  • Nifurtimox
6. J Immunol. 2009 Dec 15;183(12):8015-25.

The heavy chain variable segment gene repertoire in chronic Chagas' heart disease.

Grippo V, Mahler E, Elias FE, Cauerhff A, Gómez KA, Tentori MC, Ruiz A, Vigliano CA, Laguens RP, Berek C, Levin MJ.

Laboratory of Molecular Biology of Chagas' Disease, Institute for Genetic Engineering and Molecular Biology, CONICET, Buenos Aires, Argentina.

Patients chronically infected with Trypanosoma cruzi develop chronic Chagas' heart disease (cChHD). Their Ab response is suspected to be involved in the cardiac pathogenesis. Reactivity of serum Abs from these patients has been extensively studied but little is known about the diversity of the in vivo IgG repertoire. We analyzed 125 variable H chain (VH) genes and compared it to repertoires from healthy individuals, and patients with autoimmune processes and other infections. VH were from plasma cells isolated from heart tissue of three cChHD patients and from a Fab combinatorial library derived from bone marrow of another cChHD patient. The role of the parasite in shaping the Ab repertoire was assessed analyzing VH genes before and after panning against T. cruzi Ag. Among recovered VH genes, a significantly increased representation of VH4 was observed. Plasma cells at the site of cardiac infiltration showed an increased VH1 usage. CDR3 lengths were similar to the ones found in the healthy repertoire and significantly shorter than in other infections. VH derived from anti-T. cruzi Fab and plasma cells showed a higher proportion of hypermutated genes, 46.9% and 43.75%, respectively, vs 30.9% of the cChHD patient repertoire, pointing to the role of parasite Ags in the shaping of the humoral response in Chagas' disease. No histological evidence of germinal center-like structures was observed in heart tissue. In accordance, VH analysis of heart plasmocytes revealed no evidence of clonal B cell expansion, suggesting that they migrated into heart tissue from secondary lymphoid organs.

PMID: 19933850 [PubMed - indexed for MEDLINE]
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Publication Types:

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH Terms:

  • Adult
  • Amino Acid Sequence
  • Antibodies, Protozoan/biosynthesis
  • Antibodies, Protozoan/genetics*
  • Antigens, Protozoan/immunology
  • B-Lymphocytes/immunology
  • B-Lymphocytes/parasitology
  • B-Lymphocytes/pathology
  • Chagas Cardiomyopathy/immunology*
  • Chagas Cardiomyopathy/parasitology
  • Chagas Cardiomyopathy/pathology
  • Chronic Disease
  • Complementarity Determining Regions/biosynthesis
  • Complementarity Determining Regions/genetics
  • Female
  • Gene Rearrangement, B-Lymphocyte/genetics*
  • Humans
  • Immunoglobulin Heavy Chains/biosynthesis*
  • Immunoglobulin Heavy Chains/genetics*
  • Immunoglobulin Variable Region/biosynthesis*
  • Immunoglobulin Variable Region/genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Somatic Hypermutation, Immunoglobulin/genetics
  • Trypanosoma cruzi/immunology

Substances:

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
7. Nucleic Acids Res. 2010 Jan;38(1):e5. Epub 2009 Oct 23.

'RNA walk' a novel approach to study RNA-RNA interactions between a small RNA and its target.

Lustig Y, Wachtel C, Safro M, Liu L, Michaeli S.

The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel.

In this study we describe a novel method to investigate the RNA-RNA interactions between a small RNA and its target that we termed 'RNA walk'. The method is based on UV-induced AMT cross-linking in vivo followed by affinity selection of the hybrid molecules and mapping the intermolecular adducts by RT-PCR or real-time PCR. Domains carrying the cross-linked adducts fail to efficiently amplify by PCR compared with non-cross-linked domains. This method was calibrated and used to study the interaction between a special tRNA-like molecule (sRNA-85) that is part of the trypanosome signal recognition particle (SRP) complex and the ribosome. Four contact sites between sRNA-85 and rRNA were identified by 'RNA walk' and were further fine-mapped by primer extension. Two of the contact sites are expected; one contact site mimics the interaction of the mammalian Alu domain of SRP with the ribosome and the other contact sites include a canonical tRNA interaction. The two other cross-linked sites could not be predicted. We propose that 'RNA walk, is a generic method to map target RNA small RNAs interactions in vivo.

PMCID: PMC2800229

PMID: 19854950 [PubMed - indexed for MEDLINE]
Related articles Free article
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Publication Types:

  • Research Support, Non-U.S. Gov't

MeSH Terms:

  • Base Sequence
  • Binding Sites
  • Cross-Linking Reagents/chemistry
  • Molecular Mimicry
  • Molecular Sequence Data
  • RNA, Protozoan/chemistry*
  • RNA, Protozoan/metabolism
  • RNA, Ribosomal/chemistry*
  • RNA, Ribosomal/metabolism
  • RNA, Transfer/chemistry
  • RNA, Untranslated/chemistry*
  • RNA, Untranslated/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonuclease H
  • Signal Recognition Particle/chemistry*
  • Trioxsalen/analogs & derivatives
  • Trioxsalen/chemistry
  • Trypanosomatina/genetics

Substances:

  • Cross-Linking Reagents
  • RNA, Protozoan
  • RNA, Ribosomal
  • RNA, Untranslated
  • Signal Recognition Particle
  • Trioxsalen
  • aminomethyltrioxsalen
  • RNA, Transfer
  • Ribonuclease H

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