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Sent on Tuesday, 2012 January 10Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Parasitol Res. 2012 Jan 6. [Epub ahead of print]Cationic liposomes containing soluble Leishmania antigens (SLA) plus CpG ODNs induce protection against murine model of leishmaniasis.Heravi Shargh V, Jaafari MR, Khamesipour A, Jalali SA, Firouzmand H, Abbasi A, Badiee A.SourceNanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. AbstractDevelopment of an effective vaccine against leishmaniasis is possible due to the fact that individuals cured from cutaneous leishmaniasis (CL) are protected from further infection. First generation Leishmania vaccines consisting of whole killed parasites reached to phase 3 clinical trials but failed to show enough efficacies mainly due to the lack of an appropriate adjuvant. In this study, an efficient liposomal protein-based vaccine against Leishmania major infection was developed using soluble Leishmania antigens (SLA) as a first generation vaccine and cytidine phosphate guanosine oligodeoxynucleotides (CpG ODNs) as an immunostimulatory adjuvant. 1, 2-Dioleoyl-3-trimethylammonium-propane was used as a cationic lipid to prepare the liposomes due to its intrinsic adjuvanticity. BALB/c mice were immunized subcutaneously (SC), three times in 2-week intervals, with Lip-SLA-CpG, Lip-SLA, SLA + CpG, SLA, or HEPES buffer. As criteria for protection, footpad swelling at the site of challenge and spleen parasite loads were assessed, and the immune responses were evaluated by determination of IFN-γ and IL-4 levels of cultured splenocytes, and IgG subtypes. The group of mice that received Lip-SLA-CpG showed a significantly smaller footpad swelling, lower spleen parasite burden, higher IgG2a antibody, and lower IL-4 level compared to the control groups. It is concluded that cationic liposomes containing SLA and CpG ODNs are appropriate to induce Th1 type of immune response and protection against leishmaniasis. |
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| 2. | BMC Syst Biol. 2012 Jan 5;6(1):1. [Epub ahead of print]Modelling of leishmaniasis infection dynamics: novel application to the design of effective ther apies.Laenger BM, Pou-Barreto C, Gonzalez-Alcon C, Valladares B, Wimmer B, Torres NV.AbstractABSTRACT: BACKGROUND:The WHO considers leishmaniasis as one of the six most important tropical diseases worldwide. It is caused by parasites of the genus Leishmania that are passed on to humans and animals by the phlebotomine sandfly. Despite all of the research, there is still a lack of understanding on the metabolism of the parasite and the progression of the disease. In this study, a mathematical model of disease progression was developed based on experimental data of clinical symptoms, immunological responses, and parasite load for Leishmania amazonensis in BALB/c mice. RESULTS:Four biologically significant variables were chosen to develop a differential equation model based on the GMA power-law formalism. Parameters were determined to minimize error in the model dynamics and time series experimental data. Subsequently, the model robustness was tested and the model predictions were verified by comparing them with experimental observations made in different experimental conditions. The model obtained helps to quantify relationships between the selected variables, leads to a better understanding of disease progression, and aids in the identification of crucial points for introducing therapeutic methods. CONCLUSIONS:Our model can be used to identify the biological factors that must be changed to minimize parasite load in the host body, and contributes to the design of effective therapies. |
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| 3. | Chem Biol Drug Des. 2011 Dec 16. doi: 10.1111/j.1747-0285.2011.01300.x. [Epub ahead of print]Inhibitors incorporating zinc binding groups tar get the GlcNAc-PI de-N-acetylase in Trypanosoma brucei, the causative agent of African sleeping sickness.Abdelwahab NZ, Crossman AT, Sullivan L, Ferguson MA, Urbaniak MD.SourceDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. AbstractDisruption of glycosylphosphatidylinositol (GPI) biosynthesis is genetically and chemically validated as a drug target against the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. The N-acetylglucosamine-phosphatidylinositol de-N-acetylase (deNAc) is a zinc metalloenzyme responsible for the second step of GPI biosynthesis. We recently reported the synthesis of eight deoxy-2-C-branched monosaccharides containing carboxylic acid, hydroxamic acid or N-hydroxyurea substituents at the C2 position that may act as zinc binding groups. Here, we describe the synthesis of a glucocyclitol-phospholipid incorporating a hydroxamic acid moiety, and report the biochemical evaluation of the monosaccharides and the glucocyclitol-phospholipid as inhibitors of the trypanosome deNAc in the cell free system and against recombinant enzyme. Monosaccharides with carboxylic acid or hydroxamic acid substituents were found to be inhibitors of the trypanosome deNAc with IC(50) values 0.1-1.5 mM, and the glucocyclitol-phospholipid was found to be a dual inhibitor of the deNAc and the α1-4-mannose transferase with an apparent IC(50) = 19 ± 0.5 μM. © 2011 John Wiley & Sons A/S. © 2011 John Wiley & Sons A/S. |
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| 4. | J Travel Med. 2012 Jan;19(1):44-53. doi: 10.1111/j.1708-8305.2011.00576.x. Epub 2011 Dec 8.Human african trypano somiasis in non-endemic countries (2000-2010).Simarro PP, Franco JR, Cecchi G, Paone M, Diarra A, Ruiz Postigo JA, Jannin JG.SourceWorld Health Organization, Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management, Geneva, Switzerland Food and Agriculture Organization of the United Nations (FAO), Animal Production and Health Division, Rome, Italy World Health Organization, Regional Office for Africa, Brazzaville, Congo World Health Organization, Regional Office for the Eastern Mediterranean, Cairo, Egypt. AbstractBackground. Human African trypanosomiasis (HAT) can affect travelers to sub-Saharan Africa, as well as migrants from disease endemic countries (DECs), posing diagnosis challenges to travel health services in non-disease endemic countries (non-DECs). Methods. Cases reported in journals have been collected through a bibliographic research and complemented by cases reported to the World Health Organization (WHO) during the process to obtain anti-trypanosome drugs. These drugs are distributed to DECs solely by WHO. Drugs are also provided to non-DECs when an HAT case is diagnosed. However, in non-DEC pentamidine can also be purchased in the market due to its indication to treat Pneumocystis and Leishmania infections. Any request for drugs from non-DECs should be accompanied by epidemiological and clinical data on the patient. Results. During the period 2000 to 2010, 94 cases of HAT were reported in 19 non-DECs. Seventy-two percent of them corresponded to the Rhodesiense form, whereas 28% corresponded to the Gambiense. Cases of Rhodesiense HAT were mainly diagnosed in tourists after short visits to DECs, usually within a few days of return. The majority of them were in first stage. Initial misdiagnosis with malaria or tick-borne diseases was frequent. Cases of Gambiense HAT were usually diagnosed several months after initial examination and subsequent to a variety of misdiagnoses. The majority were in second stage. Patients affected were expatriates living in DECs for extended periods and refugees or economic migrants from DECs. Conclusions. The risk of HAT in travelers and migrants, albeit low, cannot be overlooked. In non-DECs, rarity, nonspecific symptoms, and lack of knowledge and awareness in health staff make diagnosis difficult. Misdiagnosis is frequent, thus leading to invasive diagnosis methods, unnecessary treatments, and increased risk of fatality. Centralized distribution of drugs for HAT by WHO enables an HAT surveillance system for non-DECs to be maintained. This system provides valuable information on disease transmission and complements data collected in DECs. © 2011 International Society of Travel Medicine. |
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| 5. | Asian Pac J Trop Med. 2012 Feb;5(2):117-20.Preparation and evaluation of a glycerol-preserved direct agglutination antigen for long-term preservation: a comparative study of the detection of anti-Leishmania infantum antibodies in human and dog.Akhoundi B, Mohebali M, Edrissian GH, Eslami MB, Keshavarz H, Malekafzali H, Rokni MB.SourceDepartment of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. AbstractOBJECTIVE:To prepare and evaluate a glycerol-preserved antigen from an Iranian strain of Leishmania infantum (L. infantum) for use in glycerol-preserved direct agglutination tests (GP-DAT) as an alternative to freeze dried direct agglutination tests (FD-DAT) that use freeze-dried antigen. METHODS:Glycerol-preserved DAT antigen was prepared and stored at different temperatures. We tested antigen stored at 4 °C, 22-37 °C and 50 °C over a period of 365 days. Seven hundred twenty-nine serum samples were collected from different geographical zones of Iran from 2007-2009, and 80 of these samples were pooled to produce sera. Each pooled serum contained 10 sera. All positive and negative pooled sera were separately tested for anti-L. infantum antibodies with GP-DAT, FD-DAT and formaldehyde-fixed direct agglutination test (FF-DAT) antigens; tests were performed on both human and dog sera over a period of 12 months. RESULTS:There was strong agreement between the results obtained using GP-DAT and FD-DAT antigens stored at 22-37 °C for 12 months for both human (100%) and dog (100%) pooled sera. The direct agglutination test results were highly reproducible (weighted kappa: GP=0.833, FD=0.979 and FF=0.917). CONCLUSIONS:Because GP-DAT antigen is highly stable over a range of temperatures and is easy to transport in the field, this type of antigen may be particularly useful in areas with endemic visceral leishmaniasis. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved. |
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| 6. | Mol Microbiol. 2012 Jan 4. doi: 10.1111/j.1365-2958.2011.07938.x. [Epub ahead of print]TbPIF8, a Trypanosoma brucei protein related to the yeast Pif1 helicase, is essential for cell viability and mitochondrial genome maintenance.Wang J, Englund PT, Jensen RE.SourceDepartments of Biological Chemistry Cell Biology, Johns Hopkins Medical School, Baltimore, MD 21205, USA. AbstractThe trypanosome mitochondrial genome, kinetoplast DNA (kDNA), is a massive network of interlocked DNA rings, including several thousand minicircles and dozens of maxicircles. The unusual complexity of kDNA would indicate that numerous proteins must be involved in its condensation, replication, segregation and gene expression. During our investigation of trypanosome mitochondrial PIF1-like helicases, we found that TbPIF8 is the smallest and most divergent. It lacks some conserved helicase domains, thus implying that unlike other mitochondrial PIF1-like helicases, this protein may have no enzymatic activity. TbPIF8 is positioned on the distal face of kDNA disk and its localization patterns vary with different kDNA replication stages. Stem-loop RNAi of TbPIF8 arrests cell growth and causes defects in kDNA segregation. RNAi of TbPIF8 causes only limited kDNA shrinkage but the networks become disorganized. Electron microcopy of thin sections of TbPIF8-depleted cells shows heterogeneous electron densities in the kinetoplast disk. Although we do not yet know its exact function, we conclude that TbPIF8 is essential for cell viability and is important for maintenance of kDNA. © 2012 Blackwell Publishing Ltd. |
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| 7. | Cell Microbiol. 2011 Oct;13(10):1518-29. doi: 10.1111/j.1462-5822.2011.01636.x. Epub 2011 Jul 12.Tumour necrosis f actor (TNF)-mediated NF-κB activation facilitates cellular invasion of non-professional phagocytic epithelial cell lines by Trypanosoma cruzi.Pinto AM, Sales PC, Camargos ER, Silva AM.SourceDepartamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627 - ICB, UFMG, 31270-901, Belo Horizonte, MG, Brazil. AbstractAt the site of infection, pro-inflammatory cytokines locally produced by macrophages infected with Trypanosoma cruzi can activate surrounding non-professional phagocytes such as fibroblasts, epithelial and endothelial cells, which can be further invaded by the parasite. The effect of secreted soluble factors on the invasion of these cells remains, however, to be established. We show here that two epithelial cell lines become significantly susceptible to the infection by the Y strain of T. cruzi after tumour necrosis factor (TNF) treatment. The increase in the invasion was correlated with the increasing concentration of recombinant TNF added to cultures of HEK293T or LLC-MK2 cells. Supernatants taken from PMA-differentiated human monocytes infected with T. cruzi also increased the permissiveness of epithelial cells to subsequent infection with the parasite, which was inhibited by a TNF monoclonal antibody. Furthermore, the permissiveness induced by TNF was inhibited by TPCK, and led to significant decrease in the number of intracellular parasites, providing evidence that activation of NF-κB induced by TNF favours the invasion of the epithelial cell lines by T. cruzi through yet an unidentified mechanism. Our data indicate that soluble factors released from macrophages early in the infection favours T. cruzi invasion of non-professional phagocytic cells. © 2011 Blackwell Publishing Ltd. |
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