Tuesday, July 21, 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 15

1: Neotrop Entomol. 2009 May-Jun;38(3):303-10.Click here to read

Control of phlebotomine (Diptera: Psychodidae) leishmaniasis vectors.

Amóra SS, Bevilaqua CM, Feijó FM, Alves ND, Maciel Mdo V.

Programa de Pós-Graduação em Ciências Veterinárias, Univ. Estadual do Ceará, Fortaleza, CE, 60740-000.

Phlebotomines are of medical and veterinary concern as they vector leishmaniasis, bartonellosis and some arboviruses. The adaptations of some species to places modified by humans bring these vectors into contact with dwellings, which can facilitate disease transmission, and the vector control strategies adopted have rendered controversial results. Regarding leishmaniasis, for instance, which vector and reservoirs control can be effective, there is an assumption that the incidence of human infection is directly related to the number of infectious dogs, as well as to entomological factors. Therefore, vector control can provide a cheaper and more practical solution to prevent cases of leishmaniasis. Nevertheless, due to the complexity of the factors involved, chemical control is still essential, and biological insecticides and insecticide plants, for example, represent areas for study that should be encouraged and developed since they show promising results. This paper summarizes the control strategies adopted so far, especially the methods and efficiency of the entomological components of leishmaniasis control programs.

PMID: 19618043 [PubMed - in process]

2: Eukaryot Cell. 2009 Jul 17. [Epub ahead of print]Click here to read

Down regulation of mitochondrial Porin inhibits cell growth and alters respiratory phenotype in Trypanosoma brucei.

Singha UK, Sharma S, Chaudhuri M.

Department of Microbial Pathogenesis and Immune Response, Meharry Medical College, Nashville, Tennessee 37208.

Porin is the most abundant outer membrane (OM) protein of mitochondria. It forms the aqueous channel on mitochondrial OM and mediates major metabolite flux between mitochondria and cytosol. Mitochondrial Porin in Trypanosoma brucei, a unicellular parasitic protozoa and the causative agent of African trypanosomiasis, possesses a beta-barrel structure similar to bacterial OM porin, OmpA. T. brucei Porin (TbPorin) is present as a monomer as well as oligomer on mitochondrial OM and its expression is developmentally regulated. In spite of its distinct structure, TbPorin function is similar to other eukaryotic Porins. TbPorin RNAi reduced cell growth in both procyclic and bloodstream forms. Depletion of TbPorin decreased ATP production by inhibiting metabolite flux through OM. Additionally, the level of trypanosome alternative oxidase (TAO) decreased whereas the levels of the cytochrome-dependent respiratory complex III and complex IV increased in TbPorin depleted mitochondria. Furthermore, depletion of TbPorin reduced cellular respiration via TAO, which is not coupled with oxidative phosphorylation, but increased the capacity of the cyanide-sensitive respiration. Together, these data reveal that TbPorin KD reduced mitochondrial ATP level, which in turn increased the capacity of the cytochrome-dependent respiratory pathway (CP), in an attempt to compensate for the mitochondrial energy crisis. However, a simultaneous decrease in the substrate level phosphorylation due to TbPorin RNAi caused growth inhibition in the procyclic form. We also found that the expression of TAO and CP proteins are coordinately regulated in T. brucei according to mitochondrial energy demand.

PMID: 19617393 [PubMed - as supplied by publisher]

3: Trends Parasitol. 2009 Jul 17. [Epub ahead of print]Click here to read

The role of host genetics in leishmaniasis.

Sakthianandeswaren A, Foote SJ, Handman E.

Infection and Immunity Division, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville 3050, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville 3050, Victoria, Australia.

Leishmaniasis is one of the world's important infectious diseases. It is prevalent in tropical and subtropical regions of the world and endemic in 88 countries, with two million new cases of leishmaniasis reported annually. As a complex disease, the pathology of leishmaniasis varies and is determined by factors such as the environment, the insect vector, and parasite and host genetics. The contributing host genetics involve multiple genes; thus, the mouse model of leishmaniasis has been exploited extensively in an attempt to identify and dissect the contribution of disease modifier genes to pathogenesis. This review summarizes recent advances in the identification of genetic loci involved in the host response to Leishmania spp. in the mouse model and in the human situation.

PMID: 19617002 [PubMed - as supplied by publisher]

4: Eur J Med Chem. 2009 Jun 18. [Epub ahead of print]Click here to read

Second generation of 2H-benzimidazole 1,3-dioxide derivatives as anti-trypanosomatid agents: Synthesis, biological evaluation, and mode of action studies.

Boiani M, Boiani L, Merlino A, Hernández P, Chidichimo A, Cazzulo JJ, Cerecetto H, González M.

Departamento de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Igua 4225, 11400 Montevideo, Uruguay.

Exploring the influence of different substitution patterns of 2H-benzimidazole 1,3-dioxide derivatives (BzNO) we prepared fifteen new derivatives. Initially the BzNO were tested against Trypanosoma cruzi Tulahuen 2 strain epimastigote form rendering very potent anti-T. cruzi agents. Moreover, the BzNO were able to inhibit the growth of virulent and resistant to Benznidazole strains (CL Brener clone, Colombiana, and Y strains) and to Leishmania braziliensis. Interestingly, BzNO exhibited very high selectivity index and particularly the spiro-BzNO 13 provokes an important diminution of amastigotes in Vero cells. Besides, it was found a diminution of acetate and glycine as excreted metabolites but without increase of parasite glucose uptake indicating that the glycosome is probably not involucrate in the 2H-benzimidazole 1,3-dioxides mechanism of action.

PMID: 19616875 [PubMed - as supplied by publisher]

5: Cell Host Microbe. 2009 Jul 23;6(1):23-33.

A Dynamic Map of Antigen Recognition by CD4 T Cells at the Site of Leishmania major Infection.

Filipe-Santos O, Pescher P, Breart B, Lippuner C, Aebischer T, Glaichenhaus N, Späth GF, Bousso P.

Institut Pasteur, G5 Dynamiques des Réponses Immunes, Paris F-75724, France; Inserm U668, Equipe Avenir, Paris F-75724, France.

CD4 T helper cells play a central role in the control of infection by intracellular parasites. How efficiently pathogen-specific CD4 T cells detect infected cells in vivo is unclear. Here, we employed intravital two-photon imaging to examine the behavior of pathogen-specific CD4 T cells at the site of Leishmania major infection. While activated CD4 T cells enter the inflamed tissue irrespective of their antigen specificity, pathogen-specific T cells preferentially decelerated and accumulated in infected regions of the dermis. Antigen recognition by CD4 T cells was heterogeneous, involving both stable and dynamic contacts with infected phagocytes. However, not all infected cells induced arrest or deceleration of pathogen-specific T cells, and dense clusters of infected cells were poorly accessible to migrating T cells. Thus, disparities in the dynamics of T cell contacts with infected cells and local variation in T cell access to infected cells are important elements of the host-pathogen interplay.

PMID: 19616763 [PubMed - in process]

6: Cell Host Microbe. 2009 Jul 23;6(1):3-4.

Finding Leishmania: A Deadly Game of Hide-and-Seek.

Scott P.

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Leishmaniasis is a chronic infection in which intracellular parasites avoid destruction by the immune system. Using intravital imaging, Filipe-Santos et al. (2009) demonstrate that some parasitized dendritic cells receive much less attention than others during their choreographed dance with T cells, suggesting that these "wallflowers" could allow for parasite survival.

PMID: 19616760 [PubMed - in process]

7: Colloids Surf B Biointerfaces. 2009 Jun 23. [Epub ahead of print]Click here to read

Enhancement of immune response and protection in BALB/c mice immunized with liposomal recombinant major surface glycoprotein of Leishmania (rgp63): The role of bilayer composition.

Badiee A, Jaafari MR, Khamesipour A, Samiei A, Soroush D, Kheiri MT, Barkhordari F, McMaster WR, Mahboudi F.

School of Pharmacy, Biotechnology Research Center and Pharmaceutical Research Center, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.

Development of new generation vaccines requires adjuvants to elicit the type and intensity of immune response needed for protection. Liposomes have been shown to be an effective adjuvant formulation. In this study, the role of liposome bilayer composition with different phase transition temperature (T(c)) to induce a T helper 1 (Th1) type of immune response and protection against leishmaniasis in BALB/c mice was assessed. Liposome formulations with different bilayer compositions consisting of egg phosphatidylcholine (EPC, T(c)<0 degrees C), dipalmitoylphosphatidylcholine (DPPC, T(c) 41 degrees C), or distearoylphosphatidylcholine (DSPC, T(c) 54 degrees C) were prepared. All liposomes were contained rgp63 as a recombinant antigen and used to immunize mice subcutaneously 3 times in 3-week intervals. Evaluation of lesion development and splenic parasite burden after challenge with L. major, evaluation of Th1 cytokine (IFN-gamma) and Th2 cytokine (IL-4), and titration of IgG isotypes were carried out to assess the type of generated immune response and extent of protection. The results indicated the generated immune response in mice was influenced by the bilayer composition of liposomes, so that mice immunized with liposomes consisting of EPC induced a Th2 type of immune response while liposome consisting of DPPC or DSPC induced Th1 type of immune response. It seems that liposomes prepared with higher Tm phospholipids are suitable formulation to induce Th1 type of immune response and protection, and so might be used for further investigations to develop an effective vaccine against leishmaniasis.

PMID: 19615870 [PubMed - as supplied by publisher]

8: Trans R Soc Trop Med Hyg. 2009 Jul 15. [Epub ahead of print]Click here to read

A cross-sectional study on the clinical and immunological spectrum of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region.

Crescente JA, Silveira FT, Lainson R, Gomes CM, Laurenti MD, Corbett CE.

Tropical Medicine Institute, Pará Federal University, Belém, PA, Brazil.

The objectives of this study were to identify individuals with symptomatic and/or asymptomatic infection due to Leishmania (L.) infantum chagasi; to study the two types of infection, both clinically and immunologically, and to determine the prevalence rate of infection at the beginning of the study. This was a cross-sectional study with a cohort of 946 individuals, of both genders, from the age of 1 year, living in the municipality of Barcarena, PA, Brazil, an area endemic for American visceral leishmaniasis (AVL). The leishmanin skin test (LST) and the indirect fluorescent test (IFAT), were used for the diagnosis of infection. One hundred and twenty cases of infection were diagnosed, with a prevalence rate of 12.6%; eight cases showed high seroreactivity (1280-10240, IgG) in IFAT and no LST reaction; four of these cases were typical AVL and four had subclinical oligosymptomatic infection. Using two immunological methods with a clinical examination of the infected individuals enabled the identification of five clinical-immunological profiles which may promote a better understanding of the interaction between L. (L.) i. chagasi and the human immune response: asymptomatic infection (AI) 73.4%; subclinical resistant infection (SRI) 15%; subclinical oligosymptomatic infection (SOI) 3%; symptomatic infection (AVL) 3% and indeterminate initial infection (III) 5%.

PMID: 19615710 [PubMed - as supplied by publisher]

9: J Ayub Med Coll Abbottabad. 2008 Jul-Sep;20(3):40-3.

Haematological findings in relation to clinical findings of visceral Leishmaniasis in Hazara Division.

Rai ME, Muhammad Z, Sarwar J, Qureshi AM.

Department of Paediatrics, Women Medical College Abbottabad, Pakistan.

BACKGROUND: Visceral Leishmaniasis (VL) has worldwide distribution including Pakistan. The disease is characterized by a spectrum of clinical features along with serious complications in untreated cases. This study describes the correlation between clinical manifestations with haematological changes of VL in Hazara Division. METHODS: This cross sectional study was carried out in the children wards of Women & Children Hospital an Ayub Teaching Hospital Abbottabad. Seventy cases were included in this study, Sign, symptoms, complications and haematological parameters were recorded in detail and their comparison was carried out. RESULTS: Majority of the patients (98.57%) presented with fever followed by abdominal distension (47%) Pallor, (44%) weight loss (43%) diarrhoea (17%), vomiting (15%) and epitasis (8%) and hepatosplenomegaly was found in about 83% along with lymphadenopathy (20%) purpura (13%) and peripheral oedema (11%). Laboratory findings revealed anaemia in all the cases followed by neutropenia 43%, lymphocytosis 86% with thrombocytopenia 79%. Bone marrow in most of these cases showed myeloid hyperplasia with increased megakaryocytosis. CONCLUSION: There exists a new focus of visceral leishmaniasis in Hazara Division. The disease mainly affects children below 5 years and is more common in males than in female children. Bone marrow examination provides a reliable and simple tool for diagnosis of visceral leishmaniasis and the condition can be affectively managed with Sodium stibogluconate or meglumine antimoniate.

PMID: 19610513 [PubMed - in process]

10: Genes Dev. 2009 Jul 15;23(14):1650-64.Click here to read LinkOut

SMN-assisted assembly of snRNP-specific Sm cores in trypanosomes.

Palfi Z, Jaé N, Preusser C, Kaminska KH, Bujnicki JM, Lee JH, Günzl A, Kambach C, Urlaub H, Bindereif A.

Institute of Biochemistry, Justus Liebig University of Giessen, Giessen, Germany.

Spliceosomal small nuclear ribonucleoproteins (snRNPs) in trypanosomes contain either the canonical heptameric Sm ring (U1, U5, spliced leader snRNPs), or variant Sm cores with snRNA-specific Sm subunits (U2, U4 snRNPs). Searching for specificity factors, we identified SMN and Gemin2 proteins that are highly divergent from known orthologs. SMN is splicing-essential in trypanosomes and nuclear-localized, suggesting that Sm core assembly in trypanosomes is nuclear. We demonstrate in vitro that SMN is sufficient to confer specificity of canonical Sm core assembly and to discriminate against binding to nonspecific RNA and to U2 and U4 snRNAs. SMN interacts transiently with the SmD3B subcomplex, contacting specifically SmB. SMN remains associated throughout the assembly of the Sm heteroheptamer and dissociates only when a functional Sm site is incorporated. These data establish a novel role of SMN, mediating snRNP specificity in Sm core assembly, and yield new biochemical insight into the mechanism of SMN activity.

PMID: 19605687 [PubMed - indexed for MEDLINE]

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