Friday, December 25, 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. J Invest Dermatol. 2009 Dec 24. [Epub ahead of print]

Enhanced Lesional Foxp3 Expression and Peripheral Anergic Lymphocytes Indicate a Role for Regulatory T Cells in Indian Post-Kala-Azar Dermal Leishmaniasis.

Ganguly S, Mukhopadhyay D, Das NK, Chaduvula M, Sadhu S, Chatterjee U, Rahman M, Goswami RP, Guha SK, Modak D, Mallik S, Gonju D, Pramanik N, Barbhuiya JN, Saha B, Chatterjee M.

Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India.

Indian post-kala-azar dermal leishmaniasis (PKDL) is a low-frequency (5-10%) dermal sequela of visceral leishmaniasis (VL) caused by Leishmania donovani; importantly, affected individuals are speculated to be parasite reservoirs. Insight into its immunopathogenesis could translate into rational immunomodulatory therapeutic approaches against leishmaniases. In patients with PKDL (n=21), peripheral lymphocytes were analyzed for surface markers, intracellular cytokines, and lymphoproliferative responses using flow cytometry. In lesional tissue biopsies (n=12), expression of counter-regulatory cytokines (IFN-gamma and IL-10) and the T-regulatory transcription factor forkhead box protein 3 (Foxp3) was analyzed using reverse transcriptase-PCR, along with immunohistochemical detection (n=8) of CD3 and Foxp3 positivity. In patients with PKDL, circulating CD8(+)CD28(-) and antigen-induced IL-10(+)CD3(+) lymphocytes were increased and receded with treatment. CD8(+) lymphocytes showed impaired proliferative responses to L. donovani antigen (LDA) and phytohemagglutinin, which were reinstated after treatment. At presentation, the upregulated lesional IFN-gamma and IL-10 messenger RNA (mRNA), Foxp3 mRNA, and protein were curtailed after treatment. In Indian patients with PKDL, increased frequency of the CD8(+)CD28(-) phenotype, enhanced antigen-specific IL-10 production, and accompanying anergy of circulating lymphocytes suggest their regulatory nature. Furthermore, the concomitantly elevated lesional expression of Foxp3 suggests their possible recruitment into the lesional site, which would sustain disease pathology.Journal of Investigative Dermatology advance online publication, 24 December 2009; doi:10.1038/jid.2009.393.

PMID: 20032994 [PubMed - as supplied by publisher]
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2. J Vet Med Sci. 2009 Dec 22. [Epub ahead of print]

Evaluation of Myanmar Medicinal Plant Extracts for Antitrypanosomal and Cytotoxic Activities.

Bawm S, Tiwananthagorn S, Lin KS, Hirota J, Irie T, Htun LL, Maw NN, Myaing TT, Phay N, Miyazaki S, Sakurai T, Oku Y, Matsuura H, Katakura K.

Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University.

Current chemotherapeutic options for African trypanosomiasis in humans and livestock are very limited. In the present study, a total of 71 medicinal plant specimens from 60 plant species collected in Myanmar were screened for antitrypanosomal activity against trypomastigotes of Trypanosoma evansi and cytotoxicity against MRC-5 cells in vitro. The methanol extract of dried rootbark of Vitis repens showed the highest antitrypanosomal activity with IC(50) value of 8.6 +/- 1.5 mug/ml and the highest selectivity index of 24.4. The extracts of Brucea javanica, Vitex arborea, Eucalyptus globulus and Jatropha podagrica had also remarkable activity with IC(50) values and selectivity indices in the range of 27.2-52.6 mug/ml and 11.4-15.1, respectively.

PMID: 20032625 [PubMed - as supplied by publisher]
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3. Blood. 2009 Dec 23. [Epub ahead of print]

Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function.

Morales-Tirado V, Sojka DK, Katzman SD, Lazarski CA, Finkelman FD, Urban JF, Fowell DJ.

David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, Rochester, NY, United States;

Wiskott Aldrich Syndrome patients have numerous immune cell deficiencies but it remains unclear how abnormalities in individual cell types contribute to the pathologies of the Wiskott-Aldrich Syndrome (WAS). In T cells, the WAS protein (WASp) regulates actin polymerization, transcription and plays a role in the dynamics of the immunological synapse. To examine how these events influence CD4 function we isolated the WASp deficiency to CD4+ T cells, by adoptive transfer into wild type mice, to study T cell priming and effector function. WAS-/- CD4+ T cells mediated protective Th1 responses to Leishmania major in vivo but were unable to support Th2 immunity to Nippostronglyus brasilensis or L. major. Mechanistically, WASp was not required for Th2 programming but was required for Th2 effector function. WAS-/- CD4+ T cells up-regulated IL-4 and GATA3 mRNA and secreted IL-4 protein during Th2 differentiation. In contrast, cytokine transcription was uncoupled from protein production in WAS-/- Th2-primed effectors. WAS-/- Th2s failed to produce IL-4 protein on re-stimulation despite elevated IL-4/GATA3 mRNA. Moreover, dominant negative WASp expression in WT effector T cells blocked IL-4 production, but had no effect on IFNgamma. Thus WASp plays a selective, post-transcriptional, role in Th2 effector function.

PMID: 20032499 [PubMed - as supplied by publisher]
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4. Clin Vaccine Immunol. 2009 Dec 23. [Epub ahead of print]

Immunologic indicators of clinical progression during canine Leishmania infantum infection.

Boggiatto PM, Ramer-Tait AE, Metz K, Kramer EE, Gibson-Corley K, Mullin K, Hostetter JM, Gallup JM, Jones DE, Petersen CA.

Immunobiology Program, Department of Veterinary Pathology, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Laboratory Animal Resources, Iowa State University, Ames, Iowa 50011; Molecular Microbiology and Immunology Program, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; Charles City Animal Clinic, Charles City, Iowa 50616.

In both dogs and humans Leishmania infantum infection is more prevalent than disease, as infection often does not equate with clinical disease. Previous studies additively indicate that advanced clinical visceral leishmaniasis (VL) is characterized by increased production of anti-Leishmania antibodies, Leishmania-specific lymphoproliferative unresponsiveness, and decreased production of IFN-gamma with concomitant increase of IL-10. In order to differentiate infection vs. progressive disease for better disease prognostication, we temporally evaluated humoral and cellular immunologic parameters of naturally infected dogs. The work presented here describes for the first time the temporal immune response to natural autochthonous L. infantum infection in Foxhounds within the United States. Several key changes in immunological parameters should be considered to differentiate infection versus clinical disease, including a dramatic rise in IgG production, progressive increases in antigen-specific PBMC proliferation, and IFN-gamma production. Polysymptomatic disease is precluded by increased IL-10 production and consistent detection of parasite kinetoplast DNA in whole blood. This clinical presentation and immuno-dysregulation mirrors that observed in human patients indicating that this animal model will be very useful for testing immunomodulatory anti-IL-10 or other therapies.

PMID: 20032217 [PubMed - as supplied by publisher]
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5. Sante. 2009 Apr 1;19(2):73-80.

[Epidemiological, clinical and sociodemographic characteristics of human African trypanosomiasis (HAT) in and around Kinshasa, Democratic Republic of Congo.]

[Article in French]

Tshimungu K, Okenge L, Mukeba J, Kande V, Mol PD.

Laboratoire de microbiologie médicale Université de Liège CHU Sart-Tilman (B23) 4000 Liège Belgique, Département de santé publique, épidémiologie et biostatistique Faculté de médecine, Université catholiqueNotre Dame du Kasaï Kananga Kasaï-Occidental République démocratique du Congo (RDC), Unité d'enseignement et de recherche en santé publique, épidémiologie et biostatistique Sciences infirmières Institut supérieur des techniques médicales de Kinshasa Kinshasa République démocratique du Congo, Centre neuropsychopathologique de Kinshasa Université de Kinshasa Kinshasa République démocratique du Congo, Programme national de lutte contre la trypanosomiase humaine africaine République démocratique du Congo.

BackgroundDespite efforts to control human African trypanosomiasis (HAT) in the field, this infection remains prevalent in endemic or epidemic form in most of its traditional habitats. In the Democratic Republic of Congo (DRC), HAT has extended beyond rural areas to reach large cities such as Kinshasa. The objective of this study was to analyse the characteristics of trypanosomiasis patients (cases) in Kinshasa and to compare them to those of healthy controls.Methods and population of studyThis case-control study allowed us to compare case patients and controls for some epidemiologic, clinical and sociodemographic characteristics. In all, 1764 people (588 case-patients and 1176 controls) were interviewed according to a structured questionnaire. Case-patients were infected with trypanosomiasis and entered the National Human African Trypanosomiasis Program (PNLTHA-DRC) from January 2004 through December 2005. Controls were matched for sex, age and residence to the corresponding case-patient, but had negative results from the Card Agglutination Trypanosomiasis Test (CATT-Test) whole-blood serologic analysis. Each patient was matched with two controls.ResultsCases were identified in all 24 districts of Kinshasa, but were concentrated in the outskirts (outlying areas and southern expansion) and in rural areas. Overall, 25% (144/588) of case-patients lived in urbanised areas. People in the labour market (aged 20-49 years) were affected more often than others. HAT affected men and women equally. It also affected at higher rates people who moved around a lot and those who worked in rural or domestic activities, especially those in close contact with watercourses. Sleep disorders were the primary clinical sign (85%). Cervical adenopathies were observed frequently (66%). Fever was reported in 68% of case-patients. Most (73.5%) were diagnosed at a very advanced stage of infection (meningoencephalitic or neurological stage).ConclusionThese results highlight several modifiable or avoidable characteristics associated with HAT. Interventions on them might make it possible to reduce the morbidity and mortality rates associated with HAT and prevent wider extension of this disease.

PMID: 20031514 [PubMed - as supplied by publisher]
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6. Bioorg Med Chem. 2009 Dec 11. [Epub ahead of print]

Synthesis, DNA binding, fluorescence measurements and antiparasitic activity of DAPI related diamidines.

Farahat AA, Kumar A, Say M, Barghash AE, Goda FE, Eisa HM, Wenzler T, Brun R, Liu Y, Mickelson L, Wilson WD, Boykin DW.

Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.

A novel series of extended DAPI analogues were prepared by insertion of either a carbon-carbon triple bond (16a-d) or a phenyl group (21a,b and 24) at position-2. The new amidines were evaluated in vitro against both Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.). Five compounds (16a, 16b, 16d, 21a, 21b) exhibited IC(50) values against T. b. r. of 9nM or less which is two to nine folds more effective than DAPI. The same five compounds exhibited IC(50) values against P. f. of 5.9nM or less which is comparable to that of DAPI. The fluorescence properties of these new molecules were recorded, however; they do not offer any advantage over those of DAPI. Copyright © 2009 Elsevier Ltd. All rights reserved.

PMID: 20031421 [PubMed - as supplied by publisher]
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7. Vet Parasitol. 2009 Dec 3. [Epub ahead of print]

Emerging trends in the seroprevalence of canine leishmaniosis in the Madrid region (ce ntral Spain).

Gálvez R, Miró G, Descalzo MA, Nieto J, Dado D, Martín O, Cubero E, Molina R.

Servicio de Parasitología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo s/n, Majadahonda, 28220 Madrid, Spain.

This report describes a cross-sectional serological survey of the epidemiology of canine leishmaniosis (CanL) performed in 2006 and 2007 in the Madrid region (central Spain) where the disease is endemic. The work presented here is one of the several studies conducted in different Spanish regions under the Integrated Project of the European Commission entitled Emerging Diseases in a changing European eNvironment (EDEN). The aim of this project is to identify and catalogue European ecosystems and environmental conditions that determine the spatial and temporal distributions and dynamics of several pathogenic agents including Leishmania infantum (EDEN-LEI). The study area (Madrid Autonomous Region) was selected on the grounds of its wide altitude range. This area was surveyed from NE to SW across its mountain range (Sistema Central) and plateau area. One thousand and seventy-six dogs from 32 villages were examined for clinical signs of CanL, and serum samples were obtained to determine several haematological and biochemical variables. Leishmaniosis-specific antibodies were identified using an indirect immunofluorescence antibody test (IFAT). 87 of the 1076 dogs were seropositive for the protozoan (IFAT: cut-off>/=1/80) indicating a seroprevalence of 8.1% (0-16.1% depending on the village). On the basis of a physical examination and the biochemical/haematological status of each dog, 32 of the 87 infected dogs were described as clinically healthy (37%). Seroprevalence showed a peak in young dogs (1-2 years) and a second larger peak among the older dogs (7-8 years). Factors correlated with a higher infection risk were age (OR=1.15 [95% CI: 1.07-1.22]), weight (OR=1.10 [95% CI: 1.04-1.16]), and living outdoors as opposed to in a home (OR=3.38 [95% CI: 1.42-8.05]). According to data from studies performed in 1992 in the same area, the seroprevalence of CanL has increased 1.54-fold [95% CI: 1.04-2.29]. Given that this increasing trend cannot be attributed to differences in the sociodemographic characteristics of the dog populations, it is proposed that environmental changes could have had an impact on vector and reservoir densities and their geographical distributions. Further studies designed to explain this trend should attempt to correlate sand fly densities and CanL seroprevalences with climate, land use and human changes. Copyright © 2009 Elsevier B.V. All rights reserved.

PMID: 20031330 [PubMed - as supplied by publisher]
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8. Ann Trop Med Parasitol. 2009 Dec;103(8):727-30.

Post-kala-azar dermal leishmaniasis (PKDL) developing after treatment of visceral leishmaniasis with amphotericin B and miltefosine.

Kumar D, Ramesh V, Verma S, Ramam M, Salotra P.

Institute of Pathology (ICMR), Safdarjang Hospital Campus, New Delhi - 110 029, India.

PMID: 20030997 [PubMed - in process]
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9. Ann Trop Med Parasitol. 2009 Dec;103(8):679-92.

Increase in the prevalence of canine leishmaniasis in urban Algiers (Algeria) following the 2003 earthquake.

Ait-Oudhia K, Lami P, Lesceu S, Harrat Z, Hamrioui B, Dedet JP, Pratlong F.

Ecole Nationale Supérieure Vétérinaire d'Alger, B.P. 161, Hassen Badi El-Harrach, Algiers, Algeria; Université Montpellier 1, Centre Hospitalier Universitaire de Montpellier, Génétique et Evolution des Maladies Infectieuses (UMR 2724, IRD/CNRS/UM1), Centre National de Référence des Leishmania, Laboratoire de Parasitologie-Mycologie, 39 Avenue Charles Flahault, 34295 Montpellier Cedex 5, France. khatimait@hotmail.com.

Between 2005 and 2008, a serological survey for leishmanial infection was conducted among dogs from urban and peri-urban Algiers, with the focus on the new, densely populated areas that were built after the 2003 earthquake. Serum samples were collected from 1810 animals and tested for the presence of leishmanial antibodies by IFAT, ELISA and western blotting. The overall seroprevalence recorded was 25.1%. Of the seropositive dogs, 58.8% showed no clinical signs of the disease, 25.8% had a few, minor signs and the remaining 15.4% showed more severe illness. The major clinical signs of infection were weight loss, skin lesions and lymphadenopathy. Although seropositive dogs were found in all of the boroughs (daïras) of Algiers, seroprevalences were highest in the western part of the city (i.e. in the boroughs of Bouzaréah, Chéraga and Zéralda), ranging from 23.0% to 44.5%. Statistical analysis showed a relationship between seropositivity for leishmanial infection and the dog's age and lifestyle (i.e. whether the dog lived outside and/or in areas with dense vegetation). Only two zymodemes were identified amongst the 50 isolates investigated: MON-1 (88%) and MON-281 (12%). The latter zymodeme has not been previously found in Algeria, sandflies or dogs.

PMID: 20030992 [PubMed - in process]
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10. Ann Trop Med Parasitol. 2009 Dec;103(8):671-7.

Lymphocyte phenotyping, using cluster-of-differentiation (CD) markers, in young Iraqi children with visceral leishmaniasis.

Taher JH, Al-Mulla Hummadi YM, Al-Bashir NM, Al-Araji AS.

Department of Biology, College of Science, Babylon University, P.O. Box 4, Hilla, Babylon, Iraq.

The lymphocytic phenotypes involved in the pathogenesis of visceral leishmaniasis (VL) in Iraqi children have recently been investigated, in a study based on cluster-of-differentiation (CD) markers. Each case of VL investigated was confirmed parasitologically by the observation of amastigotes in a bone-marrow smear. Compared with the values for the healthy children used as controls, a lymphocyte from an untreated VL case was significantly less likely to be CD3+ or CD4+, significantly more likely to be CD8+, and more (but not significantly more) likely to be CD22+. The untreated cases also had significantly lower CD4+/CD8+ ratios than the controls. Among the untreated cases, gender and age had no apparent effect on any of these variables. After 28 days of treatment with sodium stibogluconate, there was a trend towards normalization in the lymphocytic phenotypes of the VL cases, with significant increases in the CD4+/CD8+ ratios and the percentages of lymphocytes that were CD3+ or CD4+, and a significant decrease in the percentages of lymphocytes that were CD22+.

PMID: 20030991 [PubMed - in process]
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