Wednesday, July 20, 2011

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 27

1. Indian J Nephrol. 2011 Apr;21(2):128-31.

Cytomegalovirus and Leishmania donovani coinfection in a renal allograft recipient.

Prasad N, Gupta A, Sharma RK, Gopalakrishnan S, Agrawal V, Jain M.

Source

Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Abstract

Infection is a leading cause of death in renal allograft recipients. Apart from the immunosuppressive drugs, immunomodulatory viral infections also predispose the recipient to many opportunistic infections. Kala-azar in renal allograft recipients is infrequently reported even in endemic areas. In majority of cases, there was delay in diagnosis and treatment. We report a case of renal allograft recipient, where we faced a diagnostic dilemma because of coinfection of cytomegalovirus and visceral leishmaniasis (kala-azar). Kala-azar was successfully treated with amphotericin B. Kala-azar should always be kept as differential diagnosis in patients with pyrexia and cytopenia, even in the absence of splenomegaly in patients residing in an endemic zone.

PMID:
21769179
[PubMed - in process]
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2. Vet Parasitol. 2011 Jun 30. [Epub ahead of print]

Molecular detection of Leishmania braziliensis in Rattus norvegicus in an area endemic for cutaneous leishmaniasis in Brazil.

Marcelino AP, Ferreira EC, Avendanha JS, Costa CF, Chiarelli D, Almeida G, Moreira EC, Leite RC, Dos Reis JK, Gontijo CM.

Source

Escola de Veterinária, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Minas Gerais, Brasil.

Abstract

Leishmania nested PCR (LnPCR) targeted to the SSUrRNA gene and DNA sequencing were used to analyze 315 tissue samples from 80 Rattus norvegicus specimens trapped in an area endemic for leishmaniasis in Belo Horizonte, Minas Gerais, Brazil. Of the samples analyzed, 17.46% (55/315) of all tissues, 10% (8/80) of skin, 26.92% (21/78) of blood, 30.76% (24/78) of bone marrow and 2.53% (2/79) of spleen were positive for Leishmania. The overall infection prevalence was 36.25% (29/80) The DNA sequencing showed that 65.51% (19/29) of the positive animals were infected by parasites belonging to the Leishmania braziliensis complex. The identification of L. braziliensis DNA in R. norvegicus in an area with a high prevalence of leishmaniasis might imply a zoonotic role of this species. The rodent control programs and health education may represent important measures toward the control of leishmaniasis.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID:
21767914
[PubMed - as supplied by publisher]
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3. Mol Biochem Parasitol. 2011 Jul 7. [Epub ahead of print]

The characterization of a unique Trypanosoma brucei β-hydroxybutyrate dehydrogenase.

Shah TD, Hickey MC, Capasso KE, Palenchar JB.

Source

Department of Chemistry, Villanova University, 800 E. Lancaster Ave., Villanova, PA 19085, United States.

Abstract

A putative β-hydroxybutyrate dehydrogenase (βHBDH) ortholog was identified in Trypanosoma brucei, the unicellular eukaryotic parasite responsible for causing African Sleeping Sickness. The trypanosome enzyme has greater sequence similarity to bacterial sources of soluble βHBDH than to membrane-bound Type I βHBDH found in higher eukaryotes. The βHBDH gene was cloned from T. brucei genomic DNA and active, recombinant His-tagged enzyme (His(10)-TbβHBDH) was purified to approximate homogeneity from E. coli. βHBDH catalyzes the reversible NADH-dependent conversion of acetoacetate to d-3-hydroxybutyrate. In the direction of d-3-hydroxybutyrate formation, His(10)-TbβHBDH has a k(cat) value of 0.19s(-1) and a K(M) value of 0.69mM for acetoacetate. In the direction of acetoacetate formation, His(10)-TbβHBDH has a k(cat) value of 11.2s(-1) and a K(M) value of 0.65mM for d-3-hydroxybutyrate. Cofactor preference was examined and His(10)-TbβHBDH utilizes both NAD(H) and NADP(H) almost equivalently, distinguishing the parasite enzyme from other characterized βHBDHs. Furthermore, His(10)-TbβHBDH binds NAD(P)(+) in a cooperative fashion, another unique characteristic of trypanosome βHBDH. The apparent native molecular weight of recombinant His(10)-TbβHBDH is 112kDa, corresponding to tetramer, as determined through size exclusion chromatography. RNA interference studies in procyclic trypanosomes were carried out to evaluate the importance of TbβHBDH in vivo. Upon knockdown of TbβHBDH, a small reduction in parasite growth was observed suggesting βHBDH has an important physiological role in T. brucei.

Copyright © 2011. Published by Elsevier B.V.

PMID:
21767577
[PubMed - as supplied by publisher]
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4. Exp Parasitol. 2011 Jul 15. [Epub ahead of print]

Alginate microspheres encapsulated with autoclaved Leishmania major (ALM) and CpG-ODN induced partial protection and enhanced immune response against murine model of leishmaniasis.

Tafaghodi M, Eskandari M, Khamesipour A, Jaafari MR.

Source

Nanotechnology Research Center, Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

A suitable adjuvant and delivery system are needed to enhance efficacy of vaccines against leishmaniasis. In this study, alginate microspheres as an antigen delivery system and CpG-ODN as an immunoadjuvant were used to enhance immune response and induce protection against an experimental autoclaved Leishmania major (ALM) vaccine. Alginate microspheres were prepared by an emulsification technique and the characteristics of the preparation such as size, encapsulation efficiency and release profile of encapsulates were studied. Mean diameter of microspheres was determined using SEM (Scanning Electron Microscopy) and particle size analyzer. The encapsulation efficiency was determined using Lowry protein assay method. The integrity of ALM antigens was assessed using SDS-PAGE. Mean diameter of microspheres was 1.8±1.0μm. BALB/c mice were immunized three times in 3-weeks intervals with ALM+CpG-ODN loaded microspheres [(ALM+CpG)(ALG)], ALM encapsulated alginate microspheres [(ALM)(ALG)], (ALM)(ALG)+CpG, ALM+CpG, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection was observed in group of mice immunized with (ALM+CpG)(ALG). The groups of mice received (ALM+CpG)(ALG), (ALM)(ALG)+CpG, (ALM)(ALG) and ALM+CpG were also showed a significantly (P<0.05) smaller footpad swelling compared with the group that received either ALM alone or PBS. The mice immunized with (ALM+CpG)(ALG) or ALM+CpG showed the significantly (P<0.05) highest IgG2a/IgG1 ratio. The IFN-γ level was significantly (P<0.0001) highest in group of mice immunized with either (ALM)(ALG)+CpG or ALM+CpG. It is concluded that alginate microspheres and CpG-ODN adjuvant when are used simultaneously induced protection and enhanced immune response against ALM antigen.

Copyright © 2011. Published by Elsevier Inc.

PMID:
21767536
[PubMed - as supplied by publisher]
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5. Parasitology. 2011 Jul 18:1-9. [Epub ahead of print]

Characterization of monomeric DNA-binding protein Histone H1 in Leishmania braziliensis.

Carmelo E, González G, Cruz T, Osuna A, Hernández M, Valladares B.

Source

Instituto de Enfermedades Tropicales y Salud Pública de Canarias. Universidad de La Laguna. Av. Astrofisico Fco. Sanchez, s/n. 38202 La Laguna, Tenerife, Spain.

Abstract

SUMMARYHistone H1 in Leishmania presents relevant differences compared to higher eukaryote counterparts, such as the lack of a DNA-binding central globular domain. Despite that, it is apparently fully functional since its differential expression levels have been related to changes in chromatin condensation and infectivity, among other features. The localization and the aggregation state of L. braziliensis H1 has been determined by immunolocalization, mass spectrometry, cross-linking and electrophoretic mobility shift assays. Analysis of H1 sequences from the Leishmania Genome Database revealed that our protein is included in a very divergent group of histones H1 that is present only in L. braziliensis. An antibody raised against recombinant L. braziliensis H1 recognized specifically that protein by immunoblot in L. braziliensis extracts, but not in other Leishmania species, a consequence of the sequence divergences observed among Leishmania species. Mass spectrometry analysis and in vitro DNA-binding experiments have also proven that L. braziliensis H1 is monomeric in solution, but oligomerizes upon binding to DNA. Finally, despite the lack of a globular domain, L. braziliensis H1 is able to form complexes with DNA in vitro, with higher affinity for supercoiled compared to linear DNA.

PMID:
21767437
[PubMed - as supplied by publisher]
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6. Trop Med Int Health. 2011 Jul 18. doi: 10.1111/j.1365-3156.2011.02840.x. [Epub ahead of print]

Skin disorders among travellers returning from tropical and non-tropical countries consulting a travel medicine clinic.

Herbinger KH, Siess C, Nothdurft HD, von Sonnenburg F, Löscher T.

Source

Department of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians University of Munich, Germany.

Abstract

Objective  To evaluate the causes and risks for imported skin disorders among travellers. Methods  Data of 34 162 travellers returning from tropical and non-tropical countries and presenting at the outpatient travel medicine clinic of the University of Munich, Germany, between 1999 and 2009 were analyzed for this study. Of these, 12.2% were diagnosed with skin disorders. Results  Main destinations visited were Asia (40%), Africa (27%) and Latin America (21%). Tourism in the form of adventure travel/backpacking (47%) and package holidays (23%) was the most common purpose of travel. The leading causes of skin disorders were arthropodal (23%), bacterial (22%), helminthic (11%), protozoan (6%), viral (6%), allergic (5%) and fungal (4%). The 10 most frequently diagnosed specific skin diseases associated with specific destinations were insect bites (17%, Southern Europe), cutaneous larva migrans (8%, Asia and Latin America), cutaneous leishmaniasis (2.4%, Mediterranean Region/Middle East), dengue fever (1.5%, Asia), rickettsioses (1.3%, Southern Africa), myiasis (0.8%, Central America), filarioses (0.7%, Africa), tick bites (0.6%, Central/Eastern Europe), schistosomiasis (0.6%, Africa) and tungiasis (0.6%, Africa). Travellers in sub-Saharan Africa had the highest relative risk of acquiring skin disorders. Conclusion  As more than 20% of all skin disorders among returned travellers were caused by arthropods and about 50% by infectious pathogens, pre-travel consultations should include specific prophylaxis and consider the most important risk factor for the travel destination.

© 2011 Blackwell Publishing Ltd.

PMID:
21767336
[PubMed - as supplied by publisher]
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7. Planta Med. 2011 Jul 15. [Epub ahead of print]

Three New Cycloartane Triterpenoids from Astragalus bicuspis.

Jan S, Abbaskhan A, Musharraf SG, Sattar SA, Resayes SI, Al Ottman ZA, Al-Majid AM, Choudhary MI.

Source

H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

Abstract

Three new cycloartane triterpenoids have been isolated from ASTRAGALUS BICUSPIS Fisch. Their structures were elucidated as 23( R),24( S),25( R),26( S)-16 β/23,23/26,24/25-triepoxy-26-hydroxy-9,19-cyclolanosta-3,6-dione ( 1), 6 α,23,24,25-tetraol-16 β-acetoxy-23( R),24( R)-9,19-cyclanosta-3-one ( 2), and 6 α,23,24,25-tetraol-16 β-acetoxy-23( R),24( R)-9,19-cyclolanosta-3 β- O-xyloside ( 3), based on their spectroscopic analysis. All cycloartane tritepenoids exhibited weak cytotoxicities against 3T3 fibroblast cells as compared to the standard drug cycloheximide. Compounds 3 and 4 were also tested for their antileishmanial potential, and a weak activity was observed against promastigotes of LEISHMANIA MAJOR.

© Georg Thieme Verlag KG Stuttgart · New York.

PMID:
21766268
[PubMed - as supplied by publisher]
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8. PLoS Negl Trop Dis. 2011 Jul;5(7):e1236. Epub 2011 Jul 12.

C-Terminal Domain Deletion Enhances the Protective Activity of cpa/cpb Loaded Solid Lipid Nanoparticle s against Leishmania major in BALB/c Mice.

Doroud D, Zahedifard F, Vatanara A, Taslimi Y, Vahabpour R, Torkashvand F, Vaziri B, Rouholamini Najafabadi A, Rafati S.

Source

Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.

Abstract

BACKGROUND:

We have demonstrated that vaccination with pDNA encoding cysteine proteinase Type II (CPA) and Type I (CPB) with its unusual C-terminal extension (CTE) can partially protect BALB/c mice against cutaneous leishmanial infection. Unfortunately, this protection is insufficient to completely control infection without booster injection. Furthermore, in developing vaccines for leishmaniasis, it is necessary to consider a proper adjuvant and/or delivery system to promote an antigen specific immune response. Solid lipid nanoparticles have found their way in drug delivery system development against intracellular infections and cancer, but not Leishmania DNA vaccination. Therefore, undefined effect of cationic solid lipid nanoparticles (cSLN) as an adjuvant in enhancing the immune response toward leishmanial antigens led us to refocus our vaccine development projects.

METHODOLOGY/PRINCIPAL FINDINGS:

Three pDNAs encoding L. major cysteine proteinase type I and II (with or without CTE) were formulated by cSLN. BALB/c mice were immunized twice by 3-week interval, with cSLN-pcDNA-cpa/b, pcDNA-cpa/b, cSLN-pcDNA-cpa/b(-CTE), pcDNA-cpa/b(-CTE), cSLN, cSLN-pcDNA and PBS. Mice vaccinated with cSLN-pcDNA-cpa/b(-CTE) showed significantly higher levels of parasite inhibition related to protection with specific Th1 immune response development, compared to other groups. Parasite inhibition was determined by different techniques currently available in exploration vacciation efficacy, i.e., flowcytometry on footpad and lymph node, footpad caliper based measurements and imaging as well as lymph node microtitration assay. Among these techniques, lymph node flowcytometry was found to be the most rapid, sensitive and easily reproducible method for discrimination between the efficacy of vaccination strategies.

CONCLUSIONS/SIGNIFICANCE:

This report demonstrates cSLN's ability to boost immune response magnitude of cpa/cpb(-CTE) cocktail vaccination against leishmaniasis so that the average parasite inhibition percent could be increased significantly. Hence, cSLNs can be considered as suitable adjuvant and/or delivery systems for designing third generation cocktail vaccines.

Free Article
PMID:
21765963
[PubMed - in process]
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9. PLoS Negl Trop Dis. 2011 Jul;5(7):e1198. Epub 2011 Jul 12.

Evidence that lipopolisaccharide may contribute to the cytokine storm and cellular activation i n patients with visceral leishmaniasis.

Santos-Oliveira JR, Regis EG, Leal CR, Cunha RV, Bozza PT, Da-Cruz AM.

Source

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil.

Abstract

BACKGROUND:

Visceral leishmaniasis (VL) is characterized by parasite-specific immunosuppression besides an intense pro-inflammatory response. Lipopolisaccharide (LPS) has been implicated in the immune activation of T-cell deficient diseases such as HIV/AIDS and idiopathic lymphocytopenia. The source of LPS is gram-negative bacteria that enter the circulation because of immunological mucosal barrier breakdown. As gut parasitization also occurs in VL, it was hypothesized that LPS may be elevated in leishmaniasis, contributing to cell activation.

METHODOLOGY/PRINCIPAL FINDINGS:

Flow cytometry analysis and immunoassays (ELISA and luminex micro-beads system) were used to quantify T-cells and soluble factors. Higher LPS and soluble CD14 levels were observed in active VL in comparison to healthy subjects, indicating that LPS was bioactive; there was a positive correlation between these molecules (r = 0.61;p<0.05). Interestingly, LPS was negatively correlated with CD4(+) (r = -0.71;p<0.01) and CD8(+) T-cells (r = -0.65;p<0.05). Moreover, higher levels of activation-associated molecules (HLA-DR, CD38, CD25) were seen on T lymphocytes, which were positively associated with LPS levels. Pro-inflammatory cytokines and macrophage migration inhibitory factor (MIF) were also augmented in VL patients. Consistent with the higher immune activation status, LPS levels were positively correlated with the inflammatory cytokines IL-6 (r = 0.63;p<0.05), IL-8 (r = 0.89;p<0.05), and MIF (r = 0.64;p<0.05). Also, higher plasma intestinal fatty acid binding protein (IFABP) levels were observed in VL patients, which correlated with LPS levels (r = 0.57;p<0.05).

CONCLUSIONS/SIGNIFICANCE:

Elevated levels of LPS in VL, in correlation with T-cell activation and elevated pro-inflammatory cytokines and MIF indicate that this bacterial product may contribute to the impairment in immune effector function. The cytokine storm and chronic immune hyperactivation status may contribute to the observed T-cell depletion. LPS probably originates from microbial translocation as suggested by IFABP levels and, along with Leishmania antigen-mediated immune suppression, may play a role in the immunopathogenesis of VL. These findings point to possible benefits of antimicrobial prophylaxis in conjunction with anti-Leishmania therapy.

Free Article
PMID:
21765960
[PubMed - in process]
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10. Glob Health Action. 2011;4. doi: 10.3402/gha.v4i0.5527. Epub 2011 Jul 13.

An outbreak of suspected cutaneous leishmaniasis in Ghana: lessons learnt and p reparation for future outbreaks.

Kweku MA, Odoom S, Puplampu N, Desewu K, Nuako GK, Gyan B, Raczniak G, Kronmann KC, Koram K, Botero S, Boakye D, Akuffo H.

Source

District Health Directorate, Ghana Health Service, Volta Region, Ghana.

Abstract

Human cutaneous leishmaniasis (CL) has previously been reported in West Africa, but more recently, sporadic reports of CL have increased. Leishmania major has been identified from Mauritania, Senegal, Mali, and Burkina Faso. Three zymodemes (MON-26, MON-117, and MON-74, the most frequent) have been found. The geographic range of leishmaniasis is limited by the sand fly vector, its feeding preferences, and its capacity to support internal development of specific species of Leishmania. The risk of acquiring CL has been reported to increase considerably with human activity and epidemics of CL have been associated with deforestation, road construction, wars, or other activities where humans intrude the habitat of the vector. In the Ho Municipality in the Volta Region of Ghana, a localised outbreak of skin ulcers, possibly CL, was noted in 2003 without any such documented activity. This outbreak was consistent with CL as evidenced using various methods including parasite identification, albeit, in a small number of patients with ulcers.This paper reports the outbreak in Ghana. The report does not address a single planned study but rather a compilation of data from a number of ad-hoc investigations in response to the outbreak plus observations and findings made by the authors. It acknowledges that a number of the observations need to be further clarified. What is the detailed epidemiology of the disease? What sparked the epidemic? Can it happen again? What was the causative agent of the disease, L. major or some other Leishmania spp.? What were the main vectors and animal reservoirs? What are the consequences for surveillance of the disease and the prevention of its reoccurrence when the communities see a self-healing disease and may not think it is important?

PMID:
21765823
[PubMed - in process]
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