Tuesday, June 19, 2012

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 13

1. Tetrahedron Lett. 2012 Mar 28;53(13):1624-1626. Epub 2012 Jan 28.

Antifungal Depsidone Metabolites from Cordyceps dipterigena, an Endophytic Fungus Antagonistic to the Phytopathogen Gibberella fujikuroi.

Varughese T, Riosa N, Higginbotham S, Arnold AE, Coley PD, Kursar TA, Gerwick WH, Cubilla Rios L.

Source

Laboratory of Tropical Bioorganic Chemistry, Faculty of Natural Exact Sciences and Technology, University of Panama, Republic of Panama.

Abstract

Among thirty four endophytic fungal strains screened for in vitro antagonism, the endophytic fungus Cordyceps dipterigena was found to strongly inhibit mycelial growth of the plant pathogenic fungus Gibberella fujikuroi. Two new depsidone metabolites, cordycepsidone A (1) and cordycepsidone B (2), were isolated from the PDA culture extract of C. dipterigena and identified as being responsible for the antifungal activity. Elucidation of their chemical structures was carried out using 1D and 2D NMR spectroscopy in combination with IR and MS spectroscopic data. Cordycepsidone A displayed strong and dose-dependent antifungal activity against the plant pathogenic fungus Gibberella fujikuroi. The isolates were inactive in bioassays for malaria (Plasmodium falciparum), leishmaniasis (Leishmania donovani), Chagas's disease (Trypanosoma cruzi), and cytotoxicity at 10 μg/mL. The compounds were also found to be inactive against several bacterial strains at 50 μg/mL.

PMID: 22707798 [PubMed]
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2. Parasitol Res. 2012 Jun 16. [Epub ahead of print]

A cross-sectional study on canine Leishmania (L.) infantum chagasi infection in Amazonian Brazil ratifies a higher prevalence of specific IgG-antibody response than delayed-type hypersensitivity in symptomatic and asymptomatic dogs.

Silveira FT, Carneiro LA, Ramos PK, Chagas EJ, Lima LV, Campos MB, Laurenti MD, Gomes CM, Corbett CE.

Source

Parasitology Department, Evandro Chagas Institute (Surveillance Secretary of Health, Ministry of Health), Rod. BR 316-KM 07, Levilândia, Ananindeua, 67.030-000, Pará State, Brazil, silveiraft@lim50.fm.usp.br.

Abstract

This was a cross-sectional study which analyzed the prevalence and the clinical and immunological spectrum of canine Leishmania (L.) infantum chagasi infection in a cohort of 320 mongrel dogs living in an endemic area of American visceral leishmaniasis in the Amazonian Brazil by using, mainly, the indirect fluorescence antibody test (IFAT-IgG) and the delayed-type hypersensitivity (DTH), and the parasite research by the popliteal lymph node aspiration. The IFAT and DTH reactivity recognized three different immune response profiles: (1) IFAT((+))/DTH((-)) (107 dogs), (2) IFAT((-))/DTH((+)) (18 dogs), and (3) IFAT((+))/DTH((+)) (13 dogs), providing an overall prevalence of infection of 43 % (138/320). Thus, the specific prevalence of IFAT( (+) )/DTH( (-) ) 33.4 % (107/320) was higher than those of IFAT( (-) )/DTH( (+) ) 5.6 % (18/320) and IFAT( (+) )/DTH( (+) ) 4.0 % (13/320). Moreover, the frequency of these profiles among 138 infected dogs showed that the IFAT( (+) )/DTH( (-) ) rate of 77.5 % (107/138) was also higher than those of 13.0 % (18/138) of IFAT( (-) )/DTH( (+) ) and 9.5 % (13/138) of IFAT( (+) )/DTH( (+) ) rates. The frequency of asymptomatic dogs (76 %-105) was higher than those of symptomatic (16.6 %-23) and oligosymptomatic ones (7.4 %-10). A total of 16 (11.6 %) L. (L.) i. chagasi isolates were obtained from infected dogs, all from the IFAT( (+) ) /DTH( (-) ) profile: 41 % (9/22) from symptomatic, 33.3 % (3/9) from oligosymptomatic, and 5.2 % (4/76) from asymptomatic dogs. These findings strongly suggested that despite the higher frequency of asymptomatic dogs (76 %-105), the majority (72.4 %-76) was characterized by the IFAT( (+) ) /DTH( (-) ) profile with a doubtful immunogenetic resistance against infection.

PMID: 22706905 [PubMed - as supplied by publisher]
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3. Int J Parasitol. 2012 Jun 12. [Epub ahead of print]

The presence of Tregs does not preclude immunity to reinfection with Leishmania braziliensis.

Falcão SC, de Moura TR, Clarêncio J, Brodskyn C, Barral A, de Oliveira CI.

Source

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Rua Waldemar Falcão, 121, Salvador, BA, Brazil.

Abstract

Leishmania spp. cause a broad spectrum of diseases collectively known as leishmaniasis. Leishmania braziliensis is the main etiological agent of American cutaneous leishmaniasis and mucocutaneous leishmaniasis. During experimental infection with L. braziliensis, BALB/c mice develop an adaptive immune response that is associated with lesion healing and, in parallel, parasite persistence within draining lymph nodes (dLNs). In the Leishmania major model of cutaneous leishmaniasis, regulatory T cells (Tregs) play an important role in immune regulation, preventing pathological immune responses but at the same time precluding sterile cure. In this study we investigated the role of Tregs during experimental infection with L. braziliensis. CD4(+)CD25(+) T cells were detected throughout the duration of clinical disease both at the ear and in dLNs of infected mice. These cells expressed Treg markers such as glucocorticoid-induced TNF-receptor-related protein (GITR), the chain of the 7 integrin (CD103), and the forkhead/winged helix transcription factor, Foxp3, and were able to suppress the proliferation of CD4(+)CD25(-) cells. Importantly, a high frequency of Foxp3(+) cells accumulated at the site of infection and in dLNs. We next investigated the outcome of a reinfection with L. braziliensis in terms of Treg distribution and disease reactivation. Interestingly, a secondary inoculation with L. braziliensis did not preclude an efficient recall response to L. braziliensis at a distal site, despite the presence of Tregs. Within dLNs, reinfection did not promote parasite dissemination or a differential recruitment of either CD4(+)CD25(+)Foxp3(+) or CD4(+)IL-10(+) T cells. On the contrary, parasites were mainly detected in the LN draining the primary infection site where a high frequency of CD4(+) IFN-(+) T cells was also present. Collectively these data show that during experimental infection, Tregs are present in healed mice but this population does not compromise an effective immune response upon reinfection with L. braziliensis.

Copyright © 2012. Published by Elsevier Ltd.

PMID: 22705204 [PubMed - as supplied by publisher]
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4. Vaccine. 2012 Jun 12. [Epub ahead of print]

Vaccination with Leishmania histone H1-pulsed dendritic cells confers protection in murine visceral leishmaniasis.

Agallou M, Smirlis D, Soteriadou KP, Karagouni E.

Source

Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias Ave., 115 21 Athens, Greece.

Abstract

Visceral leishmaniasis is the most severe form of leishmaniases affecting millions of people worldwide often resulting in death despite optimal therapy. Thus, there is an urgent need for the development of effective anti-infective vaccine(s). In the present study, we evaluated the prophylactic value of bone marrow-derived dendritic cells (BM-DCs) pulsed with the Leishmania (L.) infantum histone H1. We developed fully mature BM-DCs characterized by enhanced capacity of IL-12 production after ex vivo pulsing with GST-LeishH1. Intravenous administration of these BM-DCs in naive BALB/c mice resulted in antigen-specific spleenocyte proliferation and IgG1 isotype antibody production and conferred protection against experimental challenge with L. infantum independently of CpG oligonucleotides (ODNs) co-administration. Protection was associated with a pronounced enhancement of parasite-specific IFNγ-producing cells and reduction of cells producing IL-10, whereas IL-4 production was comparable in protected and non-protected mice. The polarization of immune responses to Th1 type was further confirmed by the elevation of parasite-specific IgG2a/IgG1 ratio in protected mice. The above data indicate the immunostimulatory capacity of Leishmania histone H1 and further support its exploitation as a candidate protein for vaccine development against leishmaniasis.

Copyright © 2012. Published by Elsevier Ltd.

PMID: 22704924 [PubMed - as supplied by publisher]
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5. Trends Parasitol. 2012 Jun 15. [Epub ahead of print]

An alternative form of melarsoprol in sleeping sickness.

Kennedy PG.

Source

Department of Neurology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Southern General Hospital, Glasgow G51 4TF, Scotland, UK.

Abstract

Human African trypanosomiasis (HAT), or sleeping sickness, is a major threat to human health throughout sub-Saharan Africa. Almost always fatal if untreated or inadequately treated, a commonly used drug for treating late-stage HAT, and the only drug for late-stage Trypanosoma brucei rhodesiense, is intravenous melarsoprol, which kills 5% of patients receiving it. Melarsoprol cyclodextrin inclusion complexes have been tested in a highly reliable mouse model of HAT. These complexes increase the oral bioavailability of melarsoprol making them effective orally and both curative and nontoxic in doses that are equivalent to those of intravenous melarsoprol. It is argued that a small clinical trial of this drug in HAT is justified to potentially improve the outcome of patients with late-stage rhodesiense disease.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22704910 [PubMed - as supplied by publisher]
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6. Parasit Vectors. 2012 Jun 15;5(1):120. [Epub ahead of print]

Tongue nodules in canine leishmaniosis - a case report.

Viegas C, Requicha J, Albuquerque C, Sargo T, Machado J, Dias I, Pires MA, Campino L, Cardoso L.

Abstract

ABSTRACT:

BACKGROUND:

Canine leishmaniosis (CanL) caused by Leishmania infantum is an endemic zoonosis in southern European countries. Infected dogs can present rare or atypical forms of the disease and diagnosis can be challenging. The present report describes a case of tongue nodules in a 3-year-old neutered female Labrador Retriever dog with leishmaniosis.

FINDINGS:

A fine needle aspiration of the lingual nodules revealed amastigote forms of Leishmania inside macrophages. Differential diagnosis ruled out neoplasia, calcinosis circumscripta, solar glossitis, vasculitis, amyloidosis, eosinophilic granulomas, chemical and electrical burns, uremic glossitis and autoimmune diseases. Combined therapy with antimoniate meglumine and allopurinol for 30 days resulted in the normalization of hematological and biochemical parameters. Two months after diagnosis and the beginning of treatment, a mild inflammatory infiltrate was observed by histopathology, but an anti-Leishmania immunofluorescence antibody test (IFAT) was negative as well as a PCR on both tongue lesions and a bone marrow aspirate. Seven months after diagnosis, the dog's general condition appeared good, there were no tongue lesions and a new IFAT was negative. Fifteen months after diagnosis this clinically favourable outcome continued.

CONCLUSIONS:

The dog could have suffered a relapsing episode of CanL, but a new systemic or local infection cannot be excluded. Regular clinical re-evaluation should be maintained, as a future relapse can potentially occur. In conclusion, CanL should be considered in the differential diagnosis of nodular glossitis in dogs.

PMID: 22704596 [PubMed - as supplied by publisher]
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7. J Laryngol Otol. 2012 Jun 15:1-4. [Epub ahead of print]

Auricular cutaneous leishmaniasis mimicking neoplastic disease.

Tarkan O, Cetık F, Uzun S.

Source

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Cukurova University, Adana, Turkey.

Abstract

Objective:Leishmaniasis comprises a group of diseases transmitted by the bite of infected sand flies. There are three basic clinical forms of leishmaniasis: cutaneous, mucocutaneous and visceral. Leishmaniasis may mimic neoplastic lesions and other infectious diseases because of similar disease localisation, physical characteristics and histopathological findings.Case report:A 35-year-old man was referred to our clinic with a presumed diagnosis of angiolymphoid hyperplasia of the auricle; however, this lesion proved to be cutaneous leishmaniasis. The definitive diagnosis was reached by identifying the parasites on smears obtained from the lesion.Conclusion:It should be borne in mind that cutaneous leishmaniasis presenting as isolated auricular lesions may mimic neoplasia. In the present case report, we discuss auricular cutaneous leishmaniasis and we review the relevant literature.

PMID: 22704524 [PubMed - as supplied by publisher]
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8. Soc Sci Med. 2012 May 26. [Epub ahead of print]

Cruel disease, cruel medicine: Self-treatment of cutaneous leishmaniasis with harmful chemical substances in Suriname.

Ramdas S.

Source

Amsterdam Institute for Social Science Research, University of Amsterdam, Kloveniersburgwal 48, 1012 CX Amsterdam, The Netherlands.

Abstract

Why are potentially harmful, non-biomedical chemical substances, such as battery acid, chlorine, herbicides, and insecticides, used in the treatment of cutaneous leishmaniasis (CL)? What drives people to use these products as medicine? This article is about perceptions of CL, and the quest for a cure, in Suriname, South America. It highlights the associative style of reasoning behind health seeking and discusses the use of harmful chemical substances as medicines. Cutaneous leishmaniasis, a parasitic disease, affects 1 to 1.5 million people globally. It has a spectrum of clinical manifestations, but the most prominent and disfiguring elements are extensive dermatological ulceration and scar formation from lesions. The data upon which this article is based are derived from anthropological research carried out in different parts of Suriname between September 2009 and December 2010. Data was collected through mainly qualitative methods, including interviewing 205 CL patients using structured questionnaires at the Dermatological Service in the capital Paramaribo. Almost all people with CL said they tried self-treatment, varying from the use of ethno-botanical products to non-biomedical chemical solutions. This article presents and interprets the views and practices of CL patients who sought treatment using harsh chemicals. It argues that a confluence of contextual factors - environmental, occupational, infrastructural, geographical, socio-cultural, economic, socio-psychological - leads to the use of harmful chemical substances to treat CL sores. This study is the first in Suriname - and one of the few done globally - focusing on social and cultural aspects related to CL health seeking. It aims to encourage health policy makers and health professionals to carefully initiate, provide, and evaluate CL treatment and prevention programs.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22704264 [PubMed - as supplied by publisher]
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9. Antioxid Redox Signal. 2012 Jun 15. [Epub ahead of print]

Ascorbate peroxidase acts as a novel determiner of redox homeostasis in Leishmania.

Adak S, Pal S.

Source

CSIR-Indian Institute of Chemical Biology, Structural Biology and Bio-informatics, 4, Raja S.C. Mullick Road, Kolkata, India, 700032, 91-33-24995855; adaks@iicb.res.in.

Abstract

Significance: Reactive oxygen species (ROS) are produced as natural byproducts of metabolism and respiration. While physiological levels of ROS are required for vital cellular functions (eg development and proliferation), a living organism, is faced with constant challenges due to accumulation or overproduction of ROS throughout its life. The life cycle of Leishmania parasite has led it to confront the highly oxidizing environment in the macrophage phagosomes, necessitating ROS homeostasis and signaling as key strategies for successful survival and pathogenicity. Recent Advances: Ascorbate peroxidase from L. major (LmAPX) is the only heme peroxidase identified so far in Leishmania. Structural analysis and functional characterization of LmAPX have yielded interesting and novel insight on this enzyme. The protein has been found to be a hybrid of cytochrome c peroxidase and ascorbate peroxidase. This enzyme is co-localized with cytochrome c in the inner mitochondrial membrane facing the intermembrane space and shows higher activity towards cytochrome c oxidation. Critical Issues: Overexpression of LmAPX in L. major cells confers tolerance to oxidative stress-mediated cardiolipin oxidation and consequently protects cells from extensive protein damage. LmAPX-/- mutants show higher intracellular H2O2 which might signal for cellular transformation from noninfective procyclic to infective metacyclic form and ultimately apoptosis. Future Directions: Manipulation of LmAPX expression has added significantly to the present understanding of the parasite's defense network against oxidative damage caused by H2O2. The future investigations will address more exactly the signaling pathways involved in redox homeostasis.

PMID: 22703594 [PubMed - as supplied by publisher]
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10. Chem Biol Drug Des. 2012 Jun 15. doi: 10.1111/j.1747-0285.2012.01427.x. [Epub ahead of print]

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal and anti-HIV activities.

Ahmed N, Brahmbhatt KG, Khan SI, Jacob M, Tekwani BL, Sabde S, Mitra D, Singh IP, Khan IA, Bhutani KK.

Source

Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab-160062, India National Center for Natural Products Research Department of Pharmacognosy Department of Pharmacology, School of Pharmacy, University of Mississippi, MS 38677, USA National Center for Cell Science (NCCS), Pune University Campus, Ganeshkhind, Pune, Maharashtra-411007, India.

Abstract

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC(50) 1.25 and 0.88 μM and chloroquine-resistant W2 strain with IC(50) 1.64 and 1.07 μM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC(50) 2.39 and 2.78 μM and IC(90) 11.27 and 12.76 μM respectively. Three analogues 12c, 14c and 14i were the most active against various pathogenic bacteria and fungi with IC(50) <3.02 μM and MIC/MBC/MFC <6 μM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structral class for broad spectrum activity. © 2012 John Wiley & Sons A/S.

© 2012 John Wiley & Sons A/S.

PMID: 22703590 [PubMed - as supplied by publisher]
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