Wednesday, May 4, 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 12

1. Diagn Cytopathol. 2011 Apr 28. doi: 10.1002/dc.21694. [Epub ahead of print]

Isolated leishmanial lymphadenopathy - A rare type of leishmaniasis in India: A Case Report.

Sharma M, Malhotra A.

Source

Department of Pathology, Central Hospital, South Eastern Railway, Garden Reach, Kolkata, West Bengal, India. sdmopath@ser.railnet.gov.in.

Abstract

A patient presented with isolated, soft to firm, inguinal swelling since childhood clinically thought to be a benign lipomatous lesion. Fine-needle aspiration of the swelling revealed amastigote form of Leishmania donovani in a background of reactive lymphoid hyperplasia. Excision of the swelling resulted in reversal of positive Aldehyde test. Isolated leishmanial lymphadenopathy in an immunocompetent person, is a rare manifestation of leishmaniasis in India. The possible role of transplacental transmission is discussed. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID:
21538958
[PubMed - as supplied by publisher]
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2. Infection. 2011 May 3. [Epub ahead of print]

Seronegative visceral leishmaniasis with relapsing and fatal course following rituximab treatment.

Casabianca A, Marchetti M, Zallio F, Feyles E, Concialdi E, Ferroglio E, Biglino A.

Source

Infectious and Tropical Diseases Unit, "Cardinal Massaja" Hospital, Corso Dante 202, 14100, Asti, Italy, casabianca@asl.at.it.

Abstract

Both the presentation and clinical course of visceral leishmaniasis (VL) may be atypical in immunosuppressed subjects, often resulting in delayed diagnosis and treatment. We describe a case of VL characterized by negative serologic testing, a relapsing course, and a fatal outcome 2 years after the patient had been successfully treated for non-Hodgkin's lymphoma with rituximab. Diagnosis of VL may be further delayed or even missed in patients treated with drugs that interfere with specific antibody production unless specific diagnostic methods, such as bone marrow examination and parasite DNA amplification/detection, are routinely employed.

PMID:
21538038
[PubMed - as supplied by publisher]
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3. Mem Inst Oswaldo Cruz. 2011 Mar;106(2):251-3.

In vitro activity of amphotericin B cochleates against Leishmania chagasi.

Sesana AM, Monti-Rocha R, Vinhas SA, Morais CG, Dietze R, Lemos EM.

Source

Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.

Abstract

Cochleate delivery vehicles are a novel lipid-based system with potential for delivery of amphotericin B (AmB). In this study, the efficacy of cochleates was evaluated by examining the in vitro activity of AmB cochleates (CAMB) against Leishmania chagasi in a macrophage model of infection. We demonstrate that CAMB is nontoxic to macrophages at concentrations as high as 2.5 μg/mL, whereas the conventional formulation, AmB deoxycholate, showed high toxicity at this concentration. The in vitro activity of CAMB against L. chagasi was found to be similar to that of the reference drug AmB deoxycholate, with ED50s of 0.017 μg/mL and 0.021 μg/mL, respectively. Considering that L. chagasi affects organs amenable to cochleate-mediated delivery of AmB, we hypothesize that CAMB will be an effective lipid system for the treatment of visceral leishmaniasis.

PMID:
21537689
[PubMed - in process]
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4. Mem Inst Oswaldo Cruz. 2011 Mar;106(2):207-11.

Leishmania infection in humans, dogs and sandflies in a visceral leishmaniasis endemic area in Maranhão, Brazil.

Felipe IM, Aquino DM, Kuppinger O, Santos MD, Rangel ME, Barbosa DS, Barral A, Werneck GL, Caldas Ade J.

Source

Universidade Federal do Maranhão, São Luís, MA, Brasil, 62020-660.

Abstract

Leishmania infection in humans, dogs and sandflies was examined in the endemic visceral leishmaniasis (VL) municipality of Raposa, state of Maranhão, Brazil. In this study, we examined Leishmania chagasi infection in the blood serum of both humans and Canis familiaris and the natural Leishmania sp. infection rate in the sandfly vector, Lutzomyia longipalpis. Enzyme-linked immunosorbent assay, indirect immunofluorescence reaction and polymerase chain reaction were performed to detect Leishmania infections in humans, dogs and sandflies, respectively. Overall, 186 out of 986 studied human beings were infected with L. chagasi parasites, representing an infection prevalence of 18.9%. An even higher infection rate was detected in dogs, where 66 (47.8%) out of 138 were infected. Among all Lu. longipalpis captured (n = 1,881), only 26.7% were females. The Leishmania infection frequency for the vector Lu. longipalpis was 1.56%. Remarkably, all infected sandflies were found in the peridomiciliary area. Furthermore, a high incidence of asymptomatic forms of VL in the human and canine populations was observed. The results of this study suggest autochthonous transmission of L. chagasi in this endemic area for visceral leishmaniasis because infection by Leishmania sp. was identified in all important elements of the transmission chain.

PMID:
21537682
[PubMed - in process]
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5. Mem Inst Oswaldo Cruz. 2011 Mar;106(2):190-3.

Correlation of meta 1 expression with culture stage, cell morphology and infectivity in Leishmania (Leishmania) amazonensis promastigotes.

Santos MG, Silva MF, Zampieri RA, Lafraia RM, Floeter-Winter LM.

Source

Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brasil.

Abstract

The parasitic protozoan Leishmania (Leishmania) amazonensis alternates between mammalian and insect hosts. In the insect host, the parasites proliferate as procyclic promastigotes andthen differentiate into metacyclic infective forms. The meta 1 gene is preferentially expressed during metacyclogenesis. Meta 1 expression profile determination along parasite growth curves revealed that the meta 1 mRNA level peaked at the early stationary phase then decreased to an intermediate level. No correlation was observed between meta 1 expression and infectivity. Conversely, infectivity correlated with the increase of apoptotic cells in the late stationary phase.

PMID:
21537679
[PubMed - in process]
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6. Mem Inst Oswaldo Cruz. 2011 Mar;106(2):182-9.

An experimental protocol for the establishment of dogs with long-term cellular immune reactions to Leishmania antigens.

Teixeira MC, Oliveira GG, Santos PO, Bahiense TC, Silva VM, Rodrigues MS, Larangeira DF, Dos-Santos WL, Pontes-de-Carvalho LC.

Source

Universidade Federal da Bahia, Salvador, BA, Brasil.

Abstract

Domestic dogs are considered to be the main reservoirs of zoonotic visceral leishmaniasis. In this work, we evaluated a protocol to induce Leishmania infantum/Leishmania chagasi-specific cellular and humoral immune responses in dogs, which consisted of two injections of Leishmania promastigote lysate followed by a subcutaneous inoculation of viable promastigotes. The primary objective was to establish a canine experimental model to provide positive controls for testing immune responses to Leishmania in laboratory conditions. After inoculation of viable promastigotes, specific proliferative responses of peripheral blood mononuclear cells (PBMCs) to either Leishmania lysate or recombinant proteins, the in vitro production of interferon-γ by antigen-stimulated PBMCs and a significant increase in circulating levels of anti-Leishmania antibodies were observed. The immunized dogs also displayed positive delayed-type hypersensitivity reactions to Leishmania crude antigens and to purified recombinant proteins. An important finding that supports the suitability of the dogs as positive controls is that they remained healthy for the entire observation period, i.e., more than seven years after infection. Following the Leishmania antigen lysate injections, the infection of dogs by the subcutaneous route appears to induce a sustained cellular immune response, leading to an asymptomatic infection. This provides a useful model for both the selection of immunogenic Leishmania antigens and for immunobiological studies on their possible immunoprotective activities.

PMID:
21537678
[PubMed - in process]
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7. World J Biol Chem. 2011 Mar 26;2(3):48-58.

Protease expression by microorganisms and its relevance to crucial physiolog ical/pathological events.

Dos Santos AL.

Source

André Luis Souza dos Santos, Laboratory of Multidisciplinary Studies on Microbial Biochemistry, Department of General Microbiology, Institute of Microbiology Prof. Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.

Abstract

The treatment of infections caused by fungi and trypanosomatids is difficult due to the eukaryotic nature of these microbial cells, which are similar in several biochemical and genetic aspects to host cells. Aggravating this scenario, very few antifungal and anti-trypanosomatidal agents are in clinical use and, therefore, therapy is limited by drug safety considerations and their narrow spectrum of activity, efficacy and resistance. The search for new bioactive agents against fungi and trypanosomatids has been expanded because progress in biochemistry and molecular biology has led to a better understanding of important and essential pathways in these microorganisms including nutrition, growth, proliferation, signaling, differentiation and death. In this context, proteolytic enzymes produced by these eukaryotic microorganisms are appointed and, in some cases, proven to be excellent targets for searching novel natural and/or synthetic pharmacological compounds, in order to cure or prevent invasive fungal/trypanosomatid diseases. With this task in mind, our research group and others have focused on aspartic-type proteases, since the activity of this class of hydrolytic enzymes is directly implicated in several facets of basic biological processes of both fungal and trypanosomatid cells as well as due to the participation in numerous events of interaction between these microorganisms and host structures. In the present paper, a concise revision of the beneficial effects of aspartic protease inhibitors, with emphasis on the aspartic protease inhibitors used in the anti-human immunodeficiency virus therapy, will be presented and discussed using our experience with the following microbial models: the yeast Candida albicans, the filamentous fungus Fonsecaea pedrosoi and the protozoan trypanosomatid Leishmania amazonensis.

PMID:
21537490
[PubMed - in process]
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8. Antimicrob Agents Chemother. 2011 May 2. [Epub ahead of print]

CpG-oligodeoxynucleotide (2006) and miltefosine: a potential combination for treatment of experimental VL.

Gupta S, Sane SA, Shakya N, Vishwakarma P, Haq W.

Source

Division of Parasitology.

Abstract

In view of the severe immunosuppression in VL, a rational approach to effectively combat the parasitic scourge would be to enhance the immune status of the host. Use of CpG-oligodeoxynucleotide (ODN) has previously been reported against leishmaniasis especially as immunomodulators and adjuvant with various immunogens. The experiments were carried out in BALB/c mice and hamsters, infected with Leishmania donovani. Immunostimulating class B bacterial CpG ODN namely, ODN-2006 was administered at various doses by intraperitoneal (ip) route. The dose of CpG-ODN-2006 (1 nM/single dose) showing best antileishmanial activity was given as free and liposomal form with different doses of miltefosine, namely at 5 and 10 mg/kg for five days in mice and hamsters, respectively. Among the various groups, mice co-administered with liposomal CpG-ODN and miltefosine (5 mg/kg) have shown best inhibitory effect (97% parasite inhibition) compared with free CpG-ODN plus miltefosine, miltefosine, free CpG-ODN and liposomal CpG-ODN separately. Similar responses were observed in case of hamsters also, where combination of liposomal CpG-ODN with miltefosine (10 mg/kg) gave 96% parasite inhibition. Promising antileishmanial efficacy was observed in animals treated with liposomal CpG-ODN and miltefosine.

PMID:
21537026
[PubMed - as supplied by publisher]
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9. Infect Immun. 2011 May 2. [Epub ahead of print]

Spermidine Synthase is Required for Virulence of Leishmani a donovani.

Gilroy C, Olenyik T, Roberts SC, Ullman B.

Source

Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, Oregon 97239-3098.

Abstract

Genetic lesions in the polyamine biosynthetic pathway of Leishmania donovani, the causal agent of visceral leishmaniasis, are conditionally lethal mutations that render the insect vector form of the parasite auxotrophic for polyamines. Recently, we have demonstrated that a Δodc L. donovani null mutant lacking ornithine decarboxylase (ODC), the rate limiting enzyme in polyamine biosynthesis, was profoundly compromised in its ability to infect mice indicating that ODC is essential for the infectious mammalian stage of the parasite and further validating the enzyme as a possible drug target. To assess whether other components of the polyamine biosynthetic pathway were also essential for parasite virulence, a cell line deficient in spermidine synthase (SPDSYN), the enzyme that converts putrescine to spermidine, was created by double targeted gene replacement within a virulent L. donovani background. This Δspdsyn strain was auxotrophic for polyamines, required spermidine for growth in its insect vector form, and was adversely impacted in its ability to infect mice. These findings establish that SPDSYN, like ODC, is essential for maintaining a robust infection in mammals and indicate that pharmacologic inhibition of SPDSYN - and perhaps all components of the polyamine biosynthetic pathway - is a valid therapeutic strategy for the treatment of visceral and potentially other forms of leishmaniasis.

PMID:
21536795
[PubMed - as supplied by publisher]
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10. J Exp Med. 2011 May 2. [Epub ahead of print]

Langerhans cells are negative regulators of the anti-Leishmania response.

Kautz-Neu K, Noordegraaf M, Dinges S, Bennett CL, John D, Clausen BE, von Stebut E.

Source

Department of Dermatology, Johannes-Gutenberg University, 55131 Mainz, Germany.

Abstract

Migratory skin dendritic cells (DCs) are thought to play an important role in priming T cell immune responses against Leishmania major, but DC subtypes responsible for the induction of protective immunity against this pathogen are still controversial. In this study, we analyzed the role of Langerin(+) skin-derived DCs in the Leishmania model using inducible in vivo cell ablation. After physiologically relevant low-dose infection with L. major (1,000 parasites), mice depleted of all Langerin(+) DCs developed significantly smaller ear lesions with decreased parasite loads and a reduced number of CD4(+) Foxp3(+) regulatory T cells (T reg cells) as compared with controls. This was accompanied by increased interferon γ production in lymph nodes in the absence of Langerin(+) DCs. Moreover, selective depletion of Langerhans cells (LCs) demonstrated that the absence of LCs, and not Langerin(+) dermal DC, was responsible for the reduced T reg cell immigration and the enhanced Th1 response, resulting in attenuated disease. Our data reveal a unique and novel suppressive role for epidermal LCs in L. major infection by driving the expansion of T reg cells. A better understanding of the various roles of different DC subsets in cutaneous leishmaniasis will improve the development of a potent therapeutic/prophylactic vaccine.

PMID:
21536741
[PubMed - as supplied by publisher]
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