Thursday, May 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 -8 of 8

1: J Clin Lab Anal. 2009 May 19;23(3):152-156. [Epub ahead of print]

Comparative study of amplification systems in immunoenzyme assays for the diagnosis of American tegumentary leishmaniasis.

Nascimento LD, Passos SR, Mouta-Confort E, de Almeida Santiago M, Alves AS, de Fátima Madeira M, de Oliveira Schubach A, de Almeida Marzochi MC.

Laboratório de Vigilância em Leishmanioses, Instituto de Pesquisa Clínica Evandro Chagas-IPEC/FIOCRUZ, Rio de Janeiro, RJ, Brazil.

We compared the accuracy and reliability of three amplification systems for enzyme immunoassays in the detection of specific IgG antibodies for the diagnosis of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis in patients from an endemic area in Rio de Janeiro, Brazil. Partially soluble antigens obtained from the promastigote forms of L. (V.) braziliensis were used. For development of the reaction, two chromogens, 1,2-orthophenylenediamine (OPD) and 3,3',5,5'-tetramethylbenzidine (TMB), and a fluorogen, 4-methylumbelliferylphosphate (MUP), were tested. The performance of each system was compared using the following parameters: accuracy, intraclasscorrelation coefficient (ICC), and area under the receiver operating characteristic (ROC) curve. Sensitivity was the same (97.4%) for all systems. The reliability was excellent (ICC=98.6, 98.7, and 99.1%) and specificity was 93.7, 95.8, and 97.4% for OPD, MUP, and TMB, respectively, showing no statistical significance. Despite the absence of differences in the performance of the three systems, the use of TMB is suggested because of its operational advantages, such as low cost compared with fluorogens, easy manipulation, greater stability, and lower toxicity. J. Clin. Lab. Anal. 23:152-156, 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19455633 [PubMed - as supplied by publisher]

2: J Immunol. 2009 Jun 1;182(11):7146-54.

Miltefosine promotes IFN-gamma-dominated anti-leishmanial immune response.

Wadhone P, Maiti M, Agarwal R, Kamat V, Martin S, Saha B.

National Centre for Cell Science, Ganeshkhind, Pune, India.

Leishmania donovani, a protozoan parasite, resides and replicates as amastigotes within macrophages. The parasite inflicts the disease visceral leishmaniasis by suppressing host cell function. Neither a therapeutic vaccine nor an effective anti-leishmanial drug to reverse the immunosuppression is available. Although miltefosine (hexadecylphosphocholine or HPC) is a promising orally bioavailable anti-leishmanial drug, its efficacy is seriously compromised by contra-indications in pregnant women. Further rational redesigning of the drug requires studies on its mechanism of action, which is unknown at present. Because miltefosine is proposed to have immunomodulatory functions, we examined whether miltefosine exerts its anti-leishmanial functions by activating macrophages. We observed that miltefosine's anti-leishmanial function was significantly compromised in IFN-gamma-deficient macrophages suggesting the importance of endogenous IFN-gamma in miltefosine-induced anti-leishmanial functions of macrophages. Miltefosine induced IFN-gamma, neutralization of which reduced the anti-leishmanial functions of macrophages. IFN-gamma responsiveness is reduced in L. donovani-infected macrophages but is significantly restored by miltefosine, as it enhances IFN-gamma receptors and IFN-gamma induced STAT-1 phosphorylation but reduced activation of SHP-1, the phosphatase implicated in the down-regulation of STAT-1 phosphorylation. Miltefosine induced protein kinase C-dependent and PI3K-dependent p38MAP kinase phosphorylation and anti-leishmanial function. Miltefosine promotes p38MAP kinase-dependent anti-leishmanial functions and IL-12-dependent Th1 response. Leishmania donovani-infected macrophages induced Th2 response but miltefosine treatment reversed the response to Th1-type. Thus, our data define for the first time the mechanistic basis of host cell-dependent anti-leishmanial function of miltefosine.

PMID: 19454711 [PubMed - in process]

3: J Antimicrob Chemother. 2009 May 19. [Epub ahead of print]

Activity of physalins purified from Physalis angulata in in vitro and in vivo models of cutaneous leishmaniasis.

Guimarães ET, Lima MS, Santos LA, Ribeiro IM, Tomassini TB, Dos Santos RR, Dos Santos WL, Soares MB.

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.

Objectives We have previously demonstrated the immunomodulatory effects of physalins, secosteroids purified from Physalis angulata. Here we investigate the antileishmanial activity of physalins in vitro and in vivo in a model of cutaneous leishmaniasis. Methods The antileishmanial activity of physalins B, D and F was tested in Leishmania-infected macrophage cultures. For the in vivo studies, BALB/c mice were infected with Leishmania amazonensis subcutaneously in the ear pinna and treated with physalin F by topical administration. Results Physalins B and F were able to reduce the percentage of Leishmania-infected macrophages and the intracellular parasite number in vitro at concentrations non-cytotoxic to macrophages. More importantly, topical treatment with physalin F significantly reduced the lesion size, the parasite load and histopathological alterations in BALB/c mice infected with L. amazonensis. Conclusions Our results demonstrate the potent antileishmanial activity of physalins, especially physalin F, and suggest these molecules as the basis for the development of new therapeutic options for cutaneous leishmaniasis.

PMID: 19454526 [PubMed - as supplied by publisher]

4: Parasitol Int. 2009 May 16. [Epub ahead of print]

Saliva of laboratory-reared Lutzomyia longipalpis exacerbates Leishmania (Leishmania) amazonensis infection more potently than saliva of wild-caught Lutzomyia longipalpis.

Laurenti MD, Dos Santos Silveira VM, Secundino NF, Corbett CE, Pimenta PP.

Laboratory of Pathology of Infectious Diseases (LIM-50), Department of Pathology, Medical School, University of São Paulo, Av. Dr. Arnaldo 455 - CEP: 01246-903, São Paulo (SP), Brazil.

In order to compare the saliva effect from wild-caught and lab-reared L. longipalpis on the development of experimental cutaneous leishmaniasis, C57BL/6 mice were inoculated subcutaneously into the hind footpads with promastigotes of L. (L.) amazonensis plus salivary gland lysate from wild-caught (SGL-W) and lab-colonized (SGL-C) vectors. Lesion sizes were significantly larger in the mice infected with both saliva compared to mice infected with parasites alone; moreover, the lesions caused by parasite + SGL-C were significantly larger than the lesions caused by parasite + SGL-W. Histopathological morphometric studies regarding the acute phase of infections showed lower numbers of polymorphonuclear cells, greater numbers of mononuclear cells and parasites in SGL-C infected mice compared to SGL-W infected mice. In the chronic phase of infection, the number of mononuclear cells was lower and the number of parasites was greater in SGL-C infected mice than SGL-W infected mice. In vitro studies showed increased infection index of macrophages infected with parasites plus saliva compared to infection with parasites alone, with no difference between the saliva infection indices. SDS-PAGE gel for SGL-C and SGL-W showed differences in the composition and quantity of protein bands, determined by densitometry. These results call attention to the experimental saliva model, which shows exacerbation of infection caused by sandfly saliva.

PMID: 19454323 [PubMed - as supplied by publisher]

5: Traffic. 2009 Mar 12. [Epub ahead of print]

Reversible Phosphorylation as a Molecular Switch to Regulate Plasma Membrane Targeting of Acylated SH4 Domain Proteins.

Tournaviti S, Pietro ES, Terjung S, Schafmeier T, Wegehingel S, Ritzerfeld J, Schulz J, Smith DF, Pepperkok R, Nickel W.

Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.

Acylated SH4 domains represent N-terminal targeting signals that anchor peripheral membrane proteins such as Src kinases in the inner leaflet of plasma membranes. Here we provide evidence for a novel regulatory mechanism that may control the levels of SH4 proteins being associated with plasma membranes. Using a fusion protein of the SH4 domain of Leishmania HASPB and GFP as a model system, we demonstrate that threonine 6 is a substrate for phosphorylation. Substitution of threonine 6 by glutamate (to mimic a phosphothreonine residue) resulted in a dramatic redistribution from plasma membranes to intracellular sites with a particular accumulation in a perinuclear region. As shown by both pharmacological inhibition and RNAi-mediated down-regulation of the threonine/ serine-specific phosphatases PP1 and PP2A, recycling back to the plasma membrane required dephosphorylation of threonine 6. We provide evidence that a cycle of phosphorylation and dephosphorylation may also be involved in intracellular targeting of other SH4 proteins such as the Src kinase Yes.

PMID: 19453972 [PubMed - as supplied by publisher]

6: J Eur Acad Dermatol Venereol. 2009 Apr 30. [Epub ahead of print]

Mucosal leishmaniasis: description of case management approaches and analysis of risk factors for treatment failure in a cohort of 140 patients in Brazil.

Amato VS, Tuon FF, Imamura R, de Camargo RA, Duarte MI, Amato Neto V.

Infectious and Parasitic Diseases Clinic, Hospital das Clinicas, Medical School, University of Sao Paulo, Sao Paulo, Brazil.

Abstract Background Mucosal leishmaniasis is caused mainly by Leishmania braziliensis and it occurs months or years after cutaneous lesions. This progressive disease destroys cartilages and osseous structures from face, pharynx and larynx. Objective and methods The aim of this study was to analyse the significance of clinical and epidemiological findings, diagnosis and treatment with the outcome and recurrence of mucosal leishmaniasis through binary logistic regression model from 140 patients with mucosal leishmaniasis from a Brazilian centre. Results The median age of patients was 57.5 and systemic arterial hypertension was the most prevalent secondary disease found in patients with mucosal leishmaniasis (43%). Diabetes, chronic nephropathy and viral hepatitis, allergy and coagulopathy were found in less than 10% of patients. Human immunodeficiency virus (HIV) infection was found in 7 of 140 patients (5%). Rhinorrhea (47%) and epistaxis (75%) were the most common symptoms. N-methyl-glucamine showed a cure rate of 91% and recurrence of 22%. Pentamidine showed a similar rate of cure (91%) and recurrence (25%). Fifteen patients received itraconazole with a cure rate of 73% and recurrence of 18%. Amphotericin B was the drug used in 30 patients with 82% of response with a recurrence rate of 7%. The binary logistic regression analysis demonstrated that systemic arterial hypertension and HIV infection were associated with failure of the treatment (P < 0.05). Conclusion The current first-line mucosal leishmaniasis therapy shows an adequate cure but later recurrence. HIV infection and systemic arterial hypertension should be investigated before start the treatment of mucosal leishmaniasis. Conflicts of interest The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

PMID: 19453817 [PubMed - as supplied by publisher]

Patient Drug Information

  • Itraconazole (Sporanox® )

    Itraconazole capsules are used to treat fungal infections that begin in the lungsand can spread through the body. Itraconazole capsules are also used to treat fungal infections of the fingernails and/or toenails. Itracon...

  • Source: AHFS Consumer Medication Information
7: J Nat Prod. 2009 Apr;72(4):764-8.Click here to read LinkOut

Citronamides A and B, tetrapeptides from the Australian sponge Citronia astra.

Carroll AR, Duffy S, Avery VM.

Australian Rivers Institute, Griffith University, Gold Coast, Queensland, Australia.

Two new linear tetrapeptides, citronamides A (1) and B (2), were isolated from the Australian sponge Citronia astra and their structures determined by 1D and 2D NMR spectroscopy. The peptides contain two previously unreported amino acids, 3-(2-oxo-2,3-dihydro-1H-imidazol-4-yl)serine and 6-amino-7-(4-methoxyphenyl)heptanoic acid, and alpha-iduronic acid modified at either C-3 or C-4 with a carbamate. Citronamide A showed moderate antifungal activity against Saccharomyces cerevisiae.

PMID: 19260701 [PubMed - indexed for MEDLINE]

8: J Nat Prod. 2009 Apr;72(4):696-9.Click here to read LinkOut

Leptoclinidamines A-C, indole alkaloids from the Australian ascidian Leptoclinides durus.

Carroll AR, Avery VM.

Australian Rivers Institute, Griffith University, Gold Coast, Queensland, Australia. A.Carroll@griffith.edu.au

Three new indole alkaloids, leptoclinidamines A-C (1-3), were isolated from the Australian ascidian Leptoclinides durus. Their structures were determined by analysis of 2D NMR spectra. Leptoclinidamines A and B both contain an indoleglyoxylic acid attached to an L-arginine. The structure of leptoclinidamine A was confirmed by total synthesis. Leptoclinidamine C contains the naturally rare 1,3-dimethyl-5-(methylthio)histidine attached to a 6-bromoindole-3-carboxylic acid. Leptoclinidamine C (3) and both enantiomers of leptoclinidamine A (1) were tested for antimalarial, antitrypanosomal, and cytotoxic activity, but none of the compounds were bioactive.

PMID: 19236031 [PubMed - indexed for MEDLINE]

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