Thursday, June 18, 2009

What's new for 'Trypanosomatids' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

Sender's message:

Sent on Thursday, 2009 Jun 18
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
Click here to view complete results in PubMed. (Results may change over time.)
To unsubscribe from these e-mail updates click here.



PubMed Results
Items 1 -5 of 5

1: Lasers Surg Med. 2009 Jun 16;41(5):358-365. [Epub ahead of print]Click here to read

Optimization of topical photodynamic therapy with 3,7-bis(di-n-butylamino)phenothiazin-5-ium bromide for cutaneous leishmaniasis.

Akilov OE, Yousaf W, Lukjan SX, Verma S, Hasan T.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) has evolved as a promising therapeutic measure for the treatment of cutaneous leishmaniasis (CL). In particular, phenothiazine compounds have demonstrated efficacy for PDT of CL. The objective of our present study is to define the use of a new specific phenothiazine photosensitizer, 3,7-bis(di-n-butylamino)phenothiazin-5-ium bromide (PPA904) applied topically as a cream to treat CL. MATERIALS AND METHODS: To establish the optimal conditions for this treatment, we compared two different ways to improve current regimens of PDT with PPA904 cream (500 microM of PPA904 in Unguentum M) by changing the duration of topical application, and by administration of several consecutive PDT procedures. An initial regimen recommended by the manufacturer (Photopharmica Co. Ltd., Leeds, UK) was maintained as a control: the cream was applied topically for 30 minutes at a final concentration of PPA904 at 500 microM, and the designated treatment area was irradiated with a broad band light source of 665+/-15 nm at a fluence of 50 J/cm(2) (50 mW/cm(2)). RESULTS: The best curative PPA904-PDT regimen was achieved under the conditions of a longer duration of topical application time (90 minutes) and several (three) consecutive treatments with 4-day intervals between treatments. The mechanisms responsible for such improvements (kinetics of drug penetration, depth of necrosis of the CL lesions after PDT, and daily changes in the parasitic load after PDT) are discussed in the present study. CONCLUSION: Topical PPA904-PDT, implemented as described above, is a promising treatment for CL, and clinical studies will be initiated to establish efficacy in humans. Lasers Surg. Med. 41:358-365, 2009. (c) 2009 Wiley-Liss, Inc.

PMID: 19533767 [PubMed - as supplied by publisher]

2: Nucleic Acids Res. 2009 Jun 16. [Epub ahead of print]Click here to read

Bidirectional silencing of RNA polymerase I transcription by a strand switch region in Trypanosoma brucei.

Haenni S, Studer E, Burkard GS, Roditi I.

Institute of Cell Biology, University of Bern, Bern, Switzerland.

The procyclin genes in Trypanosoma brucei are transcribed by RNA polymerase I as part of 5-10 kb long polycistronic transcription units on chromosomes VI and X. Each procyclin locus begins with two procyclin genes followed by at least one procyclin-associated gene (PAG). In procyclic (insect midgut) form trypanosomes, PAG mRNA levels are about 100-fold lower than those of procyclins. We show that deletion of PAG1, PAG2 or PAG3 results in increased mRNA levels from downstream genes in the same transcription unit. Nascent RNA analysis revealed that most of the effects are due to increased transcription elongation in the knockouts. Furthermore, transient and stable transfections showed that sequence elements on both strands of PAG1 can inhibit Pol I transcription. Finally, by database mining we identified 30 additional PAG-related sequences that are located almost exclusively at strand switch regions and/or at sites where a change of RNA polymerase type is likely to occur.

PMID: 19531741 [PubMed - as supplied by publisher]

3: J Liposome Res. 2009 Jun 16. [Epub ahead of print]Click here to read

Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis.

Carneiro G, Santos DC, Oliveira MC, Fernandes AP, Ferreira LS, Ramaldes GA, Nunan EA, Ferreira LA.

Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Belo Horizonte (MG), Brazil.

The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362 nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2 +/- 0.2%) and PC/Chol (4.8 +/- 0.2%) liposomes was higher than solution (1.9 +/- 0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA.

PMID: 19530897 [PubMed - as supplied by publisher]

4: J Egypt Soc Parasitol. 2009 Apr;39(1):227-46.

Diagnosis of clinical samples spotted on FTA cards using PCR-based methods.

Jamjoom M, Sultan AH.

Department of Medical Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. mjamjoom@kau.edu.sa

The broad clinical presentation of Leishmaniasis makes the diagnosis of current and past cases of this disease rather difficult. Differential diagnosis is important because diseases caused by other aetiologies and a clinical spectrum similar to that of leishmaniasis (e.g. leprosy, skin cancers and tuberculosis for CL; malaria and schistosomiasis for VL) are often present in endemic areas of endemicity. Presently, a variety of methods have been developed and tested to aid the identification and diagnosis of Leishmania. The advent of the PCR technology has opened new channels for the diagnosis of leishmaniasis in a variety of clinical materials. PCR is a simple, rapid procedure that has been adapted for diagnosis of leishmaniasis. A range of tools is currently available for the diagnosis and identification of leishmaniasis and Leishmania species, respectively. However, none of these diagnostic tools are examined and tested using samples spotted on FTA cards. Three different PCR-based approaches were examined including: kDNA minicircle, Leishmania 18S rRNA gene and PCR-RFLP of Intergenic region of ribosomal protein. PCR primers were designed that sit within the coding sequences of genes (relatively well conserved) but which amplify across the intervening intergenic sequence (relatively variable). These were used in PCR-RFLP on reference isolates of 10 of the most important Leishmania species: L. donovani, L. infantum, L. major & L. tropica. Digestion of PCR products with restriction enzymes produced species-specific restriction patterns allowed discrimination of reference isolates. The kDNA minicircle primers are highly sensitive in diagnosis of both bone marrow and skin smears from FTA cards. Leishmania 18S rRNA gene conserved region is sensitive in identification of bone marrow smear but less sensitive in diagnosing skin smears. The intergenic nested PCR-RFLP using P5 & P6 as well as P1 & P2 newly designed primers showed high level of reproducibility and sensitivity. Though, it was less sensitive than kDNA minicircle primers, but easily discriminated between Leishmania species.

PMID: 19530624 [PubMed - in process]

5: J Leukoc Biol. 2009 Jun;85(6):1005-14. Epub 2009 Mar 17.Click here to read LinkOut

Proteolytic generation of kinins in tissues infected by Trypanosoma cruzi depends on CXC chemokine secretion by macrophages activated via Toll-like 2 receptors.

Schmitz V, Svensjö E, Serra RR, Teixeira MM, Scharfstein J.

373 Cidade Universitária, Edifício do Centro de Ciências da Saúde (CCS)-Bloco D-sala 7, Rio de Janeiro, RJ, Brazil, CEP 21941-902.

Previous analysis of the endogenous innate signals that steer T cell-dependent immunity in mice acutely infected by the protozoan Trypanosoma cruzi revealed that bradykinin (BK) or lysyl-BK, i.e., the short-lived peptides excised from plasma-borne kininogens through the activity of cruzipain, induces dendritic cell maturation via BK B(2) receptors (B(2)R). Here, we used the s.c. model of T. cruzi infection to study the functional interplay of TLR2, CXCR2, and B(2)R in edema development. Using intravital microscopy, we found that repertaxin (CXCR2 antagonist) blocked tissue-culture trypomastigotes (TCT)-induced plasma leakage and leukocyte accumulation in the hamster cheek pouch topically exposed to TCT. Furthermore, we found that TCT-evoked paw edema in BALB/c mice was blocked by repertaxin or HOE-140 (B(2)R antagonist), suggesting that CXCR2 propels the extravascular activation of the kinin/B(2)R pathway. We then asked if TLR2-mediated sensing of TCT by innate sentinel cells could induce secretion of CXC chemokines, which would then evoke neutrophil-dependent plasma leakage via the CXCR2/B(2)R pathway. Consistent with this notion, in vitro studies revealed that TCT induce robust secretion of CXC chemokines by resident macrophages in a TLR2-dependent manner. In contrast, TLR2(+/+) macrophages stimulated with insect-derived metacyclic trypomastigotes or epimastigotes, which lack the developmentally regulated TLR2 agonist displayed by TCT, failed to secrete keratinocyte-derived chemokine/MIP-2. Collectively, these results suggest that secretion of CXC chemokines by innate sentinel cells links TLR2-dependent recognition of TCT to the kinin system, a proteolytic web that potently amplifies vascular inflammation and innate immunity through the extravascular release of BK.

PMID: 19293401 [PubMed - indexed for MEDLINE]

Posted by at

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)