Wednesday, May 11, 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 - 7 of 7

1. Rev Soc Bras Med Trop. 2011 Apr;44(2):136-139. Epub 2011 Mar 18.

Phlebotomine sandflies (Diptera: Psychodidae) in Governador Valadares, a transmission area for American tegumentary leishmaniasis in State of Minas Gerais, Brazil.

Barata RA, Paz GF, Bastos MC, Andrade RC, Barros DC, Silva FO, Michalsky EM, Pinheiro AD, Dias ES.

Source

Departamento de Ciências Biológicas, Universidade Federal do Vale do Jequitinhonha e Mucuri, Diamantina, MG.

Abstract

INTRODUCTION:

A study on the phlebotomine sandfly fauna was carried out in an endemic area for American tegumentary leishmaniasis in the municipality of Governador Valadares, in the State of Minas Gerais, Brazil.

METHODS:

Captures were undertaken using HP light traps in four districts, on three nights per month, for one year (from January to December 2008). Correlations between climatic factors (temperature, relative air humidity and rainfall) and the numbers of sandflies collected was observed.

RESULTS:

5,413 phlebotomine specimens were caught and were identified as belonging to 12 species. Of these specimens, 2,851 (52%) were females and 2,562 (48%) were males.

CONCLUSIONS:

Lutzomyia intermedia predominated (29.9% of the species caught), thus suggesting that they were responsible for transmission of American tegumentary leishmaniasis, together with L. whitmani, which was also found in the area (4.3%). The presence of L. longipalpis (11.9%), the main vector for visceral leishmaniasis in Brazil, is an important finding, which makes rigorous entomological surveillance of the area necessary.

PMID:
21556488
[PubMed - as supplied by publisher]
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2. Int J Antimicrob Agents. 2011 May 7. [Epub ahead of print]

Clinical isolates of New World Leishmania from cutaneous and visceral leishmaniasis patients are uniformly sensitive to tamoxifen.

Miguel DC, Zauli-Nascimento RC, Yokoyama-Yasunaka JK, Pereira LI, Jerônimo SM, Ribeiro-Dias F, Dorta ML, Uliana SR.

Source

Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

PMID:
21555208
[PubMed - as supplied by publisher]
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3. Eur J Med Chem. 2011 Apr 15. [Epub ahead of print]

Synthesis and evaluation of monoamidoxime derivatives: Toward new antileishmanial compounds.

Paloque L, Bouhlel A, Curti C, Dumètre A, Verhaeghe P, Azas N, Vanelle P.

Source

UMR-MD3-Relations Hôte-Parasites, Pharmacologie et Thérapeutique, Faculté de Pharmacie, Université d'Aix-Marseille II, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.

Abstract

A new series of monoamidoxime derivatives was synthesized using manganese(III) acetate by microwave irradiation. Several amidoximes (27-31, 33, 38) showed valuable in vitro activities toward Leishmania donovani promastigotes, exhibiting IC(50) values between 5.21 and 7.89 μM. In parallel, the cytotoxicity of these compounds was evaluated on murine J774A.1 cells, revealing the corresponding selectivity index (SI). Among the 13 tested compounds, 4 monoamidoximes (27-30) exhibited an SI more than 20 times better than pentamidine. Moreover, monoamidoxime 28 (4-[5-Benzyl-3-(4-fluorophenylsulfonyl)-5-methyl-4,5-dihydrofuran-2-yl]-N'-hydroxybenzimidamide) is 40 times more selective than pentamidine, and 1.6 times more than amphotericin B, used as reference drug compounds.

Copyright © 2011 Elsevier Masson SAS. All rights reserved.

PMID:
21555166
[PubMed - as supplied by publisher]
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4. Parasitology. 2011 Apr 18:1-8. [Epub ahead of print]

Latent Trypanosoma brucei gambiense foci in Uganda: a silent epidemic in children and adults?

Wastling SL, Picozzi K, Wamboga C, VON Wissmann B, Amongi-Accup C, Wardrop NA, Stothard JR, Kakembo A, Welburn SC.

Source

Centre for Infectious Diseases, Division of Pathway Medicine, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Summerhall, Edinburgh, EH9 1QH.

Abstract

SUMMARYTrypanosoma brucei gambiense sleeping sickness follows a long asymptomatic phase and persists in ancient foci from which epidemic clinical disease arises. A putative focus of T. b. gambiense infections has been identified, initially in mothers and young children, on the Lake Albert shoreline of Western Uganda leading to mass screening of 6207 individuals in September 2008. T. b. gambiense infections were identified by Card Agglutination Test for Trypanosomiasis (CATT) and sub-species-specific PCR although parasitological methods failed to confirm any patent trypanosome infections. In April 2009, CATT positives were re-visited; diagnosis of individuals by CATT and PCR was unstable over the two time points and parasites remained undetected, even using mini Anion Exchange Centrifugation Technique (mAECT). These observations suggest the possibility of a silent focus of disease, where all infected individuals are in a latent stage, and highlight our limited understanding of the local natural history and disease progression of T. b. gambiense in children and adults.

PMID:
21554841
[PubMed - as supplied by publisher]
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5. Parasit Vectors. 2011 May 9;4(1):69. [Epub ahead of print]

The prevalence of canine Leishmania infantum infection in western China detected by PCR and serological tests.< /h1>Wang JY, Ha Y, Gao CH, Wang Y, Yang YT, Chen HT.

Abstract

ABSTRACT:

BACKGROUND:

Canine leishmaniasis (CanL) is endemic in western China, resulting in important public health problem. It is essential to evaluate the prevalence of canine Leishmania infantum infection for designing control policy. In the present study we report for the first time prevalence of Leishmania infection in dogs living in Jiuzhaigou County (Sichuan Provence, China), which is not only an important endemic area of CanL but also a tourism scenic spot, detected by PCR, ELISA and dipstick test. The results could provide key information for designing control programs against canine and human leishmaniasis. In addition, the complete sequence of the Leishmania isolate from Sichuan Province has not been reported to date and we present the sequences of 116 base-pair (bp) fragment of the conserved region in the minicircle kinetoplast DNA (kDNA) and the results of phylogenetic analyses based on the sequence of the amplified fragment.

RESULTS:

The proportion of dogs infected with Leishmania in Jiuzhaigou County was 36.79%, 9.43%, and 51.88% detected by ELISA, dipstick test, and PCR, respectively. The ELISA and PCR tests were more sensitive than dipstick test. The PCR method is the most sensitive way to detect dogs infected with Leishmania parasites. The total positive rate for infected dogs in the area was 59.43% by the three methods. The PCR products of 116-bp fragment amplified from the kDNA conserved region of dog blood samples and laboratory maintained L. infantum were DNA sequenced and the variation of the sequences was observed. The phylogenetic tree based on the sequences of 116-bp fragment reveals that L. infantum is more genetically related to visceralizing species L. donovani than to the Leishmania species associated with cutaneous disease.

CONCLUSIONS:

More than half of dogs living in the endemic Jiuzhaigou County were infected by L. infantum. Control measures, such as treatment or eradication of infected dogs, or prohibition of maintaining dogs, must be taken against these infected dogs due to their role in the transmission of the infection to vectors. The phylogenetic tree based on the sequences of conserved region in kDNA of Leishmania can effectively distinguish species of Leishmania.

PMID:
21554677
[PubMed - as supplied by publisher]
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6. J Med Food. 2011 May 9. [Epub ahead of print]

Natural Products from Garcinia brasiliensis as Leishmania Protease Inhibitors.

Pereira IO, Assis DM, Juliano MA, Cunha RL, Barbieri CL, do Sacramento LV, Marques MJ, Dos Santos MH.

Source

1 Department of Pharmacy, Laboratory of Phytochemistry and Medicinal Chemistry, Federal University of Alfenas , Minas Gerais, Brazil .

Abstract

Abstract The infections by protozoans of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which cause renal and cardiac toxicity. As part of a search for new drugs against leishmaniasis, we evaluated the in vitro Leishmania protease inhibition activity of extracts (hexanic, ethyl-acetate, and ethanolic) and fukugetin, a bioflavonoid purified from the ethyl-acetate extract of the pericarp of the fruit of Garcinia brasiliensis, a tree native to Brazilian forests. The isolated compound was characterized by using spectral analyses with nuclear magnetic resonance, mass spectroscopy, ultraviolet, and infrared techniques. The ethyl-acetate extract and the compound fukugetin showed significant activity as inhibitors of Leishmania's proteases, with mean (±SD) IC(50) (50% inhibition concentration of protease activity) values of 15.0±1.3 μg/mL and 3.2±0.5 μM/mL, respectively, characterizing a bioguided assay. In addition, this isolated compound showed no activity against promastigote and amastigote forms of L. (L.) amazonensis and mammalian cells. These results suggest that fukugetin is a potent protease inhibitor of L. (L.) amazonensis and does not cause toxicity in mammalian or Leishmania cells in vitro. This study provides new perspectives on the development of novel drugs that have leishmanicidal activity obtained from natural products and that target the parasite's proteases.

PMID:
21554130
[PubMed - as supplied by publisher]
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7. Biochemistry. 2011 May 9. [Epub ahead of print]

Wildtype and Engineered Monomeric Triosephosphate Isomerase from Trypanosoma brucei: Partitioning of Reaction Intermediates in D2O and Activation by Phosphite Dianion‡

Malabanan MM, Go MK, Amyes TL, Richard JP.

Abstract

Product yields for the reactions of (R)-glyceraldehyde 3-phosphate (GAP) in D2O at pD 7.9 catalyzed by wildtype triosephosphate isomerase from Trypanosoma brucei brucei (Tbb TIM) and a monomeric variant (monoTIM) of this wildtype enzyme were determined by 1H NMR spectroscopy, and were compared with the yields determined in earlier work for the reactions catalyzed by TIM from rabbit and chicken muscle [O'Donoghue, A. C, Amyes, T. L. and Richard J.P. (2005), Biochemistry 44, 2610-2621]. Three products were observed from the reactions catalyzed by TIM: dihydroxyacetone phosphate (DHAP) from isomerization with intramolecular transfer of hydrogen, d-DHAP from isomerization with incorporation of deuterium from D2O into C-1 of DHAP, and d GAP from incorporation of deuterium from D2O into C-2 of GAP. The yield of DHAP formed by intramolecular transfer of hydrogen decreases from 49% for the muscle enzymes to 40% for wildtype Tbb TIM to 34% for monoTIM. There is no significant difference in the ratio of the yields of d DHAP and d GAP for wildtype TIM from muscle sources and Trypanosoma brucei brucei, but partitioning of the enediolate intermediate of the monoTIM reaction to form d DHAP is less favorable ((kC1)D/(kC2)D = 1.1) than for the wildtype enzyme ((kC1)D/(kC2)D = 1.7). Product yields for the wildtype Tbb TIM and monoTIM-catalyzed reactions of glycolaldehyde labeled with carbon-13 at the carbonyl carbon ([1-13C]-GA) at pD 7.0 in the presence of phosphite dianion and in its absence were determined by 1H NMR spectroscopy [Go, M. K., Amyes, T. L., and Richard, J. P. (2009) Biochemistry 48, 5769-5778]. There is no detectable difference in the yields of the products of wildtype muscle and Tbb TIM-catalyzed reactions of [1-13C]-GA in D2O. The kinetic parameters for phosphite dianion activation of the reactions of [1-13C]-GA catalyzed by wildtype Tbb TIM are similar to those reported for the enzyme from rabbit muscle TIM [Amyes, T. L., and Richard, J. P. (2007), Biochemistry 46, 5841-5854], but there is no detectable dianion activation of the reaction catalyzed by monoTIM. The engineered disruption of subunit contacts at monoTIM causes movement of the essential side chains of Lys-13 and His 95 away from the catalytic active positions. We suggest that this places an increased demand that the intrinsic binding energy of phosphite dianion be utilized to drive the change in the conformation of monoTIM back to the active structure for wildtype TIM, with the result that there is insufficient binding energy remaining to give a detectable stabilization of the transition state for the monoTIM-catalyzed reaction of [1-13C]-GA.

PMID:
21553855
[PubMed - as supplied by publisher]
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