Saturday, July 25, 2009

What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2009 Jul 25
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 11

1: Curr Microbiol. 2009 Jul 23. [Epub ahead of print]Click here to read

Leishmania amazonensis Growth Inhibitors: Biological and Theoretical Features of Sulfonamide 4-Methoxychalcone Derivatives.

Souza AM, Castro HC, Brito MA, Andrighetti-Fröhner CR, Magalhães U, Oliveira KN, Gaspar-Silva D, Pacheco LK, Joussef AC, Steindel M, Simões CM, Santos DO, Albuquerque MG, Rodrigues CR, Nunes RJ.

ModMolQSAR, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, CEP 21941-590, Brazil.

Current drugs for treating leishmaniasis are still associated with significant toxicity and failure rates. Thus, new effective and less toxic antileishmanial agents are still in need. Herein, we tested a series of sulfonamide 4-methoxychalcone derivatives against L. amazonensis promastigote and amastigote forms to identify its antileishmanial profile against this species compared to L. braziliensis. In addition, we used molecular modeling tools to determine stereoelectronic features that may lead to the antileishmanial profile. Interestingly, all tested compounds were able to affect L. amazonensis promastigote form in a concentration-dependent manner and with low cytotoxicity, except for derivative 3g. However, our results showed that compound 3f (para-Cl) presents the best profile against both L. amazonensis forms (promastigote and amastigote), differently from that observed for L. braziliensis, when compound 3i was the most active. Structure-activity relationship (SAR) analysis of these derivatives pointed molecular volume, HOMO density, and conformational aspects as important characteristics for parasitic profile. Overall, sulfonamide 4-methoxychalcone derivatives may be pointed out not only as lead compounds for treating leishmaniasis (i.e., 3f) but also as experimental tools presenting parasite-selectivity (i.e., 3i).

PMID: 19629593 [PubMed - as supplied by publisher]

2: EMBO J. 2009 Jul 23. [Epub ahead of print]Click here to read

Distinct donor and acceptor specificities of Trypanosoma brucei oligosaccharyltransferases.

Izquierdo L, Schulz BL, Rodrigues JA, Güther ML, Procter JB, Barton GJ, Aebi M, Ferguson MA.

Division of Biological Chemistry and Drug Discovery, The College of Life Sciences, University of Dundee, Dundee, UK.

Asparagine-linked glycosylation is catalysed by oligosaccharyltransferase (OTase). In Trypanosoma brucei OTase activity is catalysed by single-subunit enzymes encoded by three paralogous genes of which TbSTT3B and TbSTT3C can complement a yeast Deltastt3 mutant. The two enzymes have overlapping but distinct peptide acceptor specificities, with TbSTT3C displaying an enhanced ability to glycosylate sites flanked by acidic residues. TbSTT3A and TbSTT3B, but not TbSTT3C, are transcribed in the bloodstream and procyclic life cycle stages of T. brucei. Selective knockdown and analysis of parasite protein N-glycosylation showed that TbSTT3A selectively transfers biantennary Man(5)GlcNAc(2) to specific glycosylation sites whereas TbSTT3B selectively transfers triantennary Man(9)GlcNAc(2) to others. Analysis of T. brucei glycosylation site occupancy showed that TbSTT3A and TbSTT3B glycosylate sites in acidic to neutral and neutral to basic regions of polypeptide, respectively. This embodiment of distinct specificities in single-subunit OTases may have implications for recombinant glycoprotein engineering. TbSTT3A and TbSTT3B could be knocked down individually, but not collectively, in tissue culture. However, both were independently essential for parasite growth in mice, suggesting that inhibiting protein N-glycosylation could have therapeutic potential against trypanosomiasis.

PMID: 19629045 [PubMed - as supplied by publisher]

3: Am J Pathol. 2009 Jul 23. [Epub ahead of print]Click here to read

IL-4R{alpha} Responsiveness of Non-CD4 T Cells Contributes to Resistance in Schistosoma mansoni Infection in Pan-T Cell-Specific IL-4R{alpha}-Deficient Mice.

Dewals B, Hoving JC, Leeto M, Marillier RG, Govender U, Cutler AJ, Horsnell WG, Brombacher F.

From the International Centre for Genetic Engineering and Biotechnology and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, University of Cape Town, Cape Town, South Africa.

Interleukin(IL)-4 and IL-13 are T helper 2 cytokines whose biological functions are induced through a common IL-4 receptor alpha chain (IL-4Ralpha). CD4(+) T cell-specific IL-4Ralpha-mediated signaling drives susceptibility to Leishmania major infection, but is not essential to host survival following Schistosoma mansoni infection. Here we generated a novel mouse model lacking IL-4Ralpha expression specifically on all T cells (iLck(cre)Il4ra(-/lox)), which was compared with CD4(+) T cell-specific IL-4Ralpha-deficient mice (Lck(cre)Il4ra(-/lox)), to investigate the possible roles of IL-4Ralpha responsive non-CD4(+) T cells during either L. major or S. mansoni infection. Our results demonstrate a successful generation of transgene-bearing hemizygous iLck(cre)Il4ra(-/lox) BALB/c mice that have effective deletion of IL-4Ralpha on all T-cell populations. We show that iLck(cre)Il4ra(-/lox) mice infected with L. major developed a healing disease phenotype as previously observed in Lck(cre)Il4ra(-/lox) mice, demonstrating that absence of IL-4Ralpha-responsive non-CD4(+) in addition to CD4(+) T cells does not further affect transformation of BALB/c to a healer phenotype. In acute schistosomiasis, however, iLck(cre)Il4ra(-/lox) mice showed enhanced mortality compared with Il4ra(-/lox) and Lck(cre)Il4ra(-)(/lox) mice. iLck(cre)Il4ra(-/lox) mice died with similar kinetics to highly susceptible Il4ra(-/-) mice, despite controlling gut inflammation. In addition, iLck(cre)Il4ra(-/lox) mice presented increased liver granuloma sizes, as compared with Lck(cre)Il4ra(-/lox) mice, with similar eosinophils, fibrosis, and liver damage. In conclusion, IL-4Ralpha-responsive non-CD4(+) T cells prolong survival to acute schistosomiasis and contribute to the better control of hepatic granulomatous inflammation.

PMID: 19628763 [PubMed - as supplied by publisher]

4: Proc Natl Acad Sci U S A. 2009 Jul 22. [Epub ahead of print]Click here to read

Acetate produced in the mitochondrion is the essential precursor for lipid biosynthesis in procyclic trypanosomes.

Rivière L, Moreau P, Allmann S, Hahn M, Biran M, Plazolles N, Franconi JM, Boshart M, Bringaud F.

Laboratoire de Microbiologie Cellulaire et Moléculaire et Pathogénicité, Unité Mixte de Recherche 5234 Centre National de la Recherche Scientifique.

Acetyl-CoA produced in mitochondria from carbohydrate or amino acid catabolism needs to reach the cytosol to initiate de novo synthesis of fatty acids. All eukaryotes analyzed so far use a citrate/malate shuttle to transfer acetyl group equivalents from the mitochondrial matrix to the cytosol. Here we investigate how this acetyl group transfer occurs in the procyclic life cycle stage of Trypanosoma brucei, a protozoan parasite responsible of human sleeping sickness and economically important livestock diseases. Deletion of the potential citrate lyase gene, a critical cytosolic enzyme of the citrate/malate shuttle, has no effect on de novo biosynthesis of fatty acids from (14)C-labeled glucose, indicating that another route is used for acetyl group transfer. Because acetate is produced from acetyl-CoA in the mitochondrion of this parasite, we considered genes encoding cytosolic enzymes producing acetyl-CoA from acetate. We identified an acetyl-CoA synthetase gene encoding a cytosolic enzyme (AceCS), which is essential for cell viability. Repression of AceCS by inducible RNAi results in a 20-fold reduction of (14)C-incorporation from radiolabeled glucose or acetate into de novo synthesized fatty acids. Thus, we demonstrate that the essential cytosolic enzyme AceCS of T. brucei is responsible for activation of acetate into acetyl-CoA to feed de novo biosynthesis of lipids. To date, Trypanosoma is the only known eukaryotic organism that uses acetate instead of citrate to transfer acetyl groups over the mitochondrial membrane for cytosolic lipid synthesis.

PMID: 19625628 [PubMed - as supplied by publisher]

5: Vet Parasitol. 2009 Jun 27. [Epub ahead of print]Click here to read

Leishmania spp. and/or Trypanosoma cruzi diagnosis in dogs from endemic and nonendemic areas for canine visceral leishmaniasis.

Troncarelli MZ, Camargo JB, Machado JG, Lucheis SB, Langoni H.

School of Veterinary Medicine and Animal Science - FMVZ, Sao Paulo State University - UNESP, Distrito de Rubião Júnior, s/n, Botucatu, São Paulo 18618-000, C.P. 560, Brazil.

Due to the phylogenetic similarity between Leishmania spp. and Trypanosoma cruzi (T. cruzi), serological cross-reactions and false-positive results are quite common. This study aimed to elucidate canine leishmaniasis and trypanosomiasis diagnosis by the indirect fluorescent antibody test (IFAT) on serum samples, and direct parasitological examination and polymerase chain reaction (PCR) in liver and spleen samples. One hundred dogs from Zoonosis Control Center (ZCC) in Bauru, SP, an endemic area for visceral leishmaniasis (VL), and 100 dogs from the Dog Warden Service in Botucatu, SP, a nonendemic area for VL, were studied. IFAT showed positive results for Leishmania spp. in 65% of canine serum samples from Bauru while 40% of the samples were positive for T. cruzi by this test. All samples from Botucatu were negative for leishmaniasis in IFAT, and only 4% were positive for T. cruzi. Out of 200 serum samples tested, 33 (16.5%) showed positive serological results for both the parasites. Direct parasitological examination and PCR found, respectively, 59% and 76% of the liver samples and 51% and 72% of the spleen samples of dogs from Bauru positive for Leishmania spp. Twenty-six (78.8%) of 33 dogs that showed anti-Leishmania spp. and anti-T. cruzi antibodies also tested positive by direct parasitological examination and PCR for Leishmania spp., which indicates that these dogs presented leishmaniasis. No liver or spleen sample from the 200 dogs analyzed showed a positive PCR result for T. cruzi. These findings support the occurrence of cross-reactions between Leishmania spp. and T. cruzi in IFAT; they also corroborate the need for simultaneous PCR and/or parasitological examination to establish canine leishmaniasis (CL) diagnosis.

PMID: 19625128 [PubMed - as supplied by publisher]

6: Conserv Biol. 2009 Jul 16. [Epub ahead of print]

Bioactivity as an Options Value of Sea Cucumbers in the Egyptian Red Sea.

Lawrence AJ, Afifi R, Ahmed M, Khalifa S, Paget T.

Department of Life Sciences, University of the West Indies, St. Augustine, Trinidad & Tobago, email andrew.lawrence@sta.uwi.edu.

The utility of a species can be divided into its direct, indirect, and options values. In the marine environment, direct consumptive values predominate and often lead to overexploitation at the expense of significant options values derived through bioprospecting for natural products. We surveyed the waters of the Egyptian Red Sea coast (Gulf of Aqaba [north] and the Red Sea [south]) for species of sea cucumbers and analyzed extracts from species for a range of bioactivities with potential biomedical applications. All habitat types were surveyed within these regions. We found 22 species of sea cucumber of which two, Holothuria fuscogilva and Holothuria flavomaculata, were recorded in Egypt for the first time. Although none of the species identified were unique to the Gulf of Aqaba, 10 species were only found in the Red Sea sector. Bioassay results showed that although no species had antibacterial activity, most extracts exhibited activity against Candida and Leishmania but were most active against a LoVo mammalian carcinoma cell line. Our most significant finding was the intraspecific variation in bioactivity in individuals collected from different habitat types and sectors of the coast. This variation may reflect the effect of environment on secondary metabolite production or may indicate significant genetic diversity between populations within a species. Our results indicate a potentially significant options value to sea cucumbers through bioprospecting. Given the importance of economic development in countries such as Egypt and the perceived low conservation value of invertebrates such as sea cucumbers, the linking of these factors to conservation is vital for the maintenance and sustainable exploitation of these animals.

PMID: 19624530 [PubMed - as supplied by publisher]

7: Trop Med Int Health. 2009 Jul 14. [Epub ahead of print]Click here to read

Geographical distribution and epidemiological features of Old World cutaneous leishmaniasis foci, based on the isoenzyme analysis of 1048 strains.

Pratlong F, Dereure J, Ravel C, Lami P, Balard Y, Serres G, Lanotte G, Rioux JA, Dedet JP.

Université Montpellier 1, Centre National de Référence des Leishmania, Génétique et Evolution des Maladies infectieuses, Laboratoire de Parasitologie-Mycologie, CHU de Montpellier, France.

Summary A series of 1048 Leishmania strains from Old World cutaneous leishmaniasis foci, isolated between 1981 and 2005, were studied by isoenzyme analysis. The strains were obtained from humans, rodents, dogs and sandflies from 33 countries. The four typically dermotropic species, Leishmania major, L. tropica, L. aethiopica and L. killicki, were found. The viscerotropic species L. donovani and L. infantum, which can occasionally be responsible for cutaneous leishmaniasis, are not considered in this paper. Leishmania major was the least polymorphic species (12 zymodemes, 638 strains). Leishmania tropica was characterized by a complex polymorphism varying according to focus (35 zymodemes, 329 strains). Leishmania aethiopica, a species restricted to East Africa, showed a high polymorphism, in spite of a limited number of strains (23 zymodemes, 40 strains). Leishmania killicki, mainly restricted to Tunisia had a single zymodeme for 39 strains. Recently a parasite close to L. killicki (one zymodeme, two strains) was isolated in Algeria, which lead us to revise the taxonomic status of this taxon.

PMID: 19624480 [PubMed - as supplied by publisher]

8: J Indian Med Assoc. 2008 Oct;106(10):669-70, 672.LinkOut
Comment on:
J Indian Med Assoc. 2008 Oct;106(10):664, 666-8.

Note on Kala-azar control programme in India.

Sharma SN.

PMID: 19552102 [PubMed - indexed for MEDLINE]

9: J Indian Med Assoc. 2008 Oct;106(10):664, 666-8.LinkOut
Comment in:
J Indian Med Assoc. 2008 Oct;106(10):669-70, 672.

Kala-azar elimination programme in India.

Dhillon GP, Sharma SN, Nair B.

National Vector Borne Disease Control Programme, Ministry of Health and Family Welfare, Government of India, Delhi.

Kala-azar has been endemic in India for a long time. Phlebotomus argentipes, the vector became resurgent during 70s in four districts of Bihar and slowly spread to other parts of south Bihar and several districts of West Bengal. Kala-azar is a present endemic in 31 districs of Bihar, 4 districts of Jharkhand, 11 districts of West Bengal besides occurring is sporadic form in far districts of eastern UP. With enhanced central support to states from December, 2003 the case registration has improved. Elimination strategy lies in the followings: Case detection and treatment; interruption of transmission through vector control; advocacy, communication for behavioral impact and inter-sectoral convergence; capacity building; monitoring, supervision and evaluation and operational research. Moreover, inter-country co-ordination and assistance by Government of India are very important in elimination of kala-azar.

PMID: 19552101 [PubMed - indexed for MEDLINE]

10: Adv Carbohydr Chem Biochem. 2009;62:311-66.Click here to read LinkOut

Glycobiology of Trypanosoma cruzi.

de Lederkremer RM, Agusti R.

Departamento de Quimica Organica, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.

PMID: 19501708 [PubMed - indexed for MEDLINE]

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