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Sent on Friday, 2010 Jul 30Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Parasitol Res. 2010 Jul 29. [Epub ahead of print]Serine protease activities in Leishmania (Leishmania) chagasi promastigotes.da Silva-López RE, Dos Santos TR, Morgado-Díaz JA, Tanaka MN, de Simone SG.Laboratório de Bioquímica de Proteínas e Peptídeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil, rlopez@far.fiocruz.br. AbstractThe present work reports the isolation, biochemical characterization, and subcellular location of serine proteases from aqueous, detergent soluble, and culture supernatant of Leishmania chagasi promastigote extracts, respectively, LCSII, LCSI, and LCSIII. The active enzyme molecular masses of LCSII were about 105, 66, and 60 kDa; of LCSI, 60 and 58 kDa; and of LCSIII, approximately 76 and 68 kDa. Optimal pH for the enzymes was 7.0 for LCSI and LCSIII and 8.5 for LCSII, and the optimal temperature for all enzymes was 37 degrees C, using alpha-N-rho-tosyl-L: -arginine methyl ester as substrate. Assay of thermal stability indicated that LCSIII is the more stable enzyme. Hemoglobin, bovine serum albumin, and ovalbumin were hydrolyzed by LCSII and LCSI but not by LCSIII. Inhibition studies suggested that enzymes belong to the serine protease class modulated by divalent cations. Rabbit antiserum against 56-kDa serine protease of Leishmania amazonensis identified proteins in all extracts of L. chagasi. Furthermore, immunocytochemistry demonstrated that serine proteases are located in flagellar pocket region and cytoplasmic vesicles of L. chagasi promastigotes. These findings indicate that L. chagasi serine proteases differ from L. amazonensis proteases and all known flagellate proteases, but display some similarities with serine proteases from other Leishmania species, suggesting a conservation of this enzymatic activity in the genus. |
| PMID: 20668879 [PubMed - as supplied by publisher] | |
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| 2. | Kidney Int. 2010 Jul 28. [Epub ahead of print]A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9.Genovese G, Tonna SJ, Knob AU, Appel GB, Katz A, Bernhardy AJ, Needham AW, Lazarus R, Pollak MR.[1] Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA [2] Department of Mathematics, Dartmouth College, Hanover, New Hampshire, USA. AbstractGenetic variation at the MYH9 locus is linked to the high incidence of focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease among African Americans. To further define risk alleles with FSGS we performed a genome-wide association analysis using more than one million single-nucleotide polymorphisms in 56 African-American and 61 European-American patients with biopsy-confirmed FSGS. Results were compared to 1641 European Americans and 1800 African Americans as unselected controls. While no association was observed in the cohort of European Americans, the case-control comparison of African Americans found variants within a 60 kb region of chromosome 22 containing part of the APOL1 and MYH9 genes associated with increased risk of FSGS. This region spans different linkage disequilibrium blocks, and variants associating with disease within this region are in linkage disequilibrium with variants which have shown signals of natural selection. APOL1 is a strong candidate for a gene that has undergone recent natural selection and is known to be involved in the infection by Trypanosoma brucei, a parasite common in Africa that has recently adapted to infect human hosts. Further studies will be required to establish which variants are causally related to kidney disease, what mutations caused the selective sweep, and to ultimately determine if these are the same.Kidney International advance online publication, 28 July 2010; doi:10.1038/ki.2010.251. |
| PMID: 20668430 [PubMed - as supplied by publisher] | |
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| 3. | J Eur Acad Dermatol Venereol. 2010 Jul 27. [Epub ahead of print]Efficacy of CO(2) laser for treatment of anthroponotic cutaneous leishmaniasis, compared with combination of cryotherapy and intralesional meglumine antimoniate.Shamsi Meymandi S, Zandi S, Aghaie H, Heshmatkhah A.Kerman Leishmania Research Center, Dermatology Department, Afzalipour Hospital, Kerman, Iran. AbstractAbstract Background Cutaneous leishmaniasis (CL) is endemic in developing countries. Several types of treatments have been suggested, but none of them is completely effective and without side-effects. CO(2) laser has a specific thermolysis effect on infected tissues in CL. Objectives To determine the efficacy and safety of CO(2) laser vs. combined cryotherapy and intralesional meglumine antimoniate (glucantime) in dry-type CL. Methods This is a prospective, randomized open trial study (Kerman, Iran) from November 2007 to August 2009. A total of 96 patients were randomly assigned to receive one session of CO(2) laser therapy and 95 patients on combined cryotherapy biweekly with intralesional meglumine antimoniate weekly until complete cure or up to 12 weeks, whichever is earlier. Clinical and laboratory cure, defined as complete re-epithelialization of 100%, complete flattening of induration and negative smear of lesions compared with baseline at weeks 2, 6, 12 and 16, and also at the time of complete cure (week 2, 6, 12 or 16). Results Of 191 participants, 80 patients with 95 lesions in group A and 80 patients with 95 lesions in group B completed the study. Complete cure was 93.7% (89/95 lesions) in group A and 78% (74/95 lesions) in group B. Complications were similar in the two groups and were limited to the ulcer sites. Conclusions The CO(2) laser was more effective in treating dry-type cutaneous leishmaniasis than combined cryotherapy and intralesional glucantime and resulted in a shorter healing time (6 weeks vs. 12 weeks) with a single treatment session. |
| PMID: 20666876 [PubMed - as supplied by publisher] | |
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| 4. | J Med Chem. 2010 Jul 28. [Epub ahead of print]Aryl Phosphoramidates of 5-Phospho Erythronohydroxamic Acid, A New Class of Potent Trypanocidal Compounds.Ruda GF, Wong PE, Alibu VP, Norval S, Read KD, Barrett MP, Gilbert IH.Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee DD1 5EH, U.K. AbstractRNAi and enzymatic studies have shown the importance of 6-phosphogluconate dehydrogenase (6-PGDH) in Trypanosoma brucei for the parasite survival and make it an attractive drug target for the development of new treatments against human African trypanosomiasis. 2,3-O-Isopropylidene-4-erythrono hydroxamate is a potent inhibitor of parasite Trypanosoma brucei 6-phosphogluconate dehydrogenase (6-PGDH), the third enzyme of the pentose phosphate pathway. However, this compound does not have trypanocidal activity due to its poor membrane permeability. Consequently, we have previously reported a prodrug approach to improve the antiparasitic activity of this inhibitor by converting the phosphate group into a less charged phosphate prodrug. The activity of prodrugs appeared to be dependent on their stability in phosphate buffer. Here we have successfully further extended the development of the aryl phosphoramidate prodrugs of 2,3-O-isopropylidene-4-erythrono hydroxamate by synthesizing a small library of phosphoramidates and evaluating their biological activity and stability in a variety of assays. Some of the compounds showed high trypanocidal activity and good correlation of activity with their stability in fresh mouse blood. |
| PMID: 20666371 [PubMed - as supplied by publisher] | |
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| 5. | Adv Exp Med Biol. 2010;679:57-69.Metalloid transport by aquaglyceroporins: consequences in the treatment of human diseases.Mukhopadhyay R, Beitz E.Department of Pharmaceutical and Medicinal Chemistry University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany. rmukhop@fiu.edu AbstractMetalloids can severely harm human physiology in a toxicological sense if taken up from the environment in acute high doses or chronically. However, arsenic or antimony containing drugs are still being used as treatment and are often the sole regime for certain forms of cancer, mainly types of leukemia and diseases caused by parasites, such as sleeping sickness or leishmaniasis. In this chapter, we give an outline of the positive effects of arsenicals and antimonials against such diseases, we summarize data on uptake pathways through human and parasite aquaglyceroporins and we discuss the progress and options in the development of therapeutic aquaporin and aquaglyceroporin inhibitor compounds. |
| PMID: 20666224 [PubMed - in process] | |
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| 6. | Biochem J. 2010 Jul 14;429(3):533-43.Identification of a novel UDP-sugar pyrophosphorylase with a broad substrate specificity in Trypa nosoma cruzi.Yang T, Bar-Peled M.Department of Biochemistry and Molecular Biology, University of Georgia, Athens, 30602, USA. AbstractThe diverse types of glycoconjugates synthesized by trypanosomatid parasites are unique compared with the host cells. These glycans are required for the parasite survival, invasion or evasion of the host immune system. Synthesis of those glycoconjugates requires a constant supply of nucleotide-sugars (NDP-sugars), yet little is known about how these NDP-sugars are made and supplied. In the present paper, we report a functional gene from Trypanosoma cruzi that encodes a nucleotidyltransferase, which is capable of transforming different types of sugar 1-phosphates and NTP into NDP-sugars. In the forward reaction, the enzyme catalyses the formation of UDP-glucose, UDP-galactose, UDP-xylose and UDP-glucuronic acid, from their respective monosaccharide 1-phosphates in the presence of UTP. The enzyme could also convert glucose 1-phosphate and TTP into TDP-glucose, albeit at lower efficiency. The enzyme requires bivalent ions (Mg2+ or Mn2+) for its activity and is highly active between pH 6.5 and pH 8.0, and at 30-42 degrees C. The apparent Km values for the forward reaction were 177 microM (glucose 1-phosphate) and 28.4 microM (UTP) respectively. The identification of this unusual parasite enzyme with such broad substrate specificities suggests an alternative pathway that might play an essential role for nucleotide-sugar biosynthesis and for the regulation of the NDP-sugar pool in the parasite. |
| PMID: 20482518 [PubMed - indexed for MEDLINE] | |
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| 7. | Biophys J. 2010 May 19;98(9):L38-40.Tryptophan as a molecular shovel in the glycosyl transfer activity of Trypanosoma cruzi trans-sialidase.< a href="http://www.ncbi.nlm.nih.gov/pubmed?term=%22Mitchell%20FL%22%5BAuthor%5D">Mitchell FL, Miles SM, Neres J, Bichenkova EV, Bryce RA.School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, United Kingdom. AbstractMolecular dynamics investigations into active site plasticity of Trypanosoma cruzi trans-sialidase, a protein implicated in Chagas disease, suggest that movement of the Trp(312) loop plays an important role in the enzyme's sialic acid transfer mechanism. The observed Trp(312) flexibility equates to a molecular shovel action, which leads to the expulsion of the donor aglycone leaving group from the catalytic site. These computational simulations provide detailed structural insights into sialyl transfer by the trans-sialidase and may aid the design of inhibitors effective against this neglected tropical disease. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved. |
| PMID: 20441732 [PubMed - indexed for MEDLINE] | |
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| 8. | J Eukaryot Microbiol. 2010 Jan 1;57(1):87-93. Epub 2009 Dec 11.In vitro cultivation and morphological characterization of phloemic trypanoso matids isolated from coconut trees.Keller DG, Miguens FC.Laboratório de Biologia Celular e Tecidual, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Avenida Alberto Lamego 2000, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil. AbstractPlant trypanosomatids cause lethal vascular wilting in palms of the Arecaceae family. Infections, affecting plants in South and Central America, can result in significant economic loss. The study of trypanosomatids that cause these diseases has been complicated due to the inability to culture these organisms for in vitro analyses. To develop a protocol that would facilitate studies of trypanosomatids, continuous in vitro cultures of phloemic trypanosomatids were established from apical stems of diseased coconut trees collected in endemic and non-endemic regions of Brazil (the states of Bahia and Rio de Janeiro, respectively). Although attempts at establishing axenic cultures were unsuccessful, it was found that trypanosomatid co-cultures could be successfully established and maintained. The procedure was to preculture media with 10(4)Aedes albopictus cells in Grace's medium supplemented with 10% heat-inactivated fetal bovine serum (without antibiotics or fungicides) for 3 d before adding 10(6) trypanosomatids/ml harvested from either fresh apical stem extracts or with 2 mm(3) fragments of coconut apical stems. By day 7 under these conditions the parasites grew exponentially. Using this strategy, two isolates were identified and have been maintained in our laboratory for over 400 passages, demonstrating the efficacy of this culturing procedure. In situ the organisms were observed in vascular bundles and inside sieve elements of the phloem of diseased palms. In vitro parasites retained their mobility. Morphometric analysis revealed differences between Bahia and Rio de Janeiro isolates. |
| PMID: 20002871 [PubMed - indexed for MEDLINE] | |
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