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Sent on Friday, 2010 Aug 06Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Cochrane Database Syst Rev. 2010 Aug 4;8:CD006201.Chemotherapy for second-stage Human African trypanosomiasis.Lutje V, Seixas J, Kennedy A.International Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK, L3 5QA. AbstractBACKGROUND: Human African trypanosomiasis, or sleeping sickness, is a painful and protracted disease affecting people in the poorest parts of Africa and is fatal without treatment. Few drugs are currently available for second-stage sleeping sickness, with considerable adverse events and variable efficacy. OBJECTIVES: To evaluate the effectiveness and safety of drugs for treating second-stage human African trypanosomiasis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (May 2010), CENTRAL (The Cochrane Library Issue 3 2010) , MEDLINE (1966 to May 2010), EMBASE (1974 to May 2010), LILACS (1982 to May 2010 ), BIOSIS (1926-May 2010), mRCT (May 2010) and reference lists. We contacted researchers working in the field and organizations. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials. DATA COLLECTION AND ANALYSIS: Two authors (VL and AK) extracted data and assessed methodological quality; a third author (JS) acted as an arbitrator. Included trials only reported dichotomous outcomes, and we present these as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: Nine trials with 2577 participants, all with Trypansoma brucei gambiense HAT, were included. Seven trials tested currently available drugs: melarsoprol, eflornithine, nifurtimox, alone or in combination; one trial tested pentamidine, and one trial assessed the addition of prednisolone to melarsoprol. Fixed 10-day regimens of melarsoprol were found to be as effective as those of 26 days, with similar numbers of adverse events. Melarsoprol monotherapy gave fewer relapses than pentamidine or nifurtimox, but resulted in more adverse events.Later trials evaluate nifurtimox combined with eflornithine (NECT), showing this gives few relapses and is well tolerated. It also has practical advantages in reducing the burden on health personnel and patients, when compared to eflornithine monotherapy. AUTHORS' CONCLUSIONS: Choice of therapy for second stage Gambiense HAT will continue to be determined by what is locally available, but eflornithine and NECT are likely to replace melarsoprol, with careful parasite resistance monitoring. We need research on reducing adverse effects of currently used drugs, testing different regimens, and experimental and clinical studies of new compounds, effective for both stages of the disease. |
| PMID: 20687080 [PubMed - in process] | |
| 2. | Clin Rheumatol. 2010 Aug 5. [Epub ahead of print]Antibodies against cyclic citrullinated peptides in infectious diseases-a systematic review.Lima I, Santiago M.Rheumatology Service, Hospital Santa Izabel/Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil. AbstractRheumatoid arthritis (RA) is a disease characterized by symmetrical polyarthritis of the large and small joints, and in the majority of patients, there is a presence of the rheumatoid factor and erosions in the X-ray of the joints. More recently, the presence of anti-cyclic citrullinated peptide antibodies (anti-CCP) in this disease has been described, with diagnostic and prognostic value. Nevertheless, these antibodies have also been described in infectious diseases. The aim of the present study was to make a systematic review of the presence of antibodies against citrullinated peptides in infectious diseases. Search was conducted in the MEDLINE (1966 to 2010), Cochrane, SCielo, and LILACS databases, using the terms: "anti-CCP, anti-MCV, and infectious diseases"; "anti-CCP, anti-MCV, and virus"; "anti-CCP, anti-MCV, and mycobacteria"; "anti-CCP, anti-MCV, and tuberculosis"; "anti-CCP, anti-MCV, and leprosy"; "anti-CCP, anti-MCV, and leishmaniasis"; "anti-CCP, anti-MCV, and HIV"; "anti-CCP and HTLV"; "anti-CCP, anti-MCV, and Chagas disease"; "anti-CCP, anti-MCV, and Lyme disease", and the corresponding terms in Portuguese. Twenty-five publications were found, which dealt with anti-CCP and infection, and only one on anti-MCV and infection. Of these, 23 were cross-sectional and three cohort studies. Anti-CCP antibodies were found in various frequencies, reaching 37% in tuberculosis. In the other infections, it was a rare finding. In only one publication, anti-MCV was found in only one patient with hepatitis. Since infectious diseases are capable of running their course with osteoarticular symptoms, sometimes difficult to differentiate from RA, additional studies are necessary to define the performance of the test for the detection of anti-CCP antibodies in populations in which the frequency of such infections is high. |
| PMID: 20686805 [PubMed - as supplied by publisher] | |
| 3. | PLoS Genet. 2010 Jul 29;6(7):e1001044.Genome-Wide Analysis Reveals Novel Genes Essential for Heme Homeostasis in Caenorhabditis elegans.Severance S, Rajagopal A, Rao AU, Cerqueira GC, Mitreva M, El-Sayed NM, Krause M, Hamza I.Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America. AbstractHeme is a cofactor in proteins that function in almost all sub-cellular compartments and in many diverse biological processes. Heme is produced by a conserved biosynthetic pathway that is highly regulated to prevent the accumulation of heme-a cytotoxic, hydrophobic tetrapyrrole. Caenorhabditis elegans and related parasitic nematodes do not synthesize heme, but instead require environmental heme to grow and develop. Heme homeostasis in these auxotrophs is, therefore, regulated in accordance with available dietary heme. We have capitalized on this auxotrophy in C. elegans to study gene expression changes associated with precisely controlled dietary heme concentrations. RNA was isolated from cultures containing 4, 20, or 500 microM heme; derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. We identified 288 heme-responsive genes (hrgs) that were differentially expressed under these conditions. Of these genes, 42% had putative homologs in humans, while genomes of medically relevant heme auxotrophs revealed homologs for 12% in both Trypanosoma and Leishmania and 24% in parasitic nematodes. Depletion of each of the 288 hrgs by RNA-mediated interference (RNAi) in a transgenic heme-sensor worm strain identified six genes that regulated heme homeostasis. In addition, seven membrane-spanning transporters involved in heme uptake were identified by RNAi knockdown studies using a toxic heme analog. Comparison of genes that were positive in both of the RNAi screens resulted in the identification of three genes in common that were vital for organismal heme homeostasis in C. elegans. Collectively, our results provide a catalog of genes that are essential for metazoan heme homeostasis and demonstrate the power of C. elegans as a genetic animal model to dissect the regulatory circuits which mediate heme trafficking in both vertebrate hosts and their parasites, which depend on environmental heme for survival. |
| PMID: 20686661 [PubMed - in process] | |
| 4. | PLoS Pathog. 2010 Jul 29;6(7):e1001023.Bottlenecks and the Maintenance of Minor Genotypes during the Life Cycle of Trypanosoma brucei.Oberle M, Balmer O, Brun R, Roditi I.Swiss Tropical and Public Health Institute, Basel, Switzerland. AbstractAfrican trypanosomes are digenetic parasites that undergo part of their developmental cycle in mammals and part in tsetse flies. We established a novel technique to monitor the population dynamics of Trypanosoma brucei throughout its life cycle while minimising the confounding factors of strain differences or variation in fitness. Clones derived from a single trypanosome were tagged with short synthetic DNA sequences in a non-transcribed region of the genome. Infections were initiated with mixtures of tagged parasites and a combination of polymerase chain reaction and deep sequencing were used to monitor the composition of populations throughout the life cycle. This revealed that a minimum of several hundred parasites survived transmission from a tsetse fly to a mouse, or vice versa, and contributed to the infection in the new host. In contrast, the parasites experienced a pronounced bottleneck during differentiation and migration from the midgut to the salivary glands of tsetse. In two cases a single tag accounted for >/=99% of the population in the glands, although minor tags could be also detected. Minor tags were transmitted to mice together with the dominant tag(s), persisted during a chronic infection, and survived transmission to a new insect host. An important outcome of the bottleneck within the tsetse is that rare variants can be amplified in individual flies and disseminated by them. This is compatible with the epidemic population structure of T. brucei, in which clonal expansion of a few genotypes in a region occurs against a background of frequent recombination between strains. |
| PMID: 20686656 [PubMed - in process] | |
| 5. | Mol Biochem Parasitol. 2010 May 31. [Epub ahead of print]The small GTPase ARL2 is required for cytokinesis in Trypanosoma brucei.Price HP, Peltan A, Stark M, Smith DF.Centre for Immunology and Infection, Department of Biology/Hull York Medical School, University of York, York YO10 5YW, UK. AbstractThe Arf-like (Arl) small GTPases have a diverse range of functions in the eukaryotic cell. Metazoan Arl2 acts as a regulator of microtubule biogenesis, binding to the tubulin-specific chaperone cofactor D. Arl2 also has a mitochondrial function through its interactions with BART and ANT-1, the only member of the Ras superfamily to be found in this organelle to date. In the present study, we describe characterization of the Arl2 orthologue in the protozoan parasite Trypanosoma brucei. Modulation of TbARL2 expression in bloodstream form parasites by RNA interference (RNAi) causes inhibition of cleavage furrow formation, resulting in a severe defect in cytokinesis and the accumulation of multinucleated cells. RNAi of TbARL2 also results in loss of acetylated alpha-tubulin but not of total alpha-tubulin from cellular microtubules. While overexpression of TbARL2(myc) also leads to a defect in cytokinesis, an excess of untagged protein has no effect on cell division, demonstrating the importance of the extreme C-terminus in correct function. TbARL2 overexpressing cells (either myc-tagged or untagged) have an increase in acetylated alpha-tubulin. Our data indicate that Arl2 has a fundamentally conserved role in trypanosome microtubule biogenesis that correlates with alpha-tubulin acetylation. Copyright © 2010. Published by Elsevier B.V. |
| PMID: 20685283 [PubMed - as supplied by publisher] | |
| 6. | Exp Parasitol. 2010 May 26. [Epub ahead of print]Leishmania tarentolae: Utility as an in vitro model for screening of antileishmanial agents.Taylor VM, Muñoz DL, Cedeño DL, Vélez ID, Jones MA, Robledo SM.PECET, School of Medicine, Universidad de Antioquia, Medellín, Colombia. AbstractPrimary screens for antileishmanial compounds use Leishmania species pathogenic to humans that must be handled under biosafety conditions that cannot be adopted or guaranteed everywhere. Leishmania tarentolae, a parasite isolated from the gecko Tarentolae annularis, has not been considered pathogenic to humans. Promastigotes of L. tarentolae have been previously used as a eukaryotic expression system for the production of recombinant proteins and in the amplification of genes involved in resistance to antileishmanial drugs. To validate the use of this Leishmania species in the screening of antileishmanial drugs, the sensitivity of axenic and intracellular amastigotes of L. tarentolae was compared to the sensitivity showed by Leishmania species causative of human leishmaniasis. The ability of L. tarentolae to grow as axenic amastigotes is first described while its ability to infect several mammalian cells has been confirmed. L. tarentolae amastigotes offer a suitable model for the in vitro screening of compounds for antileishmanial activity. Copyright © 2010. Published by Elsevier Inc. |
| PMID: 20685203 [PubMed - as supplied by publisher] | |
| 7. | Science. 2010 Jul 16;329(5989):342-5.Chemoattraction to dimeth ylsulfoniopropionate throughout the marine microbial food web.Seymour JR, Simó R, Ahmed T, Stocker R.Ralph M. Parsons Laboratory, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Justin.Seymour@uts.edu.au AbstractPhytoplankton-produced dimethylsulfoniopropionate (DMSP) provides underwater and atmospheric foraging cues for several species of marine invertebrates, fish, birds, and mammals. However, its role in the chemical ecology of marine planktonic microbes is largely unknown, and there is evidence for contradictory functions. By using microfluidics and image analysis of swimming behavior, we observed attraction toward microscale pulses of DMSP and related compounds among several motile strains of phytoplankton, heterotrophic bacteria, and bacterivore and herbivore microzooplankton. Because microbial DMSP cycling is the main natural source of cloud-forming sulfur aerosols, our results highlight how adaptations to microscale chemical seascapes shape planktonic food webs, while potentially influencing climate at the global scale. |
| PMID: 20647471 [PubMed - indexed for MEDLINE] | |
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| 8. | Science. 2010 Jul 16;329(5989):263.Genetics. Kidney disease is parasite-slaying protein's downside.Leslie M. |
| PMID: 20647431 [PubMed - indexed for MEDLINE] | |
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