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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 29 (2002), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) reduce serum cholesterol and have proven benefits in the treatment of cardiovascular disease. However, recent work suggests that statins may exert immunosuppressive effects in isolated lymphocytes and in solid organ transplant recipients. Fluvastatin does not interfere with the metabolism of commonly used immunosuppressive agents and, therefore, may have benefits in transplant recipients.2. The aim of the present study was to investigate the potential immunomodulatory effects of fluvastatin in vitro in human lymphocytes and the underlying effects on signal transduction.3. In vitro, fluvastatin (10 μmol/L) caused a time-dependent inhibition of T cell proliferation in response to cross-linking of CD3.4. Thymidine incorporation was reduced by 22, 81 and 92% at days 1, 3 and 5, respectively.5. Mevalonate (1 μmol/L) treatment for 4 or 24 h significantly reduced the inhibitory effects of fluvastatin; the reversal was abrogated by simultaneous exposure to mevalonate and a farnesyl transferase inhibitor.6. At a subcellular level, fluvastatin treatment was associated with reduced functional activity of Ras-dependent extracellular signal-regulated kinase pathways and of Rho-dependent p38 activation.7. These data suggest that the potential immunosuppressive actions of statins involve inhibition of subcellular pathways dependent on isoprenylation of signal peptides, including Ras, Rho and related G-proteins.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2016-08-12
    Description: As with many anti-cancer drugs, the topoisomerase II inhibitor etoposide is considered safe for administration to women in the second and third trimesters of pregnancy, but assessment of effects on the develop...
    Electronic ISSN: 1471-2407
    Topics: Medicine
    Published by BioMed Central
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  • 3
    Publication Date: 2012-07-24
    Description: Background: Duikers in the subfamily Cephalophinae are a group of tropical forest mammals believed to have first originated during the late Miocene. However, knowledge of phylogenetic relationships, pattern and timing of their subsequent radiation is poorly understood. Here we present the first multi-locus phylogeny of this threatened group of tropical artiodactyls and use a Bayesian uncorrelated molecular clock to estimate divergence times. Results: A total of 4152 bp of sequence data was obtained from two mitochondrial genes and four nuclear introns. Phylogenies were estimated using maximum parsimony, maximum likelihood, and Bayesian analysis of concatenated mitochondrial, nuclear and combined datasets. A relaxed molecular clock with two fossil calibration points was used to estimate divergence times. The first was based on the age of the split between the two oldest subfamilies within the Bovidae whereas the second was based on the earliest known fossil appearance of the Cephalophinae and molecular divergence time estimates for the oldest lineages within this group. Findings indicate strong support for four major lineages within the subfamily, all of which date to the late Miocene/early Pliocene. The first of these to diverge was the dwarf duiker genus Philantomba, followed by the giant, eastern and western red duiker lineages, all within the genus Cephalophus. While these results uphold the recognition of Philantomba, they do not support the monotypic savanna-specialist genus Sylvicapra, which as sister to the giant duikers leaves Cephalophus paraphyletic. BEAST analyses indicate that most sister species pairs originated during the Pleistocene, suggesting that repeated glacial cycling may have played an important role in the recent diversification of this group. Furthermore, several red duiker sister species pairs appear to be either paraphyletic (C.callipygus/C. ogilbyi and C. harveyi/C. natalensis) or exhibit evidence of mitochondrial admixture (C. nigrifrons and C. rufilatus), consistent with their recent divergence and/or possible hybridization with each other. Conclusions: Molecular phylogenetic analyses suggest that Pleistocene-era climatic oscillations have played an important role in the speciation of this largely forest-dwelling group. Our results also reveal the most well supported species phylogeny for the subfamily to date, but also highlight several areas of inconsistency between our current understanding of duiker taxonomy and the evolutionary relationships depicted here. These findings may therefore prove particularly relevant to future conservation efforts, given that many species are presently regulated under the Convention for Trade in Endangered Species.
    Electronic ISSN: 1471-2148
    Topics: Biology
    Published by BioMed Central
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