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11.
Rodenburg J Vissers MN Wiegman A Trip MD Bakker HD Kastelein JJ 《Current opinion in lipidology》2004,15(4):405-411
PURPOSE OF THIS REVIEW: This review provides an update on recent advances in the diagnosis and management of children with familial hypercholesterolemia. RECENT FINDINGS: A large cross-sectional cohort study of paediatric familial hypercholesterolemia demonstrated that affected children had a 5-fold more rapid increase of carotid arterial wall intima-media thickness during childhood years than their affected siblings. This faster progression led to a significant deviation in terms of intima-media thickness from the age of 12 years and onwards. Low-density lipoprotein cholesterol was a strong and independent predictor of carotid artery intima-media thickness in these children, which confirms the pivotal role of low-density lipoprotein cholesterol for the development of atherosclerosis. In this condition lipid lowering by statin therapy is accompanied by carotid intima-media thickness regression in familial-hypercholesterolemic children, which suggests that initiation of low-density lipoprotein cholesterol-reducing medication in childhood already can inhibit or possibly reduce the faster progression of atherosclerosis. Furthermore, these trials demonstrated that statins are safe and do not impair growth or sexual development in these children. Conversely, products containing plant sterols reduced low-density lipoprotein cholesterol levels by 14%, but did not improve endothelial dysfunction as assessed by flow-mediated dilatation. SUMMARY: Children with familial hypercholesterolemia clearly benefit from lipid-lowering strategies. Statins are safe agents and have been proven to reduce elevated low-density lipoprotein cholesterol levels significantly. In addition, statins improve surrogate markers for atherosclerosis. Therefore these agents should become the pivotal therapy in children with familial hypercholesterolemia. 相似文献
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Michael Wong‐Stringer Onkar S. Game Joel A. Smith Thomas J. Routledge Bakhet A. Alqurashy Benjamin G. Freestone Andrew J. Parnell Naoum Vaenas Vikas Kumar Majed O. A. Alawad Ahmed Iraqi Cornelia Rodenburg David G. Lidzey 《Liver Transplantation》2018,8(24)
An encapsulation system comprising of a UV‐curable epoxy, a solution processed polymer interlayer, and a glass cover‐slip, is used to increase the stability of methylammonium lead triiodide (CH3NH3PbI3) perovskite planar inverted architecture photovoltaic (PV) devices. It is found this encapsulation system acts as an efficient barrier to extrinsic degradation processes (ingress of moisture and oxygen), and that the polymer acts as a barrier that protects the PV device from the epoxy before it is fully cured. This results in devices that maintain 80% of their initial power conversion efficiency after 1000 h of AM1.5 irradiation. Such devices are used as a benchmark and are compared with devices having initially enhanced efficiency as a result of a solvent annealing process. It is found that such solvent‐annealed devices undergo enhanced burn‐in and have a reduced long‐term efficiency, a result demonstrating that initially enhanced device efficiency does not necessarily result in long‐term stability. 相似文献
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Esterhuizen Karien Lindeque J. Zander Mason Shayne van der Westhuizen Francois H. Rodenburg Richard J. de Laat Paul Smeitink Jan A. M. Janssen Mirian C. H. Louw Roan 《Metabolomics : Official journal of the Metabolomic Society》2021,17(1):1-11
Metabolomics - Studies investigating crop resistance to abiotic and biotic stress have largely focused on plant responses to singular forms of stress and individual biochemical pathways that only... 相似文献
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Thatjana Gardeitchik Miski Mohamed Benedetta Ruzzenente Daniela Karall Sergio Guerrero-Castillo Daisy Dalloyaux Mariël van den Brand Sanne van Kraaij Ellyze van Asbeck Zahra Assouline Marlene Rio Pascale de Lonlay Sabine Scholl-Buergi David F.G.J. Wolthuis Alexander Hoischen Richard J. Rodenburg Wolfgang Sperl Zsolt Urban Eva Morava 《American journal of human genetics》2018,102(4):685-695
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Gerwin D. Rodenburg Elisabeth A. M. Sanders Elske J. M. van Gils Reinier H. Veenhoven Tomasz Zborowski Germie P. J. M. van den Dobbelsteen Andries C. Bloem Guy A. M. Berbers Debby Bogaert 《PloS one》2012,7(10)
Background
The CRM197-conjugated 7-valent pneumococcal vaccine (PCV7) is protective against vaccine serotype disease and nasopharyngeal carriage. Data on PCV7-induced mucosal antibodies in relation to systemic or natural anticapsular antibodies are scarce.Methods
In a randomized controlled setting, children received PCV7 at age 2 and 4 months (2-dose group), at age 2, 4 and 11 months (2+1-dose group) or no PCV7 (control group). From 188 children paired saliva samples were collected at 12 and 24 months of age. From a subgroup of 15 immunized children also serum samples were collected. IgG and IgA antibody-levels were measured by multiplex immunoassay.Results
At 12 months, both vaccine groups showed higher serum and saliva IgG-levels against vaccine serotypes compared with controls which sustained until 24 months for most serotypes. Salivary IgG-levels were 10–20-fold lower compared to serum IgG, however, serum and saliva IgG-levels were highly correlated. Serum and salivary IgA-levels were higher in both vaccine groups at 12 months compared with controls, except for serotype 19F. Higher salivary IgA levels remained present for most serotypes in the 2+1-dose group until 24 months, but not in the 2-dose group. Salivary IgA more than IgG, increased after documented carriage of serotypes 6B, 19F and 23F In contrast to IgG, salivary IgA-levels were comparable with serum, suggesting local IgA-production.Conclusions
PCV7 vaccination results in significant increases in salivary IgG and IgA-levels, which are more pronounced for IgG when compared to controls. In contrast, salivary anticapsular IgA-levels seemed to respond more to natural boosting. Salivary IgG and IgA-levels correlate well with systemic antibodies, suggesting saliva might be useful as potential future surveillance tool. 相似文献17.
Brüning M Lummer M Bentele C Smolenaars MM Rodenburg KW Ragg H 《The Biochemical journal》2007,401(1):325-331
By alternative use of four RSL (reactive site loop) coding exon cassettes, the serpin (serine protease inhibitor) gene Spn4 from Drosophila melanogaster was proposed to enable the synthesis of multiple protease inhibitor isoforms, one of which has been shown to be a potent inhibitor of human furin. Here, we have investigated the inhibitory spectrum of all Spn4 RSL variants. The analyses indicate that the Spn4 gene encodes inhibitors that may inhibit serine proteases of the subtilase family (S8), the chymotrypsin family (S1), and the papain-like cysteine protease family (C1), most of them at high rates. Thus a cohort of different protease inhibitors is generated simply by grafting enzyme-adapted RSL sequences on to a single serpin scaffold, even though the target proteases contain different types and/or a varying order of catalytic residues and are descendents of different phylogenetic lineages. Since all of the Spn4 RSL isoforms are produced as intracellular residents and additionally as variants destined for export or associated with the secretory pathway, the Spn4 gene represents a versatile defence tool kit that may provide multiple antiproteolytic functions. 相似文献
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Valsecchi F Monge C Forkink M de Groof AJ Benard G Rossignol R Swarts HG van Emst-de Vries SE Rodenburg RJ Calvaruso MA Nijtmans LG Heeman B Roestenberg P Wieringa B Smeitink JA Koopman WJ Willems PH 《Biochimica et biophysica acta》2012,1817(10):1925-1936
Human mitochondrial complex I (CI) deficiency is associated with progressive neurological disorders. To better understand the CI pathomechanism, we here studied how deletion of the CI gene NDUFS4 affects cell metabolism. To this end we compared immortalized mouse embryonic fibroblasts (MEFs) derived from wildtype (wt) and whole-body NDUFS4 knockout (KO) mice. Mitochondria from KO cells lacked the NDUFS4 protein and mitoplasts displayed virtually no CI activity, moderately reduced CII, CIII and CIV activities and normal citrate synthase and CV (F(o)F(1)-ATPase) activity. Native electrophoresis of KO cell mitochondrial fractions revealed two distinct CI subcomplexes of ~830kDa (enzymatically inactive) and ~200kDa (active). The level of fully-assembled CII-CV was not affected by NDUFS4 gene deletion. KO cells exhibited a moderately reduced maximal and routine O(2) consumption, which was fully inhibited by acute application of the CI inhibitor rotenone. The aberrant CI assembly and reduced O(2) consumption in KO cells were fully normalized by NDUFS4 gene complementation. Cellular [NAD(+)]/[NADH] ratio, lactate production and mitochondrial tetramethyl rhodamine methyl ester (TMRM) accumulation were slightly increased in KO cells. In contrast, NDUFS4 gene deletion did not detectably alter [NADP(+)]/[NADPH] ratio, cellular glucose consumption, the protein levels of hexokinases (I and II) and phosphorylated pyruvate dehydrogenase (P-PDH), total cellular adenosine triphosphate (ATP) level, free cytosolic [ATP], cell growth rate, and reactive oxygen species (ROS) levels. We conclude that the NDUFS4 subunit is of key importance in CI stabilization and that, due to the metabolic properties of the immortalized MEFs, NDUFS4 gene deletion has only modest effects at the live cell level. This article is part of a special issue entitled: 17th European Bioenergetics Conference (EBEC 2012). 相似文献
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