Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm

Bernd Muehling1, Alexander Oberhuber1, Hubert Schelzig1, Gisela Bischoff1, Nikolaus Marx2, Ludger Sunder-Plassmann1, Karl H Orend11Department of Thoracic and Vascular surgery; 2Department of Internal Medicine, University of Ulm, Ulm, GermanyBackground and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL).Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter.Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter.Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated.Keywords: biomarkers, aneurismal disease, statin therap

The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

<p>Abstract</p> <p>Background</p> <p>The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization.</p> <p>Results</p> <p>Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types.</p> <p>Conclusion</p> <p>The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel insights into the relation of the quiescent and stimulus-induced transcriptome in different cells, and provide a large dataset to the research community, both for mapping purposes, as well as for physiological and pathophysiological research.</p

Kommunalfinanzen in und nach der Covid-19-Pandemie

Städte, Gemeinden und Landkreise haben in der COVID-19-Pandemie einen entscheidenden Beitrag zur Bewältigung der Krise geleistet. Zugleich wurde noch einmal offensichtlich, wie krisenanfällig und wenig resilient die kommunalen Finanzen und damit wie abhängig die Kommunen von Zuweisungen von Bund und Ländern sind, um ihre Aufgaben vor Ort verantwortlich zu erfüllen. Dabei wurden auch die durch Corona forcierten fiskalisch aufwendigen Herausforderungen für die Sanierung der Innenstädte/Ortskerne und bei der Digitalisierung der Kommunalverwaltungen einbezogen. Das vorliegende Positionspapier eines Anfang 2021 eingesetzten Ad-hoc-Arbeitskreises der ARL setzt sich mit den durch die Pandemie offenbarten strukturellen Defiziten der kommunalen Finanzausstattung auseinander und legt Reformvorschläge vor, wie eine für die kommunalen Aufgaben auskömmliche, die Selbstverantwortung stärkende und krisenfeste(re) Finanzierung der kommunalen Haushalte gestaltet werden sollte.Cities, municipalities and rural districts have made a decisive contribution to tackling the crisis caused by the COVID-19 pandemic. At the same time, the lack of resilience and vulnerability of municipal finances has again become obvious. In order to responsibly carry out their local tasks, the municipalities are thus dependent on allocations from the federal and state governments. This is also relevant to the fiscally costly challenges related to the redevelopment of inner cities/town centres and the digitalisation of local administrations, requirements that have been heightened by the Covid-19 pandemic. This Position Paper of an ad-hoc ARL Working Group, which was set up at the beginning of 2021, examines the structural deficits of municipal financial resources as revealed by the pandemic. The discussion includes reform proposals concerning the design of adequate and crisis-proof financing for municipal budgets that would strengthen the autonomy of municipal tasks. This also includes, in particular, making the municipalities more autonomous in terms of taxation and their right to set tax rates, compensating municipalities for their additional responsibilities with a higher share of VAT, objective criteria for determining municipal financial needs in the municipal financial compensation scheme, and an end to the condoning of regular financing via short-term loans

Erfassung regionaler Innovationsdefizite

UuStB Koeln(38)-850106070 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia-4

<p><b>Copyright information:</b></p><p>Taken from "The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia"</p><p>http://www.biomedcentral.com/1471-2164/8/370</p><p>BMC Genomics 2007;8():370-370.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2194787.</p><p></p>ischemic animals and the non-ischemic controls (means of n = 4 experiments for each region). In each of the hippocampal subregions more than 5000 genes could be identified exhibiting differential expression upon ischemia. A. 5243 differentially expressed genes were detected in the CA3 region. B. 5511 differentially expressed genes were detected in the CA1 region. Red: significantly regulated genes (p< 0.05; differentially regulated genes in blue). C, A total of 97 genes is significantly different between ischemic CA3 and ischemic CA1 regions (scatterplot; blue are significantly regulated genes p< 0.05). D, Bar graph showing the 5 most different genes with preference for CA3 or CA1 with their relative enrichment factors (prdma, pr-domain containing protein 8; Inhba, Inhibin beta A; Bok, Bcl-2 related ovarian killer; Sytl4, synaptotagmin-like 4; rbp 4, retinol binding protein 4; mpped1, metallophosphoesterase domain containing 1; mrg1, myeloid ecotropic viral integration site-related gene 1, alternative names: meis2, stra10)

The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia-5

<p><b>Copyright information:</b></p><p>Taken from "The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia"</p><p>http://www.biomedcentral.com/1471-2164/8/370</p><p>BMC Genomics 2007;8():370-370.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2194787.</p><p></p>tting CA3/CA1 ratios in ischemia vs. sham reveals deviation from the diagonal. Difference ratios are attenuated by ischemia regardless of preferential CA3 or CA1 expression (red: p< 0.05). C, Inhibin beta A displays the highest change in preference between the native and ischemic state. The gene expression preference actually reverses from higher expression in CA1 in the native brain to higher expression in CA3 in the ischemic state. Verification with quantitative PCR shows comparable values to the array-derived ratios