Increased Expression of AQP 1 and AQP 5 in Rat Lungs Ventilated with Low Tidal Volume is Time Dependent

Background and GoalsMechanical ventilation (MV) can induce or worsen pulmonary oedema. Aquaporins (AQPs) facilitate the selective and rapid bi-directional movement of water. Their role in the development and resolution of pulmonary oedema is controversial. Our objectives are to determine if prolonged MV causes lung oedema and changes in the expression of AQP 1 and AQP 5 in rats.Methods25 male Wistar rats were subjected to MV with a tidal volume of 10 ml/kg, during 2 hours (n = 12) and 4 hours (n = 13). Degree of oedema was compared with a group of non-ventilated rats (n = 5). The expression of AQP 1 and AQP 5 were determined by western immunoblotting, measuring the amount of mRNA (previously amplified by RT-PCR) and immunohistochemical staining of AQPs 1 and 5 in lung samples from all groups.ResultsLung oedema and alveolar-capillary membrane permeability did not change during MV. AQP-5 steady state levels in the western blot were increased (p<0.01) at 2 h and 4 h of MV. But in AQP-1 expression these differences were not found. However, the amount of mRNA for AQP-1 was increased at 2 h and 4 h of MV; and for AQP 5 at 4 h of MV. These findings were corroborated by representative immunohistochemical lung samples.ConclusionIn lungs from rats ventilated with a low tidal volume the expression of AQP 5 increases gradually with MV duration, but does not cause pulmonary oedema or changes in lung permeability. AQPs may have a protective effect against the oedema induced by MV

Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing

<p>Abstract</p> <p>Background</p> <p>The sheep is an important model organism for many types of medically relevant research, but molecular genetic experiments in the sheep have been limited by the lack of knowledge about ovine gene sequences.</p> <p>Results</p> <p>Prior to our study, mRNA sequences for only 1,556 partial or complete ovine genes were publicly available. Therefore, we developed a composite <it>de novo </it>transcriptome assembly method for next-generation sequence data to combine known ovine mRNA and EST sequences, mRNA sequences from mouse and cow, and sequences assembled <it>de novo </it>from short read RNA-Seq data into a composite reference transcriptome, and identified transcripts from over 12 thousand previously undescribed ovine genes. Gene expression analysis based on these data revealed substantially different expression profiles in standard versus delayed bone healing in an ovine tibial osteotomy model. Hundreds of transcripts were differentially expressed between standard and delayed healing and between the time points of the standard and delayed healing groups. We used the sheep sequences to design quantitative RT-PCR assays with which we validated the differential expression of 26 genes that had been identified by RNA-seq analysis. A number of clusters of characteristic expression profiles could be identified, some of which showed striking differences between the standard and delayed healing groups. Gene Ontology (GO) analysis showed that the differentially expressed genes were enriched in terms including <it>extracellular matrix</it>, <it>cartilage development</it>, <it>contractile fiber</it>, and <it>chemokine activity</it>.</p> <p>Conclusions</p> <p>Our results provide a first atlas of gene expression profiles and differentially expressed genes in standard and delayed bone healing in a large-animal model and provide a number of clues as to the shifts in gene expression that underlie delayed bone healing. In the course of our study, we identified transcripts of 13,987 ovine genes, including 12,431 genes for which no sequence information was previously available. This information will provide a basis for future molecular research involving the sheep as a model organism.</p

Die Bedeutung der remissionserhaltenden Dauertherapie bei Kindern mit akuter lymphoblastischer Leukämie im Rahmen der Therapieoptimierungsstudie ALL-BFM-2000

Die Arbeit behandelt eine Zufallsstichprobe von 50 Kindern mit akuter lymphoblastischer Leukämie (ALL), die in der Studie ALL-BFM 2000 therapiert wurden. Während Induktion, Konsolidierung und Reintensivierung erhalten die Patienten risikoadaptierte Therapie. Darauf folgt, bis zwei Jahre nach Diagnose, die mehrmonatige Dauertherapie mit 6-Mercaptopurin und Methotrexat. Die Dosis der Medikamente soll toxizitäts- und blutbildabhängig reguliert werden. Ziel der Arbeit ist die Objektivierung von Therapieintensität, Blutbildeinstellung und Therapienebenwirkungen unter Dauertherapie, sowie eine Hypothesenbildung über Regulationseffekte. Hierzu wird die Therapiedokumentation retrograd erfasst. Therapiezwischenfälle werden nach den Common Terminology Criteria for Adverse Events v3.0 (CTCAE) codiert. Die Aggregatparameter der Patienten werden auf Korrelationen überprüft. Die Vorgaben des Studienprotokolls zur Regulierung der Dauertherapieintensität können großteilig nicht erreicht werden. Die sich durch Therapiezwischenfälle ergebenden Therapiepausen haben einen negativen Einfluss auf das Outcome der Patienten. Enthält: - Teil 1: Hauptband - Teil 2: Anhang Auswertung - 0: Grundgesamtheit und Stichprobe - Teil 3: Anhang Auswertung - 1: Allgemeine Beschreibung der Dauertherapie - Teil 4: Anhang Auswertung - 2: Die Dauertherapie im Verlauf - Teil 5: Anhang Auswertung - 3: Klassenkorrelationsanalyse, 1 - Teil 6: Anhang Auswertung - 3: Klassenkorrelationsanalyse, 2 - Teil 7: Anhang Auswertung - 3: Klassenkorrelationsanalyse, 3 - Teil 8: Anhang Auswertung - 4: Auswertung nach Outcom

Ultrashort pulse processing of transparent ceramics: The role of electronic and thermal damage mechanisms

In this study, we investigate the ultrashort pulse processing of the transparent, so-called, spinel ceramic (MgAl2O4). We examine the dominant underlying damage mechanisms by an adjustment of the processing parameters. The applied pulse duration is varied from 2 ps to 80 fs to investigate the impact of the electronic and thermal damage mechanisms on the observed modifications in the material. For surface structuring or ablation cutting conditions, pulse repetition rates below 1 MHz are used leading to electronic damages in form of micro-cracks and spikes inside the volume for pulse durations from 1 ps to 2 ps. By a decrease of the pulse duration to 80 fs, we are able to reduce the electronic damages due to a higher absorption of the laser pulse energy at the spinel surface. By an increase of the pulse repetition rate to 2 MHz, we find evidence for thermal melting of the spinel surface due to the impact of heat accumulation, which leads to a loss of the unique structural proper-ties of the spinel