Fast and effective anesthesia is the key for refining many invasive procedures in fish and gaining reliable data. For fish as for all vertebrates, it is also required by European law to reduce pain, suffering, and distress to the unavoidable minimum in husbandry and experiments. The most often used substance to induce anesthesia in zebrafish is tricaine (MS-222).
View Article and Find Full Text PDFSomatosensory evoked potentials are frequently acquired by stimulation of the median or tibial nerves (mSEPs and tSEPs) for intraoperative monitoring of sensory pathways. Due to their low amplitudes it is common practice to average 200 or more sweeps to discern the evoked potentials from the background EEG. The aim of this study was to investigate if an algorithm designed to determine the lowest sweep count needed to obtain reproducible evoked potentials in each patient significantly reduces the median necessary sweep count to under 200.
View Article and Find Full Text PDFBackground: Macrophages are involved in tissue homeostasis, angiogenesis and immunomodulation. Proangiogenic and anti-inflammatory macrophages (regulatory macrophages, Mreg) can be differentiated in-vitro from CD14 monocytes by using a defined cell culture medium and a stimulus of IFNγ.
Aim Of The Study: To scrutinize the potential impact of temporal IFNγ exposure on macrophage differentiation as such exposure may lead to the emergence of a distinct and novel macrophage subtype.
Throughout life, continuous remodelling is part of human bone biology and depends on the simultaneous action of physicochemical parameters such as oxygen tension and varying mechanical load. Thus, suitable model systems are needed, which allow concomitant modulation of these factors to recapitulate bone formation. Here, we report on the development of a first microphysiological system (MPS) that enables perfusion, environment-independent regulation of the oxygen tension as well as precise quantification and control of mechanical load.
View Article and Find Full Text PDFBackground: Large extracellular vesicles (L-EV) with a diameter between 1 and 10 µm are released by various cell types. L-EV contain and transport active molecules which are crucially involved in cell to cell communication. We have shown that secretory products of human regulatory macrophages (Mreg) bear pro-angiogenic potential in-vitro and our recent findings show that Mreg cultures also contain numerous large vesicular structures similar to L-EV with so far unknown characteristics and function.
View Article and Find Full Text PDFThe role of the alternate G protein-coupled estrogen receptor 1 (GPER1) in colorectal cancer (CRC) development and progression is unclear, not least because of conflicting clinical and experimental evidence for pro- and anti-tumorigenic activities. Here, we show that low concentrations of the estrogenic GPER1 ligands, 17β-estradiol, bisphenol A, and diethylstilbestrol cause the generation of lagging chromosomes in normal colon and CRC cell lines, which manifest in whole chromosomal instability and aneuploidy. Mechanistically, (xeno)estrogens triggered centrosome amplification by inducing centriole overduplication that leads to transient multipolar mitotic spindles, chromosome alignment defects, and mitotic laggards.
View Article and Find Full Text PDFRemote ischemic preconditioning (RIPC) protects the heart against myocardial ischemia/reperfusion (I/R) injury and recent work also suggested chronic remote ischemic conditioning (cRIPC) for cardiovascular protection. Based on current knowledge that systemic immunomodulatory effects of RIPC and the anti-inflammatory capacity of monocytes might be involved in cardiovascular protection, the aim of our study was to evaluate whether RIPC/cRIPC blood plasma is able to induce in-vitro angiogenesis, identify responsible factors and evaluate the effects of RIPC/cRIPC on cell surface characteristics of circulating monocytes. Eleven healthy volunteers were subjected to RIPC/cRIPC using a blood pressure cuff inflated to > 200 mmHg for 3 × 5 min on the upper arm.
View Article and Find Full Text PDFBackground: Intestinal ischemia/reperfusion (I/R)-injury often results in sepsis and organ failure and is of major importance in the clinic. A potential strategy to reduce I/R-injury is the application of ischemic preconditioning (IPC) during which repeated, brief episodes of I/R are applied. The aim of this study was to evaluate physiological and cellular effects of intestinal I/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded.
View Article and Find Full Text PDFAlthough beneficial effects of an early goal directed therapy (EGDT) after cardiac arrest and successful return of spontaneous circulation (ROSC) have been described, clinical implementation in this period seems rather difficult. The aim of the present study was to investigate the feasibility and the impact of EGDT on myocardial damage and function after cardiac resuscitation. A translational pig model which has been carefully adapted to the clinical setting was employed.
View Article and Find Full Text PDFBackground: Numerous tissue-derived factors have been postulated to be involved in tissue migration of circulating monocytes. The aim of this study was to evaluate whether a defined hypoxic gradient can induce directed migration of naïve human monocytes and to identify responsible autocrine/paracrine factors.
Methods: Monocytes were isolated from peripheral blood mononuclear cells, transferred into chemotaxis chambers and subjected to a defined oxygen gradient with or without the addition of CCL26.
Pharmacol Biochem Behav
April 2020
Buprenorphine is a commonly used opioid to treat moderate to severe pain in mice. Although strain differences regarding basal pain sensitivity and the analgesic effect of other opioids have been described for mice, the data for buprenorphine is incomplete. Hence, we investigated basal pain sensitivity and the analgesic effect of buprenorphine (0.
View Article and Find Full Text PDFObjectives: The sequence of initial tissue ischaemia and consecutive blood flow restoration leads to ischaemia/reperfusion (I/R) injury, which is typically characterized by a specific inflammatory response. Migrating monocytes seem to mediate the immune response in ischaemic tissues and influence detrimental as well as regenerative effects during I/R injury.
Materials And Methods: To clarify the role of classical monocytes in I/R injury, isolated human monocytes were subjected to I/R in vitro (3 hours ischaemia followed by 24 hours of reperfusion).
Extended postoperative care and intensive care unit capacity is limited and efficient patient allocation is mandatory. This study aims to develop an effective yet simple score to predict indication for extended postoperative care, as there is a lack of objective criteria for early prediction of admission to extended care in surgical patients. This prospective observational study was divided into two periods (Period 1: Extended Postoperative Care-Score (EXPO)-Score generation; Period 2: EXPO-Score validation) and it was performed at a tertiary university center in Germany.
View Article and Find Full Text PDFPatients undergoing elective surgery are at risk for inadvertent postoperative hypothermia, defined as a core body temperature below 36°C. This study was conducted to investigate the acceptance of the recommendations of the German S3 Guideline, in particular with respect to the concept of pre-warming and sublingual temperature measurement. The main focus was to gather data concerning the postoperative core temperature and the frequency of perioperative hypothermia in patients receiving a pre-warming regime and those without.
View Article and Find Full Text PDFIschemia/reperfusion- (I/R-) induced organ damage represents one of the main causes of death worldwide, and new strategies to reduce I/R injury are urgently needed. We have shown that programmable cells of monocytic origin (PCMO) respond to I/R with the release of angiogenic mediators and that transplantation of PCMO results in increased neovascularization. Human regulatory macrophages (Mreg), which are also of monocytic origin, have been successfully employed in clinical transplantation studies due to their immunomodulatory properties.
View Article and Find Full Text PDFHydroxyethyl starch (HES) is employed to sustain normovolemia in patients. Using a perfused organ model, we recently showed that HES impairs the intestinal barrier which is constituted of endothelial and epithelial cell layers. However, the target cells and molecular actions of HES in the intestine are mainly unknown.
View Article and Find Full Text PDFBackground: Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia-reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury.
View Article and Find Full Text PDFWe developed a new probabilistic model to assess the impact of recommendations rectifying the reproducibility crisis (by publishing both positive and 'negative' results and increasing statistical power) on competing objectives, such as discovering causal relationships, avoiding publishing false positive results, and reducing resource consumption. In contrast to recent publications our model quantifies the impact of each single suggestion not only for an individual study but especially their relation and consequences for the overall scientific process. We can prove that higher-powered experiments can save resources in the overall research process without generating excess false positives.
View Article and Find Full Text PDFPerinatal asphyxia represents one of the major causes of neonatal morbidity and mortality. Hypothermia is currently the only established treatment for hypoxic-ischemic encephalopathy (HIE), but additional pharmacological strategies are being explored to further reduce the damage after perinatal asphyxia. The aim of this study was to evaluate whether 2-iminobiotin (2-IB) superimposed on hypothermia has the potential to attenuate hypoxia-induced injury of neuronal cells.
View Article and Find Full Text PDFIn the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State.
View Article and Find Full Text PDFBackground: For intraocular surgery, most authors recommend general anesthesia including intubation and neuromuscular blockade to avoid complications by patient movements. However, anesthesia using a laryngeal mask and avoidance of muscle relaxants is common clinical practice. Purpose of this prospective observational study was to compare the incidence of eye movement and deviation of the eye axis during general anesthesia adjusted to minimal alveolar concentration (MAC) for pars plana-vitrectomy (PPV) using a laryngeal mask without neuromuscular blockade (LM) versus endotracheal intubation and neuromuscular blockade (INT).
View Article and Find Full Text PDF