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  • 1
    Electronic Resource
    Electronic Resource
    Oxygen consumption and mitochondrial membrane potential indicate developmental adaptation in energy metabolism of rat cortical neurons (2005)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 21 (2005), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neuronal energy needs are mainly covered via mitochondrial oxidative phosphorylation. Even if the energy supply appears identical in immature and adult brain, nevertheless quantitative differences exist. The present study focuses on the adaptations in cellular energy metabolism caused by the neuronal maturation. As main parameters of oxidative phosphorylation, cellular oxygen consumption and mitochondrial membrane potential were measured in isolated rat cortical cells using a Clark-type oxygen electrode and microfluorometric techniques. In four age groups (E18–P2, P8–P12, P16–P20, ≥ P28), unstimulated neurons showed a significant age-dependent increase in basal oxygen consumption (6.1 up to 10.2 nm/min/107 cells). The excitatory neurotransmitter glutamate induced a further, but age- and concentration-independent, elevation of oxygen consumption to a plateau ≥ 14 nm/min/107 cells and a complete depolarization of mitochondrial membrane in neurons ≥ P8. Stimulation using K+ (5–50 mm) effected a concentration- and age-dependent increase in oxygen consumption, but a similar nearby complete depolarization of mitochondrial membrane in all tested age groups. Furthermore, uncoupling mitochondrial membrane function followed by a complete depolarization of mitochondrial membrane showed a maximal oxygen consumption (14–15 nm/min/107 cells) only in neurons ≥ P8. These data suggest that developing and adult cortical neurons cover their increased need of energy following stimulation by an efficiency improvement of mitochondrial oxidative phosphorylation. The age-independent limited capacity of mitochondrial oxidative phosphorylation, however, causes a reduction in cellular energy disposal in mature neurons and therefore may play a critical role in the increased sensitivity of adult neurons against excitotoxicity and ischaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2005.04109.x
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  • 2
    Electronic Resource
    Electronic Resource
    The influence of obesity on perioperative morbidity and mortality in revision total hip arthroplasty (2000)
    Springer
    Archives of orthopaedic and trauma surgery 120 (2000), S. 267-271 
    Details
    ISSN: 1434-3916
    Keywords: Key words Obesity ; Revision total hip replacement ; Morbidity ; Risk factor ; Operation time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The significance of obesity as a risk factor for postoperative complications was determined in a consecutive series of 229 cases of revision total hip replacement. The body mass index (BMI) was used as an objective measure to classify the patients. The group-wise analysis of data included all medical and procedure-related complications, the number of fatal cases, operative time, requirement for analgesics, the number of transfusions and perioperative haemoglobin levels. The results of our study demonstrate a clear association between obesity and operative time, whereas no statistically significant relationships were observed between obesity and the other parameters. We conclude that obesity does not have any significant influence on perioperative morbidity and mortality but is clearly related to operation time and, therefore, to higher costs per operation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004020050462
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Bioenergetics of Human Peripheral Blood Mononuclear Cell Metabolism in Quiescent, Activated, and Glucocorticoid-Treated States (2000)
    Springer
    Bioscience reports 20 (2000), S. 289-302 
    Details
    ISSN: 1573-4935
    Keywords: bioenergetics of immune functions ; human peripheral blood mononuclear cells ; energy metabolism ; concanavalin A ; nongenomic glucocorticoid effects ; relative drug potencies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The first quantitative findings on the energy metabolism of human immunecells are presented. In quiescent peripheral blood mononuclear cells(PBMC) protein biosynthesis and Na+,K+-ATPase activity eachaccounted for 8% of cellular oxygen consumption. Stimulation with 25, 50,and 75 μg Con A/ml (1.25, 2.5 or 3.75 μg/106 cells) increased totaloxygen consumption within seconds by 8, 36, and 53%, respectively. Afteraddition of 75 μg Con A/ml, the proportion of cellular oxygenconsumption due to protein biosynthesis, Na+,K+-ATPase activity,and Ca2+-ATPase activity was 15% each and that due to DNA/RNAsynthesis was 8%. On the basis of these findings the immediate effectsof five different glucocorticoids on cellular energy metabolism wereinvestigated. The various glucocorticoids exerted basically the sameinhibitory effects on Con A-stimulated cellular respiration and individualATP-consuming processes, but differed significantly in potency. Similar toprevious studies on rat thymocytes, the relative potencies of theglucocorticoids were found to be: prednylidene (1.7)〈dexamethasone(1.5)〈methylprednisolone (1.0)〈prednisolone (0.3)〈betamethasone(〉0.2). Given their rapidity of onset, these effects must benongenomically mediated. The differences between the relative potencies ofthe various glucocorticoids for these effects and those for the classicalgenomic effects have important clinical implications, in particular forhigh-dose systemic and local glucocorticoid therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026445108136
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of methylprednisolone on the energy metabolism of quiescent and conA-stimulated thymocytes of the rat (1993)
    Springer
    Bioscience reports 13 (1993), S. 41-52 
    Details
    ISSN: 1573-4935
    Keywords: methylprednisolone ; thymocytes ; ConA ; energy metabolism ; oxygen consumption ; Ca2+ metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The short-term effects of high concentrations of Methylprednisolone (MP) on the energy metabolism of quiescent and Concanavalin A-stimulated rat thymocytes were investigated in vitro. Concanavalin A (ConA) stimulated the respiration rate of quiescent thymocytes by 35%. Addition of more than 0.15 mg MP/107 cells to ConA-stimulated cells reversed this respiratory stimulation; in addition, higher concentrations of MP caused a similar progressive decrease in the rate of respiration of both quiescent and ConA-stimulated cells. Similarly, the stimulation of respiration by ConA was greatly reduced in MP-treated cells. MP addition lowered cytoplasmic [Ca2+] and, at high concentrations, abolished the ability of ConA to increase [Ca2+]. Thus MP both reverses and prevents the immediate stimulation of thymocytes by ConA. In quiescent thymocytes, MP strongly inhibited that part of the oxygen consumption used to drive the cycle of Na+ influx across the plasma membrane and Na+ efflux on the Na+K+-ATPase, but did not inhibit oxygen consumption used to drive protein synthesis. In ConA-stimulated thymocytes MP had the same effects and also strongly inhibited oxygen consumption dependent on the cycle of Ca2+ influx across the plasma membrane and Ca2+ efflux on the Ca2+-ATPase, but had little effect on oxygen consumption used to drive RNA and DNA synthesis. These results show that MP prevents cation cycling in thymocytes (either by preventing cation influx or by inhibiting cation pumps) and prevents mitogenic stimulation of the cells. The high MP concentration required and the speed of onset of the effect (lless than 30s) provide strong evidence that these effects of MP are not mediated by glucocorticoid receptors and subsequent activation of gene expression. They may be caused by direct effects of MP on the properties of the plasma membrane. These effects are considered to be, at least partially, responsible for the beneficial results that currently have been obtained using MP megadoses in various clinical situations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01138177
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    The influence of Methylprednisolone on the energy metabolism of Ehrlich ascites tumour cells (1994)
    Springer
    Bioscience reports 14 (1994), S. 283-290 
    Details
    ISSN: 1573-4935
    Keywords: Ehrlich ascites tumour cells ; energy metabolism ; methylprednisolone ; cell membrane ; phospholipid turnover ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Using Ehrlich ascites tumour cells, the short-term effects of the therapeutic glucocorticoid Methylprednisolone (MP) on the cellular energy metabolism were studied. ATP-consuming processes involved in the rapid MP effects were identified indirectly from the effects of MP on cellular oxygen consumption related to the inhibition of respiration by selective inhibitors of Ca2+-ATPase and protein synthesis. The effects of MP on plasma membrane permeability for Ca2+ ions and phospholipid turnover were studied directly by using confocal laser scanning microscopy and tracerkinetic measurements, respectively. MP inhibited cellular oxygen consumption, suppressed the inhibitory effect of lanthanum but not that of cycloheximide on oxygen consumption, blocked the [Ca2+]i rise in response to calcium ionophore A 23187, and decreased phospholipid turnover. MP acted instantly in a dose-dependent manner. The observed effects of MP are discussed in relation to the hypothesis that the drug has direct membrane effect affecting plasma membrane permeability and function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01199052
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    Paper (German National Licenses)
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  • 6
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    In silico Methods - Computational Alternatives to Animal Testing (2018)
    Details
    Publication Date: 2020-03-11
    Description: A seminar and interactive workshop on “In silico Methods – Computational Alternatives to Animal Testing” was held in Berlin, Germany, organized by Annemarie Lang, Frank Butt- gereit and Andrea Volkamer at the Charité-Universitätsmedizin Berlin, on August 17-18, 2017. During the half-day seminar, the variety and applications of in silico methods as alternatives to animal testing were presented with room for scientific discus- sions with experts from academia, industry and the German fed- eral ministry (Fig. 1). Talks on computational systems biology were followed by detailed information on predictive toxicology in order to display the diversity of in silico methods and the potential to embrace them in current approaches (Hartung and Hoffmann, 2009; Luechtefeld and Hartung, 2017). The follow- ing interactive one-day Design Thinking Workshop was aimed at experts, interested researchers and PhD-students interested in the use of in silico as alternative methods to promote the 3Rs (Fig. 2). Forty participants took part in the seminar while the workshop was restricted to sixteen participants.
    Language: English
    Type: article , doc-type:article
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  • 7
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    In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis (2019)
    Details
    Publication Date: 2022-01-07
    Description: Understanding the pathophysiological processes of osteoarthritis (OA) require adequate model systems. Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific parts of the disease. This study aimed to combine in vitro and in silico modeling to describe cellular and matrix-related changes during the early phase of OA. We developed an in vitro OA model based on scaffold-free cartilage-like constructs (SFCCs), which was mathematically modeled using a partial differential equation (PDE) system to resemble the processes during the onset of OA. SFCCs were produced from mesenchymal stromal cells and analyzed weekly by histology and qPCR to characterize the cellular and matrix-related composition. To simulate the early phase of OA, SFCCs were treated with interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and examined after 3 weeks or cultivated another 3 weeks without inflammatory cytokines to validate the regeneration potential. Mathematical modeling was performed in parallel to the in vitro experiments. SFCCs expressed cartilage-specific markers, and after stimulation an increased expression of inflammatory markers, matrix degrading enzymes, a loss of collagen II (Col-2) and a reduced cell density was observed which could be partially reversed by retraction of stimulation. Based on the PDEs, the distribution processes within the SFCCs, including those of IL-1β, Col-2 degradation and cell number reduction was simulated. By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and new therapeutic strategies.
    Language: English
    Type: article , doc-type:article
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  • 8
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    Combining in vitro simulation and in silico modelling towards a sophisticated human osteoarthritis model (2019)
    Details
    Publication Date: 2021-03-12
    Description: Our project aimed at building an in silico model based on our recently developed in vitro osteoarthritis (OA) model seeking for refinement of the model to enhance validity and translatability towards the more sophisticated simulation of OA. In detail, the previously 3D in vitro model is based on 3D chondrogenic constructs generated solely from human bone marrow derived mesenchymal stromal cells (hMSCs). Besides studying the normal state of the model over 3 weeks, the in vitro model was treated with interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα) to mimic an OA-like environment.
    Language: English
    Type: article , doc-type:article
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  • 9
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    Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation (2020)
    Details
    Publication Date: 2021-03-05
    Description: Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and i) characterized regarding their cellular and matrix composition or secondly ii) treated with interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate distribution of IL-1β, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aim to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.
    Language: English
    Type: article , doc-type:article
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  • 10
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    Metacarpophalangeal joint stiffness is reduced in patients affected by rheumatoid arthritis after glucocorticoid medication (2012)
    Details
    Publication Date: 2023-11-03
    Language: English
    Type: conferenceobject , doc-type:conferenceObject
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