Untersuchung von Magnetronsputterpozessen zur Herstellung optischer Präzisionsbeschichtungen

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Influence of combined functional resistance and endurance exercise over 12 weeks on matrix metalloproteinase-2 serum concentration in persons with relapsing-remitting multiple sclerosis-a community-based randomized controlled trial

Background: The relevance of regular moderate to intense exercise for ameliorating psychomotor symptoms in persons with multiple sclerosis (pwMS) is becoming increasingly evident. Over the last two decades, emerging evidence from clinical studies and animal models indicate immune regulatory mechanisms in both periphery and the central nervous system that may underlie these beneficial effects. The integrity of the blood-brain barrier as the main structural interface between periphery and brain seems to play an important role in MS. Reducing the secretion of proteolytic matrix metalloproteinases (MMP), i.e. MMP-2, as disruptors of blood-brain barrier integrity could have profound implications for MS. Methods: In this two-Armed randomized controlled trial 64 participants with relapsing-remitting MS (RRMS) (EDSS 0-4.0) will be allocated to either an intervention group or a passive wait list control group. The intervention group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks in a community-based and publicly available setting. Changes in serum concentration of MMP-2 will be the primary outcome. Secondary outcomes are numbers of immune cell subsets, soluble (anti-) inflammatory factors, physical capacity, cognitive performance, physical activity behavior, gait performance, and patient-reported outcomes. All outcome measures will be assessed at baseline and after week 12 with an additional blood sampling before, during and immediately after a single training session in week 6. Discussion: To our knowledge, this will be the first RCT to investigate both the acute and chronic effects of a community-based intense functional resistance and endurance exercise regimen in persons with RRMS. Combining analysis of biological and cognitive or psychological outcomes may provide a better understanding of the MS-specific symptomology. Trial registration: DRKS00017091; 05th of April, 2019; International Clinical Trials Registry Platform

High-intensity interval training reduces neutrophil-to-lymphocyte ratio in persons with multiple sclerosis during inpatient rehabilitation

In persons with multiple sclerosis (PwMS), the neutrophil-to-lymphocyte ratio (NLR) is associated with disability status, symptomatology and disease activity. High-intensity interval training (HIIT) improves many symptoms in PwMS and may positively influence disease progression. Here, we present results from a randomized controlled trial during inpatient rehabilitation on immediate (single bout) and training (3-week intervention) effects of HIIT versus moderate continuous training on NLR and related cellular inflammation markers. Only HIIT reduced the NLR over the 3-week intervention period. These training effects might be due to repetitive inflammatory states with compensatory anti-inflammatory counterbalancing after each HIIT session

Influence of different rehabilitative aerobic exercise programs on (anti-) inflammatory immune signalling, cognitive and functional capacity in persons with MS – study protocol of a randomized controlled trial

Abstract Background Studies have shown positive effects of therapeutic exercise on motor- and cognitive function as well as on psychosocial outcomes in persons with multiple sclerosis (MS). A reduction of inflammatory stress through physical exercise has been suspected as one key mechanism, mediating the positive effects of exercise in the context of MS. The primary objective of this trial is to investigate the acute and chronic effects of different exercise modalities on (anti-)inflammatory immune signalling as well as on cognitive and functional capacity in persons with MS. Methods A two armed single-blind randomized controlled design will investigate 72 persons with relapsing remitting or secondary progressive MS (EDSS 3.0–6.0), during 3 weeks of inpatient rehabilitation. Participants will be randomized into either a high-intensity interval training (HIIT) or a moderate continuous training group; the latter represents the local standard therapy (ST). Both groups will exercise 3x per week. The HIIT group will perform 5 × 1.5-min high-intensive exercise bouts at 95–100% of their maximum heart rate (HRmax) followed by active breaks of unloaded pedalling (60% HRmax) for 2 min. In contrast, the ST group will exercise for 24 min continuously at 65% of HRmax. The proportion of circulating regulatory T-cells will be measured as primary outcome. Secondary outcomes comprise numbers and proportions of further immune cells including Th17-cells, soluble factors ((anti-) inflammatory cytokines, tryptophan metabolites), endurance capacity, cognitive performance, processing skills for activities of daily living, fatigue, depression and healthcare-related quality of life. Outcomes will be assessed before (T0) and after (T3) the 3-week exercise intervention program. Blood samples of T0 will be taken immediately before the first exercise session. Additionally, blood samples for the soluble factors will be collected immediately after (T1) and three hours (T2) after the first exercise session of each group. Discussion This study will be the first to investigate both acute and chronic effects of aerobic exercise on immune function and disease associated biomarkers in persons with MS. Combining biological analyses with cognitive and functional capacity assessments may contribute to a better understanding of responses to rehabilitative training, needed to improve exercise recommendations for persons with MS. Trial registration This trial was prospectively registered at ClinicalTrials.gov (NCT03652519; 29 August 2018)

Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis

Objective To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS). Methods Sixty-nine pwMS (Expanded Disability Status Scale score 3.0-6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention. Results Acute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT. Conclusion Future studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS. Classification of Evidence This study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS

Genetic regulation of mouse glycosylphosphatidylinositol-phospholipase D

Glycosylphosphatidylinositol phospholipase D (GPI-PLD) has been proposed to be responsible for cleaving membrane-associated glycosylphosphatidyl inositol (GPI) molecules to generate inositol phosphoglycan (IPGs), which have growth factor-mimetic properties. We have cloned the mouse liver GPI-PLD cDNA, which has a sequence that differs from that previously isolated from a mouse glucagonoma cell library. Using a highly specific and very sensitive RNase protection assay, we found that the GPI-PLD expressed in adult/post-natal brain, antrum and insulin-producing cells is identical to that isolated from liver. The expression of mouse GPI-PLD in liver shows a complex genetic regulation with a mouse strain-specific variation. In addition, GPI-PLD mRNA levels were higher in 4-week old animals compared to older animals, and the GPI-PLD mRNA levels increased in mice that developed insulin dependent type 1 diabetes spontaneously. This suggests that the expression of liver GPI-PLD in mice is highly regulated