@misc{WochatzSchraplauEngeletal.2022, author = {Wochatz, Monique and Schraplau, Anne and Engel, Tilman and Zecher, Mahli Megan and Sharon, Hadar and Alt, Yasmin and Mayer, Frank and Kalron, Alon}, title = {Application of eccentric training in various clinical populations}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {833}, issn = {1866-8364}, doi = {10.25932/publishup-58849}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-588493}, pages = {15}, year = {2022}, abstract = {Physical activity and exercise are effective approaches in prevention and therapy of multiple diseases. Although the specific characteristics of lengthening contractions have the potential to be beneficial in many clinical conditions, eccentric training is not commonly used in clinical populations with metabolic, orthopaedic, or neurologic conditions. The purpose of this pilot study is to investigate the feasibility, functional benefits, and systemic responses of an eccentric exercise program focused on the trunk and lower extremities in people with low back pain (LBP) and multiple sclerosis (MS). A six-week eccentric training program with three weekly sessions is performed by people with LBP and MS. The program consists of ten exercises addressing strength of the trunk and lower extremities. The study follows a four-group design (N = 12 per group) in two study centers (Israel and Germany): three groups perform the eccentric training program: A) control group (healthy, asymptomatic); B) people with LBP; C) people with MS; group D (people with MS) receives standard care physiotherapy. Baseline measurements are conducted before first training, post-measurement takes place after the last session both comprise blood sampling, self-reported questionnaires, mobility, balance, and strength testing. The feasibility of the eccentric training program will be evaluated using quantitative and qualitative measures related to the study process, compliance and adherence, safety, and overall program assessment. For preliminary assessment of potential intervention effects, surrogate parameters related to mobility, postural control, muscle strength and systemic effects are assessed. The presented study will add knowledge regarding safety, feasibility, and initial effects of eccentric training in people with orthopaedic and neurological conditions. The simple exercises, that are easily modifiable in complexity and intensity, are likely beneficial to other populations. Thus, multiple applications and implementation pathways for the herein presented training program are conceivable.}, language = {en} } @article{WochatzSchraplauEngeletal.2022, author = {Wochatz, Monique and Schraplau, Anne and Engel, Tilman and Zecher, Mahli Megan and Sharon, Hadar and Alt, Yasmin and Mayer, Frank and Kalron, Alon}, title = {Application of eccentric training in various clinical populations}, series = {PLoS ONE}, volume = {17}, journal = {PLoS ONE}, number = {12}, publisher = {Public Library of Science}, address = {San Francisco, California, USA}, issn = {1932-6203}, doi = {10.1371/journal.pone.0270875}, pages = {15}, year = {2022}, abstract = {Physical activity and exercise are effective approaches in prevention and therapy of multiple diseases. Although the specific characteristics of lengthening contractions have the potential to be beneficial in many clinical conditions, eccentric training is not commonly used in clinical populations with metabolic, orthopaedic, or neurologic conditions. The purpose of this pilot study is to investigate the feasibility, functional benefits, and systemic responses of an eccentric exercise program focused on the trunk and lower extremities in people with low back pain (LBP) and multiple sclerosis (MS). A six-week eccentric training program with three weekly sessions is performed by people with LBP and MS. The program consists of ten exercises addressing strength of the trunk and lower extremities. The study follows a four-group design (N = 12 per group) in two study centers (Israel and Germany): three groups perform the eccentric training program: A) control group (healthy, asymptomatic); B) people with LBP; C) people with MS; group D (people with MS) receives standard care physiotherapy. Baseline measurements are conducted before first training, post-measurement takes place after the last session both comprise blood sampling, self-reported questionnaires, mobility, balance, and strength testing. The feasibility of the eccentric training program will be evaluated using quantitative and qualitative measures related to the study process, compliance and adherence, safety, and overall program assessment. For preliminary assessment of potential intervention effects, surrogate parameters related to mobility, postural control, muscle strength and systemic effects are assessed. The presented study will add knowledge regarding safety, feasibility, and initial effects of eccentric training in people with orthopaedic and neurological conditions. The simple exercises, that are easily modifiable in complexity and intensity, are likely beneficial to other populations. Thus, multiple applications and implementation pathways for the herein presented training program are conceivable.}, language = {en} } @article{NeuschaeferRubeSchraplauScheweetal.2015, author = {Neuschaefer-Rube, Frank and Schraplau, Anne and Schewe, Bettina and Lieske, Stefanie and Kruetzfeldt, Julia-Mignon and Ringel, Sebastian and Henkela, Janin and Birkenfeld, Andreas L. and P{\"u}schel, Gerhard Paul}, title = {Arylhydrocarbon receptor-dependent mIndy (SIc13a5) induction as possible contributor to benzo[a]pyrene-induced lipid accumulation in hepatocytes}, series = {Toxicology}, volume = {337}, journal = {Toxicology}, publisher = {Elsevier}, address = {Clare}, issn = {0300-483X}, doi = {10.1016/j.tox.2015.08.007}, pages = {1 -- 9}, year = {2015}, abstract = {Non-alcoholic fatty liver disease is a growing problem in industrialized and developing countries. Hepatic lipid accumulation is the result of an imbalance between fatty acid uptake, fatty acid de novo synthesis, beta-oxidation and secretion of triglyceride-rich lipoproteins from the hepatocyte. A central regulator of hepatic lipid metabolism is cytosolic citrate that can either be derived from the mitochondrium or be taken up from the blood via the plasma membrane sodium citrate transporter NaCT, the product of the mammalian INDY gene (SLC13A5). mINDY ablation protects against diet-induced steatosis whereas mINDY expression is increased in patients with hepatic steatosis. Diet-induced hepatic steatosis is also enhanced by activation of the arylhyrocarbon receptor (AhR) both in humans and animal models. Therefore, the hypothesis was tested whether the mINDY gene might be a target of the AhR. In accordance with such a hypothesis, the AhR activator benzo[a]pyrene induced the mINDY expression in primary cultures of rat hepatocytes in an AhR-dependent manner. This induction resulted in an increased citrate uptake and citrate incorporation into lipids which probably was further enhanced by the benzo[a]pyrene-dependent induction of key enzymes of fatty acid synthesis. A potential AhR binding site was identified in the mINDY promoter that appears to be conserved in the human promoter. Elimination or mutation of this site largely abolished the activation of the mINDY promoter by benzo[a]pyrene. This study thus identified the mINDY as an AhR target gene. AhR-dependent induction of the mINDY gene might contribute to the development of hepatic steatosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.}, language = {en} } @misc{HenkelColemanMacGregorofInneregnySchraplauetal.2018, author = {Henkel, Janin and Coleman Mac Gregor of Inneregny, Charles Dominic and Schraplau, Anne and J{\"o}hrens, Korinna and Weiss, Thomas Siegfried and Jonas, Wenke and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul}, title = {Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {483}, issn = {1866-8372}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-420879}, pages = {11}, year = {2018}, abstract = {In a subset of patients, non-alcoholic fatty liver disease (NAFLD) is complicated by cell death and inflammation resulting in non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and subsequent organ failure. Apart from cytokines, prostaglandins, in particular prostaglandin E-2 (PGE(2)), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE(2) synthesis, cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), was increased in human NASH livers in comparison to controls and correlated with the NASH activity score. Both enzymes were also induced in NASH-diet-fed wild-type mice, resulting in an increase in hepatic PGE(2) concentration that was completely abrogated in mPGES-1-deficient mice. PGE(2) is known to inhibit TNF-alpha synthesis in macrophages. A strong infiltration of monocyte-derived macrophages was observed in NASH-diet-fed mice, which was accompanied with an increase in hepatic TNF-alpha expression. Due to the impaired PGE(2) production, TNF-alpha expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-alpha resulted in an enhanced IL-1 beta production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE(2) production by mPGES-1 ablation enhanced the TNF-alpha-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.}, language = {en} } @article{HenkelColemanMacGregorofInneregnySchraplauetal.2018, author = {Henkel, Janin and Coleman Mac Gregor of Inneregny, Charles Dominic and Schraplau, Anne and J{\"o}hrens, Korinna and Weiss, Thomas Siegfried and Jonas, Wenke and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul}, title = {Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model}, series = {Scientific Reports}, journal = {Scientific Reports}, number = {8}, publisher = {Nature Research}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-018-34633-y}, pages = {1 -- 11}, year = {2018}, abstract = {In a subset of patients, non-alcoholic fatty liver disease (NAFLD) is complicated by cell death and inflammation resulting in non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and subsequent organ failure. Apart from cytokines, prostaglandins, in particular prostaglandin E-2 (PGE(2)), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE(2) synthesis, cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), was increased in human NASH livers in comparison to controls and correlated with the NASH activity score. Both enzymes were also induced in NASH-diet-fed wild-type mice, resulting in an increase in hepatic PGE(2) concentration that was completely abrogated in mPGES-1-deficient mice. PGE(2) is known to inhibit TNF-alpha synthesis in macrophages. A strong infiltration of monocyte-derived macrophages was observed in NASH-diet-fed mice, which was accompanied with an increase in hepatic TNF-alpha expression. Due to the impaired PGE(2) production, TNF-alpha expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-alpha resulted in an enhanced IL-1 beta production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE(2) production by mPGES-1 ablation enhanced the TNF-alpha-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.}, language = {en} } @article{HenkelColemanSchraplauetal.2018, author = {Henkel, Janin and Coleman, Charles Dominic and Schraplau, Anne and Joehrens, Korinna and Weiss, Thomas Siegfried and Jonas, Wenke and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul}, title = {Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model}, series = {Scientific reports}, volume = {8}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-018-34633-y}, pages = {11}, year = {2018}, abstract = {In a subset of patients, non-alcoholic fatty liver disease (NAFLD) is complicated by cell death and inflammation resulting in non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and subsequent organ failure. Apart from cytokines, prostaglandins, in particular prostaglandin E-2 (PGE(2)), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE(2) synthesis, cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), was increased in human NASH livers in comparison to controls and correlated with the NASH activity score. Both enzymes were also induced in NASH-diet-fed wild-type mice, resulting in an increase in hepatic PGE(2) concentration that was completely abrogated in mPGES-1-deficient mice. PGE(2) is known to inhibit TNF-alpha synthesis in macrophages. A strong infiltration of monocyte-derived macrophages was observed in NASH-diet-fed mice, which was accompanied with an increase in hepatic TNF-alpha expression. Due to the impaired PGE(2) production, TNF-alpha expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-alpha resulted in an enhanced IL-1 beta production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE(2) production by mPGES-1 ablation enhanced the TNF-alpha-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.}, language = {en} } @misc{SchomoellerRischKaplicketal.2020, author = {Schom{\"o}ller, Anne and Risch, Lucie and Kaplick, Hannes and Schraplau, Anne and Wochatz, Monique and Engel, Tilman and Sonnenburg, Dominik and Mayer, Frank}, title = {Changes in paraspinal muscle T2 times and creatine kinase after a bout of eccentric exercise}, series = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine}, volume = {52}, journal = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine}, number = {17}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0195-9131}, doi = {10.1249/01.mss.0000685648.68626.f1}, pages = {929 -- 929}, year = {2020}, abstract = {Eccentric (ECC) exercises might cause muscle damage, characterized by delayed-onset muscle soreness, elevated creatine kinase (CK) levels and local muscle oedema, shown by elevated T2 times in magnet resonance imaging (MRI) scans. Previous research suggests a high inter-individual difference regarding these systemic and local responses to eccentric workload. PURPOSE: To analyze ECC exercise-induced muscle damage in lumbar paraspinal muscles assessed via MRI. METHODS: Ten participants (3f/7m; 33±6y; 174±8cm; 71±12kg) were included in the study. Quantitative paraspinal muscle constitution of M. erector spinae and M. multifidius were assessed in supine position before and 72h after an intense eccentric trunk exercise bout in a mobile 1.5 tesla MRI device. MRI scans were recorded on spinal level L3 (T2-weighted TSE echo sequences, 11 slices, 2mm slice thickness, 3mm gap, echo times: 20, 40, 60, 80, 100ms, TR time: 2500ms). Muscle T2 times were calculated for manually traced regions of interest of the respective muscles with an imaging software. The exercise protocol was performed in an isokinetic device and consisted of 120sec alternating ECC trunk flexion-extension with maximal effort. Venous blood samples were taken before and 72h after the ECC exercise. Descriptive statistics (mean±SD) and t-testing for pre-post ECC exercises were performed. RESULTS: T2 times increased from pre- to post-ECC MRI measurements from 55±3ms to 79±28ms in M. erector spinae and from 62±5ms to 78±24ms in M. multifidius (p<0.001). CK increased from 126±97 U/L to 1447±20579 U/L. High SDs of T2 time and CK in post-ECC measures could be due to inter-individual reactions to ECC exercises. 3 participants showed high local and systemic reactions (HR) with T2 time increases of 120±24\% (M. erector spinae) and 73±50\% (M. multifidius). In comparison, the remaining 7 participants showed increases of 11±12\% (M. erector spinae) and 7±9\% (M. multifidius) in T2 time. Mean CK increased 9.5-fold in the 3 HR subjects compared with the remaining 7 subjects. CONCLUSIONS: The 120sec maximal ECC trunk flexion-extension protocol induced high amounts of muscle damage in 3 participants. Moderate to low responses were found in the remaining 7 subjects, assuming that inter-individual predictors play a role regarding physiological responses to ECC workload.}, language = {en} } @misc{SchraplauSonnenburgWochatzetal.2020, author = {Schraplau, Anne and Sonnenburg, Dominik and Wochatz, Monique and Engel, Tilman and Schom{\"o}ller, Anne and Risch, Lucie and Kaplick, Hannes and Mayer, Frank}, title = {Characterization of muscle damage and inflammation following repeated maximal eccentric loading of the trunk}, series = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine}, volume = {52}, journal = {Medicine and science in sports and exercise : official journal of the American College of Sports Medicine}, number = {7S}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0195-9131}, doi = {10.1249/01.mss.0000679532.65880.af}, pages = {497 -- 497}, year = {2020}, abstract = {Eccentric exercises (ECC) induce reversible muscle damage, delayed-onset muscle soreness and an inflammatory reaction that is often followed by a systemic anti-inflammatory response. Thus, ECC might be beneficial for treatment of metabolic disorders which are frequently accompanied by a low-grade systemic inflammation. However, extent and time course of a systemic immune response after repeated ECC bouts are poorly characterized. PURPOSE: To analyze the (anti-)inflammatory response after repeated ECC loading of the trunk. METHODS: Ten healthy participants (33 ± 6 y; 173 ± 14 cm; 74 ± 16 kg) performed three isokinetic strength measurements of the trunk (concentric (CON), ECC1, ECC2, each 2 wks apart; flexion/extension, velocity 60°/s, 120s MVC). Pre- and 4, 24, 48, 72, 168h post-exercise, muscle soreness (numeric rating scale, NRS) was assessed and blood samples were taken and analyzed [Creatine kinase (CK), C-reactive protein (CRP), Interleukin-6 (IL-6), IL-10, Tumor necrosis factor-α (TNF-α)]. Statistics were done by Friedman's test with Dunn's post hoc test (α=.05). RESULTS: Mean peak torque was higher during ECC1 (319 ± 142 Nm) than during CON (268 ± 108 Nm; p<.05) and not different between ECC1 and ECC2 (297 ± 126 Nm; p>.05). Markers of muscle damage (peaks post-ECC1: NRS 48h, 4.4±2.9; CK 72h, 14407 ± 19991 U/l) were higher after ECC1 than after CON and ECC2 (p<.05). The responses over 72h (stated as Area under the Curve, AUC) were abolished after ECC2 compared to ECC1 (p<.05) indicating the presence of the repeated bout effect. CRP levels were not changed. IL-6 levels increased 2-fold post-ECC1 (pre: 0.5 ± 0.4 vs. 72h: 1.0 ± 0.8 pg/ml). The IL-6 response was enhanced after ECC1 (AUC 61 ± 37 pg/ml*72h) compared to CON (AUC 33 ± 31 pg/ml*72h; p<.05). After ECC2, the IL-6 response (AUC 43 ± 25 pg/ml*72h) remained lower than post-ECC1, but the difference was not statistically significant. Serum levels of TNF-α and of the anti-inflammatory cytokine IL-10 were below detection limits. Overall, markers of muscle damage and immune response showed high inter-individual variability. CONCLUSION: Despite maximal ECC loading of a large muscle group, no anti-inflammatory and just weak inflammatory responses were detected in healthy adults. Whether ECC elicits a different reaction in inflammatory clinical conditions is unclear.}, language = {en} } @article{SchraplauScheweNeuschaeferRubeetal.2015, author = {Schraplau, Anne and Schewe, Bettina and Neusch{\"a}fer-Rube, Frank and Ringel, Sebastian and Neuber, Corinna and Kleuser, Burkhard and P{\"u}schel, Gerhard Paul}, title = {Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital}, series = {Toxicology}, volume = {328}, journal = {Toxicology}, publisher = {Elsevier}, address = {Clare}, issn = {0300-483X}, doi = {10.1016/j.tox.2014.12.004}, pages = {21 -- 28}, year = {2015}, abstract = {Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. (C) 2014 Elsevier Ireland Ltd. All rights reserved.}, language = {en} } @article{EngelSchraplauWochatzetal.2021, author = {Engel, Tilman and Schraplau, Anne and Wochatz, Monique and Kopinski, Stephan and Sonnenburg, Dominik and Schom{\"o}ller, Anne and Risch, Lucie and Kaplick, Hannes and Mayer, Frank}, title = {Feasability of An Eccentric Isokinetic Protocol to Induce Trunk Muscle Damage: A Pilot Study}, series = {Sports Medicine International Open}, volume = {6}, journal = {Sports Medicine International Open}, edition = {1}, publisher = {Thieme}, address = {Stuttgart}, issn = {2367-1890}, doi = {10.1055/a-1757-6724}, pages = {E9 -- E17}, year = {2021}, abstract = {Eccentric exercise is discussed as a treatment option for clinical populations, but specific responses in terms of muscle damage and systemic inflammation after repeated loading of large muscle groups have not been conclusively characterized. Therefore, this study tested the feasibility of an isokinetic protocol for repeated maximum eccentric loading of the trunk muscles. Nine asymptomatic participants (5 f/4 m; 34±6 yrs; 175±13 cm; 76±17 kg) performed three isokinetic 2-minute all-out trunk strength tests (1x concentric (CON), 2x eccentric (ECC1, ECC2), 2 weeks apart; flexion/extension, 60°/s, ROM 55°). Outcomes were peak torque, torque decline, total work, and indicators of muscle damage and inflammation (over 168 h). Statistics were done using the Friedman test (Dunn's post-test). For ECC1 and ECC2, peak torque and total work were increased and torque decline reduced compared to CON. Repeated ECC bouts yielded unaltered torque and work outcomes. Muscle damage markers were highest after ECC1 (soreness 48 h, creatine kinase 72 h; p<0.05). Their overall responses (area under the curve) were abolished post-ECC2 compared to post-ECC1 (p<0.05). Interleukin-6 was higher post-ECC1 than CON, and attenuated post-ECC2 (p>0.05). Interleukin-10 and tumor necrosis factor-α were not detectable. All markers showed high inter-individual variability. The protocol was feasible to induce muscle damage indicators after exercising a large muscle group, but the pilot results indicated only weak systemic inflammatory responses in asymptomatic adults.}, language = {en} }