@article{ZulloFleckensteinSchleipetal.2020,
  author    = {Zullo, Alberto and Fleckenstein, Johannes and Schleip, Robert and Hoppe, Kerstin and Wearing, Scott and Klingler, Werner},
  title     = {Structural and Functional Changes in the Coupling of Fascial Tissue, Skeletal Muscle, and Nerves During Aging},
  series = {Frontiers in Physiology},
  volume    = {11},
  journal   = {Frontiers in Physiology},
  number    = {592},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2020.00592},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206890},
  year      = {2020},
  abstract  = {Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.},
  language  = {en}
}
@article{JohannsenSchickRoeweretal.2018,
  author    = {Johannsen, Stephan and Schick, Martin and Roewer, Norbert and Schuster, Frank},
  title     = {Microdialysis and ultrasound elastography for monitoring of localized muscular reaction after pharmacological stimulation in rats},
  series = {BMC Research Notes},
  volume    = {11},
  journal   = {BMC Research Notes},
  number    = {636},
  doi       = {10.1186/s13104-018-3742-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176977},
  year      = {2018},
  abstract  = {Objective: Halothane and caffeine are known to cause skeletal muscular contractions in vitro and have been proven to induce circumscribed metabolic reactions when injected into rat skeletal muscle. In this study 26 rats were investigated by either continuous application of calcium 160 mM or bolus injection of caffeine 160 mM or halothane 10\% vol via a microdialysis probe in the tibialis anterior muscle. Tissue elasticity at the injection site was monitored by ultrasound strain elastography. Aim of this study was to detect (I) changes in local lactate concentrations and (II) whether these can be attributed to a muscular contraction detected by ultrasound elastography. Results: Localized metabolic reactions were verified by increasing intramuscular lactate concentrations following continuous application of calcium (0.6 [0.3;0.6] to 3.6 [3.0;4.3] mmol/l after 60 min) and bolus application of caffeine (0.2 [0.2;0.3] to 1.6 [0.9;1.9] mmol/l after 30 min) and halothane (0.3 [0.1;0.3] to 4.7 [4.3;6.3] mmol/l after 30 min). However, ultrasound elastography did not detect any differences in tissue elasticity compared to control animals. The authors identified potential limitations of the study conditions, which might be crucial to avoid for future investigations.},
  language  = {en}
}
@article{BoehmVasliMaureretal.2013,
  author    = {B{\"o}hm, Johann and Vasli, Nasim and Maurer, Marie and Cowling, Belinda and Shelton, G. Diane and Kress, Wolfram and Toussaint, Anne and Prokic, Ivana and Schara, Ulrike and Anderson, Thomas James and Weis, Joachim and Tiret, Laurent and Laporte, Jocelyn},
  title     = {Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy},
  series = {PLOS Genetics},
  volume    = {9},
  journal   = {PLOS Genetics},
  number    = {6},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1003430},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127590},
  pages     = {e1003430},
  year      = {2013},
  abstract  = {Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies.},
  language  = {en}
}
@article{KlinglerHeiderichGirardetal.2014,
  author    = {Klingler, Werner and Heiderich, Sebastian and Girard, Thierry and Gravino, Elvira and Heffron, James J. A. and Johannsen, Stephan and Jurkat-Rott, Karin and R{\"u}ffert, Henrik and Schuster, Frank and Snoeck, Marc and Sorrentino, Vincenzo and Tegazzin, Vincenzo and Lehmann-Horn, Frank},
  title     = {Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {9},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {8},
  issn      = {1750-1172},
  doi       = {10.1186/1750-1172-9-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117630},
  year      = {2014},
  abstract  = {Background: Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers. Methods: In a multi-centre study including seven European MH units, patients with a history of a clinical MH episode confirmed by susceptible (MHS) or equivocal (MHE) in vitro contracture tests (IVCT) were investigated. A test result is considered to be MHE if the muscle specimens develop pathological contractures in response to only one of the two test substances, halothane or caffeine. Crises were evaluated using a clinical grading scale (CGS), results of IVCT and genetic screening. The effects of SCh and volatile anesthetics on Ca2+ release from sarcoplasmic reticulum (SR) were studied in vitro. Results: A total of 200 patients met the inclusion criteria. Two MH crises (1\%) were triggered by SCh (1 MHS, 1 MHE), 18\% by volatile anesthetics and 81\% by a combination of both. Patients were 70\% male and 50\% were younger than 12 years old. Overall, CGS was in accord with IVCT results. Crises triggered by enflurane had a significantly higher CGS compared to halothane, isoflurane and sevoflurane. Of the 200 patients, 103 carried RyR1 variants, of which 14 were novel. CGS varied depending on the location of the mutation within the RyR1 gene. In contrast to volatile anesthetics, SCh did not evoke Ca2+ release from isolated rat SR vesicles. Conclusions: An MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.},
  language  = {en}
}
@phdthesis{Guenzel2002,
  author    = {G{\"u}nzel, Jane},
  title     = {Methodische Untersuchung zur Mikrodialyse von Laktat aus dem Skelettmuskel der Ratte - eine Studie im Rahmen der Entwicklung einer minimal-invasiven Diagnostik zur Malignen Hyperthermie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-5796},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {Die Maligne Hyperthermie ist eine autosomal-dominant vererbbare Erkrankung, die sich klinisch unter Allgemeinnarkose mit einem erh{\"o}hten Metabolismus, Azidose, Muskelrigidit{\"a}t und Hyperthermie manifestiert. Als Pathogenese wird eine Dysregulation der intrazellul{\"a}ren Kalziumhom{\"o}ostase angenommen. Ihre Pr{\"a}valenz in der Bev{\"o}lkerung wird auf 1:10'000 bis 1:20'000 gesch{\"a}tzt, ihre Mortalit{\"a}tsrate betr{\"a}gt 5-10 \%. Gegenw{\"a}rtig stellt der in vitro-Kontrakturtest mit Halothan und Koffein die einzige M{\"o}glichkeit zur pr{\"a}symptomatischen Diagnose der MH dar. Vorliegender Arbeit liegt die These zugrunde, daß mithilfe von durch MD-Sonden applizierten Substanzen eine lokale MH-Reaktion im Skelettmuskel ausgel{\"o}st und deren Eintreten anhand einer Analyse des Laktatwerts diagnostiziert werden kann. Die bislang f{\"u}r die Koffeinstimulation entwickelte Methode wurde modifiziert, um eine Akzeleration der Versuchsdauer bei maximaler Stimulation der Laktatproduktion durch Koffein zu erreichen. Es wurden 43 Ratten der Gattung Sprague-Dewley pr{\"a}pariert und unter Verwendung verschiedener Flussraten unilateral mit Koffein stimuliert, kontralateral nur mit Ringerl{\"o}sung perfundiert und die daraus resultierenden Laktatwerte im Dialysat gemessen. Mithilfe einer Injektion von 100 bzw. 200 µl 80 mmolaren Koffeins vor Implantation der Sonden kann ein signifikanter Unterschied zwischen Kontroll- und Reaktionsseite bereits nach 30 min induziert werden. Eine Versuchsreihe an MH-unempfindlichen Schweinen best{\"a}tigt die Verwendbarkeit der Methode in vivo. Best{\"a}tigt sich die These, daß sich mithilfe der Mikrodialyse eine lokale MH-Reaktion ausl{\"o}sen l{\"a}ßt, w{\"a}re damit m{\"o}glicherweise ein vielversprechendes Testverfahren in Hinblick auf ein MH-Screening gefunden.},
  language  = {de}
}