@article{SchraderRieseKurlbaumetal.2021,
  author    = {Schrader, Nikolas and Riese, Thorsten and Kurlbaum, Max and Meybohm, Patrick and Kredel, Markus and Surat, G{\"u}zin and Scherf-Clavel, Oliver and Strate, Alexander and Pospiech, Andreas and Hoppe, Kerstin},
  title     = {Personalized antibiotic therapy for the critically ill: Implementation strategies and effects on clinical outcome of piperacillin therapeutic drug monitoring — a descriptive retrospective analysis},
  series = {Antibiotics},
  volume    = {10},
  journal   = {Antibiotics},
  number    = {12},
  issn      = {2079-6382},
  doi       = {10.3390/antibiotics10121452},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250052},
  year      = {2021},
  abstract  = {Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians' alertness.},
  language  = {en}
}
@article{HoppeSartoriusChaikliengetal.2020,
  author    = {Hoppe, Kerstin and Sartorius, Tina and Chaiklieng, Sunisa and Wietzorrek, Georg and Ruth, Peter and Jurkat-Rott, Karin and Wearing, Scott and Lehmann-Horn, Frank and Klingler, Werner},
  title     = {Paxilline Prevents the Onset of Myotonic Stiffness in Pharmacologically Induced Myotonia: A Preclinical Investigation},
  series = {Frontiers in Physiology},
  volume    = {11},
  journal   = {Frontiers in Physiology},
  doi       = {10.3389/fphys.2020.533946},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218152},
  year      = {2020},
  abstract  = {Reduced Cl\(^{-}\) conductance causes inhibited muscle relaxation after forceful voluntary contraction due to muscle membrane hyperexcitability. This represents the pathomechanism of myotonia congenita. Due to the prevailing data suggesting that an increased potassium level is a main contributor, we studied the effect of a modulator of a big conductance Ca\(^{2+}\)- and voltage-activated K\(^{+}\) channels (BK) modulator on contraction and relaxation of slow- and high-twitch muscle specimen before and after the pharmacological induction of myotonia. Human and murine muscle specimens (wild-type and BK\(^{-/-}\)) were exposed to anthracene-9-carboxylic acid (9-AC) to inhibit CLC-1 chloride channels and to induce myotonia in-vitro. Functional effects of BK-channel activation and blockade were investigated by exposing slow-twitch (soleus) and fast-twitch (extensor digitorum longus) murine muscle specimens or human musculus vastus lateralis to an activator (NS1608) and a blocker (Paxilline), respectively. Muscle-twitch force and relaxation times (T\(_{90/10}\)) were monitored. Compared to wild type, fast-twitch muscle specimen of BK\(^{-/-}\) mice resulted in a significantly decreased T\(_{90/10}\) in presence of 9-AC. Paxilline significantly shortened T\(_{90/10}\) of murine slow- and fast-twitch muscles as well as human vastus lateralis muscle. Moreover, twitch force was significantly reduced after application of Paxilline in myotonic muscle. NS1608 had opposite effects to Paxilline and aggravated the onset of myotonic activity by prolongation of T\(_{90/10}\). The currently used standard therapy for myotonia is, in some individuals, not very effective. This in vitro study demonstrated that a BK channel blocker lowers myotonic stiffness and thus highlights its potential therapeutic option in myotonia congenital (MC).},
  language  = {en}
}
@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}
}
@phdthesis{Hoppe2008,
  author    = {Hoppe, Kerstin},
  title     = {Die Aktivierung von Protease-activated receptors (PARs) mit selektiven Liganden hemmt die D{\"u}nndarmmotilit{\"a}t in vitro},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-37195},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Die Darmatonie bei Intensivpatienten beruht auf vielen Ursachen, die im Einzelnen bisher nur unvollst{\"a}ndig untersucht sind. K{\"u}rzlich wurde eine neue Klasse von Rezeptoren, sog. Protease-Activated Receptors (PAR1, PAR2) in verschiedenen Organen, u.a. im Darm beschrieben. {\"U}ber die physiologische Funktion der PARs im Darm ist wenig bekannt. In der vorliegenden Studie wird die Wirkung von der nat{\"u}rlichen Liganden (PAR1: Thrombin; PAR2: Trypsin) sowie der synthetisch hergestellten Liganden (PAR1: TRAP; PAR2: SLIGRL) auf die D{\"u}nndarmperistaltik untersucht. Hierzu wurden Segmente des Meerschweinchend{\"u}nndarms im Organbad kontinuierlich mit Tyrodel{\"o}sung gegen einen Druck von 400 Pa perfundiert. Dabei wird ab einer konstanten Schwelle des intraluminalen Drucks (peristaltik pressure threshold, PPT) eine von oral nach aboral verlaufende peristaltische Kontraktionswelle ausgel{\"o}st und der Darminhalt ausgeworfen. Unter Einfluss einer inhibitorisch wirkenden Substanz stieg die PPT an oder es waren bei kompletter Hemmung {\"u}berhaupt keine peristaltischen Kontraktionen mehr auszul{\"o}sen. Eine peristaltikanregende Wirkung zeigte sich hingegen in einer Absenkung der PPT. Untersucht wurden je Substanz bzw. Substanzkombination sechs Segmente von sechs verschiedenen Meerschweinchen, wobei jedes Darmsegment nur mit einer Konzentration einer Substanz behandelt wurde. Die Signifikanzpr{\"u}fung erfolgte auf dem Niveau von p<0,05 (Kolmogorov-Smirnov-Test, ANOVA). Wesentliches Ergebnis dieser Arbeit ist, dass die synthetisch hergestellten Liganden an PAR1 und PAR2, SLIGRL und TRAP, die D{\"u}nndarmmotilit{\"a}t konzentrationsabh{\"a}ngig hemmen. Im Gegensatz dazu zeigten die nat{\"u}rlichen Liganden an PAR1 und PAR2, Thrombin und Trypsin, keinen Effekt auf die D{\"u}nndarmmotilit{\"a}t. Durch Vorbehandlung des Darms mit Antagonisten und Inhibitoren der vermuteten Signaltransduktionswege wurden die der Hemmung zugrunde liegenden Mechanismen untersucht. Die Hemmwirkung von TRAP und SLIGRL ließ sich durch Vorbehandlung des Darms mit Naloxon, nicht jedoch mit Apamin aufheben. Somit sind an der inhibitorischen Wirkung der PAR1- und PAR2-Agonisten am Meerschweinchend{\"u}nndarm enterische, m{\"o}glicherweise unspezifische opioiderge Mechanismen beteiligt, allerdings keine „low conductance Ca2+ activated K+ Channels". Die motilit{\"a}tshemmende Wirkung des Benzodiazepins Midazolam wurde durch PAR1- (Thrombin, TRAP), nicht jedoch durch PAR2-Agonisten (Trypsin, SLIGRL) verst{\"a}rkt. Der hemmende Effekt des Opiates Fentanyl wurde weder durch PAR1- oder PAR2-Agonisten beeinflusst.},
  subject      = {Darm},
  language  = {de}
}