TY - JOUR A1 - Saunders, Rhodri A1 - Davis, Jason A. A1 - Kranke, Peter A1 - Weissbrod, Rachel A1 - Whitaker, David K A1 - Lightdale, Jenifer R T1 - Clinical and economic burden of procedural sedation-related adverse events and their outcomes: analysis from five countries JF - Therapeutics and Clinical Risk Management N2 - Background: Studies have reported on the incidence of sedation-related adverse events (AEs), but little is known about their impact on health care costs and resource use. Methods: Health care providers and payers in five countries were recruited for an online survey by independent administrators to ensure that investigators and respondents were blinded to each other. Surveys were conducted in the local language and began with a "screener" to ensure that respondents had relevant expertise and experience. Responses were analyzed using Excel and R, with the Dixon's Q statistic used to identify and remove outliers. Global and country-specific average treatment patterns were calculated via bootstrapping; costs were mean values. The sum product of costs and intervention probability gave a cost per AE. Results: Responses were received from 101 providers and 26 payers, the majority having. 5 years of experience. At a minimum, the respondents performed a total of 3,430 procedural sedations per month. All AEs detailed occurred in clinical practice in the last year and were reported to cause procedural delays and cancellations in some patients. Standard procedural sedation costs ranged from (sic)74 (Germany) to $2,300 (US). Respondents estimated that AEs would increase costs by between 16% (Italy) and 179% (US). Hypotension was reported as the most commonly observed AE with an associated global mean cost (interquartile range) of $43 ($27-$68). Other frequent AEs, including mild hypotension, bradycardia, tachycardia, mild oxygen desaturation, hypertension, and brief apnea, were estimated to increase health care spending on procedural sedation by $2.2 billion annually in the US. Conclusion: All sedation-related AEs can increase health care costs and result in substantial delays or cancellations of subsequent procedures. The prevention of even minor AEs during procedural sedation may be crucial to ensuring its value as a health care service. KW - costs KW - complications KW - moderate sedation KW - questionnaire KW - survey KW - health care payers Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227508 VL - 14 ER - TY - JOUR A1 - Reinhold, Ann Kristin A1 - Schwabe, Joachim A1 - Lux, Thomas J. A1 - Salvador, Ellaine A1 - Rittner, Heike L. T1 - Quantitative and Microstructural Changes of the Blood-Nerve Barrier in Peripheral Neuropathy JF - Frontiers in Neuroscience N2 - Peripheral neuropathy is accompanied by changes in the neuronal environment. The blood-nerve barrier (BNB) is crucial in protecting the neural homeostasis: Tight junctions (TJ) seal paracellular spaces and thus prevent external stimuli from entering. In different models of neuropathic pain, the BNB is impaired, thus contributing to local damage, immune cell invasion and, ultimately, the development of neuropathy with its symptoms. In this study, we examined changes in expression and microstructural localization of two key tight junction proteins (TJP), claudin-1 and the cytoplasmic anchoring ZO-1, in the sciatic nerve of mice subjected to chronic constriction injury (CCI). Via qPCR and analysis of fluorescence immunohistochemistry, a marked downregulation of mRNA as well as decreased fluorescence intensity were observed in the nerve for both proteins. Moreover, a distinct zig-zag structure for both proteins located at cell-cell contacts, indicative of the localization of TJs, was observed in the perineurial compartment of sham-operated animals. This microstructural location in cell-cell-contacts was lost in neuropathy as semiquantified via computational analysis, based on a novel algorithm. In summary, we provide evidence that peripheral neuropathy is not only associated with decrease in relevant TJPs but also exhibits alterations in TJP arrangement and loss in barrier tightness, presumably due to internalization. Specifically, semiquantification of TJP in cell-cell-contacts of microcompartments could be used in the future for routine clinical samples of patients with neuropathy. KW - neuropathic pain KW - chronic constriction injury KW - blood-nerve barrier KW - tight junction protein KW - claudin-1 KW - ZO-1 KW - Expression KW - Pain Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225179 VL - 12 ER - TY - JOUR A1 - Kaiser, Mathias A1 - Burek, Malgorzata A1 - Britz, Stefan A1 - Lankamp, Frauke A1 - Ketelhut, Steffi A1 - Kemper, Björn A1 - Förster, Carola A1 - Gorzelanny, Christian A1 - Goycoolea, Francisco M. T1 - The influence of capsaicin on the integrity of microvascular endothelial cell monolayers JF - International Journal of Molecular Sciences N2 - Microvascular endothelial cells are an essential part of many biological barriers, such as the blood–brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB could lead to improved therapies due to enhanced drug bioavailability. Vanilloids, such as capsaicin, are known to reversibly open tight junctions of epithelial and endothelial cells. In this study, we used several in vitro assays with the murine endothelial capillary brain cells (line cEND) as a BBB model to characterize the interaction between capsaicin and endothelial tight junctions. KW - tight junctions KW - capsaicin KW - endothelial cells Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284865 SN - 1422-0067 VL - 20 IS - 1 ER - TY - JOUR A1 - Schuster, Frank A1 - Johannsen, Stephan A1 - Isbary, Susanne A1 - Türkmeneli, Ismail A1 - Roewer, Norbert T1 - In vitro effects of levosimendan on muscle of malignant hyperthermia susceptible and non-susceptible swine JF - BMC Anesthesiology N2 - Background: The calcium sensitizer levosimendan is increasingly used to improve hemodynamics in patients with acutely decompensated heart failure. By binding to cardiac troponin C the conformation of the calcium-troponin C complex is stabilized, which leads to acceleration of actin-myosin crossbrigde formation and increased force generating capacity of muscle fibers. Besides indications in cardiac failure, beneficial effects of levosimendan in skeletal muscle disorders are currently evaluated. The aim of this study was to investigate differential effects of levosimendan on skeletal muscle of pigs with and without susceptibility to malignant hyperthermia (MH) in order to identify possible risks of this emerging drug for patients with predisposition to MH. Methods: Muscle bundles of 17 pigs (9 MH susceptible (MHS); 8 MH non-susceptible (MHN)) were excised under general anesthesia and examined in the tissue bath with increasing concentrations of levosimendan (0.065; 0.125; 0.5; 1.0; 10 and 50 μg/ml). Baseline tension and twitch force were monitored continuously. Data are presented as median and interquartile range. Statistical evaluation was performed using D’Agostino & Pearson test for normal distribution and student’s t test and 2-way ANOVA for differences between the groups. P < 0.05 was considered significant. Results: There were no differences between the groups concerning length, weight, initial twitch force and pre-drug resting tension of the investigated muscle strips. After an initial decrease in both groups, twitch amplitude was significantly higher in MHN (− 3.0 [− 5.2–0.2] mN) compared to MHS (− 7.5 [− 10.8- -4.5] mN) (p = 0.0034) muscle at an applied levosimendan concentration of 50 μg/ml. A marked increase in resting tension was detected following levosimendan incubation with 50 μg/ml in MHS muscle bundles (3.3 [0.9–6.1] mN) compared to MHN (− 0.7 [− 1.3–0.0] mN) (p < 0.0001). Conclusions: This in vitro investigation revealed the development of significant contractures in muscle bundles of MHS pigs after incubation with levosimendan. However, the effect appeared only at supra-therapeutic concentrations and further research is needed to determine the impact of levosimendan on MHS individuals in vivo. KW - malignant hyperthermia KW - levosimendan KW - muscle KW - pigs KW - in vitro contracture test Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176991 VL - 18 IS - 182 ER - TY - JOUR A1 - Chen, Shasha A1 - Lotz, Christopher A1 - Roewer, Norbert A1 - Broscheit, Jens-Albert T1 - Comparison of volatile anesthetic-induced preconditioning in cardiac and cerebral system: molecular mechanisms and clinical aspects JF - European Journal of Medical Research N2 - Volatile anesthetic-induced preconditioning ( APC) has shown to have cardiac and cerebral protective properties in both pre-clinical models and clinical trials. Interestingly, accumulating evidences demonstrate that, except from some specific characters, the underlying molecular mechanisms of APC-induced protective effects in myocytes and neurons are very similar; they share several major intracellular signaling pathways, including mediating mitochondrial function, release of inflammatory cytokines and cell apoptosis. Among all the experimental results, cortical spreading depolarization is a relative newly discovered cellular mechanism of APC, which, however, just exists in central nervous system. Applying volatile anesthetic preconditioning to clinical practice seems to be a promising cardio- and neuroprotective strategy. In this review, we also summarized and discussed the results of recent clinical research of APC. Despite all the positive experimental evidences, large-scale, long-term, more precisely controlled clinical trials focusing on the perioperative use of volatile anesthetics for organ protection are still needed. KW - APC KW - ischemia-reperfusion injury KW - mitochondria KW - apoptosis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175509 VL - 23 IS - 10 ER - TY - JOUR A1 - Wurmb, T A1 - Schorscher, N A1 - Justice, P A1 - Dietz, S A1 - Schua, R A1 - Jarausch, T A1 - Kinstle, U A1 - Greiner, J A1 - Möldner, G A1 - Müller, J A1 - Kraus, M A1 - Simon, S A1 - Wagenhäuser, U A1 - Hemm, J A1 - Roewer, N A1 - Helm, M T1 - Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators JF - Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine N2 - Background: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. Methods: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. Results: Five important “lessons learned” have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres (“red phone”) is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. Conclusion: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events. KW - terror attack KW - mass casualties KW - evaluation KW - quality indicators KW - rescue mission Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177054 VL - 26 IS - 87 ER - TY - JOUR A1 - Khan, Muhammad Usman A1 - Pirzadeh, Maryam A1 - Förster, Carola Yvette A1 - Shityakov, Sergey A1 - Shariati, Mohammad Ali T1 - Role of milk-derived antibacterial peptides in modern food biotechnology: their synthesis, applications and future perspectives JF - Biomolecules N2 - Milk-derived antibacterial peptides (ABPs) are protein fragments with a positive influence on the functions and conditions of a living organism. Milk-derived ABPs have several useful properties important for human health, comprising a significant antibacterial effect against various pathogens, but contain toxic side-effects. These compounds are mainly produced from milk proteins via fermentation and protein hydrolysis. However, they can also be produced using recombinant DNA techniques or organic synthesis. This review describes the role of milk-derived ABPs in modern food biotechnology with an emphasis on their synthesis and applications. Additionally, we also discuss the mechanisms of action and the main bioproperties of ABPs. Finally, we explore future perspectives for improving ABP physicochemical properties and diminishing their toxic side-effects. KW - milk proteins KW - bioactive peptide KW - antibacterial activity KW - fermentation KW - protein hydrolysis KW - recombinant DNA KW - peptide synthesis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197610 SN - 2218-273X VL - 8 IS - 4 ER - TY - JOUR A1 - Johannsen, Stephan A1 - Schick, Martin A1 - Roewer, Norbert A1 - Schuster, Frank T1 - Microdialysis and ultrasound elastography for monitoring of localized muscular reaction after pharmacological stimulation in rats JF - BMC Research Notes N2 - 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. KW - skeletal muscle KW - ultrasound strain elastography KW - microdialysis KW - halothane KW - caffeine Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176977 VL - 11 IS - 636 ER - TY - JOUR A1 - Sarukhanyan, Edita A1 - Shityakov, Sergey A1 - Dandekar, Thomas T1 - In silico designed Axl receptor blocking drug candidates against Zika virus infection JF - ACS Omega N2 - After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2′ was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies. KW - free energy KW - molecular docking KW - molecular dynamics KW - simulation KW - pharmacology KW - proteins KW - structure-activity relationship KW - viruses KW - Zika virus Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176739 VL - 3 IS - 5 ER -