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Katharina Wulf, Michael Teske, Claudia Matschegewski, Daniela Arbeiter, Dalibor Bajer, Thomas Eickner, Klaus-Peter Schmitz, Niels Grabow
The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated...
March 12, 2018: Drug Delivery and Translational Research
Marie Hervé, Bertrand Dupé, Rafael Lopes, Marie Böttcher, Maximiliano D Martins, Timofey Balashov, Lukas Gerhard, Jairo Sinova, Wulf Wulfhekel
Skyrmions are topologically protected non-collinear magnetic structures. Their stability is ideally suited to carry information in, e.g., racetrack memories. The success of such a memory critically depends on the ability to stabilize and manipulate skyrmions at low magnetic fields. The non-collinear Dzyaloshinskii-Moriya interaction originating from spin-orbit coupling drives skyrmion formation. It competes with Heisenberg exchange and magnetic anisotropy favoring collinear states. Isolated skyrmions in ultra-thin films so far required magnetic fields as high as several Tesla...
March 9, 2018: Nature Communications
Peter Hart, Alastair Copland, Gil Reynolds Diogo, Shane Harris, Ralf Spallek, Wulf Oehlmann, Mahavir Singh, Juan Basile, Martin Rottenberg, Matthew John Paul, Rajko Reljic
Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Calmette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Anne von Mässenhausen, Wulf Tonnus, Nina Himmerkus, Simon Parmentier, Danish Saleh, Diego Rodriquez, Jiraporn Ousingsawat, Rosalind L Ang, Joel M Weinberg, Ana B Sanz, Alberto Ortiz, Adrian Zierleyn, Jan Ulrich Becker, Blandine Baratte, Nathalie Desban, Stéphane Bach, Ina Maria Schiessl, Shoko Nogusa, Siddharth Balachandran, Hans Joachim Anders, Adrian T Ting, Markus Bleich, Alexei Degterev, Karl Kunzelmann, Stefan R Bornstein, Douglas R Green, Christian Hugo, Andreas Linkermann
Receptor-interacting protein kinases 1 and 3 (RIPK1/3) have best been described for their role in mediating a regulated form of necrosis, referred to as necroptosis. During this process, RIPK3 phosphorylates mixed lineage kinase domain-like (MLKL) to cause plasma membrane rupture. RIPK3-deficient mice have recently been demonstrated to be protected in a series of disease models, but direct evidence for activation of necroptosis in vivo is still limited. Here, we sought to further examine the activation of necroptosis in kidney ischemia-reperfusion injury (IRI) and from TNFα-induced severe inflammatory response syndrome (SIRS), two models of RIPK3-dependent injury...
March 2, 2018: Cell Death & Disease
Evgenii Shumilov, Ulrike Bacher, Christina Perske, Alexander Mohr, Helmut Eiffert, Justin Hasenkamp, Lorenz Trümper, Gerald G Wulf, Philipp Ströbel, Ashraf S Ibrahim, Vivek Venkataramani
Mucormycosis is probably the most devastating and hard to diagnose invasive mold infection caused by fungi belonging to the order Mucorales.….
February 26, 2018: Antimicrobial Agents and Chemotherapy
Jörn Karhausen, Joshua D Bernstock, Kory R Johnson, Huaxin Sheng, Qing Ma, Yuntian Shen, Wei Yang, John M Hallenbeck, Wulf Paschen
The intestinal epithelium constitutes a crucial defense to the potentially life-threatening effects of gut microbiota. However, due to a complex underlying vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk to function and integrity of the epithelium. The small ubiquitin-like modifier (SUMO) conjugation pathway critically regulates adaptive responses to metabolic stress and is of particular significance in the gut, as inducible knockout of the SUMO-conjugating enzyme Ubc9 results in rapid intestinal epithelial disintegration...
February 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Maysa Sarhan, Walter G Land, Wulf Tonnus, Christian P Hugo, Andreas Linkermann
When cells undergo necrotic cell death in either physiological or pathophysiological settings in vivo, they release highly immunogenic intracellular molecules and organelles into the interstitium and thereby represent the strongest known trigger of the immune system. With our increasing understanding of necrosis as a regulated and genetically determined process (RN, regulated necrosis), necrosis and necroinflammation can be pharmacologically prevented. This review discusses our current knowledge about signaling pathways of necrotic cell death as the origin of necroinflammation...
April 1, 2018: Physiological Reviews
M D Kleinhenz, P J Gorden, J S Smith, J A Schleining, K E Kleinhenz, L L Wulf, P K Sidhu, D Rea, J F Coetzee
A transdermal formulation of the nonsteroidal anti-inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single-dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software...
February 20, 2018: Journal of Veterinary Pharmacology and Therapeutics
Alejandro Schuler, David A Wulf, Yun Lu, Theodore J Iwashyna, Gabriel J Escobar, Nigam H Shah, Vincent X Liu
OBJECTIVES: To estimate the impact of each of six types of acute organ dysfunction (hepatic, renal, coagulation, neurologic, cardiac, and respiratory) on long-term mortality after surviving sepsis hospitalization. DESIGN: Multicenter, retrospective study. SETTINGS: Twenty-one hospitals within an integrated healthcare delivery system in Northern California. PATIENTS: Thirty thousand one hundred sixty-three sepsis patients admitted through the emergency department between 2010 and 2013, with mortality follow-up through April 2015...
February 9, 2018: Critical Care Medicine
P J Gorden, M Burchard, J A Ydstie, M D Kleinhenz, L W Wulf, S J Rajewski, C Wang, R Gehring, J P Mochel, J F Coetzee
The objective of this study reported here was determine whether differences occurred in meloxicam pharmacokinetics between postpartum cows and mid-lactation cows. Preliminary data from a separate study (P. J. Gorden, unpublished data) in postpartum cows demonstrated elevated plasma and milk concentration profiles compared to previously published data (Malreddy, Coetzee, KuKanich, & Gehring, ). Two different groups were enrolled, each with 10 cows. The treatment group (TRT) was postpartum cows treated with meloxicam, and the positive control (PC) group was cows in mid-lactation treated with meloxicam...
February 11, 2018: Journal of Veterinary Pharmacology and Therapeutics
Matthias Wulf, Stephan Alexander Pless
Fluorescent labels offer the capability to follow conformational dynamics of membrane proteins, but signal detection in such recordings is inherently difficult to achieve in a cell membrane and lacks sufficient time resolution to follow physiologically relevant transitions. Here, we develop high-sensitivity patch-clamp fluorometry (hsPCF), a fluorescence-based approach that results in up to 10-fold increased signals and affords 50-fold faster fluorescence recordings than previous methods. The increased time resolution is paired with a very high versatility in terms of the choice of fluorescent dye, cell type, and protein of interest...
February 6, 2018: Cell Reports
Hagen Bomberg, Ina Bayer, Stefan Wagenpfeil, Paul Kessler, Hinnerk Wulf, Thomas Standl, André Gottschalk, Jens Döffert, Werner Hering, Jürgen Birnbaum, Claudia Spies, Bernd Kutter, Jörg Winckelmann, Simone Liebl-Biereige, Winfried Meissner, Oliver Vicent, Thea Koch, Daniel I Sessler, Thomas Volk, Alexander Raddatz
BACKGROUND: Prolonged catheter use is controversial because of the risk of catheter-related infection, but the extent to which the risk increases over time remains unknown. We thus assessed the time-dependence of catheter-related infection risk up to 15 days. METHODS: Our analysis was based on the German Network for Regional Anesthesia, which includes 25 centers. We considered 44,555 patients who had surgery between 2007 and 2014 and had continuous regional anesthesia as well as complete covariable details...
February 8, 2018: Anesthesiology
Thomas Wiesmann, Stefan Müller, Hans-Helge Müller, Hinnerk Wulf, Thorsten Steinfeldt
Background: Nerve blood flow has a critical role in acute and chronic pathologies in peripheral nerves. Influences of local anesthetics and adjuvants on tissue perfusion and oxygenation are deemed as relevant factors for nerve damage after peripheral regional anesthesia. The link between low tissue perfusion due to local anesthetics and resulting tissue oxygenation is unclear. Methods: Combined tissue spectrophotometry and laser-Doppler flowmetry were used to assess nerve blood flow in 40 surgically exposed median nerves in pigs, as well as nerve tissue oximetry for 60 min...
2018: Journal of Pain Research
Essraa M Al-Essawe, Anders Johannisson, Manuela Wulf, Christine Aurich, Jane M Morrell
Addition of seminal plasma (SP) prior to cryopreservation may influence stallion sperm cryosurvival. The objective of this study was to investigate the addition of pooled SP from "good" or "bad" freezer stallions to spermatozoa selected by single layer centrifugation (SLC) prior to cryopreservation on post-thaw sperm quality. Semen from 12 stallions was collected; 5 mL was frozen as control (C) and the remainder was processed by SLC to remove SP and was divided into three aliquots: i) SLC sample without SP (SLC); ii) SLC plus pooled SP from "good freezer" stallions (SLC-GF); iii) SLC plus pooled SP from "bad freezer" stallions (SLC-BF)...
February 1, 2018: Cryobiology
Huaqin Liu, Zhui Yu, Ying Li, Bin Xu, Baihui Yan, Wulf Paschen, David S Warner, Wei Yang, Huaxin Sheng
Experimental cardiac arrest (CA) in aging research is infrequently studied in part due to the limitation of animal models. We aimed to develop an easily performed mouse CA model to meet this need. A standard mouse KCl-induced CA model using chest compressions and intravenous epinephrine for resuscitation was modified by blood withdrawal prior to CA onset, so as to decrease the requisite KCl dose to induce CA by decreasing the circulating blood volume. The modification was then compared to the standard model in young adult mice subjected to 8 min CA...
February 2018: Aging and Disease
Mariangela Sociale, Anna-Lena Wulf, Bernadette Breiden, Kathrin Klee, Melanie Thielisch, Franka Eckardt, Julia Sellin, Margret H Bülow, Sinah Löbbert, Nadine Weinstock, André Voelzmann, Joachim Schultze, Konrad Sandhoff, Reinhard Bauer
Maintenance of metabolic homeostasis requires adaption of gene regulation to the cellular energy state via transcriptional regulators. Here, we identify a role of ceramide synthase (CerS) Schlank, a multiple transmembrane protein containing a catalytic lag1p motif and a homeodomain, which is poorly studied in CerSs, as a transcriptional regulator. ChIP experiments show that it binds promoter regions of lipases lipase3 and magro via its homeodomain. Mutation of nuclear localization site 2 (NLS2) within the homeodomain leads to loss of DNA binding and deregulated gene expression, and NLS2 mutants can no longer adjust the transcriptional response to changing lipid levels...
January 23, 2018: Cell Reports
David Krug, René Baumann, Wilfried Budach, Jürgen Dunst, Petra Feyer, Rainer Fietkau, Wulf Haase, Wolfgang Harms, Thomas Hehr, Marc D Piroth, Felix Sedlmayer, Rainer Souchon, Frederik Wenz, Rolf Sauer
PURPOSE: To review the evidence regarding post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NACT) for breast cancer, with a special focus on individualization of adjuvant radiotherapy based on treatment response. METHODS: A systematic literature search using the PubMed/Medline database was performed. We included prospective and retrospective reports with a minimum of 10 patients that had been published since 1st  January 2000, and provided clinical outcome data analyzed by treatment response and radiotherapy...
January 30, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
Ziyan Xu, Mario Müller, Barbara Lay, Nathalie Oexle, Thekla Drack, Marco Bleiker, Silke Lengler, Christina Blank, Stefan Vetter, Wulf Rössler, Nicolas Rüsch
People with severe mental illness and a history of involuntary hospitalization may experience stigma-related stress and suffer negative consequences as a result. However, the long-term impact of stigma stress on suicidality in this population remains unknown. This longitudinal study therefore examined stigma stress, self-stigma, self-esteem and suicidal ideation among 186 individuals with mental illness and recent involuntary hospitalization. After adjusting for age, gender, diagnoses and symptoms, more stigma stress at baseline predicted suicidal ideation after 2 years, mediated by increased self-stigma and decreased self-esteem after 1 year...
January 27, 2018: Social Psychiatry and Psychiatric Epidemiology
Maria Avramidou, Felix Angst, Jules Angst, André Aeschlimann, Wulf Rössler, Ulrich Schnyder
BACKGROUND: Although subacute and chronic gastrointestinal symptoms are very common in primary care, epidemiological date are sparse. The aim of the study was to examine and quantify the prevalence of subacute and chronic gastrointestinal symptoms and their associations with somatic and mental disorders in the general population. METHODS: Data were collected prospectively between 1981 (age m = 22, f = 23) and 2008 (age 49/50) from the Zurich Cohort Study (n = 292 men, 299 women), a representative general population survey...
January 27, 2018: BMC Gastroenterology
Wulf Dieker, Michael Behnes, Christian Fastner, Benjamin Sartorius, Annika Wenke, Ishar Sing-Gill, Ibrahim El-Battrawy, Jürgen Kuschyk, Theano Papavassiliu, Ursula Hoffmann, Kambis Mashayekhi, Stefan O Schoenberg, Martin Borggrefe, Thomas Henzler, Ibrahim Akin
A standardized imaging algorithm by cardiac computed tomography angiography (cCTA) (LOVE-view) was used in 30 patients to evaluate the influence of different left atrial appendage (LAA) morphologies on development of thrombosis in the LAA 6 months after implantation of an occlusion device (Watchman or Amplatzer-Cardiac-Plug) in patients with non-valvular atrial fibrillation, CHA2DS2-VASc-Score >1 and a contraindication for oral anticoagulation. The distribution of different LAA morphologies was 40% windsock, 17% broccoli and 43% chicken wing type...
January 26, 2018: Scientific Reports
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