Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease

Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted, for example, in pulmonary hypertension. Its dysregulation in disease is incompletely understood. Here we show in pulmonary artery endothelial cells that feedback inhibition by NO of the NO receptor, the cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous NO from endothelial NO synthase and exogenous NO from NO donor compounds decreased sGC protein and activity. This effect was not mediated by cGMP as the NO-independent sGC stimulator, or direct activation of cGMP-dependent protein kinase did not mimic it. Thiol-sensitive mechanisms were also not involved as the thiol-reducing agent N-acetyl-L-cysteine did not prevent this feedback. Instead, both in-vitro and in-vivo and in health and acute respiratory lung disease, chronically elevated NO led to the inactivation and degradation of sGC while leaving the heme-free isoform, apo-sGC, intact or even increasing its levels. Thus, NO regulates sGC in a bimodal manner, acutely stimulating and chronically inhibiting, as part of self-limiting direct feedback that is cGMP independent. In high NO disease conditions, this is aggravated but can be functionally recovered in a mechanism-based manner by apo-sGC activators that re-establish cGMP formatio

Influence of airway management strategy on "no-flow-time" during an "Advanced life support course" for intensive care nurses – A single rescuer resuscitation manikin study

<p>Abstract</p> <p>Background</p> <p>In 1999, the laryngeal tube (VBM Medizintechnik, Sulz, Germany) was introduced as a new supraglottic airway. It was designed to allow either spontaneous breathing or controlled ventilation during anaesthesia; additionally it may serve as an alternative to endotracheal intubation, or bag-mask ventilation during resuscitation. Several variations of this supraglottic airway exist. In our study, we compared ventilation with the laryngeal tube suction for single use (LTS-D) and a bag-mask device. One of the main points of the revised ERC 2005 guidelines is a low no-flow-time (NFT). The NFT is defined as the time during which no chest compression occurs. Traditionally during the first few minutes of resuscitation NFT is very high. We evaluated the hypothesis that utilization of the LTS-D could reduce the NFT compared to bag-mask ventilation (BMV) during simulated cardiac arrest in a single rescuer manikin study.</p> <p>Methods</p> <p>Participants were studied during a one day advanced life support (ALS) course. Two scenarios of arrhythmias requiring defibrillation were simulated in a manikin. One scenario required subjects to establish the airway with a LTS-D; alternatively, the second scenario required them to use BMV. The scenario duration was 430 seconds for the LTS-D scenario, and 420 seconds for the BMV scenario, respectively. Experienced ICU nurses were recruited as study subjects. Participants were randomly assigned to one of the two groups first (LTS-D and BMV) to establish the airway. Endpoints were the total NFT during the scenario, the successful airway management using the respective device, and participants' preference of one of the two strategies for airway management.</p> <p>Results</p> <p>Utilization of the LTS-D reduced NFT significantly (p < 0.01). Adherence to the time frame of ERC guidelines was 96% in the LTS-D group versus 30% in the BMV group. Two participants in the LTS-D group required more than one attempt to establish the LTS-D correctly. Once established, ventilation was effective in 100%. In a subjective evaluation all participants preferred the LTS-D over BMV to provide ventilation in a cardiac arrest scenario.</p> <p>Conclusion</p> <p>In our manikin study, NFT was reduced significantly when using LTS-D compared to BMV. During cardiac arrest, the LTS-D might be a good alternative to BMV for providing and maintaining a patent airway. For personnel not experienced in endotracheal intubation it seems to be a safe airway device in a manikin use.</p

Multi-Chip Integration by Photonic Wire Bonding: Connecting Surface and Edge Emitting Lasers to Silicon Chips

We demonstrate coupling of surface and edge emitting InP lasers to silicon photonic chips using photonic wire bonding. We confirm that back-reflections from the silicon chip do not deteriorate the linewidth of the lasers

A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles

Transient effects in friction: fractal asperity creep

Transient friction effects determine the behavior of a wide class of mechatronic systems. Classic examples are squealing brakes, stiction in robotic arms, or stick-slip in linear drives. To properly design and understand mechatronic systems of this type, good quantitative models of transient friction effects are of primary interest. The theory developed in this book approaches this problem bottom-up, by deriving the behavior of macroscopic friction surfaces from the microscopic surface physics. The model is based on two assumptions: First, rough surfaces are inherently fractal, exhibiting roughness on a wide range of scales. Second, transient friction effects are caused by creep enlargement of the real area of contact between two bodies. This work demonstrates the results of extensive Finite Element analyses of the creep behavior of surface asperities, and proposes a generalized multi-scale area iteration for calculating the time-dependent real contact between two bodies. The toolset is then demonstrated both for the reproduction of a variety of experimental results on transient friction as well as for system simulations of two example systems