Chronic wounds are an increasing problem in our ageing population and can arise in many different ways. Over the past decades it has become evident that sufficient oxygen supply is an essential ...factor of appropriate wound healing. Sustained oxygen deficit has a detrimental impact on wound healing, especially for patients with chronic wounds. This has been proven for wounds associated with peripheral arterial occlusive disease (PAOD) and diabetic foot ulcers (particularly in combination with PAOD). However, this is still under debate for other primary diseases. In the past few years several different new therapeutic approaches for topical oxygen therapies have been developed to support wound healing. These tend to fall into one of four categories: (1) delivery of pure oxygen either under pressurised or (2) ambient condition, (3) chemical release of oxygen via an enzymatic reaction or (4) increase of oxygen by facilitated diffusion using oxygen binding and releasing molecules. In this review article, the available therapeutic topical oxygen-delivering approaches and their impact on wound healing are presented and critically discussed. A summary of clinical data, daily treatment recommendations and practicability is provided.
J. Dissemond received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: 3M, B. Braun, BSN, Coloplast, Convatec, Draco, Hartmann, KCI, Lohmann&Rauscher, Medoderm, Merz, Sastomed, Systagenix, UCB-Pharma, Urgo. K. Kröger received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: Bayer, Sanofi, GSK, Hartmann, Sastomed, UCB-Pharma, Urgo. M. Storck received an honorarium for lectures for the following companies: KCI, Systagenix, and UCB-Pharma. A. Risse received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: Bracco, Coloplast, Draco, Lilly Deutschland, NovoNordisk, Sastomed, Urgo. P. Engels received an honorarium for lectures, and consulting from the following companies: Sastomed, Oculus.
A composition analysis of KASCADE air shower data is performed by means of unfolding the two-dimensional frequency spectrum of electron and muon numbers. Aim of the analysis is the determination of ...energy spectra for elemental groups representing the chemical composition of primary cosmic rays. Since such an analysis depends crucially on simulations of air showers the two different hadronic interaction models QGSJet and SIBYLL are used for their generation. The resulting primary energy spectra show that the knee in the all particle spectrum is due to a steepening of the spectra of light elements but, also, that neither of the two simulation sets is able to describe the measured data consistently over the whole energy range with discrepancies appearing in different energy regions.
Nutrient-deprivation autophagy factor-1 (NAF-1) was identified as an endoplasmic reticulum (ER) BCL-2-interacting protein, which functions to mediate the ability of ER BCL-2 to antagonize Beclin ...1-dependent autophagy and depress ER calcium stores. In humans, a point mutation in Naf-1 (synonyms: Cisd2, Eris, Miner1 and Noxp70) is responsible for the neurodegenerative disorder Wolfram Syndrome 2. Here, we describe the generation and characterization of the Naf-1 gene deletion in mice. Naf-1 null mice display discernable clinical signs of degeneration at 2-3 months of age, with early evidence of significant defects in the structure and performance of skeletal muscle. Skeletal muscles from Naf-1 knockout mice demonstrate a significant shift towards slow-twitch (type I) fibers and greater resistance to muscle fatigue. Force-generating capacity is dramatically reduced in Naf-1(-/-) muscle. Consistent with its role in ER BCL-2-mediated regulation of autophagy and calcium flux, these physiological deficiencies were accompanied by augmented autophagy and dysregulated calcium homeostasis. In contrast, this also included adaptive enlargement of mitochondria with extensive cristae structures. Thus, NAF-1, a BCL-2-associated autophagy regulator, is required for homeostatic maintenance of skeletal muscle. Our findings uncover a novel pathway that is required for normal muscle maintenance, which may ultimately provide a novel therapeutic target for treating certain muscle pathologies.
Patients with cystic fibrosis (CF) often suffer from gastrointestinal cramps and intestinal obstruction. The CF transmembrane conductance regulator (CFTR) channel has been shown to be expressed in ...vascular and airway smooth muscle (SM). We hypothesized that the absence of CFTR expression alters the gastrointestinal SM function and that these alterations may show strain-related differences in the mouse. The aim of this study was to measure the contractile properties of the ileal SM in two CF mouse models. CFTR(-/-) and CFTR(+/+) mice were studied on BALB/cJ and C57BL/6J backgrounds. Responsiveness of ileal strips to electrical field stimulation (EFS), methacholine (MCh), and isoproterenol was measured. The mass and the cell density of SM layers were measured morphometrically. Finally, the maximal velocity of shortening (Vmax) and the expression of the fast (+)insert myosin isoform were measured in the C57BL/6J ileum. Ileal hyperreactivity was observed in response to EFS and MCh in CFTR(-/-) compared with CFTR(+/+) mice in C57BL/6J background. This latter observation was not reproduced by acute inhibition of CFTR with CFTR(inh)172. BALB/cJ CFTR(-/-) mice exhibited a significant increase of SM mass with a lower density of cells compared with CFTR(+/+), whereas no difference was observed in the C57BL/6J background. In addition, in this latter strain, ileal strips from CFTR(-/-) exhibited a significant increase in Vmax compared with control and expressed a greater proportion of the fast (+)insert SM myosin isoform with respect to total myosin. BALB/cJ CFTR(-/-) ilium had a greater relaxation to isoproterenol than the CFTR(+/+) mice when precontracted with EFS, but no difference was observed in response to exogeneous MCh. In vivo, the lack of CFTR expression induces a different SM ileal phenotype in different mouse strains, supporting the importance of modifier genes in determining intestinal SM properties.
Currently, there are no generally accepted definitions for wounds at risk of infection. In clinical practice, too many chronic wounds are regarded as being at risk of infection, and therefore many ...topical antimicrobials – in terms of frequency and duration of use – are applied to wounds. Based on expert discussion and current knowledge, a clinical assessment score was developed. The objective of this wounds at risk (W.A.R.) score is to allow decision-making on the indication for the use of antiseptics on the basis of polihexanide. The proposed clinical classification of W.A.R. shall facilitate the decision for wound antisepsis and allow an appropriate general treatment regimen with the focus on the prevention of wound infection. The W.A.R. score is based on a clinically oriented risk assessment using concrete patient circumstances. The indication for the use of antiseptics results from the addition of differently weighted risk causes, for which points are assigned. Antimicrobial treatment is justified in the case of 3 or more points.
Therapy and diagnosis of the diabetic foot syndrome are almost standardized, all procedures are well established. There are no challenges in technical dimensions. But the rate of major amputations ...remains unacceptably high in Germany. Because there are other causes than lack of medical knowledge, this review describes the somatologic, psychiatric, and philosophic perspectives of the problem.
We present the results of an analysis of the large-scale anisotropy of cosmic rays in the PeV range. The Rayleigh formalism is applied to the right ascension distribution of extensive air showers ...measured by the KASCADE (Karlsruhe Shower Core and Array Detector) experiment. The data set contains about 10 super(8) extensive air showers in the energy range 0.7-6 PeV. No hints of anisotropy are visible in the right ascension distributions in this energy range. This accounts for all showers, as well as for subsets containing showers induced by predominantly light or heavy primary particles, respectively. Upper flux limits for Rayleigh amplitudes are determined to be between 10 super(-3) at a primary energy of 0.7 PeV and 10 super(-2) at 6 PeV.
Context.The detection of radio pulses from cosmic ray air showers is a potentially powerful new detection mechanism for studying spectrum and composition of ultra high energy cosmic rays that needs ...to be understood in greater detail. The radiation consists in large part of geosynchrotron radiation. The intensity of this radiation depends, among other factors, on the energy of the primary particle and the angle of the shower axis with respect to the geomagnetic field. Aims.Since the radiation mechanism is based on particle acceleration, the atmospheric electric field can play an important role. Especially inside thunderclouds large electric fields can be present. In this paper we examine the contribution of an electric field to the emission mechanism theoretically and experimentally. Methods.Two mechanisms of amplification of radio emission are considered: the acceleration radiation of the shower particles and the radiation from the current that is produced by ionization electrons moving in the electric field. For both mechanisms analytical estimates are made of their effects on the radio pulse height. We selected lopes data recorded during thunderstorms, periods of heavy cloudiness and periods of cloudless weather. We tested whether the correlations with geomagnetic angle and primary energy vary with atmospheric conditions. Results.We find that during thunderstorms the radio emission can be strongly enhanced. The present data suggests that the observed amplification is caused by acceleration of the shower electrons and positrons. In the near future, extensions of lopes and the construction of lofar will help to identify the mechanism in more detail. No amplified pulses were found during periods of cloudless sky or heavy cloudiness, suggesting that the electric field effect for radio air shower measurements can be safely ignored during non-thunderstorm conditions.