The Importance of Hydration in Wound Healing: Reinvigorating the clinical perspective

Balancing skin hydration levels is important as any disruption in skin integrity will result in disturbance of the dermal water balance. The discovery that a moist wound healing environment actively supports the healing response when compared to a dry environment highlights the importance of water and good hydration levels for optimal wound healing. The benefits of “wet” or “hyper-hydrated” wound healing appears to offer benefits that are similar to those offered by moist wound healing over wounds healing in a dry environment. This suggests that the presence of free water itself during wound healing may not be detrimental to healing but that any adverse effects of wound fluid on tissues is more likely related to the biological components contained within chronic wound exudate (e.g. elevated protease levels). Appropriate dressings applied to wounds must be able to absorb not only the exudate but also retain this excess fluid together with its protease solutes while concurrently preventing desiccation. This is particularly important in the case of chronic wounds where peri-wound skin barrier properties are compromised and there is increased permeation across the injured skin barrier. This review discusses the importance of appropriate levels of hydration in skin with a particular focus on the need for optimal hydration levels for effective healing

Water permeation through stratum corneum lipid bilayers from atomistic simulations

Stratum corneum, the outermost layer of skin, consists of keratin filled rigid non-viable corneocyte cells surrounded by multilayers of lipids. The lipid layer is responsible for the barrier properties of the skin. We calculate the excess chemical potential and diffusivity of water as a function of depth in lipid bilayers with compositions representative of the stratum corneum using atomistic molecular dynamics simulations. The maximum in the excess free energy of water inside the lipid bilayers is found to be twice that of water in phospholipid bilayers at the same temperature. Permeability, which decreases exponentially with the free energy barrier, is reduced by several orders of magnitude as compared to with phospholipid bilayers. The average time it takes for a water molecule to cross the bilayer is calculated by solving the Smoluchowski equation in presence of the free energy barrier. For a bilayer composed of a 2:2:1 molar ratio of ceramide NS 24:0, cholesterol and free fatty acid 24:0 at 300K, we estimate the permeability P=3.7e-9 cm/s and the average crossing time \tau_{av}=0.69 ms. The permeability is about 30 times smaller than existing experimental results on mammalian skin sections.Comment: latex, 8 pages, 6 figure

Percutaneous drug penetration: Choosing candidates for transdermal development

There is currently a high level of interest in using the skin as a route for delivering drugs. One hears the questions: What are the attributes of a drug that make it a serious candidate for transdermal delivery? By what a priori analysis might one zero in on the best transdermal candidate within a family of drugs? Answers to these questions lie in understanding the molecular factors that make a drug a facile permeant of the skin. Among other properties, it must have a high absolute affinity for the skin's phases, which provide for its diffusive conduction. Other factors in evaluation are the potency of the drug and the relative efficiency of the drug's systemic presentation once it has gained access to the body. One also considers the potential for the drug to elicit adverse responses in the skin. Fortunately, parallels between the drug's ability to partition between oil and water and its ease of mass transfer across the skin can be used to ferret out a working mass transfer coefficient. If not already known, solubilities are easily experimentally deduced. The extent of first-pass metabolism by the oral route, presumed to be a known quantity, is compared with the relative amount of metabolism of the drug in the course of its diffsion through the skin, an experimentally determined quantity, in order to set the transdermal dose. These bits of information can then be used to form an early, reasonably faithful picture of the feasibility of delivering a particular drug transdermally and to make a first estimate of the size of patch required for the drug.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50213/1/430130209_ftp.pd

El impacto de las empresas de capital de riesgo en el empleo y la co-determinación: el caso de Alemania

Studies of the effects of private equity in the United States have shown that the short-term, return-oriented business model can put a strain on industrial relations between employers and employees. This is similarly assumed to be the case for the coordinated market economy in Germany. Firstly, the article shows for the years 2013 to 2018 the volume of employees affected by private equity takeovers in Germany and the industries in which these employees work. Secondly, it examines whether equal co-determination, which German law requires of companies with more than 2,000 employees, is avoided or ignored by private equity companies to a greater extent than by other types of employers. Thirdly, the change in the activity of works councils whose companies have been taken over by a private equity firm is considered. Overall, it is becoming apparent that private equity companies are more restrictive at the company level than other types of employer and that it is becoming more difficult for works councils to adequately represent employees’ interests.Los estudios sobre los efectos de las empresas de capital riesgo o sociedades de inversión en los Estados Unidos han demostrado que el modelo de negocio a corto plazo y orientado al retorno de la inversión puede ejercer presión sobre las relaciones laborales entre empleadores y empleados. De igual manera, se supone que este es el caso de la economía de mercado coordinada en Alemania. En primer lugar, el artículo muestra para los años 2013 a 2018 el volumen de empleados afectados por adquisiciones de empresas de capital riesgo o sociedades de inversión en Alemania y las industrias en las que trabajan estos empleados. En segundo lugar, se examina hasta qué punto la co-determinación igualitaria, que la ley alemana exige a las empresas con más de 2000 empleados, es ignorada o evitada en mayor o menor medida por parte de dichas empresas en comparación con otras. En tercer lugar, se analiza el cambio en la actividad de los comités de empresa de aquellos casos que han sido asumidos por una sociedad de inversión. En general, se evidencia que las sociedades de inversión son más restrictivas a nivel de empresa en comparación con otros modelos y que se está volviendo más difícil para los comités de empresa representar adecuadamente los intereses de los empleados

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

Wound healing and hyper-hydration - a counter intuitive model

Winters seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model ‘hyper-hydration’ of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration

Private Equity in Germany: An assessment of transactions, structures and players

Since the last global financial crisis, private equity activities have increased again in Germany. This article provides an overview of developments between 2012 and 2018 from an employee perspective. It shows the volume and sectoral focus of company takeovers, the new owners after the exit of financial investors, and the proportion of companies in which parity co-determination is practiced. It also examines the most active private equity firms, their funds, their returns and their use of tax havens

The Global Wealth Chains of Private-Equity-run Physician Practices

Currently, numerous physician practices in industrial and emerging countries are being taken over by private equity firms and integrated into novel physician corporations. This involves private equity firms producing a global wealth chain (GWC) between their investors and the target asset, using offshore financial centres to facilitate tax-avoiding reflux of capital. Moreover, they are opening up ambulatory health care as an asset for capital investment by overcoming previous market barriers to ambulatory health care via a legal construct. In this paper, we trace the spatial links of these finance-side and sector-specific corporate chains based on a capital flow analysis of private equity takeovers of Medical Care Centres (MCCs) in Bavaria, Germany. With our heuristics of a double-layered GWC, which enables the extraction of value from the German health system, we contribute to the emerging GWC debate that aims to conceptualise the complex and often opaque spatialisations of financialisation processes

Do Company Builders Create Jobs? Examining the Rise of Incubation Finance in Germany

Over the past decade, new types of business incubation have been developed. One particularly prominent example is company builders, which use their own resources to build up companies, establishing numerous companies in a series. In doing so, this investor type facilitates internal and external business ideas. It offers a new organizational solution that combines both the innovative capacity of founders and the financial resources of a large company with the desire for long-term employment and corporate affiliation. This article examines the economic impact of company builders in Germany compared with other venture capital (VC) investor types on the basis of employment trends in the portfolio companies from 2011 to 2015. It is shown that company builders promote more dynamic employment growth than do other types of investors. This finding suggests that this type of investor is particularly well positioned to take advantage of the institutional deficiency in the German VC market. The results are also discussed in the context of the growth of the Berlin-based VC and start-up ecosystem