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Topical retinoids are frequently applied for therapeutic and cosmeceutical reasons although their bioavailability is low due to their chemical and photochemical instability. Moreover, skin irritation is a common side effect. Therefore, proretinal nanoparticles (PRN) as a novel formulation of topical retinoids, which are based on chitosan grafted with retinal through reversible linkage, were developed and their skin penetration behavior was studied. As nanoparticles preferably penetrate into the hair follicles, the follicular penetration depths of PRN at different time points were investigated. Moreover, the release capacity of the nanoparticulate system was studied using fluorescein as a model drug. Additionally, the concentration of retinal in the stratum corneum and in the hair follicles was quantified after application in particulate and non-particulate form. The results showed that the nanocarriers reached the infundibular area of the hair follicles, irrespective of the incubation time. The nanoparticles were able to release their model drug within the hair follicle. The retinal concentration delivered to the stratum corneum and the hair follicles was significantly higher when retinal was applied in the particulate form. In conclusion, the presented proretinal nanoparticle system may help to overcome the main problems of topical retinoid therapy, which are skin irritation, chemical and photochemical instability and low bioavailability, thus improving the topical retinoid therapy.

Background Skin diseases can develop upon disadvantageous microclimate in relation to skin contact with textiles of supporting devices. Increased temperature, moisture, mechanical fracture, pressure, and inflammatory processes often occur mutually and enhance each other in their adverse effects. Therefore, the early prevention of skin irritations by improvement of microclimatic properties of skin in contact with supporting devices is important. Materials and methods In this study, the microclimate under occlusion with polyester, cotton, chloroprene rubber, and silicone textiles, used for supporting devices, was analyzed by determining several characteristic physiologic skin parameters in vivo, including temperature, moisture, and transepidermal water loss (TEWL). This is achieved by comparing a miniaturized in vivo detection device with several established optical and sensory methods in vivo. Results A highly significant TEWL decrease was found after polyester, chloroprene rubber, and silicone application. The application of all materials showed highly significant decrease in skin surface temperature, with chloroprene rubber showing the lowest. Similarly, all materials showed highly significant increase in relative moisture, where the highest increase was found for chloroprene rubber and silicone and the lowest increase for cotton. The cutaneous carotenoid concentration of chloroprene rubber, silicone, and polyester decreased. A manipulation of the surface structure of the stratum corneum was recognized for all materials except for cotton by laser scanning microscopy. Conclusion The skin parameters temperature, relative moisture, antioxidant status, and TEWL can effectively characterize the microclimatic environment during occlusion with medical supporting materials. These parameters could potentially be used to develop standardized testing procedures for material evaluation.

Der Haarfollikel stellt einen bedeutenden Penetrationsweg fur topisch applizierte Substanzen dar. Die perkutane Absorption von bestimmten Substanzen kann durch die Beteiligung der Haarfollikel deutlich gesteigert und beschleunigt werden. Ferner haben Nanopartikel die Eigenschaft, besonders tief und effektiv in die Haarfollikel hinein zu penetrieren. Dies bietet die Moglichkeit, den Wirkstofftransport fur topisch applizierte Substanzen zu optimieren, indem die Nanocarrier allein als Transporter fur die Wirkstoffe in den Haarfollikel fungieren. Innerhalb des Haarfollikels muss nach erfolgter Penetration eine Freisetzung des Wirkstoffs vom Nanocarrier erfolgen. Dies kann durch verschiedene Mechanismen getriggert werden. Die freigesetzten Nanocarrier konnen somit unabhangig vom Nanopartikel in das den Haarfollikel umgebende lebende Gewebe ubergehen. Mithilfe dieser innovativen Strategie kann die Bioverfugbarkeit von topisch applizierten Substanzen deutlich verbessert werden. Ein Transport von Wirkstoffen in die Haarfollikel mithilfe von Partikeln und die dortige Wirkstofffreisetzung stellen eine sehr effektive neue Methode dar, Wirkstoffe durch die Hautbarriere zu transportieren.

In this retrospective multicentric cohort study, we evaluate the potential benefits of a clinical decision support system (CDSS) for the automated detection of Acute kidney injury (AKI). A total of 80,389 cases, hospitalized from 2017 to 2019 at a tertiary care hospital (University of Leipzig Medical Center (ULMC)) and two primary care hospitals (Muldentalkliniken (MTL)) in Germany, were enrolled. AKI was defined and staged according to the Kidney disease: improving global outcomes (KDIGO) guidelines. Clinical and laboratory data was automatically collected from electronic patient records using the frameworks of the CDSS. In our cohort, we found an overall AKI incidence proportion of 12.1%. We identified 6,393/1,703/1,604 cases as AKI stage 1/2/3 (8.0%/2.1%/2.0%, respectively). Administrative coding with N17 (ICD-10-GM) was missing in 55.8% of all AKI cases with the potential for additional diagnosis related groups (DRG) reimbursement of 1,204,200 € in our study. AKI was associated with higher hospital mortality, increased length of hospitalisation and more frequent need of renal replacement therapy. A total of 19.1% of AKI cases (n = 1,848) showed progression to higher AKI stages (progressive AKI) during hospitalization. These cases presented with considerably longer hospitalization, higher rates of renal replacement therapy and increased mortality (p

Summary The modular seismic acquisition system at the GFZ is basically suitable for underground exploration in crystalline, salt and clay rocks. Special features of the application result from the different properties of the media such as degree of heterogeneity, damping, anisotropy and their interaction with the excavation zone (EDZ) induced by the cavity (drifts, tunnels). This manifests itself in different frequency damping behaviour for compressional, shear and surface waves, which require a specific use of impulse and vibration sources at the joint depending on the task. Seismic borehole measurements can contribute to a significant improvement of the resolution.

Background: The chronicity of psoriasis often requires continuous topical treatment. Materials and Methods: Here, the radical protection of a cream containing various herbal oils was evaluated in vivo by electron paramagnetic resonance (EPR) spectroscopy and its skin penetration by Raman microscopy in intact and barrier-disturbed skin. Changes in skin barrier properties were evaluated after 4 weeks of daily topical application using in vivo laser scanning microscopy (LSM) and transepidermal water loss in 26 healthy volunteers. A randomized, controlled, double-blind, three-arm parallel clinical study evaluated the efficacy of the herbal oil cream compared to a 0.05% calcipotriol-containing cream and to a vehicle cream, in 135 patients with mild to moderate plaque psoriasis with the change in Psoriasis Area and Severity Index (PASI) from baseline to week 12 as the primary endpoint. Results: EPR spectroscopy disclosed a significantly higher radical formation in untreated than skin treated with the herbal oil cream (p ≤ 0.05). LSM measurements indicated a protective skin barrier effect in treated compared to untreated skin. In the clinical trial, the topical application of herbal oils showed a significant reduction of the PASI score compared to topical calcipotriol at week 12 (p = 0.016). The mean reduction in PASI was 49% for the herbal oil cream, 38% for calcipotriol, and 55% for the vehicle cream. The percentage of patients, who reached PASI 50 and 75 at any time point, was 55.9% and 29.4% for the herbal oil cream, 47.4% and 15.8% for calcipotriol, and 23 (60.5%) and 13 (34.2%) for the vehicle, respectively (p > 0.05). The vehicle, originally designed as a placebo, contained a main ingredient of the herbal oil cream and therefore showed corresponding results. Conclusion: The herbal oil cream demonstrated effectiveness in the treatment of mild to moderate plaque psoriasis.

In this paper, we present an in-situ study of the marginal area of a CO2- and brine-rich cavernous structure in an underground rock salt mine. To reveal sources and dynamics of fluid movement, the temporal and spatial distribution of fluids in the potentially weakened cavern rim in salt were investigated. Seismic imaging, followed by long-term gas monitoring were applied along a transect from the cavernous structure to the undisturbed rock formation. The underground seismic survey comprised travel time tomography and pre-stack depth migration and showed, in agreement with the results of gas monitoring, disturbed areas without correlation to the cavernous structure. During two years, the monthly gas inflow into isolated borehole sections revealed insights into short term changes of gas migration pattern in rock salt. The measurements showed gas influx of up to 4 kPa/day and CO2 concentrations of up to 1.2%, especially during the beginning of the campaign. The gas migration is coupled to discrete fracturing and was observed to be spatially and temporary confined. Overall, no correlation between gas occurrences and their distance to the cavern exists, suggesting no wide-ranging fluid-rock interaction in the rim of the investigated natural cavernous structure in rock salt. The occurrence of gas is coupled to spatially and temporary limited fracturing which evidently healed and regained rock salt typical tightness.

Nanoparticles can be applied to the hair follicles, which can serve as reservoirs for triggered drug release. A valid measurement method for the determination of the pH within the hair follicle in vivo has not been shown yet. Here, melamine formaldehyde particles up to 9 µm in size were applied on 40 freshly plucked scalp hairs of eight individuals to determine the pH along the hair shaft down to the root area of the hair. For fluorescent pH indicators, pyranine and Nile blue were incorporated into the particles. Measurements were conducted using confocal laser scanning microscopy. A pH decay gradient could be found from the hair sheath towards the external hair shaft (p = 0.012) with pH values at the hair sheath of 6.63 ± 0.09, at the hair sheath end at 6.33 ± 0.11, and at the external hair shaft at 6.17 ± 0.09 (mean ± SE). The pH difference between the hair sheath end and the external hair shaft was found to be significant (p = 0.036). The results might be comparable with the pH within the hair follicle in vivo indicating a pH increase towards the hair root.

BACKGROUND Laboratory results are of central importance for clinical decision making. The time span between availability and review of results by clinicians is crucial to patient care. Clinical decision support systems (CDSS) are computational tools that can identify critical values automatically and help decrease treatment delay. OBJECTIVE With this work, we aimed to implement and evaluate a CDSS that supports health care professionals and improves patient safety. In addition to our experiences, we also describe its main components in a general manner to make it applicable to a wide range of medical institutions and to empower colleagues to implement a similar system in their facilities. METHODS Technical requirements must be taken into account before implementing a CDSS that performs laboratory diagnostics (labCDSS). These can be planned within the functional components of a reactive software agent, a computational framework for such a CDSS. RESULTS We present AMPEL (Analysis and Reporting System for the Improvement of Patient Safety through Real-Time Integration of Laboratory Findings), a labCDSS that notifies health care professionals if a life-threatening medical condition is detected. We developed and implemented AMPEL at a university hospital and regional hospitals in Germany (University of Leipzig Medical Center and the Muldental Clinics in Grimma and Wurzen). It currently runs 5 different algorithms in parallel: hypokalemia, hypercalcemia, hyponatremia, hyperlactatemia, and acute kidney injury. CONCLUSIONS AMPEL enables continuous surveillance of patients. The system is constantly being evaluated and extended and has the capacity for many more algorithms. We hope to encourage colleagues from other institutions to design and implement similar CDSS using the theory, specifications, and experiences described in this work.

Background Laboratory results are of central importance for clinical decision making. The time span between availability and review of results by clinicians is crucial to patient care. Clinical decision support systems (CDSS) are computational tools that can identify critical values automatically and help decrease treatment delay. Objective With this work, we aimed to implement and evaluate a CDSS that supports health care professionals and improves patient safety. In addition to our experiences, we also describe its main components in a general manner to make it applicable to a wide range of medical institutions and to empower colleagues to implement a similar system in their facilities. Methods Technical requirements must be taken into account before implementing a CDSS that performs laboratory diagnostics (labCDSS). These can be planned within the functional components of a reactive software agent, a computational framework for such a CDSS. Results We present AMPEL (Analysis and Reporting System for the Improvement of Patient Safety through Real-Time Integration of Laboratory Findings), a labCDSS that notifies health care professionals if a life-threatening medical condition is detected. We developed and implemented AMPEL at a university hospital and regional hospitals in Germany (University of Leipzig Medical Center and the Muldental Clinics in Grimma and Wurzen). It currently runs 5 different algorithms in parallel: hypokalemia, hypercalcemia, hyponatremia, hyperlactatemia, and acute kidney injury. Conclusions AMPEL enables continuous surveillance of patients. The system is constantly being evaluated and extended and has the capacity for many more algorithms. We hope to encourage colleagues from other institutions to design and implement similar CDSS using the theory, specifications, and experiences described in this work.

Background The recommended amount of sunscreen by hand application (2 mg/cm2 ) is in reality not achieved, which decreases the homogeneity and thereby the effective sun protection factor (SPF). Materials and methods The homogeneity of sunscreen applied by a newly developed spray applicator using an electrostatically charged aerosol, for which a hand rubbing of the formulation is not necessary, is evaluated. In vivo experiments were performed on the volar forearms of human volunteers using the spray applicator compared to the standardized hand application according to ISO 24444. Results The distribution homogeneity was assessed qualitatively using in vivo laser scanning microscopy and quantitatively by absorption spectroscopy after tape stripping and by the standard deviation of multiple spatially displaced reflectance measurements for non-invasive SPF determination below the minimal erythemal dose, which showed a significantly higher homogeneity by 20.9% after spray application compared to hand application. Conclusion Non-invasive SPF determination of multiple spatially displaced reflectance measurements was proven to be a suitable method for the non-invasive determination of the sunscreen distribution homogeneity. Electrostatically charged spray application increased the sunscreen distribution homogeneity on the skin and can reduce the amount of overspray.

Background The decontamination of the skin is indispensable if airborne particulate contaminants deposit on the skin surface. Skin washing can have adverse effects as by skin rubbing the particles can be transferred deeply into the hair follicles, where they can be entrapped for a period of more than 10 days. Thus, alternative skin decontamination strategies are necessary. Materials and Methods For imaging the contaminants in the skin, sodium fluorescein-labeled soot particles of submicron size (approximate to 600 nm) were visualized using laser scanning microscopy. Results In the present ex vivo pilot study on porcine ear skin, it was shown that sodium fluorescein-labeled soot particles of submicron size (approximate to 600 nm) could be efficiently removed from the skin with highly absorbent textile nanofiber material, whose efficacy could be further increased by spraying the contaminated skin area with the viscous fluid PEG-12 dimethicone before textile application. Conclusion In case of skin contamination with particulates, the contact washing should be avoided due to rubbing particles deeply into the hair follicles, where they can accumulate for a long time and induce negative consequences. Efficient skin decontamination could include pretreatment of skin surface with the viscous fluid PEG-12 dimethicone and subsequent application of highly absorbent textile nanofiber material.

Salt rocks serve as host rock for technical caverns due to their impermeability but their can also be influenced by fluid migration due to geological fracture zones. Seismic methods can be used to monitor cavernous structures in the transition zone between cavity and undisturbed salt rocks. Around an artificially created cavity (field-test cavern) in a salt pillar with a volume of approximately 100 litre, travel time tomography was utilized to image structures related to caverns and fluid-storage. Seismic surveys were performed at different stages of an experimental simulation of gas-water-rock interaction in the field-test cavern aiming for a better understanding of the multiphase system in the cavern-near area. The baseline survey (1) was carried out using 8 three-component piezo-electrical sensor rods and a seismic vibrator source at the surface of the salt pillar, first without an installed field-test cavern. After drilling and installing the field-test cavern, seismic cross-hole measurements were performed after producing partial vacuum in the test cavern (2) and infill of gas (3) and water (4). To finalize the field experiments the last seismic survey (5) was again conducted at the surface of the salt pillar as a repeat measurement to the baseline survey. The seismic monitoring of the salt pillar was carried out in a frequency range of 100 Hz to 14000 Hz allowing a spatial resolution in the cm-range. This was followed by pre-processing of the seismic data sets to apply the picked travel times in a tomography program. On the basis of the tomography results and reflection seismic data we want to assess the potential enlargement of the field-test cavern due to water-infill and to image the differences between unaffected salt rocks, cavernous structures and developing transition zones.

Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles.

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.

Recent studies have shown that pollen proteins can penetrate the impaired skin barrier of atopic patients and exacerbate their disease. In the presented study the effect of a topically applied barrier-enhancing formulation was investigated for its preventive effect on the uptake of pollen allergens into CD1c+ epidermal cells. The pollen proteins were fluorescence labelled and applied on barrier-disrupted excised human skin. CD1c+ cells were selected after magnetic cell sorting and analysed using laser scanning microscopy. In untreated disrupted skin, 81% of the CD1c+ cells contained the fluorescence-labelled pollen allergens. In formulation-pretreated skin only 12% of the CD1c+ cells showed an uptake of pollen allergens. These results encourage the treatment of atopic patients with barrier-enhancing formulations to reduce the impact of pollen on air-exposed skin areas and hence the exacerbation of cutaneous symptoms.

Die Auszubildenden erarbeiten sich einen Uberblick uber die Strukturen und die Organisation eines Krankenhauses. Sie erkennen die Bedeutung der OP-Abteilung als wichtigem Leistungserbringer im Krankenhaus sowie die Bedeutung gesundheitspolitischer Entscheidungen fur die Leistungserbringung eines Krankenhauses, insbesondere die Leistungserbringung in den Operations- und Funktionsbereichen. Die Auszubildenden sind uber die Bedeutung des OP-Managements informiert und verstehen wesentliche Aufgaben. Sie ubernehmen Verantwortung fur umweltbewusstes Handeln in ihrem Beruf und in der Gesellschaft und sind sich des Spannungsfelds zwischen okonomischen und okologischen Anspruchen bewusst. Sie tragen aktiv dazu bei, die Behandlung und Versorgung der Patienten mit okologisch moglichst sinnvollen Mitteln und Methoden unter Aufrechterhaltung der erforderlichen medizinischen Standards zu gewahrleisten.

Drug delivery through the skin barrier is a topic of high interest in cosmetology and dermatology. The disruption of the skin barrier is a common method to stimulate skin penetration. In the present chapter tissue tolerable plasma is used to damage the skin barrier, enabling topically applied substances to effectively pass the stratum corneum. Subsequently to plasma-tissue interaction the skin barrier recovers immediately. Topically applied drugs have to be applied before the plasma treatment onto the skin. In this case, the plasma chemical reaction of the drug has to be prevented by using plasma resistant nanocontainers.

The choice of an appropriate seismic source for a specific application is crucial for the success of seismic surveys. In this study, the utilization of two novel seismic sources is discussed for geoengineering applications in the bandwidth of 80–3000 Hz. These are a pneumatic impact and a magnetostrictive vibrator source mainly designed for seismic transmission and reflection applications. Seismic test surveys were carried out on Paleozoic sediment deposits to study a near surface fault zone at the southern rim of the Taunus mountain range in Germany and in crystalline rocks to investigate fracture zones along the Piora Adit of the Gotthard Base Tunnel in Switzerland, respectively. Both sources are evaluated with respect to their seismic wave energy, the sum of the squared amplitudes of first P- and S-arrivals and frequency content, signal to random noise ratio, as well as their suitability with regard to the specific site conditions and applications. Common Midpoint-stacked data of the Taunus survey and pre-stack depth migrated data of the Piora survey were analysed to assess the ability of the seismic sources to image geological structures and to give support for geotechnical aspects. For both test sites, the vibrator source proved to be more suitable to generate body waves than the impact source, which generates strong ground roll noise signals due to its non-controlled signal amplitude spectrum. In fact the control system of the vibrator source enabled improved adaption to varying ground conditions due to a controlled adjustment of the signal amplitude spectrum to optimize resolution and penetration for a given exploration depth.

Background/Aims: Airborne pollutants, such as nano-sized soot particles, are increasingly being released into the environment as a result of growing population densities and industrialization. They can absorb organic and metal compounds with potential biological activity, such as polycyclic aromatic hydrocarbons and airborne pollen allergens. Local and systemic toxicities may be induced in the skin if the particulates release their harmful components upon dermal contact. Methods: In the present study, skin pretreatments with serum and/or shield as barrier formulations prior to exposure and washing with a cleanser subsequent to exposure were evaluated as a protection and decontamination strategy using laser scanning microscopy. Results: The results indicate that while the application of serum and a cleanser was insufficient for decontamination, the pretreatment with shield prior to nanoparticle exposure followed by washing led to the removal of a considerable amount of the carbon black particles. The combined application of serum and shield before the administration of carbon black particles and subsequent washing led to their elimination from the skin samples. Conclusion: The application of barrier-enhancing formulations in combination with a cleanser may reduce the penetration of harmful airborne particulates by preventing their adhesion to the skin and facilitating their removal by subsequent washing with the cleanser.

Penetration studies are essential for the evaluation and optimization of topically applied substances. Stripping techniques are well suited for such penetration measurements. In this chapter the methods of tape stripping and cyanoacrylate biopsy are presented and discussed. While the tape stripping method is applied to analyze the penetration of topically applied substances into the stratum corneum, combined application of tape stripping and cyanoacrylate biopsy, which is known as differential stripping, permits to analyze the penetration of topically applied substances into the stratum corneum and into the hair follicles, separately. Although the described methods are relatively simple, their application requires adherence to standard protocols to avoid mistakes. The present chapter provides not only an overview of the scientific application methods for both tape stripping and differential stripping, but also useful recommendations for standardized work.

Two state-of-the-art microscopic optical methods, namely, confocal laser scanning microscopy in the fluorescence and reflectance regimes and multiphoton tomography in the autofluorescence and second harmonic generation regimes, are compared for porcine skin ex vivo and healthy human skin in vivo. All skin layers such as stratum corneum (SC), stratum spinosum (SS), stratum basale (SB), papillary dermis (PD) and reticular dermis (RD) as well as transition zones between these skin layers are measured noninvasively at a high resolution, using the above mentioned microscopic methods. In the case of confocal laser scanning microscopy (CLSM), measurements in the fluorescence regime were performed by using a fluorescent dye whose topical application on the surface is well suited for the investigation of superficial SC and characterisation of the skin barrier function. For investigations of deeply located skin layers, such as SS, SB and PD, the fluorescent dye must be injected into the skin, which markedly limits fluorescence measurements using CLSM. In the case of reflection CLSM measurements, the obtained results can be compared to the results of multiphoton tomography (MPT) for all skin layers excluding RD. CLSM cannot distinguish between dermal collagen and elastin measuring their superposition in the RD. By using MPT, it is possible to analyse the collagen and elastin structures separately, which is important for the investigation of anti-aging processes. The resolution of MPT is superior to CLSM. The advantages and limitations of both methods are discussed and the differences and similarities between human and porcine skin are highlighted.

Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds.

Resonance Raman spectroscopy and multi-photon tomography were used in vivo to analyse the influence of sun exposure on the cutaneous carotenoids and collagen/elastin fibers. Comparing Berlin (low sun exposure) and Monegasque (high sun exposure) volunteers, it could be demonstrated that extended sun exposure significantly reduces the cutaneous carotenoids and collagen/elastin concentration (p < 0.05). The tendency towards correlation (R(2) = 0.41) between the dermal collagen/elastin (SAAID) and carotenoids confirms the important role of antioxidants in the protection against sun-induced negative effects. The application of sunscreen was shown to be effective, protecting cutaneous carotenoids and collagen/elastin from being damaged subsequent to sun exposure.

The aim of the present study was to solve the water insolubility limitation of the medically and cosmetically interesting substance Garcinia mangostana Linn (GML) extract by encapsulation, and to evaluate and investigate the penetration efficacy of free and encapsulated GML in two different vehicles (water and cream) in porcine ear skin. The follicular penetration depth was determined in 50 hair follicles for each of the four formulations by means of fluorescence microscopy. Tape stripping was used to compare the distribution properties of GML with all formulations on the stratum corneum. The results showed that encapsulated and free GML in the cream base penetrated deeper into hair follicles than if applied in an aqueous base. In addition, encapsulated GML could be distributed more homogeneously on the stratum corneum than the free GML. In conclusion, it was found that encapsulated GML in a cream base had the most effective penetration level in porcine ear skin.

Liposomes are frequently described as drug delivery systems for dermal and transdermal applications. Recently, it has been shown that particulate substances penetrate effectively into hair follicles and that the follicular penetration depth can be increased by massaging the skin, which simulates the in vivo movement of hairs in the hair follicles. In the present study, massage was applied to skin mounted to Franz diffusion cells. By means of confocal laser scanning microscopy, the influence of massage and occlusion on the follicular penetration depths of rigid and flexible liposomes loaded with a hydrophilic and lipophilic dye was investigated. The application of massage increased follicular penetration significantly. Occlusion resulted in an increased follicular penetration depth only for rigid liposomes, whereas invasomes did not penetrate more effectively if occlusion was applied. The results confirm that massage is an important tool for increasing follicular penetration in ex vivo studies using Franz diffusion cells. Occlusion may reduce the efficacy of follicular penetration depending on the specific liposomal preparation. Rigidity in particular appears to be a relevant parameter. (c) 2013 Elsevier B.V. All rights reserved.

Sei es in der Behandlung von Erkrankungen, die mit einer Hyperaziditat des Magens einhergehen, oder als Magenschutz: Protonenpumpenhemmerund H2-Blocker sind als Saureblocker in der Schulmedizin kaum wegzudenken. Zahlreiche Neben- und Wechselwirkungen machen jedoch ein sorgfaltiges Medikationsmanagement notwendig. Apothekerin Heike Richter erlautert, wie beide Arzneimittelgruppen wirken und was besonders bei langerfristiger Einnahmedauer beachtet werden muss.

The results of the risk assessment of the tissue-tolerable plasma (TTP) jet kINPen med ® and first results of pilot clinical studies are presented. Producing an atmospheric pressure plasma, this plasma jet entails no risk for humans in terms of temperature increase, UV radiation or free radical formation by the plasma. The antiseptic efficacy in vitro on porcine skin and in vivo on human skin was compared to that of octenidine. TTP could significantly reduce the bacterial load in comparison to untreated skin. However, the slightly reduced antiseptic properties of TTP are attributed to the current parameter set-up and technical limitations.

More and more investigations confirm that nanoparticles are incapable of overcoming the intact skin barrier in vivo. Do nanoparticles still have a future in dermal drug delivery? Unlike many other topically applied substances, nanoparticles have not been reported to utilize the intercellular penetration pathway and preferentially make use of the follicular penetration pathway. Deep penetration into the follicular ducts has been described for a variety of particles and appears to be strongly influenced by particle size. For targeted drug delivery, smart nanoparticles are required which are able to release their loaded drugs subsequent to internal or external trigger stimuli, and thereby enable the translocation of the active agents into the viable epidermis. In the recent manuscript, three nanoparticles systems are summarized and compared which release their model drugs upon different trigger mechanisms. The BSA hydrogel nanoparticles release their model drug TRITC-dextran by passive diffusion due to a concentration gradient via a porous surface. The protease-triggered controlled release BSA nanoparticles release their model drug if they are applied simultaneously with protease nanoparticles, resulting in an enzymatic degradation of the particles and a release of the model drug FITC. Finally, the IR-triggered controlled release AuNP-doped BSA nanoparticles release their model drug FITC after photoactivation with wIRA. For all three nanoparticle systems, the release of their model drugs could be observed. For the first nanoparticle system, only low follicular penetration depths were found which might by due do an agglomeration effect. For the last two nanoparticle systems, deep follicular penetration and even an uptake by the sebaceous glands were verified. In conclusion, it could be demonstrated that nanoparticles do have a future in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle.

The requirements on nanoparticles for cosmetic and medical applications are very different. While nanoparticles applied in sunscreens shall remain on the skin surface or in the upper cell layers of the stratum corneum, nanoparticles for medical drug delivery shall penetrate through the skin barrier to the target structures in the living cells. Under the Collaborative Research Project 1112 various methods are used at the CCP to investigate the cutaneous penetration and storage of nanoparticles, hair follicles being in the focus of attention. Human hair follicles are ideal target structures for drug delivery. Hosting both the stem and dendritic cells, they are surrounded by a dense network of blood vessels. Investigating nanoparticles of different size and materials, particles of approximately 600 nm in diameter were found to penetrate best into the hair follicles, where they can be stored for maximally 10 days. Their retention time in the hair follicles exceeds that in the stratum corneum by almost one order of magnitude. Particles penetrate more efficiently into the hair follicles than non-particulate substances. For particles from 40 nm-1 µm in diameter, however, no follicular penetration has been detectable if the skin barrier was intact. This is plausible as the hair follicle has its own barrier. It will be demonstrated that the best way for drug delivery is the application of drug-loaded particulate carrier systems. In the hair follicles the particles may either dissolve and release the drug, or an external signal must trigger the drug release from the particle.

An improvement of the penetration efficiency combined with the controlled release of actives in the skin can facilitate the medical treatment of skin diseases immensely. Dexamethasone (Dx), a synthetic glucocorticoid, is frequently used for the treatment of inflammatory skin diseases. To investigate the penetration of nano-sized lipid particles (NLP) loaded with Dx in comparison to a commercially available base cream, different techniques were applied. Electron paramagnetic resonance (EPR) spectroscopy was used to monitor the penetration of Dx, which was covalently labeled with the spin probe 3-(Carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA). The penetration into hair follicles was studied using confocal laser scanning microscopy (CLSM) with curcumin-loaded NLP. The penetration of the vehicle was followed by confocal Raman microscopy (CRM). Penetration studies using excised porcine skin revealed a more than twofold higher penetration efficiency for DxPCA into the stratum corneum (SC) after 24h incubation compared to 4h incubation when loaded to the NLP, whereas when applied in the base cream, almost no further penetration was observed beyond 4h. The distribution of DxPCA within the SC was investigated by consecutive tape stripping. The release of DxPCA from the base cream after 24h in deeper SC layers and the viable epidermis was shown by EPR. For NLP, no release from the carrier was observed, although DxPCA was detectable in the skin after the complete SC was removed. This phenomenon can be explained by the penetration of the NLP into the hair follicles. However, penetration profiles measured by CRM indicate that NLP did not penetrate as deeply into the SC as the base cream formulation. In conclusion, NLP can improve the accumulation of Dx in the skin and provide a reservoir within the SC and in the follicular infundibula.

Background Gaining a new voice is one of the major aims after total laryngectomy. The objective of this study was to describe the process and results of speech rehabilitation during the first year after surgery. Methods Speech intelligibility was measured 6 months (n = 273) and 1 year (n = 225) after total laryngectomy. Results Objective (23.4 to 47.5 points, p < .0001) and subjective (51.6 to 64.7 points, p < .0001) speech intelligibility improved between 6 months and 1 year after total laryngectomy. Patients who used tracheoesophageal puncture (TEP) had the best results in speech intelligibility 6 months and 1 year after total laryngectomy. In all, 12% of the patients who used TEP initially no longer used it 1 year later. Patients who had received rehabilitation had better objective speech intelligibility than those who did not. Conclusions Speech improves considerably between 6 months and 1 year after total laryngectomy. Nonattendance of rehabilitation is associated with a worse functional outcome in speech rehabilitation. Head Neck, 35: 1583–1590, 2013

SynopsisThe efficacy of a drug is characterized by its action mechanismand its ability to pass the skin barrier. In this article, differentmethods are discussed, which permit this penetration process tobe analysed non-invasively. Providing qualitative and quantita-tive information, tape stripping is one of the oldest procedures forpenetration studies. Although single cell layers of corneocytes areremoved from the skin surface, this procedure is considered asnon-invasive and is applicable exclusively to the stratum corne-um. Recently, optical and spectroscopic methods have been usedto investigate the penetration process. Fluorescence-labelleddrugs can be easily detected in the skin by laser scanning micros-copy. This method has the disadvantage that the dye labellingchanges the molecular structures of the drug and consequentlymight influence the penetration properties. The penetrationprocess of non-fluorescent substances can be analysed by Ramanspectroscopy, electron paramagnetic resonance, CARS and mul-tiphoton microscopic measurements. Using these methods, theconcentration of the topically applied formulations in differentdepths of the stratum corneum can be detected by moving thelaser focus from the skin surface deeper into the stratum corne-um. The advantages and disadvantages of these methods will bediscussed in this article.Re´sume´L’efficacite´ d’un me´dicament se caracte´rise par son me´canismed’action et sa capacite´ a` passer la barrie`re de la peau. Dans le pre´sentdocument les diffe´rentes me´thodes sont discute´es, qui permettentd’analyser le processus de la pe´ne´tration de fac¸on non invasive. L’ar-rachage (tape stripping) est l’une des plus anciennes me´thodes pourles e´tudes de pe´ne´tration puisqu’elle fournit de l’information qualita-tive et quantitative. Bien que des cellules isole´es des couches de cor-ne´ocytes soient retire´es de la surface de la peau, cette proce´dure estconside´re´e comme non-invasive; elle est applicable exclusivement a` lacouche corne´e. Re´cemment, des me´thodes spectroscopiques etoptiques et ont e´te´ utilise´es pour e´tudier le processus de pe´ne´tration.Les me´dicaments marque´s par fluorescence peuvent eˆtre de´tecte´sfacil-ement dans la peau par la microscopie a` balayage laser. Cette me´thodepre´sente l’inconve´nient que le label colore´ change les structuresmole´culaires de la drogue et par conse´quent sont susceptibles d’influ-encer les proprie´te´sdepe´ne´tration. Le processus de pe´ne´tration dessubstances non-fluorescentes peut eˆtre analyse´ par spectroscopieRaman, par la re´sonance paramagne´tique e´lectronique, CARS et pardes mesures de microscopie multiphotonique. En utilisant ces me´th-odes, la concentration des formulations topiques a` des profondeursdiffe´rentes du stratum corneum peut eˆtre de´tecte´e par le de´placementdu focus laser a` partir de la surface de la peau vers les couches plusprofondes de la couche corne´e. Les avantages et les inconve´nients deces me´thodes seront discute´sdanslepre´sent document.IntroductionSubstances are often topically applied in dermatology and cosmetol-ogy to improve the skin barrier and to treat dermatological diseases[1–4]. Whereas in the first case, the action of the drug is related tothe uppermost cell layers of the skin – the stratum corneum, in thesecond case, it is related to the living cells. Penetration of the skinbarrier is, therefore, indispensable. The investigation of this penetra-tion process is essential for the development and optimization of newpharmaceutics and cosmetic products [5, 6]. Whereas in the past, ithad been assumed that topically applied substances pass the skin bar-rier via the intercellular route [7, 8], it could be demonstrated thatalso the follicular route can represent an important penetration path-way [9, 10]. It was found, for example, for caffeine [11] and minoxi-dil [12], that these substances penetrate the skin barrier veryefficiently via the follicular route. For these investigations, the orificesof the hair follicles were artificially closed [11]. When these orificeswere blocked, the penetration of both substances into the blood circu-lation was considerably delayed. Previously, penetration investiga-tions had been based inter alia on diffusion cells or attenuated totalreflectance Fourier transform infrared spectroscopy, which describeonly the intercellular penetration in vitro [13, 14]. Today, however,methods considering also the influence of the follicular penetrationare to be used. In this article, different methods for the analysis of thepenetration process are described and discussed in terms of theiradvantages and limitations.This article elucidates both conventional penetration in vivo pro-cedures and recent developments in the field of optical technologiesused in in vivo penetration research.

Background An increasing number of people is reported to have sensitive skin. Consequently, the development of textile materials with comfortable wearing properties has become a major interest. One method to create a pleasant sensation of textile materials on the skin is to coat them with silk proteins. This technologically complex procedure requires both optimization and control. Methods The present study was aimed to characterize the subjective perception of different textiles and to objectively assess their influence on skin morphology with non-invasive optical techniques like optical coherence tomography (OCT), laser scanning microscopy (LSM) and optical surface profilometry (OP). Furthermore, optical methods were used to characterize surface properties of different textile fabrics. Results In the present study it could be shown that optical non-invasive methods, as applied in cosmetology and dermatology are suited to characterize the structural properties of fabrics and the effects that textile materials have on the skin. Here, both unfinished textile materials and fabrics finished with silk protein coating were investigated by OCT, LSM and OP. In addition, volunteers were interviewed about their subjective sensation when these fabrics were in contact with their skin. Conclusion The study showed that optical methods could be applied to compare textile materials in vitro, which permit the wearing comfort to be predicted and in vivo perception on the skin.

Earlier investigations regarding the distribution of the bacterial flora on the human skin demonstrate that the hair follicle acts as a bacterial reservoir, providing a quick source for secondary recontamination. These findings highlight the importance of the hair follicle as a target for modern antiseptics. In the present study, we have assessed the follicular penetration of a curcumin-labeled particle-associated antiseptic into porcine skin by laser scanning microscopy. Therefore, the follicular penetration depth of the curcumin-labeled particle-associated antiseptic was compared to the follicular penetration depth of curcumin-labeled particles without antiseptic. The investigation was performed in vitro using porcine skin biopsies. By superposition of the images acquired in the transmission and the fluorescent modus, it was possible to visualize the distribution of the fluorescent dye inside the hair follicles. Quantitative and qualitative results showed that both dispersions penetrated efficiently into the hair follicles. The average penetration depth of the particles with attached antiseptic polihexanide was significantly higher than that of particles without the attached antiseptic. Also, whilst very little sample preparation was needed, laser scanning microscopy was found to be an efficient tool to visualize the skin relief and in particular the hair follicle shaft and localize fluorescent markers within the skin tissue and hair follicles.

Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area.

The antimicrobial treatment of wounds is still a major problem. Tissue-tolerable electrical plasma (TTP) is a new approach for topical microbial disinfection of the skin surface. The aim of the present study was to investigate the influence of TTP on a carotenoid profile in relation to skin physiology parameters (epidermal barrier function, stratum corneum (SC) hydration, surface temperature and irritation parameters). We were interested in the interaction of TTP and the antioxidative network, as well as the consequences for skin physiology parameters. These parameters are also indicative of TTP safety in vivo. For plasma application, 'Kinpen 09' was used (surface exposure 30-43°C) for 3 s. Beta-carotene and water profiles were assessed by in vivo Raman microspectroscopy (skin composition analyzer 3510). Skin physiology parameters were measured with Tewameter TM 300, Corneometer CM 825, skin thermometer and Chromameter CR 300. All parameters were assessed non-invasively on seven healthy volunteers before and after plasma application in vivo. We could show that TTP application leads to a decrease in beta-carotene especially in the superficial SC. Skin-surface temperature increased by 1.74°C, while the transepidermal water loss (TEWL) increase indicated an impaired barrier function. SC hydration decreased as seen in water profile especially in the superficial layers and capacitance values. A slight increase in skin redness was measurable. The induction of reactive oxygen species is probably the major contributor of TTP efficacy in skin disinfection. Skin physiology parameters were influenced without damaging the skin or skin functions, indicating the safety of TTP under in vivo conditions.

The analysis of the skin barrier properties is important in various fields of medical treatment and cosmetology. The development and improvement of topically applied substances require an objective analysis of the skin barrier characteristics. Transepidermal water loss (TEWL) measurement is the standard method to characterize epidermal barrier function. The most important disadvantage of this method though, is that it can be affected by different exogenous and endogenous factors, e.g. water content of the applied formulation and room temperature. In the present study, TEWL measurements are compared to laser scanning microscopic (LSM) measurements, concerning the use of these two methods for the non-invasive in vivo characterization of the epidermal barrier function. The investigations were performed prior and subsequent to treatment of dry skin with a gel mixture, developed for skin treatment after radiotherapy for cancer. The present results indicate that in vivo laser scanning microscopy is an appropriate method for the characterization of the skin barrier structure without interference by external factors. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)