Intestinal barrier function

Recognition of bacterial products by the innate immune system is dependent on pattern-recognition receptors: toll-like receptor 9 (TLR-9) in the case of bacterial DNA. We hypothesized that bacterial DNA can directly affect enteric epithelial cells. RT-PCR revealed constitutive TLR-9 mRNA expression in three human colonic epithelial cell lines (T84, HT-29, Caco-2) and THP-1 monocytes. Epithelial cells, in six-well culture plates or on filter supports, were exposed to E. coli DNA (1-50 microg/ml), synthetic CpG-rich oligonucleotides, or calf thymus DNA for 6-48 h. Exposure to E. coli DNA resulted in an increase in IL-8 mRNA, and a time- and dose-dependent increase in IL-8 secretion. Also, CpG oligonucleotides induced epithelial IL-8 production, whereas calf thymus DNA did not. Exposure to E. coli DNA resulted in phosphorylation of ERK 1/2 MAPK and inhibitors of ERK activity (PD98059, UO126) significantly reduced the evoked IL-8 production. In contrast, inhibitors of NFkappaB activity ...

Epidermal permeability barrier homeostasis requires the postsecretory processing of polar lipid precursors into nonpolar lipid products within the stratum corneum (SC) interstices by a family of lipid hydrolases. A specific requirement for -glucocerebrosidase ( -GlcCer'ase), which exhibits a distinct acidic pH optimum, is particularly well documented. Therefore, we sought to determine whether the recovery of the barrier after acute insults requires acidification of the SC. We examined permeability barrier recovery by assessing changes in transepidermal water loss (TEWL), SC membrane ultrastructure utilizing ruthenium tetroxide (RuO 4 ) postfixation, and β-Glc-Cer'ase activity by in situ zymography at an acidic vs neutral pH. Barrier recovery proceeded normally when acetone-treated skin was exposed to solutions buffered to an acidic pH. In contrast, the initiation of barrier recovery was slowed when treated skin was exposed to neutral or alkaline pH, regardless of buffer composition. In addition, enhancement of the alkaline buffer-induced delay in barrier recovery occurred with Ca 2+ and K + inclusion in the buffer. Moreover, the pH-dependent alteration in barrier recovery appeared to occur through a mechanism that was independent of Ca 2+ -or K + -controlled lamellar body secretion, since both the formation and secretion of lamellar bodies proceeded comparably at pH 5.5 and pH 7.4. In contrast, exposure to pH 7.4 (but not pH 5.5) resulted in both the persistence of immature, extracellular lamellar membrane structures, and a marked decrease in the in situ activity of -GlcCer'ase. These results suggest first that an acidic extracellular pH is necessary for the initiation of barrier recovery, and second that the delay in barrier recovery is a consequence of inhibition of postsecretory lipid processing.

Background Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. Objectives To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. Methods Volunteers (n ¼ 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. Results Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. Conclusions Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level.

The application of rice wine on skin is known to have beneficial effects such as enhancement of the skin barrier function and skin whitening. In this study, we focused on examination of the anti-aging effects of rice wine. The treatment of fibroblasts with rice wine in vitro increased the expression of procollagen and laminin-5, a key basement membrane component in cultured human fibroblasts. Rice wine significantly reduced the expression of UV-induced matrix metalloproteinase-1 (MMP-1) in a dose-dependent manner in both cultured human fibroblasts and keratinocytes. In addition, treatment with rice wine decreased UV-induced tumor necrosis factor-α (TNF-α) production in human keratinocytes. An in vivo study using hairless mice showed that topical application of rice wine protected mouse skin from photoaging. Thus, we suggest that rice wine may have potential as an effective agent for the prevention and treatment of UV-induced skin aging.

One back end option for spent HTR fuel elements proposed for future HTR fuel cycles in the EC is an open fuel cycle with direct disposal of conditioned or non-conditioned fuel elements. This option has already been chosen in Germany due to the political decision to terminate the use of HTR technology. First integral leaching investigations at the Research Centre Juelich on the behaviour of spent HTR fuel in salt brines, typical for accident scenarios in a repository in salt, proved, that the main part of the radionuclide inventory cannot be mobilised as long as the coated particles do not fail. However such experiments will not lead to a useful model for performance assessment calculations, because a failure of the coatings by corrosion will not occur during experimental times of few years. In order to get a robust and realistic model for the long term behaviour in aqueous phases of host rock systems, it is necessary to understand the barrier function of the different parts of a HTR fuel element, which are the matrix graphite, the different coating materials and the fuel kernel. Therefore our is focused on the understanding and modelling of the barrier performance of the different parts of a HTR fuel element with respect to their barrier function, and on the development of an overall model for performance assessment. In order to understand the behaviour, it is necessary to start with investigations of unirradiated material, and to proceed with experiments with external gamma-irradiation to determine the effects of oxidising radiolysis species. Further experiments with irradiated material have to be performed, to investigate the influence of the irradiation damages, and finally the investigation of irradiated material plus additional gamma-irradiation. Experimental data are now available for the diffusive transport of radionuclides in the water saturated graphite pore system, the corrosion rates of unirradiated graphite without and with external gamma-irradiation and unirradiated and irradiated silicon carbide, and for the dissolution rates of UO 2 and (Th,U)O 2 fuel kernels without and with external gamma-irradiation. All investigations have been performed in aquatic phases from salt, granite and clay host rock.

The skin is the organ that receives the greatest exposure to light and shows a high-amplitude circadian rhythm in epidermal cell proliferation. We have previously demonstrated that the skin barrier function has a significant circadian rhythm. Corticosteroids (CS) are the most commonly used topical treatment in dermatology. Timedependent differences in their efficacy and side-effects would be of considerable interest. The aims of the current study were to examine time-dependent cycles in the effect of topical CS application in healthy and irritated skin on skin blood flow and its relationship to barrier function. Twenty clinically healthy, diurnally active subjects were examined at eight and nine time points over a 24 or 28 h span respectively, using non-invasive skin bioengineering techniques of laser Doppler imaging, a transepidermal water loss (TEWL) device and a skin thermometer in a 28 h session. The results of this current study demonstrate circadian and ultradian (12 h) variations in skin blood flow. A significant correlation was found between skin temperature and skin blood flow but not with TEWL. Circadian and ultradian rhythms are maintained during treatment with high-potency and mid-potency CS in healthy skin. These rhythms persist during stratum corneum disruption with and without CS application.

A phylogeographic analysis of eight species complexes of European reptiles was performed using different molecular methods. While mitochondrial genes (mainly cytochrome b sequences) enabled conclusions about phylogeography and differentiation, additional application of bisexually inherited markers provided information about speciation stages. As species with similar distribution patterns in southern and Central Europe were selected, matching phylogeographic patterns are useful for drawing general conclusions: