Home About us Contact
|
Home About us Contact | ||
|
|
||
Barrier Function (barrier + function)
Kinds of Barrier Function Selected AbstractsEffects of Chronic Alcohol Abuse on Alveolar Epithelial Barrier Function and Glutathione HomeostasisALCOHOLISM, Issue 7 2003Ellen L. Burnham Background: An association between the development and severity of the acute respiratory distress syndrome has been described in individuals who abuse alcohol chronically, possibly through a mechanism involving the deficiency of pulmonary glutathione. In a rodent model of chronic alcohol abuse, this antioxidant contributes to the maintenance of alveolar-capillary membrane integrity. We postulated that humans who chronically abuse alcohol will have similar alterations in alveolar-capillary barrier function. Methods: Bronchoalveolar lavage was performed in 18 healthy chronic alcoholics and 18 control subjects; total protein and glutathione concentrations were measured within the epithelial lining fluid. To examine possible protracted effects of alcohol abuse, a subset of 11 chronic alcoholic subjects underwent a second bronchoalveolar lavage after a week of abstinence. Results: Chronic alcoholic subjects had significantly elevated protein concentrations compared with controls (8.64 ,g protein/ng immunoglobulin A vs. 5.91 ,g protein/ng immunoglobulin A, p= 0.01). After a week of abstinence, no significant increase in either the glutathione levels or normalization of the protein concentrations in the epithelial lining fluid was demonstrable. Conclusions: Increased protein levels in the epithelial lining fluid of individuals who abuse alcohol chronically may signify abnormal alveolar epithelial barrier function that does not appear to readily reverse after a period of abstinence. [source] Effect of Standardized Skin Care Regimens on Neonatal Skin Barrier Function in Different Body AreasPEDIATRIC DERMATOLOGY, Issue 1 2010Natalie Garcia Bartels M.D. In a prospective, randomized clinical study, we compared the influence of three skin care regimens to bathing with water on skin barrier function in newborns at four anatomic sites. A total of 64 healthy, full-term neonates (32 boys and 32 girls) aged <48 hours were randomly assigned to four groups receiving twice-weekly: WG, bathing with wash gel (n = 16); C, bathing and cream (n = 16); WG + C, bathing with wash gel plus cream (n = 16); and B, bathing with water (n = 16). Transepidermal water loss, stratum corneum hydration, skin pH, sebum were measured on day 2, week 2, 4, 8 of life on front, abdomen, upper leg, and buttock. Skin condition was scored and microbiologic colonization was documented. After 8 weeks, group WG + C showed significantly lower transepidermal water loss on front, abdomen, and upper leg as well as higher stratum corneum hydration on front and abdomen compared with group B. Similarly, group C showed lower transepidermal water loss and higher stratum corneum hydration on these body regions. Group WG revealed significantly lower pH on all sites compared with group B at week 8. No differences in sebum level, microbiologic colonization and skin condition score were found. Skin care regimens did not harm physiologic neonatal skin barrier adaptation within the first 8 weeks of life. However, significant influence of skin care on barrier function was found in a regional specific fashion. [source] Tumor necrosis factor-, and interferon-, directly impair epithelial barrier function in cultured mouse cholangiocytesLIVER INTERNATIONAL, Issue 1 2003Hanada Shinichiro Abstract:Background/Aims: In primary biliary cirrhosis (PBC), cytokines from CD4 + T lymphocytes were suggested to contribute to the intralobular bile duct damage together with cellular immunity by CD8 + T lymphocytes. Recently, we reported that immunolocalization of 7H6 , a tight junction (TJ)-associated protein , was significantly diminished in cholangiocytes in the PBC liver. In this study, we examined the direct effects of several cytokines , tumor necrosis factor-, (TNF-,), interferon-, (IFN-,), interleukin-2 and 4 (IL-2 and 4) , on TJ in immortalized mouse cholangiocytes. Moreover, we examined the inhibitory effect of ursodeoxycholic acid (UDCA)on cytokine-induced changes in paracellular permeability. Methods: Barrier function of TJ was evaluated by measuring transepithelial electrical resistance (TER) and 3H-inulin flux. We also performed immunostaining and immunoblotting for TJ-associated proteins , claudin-1 and -3, occludin, zonula occluden-1 (ZO-1) and 7H6. Results: TNF-, and IFN-,, but neither IL-2 nor IL-4, significantly decreased TER (P < 0.005). 3H-inulin flux studies confirmed IFN-,-induced increases in paracellular permeability of cholangiocytes (P < 0.001). In immunostaining and immunoblotting studies, TJ-associated proteins were well preserved in TNF-,- or IFN-,-treated cells. Ursodeoxycholic acidhas been found to have no inhibitory effect on increased paracellular permeability induced by TNF-, or IFN-,. Conclusion: These findings show that TNF-, and IFN-, disrupt barrier function of TJ in cholangiocytes without major structural changes to TJ and suggest that disruption of TJ function and subsequent leakage of the bile constituents may influence the aggravation of cholestasis in PBC. [source] Non-invasive bioengineering methods in an intervention study in 1020 male metal workers: results and implications for occupational dermatologyCONTACT DERMATITIS, Issue 5 2010Birgitta Kütting Background: Measurements of transepidermal water loss (TEWL) as an indicator of skin barrier function and colorimetry for quantifying erythema have been recommended for monitoring persons at risk of occupational hand dermatitis. Objective: This study examines the practicability and usefulness of biophysical measurements at the workplace. Patients/Material/Methods: A sample of 1020 male metal workers was enrolled; 800 participants were followed up for 1 year. TEWL results and colorimetry (a* value), respectively, were used as effectiveness outcomes, comparing the findings in the four study arms (skin care, skin protection, both combined, and control group). Results: At 1 year follow-up, the TEWL was slightly but significantly lower in the group of participants randomized for application of barrier cream alone, indicating a protective effect. However, addressing both the individual absolute change of a* value and the differences of TEWL (delta-TEWL) of the dominant hand over the study period, no significant difference was found between the four groups. Conclusions: Dermatological examinations at the workplace cannot be replaced by bioengineering techniques. The supplementary benefit is apparently low, possibly because of difficulties in achieving standardized measurement conditions and other technical reasons. [source] Lipids and skin barrier function , a clinical perspectiveCONTACT DERMATITIS, Issue 5 2008Jakob Mutanu Jungersted The stratum corneum (SC) protects us from dehydration and external dangers. Much is known about the morphology of the SC and penetration of drugs through it, but the data are mainly derived from in vitro and animal experiments. In contrast, only a few studies have the human SC lipids as their focus and in particular, the role of barrier function in the pathogenesis of skin disease and its subsequent treatment protocols. The 3 major lipids in the SC of importance are ceramides, free fatty acids, and cholesterol. Human studies comparing levels of the major SC lipids in patients with atopic dermatitis and healthy controls have suggested a possible role for ceramide 1 and to some extent ceramide 3 in the pathogenesis of the disease. Therapies used in diseases involving barrier disruption have been sparely investigated from a lipid perspective. It has been suggested that ultraviolet light as a treatment increases the amount of all 3 major SC lipids, while topical glucocorticoids may lead to a decrease. Such effects may influence the clinical outcome of treatment in diseases with impaired barrier function. We have, therefore, conducted a review of the literature on SC lipids from a clinical perspective. It may be concluded that the number of human studies is very limited, and in the perspective of how important diseases of impaired barrier function are in dermatology, further research is needed. [source] Moisturizer effect on Irritant Dermatitis: an overviewCONTACT DERMATITIS, Issue 2 2006Miki Yokota Moisturizers are empirically used as prevention and treatment of surfactant and irritant dermatitis. Some products state they not only improve barrier function by providing moisturization but also create an environment optimal for healing. Yet, moisturizer clinical efficacy remains a topic of controversy. We reviewed publication from 1992 to 2006 that quantitatively examines moisturizer effectiveness, as an update of our prior overview, Zhai and Maibach in 1998 (2). We intuitively (in a testimonial sense) believe that moisturizers are sometimes effective for preventing and treating irritant dermatitis. However, moisturizer may not be broadly effective (8, 12) and may be relatively specific against certain acids, bases, hydrophilics, and lipophilics. We need to develop principles of what is formulated in moisturizers to improve efficacy; for this purpose, there is a need for experimental moisturizer models for comparative studies. [source] An in vivo model to evaluate the efficacy of barrier creams on the level of skin penetration of chemicalsCONTACT DERMATITIS, Issue 1 2006Alexa Teichmann The reservoir function and the barrier function are important properties of the skin. The reservoir function is dependent on the barrier function which, however, needs support by protective measures, in particular under working conditions. Barrier creams represent a possibility to protect the skin. In the present study, a method was developed to investigate the effectiveness of reservoir closure by different formulations. Patent Blue V in water was used as a model penetrant. Its penetration, with and without barrier cream treatment, was analyzed by tape stripping in combination with UV/VIS spectroscopic measurements. The investigations showed that the stratum corneum represents a reservoir for topically applied Patent Blue V in water. Furthermore, the barrier investigations showed that vaseline and bees wax form a 100% barrier on the skin surface. The third barrier cream, containing waxes and surfactant, only partially showed a protective effect against the penetration of Patent Blue V in water. Strong interindividual differences were observed for this barrier product. In conclusion, it was assumed that the application of barrier creams cannot replace other protective measures and should be maximally used to inhibit low-grade irritants or in combination with other protectants or in body areas where other protective measures are not applicable. [source] Childhood encephalopathy: viruses, immune response, and outcomeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2006Michael Clarke BSc MB ChB FRCPCH This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood-brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF: serum albumin ratio indicative of impairment of the blood,CSF and blood,brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-, levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood-brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood-brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-, was associated with a good prognosis. [source] Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalusEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2007M. Tullberg Normal pressure hydrocephalus (NPH) is characterized by disturbed cerebrospinal fluid (CSF) dynamics and white matter lesions (WML). Although the morphology of these lesions is described, little is known about the biochemistry. Our aim was to explore the relationship between ventricular CSF markers, periventricular WML and postoperative clinical outcome in patients with NPH. We analysed lumbar and ventricular concentrations of 10 CSF markers, 12 clinical symptoms and signs, magnetic resonance imaging (MRI) periventricular white matter hyperintensities (PVH) and ventricular size before and 3 months after shunt surgery in 35 patients with NPH. Higher ventricular CSF neurofilament protein (NFL), an axonal marker, correlated with more extensive PVH. A larger postoperative reduction in NFL correlated with larger reduction in PVH and a more pronounced overall improvement. Albumin ratio, HMPG, NPY, VIP and GD3 increased postoperatively whereas NFL, tau and HVA decreased. Variations in ventricular size were not associated with CSF concentrations of any marker. We conclude that NPH is characterized by an ongoing periventricular neuronal dysfunction seen on MRI as PVH. Clinical improvement after shunt surgery is associated with CSF changes indicating a restitution of axonal function. Other biochemical effects of shunting may include increased monoaminergic and peptidergic neurotransmission, breakdown of blood brain barrier function, and gliosis. [source] Bifidobacterium longum lysate, a new ingredient for reactive skinEXPERIMENTAL DERMATOLOGY, Issue 8 2010Audrey Guéniche Please cite this paper as: Bifidobacterium longum lysate, a new ingredient for reactive skin. Experimental Dermatology 2010; 19: e1,e8. Abstract:, Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non-replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF-alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3,1%), the probiotic lysate significantly inhibited capsaicin-induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double-blind, placebo-controlled trial. Sixty-six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans-epidermal water loss following barrier disruption induced by repeated tape-stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self-assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin. [source] Functional skin adaptation in infancy , almost complete but not fully competentEXPERIMENTAL DERMATOLOGY, Issue 6 2010Joachim W. Fluhr Please cite this paper as: Functional skin adaptation in infancy , almost complete but not fully competent. Experimental Dermatology 2010; 19: 483,492. Abstract:, Early postnatal life is a period of active functional reorganization and cutaneous physiological adaptation to the extrauterine environment. Skin as the outermost organ of mammalians is endowed of multiple functions such as protection, secretion, absorption and thermoregulation. Birth stimulates the epidermal barrier maturation and the skin surface acidification especially in premature infants. In full-term infants the developed stratum corneum accomplishes competent barrier function, in contrast to prematures. Complete barrier maturation in preterm infants is fulfilled by 2,4 weeks of the postnatal life. However, in preterms with 23,25 weeks gestational age this process takes longer. Versatile regulatory mechanisms, namely skin surface acidity, calcium ion gradient and nuclear hormone receptors/ligands are interrelated in the complex postnatal newborn adaptation. The skin of newborns is adjusting quickly to the challenging environmental conditions of the postpartum. However, certain functions, for example, microcirculation, continue to develop even beyond the neonatal period, that is, up to the age of 14,17 weeks. Different environmental factors (for instance, dry and cold climate, diapers and cosmetic care procedures) influence the postnatal development of skin functional parameters such as stratum corneum hydration and the permeability barrier especially in premature infants. The aim of this article is to summarize the current knowledge on skin physiology in newborn and infants with a practical approach and to discuss the possible clinical consequences. This review offers the readership a critical and practical overview of skin physiology in newborns and infants. It emphasizes possible new research fields in neonatal and infantile skin physiology. [source] Transepidermal water loss reflects permeability barrier status: validation in human and rodent in vivo and ex vivo modelsEXPERIMENTAL DERMATOLOGY, Issue 7 2006Joachim W. Fluhr Abstract:, Permeability barrier function is measured with instruments that assess transepidermal water loss (TEWL), either with closed- or open-loop systems. Yet, the validity of TEWL as a measure of barrier status has been questioned recently. Hence, we tested the validity of this measure by comparing TEWL across a wide range of perturbations, with a variety of methods, and in a variety of models. TEWL rates with two closed-chamber systems (VapoMeter and H4300) and one closed-loop system (MEECO) under different experimental in vivo conditions were compared with data from four open-loop instruments, i.e. TM 210, TM 300, DermaLab and EP 1. The instruments were compared in vivo both in humans and hairless mice skin subjected to different degrees of acute barrier disruption. The values obtained with bioengineering systems were correlated with absolute water loss rates, determined gravimetrically. Measurements with both closed and open systems correlated not only with each other, but each method detected different degrees of barrier dysfunction. Although all instruments differentiated among gradations in TEWL in the mid-range of barrier disruption in vivo, differences in very low and very high levels of disruption were less accurately measured with the H4300 and DermaLab systems. Nevertheless, a high Pearson correlation coefficient (r) was calculated for data from all instruments vs. gravimetrically assessed TEWL. Together, these results verify the utility of TEWL as a measure of permeability barrier status. Moreover, all tested instruments are reliable tools for the assessment of variations in permeability barrier function. [source] Carbohydrate expression and modification during keratinocyte differentiation in normal human and reconstructed epidermisEXPERIMENTAL DERMATOLOGY, Issue 5 2003Bruno Méhul Abstract:, Using fluorescein isothiocyanate (FITC)-labeled lectins we were able to demonstrate the presence of specific carbohydrate moieties in normal human and reconstructed epidermis. Evidence is provided that in both cases the strongly reduced lectin staining at the level of the stratum corneum is the result of a hindered accessibility of the lectins in this lipid-rich hydrophobic environment. Isolated corneocytes and purified cornified envelopes (CEs) exhibited clearly glycosylated structures reacting with distinct lectins. The presence of glycosidase activity, particularly in the upper layers of the epidermis characterized by an acidic environment (pH 5.5), indicates that modifications of the sugar residues might be important in epidermal homeostasis, barrier behavior and desquamation. Absent or strongly reduced glycosidase activity in the stratum corneum of reconstructed epidermis with an impaired pH gradient could be in part responsible for the reduced barrier function and the lack of desquamation in this model. [source] Functional analysis of the sea urchin-derived arylsulfatase (Ars)-element in mammalian cellsGENES TO CELLS, Issue 9 2006Satoshi Watanabe An insulator is a DNA sequence that has both enhancer-blocking activity, through its ability to modify the influence of neighboring cis -acting elements, and a barrier function that protects a transgene from being silenced by surrounding chromatin. Previously, we isolated and characterized a 582-bp-long element from the sea urchin arylsulfatase gene (Ars). This Ars -element was effective in sea urchin and Drosophila embryos and in plant cells. To investigate Ars -element activity in mammalian cells, we placed the element between the cytomegalovirus enhancer and a luciferase (luc) expression cassette. In contrast to controls lacking the Ars -element, NIH3T3 and 293T cells transfected with the element-containing construct displayed reduced luciferase activities. The Ars -element therefore acts as an enhancer-blocking element in mammalian cells. We assessed the barrier activity of the Ars -element using vectors in which a luc expression cassette was placed between two elements. Transfection experiments demonstrated that luc activity in these vectors was approximately ten-fold higher than in vectors lacking elements. Luc activities were well maintained even after 12 weeks in culture. Our observations demonstrate that the Ars -element has also a barrier activity. These results indicated that the Ars -element act as an insulator in mammalian cells. [source] Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic ParkinsonismHELICOBACTER, Issue 4 2005Part 1: Eradication of Helicobacter in the Cachexia of Idiopathic Parkinsonism ABSTRACT Background., Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. Aim., To consider the candidature of Helicobacter in parkinsonism with cachexia. Methods., We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. Results., Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being , 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti- Helicobacter therapy where eradication repeatedly failed (one case), and in non- Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. Conclusion., Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism. [source] Campylobacter and IFN, interact to cause a rapid loss of epithelial barrier integrityINFLAMMATORY BOWEL DISEASES, Issue 3 2008Louisa E.N. Rees PhD Abstract Background: The intestinal epithelium is a single layer of polarized cells and is the primary barrier separating foreign antigen and underlying lymphoid tissue. IFN, alters epithelial barrier function during inflammation by disrupting tight cell junctions and facilitating the paracellular transport of luminal antigens. The aim of this work was to determine whether Campylobacter infection of cells exposed to IFN, would lead to greater disruption of cell monolayers and hence increased bacterial translocation. Methods: Monolayers were polarized on Transwell polycarbonate membranes for 14 days and then cultured in the presence or absence of 100 U/mL IFN,. Campylobacter was added to the apical side of the monolayer at an MOI of 30. Transepithelial electrical resistance (TEER) was recorded and bacteria in the basal well counted every 2 hours. Cells were stained for occludin, actin, and nuclear DNA, and cell viability determined by measurement of apoptosis. Results: In the presence of IFN,, TEER dropped significantly after 18 hours, indicating a reduction in barrier function. A further significant decrease was seen in the presence of both IFN, and Campylobacter, indicating a synergistic effect, and cellular morphology and viability were affected. Bacterial translocation across the monolayer was also significantly greater in the presence of IFN,. Conclusions: These combined effects indicate that Campylobacter infection concomitant with intestinal inflammation would result in a rapid and dramatic loss of epithelial barrier integrity, which may be a key event in the pathogenesis of Campylobacter -mediated colitis and the development of bloody diarrhea. (Inflamm Bowel Dis 2007) [source] Probiotics and the management of inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2004FRCPC, Richard N. Fedorak MD Abstract The demonstration that immune and epithelial cells can discriminate between different microbial species has extended our understanding of the actions of probiotics beyond simple barrier and antimicrobial concepts. Several probiotic mechanisms of action, relative to inflammatory bowel disease, have been elucidated: (1) competitive exclusion, whereby probiotics compete with microbial pathogens for a limited number of receptors present on the surface epithelium; (2) immunomodulation and/or stimulation of an immune response of gut-associated lymphoid and epithelial cells; (3) antimicrobial activity and suppression of pathogen growth; (4) enhancement of barrier function; and (5) induction of T cell apoptosis in the mucosal immune compartment. The unraveling of these mechanisms of action has led to new support for the use of probiotics in the management of clinical inflammatory bowel disease. Though level 1 evidence now supports the therapeutic use of probiotics in the treatment of postoperative pouchitis, only levels 2 and 3 evidence is currently available in support of the use of probiotics in the treatment of ulcerative colitis and Crohn's disease. Nevertheless, one significant and consistent finding has emerged during the course of research in the past year: not all probiotic bacteria have similar therapeutic effects. Rigorously designed, controlled clinical trials are vital to investigate the unresolved issues related to efficacy, dose, duration of use, single or multi-strain formulation, and the concomitant use of prebiotics, synbiotics, or antibiotics. [source] Inducible and constitutive ,-defensins are differentially expressed in Crohn's disease and ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 4 2003Jan Wehkamp Abstract Antimicrobial peptides such as defensins provide nonspecific mucosal defense against a multitude of microorganisms. Recently, it has been shown that luminal bacteria may invade the mucosa in inflammatory bowel diseases, suggesting a defect in innate mucosal immunity. The aim of this study was to investigate the expression of human ,-defensins (HBD) in controls, Crohn's disease (CD), ulcerative colitis (UC), and unspecific inflammation. Up to 4 biopsies were taken from 103 patients (33 controls, 24 with Crohn's disease, 36 with ulcerative colitis, 10 with unspecific colitis). Mucosal mRNA was measured using real-time fluorescence temperature cycler reverse-transcription polymerase chain reaction with primers for HBD-1, HBD-2, HBD-3, tumor necrosis factor ,, and interleukin 8. Mucosal HBD-1 expression was marginally decreased in both CD and UC. HBD-2 was increased exclusively in UC but not in CD. The expression of the novel defensin HBD-3 was strongly correlated with HBD-2 and also raised predominantly in UC. The expression of both inducible ,-defensins was enhanced in the state of inflammation. Expression of HBD-2 showed a weak correlation with interleukin 8 only in inflamed CD biopsies but not with tumor necrosis factor ,. The missing induction of both inducible ,-defensins in CD as compared with UC may cause a defect in barrier function that predisposes to bacterial invasion. [source] Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapyINTERNATIONAL JOURNAL OF CANCER, Issue 2 2003Eiichi Tsuji Abstract Chemotherapy is 1 method for the treatment of cancer, but serious side effects can sometimes limit the dosage given. Mild fever and diarrhea are common side effects of cancer chemotherapy. Gastrointestinal injury induced by chemotherapeutic agents may result in bacterial/endotoxin translocation from the gut into the systemic circulation. An experimental study was therefore conducted to clarify the effect of systemic chemotherapeutic agents on gastrointestinal barrier function. Male Wistar rats were divided into a 5-fluorouracil (5-FU) group (100 mg/kg/day for 4 days; n = 27) and a control group (n = 5). All rats were fasted and central venous catheterization was performed for total parenteral nutrition and blood sampling. Intestinal tissue was also sampled for pathological examination. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor , (TNF,) were determined by ELISA, bacterial translocation was quantified by lymph node culture and plasma endotoxin content of portal blood was measured by the Limulus -amebocyte-lysate test. In the 5-FU group on day 4, a proportion of rats exhibited severe watery diarrhea (73.9%) and occasional vomiting (86.2%). The levels of plasma TNF, and IL-6 were seen to increase, peaking at day 6 (IL-6, 350.0 ± 67.8 pg/ml; TNF,, 26.1 ± 3.2 pg/ml). The pathological findings also changed on day 4. On day 6, 90% of the rats in the 5-FU group showed dramatic sepsis-like manifestations, whereas the control group did not. Within the 5-FU group, only at day 6 was bacterial translocation in the rat mesenteric lymph nodes or significantly elevated levels of endotoxin evident. These results suggest that bacterial/endotoxin translocation might cause sepsis-like manifestations after systemic chemotherapy. © 2003 Wiley-Liss, Inc. [source] Abstracts: The effects of licorice leaf extract on ceramide and hyaluronan synthesisINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2010Akinori Kiso pp.267,273 Both water-holding and permeability barrier function in the stratum corneum (SC) are essential for keeping skin moisture. Intercellular lipids in SC, which are composed mainly of cholesterol, fatty acids, and ceramides, play a crucial role for maintaining the function in SC. The object of our study is to find active ingredients from plant extracts for enhancing the abilities of skin hydration and barrier repair by focusing on the synthesis of ceramides. As a result, we found that licorice leaf extract is a promising ingredient showing not only an increase of mRNA expression levels of serine palmytoyltransferase (SPT) and sphingomyelinase related to ceramide biosynthesis in keratinocytes but also syntheses of ceramides in a 3D skin model and in human skin. Furthermore, licorice leaf extract showed an increase of mRNA expression levels of HMG-CoA reductase (HMGCR) related to cholesterol biosynthesis and an increase of hyaluronan (HA) production in in vitro tests. One of the principles isolated from licorice leaf extract, 6-prenyl-naringenin, was thought to be one of the active components. These results suggested that licorice leaf extract may be a useful ingredient for skin care due to the synthesis of intercellular lipids and HA [source] Location-related differences in structure and function of the stratum corneum with special emphasis on those of the facial skinINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2008H. Tagami Synopsis Between the two different kinds of the skin covering the body, the glabrous skin is found only on the palmo-plantar surface because of its rather simple function to protect the underlying living tissue with its remarkably thick stratum corneum (SC) from strong external force and friction. Thus, its barrier function is extremely poor. In contrast, the hair-bearing skin covers almost all over the body surface regardless of the presence of long hair or vellus hair. In regard to its SC, many dermatologists and skin scientists think that it is too thin to show any site-specific differences, because the SC is just present as an efficient barrier membrane to protect our body from desiccation as well as against the invasion by external injurious agents. However, there are remarkable regional differences not only in the living skin tissue but also even in such thin SC reflecting the function of each anatomical location. These differences in the SC have been mostly disclosed with the advent of non-invasive biophysical instruments, particularly the one that enables us to measure transepidermal water loss (TEWL), the parameter of the SC barrier function, and the one that evaluates the hydration state of the skin surface, the parameter of the water-holding capacity of the SC that brings about softness and smoothness to the skin surface. These in vivo instrumental measurements of the SC have disclosed the presence of remarkable differences in the functional properties of the SC particularly between the face and other portions of the body. The SC of the facial skin is thinner, being composed of smaller layers of corneocytes than that of the trunk and limbs. It shows unique functional characteristics to provide hydrated skin surface but relatively poor barrier function, which is similar to that observed in retinoid-treated skin or to that of fresh scar or keloidal scars. Moreover, there even exist unexpected, site-dependent differences in the SC of the facial skin such as the forehead, eyelid, cheek, nose and perioral regions, although each location occupies only a small area. Between these locations, the cheek shows the lowest TEWL in contrast to the perioral region that reveals the highest one. Moreover, these features are not static but change with age particularly between children and adults and maybe also between genders. Among various facial locations, the eyelid skin is distinct from others because its SC is associated with poor skin surface lipids and a thin SC cell layer composed of large corneocytes that brings about high surface hydration state but poor barrier function, whereas the vermillion borders of the lips that are covered by an exposed part of the oral mucosa exhibit remarkably poor barrier function and low hydration state. Future studies aiming at the establishment of the functional mapping in each facial region and in other body regions will shed light on more delicate site-dependent differences, which will provide us important information in planning the strategy to start so called tailor-made skin care for each location of the body. Résumé Entre les deux types différents de peau couvrant le crops, on trouve la peau glabre uniquement sur la surface palmo-plantaire du fait de sa fonction plutôt simple de protection du tissu vivant sous-jacent par un stratum corneum (SC) trés épais vis-à-vis des forces extérieures et de la friction. De ce fait, sa fonction barrière est extrêmement pauvre. Au contraire, la peau velue courve la presque totalité de la surface du crops, que ce soit par la présence de longs cheveux ou de duvet. En ce qui concerne son SC, la plupart des dermatologues et des scientifiques de la peau pensent qu'il est trop mince pour montrer une différence spécifique au site, attendu que le SC est simplement présent en tant que membrane barriére efficace pour protéger notre corps de la dessiccation ainsi que pour lutter contre l'invasion d'agents nuisibles externes. Cependant, il existe des différences importantes entre les sites, non seulement dans la peau vivante, mais également dans ce SC aussi mince, qui révèlent la fonctin de chaque site anatomique. Ces différences dans le SC ont surtout été révélées avec l'apparition d'instruments biophysiques non invasifs, en particulier celui qui nous permet de mesurer la perte transépidermale en eau (TEWL), le paramétre de la fonction barrière du SC et celui qui évalue l'état d'hydratation de la surface de peau, le paramètre de la capacité en rétention de l'eau du SC qui est liéà la souplesse et à la douceur à la surface de peau. Ces mesures instrumentales in vivo du SC ont révélé la présence de différences remarquables entre les propriétés fonctionnelles du SC particulièrement entre le visage et d'autres parties du corps. Le SC de la peau de la face est plus mince, car li est composé de couches plus petites de corneocytes que celui du tronc et des membres. Il montre des caractéristiques fonctionnelles uniques pour permettre l'hydratation de la surface de peau, mais une fonction barrière relativement faible, semblable à celle observée dans la peau traitée avec un rétinoïde ou à celle d'une cicatrice récente ou de cicatrices kéloidales. De plus, il existe des différences sites-dépendantes inattendues dans le SC de la peau de la face comme le front, la paupière, la joue, le nez et les régions périorales, et ce, bien que chaque emplacement occupe seulement un petit secteur. Entre ces divers emplacements, la joue montre le TEWL le plus bas par comparaison avec la région périorale qui montre le plus élevé. De plus, ces caractéristiques ne sont pas fixes, mais changent avec l'âge en particulier entre enfants et adultes et peut-être aussi entre sexes. Entre les diverses régions de la face, la peau de la paupière se distingue parce que son SC est associéà une peau pauvre en lipides de surface constituée par une mince couche de cellule composée de grand cornéocytes qui provoquent un haut état d'hydratation superficiel, mais une faible fonction barrière. A l'inverse les bordures vermillion des lévres recouvertes par une partie exposée de muqueuse orale, possèdent une fonction barrière très faible et un état d'hydratation bas. Les études futures visant àétablir la configuration fonctionnelle de chaque région de la face et d'autres régions du corps mettrons en lumière des différences sites-dépendantes plus subtiles, qui nous fourniront des informations importantes pour planifier la stratégie pour commencer le soin de la peau sur mesure si attendu pour chaque partie du corps. [source] Is the axilla a distinct skin phenotype?INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1 2007A. Watkinson The axillary skin is cosmetically important with millions of consumers daily applying antiperspirant/deodorant products. Despite this, we know virtually nothing about axillary skin or how antiperspirant use impacts upon it. To characterize axillary stratum corneum and determine whether this is a unique skin type, we have evaluated a range of skin parameters, comparing these with the volar forearm. Trans-epidermal water loss and corneosurfametry revealed a reduced barrier function in the axilla. However, application of antiperspirant had no effect upon these barrier properties. High performance thin layer chromatography analysis of stratum corneum lipids demonstrated statistically elevated levels of fatty acids, ceramide and particularly cholesterol in the axilla. This modification of barrier lipid ratios appeared to result in a more ordered lipid lamellae phase behaviour, as determined by attenuated total reflectance Fourier transform infrared spectroscopy, with transition phase changes occurring at higher temperatures. Morphological differences were also seen in the cells of the axillary stratum corneum. Microscopic evaluation of axillary-cornified envelopes revealed them to be smaller, indicative of a shorter stratum corneum turnover. However, there appeared to be no significant difference corneocyte maturation. ,Skin dryness' squamometry measurements indicated that the axillary stratum corneum retained desquamated material on its surface more than on the forearm. This correlated with decreased levels of the desquamatory stratum corneum chymotryptic enzyme in the surface layers of the skin. These results indicate that the axilla has a distinct phenotype. Paper presented at the 22nd IFSCC Congress 2002, Edinburgh, Scotland [source] Ethnic skin types: are there differences in skin structure and function?,INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2006A. V. Rawlings Synopsis People of skin of colour comprise the majority of the world's population and Asian subjects comprise more than half of the total population of the earth. Even so, the literature on the characteristics of the subjects with skin of colour is limited. Several groups over the past decades have attempted to decipher the underlying differences in skin structure and function in different ethnic skin types. However, most of these studies have been of small scale and in some studies interindividual differences in skin quality overwhelm any racial differences. There has been a recent call for more studies to address genetic together with phenotypic differences among different racial groups and in this respect several large-scale studies have been conducted recently. The most obvious ethnic skin difference relates to skin colour which is dominated by the presence of melanin. The photoprotection derived from this polymer influences the rate of the skin aging changes between the different racial groups. However, all racial groups are eventually subjected to the photoaging process. Generally Caucasians have an earlier onset and greater skin wrinkling and sagging signs than other skin types and in general increased pigmentary problems are seen in skin of colour although one large study reported that East Asians living in the U.S.A. had the least pigment spots. Induction of a hyperpigmentary response is thought to be through signaling by the protease-activated receptor-2 which together with its activating protease is increased in the epidermis of subjects with skin of colour. Changes in skin biophysical properties with age demonstrate that the more darkly pigmented subjects retaining younger skin properties compared with the more lightly pigmented groups. However, despite having a more compact stratum corneum (SC) there are conflicting reports on barrier function in these subjects. Nevertheless, upon a chemical or mechanical challenge the SC barrier function is reported to be stronger in subjects with darker skin despite having the reported lowest ceramide levels. One has to remember that barrier function relates to the total architecture of the SC and not just its lipid levels. Asian skin is reported to possess a similar basal transepidermal water loss (TEWL) to Caucasian skin and similar ceramide levels but upon mechanical challenge it has the weakest barrier function. Differences in intercellular cohesion are obviously apparent. In contrast reduced SC natural moisturizing factor levels have been reported compared with Caucasian and African American skin. These differences will contribute to differences in desquamation but few data are available. One recent study has shown reduced epidermal Cathepsin L2 levels in darker skin types which if also occurs in the SC could contribute to the known skin ashing problems these subjects experience. In very general terms as the desquamatory enzymes are extruded with the lamellar granules subjects with lowered SC lipid levels are expected to have lowered desquamatory enzyme levels. Increased pores size, sebum secretion and skin surface microflora occur in Negroid subjects. Equally increased mast cell granule size occurs in these subjects. The frequency of skin sensitivity is quite similar across different racial groups but the stimuli for its induction shows subtle differences. Nevertheless, several studies indicate that Asian skin maybe more sensitive to exogenous chemicals probably due to a thinner SC and higher eccrine gland density. In conclusion, we know more of the biophysical and somatosensory characteristics of ethnic skin types but clearly, there is still more to learn and especially about the inherent underlying biological differences in ethnic skin types. Résumé, Les gens qui ont une peau de couleur représentent la majorité de la population mondiale et les sujets asiatiques en représentent plus de la moitié. Pourtant la littérature consacrée aux caractéristiques de ces sujets est limitée. Plusieurs groupes de travail ont essayé au cours des dernières années de comprendre les différences sous-jacentes de la structure et de la fonction de la peau de différentes ethnies. Maisla plupart de ces études ont été réalisées à petite échelle et dans certains cas les différences observées entre les individus au niveau de la qualité de la peau ne font pas ressortir de différence entre races. Récemment, un besoin d'études reliant les diffèrences génétiques et phénotypiques entre différents groupes raciaux s'est fait sentir et de ce fait beaucoup d'études à grande èchelle ont été entreprises. La différence la plus évidente, entre les peaux ethniques, est leur couleur liée à la présence de la mélanine. La photoprotection induite par ce polymère influence le taux de vieillissement de la peau entre les différents groupes raciaux qui finalement sont tous sujets au processus de photovieillissement. Généralement, les caucasiens ont des signes plus précoces et plus importants de formation de rides et de relâchement de la peau; en général, les problèmes d'augmentation de la pigmentation sont observés sur les peaux de couleur, bien qu'une grande étude ait rapporté que des sujets originaires de l'Asie de l'Est vivant aux U.S.A. avaient le moins de taches pigmentaires. On pense que la réponse d'une induction hyperpigmentaire est due à un signal envoyé par le récepteur 2 activé par une protéase. Le récepteur 2 augmente en même temps que la protéase activatrice dans l'épiderme des sujets ayant une peau de couleur. Les changements dans les propriètés biophysiques de la peau en fonction de l'âge montrent que les sujets qui ont la pigmentation la plus sombre gardent une peau plus jeune par comparaison aux groupes qui possèdent une pigmentation moins forte. Toutefois, bien qu'ayant un stratum corneum plus compact, il existe des rapports divergents sur la fonction barrière de ces sujets. Dans le cas d'agression chimique ou mécanique, la fonction barrière du stratum corneum est considérée plus forte chez les sujets à peau plus foncée, malgré leurs taux plus faibles encéramide. On doit garder à l'esprit que la fonction barrière du stratum corneum dépend de toute son architecture et pas seulement de sa teneur en lipides. On considère que la peau asiatique à unePIE (TEWL) basale similaire à la peau caucasienne, ainsi que des taux en céramides comparables, mais on constate que dans le cas d'agression mécanique, elle possède un effet barrière le plus faible. Des différences dans la cohésion intercellulaire sont évidentes. A contrario, on a mis en évidence des taux d'hydratation (NMF) plus faibles dans son stratum corneum, comparativement à la peau caucasienne et afro-américaine. Ces différences expliquent les variations au niveau de la desquamation, mais on a très peu de données sur ce sujet. Une étude récente a mis en évidence des taux réduits de Cathepsin L2 dans l'épiderme des types de peau plus sombre, ce qui, si cela se produisait dans le stratum corneum, expliquerait les problèmes biens connus de cendrage de la peau que ces sujets connaissent. En terme très gènéral, étant donné que les enzymes liées à la desquamation sont libérées avec les granules lamellaires, on s'attend à ce que les sujets ayant des taux de lipides faibles dans le stratum corneum aient des taux d'enzymes liés à la desquamation faibles. On constate chez les sujets noirs une augmentation de la taille des pores, de la sécrétion du sébum et de la microflore cutanée. On observe également chez ces sujets une augmentation de la taille des granules mastocellulaires. Le phénomène de peau sensible se retrouve à une fréquence similaire dans les différents groupes raciaux, mais il existe des différences subtiles dans lesstimuli nécessaires pour l'induire. En tout cas, plusieurs études montrent que la peau asiatique est peut-être plus sensible aux produits chimiques exogènes, ce qui probablement est dûà un stratum corneum plus mince et à une densité de glandes eccrines plus élevées. En conclusion, c'est sur les caractéristiques biophysiques et somato-sensorielles des différents types de peaux ethniques que nous en savons plus, mais il est clair qu'il nous reste à comprendre encore beaucoup de choses principalement sur leurs différences biologiques. [source] Influence of environmental stress on skin tone, color and melanogenesis in Japanese skinINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1 2005K. Kikuchi Introduction It is needless to say that one of the most potent environmental stress for melanogenesis of the human skin is the effect of ultraviolet (UV) light from the sunlight. Characteristic skin aging as a result of this UV light is recognized as photoaging. Clinical features in photoaging are wrinkles, skin laxity, coarseness, leathery, yellowing, lentigenes, mottled pigmentation, telangiectasia, sebaceous hypertrophy and purpura. There is an apparent difference in clinical features in photoaging among different races, i.e. between Caucasians, African American and Asians that include Japanese. Not only photo skin type but also environmental factors, such as climate, latitude, altitude and their habit of sunbathing, smoking and skin care influence the characteristic development of their photoaging. Racial difference in photoaging Caucasians tend to develop skin laxity and fine wrinkles more than Asians [1]. Asians tend to produce coarser wrinkles than the Caucasians although their development is rather late in life. There is also a difference in the skin color. Pigmentation is an earliest and prominent skin changes in Asians [1] and it increases with age [2]. In contrast, pigmentation is not apparent in the Caucasians although redness probably because of an increase in cutaneous vascularization becomes prominent in middle aged Caucasians [2]. Chung reported that seborrheic keratosis is a major pigmentary lesion in men, whereas hyperpigmented macules are prominent features in women in Koreans [3]. Melanogenesis pigmentation disorders in Japanese Ephelides (freckles) are commonly found in those with photo skin type I who have fair skin and red eyes and blond hair. They are also found in the Japanese. Clinical feature reveals that multiple small pigmentary macules on sun-exposed areas mainly on the mid-portion of the face. These lesions seem to be familial, becoming apparent even in early childhood after sun exposure. Melasma is an acquired pigmentary disorder commonly found in middle aged Japanese women characterized by irregular brown macules and patches on the sun-exposed areas on the face typically as bilaterally present macules on the cheeks. An increase in sex hormones as a result of pregnancy and intake of contraceptive pills is one of the etiological factors to develop melasma. Sun exposure also worsens it. Nevus of Ota is also a common pigmentary disorder found in the Japanese. It is usually unilateral, blue-brown to slate-gray pigmentary macules on the eyelid and cheek that appear in early childhood or in puberty. Acquired dermal melanocytosis is also a pigmentary disorder, in which dermal melanocytes are found as shown in nevus of Ota, characterized by bilateral brown to blue-gray macules on the forehead, temple, eyelid and malar areas in middle aged Japanese women. This tends to be misdiagnosed as melasma. Solar lentigo is an acquired pigmented macule induced by sun exposure. Solar lentigines are usually multiple, circumscribed brown macules. There are two types of solar lentigo. One is a small macular type, characterized by multiple, small brown macules whose diameter is less than 5 mm, being similar to ephelides (freckles). The other type is a large macular type, characterized by a few round to oval, brown macules whose diameter is beyond 1 cm. Some of their surface are hyperkeratotic and become elevated to produce seborrheic keratosis. Again, the early sign of photoaging in Japanese is pigmentated spots and these pigmentation disorders increase with age. Among the pigmentary changes, nevus of Ota, acquired dermal melanocytosis, melasma and large macular type of solar lentigo are characteristic skin changes found in the Japanese in addition to ephelides and small macular type of solar lentigo. Seasonal changes of the various functional properties of the skin including skin color assessed by non-invasive bioengineering techniques [4]. When we consider skin tone, color and melanogenesis, UV light from the sunlight is the most potent environmental stress, although we cannot forget also the important influence of environmental relative humidity affects our skin functions as well as its appearance. We investigated seasonal influences on the various properties of the skin in 39 healthy Japanese females consisting of different age groups. Their skin is thought to be affected by the UV light in summer, and by the exposure to the dry and cold air in winter. Materials and methods Biophysical, non-invasive measurements, including transepidermal water loss (TEWL) as a parameter for the barrier function of the stratum corneum (SC), high frequency conductance as a parameter for the hydration state of the SC, skin color and casual surface lipid levels, were conducted during late summer and winter months. Skin color was determined with a chromameter according to the L*a*b* CIE 1976 system, where L* is an attribute on the luminance scale, a* that on the red versus green scale and b* that on the yellow versus blue scale. All the measurements were conducted in an environment controlled-chamber (21 ± 1 °C room temperature, and 50 ± 3% relative humidity). Results The barrier function of the SC was found to be significantly impaired in winter on the cheek as compared with that measured in summer, whereas no such seasonal change was apparent both in the hydration state of the SC and sebum levels on the cheek. In the assessment of the skin color on the cheek, a significant increase in a* (redness) and a decrease in b* (yellowness) were observed in winter. In contrast, on the flexor forearm, the values of L* (luminescence) increased in winter, but no seasonal change was noted in the values of a* and b*. In this study, skin changes with aging were also found by the non-invasive bioengineering methods. The value of TEWL on the cheek tended to increase with age, whereas no significant change was observed in the value of TEWL on the forearm. In the assessment of skin color, b* value on the cheek significantly increased with age whereas a* and L* values on the cheek did not show any significant change with age. Summary of this study We think that such an increase in yellowness with aging of the cheek skin is a phenomenon unique to the Japanese (Asians) since an increase in b* value was not observed in Caucasians [2]. The facial skin that is always exposed shows barrier impairment in a dry and cold winter environment and demonstrates increased yellowness in skin color because of a prolonged exposure to the UV light from the sun in the summer season. The non-invasive bioengineering methods are useful to demonstrate even invisible seasonal changes occurring in the same individuals and changes with age occurring in the skin. References 1.,Goh, S.H. The treatment of visible signs of senescence: the Asian experience. Br. J. Dermatol.122, 105,109 (1990). 2.,LeFur, I., Numagami, K., Guinot, C. et al. Age-related reference values of skin color in Caucasian and Japanese healthy women according to skin site. Pigment Cell Res. 7, 67 (1999). 3.,Chung, J.H., Lee, S.H., Youn, C.S. et al. Cutaneous photodamage in Koreans: influence of sex, sun exposure, smoking, and skin color. Arch. Dermatol. 137, 1043,1051 (2001). 4.,Kikuchi, K., Kobayashi, H., Le Fur, I. et al. Winter season affects more severely the facial skin than the forearm skin: comparative biophysical studies conducted in the same Japanese females in later summer and winter. Exog. Dermatol. 1, 32,38 (2002). [source] A 7-step consultation plan for health care workers and hairdressersJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 9 2007Stephanie Soost Summary Background: Skin diseases are among the most common occupational disor-ders in health care workers and hairdressers. Optimal prevention methods make it possible for more individuals to remain active in their profession. We devised a 7-step consultation plan which was employed in a standard fashion and then evaluated. Patients and Methods: 264 employes were evaluated in the Education and Support Center of the German Accident Prevention and Insurance Association in the Health and Welfare Services (BGW schu.ber.z Berlin) from 2003 to 2005 in a standardized manner. Included were detailed history, physical examination, skin physiology measurements (transepidermal water loss, corneometry, sebumetry) and then making a diagnosis and therapeutic recommendations. Results: Within the study group of 264 employes the most frequent diagnosis were toxic-irritant hand eczema (28.4%), allergic contact eczema (19.7%), atopic eczema (15.5%) and irritant contact eczema with atopic diathesis (13.6%). The frequency of contact sensitivity was high in the study group (80.7%). The skin physiological parameters were not remarkably altered and did not differ between individuals with an atopic diathesis versus without an atopic diathesis. Conclusion: This standardized protocol for a "7-step consultation plan"when applied in a standardized manner offers quality-controlled but also individually-adapted support considering dermatological, educational and occupational aspects. Skin physiology parameters did not provide any further information indicating the need of the development of novel techniques to measure skin barrier function. [source] Toxicologic implications of cutaneous barriers: a molecular, cellular, and anatomical overviewJOURNAL OF APPLIED TOXICOLOGY, Issue 7 2009Abraar Karan Abstract The skin barrier is a complex system of chemical, biological and physical processes that together regulate the admission and expulsion of foreign agents in contact with the skin. The eggresive movement of the stratum corneum (SC) is often a measure of its integrity, and transepidermal water loss has typically been a gold standard. However, the skin barrier has several barrier systems, such as ion flux, O2, CO2 and pH, which can give an informative and sometimes more sensitive measure of the SC condition. Furthermore, the penetrative interactions with the barrier have focused around occlusive methods to promote drug delivery, the interactions of topically applied drugs with the barrier and the presence of environmental agents that can harm the barrier. However, the nature of penetrative barrier interactions must also be elucidated on a microscopic level. The variable nature of barrier function is demonstrated when comparing the skin properties of neonates and adults. In addition, new biochemical methods have used keratin metrics to improve diagnostic efficacy and barrier integrity analysis. This review addresses the aforementioned aspects of the skin barriers that require further study to help discern the complexity of this essential organ as it relates to dermatotoxicology and dermatopharmacology. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cadmium accumulation and binding characteristics in intact Sertoli/germ cell units, and associated effects on stage-specific functions in vitro: insights from a shark testis modelJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2008Leon M. McClusky Abstract The increased human use of cadmium (Cd) and its increased occurrence in the environment is of concern. The testis is sensitive to Cd because of the steroid-mediated regulation of spermatogenesis, high levels of DNA synthesis and gene transcription, all of which varies in a stage-related manner. Validated techniques (acridine orange vital staining to detect apoptosis and dextran-rhodamine exclusion to assess blood,testis barrier function) were recently developed and the shark testis was proposed as an alternative model for assessing stage-specific functions in living testicular tissue and to study toxicant actions on spermatogenesis. The present paper shows that 109Cd accumulation and binding in vitro was stage-dependent (premeiotic, PrM > meiotic, M > postmeiotic, PoM), rapid and persisted in spermatocysts (intact germ cell/Sertoli cell units) 49 h after washout. In competitive binding analyses of all three spermatocyst stages, Hg, but not Zn, could replace bound 109Cd, suggesting that Cd binding was specific. These findings were associated with a biphasic apoptotic response in the PrM spermatocysts, which was maximal at 10 µm CdCl2 and 1 µm CdCl2 after 2 and 4 days in culture, respectively. Although Cd uptake in PoM cysts was more than 2-fold less than uptake in PrM cysts, the percentage dextran-rhodamine permeant PoM cysts was ,8-fold greater than in controls in the presence of both 10 µm CdCl2 and 30 µm CdCl2 after 4 days culture, indicating that blood,testis barrier function in PoM spermatocysts was compromised. These findings demonstrate that this model has utility for use in screening assays of environmental toxicants. Copyright © 2007 John Wiley & Sons, Ltd. [source] In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epitheliumJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2009D. R. De Vries Abstract Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6,12% and SAP , 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P -value < 1E, 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell,cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function. [source] Caldesmon is a cytoskeletal target for PKC in endotheliumJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2006Natalia V. Bogatcheva Abstract We have previously shown that treatment of bovine endothelial cell (EC) monolayers with phorbol myristate acetate (PMA) leads to the thinning of cortical actin ring and rearrangement of the cytoskeleton into a grid-like structure, concomitant with the loss of endothelial barrier function. In the current work, we focused on caldesmon, a cytoskeletal protein, regulating actomyosin interaction. We hypothesized that protein kinase C (PKC) activation by PMA leads to the changes in caldesmon properties such as phosphorylation and cellular localization. We demonstrate here that PMA induces both myosin and caldesmon redistribution from cortical ring into the grid-like network. However, the initial step of PMA-induced actin and myosin redistribution is not followed by caldesmon redistribution. Co-immunoprecipitation experiments revealed that short-term PMA (5 min) treatment leads to the weakening of caldesmon ability to bind actin and, to the lesser extent, myosin. Prolonged incubation (15,60 min) with PMA, however, strengthens caldesmon complexes with actin and myosin, which correlates with the grid-like actin network formation. PMA stimulation leads to an immediate increase in caldesmon Ser/Thr phosphorylation. This process occurs at sites distinct from the sites specific for ERK1/2 phosphorylation and correlates with caldesmon dissociation from the actomyosin complex. Inhibition of ERK-kinase MEK fails to abolish grid-like structure formation, although reducing PMA-induced weakening of the cortical actin ring, whereas inhibition of PKC reverses PMA-induced cytoskeletal rearrangement. Our results suggest that PKC-dependent phosphorylation of caldesmon is involved in PMA-mediated complex cytoskeletal changes leading to the EC barrier compromise. J. Cell. Biochem. 99: 1593,1605, 2006. © 2006 Wiley-Liss, Inc. [source] Selective induction of mucin-3 by hypoxia in intestinal epitheliaJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2006Nancy A. Louis Abstract Epithelial cells line mucosal surfaces (e.g., lung, intestine) and critically function as a semipermeable barrier to the outside world. Mucosal organs are highly vascular with extensive metabolic demands, and for this reason, are particularly susceptible to diminished blood flow and resultant tissue hypoxia. Here, we pursue the hypothesis that intestinal barrier function is regulated in a protective manner by hypoxia responsive genes. We demonstrate by PCR confirmation of microarray data and by avidin blotting of immunoprecipitated human Mucin 3 (MUC3), that surface MUC3 expression is induced in T84 intestinal epithelial cells following exposure to hypoxia. MUC3 RNA is minimally detectable while surface protein expression is absent under baseline normoxic conditions. There is a robust induction in both the mRNA (first evident by 8 h) and protein expression, first observed and maximally expressed following 24 h hypoxia. This is followed by a subsequent decline in protein expression, which remains well above baseline at 48 h of hypoxia. Further, we demonstrate that this induction of MUC3 protein is associated with a transient increase in the barrier restorative peptide, intestinal trefoil factor (ITF). ITF not only colocalizes with MUC3, by confocal microscopy, to the apical surface of T84 cells following exposure to hypoxia, but is also found, by co-immunoprecipitation, to be physically associated with MUC3, following 24 h of hypoxia. In exploration of the mechanism of hypoxic regulation of mucin 3 expression, we demonstrated by luciferase assay that the full-length promoter for mouse Mucin 3 (Muc3) is hypoxia-responsive with a 5.08,±,1.76-fold induction following 24 h of hypoxia. Furthermore, analysis of both the human (MUC3A) and mouse (Muc3) promoters revealed potential HIF-1 binding sites which were shown by chromatin immunoprecipitation to bind the pivotal hypoxia-regulating transcription factor HIF-1,. Taken together, these studies implicate the HIF-1, mediated hypoxic induced expression of mucin 3 and associated ITF in the maintenance of intestinal barrier function under hypoxic conditions. J. Cell. Biochem. 99: 1616,1627, 2006. © 2006 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||