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Background Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC). Objectives To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity. Methods We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped. Results Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm–1 (full width half maximum) and 1340 cm–1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = –0.59, carboxylate peak area r = –0.50). Conclusions ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies. [ABSTRACT FROM AUTHOR]

Introduction: Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin. Methods: The assessment for local severity of AD was done with the Scoring Atopic Dermatitis Index (SCORAD) and skin dryness was assessed by capacitance measurement. Results: The results showed that the test product lowered skin pH and improved AD skin lesions from moderate to mild during 2 weeks of application. In the treated area a lowered pH of about 0.85 units was found. Together with the lowering of pH, the local SCORAD significantly improved from 8.3 on average down to 4.0, while in the untreated area, only a slight improvement (from 8.2 to 6.4) was found. Conclusion: Synergistic effects of the test product's pH lowering and emollient properties might explain the observed improvements in clinical signs of AD and further research against a comparator would allow the specific contribution of pH modulation to these improvements to be unambiguously isolated. [ABSTRACT FROM AUTHOR]

Background: Washing hands with soap and lukewarm water for 20 s is a fundamental measure advocated especially within the UK to help control the spread of viral disease. However, these practices can induce irritant contact dermatitis, particularly in healthcare professionals (HCPs). HCPs typically manage their condition by replacing soap or alcohol-based hand sanitizers with cleansers containing mild surfactants and/or emollient ingredients [skin-friendly cleansers (SFCs)] to mitigate skin damage and/or using topical emollients after washing for repair. Despite this widespread practice, there is very limited evidence supporting the efficacy of these interventions in the prevention of viral propagation. Methodology: Within this study a range of viruses comprising human coronavirus (HCoV), herpes simplex virus (HSV)-1, influenza (IVA), adenovirus (Ad), and murine norovirus (MNV) were tested against multiple hand wash products, including SFCs. In vitro analysis using plaque assays and tissue culture infectious dose 50 (TCID50) were used to assess virus infectability after incubation with the test products (soaps and SFCs) over a range of concentrations and time points. Transmission electron microscopy (TEM) was used to determine virus architecture and size, while viral replication genes were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results/conclusions: Enveloped viruses demonstrated greater susceptibility over a range of test products, suggesting some SFCs are a suitable alternative to soap (depending on the presence of a viral envelope). However, no virucidal activity was observed for non-enveloped viruses. Water type (i.e., soft/hard) and pre-exposed hand hygiene conditions (i.e., clean/dirty) made little difference to the effectiveness of both soaps and SFCs. Therefore, new hand hygiene regimens should be implemented based on trying to encompass all viruses with varying structures, with specific emphasis on the absence of a viral envelope. [ABSTRACT FROM AUTHOR]

The article discusses the role of emollients in preventing atopic dermatitis (AD) and the mixed results from studies on this topic. The article highlights a recent study by Rehbinder et al. that examined the effects of emollient intervention on the skin barrier in babies. The study found that the intervention had a disruptive effect on the condition of the skin barrier, which was unexpected. The article also mentions that some emollients can harm the skin and discusses their different effects on corticosteroid uptake and cutaneous sensitivity to irritants. Despite the mixed results, the article suggests that there is still potential for exploring the use of barrier-enhancing emollients in preventing AD. [Extracted from the article]

Skin irritancy to topically applied chemicals is a significant problem that affects millions of people worldwide. New or modified chemical entities must be tested for potential skin irritancy by industry as part of the safety and toxicity profiling process. Many of these tests have now moved to a non‐animal‐based format to reduce experiments on animals. However, these tests for irritancy potential often rely on monolayer cultures of keratinocytes that are not representative of the skin architecture or tissue‐engineered human skin equivalents (HSE) using complex multi‐gene expression panels that are often cumbersome and not amenable for high throughput. Here, we show that human skin equivalents increase abundance of several phosphorylated kinases (c‐Src, c‐Jun, p53, GSK3α/β) in response to irritant chemical stimulation by phosphokinase array analysis. Specific phosphorylation of c‐SrcY419 was confirmed by immunoblotting and was plasma membrane‐associated in basal/spinous cells by phospho‐specific immunohistochemistry. Moreover, c‐SrcY419 phosphorylation in response to the irritants lactic acid and capsaicin was inhibited by the c‐Src inhibitors KB‐SRC and betaine trimethylglycine. These data provide the first evidence for c‐Src specific activation in response to chemical irritants and point to the development of new modes of rapid testing by immunodetection for first‐pass screening of potential irritants. This study demonstrates that specific kinases, in particular c‐Src, are activated in HSE in response to chemical irritants. The rapid increase in specific phosphorylated signal transduction molecules upon exposure to irritants may prove ideal targets to rapidly identify and differentiate potential chemical irritants from non‐irritants. [ABSTRACT FROM AUTHOR]

Summary: Background: Eczema (atopic dermatitis; AD) is a very common itchy skin condition affecting 1 in 5 children and up to 1 in 10 adults worldwide. The skin of eczema sufferers is prone to redness, irritation and dryness because it does not form an effective barrier, i.e. the ability of the skin to stop irritants, allergens and microorganisms getting into the body. Skin barrier dysfunction is a hallmark of AD. The regular and liberal (600 g/week for an adult) use of emollients is recommended for all patients with eczema), even between episodes of itching and redness, to soften and soothe the skin. In England alone, almost 9 million prescriptions for emollient creams were issued in 2018, at a cost of over £50 million. Despite this widespread use, relatively little is known about how commonly prescribed emollient creams affect the skin's barrier, and thus the role of moisturizers in AD development and progression remains unclear. We set out to compare three different types of emollient cream and a no‐treatment control. Aim: To compare the barrier‐strengthening properties of a new moisturizer containing urea and glycerol (urea–glycerol cream; UGC), with those of a glycerol‐containing moisturizer (glycerol cream; GC), a simple paraffin cream (PC) with no humectant, and a no‐treatment control (NTC). Methods: This was an observer‐blinded prospective Phase 2 within‐subject multilateral single‐centre randomized controlled trial in adults with AD (Clinical Trials #NCT03901144). The intervention involved 4 weeks of treatment, twice daily, with the three products applied to one of four areas on the forearms the (the fourth area was the untreated control, randomized allocation). Skin properties [dryness, transepidermal water loss (TEWL), hydration and natural moisturizing factor (NMF) levels] were assessed before, during and after treatment to see what happened to the skin's barrier. The primary outcome was skin sensitivity to the irritant sodium lauryl sulfate (SLS) after treatment. We performed tests on the skin before and after treatment to see what happened to the skin's barrier. Results: In total, 49 patients were randomized, completed treatment and included in the analysis. UGC significantly reduced the response to SLS as indicated by a reduction in TEWL compared with NTC (−9.0 g/m2/h; 95% CI −12.56 to −5.49), with PC (−9.0 g/m2/h; 95% CI −12.60 to −5.44) and with GC −4.2 g/m2/h; 95% CI 7.76 to −0.63). Skin moisturization improved at sites treated with UGC compared with NTC and PC, and this was accompanied by concordant changes in dryness and NMF levels. Subgroup analysis suggested FLG‐dependent enhancement of treatment effects. Conclusion: The study showed that not all emollient creams for eczema are equal. The simple paraffin‐based emollient, which represents the most widely prescribed type of emollient cream in England, had no effect on the skin's barrier and reduced the skin's NMF. UGC markedly improved the skin's barrier and protected against irritation. GC performed better than PC, but not as well as UGC. UGC strengthened the skin barrier through a mechanism involving increased NMF levels in the skin, and imparted protection from SLS‐induced irritation. By helping correct a major pathophysiological process, UGC has the potential to improve the long‐term control of AD. The results show that different emollient creams have different effects on our skin, and only certain types have the ability to improve the skin's barrier and protect against irritants that trigger eczema. [ABSTRACT FROM AUTHOR]

Summary: Background: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. Objectives: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation. Methods: A randomized observer‐blind intrapatient‐controlled study in 34 adults with dry, eczema‐prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier‐transform infrared spectroscopy using a novel interface. Results: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve −162, 95% confidence interval (CI) −206 to −118]. Skin sensitivity to sodium lauryl sulfate was reduced (−0·5 points visual redness, 97·57% CI −1·00 to −0·25), as was transepidermal water loss (−15·3 g m−2 h−1, 95% CI −20·3 to −10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61–10·6) and decreased signs of dryness. Conclusions: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin. [ABSTRACT FROM AUTHOR]

A topical vehicle is a 'carrier system' for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its own as an emollient to ameliorate dry skin. It is well established that the vehicle plays an important role in determining the bioavailability of a given drug at its ultimate target within the skin. Yet in the treatment of atopic eczema/dermatitis (AD), wherein the structure and function of the skin's outer barrier play a pivotal role in the development and course of the condition, the interaction of the vehicle with this barrier carries a particular importance. It is now clear that the often-considered inert excipients of a vehicle bring about changes within the skin at the molecular level that promote barrier restoration and enhance innate immune defenses with therapeutic value to AD patients. Moreover, the vehicle control in randomized controlled trials (RCTs) increasingly displays significant efficacy. In light of this, we consider the implications of vehicle design in relation to AD pathophysiology and the role vehicles play as controls in RCTs of new drug treatments for this condition. [ABSTRACT FROM AUTHOR]

Nevertheless, we share the authors' caution over corneometer measurements, and included visual skin dryness scoring in this study and have included additional measures of skin water content in our second study [[4]]. The authors offer evidence of the inferiority of the test products compared with another glycerol-containing but non-skin lipid/ceramide-containing product in the form of a single figure in a review article. The authors suggest that "The skin capacitance measures give the expected hydration improvements... due to the presence of glycerol in the products based upon its dielectric constant". [Extracted from the article]

Background: Hard domestic water has been reported to worsen atopic eczema (AE) and may contribute to its development in early life. Objective: To review the literature on the relationship between the effect of water hardness (high calcium carbonate; CaCO3) on (a) the risk of developing AE, (b) the treatment of existing AE and (c) skin barrier function in human and animal studies. Design , data sources and eligibility criteria: We systematically searched databases (MEDLINE, Embase, Cochrane CENTRAL, GREAT and Web of Science) from inception until 30/6/2020. Human and animal observational and experimental studies were included. The primary outcomes were risk of AE and skin barrier function. Studies were meta‐analysed using a random effects model. Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: Sixteen studies were included. Pooled observational data from seven studies on 385,901 participants identified increased odds of AE in children exposed to harder versus softer water (odds ratio 1.28, 95% CI 1.09, 1.50; GRADE certainty: very low). Two mechanistic studies in humans reported higher deposition of the detergent sodium lauryl sulphate in those exposed to harder versus softer water. Two randomized controlled trials comparing water softeners with standard care did not show a significant difference in objective AE severity with softened water (standardized mean difference 0.06 standard deviations higher, 95% CI 0.16 lower to 0.27 higher; GRADE certainty: moderate). Conclusions & Clinical Relevance: There was a positive association between living in a hard water (range: 76 to > 350 mg/L CaCO3) area and AE in children. There is no evidence that domestic water softeners improve objective disease severity in established AE. There may be a role of water hardness in the initiation of skin inflammation in early life, but there is a need for further longitudinal and interventional studies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin condition associated with a significant health-related and socioeconomic burden, and is characterized by intense itch, disruption of the skin barrier, and upregulation of type 2-mediated immune responses. The United Kingdom (UK) has a high prevalence of AD, affecting 11–20% of children and 5–10% of adults. Approximately 2% of all cases of childhood AD in the UK are severe. Despite this, most AD treatments are performed at home, with little contact with healthcare providers or services. Here, we discuss the course of AD, treatment practices, and unmet need in the UK. Although the underlying etiology of the disease is still emerging, AD is currently attributed to skin barrier dysfunction and altered inflammatory responses. Management of AD focuses on avoiding triggers, improving skin hydration, managing exacerbating factors, and reducing inflammation through topical and systemic immunosuppressants. However, there is a significant unmet need to improve the overall management of AD and help patients gain control of their disease through safe and effective treatments. Approaches that target individual inflammatory pathways (e.g. dupilumab, anti-interleukin (IL)-4 receptor α) are emerging and likely to provide further therapeutic opportunities for patient benefit. [ABSTRACT FROM AUTHOR]

Recently, there has been some evidence of an increased incidence of food allergy in infants regularly applying some types of emollients. Considering that emollient vehicles can modify the delivery of 'actives' into the skin, it is important to examine their effects on epicutaneous sensitization to environmental allergens. The aim was to determine the effects of regular emollient use on cutaneous reactions to house dust mite allergen. An observer-blind within-participant multilateral controlled interventional study in 40 adults with confirmed house dust mite allergy was carried out. Participants underwent 4 weeks of treatment with olive oil, coconut oil and a basic emollient cream (no added moisturizers) applied to three different areas of both forearms with a fourth area left as a no-treatment control (NTC). At the end of treatment, skin barrier integrity was assessed by performing transepidermal water loss (TEWL) measurements in conjunction with tape-stripping. At adjacent locations, atopy patch tests (APTs) using house dust mite allergen were performed. This interim analysis includes data from the first 16 participants. Skin barrier integrity was reduced by all three treatments relative to NTC as indicated by elevated TEWL [mean (SD) olive oil 35.10 (15.17), coconut oil 36.56 (17.17) and emollient cream 39.18 (20.91) vs. NTC 28.76 (13.06) g m–2 h–1; P < 0.05]. Pretreatment of the skin had a significant effect on APT reactions (P = 0.0401, graded from 0 to 4). The strongest reactions were seen following pretreatment with emollient cream [2.31 (1.12)], olive oil [2.22 (0.91)] and coconut oil [1.94 (0.91)] vs. NTC [1.50 (0.80)]. These preliminary results suggest that some commonly used emollients decrease skin barrier integrity and increase the severity of reactions to house dust mite allergens. This implies that regular use of emollients that damage the skin may directly affect allergy development arising from epicutaneous sensitization. Some sophisticated emollients (with moisturizers) have been shown to improve skin barrier function. Clinical trials are therefore needed to determine if they impart protection against epicutaneous sensitization. [ABSTRACT FROM AUTHOR]

Skin physiology is dynamically changing over the first years of postnatal life; however, ethnic variations are still unclear. The aim of this study was to characterize infant skin barrier function, epidermal structure, and desquamation-related enzymatic activity as compared to that of adult skin in an East Asian population. The skin properties of 52 infants (3-24 months) and 27 adults (20-40 years) were assessed by noninvasive methods at the dorsal forearm and upper inner arm. Transepidermal water loss and skin surface conductance values were higher and more dispersed for infants compared to adults. Infant skin surface pH was slightly lower than adult on the dorsal forearm. The infant SC and viable epidermis were thinner compared to adults with differences that were site-specific. Although the chymotrypsin-like activity for infant skin was comparable to adult level, the caseinolytic specific activity was significantly higher for the infant cohort. These observations indicate a differently controlled pattern of corneocyte desquamation in infants. In conclusion, structural and functional differences exist between infant and adult skin in the East Asian population pointing to dynamic maturation of the epidermal barrier early in life. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common disorder characterized by skin barrier defects often measured by traditional biophysical tools that give little molecular insight into disease pathogenesis. The objective was to employ in vivo infrared spectroscopy as a complimentary technique to biophysical measurements to analyse changes in the chemical composition of the stratum corneum (SC) in relation to AD severity. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside transepidermal water loss (TEWL), skin surface pH and capacitance in a cohort of 75 participants, stratified by AD severity. Skin tape stripping was performed to allow measurements at greater SC depth. The five common filaggrin (FLG) loss-of-function mutations were genotyped. Skin hydration, TEWL and redness were all affected by AD severity with molecular analysis showing concomitant changes in lipid structure, and the amount of lipid, polyamide and carboxylate. Correlation analysis showed associations between Eczema Area and Severity Index and lipid structure (r = –0.58), as well as amount of carboxylate (r = –0.49). Principal component analysis showed spectra collected on participants with AD lesions or FLG mutations clustered away from healthy and nonlesional skin sites. Our findings showed that ATR-FTIR spectroscopy is able to characterize structural skin barrier defects in people with AD vs. controls. Spectral peak analysis showed associations between defective lipid and natural moisturizing factor (NMF) components with worsening disease severity. Through combined assessment of peaks associated with lipid structure and carboxylate amount, we have shown the potential of ATR-FTIR in identifying filaggrin deficiency, through either genetic predisposition (FLG mutations) or through inflammatory action, which is related to the presence of NMFs in the SC, skin hydration and overall severity of AD. [ABSTRACT FROM AUTHOR]

Xerosis affects up to 75% of older people and develops as a result of a skin barrier defect. Emollients are widely used to treat xerosis; however, there is limited understanding of the differences between them and their effects on the skin barrier in older people. This study aimed to compare the effect of a commercially available emollient containing 5% urea, ceramide NP and lactate (test emollient) to an alternative emollient without these additives (control emollient) on the properties of the skin barrier in older people. Two cohorts of 21 volunteers aged >60 years with dry skin were recruited. The first applied the test emollient to one forearm and no treatment to the other for 28 days. The second compared the test emollient to the control emollient observing the same parameters. Effects on the skin barrier were determined by measuring skin barrier function, hydration, skin surface pH and by analysing Fourier transform infrared spectra before and after treatment. A third cohort of 6 young adults was re-cruited to investigate the effect of a single treatment with the test emollient on the molecular structure of the skin barrier at greater depths by employing the tape-stripping technique. The test emollient hydrated the skin to a significantly greater extent and for a longer period of time compared to the control emollient, an effect associated with a significant elevation of carboxylate groups (a marker of natural moisturizing factor content) within the stratum corneum. Furthermore, the test emollient imparted additional benefits to the structure and function of the skin barrier not exhibited by the control emollient. In conclusion, the test emollient addressed the pathological features of xerotic aged skin, supporting its use as first-line therapy for xerotic skin conditions in this population. [ABSTRACT FROM AUTHOR]

Topical oils on baby skin may contribute to development of childhood atopic eczema. A pilot, assessor-blinded, randomized controlled trial assessed feasibility of a definitive trial investigating their impact in neonates. Onehundred and fifteen healthy, full-term neonates were randomly assigned to olive oil, sunflower oil or no oil, twice daily for 4 weeks, stratified by family history of atopic eczema. We measured spectral profile of lipid lamellae, trans-epidermal water loss (TEWL), stratum corneum hydration and pH and recorded clinical observations, at baseline, and 4 weeks post-birth. Recruitment was challenging (recruitment 11.1%; retention 80%), protocol adherence reasonable (79-100%). Both oil groups had significantly improved hydration but significantly less improvement in lipid lamellae structure compared to the no oil group. There were no significant differences in TEWL, pH or erythema/skin scores. The study was not powered for clinical significance, but until further research is conducted, caution should be exercised when recommending oils for neonatal skin. [ABSTRACT FROM AUTHOR]

The proactive use of topical anti-inflammatory (TAI) therapy to address subclinical inflammation is an effective, contemporary clinical strategy for the management of atopic dermatitis (AD). The interaction of a proactive TAI dose with the subclinical epidermal barrier defect in AD is yet to be determined. A randomised, observerblind, functional mechanistic study in 17 subjects with quiescent AD was performed to compare the effect of a twice-weekly dose of betamethasone valerate (0.1%) cream (BMVc), against tacrolimus (0.1%) ointment (TACo) on the biophysical and biological properties of the epidermal barrier. Application of BMVc preserved epidermal barrier function and stratum corneum (SC) integrity, but significantly elevated skin-surface pH with concomitant loss of SC cohesion. By contrast, TACo improved SC integrity, exerted an overall hydrating action, and significantly reduced caseinolytic and trypsin-like protease activity. The differential effects reported support the proactive use of TACo to promote reparation of the subclinical barrier defect in AD. [ABSTRACT FROM AUTHOR]

Olive oil is commonly recommended by health professionals to new parents for use in the prevention and treatment of the term baby's dry skin, and for baby massage. There is no evidence to support this practice. The use of olive oil may be harmful to skin, affecting skin barrier function. This effect may be a contributory factor in the prevalence of childhood conditions such as atopic eczema. This paper discusses a national online audit of UK maternity hospitals (n = 67) and neonatal units (n = 33) performed between November 2010 and January 2011. Our findings confirm that oil use on babies' skin is common practice. As the direct cost to the NHS for treatment of atopic eczema is high, it is imperative that further research in this area is performed, preferably in the form of a randomized controlled trial. Health professionals will then be in a position to provide accurate information to parents with regard to oil in baby skin care regimens. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a multifactorial, heterogenous disease that arises as a result of the interaction between both environmental and genetic factors. Changes in at least three groups of genes encoding structural proteins, epidermal proteases, and protease inhibitors predispose to a defective epidermal barrier and increase the risk of developing AD. Loss-of-function mutations found within the FLG gene encoding the structural protein, filaggrin, represent the most significant genetic factor predisposing to AD identified to date. Enhanced protease activity and decreased synthesis of the lipid lamellae lead to exacerbated breakdown of the epidermal barrier. Environmental factors, including the use of soap and detergents, exacerbate epidermal barrier breakdown, attributed to the elevation of stratum corneum pH. A sustained increase in pH enhances the activity of degradatory proteases and decreases the activity of the lipid synthesis enzymes. The strong association between both genetic barrier defects and environmental insults to the barrier with AD suggests that epidermal barrier dysfunction is a primary event in the development of this disease. Our understanding of gene−environment interactions should lead to a better use of some topical products, avoidance of others, and the increased use and development of products that can repair the skin barrier.Journal of Investigative Dermatology (2009) 129, 1892–1908; doi:10.1038/jid.2009.133; published online 4 June 2009 [ABSTRACT FROM AUTHOR]

Breakdown of the skin barrier is the first event in the development of atopic eczema (atopic dermatitis). Research over the past five years has indicated that this arises as a result of the interaction of environmental agents such as soap and other detergents with the products of changes in several genes. These genetic changes predispose to the breakdown of the skin barrier, which allows the penetration of allergens, triggering a flare of atopic eczema. This new understanding of how breakdown of the skin barrier is the first event in the development of atopic eczema provides a rationale for a renaissance in the use of a complete emollient therapy regimen in atopic eczema and related skin barrier breakdown diseases, such as asteatotic eczema and irritant contact dermatitis. [ABSTRACT FROM AUTHOR]

Intrinsic antimicrobial resistance of Escherichia coli is elicited by the gene products of the multidrug efflux acrAB-tolC operon. In this paper, we have shown that acrAB is regulated as a function of the growth rate of E. coli during growth in batch and chemostat culture. In chemostat culture, expression of acrAB is inversely related to growth rate irrespective of the limiting nutrient. The level of expression of acrAB is greater under glucose limitation compared with either iron or nitrogen limitation. Increase in expression of acrAB confers a greater resistance to ciprofloxacin, and the implications for a clinical situation are discussed. Slow growth rate regulation of acrAB transcription does not require the presence of the stationary-phase sigma factor. A putative gearbox consensus sequence was identified at the −10 region of the acrAB promoter. [Copyright &y& Elsevier]