Atopic Dermatitis and the Stratum Corneum: Part 3: The Immune System in Atopic Dermatitis

Part 3 of this three-part review of atopic dermatitis and the stratum corneum barrier discerns how immune dysregulation, including upregulation of a TH2 inflammation pattern, augmented allergic sensitization, sustained wound healing inflammation, and impaired innate immunity, plays an integral role in the pathogenesis of atopic dermatitis. An increased understanding of the interdependence, polymorphisms, and dysregulations of epidermal barrier functions, including the stratum corneum permeability barrier, immune defense, and antimicrobial barriers, should provide further knowledge about the pathophysiological mechanisms that are clinically relevant and that contribute to the development of atopic dermatitis. Further understanding of these mechanisms should lead to newer therapies that target specific pathogenic components of atopic dermatitis.     

Atopic Dermatitis and the Stratum Corneum: Part 1: The Role of Filaggrin in the Stratum Corneum Barrier and Atopic Skin

This three-part review presents what is currently known about the involvement and interdependency of the barrier properties of the epidermis, especially the stratum corneum and various specific immunological responses in the etiopathogenesis of atopic dermatitis. Part 1 of this review depicts the role of filaggrin in atopic dermatitis while Part 2 (which will be published in an upcoming issue of The Journal of Clinical and Aesthetic Dermatology) evaluates the role of serine proteases and specific lipids in the structural and functional integrity of the stratum corneum and related barrier functions in atopic dermatitis. Filaggrin is a key component of the stratum corneum that is derived from a larger precursor protein and contributes to its physical strength, hydration status, skin pH, and buffering capacity among other physiochemical properties. Filaggrin gene loss of function mutations appear to play a pathophysiological role; however, they are not the sole pathogenic factor in atopic dermatitis. Adverse structural changes of the stratum corneum are caused by upregulation of serine proteases activity, which causes degradation of certain stratum corneum proteins that are integral to barrier functions; interference with the formation of the stratum corneum intercellular lipid membrane, which normally regulates epidermal water flux and gradient; and induction of a TH2 pattern of inflammation, which is characteristic of atopic skin. Alteration in lipid ratios and changes in lipid-directed enzymes may play a role in the impairment of epidermal barrier functions that are associated with atopic dermatitis. Part 3 of this review (which will be published in an upcoming issue of The Journal of Clinical and Aesthetic Dermatology) discusses how immune dysregulation, including upregulation of a TH2 inflammation pattern, augmented allergic sensitization, sustained wound healing inflammation, and impaired innate immunity all play a role in the development of atopic dermatitis. An increased understanding of the interdependence, polymorphisms, and dysregulations of epidermal barrier functions, including the stratum corneum permeability barrier, immune response barrier, and antimicrobial barrier, should provide further knowledge about the pathophysiological mechanisms that are related to the development of atopic dermatitis, are clinically relevant, and can better direct researchers to develop therapies that are targeted at important pathogenic components of the disease state.     

Investigation of Antinuclear Antibodies in Canine Atopic Dermatitis

Serum samples from 40 atopic dogs and 20 healthy dogs were assayed for antinuclear antibodies (ANA) using a human epithelial cell line (HEp‐2) and standard indirect immunofluorescent methods. Samples from the atopic dogs were grouped according to the presence (n=28) or absence (n=12) of facial lesions at any moment during the follow‐up period. Positive ANA titres were found in 10 of the 40 atopic dogs analysed (25 %) whereas samples from the control group were negative. Eight atopic dogs with facial lesions had a positive titre (28.57 %) in contrast with atopic dogs without facial lesions where two positive samples (16.67 %) were found; however, the differences were statistically not significant. Endpoint titres were low (1/40), only two samples yielded a 1/80 positive titre and one sample had a 1/320 titre, all of them from the facial lesions group. Response to immunotherapy was classified as positive only in four of the 10 ANA‐positive patients (40 %) compared with a response rate of 73 % (22 of 30) in the ANA‐negative atopic dogs. However, a Fisher’s exact test showed a two‐sided P‐value of 0.122 which was considered statistically not significant. The overall response rate to immunotherapy for all atopic dogs was 65 % (26 of 40). In conclusion, the prevalence of ANA is higher in atopic than in healthy dogs, especially if facial lesions are present. Although a clinically significant pathogenic contribution is not probable, this higher prevalence should be taken into account in the differential diagnosis of canine autoimmune dermatitis.     

儿童特应性皮炎的发病机制与临床研究进展

特应性皮炎（atopic dermatitis,AD）是临床常见的儿童皮肤病,具有治疗周期长、发作反复等特 征,对儿童的成长发育造成负面影响。有关AD发病机制目前尚未得出统一定论,普遍认为AD的发生与遗 传、过敏、免疫等因素有关,而病因的复杂性进一步增加了该疾病治疗的难度。此外,儿童AD的表现不 一,皮疹形态及分布各不相同,增加了临床诊断的难度。本文将对儿童AD的发病机制及其药物治疗方法 作一综述,以供未来临床治疗参考。     

Gender Differences in Self-assessed Health-related Quality of Life in Children with Atopic Dermatitis

Background: Atopic dermatitis has a significant impact on quality of life of children and families. Objective: It is important to assess gender differences in health-related quality of life in children with atopic dermatitis in order to effectively use health-related quality of life results. Methods: Children 5- to 16-years of age with atopic dermatitis from Italy, Singapore, Czech Republic, and Ukraine were divided into two groups (boys and girls). Each child in the group of boys was matched to a corresponding child in the group of girls from the same country whose age and scoring atopic dermatitis value were almost identical. Self-assessed health-related quality of life was measured by the Children’s Dermatology Life Quality Index. Results: The difference in overall Children’s Dermatology Life Quality Index between boys and girls was not significant (P=0.33). Girls with atopic dermatitis assessed Children’s Dermatology Life Quality Index item on embarrassment significantly higher (0.78±0.93 for boys and 1.14±0.93 for girls, P<0.05). Lowest scored items were the same and overall Children’s Dermatology Life Quality Index results significantly correlated with scoring atopic dermatitis values in both groups. Two separate Children’s Dermatology Life Quality Index items in boys and five items in girls significantly correlated with atopic dermatitis severity. The Children’s Dermatology Life Quality Index item on affected sleep significantly correlated with the age of boys (r=0.38, P=0.02) and another Children’s Dermatology Life Quality Index item on school work/holiday with the age of girls (r=0.59, P<0.01). Conclusion: Despite that the authors did not find differences in overall health-related quality of life results, girls were more embarrassed, self-conscious, upset, and sad because of atopic dermatitis. The authors’ results may influence the educational part of consultations of children with atopic dermatitis.Atopic dermatitis (AD) has a significant impact on the quality of life (QoL) of affected children and their families.1-3 As in adults, childhood health-related (HR) QoL is commonly assessed by means of generic and/or specific instruments, including dermatology-specific and disease-specific measures.4 Measurement of HRQoL in pediatric dermatology helps to assess the impact of a single skin disease on a child’s life, to register the patient’s view on the efficacy of different treatment methods, educational programs, and consultations. It makes it possible to compare the impact of skin diseases and results of the treatment in children from different age groups on local, regional, national, and international levels.5 The vast majority of publications concerning HRQoL assessment in children with skin conditions is dedicated to AD.4 For the effective use of HRQoL results, it is important to know about existing gender differences in HRQoL assessment.Contradictory results concerning gender differences in HRQoL of children with AD under four years measured by the Infant’s Dermatitis Quality of Life Index (IDQoL) questionnaire were previously reported. Park et al6 found more severe impact of AD on boys in 48 non-matched boys and 53 girls. Meanwhile, Alzolibani7 did not find gender differences in non-matched AD children. Chernyshov8 also had not found a significant gender difference of the overall IDQoL scores in 102 non-matched AD children, but found significant gender differences when each child in the group of boys was matched to a corresponding child in the group of girls whose age in months and scoring atopic dermatitis (SCORAD) value were almost identical.8Open in a separate windowFigure 1.CDLQI results in boys and girls with atopic dermatitisKiebert et al9 found a significant gender difference in self-assessed HRQoL of older children with AD. The Children’s Dermatology Life Quality Index (CDLQI) scores were significantly higher in girls in that study. Hon et al10 and Ang et al11 reported that girls had more problems with issues of clothes and shoes than did boys10 and had higher scores on the swimming and other sports item.11 Recently, the authors did not find significant gender differences in self-assessed HRQoL of non-matched children from Ukraine, Italy, Czech Republic, and Singapore.12In this study, the authors decided to analyze gender differences in self-assessed HRQoL of children with AD matched by country, age, and disease severity.     

Daily Application of Fluocinonide 0.1% Cream for the Treatment of Atopic Dermatitis

Objective: To assess the efficacy and safety of topical fluocinonide 0.1% cream for the treatment of atopic dermatitis. Design: In this double-blind, vehicle-controlled study, patients were randomized to receive treatment with fluocinonide 0.1% cream applied once (n=109) or twice daily (n=102) or vehicle applied once (n=50) or twice daily (n=52) for two weeks. Setting: Multicenter, outpatient. Participants: Patients aged 18 years or older with atopic dermatitis affecting at least two percent but less than 10 percent of body surface area. Measurements: Efficacy and safety measures included lesion severity, pruritus, hypothalamic-pituitary-adrenal axis suppression, and adverse events. Results: Fluocinonide 0.1% cream applied once or twice daily was more effective than cream vehicle. Both regimens were similarly efficacious after two weeks of treatment. At the end of treatment, lesions were cleared or almost cleared in 59 percent of subjects treated once daily and 57 percent of subjects treated twice daily with fluocinonide 0.1% cream. Further, considerable residual benefit remained after cessation of twice-daily versus once-daily treatment. Skin safety evaluations showed no significant adverse effects of treatment on signs or symptoms of skin atrophy. Fluocinonide 0.1% cream and vehicle treatments did not differ significantly in their suppression of the hypothalamic-pituitary-adrenal axis, nor did hypothalamic-pituitary-adrenal axis suppression differ significantly following once- or twice-daily treatment with fluocinonide 0.1% cream. Fluocinonide 0.1% cream was well tolerated. Conclusion: Once- or twice-daily topical application of fluocinonide 0.1% cream for 14 days was safe and effective for treating atopic dermatitis in this adult patient population. The efficacy of once-daily application was comparable to twice-daily application.Atopic dermatitis is a chronic disease with acute flare-ups and periods of remission. It is often the first manifestation of a group of allergic disorders that includes asthma, allergic rhinitis, and food allergy.^1,2 Both genetic and environmental factors influence development of the disease.³ Approximately 10 to 20 percent of children and 1 to 3 percent of adults are diagnosed with atopic dermatitis.² The disease develops during the first 12 months of life in 75 percent of children who are affected and clears completely at, or shortly after, puberty in 40 to 60 percent^4,5; however, atopic dermatitis may persist in more than 20 percent of adolescents, and up to 17 percent of adults may experience the onset of atopic dermatitis after adolescence.^6,7The clinical presentation of atopic dermatitis varies with age and disease activity.^2,5,8,9 In children between two years of age and puberty, the exudative lesions observed in infancy are less common.^2,9 Rather, lesions tend to be more chronic and characterized by severe pruritus with excoriations and lichenified papules and plaques and involve the hands, feet, wrists, ankles, and antecubital and popliteal regions.^2,5 After puberty and continuing into adulthood, main areas of involvement include the flexural folds; face and neck; upper arms and back; and the dorsa of the hands, feet, fingers, and toes.^2,5 Dry, scaling, erythematous papules and plaques are characteristic, and large lichenified plaques are formed as the lesions become more chronic.^2,5 Although weeping, crusting, and exudation may occur, these findings are usually due to staphylococcal skin infection.⁵Managing atopic dermatitis requires a multifactorial approach that includes regular use of emollients and skin hydration, antipruritic therapy, topical anti-inflammatory agents, identification and elimination of possible triggers, and systemic antibiotic treatment if widespread secondary bacterial infection, mainly due to Staphylococcus aureus, is present.^2,9 For more than 40 years, topical corticosteroids have been a key component of the management of atopic dermatitis¹⁰ and continue to be important agents, particularly for the control of acute flare-ups.⁹ In addition to their anti-inflammatory effect, the use of topical steroids reduces skin colonization with S. aureus.^9,11Topical corticosteroid formulations ranging from low potency to super potency are available.⁵ Recent guidelines recommend using low- to mid-potency topical corticosteroids for the treatment of mild-to-moderate atopic dermatitis and more potent preparations for moderate-to-severe disease and for patients with lichenified plaques.⁹ The general rule has been to use the least potent, most effective topical corticosteroid for the treatment of atopic dermatitis. A possible disadvantage of using a lower-potency preparation initially is that this may fail to improve or even worsen the disease, resulting in poor treatment adherence.¹² An emerging strategy is to “hit hard and hit fast” by initiating treatment with a mid- or high-potency topical corticosteroid (except for lesions on the face, axillae, or groin) to gain rapid control of the disease, and then maintain improvement with a low-potency preparation, or to use a potent preparation intermittently (e.g., twice weekly or two consecutive days each week) to reduce flares.^12,13The optimal dosage frequency of topical corticosteroids in atopic dermatitis has not been fully evaluated and remains unclear^14,15; however, twice-daily (BID) application, the most commonly recommended regimen based on approved product labeling of many topical corticosteroids, has evolved empirically over time.^14,15 Frequency of application is an important clinical consideration, as it is likely to be a major factor influencing patient adherence to treatment. Data from 76 studies indicate that the rate of adherence with BID dosing is lower than with once-daily (QD) dosing (69% vs. 79%).¹⁶ A recent systematic review of the literature comparing QD versus BID application of topical corticosteroids identified only seven randomized, controlled trials of the same active compound and three comparing different agents of the same potency that met the inclusion criteria of the review.¹⁴ It was concluded that the efficacy of the same potency topical corticosteroids used QD and BID was similar and did not favor one regimen over another¹⁴; however, an earlier, similar systematic review concluded that, in the absence of clear evidence from randomized, controlled trials to support BID over QD topical corticosteroid application, initiating therapy in all patients with a QD regimen would be reasonable.¹⁰ It was also noted that the vehicle used in the topical formulation may enhance efficacy, and that when two treatments are equally effective, the cosmetic acceptability of one vehicle over another may facilitate long-term use.¹⁰Fluocinonide 0.1% cream, a super-potent topical corticosteroid, is currently available in the United States. Although this formulation contains a two-fold higher concentration of fluocinonide than what is found in earlier products (0.05%), the vehicle characteristic of the cream allows for marked retention of the active ingredient in the stratum corneum, epidermis, and dermis, with a lesser propensity for systemic absorption.¹⁷ Additionally, the cream vehicle is similar to a conventional ointment base in that its water content is very low (<1%); however, it is devoid of the greasiness of an ointment.¹⁷ Similar to the other available super-potent topical corticosteroids, with the exception of clobetasol propionate 0.05% formulations, fluocinonide 0.1% is approved for QD or BID application.¹⁸The following Phase 3 clinical trial was undertaken to evaluate the efficacy and safety of fluocinonide 0.1% cream compared to vehicle when applied topically QD or BID for two weeks for the treatment of adults with atopic dermatitis.     

基于特应性皮炎积分的针对性护理对婴儿期特应性皮炎患儿的影响

目的 探讨对婴儿期特应性皮炎（AD）患儿采取基于特应性皮炎积分（SCORAD）的针对性护理干预的效果。方法 选择广元市第一人民医院2020年9月-2023年2月收治的48例婴儿期AD患儿为研究对象,按照随机数字表法分为对照组和观察组,每组24例。对照组给予常规护理,观察组在对照组的基础上给予基于SCORAD的针对性护理,比较两组睡眠质量、临床症状积分及护理满意度。结果 两组干预后PSQI评分均低于干预前,且观察组低于对照组（P ＜0.05）;两组干预后皮损范围、皮损严重程度、主观症状、综合评分均低于干预前,且观察组低于对照组（P ＜0.05）;观察组患儿家属的护理满意度为95.83%,高于对照组的70.83%（P ＜0.05）。结论 对婴儿期AD患儿采用基于SCORAD的针对性护理干预的效果良好,可有效减轻患儿的临床症状,改善其睡眠质量,有利于促进康复,提升患儿家属对护理服务的满意度。     

Atopic Dermatitis and the Stratum Corneum: Part 2: Other Structural and Functional Characteristics of the Stratum Corneum Barrier in Atopic Skin

This three-part review presents what is currently known about the involvement and interdependency of the epidermal barrier and immune response in the etiopathogenesis of atopic dermatitis. Part 1 of this review depicted the role of filaggrin in atopic dermatitis while this article, Part 2, evaluates the role of serine proteases and specific lipids in the structural and functional integrity of the stratum corneum and its multiple barrier functions in atopic dermatitis. Upregulation of serine protease activity causes adverse structural changes of the stratum corneum due to degradation of certain stratum corneum proteins that are integral to epidermal structure and functions, interference with the formation of the stratum corneum intercellular lipid membrane, which normally regulates epidermal water flux and gradient, and induction of a TH2 pattern of inflammation, which is the hallmark profile of atopic skin. Alteration in lipid ratios and changes in lipid-directed enzymes may play a role in the impairment of barrier functions that are associated with atopic dermatitis. In Part 3, immune dysregulation, including upregulation of a TH2 inflammation pattern, augmented allergic sensitization, sustained wound healing inflammation, and impaired innate immunity are discussed. The roles of the stratum corneum permeability barrier, the immune defense barrier, and antimicrobial barrier in AD pathogenesis are explained in detail. With this explanation, the interdependence of the multitude of polymorphisms and dysregulations seen in AD skin will become clear. The condensing of these impaired and/or dysregulated functions and how they interact should provide further knowledge about the pathogenic mechanisms that cause atopic dermatitis, how they are clinically relevant, and how they may assist in developing more specific therapies directed at the pathogenesis of atopic dermatitis.     

Evaluating Clinical Use of a Ceramide-dominant, Physiologic Lipid-based Topical Emulsion for Atopic Dermatitis

Objectives: The objective of this study was to evaluate the efficacy of a ceramide-dominant, physiologic lipid-based topical emulsion, inclusive of ceramides, cholesterol, and fatty acids in a 3:1:1 ratio, in the clinical practice setting in subjects with mild-to-moderate atopic dermatitis. The included subjects presented with a wide range of demographic characteristics thus building upon the results reported with this agent from an earlier clinical trial in atopic dermatitis subjects. In addition, the utility of this important treatment approach of starting with a product directed at epidermal barrier repair was explored. Methods: In a 50-center, open-label, interventional study, the ceramide-dominant, physiologic lipid barrier repair emulsion was evaluated for three weeks in 207 patients either as monotherapy or in combination with another atopic dermatitis treatment. Outcome measures included investigator global assessment, investigator and subject satisfaction, subject-perceived improvement in atopic dermatitis, pruritus severity, and two quality-of-life questions. Results: Overall, approximately half of the subjects achieved success with investigator global assessment (clear or almost clear investigator global assessment scores) after three weeks of treatment with the ceramide-dominant, physiologic lipid barrier repair emulsion as monotherapy or in combination with another treatment. A large proportion of subjects (75% of subjects) and investigators (for 77% of subjects) reported satisfaction after three weeks of treatment. Pruritus and quality of life improved during the study. Conclusion: The ceramide-dominant, physiologic lipid-based product was shown to be an effective agent, with or without additional topical therapy, to provide good clinical efficacy and high levels of investigator and patient satisfaction for many patients with mild-to-moderate atopic dermatitis. The results of this study are consistent with results noted in a previous study of atopic dermatitis patients using this same barrier repair agent. The treatment approach of using a skin barrier repair cream as an integral and standard component of initial atopic dermatitis therapy, either as monotherapy or as a part of combination topical therapy, is supported by the outcomes observed in this study. This specific ceramide-dominant, physiologic lipid-based product may be used when initiating topical therapy for atopic dermatitis based on results from this and other studies.     

海藻酸钠修护敷料联合他克莫司软膏辅助治疗儿童特应性皮炎的临床疗效

目的 探究海藻酸钠修护敷料联合他克莫司软膏辅助治疗儿童特应性皮炎的应用效果。方法 选 择2022年1月-12月于我院就诊的儿童特应性皮炎患者64例,随机分为对照组和观察组,各32例。对照组 采用他克莫司软膏治疗,观察组在此基础上加用海藻酸钠修护敷料治疗,比较两组临床疗效、不良反 应发生情况、生活质量、睡眠质量、皮损面积、疼痛评分及皮肤屏障相关指标。结果 观察组治疗总有 效率为93.75%,高于对照组的84.38%（P ＜0.05）;观察组不良反应发生率为9.38%,低于对照组的18.75% （P ＜0.05）;观察组生活质量评分为（85.47±8.62）分,高于对照组的（74.62±6.14）分（P ＜0.05）;观 察组皮损面积为（18.74±2.61）mm2,低于对照组的（25.47±3.58）mm2（P ＜0.05）;观察组疼痛评分为 （2.74±0.28）分,低于对照组的（4.52±0.56）分（P ＜0.05）;观察组治疗后角质层含水量及皮脂含量均 高于对照组（P ＜0.05）。结论 儿童特应性皮炎患者应用海藻酸钠修护敷料联合他克莫司软膏治疗,能够 提高临床疗效,改善生活质量、睡眠质量,缩小皮损面积,减轻疼痛感,修复皮肤屏障,减少不良反应发 生情况,值得临床应用。     

基于 CiteSpace 可视化分析中医药治疗特应性皮炎的研究热点

目的 对中医药治疗特应性皮炎的相关文献进行计量与可视化分析,探讨其研究热点和发展趋 势,为其治疗提供一定参考。方法 以中国知网数据库（CNKI）为数据源检索2010年6月-2022年6月中医 药治疗特应性皮炎相关文献,利用CiteSpace 6.1.R2软件对关键词进行共现分析、聚类分析和突现分析,并 绘制相关图谱。结果 共纳入文献361篇,涉及的关键词有中药、儿童、龙牡汤、临床观察、辨证论治、临 床研究、针刺、生活质量、中医药、中医证型、中药药浴、中医。热点关键词为儿童、辨证论治、生活质 量、龙牡汤。聚类分析所产生的主要聚类有儿童、血虚风燥、龙牡汤、辨证分型、心火、生活质量等。突 现强度位于前3位的关键词为龙牡汤、针刺、中医药,其次分别为用药规律、辨证论治、中药、湿疮、血 虚风燥、健脾化湿等。结论 中医药治疗特应性皮炎的研究热点集中在儿童、血虚风燥、龙牡汤、辨证分 型、心火、生活质量等方面。     

Multifaceted Role of Rho Proteins in Angiogenesis

The Rho family of GTPases is part of the Ras superfamily. The Rho, Rac, and Cdc42 members of the family are present in mammalian cells and have been the subject of attention of researchers due to their vast spectrum of functions. Rac 1, Cdc42, and RhoA are well-known for their role in the regulation of the actin cytoskeleton in promoting the formation of lamellipodia, filopodia, and stress fibers, respectively. The Rho proteins also participate in the control of cell growth, motility, cell–cell adhesions, morphogenesis, cytoskeletal dynamics, and cellular trafficking. The mechanisms for eliciting these functions have become clearer during the last decade. Concordant with their roles in multiple processes of cellular control, the Rho proteins have been shown to be involved in tumor growth, progression, metastasis, and now angiogenesis.The authors acknowledge support for this work from NIH CA-77612, the Burroughs Wellcome Fund and the Breast Cancer Research Foundation.     

0.03% 他克莫司软膏联合舒缓保湿修护霜治疗儿童特应性皮炎的效果及安全性

目的 探究0.03%他克莫司软膏联合舒缓保湿修护霜治疗儿童特应性皮炎的临床效果及安全性。 方法 选取2020年8月30日-2021年8月30日我院收治的64例儿童特应性皮炎患者为研究对象,采用随机数字表 法分为观察组和对照组,各32例。对照组给予0.03%他克莫司软膏及凡士林软膏治疗,观察组给予0.03%他克 莫司软膏联合舒缓保湿修护霜治疗,比较两组皮炎严重程度[特应性皮炎（SCORAD）评分]、临床疗效、不 良反应发生情况及复发情况。结果 观察组治疗2、4周后SCORAD评分均低于对照组（P＜0.05）;观察组治 疗总有效率93.75%,高于对照组的68.75%（P＜0.05）;两组不良反应发生率及复发率比较,差异无统计学意 义（P＞0.05）。结论 0.03%他克莫司软膏联合舒缓保湿修护霜治疗儿童特应性皮炎的效果良好,可有效改善 患儿的临床症状,减轻皮炎严重程度,且不会增加不良反应发生率及复发率,用药安全性较高。     

Randomized Controlled Trial of Desonlde Hydrogel 0.05% versus Desonide Ointment 0.05% in the Treatment of Mild-to-moderate Atopic Dermatitis

Objective: Desonide hydrogel 0.05%, an effective treatment for mild-to-moderate atopic dermatitis, is United States Food and Drug Administration approved as a treatment for patients as young as three months of age. Previous studies have also demonstrated that this hydrogel formulation of desonide 0.05% improved moisturization and reduced transepidermal water loss. Increased skin hydration has been correlated with improved and sustained integrity of the epidermal barrier in patients with atopic dermatitis. The objective of this clinical noninferiority study was to compare the efficacy of desonide hydrogel 0.05% with desonide ointment 0.05%, the clinical standard for the treatment of mild-to-moderate atopic dermatitis. Design and setting: Randomized, investigator-blinded, parallel-group, noninferiority study in an outpatient setting. Participants: Individuals 12 years of age and older with atopic dermatitis. Measurements: Outcome measures included disease severity, body surface area involvement, subjective assessments of symptoms, corneometry, transepidermal water loss, and the patient's preference for vehicle attributes. Patients were assessed at Baseline, Week 2, and Week 4. Results: Desonide hydrogel 0.05% was shown, through visual grading assessments and noninvasive instrumentation measurements, to be as effective as generic desonide ointment 0.05% in reducing the signs and symptoms of mild-to-moderate atopic dermatitis in patients aged 12 to 65 years during a four-week period. In addition, patients rated desonide hydrogel significantly better than desonide ointment for absorbability and (lack of) greasiness. Conclusion: Desonide hydrogel, which uses a hydrogel vehicle, was preferred by patients and shown to restore the skin barrier, thus offering an efficacious alternative to desonide ointment.     

The Role of Prenylated Small GTP-Binding Proteins in the Regulation of Osteoclast Function

The Ras superfamily of small GTP-binding proteins (also known as small GTPases) comprises more than 80 highly conserved proteins of the Ras, Rho, and Rab subfamilies that are involved in multiple intracellular signalling pathways. These proteins are able to function as molecular switches in the transduction of signals from membrane receptors by cycling between an inactive, GDP-bound state and an active, GTP-bound state, which can then interact with a number of different effector molecules (Fig. 1). The activity of small GTPases is regulated by three classes of regulatory proteins: guanine nucleotide exchange factors (GEFs), which catalyse the exchange of GDP for GTP, thereby activating the small GTPase; GTPase-activating proteins (GAPs), which enhance the intrinsic ability of small GTPases to hydrolyse GTP, resulting in reversion to the inactive GDP-bound state; and guanine nucleotide dissociation inhibitors (GDIs), which preferentially bind to the GDP-bound GTPases in the cytoplasm, thereby inhibiting the release of GDP and maintaining the GTPase in the inactive state [1]. GDIs have not been identified for all small GTPases, but play an important role in the control of the Rho family GTPases.     

Role of Insulin-Like Growth Factor Binding Proteins in Mammary Gland Development

Insulin-like growth factors (IGFs) play an important role in mammary gland development and their effects are, in turn, influenced by a family of 6 IGF-binding proteins (IGFBPs). The IGFBPs are expressed in time- and tissue-specific fashion during the periods of rapid growth and involution of the mammary gland. The precise roles of these proteins in vivo have, however, been difficult to determine. This review examines the indirect evidence (evolution, chromosomal location and roles in lower life-forms) the evidence from in vitro studies and the attempts to examine their roles in vivo, using IGFBP-deficient and over-expression models. Evidence exists for a role of the IGFBPs in inhibition of the survival effects of IGFs as well as in IGF-enhancing effects from in vitro studies. The location of the IGFBPs, often associated with the extracellular matrix, suggests roles as a reservoir of IGFs or as a potential barrier, restricting access of IGFs to distinct cellular compartments. We also discuss the relative importance of IGF-dependent versus IGF-independent effects. IGF-independent effects include nuclear localization, activation of proteases and interaction with a variety of extracellular matrix and cell surface proteins. Finally, we examine the increasing evidence for the IGFBPs to be considered as part of a larger family of extracellular matrix proteins involved in morphogenesis and tissue re-modeling.     

谷氨酰胺诱导热休克蛋白在感染性休克中的作用

热休克蛋白(heatshockproteins,HSPs)为一组高度保守的蛋白质,因其独特的生物学特性及功能,在生物体内广泛参与了多种复杂的功能活动,人们将其生物活性比喻为“瑞士军刀”[1]。已有研究证明HSPs对感染性休克动物具有保护作用,但是诱导热休克蛋白产生的因素多数对机体有害,体内外实验研究发现Gln能诱导动物的热休克反应,特异性增强起主要保护作用的HSP72和HSP27的表达,从而改善感染性休克动物的生存率。本文对应用Gln诱导体内HSPs表达,从而提高机体对感染性休克的防御作用及可能机制作一综述。1谷氨酰胺对热休克蛋白表达的影响Gln是…     

Role of Plasma and Extracellular Matrix Proteins in the Physiopathology of Foreign Body Infections

S. epidermidis ) or involve more virulent strains (such as S. aureus). The common denominator for the three main elements that play a role in the physiopathology of such infections (bacteria, neutrophils, and different biomaterials) are host proteins deposited over the surface of the devices immediately after their implantation. These proteins modulate that host cells response but can also promote Staphylococcus adhesion to the biomaterial. Neutrophils and other cells such as fibroblasts adhere to several extracellular matrix proteins such as fibronectin, fibrinogen, collagen, vitronectin, via specific cell surface receptor. The evolution of the technology and the increasing numbers of long-term artificial implants require a better understanding of fundamental mechanisms of foreign body infections to reduce their incidence and optimize their treatment.