No description available.

Atopic eczema is a common condition that can interfere with social function, sleep and employment. Its persistence and accompanying pruritis may be stressful and frustrating for patients (Zug and McKay 1996 : 1243). The purpose of this randomised, double-blind, placebo-controlled study was to evaluate the efficacy of a homoeopathic complex (Arsenicum album 12CH, Graphites 12CH, Petroleum 12CH, Rhus toxicodendron 12CH, Sulphur 12CH and Urtica urens 12CH), in the treatment of atopic eczema in terms of its clinical manifestations and the impact on the quality of life of the patient. Thirty patients between the ages of eighteen and sixty years who met the Diagnostic criteria (Appendix A), were selected to participate in this study. Simple random sampling was used to divide them into two equal groups of fifteen i.e. the treatment group (Group 1) and the placebo group (Group 2). The trial lasted three months; at the initial consultation patients filled in the Clinical Evaluation Index (Appendix C), the Patients’ Perception questionnaire (Appendix D) and the General Well Being Schedule (Appendix E). Patients then received their three months supply of medication or placebo. Patients returned after three weeks and filled in the questionnaires and repeated this procedure every two weeks until the end of the trial. This amounted to six consultations per patient. Statistical evaluation of the data obtained from the questionnaires were analysed using the SPSS ver. 9 package. The Friedman test and Wilcoxon signed rank test were used to analyse the intra group comparisons. These are non parametric tests. The Mann-Whitney U-test was used for the inter group comparison. Both groups showed improvements with regards to all three questionnaires. The placebo group showed consistent improvement throughout the study. Therefore, statistically there was no difference between the two groups. The results of this study demonstrated that the use of a homoeopathic complex (Arsenicum album 12CH, Graphites 12CH, Petroleum 12CH, Rhus toxicodendron 12CH, Sulphur 12CH and Urtica urens 12CH) was no more effective than the placebo in the treatment of atopic eczema. / Dr. M. R. A. Moiloa Dr. D. Naude Dr. C. Hall

Skin and nasal bacterial dysbiosis is common in children with atopic dermatitis (AD). However, there is limited data of these bacterial changes in sub-Saharan children with AD. Therefore, this study investigated the bacterial alterations in skin and nasal bacterial communities in AD compared to healthy children in rural and urban South African settings. Staphylococcus aureus was more common in children with AD (cases) than healthy children (controls). S. aureus carriage was also associated with increased disease severity. Using spa typing, we also showed that cases and controls were colonised by distinct spa types. This led us to comprehensively explore genomic differences of S. aureus in cases and controls using whole-genome sequencing. Here, we showed that S. aureus strains from cases and controls had distinct genomic features, with cases harbouring genes associated with antibiotic resistance, DNA damage repair and virulence while controls had genes associated with adhesion. Recent reports indicate the potential role of coagulase-negative Staphylococcus (CoNS) in AD pathology. This study found that CoNS and S. aureus were commonly co-carried on nonlesional skin among cases (regardless of location) and anterior nares among urban cases than the control group. The carriage of S. capitis on nonlesional skin and anterior nares was positively associated with more severe disease in both rural and urban cases. 16S rDNA amplicon sequencing analysis revealed that bacterial diversity was higher on the nonlesional skin and anterior nares of controls. Bacterial community structure differed on lesional skin, nonlesional skin and anterior nares based on AD disease status. The relative abundance of Streptococcus, Granulicatela, Veillonella and Prevotella was high in lesional skin specimens, Anoxybacillus and Cutibacterium on nonlesional skin, and Staphylococcus, Veillonella and Sphingomonas in the anterior nares among cases Overall, the findings presented in this thesis indicate that S. aureus and other CoNS, particularly S. capitis, may predominate among cases and are associated with increased disease severity. However, the increased relative abundance of genera such as Streptococcus, especially among skin samples, indicates that other bacterial genera may be contributing to disease activity on lesional skin in AD than the traditionally reported Staphylococcus.

M.A. (Clinical Psychology) / The purpose of this study was to determine whether a behavioural intervention could reduce scratching behaviour in atopic dermatitis. The literature dealing with the psychological aspects, and existing approaches to the treatment of atopic dermatitis and related dermatoses was reviewed. It was hypothesized that if subjects with atopic dermatitis were able to reduce their scratching behaviour they would show a corresponding reduction in size of identified lesions. In order to test these hypotheses, SUbjects with atopic dermatitis participated in a self-control programme lasting between eight and ten weeks. Of the seven subj ects that originally started the programme, four completed it. SUbjects' self-monitoring details reflected changes in scratching behaviour, and a specially designed grid was used to measure changes in lesion size. Inspection of the data showed that two SUbjects eliminated their scratching behaviour and lesions entirely; the other two showed marked reduction. The results of this study indicate that self-control procedures could be usefully applied as adjuncts to the conventional dermatological management of atopic dermatitis.

La marche atopique désigne la progression séquentielle des maladies atopiques, en particulier l’apparition d’asthme chez les enfants précédée par celle d’une dermatite atopique (DA) sévère chez les nourrissons. De plus, l’asthme est influencé par le degré de sévérité de la DA, qui pourrait ainsi être considérée comme la porte d’entrée pour le développement ultérieur d’une inflammation allergique des voies aériennes.Mon travail de thèse a consisté à déterminer l’implication de la cytokine TSLP produite par les kératinocytes pendant la marche atopique et implication de la cytokine TSLP pendant le développement de la DA. Pour atteindre ces objectifs, j’ai utilisé des modèles murins de maladies atopiques, en combinaison avec plusieurs lignées de souris génétiquement modifiées.Dans la première partie de mon travail de thèse, nous avons montré que la production de la cytokine TSLP dans les kératinocytes est un facteur nécessaire, non seulement pour l’inflammation cutanée, mais aussi pour générer une réponse immunitaire systémique à l’allergène.Dans la deuxième partie de mon travail de thèse, nous avons montré que la cytokine TSLP induise un recrutement de basophiles d’une façon innée, suite d’une augmentation de ce recrutement induit par l'immunité adaptative. De plus, nous avons montré que la réponse de type “Th2” induit par la cytokine TSLP ce le résultat de une coopération coordonnée de cellules dendritiques, de cellules T CD4+ et de basophiles. Des études cliniques sont nécessaires pour déterminer si l’inhibition de l’expression de la cytokine TSLP et/ou son activité pendant une DA peut réduire l’inflammation cutanée et prévenir la sensibilisation aux allergènes. / Atopic march refers to the natural history of allergic diseases, which is characterized by a typical sequence of sensitization and manifestation of symptoms in different tissues. Commonly, the clinical manifestation of atopic dermatitis (AD) appears in the early life and precedes the development of airway allergic diseases. AD has been proposed as an entry point for subsequent atopic diseases.The objective of my thesis was to better understand the role of TSLP in the atopic march and the cascade events initiated by TSLP in vivo in the development of AD. To reach my thesis objectives we used mouse models of atopic diseases in combination with various deficient-mouse lines.In the first part of this work, using a atopic march mouse model developed during my PhD work, we demonstrated that keratinocytic TSLP is essentially required not only for the development of allergic skin inflammation, but also for the generation of the allergen-specific immune response. In the second part of this work, using a cytokine TSLP-induced AD mouse model (topical MC903 treatment), we demonstrated that skin TSLP induces an early innate recruitment of basophils in the skin, followed by a late recruitment involving adaptive immunity. In addition, we demonstrate that TSLP-induced Th2 response requires an orchestrated cooperation of dendritic cells, CD4+ T cells and basophils.This work provide new knowledge in the cellular and molecular mechanisms implicated in atopic diseases involving TSLP and should provide new insight for the development of therapeutic options of these diseases.

No description available.

No description available.

Atopic dermatitis, AD (synonym eczema) is a chronic inflammatory skin disease. It affects between 10 to 20% of children and 1 to 3% of adults worldwide. It is an important cause of morbidity and is estimated to cost £465 million per annum to the UK. AD is part of a family of Th-2 driven diseases and is often the first of these atopic diseases to manifest. The development of AD is often followed by asthma and allergic rhinitis later in life (a phenomenon known as the ‘atopic march’). Up to 50% of moderate to severe AD cases have been associated with genetic mutations affecting the epidermal barrier protein filaggrin. Filaggrin aggregates keratin filaments during terminal keratinocyte differentiation, allowing normal epidermal stratification. The role of filaggrin in maintaining a functional skin barrier is further supported by a clinical study conducted by ourselves. This is the first clinical study on a European cohort (58 participants) which showed that FLG mutations were associated with experimentally demonstrable defects of skin barrier function (increased baseline transepidermal water loss), more so following exposure to a chemical irritant. However, the majority of patients with AD, especially the milder cases, do not have FLG mutations. Some of the wild-type patients in our study were noticed to have accumulation of the large filaggrin proprotein and a lack of filaggrin monomers, indicating defective proteolysis of profilaggrin into the functional monomers. Our study also found disproportionately raised protease inhibitory activities amongst the AD participants. This inappropriately raised protease inhibition may interfere with profilaggrin proteolysis, leading to the development of AD in some wild-type patients. Having demonstrated that deficiency of filaggrin monomers is associated with a defective skin barrier, we focused on the function of filaggrin in the skin and attempted to improve the skin barrier function. In addition to keratin aggregation, filaggrin constitutes the natural moisturizing factors in the epidermis following its natural breakdown into amino acids. We note that filaggrin is disproportionately rich in amino acid histidine, implying that this amino acid may have a particular significance in maintaining a functional epidermal barrier. Using an in-house skin-equivalent model, we have shown that by increasing the histidine content in the cell culture media, we could increase the expression of filaggrin monomers and reduce the penetration of a fluorescent dye into the skin-equivalents. The latter indicates improved barrier function. Finally, we conducted a pilot human study which showed that histidine, when applied to mechanically damaged skin in AD and healthy participants, was associated with a faster recovery of the skin barrier function. These studies suggest that histidine is of therapeutic benefits in AD. A histidine-based treatment may be developed as an alternative to current anti-inflammatory and immunosuppressive agents used to treat AD.

Wong Kin Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 151-166). / Abstracts in English and Chinese. / Chapter (I) --- ABSTRACT (IN ENGLISH) --- p.i / Chapter (II) --- Abstract (in Chinese) --- p.iv / Chapter (III) --- ACKNOWLEDGEMENTS --- p.vii / Chapter (IV) --- PERSONAL CONTRIBUTION TO THE WORK --- p.ix / Chapter (V) --- PUBLICATIONS --- p.x / Chapter (VI) --- TABLE OF CONTENTS --- p.xi / Chapter (VII) --- List of Abbreviations --- p.xvi / Chapter (VIII) --- LIST OF FIGURES --- p.xx / Chapter (IX) --- LIST OF TABLES --- p.xxii / Chapter Section 1: --- GENERAL INTRODUCTION / Chapter CHAPTER 1 --- General Introduction of Atopic Dermatitis --- p.1-8 / Chapter 1.1. --- Definition of Atopic Dermatitis --- p.1 / Chapter 1.2. --- Epidemiology and Classification --- p.3 / Chapter 1.3. --- Factors Provoking Flares of AD / Chapter 1.3.1. --- Genetics --- p.5 / Chapter 1.3.2. --- "Allergens-Food Allergens, Aeroallergens and Autoallergens" --- p.6 / Chapter 1.3.3. --- Microbial Colonization: Staphylococcus Aureus (S. aureus) --- p.7 / Chapter CHAPTER 2 --- Measurements of AD Severity and Quality of Life Impairment --- p.9-14 / Chapter 2.1. --- Scoring of Atopic Dermatitis severity and the SCORing Atopic Dermatitis (SCORAD) Index --- p.9 / Chapter 2.2. --- Quality of life Measurement --- p.10 / Chapter 2.3. --- The Children's Dermatology Life Quality Index --- p.11 / Chapter CHAPTER 3 --- Management of AD --- p.15-19 / Chapter 3.1. --- Current Management of AD and Their Drawbacks --- p.15 / Chapter 3.2. --- Traditional Chinese Herbal Medicne (TCHM) / Chapter 3.2.1. --- General Principle of TCHM --- p.17 / Chapter 3.2.2. --- Side Effects of Using TCHM --- p.18 / Chapter 3.2.3. --- Literature Reviews of TCHM Use in Treating AD --- p.18 / Chapter CHAPTER 4 --- The Pentaherbs Formula for AD Treatment --- p.20-26 / Chapter 4.1. --- Pilot study: Pentaherbs Capsule as Treatment Option of AD Children --- p.20 / Chapter 4.2. --- Literature Review: Nature of Five Herbs / Chapter 4.2.1. --- PHF as Treatment Option of AD under TCHM Concepts --- p.22 / Chapter 4.2.2. --- PHF as Treatment Option of AD from Modern Research Literature --- p.22 / Chapter CHAPTER 5 --- Pathobiology of Atopic Dermatitis --- p.27-40 / Chapter 5.1. --- Nature of Complexity of Pathogenesis --- p.27 / Chapter 5.2. --- Skin barrier-impairment of epidermal barrier --- p.28 / Chapter 5.3. --- Biphasic T cell response in skin of AD --- p.29 / Chapter 5.4. --- Nature of Immunoglobulin-E and its Role in Atopic Dermatitis --- p.32 / Chapter 5.5. --- Innate Immunity Defect in AD --- p.33 / Chapter 5.6. --- Role of Superantigen in Pathogenesis of AD --- p.35 / Chapter 5.7. --- "Cytokines, Chemokines and Inflammatory Mediators in Pathogenesis of Atopic Dermatitis" / Chapter 5.7.1. --- Proinflammatory Cytokines --- p.37 / Chapter 5.7.2. --- Th1/Th2 Cytokines --- p.37 / Chapter 5.7.3. --- Chemokines --- p.38 / Chapter 5.7.4. --- Pruritus Mediators --- p.39 / Chapter Section 2: --- CLINICAL TRIAL OF PENTAHERBS / Chapter CHAPTER 1 --- Objective --- p.41 / Chapter CHAPTER 2 --- Materials and Methods (RCT) --- p.42-51 / Chapter 2.1. --- Materials / Chapter 2.1.1. --- SCORAD worksheet --- p.42 / Chapter 2.1.2. --- CDLQI questionnaire --- p.42 / Chapter 2.1.3. --- Allergic Rhinitis Score (ARS) --- p.43 / Chapter 2.1.4. --- ELISA Assay Kits --- p.43 / Chapter 2.1.5. --- EDTA blood collestion tubes --- p.43 / Chapter 2.2. --- Methods / Chapter 2.2.1. --- Design --- p.45 / Chapter 2.2.2. --- Intervention --- p.45 / Chapter 2.2.3. --- Treatment / Chapter 2.2.3.1 --- The Pentaherbs Formula --- p.45 / Chapter 2.2.3.2 --- Randomization --- p.48 / Chapter 2.2.3.3 --- Concomitant Treatment in Study Period --- p.48 / Chapter 2.2.4. --- Participants --- p.49 / Chapter 2.2.5. --- Outcome Measures --- p.50 / Chapter 2.2.6. --- Statistical Analysis --- p.50 / Chapter CHAPTER 3 --- Results (RCT) --- p.52-67 / Chapter 3.1. --- Demographics --- p.52 / Chapter 3.2. --- Drug Compliance --- p.55 / Chapter 3.3. --- Efficacy / Chapter 3.3.1. --- SCORAD Score --- p.56 / Chapter 3.3.2. --- Quality of Life Score --- p.56 / Chapter 3.3.3. --- Duration and Amount of CS Usage --- p.59 / Chapter 3.3.4. --- Amount of Antihistamine Usage --- p.61 / Chapter 3.3.5. --- Allergic Rhinitis Score --- p.61 / Chapter 3.3.6. --- Blood chemistry and Haematology --- p.63 / Chapter 3.3.7. --- Plasma TARC and BDNF level --- p.63 / Chapter 3.4. --- Tolerability --- p.65 / Chapter Section 3: --- IN VITRO STUDY OF PENTAHERBS / Chapter CHAPTER 1 --- Objectives and Study Design --- p.68 / Chapter CHAPTER 2 --- Materials and Methods (In vitro Study) --- p.69-86 / Chapter 2.1. --- Materials for in vitro study / Chapter 2.1.1. --- Preparation of the Water Extracts of PHF Capsules --- p.69 / Chapter 2.1.2. --- Endotoxin Assay --- p.69 / Chapter 2.1.3. --- Cell isolation and culture ofPBMC / Chapter 2.1.3.1 . --- Cell Isolation from Human Peripheral Blood --- p.70 / Chapter 2.1.3.2. --- Culture of Peripheral Blood Mononuclear Cells --- p.70 / Chapter 2.1.4. --- Trypan Blue Exclusion Assay --- p.72 / Chapter 2.1.5. --- [3H]-Thymidine incorporation Assay --- p.72 / Chapter 2.1.6. --- Supernatant Collection and ELISA --- p.72 / Chapter 2.1.7. --- RNA Extraction and RT-PCR / Chapter 2.1.7.1. --- Reagents for RNA Extraction --- p.73 / Chapter 2.1.7.2. --- Reagents for Reverse Transcription --- p.73 / Chapter 2.1.7.3. --- Reagents for Polymerase Chain Reaction --- p.74 / Chapter 2.1.7.4. --- Reagents for Gel Electrophoresis --- p.74 / Chapter 2.2. --- Methods / Chapter 2.2.1. --- Isolation and Culture PBMC / Chapter 2.2.1.1. --- Isolation of PBMC --- p.76 / Chapter 2.2.1.2. --- Culture of Isolated PBMC --- p.76 / Chapter 2.2.1.3. --- PHA/SEB Treatment --- p.77 / Chapter 2.2.2. --- Preparation of PHF Water Extracts and Endotoxin Level / Chapter 2.2.2.1. --- Hot Water Extraction --- p.78 / Chapter 2.2.2.2. --- Limulus Amebocyte Lysate Assay --- p.78 / Chapter 2.2.3. --- Study on the Cytotoxic and Mitogenic Effects of PHF on PBMC / Chapter 2.2.3.1. --- Trypan Blue Exclusion Assay --- p.80 / Chapter 2.2.3.2. --- [3H]-Thymidine Incorporation Assay --- p.80 / Chapter 2.2.4. --- Study on the Effect of PHF on PBMC Inflammatory Mediator Production / Chapter 2.2.4.1. --- Determination of Inflammatory Mediator Expression Levels by ELISA --- p.82 / Chapter 2.2.4.2. --- Semi-quantification of Inflammatory Mediator mRNA Levels by RT-PCR --- p.83 / Chapter 2.2.5. --- Statistical Analysis --- p.86 / Chapter CHAPTER 3 --- Results(In vitro) --- p.87-114 / Chapter 3.1. --- preparation of PHF Water Extracts and Endotxin Level --- p.87 / Chapter 3.2. --- Cytotoxicity Effect of PHF on PBMC --- p.88 / Chapter 3.3. --- Mitogenicity Effect of PHF on PBMC --- p.93 / Chapter 3.4. --- Effects of PHF on Expression of Inflammatory Mediators from PBMC Following Mitogen (PHA) Stimulation / Chapter 3.4.1. --- Effects of PHF on mRNA Expression of Inflammatory Mediators from PHA-stimulated PBMC --- p.98 / Chapter 3.4.2. --- Effects of PHF on Secretion of Inflammatory Mediators from PHA-stimulated PBMC --- p.101 / Chapter 3.5 --- Effects of PHF on Expression of Inflammatory Mediators from SEB-stimulated PBMC / Chapter 3.5.1. --- Effects of PHF on mRNA Expression of Inflammatory --- p.106 / Chapter 3.5.2. --- Effescts of PHF on secretion of inflammatory Mediatorsfrom SEM-Stimulated PBMC --- p.109 / Chapter 3.6. --- Summarization of Effects of PHF on Expression of Inflammatory Mediators from PHA- and SEB-stimulated PBMC / Chapter 3.6.1. --- Mitogen (PHA) Stimulation --- p.114 / Chapter 3.6.2. --- Superantigen (SEB) Stimulation --- p.114 / Chapter Section 4: --- DISCUSSIONS / Chapter CHAPTER 1 --- Discussions on RCT of PHF --- p.115-122 / Chapter 1.1. --- Clinical Efficacy and Tolerability of PHF for Treatment of Children AD: a RCT study / Chapter 1.2. --- Efficacy of PHF for Treatment of Children with AD --- p.117 / Chapter 1.3. --- Safety and Tolerability of PHF Use for Treatment of Children with AD --- p.119 / Chapter 1.4. --- Rounding up --- p.121 / Chapter CHAPTER 2 --- Discussions on In vitro Immunomodulatory Activities of PHF --- p.123-130 / Chapter 2.1. --- General Effects of PHF on PBMC --- p.123 / Chapter 2.2. --- Effects of PHF on Inflammatory Mediators Expression in PBMC --- p.124 / Chapter CHAPTER 3 --- Limitations of the Present Study --- p.131-132 / Chapter Section 5: --- CONCLUSIONS AND FUTURE PROSPECTS / Chapter CHAPTER 1 --- Conclusions --- p.133 / Chapter CHAPTER 2 --- Future Prospects --- p.134-135 / Chapter Section 6: --- APPENDICES / Appendix1 --- p.137 / Appendix2 --- p.142 / Appendix3 --- p.149 / Chapter Section 7: --- BIBLIOGRAPHY --- p.151-166

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences