Orientador: Oslei Paes de Almeida / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-14T03:19:43Z (GMT). No. of bitstreams: 1 ToralRizo_VictorHugo_M.pdf: 5977803 bytes, checksum: e23d73a627c912289b1e0630bf6ccfff (MD5) Previous issue date: 2009 / Resumo: O prurigo actínico (PA) é uma fotodermatose familiar específica que afeta principalmente os mestiços, fruto da miscigenação entre índios e europeus, que habitam vários países da América do Norte, Central e do Sul. Pode manifestar-se em qualquer idade, no entanto a doença inicia-se freqüentemente na infância, entre os seis e oito anos de idade. É mais freqüente em mulheres, e atinge principalmente pessoas que vivem em regiões acima de mil metros de altitude. O PA afeta principalmente áreas da pele expostas ao sol. Clinicamente se apresenta de forma polimórfica. O objetivo deste estudo foi analisar as características clínicas, histopatológicas e a expressão de marcadores imunoistoquímicos de 43 casos de PA de lábio. Dezesseis casos envolviam pacientes do gênero masculino e 27 casos (62,80%) do gênero feminino, com idade média de 28,6 anos. Todos os casos envolviam o lábio inferior e outras áreas da face e do corpo, e 17 casos (39,54%) somente apresentavam manifestação em lábio inferior. As principais alterações clínicas eram: crosta, pápulas eritematosas, hiperpigmentação, descamação, placas, úlceras e edema. Microscopicamente observou-se no epitélio superficial principalmente hiperqueratose, ulceração, vacuolização das células da camada basal e exocitose. No conjuntivo subjacente observou-se quadro inflamatório crônico, em muitos casos predominando a presença de folículos linfóides em diversos graus de organização. Nenhum dos casos apresento elastose solar. Os marcadores imunoistoquímicos mostraram que os folículos linfóides apresentavam organização semelhante ao normal. Syndecan-1 marcou as células da camada espinhosa de forma homogênea, mas estava ausente nas células basais e suprabasais. D2-40 com marcação positiva e forte nas células dendríticas do centro folicular e camada basal do epitélio superficial. Mastócitos, eosinófilos e macrófagos estavam distribuídos entre as células linfoplasmocitárias. / Abstract: Actinic prurigo (AP) is a specific familial photodermatosis that affects mainly mestizos, who live in many parts of North, Central and South America. AP can be clinically evident at any age, but it starts in infancy, between 6 and 8 years of age. It is more frequent in women. AP affects mainly persons living in regions above one thousand meters sea level. The disease affects mainly sun exposed skin, andclinically it is polymorphic. The objective of this study was to evaluate the clinical, histological and immunohistochemistry characteristics of 43 cases of AP of the lower lip. Sixteen cases were in males and 24 females (62.8%), with mean age of 28.6%. All cases involved the lower lip and other skin sites, but in 17 cases the lesions occurred only in the lower lip (39.54%). Hyperpigmentation, descamation, plaques, ulcers and edema were the main clinical alterations in our series. Microscopically on the superficial epithelial it was found mainly hyperqueratosis, ulceration, vacuolization of the basal and supra basal layer cells and exocytosis. In the subjacent connective tissue predominated a chronic inflammatory process, in many cases rich in lymphoid follicles in various degrees of organization. In none of the cases it was observed elastosis in the connective tissue. Immunohistochemistry markers confirmed that the follicles showed an organization similar to normal follicles. Syndecan-1 was expressed homogenously in the spinous layers of the superficial epithelium, but it was negative in the basal and suprabasal layers. D2-40 was positive in the dendritic cells of the follicular centers and basal cells of the superficial epithelium. Mast cell, eosinophils, and macrophages were found among the plasmatic cells. / Mestrado / Patologia / Mestre em Estomatopatologia

A dermatite seborrÃica (DS) Ã uma das doenÃas mais comum entre os pacientes portadores do vÃrus HIV afetando entre 40 a 80% dos pacientes com AIDS e 20 a 40% dos pacientes soropositivos para o vÃrus HIV. Com o intuito de avaliar a eficÃcia terapÃutica e seguranÃa do pimecrolimo creme 1% na DS de face de pacientes HIV-positivos, foi realizado estudo fase II. Inicialmente quatro pacientes (Grupo A) portadores de DS leve a severa foram tratados com o pimecrolimo duas vezes por dia por 7 dias e o segundo grupo (Grupo B) vinte e um pacientes, foram tratados com pimecrolimo duas vezes por dia por 14 dias. Em seguida o tratamento era descontinuado e os pacientes foram acompanhados por mais 5 semanas. A avaliaÃÃo das lesÃes foi realizada no dia inicial, 7Â, 14Â, 21Â, 35Â e 49Â dia utilizando-se uma escala com pontuaÃÃo de zero a quatro para cada parÃmetro avaliado (eritema, descamaÃÃo, ardor, prurido, infiltraÃÃo/papulaÃÃo, escoriaÃÃo, liquenificaÃÃo), e tambÃm por meio de fotografia digital. Obteve-se importante melhora em todos os parÃmetros clÃnicos avaliados no 7Â dia; no 14Â dia 90% dos pacientes apresentavam-se livres de sinais. O eritema e a descamaÃÃo apresentaram recidiva em aproximadamente 50% dos pacientes no 35Â dia do estudo, mas o quadro clÃnico era menos intenso que o quadro clÃnico inicial. Todos os pacientes responderam a terapÃutica independente do seu âstatusâ imunolÃgico. O pimecrolimo creme 1% representa uma nova, atrativa e eficaz, opÃÃo terapÃutica para o tratamento da DS de face em pacientes HIV-positivos. / Seborrheic dermatitis (SD) is a one of the most common dermatosis in HIV-positive patients affecting between 40 to 80% of AIDS patients and 20 to 40% of HIV-positive patients. To investigate efficacy and safety of pimecrolimus cream 1% in HIV-positive patients with facial SD a phase II study was done. First of all 4 HIV-infected patients (Group A) with mild/severe SD were treated twice-daily with pimecrolimus cream 1% for 7 days and after this 21 HIV-infected patients (Group B) with mild/severe SD were treated twice-daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement (erythema, scaling, burning, pruritus, infiltration/papulation, excoriation and lichenification) at baseline, Days 7, 14, 21, 35 and 49 was assessed using a 4-point clinical score and digital photographs. Marked improvement was seen in clinical parameters at Day 7, with >= 90% patients clear of symptoms at Day 14. Erythema and scaling relapsed at Day 35 in approximately 50% of patients, but all symptoms were milder than at baseline. All patients responded to therapy, despite their immunologic status. Pimecrolimus cream represents a new, attractive and effective therapeutic option for facial SD in HIV-patients.

A atopia ou dermatite atópica é uma doença inflamatória pruriginosa, crônica e recorrente reconhecida como a segunda alergopatia mais comum, estando aquém apenas da dermatite alérgica à picada de pulgas. Esta doença é caracterizada pela presença exacerbada de prurido corpóreo, infringindo sofrimento ao paciente e desalentando seu proprietário. A busca a uma boa \"qualidade de vida\" está sendo cada vez mais demandada pelos proprietários de animais alergopatas ou portadores de outras doenças crônicas. Por se tratar de uma doença de longo decurso, o tratamento com glicocorticóides pode causar diversos efeitos colaterais, além de doenças mais graves como diabetes melitus e hiperadrenocorticismo iatrogênico. Como alternativa ao tratamento de cães atópicos, a ciclosporina (CsA) acaba tornando-se uma boa opção terapêutica. A CsA inibe as funções das células que iniciam a resposta imunológica (células de Langerhans e linfócitos) e das células que efetuam a resposta alérgica (mastócitos e eosinófilos) e, também, diminui a liberação de histamina e de várias citocinas. Os objetivos do presente estudo incluíram: análise da eficácia da CsA na redução de lesões corpóreas e do prurido com auxílio do CADESI-03 (Olivry et al.,2007) e de duas escalas de prurido corpóreo; detecção de ocorrência de eventuais efeitos adversos (tegumentares ou sistêmicos) decorrentes da terapia imunomodulatória através da realização de hemograma, função renal, função hepática e mensuração da pressão arterial; avaliação e monitoramento da qualidade de vida de 21 animais atópicos tratados com ciclosporina (5 mg/Kg, SID durante 60 dias) com auxílio de uma escala validada para cães. A CsA mostrou-se eficaz no tratamento da dermatite atópica canina pois reduziu as lesões corpóreas em 70% após 60 dias de terapia. Nesse mesmo período ocorreu redução da intensidade do prurido corpóreo em 52,6%, avaliado através da escala numérica verbal; e observou-se redução significativa na escala qualitativa de prurido corpóreo (Hill, 2002; modificada), uma vez que os níveis máximos de prurido (\"três\" e \"quatro\") quase não foram observados após a terapia imunomodulatória. Os efeitos adversos observados foram relacionados a distúrbios gastrintestinais e, ocorreram com maior freqüência nos primeiros 15 dias de tratamento. Alterações laboratoriais não foram observadas. Os animais portadores de dermatite atópica apresentaram melhora no escore de qualidade de vida em 32%. A CsA mostrou-se eficaz no tratamento da dermatite atópica canina. / Atopic dermatitis (AD) is an inflammatory, pruritic and chronic allergic skin disease. It´s recognized as the second most common allergic skin disease of dogs after flea allergy. Pruritus is the predominant sign of canine AD affecting a variety of areas of the body, leading to intense suffering to the animal and its owner. \"Quality of life\" (QL) is being much more requested from owner of animals with allergic skin diseases or with any kind of chronic disease. The long-term use of glucocorticoids therapy can be devastating because of its inumerous adverse effects and secondary diseases like diabetes mellitus and iatrogenic hiperadrenocorticism. Cyclosporine (CsA) has been considered a good therapeutic option in the treatment of canine atopic dermatitis. It inhibits the activation of cells that initiate cutaneous immune response (Langerhans\' cells and lymphocytes) and cells that mediate allergic reactions (mast cell and eosinophils). It also decreases histamine and other citocines release. The objectives of this study included: analysis of the efficacy of CsA in reducing skin lesions and pruritus of 21 atopic dogs using CADESI-03 (Olivry ey al., 2007) and two scales to quantify levels of body itching; detection of any possible adverse effects (dermatologic or systemic) secondary to immunomodulatory therapy, by performing complete blood count, renal and hepatic function and measurement of blood pressure; evaluation and monitoring QL from dogs treated with CsA (5 mg/Kg, SID during 60 days) with a validated scale; This immunomodulatory therapy was considered an effective treatment for atopic dogs because it reduced skin lesions in 70% after 60 days of therapy. During that period there was a reduction of body itching in 52,6% by verbal numeric scale, and there was significant reduction on qualitative scale of body itching (Hill, 2002; modified), since maximum levels of pruritus (\"three\" and \"four\") were hardly observed after immunomodulatory therapy. Gastrointestinal disorders were observed and appeared most often in the first 15 days of therapy. Laboratory abnormalities were not detected. The quality of life of these atopic dogs treated with CsA for 60 days was improved by 32%. CsA was effective and safe in the treatment of canine atopic dermatitis.

Le psoriasis et la dermatite atopique sont des pathologies inflammatoires cutanées chroniques, fréquentes et invalidantes. Dans la peau des patients souffrant de ces pathologies, un dérèglement de la réponse immunitaire aboutissant à une inflammation chronique est toujours observé. Le réseau cytokinique joue un rôle essentiel dans la physiopathologie cutanée en permettant la communication entre les cellules cutanées et les cellules immunitaires. Dans le psoriasis et la dermatite atopique, ce réseau est largement perturbé. En effet, un grand nombre de cytokines proinflammatoires sont surexprimées au détriment des cytokines anti-inflammatoires. Cette inflammation chronique est directement responsable de l'apparition des lésions cutanées. Parmi les cytokines surexprimées dans ces pathologies, des études antérieures du LITEC ont montré in vitro que l'Oncostatine M (OSM) est impliquée dans la production de peptides antimicrobiens et de médiateurs de l'inflammation, ainsi que dans l'inhibition de la différenciation des kératinocytes. Notre objectif était de poursuivre ces travaux en étudiant le rôle de l'OSM dans l'inflammation cutanée in vitro et in vivo chez la souris. Nous avons pour cela, comparé le rôle de l'OSM à celui d'autres cytokines de la famille de l'IL-6, l'IL-6 et l'IL-31, qui présentent également une activité sur le kératinocyte. L'activité de ces cytokines a été étudiée in vitro sur des cultures primaires de kératinocytes murins en monocouche, sur des épidermes reconstruits murins ainsi qu'in vivo dans différents modèles d'inflammation cutanée. Nous montrons que l'OSM est plus active que l'IL-6 et l'IL-31 sur les kératinocytes en culture et que la surexpression de cette cytokine in vivo dans la peau de souris à l'aide d'adénovirus recombinants induit une inflammation cutanée forte, présentant des caractéristiques communes avec le psoriasis et la dermatite atopique. Néanmoins, les souris déficientes pour le gène codant l'OSM ne présente aucune diminution du phénotype inflammatoire cutané dans le modèle de psoriasis induit par application d'Imiquimod et dans un modèle de dermatite atopique induit par application de Calcipotriol, suggérant l'existence de mécanismes de compensation par d'autres cytokines proinflammatoires. En parallèle de cette étude, nous avons mis au point un nouveau modèle d'épidermes reconstruits murins permettant l'étude de l'activité des cytokines sur les kératinocytes. Ce modèle présente l'avantage de reproduire plus finement la physiologie d'un épiderme normal par rapport aux autres modèles préalablement décrits et ouvre la perspective de développer des épidermes reconstruits à partir de kératinocytes de souris transgéniques. En conclusion, ces travaux démontrent le rôle pro-inflammatoire de l’OSM dans l'inflammation cutanée et son activité majeure sur les kératinocytes en comparaison à celles décrites pour l'IL-6 et l'IL-31. Néanmoins, la pertinence du ciblage thérapeutique de cette cytokine dans le psoriasis et la dermatite atopique reste encore à démontrer. / Psoriasis and atopic dermatitis are the most prevalent cutaneous inflammatory disease in worldwide. An imbalance immune response is a characteristic feature of these diseases and through their role in the communication between cutaneous and immune cells; cytokines are key players in these diseases. Indeed, in the psoriatic and atopic lesions, an altered cytokine network is always described and mainly in favor of proinflammatory cytokines. Among them, our laboratory previously described that Oncostatin M, an IL-6 family member is up-regulated in psoriasis and atopic dermatitis lesions. In vitro, we have demonstrated that OSM induces a proinflammatory signature on human keratinocytes including the up-regulation of antimicrobials peptides and proinflammatory mediators as well as inhibiting the epidermal differentiation. The aim of this work was to confirm the role of OSM in cutaneous inflammatory diseases and compare it to others IL-6 family members such as IL-6 and IL-31 also described for their potent activities on keratinocytes. The activity of theses cytokines was study in vitro on normal murine epidermal keratinocytes or in reconstituted murine epidermis and in vivo in inflammatory murine models. Compared to IL-6 and IL-31, OSM is a strong inducer of proinflammatory signature in vitro on keratinocyte and in vivo using recombinant adenovirus overexpressing theses cytokines. The inflammatory phenotype induces by overexpression of OSM in mouse ears mimics key features of psoriatic and atopic skins. However, deficiency mice for the gene encoding OSM dot not demonstrated reduced phenotype in a mouse model of psoriasiform dermatitis induce by imiquimod or in a mouse model of atopic dermatitis induced by calcipotriol suggesting that compensatory cytokines are sufficient to maintain phenotype in the absence of OSM. Concurrent to this study, we also developed a model of reconstituted murine epidermis in order to test the activity of cytokines in a model reproducing more closely the epidermal physiology. The in vitro model could be used to study the function of numerous epidermal proteins of cytokine using transgenic mice and will provide a useful tool in the dermatological research field. Finally this work demonstrated the proinflammatory role of OSM in cutaneous inflammation through its major activities on keratinocytes in comparison to IL-6 and IL-31. However, the relevance of therapeutic strategies to block the activity of this cytokine in inflammatory skin diseases remains to be demonstrated.

The aim of this thesis is to analyze the prevalence of the phenomenon of non-compliance patiens with a diagnosis of atopic dermatitis using the questionnaire survey in two selected dermatology clinics in Prague. The result obtained were tested using standard statistics methods. The results suggest the non-compliance depends mainly on attitude of physisians.

Memoria para optar al Título Profesional de Médico Veterinario / La Dermatitis atópica (DA) es una enfermedad multifactorial, con signos clínicos confusos, cuyos motivos de consulta principales son prurito, eritema, alopecia, entre otros. Se define como una enfermedad alérgica de la piel, de predisposición genética, con características clínicas inflamatorias y pruriginosas asociadas a la producción de anticuerpos IgE dirigidos contra alérgenos ambientales. Se ha convertido en un cuadro frecuente en perros, del cual no hay suficientes investigaciones que permitan recabar información sobre la misma, por lo que el objetivo de este estudio sobre perros diagnosticados con DA en el Hospital Clínico Veterinario de la Universidad de Chile, fue describir a los pacientes y sus características clínicas. Para esto se analizaron las fichas de los caninos atendidos con motivo de consulta (MC) dermatológico entre los años 2002 y 2012. Tan solo se utilizaron las fichas de aquellos pacientes con diagnostico definitivo de DA. En este estudio se consideraron las variables de presentación tales como edad, raza, residencia, alimentación, estacionalidad y signos clínicos. De un total de 1321 fichas de pacientes caninos con MC dermatológico, 66 pertenecieron a perros con DA, correspondiendo a un 6% del total. La mayor cantidad de perros afectados tenían entre 1 y 3 años de edad, lo que equivale a un 36% de los 66 pacientes. Un 77% de los perros diagnosticados con DA, fueron de raza pura, entre ellas Labrador Retriever, Pastor Alemán, Poodle y Boxer. Dichos pacientes vivían principalmente en zonas urbanas, y un 76% de ellos habitaban en casas donde había patio. Los signos clínicos más frecuentemente observados fueron prurito con un 83%, y lesiones que se clasificaron en primarias y secundarias. Se consideraron como lesiones primarias eritema (50%), seborrea (24%), pápulas (20%) y pústulas (11%), y como lesiones secundarias alopecia (47% ), la que surge principalmente como consecuencia de un auto trauma para aliviar el prurito, excoriaciones o costras (27%), hiperpigmentacion (17%), hiperqueratosis (12%) y liquenificación (6%). Con este estudio retrospectivo se entrega información que permite una mejor comprensión de la enfermedad y que da sustento a futuras investigaciones. / Atopic Dermatitis (AD) is a multifactorial disease that involves confusing clinical symptoms which its main query motives are pruritus, erythema, alopecia among others. It is defined as an allergic skin disease, caused by a genetic predisposition, with inflammatory and pruritic clinical features associated with IgE antibodies production directed against environmental allergen. Lately AD had become into a recurrent diagnosis amongst dogs, from which there is no sufficient research that allows to gather information regarding this topic. Because of this, the aim of the present study upon dogs's diagnosis with AD at the Clinical Veterinary Hospital from Universidad de Chile was to describe the patients and their clinical characteristics. In order to do so, the attended dog's files were analyzed due the dermathological features between the years 2002 and 2012. The files under analysis were the ones which had AD diagnosis. In this study, the variables to consider were: age, breed, recidence, feeding, seasonality presentation of clinical signs. Overall 1321 canine files dignosed with MC dermathological, 66 correspond to dogs with AD, which equals to 6% from the total. The largest amount of affected canines are between 1 and 3 years old, which is the equivalent to a 36% from the 66 patients. The 77% of the diagnosed canines with AD are pure bred, between them German Shepard, Labrador Retriever, Poodle and Boxer. These patients were mainly living in urban areas, and a 76% of them lived in houses with terraces. The clinical signs presented were pruritus with an 83%, and injuries classified as primaries and secundaries. As primary injuries were considered: erythema (50%), seborrhea (24%), papules (20%) y pustules (11%). Consequently, as secondary injuries: alopecia (47%), which appears primarily as a consequence from a self trauma to relief pruritu's damage, excoriations o scabs (27%), hyperpigmentation (17%), hyperkeratosis (12%) y lichenification (6%). With this retrospective study, the provided information will deliver a better comprehension of the disease widening the scope for future investigations.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The Atopic Dermatitis (AD) is a chronic inflammatory skin disease that affects patients with disabilities in the skin barrier and low immune response. Tacrolimus ointment for topical use is an immunomodulator that has shown to be a good alternative for the treatment of AD. However, it also has adverse effects such as low and variable bioavailability, burning sensation and itching at the application site. Thus, the development of new dosage forms that overcome these drawbacks is crucial to the success of the therapy. The objective of this study was to obtain lipid nanoparticles (LN) of tacrolimus for future application in AD therapy. The LN were obtained by solvent diffusion method associated with ultrasonication using stearic acid (SA) and beeswax as solid lipid in the solid lipid nanoparticles (SLN) and oleic acid (OA) incorporated into the solid lipid matrix in the carriers lipid nanostructured (NLC). Lipid dispersions were characterized by determining the particle size, Polydispersity Index (PDI), Zeta Potential (ZP) and and drug content in the NL. Evaluation by Transmission Electron Microscopy (TEM), analysis by Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD) and Infrared Spectroscopy in the region Fourier Transform (FT-IR). As results, LN presented nano-sized spherical shape with an average diameter ranging from 139 – 274, 9 nm and IPD from 0.3 - 0.5. PZ of LN was higher than -|25 mV|, which ensures the stability of the dispersion. In the results of DSC, it was observed that the endothermic event in the NLC was shifted to lower temperatures. Drug loading of 2,3 a 3,2%. The results of XRD also showed low crystallinity when NLC was compared with SLN. The results of FTIR was not observed interaction between the drug and the lipid components of the matrix. Then, it can be concluded that NL develop were successfully obtained and may represent promising system for the placement of tacrolimus in topical formulations. / A Dermatite Atópica (DA) é uma doença inflamatória cutânea crônica que acomete principalmente pacientes com deficiência na barreira cutânea e com baixa resposta imunológica. O tacrolimo para uso tópico em pomada é um imunomodulador que tem mostrado ser uma boa alternativa para o tratamento da DA. Porém, ele também apresenta efeitos adversos, tais como baixa e variável biodisponibilidade cutânea, sensação de queimação e prurido no sítio de aplicação. Assim, o desenvolvimento de novas formas farmacêuticas que contornem estas desvantagens é crucial para o sucesso da terapia. Desta forma, o objetivo deste trabalho foi obter nanopartículas lipídicas (NL) contendo tacrolimo para uso tópico. As NL foram obtidas pelo método de difusão do solvente associado a ultrassonicação, utilizando o ácido esteárico (AE) e a cera de abelha (CA) como lipídios sólidos nas nanopartículas lipídicas sólidas (NLS) e ácido oléico (AO) incorporado à matriz lipídica sólida nos carreadores lipídicos nanoestruturados (CLN). As dispersões lipídicas foram caracterizadas através da determinação do tamanho de partícula, Índice de Polidispersidade (IPD), Potencial Zeta (PZ) e teor de fármaco nas NL, avaliação por Microscopia Eletrônica de Transmissão (MET), análises através de Calorimetria Exploratória Diferencial (DSC), Difração de raio-X (DRX) e Espectroscopia na região do Infravermelho com Transformada de Fourier (FTIR). Como resultados, as NL apresentaram tamanho nanométrico, com um diâmetro médio variando de 139 – 274,9 nm e IPD de 0,3 - 0,5. O PZ das NL foi maior do que - |25 mV|. O teor de fármaco encontrado nas NL foi de 2,3 a 3,2 %. Nos resultados de DSC foi observado que o evento endotérmico nas CLN e nas NLS com fármaco foi deslocado para temperaturas menores, sugerindo maior desorganização da estrutura assim como os resultados de DRX, que também revelaram menor cristalinidade. Nos resultados de FTIR não foi observado interação entre o fármaco e os componentes da matriz lipídica. Então, pode ser concluído que as NL desenvolvidas foram obtidas com sucesso e podem representar futuros sistemas promissores para a veiculação do tacrolimo em formulações tópicas.

No description available.

Staphylococcus aureus is a gram-positive opportunistic pathogen responsible for more deaths every year than HIV/AIDS. Its formidable repertoire of virulence factors, ubiquitous nature, and ability to acquire antibiotic resistance quickly allow S. aureus to colonize and persist in nearly any body site if given the opportunity. S. aureus is the leading cause of many common and severe skin diseases, i.e. atopic dermatitis and surgical site infections, which can result in significant morbidity and mortality due to lack of available treatments and chronic non-healing nature of each infection. The human body is capable of producing many antimicrobial factors, such as defensins in the epidermis, in conjunction with providing a seamless barrier to many environmental threats, i.e. the skin, yet when given the opportunity, S. aureus can overtake these innate defenses, colonize, and cause disease. Despite S. aureus being a prominent organism in skin infections, little has been done to identify critical factors of S. aureus to cause skin infections. This document demonstrates the capacity of specific S. aureus virulence factors, superantigens and cytotoxins, to alter re-epithelialization and wound healing, as indicated by altered keratinocyte migration and proliferation. In an attempt to harness natural occurring host defenses, we have also identified and generated novel antimicrobial peptides capable of ablating toxin production independent of bacterial growth inhibition. Evidence presented should convince the reader that S. aureus exotoxin production is critical in perpetuating chronic wounds through local keratinocyte interaction. This suggests targeting production of these toxins to prevent cell toxicity and inflammatory responses, could allow the host to repair damaged tissue effectively.

Atopic dermatitis (AD) typically develops in patients with a history of allergic ailments, and is characterised by an itchy, inflammatory skin condition with scaling, lichenification, papules, excoriations and pruritus. In AD patients a chronic relapsing inflammatory condition is seen, associated with IgE hyper production. AD flares are largely triggered by environmental factors. However, the exact etiology of AD is unclear and there is a pressing need for new treatment regimens as AD is a chronic condition and requires long term treatment. Historically Aloe has been used to treat skin conditions as well as a variety of other diseases. To further explore the pathogenesis and treatment of AD, Balb/c mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB) for atopic dermatitis induction. Thereafter, mice were treated with either Aloe ferox or Aloe vera applied daily on the dorsal skin for 10 consecutive days. A placebo gel was used for the control mice. Blood was collected at the end of the treatment period and serum IgE levels measured. Serum IgE levels were significantly lowered in the Aloe ferox group than in the Aloe vera group. This study demonstrated Aloe’s immunoregulatory potential for alleviating atopic dermatitis through influencing of Th2 cell activation. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Pharmacology / unrestricted