The human cytochrome P450 (CYP) family of monooxygenases is important for metabolism of drugs and endogenous compounds, e.g., vitamin A and D, cholesterol, steroids, fatty acids, and eicosanoids. This thesis describes the tissue distribution, catalytic properties, and possible function of CYP4F8 and CYP4F12. To this respect, methods for immunohistological analysis, and real-time PCR for analysis of their transcripts, were developed. CYP4F8 was originally cloned from human seminal vesicles and proposed to catalyze 19-hydroxylation of prostaglandin H2 (PGH2). This notion could now be supported, as cyclooxygenase-2, CYP4F8, and microsomal prostaglandin E synthase-1 were found to be co-localized in the epithelial linings of seminal vesicles. The three enzymes were also co-localized in the suprabasal layers of epidermis, suggesting a similar function of CYP4F8 in skin. Real-time PCR showed that CYP4F8 mRNA was more than 10-fold increased in psoriatic lesions compared to non-lesional skin. CYP4F8 immunoreactivity was also found in kidney cortex, transitional epithelium, corneal epithelium, and retina. Although transcripts of all three enzymes were detectable in retina, no co-localization was found. Pro inflammatory stimuli were found to increase CYP4F8 mRNA expression in cultured epidermal and corneal keratinocytes. In these tissues CYP4F8 might oxidize fatty acids or other eicosanoids than PGH2. CYP4F12 was originally cloned from the liver and small intestine, and found to oxidize arachidonic acid and two anti-histamines. Immunohistological studies showed that CYP4F12 immunoreactivity was present mainly in the gastrointestinal tract, e.g., stomach, ilium, and colon, but also in placenta. Although CYP4F8 and CYP4F12 have catalytic properties in common, there are important differences. CYP4F12 does not oxidize PGH2, certain eicosanoids, and fatty acids. The prominent expression in the gut suggests that CYP4F12 might be involved in oxidation of drugs.

Esta investigación explora las relaciones entre la enfermedad dermatológica y las variables de personalidad. Se recoge una muestra de 108 pacientes de enfermedades de piel consideradas influenciables por variables psicológicas. Las enfermedades estudiadas fueron neurodermitis, psoriasis y boca urente. La enfermedad de neurodermitis se produce por rascado intenso en localizaciones accesibles al paciente y produce liquenificación de la piel en respuesta a ese rascado, frecuentemente asociado a situaciones emocionales estresantes. Como consecuencia se produce picor intenso que mantiene el ciclo de rascado, provocando unas lesiones características crónicas. Se comparan los perfiles de personalidad en estas enfermedades, con la población normal para obtener las características de personalidad en este grupo dermatológico. Los resultados avalan la hipótesis de que existen estilos de personalidad en la grupo dermatológico analizado que se diferencian de la población normal. Estas diferencias son interpretadas a la luz de la teoría de la personalidad de Millon. / This research explores the relationships between dermatologic disease and personality. 108 dermatologic patients affected with skin diseases influenced by psychological variables were recruited. The dermatologic diseases were Lichen simplex Chronicus, Psoriasis and Burning Mouth syndrome. Lichen Simplex Chronicus is produced by a intense scratching in locations accessible to the patient witch produces lichenification of the skin in response to the scratching, usually associated with emotionally stressful situations. As a consequence, itching is produced and maintains the scratching cycle witch provokes the lesions. The personality profiles of these dermatologic conditions are compared with those in normal population to obtain the personality characteristics of this dermatologic group.Results support the hypothesis that different personality styles exist between dermatologic and normal group. These differences are interpreted following the Millon theory of Personality.

Background: It has been proposed that depression plays a role in how psoriasis affects quality of life. However, primary data are limited. Objective: To investigate the role depression plays in how patients experience psoriasis. Methods: Cross-sectional study conducted between January and May 2005. Recruitment of 265 adults with prevalent psoriasis through Internet advertisements. Standardized assessment of depressive symptoms, health-related quality of life (HRQL), illness-related stress, and clinical severity of psoriasis using validated scales. Results: Thirty-two percent of all participants screened positive for depression. We observed a graded relationship between depressive symptoms and HRQL impairment (p < 0.001). Only 16.5% of those with high depression scores were currently treated for depression. Both dissatisfaction with antipsoriatic treatment and illness-related stress were highly associated with depression. After adjustment for HRQL, patients with more severe psoriasis were less likely depressed, although this association failed to reach statistical significance (multiadjusted odds ratio 0.37; 95% CI 0.13–1.02; p = 0.06). Conclusion: Patients with high subjective distress and low objective measures of psoriasis should be evaluated for depression. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-21T19:19:52Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Gaya Freitas.pdf: 1529179 bytes, checksum: c9caac96378af20cf153b0fd3adead1b (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-21T19:20:09Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Gaya Freitas.pdf: 1529179 bytes, checksum: c9caac96378af20cf153b0fd3adead1b (MD5) / Made available in DSpace on 2016-09-21T19:20:09Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Gaya Freitas.pdf: 1529179 bytes, checksum: c9caac96378af20cf153b0fd3adead1b (MD5) Previous issue date: 2015-08-12 / A dapsona é uma sulfona com atividade antibiótica utilizada para doenças crônicas de pele como a psoríase, contudo seu uso pela via oral apresenta elevada incidência de eventos adversos. Uma abordagem para reduzir os efeitos colaterais é a aplicação da dapsona diretamente na área afetada, o que pode ser feito com a utilização de nanocápsulas (NC), visando aumentar a permeabilidade do fármaco na pele. Dentre os componentes que podem ser utilizados como núcleo oleoso de NC, está o óleo de arroz (Oryza sativa), devido a suas propriedades hidratantes, umectantes, antioxidantes e de proteção à radiação UV. Desta maneira, este trabalho teve por objetivo desenvolver e caracterizar NC de dapsona com diferentes polímeros - poli-ε-caprolactona (NC-P) e Eudragit® RS100 (NC-E) - utilizando diferentes quantidades de óleo de arroz e fármaco. As NC apresentaram pH levemente ácido, diâmetro de partícula inferior a 334 nm, distribuição granulométrica estreita, potencial zeta negativo (-9,9 a -33,7 mV) e eficiência de encapsulação superior a 83%. O estudo da liberação in vitro, realizado em sacos de diálise, demonstrou que as NC foram eficientes em controlar a liberação da dapsona, sendo o modelo monoexponencial o mais adequado para descrever os perfis de liberação. A nanoencapsulação diminuiu a degradação fotolítica da dapsona frente à luz UVA, obtendo-se percentuais de fármaco residual de 80,6%; 91,9% e 1,4% para NC-P1, NC-E e fármaco livre, respectivamente. Além disso, hidrogéis preparados com NC-P1 (HG-NCP1) e NC-E (HG-NCE) apresentaram pH adequado para aplicação cutânea, teor próximos a 100% e comportamento não-newtoniano pseudoplástico (HG-NCE) e plástico (HG-NCP1). Na avaliação da oclusão in vitro, observou-se que o HG-NCP1 aumentou consideravelmente a oclusão quando comparado ao HG-NCE e ao hidrogel contendo fármaco livre. Assim, estas formulações apresentam-se como sistemas promissores para aplicação cutânea de dapsona, com potencial para constituir-se em um tratamento tópico eficaz para a psoríase. / Dapsone is a sulfone with antibiotic activity used for chronic skin diseases such as psoriasis. The use of dapsone by oral route presents high incidence of adverse events. An approach to reduce side effects is the application of dapsone directly into the skin, which can be done by use of nanocapsules (NC), in order to increase the skin permeability of the drug. The rice (Oryza sativa) oil is a component that can be used as NC oil core due to its moisturizing, humectant, antioxidant and UV protection properties. Thus, this study aimed to develop and characterize dapsone-loaded NC using different polymers - poly-ε-caprolactone (NC-P) and Eudragit® RS100 (NC-E) - using different rice oil and drug concentration. The NC showed slightly acidic pH, particle diameter less than 334 nm, narrow particle size distribution, negative zeta potential (-9.9 to -33.7 mV) and encapsulation efficiency higher than 83%. The in vitro release study, carried out in dialysis bags, showed that both NC were effective in controlling the release of dapsone. The monoexponential equation was the most appropriate model to describe the release profiles. The nanoencapsulation decreases photolytic degradation of dapsone in UVA light, yielding drug remaining percentage of 80.6%, 91.9% and 1.4% for NC-P1, NC-E and free drug, respectively. In addition, hydrogels prepared with NC-P1 (HG-NCP1) and NC-E (HG-NCE) showed pH suitable for cutaneous application, content close to 100% and non-Newtonian pseudoplastic (HG-NCE) or plastic (HG-NCP1) behavior. In vitro occlusion evaluation showed that the HG-NCP1 significantly increased the occlusion factor when compared to HG-NCE and the free drug hydrogel. Thus, these formulations are promising systems for topical application of dapsone, with the potential to constitute in an effective topical treatment for psoriasis.

As doenças crônico-inflamatórias são responsáveis por grande impacto na qualidade de vida dos pacientes, causando incapacidade funcional e fadiga. Muitos instrumentos têm sido utilizados para medir tais variáveis. A presença de comorbidade psiquiátrica também tem papel relevante na sensação de fadiga. O objetivo deste estudo foi verificar a prevalência da fadiga em pacientes com artrite psoriásica dos ambulatórios de espondiloartrites do HUPE/UERJ e de doenças cutâneo-articulares do HUCFF/UFRJ e correlacioná-la com índices de qualidade de vida, com a capacidade funcional, com os sintomas de ansiedade e depressão e com a atividade de doença. Estudo observacional, transversal, realizado em pacientes ambulatoriais maiores de 18 anos com diagnóstico clínico e/ou radiológico de artrite psoriásica. A fadiga foi avaliada pelo Fatigue Assessment of Chronic Illness Therapy Scale (FACIT F); a qualidade de vida foi avaliada pelo Health Survey-36 (SF-36) e pelo Psoriasis Disability Index (PDI); a ansiedade e depressão pelo Hospital Anxiety and Depression Scale (HAD); a capacidade funcional pelo Health Assessment Questionnaire (HAQ) e a atividade de doença pelo Psoriasis Area and Severity Index (PASI), pelo Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) e pelo Clinical Disease Activity Index (CDAI). Cento e um pacientes, 57 homens e 44 mulheres com idade média de 50,77 anos, foram avaliados e responderam aos questionários. Destes, 48 pacientes tinham artrite periférica, 14 só doença axial e 39 ambos. O valor médio do PDI foi 8,01; o do PASI, 9,88; o do BASDAI, 3,59; o do HAQ, 0,85; o do HAD A, 7,39; o do HAD D, 5,93, o do FACIT F, 38,3 e o do CDAI 24,65. O FACIT_F se correlacionou significativamente com o PASI (rs - 0,345, p<0,001), com o PDI (rs - 0,299, p<0,002); com o HAQ (rs - 0, 460) com o HAD A (rs - 0,306), com o HAD D (rs - 0,339). Correlacionou ainda com todos os domínios do SF-36 e com todos os domínios do FACIT IV. Não houve correlação com o CDAI nem com o BASDAI. Houve prevalência de fadiga de moderada a intensa em menos de vinte e cinco por cento dos pacientes com artrite psoriásica. A fadiga parece estar mais relacionada aos aspectos emocionais e sociais da doença do que propriamente aos aspectos inflamatórios articulares, confirmando que a visibilidade da doença é o aspecto mais perturbador para o paciente e que a dor da pele é mais intensa que a dor articular. / Chronic inflammatory diseases are associated with significant psychosocial morbidity and a decrease in health-related quality of life causing disabilities and fatigue. Psychiatric comorbidity, often found in dermatologic patients, also plays an important role on the impairment of quality of life and fatigue The aim of this study is to to assess the prevalence of fatigue on patients with psoriatic arthritis of specific ambulatories of HUCFF/UFRJ and HUPE/UERJ and to correlate it to quality of life indices, function, anxiety and depression and activity of the disease. This is a cross-sectional study performed on outpatient clinic patients older than 18 years-old. The Fatigue Assessment of Chronic Illness Therapy Scale (FACIT F) was used to measure the fatigue; The Health Survey-36 (SF-36) by the Psoriasis Disability Index (PDI) to measure the quality of life; the Health Assessment Questionnaire (HAQ), to function; the Hospital Anxiety and Depression Scale (HAD) to measure anxiety and depression symptoms Psoriasis Area and Severity Index (PASI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI and Clinical Disease Activity Index (CDAI) to evaluate the clinical activity. 101 patients (57 male and 44 female) with mean age of 50, 77 were evaluated and answered the questionnaires. The mean PDI score was 8.01; the PASI score, 9.88; the BASDAI score, 3.59; the HAQ score, 0.85; the HAD A score, 7.39; the HAD D score, 5.93, the FACIT F score, 38.3 and the CDAI, score, 2. 65. FACIT_F was statically associated with PASI (rs-0,345, p<0.001), PDI (rs-0,299, p<0.002); HAQ (rs-0.460); HAD A (rs-0,306); HAD D (rs -0,339). There was statistically significant correlation with all of the domains of SF-36 and FACIT IV. There was not correlation with CDAI or BASDAI. There was a prevalence of fatigue from moderate to intense in less than 25% of patients with psoriatic arthritis. Fatigue seems to be more related to the emotional and social aspects of the disease rather than to the joint inflammatory aspects proper, confirming that the diseases visibility is the most disturbing aspect for the patient and that skin pain" is more intense than the joint pain.

As doenças crônico-inflamatórias são responsáveis por grande impacto na qualidade de vida dos pacientes, causando incapacidade funcional e fadiga. Muitos instrumentos têm sido utilizados para medir tais variáveis. A presença de comorbidade psiquiátrica também tem papel relevante na sensação de fadiga. O objetivo deste estudo foi verificar a prevalência da fadiga em pacientes com artrite psoriásica dos ambulatórios de espondiloartrites do HUPE/UERJ e de doenças cutâneo-articulares do HUCFF/UFRJ e correlacioná-la com índices de qualidade de vida, com a capacidade funcional, com os sintomas de ansiedade e depressão e com a atividade de doença. Estudo observacional, transversal, realizado em pacientes ambulatoriais maiores de 18 anos com diagnóstico clínico e/ou radiológico de artrite psoriásica. A fadiga foi avaliada pelo Fatigue Assessment of Chronic Illness Therapy Scale (FACIT F); a qualidade de vida foi avaliada pelo Health Survey-36 (SF-36) e pelo Psoriasis Disability Index (PDI); a ansiedade e depressão pelo Hospital Anxiety and Depression Scale (HAD); a capacidade funcional pelo Health Assessment Questionnaire (HAQ) e a atividade de doença pelo Psoriasis Area and Severity Index (PASI), pelo Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) e pelo Clinical Disease Activity Index (CDAI). Cento e um pacientes, 57 homens e 44 mulheres com idade média de 50,77 anos, foram avaliados e responderam aos questionários. Destes, 48 pacientes tinham artrite periférica, 14 só doença axial e 39 ambos. O valor médio do PDI foi 8,01; o do PASI, 9,88; o do BASDAI, 3,59; o do HAQ, 0,85; o do HAD A, 7,39; o do HAD D, 5,93, o do FACIT F, 38,3 e o do CDAI 24,65. O FACIT_F se correlacionou significativamente com o PASI (rs - 0,345, p<0,001), com o PDI (rs - 0,299, p<0,002); com o HAQ (rs - 0, 460) com o HAD A (rs - 0,306), com o HAD D (rs - 0,339). Correlacionou ainda com todos os domínios do SF-36 e com todos os domínios do FACIT IV. Não houve correlação com o CDAI nem com o BASDAI. Houve prevalência de fadiga de moderada a intensa em menos de vinte e cinco por cento dos pacientes com artrite psoriásica. A fadiga parece estar mais relacionada aos aspectos emocionais e sociais da doença do que propriamente aos aspectos inflamatórios articulares, confirmando que a visibilidade da doença é o aspecto mais perturbador para o paciente e que a dor da pele é mais intensa que a dor articular. / Chronic inflammatory diseases are associated with significant psychosocial morbidity and a decrease in health-related quality of life causing disabilities and fatigue. Psychiatric comorbidity, often found in dermatologic patients, also plays an important role on the impairment of quality of life and fatigue The aim of this study is to to assess the prevalence of fatigue on patients with psoriatic arthritis of specific ambulatories of HUCFF/UFRJ and HUPE/UERJ and to correlate it to quality of life indices, function, anxiety and depression and activity of the disease. This is a cross-sectional study performed on outpatient clinic patients older than 18 years-old. The Fatigue Assessment of Chronic Illness Therapy Scale (FACIT F) was used to measure the fatigue; The Health Survey-36 (SF-36) by the Psoriasis Disability Index (PDI) to measure the quality of life; the Health Assessment Questionnaire (HAQ), to function; the Hospital Anxiety and Depression Scale (HAD) to measure anxiety and depression symptoms Psoriasis Area and Severity Index (PASI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI and Clinical Disease Activity Index (CDAI) to evaluate the clinical activity. 101 patients (57 male and 44 female) with mean age of 50, 77 were evaluated and answered the questionnaires. The mean PDI score was 8.01; the PASI score, 9.88; the BASDAI score, 3.59; the HAQ score, 0.85; the HAD A score, 7.39; the HAD D score, 5.93, the FACIT F score, 38.3 and the CDAI, score, 2. 65. FACIT_F was statically associated with PASI (rs-0,345, p<0.001), PDI (rs-0,299, p<0.002); HAQ (rs-0.460); HAD A (rs-0,306); HAD D (rs -0,339). There was statistically significant correlation with all of the domains of SF-36 and FACIT IV. There was not correlation with CDAI or BASDAI. There was a prevalence of fatigue from moderate to intense in less than 25% of patients with psoriatic arthritis. Fatigue seems to be more related to the emotional and social aspects of the disease rather than to the joint inflammatory aspects proper, confirming that the diseases visibility is the most disturbing aspect for the patient and that skin pain" is more intense than the joint pain.

京都大学 / 0048 / 新制・課程博士 / 博士(生命科学) / 甲第21403号 / 生博第404号 / 新制||生||53(附属図書館) / 京都大学大学院生命科学研究科高次生命科学専攻 / (主査)教授 垣塚 彰, 教授 HEJNA,James, 教授 渡邊 直樹 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

No description available.

Rates of immune-mediated diseases (IMDs) have rapidly increased. Although the exact etiology has not yet been fully elucidated, disruptions to the microbiome has been proposed as a potential mechanism. We conducted a retrospective, longitudinal, birth cohort study utilizing electronic health records (EHR) to investigate the association between early life antibiotic exposure and the risk of developing juvenile idiopathic arthritis (JIA), pediatric psoriasis, or type 1 diabetes. Incident rate ratios (IRR) were estimated using modified Poisson regression models and adjusted for significant confounders. Children exposed to two or more antibiotics prior to 12 months of age had a 69% increased risk of developing JIA (1.69 IRR, 95% CI [1.04-2.73]), which rose to 97% when exposed prior to 6 months (1.97 IRR, 95% CI [1.11-3.49]). Children exposed to a penicillin antibiotic had a 62% increase in risk for psoriasis (1.62 IRR, 95% CI [1.06-2.49]), which rose slightly to 64% when exposure occurred between 6 and 12 months of age [(1.64 IRR, 95% CI [1.04-2.59]). We found a moderate to strong association between early antibiotic exposure and risk for JIA and psoriasis when exposure was examined by age, frequency, and type of antibiotic, but not for type 1 diabetes. Potential interactions effects between infection and antibiotics with an increased susceptibility to early life infections among children with an IMD was also observed. Overall, children exposed to antibiotics at an early age have an increased probability of developing an IMD after 12 months of age. However, alternative explanations for this association should be considered. / Public Health