Made available in DSpace on 2014-06-11T19:22:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2003-03-07Bitstream added on 2014-06-13T19:28:25Z : No. of bitstreams: 1 morsoleto_mjms_me_rcla.pdf: 7645060 bytes, checksum: 099c490ad0b826dfff563df09d42b8e0 (MD5) / Este trabalho apresenta uma série de resultados referentes à utilização da transmissão de fármacos tópicos através de ondas ultra-sônicas (fonoforese), em lesão cirúrgica produzida no músculo tibial anterior de ratos Wisttar. O fármaco utilizado foi a hidrocortisona gel manipulada a 10%. Foram utilizados 42 ratos Wisttar machos, com 60 dias de idade e peso médio de 300,0 g ( 50,0 g), que foram submetidos à lesão cirúrgica na pata direita no músculo tibial anterior. Após 24 horas a área da lesão foi tratada com ultra-som tendo como gel acoplante hidrocortisona a 10%. A freqüência utilizada foi de 1,0 MHz e intensidade de 0,4 W/cm2 por 1 minuto, durante 14 dias consecutivos. Depois da terapia aplicada os ratos foram sacrificados, o músculo criofixado e cortado em criostato. As lâminas obtidas foram coradas por H/E, Tricrômico de Masson e Tricrômico de Mallory para serem fotografadas em fotomicroscópio Zeiss. O tecido analisado proveniente dos animais lesados, tratados com ultra-som e hidrocortisona a 10% (fonoforese) apresentam: após 1 dia de tratamento, fibras musculares seccionadas pela incisão já fagocitada com predomínio de células mononucleadas. Nos animais sacrificados após 3 dias de tratamento notamos a presença de mioblastos, alguns miotubos e neovascularização. Quando analisamos os tecidos dos animais sacrificados após 7 dias de tratamento, observamos a presença de reorganização dos tecidos musculares. Nos animais sacrificados 14 dias após o tratamento, as fibras musculares mostram-se em avançado estado de regeneração. O aparecimento precoce de mioblastos e raras fibras necróticas, a partir do terceiro dia de aplicação, levam-nos a concluir que o fármaco tópico anti-inflamatório consegue atravessar a barreira de tecidos biológicos através da transmissão da energia ultra-sônica, e assim acelerar a reconstituição do tecido lesado. / This work presents a series of referring results to the use of the transmission of topical pharmacs through ultrasonic waves (Phonophoresis) in a produced surgical injuries in previous in the tibialis anterior muscle of Wisttar rats. The used pharmac was hydrocortisone gel to 10%. We had been used, in these experiment 42 rats with 60 days years' old and 300,0 average weight of g ( 50,0 g). The animals had been submitted to the chirurgical injury in the right leg, in previous the tibiae muscle. After 24 hours the area of the injury was dealt with ultrasound with faceplate hydrocortisone gel to 10%. The used frequency was of 1,0 MHz and the intensity of 0,4 W/cm2, with a time of 1 minute of insomniac, during 14 days. After the therapeutically one applied the rats they had been sacrificed, the frost fixed and cut muscle in cryostat. The gotten blades had been stain by H/E, Gomori's Trichrome, Masson's Trichrome and Mallory's Trichrome to be photographed in Zeiss photomicroscope. The analyzed proceeding from the animals injured, treated with ultra-sound and hydrocortisone present: after 1 day of treatment, skeletal muscle staple fibers parted by the phagocyte incision already with predominance of mononuclear cells. After 3 days of treatment, in the sacrificed animals, it is noticed myoblasts, some multinucleated myofibers and new vessel. When one analyzes of the sacrificed animals after 7 days of treatment, observes it presence of reorganization of muscular. In the sacrificed animals 14 days after the treatment, visualizes muscular fibers in advanced state of regeneration. The precocious appearance of myoblasts and rare necrotic tissue as fibers to leaving of the third day of application of treatment lever to conclude that the topical pharmac obtained to cross the biological barrier through the transmission of the ultrasonic energy. Of this form the hydrocortisone is taken until the small farm of lesion.

A exodontia de terceiros molares pode afetar significativamente a qualidade de vida dos pacientes no período pós-operatório. A resposta inflamatória gerada pelo dano tecidual inerente ao procedimento pode apresentar edema e dor de duração e intensidade variáveis. No presente estudo foi avaliada a eficácia do corticosteroide hidrocortisona, como solução de irrigação durante exodontias de terceiros molares no controle do edema e da dor pós-operatória. Vinte e oito pacientes foram incluídos no estudo e após randomização foram submetidos a exodontia de ambos os terceiros molares inferiores em tempos cirúrgicos distintos, pelo mesmo cirurgião. Foram distribuídos aleatoriamente para receber 250ml de solução contendo 500mg de hidrocortisona (grupo H) ou 250ml de solução salina a 0,9% (grupo C). Para avaliação da eficácia da hidrocortisona no controle da dor pós-operatória três mensurações foram utilizadas: a quantidade de medicação analgésica de resgate consumida, o tempo entre o término da cirurgia e o uso do primeiro comprimido de resgate e a EVA em seis momentos. Para aferição da eficácia da hidrocortisona no controle do edema foram criadas 3 medidas faciais e o edema foi medido por meio da diferença em milímetros entre o segundo dia de pós-operatório e o pré-operatório. A comparação entre os grupos mostrou que a hidrocortisona foi eficaz no controle pós-operatório do edema em duas das medidas aferidas. A dor acompanhou a diminuição do edema, sendo que na média a EVA foi menor no grupo H, no entanto não houve diferença estatisticamente significativa nas outras duas aferições de dor. Conclui-se que a utilização local da hidrocortisona, como solução de irrigação trans-operatória em exodontias de terceiros molares é efetiva na redução do edema e da percepção de dor pós-operatória. / The third molar removal can significantly affect the quality of life of patients in the postoperative period. The inflammatory response caused by tissue damage inherent to the procedure may include edema and pain with variable duration and intensity. In the present study, we evaluated the efficacy of hydrocortisone as irrigation solution during third molars removal for postoperative pain and edema control. Twenty-eight patients were included in the study after randomization and were subjected to removal of both mandibular third molars in different surgical times by the same surgeon. They were randomly assigned to receive 250ml solution containing 500 mg of hydrocortisone (group H) or 250ml 0.9% saline solution (group C). To evaluate the efficacy of hydrocortisone in controlling postoperative pain three measurements were applied: the amount of analgesic medication taken, the time between the end of surgery and the use of the first analgesic tablet and VAS in six moments. To measure the effectiveness of hydrocortisone in edema control three facial measurements were created and swelling was measured by the difference in millimeters between the second postoperative day and preoperative. The comparison between the groups showed that hydrocortisone was effective in postoperative edema control in two of the measurements taken. Pain accompanied the edema reduction and the average VAS was lower in H group, however there was no statistically significant difference in the other two measurements of pain. We concluded that the local use of hydrocortisone as intraoperative irrigation solution for third molar removal is effective in reducing postoperative edema and pain perception.

Orientador: Regina Celia Spadari / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-11T10:54:34Z (GMT). No. of bitstreams: 1 Souza_AglecioLuizde_M.pdf: 1332866 bytes, checksum: 5e6eb15dfbfa806199261b6c88b3e135 (MD5) Previous issue date: 2007 / Resumo: Muitos estudos demonstram associação entre baixo status socioeconômico e alta prevalência de morbidade psiquiátrica. Entretanto, em países da América Latina, incluindo o Brasil, nos quais as diferenças sociais são maiores, estes estudos são escassos. Fatores psicossociais são importantes mediadores da relação entre saúde e status socioeconômico, e as respostas neuroendócrinas e imunológicas podem explicar a patogênese de morbidade psiquiátrica associada ao estresse psicossocial. Esta resposta é modulada pelo cortisol e por mediadores inflamatórios. O objetivo deste estudo foi avaliar a associação entre índice de estresse percebido, prevalência de morbidade psiquiátrica, concentrações séricas de interleucina 6 (IL-6), fator de necrose tumoral-a (TNF-a) e proteína C reativa (PCR), bem como de cortisol salivar em indivíduos de baixo status socioeconômico. Sessenta e cinco indivíduos foram submetidos a análises psicométricas utilizando-se a Entrevista Clínica Estruturada Revisada (CIS-R), o Questionário de Estresse Percebido (QEP) e a Escala Hospitalar de Ansiedade e Depressão, e forneceram amostras de sangue e saliva para determinação da concentração dos marcadores acima mencionados. Os resultados mostraram alto índice de estresse percebido e alta prevalência de morbidade psiquiátrica, os quais apresentaram associação entre si. Os sujeitos apresentaram também alta concentração salivar de cortisol e resposta do cortisol ao acordar, sendo esta última negativamente correlacionada com a renda per capita. A concentração sérica dos marcadores inflamatórios foi maior do que a apontada na literatura em indivíduos saudáveis, porém, não houve associação entre estes marcadores inflamatórios, o estresse percebido e a prevalência de morbidade psiquiátrica. Nós concluímos que exposição crônica a estressores psicossociais, presentes no ambiente dos indivíduos avaliados, pode explicar o alto índice de estresse percebido e a alta prevalência de morbidade psiquiátrica encontrados neste trabalho. O estresse psicossocial crônico, através da concentração aumentada de cortisol, deixaria o indivíduo vulnerável à morbidade psiquiátrica. Além disso, as altas concentrações de marcadores inflamatórios encontradas indicam um estado sub-clínico de inflamação, o qual poderia contribuir para a alta prevalência de morbidade psiquiátrica e para a manutenção de concentrações elevadas de cortisol. Assim, devido às características socioeconômicas, o Brasil, comparado com países desenvolvidos, possui uma significativa parcela da população sujeita a transtornos mentais, os quais têm forte impacto negativo sobre a saúde pública, exigindo políticas de prevenção e intervenção especificamente direcionadas à população de baixo status socioeconômico / Abstract: The association between low socioeconomic status (SES) and high psychiatric morbidity prevalence has been established throughout studies performed in rich countries rather than developing countries where the social differences are huge. The aim of this work was to investigate the association between the perceived stress level, psychiatric morbidity prevalence, interleukin-6 (IL-6), a- tumoral necrose factor (a TNF) and reactive C protein (PCR) serum levels, as well as salivary cortisol concentration in individuals of low SES. Sixty-five adult male classified as belonging to low SES were submitted to a psychometric analysis by the Revised Clinical Interview Schedule (CIS-R), the Perceived Stress Questionnaire (QSP) and the Hospital Anxiety and Depression Scale (HAD). The subjects also provided blood and saliva samples for the analysis of the biological markers of stress and inflammation. The results showed association between perceived stress level and prevalence of psychiatric morbidity, with both indicators showing high scores. The salivary cortisol concentration and the awakening cortisol response (CAR) were high and the CAR showed a negative correlation to per capita income. The inflammatory markers levels were higher compared to data for healthy subjects in the literature. However, there was no association between inflammatory markers, perceived stress and psychiatric morbidity prevalence. We concluded that chronic exposure to psychosocial stressors, present in low SES environmental, might explain the higher perceived stress level and psychiatric morbidity prevalence found in this work. The chronic psychosocial stress, through the high cortisol levels, might lead to psychiatric morbidity vulnerability. Inasmuch, the higher inflammatory markers levels indicate an inflammatory state, which probably contribute to psychiatric morbidity prevalence. Therefore, considering the socioeconomic features of the Brazilian population, there is a great percentage of people exposed to high risk of mental health diseases. This picture might have a negative impact on public health and imposes the need for public actions of prevention and of intervention specifically directed toward this socioeconomic class / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

Orientador: Maria Beatriz Duarte Gavião / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-19T03:55:15Z (GMT). No. of bitstreams: 1 Barbosa_TaisdeSouza_D.pdf: 2256119 bytes, checksum: 3808ee42c3ee4cc2ff40e2c4e22d3027 (MD5) Previous issue date: 2011 / Resumo: Nas últimas duas décadas, houve aumento substancial do interesse sobre a qualidade de vida relacionada à saúde bucal (QVRSB) de crianças e adolescentes, o que se deve ao fato das doenças bucais comprometerem significativamente os aspectos físicos, emocionais e sociais destes indivíduos. Assim, o objetivo geral desta pesquisa foi avaliar a QVRSB e fatores associados em crianças e pré-adolescentes, de oito a catorze anos, de ambos os gêneros, escolares da rede pública do município de Piracicaba, SP. Na avaliação de saúde bucal as seguintes variáveis foram consideradas: presença e severidade de cárie, maloclusão, fluorose, gengivite, de acordo com os critérios da Organização Mundial da Saúde, e sinais e sintomas de disfunção temporomandibular (DTM), por meio do Research Diagnostic Criteria/Temporomandibular Disorders - eixo I. A auto-percepção da QVRSB foi avaliada por meio de questionários específicos para os grupos etários, as versões brasileiras do Child Perceptions Questionnaire (CPQ), para crianças de oito a dez e onze anos (CPQ8-10) e pré-adolescentes de onze a catorze anos (CPQ11-14). Duas questões destes questionários também foram utilizadas para avaliar as percepções globais de saúde bucal (SB) e bem-estar (BE). Na avaliação dos fatores associados à QVRSB, as variáveis consideradas foram: características sociodemográficas (idade e gênero da criança, número de adultos em casa e nível educacional da mãe), utilização de serviços odontológicos (experiência passada e atual) e hábitos de higiene bucal (frequência de escovação). Os sintomas de ansiedade e depressão foram avaliados por meio das versões brasileiras do Revised Children's Manifest Anxiety Scale (RCMAS) e do Children's Depression Inventory (CDI), respectivamente. Para avaliar as concentrações de cortisol salivar foram coletadas amostras de saliva 30 minutos após acordar (jejum) e à noite (antes de dormir) para determinar o declínio diurno de cortisol salivar (?g/dl), calculado pela diferença entre os valores da primeira e segunda coletas. As concentrações de cortisol salivar foram determinadas por meio de análise imunoenzimática. Os dados obtidos foram discutidos em quatro estudos, denominados capítulos no presente trabalho. Os objetivos específicos do primeiro (Evaluating oral health-related quality of life measure for children and preadolescents with temporomandibular disorder) e segundo (Oral health-related quality of life in children and preadolescents with dental caries, malocclusions or temporomandibular disorders) capítulos foram, respectivamente, avaliar as propriedades psicométricas dos questionários para uso em crianças e pré-adolescentes com sinais e sintomas de DTM e comparar a percepção de QVRSB entre grupos com diferentes condições bucais (cárie, maloclusão e DTM) e grupo controle. O segundo estudo também objetivou identificar os conceitos associados às respostas sobre SB e BE em cada grupo clínico. Os questionários mostraram-se válidos e confiáveis para uso em crianças e pré-adolescentes com sinais e sintomas de DTM. Além disso, os instrumentos apresentaram propriedade discriminativa entre indivíduos com diferentes condições clínicas e o grupo controle, mas não entre os grupos clínicos. Por fim, os resultados sugeriram que as crianças e pré-adolescentes apresentam visão multidimensional sobre os conceitos de SB e BE. Estes resultados possibilitaram testar as propriedades psicométricas dos questionários em indivíduos com diferentes condições clínicas e iniciar uma série de estudos sobre os fatores associados à auto-percepção da QVRSB. Sendo assim, o terceiro estudo (Factors associated with oral health-related quality of life in children and preadolescents) objetivou avaliar os fatores associados à auto-percepção de QVRSB. Sinais e sintomas de DTM e sintomas de ansiedade em crianças e depressão em pré-adolescentes estiveram associadas com maior impacto na QVRSB destes indivíduos. Para melhorar o entendimento sobre a relação entre os fatores psicológicos e as percepções de SB e BE destes indivíduos, o quarto estudo (Relationships among oral conditions, global ratings of oral health, overall well-being and emotional statuses of children and preadolescents) objetivou avaliar a associação entre as condições bucais, percepções globais de SB e BE e variáveis psicológicas (sintomas de ansiedade e depressão) e fisiológicas (declínio diurno de cortisol salivar) desta população. O aumento na idade e maiores concentrações de cortisol salivar estiveram associados com maiores impactos na percepção global de saúde bucal, enquanto que sinais e sintomas de disfunção temporomandibular e sintomas de depressão estiveram associados ao maior comprometimento do bem-estar geral / Abstract: Over the past two decades, there has been substantial increase in concern about the impact of oral health-related quality of life (OHRQoL) of children and adolescents, which has been due to the fact that oral diseases significantly compromise the physical, emotional and social needs of these individuals. Thus, this research aimed to evaluate the OHRQoL and associated factors in 8- to 14-yr-old children and preadolescents, of both genders, students of public schools of Piracicaba, SP. To evaluate the oral health, the following variables were considered: presence and severity of dental caries, malocclusion, fluorosis, gingivitis according to World Health Organization, and signs and symptoms of temporomandibular disorder (TMD), using the Research Diagnostic Criteria/Temporomandibular Disorders - axis I. Self-perceived of OHRQoL was assessed using age-specific questionnaires, the Brazilian versions of the Child Perceptions Questionnaire (CPQ) for 8- to 10 yr-old children (CPQ8-10) and 11- to 14-yr-old preadolescents (CPQ11-14). Two questions of these questionnaires were also used to assess the global ratings of oral health (OH) and overall well-being (OWB). Sociodemographic characteristics (the child?s age and gender, the number of adults in the household and the mother's educational level), dental service utilization (past and current actual experience) and the child?s oral hygiene habits (tooth brushing frequency) were evaluated as part of the factors associated with OHRQoL. Symptoms of anxiety and depression were assessed using the Portuguese versions of the Revised Children's Manifest Anxiety Scale (RCMAS) and the Children's Depression Inventory (CDI), respectively. To evaluate the salivary cortisol concentrations, saliva sampling was collected 30 minutes after awakening (fasting) and at night (bedtime) to determine the diurnal decline of salivary cortisol (in ?g/dl), then, the difference between the values of the first and second samples were obtained. Salivary cortisol concentrations were determined by enzyme immunoassay analysis. The data were discussed in four studies, denominated as chapters in this work. The specific objectives of the first (Evaluating oral health-related quality of life measure for children and preadolescents with temporomandibular disorder) and second (Oral health-related quality of life in children and preadolescents with dental caries, malocclusions or temporomandibular disorders) chapters were to evaluate the psychometric properties of the questionnaires for using in children and preadolescents with signs and symptoms of TMD, to compare the OHRQoL of groups with different oral conditions (caries, malocclusion and TMD) and controls, respectively. The second study also aimed to identify the concepts associated with the responses of each clinical group to OH and OWB. The questionnaires showed to be valid and reliable for use in children and preadolescents with signs and symptoms of TMD. In addition, the questionnaires discriminated between individuals with different clinical conditions and controls, but not within clinical groups. Finally, the results suggested that children and preadolescents view their OH and OWB as multidimensional concepts. These results provide the opportunity to test the psychometric properties of the questionnaires among individuals presenting a variety of clinical conditions and to start a series of studies about the factors associated with the self-perception of OHRQoL. In this way, the third study (Factors associated with oral health-related quality of life in children and preadolescents) aimed to evaluate the factors associated with self-perception of OHRQoL. Signs and symptoms of TMD and symptoms of anxiety in children and depression in preadolescents were associated with higher impact on their OHRQoL. To improve the understanding about the relation between psychological factors and the perception of OH and OWB of these individuals, the fourth study ("Relationships among oral conditions, global ratings of oral health, overall well-being and emotional statuses of children and preadolescents") aimed to evaluate the associations between oral conditions, global ratings of OH and OWB and psychological (symptoms of anxiety and depression) and physiological (diurnal decline of salivary cortisol) variables. Older children and higher levels of salivary cortisol were associated with negative impacts on global ratings of OH, while signs and symptoms of TMD and symptoms of depression were associated with negative impacts on global ratings of OWB / Doutorado / Odontopediatria / Doutor em Odontologia

Abstract The aim of the study was to evaluate the efficacy and safety of antenatal and postnatal corticosteroids in the prevention for mortality and acute and long-term morbidity in preterm infants. Altogether 109 eligible preterm infants participated in a randomized, multi-center, double-blinded controlled trial studying the efficacy of early dexamethasone (DX) treatment. The infants received either four doses of DX or placebo. DX treatment did not have a detectable influence on survival without bronchopulmonary dysplasia (BPD), severe intracranial hemorrhage, or periventricular leukomalacia. In a meta-analysis of 15 trials, we found that early prolonged DX treatment (> 96 h, n = 1594 infants) decreased the risk of BPD (RR 0.72 95% CI 0.61–0.87), whereas early short DX course did not (n = 1069 infants). However, prolonged DX increased the risk of gastrointestinal (GI) complications (RR 1.59 95% CI 1.02–2.46). Fifty-one very preterm infants participated in a randomized placebo-controlled trial studying early hydrocortisone (HC) started before 36 hours of age and continued for 10 days. The basal and stimulated serum cortisol levels were measured before the intervention. The study was interrupted because of GI perforations in the HC group. HC decreased the risk of patent ductus arteriosus. HC-treated infants with serum cortisol concentrations above the median had a high risk of GI perforation. HC increased survival without BPD among infants with low endogenous cortisol levels. Altogether 45 surviving infants were enrolled in the follow-up of the early HC trial at 2 years of age. None of the study patients had died after discharge. There was no difference in the recorded rehospitalization rate, growth characteristics, or neurological development between HC and placebo-treated children. Altogether 249 women pregnant at less than 34.0 gestational weeks participated in a randomized trial studying the efficacy of a single additional dose of betamethasone (BM). All of the 159 infants in the BM group and 167 in the placebo group were born before 36 weeks of gestation. Intact survival was comparable between the BM and placebo groups, whereas the need for surfactant therapy in RDS was increased in the BM group. According to a post hoc analysis of 206 infants delivered within 1–24 hours, the BM booster tended to increase the risk of RDS and to decrease intact survival.

Chronic inflammation is intimately linked with cancer development and progression and therefore reducing or eliminating inflammation represents a logical treatment and prevention strategy. Studies have shown that anti-inflammatory agents have anti-tumour effects in cancers, with reduced metastases and mortality. Current use of anti-inflammatory agents in the treatment and prevention of cancer is limited by their toxicity and side effects. The emerging field of nanotechnology allows the fundamental properties of a drug to be altered, creating a product with improved reactivity and bioavailability, leading to more targeted treatments and reduced dosage. In the present study, the genotoxic effects of three commonly used anti-inflammatory drugs; aspirin, ibuprofen and hydrocortisone, in their bulk and nano forms were evaluated on peripheral blood lymphocytes of healthy donors using the comet assay and the micronucleus assay. In order to determine any anti-cancer effects, these agents were also tested in peripheral blood lymphocytes in patients with haematological cancers. The glucocorticoid hydrocortisone was also evaluated for anti-oxidant capacity. Our results demonstrate that the nano versions of each drug produced a different response than the bulk counterpart, indicating that a reduction in particle size had an impact on the reactivity of the drug. Our results also indicate that the nano versions of each drug were less genotoxic than the bulk formulation, further emphasising the potential of nanoparticles as an improvement to current treatment options. We also found an anti-oxidant effect with hydrocortisone, with a more profound effect seen with the nano formulation.

Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may benefit of hydrocortisone treatment depending on their individual immune response. We performed an exploratory analysis of the database from the international randomized controlled clinical trial Corticosteroid Therapy of Septic Shock (CORTICUS) employing machine learning to a panel of 137 variables collected from the Berlin subcohort comprising 83 patients including demographic and clinical measures, organ failure scores, leukocyte counts and levels of circulating cytokines. The identified theranostic marker was validated against data from a cohort of the Hellenic Sepsis Study Group (HSSG) (n = 246), patients enrolled in the clinical trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT, n = 118), and another, smaller clinical trial (Crossover study, n = 20). In addition, in vitro blood culture experiments and in vivo experiments in mouse models were performed to assess biological plausibility. A low serum IFNg/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this marker for a decision rule, we applied it to three validation sets and observed the same trend. Experimental studies in vitro revealed that IFNg/IL10 was negatively associated with the load of (heat inactivated) pathogens in spiked human blood and in septic mouse models. Accordingly, an in silico analysis of published IFNg and IL10 values in bacteremic and non-bacteremic patients with the Systemic Inflammatory Response Syndrome supported this association between the ratio and pathogen burden. We propose IFNg/IL10 as a molecular marker supporting the decision to administer hydrocortisone to patients in septic shock. Prospective clinical studies are necessary and standard operating procedures need to be implemented, particularly to define a generic threshold. If confirmed, IFNg/IL10 may become a suitable theranostic marker for an urging clinical need.

L'obésité est un problème de santé mondial et grandissant qu'on qualifie d'épidémie. Les problèmes de santé associés au stress sont aussi en croissance. Ces deux phénomènes découlent de nouvelles habitudes de vie. Les travaux de cette thèse visaient à caractériser davantage le lien entre le stress et l'obésité. Premièrement, nous avons tenté d'élargir les connaissances au sujet de l'influence de l'obésité, mais aussi de la perte de poids, sur la réactivité de l'axe hypothalamo-hypophysosurrénalien (HHS), chez des hommes à distribution centrale et des femmes à distribution périphérique du tissu adipeux. La réponse à trois types de stimulations de l'axe HHS a été mesurée chez des individus minces, obèses et à obésité réduite: le test acoustique de sursaut, le test social de stress de Trier et la sécrétion de cortisol en réponse au réveil (SCR). Le test acoustique de sursaut n'a révélé aucune différence marquée entre les différents groupes alors que les deux autres stimulations de l'axe HHS se sont avérées complémentaires. Globalement, les résultats obtenus confirment une hyperréactivité de l'axe HHS dans l'état d'obésité abdominale chez les hommes, alors qu'après une perte de poids, la réactivité s'atténue. Chez les femmes, bien que l'accumulation de graisse périphérique ne semble pas modifier l'état de l'axe HHS, la perte de poids est associée à une réactivité accrue de celui-ci. Deuxièmement, nous avons voulu déterminer si ce lien entre le statut pondéral et l'axe corticotrope était associé aux comportements alimentaires et à la préoccupation à l'égard du poids corporel. Une série de questionnaires nous ont permis d'établir que la SCR chez les femmes est négativement associée à plusieurs des variables mesurées, la susceptibilité émotionnelle à la désinhibition alimentaire ressortant parmi celles-ci. Ainsi, malgré que nous soyons encore loin d'avoir fait toute la lumière sur le lien entre le stress et l'obésité, ces travaux nous ont permis de consolider des observations faites par d'autres groupes de recherche et de faire un pas en avant concernant la mesure de la SCR qui est non seulement reliée au statut pondéral, mais à des comportements qui influencent le poids corporel et l'état de stress des individus. / Obesity is a health problem reaching more and more people and is now considered as a world-wide epidemic. Stress-related health problems also increased during the last decades. The parallel evolution of these two phenomena is not that surprising, since they are both ensuing from our modem life habits. The work of this thesis consisted in better understanding the link between stress and obesity. First, we attempted to enlarge our knowledge about the influence of obesity, but also weight loss, on the hypothalamic-pituitary-adrenal (HPA) axis in men with central and women with peripheral body fat distribution. The response to three types of HPA axis stimulations was assessed in lean, obese and reduced obese subjects: the acoustic startle test (AST), the Trier social stress test and the awakening cortisol response (ACR). The AST revealed no marked difference between the three different weight status groups, while the two other HPA axis stimulations turned out complementary. Globally, the obtained results confirm a hyperreactivity of the HPA axis in abdominal obesity state in men, whereas the reactivity is attenuating with weight loss. In women, although peripheral fat accumulation does not seem to modify the HPA axis status, weight loss is associated with a heightened reactivity of the latter. Secondly, we tried to determine if this link between weight status and HPA axis was related to eating behavior and preoccupation towards body weight. A set of questionnaires permitted us to observe that ACR in women is negatively associated with many of the measured variables; and emotional susceptibility to disinhibition was the most relevant among them. Thus, despite the fact that we are still far to get right from the bottom of the link between stress and obesity, this work allowed us to strengthen the observations made by other research groups and to make a great leap forward concerning the ACR, that revealed a measure related not only to weight status, but also to eating behavior influencing body weight and psychological stress state of individuals.

Le stress fait partie intégrante du quotidien et est très présent dans notre société moderne. En plus d'avoir des répercussions d'ordre psychologique, le stress peut se traduire physiologiquement par une sécrétion accrue de Cortisol. Or, l'élévation de ce glucocorticoïde de stress a été associée à une augmentation de la graisse viscérale. De plus, le stress semble provoquer un accroissement de l'apport calorique, possiblement en raison de l'adoption de comportements alimentaires non souhaitables tels que la restriction et la désinhibition alimentaire. Les travaux présentés dans ce mémoire avaient donc pour but de vérifier les associations entre le niveau de stress, mesuré par le Cortisol salivaire, et les comportements alimentaires chez des femmes préménopausées présentant un surplus de poids. Les résultats obtenus démontrent que Cortisol est associé à la désinhibition alimentaire alors que la restriction semblerait plutôt moduler cette association.

A proposta deste estudo foi comparar a eficácia de tratamento da aplicação tópica de hidrocortisona, do ultra-som terapêutico e da fonoforese no processo de reparo do tendão de Aquiles (tendo calcaneus) de ratos, após tenotomia. O grupo controle foi definido como tenotomizados com simulação da aplicação sônica e tendões não tenotomizados. Os dois grupos tratados com ultra-som terapêutico foram no modo pulsado. A irradiação do ultra-som terapêutico foi realizada na freqüência de 1 MHz e uma intensidade de 0.5 Watts por centímetro ao quadrado (SATA), por cinco minutos cada sessão. No 13° dia de pós-operatório, os tendões foram removidos e analisados por meio da microscopia de luz polarizada, com o propósito de investigar e medir a organização das fibras de colágeno, por meio da birrefringência. Os resultados demonstraram que o grupo tratado com a aplicação tópica de hidrocortisona apresentou valores estatísticos similares ao grupo que recebeu simulação sônica, indicando que não houve penetração da hidrocortisona e que as moléculas de colágeno responderam a estimulação ultra-sônica. Tal fato acontece provavelmente originado pelo efeito piezoelétrico que o ultra-som causa no tecido. O tratamento com fonoforese demonstrou ser o método mais eficiente, devido a maior birrefringência, revelando melhor organização e agregação das fibras de colágeno. Esses achados permitem concluir que o ultra-som terapêutico estimula a aceleração do processo de reparo tecidual e induz a penetração transcutânea da hidrocortisona a 10% numa concentração terapêutica / The purpose of this study was to compare the treatment efficacy of topic hydrocortisone appliance, therapeutic ultrasound and phonophoresis on the rats’ Achilles tendon (tendo calcaneus) repair process after tenotomy. The control group was designed in tenotomized with sham sonic application and non-tenotomized tendons. The two treated groups with therapeutic ultrasound was made in a pulsed mode. The irradiation of therapeutic ultrasound was performed at a frequency of 1 MHz and an intensity of 0.5 Watts for square centimeter (SATA), for five minutes each session. On the 13 th postoperative day, the tendons were removed and analyzed using the polarized light microscopy, with the purpose to detect and measure the organization of collagen fibers through birefringence. The results showed that the treated group with the hydrocortisone topic appliance showed similar statistician values of group that received sham sonic treatment, indicating that not have delivery transdermal and that the molecule of collagen respond to the ultrasonic stimulation. This fact occurs probably by piezoelectric effect originated by ultrasound on the tissue. The treatment with phonophoresis demonstrated being the method more efficient, due the high birefringence, revealing the best organization and aggregation of collagen fibers. These findings allow conclude that the therapeutic ultrasound stimulate the acceleration of tissue repair process and induce the transdermal delivery of hydrocortisone 10% in a therapeutic concentration