Orientador: Sergio Tadeu Martins Marba / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T01:41:15Z (GMT). No. of bitstreams: 1 Vinagre_LuisEduardodeFigueiredo_M.pdf: 699641 bytes, checksum: f53b941c432fcc025a8d30c2ff8a4493 (MD5) Previous issue date: 2009 / Resumo: O objetivo deste trabalho foi avaliar o efeito do uso antenatal do corticosteróide na incidência da hemorragia peri-intraventricular global e em seus graus, levando-se em consideração o efeito do número de doses e o intervalo entre a administração da primeira ou segunda dose e o parto, em recém-nascidos com peso de nascimento entre 500 e 1.500 g. Para tanto foi realizado um estudo analítico retrospectivo, no qual foram incluídos 176 recém-nascidos internados em um hospital terciário do Município de Campinas no período de janeiro de 2000 a dezembro de 2001. Os recém-nascidos foram divididos em dois grupos: um em que se fez uso antenatal do corticosteróide que incluiu 143 participantes e outro que não recebeu este tratamento que abrangeu 33 participantes. Os dados foram analisados inicialmente através de tabelas descritivas e também foram utilizados, quando indicado, o teste do quiquadrado, o teste exato de exato de Ficher, o teste t de Student, o teste de Mann-Whitney e odds ratio. O nível de significância aceito foi de p<0,05 (intervalo de confiança de 95%). Os grupos foram comparáveis na maioria das variáveis; entretanto, houve diferença estatística em relação à idade materna (p = 0,0313), na hipertensão arterial materna (p < 0,0001), no trabalho de parto (p = 0,0059), tipo de parto (p = 0,0152) e infecção neonatal (p = 0,0093). Não houve diferença estatisticamente significativa entre os grupos em relação à idade gestacional, peso de nascimento e escore de Apgar. A incidência global da hemorragia periintraventricular foi de 12,5%, sendo 11,2% para o grupo que fez uso antenatal do corticosteróide e 18,2% para o grupo que não fez uso do tratamento. Este resultado não alcançou significância estatística (OR: 0,57 com IC 95% = 0,19 - 1,80). Não foi observada significância estatística também, ao analisar o período de tempo entre a administração da dose de corticosteróide e o parto e em relação ao número de doses. Apesar da literatura demonstrar um efeito protetor do uso antenatal do corticosteróide na prevenção da hemorragia peri-intraventricular, este trabalho não evidenciou tal efeito. A baixa incidência global da hemorragia peri-intraventricular, juntamente com a elevada taxa de mães hipertensas e de recém-nascidos pequenos para idade gestacional podem ter interferido na análise do uso antenatal do corticosteróide na prevenção desta patologia, ou mais algum outro fator, não identificado, que contribuiu na redução da hemorragia peri-intraventricular, esteve associado ao uso do corticosteróide, ocultando o seu efeito protetor / Abstract: The aim of this study is to evaluate the effects of antenatal corticosteroid therapy on the incidence of intraventricular hemorrhage and in its grade, regarding the effect of number of doses and the timing between the application of the first or second dose and delivery, in newborn with birth weight between 500 and 1,500 grams. An analytic retrospective trial was carried out enrolling 176 newborn admitted at a tertiary center hospital in Campinas city, São Paulo, Brazil, from January 2000 to December 2001. The newborns have been divided into two groups: one received antenatal corticosteroid therapy (143/176) and another (33/176) who have not received the treatment. Data were analyzed through descriptive chart, also when indicated, quisquare test and Fisher exact test, Student's t-test, Mann-Whitney test and odds ratio. The groups were comparable in majority of the variables; nevertheless there was statistically significant difference in maternal age, (p = 0,0313), maternal hypertension (p < 0,0001), labor (p = 0,0059), method of delivery (p = 0,0152) and neonatal sepse (p = 0,0093). There was no statistically significant difference among the groups regarding the gestational age, birth weight and in 5 minutes Apgar score. The global incidence of intraventricular hemorrhage was 12,5%. The incidence for the group which had been treated with antenatal corticosteroid therapy was 11,2%, and the other group it was 18,2%. This outcome didn't reach statistic significance (OR: 0,57; CI 95% = 0,19 - 1,80). Also, there was no statistic significance in the time between the dose application and delivery, and in regarding the number of doses. Despite literature demonstrating a protective effect of the use of antenatal corticosteroid therapy for prevention of intraventricular hemorrhage, this study showed no such effect. The low overall incidence of intraventricular hemorrhage along with high rate of maternal hypertension and small-for-gestational-age infant may have interfered in the analysis of the antenatal corticosteroid therapy in the prevention of this disease, or some other factor that contributes to reduce intraventricular hemorrhage, that couldn't be predicted, was associated with antenatal corticosteroid, obscuring its protective effect / Mestrado / Pediatria / Mestre em Saude da Criança e do Adolescente

Orientadores: Lilian Tereza Lavras Costallat, Fernando Cendes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T06:36:35Z (GMT). No. of bitstreams: 1 Appenzeller_Simone_D.pdf: 2923218 bytes, checksum: ead37b4a881b531bfab95cbff3f95dff (MD5) Previous issue date: 2006 / Resumo: As manifestações do sistema nervoso central (SNC) no Lúpus Eritematoso Sistêmico (LES) são complexas, podendo ser causadas diretamente pela atividade do LES ou serem secundárias a comorbidades. O nosso objetivo foi avaliar as manifestações do SNC no LES e orrelacioná-las às alterações cerebrais estruturais e funcionais à ressonância magnética. Todos os pacientes preenchiam quatro ou mais critérios classificatórios de LES e foram selecionados no ambulatório de Reumatologia da UNICAMP. Observamos que crises epilépticas ocorreram em 11,6% dos pacientes, estando associadas a acidente vascular cerebral e a presença de anticorpos antifosfolípides. A recorrência de crises foi rara, associada somente a presença de anticorpos antifosfolípides. A migrânea ocorreu mais frequentemente no LES que no grupo controle e estava associada a atividade de doença, ao Fenômeno de Raynaud e a presença de anticorpos antifosfolípides. Pacientes com história pregressa de migrânea apresentavam mais dano permanente. Analisando as ressonâncias magnéticas em pacientes com LES, observamos tanto atrofia de substância branca como de substância cinzenta. Embora ambos estivessem associados à presença de manifestações pregressas do SNC e ao maior tempo de doença, somente a atrofia de substância cinzenta esteve associada à dose cumulativa de corticosteróides. Pacientes com distúrbios cognitivos apresentaram mais frequentemente atrofia de corpo caloso e de hipocampo. Observamos também uma disfunção axonal no LES, associada a atividade de doença. De acordo com os nossos resultados, os métodos de neuroimagem estruturais e funcionais são úteis na confirmação do envolvimento do SNC e também na identificação do envolvimento subclínico no LES / Abstract: Central nervous system (CNS) manifestations in systemic lupus erythematosus (SLE) arecomplex. They may be directly caused by SLE disease activity or may be secondary to comorbities. Our objective was to determine CNS manifestations in SLE patients and to determine structural and functional neuroimaging abnormalities associated with its occurrence. Patients with four or more classification criteria for SLE, followed at the Rheumatology Unit of the State University of Campnas were included. We observed 11.6% of epileptic seizures in SLE patients. The occurrence of epileptic seizures was associated with the presence of stroke and antiphospholipid antibodies. Recurrence of seizures was rare and associated only with the presence of antiphospholipid antibodies. Migraine was more frequently observed in SLE patients than controls and was associated with disease activity, Raynaud¿s phenomenon and antiphospholipid antibodies. Pacients with past history of migraine had more frequently organ damage. We observed white and gray matter atrophy in SLE patients. Although both were associated with disease duration and past history of CNS involvement, only gray matter atrophy was associated with the total corticosteroid dose. Patients with cognitive impairment had more frequently corpus callosum and hippocampal atrophy. A transient axonal dysfunction, secondary to disease activity and not to CNS involvement, was observed in SLE. Our results suggest that structural and functional neuroimaging methods are useful in confirming CNS involvement, but also identify subclinical involvement in SLE patients / Doutorado / Clinica Medica / Doutor em Clínica Médica

Stress can be defined as a condition in which the dynamic equilibrium of the body is disturbed and several studies have demonstrated the action of some corticosteroids modulating stress situations, such as reproduction. However, the role of corticosteroids in fish reproduction can be either positive or deleterious, depending on many variables. In the Astyanax genus, the same stress stimulus can successfully induce the reproduction in Astyanax altiparanae, but not in other species of the same genus. Therefore, the aim of this study was to analyze cortisol and progestogens plasma levels and receptor gene expression in the ovaries of A. altiparanae, a teleost species that successfully reproduce using crowding and water level drawdown as stimulus. Three experimental groups were considered: Stress (high stocking density and water level drawdown); human chorionic gonadotropin (hCG, a positive control); and Saline (a control group). Females were sampled at three different moments of the artificial reproduction experiment, initial, intermediary and at spawning. Indices of spawning performance as, fertilization rate, Gonadosomatic Index (GSI), as well as histological analysis of the ovaries were carried out. 17&alpha;-hydroxiprogesterone (17 OHP) and cortisol (CORT) levels were measured in plasma by ELISA. Additionally, the ovarian gene expression of CORT and 17 OHP receptors (CR and PR) were carried out by Real-time quantitative PCR. Females from Stress and hCG groups released a larger volume of eggs when compared with females from the Saline (Control) group. Females from Stress group presented a decrease in GSI and ovaries mass at spawning, and many post ovulatory follicles (POFs) were present in the ovaries after spawning. At the intermediary sampling, plasma levels of CORT increased in females from the Stress group, but not in the hCG and Saline groups. 17 OHP levels did not change during the experiment. PR gene was more expressed in females from hCG group throughout the experiment, but CR gene expression did not change. We suggest a possible role of CORT as an inducing agent in ovulation and/or spawning of A. altiparanae. CR and PR did not seem to be the candidates for triggering ovulation, so the relationship between the derivative of progesterone (17,20DHP) should be deeper studied, as well as the role of CORT and different progestagens in A. altiparanae reproduction / O estresse pode ser definido como uma condição na qual o equilíbrio dinâmico do corpo é perturbado e muitos estudos têm demonstrado a ação de alguns corticosteroides modulando situações de stress, tal como a reprodução. No entanto, o papel dos corticosteroides na reprodução de peixes pode ser positivo ou deletério, dependendo de muitas variáveis. No gênero Astyanax, o mesmo estímulo de estresse pode induzir com sucesso a reprodução em A. altiparanae, mas não em outras espécies do mesmo gênero. Portanto, o objetivo deste estudo foi analisar os níveis de cortisol e progestágenos no plasma e a expressão dos receptores destes esteroides nos ovários de A. altiparanae, espécie de teleósteo que consegue se reproduzir com sucesso usando o aumento da densidade e variação no nível da água como um estímulo. Três grupos experimentais foram considerados: Estresse (alta densidade de estocagem e intenso fluxo de água); Gonadotropina Coriônica Humana (hCG, um controle positivo); e Salina (grupo controle). As fêmeas foram amostradas em três diferentes momentos do experimento de reprodução artificial, inicial, intermediário e na desova. Índices de desempenho de desova como, taxa de fertilização, Índice Gonadossomático (IGS), bem como a análise histológica dos ovários foram considerados. Os níveis de 17&alpha;-hydroxiprogesterone (17 OHP) e cortisol (CORT) foram medidos em amostras de plasma por ELISA. Além disso, a expressão de genes de receptores de CORT (CR) e 17 OHP (PR) foram analisadas nos ovários por qPCR. Fêmeas dos grupos Estresse e hCG desovaram um volume maior de ovos quando comparadas às fêmeas do grupo Salina (controle). As fêmeas do grupo Estresse apresentaram também uma redução nos valores do IGS e na massa dos ovários no momento da desova, e muitos folículos pós - ovulatórios estavam presentes nos ovários após a desova. Na amostragem do período intermediário, os níveis plasmáticos de CORT aumentaram nas fêmeas do grupo de Estresse, mas não nos grupos de hCG e Salina. A concentração de 17OHP não se alterou durante o experimento ou entre os grupos. O PR foi mais expresso em fêmeas do grupo hCG ao longo do experimento, e a expressão do CR não se alterou. Sugerimos um possível papel de CORT como um agente indutor na ovulação e / ou de desova de A. altiparanae. No entanto, CR e PR não parecem ser os candidatos para desencadear a ovulação, de modo que a relação entre receptores derivados PR (17,20DHP) devem ser mais profundamente estudados, bem como a efetiva ação de CORT e diferentes progestágenos na reprodução de A. altiparanae

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13439号 / 論医博第2238号 / 新制||医||1054(附属図書館) / (主査)教授 万代 昌紀, 教授 小杉 眞司, 教授 稲垣 暢也 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Objectives: Mental and physical stress can suppress the immune system in both humans and animals. The mechanism by which stress affects immune responses, however, remains poorly defined. Toll-like receptors (TLRs) play a key role in modulating immune responses and cell survival. The mechanisms by which TLRs modulate chronic stress are largely unexplored. Methods: Six- to 8-week-old male mice were subjected to chronic 12-hour daily physical restraint stress. Apoptotic cells were determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. We examined cytokine levels by enzyme-linked immunosorbent Assay (ELISA). The expression of CYP11A1 was determined by quantitative real-time RT-PCR. Results: TLR9-deficient mice were resistant to chronic stress-induced lymphocyte apoptosis. In addition, in TLR9 knockout (KO) mice, chronic stress-induced upregulation of corticosterone levels was significantly decreased. Notably, lymphocytes from both TLR9 KO and wild-type mice were similarly sensitive to corticosteroid-induced cell apoptosis. Moreover, TLR9 deficiency blocked the chronic stress-induced imbalance in T helper (Th) 1 and Th2 cytokine levels. Conclusion: Taken together, our findings reveal that TLR9 plays an essential role in chronic stress-induced immune suppression.

Objectives: Mental and physical stress can suppress the immune system in both humans and animals. The mechanism by which stress affects immune responses, however, remains poorly defined. Toll-like receptors (TLRs) play a key role in modulating immune responses and cell survival. The mechanisms by which TLRs modulate chronic stress are largely unexplored. Methods: Six- to 8-week-old male mice were subjected to chronic 12-hour daily physical restraint stress. Apoptotic cells were determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. We examined cytokine levels by enzyme-linked immunosorbent Assay (ELISA). The expression of CYP11A1 was determined by quantitative real-time RT-PCR. Results: TLR9-deficient mice were resistant to chronic stress-induced lymphocyte apoptosis. In addition, in TLR9 knockout (KO) mice, chronic stress-induced upregulation of corticosterone levels was significantly decreased. Notably, lymphocytes from both TLR9 KO and wild-type mice were similarly sensitive to corticosteroid-induced cell apoptosis. Moreover, TLR9 deficiency blocked the chronic stress-induced imbalance in T helper (Th) 1 and Th2 cytokine levels. Conclusion: Taken together, our findings reveal that TLR9 plays an essential role in chronic stress-induced immune suppression.

The perinate is particularly risk-prone to chemical species which have the potential of inducing neuronal apoptosis or necrosis and thereby adversely altering development of the brain, to produce life-long functional and behavioral deficits. This paper is an overview for many substances of abuse, but the purview is much more broadened by the realization that even elevated levels of estrogens and corticosteroids in the pregnant mother can act as neuroteratogens, by passing via the placenta and altering neural development or inducing apoptosis in the perinate. Finally, therapeutic risks of anesthetics are highlighted, as these too induce neuronal apoptosis in the neonate by either blocking N-methyl-D-aspartate receptors or by acting as gamma-aminobutyric acid agonists. By understanding the mechanisms involved it may ultimately be possible to interrupt the mechanistic scheme and thereby prevent neuroteratological processes.

No description available.

京都大学 / 新制・課程博士 / 博士(社会健康医学) / 甲第24808号 / 社医博第132号 / 新制||社医||12(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 川上 浩司, 教授 西浦 博, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Inhaled corticosteroids (ICS) are used to address inflammatory illnesses including asthma and COPD, with delivery commonly achieved using pressurised metered dose inhalers (pMDI). Hydrofluoroalkanes (HFAs) have been introduced as an alternative propellant to chlorofluorocarbons (CFCs) to reduce their environmental impact. However, the thermodynamic properties of HFAs are poorly understood and are different to those of CFCs. It is essential, therefore, to characterise the drugs and excipients used in HFA inhalers in order to obtain a comprehensive understanding of the device performance and the therapeutic efficacy. This work has developed different analytical methods to study the complexation between ICS and CD which are added to enhance the solubility of inhaled drugs in pMDI propellant systems providing rational control of suspension vs. solution formulations and hence their dose uniformity and stability. The Nuclear Magnetic Resonance (NMR) method developed has shown weaker complexation between budesonide and the derivatised CDs DIMEB and TRIMEB in organic solvents compared to D2O with the strength of the complex formed being ranked as D2O > MeOD > CDCl3 > CD3CN. The derivatisation of the CD also shows a marked difference in complexation with budesonide with the strength of the association being ranked as DIMEB > βCD > TRIMEB. Studies of various ICS compounds with TRIMEB in the fluorinated propellant HPFP showed the association to be greatest in budesonide, followed by beclomethasone dipropionate, momestasone furoate and fluticasone propionate. Surface-enhanced Raman scattering (SERS) has been used for the detection of corticosteroids in water using thiol functionalised βCD as a complementary study to NMR. This has been utilised to evaluate the host-guest complexes formed and provides further insight into the complexation of the compounds by their inclusion into the CD cavity. The structural data obtained using the NMR and SERS approaches developed have provided a fundamental insight into the physical chemistry of these interactions at a molecular level.