Orientador: Rogério Dias / Coorientador: Daniel Spadoto Dias / Banca: Nilton José Leite / Banca: Reginaldo Guedes Coelho Lopes / Resumo: Objetivo do estudo. Comparar os resultados entre duas técnicas de ablação endometrial de primeira geração. Tipo de estudo. Estudo prospectivo, longitudinal e analítico (Canadian Task Force II-2). Local do estudo. Hospital público terciário, centro universitário de ensino. Pacientes e métodos. Durante o período de outubro de 2011 a setembro de 2013, 73 pacientes com história de sangramento uterino anormal (SUA) e resposta insatisfatória ao tratamento clínico por um período mínimo de 12 meses, foram randomizadas e submetidas à ablação endometrial por ressecção com eletrodo monopolar em alça "U" seguida de eletrocoagulação com rollerball no grupo A (36 pacientes) e eletrocoagulação apenas com rollerball no grupo B (37 pacientes). As mulheres foram acompanhadas por período médio de 359 dias (280;751) e 370 dias (305;766), respectivamente. Intervenções. As pacientes foram submetidas à ablação endometrial conforme a técnica de cada grupo. Avaliações nos tempos 30, 90, 180 e 360 dias foram realizadas através de protocolo de pesquisa, que procurou avaliar o padrão de sangramento, sintomas associados, índice de falha e taxa de satisfação. Resultados. Os grupos foram clínico-epidemiologicamente homogêneos (P ≥ 0,05). O tempo cirúrgico e o volume utilizado do meio distensor foram menores nas pacientes do grupo B [média de 48,5 (±12,0) vs. 31,9 (±5,6) minutos; P < 0,001 e 5.700 mL vs. 3.500 mL; P < 0,01]. Observou-se uma considerável melhora no quadro clínico após ablação endometrial, em ambos os grupos, com redução do número de dias de sangramento (P < 0,01), assim como do número de absorventes utilizados no dia de maior fluxo (P < 0,01) e durante todo o período menstrual (P < 0,01). Houve também menor incidência de infecção do sítio cirúrgico no grupo B (30,5% vs. 8,1%; P < 0,05). A taxa de histerectomia observada no estudo foi de 9,6%, decorrente de ... / Abstract: Purpose of the study. Compare the results of two techniques of endometrial ablation first generation. Type of study. Prospective, longitudinal and analytical study (Canadian Task Force II-2). The study site. Tertiary public hospital, university teaching center. Patients and methods. During the period October 2011 to September 2013, 73 patients with a history of abnormal uterine bleeding (AUB) and poor response to medical treatment for a minimum period of 12 months, were randomized and underwent endometrial ablation with monopolar resection electrode handle "U" followed by rollerball electrocoagulation with the group a (36 patients) with rollerball electrocoagulation only in group B (37 patients). The women were followed for an average period of 359 days (280;751) and 370 days (305;766), respectively. Interventions. The patients were submitted to endometrial ablation technique according to each group. Ratings at 30, 90, 180 and 360 days were accomplished through research protocol, which sought to assess the pattern of bleeding, associated symptoms, failure rate and satisfaction rate. Results. The groups were homogeneous clinical and epidemiologically (P ≥ 0.05). Surgical time and the volume of distension medium used were lower in group B patients [mean of 48.5 (±12.0) vs. 31.9 (±5.6) minutes; P < 0.001 and 5.700 mL vs. 3.500 mL; P < 0.01]. There was a significant improvement in clinical symptoms after endometrial ablation in both groups, reducing the number of bleeding days (P < 0.01), as well as the number of pads used on the day of the flow rate (P < 0.01) and throughout the menstrual cycle (P < 0.01). There was also a lower incidence of surgical site infection in group B (30.5% vs. 8.1%; P < 0.05). The hysterectomy rate observed in the study was 9.6%, due to technical difficulties and intraoperative hemorrhage, persistence of SUA, development of incapacitating dysmenorrhea and / or pelvic pain ... / Mestre

No description available.

Endogenous brain compounds and xenobiotics, including the neurotoxins such as the amphetamine analogs 3,4-methylenedioxymethamphetamine (MDMA,Ecstasy), methamphetamine (METH, Speed) and methylenedioxyamphetamine (MDA, active metabolite of MDMA), may be bioactivated by prostaglandin H synthase (PHS) to free radicals that generate reactive oxygen species (ROS). In the absence of adequate antioxidant or repair mechanisms, ROS oxidize macromolecules such as DNA, protein and lipids, which can lead to toxicity. In vitro, we evaluated bioactivation using both purified ovine PHS-1 and cultured cells stably overexpressing either human PHS-1 or hPHS-2 isozymes. We found the neurotransmitter dopamine, its precursors and some metabolites, as well as METH and MDA, can be bioactivated by ovine and/or human PHS in an isozyme-dependent fashion that generates ROS, which oxidize DNA and protein and increase toxicity. This process is blocked by both the PHS inhibitor acetylsalicylic acid (ASA) and the ROS detoxifying enzyme catalase. Our data are the first to reveal isozyme-dependent bioactivation by PHS as a potential mechanism for enhanced susceptibility to both exogenous and endogenous neurotoxins, the latter of which may be particularly important in aging. METH-initiated ROS can also activate redox-sensitive transcription factors such as nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in the induction of an array of protective mechanisms in both adult and fetal brain. Using Nrf2 knockout mice, we showed Nrf2 has a novel neuroprotective role in METH-initiated oxidative stress, neurotoxicity and functional deficits in both fetal development and adulthood, especially with multiple exposures allowing time for the induction of neuroprotective mechanisms. Our studies are the first to show that Nrf2 afforded protection against both motor coordination deficits and olfactory deficits caused by METH in utero and in adults, suggesting that deficiencies in Nrf2 activation constitute a risk factor for ROS-mediated neurotoxicity in the fetus and adult.

Endogenous brain compounds and xenobiotics, including the neurotoxins such as the amphetamine analogs 3,4-methylenedioxymethamphetamine (MDMA,Ecstasy), methamphetamine (METH, Speed) and methylenedioxyamphetamine (MDA, active metabolite of MDMA), may be bioactivated by prostaglandin H synthase (PHS) to free radicals that generate reactive oxygen species (ROS). In the absence of adequate antioxidant or repair mechanisms, ROS oxidize macromolecules such as DNA, protein and lipids, which can lead to toxicity. In vitro, we evaluated bioactivation using both purified ovine PHS-1 and cultured cells stably overexpressing either human PHS-1 or hPHS-2 isozymes. We found the neurotransmitter dopamine, its precursors and some metabolites, as well as METH and MDA, can be bioactivated by ovine and/or human PHS in an isozyme-dependent fashion that generates ROS, which oxidize DNA and protein and increase toxicity. This process is blocked by both the PHS inhibitor acetylsalicylic acid (ASA) and the ROS detoxifying enzyme catalase. Our data are the first to reveal isozyme-dependent bioactivation by PHS as a potential mechanism for enhanced susceptibility to both exogenous and endogenous neurotoxins, the latter of which may be particularly important in aging. METH-initiated ROS can also activate redox-sensitive transcription factors such as nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in the induction of an array of protective mechanisms in both adult and fetal brain. Using Nrf2 knockout mice, we showed Nrf2 has a novel neuroprotective role in METH-initiated oxidative stress, neurotoxicity and functional deficits in both fetal development and adulthood, especially with multiple exposures allowing time for the induction of neuroprotective mechanisms. Our studies are the first to show that Nrf2 afforded protection against both motor coordination deficits and olfactory deficits caused by METH in utero and in adults, suggesting that deficiencies in Nrf2 activation constitute a risk factor for ROS-mediated neurotoxicity in the fetus and adult.

Made available in DSpace on 2015-05-14T16:53:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-10Bitstream added on 2015-05-14T16:59:16Z : No. of bitstreams: 1 000825160.pdf: 709651 bytes, checksum: 51e908d6fe4712ab7da7bea551017d14 (MD5) / Objetivo do estudo. Comparar os resultados entre duas técnicas de ablação endometrial de primeira geração. Tipo de estudo. Estudo prospectivo, longitudinal e analítico (Canadian Task Force II-2). Local do estudo. Hospital público terciário, centro universitário de ensino. Pacientes e métodos. Durante o período de outubro de 2011 a setembro de 2013, 73 pacientes com história de sangramento uterino anormal (SUA) e resposta insatisfatória ao tratamento clínico por um período mínimo de 12 meses, foram randomizadas e submetidas à ablação endometrial por ressecção com eletrodo monopolar em alça U seguida de eletrocoagulação com rollerball no grupo A (36 pacientes) e eletrocoagulação apenas com rollerball no grupo B (37 pacientes). As mulheres foram acompanhadas por período médio de 359 dias (280;751) e 370 dias (305;766), respectivamente. Intervenções. As pacientes foram submetidas à ablação endometrial conforme a técnica de cada grupo. Avaliações nos tempos 30, 90, 180 e 360 dias foram realizadas através de protocolo de pesquisa, que procurou avaliar o padrão de sangramento, sintomas associados, índice de falha e taxa de satisfação. Resultados. Os grupos foram clínico-epidemiologicamente homogêneos (P ≥ 0,05). O tempo cirúrgico e o volume utilizado do meio distensor foram menores nas pacientes do grupo B [média de 48,5 (±12,0) vs. 31,9 (±5,6) minutos; P < 0,001 e 5.700 mL vs. 3.500 mL; P < 0,01]. Observou-se uma considerável melhora no quadro clínico após ablação endometrial, em ambos os grupos, com redução do número de dias de sangramento (P < 0,01), assim como do número de absorventes utilizados no dia de maior fluxo (P < 0,01) e durante todo o período menstrual (P < 0,01). Houve também menor incidência de infecção do sítio cirúrgico no grupo B (30,5% vs. 8,1%; P < 0,05). A taxa de histerectomia observada no estudo foi de 9,6%, decorrente de ... / Purpose of the study. Compare the results of two techniques of endometrial ablation first generation. Type of study. Prospective, longitudinal and analytical study (Canadian Task Force II-2). The study site. Tertiary public hospital, university teaching center. Patients and methods. During the period October 2011 to September 2013, 73 patients with a history of abnormal uterine bleeding (AUB) and poor response to medical treatment for a minimum period of 12 months, were randomized and underwent endometrial ablation with monopolar resection electrode handle U followed by rollerball electrocoagulation with the group a (36 patients) with rollerball electrocoagulation only in group B (37 patients). The women were followed for an average period of 359 days (280;751) and 370 days (305;766), respectively. Interventions. The patients were submitted to endometrial ablation technique according to each group. Ratings at 30, 90, 180 and 360 days were accomplished through research protocol, which sought to assess the pattern of bleeding, associated symptoms, failure rate and satisfaction rate. Results. The groups were homogeneous clinical and epidemiologically (P ≥ 0.05). Surgical time and the volume of distension medium used were lower in group B patients [mean of 48.5 (±12.0) vs. 31.9 (±5.6) minutes; P < 0.001 and 5.700 mL vs. 3.500 mL; P < 0.01]. There was a significant improvement in clinical symptoms after endometrial ablation in both groups, reducing the number of bleeding days (P < 0.01), as well as the number of pads used on the day of the flow rate (P < 0.01) and throughout the menstrual cycle (P < 0.01). There was also a lower incidence of surgical site infection in group B (30.5% vs. 8.1%; P < 0.05). The hysterectomy rate observed in the study was 9.6%, due to technical difficulties and intraoperative hemorrhage, persistence of SUA, development of incapacitating dysmenorrhea and / or pelvic pain ...

Orientador: Iracema de Mattos Paranhos Calderon / Coorientador: Cláudia Garcia Magalhães / Banca: Marilza Vieira da Cunha Rudge / Banca: Roseli Mieko Yamamoto Nomura / Resumo: Construir uma curva de PI umbilical exclusiva de gestações complicadas por diabete melito (DM) ou hiperglicemia e compará-la com curvas de referência (Arduini e Rizzo, 1990; Sakamoto, 2007). Estudo longitudinal, onde foram incluídas 163 gestantes e excluídos os casos de gemelaridade, malformação, dificuldade técnica e menos de cinco consultas no pré-natal. Foram avaliados idade materna, índice de massa corporal (IMC) pré-gestacional, número de gestações e associação com tabagismo e hipertensão arterial (HA), além dos níveis de hemoglobina glicada (HbA1c) no final da gestação. No total, foram avaliadas 431 medidas de PI umbilical, entre 24 e 41 semanas de gestação. Para cada semana gestacional foram realizadas medidas de tendência central e de dispersão dos valores atribuídos e calculados os índices dos respectivos percentis (P5, 10, 25, 50 e 95). A correlação, a equação de predição e os intervalos de confiança (IC 95%) foram estimados por análise de regressão linear simples. Realizou-se comparação qualitativa por sobreposição das três curvas e, quantitativa, entre as curvas do estudo e de Sakamoto (2007). Adotou-se o limite de significância de 95% (p < 0,05). A equação de predição do PI umbilical foi expressa por [PI umb = 1,521 - 0,018* semana de gestação]. Os limites de P95 do PI umbilical evoluíram sempre abaixo dos limites da curva de referência de Arduini e Rizzo (1990) e apresentaram queda acentuada a partir da 37ª. semana, quando se confirmou diferença estatística em relação aos índices de Sakamoto (2007). Antes de sua proposição, outros estudos deverão validar a curva desenvolvida nesse estudo / Abstract: To construct a curve PI umbilical exclusive of pregnancies complicated by diabetes mellitus (DM) or hyperglycemia and compare it with reference curves (Arduini and Rizzo, 1990; Sakamoto, 2007). A longitudinal study where 163 women were included and excluded cases of multiple births, malformations, technical difficulty and less than five prenatal visits. We assessed maternal age, body mass index (BMI) before pregnancy, number of pregnancies and is associated with smoking and hypertension (HA), and levels of glycated hemoglobin (HbA1c) in late pregnancy. In total, 431 measurements were evaluated umbilical PI, between 24 and 41 weeks gestation. For each gestational week were performed measures of central tendency and dispersion values assigned and calculated indices of the respective percentiles (P5, 10, 25, 50 and 95). The correlation equation prediction and confidence intervals (95% CI) were estimated by linear regression analysis. We carried out a qualitative comparison of the three curves overlap and quantitative study between the curves and Sakamoto (2007). The adopted threshold of significance of 95% (p <0.05).The prediction equation was expressed by umbilical PI [PI umb = 1.521 - 0.018 * week of pregnancy]. The limits of the P95 evolved umbilical PI always below the limits of the reference curve of Arduini ... / Mestre

Orientador: Marco Antonio Alvarenga / Banca: Marco Antonio Alvarenga / Banca: José Antonio Dell'Aqua Jr. / Banca: Rodrigo Costa Mattos / Resumo: A endometrite persistente pós-cobertura (EPPC) é a principal causa de redução da fertilidade nas éguas, causando impactos importantes dentro do mercado do cavalo. Os tratamentos comumente utilizados para EPPC visam apenas minimizar os fatores predisponentes a sua instalação, não atuando diretamente no processo inflamatório. Com o intuito de reduzir a resposta inflamatória, estudos recentes têm demonstrado um aumento da fertilidade de animais acometidos por EPPC, quando se utiliza agentes imunomoduladores. O PRP é modulador da resposta inflamatória que está sendo largamente utilizado na medicina veterinária. Este concentrado de plaquetas contém diversos fatores de crescimento que atuam diretamente nos mediadores inflamatórios, reduzindo o processo e promovendo reparação tecidual. O PRP é benéfico no tratamento de inflamações tendíneas e osteoarticulares, modulando a inflamação e acelerando a regeneração do tecido lesionado. Mais recentemente alguns pesquisadores demonstraram o efeito benéfico do PRP em tratamentos intrauterinos de éguas. Desta forma o presente estudo tem por objetivo revisar os aspectos relacionados a EPPC assim como ao PRP e seu mecanismo de ação. / Abstract: The persistent breeding-induced endometritis (PBIE) is the main cause of decrease fertility in the horses, thereby causing significant impact in the horse's market. The treatments commonly used for PBIE view only minimize the predisposing factors and do not act directly in the inflammatory process. Aiming to reduce the inflammatory response, recent studies have shown an increase in fertility of animals with PBIE when used immunomodulatory agents. A modulator of the inflammatory response that has been largely used in veterinary medicine is the platelet-rich plasma (PRP). This platelet concentrate contains many growth factors which act directly on inflammatory mediators, reducing process and promoting tissue repair. Several studies have shown that PRP is beneficial in the treatment of osteoarticular and tendon inflammations, modulating inflammation and accelerates the regeneration of injured tissue. More recently some researchers have demonstrated the beneficial effect of PRP in intrauterine treatment of mares. Thus, the present study aimed to do a literature review on the aspects related to PBIE, as well as the PRP and its mechanism of action. / Mestre

No description available.

No description available.

Les pathologies vasculaires placentaires (PVP), prééclampsie (PE) et retard de croissance intra-utérin (RCIU), sont une des causes majeures de morbidité et mortalité maternelles et périnatales dans les pays développés. Un défaut de vascularisation utéro-placentaire est présent dans ces deux pathologies. Le Doppler énergie 3D (3DPD) est un outil facile à utiliser en clinique, les indices quantitatifs calculés à partir de volume utéro-placentaire semblent prometteurs pour dépistage de la PE. Le but principal de cette thèse est d’évaluer cette technique sur le plan de sa valeur discriminative entre situation physiologique et pathologique, ainsi que sur le plan de ses limites techniques en clinique et sur modèles animaux. La performance des indices 3DPD au 1er trimestre pour dépister la PE et/ou RCIU a été étudiée dans une étude prospective multicentrique. Une évaluation de la corrélation entre les indices 3DPD et les indices morphométrique a été ensuite réalisée chez les femmes enceintes à la fin de grossesse. Une corrélation entre le phénotype des villosités placentaire et la qualité de la perfusion placentaire a été mise en évidence. À la fin, l’intérêt de la technique a été démontré dans un modèle de RCIU chez brebis gestante. / Placental vascular pathologies (PVP), preeclampsia (PE) and intra uterine growth restriction (IUGR), are a major cause of maternal and perinatal morbidity and mortality in developed countries. A default of utero-placental vascularization is present in these two pathologies. 3D Power Doppler (3DPD) is an easy tool to use in clinic, its quantitative indices calculated from obtained utero-placental volume seem promising for PE prediction. The major objective of this thesis was to evaluate the discriminative value of this technique between physiological and pathological situations, as well as its limitations in clinical and animal models. The screening performance of PE and/or IUGR by 3DPD indices in the first trimester was studied in a prospective multicenter study. An evaluation of the correlation between 3DPD indices and morphometric indices was then carried out among pregnant women at term. At the end, the interest of the technique was demonstrated in an ewe model of IUGR (treated with testosterone).