In the present study samples were collected from abdominal linea alba aponeurosis of 30 patients (15 males and 15 females) aged from twenty to sixty years [30-59], (Mean=44.9±SD=7.3), with hernia of the anterior abdominal wall to evaluate the immunohistochemistry expression and morphometry of the elastic fibers. Nine of the patients were submitted to surgery at the Hospital de Clínicas in Porto Alegre (HCPA), ten of then at the Santa Casa de Misericórdia do Rio de Janeiro (SCMRJ), seven of them at the author’s private clinic (CA) in Caxias do Sul, and four of them at the Hospital Pompeia (HP) in Caxias do Sul. All patients had a hernia of the anterior abdominal wall. Fourteen of these cases were umbilical hernias, ten epigastric hernias and six incisional hernias. Specimens were collected from the midline three centimeters above the umbilical scar and from two centimeters below it. At the laboratory, the specimens were subdivided in two parts. One of these specimens was stained with orcein and the elastic fibers were counted by digital analysis using the applicative Image Pro Plus (Media Cybernetics, Silver Spring, USA). The other specimen was submitted to evaluation through immunohistochemistry analysis utilizing monoclonal anti-Emilin Antibody to EMILIN1 GP115 Elastin microfibril interface located protein TNF (Proteintech Group), in 1:100 dilution. Findings obtained from these patients were compared to findings obtained in a control group of non formolized cadavers from the Medical Examiner’s Office of Caxias do Sul. In this cadaver control group without hernias, aged from twenty to sixty years [20-59] (Mean= 40.5±SD=11.8), the same studies were carried out as in the surgical group with hernias to evaluate the differences in quantity and morphometry of elastic fibers between the two groups. Results show that the total amount of elastic fibers was 35% higher in patients with hernia of the anterior wall of the abdomen than in the cadaver control group with no hernias (p<.05). / In the present study samples were collected from abdominal linea alba aponeurosis of 30 patients (15 males and 15 females) aged from twenty to sixty years [30-59], (Mean=44.9±SD=7.3), with hernia of the anterior abdominal wall to evaluate the immunohistochemistry expression and morphometry of the elastic fibers. Nine of the patients were submitted to surgery at the Hospital de Clínicas in Porto Alegre (HCPA), ten of then at the Santa Casa de Misericórdia do Rio de Janeiro (SCMRJ), seven of them at the author’s private clinic (CA) in Caxias do Sul, and four of them at the Hospital Pompeia (HP) in Caxias do Sul. All patients had a hernia of the anterior abdominal wall. Fourteen of these cases were umbilical hernias, ten epigastric hernias and six incisional hernias. Specimens were collected from the midline three centimeters above the umbilical scar and from two centimeters below it. At the laboratory, the specimens were subdivided in two parts. One of these specimens was stained with orcein and the elastic fibers were counted by digital analysis using the applicative Image Pro Plus (Media Cybernetics, Silver Spring, USA). The other specimen was submitted to evaluation through immunohistochemistry analysis utilizing monoclonal anti-Emilin Antibody to EMILIN1 GP115 Elastin microfibril interface located protein TNF (Proteintech Group), in 1:100 dilution. Findings obtained from these patients were compared to findings obtained in a control group of non formolized cadavers from the Medical Examiner’s Office of Caxias do Sul. In this cadaver control group without hernias, aged from twenty to sixty years [20-59] (Mean= 40.5±SD=11.8), the same studies were carried out as in the surgical group with hernias to evaluate the differences in quantity and morphometry of elastic fibers between the two groups. Results show that the total amount of elastic fibers was 35% higher in patients with hernia of the anterior wall of the abdomen than in the cadaver control group with no hernias (p<.05).

Dissertação (mestrado) - Pontifícia Universidade Católica do Paraná, Curitiba, 2005 / Inclui bibliografia / As hérnias incisionais são complicações freqüentes e ocorrem em 2% a 8% das cirurgias abdominais. As técnicas para a hernioplastia incisional vem evoluindo muito nos últimos anos, especialmente, as que se utilizam de telas. Porém em situações de urgência,

WINKELER, Georgia Freire Paiva. Efeitos agudos da administração de pressão positiva contínua em vias aéreas de modo não invasivo sobre o parênquima pulmonar de voluntários sadios nas posições supina e prona : alterações na tomografia computadorizada de alta resolução. 2006. 133 f. Dissertação (Mestrado em Medicina) - Universidade Federal do Ceará, Fortaleza, 2006. / Submitted by denise santos (denise.santos@ufc.br) on 2011-10-27T11:45:56Z No. of bitstreams: 1 2006_dis_gfpwinkeler.pdf: 6533137 bytes, checksum: 7461eccbce139fb3d37c13df801fe7a5 (MD5) / Approved for entry into archive by Eliene Nascimento(elienegvn@hotmail.com) on 2011-11-01T13:21:03Z (GMT) No. of bitstreams: 1 2006_dis_gfpwinkeler.pdf: 6533137 bytes, checksum: 7461eccbce139fb3d37c13df801fe7a5 (MD5) / Made available in DSpace on 2011-11-01T13:21:03Z (GMT). No. of bitstreams: 1 2006_dis_gfpwinkeler.pdf: 6533137 bytes, checksum: 7461eccbce139fb3d37c13df801fe7a5 (MD5) Previous issue date: 2006 / Introduction: Noninvasive positive-pressure ventilation (NIPPV) is an effective means of treating patients with acute respiratory failure and its use has been well established in cardiogenic pulmonary edema and in exacerbations of chronic obstructive pulmonary disease (COPD), reducing the need for endotracheal intubation and improving survival. Furthermore the continuous positive airway pressure (CPAP) – a mode of NIPPV – is the recommended treatment for obstructive sleep apnea syndrome (OSAS), where frequently there is no abnormality in pulmonary parenchyma. Also in the acute respiratory distress syndrome (ARDS), the application of positive end-expiratory pressure (PEEP) may result in alveolar recruitment of nonaerated units as well as in overinflation of the aerated lung areas. Alveolar overinflation is considered an important factor related to ventilator-induced lung injury causing higher mortality. The prone position has beneficial effects on oxygenation in these patients and the additive effect of PEEP with this maneuver is debatable. High resolution computed tomography (HRCT) is an excellent imaging method to evaluate the effects of positive pressure and prone position on pulmonary parenchyma. Objectives: To evaluate the effects of CPAP applied by a nasal mask on pulmonary inflation in normal subjects in supine and prone positions. Patients and methods: This is an interventionist study that evaluated eight healthy volunteers. A protocol of HRCT of the lung was performed in three regions: at the apex (2 cm above the aortic level), hilum (1 cm below the carina) and basis (2 cm above the right diaphragm) in the supine position, without and with CPAP of 5, 10 and 15 cmH2O. Also HRCT slices were performed in the prone position at the lung basis, without and with CPAP of 10 cmH2O. All HRCT slices were obtained at the functional residual capacity. Each CPAP level was maintened at least five minutes and the period between the different levels of CPAP was similar. For analysis the results were divided into regions ventral, medial and dorsal and with slices of apex, hilum and basis together. The mean lung densities (MLD) and the percentual of units with densities lower than -950 UH (overinflated) were calculated for each region. Results: There was no difference between the MLD of apex, hilum and basis for the same level pressure. In the supine position, there were a MLD reduction and an increase of the number of pixels on hyperinflated areas according to CPAP levels: without CPAP -761 HU e 7,25%; CPAP 5: -780 HU e 8,57%; CPAP 10: -810 HU e 11,62%; CPAP 15: -828 UH e 14,65% (p< 0,05). The same occurred in the prone position without CPAP: -759 UH e 6,30% and with CPAP 10: -803 UH e 9,94% (p < 0,05). It was observed a crescent ventro-dorsal density gradient in supine position that was inverse in prone position. At CPAP of 10 cmH2O there was lower percentage of pixels on hyperinflated areas in the prone position than in supine. In the non dependent lung regions (ventral in supine and dorsal in prone) there were lower percentage of pixels on hyperinflated areas and higher on normoaerated areas in the prone position than in supine with little differences in the dependent regions. Conclusions: Non invasive CPAP in normal subjects induces progressive overdistension with increase of pressure levels in supine and prone positions. CPAP of 10 cmH2O causes less overdistension of the non dependent regions than the same level of CPAP in supine position, without inducing significant overinflation of the dependent regions. So that the prone position causes a more homogeneous air distribution through the lungs. / Introdução: A ventilação não invasiva com pressão positiva (VNI) vem tendo uma crescente utilidade na prática clínica e o seu uso está bem estabelecido em casos de edema agudo de pulmão e nas exacerbações da doença pulmonar obstrutiva crônica (DPOC), diminuindo a necessidade de intubação orotraqueal e melhorando a sobrevida. Além disso, a pressão positiva contínua em vias aéreas (CPAP) – modo de VNI – constitui o tratamento de escolha para pacientes portadores da síndrome de apnéia obstrutiva do sono (SAOS), onde geralmente não há alteração no parênquima pulmonar. Ainda a aplicação de níveis elevados de pressão positiva expiratória final (PEEP) no manejo da síndrome do desconforto respiratório agudo (SDRA) está associada tanto ao recrutamento alveolar como à hiperdistensão de áreas previamente normoaeradas, com resultados ainda indefinidos quanto ao impacto na sobrevida. Um dos recursos para melhora da oxigenação nestes pacientes é a posição prona e os efeitos da associação desta manobra com pressão positiva permanecem controversos. A tomografia computadorizada de alta resolução (TCAR) constitui um excelente método de imagem para avaliação qualitativa e quantitativa do parênquima pulmonar. O emprego da TCAR pode auxiliar na investigação dos efeitos da CPAP de modo não invasivo sobre o parênquima pulmonar, contribuindo para a elucidação dos efeitos fisiológicos da pressão positiva e da posição prona. Objetivos: Avaliar e comparar os efeitos de diferentes níveis de CPAP de modo não invasivo sobre o parênquima pulmonar em indivíduos sadios nas posições supina e prona. Casuística e métodos: Estudo intervencionista com oito voluntários sadios, sem doença cardiopulmonar. Foram realizados cortes tomográficos de alta resolução em três regiões: ápice (2 cm acima do arco aórtico), hilo (1 cm abaixo da carina) e base (2 cm acima do diafragma) na posição supina, sem CPAP (basal) e com CPAP de 5, 10 e 15 cmH2O; e na posição prona, corte em base, sem CPAP e com CPAP de 10 cmH2O. A seqüência das posições e da ordem das pressões aplicadas foi randomizada. Aguardava-se um período de no mínimo 5 minutos após completa adaptação da máscara para realização do exame e o mesmo período de tempo entre um nível de pressão e outro. Os dados foram analisados agrupando-se os cortes tomográficos das três regiões e por subdivisões em regiões ventral, medial e dorsal, sendo calculadas as médias das densidades pulmonares e o percentual do número de unidades com densidade menor que -950 UH (hiperaeradas) para cada uma das regiões. Resultados: Não houve diferença das médias das densidades pulmonares entre ápice, hilo e base para o mesmo nível de pressão. Na posição supina, houve redução da densidade pulmonar e aumento do percentual de pixels nas áreas hiperaeradas com níveis crescentes de pressão: basal -761 UH e 7,25%; CPAP 5: -780 UH e 8,57%; CPAP 10: -810 UH e 11,62%; CPAP 15: -828 UH e 14,65% (p < 0,05). O mesmo foi observado na posição prona: basal -759 UH e 6,30%; CPAP 10: -803 UH e 9,94% (p < 0,05). Este aumento da aeração também foi observado nas regiões ventral, medial e dorsal. Foi encontrado um gradiente crescente no sentido ventro-dorsal de densidades pulmonares na posição supina e o inverso na posição prona. A CPAP de 10 cmH2O, na posição prona, ocasionou menor aumento do percentual de pixels nas áreas hiperaeradas em relação à supina. Nas regiões não dependentes do pulmão (ventral em supina e dorsal em prona), observou-se um menor percentual de pixels nas áreas hiperaeradas e aumento nas normoaeradas na posição prona em relação à supina, praticamente sem diferença nas regiões dependentes. Conclusões: A aplicação de diferentes níveis de CPAP, de modo não invasivo, em voluntários sadios, resultou em maior aeração com níveis crescentes de pressão e maior homogeneização da aeração pulmonar, tanto na posição supina como na prona. Houve menor hiperaeração nas regiões não dependentes na posição prona, em relação à supina, sem CPAP e com CPAP de 10 cmH2O, com melhor distribuição da aeração pulmonar naquela posição.

In the present study samples were collected from abdominal linea alba aponeurosis of 30 patients (15 males and 15 females) aged from twenty to sixty years [30-59], (Mean=44.9±SD=7.3), with hernia of the anterior abdominal wall to evaluate the immunohistochemistry expression and morphometry of the elastic fibers. Nine of the patients were submitted to surgery at the Hospital de Clínicas in Porto Alegre (HCPA), ten of then at the Santa Casa de Misericórdia do Rio de Janeiro (SCMRJ), seven of them at the author’s private clinic (CA) in Caxias do Sul, and four of them at the Hospital Pompeia (HP) in Caxias do Sul. All patients had a hernia of the anterior abdominal wall. Fourteen of these cases were umbilical hernias, ten epigastric hernias and six incisional hernias. Specimens were collected from the midline three centimeters above the umbilical scar and from two centimeters below it. At the laboratory, the specimens were subdivided in two parts. One of these specimens was stained with orcein and the elastic fibers were counted by digital analysis using the applicative Image Pro Plus (Media Cybernetics, Silver Spring, USA). The other specimen was submitted to evaluation through immunohistochemistry analysis utilizing monoclonal anti-Emilin Antibody to EMILIN1 GP115 Elastin microfibril interface located protein TNF (Proteintech Group), in 1:100 dilution. Findings obtained from these patients were compared to findings obtained in a control group of non formolized cadavers from the Medical Examiner’s Office of Caxias do Sul. In this cadaver control group without hernias, aged from twenty to sixty years [20-59] (Mean= 40.5±SD=11.8), the same studies were carried out as in the surgical group with hernias to evaluate the differences in quantity and morphometry of elastic fibers between the two groups. Results show that the total amount of elastic fibers was 35% higher in patients with hernia of the anterior wall of the abdomen than in the cadaver control group with no hernias (p<.05). / In the present study samples were collected from abdominal linea alba aponeurosis of 30 patients (15 males and 15 females) aged from twenty to sixty years [30-59], (Mean=44.9±SD=7.3), with hernia of the anterior abdominal wall to evaluate the immunohistochemistry expression and morphometry of the elastic fibers. Nine of the patients were submitted to surgery at the Hospital de Clínicas in Porto Alegre (HCPA), ten of then at the Santa Casa de Misericórdia do Rio de Janeiro (SCMRJ), seven of them at the author’s private clinic (CA) in Caxias do Sul, and four of them at the Hospital Pompeia (HP) in Caxias do Sul. All patients had a hernia of the anterior abdominal wall. Fourteen of these cases were umbilical hernias, ten epigastric hernias and six incisional hernias. Specimens were collected from the midline three centimeters above the umbilical scar and from two centimeters below it. At the laboratory, the specimens were subdivided in two parts. One of these specimens was stained with orcein and the elastic fibers were counted by digital analysis using the applicative Image Pro Plus (Media Cybernetics, Silver Spring, USA). The other specimen was submitted to evaluation through immunohistochemistry analysis utilizing monoclonal anti-Emilin Antibody to EMILIN1 GP115 Elastin microfibril interface located protein TNF (Proteintech Group), in 1:100 dilution. Findings obtained from these patients were compared to findings obtained in a control group of non formolized cadavers from the Medical Examiner’s Office of Caxias do Sul. In this cadaver control group without hernias, aged from twenty to sixty years [20-59] (Mean= 40.5±SD=11.8), the same studies were carried out as in the surgical group with hernias to evaluate the differences in quantity and morphometry of elastic fibers between the two groups. Results show that the total amount of elastic fibers was 35% higher in patients with hernia of the anterior wall of the abdomen than in the cadaver control group with no hernias (p<.05).

In the present study samples were collected from abdominal linea alba aponeurosis of 30 patients (15 males and 15 females) aged from twenty to sixty years [30-59], (Mean=44.9±SD=7.3), with hernia of the anterior abdominal wall to evaluate the immunohistochemistry expression and morphometry of the elastic fibers. Nine of the patients were submitted to surgery at the Hospital de Clínicas in Porto Alegre (HCPA), ten of then at the Santa Casa de Misericórdia do Rio de Janeiro (SCMRJ), seven of them at the author’s private clinic (CA) in Caxias do Sul, and four of them at the Hospital Pompeia (HP) in Caxias do Sul. All patients had a hernia of the anterior abdominal wall. Fourteen of these cases were umbilical hernias, ten epigastric hernias and six incisional hernias. Specimens were collected from the midline three centimeters above the umbilical scar and from two centimeters below it. At the laboratory, the specimens were subdivided in two parts. One of these specimens was stained with orcein and the elastic fibers were counted by digital analysis using the applicative Image Pro Plus (Media Cybernetics, Silver Spring, USA). The other specimen was submitted to evaluation through immunohistochemistry analysis utilizing monoclonal anti-Emilin Antibody to EMILIN1 GP115 Elastin microfibril interface located protein TNF (Proteintech Group), in 1:100 dilution. Findings obtained from these patients were compared to findings obtained in a control group of non formolized cadavers from the Medical Examiner’s Office of Caxias do Sul. In this cadaver control group without hernias, aged from twenty to sixty years [20-59] (Mean= 40.5±SD=11.8), the same studies were carried out as in the surgical group with hernias to evaluate the differences in quantity and morphometry of elastic fibers between the two groups. Results show that the total amount of elastic fibers was 35% higher in patients with hernia of the anterior wall of the abdomen than in the cadaver control group with no hernias (p<.05). / In the present study samples were collected from abdominal linea alba aponeurosis of 30 patients (15 males and 15 females) aged from twenty to sixty years [30-59], (Mean=44.9±SD=7.3), with hernia of the anterior abdominal wall to evaluate the immunohistochemistry expression and morphometry of the elastic fibers. Nine of the patients were submitted to surgery at the Hospital de Clínicas in Porto Alegre (HCPA), ten of then at the Santa Casa de Misericórdia do Rio de Janeiro (SCMRJ), seven of them at the author’s private clinic (CA) in Caxias do Sul, and four of them at the Hospital Pompeia (HP) in Caxias do Sul. All patients had a hernia of the anterior abdominal wall. Fourteen of these cases were umbilical hernias, ten epigastric hernias and six incisional hernias. Specimens were collected from the midline three centimeters above the umbilical scar and from two centimeters below it. At the laboratory, the specimens were subdivided in two parts. One of these specimens was stained with orcein and the elastic fibers were counted by digital analysis using the applicative Image Pro Plus (Media Cybernetics, Silver Spring, USA). The other specimen was submitted to evaluation through immunohistochemistry analysis utilizing monoclonal anti-Emilin Antibody to EMILIN1 GP115 Elastin microfibril interface located protein TNF (Proteintech Group), in 1:100 dilution. Findings obtained from these patients were compared to findings obtained in a control group of non formolized cadavers from the Medical Examiner’s Office of Caxias do Sul. In this cadaver control group without hernias, aged from twenty to sixty years [20-59] (Mean= 40.5±SD=11.8), the same studies were carried out as in the surgical group with hernias to evaluate the differences in quantity and morphometry of elastic fibers between the two groups. Results show that the total amount of elastic fibers was 35% higher in patients with hernia of the anterior wall of the abdomen than in the cadaver control group with no hernias (p<.05).

Orientador: Valeria Helena Alves Cagnon Quitete / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-13T16:32:13Z (GMT). No. of bitstreams: 1 Pinto_LeslieCristina_M.pdf: 6161359 bytes, checksum: e53c13123d8d830910aa70a9f89b179c (MD5) Previous issue date: 2009 / Resumo: A distroglicana (DG) é uma importante proteína estrutural a qual está envolvida no desenvolvimento celular epitelial, formação de membrana basal e manutenção da integridade de diferentes tecidos. Estudos indicaram que a alteração na expressão da DG é um evento freqüente nas malignecências humanas e sugerem que esta molécula tem um papel importante no desenvolvimento de tumor. No câncer de próstata, verificou-se expressiva redução das distroglicanas, especialmente da _-DG, acarretando em progressão tumoral e ocorrência de metástases. Desta maneira, alterações na expressão das distroglicanas podem ser relevantes na patogênese das doenças prostáticas. Além disto, estas moléculas fazem parte de um complexo glicoproteíco e estão relacionadas a uma série de proteínas tais como, agrinas, lamininas e a distrofina. Devido à deficiência de distrofina, este complexo está desestruturado na distrofia muscular de Duchenne e, no camundongo mdx. Este trabalho teve como objetivos caracterizar a estrutura epitelial e estromal do lobo ventral da próstata do camundongo mdx, identificar a ocorrência de receptores para distroglicanas _ e _, IGF-1, laminina _-3, estabelecer correlações entre os processos de proliferação e morte celular e analisar a viabilidade do camundongo mdx como modelo experimental no estudo de patologias prostáticas. Um total de 30 animais (15 C57BL10 e 15 mdx) foi dividido em 2 grupos experimentais: controle e mdx. Amostras do lobo ventral da próstata foram coletadas para análises macroscópicas, imunohistoquímicas, microscopias de luz e eletrônica de transmissão e análises morfométricas. Dosagens sorológicas de estradiol e testosterona foram realizadas. Os resultados mostraram que os níveis séricos de testosterona foram significativamente diminuídos nos camundongos mdx em relação aos controles. Em contraste, os níveis séricos de estradiol do grupo mdx mostraram-se significativamente aumentados em relação ao controle. Acentuada atrofia celular, ocorrência de neoplasia intraepitelial prostática, hipertrofia estromal, presença de células inflamatórias e hipertrofia estromal foram evidenciadas nos animais mdx. A intensidade da reação de imunolocalização da distroglicana foi de fraca expressão em relação ao controle, assim como a da laminina. Já a imunolocalização do IGF foi intensa em relação ao controle. Conclui-se que os animais mdx apresentaram alterações significativas na integridade estrutural e molecular prostática, com sinais de aumento do processo proliferativo, comprometendo a homeostase glandular e o processo reprodutivo destes animais. / Abstract: The prostate is a fundamental accessory sex gland for the male reproductive process and the stroma-epithelium interaction has an important role in prostate structural maintenance and function. The basal membrane is an interaction link, offering mechanical and physiological support. Nowadays, different studies suggest that dystroglycan (DG), which is an adhesion protein, plays a role in different types of cancer development and progression, including that of the prostate. Thus, the aims of this work were to characterize structural, ultrastructural and proliferative features of the prostatic stroma and epithelium of mdx mice; to verify the immunolocalization of the _ and ß dystroglycan, IGF-I and laminin _3 receptors; and to relate those structural and molecular events to prostate pathogenesis as well as to verify the viability of this experimental model in prostate disease studies. Thirty male mice (mdx and C57BL10/Uni) were divided into two groups: control and mdx. Samples from the ventral prostate were collected for immunological, Western Blotting, transmission electron and light microscopies and morphometrical analyses. Estradiol and testosterone measurements were verified. The results showed diminished testosterone and increased estradiol levels in the mdx group. Atrophied cells, stromal hypertrophy and prostatic intraepithelial were verified in the mdx mice. Weak _ and ß dystroglycan and laminin _3 immunolocalization was verified in the mdx group. However, intense IGF-I receptor localization was identified in the mdx animals. Thus, it was concluded that mdx animals presented changes in the molecular and structural integrity and proliferation signals, leading to glandular pathogenesis, compromising prostate homeostasis and the reproductive process. Apart from this, the destructuring of the dystroglycandystrophin complex can be considered a trigger factor for prostate pathogenesis. It can also point towards that the steroid-hormone and IGF relationship can be an alternative towards new therapies to treat prostatic diseases. / Mestrado / Anatomia / Mestre em Biologia Celular e Estrutural

Thesis advisor: Elizabeth A. Kensinger / Research in four parts examines the effects of valence on the neural processes that support emotional memory formation and retrieval. Results show a consistent valence-specific enhancement of visuocortical engagement along the ventral visual stream and occipital cortex that supports negative memories to a greater extent than positive memories. Part I investigated the effects of valence on the interactions between trial-level physiological responses to emotional stimuli (i.e., heart rate deceleration) during encoding and subsequent memory vividness. Results showed that negative memory vividness, but not positive or neutral memory vividness, is tied to arousal-related enhancements of amygdala coupling with early visual cortex during encoding. These results suggest that co-occurring parasympathetic arousal responses and amygdala connectivity with early visual cortex during encoding influence subsequent memory vividness for negative stimuli, perhaps reflecting enhanced memory-relevant perceptual enhancements during encoding of negative stimuli. Part II examined links between individual differences in post-encoding increases is amygdala functional connectivity at rest and the degree and direction of emotional memory biases at retrieval. Results demonstrated that post-encoding increases in amygdala resting state functional connectivity with visuocortical and frontal regions predicted the degree of negative memory bias (i.e., better memory for unpleasant compared to pleasant stimuli) and positive memory bias, respectively. Further, the effect of amygdala-visuocortical post-encoding coupling on behavioral negative memory bias was completely mediated by greater retrieval-related activity for negative stimuli in visuocortical areas. These findings suggest that those individuals with a negative memory bias tend to engage visual processing regions across multiple phases of memory more than individuals with a positive memory bias. While Parts I-II examined encoding-related memory processes, Part III examined the effects of valence on true and false subjective memory vividness at the time of retrieval. The findings showed valence-specific enhancements in regions of the ventral visual stream (e.g., inferior temporal gyrus and parahippocampal cortex) support negative memory vividness to a greater extent than positive memory vividness. However, activation of the parahippocampal cortex also drove a false sense of negative memory vividness. Together, these findings suggest spatial overlap in regions that support negative true and false memory vividness. Lastly, Part IV utilized inhibitory repetitive transcranial magnetic stimulation (rTMS) to test if a portion of occipito-temporal cortex that showed consistent valence-specific effects of negative memory in Parts I-III was necessary for negative memory retrieval. Although some participants showed the hypothesized effect, there was no group-level evidence of a neuromodulatory effect of occipito-temporal cortex rTMS on negative memory retrieval. Together, the results of the current dissertation work highlight the importance of valence-based models of emotional memory and consistently implicated enhanced visuosensory engagement across multiple phases of memory. By identifying valence-specific effects of trial-level physiological arousal during encoding, post-encoding amygdala coupling during early consolidation, and similarities and differences between true and false negative memories, the present set of work has important implications for how negative and positive memories are created and remembered differently. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Indiana University-Purdue University Indianapolis (IUPUI) / Alcohol use disorder (AUD) and nicotine dependence often result in serious health problems and are top contributors to preventable deaths worldwide. Co-addiction to alcohol and nicotine is the most common form of polysubstance abuse. Epidemiological studies indicate that more than 80% of individuals diagnosed with AUD concurrently use nicotine. The prevalence of alcohol and nicotine comorbidity may stem from interconnected mechanisms underlying these disorders. A better understanding of how these drugs interact and the biological basis behind the high comorbidity rates could generate key targets for the development of more effective treatments for AUD and nicotine dependence. The following experiments utilized four similar overall groups consisting of vehicle, ethanol (EtOH), nicotine (NIC), and EtOH+NIC. Chapter Two investigated the efficacy of naltrexone and varenicline, the pharmacological ‘gold standards’ for treating AUD and nicotine dependence, on voluntary drug intake by rats selectively bred for high EtOH drinking. The results indicated that the standard treatments for AUD and nicotine dependence were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. Chapter Three examined the effects of peri-adolescent EtOH drinking on the ability of NIC infused into the posterior ventral tegmental area (pVTA) to stimulate dopamine release within the nucleus accumbens (NAc) shell during adulthood. The results suggest a cross-sensitization to NIC produced by peri-adolescent EtOH consumption demonstrated by a leftward and upward shift in the dose response curve. Chapter Four investigated the effects of intra-pVTA infusions on NAc shell neurochemistry, EtOH reward within the NAc shell, and the role of brain-derived neurotrophic factor (BDNF) on EtOH reward within that region. The data indicated that only EtOH+NIC significantly increased glutamate, dopamine, and BDNF in the NAc shell. Repeated pretreatment with EtOH+NIC also enhanced EtOH reward in the NAc shell and BDNF infusions were sufficient to recapitulate these findings. Collectively, the data indicate that concurrent exposure to EtOH and NIC results in unique neuroadaptations that promote future drug use. The failure to develop effective pharmacotherapeutics for AUD or nicotine dependence could be associated with examining potential targets in models that fail to reflect the impact of polydrug exposure. / 2020-04-03

Female sheep exposed to excess testosterone (T) in utero display symptoms similar to those observed in women with polycystic ovarian syndrome (PCOS). Prenatal T-treated ewes display masculinized sexual behavior and increased food-reward seeking behavior. A neural substrate critical for these goal-directed behaviors is the dopaminergic system in the ventral tegmental area. We have recently shown that in adult ewes dopamine expression in the VTA is increased by prenatal T exposure. In this thesis, I tested the hypothesis that alterations of the VTA dopamine system by prenatal-T are caused via activation of androgen (AR) and/or insulin receptors (IR). Analysis of immunohistochemical staining shows an increase of tyrosine hydroxylase (TH) expression, AR, or IR, along with changes in co-expression of AR/TH and IR/TH. These changes were blocked or reversed by prenatal treatments with flutamide or rosiglitazone, or postnatal treatments with rosiglitazone or metformin, implicating AR and IR in alterations of the VTA

No description available.