Thesis -- Departmental honors in Psychobiology. / Spine title: Effects of bisphenol A on adult female ovariectomized rats. Bibliography: ℓ. 46-55.

Theses (M.A.)--Marshall University, 2006. / Title from document title page. Includes abstract. Document formatted into pages: contains v, 17 p. Bibliography: p. 14-17.

Orientador: Francisco Carlos Groppo / Tese (doutorado) - Universidade Estadual de Campinas, Faculda de Odontologia de Piracicaba / Made available in DSpace on 2018-08-19T03:56:37Z (GMT). No. of bitstreams: 1 FiguerobaRaimundo_Sidney_D.pdf: 3233754 bytes, checksum: c6124f5e2bd9635cb391d21ebcba7ea6 (MD5) Previous issue date: 2011 / Resumo: As desordens da articulação temporomandibular (DTM) estão associadas com o processo inflamatório, incluindo os componentes biológico e comportamental. O objetivo foi avaliar o efeito de dois anti-inflamatórios (parecoxibe e dexametasona) na morfologia da ATM e produção de interleucinas pro-inflamatórias em ratas ovariectomizadas (OVX), com ou sem deslocamento posterior funcional (DPFM). Foram utilizadas 72 ratas em quatro grupos: G1 - sem DPFM e não OVX; G2 - com DPFM e não OVX; G3 - sem DPFM e OVX; G4 - com DPFM e OVX. O DPFM da mandíbula foi induzido por meio de um dispositivo confeccionado com bandas ortodônticas nos incisivos superiores. Após 7 dias da indução do DPFM, as ratas foram tratadas com NaCl 0,9% (CONT) ou parecoxibe 0,3mg/kg/dia (PARE) ou dexametasona 0,1mg/kg/dia (DEXA), via intramuscular. Após 7 dias de tratamento, as ATM de ambos os lados foram retiradas em bloco. Uma das ATM foi submetida ao processamento histológico (hematoxilina-eosina). A ATM contralateral foi macerada e centrifugada e o sobrenadante submetido ao imunoensaio (ELISA) para avaliação das interleucinas IL1-beta e IL-6. A leitura foi feita por espectrofotometria. Todos os animais foram pesados com a mesma idade, previamente à sua morte. Foi possível observar que, independentemente do tratamento, as fêmeas que não foram submetidas ao DPFM mostraram variação de peso corporal em média (±erro padrão) de -0,41±0,72%; aquelas submetidas ao DPFM de -4,8±1,1%; as submetidas à OVX de 26,9±1,2% e aquelas submetidas ao DPFM e OVX de 8,3±2,5%. Estes dados em conjunto mostram que houve ganho de peso nos animais submetidos à OVX, mas não houve alteração de peso nos animais submetidos ao DPFM. O PARE e a DEXA diminuíram (Kruskal-Wallis, p<0,05) a área da cartilagem articular nos animais do Grupo sem-DPFM em relação ao controle, mas o PARE aumentou a área em relação à DEXA, não havendo diferenças entre ambos e o controle. Os tratamentos não influenciaram a concentração de IL1-beta no Grupo sem-DPFM, mas no Grupo com-DPFM, a concentração foi maior (Kruskal-Wallis, p<0,05) para DEXA. Nos demais Grupos não houve diferenças (p>0,05) entre os tratamentos. Independentemente do tratamento, a IL1-beta foi menor no Grupo sem-DPFM do que nos demais grupos. O nível de IL1-beta no Grupo com-DPFM foi maior do que no grupo sem- DPFM+OVX, mas não apresentou diferenças com o grupo com-DPFM+OVX, exceto para a DEXA. A concentração de IL-6 não foi afetada pelos tratamentos em nenhum dos quatro grupos. Entretanto, a comparação entre os grupos revelou que o Grupo com-DPFM apresentou maior concentração de IL-6, considerando todos os tratamentos. Não houve diferenças estatisticamente significantes entre os níveis de IL-6 dos Grupos sem-DPFM, sem-DPFM+OVX e com-DPFM+OVX. Os parâmetros histológicos não foram afetados pelo DPFM ou OVX, mas sim pelos tratamentos. Concluímos que o DPFM aumentou os níveis das interleucinas pró-inflamatórias IL1-beta e IL-6, sendo que as ratas com DPFM tiveram as concentrações das interleucinas atenuadas pela ovariectomia. Os anti-inflamatórios parecoxibe e dexametasona não interferiram com as concentrações das citocinas. A área da cartilagem articular não foi influenciada pelo DPFM, mas a associação ao PARE gerou aumento na área da cartilagem articular / Abstract: Temporomandibular disorders (TMD) are associated with pain/inflammatory process, including biological and behavioral parameters. The aim of the present study was to evaluate the effect of two anti-inflammatories (parecoxib and dexamethasone) in the TMJ morphology of ovariectomized rats (OVX) with or without retrusive displacement of mandible (RDM). 72 rats were distributed into 4 groups: G1 - no RDM and no OVX; G2 - with RDM and no OVX; G3 - no RDM, but with OVX; G4 - with both RDM and OVX. The RDM induction was achieved by placing an oral device made with steel strips (orthodontic band) in the rat upperincisors. After 7 days of RDM, the animals were submitted to one of the following treatments: 0.9% NaCl (CONT); 0.30mg/kg/im/day parecoxib (PARE); or 0.1mg/kg/im/day dexamethasone (DEXA). After 7 days of treatment, the TMJs of both sides were removed. One of them was submitted to histological procedure (HE) after fixation and decalcification. The contralateral TMJ was macerated, centrifuged and the supernatant was submitted to the immunoassay (ELISA) in order to evaluate the pro-inflammatory cytokines (IL1-beta and IL-6). The readings were performed by spectrophotometry. All animals were weighed with the same age and before they were killed. It was possible to observe that the rats without RDM showed a mean (±SE) variation of body weight of -0.41±0.72%; the ones not submitted to RDM was -4.8±1.1%; with OVX of 26.9±1.2% and the ones submitted to both RDM and OVX was 8.3±2.5%. In general, these data showed a body weight gain in the animals with OVX, but not in the ones with RDM. Both PARE and DEXA decreased (Kruskal-Wallis, p<0.05) the articular cartilage area in G1 when compared to CONT, but PARE increased the area in relation to DEXA. None of the treatments influenced the IL1-beta levels in G1, but it was higher in G2 (Kruskal-Wallis, p<0.05) for DEXA. No differences were observed among treatments for groups 3 and 4 (p>0.05). IL1-beta levels were lower in G1 when compared to the other ones, disregarding of treatments. These levels were higher in G2 than G3 but not G4 (except for DEXA). None of the treatments affected the IL-6 levels considering each group. G2 showed the highest IL-6 levels than the other groups, irrespectively of the treatments. No statistically significant differences among the levels of IL-6 of G1, G3 and G4 were found. The morphological parameters were not affected by RDM or by OVX, but the treatments. We concluded that RDM increased the levels of both cytokines, being reduced by OVX. Both PARE and DEXA did not interfere with cytokines levels. The articular cartilage area was not influenced by RDM, but it increased this area when associated with PARE / Doutorado / Farmacologia, Anestesiologia e Terapeutica / Doutor em Odontologia

Thesis--Lantbrukshögskolan, Stockholm. / Extra t.p. with thesis statement inserted. Stamped on cover: Lantbrukshögskolan. Diss. 78. Summary of the 5 articles which comprise the author's thesis. Bibliography: p. 15-16.

Made available in DSpace on 2014-06-11T19:25:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-04-24Bitstream added on 2014-06-13T19:06:09Z : No. of bitstreams: 1 000739066.pdf: 1353366 bytes, checksum: 79588e032afad6fbaa7b61c5b96b8b56 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A fragilidade óssea, resultante da osteoporose, aumenta a possibilidade da ocorrência de fraturas e de morbimortalidade. A deficiência de estrogênio que acomete a mulher durante a menopausa, exerce ação primordial no desenvolvimento desta patologia. Entre os fármacos estudados como possíveis agentes terápicos para a osteoporose, o cloridrato de raloxifeno (RLX) mimetiza os efeitos benéficos do estrógeno sem estimular tecidos como mama e endométrio. A realização de exercícios resistidos tem se mostrado grande aliado para o aumento da densidade mineral óssea, pelo recrutamento de células ósseas. Desta forma, este estudo analisou se o treinamento resistido (EX), o raloxifeno ou a associação destes propícia alteração óssea no colo do fêmur de ratas no período do envelhecimento. Para tanto, ratas Wistar (14 meses) foram divididas aleatoriamente nos grupos experimentais: G1- Sham/NaCl; G2 – Sham/NaCl + EX; G3– Sham/RLX; G4 – Sham/RLX + EX; G5- OVX/NaCl; G6- OVX/NaCl + EX; G7- OVX/RLX; G8 - OVX/RLX + EX. Durante 120 dias as ratas receberam, por gavagem diária, solução fisiológica (grupos 1, 2, 5 e 6) ou RLX (grupos 3, 4, 7 e 8). Os animais dos grupos 2, 4, 6 e 8 realizaram 4 séries de 5 repetições de exercício em escada, com peso equivalente a 80% da sua força durante 3 vezes na semana. A região da epífise proximal dos fêmures destes animais foi analisada por densitometria e microtomografia óssea bem como dosagens plasmáticas de Fosfatase Ácida Resistente ao Tartarato (TRAP), Osteocalcina (OC), Osteoprotegerina (OPG) e Fosfatase Alcalina total (FAL) como indicadores de predisposição à reabsorção ou formação de tecido ósseo. Os resultados evidenciam alterações morfológicas e nas concentrações plasmáticas de FAL, OC, OPG e TRAP. Nos animais sham-OVX, a associação de RLX e EX desencadeou aumento na atividade de FAL e diminuição... / The bone fragility resulting from osteoporosis increases the possibility of fractures and mortality occurrences. The estrogen deficiency that affects women during menopause exerts a major action on the development of this pathology. Among the drugs we’ve studied as possible therapeutic agents for osteoporosis, raloxifene hydrochloride (RLX) mimics the beneficial effects of estrogen without stimulating tissues such as the breast and the endometrium. Moreover, it turned out resistance exercises is a great ally to the increasing of bone mineral density through the recruitment of bone cells. Thus, this study examined whether the resistant training, raloxifene hydrochloride or combination of these provided favorable changes in the femur of rats on their aging period. Therefore, 14 months old (Wistar) rats, after analysis of the estrous cycle, were randomly divided in experimental groups: G1-Sham/NaCl; G2 – Sham/ NaCl + EX; G3-Sham/ RLX; G4 – Sham/ RLX + exercise; G5-OVX / NaCl; G6-OVX /NaCl + exercise; G7-OVX / RLX; G8-OVX/RLX + exercise. For 120 days the rats received by gavage daily physiological solution (Group 1,2,5 and 6) or RLX(Group 3,4,7 and 8). Animals in group 2, 4, 6 and 8 underwent 4 series of 5 repetition of ladder exercises, with the equivalent weight of 80% of their strength for 3 times a week. The region of epiphysis proximal femurs of these animals were analyzed by microtomography and bone densitometry as well as plasma tartrate-resistant acid phosphatase (ALP), Osteocalcin (OC), Osteoprotegerin (OPG) and Alkaline phosphatase indicates of a predisposition to resorption or formation of bone tissue. The results show changes in plasma concentrations of ALP, OC, OPG, and TRAP. In sham- OVX animals, the combination of RLX and EX triggered increased...

Abstract Dietary xylitol supplementation increases bone calcium and phosphorus concentrations in healthy rats, as well as protects against the decrease of bone minerals and bone density during experimental osteoporosis. This suggests that dietary xylitol might have a favorable effect on the prevention of osteoporosis. However, before any conclusions can be drawn about the usefulness of a compound, studies including structural evaluation and biomechanical testing of bones must first be performed. Thus, the aim of the present study was to clarify whether dietary xylitol affects bone resorption, bone structure, and bone biomechanics in healthy rats, and whether dietary xylitol offers some preventive effects against the increased bone resorption, decreased bone trabeculation, and weakened bone biomechanical properties during experimental osteoporosis. Dietary xylitol reduced bone resorption in 3-mo old healthy male rats, and protected significantly against the increase of bone resorption in 3-mo old ovariectomized rats, as measured by the urinary excretion of 3H following [3H]tetracycline-prelabeling. In addition, increased trabecular bone volume of proximal tibia in 4-mo old healthy male rats was detected after a 1-mo xylitol feeding period, and significant protection against the decrease of trabecular bone volume in 6-mo old ovariectomized rats was observed after a 3-mo xylitol feeding period. Furthermore, dietary xylitol increased the strength properties of long bones in 6-mo old healthy male rats after a 3-mo feeding period, without affecting the bone elastic properties as tested by three-point bending of tibia, torsion of femur, and loading of femoral neck. Accordingly, dietary xylitol protected significantly against the weakening of bone biomechanical properties in 6-mo old ovariectomized rats after a 3-mo feeding period. In conclusion, the above results strongly support the hypothesis that oral administration of xylitol protects effectively against the progression of experimental osteoporosis. Dietary xylitol was effective both in increasing bone mass in healthy rats, and in preventing bone loss in ovariectomized rats, suggesting a favorable effect of xylitol on both main targets in the prevention of osteoporosis. As dietary xylitol was effective also in protecting against the experimental osteoporosis-caused changes in bone structure and weakening of bone biomechanical properties, oral xylitol administration seems to provide interesting possibilities when searching for new physiological choices for the prevention of osteoporosis.

Ovarian secretions and growth hormone (GH) are major endocrine regulators of mammary growth and development in bovine mammary gland; but information on endocrine regulation during early prepubertal period is limited. Our overall objective was to study the regulation of mammary growth and development as well as transcript abundance in early prepubertal bovine mammary gland by ovarian secretions and exogenous bovine somatotropin (bST). In the first study, we determined the effect of staged ovariectomy on mammary growth and development in two to four month old Holstein heifers. In the second study, effects of bST on mammary growth and development, and also on putative stem cell population were evaluated by beginning bST treatment in one month old Holstein heifers. Mammary growth and development was determined by mass of mammary tissue, biochemical analyses, histological examination, transcript abundance and protein expression in mammary parenchyma (PAR) and fat pad (MFP). Ovariectomy reduced mass and lipid content of PAR without affecting the histological characteristics or rate of epithelial cell proliferation. There was a marked reduction in progesterone receptor expression both at the mRNA and protein level. Ovariectomy also reduced transcript abundance in GH receptor (R), insulin-like growth factor (IGF)-1, IGF binding protein -6, estrogen responsive and proliferation marker genes, but increased the mRNA abundance of IGF-1R in PAR. On the other hand, administration of bST did not have an impact on PAR growth, epithelial proliferation, putative stem cell population or transcript abundance of IGF-axis genes. However, bST reduced the relative abundance of GHR, signal transducers and activators of transcription-5b and suppressors of cytokine signaling-2 in mammary PAR. Transcript abundance of IGF-axis molecules, estrogen responsive genes and proliferation markers in MFP was not affected by ovariectomy or bST. Overall, our data suggest that ovary is a predominant regulator of mammary growth and development in prepubertal heifers and that exogenous bST is not effective as a mammary specific mitogen in very young prepubertal heifers. / Ph. D.

Orientador: Rita Cássia Menegatti Dornelles / Banca: Sérgio Eduardo de Andrade Perez / Banca: Ismael Forte Freitas Júnior / Resumo: A fragilidade óssea, resultante da osteoporose, aumenta a possibilidade da ocorrência de fraturas e de morbimortalidade. A deficiência de estrogênio que acomete a mulher durante a menopausa, exerce ação primordial no desenvolvimento desta patologia. Entre os fármacos estudados como possíveis agentes terápicos para a osteoporose, o cloridrato de raloxifeno (RLX) mimetiza os efeitos benéficos do estrógeno sem estimular tecidos como mama e endométrio. A realização de exercícios resistidos tem se mostrado grande aliado para o aumento da densidade mineral óssea, pelo recrutamento de células ósseas. Desta forma, este estudo analisou se o treinamento resistido (EX), o raloxifeno ou a associação destes propícia alteração óssea no colo do fêmur de ratas no período do envelhecimento. Para tanto, ratas Wistar (14 meses) foram divididas aleatoriamente nos grupos experimentais: G1- Sham/NaCl; G2 - Sham/NaCl + EX; G3- Sham/RLX; G4 - Sham/RLX + EX; G5- OVX/NaCl; G6- OVX/NaCl + EX; G7- OVX/RLX; G8 - OVX/RLX + EX. Durante 120 dias as ratas receberam, por gavagem diária, solução fisiológica (grupos 1, 2, 5 e 6) ou RLX (grupos 3, 4, 7 e 8). Os animais dos grupos 2, 4, 6 e 8 realizaram 4 séries de 5 repetições de exercício em escada, com peso equivalente a 80% da sua força durante 3 vezes na semana. A região da epífise proximal dos fêmures destes animais foi analisada por densitometria e microtomografia óssea bem como dosagens plasmáticas de Fosfatase Ácida Resistente ao Tartarato (TRAP), Osteocalcina (OC), Osteoprotegerina (OPG) e Fosfatase Alcalina total (FAL) como indicadores de predisposição à reabsorção ou formação de tecido ósseo. Os resultados evidenciam alterações morfológicas e nas concentrações plasmáticas de FAL, OC, OPG e TRAP. Nos animais sham-OVX, a associação de RLX e EX desencadeou aumento na atividade de FAL e diminuição... / Abstract: The bone fragility resulting from osteoporosis increases the possibility of fractures and mortality occurrences. The estrogen deficiency that affects women during menopause exerts a major action on the development of this pathology. Among the drugs we've studied as possible therapeutic agents for osteoporosis, raloxifene hydrochloride (RLX) mimics the beneficial effects of estrogen without stimulating tissues such as the breast and the endometrium. Moreover, it turned out resistance exercises is a great ally to the increasing of bone mineral density through the recruitment of bone cells. Thus, this study examined whether the resistant training, raloxifene hydrochloride or combination of these provided favorable changes in the femur of rats on their aging period. Therefore, 14 months old (Wistar) rats, after analysis of the estrous cycle, were randomly divided in experimental groups: G1-Sham/NaCl; G2 - Sham/ NaCl + EX; G3-Sham/ RLX; G4 - Sham/ RLX + exercise; G5-OVX / NaCl; G6-OVX /NaCl + exercise; G7-OVX / RLX; G8-OVX/RLX + exercise. For 120 days the rats received by gavage daily physiological solution (Group 1,2,5 and 6) or RLX(Group 3,4,7 and 8). Animals in group 2, 4, 6 and 8 underwent 4 series of 5 repetition of ladder exercises, with the equivalent weight of 80% of their strength for 3 times a week. The region of epiphysis proximal femurs of these animals were analyzed by microtomography and bone densitometry as well as plasma tartrate-resistant acid phosphatase (ALP), Osteocalcin (OC), Osteoprotegerin (OPG) and Alkaline phosphatase indicates of a predisposition to resorption or formation of bone tissue. The results show changes in plasma concentrations of ALP, OC, OPG, and TRAP. In sham- OVX animals, the combination of RLX and EX triggered increased... / Mestre

Basic research into the histology, endocrine control, and local regulation of prepuberal ruminant mammogenesis was conducted to provide a better understanding of this important developmental period. Histologic features of prepuberal ruminant mammary parenchymal morphogenesis were examined in tissue samples taken from ewe lambs at 2 (n = 5), 3 (n = 15), 6 (n = 26), 9 (n = 7), 12 (n = 5), and 13 wk (n = 20), and from Holstein heifers at 4 (n = 1) and 6 mo (n = 2). Examination of approximately 8000 histologic sections revealed that mammary parenchymal morphogenesis in sheep and cattle occurs through the proliferation of highly arborescent ductal structures embedded in a dense stroma. These observations contrast strongly with models of mammogenesis based on murine mammary development. The formation of luminal spaces and the expansion of ducts also differed from murine mammogenesis models. Luminal spaces were shown to develop through a progressive separation of opposing sides in initially solid ductal structures. Likewise, our investigation of prepubertal ovine mammogenesis revealed that parenchymal weight, 3H-thymidine labeling, stromal weight, and parenchymal DNA were all unaffected by ovariectomy (P > 0.05), in marked contrast to the dramatic reduction in mammary development following ovariectomy in rats, mice, and heifers. Responsiveness to exogenous estrogen (0.1 mg/kg) was demonstrated by increased 3H-thymidine labeling (P < 0.05) in both intact and ovariectomized lambs. Three dimensional collagen gel cultures of bovine mammary organoids from the peripheral (OUTER) and medial (INNER) parenchymal zones were used to characterize the proliferative and morphogenetic responses to local-acting growth factors. The proliferation of OUTER cells was 2 to 3 times greater than INNER cells (P < 0.0001) in response to IGF-I stimulation. Dramatic differences in the morphology of INNER and OUTER organoids were also observed. INNER cells grew into smooth-edged colonies when treated with heifer serum but stellate colonies when treated with other mitogens. OUTER cells grew into stellate colonies regardless of mitogen treatment. These investigations highlight the fact that a great deal more research into the basic physiology of prepuberal ruminant mammogenesis is required and that dogma developed in murine model systems may not be applicable to ruminant mammary physiology. / Ph. D.

Currently cardiovascular disease (CVD) is the leading cause of death globally accounting for nearly 17.9 million deaths every year. Studies show that CVD affects men and women differently. A significant increase in CVD incidence is marked by the onset of menopause in women compared to age matched males. A commonality seen in CVD is the use of ꞵ-adrenergic receptors (ꞵ-ARs), as studies have shown that estrogen loss exacerbates the signaling of these ꞵ-AR’s. Changes within this signaling molecule can lead to structural and functional modifications in the heart, including systolic or diastolic dysfunction. This leads to the hypothesis that estrogen loss exacerbates cardiac function with acute sympathetic stimulation and hypertrophy, but prolonged stimulation blunts the sympathetic response. Female mice were ovariectomized (OVX) or underwent SHAM surgery at 2.5 months of age. These mice were treated with isoproterenol (ISO) to simulate chronic sympathetic stimulation for 7, 14, 21 and 28 days continuously through mini osmotic pumps 3 months post ovariectomy. Echocardiography parameters were analyzed using diastolic diameter (DD), systolic diameter (SD), fractional shorting (%FS), and ejection fraction (%EF). Preliminary results showed that %FS and %EF did not change in the OVX and ISO groups compared to SHAM at 7, 14, and 28 days. Similar results were observed in the OVX compared to ISO + OVX groups at 7 days. Even though %FS and %EF did not change, the DD increased at all time points in OVX and ISO groups compared to SHAM. When comparing OVX and ISO + OVX, SD decreased at 14 and 21 days. There is however a significant increase in %FS and %EF at 21 days for all treatment groups. These preliminary results give a better insight to heart function over the course of multiple time points, suggesting that estrogen loss combined with chronic sympathetic stimulation significantly exacerbates the function of the heart.