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

Objective - To evaluate a surgical technique for performing laparoscopic bilateral ovariectomy in standing horses. Study Design - Experimental study. Animals or Sample population - 8 mares, age 2-20 years, weight 410-540 kg. Methods - Standing laparoscopic bilateral ovariectomy was performed in 8 mares with normal anatomy of the reproductive tract. The Harmonic Scalpel (an ultrasonically activated instrument) was used to transect the ovarian pedicle and to obtain hemostasis simultaneously. Necropsy was performed on 4 mares 3 days after surgery and 30 days following surgery on the remaining 4 mares. Gross and histopathologic evaluation of the ovarian pedicles was performed to characterize the effects of the Harmonic Scalpel on the transected tissue. Results - The Harmonic Scalpel achieved complete hemostasis of the vasculature of the ovarian pedicles in all mares. Median transection time for the ovarian pedicle was 28 minutes. Postoperative complications included transient fever in one mare, moderate subcutaneous emphysema in another, and incisional seroma formation in a third mare. Post-mortem examination 3 and 30 days postoperatively revealed no signs of generalized peritonitis, postoperative hemorrhage or adhesion formation. Mild to moderate acute inflammation, and scar formation with moderate chronic inflammation at the ovarian pedicle was found 3 and 30 days after surgery, respectively. Median depth of coagulation necrosis 3 days postoperatively was 2.87 mm. Conclusions - The Harmonic Scalpel appears to provide reliable hemostasis of the ovarian pedicle during elective laparoscopic ovariectomy in horses. Clinical Relevance - The Harmonic Scalpel represents a safe alternative to other means of hemostasis during elective laparoscopic ovariectomy in horses. / Master of Science

The highly regulated maturation of the mammary gland is poorly understood. Our studies were designed to further characterize the role of ovarian hormones, growth hormone (GH)/IGF axis proteins and extracellular matrix (ECM) in the growth and development of prepubertal mammary glands. Prepubertal heifers were injected with either exogenous GH or subjected to ovariectomy (OVX). Mammary parenchyma (PAR) and mammary fat pad (MFP) were harvested for DNA, protein, lipid, and western blot analysis. Remaining tissues were preserved for histological staining or snap frozen for quantitative real-time PCR. We examined 13 genes that work in conjunction with the extracellular matrix to regulate mammary proliferation and morphogenesis. Administration of GH, while impacting composition of MFP, had no effect on expression of the selected genes; there was a decrease in expression of fibronectin in PAR. Ovariectomy had no effect on gene expression in MFP but decreased expression of epimorphin, a potent regulator of morphogenesis, in PAR. In both experiments, the presence of a 55 kDa band corresponding to androgen converting enzyme aromatase was detected but its expression was unaffected. In another study, we used in vitro cell culture to evaluate the role of ECM in mammary gland maturation and employed quantitative real-time PCR to evaluate gene expression profiles of select genes involved in proliferation and differentiation. Expression of Rac1 was decreased in response to bovine insulin (BI) but increased on collagen I (Col). Expression of aldehyde dehydrogenase was decreased in BI and serum on plastic and on Col in the presence of BI. Expression of IGF binding proteins (BP) 3, -4, and -6 were decreased in the presence of serum on laminin (LM). Also, IGF-BP2 expression was decreased on Col while IGF-BP6 was increased on LM with BI. Clusterin, a ubiquitous non-adhesive ECM protein was not affected by ECM substrate but did increase over time. In conclusion, we propose that the mammary gland is not able to respond to GH at this age and that while OVX did effect the expression of some genes, the presence of aromatase maintained local estrogen concentrations. Furthermore, ECM alone is insufficient to regulate mammary gland development and growth. / Ph. D.