<p>Natural steroidal estrogen hormones in swine wastes generated from Concentrated Animal Feeding Operations (CAFOs) have become a potential pollutant to many aquatic environments due to their adverse impacts on the reproductive biology of aquatic organisms. In North Carolina, the swine CAFO industry is a major agricultural economic enterprise that is responsible for the generation of large volumes of waste. However, there is limited scientific understanding regarding the concentration, fate, and transport of the estrogenic compounds from these swine facilities into terrestrial and aquatic environments. To address this issue, my research involved the development and application of integrated Bayesian networks (BNs) models that can be used to better characterize and assess the generation, fate, and transport of site-specific swine CAFO-derived estrogen compounds. The developed model can be used as decision support tool towards estrogen risk assessment. Modularized and melded BN approaches were used to capture the predictive and casual relationships of the estrogen budget and its movement within and between the three major systems of a swine farrowing CAFO. These systems include the animal barns, the anaerobic waste lagoon, and the spray fields. For the animal barn system, a facility-wide estrogen budget was developed to assess the operation-specific estrogen excretion, using an object-oriented BN (OOBN) approach. The developed OOBN model provides a means to estimate and predict estrogen fluxes from the whole swine facility in the context of both estrogen type and animal operating unit. It also accounts for the uncertainties in the data and in our understanding of the system. Next, mass balance melding BN models were developed to predict the natural estrogen fates and budgets in two lagoon compartments, the slurry and the sludge storage. This involved utilizing mass balance equations to account for the mechanisms of flushing, sorption, transformation, settling, and burial reactions of estrogen compounds in the slurry and sludge storages. As an alternative approach, a regression based BN melding approach was developed to both characterize estrogen fate and budgets as a result of the sequential transformation processes between natural estrogen compounds and to assess the seasonal effects on the estrogen budgets in the two different lagoon compartments. Finally, a dynamic BN model was developed to characterize rainfall-driven estrogen runoff processes from the spray fields. The dynamic BN models were used to assess the potential risk of estrogen runoff to adjacent waterways. In addition, the dynamic model was used to quantify the effects of manure application rates, rainfall frequency, the time of rainfall and irrigation, crop types, on-farm best management practices, seasonal variability, and successive rainfall and manure application events on estrogen runoff. </p><p>The model results indicate that the farrowing barn is the biggest contributor of total estrogen as compared to the breeding and gestation operating barns. Once the estrogen reaches the anaerobic lagoon, settling and burial reactions were shown to be the most significant factors influencing estrogen levels in the slurry and sludge, respectively. The estrogen budgets in the lagoon were also found to vary by season, with higher slurry and sludge estrogen levels in the spring as compared to the summer. The risk of estrogen runoff was predicted to be lower in the summer as compared to the spring, primarily due to the spray field crop management plans adopted. The results also indicated that Bermuda grass performed more favorably when compared to soybean, when it came to retaining surface water runoff in the field. Model predictions indicated that there is a low risk of estrogen runoff losses from the spray fields under multiple irrigation and rainfall events, unless the time interval between irrigation was less than 10 days and/or in the event of a prolonged high magnitude rainstorm event. Overall, the estrone was the most persistent form of natural estrogens in the three major systems of the swine farrowing CAFO.</p> / Dissertation

The place of estrogen in women's health remains controversial. Premenopausal women have a lower prevalence of cardiovascular disease (CVD) than men and in observational studies hormone replacement therapy (HRT) decreases CVD in postmenopausal women. However, prospective randomized trials of secondary and primary prevention have failed to substantiate an overall protective effect from HRT and have even shown some harm. To explain this paradox it is necessary to better understand the effects of estrogen on the vascular wall. Estrogen rapidly mediates the activation of eNOS and increases the production of nitric oxide (NO), an important factor for endothelial health. In ovariectomized rats estrogen reduces production of superoxide (O2-) by NAD(P)H oxidase. The decreased function is associated with a decrease in the p47phox component of NAD(P)H oxidase and its interaction with the multicomponent enzyme. In these rats estrogen did not alter eNOS expression and bioavailability of NO, which is in contrast to its acute effects. This highlights the difference between chronic and acute studies. The decrease in O2-production suggests the intracellular signaling. / Estrogen has antiapoptotic effects. Oxidized low-density lipoprotein (oxLDL) and the inflammatory cytokine TNFalpha increased apoptosis which is associated with atherosclerosis. In human umbilical vein endothelial cells (HUVEC), estrogen decreased the extent of TNFalpha and oxLDL induced apoptosis as indicated by the expression of cleaved caspase-3 and FACS assay. Estrogen also preserves the antiapoptotic mitochondrial Bcl-2 and Bcl-xL proteins. / Estrogen has angiogenic properties that can help a healthy endothelium respond to injury. However, estrogen increases the angiogenesis caused by TNFalpha and this could lead to revascularization in the plaques of women with advanced disease. / Overall the balance between the positive and negative aspects of the effects of estrogen on the vascular wall could explain the paradoxical response in older women.

Steroidal estrogens and antibiotics used in veterinary and human medicine are detected in livestock manure or sewage sludge and biosolids. Biodegradation is an important process by which estrogenic compounds are removed from organic amendments, but antibiotics have been shown to impede microbial communities. Although both compounds are often present in these media, the fate of estrogens in association with antibiotics has not been previously studied. In this study, both rates of tetracycline (40 and 200 mg kg-1) in liquid swine manure induced a lag phase of 40 to 50 days prior to the onset of a log phase of estrone and 17 β-estradiol mineralization, and tetracycline at 200 mg kg-1 significantly reduced maximum mineralization of estrone and 17 β-estradiol in manure. In soils amended with a high rate of manure, penicillin at 200 mg kg1 also significantly decreased maximum mineralization of estrone and 17 β-estradiol relative to soils free of antibiotics. Estrogen mineralization almost always significantly decreased in the order of: manure > soil amended with a low rate of manure = soil > soil amended with a high rate of manure. In order to examine the relationship between physical and chemical parameters of media and estrogen mineralization, sewage sludge and biosolid samples with vastly different characteristics were selected for a study of 17 β-estradiol and 17 α-ethinylestradiol mineralization in the presence of ciprofloxacin, an antibiotic commonly used to treat urinary and intestinal infections in humans. Ciprofloxacin was persistent in all media, as less than 0.05% mineralization was observed over 133 d. Despite this persistence, no significant effect of ciprofloxacin addition on 17 β-estradiol or 17 α-ethinylestradiol mineralization was observed at 133 days. Consistent with its chemical structure, maximum mineralization of 17 α-ethinylestradiol was always less than that of 17 β-estradiol, indicating resistance to microbial degradation. PCA analysis indicated that total nitrogen, ammonium-nitrogen and total carbon demonstrated a positive association with respiration and maximum mineralization of 17 β-estradiol, but a negative association with 17 α-ethinylestradiol maximum mineralization. Sorption of 17 α-ethinylestradiol was greater than 17 β-estradiol in all media, limiting maximum mineralization of 17 α-ethinylestradiol.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

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Made available in DSpace on 2014-06-11T19:28:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-03-02Bitstream added on 2014-06-13T20:57:35Z : No. of bitstreams: 1 gualbertojunior_ec_me_araca_parcial.pdf: 636906 bytes, checksum: 30b5eac1385afd759fc12c6f7102d1ac (MD5) Bitstreams deleted on 2015-01-16T10:37:52Z: gualbertojunior_ec_me_araca_parcial.pdf,Bitstream added on 2015-01-16T10:38:36Z : No. of bitstreams: 1 000620078.pdf: 2149145 bytes, checksum: f1633139b567f0389855aac6984d0cbc (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo deste estudo foi avaliar histológica, histometrica e imunoistoquimicamente os efeitos do laser (LLLT) e da terapia fotodinâmica (PDT) no tratamento periodontal de ratas ovariectomizadas com ou sem reposição hormonal. Duzentas e setenta ratas foram divididas em 3 grupos de 90 animais: (A) SHAM; (B) Ovariectomizadas; (C) Ovariectomizadas tratadas com reposição hormonal. Nos primeiros molares inferiores esquerdos, de todos os animais, a doença periodontal foi induzida por ligadura. Após 7 dias, esta foi removida e nestes dentes procedeu-se a raspagem e alisamento corono-radicular (RAR). A seguir foram dividos em subgrupos de acordo com os tratamentos locais: I (n = 90) - Irrigação com 1 ml de soro fisiológico (RAR); II (n = 90) - Irrigação com 1 ml de soro fisiológico associado a aplicação de laser de baixa intensidade (LLLT) e III (n = 90) - Irrigação com 1 ml de azul de toluidina-O e, após 1 minuto, aplicação de laser em baixa intensidade (PDT). Dez animais de cada subgrupo foram sacrificados aos 7, 15 e 30 dias. Os animais do grupo A apresentaram perda óssea (PO) significativamente maior (p<0,01) no tratamento com RAR (1.11±0.26; 0.84±0.47) comparado à PDT (0.70±0.30; 0.42±0.20) nos períodos de 7 e 15 dias respectivamente. Os espécimes tratados com LLLT aos 30 dias demonstraram PO significativamente menor (p<0,01) no grupo A (0.35±0.18) comparado aos grupos B (0.82±0.21) e C (0.83±0.19). No tratamento com PDT, observou-se PO significativamente menor (p<0,01) no grupo A (0.42±0.20) comparado aos grupos B (0.95±0.20) e C (0.81±0.32) aos 15 dias. No entanto, no grupo C aos 30 dias a PDT demonstrou PO (0.52±0.23) em nível próximo ao observado nos espécimes do grupo A, no mesmo período (0.50±0.26). Na análise entre períodos, no mesmo grupo e tratamento, observou-se no grupo A, que o tratamento I apresentou PO significativamente maior... / The aim of this study was to evaluate histological, histometrically and immunohistochemistry the influence of laser and photodynamic therapy (PDT) as an adjuvant treatment on the experimentally induced periodontitis in ovariectomy rats with or without replacement hormone. Two hundred and seventy females rats were divided into 3 groups of 90 animals. (A) Normal female rats; (B) Control - Ovarectomy; (C) Ovarectomy treated with replacement hormone. The periodontal disease was induced by ligation and after 7 days was removed and the animals divided into subgroups who received the treatments: I - scaling and root planing (SRP) and irrigation with saline; II – SRP and irrigation with saline solution and LLLT (Laser -AsGaAl - 685 nm); III - SRP, irrigation with 1ml of Toluidine Blue (TBO) and, after 1 minute, application of laser (685 nm), performing photodynamic therapy (PDT). Ten animals of each subgroup were sacrificed at 7, 15 and 30 days. The animals of the group A presented bony loss (BL) significantly larger (p <0,01) in the treatment with RAR (1.11±0.26; 0.84±0.47) compared to PDT (0.70±0.30; 0.42±0.20) at 7 and 15 days respectively. In the specimens treated with LLLT at 30 days showed BL significantly less (p <0,01) in the group A (0.35±0.18) compared at groups B (0.82±0.21) and C (0.83±0.19). In the treatment with PDT, it was observed BL significantly less (p <0,01) in the group A (0.42±0.20) than groups B (0.95±0.20) and C (0.81±0.32) at 15 days. However, in the group C at 30 days PDT showed BL (0.52±0.23) in close level that observed in the specimens of the group A, in the same period (0.50±0.26). In the analysis among periods, in the same group and treatment, it was observed in the group A, that the treatment I presented BL significantly larger (p <0,01) at 7 days (1.11±0.26); that the treatment II showed larger BL (p <0,01) in the period of 7 days (0.90±0.29)... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:28:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-03-11Bitstream added on 2014-06-13T20:08:38Z : No. of bitstreams: 1 murakawa_ac_me_araca.pdf: 2456403 bytes, checksum: 0b8fd6ef9c787a2f0e9cbb4bc43f1a21 (MD5) / Objetivos: O objetivo deste estudo foi avaliar a influência da ovariectomia (depleção de estrógeno), no processo de reparo de enxertos ósseos autógenos em bloco por meio da imunomarcação da PECAM-1 e osteocalcina (OCN), em ratas jovens e senis. Material e Métodos: Foram utilizadas 96 ratas (Wistar) fêmeas, sendo 48 ratas com idade de 3 meses, divididas em subgrupo Ovx, submetidas a cirurgia de ovariectomia e subgrupo Sham submetidas ao mesmo procedimento cirúrgico sem a remoção dos ovários; e 48 ratas com idade de 12 meses, também divididas em subgrupos Ovx e Sham. Transcorridos 30 dias da Ovx ou sham, todos os animais receberam enxerto ósseo autógeno em bloco na mandíbula, tendo como área doadora o osso parietal da calvária. Os animais foram submetidos a eutanásia em 7, 14 e 28 dias. As peças foram submetidas à análises histométrica e imunoistoquímica. Esta foi realizada de forma semi-quantitativa, visando analisar as imunomarcações contra PECAM-1 e osteocalcina, avaliando-se a interferência do estrógeno neste processo. Resultados: Durante os períodos analisados, os subgrupos Sham apresentaram marcações da osteocalcina mais intensas quando comparadas com os subgrupos Ovx, independente da idade do animal. As marcações de PECAM-1 foram mais intensas nos subgrupos Sham aos 7 e 14 dias. Conclusão: Dentro dos limites deste estudo, concluímos que a depleção de estrógeno afeta negativamente o processo inicial da angiogênese e diminui a mineralização óssea. / Objectives: The aim of this study was to evaluate the influence of the ovariectomy (estrogen depletion), on healing process of autogenous bone block grafts in young and aged rats, through the immunocolocalization of the PECAM-1 and osteocalcin (OC). Material and Methods: 96 female rats (Wistar) were used, being 48 rats with 3 months-old, divided in subgroups: Ovx, submitted the ovariectomy surgery and Sham, submitted to the same surgical procedure without the removal of the ovaries; and 48 female rats with 12 months-old, also divided in Ovx and Sham subgroups. After 30 days of Ovx or sham operation, all the animals received autogenous bone block graft in the jaw, harvested from the calvaria. The animals were euthanized in 7, 14 and 28 days postoperatively. The specimens were submitted to histometric and immunohistochemistry analysis. This was accomplished in a semi-quantitative way, to analyze the immunolocalizations against PECAM-1 and osteocalcin, evaluating the interference of the estrogen in this process. Results: During the analyzed periods, the Sham subgroups presented more intenses demarcations of osteocalcin when compared with the subgroups Ovx, regardless of age. The demarcations of PECAM-1 were more intenses in the sham subgroups to the 7 and 14 days. Conclusion: Within the limits of this study, the estrogen depletion affects the initial process of angiogenesis negatively and it reduces bone mineralization.

Made available in DSpace on 2014-10-09T12:41:24Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:40Z (GMT). No. of bitstreams: 0 / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Submitted by BRUNA BERGAMIN null (brubergamin@iq.unesp.br) on 2017-07-10T23:16:27Z No. of bitstreams: 1 Dissertação final 1.pdf: 3270750 bytes, checksum: 7a706d3e4baa0dc96bb2561c2d8ab723 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-07-13T19:11:23Z (GMT) No. of bitstreams: 1 bergamin_b_me_araiq.pdf: 3270750 bytes, checksum: 7a706d3e4baa0dc96bb2561c2d8ab723 (MD5) / Made available in DSpace on 2017-07-13T19:11:23Z (GMT). No. of bitstreams: 1 bergamin_b_me_araiq.pdf: 3270750 bytes, checksum: 7a706d3e4baa0dc96bb2561c2d8ab723 (MD5) Previous issue date: 2017-06-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O desenvolvimento de métodos analíticos cada vez mais seletivos e sensíveis é de grande importância para uma melhor qualidade na determinação de espécies químicas, aumentando assim a confiabilidade dos resultados obtidos. Com isso, o emprego e otimização das etapas de separação/concentração se faz necessário. O emprego de polímeros molecularmente impressos (do inglês - “Molecularly Imprinted Polymers” - MIP) tem demonstrado ser uma eficiente ferramenta analítica com grande potencialidade para minimizar as limitações das técnicas de separação/concentração tradicionalmente empregadas. No caso deste trabalho, o template utilizado será o valerato de estradiol, principalmente pela sua importância inerente na reposição hormonal feminina e por se tratar de um disruptor endócrino (hormônio) lançado ao meio ambiente sem nenhum controle. Assim a síntese do polímero para identificação do valerato de estradiol foi realizada por diferentes rotas (bulk e precipitação) através de duas vias de polimerização (termopolimerização e fotopolimerização) variando o monômero funcional (MAA, acrilonitrila, 2-vinil-piridina e 1-vinilimidazol). O MIP e NIP foram colocados, um de cada vez, em sistema soxhlet contendo metanol/ácido acético na proporção 70/30 a 60º C, para remoção da molécula impressa, através de cinco lavagens sucessivas em períodos de 24 h. Essas águas de lavagem foram analisadas utilizando espectrofotometria UV/Vis. Posteriormente com os parâmetros otimizados o polímero que apresentou melhor resultado foi modificado com nanopartículas magnéticas (core@shell), sendo assim sintetizado MIP magnético (MMIP) para valerato de estradiol, usando ácido metacrílico (MF) e TRIM (ME); aumentando o reconhecimento do MIP e, além de, facilitar a separação do material da solução pela aplicação de um campo magnético externo. Todos os materiais sintetizados foram amplamente caracterizados, física e físico-quimicamente. O material sintetizado apresentou um excelente magnetismo (2,0 emu g-1 ), uma alta porcentagem de retenção (superior a 80%) e um Qmáx acima de 24 mg g-1 , indicando que é promissor para adsorção de valerato de estradiol. / The development of selective and sensitive analytical methods has significant importance for an improvement at determination of chemical species; increasing the reliability of the results obtained. So, the use and optimization of separation and concentration steps is necessary. The use of Molecularly Imprinted Polymers (MIP) has been shown to be an efficient analytical tool with great potential to minimize the limitations of separation/concentration techniques traditionally employed. In the case of this study, the template used will be estradiol valerate, once of its inherent importance in female hormone replacement and because it is an endocrine disruptor (hormone) released into the environment without any control. Thus, the synthesis of the polymer for the identification of estradiol valerate was performed by different routes (bulk and precipitation) through two polymerization techniques (thermopolymerization and photopolymerization) by varying the functional monomer (MAA, acrylonitrile, 2-vinyl pyridine and 1- vinylimidazole). MIP and NIP were placed in a soxhlet system containing 70/30 methanol/acetic acid at 60 ° C for removal of the imprinted molecule through five successive washes in 24 h periods. These wash waters were analyzed using UV/Vis spectrophotometry. Subsequently, with the optimized parameters, the polymer that presented the best result was modified with magnetic nanoparticles (core@shell); being synthesized magnetic MIP (MMIP) for estradiol valerate, increasing the recognition of the MIP and, furthermore, facilitating the separation of the material from the solution by the application of an external magnetic field. It was used methacrylic acid as functional monomer, TRIM as structural monomer and all the synthesized materials were widely characterized, physically and physico-chemically. The synthesized material showed excellent magnetism (2.0 emu g-1 ), an elevate percentage retention (higher than 80%) and a Qmax above 24 mg g-1 , indicating that MMIP is a promising material for adsorption of estradiol valerate. / CAPES: 33476991814