Submitted by LETÍCIA RODRIGUES ALVES null (leticiarodalves@yahoo.com.br) on 2016-08-23T15:29:42Z No. of bitstreams: 1 AlvesLR_DISSERTAÇÃO+CERTIFICADO.pdf: 2471666 bytes, checksum: bbe3b90a7ad821bca3d2ff9e298beb5f (MD5) / Rejected by Ana Paula Grisoto (grisotoana@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo a orientação abaixo: A folha de aprovação deve constar após a ficha catalográfica. A versão submetida por você é considerada a versão final da dissertação/tese, portanto não poderá ocorrer qualquer alteração em seu conteúdo após a aprovação. Corrija esta informação e realize uma nova submissão contendo o arquivo correto. Agradecemos a compreensão. on 2016-08-24T16:10:04Z (GMT) / Submitted by LETÍCIA RODRIGUES ALVES null (leticiarodalves@yahoo.com.br) on 2016-09-05T16:31:58Z No. of bitstreams: 1 Dissertação_LR Alves - atualizada2.pdf: 1845174 bytes, checksum: 6d6d5923f6f594ad941d882c5beadab0 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-09-06T12:52:43Z (GMT) No. of bitstreams: 1 alves_l_me_jabo.pdf: 1845174 bytes, checksum: 6d6d5923f6f594ad941d882c5beadab0 (MD5) / Made available in DSpace on 2016-09-06T12:52:43Z (GMT). No. of bitstreams: 1 alves_l_me_jabo.pdf: 1845174 bytes, checksum: 6d6d5923f6f594ad941d882c5beadab0 (MD5) Previous issue date: 2016-06-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A contaminação por metais pesados é um problema mundial e é uma das causas mais severas de estresse abiótico nas plantas, desencadeando perdas na produtividade e risco de contaminação para a saúde humana. A concentração de cádmio aumentou consideravelmente no meio ambiente devido a fatores antropogênicos. As plantas podem absorver o cádmio, levando a alta produção de espécies reativas de oxigênio, o que desencadeia cascatas de oxidação descontroladas, resultando em danos a planta. Com o objetivo de adicionar novas informações nesta área, foi realizada uma discussão sobre a contaminação dos solos agrícolas por metais pesados, os danos causados na homeostase celular, o sistema antioxidante de defesa e o impacto para os consumidores. Além disso, foi feito um estudo sobre a comunicação da raiz para a parte aérea durante uma condição de estresse, interconectando a resposta especifica das espécies reativas de oxigênio e a ação dos hormônios nesta comunicação. Pare este propósito, foi utilizado como ferramenta a enxertia e os mutantes hormonais para investigar a modulação da resposta antioxidante de defesa entre os órgãos. / Heavy metal contamination is a worldwide concern and one of the most severe causes of abiotic stress in plants, triggering losses in crop production and contamination risks to human health. Cadmium concentration have been increased in environment due to several anthropogenic factors. Plants can uptake cadmium, which lead to a high production of reactive oxygen species and trigger an uncontrolled oxidation cascade in cells, resulting in damages to plant. In order to gain new information about this subject, we carried out a deep discussion about heavy metal contamination in agricultural soils, damages in cell homeostasis, antioxidant defense system and the impact to food consumers. Moreover, we studied root-to-shoot communication during stress condition and the specific responses of reactive oxygen species and hormones in this communication. For this propose, we used grafted hormonal mutants as a tool to investigate the modulation of antioxidant stress responses between organs. / FAPESP: 2013/27080-4

Made available in DSpace on 2014-06-11T19:29:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-18Bitstream added on 2014-06-13T18:39:58Z : No. of bitstreams: 1 martins_mad_me_botfm.pdf: 354151 bytes, checksum: fd9ef52802847e9f7bceaa3e8157d4f3 (MD5) / O objetivo desta pesquisa foi avaliar a qualidade de vida de mulheres na pós-menopausa usuárias e não usuárias de terapia hormonal (TH) em Unidade Básica de Saúde (UBS) de Franca-SP. Foi conduzido estudo clínico transversal, com amostra de conveniência composta por 250 mulheres na pós-menopausa, idade entre 45 a 70 anos, atendidas em UBS de setembro de 2007 a agosto de 2008. As participantes foram divididas em dois grupos: usuárias de terapia hormonal (n=70) e não usuárias (controle, n=180). Foram excluídas aquelas com: doenças psiquiátricas, tireopatias não-controladas, doenças malignas, uso de antidepressivos, obesidade grau III, drogaditas e etilistas. Consideraram-se como usuárias de TH aquelas que faziam uso contínuo dessa terapia há pelo menos seis meses. Foram avaliadas as características sócio-demográficas e clínicas. Aplicou-se o Índice Menopausal de Blatt-Kupperman (IMBK) para avaliar a intensidade dos sintomas climatéricos e o Questionário de Saúde da Mulher (QSM) para a avaliação da qualidade de vida. A análise estatística foi realizada pelo teste do Qui-Quadrado ou exato de Fisher, teste de Mann-Whitney ou de Kruskal-Wallis. Os resultados não mostraram diferenças significativas na comparação entre os grupos quanto à idade, menarca, menopausa, paridade e índice massa corpórea. Observou-se que 67,2% eram casadas (168/250), 83,2% com ensino fundamental (208/250) e 53,2% se ocupavam com os trabalhos domésticos (133/250), não diferindo entre os grupos. As usuárias de TH relataram menor freqüência de sintomas climatéricos (IMBK) de intensidade moderada e acentuada, comparadas a não usuárias (p<0,001). Na avaliação do QSM, verificou-se entre as usuárias de TH, menor escore médio quanto ao déficit cognitivo (p<0,001), sintomas... / This research aims at assessing the quality of life in postmenopausal women who were users and non-users of hormone therapy (HT) in public health care unit (HCU) of Franca- SP. This cross-sectional, clinical study was undertaken in a convenience sample consisting of 250 postmenopausal women, aged 45-70 years, followed up at the HCU from September 2007 to August 2008. The patients were divided in two groups: users of HT (n=70) and non-users of HT (control, n=180). Exclusion criteria: obesity, psychiatric disturbances, antidepressants use, uncontrolled thyroid diseases, drug addicts, alcohol addicts and malignant diseases carriers. Women considered HT users were those who had undergone this treatment for at least six months. Socio-demographics and clinical characteristics were assessed. The Blatt-Kupperman Menopausal Index (BKMI) was applied to rate the intensity of climacteric symptoms and the Women’s Health Questionnaire (WHQ) was applied to assess women’s quality of life. For data statistical analysis, a Qui-square tests, a Fisher’s Exact Test, a Mann-Whitney Test and Kruskal- Wallis test were used. The results show that there is no significant difference between groups regarding age, menarche, menopause, parity and body mass index. At total 67.2% of women were married (168/250), 83.2% had received fundamental education (208/250) and 53.2% were busy with house chores (133/250), not differing among the group. HT users reported a lower frequency of moderate and severe climacteric symptoms (p<0.001). From WHQ, it was observed among the HT users lower average score of memory concentration (p<0.001), vasomotor symptoms (p=0.048), sleep problems (p<0.001) and attractiveness (p=0.024); however there were no differences between groups regarding the QSM total score. In conclusion, postmenopausal women who were users and nonusers of HT, followed up at a health care unit, not presented differences in global quality of life.

Menopause is a major reproductive-related event in a woman’s life, occurring naturally at around the age of fifty years. Accompanying menopause is a drastic decrease in estrogen levels. Estrogen receptors are present throughout the human brain: e.g., in regions such as the hippocampus and prefrontal cortex, both involved in cognition. Given that about half of the world’s population is female, it is important to examine if and how cognition is affected by the menopausal estrogen depletion, both at the level of public health, and at the individual level. Studies within the field show diverse results due to a wide range of methodology among studies. Behavioral studies foremost point towards a potential estrogenic effect on verbal short- and long-term memory. Structural and functional neuroimaging, together with animal studies, mainly show structural and functional alterations in the hippocampus and prefrontal cortex that may be related to changes in estrogen levels. Taken together, this thesis reviews estrogenic effects on different cognitive functions, as well as structural and functional changes in the brain in relation to the menopausal estrogen depletion.

A ocorrência de trombose está freqüentemente associada com a presença de um ou mais fatores de riscos, os quais podem ser genéticos e/ou adquiridos, tais como as mudanças hormonais que ocorrem durante a gravidez, a terapia de reposição hormonal e o uso de contraceptivos hormonais combinados (CHC). A inflamação, por sua vez, é uma importante resposta do organismo às agressões e envolve vários mecanismos biológicos relacionados entre si e altamente regulados, tais como: coagulação, fibrinólise, ativação do sistema complemento (SC), antioxidação e regulação hormonal. Fisiologicamente, os sistemas complemento e da coagulação compartilham componentes. A ativação do fator XII da coagulação é controlada pela mesma proteína reguladora da ativação do sistema complemento, o inibidor de C1. A deficiência do inibidor de C1 leva a uma patologia conhecida como angioedema hereditário. No entanto, uma manifestação clínica similar ao angioedema tem sido descrita em mulheres que usam CHC ou recebem terapia de reposição hormonal com estrogênio (E). Esta influência do estrogênio na coagulação e no SC também é evidenciada pela ação regulatória do E sobre a expressão do fator XII e dos seus níveis plasmáticos. Considerando o efeito pleiotrópico do E, e as interações do SC e da hemostasia, o objetivo desse estudo foi avaliar o efeito de diferentes CHC sobre: a) a atividade hemolítica (AH) do SC e ativação das vias clássica/lectina e alternativa; b) a atividade opsonizante do SC em mediar o burst oxidativo dos neutrófilos; e c) a função dos receptores para complemento (CR) em mediar o burst oxidativo dos neutrófilos. Nós estudamos 5 CHC diferentes e observamos que a) drospirenona + 30g E mostrou uma tendência a aumentar o burst oxidativo mediado por CR; b) gestodeno + 20g E mostrou redução da capacidade opsonizante do SC; c) levonorgestrel + 30g E e gestodeno + 20g E promoveram uma redução no número de neutrófilos positivos para a expressão de CR1; d) drospirenona + 30g E e drospirenona + 20g E promoveram um aumento da AH da via clássica (VC) do SC; e) levonorgestrel + 30g E promoveu uma redução da AH da VC do SC; f) drospirenona + 30g E, gestodeno + 20g E e levonorgestrel + 30g E promoveram uma diminuição do nível sérico de C4d, produto da ativação das vias clássica/lectina do SC; g) levonorgestrel + 30g E apresentou um aumento da concentração sérica de inibidor de C1; h) nenhum dos CHC mostrou diferenças na ativação da via alternativa do SC. Os resultados mostram a importância de considerar os diferentes grupos de CHC nas comparações com o Grupo Controle, uma vez que algumas diferenças foram significativas apenas para CHC em particular. Estas observações podem contribuir para o entendimento dos mecanismos envolvidos na fisiopatologia dos processos inflamatórios associados ao uso de estrogênios. / The occurrence of thrombosis is often associated with the presence of one or more risk factors, which may be genetic and/or acquired, such as hormonal changes that occur during pregnancy, hormone replacement therapy and the use of combined hormonal contraceptives (CHC). The inflammation in turn, is an important body\'s response to the aggression and involves several biological mechanisms related and highly regulated, such as coagulation, fibrinolysis, activation of the complement system (CS), oxidation and hormonal regulation. Physiologically, the complement and coagulation systems share components. Activation of coagulation factor XII is controlled by the same regulatory protein activation of the complement inhibitor C1. The deficiency of C1 inhibitor leads to a condition known as hereditary angioedema. However, a clinical manifestation similar to angioedema has been reported in women using CHC or receiving hormone replacement therapy with estrogen (E). The influence of E on coagulation and the CS is also evidenced by the regulatory action of E on the expression of factor XII and its plasma levels. Considering the pleiotropic effects of E, and the interactions of CS and hemostasis, the goal of this study was to evaluate the effect of different CHC on: a) hemolytic activity (HA) CS and activation of classical/lectin and alternative pathways, b) the opsonizing activity of the CS in mediating the oxidative burst of neutrophils, and c) the function of receptors for complement (CR) in mediating the oxidative burst (OB) of neutrophils. We studied 5 different CHC and data showed: a) drospirenone + 30g E increase of the OB neutrophils mediated by CR; b) gestodene + 20g E had a reduced opsonizing ability; c) levonorgestrel + 30g E and gestodene + 20g E promoted a reduction of neutrophils positive for the expression of CR1, d) drospirenone + 30g E and drospirenone + 20g E promoted an increase in HA for classical pathway (CP); e) levonorgestrel + 30g E reduced the HA for CP; f) drospirenone + 30g E and gestodene + 20g E and levonorgestrel + 30g E reduced the serum level of C4d; g) levonorgestrel + 30g E showed an increase of the serum level of C1 inhibitor; h) none of CHC showed differences in activation of the alternative pathway in CS. The results show the importance of considering the different groups of CHC in comparison with the control group, since some differences were significant only for CHC in particular. These observations may contribute to the understanding of the mechanisms involved in the pathophysiology of inflammatory processes associated with estrogen use.

Submitted by Mario BC (mario@bc.ufrpe.br) on 2018-03-09T14:11:37Z No. of bitstreams: 1 Priscilla Bartolomeu de Araujo.pdf: 1359264 bytes, checksum: 748f6b0ea3345a96cd11610242db1af1 (MD5) / Made available in DSpace on 2018-03-09T14:11:37Z (GMT). No. of bitstreams: 1 Priscilla Bartolomeu de Araujo.pdf: 1359264 bytes, checksum: 748f6b0ea3345a96cd11610242db1af1 (MD5) Previous issue date: 2016-02-24 / The present objective was to perform a clinical and histopathological study to investigate the serum levels of estradiol, progesterone and prolactin, as well as the gene expression of the estrogen receptors α and β, and progesterone in bitches with mammary tumors. Sixty bitches of various ages and breeds were selected: 30 with mammary neoplasia and 30 healthy bitches. Fragments of the tumors were collected for histopathology and for investigation of the gene expression of the hormone receptors. Serum samples were also collected for measurement of serum hormones and Ca15.3. Malignant neoplasms were more frequent (76.6%), with a greater number of carcinosarcomas (36.7%). The frequency of benign tumors was 23.3%. Mammary tumors were mostly multiple, larger than 5 cm, and located in the abdominal mammary glands. Owners reported that most dogs had not shown signs of pseudocyesis, had not had a prior pregnancy, nor had they used contraceptives or been spayed. Regarding serum concentrations of the Ca15.3 marker, there was no difference when comparing bitches with neoplasia and healthy bitches, or when comparing the other groups. Bitches with malignant neoplasms had higher levels of estradiol and lower levels of prolactin. Both malignant and benign neoplasms expressed hormone receptors, and there was no difference in expression between them. There was also no difference in prognostic factors between groups. Serum levels of estradiol increased significantly with clinical staging of the disease. There was also a moderate negative correlation between serum levels of estradiol and prolactin. It is concluded that the hormonal influence is evident in cases of canine mammary neoplasms, especially estrogens, which seem to be most associated with malignant characteristics. The influence of hormones is reinforced by the presence of hormone receptors even in different tumor types, which could suggest the use of hormone therapy as an alternative. However, quantification of Ca15.3 did not show any results that made its use possible as a tool for patient monitoring and evaluation. / Objetivou-se realizar um estudo clínico e histopatológico e investigar os níveis séricos de estradiol, progesterona e prolactina, e a expressão gênica dos receptores de estrógeno α e β, e de progesterona em cadelas portadoras de tumores mamários. Foram utilizadas 60 cadelas de diferentes idades e raças, sendo 30 cadelas portadoras de neoplasias mamárias e 30 cadelas hígidas. Fragmentos do tumor foram coletados para realização do exame histopatológico, e para investigação da expressão gênica dos receptores hormonais. Coletou-se ainda amostras de soro para realização das dosagens hormonais séricas e de Ca15.3. As neoplasias malignas foram mais frequentes (76,7%), destacando-se o carcinossarcoma (36,7%). A frequência dos tumores benignos foi de 23,3%. As neoplasias mamárias foram em sua maioria múltiplas, maiores que 5 cm, localizadas nas mamas abdominais. Os tutores relataram que 56,7% das cadelas não apresentaram sinais de pseudociese, 63,3% não haviam passado por gestação anterior, 76,7% não haviam feito uso de anticoncepcionais, e 90% não haviam sido castradas. Quanto às dosagens séricas do marcador Ca15.3 não foi encontrada diferença quando comparadas as cadelas portadoras de neoplasias e cadelas hígidas, ou quando comparados os demais grupos. As cadelas portadoras de neoplasias malignas apresentaram maiores níveis de estradiol e menores níveis de prolactina. Tanto os tumores malignos como os benignos expressaram receptores hormonais, não havendo diferença na expressão entre eles ou entre os outros fatores prognósticos. Os níveis séricos de estradiol aumentaram significativamente com o estadiamento clínico da doença. Verificou-se também moderada correlação negativa entre os níveis séricos de estradiol e prolactina. Conclui-se que a influência hormonal é evidente nos casos de neoplasias mamárias caninas, sobretudo dos estrógenos, que parecem estar mais associados às características de malignidade. Soma-se ainda a presença dos receptores hormonais, mesmo em tipos tumorais distintos, o que pode propor a utilização da terapia hormonal como alternativa. Já a dosagem de Ca15.3 não mostrou resultados que tornassem possível sua utilização como ferramenta para acompanhamento e avaliação das pacientes.

Orientador: Valéria Helena Alves Cagnon Quitete / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T04:47:08Z (GMT). No. of bitstreams: 1 Kido_LarissaAkemi_M.pdf: 14026607 bytes, checksum: 4b5dcdcd04b3cf312f7b62cb4cf2ac2b (MD5) Previous issue date: 2013 / Resumo: A senescência está associada a mudanças significativas no ambiente hormonal, sendo fator causador de alterações morfofuncionais na próstata. Os diferentes processos biológicos que ocorrem na próstata são regulados por polipeptídeos, dentre esses os fatores de crescimento do endotélio vascular (VEGF) e Endostatina, relacionados à angiogênese. Além disso, inibidores da enzima 5_ redutase-II, como a finasterida, tem papel importante no combate às doenças prostáticas. Assim, os principais objetivos desse estudo foram avaliar os efeitos estruturais e moleculares das terapias antiangiogênicas e da finasterida sobre a próstata ventral de camundongos durante a senescência. Noventa camundongos machos FVB de 18 e 52 semanas de idade foram divididos nos seguintes grupos: Jovem (JV) e Senil (SEN), os quais receberam injeções de Solução Fisiológica 0,9% (5 mL/Kg/dia s.c.); Finasterida (FIN): injeções de Finasterida (20 mg/Kg, s.c.); SU5416 (SU): SU5416 (6 mg/Kg, i.p.); TNP-470 (TNP): injeções de TNP-470 (15 mg/Kg, s.c.), e SU5416 + TNP-470 (SU+TNP): os mesmos tratamentos dos grupos SU e TNP. Após 21 dias de tratamento, amostras do lobo ventral da próstata foram coletadas e submetidas às análises morfológicas, imunohistoquímicas e Western Blotting. Os resultados demonstraram alterações moleculares e estruturais no microambiente prostático durante a senescência, como atrofia presença de células inflamatórias, e lesões proliferativas, as quais foram interrompidas e ou bloqueadas através dos tratamentos com as drogas antiangiogênicas e pela finasterida. Os resultados moleculares revelaram no grupo senil a diminuição das reatividades para AR e Endostatina, e aumento para ER-_, ER-_ e VEGF, quando comparados aos camundongos jovens. Os camundongos dos grupos tratados com finasterida, SU5416 e SU5416+TNP-470, quando comparados aos do grupo senil, demonstraram de forma geral diminuição das reatividades de VEGF e ER-_ e aumento de ER-_. Já o tratamento com TNP-470 foi marcado principalmente pela redução da reatividade e dos níveis protéicos de AR e ER-_, quando comparado aos grupos jovem e senil. Desta maneira, conclui-se que a senescência favoreceu a ocorrência de alterações estruturais e/ ou funcionais que sugerem o aparecimento de lesões malignas, em virtude do desequilíbrio na sinalização entre epitélio e estroma. O tratamento com finasterida, SU5416 e SU5416+TNP- 470 mostraram-se mais ativos na regulação dos processos proliferativos através da via estrogênica / Abstract: Senescence is associated with significant changes in the hormonal environment and is a cause of morphological and functional changes in the prostate. The different biological processes that occur in the prostate are influenced by different factors such as vascular endothelial growth factor (VEGF) and Endostatin, related to angiogenesis. Also, 5_-reductase inhibitors, such as finasteride, play an important role in treatment of prostatic diseases. Thus, the aims of this study were to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of mice during senescence. Ninety 52 and 18 week old male FVB mice, were divided into groups: Young (YNG) and Senile (SEN) groups, which received 0.9% saline (5 mL/kg/day sc) injections; Finasteride (FIN) group: Finasteride (20 mg/kg, sc); SU5416 (SU) group: SU5416 (6 mg/kg, ip) injections; TNP-470 (TNP) group: TNP-470 (15 mg/kg, sc) injections and SU5416+TNP-470 (SU+TNP470) group: The same treatment as the SU and TNP-470 groups. After 21 days of treatment, samples of the ventral lobe of the prostate were collected and analyzed for morphological, immunohistochemical and Western Blotting analyses. The results demonstrated structural and molecular changes in the prostatic microenvironment during senescence, such as atrophy, inflammatory cells, and proliferative lesions, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. The molecular results revealed decreased reactivity for AR and Endostatin, and an increase for ER-_, ER-_ and VEGF in the senile group, when compared to young mice. The mice in the groups treated with finasteride, SU5416 and SU5416 + TNP-470, when compared to the senile group, showed in general decreased VEGF and ER-_ reactivities and increased ER-_ reactivity. The treatment with TNP-470 however, was marked mainly by reduced AR and ER-_ reactivity and protein levels, when compared to young and senile groups. Thus, it can be concluded that senescence contributed to the occurrence of structural and/or molecular alterations that suggest the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. Treatments with finasteride, SU5416 and SU5416+TNP-470, were active in the regulation of proliferative processes by means of the estrogen pathways / Mestrado / Anatomia / Mestra em Biologia Celular e Estrutural

M.Tech. (Homoeopathy) / Menopause is the natural or iatrogenic termination of menstrual periods as a result of decreasing ovarian function. Natural menopause begins when menstrual periods have been absent for one year (Beers et al., 2006). The Climacteric is the period which encompasses the transition from the reproductive state to the non-reproductive state. Menopause, therefore, is a specific event that takes place during the climacteric (Collins et al., 2010). The symptoms are usually treated conventionally with Hormonal Replacement Therapy (HRT), but a large number of adverse side-effects are associated with its use (Harvey and Champe., 2009). De Schepper (2001) states that the true Homoeopathic Similimum strengthens a person’s vital force which results in the improvement of disease symptoms. Barton (2008) states that it is very difficult to accurately find the Homoeopathic Similimum for each case; therefore, Grant Bentley and his team have worked to develop a system of analysis, to facilitate the identification of the Similimum for each case. The Grant Bentley Method requires photography of the face and analysis of the facial features necessary to ascertain the miasmatic category into which the participant falls (Barton, 2008). There is no research verifying the effectiveness of this method in the treatment of climacteric symptoms. The aim of the study is to evaluate the effect of the Homoeopathic Similimum, using the Grant Bentley-method, on Climacteric symptoms. The study was carried out in the form of case studies over a twelve week period. Eleven females, between the ages of forty and sixty-five years, who were experiencing climacteric symptoms and who met the inclusion and exclusion criteria were recruited, using purposive sampling, by placing advertisements (Appendix A) in local newspapers, pharmacies and medical practices in the Vanderbijlpark area and at the Doornfontein Campus of the University of Johannesburg. The process of the study was explained to the participants and consent forms were signed (Appendix C and D). Participants, with the researcher’s help, completed a Suitability Criteria Questionnaire (Appendix B). During the first consultation the Menopause Rating Scale (MRS) (Appendix E and F) was completed and evaluated (Appendix G). The Homoeopathic case studies took the form of one-on-one conversations in order to complete a Case Taking Form (Appendix I) and incorporated a relevant physical examination and a Grant Bentley Evaluation of each participant’s facial features from which their miasmatic categories were determined (Appendix H). The participant’s case information was examined in accordance with the principles of homoeopathic classical prescribing, based on the entirety of symptoms. From this process the similimum was determined and given according to homoeopathic principles...

As the most frequently diagnosed cancer in North American men, prostate cancer can progress to the androgen independent stage after initial response to androgen ablation therapy. The molecular mechanisms involved in the hormonal progression of prostate cancer are not completely understood. Here, we analyze changes in the transcriptome of prostate cancer cells at different stages of progression to reveal potential mechanisms. Applying Affymetrix GeneChip technology, we identified the transcriptomes in response to stimulation of androgen and PKA pathways in human prostate cancer cells. In addition to PSA, other common target genes were identified. Genes differentially expressed in response to androgen and stimulation of the PKA pathway in vitro were also differentially expressed during hormonal progression in vivo. Upon androgen stimulation, androgen receptor binds to a functional androgen response element within the promoter region of SESN1, a p53 targeted gene, and represses its expression. The expression of SESN1 was induced by castration in LNCaP xenografts, but the expression was eventually suppressed again in the androgen independent stage of prostate cancer. Knockdown of SESN1 promoted the proliferation of prostate cancer cells. Expression patterns of androgen-regulated genes in androgen independent tumours were revealed to be more similar to that from before castration than to the tumors under androgen ablation. The β-catenin, a potent coactivator of the androgen receptor, and Wnt pathway was deregulated in androgen-independent tumours. There was increased nuclear colocalization and interaction of androgen receptor and β-catenin with hormonal progression of prostate cancer. This study provides insight into hormonal effects on prostate cancer and possible pathways involved in the development of androgen independent disease, as well as potential therapeutic targets. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

This diploma thesis is focused on the problematics of occurence and quantitative determination of hormonal active substances in biological material. The aim of experimental part was to develope and validate the analytical method, suitable for quantification of hormonal active substances in biological materials. Elaborated method is able to be used for screening determination of some steroid hormonal active substances in urine of farming animals, and for performance confirmative analysis of the same substances in the same matrix on required concentration level. Used method is determined for quantification of steroids in low concentration level in urine of farming animals. Among others performs the criteria of confirmative methods intended for monitoring of residues of hormonal active substances in biological material according to Council Directive 2002/657/EC. Determined parameters of the method answer the supposed values. The method proved to be quite suitable and offered required results. Individual analytes were identified,with certainty, they offer expressive, symmetrical and well separated peaks. This diploma thesis was prepared in Institute for State Control of Veterinary Biologicals and Medicaments in Brno.

A 69-year-old man was referred for elevated thyroid hormone levels. He had no symptoms apart from mild hyperhidrosis and heat intolerance with occasional headaches. Past medical history included a right hemithyroidectomy for a multinodular goiter and Hashimoto's disease. At presentation the patient had a firm, slightly enlarged left thyroid lobe. There were no visual abnormalities, and the rest of the physical findings were unremarkable. Laboratory findings included elevated values of free T4, free T3, total T 3, thyrotropin-secreting hormone (TSH), antithyroglobulin, and antimicrosomal antibodies. Normal values were found for cortisol, prolactin, testosterone, follicle-stimulating hormone, luteinizing hormone, a-subunit, and thyroid-stimulating immunoglobulin. Thyroid 123I scan showed an increased 5-hour uptake of 23% and a 24-hour uptake of 53% with a diffuse uniform enlargement of the left side. TSH level did not increase after a thyrotropin-releasing hormone stimulation test. Serum sex hormone binding globulin was elevated. Magnetic resonance imaging of the pituitary revealed a pituitary macroadenoma with suprasellar extension to the optic chiasm. Histologic examination of the adenoma after transsphenoidal hypophysectomy showed cells that stained positive for TSH. TSH-secreting pituitary adenomas account for 1% of functioning pituitary tumors and are an exceedingly rare cause of hyperthyroidism. To our knowledge, this is the first report of pituitary tumor inducing hyperthyroidism in the setting of Hashimoto's disease. There is a possibility that TSH elevation related to Hashimoto's disease might have contributed to the development of a TSH-secreting pituitary adenoma.