Prostate cancer (PCa) is heterogeneous containing phenotypically diverse cells. It is unclear whether these phenotypically different PCa cells are functionally distinct and possess divergent tumorigenic potential. Androgen signaling plays important roles in differentiation and survival of malignant PCa cells, and prostate specific antigen (PSA) as one of the androgen signaling target genes is used as a biomarker of AR signaling to assess tumor progression and evaluate therapeutic efficiency in clinic. Here we present evidence for discordant AR and PSA expression resulting in AR⁺/PSA⁺, AR⁺/PSA⁻, AR⁻/PSA⁻, and AR⁻/PSA⁺ PCa cells in human tumors. We also show that prostate tumor PSA mRNA levels inversely correlate with poor clinical outcomes and patient survival. By employing a lentiviral reporter system, we have fractionated bulk PCa cells into PSA⁺ and PSA⁻[superscript '/lo'] cell populations, with the former being AR⁺/PSA⁺ and the latter containing both AR⁺/PSA⁻ and AR⁻/PSA⁻ cells. The PSA⁺ and PSA⁻[superscript '/lo'] PCa cells demonstrate distinct molecular, cellular, and tumor-propagating properties. PSA⁻[superscript '/lo'] PCa cells are quiescent and refractory to stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity. They preferentially express stem cell genes and can undergo asymmetric cell division to generate PSA⁺ cells. Of great clinical interest, PSA⁻[superscript '/lo'] PCa cells can initiate robust tumor development and resist androgen ablation in castrated hosts, and they harbor highly tumorigenic castration resistant PCa cells. In contrast, PSA⁺ PCa cells possess more limited tumor-propagating capacity, undergo symmetric division, and are sensitive to castration. Systemic androgen levels dynamically regulate the relative abundance of PSA⁺/PSA⁻[superscript '/lo'] PCa cells in the tumors, which in turn impact the kinetics of tumor growth. Further studies reveal that the PSA⁻[superscript '/lo'] PCa cell population harbors several overlapping but nonidentical tumorigenic subsets including ALDH⁺, CD44⁺, and [alpha]2[beta]1⁺ cells and ALDH⁺CD44⁺[alpha]2[beta]1⁺ can further enrich castration resistant PCa cells. These observations together suggest that heterogeneous PCa cells are organized as a tumorigenic hierarchy. Our results have important implications in understanding how different subpopulations of PCa cells manifest differential responses to current androgen deprivation therapy (ADT). / text

A number of routine painful procedures such as castration and tail-docking are currently performed in swine production without the benefit of anaesthesia or analgesia. In addition, parturition is generally considered painful. Providing analgesics at the time of castration and tail-docking lowered plasma cortisol levels of the piglets suggesting a reduction in pain associated with the procedures. The use of the non-steroidal antiinflammatory drug meloxicam also resulted in less isolated behaviour of male piglets following castration. Providing meloxicam routinely following parturition did not result in reduced neonatal mortality or piglet growth, but lowered plasma cortisol suggesting a reduction in pain. Producers in the future may need to consider using pain control as part of their standard operating procedures in order improve piglet welfare and meet their consumers’ expectations, but are unlikely to see an economic return associated with improved productivity. / Please do not reject this before tomorrow afternoon. I am going to stop by the Office of Graduate Studies and hand in the necessary documents. / Boehringer Ingelheim (Canada) Ltd. and Ontario Pork

Orientador: Luis Antonio Justulin Junior / Resumo: A próstata é uma glândula do sistema genital masculino que possui grande importância na fertilidade. Estudos clássicos evidenciaram que para que se inicie o desenvolvimento prostático é necessário a presença de andrógeno produzido pelos testículos fetais. Porém, além da estimulação androgênica, estudos apontam para outros hormônios que também atuam na próstata como a Prolactina (PRL). PRL é um hormônio que é principalmente secretado por células lactotróficas da hipofise anterior e está envolvido em muitos processos biológicos, incluindo lactação e reprodução. Assim, investigamos se a modulação da sinalização PRL altera a morfofisiologia da próstata ventral (VP) em ratos castrados. Os ratos Sprague Dawley adultos (n = 6) foram castrados e após 21 dias divididos em 10 grupos experimentais: Castrado Controle (CC): animais castrados que não receberam tratamento; Castrado+testosterona (T): animais castrados que receberam T (4mg / kg); Castrado+PRL (PRL): animais castrados recebendo PRL (0,3 mg / kg); Castrado+T+PRL (TPRL): animais castrados que receberam associação de T e PRL; e Castrado+BR (BR): animais castrados que receberam Bromocriptina (BR) (0,4mg / kg). Grupo Controle: animais intactos (CTR). Os animais foram tratados durante 3 ou 10 dias consecutivos. Ao fim dos tratamentos, os animais foram anestesiados, eutanizados e a prostata ventral (VP) foi removida, pesada e processada para análise histológica e Western blot. O peso corporal não se alterou entre os grupos experiment... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

O gato doméstico (Felis catus L.) exibe uma grande flexibilidade em seu comportamento social e no seu estilo de vida. Isto é devido a vários fatores, entre eles, disponibilidade de alimento e refúgio, mudanças ambientais, interação com o homem, composição dos grupos, características genéticas e a castração. Os animais machos e fêmeas não castrados e de vida livre exibem um repertório comportamental distinto, os machos tendem a ter uma vida mais solitária vagando por amplas extensões territoriais, enquanto que as fêmeas exibem uma vida mais gregária. O objetivo deste trabalho foi examinar o comportamento social de gatos domésticos castrados, machos e fêmeas, em confinamento com a intenção de se verificar os efeitos da castração no comportamento e se o repertório comportamental de ambos é sexualmente dimórfico, através das análises de freqüência e seqüência das categorias comportamentais. Foram levantadas 18 categorias comportamentais sociais e 12 categorias não sociais e foi observado o comportamento de 40 gatos domésticos machos (n=18) e fêmeas (n=22) num ambiente confinado (gatil) com área total de 19,2 metros quadrados, durante um período de 11 meses totalizando 160 horas de observação. Cada animal foi observado durante 15 minutos em cada sessão de observação, utilizando-se o método de amostra focal do comportamento. A análise de freqüência das categorias comportamentais sociais e não socais foram feitas através do teste estatístico não paramétrico de Mann-Whitney com nível de 5% de significância (p=0,05). Os resultados do teste não mostraram diferenças significativas entre os grupos de machos e fêmeas, indicando, assim, existir influência da castração nos comportamentos de ambos os grupos, ainda que preservando a individualidade dos animais. Contudo a análise seqüencial do comportamento mostrou uma mínima diferença entre os machos e fêmeas castrados mesmo na ausência da regulação hormonal do comportamento. Portanto conclui-se que parte do comportamento dos gatos não sofre influência hormonal e que o método de análise seqüencial do comportamento é refinado o suficiente para mostrar características comportamentais que não foram mostradas pela análise de freqüência. / The domestic cat (Felis catus L.) exhibits a great flexibility in its social behavior and lifestyle. This can be due to several factors, among them, food and refuge availability, environmental changes, interaction with humans, group composition, genetic characteristics and castration. Literature states that non neutered male and female animals of free life exhibit distinct behavioral repertoires. Males tend to have a more solitary life moving throughout wide territorial extensions, while females exhibit a more gregarious life. The aim of this work was to examine the social behavior of castrated domestic cats, males and females, in confinement, to verify the effects of neutering on the behavioral repertoire, through the frequency and sequence analyses of behavior. 18 social and 12 non social behavioral categories were selected. 40 domestic cats, males (n=18) and females (n=22), were observed in an indoor confined context with 19,2 square meters in area, for a period of 11 months and 160 hours of observation. Each animal was observed for 15 minutes in each observation session, being used the focal sample method. Statistical analysis for the frequency of each behavioral category, done using the non parametric test of Mann-Whitney with 5% (p=0,05) of significance, didn\'t show any significant gender difference, suggesting that castration change natural behavior, possibly because of a probable absence of sexual hormones. Sequential analysis, however, did show subtle gender differences, possibly raised by different environmental -- i.e. \'cultural\' -- influences in both male and female cats.

Orientadores: Pedro Eduardo de Felicio, Expedito Tadeu Facco Silveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-14T20:01:44Z (GMT). No. of bitstreams: 1 Gomes_CarolinaLugnani_M.pdf: 12587746 bytes, checksum: decd1485e670c2f0e740de9d76122236 (MD5) Previous issue date: 2009 / Resumo: Odor sexual é um cheiro que está presente na carne de suínos machos não castrados, considerado repugnante e inaceitável por muitos consumidores, que é causado pelos compostos androstenona e escatol. A técnica mais comum para evitar o odor sexual é a castração cirúrgica realizada em leitões de 3 a 5 dias de idade. A vacinação contra o fator de liberação de gonadotrofinas, mais conhecida como imunocastração, é uma alternativa à castração cirúrgica, para reduzir os compostos androstenona e escatol e, ainda, aproveitar os efeitos anabolizantes naturais produzidos pelos testículos dos machos não castrados. O objetivo da pesquisa foi comparar amostras de costela suína de machos castrados imunologicamente com as de castrados cirurgicamente, por meio da avaliação sensorial da intensidade de odor e sabor de androstenona e escatol, com provadores treinados, e de aceitação e preferência com consumidores, no município de Campinas, SP. Foram usadas amostras de costela desossada de um total de 50 animais, entre eles suínos castrados cirurgicamente (realizada em leitões de 3 a 5 dias de idade) e imunocastrados (aplicação de duas doses de vacina da marca Pfizer, Vivax®, na 8ª e 4ª semanas antes do abate), obtidos de três matadouros-frigoríficos, de raças Large White, Landrace, e cruzados Danbred e Agroceres. Nas análises com provadores treinados, para o atributo odor de escatol, não foi encontrada diferença entre os tratamentos (P>0,05), enquanto que para os atributos odor e sabor de androstenona e sabor de escatol, foram observadas diferenças (P?0,05), com médias de maior intensidade destes compostos nas amostras de imunocastrados. No Teste Afetivo laboratorial realizado com 46 provadores para a avaliação de aroma, sabor e aceitação global houve diferença significante (P?0,05) entre os tratamentos. Entretanto no Teste Afetivo de localização central realizado com 135 provadores não foram encontradas diferenças (P>0,05) entre os tratamentos para a média de aceitação. Concluiuse que, do ponto de vista sensorial, a imunocastração produz resultados equivalentes em testes de localização central, podendo diferir em termos de intensidade dos compostos de odor, no teste com provadores treinados, e de aceitação no teste laboratorial / Abstract: Sexual odor is an objectionable off flavor that can be present in the meat of non-castrated male pigs, which is considered repugnant and unacceptable by many consumers. It is caused by the compounds androstenone and skatole. The most common method to control the taint is the surgical castration of the piglets from 3 to 5 days old. Vaccination against GnRF - gonadotropin releasing factor, known as immunocastration, is an alternative to surgical castration to reduce the mentioned compounds and still take advantage of the natural anabolic effects produced in by the testes of non-castrated male. The objective of this study was to compare the samples of pork rib from males submitted to immune or surgical castration through the sensory evaluation of the intensity of odour and flavour of androstenone and skatole, with trained sensory panel, and sensory evaluation of acceptability and preference, with consumers in Campinas, SP. Samples of boneless ribs from a total of 50 animals, including pigs surgically castrated (performed in piglets from 3 to 5 days old) and immunocastrated (two shots of Pfizer¿s Vivax ® vaccine at 8th and 4th weeks before harvesting), obtained in three hogs slaughterhouses, from breeds Large White, Landrace, and Danbred and Agroceres crossbreds. In the sensory analysis with the trained panel there was no difference between treatments (P> 0.05) for the odor of skatole, while for the odor and flavor of androstenone, and for flavor of skatole there were differences (P< 0. 05), with higher means or greater intensity (P<0.05) of the two compounds in samples of the imunocastrated pigs. In affective laboratory tests with 46 consumers, there were differences (P<0.05) between treatments for aroma, flavor and overall acceptability between treatments. However, in the affective tests of central location with 135 consumers, no significant differences (P>0.05) were detected between treatment means for acceptability. From the sensory viewpoint it was concluded that the immunocastration and the surgical method produce results in central location tests that are equivalent, although they may differ in terms of odor intensity of the compounds in the trained taste panel, and also in the laboratory acceptance tests / Mestrado / Mestre em Tecnologia de Alimentos

Orientador: Hernandes Faustino de Carvalho / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T10:03:30Z (GMT). No. of bitstreams: 1 Cardoso_AlexandreBruni_D.pdf: 5087353 bytes, checksum: c88d322680c216b0a0f0c99aef894042 (MD5) Previous issue date: 2010 / Resumo: Importante glândula acessória do trato reprodutor de mamíferos, a próstata é um órgão alvo de várias doenças benignas e malignas, que ocorrem principalmente com o envelhecimento. Tanto o desenvolvimento prostático pós-natal como a regressão da glândula após a ablação hormonal são caracterizados por intensa modificação no comportamento das células e remodelação da matriz extracelular (MEC). As metaloproteinases de matriz (MMP) constituem uma família de enzimas que degradam principalmente componentes de MEC. Portanto, pareceu-nos plausível que as MMPs tenham papel crucial na remodelação tecidual que ocorre em decorrência dos eventos morfogenéticos da próstata ventral (PV) e na progressiva regressão prostática pós-castração. Assim, o objetivo desse trabalho foi investigar o papel da MMP-2 no desenvolvimento prostático pós-natal em roedores e das MMP-2, -7 e - 9 na regressão da PV de ratos pós-castração. Para isso, foram empregadas técnicas moleculares, bioquímicas e análises morfológicas. A aplicação do siRNA específico para MMP-2 comprometeu o crescimento, a ramificação, a formação de lúmen e a proliferação de células epiteliais da PV de ratos in vitro, além de provocar um acúmulo de fibras colagênicas no compartimento estromal. A PV do camundongo MMP-2-/- adultos apresentou peso relativo reduzido e um menor volume epitelial, que resultaram de menor proliferação epitelial, menor ramificação ductal e maior estabilização da matriz colagênica durante a primeira semana de desenvolvimento pós-natal. Na regressão da próstata ventral de ratos após a castração encontraram-se múltiplas ondas de morte celular e uma relação direta entre a expressão e atividade das MMP-2, -7 e -9 e o pico de apoptose que ocorre 11 dias após a castração. Conclui-se através dos resultados apresentados neste trabalho, que tanto o desenvolvimento prostático pós-natal, como a regressão prostática pós-castração são dependentes da expressão e atividade das MMPs. / Abstract: The prostate is an important gland of the reproductive tract of mammals, which is a target of several benign and malign diseases affecting the elder. Both postnatal prostate development and prostate regression after androgenic ablation are characterized by intense modification in cell behavior and remodeling of extracellular matrix (ECM). MMPs constitute a family of endopeptidases which are able to cleave preferentially ECM components. Thus, it seems reasonable that these enzymes play a crucial role in tissue remodeling that happens during the ventral prostate (VP) morphogenesis and in the prostate regression after castration. In this study, we aimed to define the involvment of MMP-2 in the postnatal prostate development of rodent and the involvement of MMP-2, -7 and -9 rat ventral prostate regression after castration. For this aim, we have used molecular, biochemical and morphological approaches. siRNA specific for MMP-2 compromised the rat VP growth, branching, lumen formation and epithelial cell proliferation, besides leading an accumulation of collagen fibers in the stroma. MMP-2-/- VP showed a reduced relative weight and epithelial volume, besides displaying a decreased epithelial proliferation and branching and a stabilization of collagen matrix at the end of the first postnatal week. In the prostate regression after castration, we found multiple waves of cell death and a direct association between activity and expression of MMP-2, -7 and -9 and an apoptotic peak that occurs at the 11th Day after castration. In conclusion, the results presented here showed that both postnatal prostate development and prostate regression after castration are dependent on the expression and activity of MMPs. / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

Este trabalho foi conduzido para avaliar o efeito da condição sexual sobre o desempenho, concentração de testosterona, características de carcaça e qualidade da carne de bovinos Nelore confinados. Cinquenta e oito machos bovinos (430 ± 36 kg; 24 meses de idade), foram divididos em três grupos em um delineamento inteiramente casualizado. Foi realizado, em 15 animais, o procedimento de castração cirúrgica (CC), aos 12 meses de idade, enquanto que 21 animais receberam duas doses da vacina de imunocastração (IC), dentro de um intervalo de 30 dias, e 22 animais permaneceram não-castrados (NC). Os animais foram alocados em baias individuais e alimentados com uma dieta contendo 70% concentrado e 30% volumoso durante noventa dias precedidos por um período de adaptação de vinte e um dias. Foi avaliado o desempenho e características de carcaça a cada 28 dias. Os animais foram abatidos e foi avaliada a qualidade da carne. Animais NC apresentaram maior ganho de peso, eficiência alimentar, peso de carcaça quente e rendimento de carcaça comparado com animais CC e IC (P&lt;0.05). Animais castrados apresentaram maiores valores de cor L*, a*, b* e perda por cocção que animais NC (P&lt;0.05). A imunocastração diminuiu o desempenho dos animais, comparado com animais CC ou NC. Porém, é uma alternativa à castração cirúrgica pois possui as mesmas características de carcaça e qualidade da carne. A imunocastração melhora a cor da carne e diminui a frequência de carnes DFD comparado com animais NC. / This study was carried out to evaluate the effect of the sexual condition on performance, testosterone concentration, carcass traits and meat quality of feedlot Nellore cattle. Fifty-eight males (430 ± 36 kg BW; 24 mo old) were divided into three groups in a randomized complete design. Surgical castration (SC) procedure was performed in 15 animals at 12 months old, whereas 21 animals received two doses of immunocastration vaccine (IM), within an interval of 30 days. In addition, 22 animals remained intact (NC). The animals were allotted in individual pens and daily fed a diet containing 70% concentrate and 30% roughage during ninety days preceded by an adaptation period of twenty one days. Performance and carcass characteristics were evaluated every 28 days. The animals were slaughtered and the meat quality was evaluated. The NC animals showed greater average daily gain, feed efficiency, hot carcass weight and carcass yield compared with SC animals and IM (P &lt;0.05). Castrated animals had higher color values L *, a *, b * and cooking loss that NC animals (P &lt;0.05). Immunocastration decreased performance when compared to SC or NC animals. However, it is an alternative tool to surgical castration because it has the same carcass characteristics and meat quality. Immunocastration improves the color of the meat and reduces the frequency of DFD meat compared to NC animals.

The aim of this study was to investigate the viability of laparoscopic testicular artery ligation as an alternative to the more conventional castration methods in equids. Twelve intact male donkeys varying in age from 5 months to 13 years were used in this study. Two of these donkeys were castrated by means of an open technique. The remaining donkeys underwent testicular artery ligation under laparoscopic guidance. Ligation of the testicular artery was achieved by application of Filshie clips under laparoscopic visualisation. This was performed with the donkeys standing in stocks and sedated with a combination of detomidine hydrochloride and butorphanol tartrate. The ten donkeys which underwent testicular artery ligation were unilaterally castrated using an acceptable open castration technique on two separate occasions. The first testes were removed at a specific time period after testicular artery ligation, while the second testes were all removed on the same day 9 months after the first group of donkeys underwent laparoscopic assisted testicular artery ligation. The remaining two donkeys which acted as controls underwent a standard open bilateral castration procedure both testes being removed on the same day. All the testes removed, excluding one testis lost to the study, were evaluated histologically. Four testes were used as controls. Thirteen testes showed histological signs of ischaemic necrosis, degeneration and/or atrophy. Three testes showed histological tubular degeneration and atrophy as well as the presence of some normal tissue. The remaining three testes were histologically unchanged. One of the testes was accidentally misplaced at post mortem due to human error. Avascular necrosis of the testicular tissue was not successful in all the subjects. This technique shows promise but further research is required. / Dissertation (MMedVet)--University of Pretoria, 2008. / Companion Animal Clinical Studies / unrestricted

American lambs are often over-finished and lack consistent quality. It has been suggested that the use of intact ram lambs can decrease USDA YG and improve growth efficiency. However, ram lamb carcasses are underutilized because of potential issues, the most crucial being off-flavor development. Our hypothesis for this study is that U.S. producers can take advantage of intact ram lamb growth and performance with no detriment to product quality, as long as lambs are slaughtered before the attainment of puberty. Three breeds (Hampshire, Dorset, and Columbia), three slaughter weights (light, medium, and heavy) and two sexes (rams and wethers) were evaluated. Results indicate that ram lambs can provide a satisfactory eating experience, however, in one of our studies compounding of maturity and slaughtering intact rams increased incidence of off-flavors. It remains undetermined whether the small differences in sensory characteristics would be detectable by everyday consumers.

Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes neurogenesis and neuroprotection. Little is known about the role of CNTF in affective behavior. We investigated whether CNTF affects depressive- and anxiety-like behavior in adult mice as tested in the forced swim, sucrose preference and elevated-T maze tests. Female wild type CNTF+/+ mice more readily developed behavioral despair with increased immobility time and decreased latency to immobility in the forced swim test than male CNTF+/+ littermates. The lack of CNTF in CNTF-/- mice had an opposite effect on depressive-like behavior in female mice (reduced immobility time and increased sucrose preference) vs. male mice (increased immobility time). Female wildtype mice expressed more CNTF in the amygdala than male mice. Ovariectomy increased CNTF expression, as well as immobility time, which was significantly reduced in CNTF-/- mice, suggesting that CNTF mediates overiectomy-induced immobility time, possibly in the amygdala. Progesterone but not 17-β estradiol inhibited CNTF expression in cultured C6 astroglioma cells. Progesterone treatment also reduced CNTF expression in the amygdala and decreased immobility time in female CNTF+/+ but not in CNTF-/- mice. Castration did not alter CNTF expression in males nor their behavior. Lastly, there were no effects of CNTF on the elevated T-maze, a behavioral test of anxiety, suggesting that a different mechanism may underlie anxiety-like behavior. This study reveals a novel CNTF-mediated mechanism in stress-induced depressive-like behavior and points to opportunities for sex-specific treatments for depression, e.g. progesterone in females and CNTF-stimulating drugs in males.