Orientadores: Hernandes Faustino de Carvalho, Paulo Roberto Eleutério de Souza / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T14:18:25Z (GMT). No. of bitstreams: 1 AlmeidaNeto_Adauto_D.pdf: 4167026 bytes, checksum: ca3afd135b583810d6996e33016f9e69 (MD5) Previous issue date: 2014 / Resumo: A próstata é alvo de afecções severas que comprometem a função urinária, a qualidade de vida e que consistem em risco de vida aos indivíduos do sexo masculino, particularmente com o avançar da idade. Interações dinâmicas entre o epitélio prostático e o estroma, regulam vários aspectos do desenvolvimento, da função e das patologias prostáticas. O gene WFDC1 é expresso pelas células musculares lisas do estroma prostático normal e tem função na regulação do comportamento do epitélio, na organização da matriz extracelular e na regulação da angiogênese. Dois transcritos principais são oriundos de splicing alternativo do transcrito primário: um com todos os éxons (WFDC1) e outro sem o éxon 3 (Delta 3). Neste trabalho, investigamos as relações quantitativas entre estas duas variantes, com emprego de qRT-PCR (Taqman) e sondas para as junções dos éxons 2-3 e 2-4, em amostras de hiperplasia prostática benigna (BPH) e de câncer de próstata (PCA) provenientes de bancos de tecidos. A expressão do gene marcador MYH11 foi utilizada como estimativa do conteúdo de células musculares lisas nas amostras. Os resultados demonstraram que as amostras puderam ser dividas em dois grupos com expressão diferencial da MYH11(um com baixa expressão e outro com alta miosina, sendo o primeiro correspondente ao quartil inferior da distribuição dos valores de expressão). Foi demonstrada correlação entre a expressão de WFDC1 e MYH11 em BPH, mas não em PCA, enquanto não houve correlação entre Delta 3 e WFDC1 e nem com MYH11. O conteúdo de Delta 3 variou em cinco ordens de magnitude em comparação ao de WFDC1. A razão entre as duas variantes apresentou variação exponencial, distribuições discretas e intercaladas das amostras de BPH e de PCA, que se distribuíram em populações que preservaram as relações 10:1; 1:1 e 1:3. Poucas amostras estiveram livres de cada uma destas variantes. Em conclusão, a expressão do gene WFDC1 e de sua variante WFDC1 correlaciona-se com a diferenciação das células musculares lisas, mas não está condicionada a ela, enquanto a expressão de Delta 3 é completamente independente deste parâmetro e tem correlação positiva com o progressão do PCA, quando o sistema de classificação de Gleason (Gleason 1 + Gleason 2) foi considerado. Adicionalmente, fatores independentes da idade, incidência de BPH ou PCA, são mais influentes na determinação da quantidade total e da proporção entre as duas variantes / Abstract: The prostate gland is intimately related with reproductive and urinary functions, commonly disturbed by a series of diseases. Besides reducing the quality of life, they consist in serious life risk particularly to the aging men. Dynamic interactions between the epithelium and stroma in the gland regulate various aspects of development, function and pathologies. The WFDC1 gene is expressed by smooth muscle cells in the prostate stroma and its product ps20 was shown to control epithelial cell behavior, extracellular matrix organization and angiogenesis. It is supposed to function as a serine protease inhibitor, as other members of its family do. Two transcripts are produced as a result of alternative splicing. The first (WFDC1) retains all exons and the second (Delta 3) lacks the exon 3. In this work, we investigated the quantitative relationship among these two splicing variants, using qRT-PCR (Taqman) probing the junctions between exons 2-3 and 2-4, in benign prostatic hyperplasia (BPH) and prostate cancer (PCA) samples from tissue banks. The expression of the MYH11 gene was used to estimate the content of smooth muscle cells in the samples. The results demonstrate that the samples could be divided in two groups with low or high expression of MYH11, the first corresponding to the lower quartile of expression values). WFDC1 and MYH11 expression were correlated in the BPH samples. Delta 3 expression was independent of both WFDC1 and from WFDC1. The ratio between the variants WFDC1 and Delta 3 varied exponentially in five orders of magnitude. The the ratio between the two variants also varied exponentially, with BPH and PCA samples arranged in discrete and intercalated subgroups. The distribution of populations with different expression levels preserved the ratios 10:1, 1:1 and 1:3. Either variant was absent in only a few samples. In conclusion, the expression of WFDC1 and it WFDC1 variant correlates with but is not conditioned to the differentiation of smooth muscle cells, while Delta 3 is completely independent and is positively correlated with PCA grade (as assessed by the summed Gleason score). Unknown factors independent of age, BPH or PCA incidence are likely influencing Delta 3 expression / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

Benign paroxysmal positional vertigo (BPPV) is a specific type of short-duration vertigo that is provoked by changes in head position and usually lasts less than one minute. It is a common vestibular pathology that can have significant effects on patient safety, quality of life, and medical costs. Therefore, it is crucial that medical students are educated and trained to facilitate and coordinate care of patients who may have undiagnosed BPPV. Because there is evidence to suggest that physicians—specifically primary care physicians—may not be properly equipped in their education to manage patients with BPPV, the purpose of this study was to investigate medical students’ evaluations of their preparedness to provide evidence-based care in the diagnosis and treatment of BPPV. An anonymous survey was administered via email to medical students in their fourth and final year of medical school at East Tennessee State University’s Quillen College of Medicine. This survey includes statements about the evidence-based Clinical Practice Guideline on BPPV provided by the American Academy of Otolaryngology. Respondents rated the degree to which they agreed or disagreed with how prepared they felt to address each item using a 5-point response scale from “strongly disagree” to “strongly agree.” Of the 70 students in the current fourth year class, 41 (59%) completed the survey. Students felt prepared for some aspects of diagnosing and treating BPPV, especially with regard to their general knowledge of BPPV, its impact on patients’ lives, and the options available to manage it. They felt less prepared to know when or if it is appropriate to recommend additional testing, imaging, or medication. They did not feel confident in their ability to perform the maneuvers to diagnose and treat BPPV. Overall, these results suggest medical students have a good foundation in their knowledge of BPPV. These results also propose topics to support more specialized training during their residencies to build upon the foundational knowledge obtained during their didactic training and optimize diagnosis and management of BPPV.

Benign prostatic hyperplasia (BPH) and chronic prostatitis (CP) are common diseases in aging men. Though medications are available to alleviate these conditions, problems of possible side-effects of first-line synthetic drugs for prostatic conditions have allowed patients to switch to a safer plant-based medication. CernitinTM, a pollen extract, is used to alleviate these conditions. A recent in vitro study showed that CernitinTM inhibits cell proliferation and induce a regulatory effect on inflammatory parameters. To validate those results, the inter-batch variability of CernitinTM was assessed using the active ingredients CernitinTM T60 and CernitinTM GBX on the human prostatic cell lines BPH‐1 and WPMY‐ 1 and on human peripheral blood mononuclear cells (hPBMCs) in vitro. Cell proliferation assay was performed in prostatic cell lines, while inflammatory parameters were analyzed in hPBMCs. Results revealed that both CernitinTM active ingredients, regardless of batch production, significantly inhibited the proliferation of both prostatic cell lines after 48 and 72 hours, respectively (p < 0.05 to p < 0.001). Among the batches, there were no significant differences observed. Notably, the GBX batches 14164, 14548 and 14160 had a more pronounced effect on cell proliferation right after 48 hours on both cell lines. Whilst, T60 batches 11539 and 14144 had a pronounced effect right after 48 hours on BPH cells. In hPBMC, the production of the anti-inflammatory cytokine interleukin (IL)- 10 and its receptor IL-10 receptor subunit beta (RB), as well as pro-inflammatory cytokine IL-6 was significantly increased after treatment with the T60 formulation regardless of the batch, but not after treatment with the GBX batch. Moreover, IL-10 receptor subunit alpha (RA) and tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) expression increased after the use of both formulations (p < 0.05 to p < 0.001). The pro-inflammatory cytokine IL-8 and chemokine CXCL-10 was significantly decreased using both batches of T60 (p < 0.05 to p < 0.001). Collectively, these results support the claim of the role of CernitinTM as an anti-proliferative agent and as a cytokine regulator.

The purpose of this study was to examine the prevalence of nystagmus found in healthy individuals during the positional testing subtest of the standard vestibular test battery. Positional testing involves moving the patient's head, and sometimes the entire body, into a variety of positions while observing eye movement. The hypothesis of the current study was that a relatively low percentage of participants would display nystagmus during positional testing used routinely in clinical diagnostic procedures. The findings were then compared to those of an earlier study in which 82% of normal, healthy individuals were reported to exhibit nystagmus during this testing. Twenty-five participants were selected that had no known otologic disease and who reported normal hearing sensitivity. In addition, the participants affirmed they had not consumed any alcohol or taken any medications that are known to affect nystagmus. They were then observed in nine different positions. Forty-eight percent of the participants experienced nystagmus in at least one position. Although this percentage was considerably lower than that reported in the earlier study, methodological differences appear to account for the discrepancy. Specifically, the criterion for determining the presence/absence of nystagmus potentially explains the difference in full.

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This study investigates modifications to AWPA Standard E18-06 to develop an above-ground field test for subterranean termites native to the eastern United States. AWPA Standard E18-06 was modified in two stages to progressively increase optimum conditions for subterranean termite feeding. Modification II, which incorporated the use of house bricks and feeder strips with a solid ventilated cover, had an increase in termite attack with less variation between tests. This study also investigates the effects of adding antioxidants, both natural and synthetic, and analogues which lack antioxidant properties, to test wood blocks on feeding by Reticulitermes flavipes Kollar using AWPA Standard E1-09. Antioxidants had feeding deterrence and mortality properties to R. flavipes. Conversely, the non-antioxidant analogues, with the exception of the heterocyclic flavanone, had little effect on R. flavipes. It is concluded that R. flavipes instinctively avoids wood which contains high levels of antioxidants, such as heartwood with phenolic extractives.

<p>Benign prostatic hyperplasia (BPH) is a common urologic condition among older men, affecting approximately half of men by age 50 and nearly 80% by age 80. Lower urinary tract symptoms (LUTS) associated with BPH may significantly impact quality of life for many of these men. Inflammation has been associated with the development and progression of BPH however, the precise impact and role(s) of immune cells in these conditions remains unclear. Many previous studies over the decades have explored the roles of immune cells in prostate disease in animal models and prostate tissues from human patients, and, more recently, through transcriptomic analyses of bulk cell populations and of single cells. These and other emerging technologies continue to add to the body of knowledge related to this area.</p> <p>The prostate is a complex organ composed of multiple epithelial and mesenchymal cell types and subtypes. The growth, morphology, and function of these cells is influenced by autocrine and paracrine cell-cell interactions in ways that are largely not yet understood. A better understanding of the composition, heterogeneity, morphology, interactions, and functional features of various prostate cell types, particularly involving immune cells in the context of inflammatory processes, is expected to improve our understanding of the impact of altered cellular composition and communication on prostate homeostasis and disease.</p> <p>Inflammation has been shown to impact the growth, morphology, and function of various prostate cell types. It is hypothesized that inflammation promotes epithelial cell proliferation and differentiation in BPH despite androgen-targeted therapy. It is hypothesized that communications between and within various immune cell populations perpetuate the non-resolving inflammatory microenvironment that promotes prostate cell expansion. In this research, the POET-3 mouse model of inducible autoimmune inflammation is used to evaluate the impact of autoimmune-type inflammation on basal epithelial cell progenitor growth and differentiation in the absence of androgens mimicking the conditions of androgen deprivation therapy (ADT), and to demonstrate the enhanced growth and differentiation potential conferred on basal progenitors by inflammation. </p> <p>Additionally, this research evaluates the morphology, gene expression, and cell-cell interaction predictions of BPH prostate immune cells to explore the role of immune cells and their interactions in driving BPH inflammation. </p> <p>Overall, inflammation induced epithelial and stromal expansion and basal progenitor cell proliferation in vivo and promoted basal progenitor cell growth and differentiation in vitro under androgen-deficient conditions mimicking androgen-targeted therapy. Histologic evaluation of BPH specimens reveals the composition and distribution of immune cells, including organizing lymphoid structures resembling tertiary lymphoid structures (TLS). Also, analyses of single cell RNA sequencing data of gene expression patterns and signaling pathways reveal a mixed inflammatory microenvironment in BPH. Furthermore, predicted ligand-receptor interactions indicate mixed inflammatory signaling between and among immune cell populations, including T cells, macrophages, and mast cells, that likely to the unresolving nature of BPH inflammation.</p> <p>In all, the results of these studies demonstrate inflammation-induced epithelial and stromal expansion in a mouse model of resolving prostatitis and indicate potential roles for multiple immune cell populations and their interactions in driving the ongoing inflammation of BPH, suggesting that this ongoing inflammation may impact the progressive stromal and epithelial expansion characteristic of BPH. </p>

Mucinous cystadenomas of the ovary are benign epithelial neoplasms that can grow rapidly during pregnancy. They may cause ovarian torsion, virilization, inferior vena cava syndrome, and even preterm labor and fetal growth restriction. Various theories exist regarding the pathogenesis of these tumors. One hypothesis suggests that they may arise from teratomas. Our case report describes synchronous mucinous cystadenomas and ovarian teratomas, as well as metachronous mucinous cystadenomas in patients with a history of ovarian teratoma. There has been no report of metachronous ipsilateral teratoma after previous mucinous cystadenoma. We present a 22-year-old female with a history of bilateral ovarian tumors in a prior pregnancy noted to have a recurrent ovarian mass on her left ovary at the time of cesarean section of a subsequent pregnancy. She had two prior cystectomies for metachronous mucinous cystadenomas of her left ovary, and a right salpingo-oophorectomy for the ovarian torsion in her previous pregnancy. On her current pregnancy, she developed a mature cystic teratoma of the remaining left ovary. The rapid growth and recurrence rate of these tumors highlights the importance of close surveillance of ovarian masses during pregnancy, even those that seem benign. In this case, a history of unilateral salpingo-oophorectomy with multiple contralateral cystectomies did not appear to affect her fertility. Her future ovarian reserve is unknown, pointing to the need for adequate pre-operative counseling in similar cases of ovarian masses in pregnancy.