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A Hiperplasia Prostática Benigna (HPB) é a doença benigna mais freqüente na terceira idade. A Ressecção Transuretral (RTU) de próstata constitui-se na técnica operatória mais empregada atualmente para o tratamento da HPB. A anestesia para este procedimento possui características próprias, tornando-se um desafio para o anestesiologista o manejo de suas particularidades. Com o objetivo de avaliar a conduta anestésica, comparando técnicas empregadas, drogas e doses, eventuais complicações e respectivos tratamentos, revisou-se 300 prontuários de pacientes submetidos a RTU de próstata no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HC-FMRP-USP). Optou-se por dois períodos de quatro anos com intervalo de dez anos entre eles (1989-1992 (período 1) e 1999-2002 (período 2)) para tentar estabelecer uma suposta relação entre a evolução das técnicas anestésicas e a possível redução na incidência de complicações. Foram incluídos no estudo apenas os pacientes portadores de neoplasias benignas da próstata. Algumas características dos pacientes (média de idade e estado físico ASA) foram semelhantes entre os grupos. A média de peso foi superior no período 2. Foram pedidos menos exames pré-operatórios para os pacientes do período 1. Quanto ao tipo de anestesia houve um predomínio absoluto, nos dois períodos, da anestesia regional (sendo que o bloqueio raquidiano foi o mais utilizado). O anestésico local mais empregado foi a bupivacaína nos dois períodos. Observou-se uma maior incidência de falhas nos bloqueios realizados no período 1, com maior índice de conversão para anestesia geral. O fato pode em parte ser atribuído ao não uso de agentes opióides nas punções nessa época, que sabidamente melhoram a qualidade do bloqueio. A duração média do procedimento foi maior no período 2 (considerando 45 minutos como tempo padrão). A incidência de eventos adversos intra-operatórios, como como hipotensão, arritmias cardíacas e hipotermia foi semelhante entre os períodos. No entanto, houve um maior número de pacientes com diagnóstico de infarto agudo do miocárdio no pós-operatório de até 24 horas no período1. Provavelmente esse fato aconteceu pela falta de exames complementares e avaliação cardiológica prévia nos pacientes submetidos à cirurgia nesse período. No tocante as transfusões sangüíneas, a proporção entre os períodos foi semelhante, embora fosse prática costumeira no período 1 que os pacientes realizassem autotransfusão prévia. A autotransfusão não se mostrou eficaz, na população estudada, como fator redutor do número de transfusões sangüíneas. Na sala de recuperação anestésica o tempo de permanência foi semelhante entre os períodos, no entanto, observou-se uma maior incidência de eventos adversos no período 1. A mortalidade foi maior no período 2 mas essa diferença não foi estatisticamente significante. Palavras- chave: 1. Anestesia 2. Hiperplasia Benigna da Próstata 3. Ressecção Transuretral de Próstata 4. Síndrome da Intoxicação Hídrica / Benign Prostatic Hyperplasia (BPH) is the most common disease in the third ages. Transurethral Resection of the Prostate (TRP) is the surgery technique most frequently used for the treatment of BPH. Anaesthesia for this procedure has its own features becoming a challenge for the anaesthesiologist to manage with its peculiarities. In order to evaluate the anaesthetic behavior, to compare the techniques used, drugs and doses, possible complications and their treatments, three hundreds of medical records of patients submitted to TRP in the University Hospital, Faculty of Medicine of Ribeirão Preto (FM-USP). Two periods of four years were chosen (1989-1992 (period 1) and 1999-2002 (period 2)) in order to establish some evolution between the anaesthetics techniques used and possible reduction in the incidence of complications. Only patients who had benign prostatic hyperplasia were included in this study. Some patients characteristics were similar between the two groups (mean ages and physical status ASA). Mean weight were higher in the period 2. Less preoperative exams were applied in the period 1. In both periods, the regional anaesthesia was predominant (the spinal anaesthesia was the most used). Hyperbaric bupivacaine was the most commonly used agent for regional anaesthesia in both periods. More failed blocks were seen in the period 1 with an increased number of conversion to general anaesthesia. This fact may be attached with the lack of use of opioids agents in that period, which are known to complement and improve the quality of the block. Mean duration of the procedure were higher in period 2 (taking 45 minutes as standard time). The incidence of intra-operative adverse events like hypotension, cardiac arrhythmias and hypothermia were similar in both periods. However more patients had acute heart infarct in the 24 hours of postoperative period 1. Probably this happens because of the lack of preoperative exams and cardiology evaluation in patients submitted to surgery in this period. The proportion of blood transfusions were similar in two periods although it was usual to make an autotransfusion in the patients of the first period. Autotransfusion previous to the surgery were not an effective method to reduce the number of transfusions. In postanaesthesia care unit the length of stay was similar between the periods but the incidence of adverse events was higher in the period 1. The mortality was bigger in the period 2 but this difference were not significant. Key-words: 1. Anaesthesia 2. Benign Prostatic Hyperplasia 3. Transurethral Resection of the Prostate 4. The TURP Syndrome

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Departamento de Morfologia. Anatomia Humana / A uretra masculina humana possui uma macro estrutura uniforme. Apesar disso apresenta evidências clínicas, morfológicas e moleculares ao longo de seus segmentos, que indicam haver diferenças estruturais e patológicas entre os mesmos. A maioria das alterações da uretra prostática (UP), em homens acima dos 50 anos, são consideradas como sendo secundárias à compressão devido ao crescimento de nódulos fibromatosos hiperplásicos do tecido prostático. Os sinais obstrutivos consequentes a Hiperplasia Prostática Benigna (HPB) incluem hesitação para iniciar a micção, redução da força e calibre do jato urinário, bem como, tardiamente, retenção urinária. Para tentar explicar as alterações que ocorreram na estrutura histológica da UP, no processo da HPB, estudamos as variações qualitativas e quantitativas que ocorreram na densidade volumétrica (Vv) do componente fibroso da matriz extracelular (MEC) e do músculo liso da UP de pacientes com HPB submetidos a tratamento cirúrgico. Foram estudadas amostras obtidas da UP de 10 pacientes com HPB sintomática, submetidos à prostatectomia aberta. Os pacientes não tinham história de tratamento prévio, para HPB. A idade dos pacientes selecionados para o presente estudo variou entre 63 a 79 anos. Para fins de comparação, foram usadas amostras controle obtidas durante a necropsia de 10 indivíduos adultos jovens com idades variando de 18 a 25 anos, vítimas de morte violenta sem comprometimento do sistema urogenital e/ou manipulação uretral. Todas as Próstatas do grupo controle apresentavam peso entre 20-25g, sendo consideradas adultas e dentro dos limites da normalidade. As amostras foram fixadas em solução de formol 10% e processadas para inclusão em parafina. Para análise da Vv, foram usadas as técnicas de coloração de tricrômico de Masson e, de Weigert. Também foram submetidas a análise imunohistoquímica. A Vv do componente fibroso da MEC e do músculo liso foi determinada pela análise de 25 campos aleatórios de cada fragmento de UP usando um sistema teste M-42. Os dados quantitativos foram analisados por meio do teste de Kolmogorov-Smirnov e Mann-Whitney. A Vv (%médio±SD) nos grupos controle e HPB foram respectivamente: 20,3±0,3 e 17,12±1,1 para as fibras do sistema elástico (p <0,007); 29,7 ± 1,9 e 25,1 ± 2,4 para colágeno (p <0,03). A Vv do músculo liso apresentou aumento, não significativo, no grupo HPB, 49,9 ± 0,4 e 52,3 ± 2,3. Por outro lado, 21,9±1,5 e 29,1±1,2 para a fibronectina (P < 0. 0001). / The human male urethra has a uniform structure. Despite this, presents morphological, molecular and clinical evidence throughout their segments that indicates pathological and structural differences between them. Most of changes in prostatic urethra (PU) in men over 50 years, are considered to be secondary to compression due to the growth of fibrous hyperplastic prostate tissue nodules. The signs of obstructive Benign Prostatic Hyperplasia (BPH) reflect the decreased distendibility of the prostatic urethra; that includes hesitation to begin urination, reduced force and caliber of the urinary stream, as well as (late) retention. To explain the histological, structural changes that occurred in the prostatic urethra, studies were made to analyse the changes in quality and quantity that occurred in the volumetric density of the fibrous component of the extracellular matrix (ECM) and smooth muscle of the urethra of patients with BPH submitted to surgical treatment. Samples were obtained from the urethra of 10 patients with symptomatic BPH who had undergone open prostatectomy. No patient had a history of previous treatment for BPH. The age ranged from 63-79 years. To compare we used control samples obtained during autopsy of 10 young adults subjects aged 18-25 that died from violent death without involvement of the urogenital system or uretral manipulation. The samples were fixed in formalin 10% and processed for paraffin embedding. For analysis of Vv, were used staining techniques tricomic Masson and Weigert. Were also submitted to immunohistochemical analysis. The Vv fibrous component of MEC and smooth muscle was determined by the analysis of 25 random fields of each fragment of a test system using M-42. Quantitative data were analyzed using the olmogorov-Smirnov and Mann-Whitney test. The Vv (mean ± SD) in the control and BPH groups respectively were: 20.3±0.3 and 17.12±1.1 in the elastic fiber system (p<0.007); and 29.7±1.9 and 25.1±2.4 in the collagen compartment (p<0.03). Smooth muscle cell volume was increased in BPH cases, 49.9±0.4 and 52.3±2.3 (not statistically significant). On other hand was 21.9±1.5 and 29.1±1.2 in the fibronectin (P < 0. 0001).

[Truncated abstract] This thesis examines the potential role of dietary intake in the development of two common conditions affecting the prostate gland; prostate cancer and benign prostatic hyperplasia (BPH). Diet is of interest as a potential risk factor for prostate cancer because of geographical variations in prostate cancer incidence and increased prostate cancer risks associated with migration from Asian to western countries. Some geographical variation has been suggested for BPH, but this is less certain. However, both prostate cancer and BPH have potential links with diet through their positive associations with sex hormone levels, metabolic syndrome, increased insulin levels and chronic inflammation. In addition, zinc is an essential dietary micronutrient required for semen production in the prostate gland. The original work for this thesis is presented in six manuscripts of which, four have been published in peer-reviewed journals (at the time of thesis completion). BPH investigated in this thesis is defined as surgically-treated BPH. The following hypotheses were investigated. Regarding foods, nutrients and the risk of prostate cancer and BPH: 1. Increasing intakes of fruits, vegetables and zinc are inversely associated with the risk of prostate cancer and BPH 2. Increasing intakes of total fat and calcium are positively associated with the risk of prostate cancer and BPH. 3. Dietary patterns characterised by high meat, processed meat, calcium and fat content are positively associated with the risk of prostate cancer and BPH. 4. Dietary patterns characterised by high fruit and vegetable and low meat content are inversely associated with the risk of prostate cancer and BPH. v Regarding methodological issues related to the study of diet-disease relationships: 5. Dietary patterns (overall diet) elicited from principal components analysis yield stronger diet-disease associations than when studying isolated nutrients. 6. Remotely recalled dietary intake is reliable enough to be used in studies of chronic disease with long latency periods, such as prostate cancer and BPH. Methods: Data from two studies was used to address the hypotheses above. ... Based on the literature reviewed and the original work for this thesis, the most important dietary risk factors for prostate cancer and BPH appear to be those common to western style diets, i.e. diets high in red meat, processed meat, refined grains, dairy products, and low in fruit and vegetables. This type of diet is likely to result in marginal intakes of antioxidants and fibre, excess intakes of fat and possibly, moderate intakes of carcinogens associated with processed meat and meat cooked at high temperatures. These dietary factors have been linked with biomarkers of inflammation, and they support the hypotheses that chronic inflammation is involved in the development of both prostate cancer and BPH. In addition, this work builds on evidence that zinc is an important factor in prostate health. There is scope for more investigation into the reliability of dietary patterns and the use of nutrient patterns as an alternative to focussing on single food components. Further studies on the reliability of remote dietary intake would also be useful. Because of the latency of chronic disease, it can be theorised that remote dietary recall may uncover more robust diet-disease relationships.

INTRODUCTION Benign prostatic hyperplasia (BPH) is the most common pathological condition of aged men which significantly impairs the quality of life status. Though pharmacotherapy with adrenoblockers and 5-alpha reductase inhibitors markedly decreased the rate of surgical interventions, BPH surgery still constitutes the main workload (around ¼ of total) of urologists in the department. The results of the observational study performed by Barry et al. show that the probability of surgical treatment of BPH during the period of 4 years for subjects with mild symptoms equals to 10%, and in case of moderate and severe symptoms - 24% and 39%, respectively. According to the data of large multicenter study performed with 7,588 men in Asia and Australia, moderate and severe symptoms are present in 29%, 40%, and 56% of men in their fifth, sixth, and seventh decade of life, respectively. Symptoms are the main driving force of BPH treatment, but their correlation with residual urine, objective findings of uroflowmetry and invasive urodynamics is only poor. The association of various parameters with the outcomes of surgical treatment is complicated and still not completely investigated. Therefore finding parameters that predict the outcome of surgical BPH treatment is important. According to the literature, unfavorable outcomes of transurethral resection are present in around 15-30% of men with symptomatic BPH. This is mostly associated with inadequate preoperative evaluation, not fully... [to full text]

Patologias prostáticas como a Hiperplasia Prostática Benigna (HPB) e o Câncer de próstata (CaP) apresentam alta incidência, morbidade e mortalidade em indivíduos a partir de 40-50 anos. Fatores ambientais e nutricionais são possíveis fatores envolvidos no desenvolvimento destas doenças. Este trabalho tem por objetivo avaliar o padrão alimentar, perfil antropométrico e perfil lipídico em homens com e sem HPB e CaP e verificar se existe associação entre as variáveis consideradas e a presença de HPB ou CaP na amostra estudada. Foram entrevistados pacientes provenientes do ambulatório de Urologia do Hospital de Clínicas de Porto Alegre (pelo médico da equipe) e preenchida ficha para coleta de dados pessoais e demográficos, história médica e familiar, idade, estágio e grau do tumor, volume da próstata e valor do PSA na época do diagnóstico. Após, os pacientes foram encaminhados à nutricionista para avaliação nutricional (peso, altura, dobras cutâneas, relação cintura/quadril e Recordatório de 24h). O consumo alimentar foi avaliado pelo Recordatório de 24h e analisado pelo programa de apoio à nutrição da Escola Paulista de Medicina – EPM (DIS-EPM, versão 1.5, 2002, UNIFESP). Os pacientes foram orientados a procurar o laboratório de análises clínicas do mesmo hospital para coletar uma amostra sangüínea para dosagem sérica de testosterona total, colesterol total, colesterol HDL e triglicerídeos. O IMC e a circunferência da cintura não apresentaram diferença estatística entre os grupos avaliados. O grupo HPB apresentou consumo menor (p<0,05) de calorias e carboidrato (1875 ± 635 Kcal/dia e 253 ± 105 g/dia) quando comparado ao grupo CaP (2017 ± 476 e 283 ± 75) e ao grupo controle(2179 ± 565 e 302 ± 91). O consumo de fibra alimentar (g/dia) foi significativamente menor (p=0,01) nos grupos HPB (27 ± 12) e CaP (28 ± 10) em relação ao grupo controle (34 ± 15). O consumo aumentado de fibras parece estar relacionado a menor incidência de HPB e CaP. O consumo de calorias e demais nutrientes, o perfil antropométrico e o perfil lipídico não demonstraram relação com estas doenças. / Prostatic pathologies such as Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PCa) present high incidence, morbidity and mortality among individuals at the age of 40-50 years. Environmental and nutritional factors seem to be involved in the development of these diseases. The objective of the present study is to assess the alimentary pattern, anthropometric and lipid profiles in men with and without BPH and PCa and to verify whether there exists an association among the considered variables and the presence of BPH or PCa in the studied individuals. Urology outpatients from Hospital de Clínicas de Porto Alegre were interviewed by a physician who collected personal and demographic data, medical and familiar history, age, stage and degree of tumor, prostate volume and PSA value at diagnosis. Patients were directed to a nutritionist for nutritional evaluation (weight, height, skin folds, waist/hip ratio and 24-hours recall). Alimentary intake was assessed by 24-hours recall and analyzed by the nutrition support program of Escola Paulista de Medicina – EPM (DIS-EPM, version 1.5, 2002, UNIFESP). Patients were asked to return to the clinical analysis laboratory at the same hospital the following week, in order to collect another blood sample to dose serum total testosterone, total cholesterol, HDL cholesterol and triglycerides. Body Mass Index and waist circumference did not show statistical difference among the assessed groups. The BPH group presented with lower intake (p<0.05) of calories and carbohydrate (1875 ± 635 Kcal/day and 253 ± 105 g/day) when compared tothe PCa group (2017 ± 476 and 283 ± 75) and the control group (2179 ± 565 and 302 ± 91). Fiber intake (g/day) was significantly lower (p=0.01) on BPH (27 ± 12) and PCa groups (28 ± 10) when compared to control group (34 ± 15). Higher intake of fibers seems to be related to lower BPH and PCa incidence. Calories and other nutrients intake, anthropometric profile and lipid profile did not show relation to these diseases.

Orientador: Wilter Ricardo Russiano Vicente / Banca: Maria Denise Lopes / Banca: Maria Isabel de Mello Martins / Resumo: A hiperplasia prostática benigna (HPB) tem início no animal com um a dois anos de idade, sendo que 80% dos cães com cinco anos apresentam evidências histológicas de sua presença. A fisiopatologia da doença não está totalmente compreendida, no entanto, a diidrotestosterona é o principal hormônio envolvido. Recentemente, o efeito da toxina botulínica A (TB-A) foi investigado na próstata, mostrando que esta induz atrofia do parênquima e redução do volume. Como o cão é o único animal doméstico que apresenta esta alteração, este se apresenta como modelo experimental para novos estudos da HPB humana. Com base nisso, este estudo objetivou fornecer informações acerca dos efeitos da TB-A sobre a próstata, libido e qualidade do sêmen, comparando os dados com animais orquiectomizados. Para tanto, 18 cães adultos, com evidências ultra-sonográficas de HPB foram submetidos à castração ou administração de 250 ou 500 U de TB-A, e avaliados durante 16 semanas. A orquiectomia mostrou-se um excelente tratamento para a HPB, promovendo redução de 80% do volume prostático. Aplicação da TB-A não ocasionou alterações significativas na libido, ereção ou qualidade e características seminais. Efeitos locais e sistêmicos também não foram observados. Administração de 250 U da TB-A promoveu redução máxima de 9,4% do volume prostático, entretanto, tal redução não foi significativa. Por outro lado, a administração de 500 U de TB-A reduziu significamente as variáveis comprimento, altura e volume da próstata. Desta forma, o presente ensaio contribui de forma singular e inovadora para o conhecimento dos efeitos desta nova modalidade de tratamento na HPB canina. / Abstract: Benign prostatic hyperplasia (BPH) starts the development in animals aging about 1 - 2 years. 80% of 5 years-old dogs have histologic evidences of BPH. Despite the little knowledge concerning about this disease, dihydrotestosterone is the main involved hormone. Recently, the effect of botulinum toxin A (BT-A) on rat and human prostate was investigated, and prostatic parenchyma atrophy and decrease in glandular volume were observed. The dog is one of a few animals that can develop BPH spontaneously and is frequently used as an animal model for human prostatic hyperplasia. Based on that, this study aimed to provide information on BT-A effects on prostate, libido and semen quality, in comparison to orchiectomized dogs. For that, 18 adults dogs, with Ultrasonographic evidences of BPH were submitted to orchiectomy or administration of 250 or 500 U of BT-A, and evaluated along 16 weeks. Orchiectomy presented excellent results on BPH, reducing the prostate volume up to 80%. Administration of BT-A did not significantly interfered on libido, erection or semen characteristics. Local and systemic effects also were not observed. Administration of 250 U of BT-A has promoved a maximum decrease of 9,4% on prostatic volume. However, this reduction was not statistically significant. On the other hand, 500 U of BTA administration has shown to significantly reduce the length, height and volume of prostate. This way, the present study is an innovative and singular contribution for the knowledge of the effects of BT-A on canine prostate. / Mestre

A hiperplasia prostática benigna (HPB) e o câncer de próstata (CaP) são duas condições crônicas muito comuns em homens com idade avançada e têm sido relacionadas a processos inflamatórios. As quimiocinas são reconhecidas como mediadores críticos da resposta inflamatória por regular a migração das células imunológicas através da ativação de receptores de quimiocinas na superfície destas células. As quimiocinas estão relacionadas à patogênese tumoral, embora não seja claro de que modo afetam a progressão tumoral humana. O objetivo desse estudo foi investigar a associação de dois polimorfismos de receptores de quimiocinas, CCR2-64I e CCR5-delta32, com HPB e CaP. Neste trabalho foram genotipadas 385 amostras de DNA genômico de homens do sul do Brasil, predominantemente euro-descendentes, incluindo 130 casos de HPB, 136 casos de CaP e 119 indivíduos controle saudáveis. Para o polimorfismo CCR2-64I a genotipagem foi realizada por PCR-RFLP e para o CCR5-delta32 foi por PCR convencional. As frequências alélicas do CCR2-64I foram 14,0%; 15,8% e 11,1% nos grupos controle, HPB e CaP, respectivamente; enquanto as do CCR5-delta32 foram 5,1%; 7,1% e 6,2%, respectivamente. A mediana referente aos níveis de PSA foi de 0,79; 1,45 e 6,91 ng/mL nos grupos controle, HPB e CaP, respectivamente; diferindo significativamente entre estes (todos p<0,001). A mediana do volume da próstata foi 20,00 cm3 no grupo controle, portanto, menor que dos grupos HPB (35,35 cm3) e CaP (35,80 cm3) (ambos p<0,001); no entanto, não foi observada diferença entre pacientes com HPB e CaP (p=0,172). Algo interessante observado foi CCR2-64I como um fator protetor para CaP quando comparado com HPB (OR=0,550; IC95%=0,311–0,975), mas não quando comparado com o grupo controle (p=0,448). Não foi observada associação do CCR2-64I com os estados clinicopatológicos do CaP (estadiamento tumoral e escore de Gleason) (todos p≥0,308). Não foi observada associação significativa da variante CCR5-delta32 com HPB ou CaP (todos p≥0,072), ou com os estados clinicopatológicos do CaP (todos p≥0,253). Assim, nossos dados sugerem a influência da variante CCR2-64I, observada como fator protetor para CaP quando comparada com HPB, no desenvolvimento do câncer de próstata. / Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two chronic conditions very common in aged men and have been related to inflammatory process. Chemokines are recognized as critical mediators of inflammatory responses by regulating the migration of immune cells through the activation of chemokine receptors on the surface of these cells. Chemokines are implicated in tumor pathogenesis, although it is not clear how it affects human tumor progression. The aim of this study was to investigate the association of two chemokine receptor gene polymorphisms, CCR2-64I and CCR5-delta32, with BPH and PCa. In this study were genotyped 385 genomic DNA samples from southernmost Brazilian men, predominantly euro-descendants, including 130 BPH, 136 PCa and 119 healthy control subjects. To CCR2-64I polymorphism the genotyping was performed by PCR-RFLP and to CCR5-delta32 by conventional PCR. The allele frequencies of CCR2-64I were 14.0%, 15.8% and 11.1% in control, BPH and PCa, respectively; while of CCR5-delta32 were 5.1%, 7.1% and 6.2%, respectively. Median of serum PSA levels were 0.79, 1.45 and 6.91 ng/mL in control, BPH and PCa group, respectively (all p<0.001). The prostate volume median was 20.00 cm3 in the control group, thus, lower than BPH (35.35 cm3) and PCa (35.80 cm3) group (both p<0.001), nevertheless no difference was observed between BPH and PCa patients (p=0.172). Interestingly, CCR2-64I was detected as a protective factor to PCa when compared with BPH (OR=0.550; 95%CI=0.311–0.975), but not when compared with control group (p=0.448). No significant associations of the CCR2-64I were observed with PCa clinicopathologic states (tumor stage and Gleason score) (all p≥0.308). No significant associations of the CCR5-delta32 variant were observed with BPH or PCa (all p≥0.072), or with PCa clinicopathologic status (all p≥0.253). Thus, our data suggest a influence of the CCR2-64I variant, that was observed as a protective factor in PCa when compared with BPH, in prostate cancer development.

Doctor of Philosophy / Department of Human Nutrition / Brian L. Lindshield / The growth-inhibitory effect of saw palmetto supplements (SPS) with high long-chain fatty acids (FA)-low phytosterols (HLLP), high long-chain FA-high phytosterols (HLHP), and high medium-chain FA-low phytosterols (HMLP) was determined using androgen-sensitive LNCaP prostate cancer (PCa) cells and Syrian hamster flank organs. In vitro, all three SPS at high concentrations significantly decreased dihydrotestosterone-stimulated LNCaP cell number. HMLP and HLLP at high concentrations significantly decreased, but HLHP which significantly increased testosterone-stimulated LNCaP cell number. In Syrian hamsters, all three SPS treatments caused notable, but nonsignificant reduction in the difference between the left and right flank organ growth in the testosterone-, but not dihydrotestosterone-treated SPS groups. Results suggest SPS might be a mild 5-alpha-reductase (5-alpha-R) inhibitor. The pharmaceuticals finasteride inhibits 5-alpha-R2, and dutasteride inhibits 5-alpha-R1 and 5-alpha-R2 isoenzymes. Because finasteride inhibits only 5-alpha-R2, we hypothesized that it would not be as efficacious in preventing PCa development and/or progression in TRAMP mice as dutasteride. Six-week-old C57BL/6 TRAMP x FVB male mice were randomized to control, pre- and post- finasteride and dutasteride diet groups that began at 6 and 12 weeks of age, respectively, and terminated at 20 weeks of age. Pre and post groups received drugs before and after mice were expected to develop PCa, respectively. Post-Dutasteride treatment was significantly more effective than Pre-Dutasteride; and dutasteride treatments significantly more effective than finasteride treatments in decreasing prostatic intraepithelial neoplasia progression and PCa development. The finasteride groups and the Pre-Dutasteride group had significantly increased incidence of poorly differentiated PCa versus control. Androgen receptor and Ki-67 protein, DNA fragmentation from apoptosis, 5-alpha-R1 and 5-alpha-R2 mRNA levels were determined in mice with genitourinary weight less than 1 gram and greater than 1 gram to elucidate the discordant response in Pre-Dutasteride and finasteride groups, and Post-Dutasteride’s efficacy. Results suggest the difference in genitourinary weights is influenced more by proliferation, rather than androgen receptor and apoptosis in tumor. Mice age may not be significantly important in regulating proliferation, androgen receptor and apoptosis to promote tumor growth. In conclusion, the results with 5-alpha-reductase inhibitors may support the therapeutic use of dutasteride, but not finasteride, or saw palmetto supplements.

A hiperplasia prostática benigna (HPB) e o câncer de próstata (CaP) são duas condições crônicas muito comuns em homens com idade avançada e têm sido relacionadas a processos inflamatórios. As quimiocinas são reconhecidas como mediadores críticos da resposta inflamatória por regular a migração das células imunológicas através da ativação de receptores de quimiocinas na superfície destas células. As quimiocinas estão relacionadas à patogênese tumoral, embora não seja claro de que modo afetam a progressão tumoral humana. O objetivo desse estudo foi investigar a associação de dois polimorfismos de receptores de quimiocinas, CCR2-64I e CCR5-delta32, com HPB e CaP. Neste trabalho foram genotipadas 385 amostras de DNA genômico de homens do sul do Brasil, predominantemente euro-descendentes, incluindo 130 casos de HPB, 136 casos de CaP e 119 indivíduos controle saudáveis. Para o polimorfismo CCR2-64I a genotipagem foi realizada por PCR-RFLP e para o CCR5-delta32 foi por PCR convencional. As frequências alélicas do CCR2-64I foram 14,0%; 15,8% e 11,1% nos grupos controle, HPB e CaP, respectivamente; enquanto as do CCR5-delta32 foram 5,1%; 7,1% e 6,2%, respectivamente. A mediana referente aos níveis de PSA foi de 0,79; 1,45 e 6,91 ng/mL nos grupos controle, HPB e CaP, respectivamente; diferindo significativamente entre estes (todos p<0,001). A mediana do volume da próstata foi 20,00 cm3 no grupo controle, portanto, menor que dos grupos HPB (35,35 cm3) e CaP (35,80 cm3) (ambos p<0,001); no entanto, não foi observada diferença entre pacientes com HPB e CaP (p=0,172). Algo interessante observado foi CCR2-64I como um fator protetor para CaP quando comparado com HPB (OR=0,550; IC95%=0,311–0,975), mas não quando comparado com o grupo controle (p=0,448). Não foi observada associação do CCR2-64I com os estados clinicopatológicos do CaP (estadiamento tumoral e escore de Gleason) (todos p≥0,308). Não foi observada associação significativa da variante CCR5-delta32 com HPB ou CaP (todos p≥0,072), ou com os estados clinicopatológicos do CaP (todos p≥0,253). Assim, nossos dados sugerem a influência da variante CCR2-64I, observada como fator protetor para CaP quando comparada com HPB, no desenvolvimento do câncer de próstata. / Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two chronic conditions very common in aged men and have been related to inflammatory process. Chemokines are recognized as critical mediators of inflammatory responses by regulating the migration of immune cells through the activation of chemokine receptors on the surface of these cells. Chemokines are implicated in tumor pathogenesis, although it is not clear how it affects human tumor progression. The aim of this study was to investigate the association of two chemokine receptor gene polymorphisms, CCR2-64I and CCR5-delta32, with BPH and PCa. In this study were genotyped 385 genomic DNA samples from southernmost Brazilian men, predominantly euro-descendants, including 130 BPH, 136 PCa and 119 healthy control subjects. To CCR2-64I polymorphism the genotyping was performed by PCR-RFLP and to CCR5-delta32 by conventional PCR. The allele frequencies of CCR2-64I were 14.0%, 15.8% and 11.1% in control, BPH and PCa, respectively; while of CCR5-delta32 were 5.1%, 7.1% and 6.2%, respectively. Median of serum PSA levels were 0.79, 1.45 and 6.91 ng/mL in control, BPH and PCa group, respectively (all p<0.001). The prostate volume median was 20.00 cm3 in the control group, thus, lower than BPH (35.35 cm3) and PCa (35.80 cm3) group (both p<0.001), nevertheless no difference was observed between BPH and PCa patients (p=0.172). Interestingly, CCR2-64I was detected as a protective factor to PCa when compared with BPH (OR=0.550; 95%CI=0.311–0.975), but not when compared with control group (p=0.448). No significant associations of the CCR2-64I were observed with PCa clinicopathologic states (tumor stage and Gleason score) (all p≥0.308). No significant associations of the CCR5-delta32 variant were observed with BPH or PCa (all p≥0.072), or with PCa clinicopathologic status (all p≥0.253). Thus, our data suggest a influence of the CCR2-64I variant, that was observed as a protective factor in PCa when compared with BPH, in prostate cancer development.