INTRODUÇÃO: A bexiga neurogênica é considerada um fator de risco importante para insuficiência renal crônica. A preservação da função renal é um dos principais objetivos do tratamento nefrourológico dos portadores desta doença. OBJETIVOS: Descrever as características demográficas de 58 pacientes com bexiga neurogênica congênita, as características anatômicas e funcionais do trato urinário superior e inferior desta população ao início do seguimento e ao final da coleta dos dados e identificar fatores de risco associados à piora de função glomerular e tubular nesta população, utilizando como marcadores a quantificação do ritmo de filtração glomerular e o desenvolvimento de microalbuminúria e acidose metabólica. MÉTODOS: Estudo retrospectivo de uma coorte de 58 pacientes portadores de bexiga neurogênica congênita com seguimento mínimo de seis meses, matriculados no ambulatório de Disfunções Miccionais da Infância da Unidade de Nefrologia Pediátrica do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. O período de coleta de dados foi encerrado em janeiro de 2006. Os resultados obtidos no estudo foram descritos por médias e desvios padrões, medianas, valores mínimos e máximos, ou por frequências e percentuais. A comparação entre a avaliação inicial e a final para variáveis quantitativas contínuas foi feita usando-se o teste t de Student para amostras pareadas. A associação entre variáveis dicotômicas foi feita considerando-se o teste exato de Fisher. Para avaliação da evolução dos pacientes e comparação de subgrupos definidos por variáveis dicotômicas, foram construídas curvas de Kaplan-Meier e aplicado o teste de Long-rank. Valores de p<0,05 indicaram significância estatística. RESULTADOS: Das 58 crianças avaliadas, 33 eram do sexo feminino (56,9%). A idade média com que as crianças chegaram ao serviço foi de 4,2±3,5 anos, a média de tempo de seguimento foi de 3,8±3,1 anos. A etiologia predominante de bexiga neurogênica foi mielomeningocele, em 42 dos 58 pacientes (72,4%). O encaminhamento à Unidade ocorreu por infecção urinária em 48 (82,8%) casos, por enurese em 5 (8,6%) e por retenção urinária em 5 (8,6%). Dentre os 49/58 (84,5%) pacientes com ITU de repetição ao início do seguimento, 41/49 (83,7%) pacientes apresentaram melhora no período de seguimento. A hipertensão arterial foi diagnosticada em 11 (19,3%) das crianças na avaliação inicial e em 18 (31%) na avaliação final. A média do RFG inicial foi de 146,7±70,1 mL/1,73m2/min e a média final de 193,6±93,6 mL/1,73m2/min, com p=0,0004. A microalbuminúria estava presente em 20 (54,1%) dos exames na avaliação inicial e em 26 (61,9%) na avaliação final. A acidose metabólica estava presente em 11 (19%) dos exames na avaliação inicial e em 19 (32,8%) na avaliação final. As crianças que chegaram à Unidade de Nefrologia mais precocemente (< 3 anos) foram aquelas que mais apresentaram acidose metabólica no decorrer do acompanhamento (p=0,01). Os pacientes que não tinham acidose metabólica ao final do estudo apresentaram valores menores de Z-escore peso final (p= 0,048), Zescore altura/estatura inicial (p= 0,047) e Z-escore altura/estatura final (p=0,022) com relação aos pacientes do grupo que evoluiu com acidose. CONCLUSÃO: Pacientes com bexiga neurogênica congênita evoluem com acometimento renal glomerular e tubular precoce, cujo manejo demanda acompanhamento por profissional especializado. / INTRODUCTION: Neurogenic bladder is considered an important risk factor for chronic renal failure. In these patients, preservation of renal function is one of the most important goals of nephro-urological treatment. PURPOSE: To describe demographic data of 58 children with congenital neurogenic bladder, the anatomic and functional characteristics of their upper and lower urinary tracts at the beginning of the follow-up and at the end of the data collection period and to identify risk factors associated with worsening of the glomerular and tubular functions using as markers the quantitation of glomerular filtration rate and the development of microalbuminuria and metabolic acidosis. METHODS: Retrospective study of a cohort of 58 children with congenital neurogenic bladder treated at the Voiding Dysfunction Clinic, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, with a minimum follow-up period of 6 months. The period of data collection ended in January 2006. The obtained results were described as means, standard deviations, medians, minimum and maximum values, or as frequencies and percentages. The comparison between the initial and final evaluations for continuous quantitative variables was done using the Student´s t test for paired samples. The association between dichotomous variables was performed considering the Fisher´s exact test. For evaluation of patients` outcomes and comparison of subgroups defined by dichotomous variables, Kaplan-Meier curves were performed and Long-rank test was applied. P values < 0.05 indicated statistical significance. RESULTS: 58 children were evaluated with 33 females (56,9%). The mean age at presentation to the service was 4.2 ± 3.5 years, the mean follow-up period was 3.8 ± 3.1 years. Myelomeningocele was the leading aetiology, corresponding to 42/58 patients (72.4%). Referral to the service occurred in 48 (82.8%) patients due to urinary tract infection, in 5 (8.6%) due to enuresis and in 5 (8.6%) due to urinary retention. Recurrent urinary tract infections were found in 49/58 patients (84.5%) at the beginning and 41/49 (83.7%) had improvement during the follow-up period. Systemic Hypertension was diagnosed in 11 (19.3%) children at the first visit and in 18 (31%) in the final evaluation. The initial mean glomerular filtration rate was 146.7 ±70.1 mL/1.73m²/min and the final mean was 193.6±mL/1.73m²/min, p = 0.0004. Microalbuminuria was found in 20 (54.1%) samples in the initial evaluation and in 26 (61.9%) in the final evaluation. Metabolic acidosis was present in 11 (19%) samples in the initial evaluation and in 19 (32.8%) in the final assessment. The children who most developed metabolic acidosis during the follow-up period were those who presented earlier to the service (< 3 years of age), p= 0.01. The group of patients that did not present metabolic acidosis at the end of the study had lower values of final weight z-score (p=0.048), initial height/stature z-score (p=0.047) and final height/stature z-score (p=0.022) than the patients of the group that developed acidosis. CONCLUSIONS: Children with congenital neurogenic bladder develop early compromise of renal glomerular and tubular functions and require adequate management by specialized professionals.

Introdução: O sedentarismo e obesidade têm sido descritos como fatores de risco relevantes para o desenvolvimento de sintomas do trato urinário inferior (STUI). No presente estudo investigamos o papel da atividade física nas alterações vesicais funcionais e moleculares induzidas por dieta hiperlipídica em ratos. Material e método: Ratos machos Wistar com oito semanas de idade foram divididos aleatoriamente em quatro grupos: 1. atividade física (AF) e dieta padrão (DP); 2. AF e dieta rica em gorduras (DHL); 3. Sedentários (SED) com DP; 4. SED e DHL. Os ratos dos Grupos 1 e 2 foram submetidos a um protocolo de treinamento de natação por 10 semanas. Ao final do protocolo, realizamos estudo funcional vesical (urodinâmico) nos ratos anestesiados, e extraímos o tecido vesical para estudo molecular da via de sinalização da insulina (IRS1/IRS2/PI3K/AKT/eNOS) através do método de reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR). Resultados: Após 10 semanas, os grupos 1 e 2 apresentaram respectivamente menor ganho de peso corporal quando comparados aos grupos 3 (213,89 vs 261,63 gramas, p=0,04) e 4 (209,84 vs 257,57 gramas, p=0,04), assim como menor peso da gordura epididimária quando comparados aos grupos 3 (14,06 vs 19,74 gramas, p=0,01) e 4 (15,26 vs 20,38, p=0,02). Na soma das intervenções (sedentarismo e dieta hiperlipidica), o grupo 4 apresentou maior nível de insulina sérica (6,05 vs 4,14 ng/ml, p=0,038) e índice HOMA-IR (1,95 vs 1,09, p=0,006) em comparação ao grupo 1, sugerindo padrão de resistencia à insulina. A análise urodinâmica, na comparação do grupo 4 vs grupo 1, demonstrou padrão de hiperatividade vesical naquele: maior numero de micções (13,6 vs 6,0, p=0,04), maior pressão pós miccional (8,06 vs 5,08 mmHg, p=0,04), menor capacidade (0,29 vs 0,91 ml, p=0,008) e complacência vesical (0,027 vs 0,091ml/mmHg, p=0,016). Quanto ao estudo molecular da via de sinalização da insulina no tecido vesical, o efeito da dieta hiperlipídica resultou em subexpressão de toda a via (IRS1, IRS2, PI3K, AKT e NOS3). Em contrapartida, o efeito da atividade física resultou em superexpressão da via, em especial quando comparamos ratos com ingesta de gordura (grupo 2 x 4), assim como na comparação dos grupos \"extremos\" (grupo 1 x 4). Conclusão: A exposição dos ratos a DHL resultou em subexpressão molecular da via de sinalização de insulina no tecido vesical, assim como a AF gerou superexpressão desta, em especial nos ratos expostos a DHL. A exposição dos animais a DHL em associação a hábitos sedentários resultou em obesidade, resistência à insulina e padrão sugestivo de hiperatividade vesical em comparação aos expostos a AF e DP / Introduction: Sedentary lifestyle and obesity have been described as relevant risk factors for the development of lower urinary tract symptoms. In the present study we investigate the role of physical activity in the functional and molecular bladder alterations resulting from obesity induced by hyperlipidic diet in rats. Material and methods: Wistar male rats at eight weeks of age were randomized into groups: 1. physical activity (AF) and standard diet (DP); 2. AF and high fat diet (DHL); 3. sedentary (SED) with DP; 4.SED and DHL. Group 1 and 2 rats were subjected to a 10-week swimming training protocol. Urodynamic study was performed and expression of genes in bladder tissue (IRS1 / IRS2 / PI3K / AKT / eNOS) was evaluated. Results: Results: Groups 1 and 2 presented lower body weight gain than groups 3 (213.89 vs 261.63 grams (g), p=0.04) and 4 (209.84 vs 257.57 g, p=0.04), respectively. Group 4 had higher insulin level (6.05±1.79 vs 4.14±1.14 ng/ml, p=0.038) and higher homeostasis model assessment of insulin resistance (HOMA-IR) index (1.95 vs 1.09, p=0.006) than group 1. Group 4 had greater number of micturitions (13.6 vs 6.0, p=0.04), higher post-void pressure (8.06 vs 5.08, p=0.04), lower capacity (0.29 vs 0.91 ml, p=0.008) and lower bladder compliance (0.027 vs 0.091 ml/mmHg, p=0.016) versus group 1. HFD resulted in underexpression throughout insulin signaling pathway. Physical activity resulted in overexpression of the pathway, especially in comparisons between the rats with fat intake (groups 2 and 4) and the extreme groups (groups 1 and 4). Conclusion: Exposure of rats to hyperlipidic diet in addition to a sedentary pattern resulted in obesity, insulin resistance, urodynamic pattern suggestive of bladder hyperactivity and molecular subexpression of the IRS2 / PI3K / AKT / eNOS pathway in comparison to rats exposed to physical activity and standard diet. Physical activity generated overexpression of this molecular pathway, especially in rats exposed to a hyperlipidic diet

INTRODUÇÃO: A bexiga neurogênica é considerada um fator de risco importante para insuficiência renal crônica. A preservação da função renal é um dos principais objetivos do tratamento nefrourológico dos portadores desta doença. OBJETIVOS: Descrever as características demográficas de 58 pacientes com bexiga neurogênica congênita, as características anatômicas e funcionais do trato urinário superior e inferior desta população ao início do seguimento e ao final da coleta dos dados e identificar fatores de risco associados à piora de função glomerular e tubular nesta população, utilizando como marcadores a quantificação do ritmo de filtração glomerular e o desenvolvimento de microalbuminúria e acidose metabólica. MÉTODOS: Estudo retrospectivo de uma coorte de 58 pacientes portadores de bexiga neurogênica congênita com seguimento mínimo de seis meses, matriculados no ambulatório de Disfunções Miccionais da Infância da Unidade de Nefrologia Pediátrica do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. O período de coleta de dados foi encerrado em janeiro de 2006. Os resultados obtidos no estudo foram descritos por médias e desvios padrões, medianas, valores mínimos e máximos, ou por frequências e percentuais. A comparação entre a avaliação inicial e a final para variáveis quantitativas contínuas foi feita usando-se o teste t de Student para amostras pareadas. A associação entre variáveis dicotômicas foi feita considerando-se o teste exato de Fisher. Para avaliação da evolução dos pacientes e comparação de subgrupos definidos por variáveis dicotômicas, foram construídas curvas de Kaplan-Meier e aplicado o teste de Long-rank. Valores de p<0,05 indicaram significância estatística. RESULTADOS: Das 58 crianças avaliadas, 33 eram do sexo feminino (56,9%). A idade média com que as crianças chegaram ao serviço foi de 4,2±3,5 anos, a média de tempo de seguimento foi de 3,8±3,1 anos. A etiologia predominante de bexiga neurogênica foi mielomeningocele, em 42 dos 58 pacientes (72,4%). O encaminhamento à Unidade ocorreu por infecção urinária em 48 (82,8%) casos, por enurese em 5 (8,6%) e por retenção urinária em 5 (8,6%). Dentre os 49/58 (84,5%) pacientes com ITU de repetição ao início do seguimento, 41/49 (83,7%) pacientes apresentaram melhora no período de seguimento. A hipertensão arterial foi diagnosticada em 11 (19,3%) das crianças na avaliação inicial e em 18 (31%) na avaliação final. A média do RFG inicial foi de 146,7±70,1 mL/1,73m2/min e a média final de 193,6±93,6 mL/1,73m2/min, com p=0,0004. A microalbuminúria estava presente em 20 (54,1%) dos exames na avaliação inicial e em 26 (61,9%) na avaliação final. A acidose metabólica estava presente em 11 (19%) dos exames na avaliação inicial e em 19 (32,8%) na avaliação final. As crianças que chegaram à Unidade de Nefrologia mais precocemente (< 3 anos) foram aquelas que mais apresentaram acidose metabólica no decorrer do acompanhamento (p=0,01). Os pacientes que não tinham acidose metabólica ao final do estudo apresentaram valores menores de Z-escore peso final (p= 0,048), Zescore altura/estatura inicial (p= 0,047) e Z-escore altura/estatura final (p=0,022) com relação aos pacientes do grupo que evoluiu com acidose. CONCLUSÃO: Pacientes com bexiga neurogênica congênita evoluem com acometimento renal glomerular e tubular precoce, cujo manejo demanda acompanhamento por profissional especializado. / INTRODUCTION: Neurogenic bladder is considered an important risk factor for chronic renal failure. In these patients, preservation of renal function is one of the most important goals of nephro-urological treatment. PURPOSE: To describe demographic data of 58 children with congenital neurogenic bladder, the anatomic and functional characteristics of their upper and lower urinary tracts at the beginning of the follow-up and at the end of the data collection period and to identify risk factors associated with worsening of the glomerular and tubular functions using as markers the quantitation of glomerular filtration rate and the development of microalbuminuria and metabolic acidosis. METHODS: Retrospective study of a cohort of 58 children with congenital neurogenic bladder treated at the Voiding Dysfunction Clinic, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, with a minimum follow-up period of 6 months. The period of data collection ended in January 2006. The obtained results were described as means, standard deviations, medians, minimum and maximum values, or as frequencies and percentages. The comparison between the initial and final evaluations for continuous quantitative variables was done using the Student´s t test for paired samples. The association between dichotomous variables was performed considering the Fisher´s exact test. For evaluation of patients` outcomes and comparison of subgroups defined by dichotomous variables, Kaplan-Meier curves were performed and Long-rank test was applied. P values < 0.05 indicated statistical significance. RESULTS: 58 children were evaluated with 33 females (56,9%). The mean age at presentation to the service was 4.2 ± 3.5 years, the mean follow-up period was 3.8 ± 3.1 years. Myelomeningocele was the leading aetiology, corresponding to 42/58 patients (72.4%). Referral to the service occurred in 48 (82.8%) patients due to urinary tract infection, in 5 (8.6%) due to enuresis and in 5 (8.6%) due to urinary retention. Recurrent urinary tract infections were found in 49/58 patients (84.5%) at the beginning and 41/49 (83.7%) had improvement during the follow-up period. Systemic Hypertension was diagnosed in 11 (19.3%) children at the first visit and in 18 (31%) in the final evaluation. The initial mean glomerular filtration rate was 146.7 ±70.1 mL/1.73m²/min and the final mean was 193.6±mL/1.73m²/min, p = 0.0004. Microalbuminuria was found in 20 (54.1%) samples in the initial evaluation and in 26 (61.9%) in the final evaluation. Metabolic acidosis was present in 11 (19%) samples in the initial evaluation and in 19 (32.8%) in the final assessment. The children who most developed metabolic acidosis during the follow-up period were those who presented earlier to the service (< 3 years of age), p= 0.01. The group of patients that did not present metabolic acidosis at the end of the study had lower values of final weight z-score (p=0.048), initial height/stature z-score (p=0.047) and final height/stature z-score (p=0.022) than the patients of the group that developed acidosis. CONCLUSIONS: Children with congenital neurogenic bladder develop early compromise of renal glomerular and tubular functions and require adequate management by specialized professionals.

Orientador: Juliany Gomes Quitzan / Resumo: A diminuição da complacência da bexiga está relacionada com modificações no equilíbrio dos componentes da matriz extracelular e na concentração das fibras de colágeno, acarretando em espessamento da parede vesical e fibrose. O objetivo do estudo é analisar a relação entre suplementação oral dos glicosaminogicanos (GAGs), distribuição de pequenos proteoglicanos ricos em leucina (SRLPs) e síntese de colágeno em bexigas saudáveis e fibrosadas por obstrução parcial submetidas a cistotomia. Foram utilizados 56 ratos da linhagem Wistar, fêmeas, divididos em cinco grupos experimentais- G1 (8) – controle, sem procedimento, G2 (12) – animais não suplementados, submetidos ao procedimento de obstrução vesical e posterior cistotomia, G3 (12) – animais suplementados e submetidos ao procedimento de obstrução vesical e posterior cistotomia, G4 (12) – animais não suplementados e submetidos ao procedimento de cistotomia e G5 (12) animais suplementados e submetidos ao procedimento de cistotomia. A suplementação de glicosaminoglicanos foi realizada a cada 24 horas por via oral durante 28 dias pós cistotomia, quando então os animais foram eutanasiados. O colágeno foi avaliado pela Microscopia Cars e biglican, decorina, lumican e fibromodulina pelo método de imunofluorescência. Para análise estatística foi utilizado o teste ANOVA e T-STUDENT, com nível de significância p <0,05. Os animais dos grupos G2 e 3 foram os que apresentaram diferença estatística na seguinte constante: peso bexiga final /p... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

In this review, we focused on putatively interesting biomarkers of interstitial cystitis/bladder pain syndrome (IC/BPS) in relation to the etiopathology of this disease. Since its etiopathology is still under discussion, the development of novel biomarkers is critical for the correct classification of the patients in order to open personalized treatment options, on the one hand, and to separate true IC/BPS from the numerous confusable diseases with comparable symptom spectra on the other hand. There is growing evidence supporting the notion that the classical or Hunner-type IC (HIC) and the non-Hunner-type IC (NHIC) are different diseases with different etiopathologies and different pathophysiology at the full-blown state. While genetic alterations indicate close relationship to allergic and autoimmune diseases, at present, the genetic origin of IC/BPS could be identified. Disturbed angiogenesis and impairment of the microvessels could be linked to altered humoral signaling cascades leading to enhanced VEGF levels which in turn could enhance leucocyte and mast cell invasion. Recurrent or chronic urinary tract infection has been speculated to promote IC/BPS. New findings show that occult virus infections occurred in most IC/BPS patients and that the urinary microbiome was altered, supporting the hypothesis of infections as major players in IC/BPS. Environmental and nutritional factors may also influence IC/BPS, at least at a late state (e.g., cigarette smoking can enhance IC/BPS symptoms). The damage of the urothelial barrier could possibly be the result of many different causality chains and mark the final state of IC/BPS, the causes of this development having been introduced years ago. We conclude that the etiopathology of IC/BPS is complex, involving regulatory mechanisms at various levels. However, using novel molecular biologic techniques promise more sophisticated analysis of this pathophysiological network, resulting in a constantly improvement of our understanding of IC/BPS and related diseases.

No description available.

As Photodynamic Therapy (PDT) becomes increasingly popular as a treatment modality for some solid tumours, the need for a better understanding of the mechanism(s) of action and resistance are paramount. To this end we have generated Photofrin® PDT-induced resistant variants to numerous cell lines including the colon cancer cell line HT29. There is significant evidence indicating that stress proteins play an important role in determining the outcome of PDT on a cell. In this thesis the roles of the mitochondrial Heat Shock Protein 60 (Hsp60) as well as the endoplasmic Glucose Related Protein 78 (GRP78) were examined in the HT29 cells and their Photofrin induced resistant variant HT29-P14. The expression and role of these two stress proteins were also examined in T24 Bladder carcinoma cells and their GRP 78 stable-overexpressing clones Hsp60 protein was expressed at slightly higher basal levels in the resistant HT29-P14 cells relative to the parental HT29 cells. After incubation alone or PDT action, a temporal and dose dependent induction of Hsp60 was observed and this too was found to be significantly greater in the resistant cells. In the T24 model, no Hsp60 induction was observed following drug incubation or PDT. GRP78 protein levels were increased by PDT action but not by Photofrin® incubation alone in all cell lines tested. In the T24 model, GRP78 transfection resulted in a stable 2-fold increase in protein levels and a 10-20-fold increase in cell survival after PDT at the highest dose tested. A temporal and dose dependent response was noted in all cells and induction of GRP78 protein was lower in the stable overexpresser such that all cell lines had similar post induction levels. In the HT29 and HT29-P14 resistant cells, GRP78 protein levels were similar at basal level, and, both cell lines exhibited the same temporal and dose dependent increases in expression post PDT. Finally, broad scale expression profiling using a "stress" microarray in the HT29 and HT29-P14 resistant variants revealed a very similar expression profile for the 168 of the 169 stress proteins tested with the exception of the small Heat Shock Protein 27 (Hsp27). As confirmed by northern and western blot analysis, Hsp27 is over 20 fold greater at the transcriptional level and 10-15 fold greater at the translational level in the HT29-P14 resistant variant. These findings implicate Hsp27, Hsp60 and GRP78 as possible mediators of cellular sensitivity to Photofrin-mediated PDT. Specifically, Hsp27 appears to play a role in the increased resistance of our induced resistant HT29-P14 cells. / Thesis / Master of Science (MS)

Bladder cancer is a potentially curable malignancy; however in regards to the state of current therapy regimens, a plateau has been reached in both the non-muscle and muscle invasive types. To obtain effective treatment, and consequently a decreased mortality, it has become imperative to test and understand aspects affecting therapy response. The aim of this thesis is to illustrate a better understanding of clinical factors affecting therapy response using new drug combinations and new tumor markers alongside established risk criteria. In Paper I we reported the 5 year follow up from a multicenter, prospectively randomized study and we evaluated the 5-year outcomes of BCG alone compared to a combination of epirubicin and interferon-a2b in the treatment of patients with T1 bladder cancer. Treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant Cis was not predictive of failure of BCG therapy. Independent factor for treatment failure was remaining T1 stage at second resection. In Paper II &amp;III we investigated the validity of emmprin, survivin and CCTα proteins as biomarkers for response and survival before neoadjuvant cisplatin chemotherapy. Bladder tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry (IHC). Patients in the chemotherapy cohort with negative emmprin and CCTα expression had significantly better overall survival (OS) than those with positive expression. In Paper IV primary end point was examining STMN1 as prognostic factor in bladder cancer.  Analysis was performed on three bladder cancer patient cohorts using IHC, western blot and a bladder cancer cell line. High levels of STMN1, expression correlated to shorter disease-specific survival and the growth and migration of the cells were significantly reduced when transfecting the cells with STMN1 siRNA. Conclusion Risk assessment and predictors of outcomes could help in individualized treatment and follow up.  Biomarkers will become more important for treatment choices in bladder cancer management.

The detection of predators by prey species is crucial in order to escape the threat posed by a predator. In mammals, the olfactory sensory system is commonly used to detect odors emitted by predators, and to determine how threatening the situation actually is. However, knowledge about this ability is still sparse and in some cases conflicting. The aim of the present study was therefore to assess whether CD-1 mice (Mus musculus) show behaviors such as avoidance, anxiety and/or decreased activity when exposed to any of the three odorants: cat bladder urine, horse voided urine or a fruity odor (N-pentyl acetate), with a blank solvent as an alternative in a two-compartment test arena. I found no significant differences between avoidance (the time that the mice spent in the different compartments), anxiety (the numbers of fecal pellets dropped by the mice), or the overall activity (the number of switches between the two compartments), when the mice were exposed to the three different odors. The fact that the cat urine derived from the bladder of the cat may explain the lack of avoidance responses, since bladder urine might not contain the same chemical components as voided urine. Bladder urine might therefore also lack the chemical components that signal “predator” to the mice. In conclusion, mice do not respond differently to the odor of cat bladder urine than to horse voided urine or to the fruity odor of N-pentyl acetate.

Sources of arsenic exposure include air, water, and food from both natural and anthropogenic sources. Arsenic is categorized as a human carcinogen, and is associated with pleiotropic toxicities including cancers of the skin, lung, and bladder. Despite arsenic's long recognition as a human carcinogen, the exact mechanisms of arsenical-induced carcinogenesis are unknown. Arsenic exposure has been shown to cause DNA damage. However, because arsenic does not directly react with DNA, genotoxicity is generally considered to result from indirect mechanisms. The generation of arsenical-induced reactive oxygen species and the inhibition of critical DNA repair systems are believed to contribute to arsenical-induced carcinogenicity. The DNA damaging effects of arsenical exposure and alterations in DNA repair processes were examined within the human bladder urothelial cell line, UROtsa, following continuous exposure to the arsenic metabolite, monomethylarsonous acid [MMA(III)]. Chronic, low-level MMA(III) exposure results in the induction of DNA damage that remains elevated following the removal of MMA(III). Furthermore, data presented herein, defines the critical period in which continuous low-level MMA(III) exposure causes the malignant transformation of the UROtsa cell line. Results indicate that malignant transformation of UROtsa cells is irreversible following 12 wk of low-level MMA(III) exposure. Assessment of the MMA(III)-induced biological alterations leading to the malignant transformation of UROtsa cells following 12 wk of exposure suggest two potential interdependent mechanisms in which MMA(III) may increase the susceptibility of UROtsa cells to genotoxic insult and/or malignant transformation. These mechanisms include MMA(III)-induced DNA damage via the production of reactive oxygen species and the MMA(III)-induced inhibition of poly(ADP-ribose) polymerase-1 as a result of the direct MMA(III)-mediated displacement of zinc.