RESUMO
Despite complete resection, non-muscle invasive bladder cancers tend to recur. Therefore, their risk stratification was implemented to select adjuvant therapy. Immediate intravesical chemotherapeutic instillations were shown to decrease the risk of recurrence in those with low-risk disease. The purpose of the study was to determine the role of endoscopic assessment in the management of patients subjected to transurethral resection of the bladder tumour (TURBT). In 262 patients submitted to TURBT due to primary bladder tumour, the size and the number of the lesion(s) were noted and the stage as well as the grade of the tumour(s) were typed. The individual features were then scored according to the European Organisation of Research and Treatment of Cancer 'Bladder Calculator' and the lesions were classified into the low, intermediate and high risk of recurrence group. Clinical evaluation was then compared with pathological report and final triage. Based on the clinical data, 95 (36.25%), 105 (40.07%) and 3 (1.14%) patients were endoscopically assigned to the groups of low, intermediate and high risk of recurrence respectively. After pathological report, correct risk stratification was confirmed in 86 (90.5%), 95 (90.5%) and 3 (100%) patients respectively. Endoscopic assessment of bladder cancers allows to accurately establish the risk of recurrence and may facilitate implementation of adjuvant therapy before histological evaluation.
Assuntos
Carcinoma de Células de Transição/cirurgia , Cistoscopia/métodos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/patologia , Invasividade Neoplásica , Neoplasias Primárias Múltiplas/patologia , Medição de Risco , Carga Tumoral , Neoplasias da Bexiga Urinária/patologiaRESUMO
Vasopressin released during myocardial infarction and in response to stress regulates blood pressure through multiple actions exerted in the brain, cardiovascular system and kidney. The aim of the present study was to determine whether myocardial infarction influences expression of vasopressin V1a receptor (V1aR) mRNA and protein in the brain and kidney and whether stress has an impact on expression of these parameters during the post-infarct state. Male, adult Sprague Dawley rats were subjected to myocardial infarction or sham surgery. Seven days later some rats were exposed to mild stress for 4weeks whereas other stayed at rest. Tissue fragments were harvested from four groups of rats (control, infarct, stress, infarct+stress). Expression of V1aR mRNA (Real time PCR) was determined in the preoptic, diencephalic, mesencephalopontine and medullary regions of the brain and in the renal cortex and medulla. Protein V1aR expression (Western blotting) was determined in the brain mesencephalopontine region and in the kidney medulla. In the preoptic, diencephalic, and mesencephalopontine regions, V1aR mRNA expression was significantly lower in the infarcted rats than in the sham-operated unstressed controls. The infarcted rats manifested also lower expression of V1aR protein in the mesencephalopontine region than the other groups. The stressed group demonstrated significantly higher V1aR mRNA expression in the brain medulla and in the renal cortex and renal medulla than the control group. In all brain regions and in the kidney, V1aR mRNA expression was significantly higher in the stressed rats than in the infarcted rats. The stressed rats showed also higher expression of V1aR protein in the renal medulla than the other groups. It is concluded that myocardial infarction and chronic stress cause significant but differential changes in the regulation of V1a receptors expression in the brain and the kidney.
Assuntos
Encéfalo/metabolismo , Rim/metabolismo , Infarto do Miocárdio/metabolismo , RNA Mensageiro/metabolismo , Receptores de Vasopressinas/metabolismo , Estresse Psicológico/metabolismo , Animais , Regulação para Baixo , Masculino , Infarto do Miocárdio/genética , Ratos , Ratos Sprague-DawleyRESUMO
Previous studies showed that chronically stressed and myocardially infarcted rats respond with exaggerated cardiovascular responses to acute stress. The present experiments were designed to elucidate whether this effect can be abolished by treatment with the angiotensin converting enzyme (ACE) inhibitor captopril. Sprague Dawley rats were subjected either to sham surgery (Groups 1 and 2) or to myocardial infarction (Groups 3 and 4). The rats of Groups 2 and 4 were also exposed to mild chronic stressing. Four weeks after the operation, mean arterial blood pressure (MABP) and heart rate (HR) were measured under resting conditions and after application of acute stress. The cardiovascular responses to the acute stress were determined again 24 h after administration of captopril orally. Captopril significantly reduced resting MABP in each group. Before administration of captopril, the maximum increases in MABP evoked by the acute stressor in all (infarcted and sham-operated) chronically stressed rats and also in the infarcted nonchronically stressed rats were significantly greater than in the sham-operated rats not exposed to chronic stressing. These differences were abolished by captopril. The results suggest that ACE may improve tolerance of acute stress in heart failure and during chronic stressing.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Estresse Fisiológico/efeitos dos fármacos , Animais , Sistema Cardiovascular/efeitos dos fármacos , Insuficiência Cardíaca/patologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Infarto do Miocárdio/patologia , Peptidil Dipeptidase A , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: We analysed critically the potential usefulness of RNA- and DNA-based biomarkers in supporting conventional histological diagnostic tests for prostate carcinoma (PCa) detection. METHODS: Microarray profiling of gene expression and DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32 cancerous and non-cancerous prostate samples extracted by radical prostatectomy. The predictive value of the selected biomarkers was validated by qPCR-based methods using tissue samples extracted from the 58 prostates and, separately, using 227 prostate core biopsies. RESULTS: HOXC6, AMACR and PCA3 expression showed the best discrimination between PCa and BPH. All three genes were previously reported as the most promising mRNA-based markers for distinguishing cancerous lesions from benign prostate lesions; however, none were sufficiently sensitive and specific to meet the criteria for a PCa diagnostic biomarker. By contrast, DNA methylation levels of the APC, TACC2, RARB, DGKZ and HES5 promoter regions achieved high discriminating sensitivity and specificity, with area under the curve (AUCs) reaching 0.95-1.0. Only a small overlap was detected between the DNA methylation levels of PCa-positive and PCa-negative needle biopsies, with AUCs ranging between 0.854 and 0.899. CONCLUSIONS: DNA methylation-based biomarkers reflect the prostate malignancy and might be useful in supporting clinical decisions for suspected PCa following an initial negative prostate biopsy.
Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Transcriptoma , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores Tumorais/metabolismo , Biópsia , Proteínas de Transporte/genética , Diacilglicerol Quinase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Curva ROC , Receptores do Ácido Retinoico/genética , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. METHODS: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). RESULTS: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ≤ 60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. CONCLUSION: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment.
Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Nucleares/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Quinase do Ponto de Checagem 2 , Genes BRCA1 , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Serina-Treonina Quinases/genéticaRESUMO
The myocardial infarct causes prolonged activation of the renin-angiotensin system and profoundly influences cardiac performance and renal excretory capabilities. The aim of the present study was to determine whether the myocardial infarct is also associated with an altered expression of AT1a receptors (AT1aR) mRNA in the heart and the kidney. To this end male Sprague-Dawley rats were subjected either to the left coronary artery ligation or to the sham surgery. Four weeks after the surgery the animals were sacrificed. In 11 infarcted and 10 sham-operated rats expression of AT1aR mRNA in the walls of the left and right ventricle of the heart, and in the renal cortex and renal medulla was determined by semiquantitative PCR method. In another group of 10 infarcted and 14 sham-operated rats the diameter of cardiomyocytes in the left and right cardiac ventricle was determined. The size of the infarct in the rats used for mRNA determination and for morphometric measurements was equal to 29.4 +/- 1.8% and to 31.0 +/- 1.2 % of the left ventricular wall, respectively. Expression of AT1aR mRNA was significantly greater in the left (P< 0.01) and right ventricle (P<0.03) of the heart in the infarcted than in the sham operated rats. AT1aR mRNA expression was also significantly greater (P<0.02) in the renal medulla of the infarcted rats than in the renal medulla of the sham operated rats whereas no significant difference was found in the renal cortex. The myocardial infarct was associated with a significant increase of diameter of cardiomyocytes of the left ventricle of the heart (P< 0.0001), however there was no significant correlation between changes in AT1aR mRNA expression and diameter of cardiomyocytes. The results provide evidence that the myocardial infarct results in significant and prolonged upregulation of AT1a receptors mRNA expression in the heart and in the medullary region of the kidney.
Assuntos
Medula Renal/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Regulação para Cima , Análise de Variância , Animais , Ventrículos do Coração/metabolismo , Histocitoquímica , Masculino , Modelos Animais , Miócitos Cardíacos/citologia , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/genéticaRESUMO
The purpose of the study was to determine effect of high sodium intake on fluid and electrolyte turnover and heart remodeling in the cardiac failure elicited by myocardial infarction (MI). The experiments were performed on four groups of Sprague Dawley rats maintained on food containing 0.45% NaCl and drinking either water (groups 1, 2) or 1% NaCl (groups 3, 4). Groups 1 and 3 were sham-operated while in groups 2 and 4 MI was produced by the coronary artery ligation. In each group food and fluid as well as sodium intake, urine (Vu), sodium (UNaV), potassium (UKV) and solutes (UosmV) excretion were determined before and four weeks after the surgery. Size of the infarct, left ventricle (LV) weight and diameter of LV and right ventricle (RV) myocytes were determined during post-mortem examination. Before the surgery groups 3 and 4 ingested significantly more fluid and sodium, had higher Vu, UNaV, UKV and UosmV than the respective groups 1 and 2. In groups 2 and 4 MI resulted in significant decrease in Vu, UNaV and UosmV in comparison to the pre-surgical level. In Group 4 MI resulted also in a significant decrease of food and sodium intake. The MI size did not differ in groups 2 and 4 while diameter of LV myocytes was significantly greater in groups 2 and 4 than in groups 1 and 3, and in group 4 than in group 2. The study reveals that prolonged high sodium consumption increases fluid and electrolyte turnover both in the sham and in the MI rats and that the MI causes decrease in food and sodium intake in rats on high but not on regular sodium intake. In addition high sodium diet promotes development of greater post-MI hypertrophy of the LV myocytes.
Assuntos
Ingestão de Líquidos/efeitos dos fármacos , Eletrólitos/urina , Infarto do Miocárdio/fisiopatologia , Sódio na Dieta/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Vasos Coronários , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/urina , Ligadura , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/urina , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Sódio/urina , Sódio na Dieta/administração & dosagem , Fatores de TempoRESUMO
Previous studies revealed that the brain angiotensinergic, vasopressinergic and nitrergic systems are involved in regulation of blood pressure and that their function is altered in various forms of hypertension. The purpose of our investigation was to determine whether expression of AT1a angiotensin receptors (AT1aR) mRNA, V1a vasopressin receptors (V1aR) mRNA and neuronal nitric oxide synthase (NOS1) mRNA is altered in the brain of rats with the renovascular hypertension. Eight male Sprague Dawley (SD 2K,1C) rats were subjected to constriction of the left renal artery in order to produce the renovascular hypertension whereas nine SD rats underwent the sham surgery. In both groups blood pressure was determined before and after the surgery. Four weeks after the surgery the brain fragments were harvested for determination of mRNA expression. Competitive PCR method was applied for relative quantitative analysis of V1aR mRNA, AT1aR mRNA and NOS1 mRNA in the preoptic, diencephalic, mesencephalopontine, medullary and cerebellar fragments of the brain. Blood pressure was significantly higher in the 2K,1C than in the sham operated rats. In the preoptic, mesencephalopontine and medullary regions AT1aR mRNA expression was significantly lower in the 2K,1C rats than in the sham operated rats. The 2K,1C rats manifested also significantly higher expression of V1aR mRNA and NOS1 mRNA in the preoptic brain region in comparison to the sham operated rats. The study provides evidence for significant changes of expression of AT1aR mRNA, V1aR mRNA and NOS1 mRNA in the specific brain regions of rats with the renovascular hypertension.
Assuntos
Encéfalo/metabolismo , Hipertensão Renovascular/metabolismo , Óxido Nítrico Sintase/biossíntese , Receptor Tipo 1 de Angiotensina/biossíntese , Receptores de Vasopressinas/biossíntese , Animais , Regulação da Expressão Gênica/fisiologia , Hipertensão Renovascular/genética , Masculino , Óxido Nítrico Sintase/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/genética , Receptores de Vasopressinas/genéticaRESUMO
Angiotensin-(1-7) (Ang-[1-7]) is present in the brain of normotensive Sprague Dawley (SD) rats, and its hypothalamic content is elevated in TGRmRen2(27) rats (TGR) with renin dependent transgenic hypertension. The purpose of the present study was to determine the role of intrabrain Ang-(1-7) in the regulation of cardiovascular functions in SD and TGR rats under resting conditions and during haemodynamic challenge produced by rapid bleeding. Two groups of experiments were performed on conscious SD and TGR rats that were chronically instrumented with a lateral cerebral ventricle (LCV) cannula and an intraarterial catheter. Blood pressure (MAP) and heart rate period (Hp=distance between two systolic peaks) were continuously monitored: 1) under resting conditions during an LCV infusion of either artificial cerebrospinal fluid (aCSF, 5 microl/hr) or Ang-(1-7) in aCSF (100 pmol/5 microl/hr), and 2) before and after haemorrhage performed during LCV infusion of either aCSF or Ang-(1-7) antagonist (A-779, 4 nmol/5 microl/hr). Cerebroventricular infusion of Ang-(1-7) did not affect baseline MAP in the SD rats but it caused a significant decrease in blood pressure in the TGR rats. In the control experiments, haemorrhage significantly reduced MAP in the SD and TGR rats and heart rate in the TGR rats. Cerebroventricular infusion of Ang-(1-7) antagonist eliminated posthaemorrhagic hypotension in both strains and bradycardia in the TGR rats. The results indicate that intrabrain Ang-(1-7) may contribute to posthaemorrhagic hypotension and bradycardia. Moreover, the manner in which it centrally regulates the cardiovascular functions in the SD and TGR rats may be considerably different.
Assuntos
Angiotensina II/análogos & derivados , Angiotensina I/química , Angiotensina I/fisiologia , Animais Geneticamente Modificados/fisiologia , Hipotensão/fisiopatologia , Hipotálamo/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/fisiologia , Ratos/genética , Renina/fisiologia , Adaptação Fisiológica , Angiotensina I/farmacologia , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Ventrículos Cerebrais/efeitos dos fármacos , Líquido Cefalorraquidiano/química , Líquido Cefalorraquidiano/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Hemorragia/complicações , Hemorragia/fisiopatologia , Hipertensão/etiologia , Hipertensão/genética , Hipotensão/complicações , Hipotálamo/fisiologia , Injeções Intraventriculares , Fragmentos de Peptídeos/farmacologia , Ratos Sprague-Dawley , Renina/sangue , Renina/genética , Choque Hemorrágico/complicações , Choque Hemorrágico/fisiopatologia , Choque Hemorrágico/prevenção & controle , Especificidade da EspécieRESUMO
In short term experiments angiotensin II (Ang II) is a potent stimulant of thirst, however it is not known whether prolonged activation of the renin-angiotensin system is associated with chronic alteration of water or food intake. Renin transgenic rats TGRmRen(2)27 (TGR) exhibit significant elevation of AngII in the brain regions involved in regulation of body fluid balance. The purpose of the present study was to find out whether TGR rats manifest also different water (WI) and food (FI) intake and renal excretory functions in comparison to their parent Sprague Dawley (SD) strain. To this end 24 h WI and FI as well as urine excretion (Vu) and urinary outputs of solutes (Cosm), sodium (UNaV) and potassium (UKV) were compared under baseline conditions in 16 TGR and 15 SD rats having free access to water and food. In 15 TGR and 17 SD rats effect of 24 h dehydration on water intake was investigated. Under baseline conditions TGR rats consumed significantly greater amount of food and water than SD rats. Vu, UNaV and UKV were not significantly different in both strains. Cumulative water intakes in SD and TGR rats subjected to 24 h dehydration did not differ. The results reveal that under baseline conditions TGR rats manifest greater food and water intakes than SD rats whereas stimulation of thirst by water deprivation is similar in both strains. The results suggest that the ingestive behavior may be chronically altered by upregulation of the renin-angiotensin system.
Assuntos
Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Renina/fisiologia , Animais , Animais Geneticamente Modificados , Pressão Sanguínea/fisiologia , Desidratação , Masculino , Potássio/urina , Ratos , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/fisiologia , Sódio/urina , Regulação para Cima , Urina/fisiologia , Privação de Água/fisiologiaRESUMO
Recent evidence indicates that renin transgenic rats TGR(mRen2)27 (TGR) manifest increased activity of the central vasopressinergic system. Because one of the reasons for this finding could be an increased synthesis of vasopressin receptors, we determined in the present study expression of V1a and V1b vasopressin receptors (R) mRNA in the brain of TGR rats and of their parent Sprague-Dawley (SD) strain. Competitive PCR method was applied for quantitative analysis of V1a and V1b receptors mRNA in the preoptic, diencephalic, mesencephalopontine and medullary regions. V1aR mRNA expression was similar in SD and TGR rats in the preoptic, diencephalic and mesencephalopontine regions. In the medullary region expression of V1aR mRNA was significantly lower in TGR than in SD rats. V1bR mRNA did not differ in TGR and SD rats in the preoptic, diencephalic and medullary region whereas it was significantly elevated in the mesencephalopontine region. The results provide evidence for differential regulation of V1a and V1b receptors genes in the brain stem of TGR rats that is manifested by downregulation of V1aR mRNA in the medulla and upregulation of V1bR mRNA in the mesencephalopontine region.
Assuntos
Encéfalo/metabolismo , Receptores de Vasopressinas/biossíntese , Animais , Animais Geneticamente Modificados , Masculino , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptores de Vasopressinas/genética , Renina/genética , Renina/metabolismoRESUMO
Spontaneuosly hypertensive rats (SHR) have been shown to exhibit several alterations in function of the intrabrain vasopressinergic system. The present study was designed to find out whether centrally administered vasopressin (AVP) may influence the cardiovascular adaptation to hypotensive hypovolemia in SHR rats. Two series of experiments were performed on conscious 17 SHR rats chronically implanted with lateral cerebral ventricle (LCV) cannulas and with femoral artery catheters. Mean arterial pressure (MAP) and heart rate (HR) were monitored before and after arterial bleeding (1,3% body weight) performed during LCV infusion of 1) artificial cerebrospinal fluid 5 microl/hour (aCSF); and 2) arginine vasopressin, 100 ng/hour/5 microl of aCSF (AVP). Central administration of aCSF and AVP had no effect on MAP and HR under resting conditions. Hemorrhage evoked significant hypotension (p<0.001) and bradycardia (p<0.001). During central infusion of AVP hemorrhage resulted in significantly greater hypotension than during central infusion of aCSF alone (p<0,05). The results provide evidence that centrally applied vasopressin significantly modulates cardivascular adjustments to hypotensive hemorrhage in SHR.