Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats.

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

Chronic partial urethral obstruction in female rats: description of an experimental model and initial results.

PURPOSE: To develop an experimental model of infravesical urinary obstruction in female rats. METHODS: After median caudal laparotomy, the urethra of 14 female rats was delicately separated from the vagina and loosely wrapped with cellophane tape measuring 0.4 x 1.0 cm. The animals were evaluated 4 (n=7) and 8 (n=7) weeks later. Five additional control animals were only subjected to separation of the urethra and vagina and monitored for 12 weeks. RESULTS: After four weeks, three rats presented vesical dilation associated with discrete ureteral ectasis in 2 animals, with the third presenting discrete hydronephrosis in one kidney. After eight weeks, five rats (71.4%) presented vesical distension with bilateral ureterohydronephrosis. No significant changes (p>0.05) in serum urea or creatinine occurred in any group compared to preoperative values. CONCLUSION: We present here an inexpensive and simple method for the slow induction of urethral obstruction in adult female rats, with the development of progressive vesical hypertrophy and ureterohydronephrosis, which may be used as an experimental model for the study of different aspects of obstructive nephropathy.

Compensatory renal growth and mitochondrial function: the influence of warm ischemia and reperfusion.

PURPOSE: To evaluate the influence of ischemia/reperfusion injury on renal compensatory growth (CGR) and mitochondrial function. METHODS: Forty five Wistar rats were divided in 3 groups: Control Group (GC) - 21 rats were submitted to a sham laparotomy and sacrificed at 1st (6 rats) and 7th (15 rats) postoperative days to evaluate the dry weight of both kidneys and their growth during 1 week (6 rats) and to quantify mitochondrial respiration (9 rats); Group 1 (G1) - 12 rats underwent right nephrectomy and were sacrificed 7 days later for analysis of renal mitochondrial function (6 rats) and dry weight (6 rats). Group 2 (G2) - renal warm ischemia for 60 minutes followed by right nephrectomy was performed in 12 rats; they were sacrificed 7 days later to evaluate renal mitochondrial function (6 rats) and dry weight (6 rats). RESULTS: Dry weight (mg) of left kidneys at 7th day: GC - 219+/-18, G1 - 281+/-23 and G2 - 338+/-39 (GCxG1 p<0.01; GCxG2 p<0.001; G1xG2 p<0.01). State 4 mitochondrial respiration rate and respiratory control ratio (RCR) were similar in all groups (p>0.05). State 3 respirations (mM/min/mg) in GC, G1 and G2 was respectively: 99+/-23, 132+/-22 and 82+/-44 (p<0.02; the only statistical difference noted was between groups G1xG2 - p<0.05). CONCLUSIONS: Following unilateral nephrectomy CRG is associated with an increase in state 3 of mitochondrial respiration. Renal ischemia/reperfusion injury enhances the CRG provoked by unilateral nephrectomy but such enhancement seems independent on mitochondrial respiration.

Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation.

PURPOSE: To evaluate the influence of chlorpromazine (CPZ) on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. METHODS: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E) while the remaining 22 were used as ischemic control group (G-C). Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1st, 4th and 7th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group) and 24 hours (9 G-C and 10 of G-E) of reperfusion for malondialdehy (MDA) content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. RESULTS: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p<0.001). MDA content rose strikingly at 5 minutes of reperfusion in both groups (p>0.05) and returned near to normal levels 24 hours later. CONCLUSION: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation.

Long term evaluation of functional and morphological bladder alterations on alloxan-induced diabetes and aging: experimental study in rats.

PURPOSE: to evaluate structural and functional effects of Alloxan- induced diabetes and aging on bladder of rats. METHODS: evaluations were performed in three groups: A--8 weeks of age, B--44 weeks of age, C--44 weeks of age with alloxan-induced diabetes. Muscle layer thickness, extracellular matrix fibrosis and collagen were quantified on digital images of bladder samples. Cystometric evaluations before surgical vesical denervation (SVD), included maximum cystometric capacity (MCC), maximum bladder pressure (MBP), bladder contraction frequency (VCF), duration of bladder contraction (DC), threshold pressure (TP) and bladder compliance (BC). After SVD, maximum cystometric capacity (MCC), BC and maximum urethral closing pressure (MUCP) were also measured. RESULTS: Reduced extracellular matrix fibrosis concentration and contraction strength were found in the bladders of group C. Before SVD, bladder compliance was not different between groups. Alterations were observed in MCC after SVD. CONCLUSIONS: We did not notice smooth muscle hypertrophy in Alloxan-induced diabetic rats after 44 weeks. There was alteration in the total and relative amount of fibrosis and collagen. The cystometric studies support the idea that this morphological alterations are important to determine the different bladder functional patterns found in the aging and the Alloxan-induced diabetic animals.

Comparison of two experimental models of urodynamic evaluation in female rats.

PURPOSE: Urodynamic studies in small animals can be performed through urethral sounding or cystostomy. OBJECTIVE: To compare the two methods of urodynamic evaluation in female rats. METHODS: Ten female rats weighing on average 250 g, under anesthesia with urethane (1.25 mg/kg) were submitted in three repeats to an urethal catheter of 0,64 mm in external diameter for cystometric measurements of vesicle pressure(VP1) and contraction time (CT1). The catheter was extracted at a constant velocity of 0.05 cm/minute until complete exteriorization and determinations of maximal urethral pressure (UP1) and functional urethral length (FUL1). This was followed by a cystostomy with catheter PE50 and a new determination of the vesical pressure (VP2). After bladder denervation, a new cystometric record indirectly infered the maximum urethral closure pressure (UP2). The peak urethal pressure (UP3) and the functional urethral length (FUL2) were determined in another urethral sounding. The pressure registration system consisted of a continuous infusion pump regulated to a flow of 0.1 ml/minute connected both to the cystostomy catheter (PE-50) or the urethal catheter (0.64 mm) and the polygraph Narco-Biosystem. Statistical analysis employed the Wilcoxon non-parametric test RESULTS: Mean VP1= 48.2 mmHg (11,8 SD); Mean VP2 = 38.2 mmHg (9.0 SD) "p" (VP1 X VP2) = 0.0039. Mean CT1=30.2 s (21.5 SD); Mean CT2=20.0 s(7 SD) p (CT1 X CT2) = 1.28. Mean UP1 = 47.2 mmHg (6.5 SD); Mean UP2 = 21.3 mmHg (6.6 SD), mean UP3 = 40.7 mmHg(13.3 SD) p (UP1 X UP2) = 0.002; "p" (UP1 X UP3) = 0.084; p (UP2 X UP3) = 0.002. Mean FUL1=14.2 mm (1.9 SD); Mean FUL2= 14.1 mm (1.9 SD); p (FUL1 X FUL2) = 0.64. CONCLUSIONS: The methods employed to evaluate vesical and urethral pressures are different. The presence of the urethral catheter may be an obstructive factor. Surgical denervation up to the bladder neck level does not compromise urethral function.

Cyclosporine action on kidneys of rats submitted to normothermic ischaemia and reperfusion.

PURPOSE: To verify if rat kidneys lesioned by ischaemia followed by reperfusion are affected by cyclosporine A (CsA). METHODS: Male Wistar rats were randomly divided into three groups, control (GS) and experimental (G1 and G2). G1 was subdivided in two: G1A composed of animals submitted to 60 minutes ischaemia and G1C with the same ischaemic procedure associated to 20 mg/kg/day CsA. Group G2 was subdivided and treated in the same way as G1 except that ischaemia was applied only for 40 minutes. Clamping the left renal artery followed by right side nephrectomy induced kidney ischaemia. Serum urea and creatinine were quantified on the day of surgery (D0) and in the following day (D1). Twenty four hours after reperfusion the left kidney was removed and histologically analyzed. RESULTS: Group GS had normal values for urea and creatinine both on D0 and D1 and did not show structural alterations. Renal function was not significantly different when G2C was compared to GS (p>0.05). Tissue lesions were smaller in G2C than in the other groups. CONCLUSIONS: Renal function was protected by CsA, which also reduced tissue lesions in the kidneys of rats submitted to 40 minutes ischaemia.

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats / Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento) e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral), durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo A a função mitocondrial renal ficou desacoplada em 83,4% dos ensaios, enquanto que no grupo B isto ocorreu em apenas 38,4% dos ensaios. CONCLUSÕES: Os resultados mostram que a administração de lovastatina antes do episódio de isquemia protege a função renal. No grupo B, como a maior parte da fração mitocondrial isolada apresentou função acoplada à produção de ATP, deve-se também considerar a estabilização da membrana mitocondrial como parte da ação protetora da lovastatina na função renal durante isquemia e reperfusão.

Chronic partial urethral obstruction in female rats: description of an experimental model and initial results / Obstrução parcial uretral crônica em ratos: descrição de um modelo experimental e resultados iniciais

PURPOSE: To develop an experimental model of infravesical urinary obstruction in female rats. METHODS: After median caudal laparotomy, the urethra of 14 female rats was delicately separated from the vagina and loosely wrapped with cellophane tape measuring 0.4 x 1.0 cm. The animals were evaluated 4 (n=7) and 8 (n=7) weeks later. Five additional control animals were only subjected to separation of the urethra and vagina and monitored for 12 weeks. RESULTS: After four weeks, three rats presented vesical dilation associated with discrete ureteral ectasis in 2 animals, with the third presenting discrete hydronephrosis in one kidney. After eight weeks, five rats (71.4 percent) presented vesical distension with bilateral ureterohydronephrosis. No significant changes (p>0.05) in serum urea or creatinine occurred in any group compared to preoperative values. CONCLUSION: We present here an inexpensive and simple method for the slow induction of urethral obstruction in adult female rats, with the development of progressive vesical hypertrophy and ureterohydronephrosis, which may be used as an experimental model for the study of different aspects of obstructive nephropathy.

OBJETIVO: Desenvolver modelo experimental de obstrução urinária infravesical em ratas. MÉTODOS: Após laparotomia caudal mediana, as uretras de 14 ratas foram delicadamente separadas da vagina e frouxamente envoltas com fita de celofane medindo 0.4 x 1.0 cm. Os animais foram avaliados 4 (n=7) e 8 (n=7) semanas depois. Cinco animais adicionais (controle) foram submetidos apenas à separação da uretra e da vagina e monitoradas por 12 semanas. RESULTADOS: Após quatro semanas, três ratas apresentaram dilatação vesical associada a discreta ectasia ureteral em 2 animais, com o terceiro apresentando discreta hidronefrose em um rim. Após oito semanas, cinco ratas (71.4 por cento) apresentaram distensão vesical com ureterohidronefrose bilateral. Não ocorreram alterações significativas (p>0.05) nos valores de uréia ou creatinina em qualquer grupo, comparado com valores pré-operatórios. CONCLUSÃO: Apresentamos aqui um método barato e simples para a indução lenta de obstrução uretral em ratas adultas, com desenvolvimento progressivo de hipertrofia vesical e ureterohidronefrose, podendo ser utilizado como modelo experimental para estudo de diferentes aspectos da nefropatia obstrutiva.

Compensatory renal growth and mitochondrial function: the influence of warm ischemia and reperfusion / Hipertrofia renal compensatória e função mitocondrial: influência da isquemia quente e reperfusão

PURPOSE: To evaluate the influence of ischemia/reperfusion injury on renal compensatory growth (CGR) and mitochondrial function. METHODS: Forty five Wistar rats were divided in 3 groups: Control Group (GC) - 21 rats were submitted to a sham laparotomy and sacrificed at 1st (6 rats) and 7th (15 rats) postoperative days to evaluate the dry weight of both kidneys and their growth during 1 week (6 rats) and to quantify mitochondrial respiration (9 rats); Group 1 (G1) - 12 rats underwent right nephrectomy and were sacrificed 7 days later for analysis of renal mitochondrial function (6 rats) and dry weight (6 rats). Group 2 (G2) - renal warm ischemia for 60 minutes followed by right nephrectomy was performed in 12 rats; they were sacrificed 7 days later to evaluate renal mitochondrial function (6 rats) and dry weight (6 rats). RESULTS: Dry weight (mg) of left kidneys at 7th day: GC - 219±18, G1 - 281±23 and G2 - 338±39 (GCxG1 p<0.01; GCxG2 p<0.001; G1xG2 p<0.01). State 4 mitochondrial respiration rate and respiratory control ratio (RCR) were similar in all groups (p>0.05). State 3 respirations (mM/min/mg) in GC, G1 and G2 was respectively: 99±23, 132±22 and 82±44 (p<0.02; the only statistical difference noted was between groups G1xG2 - p<0.05). CONCLUSIONS: Following unilateral nephrectomy CRG is associated with an increase in state 3 of mitochondrial respiration. Renal ischemia/reperfusion injury enhances the CRG provoked by unilateral nephrectomy but such enhancement seems independent on mitochondrial respiration.

OBJETIVO: Avaliar a influência da lesão de isquemia/reperfusão na hipertrofia renal compensatória (HRC) e na função mitocondrial. MÉTODOS: 45 ratos Wistar foram divididos em três grupos: Grupo Controle (GC) - 21 ratos submetidos apenas à laparotomia e sacrificados no 1º dia (6 ratos) e 7º dia pós-operatório (15 ratos) para avaliar o peso seco de ambos os rins e seu crescimento durante uma semana (6 ratos) e quantificar a função mitocondrial (9 ratos); Grupo 1 (G1) - 12 ratos submetidos à nefrectomia direita e sacrificados após 7 dias para análise da função mitocondrial renal (6 ratos) e peso renal seco (6 ratos); Grupo 2 (G2) - isquemia renal quente durante 60 minutos no rim esquerdo seguida da nefrectomia direita foi realizada em 12 ratos, que foram sacrificados após 7 dias para avaliação da função mitocondrial (6 ratos) e peso seco (6 ratos). RESULTADOS: peso seco (mg) do rim esquerdo no 7º dia: GC= 219±18; G1=281±23 e G2=338±39 (GCxG1 p<0,01; GCxG2 p<0,001; G1xG2 p<0,01). O estado 4 da função mitocondrial e a Razão de Controle Respiratório (RCR) foram semelhantes em todos os grupos (p>0,05). O estado 3 da respiração mitocondrial (mMO2/min/mg) no GC, G1 e G2 foi, respectivamente: 99±23, 132±22 e 88±44 (p<0,02; a única diferença estatística foi observada entre os grupos G1xG2 - p<0,05). CONCLUSÕES: após nefrectomia unilateral a HRC está associada ao aumento do estado 3 da respiração mitocondrial. A lesão de isquemia/reperfusão renal aumenta a HRC estimulada pela nefrectomia unilateral, mas este aumento parece independer da respiração mitocondrial.

Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation / Lesão de isquemia e reperfusão renal: influência da clorpromazina na função renal e na peroxidação lipídica

PURPOSE: To evaluate the influence of chlorpromazine (CPZ) on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. METHODS: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E) while the remaining 22 were used as ischemic control group (G-C). Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1st, 4th and 7th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group) and 24 hours (9 G-C and 10 of G-E) of reperfusion for malondialdehy (MDA) content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. RESULTS: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p<0.001). MDA content rose strikingly at 5 minutes of reperfusion in both groups (p>0.05) and returned near to normal levels 24 hours later. CONCLUSION: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation.

OBJETIVO: avaliar a influência da clorpromazina (CPZ) na função renal e na peroxidação lipídica num modelo de lesão de isquemia/reperfusão renal em ratos. MÉTODOS: 48 ratos Wistar foram submetidos à laparotomia para clampamento da artéria renal esquerda durante 60 minutos, seguido da reperfusão e nefrectomia contralateral. Destes animais, 26 receberam 3 mg/kg de CPZ intravenosa 15 minutos antes da isquemia renal (G-E), sendo os 22 animais restantes utilizados como grupo controle isquêmico (G-C). Em 11 ratos do G-E e 8 do G-C foi feita a dosagem de uréia e creatinina sérica antes da isquemia renal e no 1º, 4º e 7º dia pós-operatório. Amostras de tecido do rim esquerdo foram obtidas aos 5 minutos (5 ratos de cada grupo) e 24 horas após reperfusão (9 G-C e 10 G-E) para dosagem de malondialdeído (MDA). Valores controle para níveis de MDA foram obtidos em rins retirados de 6 ratos normais. RESULTADOS: insuficiência renal aguda ocorreu em todos os animais mas os níveis séricos de uréia e creatinina foram significativamente menores no G-E (p<0,001). Os níveis de MDA apresentaram elevação acentuada na avaliação aos 5 minutos de reperfusão em ambos os grupos (p<0,05), retornando a valores próximos aos normais na avaliação com 24 horas. CONCLUSÃO: a CPZ conferiu proteção parcial da função renal aos rins submetidos à lesão de isquemia e reperfusão, aparentemente independente da inibição da peroxidação lipídica.

Comparison of two experimental models of urodynamic evaluation in female rats / Comparação de dois modelos experimentais para avaliação urodinâmica em ratas

PURPOSE: Urodynamic studies in small animals can be performed through urethral sounding or cystostomy. OBJECTIVE: To compare the two methods of urodynamic evaluation in female rats. METHODS: Ten female rats weighing on average 250g, under anesthesia with urethane (1,25 mg/kg) were submitted in three repeats to an urethal catheter of 0,64 mm in external diameter for cystometric measurements of vesicle pressure(VP1) and contraction time (CT1). The catheter was extracted at a constant velocity of 0.05 cm/minute until complete exteriorization and determinations of maximal urethral pressure (UP1) and functional urethral length (FUL1). This was followed by a cystostomy with catheter PE50 and a new determination of the vesical pressure (VP2). After bladder denervation, a new cystometric record indirectly infered the maximum urethral closure pressure (UP2). The peak urethal pressure (UP3) and the functional urethral length (FUL2) were determined in another urethral sounding. The pressure registration system consisted of a continuous infusion pump regulated to a flow of 0.1 ml/minute connected both to the cystostomy catheter (PE-50) or the urethal catheter (0.64mm) and the polygraph Narco-Biosystem. Statistical analysis employed the Wilcoxon non-parametric test RESULTS: Mean VP1= 48,2 mmHg (11,8 SD); Mean VP2 = 38,2 mmHg (9,0 SD) "p" (VP1 X VP2) = 0,0039. Mean CT1=30,2 s (21,5 SD); Mean CT2=20,0 s(7 SD) p (CT1 X CT2) = 1,28. Mean UP1 = 47,2 mmHg (6,5 SD); Mean UP2 = 21,3 mmHg (6,6 SD), mean UP3 = 40,7 mmHg(13,3 SD) p (UP1 X UP2) = 0,002; "p" (UP1 X UP3) = 0,084; p (UP2 X UP3) = 0,002. Mean FUL1=14,2 mm (1,9 SD); Mean FUL2= 14,1mm (1,9 SD); p (FUL1 X FUL2) = 0,64. CONCLUSIONS: The methods employed to evaluate vesical and urethral pressures are different. The presence of the urethral catheter may be an obstructive factor. Surgical denervation up to the bladder neck level does not compromise urethral function.

INTRODUÇÃO: O estudo urodinâmico em ratas pode ser realizado através de sondagem vesical por via uretral ou por cistostomia. O objetivo deste estudo foi comparar estes dois métodos. MÉTODOS: Foram utilizadas 10 ratas da raça Wistar, peso médio de 250 gramas, anestesiadas com uretana (1,25 mg/kg). Inicialmente foi realizado estudo por sonda uretral (0,64 mm de diâmetro externo) para determinação da pressão vesical (PV1) e tempo de contração (TC1), após isto a sonda foi tracionada a velocidade constante (0,05 cm/m) até sua exteriorização pelo meato uretral, avaliando-se a pressão uretral máxima (PU1) e o comprimento funcional uretral (CFU1). Fez-se, então, a cistostomia (sonda PE50) para determinação da pressão vesical (PV2). A seguir, realizou-se desnervação cirúrgica da bexiga e realizou-se novo registro cistométrico para se inferir a pressão uretral indireta (PU2). Logo após, foi passada sonda uretral para determinação da pressão uretral máxima (PU3) e do comprimento funcional uretral (CFU2). O sistema de registro das pressões foi constituído de uma bomba de infusão contínua regulada para 0,1 ml/minuto conectada em Y com o cateter de cistostomia (PE-50) ou cateter uretral (0,64mm) a um polígrafo Narco-Bioystem. A análise estatística foi realizada através do método não paramétrico de Wilcoxon. RESULTADOS: Média PV1= 48,2 mmHg (11,8 SD); Média PV2 = 38,2 mmHg (9,0 SD). "p" (PV1 X PV2) = 0,0039. Média TC1=30,2 s (21,5 SD); Média TC2=20,0 (7 SD) p (TC1 X TC2) = 1,28. Média PU1 = 47,2 (6,5 SD); Média PU2 = 21,3 mmHg (6,6 SD), média PU3 = 40,7(13,3 SD) p (PU1 X PU2) = 0,002; "p" (PU1 X PU3) = 0,084; p (PU2 X PU3) = 0,002. Média CFU1=14,2 (1,9 SD); Média CFU2= 14,1 (1,9 SD); p (CFU1 X CFU2) = 0,64. CONCLUSÃO: Os métodos de avaliação urodinâmica são diferentes. A presença do cateter na uretra pode ser um fator obstrutivo. A desnervação cirúrgica, até o nível do colo vesical, não compromete a função uretral.

Cyclosporine action on kidneys of rats submitted to normothermic ischaemia and reperfusion / Ação da ciclosporina em rins de ratos submetidos à isquemia normotérmica e reperfusão

PURPOSE: To verify if rat kidneys lesioned by ischaemia followed by reperfusion are affected by cyclosporine A (CsA). METHODS: Male Wistar rats were randomly divided into three groups, control (GS) and experimental (G1 and G2). G1 was subdivided in two: G1A composed of animals submitted to 60 minutes ischaemia and G1C with the same ischaemic procedure associated to 20 mg/kg/day CsA. Group G2 was subdivided and treated in the same way as G1 except that ischaemia was applied only for 40 minutes. Clamping the left renal artery followed by right side nephrectomy induced kidney ischaemia. Serum urea and creatinine were quantified on the day of surgery (D0) and in the following day (D1). Twenty four hours after reperfusion the left kidney was removed and histologically analyzed. RESULTS: Group GS had normal values for urea and creatinine both on D0 and D1 and did not show structural alterations. Renal function was not significantly different when G2C was compared to GS (p>0.05). Tissue lesions were smaller in G2C than in the other groups. CONCLUSIONS: Renal function was protected by CsA, which also reduced tissue lesions in the kidneys of rats submitted to 40 minutes ischaemia.

OBJETIVO: Verificar se a ciclosporina A (CsA) afeta a lesão provocada pela isquemia seguida de reperfusão em rins de ratos. MÉTODOS: Ratos Wistar machos foram separados em grupos: 1 grupo controle (GS) e 2 grupos experimentais (G1 e G2). O G1 foi dividido em G1A - isquemia de 60 minutos; e G1C - isquemia de 60 minutos associada a 20 mg/kg/dia de CsA. O G2 foi dividido em G2C semelhante ao G1, exceto pelo tempo de isquemia de 40 minutos. A isquemia renal foi provocada pelo pinçamento da artéria renal esquerda, após o procedimento, foi realizada a nefrectomia direita. Dosagem de uréia e creatinina séricos foram feitos no dia da cirurgia (D0) e no dia seguinte (D1). Após 24 horas de reperfusão o rim esquerdo foi removido para análise histológica. RESULTADOS: No GS não foram observados alterações de uréia e creatinina em D0 e D1, tampouco alterações estruturais. A comparação entre GS e G2C não mostrou diferença na função renal (p>0,05); o grau de lesão tecidual foi menor em G2C do que nos demais grupos experimentais. CONCLUSÃO: A CsA protegeu a função renal e reduziu a lesão tecidual em rins de ratos submetidos a 40 minutos de isquemia.

Long term evaluation of functional and morphological bladder alterations on alloxan-induced diabetes and aging: experimental study in rats / Avaliação funcional e morfológica tardia de alterações na bexiga secundárias ao diabetes induzido por aloxano e no envelhecimento: estudo experimental em ratos

PURPOSE: to evaluate structural and functional effects of Alloxan- induced diabetes and aging on bladder of rats. METHODS: evaluations were performed in three groups: A - 8 weeks of age, B - 44 weeks of age, C - 44 weeks of age with alloxan-induced diabetes. Muscle layer thickness, extracellular matrix fibrosis and collagen were quantified on digital images of bladder samples. Cystometric evaluations before surgical vesical denervation (SVD), included maximum cystometric capacity (MCC), maximum bladder pressure (MBP), bladder contraction frequency (VCF), duration of bladder contraction (DC), threshold pressure (TP) and bladder compliance (BC). After SVD, maximum cystometric capacity (MCC), BC and maximum urethral closing pressure (MUCP) were also measured. RESULTS: Reduced extracellular matrix fibrosis concentration and contraction strength were found in the bladders of group C. Before SVD, bladder compliance was not different between groups. Alterations were observed in MCC after SVD. CONCLUSIONS: We did not notice smooth muscle hypertrophy in Alloxan-induced diabetic rats after 44 weeks. There was alteration in the total and relative amount of fibrosis and collagen. The cystometric studies support the idea that this morphological alterations are important to determine the different bladder functional patterns found in the aging and the Alloxan-induced diabetic animals.

OBJETIVOS: avaliar alterações estruturais e funcionais da bexiga de ratos machos, associadas ao diabetes induzido por aloxano e ao envelhecimento. MÉTODOS: três grupos de animais: A - 8 semanas de idade; B- 44 semanas de idade; C - 44 semanas de idade com diabetes induzido por aloxano, foram avaliados. Realizadas medidas de espessura da camada muscular, fibrose de matriz extracelular e quantidade de colágeno, através de análise de imagem digital dos tecidos. Realizados também testes cistométricos, antes da desnervação vesical cirúrgica (DVC), para avaliar capacidade vesical (CV), intensidade máxima de contração vesical (IMCV) e complacência vesical. Após a DVC, foram avaliadas capacidade vesical após a desnervação (CVAD), complacência vesical (CV) e pressão de perda uretral (PPU). RESULTADOS: não foi observada hipertrofia da camada muscular nas bexigas; houve diminuição da concentração de fibrose da matriz extracelular e diminuição da força contrátil, e aumento da capacidade vesical no grupo C. CONCLUSÕES: a atrofia da camadas muscular da bexiga esta relacionada ao diabetes induzido por aloxano. O envelhecimento, como fenômeno isolado, provoca alterações nos parâmetros funcionais, porém associado ao diabetes, gera alterações na IMCV, CV e CVAD. Existe correlação entre alterações estruturais e funcionais nos animais diabéticos após a desnervação.

Açäo do estrôgeno na uretra de meninas / Estrogen action in the uretra of girls

As infecções recorrentes do trato urinário inferior (ITU) em meninas apresentam um grande número de causas etiológicas. Entretanto tem situações em que não se consegue detectar uma causa. Uma dessas seria o nível de estrógeno baixo. Assim foi objetivo do presente trabalho verificar a ação do estrógeno conjugado tópico em 12 crianças com ITUs de repetição. Dessas 12 meninas 10 tinham a urografia excretora e a uretrocistografia miccional normais e 2 apresentavam refluxo vésico-ureteral e uma delas pielonefrite crônica com disfunção vésico-uretral. O estrógeno tópico foi usado na vulva durante 30 dias, tendo sido medidos os níveis plasmáticos pré e pós-tratamento. Os exames de urina cultura e sedimento urinário também foram solicitados pré e pós-tratamento. Todas as crianças com ITU foram tratadas com antimicrobianos antes do uso do estrógeno conjugado. As crianças foram seguidas por um período de até 4 anos com culturas de urina semanais por 3 meses e depois mensais. Resultados: Onze das 12 meninas ficaram livres de infecções e tiveram suas culturas de urina negativas. Uma persistiu com bacteriúria assintomática por todo o período de seguimento. Nenhuma delas necessitou de antimicrobiano profilático. Ocorreu aumento do calibre anatômico da uretra após o tratamento e a avaliação estatística pelo teste t mostrou nível de significância com p< 0,001 Conclusões: Esses achados sugerem que o estrógeno conjugado de uso tópico pode agir de forma a aumentar a resistência uretral às bactérias, como também promover o aumento do calibre uretral e melhorar a dinâmica miccional Esses resultados necessitam de confirmação através de estudos com número maior de crianças.

Performance of PSA and of PSA density in the diagnosis of prostate carcinoma

Objective: The aim of the study was to investigate the influence of the prostate volume and PSA density on the performance of total PSA to diagnosis of prostate carcinoma. Methods: We analyzed 217 patients(PSA 0-10ng/ml) submitted to transrectal sextant prostate biopsy. Criteria for biopsy indication was PSA >2ng/ml and/or digital rectal exam suspicious of prostate cancer. Results: Fifty five patients had prostate neoplasia (25.3 percent) and 8/55 (25.3 percent) the serum PSA was under 4ng/ml. The sensitivity and specificity of the test were respectively 98.2 percent /16.6 percent at a cut-off point of 2.5ng/ml and 85,4 percent /38.8 percent at cutt-off of 4ng/ml. The corresponding values for prostates >40ml or <40ml were: 96.2 percent /8.1 percent and 100 percent /27.7 percent at the cut-off point of 2.5ng/ml, and 92.5 percent /20 percent and 78.5 percent /62.3 percent at a cut-off level of 4ng/ml. For prostates <40ml a PSA cut-off point of 4ng/ml leads to a misdiagnosis in 21.4 percent of the malignant tumors. The median PSAD of benign prostates are different according to prostate volume (.40ml or <40ml). PSAD at cut-off of 0.08 increases the PSAspecificity at both PSA cut-off points. Conclusions: Prostate volume affects the sensitivity and specificity of PSA and the median values of PSAD. PSAD of 0.08 increases the PSA specificity specially at a cut-point of 2.5ng/ml in prostates smaller than 40ml.

CD34 immunoexpression in penile carcinoma

Objective: To investigate microvessel density as a risk factor in squamous cell carcinoma of the penis. Methods: Fifty patients with penile carcinoma were evaluated retrospectively. The mean age and standard deviation were 60.8 +/- 11.8 years. All of them were treated by penectomyand with positive nodes underwent groin lymphadenectomy. Tumor grading was 36 G1 and 24 G2/3. Primary lesion stage was 22pT1 and 28pT2-4. Positive inguinal nodes were observed in 18 patients. Selected paraffin embedded sections were submitted to CD34 immunohistochemical analysis by the avidinbiotin-immunoperoxidase method with antigen retrieval. All slides were examined using an automatic analyser system and the number of micro-vessels in 10 high magnification power fields (400X) were counted in a blind analysis. Results: Median number of microvessels was 631 in G1 versus 695 in G2/3 tumors (p=0.78), and 696 in pT1 versus 566 pT2-4 tumors (p=0.23). The respective data for pN0 patients was 525 and for pN+ was 696 (p=0.01), which is an unexpected result. Conclusion: CD34 immunoexpression or microvessel density determined by this method bear no association with tumor grade, stage or prognosis.

Fatores de risco em carcinomas de células transicionais da bexiga / Risk factors in transitional cell carcinoma of the bladder

Objetivo: Investigar alguns dados epidemiológicos do câncer vesical bem como fatores de risco. Métodos: Foram selecionados 125 pacientes atendidos no período 1980-2002, com idade média de 63,6 +/- 11,3 anos, sendo 97 (77,6 por cento) homens e 28 (22,4 por cento) mulheres. As proporções de tumor G1, G2 e G3 foram: 48 por cento, 35,2 por cento e 16,8 por cento, As proporções dos estádios da lesão primária foram: pTa-5 - 85 (68 por cento) e pT2-4 - 40 (32 por cento). Entre os pacientes com tumores superficiais houve recidiva eem 41 (48,2 por cento). Resultados: O grau da lesão primária mostrou relação com o estádio T (p<0,0001) e sobrevida (p<0,0001), mas não com a taxa de recidiva vesical dos tumores superficiais (p=0,72). O estádio T também mostrou forte correlação com a sobrevida (p<0,001). Conclusões: O CCT é mais comum em homens que mulheres e acomete pacientes com idade média de 63,9 anos. O grau e o estádio T mostram forte correlação com a progressão da doença e a sobrevida.

Alça intestinal invertida como substituto do ureter: estudo experimental em cães / Inverted intestinal handle as substitute of the ureter: experimental study in dogs

Objetivo: Pesquisar a viabilidade da alça ileal invertida como substituto ureteral. Métodos: Quarenta cães foram divididos em 5 grandes grupos de 8 animais, cada um subdividido em 2 subgrupos de acordo com a data do sacrifício (I - sacrifício em 12-15 dias de pósoperatório, e II - 60 dias de pós operatório). Nos grupos A e B fez-se a substituição ureteral parcial com selo de íleo invertido, após abertura lateral do ureter direto com 2 (Grupo A) ou 4 cm (Grupo B) de extensão. Nos demais grupos fez-se a substituição do segmento completo do ureter usando-se um tubo de íleo invertido de comprimento equivalente ao segmento do ureter ressecado com 2cm (Grupo C) e 6cm (Grupo D e E) de extensão. A mucosa ileal foi removida por raspagem ou diérese. A permeabilidade ureteral foi testada por urografia excretora e por exploração anatômica com cateter após o sacrifício. As peças foram estudadas histologicamente após preparação e coloração com hematoxilina-eosina. Resultados: O número de animais com urografia normal após o seguimento foi: A-2, B-2, C-3, D-2 e E-2. A histologia revelou que a serosa ileal se reveste com urotélio, não como decorrência de metaplasia, mas do crescimento a partir da borda da mucosa ureteral. Conclusão: Concluí-se que o íleo invertido não é um bom substituto ureteral.

Expressão nuclear do P53 em carcinoma de células transicionais da bexiga / Nuclear expression of P53 protein in transitional cell carcinoma of the bladder

Objetivo: Investigar a expressão imuno-histoquímica da p53 com fator de risco em carcinoma de células transicionais da bexiga (CCT). Métodos: Foram estudados retraospectivamente 90 pacientes com CCT com idade média de 71 anos: G1-45, G2-29, G3-16, pT1-1-62 e pT2-4-28. Entre os pacientes com tumores não invasivos houve recidiva vesical em 35 casos (55,5 por cento). Os tumores superficiais foram tratados por ressecção trans-uretral associados ao BCG (>G1), e os invasivos por cistectomia radical. O tempo médio de seguimento dos pacientes foi de 55 meses e 25 deles faleceram da doença. A expressão imuno-histoquímica foi estudada em peças preservadas em formol 10 por cento e blocos de parafina pelo método da avidina-biotina-imunoperoxidase. Considerou-se p53 positivo o tumor com índice de marcação nuclear superior a 10 por cento. Resultados: A expressão da p53 mostrou associação com o grau do tumor e com o estádio da lesão primária (p+0,01), mas não com o tamanho do tumor vesical (p=0,25) ou com a taxa de recidiva dos tumores superficiais (p=0,81). Houve forte correlação entre o padrão da marcação da p53 com metástases (p=0,002) e com a sobrevida dos pacientes (p=0,003). Conclusão: A expressão da p53 mostrou valor preditivo para grau tumoral, estádio, incidência de metástase e sobrevida dos pacientes, mas não para recidiva vesical dos tumores superficiais.