Right atrium tumor extension through the inferior vena cava. considerations about nine cases operated under cardiopulmonary bypass

Abstract Introduction: Adrenocortical and renal cell carcinomas rarely invade the right atrium (RA). These neoplasms need surgical treatment, are very aggressive and have poor prognostic and surgical outcomes. Case series: We present a retrospective cohort of nine cases of RA invasion through the inferior vena cava (four adrenocortical carcinomas and five renal cell carcinomas). Over 13 years (2002-2014), nine patients were operated in collaboration with the team of urologists. Surgery was possible in all patients with different degrees of technical difficulty. All patients were operated considering the imaging examinations with the aid of CPB. In all reported cases (renal or suprarenal), the decision to use CPB with deep hypothermic circulatory arrest (DHCA) on surgical strategy was decided by the team of urological and cardiac surgeons. Conclusion: Data retrospectively collected from patients of public hospitals reaffirm: 1) Low incidence with small published series; 2) The selected cases did not represent the whole historical casuistry of the hospital, since they were selected after the adoption of electronic documentation; 3) Demographic data and references reported in the literature were presented as tables to avoid wordiness; 4) The series highlights the propensity to invade the venous system; 5) Possible surgical treatment with the aid of CPB in collaboration with the urology team; 6) CPB with DHCA is a safe and reliable option; 7) Poor prognosis with disappointing late results, even considering the adverse effects of CPB on cancer prognosis are expected but not confirmed.

Validation of self - confidence scale for clean urinary intermittent self - catheterization for patients and health - caregivers

ABSTRACT Objective To validate a measurement instrument for clean intermittent self-catheterization for patients and health-caregivers. Material and Methods Methodological study of instrument validation performed at a Rehabilitation Center in a University hospital for patients submitted to clean intermittent self-catheterization and their health-caregivers. Following ethical criteria, data were collected during interview with nurse staff using a Likert question form containing 16 items with 5 points each: “no confidence”=1, “little confidence”=2, “confident”=3, “very confident”=4 and “completely confident”=5. Questionnaire called “Self-Confident Scale for Clean Intermittent Self-catheterization” (SCSCISC) was constructed based on literature and previously validated (appearance and content). Results The instrument was validated by 122 patients and 119 health-caregivers, in a proportion of 15:1. It was observed a good linear association and sample adequacy KMO 0.931 and X2=2881.63, p<0.001. Anti-image matrix showed high values at diagonal suggesting inclusion of all factors. Screen plot analysis showed a suggestion of items maintenance in a single set. It was observed high correlation of all items with the total, alpha-Cronbach 0.944. The same results were obtained in subsamples of patients and health-caregivers. Conclusion The instrument showed good psychometric adequacy corroborating its use for evaluation of self-confidence during clean intermittent self-catheterization.

Expression profiles of eNOS, iNOS and microRNA-27b in the corpus cavernosum of rats submitted to chronic alcoholism and Diabetes mellitus

Abstract Purpose: To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. Methods: Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. Results: Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. Conclusion: The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.

Complications after bladder augmentation in children

PURPOSE : Bladder augmentation is an effective surgical procedure for increasing bladder capacity and reducing pressure on the urinary system. It is indicated for patients with anomalies such as spina bifida, myelomeningocele, urethral valve and bladder exstrophy, who progress with low tolerance of medication. CASES : This was a retrospective study conducted on pediatric patients submitted to bladder augmentation from 2000 to 2011. RESULTS : 34 patients aged 4 to 17 years were submitted to bladder augmentation, 30 of them with an ileal loop and 4 with a ureter.A continent urinary shunt was performed in 16 patients, the Mitrofanoff conduit was associated in 15, and the Macedo technique was used in one. Mean follow-up was 34.35 months (1 to 122 months). Mean creatinine was 1.5 ng/ml (0.4 to 7.5 ng/ml) preoperatively and 1.78 ng/ml postoperatively. Three patients required a renal transplant during follow-up. There was improvement or resolution of vesicoureteral reflux in 83.5% of the kidneys on the right and in 75% on the left. Bladder capacity increased, on average, from 152.5 ml to 410 ml. The main complications were vesical lithiasis in 3 patients and conduit perforation in one. CONCLUSION : Bladder augmentation showed good results in this series, preserving renal function in most of the patients.

Expression of VEGF and collagen using a latex biomembrane as bladder replacement in rabbits

OBJECTIVE: To investigate the VEGF expression and collagen deposition using a latex biomembrane as bladder replacement in rabbits. MATERIALS AND METHODS: After partial cystectomy, a patch of a non-vulcanized latex biomembrane (2 x 2 cm) was sewn to the bladder of rabbits with 5/0 monofilament polydioxanone sulfate sutures in a watertight manner. Groups of 5 animals were killed at 15, 45 and 90 days after surgery and the bladder was removed. Sections of 5µm were cut and stained with picrosirius-red in order to estimate the amount of extracellular matrix in the graft. To confirm the presence of VEGF in tissues, protein expression was determined by immunohistochemistry. RESULTS: No death, urinary leakage or graft extrusion occurred in any group. All bladders showed a spherical shape. A progressive reduction in the amount of collagen occurred in the graft area and was negatively and linearly correlated with time (p < 0.001). VEGF expression was higher in grafted areas when compared to controls at 15 and 45 days after surgery and decreased with time (p < 0.001). CONCLUSION: The latex biomembrane as a matrix for partial bladder replacement in rabbits promotes temporary collagen deposition and stimulates the angiogenic process.

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.

Giant adrenal myelolipoma associated with 21-hydroxylase deficiency: unusual association mimicking an androgen-secreting adrenocortical carcinoma / Mielolipoma adrenal gigante associado à deficiência da 21-hidroxilase: associação não usual simulando um carcinoma adrenocortical secretor de androgênios

The objective of this study was to describe a case of giant myelolipoma associated with undiagnosed congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21OH) deficiency. Five seven year-old male patient referred with abdominal ultrasound revealing a left adrenal mass. Biochemical investigation revealed hyperandrogenism and imaging exams characterized a large heterogeneous left adrenal mass with interweaving free fat tissue, compatible with the diagnosis of myelolipoma, and a 1.5 cm nodule in the right adrenal gland. Biochemical correlation has brought concerns about differential diagnosis with adrenocortical carcinoma, and surgical excision of the left adrenal mass was indicated. Anatomopathologic findings revealed a myelolipoma and multinodular hyperplasic adrenocortex. Further investigation resulted in the diagnosis of CAH due to 21OH deficiency. Concluded that CAH has been shown to be associated with adrenocortical tumors. Although rare, myelolipoma associated with CAH should be included in the differential diagnosis of adrenal gland masses. Moreover, CAH should always be ruled out in incidentally detected adrenal masses to avoid unnecessary surgical procedures.

O objetivo deste trabalho foi descrever um caso de mielolipoma gigante associado à hiperplasia adrenal congênita (HAC) por deficiência da 21-hidroxilase (21OH). Paciente do sexo masculino, 57 anos de idade, encaminhado por achado ultrassonográfico de massa adrenal esquerda. Investigação bioquímica revelou hiperandrogenismo e exames de imagem revelaram grande lesão sólida em adrenal esquerda de aspecto heterogêneo, entremeada de tecido gorduroso, compatível com diagnóstico de mielolipoma, e um nódulo de 1,5 cm na adrenal direita. Os achados bioquímicos sugeriam o diagnóstico de carcinoma adrenocortical, indicando cirurgia para retirada da massa adrenal esquerda. O anatomopatológico confirmou mielolipoma e hiperplasia multinodular do córtex adrenal. A investigação subsequente diagnosticou HAC por deficiência da 21OH. Concluiu-se que a HAC tem sido descrita em associação com tumores adrenocorticais. Apesar de raro, o mielolipoma associado à HAC deve ser incluído nas possibilidades diagnósticas de massa adrenal. Adicionalmente, a HAC deve ser sempre afastada nos casos de massa adrenal de achado incidental, evitando cirurgias desnecessárias.

Use of a latex biomembrane for bladder augmentation in a rabbit model: biocompatibility, clinical and histological outcomes

PURPOSE: To investigate histological features and biocompatibility of a latex biomembrane for bladder augmentation using a rabbit model. MATERIAL AND METHODS: After a partial cystectomy, a patch of a non-vulcanized latex biomembrane (2x4 cm) was sewn to the bladder with 5/0 monofilament polydioxanone sulfate in a watertight manner. Groups of 5 animals were sacrificed at 15, 45 and 90 days after surgery and the bladder was removed. The 5-µm preparations obtained from grafted area and normal bladder were stained with hematoxylin-eosin. Immunohistochemical staining was performed with a primary antibody against alpha-actin to assess muscle regeneration. RESULTS: No death, urinary leakage or graft extrusion occurred in any group. All bladders showed a spherical shape. Macroscopically, after 90 days, the latex biomembrane was not identifiable and the patch was indistinguishable from normal bladder. A bladder stone was found in one animal (6.6 percent). On the 90th day, histology revealed continuity of transitional epithelium of host bladder tissue on the patch area. At this time, the muscle layers were well organized in a similar fashion to native bladder muscle layers. The inflammatory process was higher on grafted areas when compared to controls: 15 days - p < 0.0001, 45 days - p < 0.001, and 90 days - p < 0.01. The anti alpha-actin immunoexpression peaked at 45 days, when the graft was observed covered by muscle cells. CONCLUSION: The latex biomembrane is biocompatible and can be used in models for bladder augmentation in rabbits. It promotes epithelium and muscle regeneration without urinary leakage.

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.

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.

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.

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.

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.

Results of novel strategies for treatment of Wilms' tumor

OBJECTIVE: To evaluate treatment outcomes in Wilms' tumor (WT). MATERIALS AND METHODS: We studied 53 children with median age of 2 years with WT, stages I-19, II-14, III-12, IV-6 and V-2. Treatment consisted of surgical excision plus adjuvant (40 children) or neoadjuvant and adjuvant chemotherapy (unresectable tumor, n = 8, or caval tumor extension, n = 5). Chemotherapy and radiotherapy followed protocols of Brazilian Wilms' Tumor Study Group excepting 16 cases with stage I disease that received a short duration postoperative treatment with vincristine (VCR - 11 doses) and dactinomycin (AMD - 4 doses). Relapsed WT was treated with multiagent regimens including cisplatin/carboplatin, cyclophosphamide, ifosfamide and etoposide. One patient with resistant relapsed WT was treated by high-dose conditioning chemotherapy with stem cell rescue. RESULTS: Overall and disease-free survival rates at 5 years were respectively 88.2 ± 5.0 percent and 76.7 ± 6.6 percent. Short duration therapy for stage I tumor showed a disease-free survival rate of 100 percent in a median time of 101 months (range 14 to 248 months). Overall and disease-free survival of 10 patients with recurrent WT at 5 years was 42.8 percent. The child treated with high-dose chemotherapy plus stem cell transplant is alive without evidence of disease 84 months from relapse. CONCLUSION: The postoperative chemotherapy in stage I disease can be reduced without compromising the cure rate. The treatment of unfavorable stage III and IV disease or relapsed tumor remains a challenge.

Calcium channel blocker and renal mitochondrial function in warm renal ischemia

OBJECTIVE: Ions, particularly calcium ions, play an important role in ischemia-reperfusion cell injury. In this study, we investigated the action of verapamil on the mitochondrial function of kidneys submitted to ischemia without blood reperfusion in order to study isolated early and late ischemic effects. MATERIALS AND METHODS: 44 rats were submitted to bilateral warm renal ischemia for 30 minutes. The kidneys were then immediately reperfused with saline or Euro-Collins (EC) solution, with and without previous administration of 0.35 mg/kg of verapamil. Mitochondrial function was assessed at the end of renal perfusion and after 24 hours of cold preservation. RESULTS: In kidneys perfused with saline, verapamil allowed a significant early preservation of state III mitochondrial respiration, a result that was no longer evident after 24 hours. In kidneys perfused with EC solution, verapamil did not change state III for either early or late evaluations. Comparison of the groups showed that the results obtained for kidneys perfused with EC were always superior to those obtained for the saline group, except for the initial analysis of kidneys treated with saline and verapamil, which showed results similar to those obtained with EC perfusion alone. CONCLUSION: Administration of verapamil before warm ischemia provides partial and short-lasting functional protection of the mitochondrial function in kidneys perfused with sodium rich saline. With Euro-Collins solution, verapamil did not show any additional beneficial effect. This fact permits us to conclude that protective action is effective only under conditions that facilitate increased sodium uptake and/or potassium loss.

Modulation of urethral alpha-sympathetic by parasympathetic before and following bethanechol chloride injection

INTRODUCTION AND OBJECTIVES: Chagas' disease causes specific parasympathetic denervation and in its digestive clinic form promotes also functional alterations in bladder. Thus, the aim was to investigate the existence of balance between sympathetic and parasympathetic systems in lower urinary tract, as occurs in other organs. We verified the urethral closing pressure before and following parasympathetic stimulus. PATIENTS AND METHODS: For that, the urethral closure pressure was studied before and after the injection of 5 mg of bethanechol chloride subcutaneously in 28 voluntary female patients, divided into 4 groups. The constitution of theses groups was: A) normal control = 6 patients; B) Chagas' disease with positive serology only = 5 patients; C) Chagas' disease with cardiac disease = 6 patients, and D) Chagas' disease with digestive disease and vesical hyporeflexia = 11 patients. Urethral profilometry was performed through perfusion urethral catheter with a 6.5 ml/minute flow and a traction rate of 5 mm/minute. RESULTS: Means and standard deviations for urethral closure pressure before bethanechol chloride were respectively: group A = 67.3 ± 7.1; group B = 69.2 ± 7.4; group C = 95.8 ± 5.1; group D = 82.1 ± 8.4. After bethanechol chloride they were: group A = 66.0 ± 6.6; group B = 77.0 ± 7.6; group C = 98.3 ± 8.8; group D = 45.9 ± 6.2. The Kruskal Wallis statistical test did not show statistically significance difference between groups A, B, C. However, it was statistically significant between groups C and D with p = 0.003. Wilcoxon test showed p = 0.001, only for values in group D before and following bethanechol chloride. CONCLUSIONS: Chagas' disease in its intestinal form seems to alter urethral function as well. Parasympathetic stimulation decreased urethral pressure, indicating potential modulation by the parasympathetic system over the sympathetic system

Is CO2 gas unsufflator necessary for laparoscopic training in animals?

Objective - To verify the efficacy and safety of compressed air to produce pneumoperitoneum for laparoscopic surgery in pigs for a training program of residence. Methods - Dalland pigs weighing 15-17kg underwent general anethesia and mechanical ventilation. They were divided in 3 groups: A - (38) the pneumoperitnoneum was established with an automatic COZ insufflator, B - (7) as in A except the C02 gas was changed by compressed air, and C - (11) abdomen insufflation was obtained with compressed air directly from hospital pipe network system. Intra-abdominal pressure in all groups was kept between 12 and 15 mmHg. The laparoscopic procedures performed were distributed proportionally among groups: 20 bilateral nephrectomy, 20 dismembered pyeloplasty and 16 partial nephrectomy. Arterial blood sampling for gasometry was obtained before and 2h after establishment of pneumoperitoneum in 5 pigs of group C. Results - The cost of 25 4,5kg COZ container used in group A was R$ 3,150.00 (U$ 1,050.00). The mean length time of surgeries in groups A, B and C were respectively: 181±30rnin, 196±39min e 210±47min (p>0.05). Respiratory alkalosis occurred in 3 out of 5 pigs of group C. No animal exhibited signs of gas embolism or died during surgery. Conclusion - The use of compressed air for laparoscopy in pigs was safe, reduced costs and did not require the use of an automatic gas insufflator.

Efeito do cloridrato de oxibutinina na hiperatividade vesical conseqüente a cistite hemorrágica / Effects of oxybutynin in bladder hyperactivity caused by hemorrhagic cystitis

INTRODUÇAO: A oxibutinina atua como agente anticolinérgico que tem ação anti-muscarínica e, principalmente, ação antiespasmódica na musculatura lisa vesical. Assim, ela causa aumento da capacidade vesical e diminui a frequência miccional e bloqueia o estímulo inicial da micção. OBJETIVO: Verificar se a oxibutinina atua sobre a hiperatividade vesical causada pela cistite hemorrágica, dependente do óxido nítrico. MÉTODOS: Foram estudados dois grupos de animais. O controle com 5 ratas e o experimental com 10 ratas, cujos pesos variaram entre 200g a 250g. A cistite hemorrágica foi provocada pela injeção intraperitoneal de ciclofosfamida 200mg/kg, na véspera do experimento. Após 24 horas, as ratas foram anestesiadas com uretana 1,25mg/kg. A seguir, foi feita cistostomia com cateter P-50. Esse cateter foi conectado em Y a uma bomba de infusão contínua com fluxo de água de 0,3ml/min e a um polígrafo para o registro da cistometria. O registro cistométrico foi feito com a velocidade do papel de 0,05cm/seg, com sensibilidade de 20 e calibração para um curso de 60mm para uma pressão de 100mmHg. Os parâmetros estudados foram: freqüência de contração (Fc), intensidade das contrações (Ic), tempo de enchimento vesical (Te), tempo de contração vesical (Tc) e capacidade vesical (Cv), que foi determinado pelo Te x Fluxo. Esses parâmetros foram determinados por suas médias durante o período de observação de 10 min. Após o registro, foi infundido por gavagem 71 mg/kg de cloridato de oxibutinina. Uma hora depois foi feita nova cistometria. A análise estatística foi feita pelo método de Kruskal-Wallis que comparou os valores do grupo controle com o experimental. O p foi considerado significante quando menor que 0,05. RESULTADOS: A comparação entre os dois grupos dos parâmetros estudados antes da infusão do cloridrato de oxibutinina mostrou: Fc - p=0,007; Ic - p=0,0002; Te - p=0,768; Tc - p=0,492; Cv - p=0,056 A comparação dos parâmetros estudados depois da droga mostrou: Fc - p= 0,055; Ic - p=0,0002; Te - p=0,957; Tc - p=0,181; Cv - p=0,206. CONCLUSÕES: O cloridrato de oxibutinina nesse modelo experimental atuou de forma a alterar somente a freqüência das miccções, controlando a hiperatividade e não promovendo alterações nos demais parâmetros estudados.

Ação do citrato de sildenafil sobre a função uretral de ratas com desnervação vesical / Effect of sildenafil citrate in the urethral function in rats with denervated bladder

O óxido nítrico atua como neurotransmissor não adrenérgico e não colinérgico na bexiga e na uretra. Sua forma de ação se faz pela ativação da guanilatociclase responsável pela transformação de GMP em GMPc que promove o relaxamento da fibra muscular lisa. O citrato de sildenafil causa aumento do GMPc, através da inibição de fosfodiesterases, que hidrolisam o GMPc. Assim, o objetivo do experimento foi verificar sua ação na uretra. MÉTODOS: Estudou-se 6 ratas com peso aproximado de 200g. A anestesia foi com uretana na dose de 1,25 mg/kg. As cistometrias, em número de 3, foram realizadas através de cistostomia com cateter P50. A primeira logo após a cistostomia; a segunda depois da desnervação cirúrgica da bexiga e a terceira uma hora após a infusão gástrica do citrato de sildenafil. O sistema de registro das pressões constou de uma bomba de infusão contínua regulada para 0,3ml/minuto conectada em Y com o cateter P50 e a um polígrafo Narco-Bioystem. Nas cistometrias avaliou-se as pressões vesicais máxima e mínima nos momentos: normais-(I); desnervadas (II) e desnervadas com citrato de sildenafil na dose de 1 mg/kg (III). A análise estatística foi feita pelo método de Wilcoxon. RESULTADOS: As médias das pressões máximas (pma) foram: momentos I (x=86,6 - SD=10,1) ; momentos II (x=42,6 - SD=15,0) e momentos III (x=30,8 - SD=12,4). As médias das pressões mínimas (pmi) foram: momentos I (x=72,1 - SD=18,9); momentos II (x=31,1 - SD=9,8); momentos III ( x=14,5 - SD=9,5). A análise estatística entre as pma e pmi no mesmo grupo mostrou p< 0,01 para o grupo III, sendo maior que 0,05 para os demais. A comparação das pma revelou p< 0,002 entre os momentos I-II e I-III, sendo maior que 0,05 entre os momentos II e III. A comparação das pmi mostrou p< 0,004 entre os momentos I-II; p< 0,002 entre os momentos I -III e p <0,01 entre os momentos II-III, havendo portanto nível de significância entre os 3 momentos. CONCLUSÕES: 1) A desnervação vesical promove queda nas pressões uretrais máxima e mínima; 2) O Citrato de sildenafil amplia a faixa pressórica de trabalho da uretra devido a diminuição da pressão mínima; 3) O citrato de sildenafil não altera a pressão uretral máxima depois da desnervação.