A. Figueiredo

Hypertension induced by immunosuppressive drugs: a comparative analysis between sirolimus and cyclosporine

The purpose of this study was to compare the effects of sirolimus (SRL) vs cyclosporine (CsA) concerning the cardiovascular mechanisms hypothetically contributing to hypertension development. Three rat groups were studied: control (vehicle), CsA (5 mg/kg/d), and SRL (1 mg/kg/d). The following parameters were evaluated after 7 weeks of treatment: blood pressured (BP) and heart rate (HR; tail cuff), lipid profile, hematology, plasma and platelet 5-HT and catecholamines (HPLC-ECD), and oxidative equilibrium (serum malondialdehyde [MDA] and total antioxidant status [TAS]). Systolic (SBP) and diastolic blood pressure (DBP) values were higher (P < .001) in both the CsA (146.2 +/- 4.5 and 124.9 +/- 4.5 mm Hg) and SRL (148.9 +/- 4.8 and 126.4 +/- 6.0 mm Hg) groups vs the controls (115.9 +/- 3.3 and 99.1 +/- 2.0 mm Hg). However, HR values were elevated in CsA but not SRL animals. The dyslipidemic pattern of CsA was even more enhanced in the SRL group, with significantly higher low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) levels vs CsA (P < .05); red blood cells, hematocrit, hemoglobin concentration, mean platelet volume, and platelet distribution width were significantly (P < .05) higher in the SRL vs CsA group. The pro-oxidative profile (increased MDA/TAS) in the CsA group was not reproduced in the SRL cohort. While plasma and platelet 5-HT were elevated in SRL rats, catecholamine content was higher in CsA animals. In conclusion, this study demonstrated that CsA and SRL produce identical hypertensive effects. However, while CsA promotes oxidative stress and sympathetic activation, SRL mainly interferes with lipid profile and hematological parameters. Thus, the hypertensive effects of CsA, a calcineurin inhibitor, and of SRL, an mTOR inhibitor, are associated with impairment of distinct cardiovascular pathways.

Training of European urology residents in laparoscopy: results of a pan-European survey

To assess the participation of European urology residents in urological laparoscopy, their training patterns and facilities available in European Urology Departments.

Surgical complications in 2000 renal transplants

INTRODUCTION Renal transplantation is the best treatment for end-stage renal disease. In the last years, we have seen improvements in immunosuppressive treatment, which have allowed patients to experience a better quality of life and graft survival. Nevertheless, surgical complications remain important problems that increase morbidity, mortality, costs, and hospitalization. Our purpose was to evaluate surgical complications among a large series of 2000 renal transplantations. PATIENTS AND METHODS We retrospectively analyzed all surgical complications among 2000 renal transplants performed between June 1980 and March 2010 in our department. RESULTS Among 318 (15.9%) surgical complications, 4.8% of patients had urologic problems. Ureteral stenosis and fistula, stent obstruction, and ureteral necrosis occurred in 2.7%, 1.8%, 0.1%, and 0.2% of patients, respectively. Vascular complications reported in 2.7% of patients included arterial or venous thrombosis (1.0% or 0.4%), both arterial and venous thrombosis (0.1%), renal infarction (0.1%), renal artery aneurysm (0.1%) as well as arterial stenosis (0.5%), kinking (0.4%), or dissection (0.1%). Other complications, not specifically related with transplantation surgery, occurred in 4.4% of patients. CONCLUSION Renal transplantation is a safe surgery by experienced teams. Our rates of surgical complications were within those reported by other series. A meticulous surgical technique is mandatory to prevent them. Prompt diagnosis and management are required to prevent graft damage and patient morbidity.

Omega-3 Fatty Acids Inhibit Tumor Growth in a Rat Model of Bladder Cancer

Omega-3 (ω-3) fatty acids have been tested on prevention and treatment of several cancer types, but the efficacy on “in vivo” bladder cancer has not been analyzed yet. This study aimed at evaluating the chemopreventive efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) mixture in an animal model of bladder cancer. Forty-four male Wistar rats were divided into 4 groups during a 20-week protocol: control; carcinogen—N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN); ω-3 (DHA + EPA); and ω-3 + BBN. BBN and ω-3 were given during the initial 8 weeks. At week 20 blood and bladder were collected and checked for the presence of urothelium lesions and tumors, markers of inflammation, proliferation, and redox status. Incidence of bladder carcinoma was, control (0%), ω-3 (0%), BBN (65%), and ω-3 + BBN (62.5%). The ω-3 + BBN group had no infiltrative tumors or carcinoma in situ, and tumor volume was significantly reduced compared to the BBN (0.9 ± 0.1 mm3 versus 112.5 ± 6.4 mm3). Also, it showed a reduced MDA/TAS ratio and BBN-induced serum CRP, TGF-β1, and CD31 were prevented. In conclusion, omega-3 fatty acids inhibit the development of premalignant and malignant lesions in a rat model of bladder cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties.

Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory Properties

To investigate the anti-carcinogenic effects of Atorvastatin (Atorva) on a rat bladder carcinogenesis model with N-butyl-N-(4-hydroxibutil)nitrosamine (BBN), four male Wistar rat groups were studied: (1) Control: vehicle; (2) Atorva: 3 mg/kg bw/day; (3) Carcinogen: BBN (0.05%); (4) Preventive Atorva: 3 mg/kg bw/day Atorva + BBN. A two phase protocol was used, in which the drug and the carcinogen were given between week 1 and 8 and tumor development or chemoprevention were expressed between week 9 and 20, when the bladders were collected for macroscopic, histological and immunohistochemical (p53, ki67, CD31) evaluation. Serum was assessed for markers of inflammation, proliferation and redox status. The incidence of bladder carcinoma was: control 0/8 (0%); Atorva 0/8 (0%); BBN 13/20 (65%) and Atorva + BBN 1/8 (12.5%). The number and volume of tumors were significantly lower in the Atorva + BBN group, with a marked reduction in hyperplasia, dysplasia and carcinoma in situ lesions. An anti-proliferative, anti-inflammatory and antioxidant profile was also observed in the preventive Atorva group. p53 and ki67 immunostaining were significantly increased in the BBN-treated rats, which was prevented in the Atorva + BBN group. No differences were found for CD31 expression. In conclusion, Atorvastatin had a clear inhibitory effect on bladder cancer development, probably due to its antioxidant, anti-proliferative and anti-inflammatory properties.

Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis.

Purpose: To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumour growth and in its prevention. Methods: Drug treatments were performed during the first 8 weeks, followed by 12 weeks for tumour expression/prevention, in the following groups: control – vehicle; carcinogen – 0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL) – 10 mg/kg/day and preventive CEL+BBN. The bladders were analysed for number and volume of tumour and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status. Results: The main findings were: a) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN+CEL: 12.5% (1/8); b) the mean tumour volume per rat with tumour and per tumour were significantly lower in the BBN+CEL group (21.2 and 5.3±0.4 mm3) vs BBN (138.5±7.5 and 112.5±6.4 mm3); c) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumours and carcinoma in situ - CIS) lesions were notoriously reduced in the CEL+BBN treatment; d) CEL significantly reduced serum TGF-β1 and CRP and increase TNF-α and IL-1β (P

Inhibition of bladder tumour growth by sirolimus in an experimental carcinogenesis model

What’s known on the subject? and What does the study add?

Characterization of a rat model of moderate chronic renal failure--focus on hematological, biochemical, and cardio-renal profiles.

The pathophysiological modifications underlying chronic renal failure seems to be dependent on the insufficiency degree, which will determine the moment to start therapy. As there is yet limited information about animal models of moderate chronic renal failure, we intended to perform a complete characterization of the hematological and cardio-renal alterations induced by partial nephrectomy. Blood samples from control and chronic renal failure rats were collected at 0, 3, 9, and 15 weeks in order to evaluate renal function, hematological parameters, iron metabolism, blood lipids, peripheral sympathetic nervous system, and inflammatory and redox status markers. BP, tissues trophy indexes, and kidney histomorphology were also assessed. Our data are consistent with a sustained moderate degree of chronic renal failure with a quickly compensated modest anaemia, though presenting iron metabolism disturbances. Despite the reasonable degree of functionality of the remnant kidney, as suggested by the anaemia correction and by the kidney hypertrophy and moderate lesions, several important cardiovascular modifications were developed. Our model presented hypertension, dyslipidemia, erythropoietic disturbances, sympathetic activation, and oxidative stress. This model might be a good tool to study the cellular/molecular mechanisms underlying moderate stages of chronic renal failure and to evaluate the therapeutic efficacy for prevention and treatment/correction of cardio-renal anaemia syndromes and complications in early stages.

Surgical complications in 1000 renal transplants

There were 154 (15.4%) postoperative surgical complications. The urological complications were as follows: urinary obstruction in 31 (3.1%) patients, ureteral fistulae in 25 (2.5%), and distal ureteral necrosis in 4 (0.4%). There were 2 (0.2%) vesical ruptures, 1 calcification of the stent, and 1 broken stent after traction. Twenty-four of the 25 fistulae occurred within 4 weeks after transplantation, while the interval to onset of obstruction ranged from 10 days to 11 years. Obstructions were cured by open surgery in 23 cases, by endoscopic incision in 4 cases, and by temporary stenting in 4 others. Among the patients with urinary leakage, 23 were treated surgically and 2 conservatively (Table 1). Vascular complications developed after 14 (1.4%) transplants: 6 (0.6%) renal artery thromboses, 3 (0.3%) venous thromboses, 2 artery aneurysms, 1 arterial stenosis, 1 arterial kinking, and 1 arterial dissection. All patients were reoperated. The lymphoceles that occurred in 26 (2.6%) patients were mostly treated conservatively, with only 6 cases requiring surgical drainage. There were 50 (5.0%) wound-related complications: 32 wound hematomas and 18 wound infections. Overall, seven (0.7%) grafts were lost, all due to vascular complications (5 to arterial thrombosis and 2 to venous thrombosis), despite early surgery. One patient died of septicemia after a urinary obstruction. The actuarial graft survival rates at 1, 3, 5, 10, and 15 years are 92%, 86%, 78%, 60%, and 50%, respectively.

Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL), on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P), and curative CEL (BBN+CEL-C) groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%), BBN 13/20(65%), CEL 0/8(0%), CEL+BBN-P 1/8(12.5%), and BBN+CEL-C 6/8(75%). The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.