Browsing by Author "Mota, A"
Now showing 1 - 10 of 50
Results Per Page
Sort Options
- Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesisPublication . Parada, B; Sereno, J; Reis, F; Teixeira-Lemos, E; Garrido, P; Pinto, AF; Xavier da Cunha, MF; Pinto, R; Mota, A; Figueiredo, A; Teixeira, FPURPOSE: 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 tumor growth and in its prevention. RESULTS: The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (V) CEL reduced MDA formation in serum (p < 0.001) and liver (p < 0.05) and also showed a trend to reduction in kidney. METHODS: Drug treatments were performed during the first 8 w, followed by 12 w for tumor 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 analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status. CONCLUSIONS: Celecoxib has demonstrated an outstanding inhibitory effect on bladder cancer chemoprevention, which might be due to its expected anti-inflammatory actions, as well as by anti-proliferatory and antioxidant actions. This data supports a pivotal role of cancer chemoprevention strategies based on COX-2 inhibition.
- Cadaveric donor factor variations during a 12-year period: influence on kidney transplant outcomesPublication . Nunes, P; Parada, B; Pratas, J; Roseiro, A; Figueiredo, A; Macário, F; Rolo, F; Mota, AOur purpose was to evaluate changes in cadaveric donor factors between 1993 and 2004 and their impact on the short- and long-term outcomes of renal transplants in a single center. PATIENTS AND METHODS: Cadaveric renal transplants performed in our unit between 1993 and 2004 were divided in two groups of identical length: A (n = 455; 1993-1998) and B (n = 465; 1999-2004). Major differences related to donor, graft, and recipient factors were analyzed between groups and correlated with main outcome parameters. Recipient age, gender, weight, etiology of end-stage renal disease, average length of dialysis, and cold ischemia were not different in the two periods. RESULTS: Grafts harvested in our hospital were more frequent in group A (92.3 vs 78.2%; P < .005). Traumatic causes of death were more frequent before 1999: 90.9 vs 70.9% (P < .001). Mean donor age was higher after 1999: 31.37 vs 35.94 years (P < .005). Female donors were more frequent in the second period: 20.5 vs 26.6% (P < .05). Mean donor weight was also higher: 52.36 vs 67.86 kg (P < .05). All of these differences were unfavourable characteristics regarding graft outcomes. Delayed graft function (A = 13%, B = 24.2%), acute rejection episodes (A = 41.2%, B = 28%), and chronic allograft dysfunction (A = 23.5%, B = 14.4%) were also significantly different between the two cohorts (P < .005). Graft function (serum creatinine at 1 and 2 years), patient and graft survivals, causes of graft loss, and of patient death were similar across time. CONCLUSION: The unfavorable tendency in the quality of cadaveric donors during the last 12 years had no negative impact on graft function and patient outcome.
- Calcineurin inhibitor-free immunosuppression in renal transplantationPublication . Parada, B; Mota, A; Nunes, P; Macário, F; Pratas, J; Bastos, C; Figueiredo, APURPOSE: To describe our initial results using a calcineurin inhibitor-free immunosuppression protocol in renal transplants. PATIENTS AND METHODS: Between October 2001 and June 2003, 56 recipients of a renal allografts were started on an immunosuppression protocol without calcineurin inhibitors, consisting of basiliximab, sirolimus, mycophenolate mofetil, and steroids. We analyzed patient and graft survival, acute rejection episodes, and renal function. RESULTS: The mean follow-up was 19.6 months. Actuarial patient survival at 1 and 2 years was 98.1% and 95.3%, respectively. Actuarial graft survival at 1 and 2 years was 92.9% and 87.6%, respectively. Acute rejection occurred in 27.8% of the patients, usually Banff 1 (73.3%). There was stable renal function with mean serum creatinine of 1.3, 1.4, 1.3, and 1.3 mg/dL at 1, 6, 12, and 24 months after transplant. CONCLUSIONS: The use of immunosuppression free of calcineurin inhibitors is effective and safe. Further follow-up is needed to evaluate the impact on long-term results.
- Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory PropertiesPublication . Parada, B; Reis, F; Pinto, A; Sereno, J; Xavier-Cunha, M; Neto, P; Rocha-Pereira, P; Mota, A; Figueiredo, A; Teixeira, FTo 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.
- De novo tacrolimus – associated hemolytic uremic syndrome after renal transplantation - Case reportPublication . Neto, P; Lopes, K; Macário, F; Alves, R; Mota, A; Campos, M
- Diabetes Mellitus após transplante renalPublication . Ruas, L; Bastos, M; Alves, R; Rodrigues, D; Barros, L; Mota, A; Carvalheiro, M; Ruas, A; Furtado, AL
- Do elderly patients deserve a kidney graft?Publication . Nunes, P; Mota, A; Parada, B; Figueiredo, A; Rolo, F; Bastos, C; Macário, FPURPOSE: Compare renal transplant long-term outcomes among recipients aged 60 years or older with those in younger patients. PATIENTS AND METHODS: We analyzed 103 transplants in recipients above 60 years of age for the influence of key factors related to the graft and patient. The results were compared with 1060 transplant recipients aged 18 to 59 years. RESULTS: The mean ages were 62.93 and 40.35 years for the older and younger group. The older group showed a higher prevalence of obesity and unknown etiologies for the end-stage renal disease. Important comorbidity was significantly more frequent among recipients aged more than 60 years, mainly of a cardiovascular nature (56% vs 18.5%). Donor age (39.75 vs 31.59 years), cold ischemia time (22.43 vs 20.49 hours) and human leukocyte antigen compatibilities (2.59 vs 2.36) were significantly greater in the older subset. After a mean follow-up of 4.72 and 6.07 years for the older versus younger group, we found no differences in initial graft function, acute rejection rate, and serum creatinine/clearance. Patient and graft survivals at 1, 5, and 10 years were lower among the 60+ group. There were no differences in graft survival censored for death with a functioning graft, namely, 95.1%, 89.4%, and 81.2% for the 60+ cohort. The main cause of graft loss in the older group was death with a functioning graft. CONCLUSION: Renal transplantation should be considered for selected patients older than 60 years. Despite a shorter life expectancy, they benefit from it similar to younger recipients.
- Early cyclosporine a withdrawal in kidney transplant recipients under a sirolimus-based immunosuppressive regimen: pathological study of graft biopsies at 1-year posttransplantPublication . Ruiz, JC; Campistol, JM; Mota, A; Prats, D; Gutiérrez, A; Castro, A; Pinto, JR
- Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesionsPublication . Ruiz, JC; Campistol, JM; Grinyó, JM; Mota, A; Prats, D; Gutiérrez, JA; Henriques, ACBACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNIs) is partially responsible for the development of chronic allograft nephropathy (CAN). Sirolimus has demonstrated its potential to substitute for CNIs because it lacks significant nephrotoxicity and shows a short-term immunosuppressive capacity comparable with that of cyclosporine. This results in the maintenance of better renal function when cyclosporine is eliminated, but it has not been demonstrated whether this benefit is associated with an improvement in the pathologic substrate and a reduction in CAN. METHODS: We analyzed pretransplant and 1-year renal-allograft biopsies from 64 patients enrolled in a multicenter trial. Patients received cyclosporine and sirolimus during the first 3 months after transplant and were then randomly assigned to continue with cyclosporine or have it withdrawn. Histologic chronic allograft lesions were compared between groups. RESULTS: The percentage of patients in whom chronic pathologic lesions progressed was lower in the group of cyclosporine elimination. Significant differences were observed in chronic interstitial and tubular lesions (70% vs. 40.9% [P<0.05] and 70% vs. 47.8% [P<0.05], respectively), whereas no differences were observed in acute lesions (subclinical rejection). Prevalence of CAN at 1 year was lower in this group, as was the severity and incidence of new cases (P<0.05). CONCLUSIONS: Early cyclosporine withdrawal associated with sirolimus administration is followed by an improvement in renal function, a reduction in the progression of chronic pathologic allograft lesions, and a lower incidence of new cases and severity of CAN during the first year after transplantation. This benefit may result in better long-term graft outcome.
- Early elimination of cyclosporine in kidney transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesionsPublication . Ruiz, JC; Campistol, JM; Mota, A; Prats, D; Gutiérrez, JA; Castro, A; Morales, JCyclosporine elimination in a regimen including sirolimus has been shown to be a safe and effective approach to improve graft function. Nevertheless, it is still unknown whether the functional benefit of CyA withdrawal coincides with a subsequent reduction in histologic lesions of chronic damage or development of chronic allograft nephropathy. This consideration would forecast a reduction in the rate of long-term graft loss. We analyzed 114 graft biopsies from a subgroup of 57 patients that had been included in a randomized study to eliminate CyA at 3 months posttransplant from a regimen including sirolimus either in group A CyA + SRL vs group B of SRL with CyA elimination at 3 months. Every patient had two biopsies, one at transplantation and another at 1 year. The biopsy reading was performed in a blinded manner by a central pathologist using the Banff 1997 and the CADI classifications. A significantly lower rate of progression of tubular and interstitial chronic lesions between basal and 1-year biopsies was observed for group B patients. In addition, the incidence of new cases of chronic allograft nephropathy during the first year was significantly lower in the group in which CyA had been eliminated at 3 months posttransplant. We conclude that early elimination of CyA in the first months posttransplant, when SRL is used as the main immunosuppressant, reduces the appearance or worsening of chronic histologic lesions, probably as a consequence of long-term CyA toxicity prevention.