Browsing by Author "Garrido, P"
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- Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene ExpressionPublication . Costa, E; Fernandes, J; Ribeiro, S; Sereno, J; Garrido, P; Rocha-Pereira, P; Coimbra, S; Catarino, C; Belo, L; Bronze-da-Rocha, E; Vala, H; Alves, R; Reis, F; Santos-Silva, AOur aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associated with INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression.
- 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.
- Hypertension induced by immunosuppressive drugs: a comparative analysis between sirolimus and cyclosporinePublication . Reis, F; Parada, B; Teixeira de Lemos, E; Garrido, P; Dias, A; Piloto, N; Baptista, S; Sereno, J; Eufrásio, P; Costa, E; Rocha-Pereira, P; Santos-Silva, A; Figueiredo, A; Mota, A; Teixeira, FThe 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
- IRIS: Um novo índice de avaliação do risco de suicídioPublication . Alte da Veiga, F; Andrade, J; Garrido, P; Neves, S; Craveiro, A; Santos, JC; Braz-Saraiva, C; Madeira, NNa introdução os autores procedem a uma revisão histórica e conceptual dos instrumentos psicométricos que têm como objectivo a avaliação do risco de suicídio em indivíduos que apenas verbalizam ideação suicida. Nas secções seguintes é apresentado todo o processo de desenvolvimento do IRIS (Índice de Risco de Suicídio) - um novo índice com o mesmo objectivo de avaliação mas construído utilizando metodologias que proporcionam avanços qualitativos em relação aos índices existentes, bem como uma melhor adequação a contingências e características da realidade portuguesa. The introduction contains a historical and conceptual review of psychometric tools that aim at assessing the risk of suicide in individuals presenting suicidal ideation. In the following sections the whole process of development of IRIS (“Índice de Risco de Suicídio” – Suicide Risk Index) is presented - a new tool with the same objective but built using methods that provide qualitative advances over existing indexes, while better accounting for the contingencies and characteristics of the Portuguese reality.