Browsing by Author "Teixeira, F"
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- 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.
- 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.
- Epworth Sleepiness Scale in obstructive sleep apnea syndrome--an underestimated subjective scalePublication . Guimarães, C; Martins, MV; Vaz Rodrigues, L; Teixeira, F; Moutinho Dos Santos, JExcessive daytime sleepiness is a major symptom in obstructive sleep apnea syndrome (OSAS) and can be evaluated using both subjective and objective methods. The Epworth Sleepiness Scale (ESS) is a simple and validated questionnaire for assessing subjective daytime sleepiness in the context of sleep disorders. Although its subjective character may limit the accurate expression of daytime sleepiness, the clinical benefit of sequential ESS is clear and demonstrates how ESS scores evolve in individual patients and how these scores may relate to various parameters. In this context we compared the severity of daytime sleepiness reported at baseline visit with severity of baseline sleepiness assessed, retrospectively, after treatment with automatic positive airway pressure (APAP). We conducted a prospective study that included 66 patients evaluated in a sleep clinic diagnosed with OSAS. The diagnosis was confirmed by in-laboratory or portable sleep studies. Their mean age was 53.3 years and the majority were men (88%, n=58). The ESS was answered during the first interview (baseline daytime sleepiness). During follow-up visits, after APAP treatment, the patient was asked to assess baseline sleepiness, retrospectively, as well as post-treatment sleepiness. The mean baseline ESS score was 11.8, mean retrospective baseline ESS 15.4, with a mean difference of 3.55 (p<0.001 t-Test) and post-treatment ESS 7.3. There was no significant correlation between the difference in ESS score (baseline - retrospective baseline) with the average daily (hours) use of APAP, the apnea-hypopnea index (AHI), the minimal recorded SatO(2), disease duration, body mass index (BMI) and age. Our findings confirm that the severity of subjective sleepiness reported before treatment with positive airway pressure is often underestimated by patients with OSAS.
- Erythrocyte damage in mild and severe psoriasisPublication . Rocha-Pereira, P; Santos-Silva, A; Rebelo, I; Figueiredo, A; Quintanilha, A; Teixeira, FBACKGROUND: Psoriasis is a common chronic and recurrent inflammatory skin disorder. Oxygen metabolites and proteases released by activated inflammatory cells may induce oxidative and proteolytic damage to plasma constituents and red blood cells (RBCs). RBCs have a limited biosynthesis capacity and poor repair mechanisms. OBJECTIVES: To study RBCs as a potential cumulative marker of oxidative and proteolytic stress in psoriasis, and as a marker of worsening of the disease. METHODS: The study was performed in 70 patients with mild or severe psoriasis and in 40 control individuals. We evaluated total and differential leucocyte count and, as markers of leucocyte activation, plasma elastase and lactoferrin. Besides the basic RBC study (RBC count, haematocrit, haemoglobin concentration and haematimetric indices) we evaluated antioxidant defences (catalase, superoxide dismutase, glutathione peroxidase and selenium), osmotic fragility and reticulocyte count; in the RBC membrane we evaluated lipid peroxidation and susceptibility to lipid peroxidation, membrane fluidity, levels of cholesterol and phospholipids, membrane-bound haemoglobin, band 3 profile and levels of vitamin E; serum levels of bilirubin, total plasma antioxidant capacity, lipid profile and lipid peroxidation were also evaluated. RESULTS: Psoriasis patients showed a rise in leucocytes, mainly neutrophils, which was associated with a rise in elastase and lactoferrin. Patients had a reduced RBC count, antioxidant defences and membrane fluidity, elevated membrane lipid peroxidation, membrane-bound haemoglobin, osmotic fragility and reticulocyte count, and a different band 3 profile. Most of these modifications were enhanced in severe psoriasis. CONCLUSIONS: In summary, our data show that the RBCs are at a lower number in psoriasis patients, and present several changes denoting an enhanced damage and/or ageing process, which seem to be strongly connected with neutrophil activation, oxidative stress and worsening of psoriasis.
- Experimental studies on the mechanisms of tiaprofenic acid photosensitizationPublication . Figueiredo, A; Fontes-Ribeiro, CA; Gonçalo, Margarida; Poiares-Baptista, A; Teixeira, FRed blood cell lysis and histidine degradation, photosensitized by tiaprofenic acid (TIA), were investigated. Photohaemolysis was markedly enhanced in oxygenated solutions, but was also intense in the presence of nitrogen. Photohaemolysis was inhibited by butylated hydroxyanisole and reduced glutathione, but was unaffected by sodium azide, superoxide dismutase and mannitol. The TIA-induced photo-oxidation of histidine was greatly enhanced in the presence of oxygen and almost completely inhibited in solutions bubbled with nitrogen. Sodium azide, butylated hydroxyanisole and reduced glutathione inhibited the photodegradation of histidine. Phototoxicity to histidine was unaffected by mannitol and superoxide dismutase. The overall results suggest that molecular mechanisms involving free radicals and singlet oxygen are responsible for TIA-photosensitized reactions. These two in vitro models (photohaemolysis and histidine degradation) represent different mechanisms of phototoxicity, but complement one another in the investigation of potential phototoxic substances.
- 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
- Photosensitivity to piroxicam: absence of cross-reaction with tenoxicamPublication . Gonçalo, Margarida; Figueiredo, A; Tavares, P; Fontes-Ribeiro, CA; Teixeira, F; Poiares-Baptista, AWe studied 2 groups of patients. One group of 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylic acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiosalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. Photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with photosensitivity to piroxicam had positive patch tests to thimerosal and thiosalicylic acid and 9 of them had positive photopatch tests to piroxicam. 20 out of 24 patients with positive patch tests to thiosalicylic acid also had positive photopatch tests to piroxicam. All the patients tested with salicyclic acid were negative. Out of the 29 patients with positive photopatch tests to piroxicam, none reacted to tenoxicam. In countries with a high incidence of contact sensitivity to thimerosal/thiosalicylic acid, the use of piroxicam should be avoided and replaced by tenoxicam, a drug without reported photosensitivity.
- Reacções adversas medicamentosas em dermatologiaPublication . Figueiredo, A; Gonçalo, Margarida; Poiares-Baptista, A; Teixeira, F
- The inflammatory response in mild and in severe psoriasisPublication . Rocha-Pereira, P; Santos-Silva, A; Rebelo, I; Figueiredo, A; Quintanilha, A; Teixeira, FBACKGROUND: Psoriasis is a chronic and recurrent inflammatory skin disease. The inflammatory response represents a fundamental ability of the organism to protect itself from infectious agents and from injury. OBJECTIVES: To evaluate the inflammatory response in mild and in severe psoriasis, to evaluate the endogenous systems counterbalancing the deleterious effects of the inflammation products, and to establish values of prognostic significance. METHODS: The study was performed in a control group (n = 40) and in 60 patients with psoriasis vulgaris, half presenting with mild psoriasis, and the other half with severe psoriasis. We evaluated total and differential leucocyte count; elastase, lactoferrin and lipid peroxidation as markers of neutrophil activation; total plasma antioxidant capacity (TAS), transferrin, ceruloplasmin, alpha(1)-antitrypsin and alpha(2)-macroglobulin as markers of the endogenous antioxidant and antiprotease systems; and fibrinogen, erythrocyte sedimentation rate, C-reactive protein (CRP), haptoglobin, C3 and C4 complement proteins as markers of inflammation. RESULTS: Our data suggested that psoriasis is an inflammatory condition in which neutrophils seem to play a crucial role by contributing to the development of oxidative and proteolytic stress. The worsening of the disease seemed to be linked to the enhancement of the inflammatory response and of the imbalance between neutrophil activation products and their inhibitors. CONCLUSIONS: We propose values for elastase, CRP, elastase/alpha(2)-macroglobulin, elastase/alpha(1)-antitrypsin, thiobarbituric acid/TAS and elastase/neutrophil ratios with prognostic significance for the worsening of psoriasis.
- The Portuguese Society of Rheumatology position paper on the use of biosimilarsPublication . Fonseca, JE; Gonçalves, J; Araújo, F; Cordeiro, I; Teixeira, F; Canhão, H; Pereira da Silva, JA; Garcês, S; Miranda, LC; Ramiro, Sofia; Roxo, Ana; Pimentel-Santos, FM; Tavares, V; Neto, A; Sepriano, A; Malcata, A; Faustino, A; Silva, C; Ambrósio, C; Duarte, C; Miguel, C; Barcelos, F; Santos, H; Cunha, I; Ramos, JC; Melo-Gomes, JA; Pimentão, JB; Costa, L; Maurício, L; Silva, M; Bernardes, M; Bogas, M; Coelho, PC; Monteiro, P; Aguiar, R; André, R; Leitão, R; Pimenta, S; Meirinhos, T; Fernandes, S; Las, V; Castelão, WBiotechnological drugs have become a fundamental resource for the treatment of rheumatic patients. Patent expiry of some of these drugs created the opportunity for biopharmaceutical manufacturers to develop biosimilar drugs intended to be as efficacious as the originator product but with a lower cost to healthcare systems. Due to the complex manufacturing process and highly intricate structure of biologicals, a biosimilar can never be an exact copy of its reference product. Consequently, regulatory authorities issued strict preclinical and clinical guidelines to ensure safety and efficacy equivalence and, in September 2013, the biosimilar of infliximab was the first biosimilar monoclonal antibody to be authorized for use in the European Union. The current document is a position statement of the "Sociedade Portuguesa de Reumatologia" (Portuguese Society of Rheumatology) on the use of biosimilar drugs in rheumatic diseases. Two systematic literature reviews were performed, one concerning clinical trials and the other one concerning international position papers on biosimilars. The results were presented and discussed in a national meeting and a final position document was discussed, written and approved by Portuguese rheumatologists. Briefly, this position statement is contrary to automatic substitution of the originator by the biosimilar, defends either a different INN or the prescription by brand name, supports that switching between biosimilars and the originator molecule should be done after at least 6 months of treatment and based on the attending physician decision and after adequate patient information, recommends the registration of all biosimilar treated patients in Reuma.pt for efficacy, safety and immunogenicity surveillance, following the strategy already ongoing for originators, and opposes to extrapolation of indications approved to the originator to completely different diseases and/or age groups without adequate pre-clinical, safety or efficacy data.