Browsing by Issue Date, starting with "2008"
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- Artropatia inflamatória como forma de apresentação de hepatite: um caso clínicoPublication . Garcia, R; Velez, J; Ferreira, P; Rodrigues, A; Reis, C; Porto, A
- Nitric oxide synthase isoforms and NF-kappaB activity in normal and osteoarthritic human chondrocytes: regulation by inducible nitric oxidePublication . Rosa, SC; Judas, F; Lopes, MC; Mendes, AFTo elucidate the role of endogenous inducible nitric oxide (NO) on the regulation of NF-kappaB activity in human chondrocytes, we evaluated (i) the pattern of expression of the neuronal (nNOS) and inducible (iNOS) NO synthase isoforms and the basal NF-kappaB activity in normal and osteoarthritic (OA) human chondrocytes, (ii) the role of cytokines and growth factors in modulating the protein levels of the two NOS isoforms, and (iii) the effect of inhibiting endogenous inducible NO production on the ability of interleukin-1beta (IL-1) to induce NF-kappaB activation. nNOS was more frequently expressed in normal than in OA chondrocytes, whereas the opposite was found for iNOS. IL-1 induced the degradation of both enzymes, but iNOS disappeared more rapidly. Although IkappaB-alpha was present in all the normal samples and in the majority of the OA samples, NF-kappaB-DNA binding activity in OA chondrocytes was increased approximately twofold relatively to normal cells. Addition of a NOS inhibitor, after induction of iNOS expression, induced IkappaB-alpha degradation and potenciated the effect of IL-1, indicating that endogenous inducible NO inhibits NF-kappaB activation. Taken together, these findings favor an inhibitory role of high NO levels on the regulation of NF-kappaB activation in chondrocytes, indicating that NF-kappaB activity is regulated, at least in part, by the balanced production of NO resulting from a dynamic process that, at any given moment, determines the availability of the constitutive and inducible NOS isoforms. Moreover, the down-regulatory role of NO on NF-kappaB activation warrants caution as to the possible utilization of NO inhibitors in the therapy of OA.
- Guia do Urostomizado: para que não se sinta sóPublication . Santos, C; Figueira, R
- Chronic rhinosinusitis with nasal polyps in allergic patientsPublication . Sousa, N; Santos, A; Loureiro, G; Tavares, B; Loureiro, C; Faria, E; Chieira, C
- Aneurismas cerebrais com ruptura: Impacto da cirurgiaPublication . Pereira, R; Gonçalves, J; Costa, G; Cabrita, F; Fernandes, R; Barbosa, MD
- Systemic granulomatosis disease in common variable immunodeficiency: case reportPublication . Sousa, N; Geraldes, I; Faria, E; Ferreira, I; Paiva, B; Chieira, C
- Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilagePublication . Rosa, SC; Gonçalves, J; Judas, F; Mobasheri, A; Lopes, C; Mendes, AFINTRODUCTION: Disorders that affect glucose metabolism, namely diabetes mellitus (DM), may favor the development and/or progression of osteoarthritis (OA). Thus far, little is known regarding the ability of chondrocytes to adjust to variations in the extracellular glucose concentration, resulting from hypoglycemia and hyperglycemia episodes, and so, to avoid deleterious effects resulting from deprivation or intracellular accumulation of glucose. The aim of this study was to compare the ability of normal and OA chondrocytes to regulate their glucose transport capacity in conditions of insufficient or excessive extracellular glucose and to identify the mechanisms involved and eventual deleterious consequences, namely the production of reactive oxygen species (ROS). METHODS: Chondrocytes, isolated from normal and OA human cartilage, were maintained in high-density monolayer cultures, in media without or with 10 or 30 mM glucose. Glucose transport was measured as the uptake of 2-deoxy-D-glucose (2-DG). Glucose transporter-1 (GLUT-1) mRNA and protein content were evaluated by real-time RT-PCR and western blot, respectively. ROS production was measured with 2',7'-dichlorodihydrofluorescein diacetate. RESULTS: Basal and IL-1beta-induced 2-DG uptake, including the affinity (1.066 +/- 0.284 and 1.49 +/- 0.59 mM) and maximal velocity (0.27 +/- 0.08 and 0.33 +/- 0.08 nmol/microg protein/hour), and GLUT-1 content were identical in normal and OA chondrocytes. Glucose deprivation increased 2-DG uptake and GLUT-1 protein both in normal and OA chondrocytes. Exposure to high glucose (30 mM) for 18 or 48 hours decreased those parameters in normal but not in OA chondrocytes. GLUT-1 mRNA levels were unaffected by high glucose, either in normal or OA chondrocytes. The high glucose-induced reduction in GLUT-1 protein in normal chondrocytes was reversed by treatment with a lysosome inhibitor. High glucose induced ROS production, which lasted significantly longer in OA than in normal chondrocytes. CONCLUSIONS: Normal human chondrocytes adjust to variations in the extracellular glucose concentration by modulating GLUT-1 synthesis and degradation which involves the lysosome pathway. Although capable of adjusting to glucose deprivation, OA chondrocytes exposed to high glucose were unable downregulate GLUT-1, accumulating more glucose and producing more ROS. Impaired GLUT-1 downregulation may constitute an important pathogenic mechanism by which conditions characterized by hyperglycemia, like DM, can promote degenerative changes in chondrocytes that can facilitate the progression of OA
- Pioderma Gangrenoso da parede abdominal após cesarianaPublication . Cardoso, JC; Coelho, S; Gonçalo, Margarida; Oliveira, H; Brites, MM; Figueiredo, A
- A evolução do refluxo vesico-ureteral com diagnóstico perinatalPublication . Leitão, H; Correia, AJ; Gomes, C; Simões, O; Rolo, V; Mimoso, G; Ramos, C
- Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2.Publication . Brás, JM; Guerreiro, RJ; Morgadinho, A; Januário, C; Dias, M; Calado, A; Semedo, C; Oliveira, CR; Hardy, J; Singleton, ABACKGROUND: Mutations in the genes PRKN and LRRK2 are the most frequent known genetic lesions among Parkinson's disease patients. We have previously reported that in the Portuguese population the LRRK2 c.6055G > A; p.G2019S mutation has one of the highest frequencies in Europe. METHODS: Here, we follow up on those results, screening not only LRRK2, but also PRKN, SNCA and PINK1 in a cohort of early-onset and late-onset familial Portuguese Parkinson disease patients. This series comprises 66 patients selected from a consecutive series of 132 patients. This selection was made in order to include only early onset patients (age at onset below 50 years) or late-onset patients with a positive family history (at least one affected relative). All genes were sequenced bi-directionally, and, additionally, SNCA, PRKN and PINK1 were subjected to gene dosage analysis. RESULTS: We found mutations both in LRRK2 and PRKN, while the remaining genes yielded no mutations. Seven of the studied patients showed pathogenic mutations, in homozygosity or compound heterozygosity for PRKN, and heterozygosity for LRRK2. CONCLUSION: Mutations are common in Portuguese patients with Parkinson's disease, and these results clearly have implications not only for the genetic diagnosis, but also for the genetic counseling of these patients.