RESUMO
We compared the proliferation of neonatal and adult airway smooth muscle cells (ASMC) with no/moderate lung disease, in glucose- (energy production by glycolysis) or glucose-free medium (ATP production from mitochondrial oxidative phosphorylations only), in response to 10% fetal calf serum (FCS) and PDGF-AA. In the presence of glucose, cell counts were significantly greater in neonatal vs. adult ASMC. Similarly, neonatal ASMC DNA synthesis in 10% FCS and PDGF-AA, and [Ca2+]i responses in the presence of histamine were significantly enhanced vs. adults. In glucose-free medium, cell proliferation was preserved in neonatal cells, unlike in adult cells, with concomitant increased porin (an indicator of mitochondrial activity) protein expression. Compared to adults, stimulated neonatal human ASMC are in a rapid and robust proliferative phase and have the capacity to respond disproportionately under abnormal environmental conditions, through increased mitochondrial biogenesis and altered calcium homeostasis.
Assuntos
Miócitos de Músculo Liso/metabolismo , Adulto , Idoso , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , DNA/metabolismo , Feminino , Glucose/farmacologia , Humanos , Recém-Nascido , Pneumopatias/metabolismo , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Canais de Cátion TRPC/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Due to the improvement in life expectancy in cystic fibrosis (CF), co-morbidities such as renal function impairment may be more frequent. AIM: To determine the prevalence of renal disease in children with CF and to identify associated risk factors. METHODS: A single-center retrospective study analyzing the genetic, clinical and therapeutic characteristics of 112 children. The estimated glomerular filtration rate (GFR), microalbuminuria and lithiasic risk factors were assessed. RESULTS: The median calculated GFR (Schwartz) was 123, 161 and 155ml/min/1.73m(2) in children aged 1, 6 and 15years, respectively. The cumulative dose of aminoglycosides was not correlated to GFR. Microalbuminuria was present in 22/38 patients. Hyperoxaluria was observed in 58/83 patients and was associated with a severe genotype, pancreas insufficiency and liver disease. Hypercalciuria, hyperuricuria and hypocitraturia were identified in 16/87, 15/83 and 57/76 patients, respectively. CONCLUSION: Renal impairment in CF has various presentations. There appears to be low levels of renal impairment in children with CF. However, the risk of oxalocalcic urolithiasis is enhanced, and GFR may be underestimated by the Schwartz formula. Further studies using measured GFR techniques are thus warranted.