RESUMO
The cyclopentenone prostaglandin A1 (PGA1) is an inducer of cell death in cancer cells. However, the mechanism that initiates this cytotoxic response remains elusive. Here we report that PGA1 triggers apoptosis by a process that entails the specific activation of H- and N-Ras isoforms, leading to caspase activation. Cells without H- and N-Ras did not undergo apoptosis upon PGA1 treatment; in these cells, the cellular demise was rescued by overexpression of either H-Ras or N-Ras. Consistently, the mutant H-Ras-C118S, defective for binding PGA1, did not produce cell death. Molecular analysis revealed a key role for the RAF-MEK-ERK signaling pathway in the apoptotic process through the induction of calpain activity and caspase-12 cleavage. We propose that PGA1 evokes a specific physiological cell death program, through H- and N-Ras, but not K-Ras, activation at endomembranes. Our results highlight a novel mechanism that may be of potential interest for tumor treatment.
Assuntos
Apoptose/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Prostaglandinas A/farmacologia , Proteínas ras/metabolismo , Animais , Calpaína/metabolismo , Linhagem Celular Tumoral , Cisteína/metabolismo , Embrião de Mamíferos/citologia , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Membranas Intracelulares/efeitos dos fármacos , Camundongos , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
AIMS: To analyse the differences in the prevalence of diabetes and dysglycaemia using fasting plasma glucose and HbA(1c) criteria. METHODS: Analytical cross-sectional study undertaken in a random sample of 2144 individuals (age 18-80 years) without known diabetes from the primary care setting in Malaga (Spain). Dysglycaemia was defined as fasting plasma glucose 5.6-6.9 mmol/l or HbA(1c) 39-46 mmol/mol (5.7-6.4%) and diabetes as fasting plasma glucose ≥ 7.0 mmol/l or HbA(1c)≥ 48 mmol/mol (≥ 6.5%). RESULTS: The proportion of subjects who were normoglycaemic was significantly higher using fasting plasma glucose than HbA(1c) (83.5 vs. 65%) (P < 0.0001). Compared with fasting plasma glucose, HbA(1c) detects more cases of dysglycaemia (32 vs. 14.8%) (P < 0.0001) and diabetes (3 vs. 1.7%) (P < 0.0001). CONCLUSIONS: In our environment, using HbA(1c) for the diagnosis of pre-diabetes and diabetes could increase the target population for preventive and therapeutic measures. Further cost-effectiveness studies are needed before the widespread diagnostic use of HbA(1c) can be recommended.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/metabolismo , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores/sangue , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Prevalência , Espanha/epidemiologia , Adulto JovemRESUMO
Endogenous endophthalmitis is a rare disease caused by hematogenic germ spread from an internal focus. Infections due to Streptococcus agalactiae are infrequent in adults although new cases had been described recently associated to inmunodepression. We present a patient with endocarditis due to Streptococcus agalactiae, endophthalmitis and multiple brain abscess. We also review the literature.
Assuntos
Abscesso Encefálico/complicações , Endocardite Bacteriana/complicações , Endoftalmite/complicações , Infecções Estreptocócicas/complicações , Streptococcus agalactiae , Abscesso Encefálico/microbiologia , Endocardite Bacteriana/microbiologia , Endoftalmite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Estreptocócicas/microbiologiaRESUMO
La endoftalmitis endógena es una rara entidad asociada a diseminación bacteriana hematógena desde un foco séptico interno. Las infecciones en adultos causadas por Streptococcus agalactiae son muy infrecuentes aunque cada vez se describen más casos, sobre todo en relación a situaciones de inmunodepresión. Presentamos un caso excepcional de endocarditis por Streptococcus agalactiae que se complicó con abscesos cerebrales múltiples y endoftalmitis. Asimismo revisamos la literatura publicada al respecto. (AU)
