RESUMEN
Inactivation of tumor-suppressor genes is one of the key hallmarks of a tumor. Unlike other tumor-suppressor genes, p53 is inactivated by missense mutations in half of all human cancers. It has become increasingly clear that the resulting mutant p53 proteins do not represent only the mere loss of wild-type p53 tumor suppressor activity, but gain new oncogenic properties favoring the insurgence, the maintenance, the spreading and the chemoresistance of malignant tumors. The actual challenge is the fine deciphering of the molecular mechanisms underlying the gain of function of mutant p53 proteins. In this review, we will focus mainly on the transcriptional activity of mutant p53 proteins as one of the potential molecular mechanisms. To date, the related knowledge is still quite scarce and many of the raised questions of this review are yet unanswered.
Asunto(s)
Neoplasias/genética , Oncogenes , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Humanos , MutaciónRESUMEN
Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 (COX-2) over cyclooxygenase-1 (COX-1). Gastrointestinal (GI) tolerability of meloxicam 7.5 and 15 mg vs piroxicam 20 mg was evaluated in a 4-week, double-blind, parallel group, placebo-controlled study in 51 healthy male volunteers, using a combination of oesphago-gastro-duodenal endoscopy, faecal blood loss measurement and symptom evaluation. Analysis of covariance found no significant difference in faecal blood loss between the groups. However, significantly higher bleeding was found with piroxicam 20 mg compared with placebo using a Student's t-test on the weighted means. Endoscopy score were significantly higher with piroxicam than with meloxicam 7.5 mg or placebo (P < 0.01). A significant difference from baseline was observed in the meloxicam 15 mg and piroxicam groups (P < 0.05), but not in the meloxicam 7.5 mg and placebo groups. Six piroxicam-treated volunteers were withdrawn following a poor endoscopic score, but no such withdrawals occurred in the meloxicam and placebo groups (P < 0.01). Meloxicam 7.5 mg caused less GI damage compared with piroxicam 20 when administered to healthy young volunteers for 28 days; a possible dose dependency effect in GI tolerability was also suggested for meloxicam 7.5 and 15 mg, in relation to endoscopic findings.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Sistema Digestivo/efectos de los fármacos , Piroxicam/efectos adversos , Tiazinas/efectos adversos , Tiazoles/efectos adversos , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Sistema Digestivo/anatomía & histología , Método Doble Ciego , Evaluación de Medicamentos , Tolerancia a Medicamentos , Endoscopía Gastrointestinal , Humanos , Masculino , Meloxicam , Sangre Oculta , Piroxicam/administración & dosificación , Piroxicam/farmacología , Tiazinas/administración & dosificación , Tiazinas/farmacología , Tiazoles/administración & dosificación , Tiazoles/farmacología , Factores de TiempoRESUMEN
The standardized scoring criteria of sleep can serve as a rough tool for monitoring the effects of psychoactive compounds, both in normal sleepers and in insomniac patients. More sensitive information on the impact of perturbing factors and drugs during sleep is supplied by the cyclic alternating pattern (CAP) parameters. In particular, CAP rate, which measures the amount of arousal instability during NREM sleep, has been proved of high reliability in a variety of clinical and pharmacological settings. The present study aimed at evaluating the activity of brotizolam (Br) 0.25 mg and triazolam (Tr) 0.25 mg on both conventional and CAP parameters in a model of situational insomnia of intermediate severity. Six middle-aged healthy subjects (three males and three females, aged 40-55 years) with no complaints about sleep, underwent a polysomnographic investigation according to a double-blind crossover design: placebo without noise (night 1), placebo with noise (night 2), brotizolam or triazolam without noise (nights 3 and 5), brotizolam or triazolam with noise (nights 4 and 6). The unperturbed nights consisted of standard recording conditions in a sound-protected sleep laboratory, whereas situational insomnia was accomplished by means of continuous white noise at 55 dBA delivered throughout the night. Subjects received medication orally at bedtime. An interval of at least 48 h was secured between consecutive recordings in the same individual. Compared to baseline conditions, situational insomnia was characterized by a shorter amount of total sleep (-40 min) and by an extension of intrasleep awakenings (+62 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Azepinas/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Triazolam/uso terapéutico , Adulto , Animales , Cricetinae , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Escalas de Valoración Psiquiátrica , Trastornos del Sueño-Vigilia/tratamiento farmacológicoRESUMEN
In 10 patients who required extracorporeal circulation (ECC) during surgery, we studied the damage induced by surgery to the pulmonary surfactant and the effectiveness of ambroxol in preventing changes in the phospholipid pool. There were 5 control patients and 5 patients who were given 1 g/day of ambroxol on the 4 days prior to and the 4 days after surgery. To follow changes in phospholipid concentrations, bronchoalveolar lavage (BAL) was performed before surgery and 24 h and 8 days after ECC. Phospholipids were assayed in the BAL liquid by two-dimensional thin-layer chromatography. There were marked decreases in total phosphorus and quantitative alterations of individual phospholipid species in the surfactant of the control group, but not in the patients treated with ambroxol.