Cytochrome P450 3A4 Activity in Premenopausal and Postmenopausal Women,Based on 6-β-Hydroxycortisol:Cortisol Ratios

Study Objective . To characterize cytochrome P450 (CYP) 3A4 activity in premenopausal and postmenopausal women by evaluating the urinary 6-β-hydroxycortisokcortisol ratio. Design . Prospective study. Subjects . Thirteen premenopausal and 13 postmenopausal women who were healthy and not receiving drugs known to affect CYP3A4 activity. Interventions . Beginning on day 2 of menses, premenopausal women collected first morning urine samples every other day for a complete menstrual cycle. Postmenopausal women collected first morning urine every other day for 28 days. Measurements and Main Results . Mean weekly 6-β-hydroxycortisol:cortisol ratios did not differ during the phase (week) of the menstrual cycle. Daily ratios did not differ in postmenopausal women. No difference between premenopausal and postmenopausal women was found on comparing overall median ratios. Conclusion . Cytochrome P450 3A4 activity as measured by 6-β-hydroxy cortisol:cortisol ratio did not differ by week of menstrual cycle, suggesting no menstrual cycle-related changes. Menopause does not appear to be associated with differences in CYP3A4 activity, compared with premenopause.     

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion

Relapse rates averaging 41% in the first year after discharge among schizophrenic patients receiving maintenance neuroleptic treatment led to the development of two disorder-relevant treatments: a patient-centered behavioral treatment and a psychoeducational family treatment. Following hospital admission, 103 patients residing in high expressed emotion (EE) households who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder were randomly assigned to a two-year aftercare study of family treatment and medication, social skills training and medication, their combination, or a drug-treated condition. First-year relapse rates among those exposed to treatment demonstrate a main effect for family treatment (19%), a main effect for social skills training (20%), and an additive effect for the combined conditions (0%) relative to controls (41%). Effects are explained, in part, by the absence of relapse in any household that changed from high to low EE. Only the combination of treatment sustains a remission in households that remain high in EE. Continuing study, however, suggests a delay of relapse rather than prevention.     

Simple non-radioactive detection of the CFTR mutation N1303K by artificial creation of a restriction site.

N1303K is one of the most frequent non-delta F508 mutations causing cystic fibrosis in Central Europe. Since no restriction site is altered by this mutation and no other frequent mutations are known so far in exon 21, the detection requires a separate and laborious test. A mismatched primer was used to create an artificial Hin dIII site in amplified wildtype DNA, which is destroyed by the mutation. This allows for rapid and convenient detection by restriction enzyme digestion.     

硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。     

An oral selective M3 cholinergic receptor antagonist in COPD.

Cholinergic antagonists have been used since the early 1900s as bronchodilators for chronic obstructive pulmonary disease (COPD). The present study investigated whether an oral muscarinic M3-selective anticholinergic agent (OrM3) would provide an improved therapeutic advantage compared with an inhaled anticholinergic agent in patients with COPD. A 6-week, multicentre, randomised, placebo- and active-controlled, parallel-group study was performed at 56 sites in the USA. In total, 412 male and female patients (aged 35-86 yrs) with a clinical history consistent with COPD were randomised to receive OrM3 0.5, 2, 3 or 4 mg orally once daily, ipratropium bromide 36 mug by inhalation four times daily or placebo. OrM3 demonstrated a significant dose-related improvement in serial forced expiratory volume in one second and a trend for dose-related improvement in patient-reported symptoms compared with placebo. However, at a dose that provided efficacy less than that of ipratropium, the incidence of dose-related, mechanism-based side-effects for OrM3 exceeded those observed for ipratropium. In patients with chronic obstructive pulmonary disease, the oral M3-selective agent did not offer a therapeutic advantage over inhaled ipratropium. These results do not support the hypothesis that high selectivity for muscarinic M3 receptors over airway neuronal M2 receptors will represent a more effective therapy than current inhaled anticholinergics in obstructive airway disease.