Characterization of CYP2C Induction in Cryopreserved Human Hepatocytes and Its Application in the Prediction of the Clinical Consequences of the Induction

CYP2C enzymes play key roles in drug metabolism, and clinical drug-drug interactions caused by CYP2C induction have been reported. The aim of this study was to establish a method to predict the potency of CYP2C inductions considering the mechanism. We first investigated the relations of CYP2C induction with CYP3A4 or CYP2B6 induction in human hepatocytes after 48-h exposure with 19 inducers. The fold-induction values of CYP2C8 and CYP2C9 were well correlated with those of CYP3A4, whereas the inducers were separated into 2 groups showing different correlations with CYP2B6 induction for CYP2C8 and CYP2C9 induction. In the regression models established, the fold-induction values of CYP2C8 and CYP2C9 were well expressed as the functions of those of CYP3A4 and CYP2B6, while no such obvious correlation was observed for CYP2C19 induction. These results suggest that CYP2Cs are not simply coinduced with CYP3A4 and that CYP2C8 and CYP2C9 inductions are regulated by both pregnane X receptor and constitutive androstane receptor with different contributions. Finally, simple correlations were proposed using the experimental E_max values obtained and plasma concentrations of CYP2C9 substrates from the literature, and positive correlations were observed. These data provide methods to estimate the clinical impact of CYP2C9 induction from in vitro data.     

Will biomarker-based diagnosis of Alzheimer’s disease maximize scientific progress? Evaluating proposed diagnostic criteria

A recently published framework for the diagnosis of Alzheimer’s disease (AD) in research studies would allow diagnosis on the sole basis of two biomarkers (β-amyloid and pathologic tau), even in people with no objective or subjective memory or cognitive changes. This revision will have substantial implications for future Alzheimer’s research, and the changes should be rigorously evaluated before widespread adoption. We propose three principles for evaluating any revision to diagnostic frameworks for AD: (1) does the revision improve the validity of the diagnosis; (2) does the revision improve the reliability or reduce the expense of the diagnosis; and (3) will the revision foster innovative and rigorous research across populations. The new diagnostic framework is unlikely to achieve any of these goals. Instead, it has the potential to handicap future researchers, and slow progress towards identifying effective strategies to prevent or treat AD.     

Risk factors associated to tobacco and alcohol use in a large French cohort of pregnant women

Archives of Women's Mental Health - Tobacco and/or alcohol use during pregnancy is a major public health concern. The aim of our study was to identify risk factors associated to maternal...     

Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.

The development of air medical services in Czechoslovakia

The Czechoslovakian system of centralized dispatch of all emergency medical services prevents competition between ground ambulances and air medical services. Although this program is less than two years old, remarkable progress has pushed Czechoslovakia to the forefront of modern-day air medical transport. However, the future of Czechoslovakian air medical transport will require the acquisition of better-performing EMS helicopters and accessibility to medical equipment using Western technology. As with all current United States helicopter EMS systems, Czechoslovakia will face many of the financial considerations required in funding this extensive and elaborate project.     

Some factors associated with open gingival embrasures following orthodontic treatment

Open gingival embrasures or "black triangles" can be an undesirable outcome of adult orthodontic treatment. The aims of the present study were to determine the prevalence of open gingival embrasures in a group of orthodontic patients, and to determine if open gingival embrasures were related to: age at the start of treatment, the severity of pretreatment crowding of the mandibular incisors, the duration of treatment or changes in alveolar bone height. The subjects were 80 orthodontic patients (33 males, 47 females) between 15 and 31 years of age. Open gingival embrasures were found in 43.7 per cent of all subjects, while in subjects over 20 years of age the prevalence was 66.7 per cent. In relation to the amount of crowding 42.8 per cent of the subjects with less than 4 mm crowding had open gingival embrasures, 41.2 per cent of those with between 4 and 8 mm crowding had open gingival embrasures, and 50 per cent of those with more than 8 mm crowding had open gingival embrasures. The groups were not significantly different. Approximately 42 per cent of the subjects in the shorter treatment group had open gingival embrasures, and 44.4 per cent of those whose treatment took longer than 3 years had open gingival embrasures. This difference was not statistically significant. Cephalometric measurements of mandibular alveolar bone height indicate that open gingival embrasures were more likely to be due to resorption of the alveolar crest rather than extrusion of the mandibular incisors. In conclusion, open gingival embrasures were more frequently found in patients over 20 years of age than in younger patients, and were associated with resorption of the alveolar crest.     

Differences in temporomandibular joint pain and age distribution between marrow edema and osteonecrosis in the mandibular condyle

This study investigated the differences of age distribution and temporomandibular joint (TMJ) pain between marrow edema and osteonecrosis in the mandibular condyle. Subjects consisted of 35 TMJs in 35 patients with abnormal bone marrow on MR images who were selected from a consecutive series of 527 patients with TMJ disorders. Proton density and T2-weighted MR images taken in the oblique sagittal and coronal planes were used to diagnose condylar marrow abnormalities and divide them into either edema or osteonecrosis. The differences in TMJ pain and age distribution for these two abnormalities were assessed with the one-sided Wilcoxon rank sum test with 0.05 alpha level. The degree of pain was higher in joints with marrow edema than in joints with osteonecrosis (p = 0.033). The mean age was higher in joints with osteonecrosis (p < 0.001). Our results suggest that there is more severe pain in TMJs with marrow edema of the mandibular condyle than in those with osteonecrosis. Since the patients with marrow edema have lower age, it also appears that marrow edema may be a precursor condition for osteonecrosis of the TMJ.