The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Patterns of femoral head migration in osteoarthritis of the hip: a reappraisal with CT and pathologic correlation

Although medial, superior, and axial patterns of migration of the femoral head in osteoarthritis of the hip have been well described, it is not clear what anatomic and biomechanical factors determine the direction of migration. The authors studied 22 patients with bilateral (11 patients) or unilateral (11 patients) osteoarthritis by means of conventional radiography and computed tomography (CT) to define any relationships between migration in the coronal plane and that in the transverse plane and to determine whether femoral anteversion, acetabular anteversion, femoral neck-shaft angle, or acetabular inclination were related to particular migration patterns. Anterior migration was evident in 14 of the 19 hips with a superior migration pattern, whereas posterior migration was present in five of the seven hips with a medial migration pattern. In the remainder of cases, no migration in the transverse plane was present. Femoral anteversion as determined with CT, femoral neck-shaft angle, angle of acetabular inclination, and acetabular anteversion angle in this relatively small sample were all found to be within normal limits and appeared to have no influence on the occurrence of a specific pattern of femoral head migration.     

Biological evaluation of calcium alginate microspheres as a vehicle for the localized delivery of a therapeutic enzyme

Gaucher disease (GD) is caused by the decreased activity and/or stability of the lysosomal enzyme glucocerebrosidase (GCR). The available treatment consists in the intravenous administration of exogenous GCR, and is effective in reverting most of the symptoms. However, in terms of bone pathology, which is among the most disabling manifestations, a slow and incomplete response is observed, indicating that adjuvant therapies are necessary to consistently restore GCR activity in bone and accelerate regeneration. In this study, calcium alginate microspheres were analyzed as a vehicle for localized GCR delivery to bone. Results demonstrated that the entrapped enzyme retained full activity and exhibited a broader pH-dependent activity profile, compared to that of free-GCR, with improved stability at physiological pH. GCR release profile was established, and it was demonstrated that GCR could be released in a sustained manner. The biological behavior of the system was evaluated by analyzing the uptake of released GCR by GCR-deficient cells from GD patients, using different techniques: GCR activity measurements, radiolabeling, and cellulose acetate electrophoresis. Results demonstrated that GCR was internalized by cells significantly enhancing the residual enzymatic activity. To achieve an activity reconstitution level comparable to that obtained using free-GCR, only half of the dose was required with entrapped-GCR.     

General practitioners' satisfaction with and attitudes to out-of-hours services

Background  

In recent years, Dutch general practitioner (GP) out-of-hours service has been reorganised into large-scale GP cooperatives. Until now little is known about GPs' experiences with working at these cooperatives for out-of-hours care. The purpose of this study is to gain insight into GPs' satisfaction with working at GP cooperatives for out-of-hours care in separated and integrated cooperatives.     

Biocompatibility and biodegradation of polycaprolactone-sebacic acid blended gels

Tissue engineering aims at creating biological body parts as an alternative for transplanting tissues and organs. A current new approach for such materials consists in injectable biodegradable polymers. Their major advantages are the ability to fill-in defects, easy incorporation of therapeutic agents or cells, and the possibility of minimal invasive surgical procedures. Polycaprolactone (PCL) is a promising biodegradable and elastic biomaterial, with the drawback of low-degradation kinetics in vivo. In this work a biodegradable injectable gel of PCL blended with sebacic acid (SA) was prepared, to improve the degradation rate of the biomaterial. SA is known for its high degradation rate, although in high concentrations it could originate a pH decrease and thus disturb the biocompatibility of PCL. Degradation tests on phosphate buffered saline were carried out using 5% of SA on the blend and the biomaterial stability was evaluated after degradation using differential scanning calorimetry, dynamical mechanical analysis, and scanning electronic microscopy. After degradation the elastic properties of the blend decreased and the material became more crystalline and stiffer, although at a lower extent when compared with pure PCL. The blend also degraded faster with a loss of the crystalline phase on the beginning (30 days), although its thermal and mechanical properties remained comparable with those of the pure material, thus showing that it achieved the intended objectives. After cell assays the PCL-SA gel was shown to be cytocompatible and capable of maintaining high cell viability (over 90%).     

Knowledge and behavior among health professionals in relation to cadaveric organ donation and transplantation: a questionnaire-based analysis in Portuguese hospitals

Objective

To assess knowledge and behavior relative to cadaveric organ donation and transplantation among physicians and nurses working at nine Portuguese hospitals.

Methods

This prospective study between May and October 2009 included 495 questionnaires that were returned among 840 that were delivered, a 59% response rate. The transplant questionnaire comprised three main sections: section 1, sociodemographic-professional variables of the participants with nine questions; section 2, generic questions on organ donation and transplantation with 12 questions; and section 3 evaluated knowledge with 20 specific questions on organ donation and transplantation.

Results

Sixty-one percent of the participants were females, with 40% of the overall cohort between 31 and 40 years old; 62% married; 63% working in the emergency department; and 78% nurses. Although 78% of the participants stated that they had undergone specific training on organ donation and transplantation, 62% felt that they needed more training. The reasons evoked for the low rate of donation included difficulties in initiating the process of organ donation, in diagnosing cerebral death and in obtaining necessary human resources. There were no significant differences in knowledge between physicians and nurses concerning specific organ donation and transplantation issues. Having had specific training on organ donation and transplantation was significantly associated with correct answers to several questions, including those pertaining to knowledge of the national legislation on organ donation and transplantation.

Conclusions

The present study showed a lack of specific knowledge and training on organ donation and transplantation issue. It also suggested that for hospital staff to successfully act as initiators of the organ procurement process, more information and education are necessary. This effort could significantly increase the rate of organ donation and transplantation in Portugal.