Impaired insulin receptor binding and postbinding defects of adipocytes from normal and diabetic pregnant women

To evaluate the relative contribution of insulin binding and postbinding defects of glucose utilization in peripheral tissue during normal and diabetic pregnancy, we have studied the in vitro insulin action of isolated adipocytes from eight nondiabetic pregnant women and nine pregnant women with insulin-dependent diabetes mellitus who were undergoing cesarian section. The pregnant women were compared with a matched group of normal nonpregnant women undergoing gynecologic surgery. Insulin binding to adipocytes measured at tracer insulin concentration was reduced by 45% (P less than 0.01) in normal pregnant women and by 30% (P less than 0.02) in pregnant women with diabetes. In contrast, no changes were found between the three groups in insulin binding to pure monocytes and erythrocytes. The glucose transport system in fat cells from both groups of pregnant women was characterized by impaired maximal (P less than 0.05) and half-maximal (P less than 0.05) response to insulin. When fat cell glucose metabolism was studied, pregnant diabetic women exhibited decreased basal lipogenesis (P less than 0.05) and decreased maximal responses of lipogenesis and glucose oxidation to insulin stimulation (P less than 0.05). Similar but less pronounced abnormalities were seen in glucose metabolism of adipocytes from nondiabetic pregnant women. In conclusion, both in late normal and diabetic pregnancy, insulin binding to adipocytes is significantly reduced and accompanied by decreased insulin sensitivity and reduced maximal insulin responsiveness of glucose transport and by impaired basal and maximally insulin-stimulated glucose metabolism.     

Neonatal reference values for ionized calcium, phosphate and magnesium. Selection of reference population by optimality criteria

Thirty-one full-term newborn babies were investigated in order to establish reference values for ionized calcium. Only children fulfilling certain optimality criteria (with best possible maternal and infant conditions and uncomplicated pregnancy and delivery) were included. All infants were breast fed. Capillary blood for analysis of ionized calcium was collected by heel puncture on day 1 (6-36 h post partum, p.p.), day 3 (60-84 h p.p.) and day 5 (108-132 h p.p.). Ionized calcium was measured with a semi-automatic electrode system ICA 1 (Radiometer A/S, Copenhagen, Denmark). The reference ranges (mean +/- 2 SD) for days 1, 3 and 5 were 1.05-1.37, 1.10-1.42 and 1.20-1.48 mmol/l, respectively. The mean ionized calcium concentration on day 1 was significantly lower than on days 3 and 5. Reference values are also given for total calcium, magnesium and phosphate. We emphasize that it is impossible to calculate ionized calcium from total calcium or vice versa.     

Finite element analysis of a bone-implant system with the proximal femur nail.

Static analysis with finite element of a realistic femur nail bone-implant system in a typical proximal femoral fracture under physiological load bearing situations provides results for stress, displacement and strain. The question to be answered is, if simulation with the finite element analysis is able to explain biomechanically clinical observed patterns of failure. Surface-Reconstruction with CT database of a proximal femur and reconstruction with CT based density data was done. Next steps were to unite the bone structure with the Proximal Femoral Nail and to model two relevant fractures (31-A2.2 and A2.3 according AO). After modelling of geometry, isotropic material behaviour and load application numeric calculation of the femur-nail system with FE-software was performed. FE simulation mainly shows an axial dislocation of the femoral head screw with nearly no dislocation of the antirotation screw. This so-called z-effect therefore means: (1) Tilting of the proximal main fragment around the sagittal axis between the screws and (2) relative movement of both screws in the frontal plane. Relative movement of the two screws against each other could be the reason for implant failure, the so called cut out. Furthermore simulation shows different gliding of the screws explaining the so called z-telescoping. The analyzed stress patterns have to be relativized, because isotropic material behaviour of cancellous bone was assumed. Further examinations for this issue are necessary.     

Review of novel particulate antigen delivery systems with special focus on treatment of type I allergy.

For the treatment of infectious diseases, cancer and allergy, the directed induction of an appropriate immune response is the ultimate goal. Therefore, with the development of pure, often very small proteins, peptides or DNA by molecular biology techniques, the research for suitable adjuvants or delivery systems became increasingly important. Particle formulations are made of a variety of materials, including lipids, proteins or amino acids, polysaccharides, polyacrylic substances or organic acids. Microparticles serve as vehicles and provide a depot for the entrapped or coupled antigen. The release occurs in a pulsatile or continuous manner, a feature, which is well controllable for many particulate systems. Particles attract antigen presenting cells to the administration site, thereby guaranteeing the efficient presentation of the antigen to the immune system. Importantly, particles also protect the entrapped substance. This is especially necessary after oral application to avoid gastric or tryptic breakdown. In this article, the design and construction of different antigen delivery systems and their immune effects, with special focus on the suitability for allergy treatment, are discussed.     

Ultrastructural changes in the blood-brain barrier after nimodipine treatment and induced hypertension

Fourty-four narcotized rats were split into two equal groups, one being treated with nimodipine and the other with a placebo. By use of norfenefrine the blood pressure was raised to values of 150 and 180 mm Hg within the limits of the autoregulation of brain perfusion and under continuous measurement. Fifteen minutes after application of the standard tracer, horseradish peroxidase, the animals were exsanguinated using a saline perfusion and then perfusion-fixed with Karnovsky's solution. After development of the peroxidase staining the brain sections were evaluated and then allocated to their respective groups. In brain tissues from the experimental group significantly more frequent perivascular accumulations of horseradish peroxidase reaction product were found (P less than 0.001). In electron micrographs it could be seen that the tight junctions were intact and that there was a neuroendothelial transport, with horseradish peroxidase-filled vesicles, in the endothelium, muscle cells, and brain parenchyma. These vesicles represent a medium of transport for all proteins of high molecular weight and can therefore result in brain edema. It is concluded that nimodipine damages the blood-brain barrier by disturbance of the autoregulation of the cerebral blood flow.