Dendron based antifouling, MRI and magnetic hyperthermia properties of different shaped iron oxide nanoparticles.

Owing to the great potential of iron oxide nanoparticles (NPs) for nanomedicine, large efforts have been made to better control their magnetic properties, especially their magnetic anisotropy to provide NPs able to combine imaging by MRI and therapy by magnetic hyperthermia. In that context, the design of anisotropic NPs appears as a very promising and efficient strategy. Furthermore, their bioactive coating also remains a challenge as it should provide colloidal stability, biocompatibility, furtivity along with good water diffusion for MRI. By taking advantage of our controlled synthesis method of iron oxide NPs with different shapes (cubic, spherical, octopod and nanoplate), we demonstrate here that the dendron coating, shown previously to be very suitable for 10 nm sized iron oxide, also provided very good colloidal, MRI and antifouling properties to the anisotropic shaped NPs. These antifouling properties, demonstrated through several experiments and characterizations, are very promising to achieve specific targeting of disease tissues without affecting healthy organs. On the other hand, the magnetic hyperthermia properties were shown to depend on the saturation magnetization and the ability of NPs to self-align, confirming the need of a balance between crystalline and dipolar magnetic anisotropies.

Evaluation of the Active Targeting of Melanin Granules after Intravenous Injection of Dendronized Nanoparticles.

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells' membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post-intravenous injection (pi), and the highest tumor uptake of the control probe [177Lu]Lu-NPs10@D1_DOTAGA at 30 min pi, probably due to the enhanced permeability and retention effect. In addition, ex vivo confocal microscopy studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.

Proof testing of ceramic femoral heads for hip joint implants.

A proof test procedure for the rejection of defective ceramic hip ball heads in the production line is presented. The procedure consists of applying a load to each ceramic ball head. This load, being somewhat higher than the maximum physiological load, should not cause any damage in cases where the highly stressed areas are free of flaws. In this procedure, a polymer ring is positioned inside the ball head bore between a socket and the head of a tie bolt. Once the tie bolt is pulled downwards, the ring creates a radial pressure on the inner bore surface of the ball head. With an iterative approach based on finite element analysis, the proof test design was optimized in order to obtain a stress distribution in the ball head similar to that resulting in in vivo conditions. The calculated results were validated by strain gauge measurements performed on an assembled proof test apparatus. Several polymers were considered for the ring. Ultrahigh-molecular-weight polyethylene (UHMWPE grade RCH 1000) showed the best durability properties and lowest wear rates. The requirement to perform 1000 reruns without significant reduction of stress in the ball head was fulfilled. Although other proof test procedures for ceramic femoral heads already exist, the procedure presented in this article shows advantages concerning maintenance and operating costs.

Optimization of the stress distribution in ceramic femoral heads by means of finite element methods.

Ceramic ball heads for total hip replacement are highly loaded in vivo and must meet the sternest requirements concerning strength and safety. High stresses inside the ball head originate from the press fit between the conical stem (made of titanium alloy or steel) and the borehole of the ball. The aim of this study was the development of an optimized contour at the fillet inside the ball head by means of numerical methods, in order to reduce local stress concentrations. The computer-aided optimization method was applied on the customary engineering fillet radius to reduce local stress peaks. The local notch stress of the examined ball head design was reduced by up to 27 per cent for the relevant load cases. Verification by rupture testing of prototypes turned out to be difficult for axisymmetric load cases, since the static fracture load is governed by the hoop stresses in the contact area of the taper (global maximum), thus making it difficult to prove a local improvement. The sensitivity of the design to asymmetric loading was clearly shown (varying the load angle and bearing type). Stress relocation in the ball-stem interface at higher burst loads indicated the necessity of optimizing each ceramic femoral head design individually (i.e. for different borehole depths).

Influence of contaminants in the stem-ball interface on the static fracture load of ceramic hip joint ball heads.

The probability of in-vivo failure of ceramic hip joint implants is very low (0.05-0.004 per cent). Besides material flaws and overloading, improper handling during implantation may induce fractures of the ceramic ball head in the long term. This study focuses on the influence of contaminants located in the stem-ball interface and on the use of damaged metal tapers on the strength of ceramic ball heads. Mechanical tests on alumina ball heads according to the standard ISO 7206-10 were performed to identify their effect on the static fracture load. A decrease of up to 90 per cent with respect to the reference static fracture load was found when contaminants such as bone chips, soft tissue, or blood were present. Reductions of 57 per cent and 27 per cent were observed for deformed stem cross-sections (from circular to elliptical) and for flattened stems respectively, making deformed stems another influential parameter. Since any alteration of the interface between the metal taper and the ceramic ball head yields a nonuniform load introduction and hence results in stress concentrations, its presence has to be avoided.

Amlodipine once-daily in systemic hypertension.

UNLABELLED: The calcium channel blocker nifedipine is widely used in children with systemic hypertension: however, because of the short duration of action, three to four daily doses of the standard preparation are required. Amlodipine once-daily, a calcium channel blocker structurally related to nifedipine with an excellent bioavailability and a long elimination half-time, has been shown to reduce blood pressure in adults. No information is available on the use of amlodipine in childhood. The effects of amlodipine once-daily (5 to 10 mg) were therefore assessed in 28 paediatric patients with hypertension. Amlodipine was withdrawn in five patients who experienced oedema and flushing. In the remaining 23 patients blood pressure was significantly reduced 3 weeks after amlodipine (on average by 7/5 mm Hg) and further decreased at 12 weeks (by 21/12 mm Hg). Heart rate and body weight were unchanged. In eight patients concomitantly treated with cyclosporine, the blood level of this agent was stable throughout the study, thus not requiring any dose adjustment. CONCLUSION: The study illustrates the antihypertensive properties of amlodipine once-daily in paediatric hypertension. Amlodipine appears particularly indicated in patients concomitantly treated with cyclosporine.

[Treatment of pharyngeal disease in general and pediatric practice]. / Das Vorgehen bei Affektionen des Rachenraums in der allgemeinärztlichen und pädiatrischen Praxis.

Based on 1351 reports by 180 physicians, it was found that pediatricians and younger physicians conducted more diagnostic tests and judged a tonsillectomy as necessary less frequently than GP's, especially those without board certification, and older physicians.