Temperature-dependent tensile properties of polyamide 12 for the use in percutaneous transluminal coronary angioplasty balloon catheters.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) balloon catheters must withstand high pressures required for the lesion treatment, pushing loads during insertion, and pulling loads during withdrawal. These loads pose a challenge especially for polymeric tubular shafts with small cross sections. In order to enable new design innovations and to better understand the mechanics of current catheter technologies, the tensile properties of polyamide (PA) 12 were investigated. PA 12 dog bone specimens and medical PA 12 tubes were either stored at ambient temperature and humidity or conditioned in water, and subjected to tensile loads at different temperatures. In addition, the effect on the tensile properties of the necking process, a forming process to reduce the wall thickness of the tubes, was determined. RESULTS: The tested tubes showed a reduction in both Young's Modulus (- 41.5%) and yield stress (- 29.2%) compared to standardized specimens. Furthermore, an increase in temperature and water absorption softens the material and reduces the mechanical properties like the Young's Modulus and the yield stress. It was found that the material strengthens during the necking process. Likely due to the orientation of the polymers chain molecules in load direction (Rösler et al., 2007), the Young's Modulus of the material could be increased by 43.5%. Furthermore, the absence of a yield point after necking allows for a greater loading capacity of the material without unstable neck growth. Besides the strengthening, the ultimate strain is reduced by 50%. This indicates that the necking process induces plastic deformation. CONCLUSION: The investigation showed that the environmental conditions like temperature and humidity can influence mechanical properties. It could also be shown that pre-forming processes such as necking can enhance the mechanical properties, such as the Young's Modulus, while reducing the wall thickness. These findings suggest possible further development of catheters with a small cross section and higher mechanical strength and highlight the importance to account for the targeted operating temperature during the design process.

Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in myeloma.

We have previously demonstrated that interleukin-17A (IL-17) producing T helper 17 cells are significantly elevated in blood and bone marrow (BM) in multiple myeloma (MM) and IL-17A promotes MM cell growth via the expression of IL-17 receptor. In this study, we evaluated anti-human IL-17A human monoclonal antibody (mAb), AIN457 in MM. We observe significant inhibition of MM cell growth by AIN457 both in the presence and the absence of BM stromal cells (BMSCs). Although IL-17A induces IL-6 production, AIN457 significantly downregulated IL-6 production and MM cell adhesion in MM-BMSC co-culture. AIN457 also significantly inhibited osteoclast cell differentiation. More importantly, in the SCIDhu model of human myeloma administration of AIN457 weekly for 4 weeks after the first detection of tumor in mice led to a significant inhibition of tumor growth and reduced bone damage compared with isotype control mice. To understand the mechanism of action of anti-IL-17A mAb, we report, here, that MM cells express IL-17A. We also observed that IL-17A knockdown inhibited MM cell growth and their ability to induce IL-6 production in co-cultures with BMSC. These pre-clinical observations suggest efficacy of AIN457 in myeloma and provide the rationale for its clinical evaluation for anti-myeloma effects and for improvement of bone disease.

Pharmacokinetics of theophylline and bioavailability of a sustained release theophylline preparation in patients with cystic fibrosis.

The elimination of theophylline after intravenous aminophylline bolus and the absorption of a sustained-release oral theophylline preparation (Theo-Dur) were studied in ten patients with cystic fibrosis (C.F.). Each patient received an I.V. bolus of aminophylline equivalent to 4 mg/kg anhydrous theophylline and 10 plasma theophylline levels were obtained over the following eight hours. Elimination half life (T1/2), total body clearance (Cl), volume of distribution (Vd) and area under the concentration curve (AUCiv) were determined. Forty-eight hours later each patient received an oral dose of sustained release theophylline equivalent to 7.47-11.42 mg/kg anhydrous theophylline and 13 plasma theophylline concentrations were measured over 24 hours. Area under the concentration curve (AUCpo) and fractional absorption (F) of the sustained release preparation were determined. Mean values (+/- S.D.) were T1/2 = 4.45 +/- 1.58 hrs, Vd = 505.8 +/- 40.7 ml/kg, Cl = 87.9 +/- 31.6 ml/kg/hr, F = 0.86 +/- 0.26. One patient did not develop detectable plasma theophylline levels until 20 hours after receiving the sustained release product, but rapidly absorbed 96% of orally administered theophylline elixir. While we could demonstrate no consistent abnormality of theophylline distribution or elimination in cystic fibrosis patients, large interindividual differences in elimination may exist. In addition, some C.F. patients may have impaired or delayed absorption of sustained release theophylline preparations.