A fluorescently labeled dendronized polymer-enzyme conjugate carrying multiple copies of two different types of active enzymes

A hybrid structure of a synthetic dendronized polymer, two different types of enzymes (superoxide dismutase and horseradish peroxidase), and a fluorescent dye (fluorescein) was synthesized. Thereby, a single polymer chain carried multiple copies of the two enzymes and the fluorescein. The entire attachment chemistry is based on UV/vis-quantifiable bis-aryl hydrazone bond formation that allows direct quantification of bound molecules: 60 superoxide dismutase, 120 horseradish peroxidase, and 20 fluorescein molecules on an average polymer chain of 2000 repeating units. To obtain other enzyme ratios the experimental conditions were altered accordingly. Moreover, it could be shown that both enzymes remained fully active and catalyzed a two-step cascade reaction.

Polymer stent coating for prevention of neointimal hyperplasia

AIMS: Restenosis has been the principal limitation of bare metal stents. Based upon the presumption that platelet and inflammatory cell recruitment initiate neointimal proliferation, we explored a novel polymer coating that reduces cell-stent interactions. The purpose of the present study was to investigate the effect of poly(L-lysine)-graft-poly(ethyleneglycol) (PLL-g-PEG) adsorbed to stent surfaces to reduce neointimal hyperplasia in the porcine restenosis model. METHODS AND RESULTS: Seven animals were instrumented each with 2 stainless steel stents (15 mm length, 2.5-3.5 mm diameter), randomly implanted in 1 major epicardial coronary artery. One stent was dip-coated with PLL-g-PEG, whereas the other stent served as the uncoated control stent. All animals were sacrificed after 6 weeks for histological examination. Neointimal hyperplasia was significantly less (-51%) in the PLL-g-PEG-coated stents (1.15 +/- 0.59 mm2) than in the uncoated control stents (2.33 +/- 1.01 mm2; p < 0.001). Conversely, lumen size was larger in the PLL-g-PEG-coated stents (2.91 +/- 1.17 mm2) than in the uncoated stents (2.04 +/- 0.64 mm2; p < 0.001). High magnification histomorphologic examination revealed no signs of inflammation or thrombus formation in either stent group. CONCLUSIONS: Polymeric steric stabilization of stents with PLL-g-PEG significantly reduces neointimal hyperplasia in the porcine restenosis model. Reduction of cell-stent interactions mediated by PLL-g-PEG appear to improve biocompatibility of stainless steel stents without evidence of adverse inflammatory or prothrombotic effects.

[Radical prostatectomy in the treatment of organ confined prostate cancer]

Open radical prostatectomy represents one possible therapeutic option for treating patients with clinically localized prostate cancer Patient selection and the surgical management have undergone important changes during the last years, resulting in lower morbidity and probably in a better tumor control due to a better standardisation of the surgical technique. Long-term functional outcome regarding continence and potency are of increasing importance and influence mainly the quality of life in these patients. Open radical retropubic prostatectomy remains the gold standard in patients with localized prostate cancer, due to its low morbidity and excellent oncological and functional results. The value of laparoscopic and robotic radical prostatectomy is still discussed controversially. Due to the relative high morbidity during the so-called learning curve and the lack of long-term oncological and functional results, these techniques seem to show less favourable results.

The long-term mechanical integrity of non-reinforced PEEK-OPTIMA polymer for demanding spinal applications: experimental and finite-element analysis

Polyetheretherketone (PEEK) is a novel polymer with potential advantages for its use in demanding orthopaedic applications (e.g. intervertebral cages). However, the influence of a physiological environment on the mechanical stability of PEEK has not been reported. Furthermore, the suitability of the polymer for use in highly stressed spinal implants such as intervertebral cages has not been investigated. Therefore, a combined experimental and analytical study was performed to address these open questions. A quasi-static mechanical compression test was performed to compare the initial mechanical properties of PEEK-OPTIMA polymer in a dry, room-temperature and in an aqueous, 37 degrees C environment (n=10 per group). The creep behaviour of cylindrical PEEK polymer specimens (n=6) was measured in a simulated physiological environment at an applied stress level of 10 MPa for a loading duration of 2000 hours (12 weeks). To compare the biomechanical performance of different intervertebral cage types made from PEEK and titanium under complex loading conditions, a three-dimensional finite element model of a functional spinal unit was created. The elastic modulus of PEEK polymer specimens in a physiological environment was 1.8% lower than that of specimens tested at dry, room temperature conditions (P<0.001). The results from the creep test showed an average creep strain of less than 0.1% after 2000 hours of loading. The finite element analysis demonstrated high strain and stress concentrations at the bone/implant interface, emphasizing the importance of cage geometry for load distribution. The stress and strain maxima in the implants were well below the material strength limits of PEEK. In summary, the experimental results verified the mechanical stability of the PEEK-OPTIMA polymer in a simulated physiological environment, and over extended loading periods. Finite element analysis supported the use of PEEK-OPTIMA for load-bearing intervertebral implants.

Resistive polymer versus forced-air warming: comparable heat transfer and core rewarming rates in volunteers

BACKGROUND: Mild perioperative hypothermia increases the risk of several severe complications. Perioperative patient warming to preserve normothermia has thus become routine, with forced-air warming being used most often. In previous studies, various resistive warming systems have shown mixed results in comparison with forced-air. Recently, a polymer-based resistive patient warming system has been developed. We compared the efficacy of a standard forced-air warming system with the resistive polymer system in volunteers. METHODS: Eight healthy volunteers participated, each on two separate study days. Unanesthetized volunteers were cooled to a core temperature (tympanic membrane) of 34 degrees C by application of forced-air at 10 degrees C and a circulating-water mattress at 4 degrees C. Meperidine and buspirone were administered to prevent shivering. In a randomly designated order, volunteers were then rewarmed (until their core temperatures reached 36 degrees C) with one of the following active warming systems: (1) forced-air warming (Bair Hugger warming cover #300, blower #750, Arizant, Eden Prairie, MN); or (2) polymer fiber resistive warming (HotDog whole body blanket, HotDog standard controller, Augustine Biomedical, Eden Prairie, MN). The alternate system was used on the second study day. Metabolic heat production, cutaneous heat loss, and core temperature were measured. RESULTS: Metabolic heat production and cutaneous heat loss were similar with each system. After a 30-min delay, core temperature increased nearly linearly by 0.98 (95% confidence interval 0.91-1.04) degrees C/h with forced-air and by 0.92 (0.85-1.00) degrees C/h with resistive heating (P = 0.4). CONCLUSIONS: Heating efficacy and core rewarming rates were similar with full-body forced-air and full-body resistive polymer heating in healthy volunteers.

Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial

BACKGROUND: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING: Biosensors Europe SA, Switzerland.

In-plane thermal conductivity modeling of carbon filled liquid crystal polymer based resins

Adding conductive carbon fillers to insulating thermoplastic resins increases composite electrical and thermal conductivity. Often, as much of a single type of carbon filler is added to achieve the desired conductivity, while still allowing the material to be molded into a bipolar plate for a fuel cell. In this study, varying amounts of three different carbons (carbon black, synthetic graphite particles, and carbon fiber) were added to Vectra A950RX Liquid Crystal Polymer. The in-plane thermal conductivity of the resulting single filler composites were tested. The results showed that adding synthetic graphite particles caused the largest increase in the in-plane thermal conductivity of the composite. The composites were modeled using ellipsoidal inclusion problems to predict the effective in-plane thermal conductivities at varying volume fractions with only physical property data of constituents. The synthetic graphite and carbon black were modeled using the average field approximation with ellipsoidal inclusions and the model showed good agreement with the experimental data. The carbon fiber polymer composite was modeled using an assemblage of coated ellipsoids and the model showed good agreement with the experimental data.

Molecular modeling of EPON 862-DETDA polymer

EPON 862 is an epoxy resin which is cured with the hardening agent DETDA to form a crosslinked epoxy polymer and is used as a component in modern aircraft structures. These crosslinked polymers are often exposed to prolonged periods of temperatures below glass transition range which cause physical aging to occur. Because physical aging can compromise the performance of epoxies and their composites and because experimental techniques cannot provide all of the necessary physical insight that is needed to fully understand physical aging, efficient computational approaches to predict the effects of physical aging on thermo-mechanical properties are needed. In this study, Molecular Dynamics and Molecular Minimization simulations are being used to establish well-equilibrated, validated molecular models of the EPON 862-DETDA epoxy system with a range of crosslink densities using a united-atom force field. These simulations are subsequently used to predict the glass transition temperature, thermal expansion coefficients, and elastic properties of each of the crosslinked systems for validation of the modeling techniques. The results indicate that glass transition temperature and elastic properties increase with increasing levels of crosslink density and the thermal expansion coefficient decreases with crosslink density, both above and below the glass transition temperature. The results also indicate that there may be an upper limit to crosslink density that can be realistically achieved in epoxy systems. After evaluation of the thermo-mechanical properties, a method is developed to efficiently establish molecular models of epoxy resins that represent the corresponding real molecular structure at specific aging times. Although this approach does not model the physical aging process, it is useful in establishing a molecular model that resembles the physically-aged state for further use in predicting thermo-mechanical properties as a function of aging time. An equation has been predicted based on the results which directly correlate aging time to aged volume of the molecular model. This equation can be helpful for modelers who want to study properties of epoxy resins at different levels of aging but have little information about volume shrinkage occurring during physical aging.