The kinetics of UV radiation-induced fast collapse and recovery in thermally cycled and rehydrated light- and thermo- double-responsive copolymer films of poly(oligo(ethylene glycol) methyl ether ...methacrylate-co-6-(4-phenylazophenoxy)hexyl acrylate), abbreviated as P(OEGMA300-co-PAHA), are probed by in situ neutron reflectivity (NR). The copolymer film is exposed to a thermal treatment starting at a temperature of 60 °C, which is well above its transition temperature (TT = 53 °C) before the temperature is rapidly decreased from 60 to 23 °C. Based on the applied protocol, the initially collapsed P(OEGMA300-co-PAHA) film is rehydrated due to the switching of polymer chains from a more hydrophobic to a more hydrophilic state when the temperature falls below its TT. The whole rehydration process can be divided into 3 stages: D2O absorption, chain rearrangement, and film reswelling. After rehydration, the thermally cycled P(OEGMA300-co-PAHA) film is switched by UV irradiation via setting the UV radiation on and off. Considering the UV-induced collapse and recovery, both processes are slower than those observed in freshly hydrated films without any thermal stimulus history. Therefore, the experienced thermal history of the film should be considered in the design of sensors and detectors based on double-responsive copolymer films.
The polymer dynamics inside a bulk heterojunction (BHJ), as used in organic solar cells, are investigated with quasielastic neutron scattering to study hydrogen motion in the polymer side chains. ...Different blend ratios of the polymer donor poly({4,8-bis(2-ethylhexyl)oxybenzo1,2-b:4,5-b′dithiophene-2,6-diyl}{3-fluoro-2-(2-ethylhexyl)carbonylthieno3,4-bthiophenediyl}) (PTB7) and the small molecule acceptor 6,6phenyl-C71-butyric acid methyl ester (PCBM) are investigated. In addition, the influence of performance-enhancing measures, such as the use of the solvent additive 1,8-diiodooctane (DIO) and the post-production treatment of the BHJ films with methanol, on the polymer dynamics is studied. The analysis of mean square displacements as well as relaxation times of diffusional motions of the hydrogen atoms, located mainly in the polymer side chains, shows a gradual stiffening of the PTB7 side chains for higher PCBM loading in the BHJ films. The presence of DIO significantly increases diffusive mobility inside the films, while the methanol treatment does not affect hydrogen motions.
Blend films of poly4,8‐bis(2‐ethylhexyl)oxybenzo1,2‐b:4,5‐b'dithiophene‐2,6‐diyl3‐fluoro‐2‐(2‐ethylhexyl)carbonylthieno3,4‐bthiophenediyl (PTB7) in combination with ...6,6‐phenyl‐C61‐butyric‐acid‐methyl‐ester (PCBM) are a model system for low bandgap organic photovoltaics. Typically, solvent additives are used to improve the power conversion efficiencies of the resulting devices but possibly also decrease the device stability. In this study, we use the binary solvent additive 1,8‐diiodooctane:diphenylether (DIO:DPE) for PTB7:PCBM blend films and study how different film drying procedures influence the physical and chemical stability of the polymer blend. The strong influence of the drying procedure on the stability against photoinduced degradation of the PTB7:PCBM films, produced with solvent additives, is shown with data from UV–visible (UV–vis), Fourier transform infrared (FTIR) and Raman spectroscopy. The addition of solvent additive molecules DIO:DPE to the PTB7:PCBM blend accelerates the degradation compared with the pristine blend. At higher annealing temperature a removal of the additives is bringing degradation back to the level of the pristine blend films, which is promising for photovoltaic applications.
The in vivo assessment of tissue metabolism represents a novel strategy for the evaluation of oncologic disease. Hepatocellular carcinoma (HCC) is a high-prevalence, high-mortality tumor entity often ...discovered at a late stage. Recent evidence indicates that survival differences depend on metabolic alterations in tumor tissue, with particular focus on glucose metabolism and lactate production. Here, we present an in vivo imaging technique for metabolic tumor phenotyping in rat models of HCC. Endogenous HCC was induced in Wistar rats by oral diethyl-nitrosamine administration. Peak lactate-to-alanine signal ratios (L/A) were assessed with hyperpolarized magnetic resonance spectroscopic imaging (HPMRSI) after 1-13Cpyruvate injection. Cell lines were derived from a subset of primary tumors, re-implanted in nude rats, and assessed in vivo with dynamic hyperpolarized magnetic resonance spectroscopy (HPMRS) after 1-13Cpyruvate injection and kinetic modelling of pyruvate metabolism, taking into account systemic lactate production and recirculation. For ex vivo validation, enzyme activity and metabolite concentrations were spectroscopically quantified in cell and tumor tissue extracts. Mean peak L/A was higher in endogenous HCC compared to non-tumorous tissue. Dynamic HPMRS revealed higher pyruvate-to-lactate conversion rates (kpl) and lactate signal in subcutaneous tumors derived from high L/A tumor cells, consistent with ex vivo measurements of higher lactate dehydrogenase (LDH) levels in these cells. In conclusion, HPMRS and HPMRSI reveal distinct tumor phenotypes corresponding to differences in glycolytic metabolism in HCC tumor tissue.
Abstract
OBJECTIVES
With the expansion of transcatheter aortic valve replacement (TAVR) into intermediate and low risk, the number of TAVR procedures is bound to rise and along with it the number of ...cases of infective endocarditis following TAVR (TIE). The aim of this study was to review a multicentre experience of patients undergoing surgical intervention for TIE and to analyse the underlying indications and operative results.
METHODS
We retrospectively identified and analysed 69 patients who underwent cardiac surgery due to TIE at 9 cardiac surgical departments across Germany. The primary outcome was operative mortality, 6-month and 1-year survival.
RESULTS
Median age was 78 years (72–81) and 48(69.6%) were male. The median time to surgical aortic valve replacement was 14 months (5–24) after TAVR, with 32 patients (46.4%) being diagnosed with early TIE. Cardiac reoperations were performed in 17% of patients and 33% underwent concomitant mitral valve surgery. The main causative organisms were: Enterococcus faecalis (31.9%), coagulase-negative Staphylococcus spp. (26.1%), Methicillin-sensitive Staphylococcus aureus (15.9%) and viridians group streptococci (14.5%). Extracorporeal life support was required in 2 patients (2.9%) for a median duration of 3 days. Postoperative adverse cerebrovascular events were observed in 13 patients (18.9%). Postoperatively, 9 patients (13.0%) required a pacemaker and 33 patients (47.8%) needed temporary renal replacement therapy. Survival to discharge was 88.4% and survival at 6 months and 1 year was found to be 68% and 53%, respectively.
CONCLUSIONS
Our results suggest that TIE can be treated according to the guidelines for prosthetic valve endocarditis, namely with early surgery. Surgery for TIE is associated with acceptable morbidity and mortality rates. Surgery should be discussed liberally as a treatment option in patients with TIE by the ‘endocarditis team’ in referral centres.
•Schwannomas and neurofibromas can be differentiated with fiber tracking.•Diffusion tensor imaging provides additional information on nerve integrity.•The nerve sheath tumors schwannoma and ...neurofibroma can be distinguished with mean diffusivity values.
To evaluate the diagnostic value of fiber tractography and diffusivity analysis generated from 3D diffusion-weighted (DW) sequences for preoperative assessment of benign peripheral nerve sheath tumors.
MR imaging at 3 T was performed in 22 patients (mean age 41.9 ± 17.1y, 13 women) with histologically confirmed schwannomas (N = 18) and histologically confirmed neurofibromas (N = 11), including a 3D DW turbo spin echo sequence with fat suppression. Diffusion tensor parameters were computed and fiber tracks were determined. Evaluation was performed by two radiologists and one orthopedic surgeon blinded for final diagnosis. Mean diffusivity was computed to allow further assessment of tumor microstructure. Preoperative fascicle visualization was graded, fascicles were categorized regarding anatomical location and amount of fascicles surrounding the tumor. The agreement of imaging findings with intraoperative findings was assessed.
On 78.3 % of the DTI images, the fascicle visualization was rated as good or very good. Tractography differences were observed in schwannomas and neurofibromas, showing schwannomas to be significantly more often located eccentrically to the nerve (94.8 %) than neurofibromas (0 %, P < 0.01). Fascicles were significantly more often continuous (87.5 %) in schwannomas, while in neurofibromas, none of the tracks was graded to be continuous (0 %, P = 0.014). A substantial agreement between fiber tracking and surgical anatomy was found regarding the fascicle courses surrounding the tumor (κ = 0.78). Mean diffusivity of schwannomas (1.5 ± 0.2 × 10−3 mm2/s) was significantly lower than in neurofibromas (1.8 ± 0.2 × 10−3 mm2/s; P < 0.001). The Youden index showed an optimal cutoff at 1.7 × 10−3 mm2/s (sensitivity, 0.91; specificity, 0.78; J = 0.69).
Preoperative diffusion tensor imaging allowed to accurately differentiate between schwannomas and neurofibromas and to describe their location in relation to the nerve fascicles for preoperative planning.
OBJECTIVES
Despite rapid progress in surgical techniques, there is still a significant lack of surgery-supportive pharmacological treatments. The aim of this study was to test the hypothesis that ...ursolic acid (UA) may prevent intimal hyperplasia of venous bypass grafts.
METHODS
The hypothesis was tested by means of primary cell isolation and culture followed by real-time polymerase chain reaction, western blotting, fluorescence microscopy and fluorescence-activated cell sorting analyses, as well as an in vivo rat model for intimal hyperplasia of venous bypass grafts and immunohistochemistry and histochemistry.
RESULTS
The local application of UA significantly inhibited intimal hyperplasia in vivo (intimal thickness control: 25 µm, UA group: 18 µM-8 weeks after surgery). The UA treatment of grafts significantly resulted in reduced endothelial vascular cell adhesion molecule-1 (VCAM-1) expression, reduced infiltration of the grafts vessel wall by CD45-positive cells and increased smooth muscle cell (SMC) death. In in vitro condition, it could be shown that UA inhibits VCAM-1 expression downstream of NF B and is likely to interfere with VCAM-1 protein synthesis in endothelial cells. Quantification of cell death in vascular smooth muscle cells treated with UA indicated that UA is a potent inducer of SMC apoptosis.
CONCLUSIONS
Our results suggest that UA-mediated inhibition of endothelial VCAM-1 expression reduces the infiltration of venous bypass grafts by CD45-positive cells and inhibits intimal hyperplasia. Apoptosis induction in SMCs may be another method in which UA reduces intimal thickening. UA may constitute a surgery-supportive pharmacon that reduces intimal hyperplasia of vein grafts.
Aims Despite the lower patency of venous compared with arterial coronary artery bypass grafts, ∼50% of grafts used are saphenous vein conduits because of their easier accessibility. In a search for ...ways to increase venous graft patency, we applied the results of a previous pharmacological study screening for non-toxic compounds that inhibit intimal hyperplasia of saphenous vein conduits in organ cultures. Here we analyse the effects and mechanism of action of leoligin (2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-ylmethyl (2Z)-2-methylbut-2-enoat, the major lignan from Edelweiss (Leontopodium alpinum Cass.). Methods and results We found that leoligin potently inhibits vascular smooth muscle cell (SMC) proliferation by inducing cell cycle arrest in the G1-phase. Leoligin induced cell death neither in SMCs nor, more importantly, in endothelial cells. In a human saphenous vein organ culture model for graft disease, leoligin potently inhibited intimal hyperplasia, and even reversed graft disease in pre-damaged vessels. Furthermore, in an in vivo mouse model for venous bypass graft disease, leoligin potently inhibited intimal hyperplasia. Conclusion Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease.
The transplanted heart is initially denervated but undergoes subsequent sympathetic reinnervation. It thus provides a unique model for studying regeneration as a specific component of autonomic nerve ...biology. The aim of this study was to determine the effect of diabetes mellitus on the regenerational capacity of sympathetic neurons using molecule-targeted PET.
Twenty-two nonrejecting, otherwise healthy cardiac transplant recipients underwent PET with the (11)C-labeled physiologic neurotransmitter epinephrine at 4.0 +/- 3.3 y after surgery. Sympathetic reinnervation was defined as regional restoration of epinephrine retention to values within normal limits.
Reinnervation was observed in 8 of 12 patients with no evidence of diabetes and in 6 of 10 patients with a long-term history of diabetes mellitus. The regional extent of reinnervation (4.7% +/- 5.3% of left ventricle vs. 19.1% +/- 20.6% for nondiabetic recipients, P = 0.04) and the regeneration rate (0.8% +/- 1.0% of left ventricle per year vs. 8.0% +/- 10.1% for nondiabetic recipients, P = 0.04) were significantly reduced in diabetic subjects. In a multivariate model, diabetes mellitus was an independent determinant of allograft reinnervation. Finally, the reappearance of innervation was found to correlate with an improved chronotropic and inotropic response to stress in a standardized, symptom-limited exercise test including radionuclide angiography.
The regenerational capacity of the sympathetic nervous system of the heart is reduced, but not abolished, by diabetes mellitus. This study on cardiac transplant recipients further supports a general link between impaired glucose handling and cardiac autonomic nerve function.
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