Dual Stimuli-Responsive Polysaccharide Hydrogels Manufactured by Radiation Technique

Featured Application Stimuli-responsive hydrogels encompassing biobased polymers are anticipated for utilization in various fields, starting from drug delivery systems through temporal actuators and water reservoirs to biodegradable microelements and nutrient delivery depots. This paper describes the results of the radiation-induced crosslinking of polysaccharides modified with hydroxypropyl and carboxymethyl functional groups, hydroxypropylcellulose (HPC) and carboxymethylcellulose (CMC), respectively, without and with poly(ethylene glycol) diacrylate (PEGDA) as a crosslinking agent, to obtain dual stimuli-responsive hydrogels. The gels were characterized in terms of water uptake and gel fraction, parameters that mainly depend on the HPC-CMC compositions, but also on the macromer crosslinker content and the absorbed dose. The swelling of hydrogels is controlled by both the temperature, due to the amphiphilic character of HPC and pH, due to the anionic functional groups of CMC. In spite of a similar degree of substitution in both cellulose derivatives, 1.4 for HPC and 1.2 for CMC, the pH response of hydrogels with an equal content of both polysaccharides is considerably higher-a reduction in swelling of up to 95% with a decrease in the pH to 2 was recorded-than the response to thermal-stimulus-wherein a reduction in swelling of less than 70% with an increasing in temperature to 55 degrees C was found. These biopolymers-based hydrogels of specific, stimuli-responsive swelling properties are anticipated in applications where a combination of two stimuli is essential and biodegradation may be required

EFOMP project on the role of biomedical physics in the education of healthcare professionals

The policy statements describing the role of the medical physicist (and engineer) published by organizations representing medical physics (and engineering) in Europe include the responsibility of providing a contribution to the education of healthcare professionals (physicians and paramedical professions). As a consequence, medical physicists and engineers provide educational services in most Faculties of Medicine / Health Science in Europe. In 2005, the EFOMP council took the decision to set up a Special Interest Group to develop the role of the medical physics educator in such faculties and to work with other healthcare professional groups to produce updated European curricula for them. The effort of the group would provide a base for the progress of the role, its relevance to contemporary healthcare professional education and provide input for future EFOMP policy documents regarding this important aspect of the role of the medical physicist. The present communication will present the group, summarise its latest research and indicate future research directions.peer-reviewe

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Catalysis over zinc-incorporated berlinite (ZnAlPO4) of the methoxycarbonylation of 1,6-hexanediamine with dimethyl carbonate to form dimethylhexane-1,6-dicarbamate

<p>Abstract</p> <p>Background</p> <p>The alkoxycarbonylation of diamines with dialkyl carbonates presents promising route for the synthesis of dicarbamates, one that is potentially 'greener' owing to the lack of a reliance on phosgene. While a few homogeneous catalysts have been reported, no heterogeneous catalyst could be found in the literature for use in the synthesis of dicarbamates from diamines and dialkyl carbonates. Because heterogeneous catalysts are more manageable than homogeneous catalysts as regards separation and recycling, in our study, we hydrothermally synthesized and used pure berlinite (AlPO₄) and zinc-incorporated berlinite (ZnAlPO₄) as heterogeneous catalysts in the production of dimethylhexane-1,6-dicarbamate from 1,6-hexanediamine (HDA) and dimethyl carbonate (DMC). The catalysts were characterized by means of XRD, FT-IR and XPS. Various influencing factors, such as the HDA/DMC molar ratio, reaction temperature, reaction time, and ZnAlPO₄/HDA ratio, were investigated systematically.</p> <p>Results</p> <p>The XRD characterization identified a berlinite structure associated with both the AlPO₄and ZnAlPO₄catalysts. The FT-IR result confirmed the incorporation of zinc into the berlinite framework for ZnAlPO₄. The XPS measurement revealed that the zinc ions in the ZnAlPO₄structure possessed a higher binding energy than those in ZnO, and as a result, a greater electron-attracting ability. It was found that ZnAlPO₄catalyzed the formation of dimethylhexane-1,6-dicarbamate from the methoxycarbonylation of HDA with DMC, while no activity was detected on using AlPO₄. Under optimum reaction conditions (i.e. a DMC/HDA molar ratio of 8:1, reaction temperature of 349 K, reaction time of 8 h, and ZnAlPO₄/HDA ratio of 5 (mg/mmol)), a yield of up to 92.5% of dimethylhexane-1,6-dicarbamate (with almost 100% conversion of HDA) was obtained. Based on these results, a possible mechanism for the methoxycarbonylation over ZnAlPO₄was also proposed.</p> <p>Conclusion</p> <p>As a heterogeneous catalyst ZnAlPO₄berlinite is highly active and selective for the methoxycarbonylation of HDA with DMC. We propose that dimethylhexane-1,6-dicarbamate is formed <it>via </it>a catalytic cycle, which involves activation of the DMC by a key active intermediate species, formed from the coordination of the carbonyl oxygen with Zn(II), as well as a reaction intermediate formed from the nucleophilic attack of the amino group on the carbonyl carbon.</p

Impaired Ca2+-handling in HIF-1α+/− mice as a consequence of pressure overload

The hypoxia-inducible factor (HIF)-1 is critically involved in the cellular adaptation to a decrease in oxygen availability. The influence of HIF-1α for the development of cardiac hypertrophy and cardiac function that occurs in response to sustained pressure overload has been mainly attributed to a challenged cardiac angiogenesis and cardiac hypertrophy up to now. Hif-1α+/+ and Hif-1α+/− mice were studied regarding left ventricular hypertrophy and cardiac function after being subjected to transverse aortic constriction (TAC). After TAC, both Hif-1α+/+ and Hif-1α+/− mice developed left ventricular hypertrophy with increased posterior wall thickness, septum thickness and increased left ventricular weight to a similar extent. No significant difference in cardiac vessel density was observed between Hif-1α+/+ and Hif-1α+/− mice. However, only the Hif-1α+/− mice developed severe heart failure as revealed by a significantly reduced fractional shortening mostly due to increased end-systolic left ventricular diameter. On the single cell level this correlated with reduced myocyte shortenings, decreased intracellular Ca2+-transients and SR-Ca2+ content in myocytes of Hif-1a+/− mice. Thus, HIF-1α can be critically involved in the preservation of cardiac function after chronic pressure overload without affecting cardiac hypertrophy. This effect is mediated via HIF-dependent modulation of cardiac calcium handling and contractility

AA-Amyloidosis Can Be Transferred by Peripheral Blood Monocytes

Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils (‘amyloid enhancing factor’) combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis