Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

Methacrylate hydrogels reinforced with bacterial cellulose

Composite hydrogels consisting of nanofibrous bacterial cellulose (BC) embedded in a biocompatible polymeric matrix of various methacrylates were synthesized by UV polymerization using the ‘ever‐wet’ technique. The effect of monomer(s) type and ratio, system dilution at polymerization, monomer(s) hydrophilicity, crosslink density and cellulose/hydrogel ratio was investigated. The effect of BC reinforcement on equilibrium swelling depends on whether the neat gel swells more when brought into contact with water. The major improvement achieved by introduction of 1%–2% BC concerns mechanical properties. Compared with neat gels, the storage shear modulus G′ increased by a factor 10‐20, and the loss part G″ also rose significantly. The compression modulus ranged from 2 to 5.5 MPa for composites swollen to equilibrium (20‐70 wt% water). The BC‐hydrogel composites are considered for application in the tissue engineering area. Copyright © 2012 Society of Chemical Industry     

A new strategy for plasticizing and stabilization of PVC mixtures

This study was undertaken to examine possible use of classic tetravalent tin‐based heat stabilizers for the preparation of a polymer plasticizer: poly(ε‐caprolactone) (PCL) and simultaneous stabilization of PVC in PVC/PCL mixtures. PCL was prepared from ε‐caprolactone (CL) by polymerization initiated by tin‐containing organic compounds and successfully used to simultaneously plasticize and stabilize PVC. Moreover, conditions under which the polymerization of CL took place directly in situ during PVC/CL mixture processing were found. The procedure yielded homogeneous plasticized PVC/PCL mixtures, which were stable and contained >90% of the original monomer content. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41066.     

Standardized tests fail to assess the effects of antibiotics on environmental bacteria

Pharmaceuticals are designed and used because of their specific biological effects. Over the past decade, compounds from various classes of pharmaceuticals have been detected in the environment. Concern has grown about the adverse effects pharmaceuticals in the environment might potentially have on human and ecological health. A sound risk assessment is therefore urgently needed for pharmaceuticals. Standardized tests for assessing the effects of chemicals on environmental organisms are widely used for this purpose. However it is questionable whether classical standardized tests give reliable data needed for environmental risk assessment. In this study we investigated the suitability of the respiration inhibition test OECD 209 for the assessment of the effects of antibiotics, disinfectants and cytotoxics on sewage sludge bacteria. We found that inhibition concentrations can strongly depend on the test period and the type of compound. We conclude that tests to assess the effects of pharmaceuticals on environmental organisms such as bacteria have to be evaluated before their results can be used in environmental risk assessment.     

Sample classification based on Bayesian spectral decomposition of metabonomic NMR data sets

1H NMR spectra of biofluids provides a wealth of biochemical information on the metabolic status of an organism. Through the application of pattern recognition and classification algorithms, the data have been shown to provide information on disease diagnosis and the beneficial and adverse effects of potential therapeutics. Here, a novel approach is described for identifying subsets of spectral patterns in databases of NMR spectra, and it is shown that the intensities of these spectral patterns can be related to the onset and recovery from a toxic lesion in both a time-related and dose-related fashion. These patterns form a new type of combination biomarker for the biological effect under study. The approach is illustrated with a study of liver toxicity in rats using NMR spectra of urine following administration of a model hepatotoxin hydrazine.     

Mixtures of poly(vinyl chloride) and copolyesters based on ε‐caprolactone and L‐lactide: Miscibility,thermal stability,and weathering resistance

Properties of the blends of Poly(vinyl chloride) (PVC) and poly(ε‐caprolactone) (PCLO) and copolyesters based on ε‐caprolactone and L‐lactide (LLA) prepared by rolling were studied. Incorporating the LLA units into the structure of PCLO the content of the crystalline phase was controlled. Miscibility of the blends was assessed using DMA, and basic mechanical properties were correlated with the type and content of the polymer plasticizer. The PVC blends containing up to 20 wt parts polyesters were miscible. The presence of the LLA units in the copolyester influenced negatively the thermal stability. On the other hand even small content of copolyester in the blend enhanced the resistivity against aging. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Investigation of the Effect of Accelerated Hydrothermal Aging on the Cu Sites in a Cu-BEA Catalyst for NH3-SCR Applications

The influence of hydrothermal aging between 500 and 900 °C for 3 h, on the structure of a Cu-Beta catalyst was studied in this work. The XRD measurements indicated a structural breakdown of the zeolite upon 900 °C hydrothermal aging. This was confirmed from the loss of surface area as measured by BET method. The temperature for the zeolite structure break down was different between the powder bed as opposed to the sample that was washcoated on a cordierite monolith, which was most likely due to slightly different aging conditions and the presence of binders. The strong increase in the intensity of the Cu2p XPS peak indicated that the surface is enriched of copper at higher temperatures due to the zeolite structure collapse. The presence of CuO is usually accompanied by a satellite peak, which was clearly observed at higher binding energies for the catalysts aged at 800 and 900 °C. The XPS results are in good agreement with the UV–Vis experiments, which also point to the formation of copper oxide after high temperature aging.     

Electronegativity Equalization Method: Parameterization and Validation for Large Sets of Organic,Organohalogene and Organometal Molecule

The Electronegativity Equalization Method (EEM) is a fast approach for charge calculation. A challenging part of the EEM is the parameterization, which is performed using ab initio charges obtained for a set of molecules. The goal of our work was to perform the EEM parameterization for selected sets of organic, organohalogen and organometal molecules. We have performed the most robust parameterization published so far. The EEM parameterization was based on 12 training sets selected from a database of predicted 3D structures (NCI DIS) and from a database of crystallographic structures (CSD). Each set contained from 2000 to 6000 molecules. We have shown that the number of molecules in the training set is very important for quality of the parameters. We have improved EEM parameters (STO-3G MPA charges) for elements that were already parameterized, specifically: C, O, N, H, S, F and Cl. The new parameters provide more accurate charges than those published previously. We have also developed new parameters for elements that were not parameterized yet, specifically for Br, I, Fe and Zn. We have also performed crossover validation of all obtained parameters using all training sets that included relevant elements and confirmed that calculated parameters provide accurate charges.     

Biodegradability of 14C-labeled antibiotics in a modified laboratory scale sewage treatment plant at environmentally relevant concentrations

For all new pharmaceuticals, an environmental risk assessment (ERA) has to be performed according to guidelines developed by the European Medicines Evaluation Agency. An important factor of this procedure is the assessment of the predicted environmental concentration in the aquatic environment, which is significantly influenced by the biodegradability of pharmaceuticals in sewage treatment plants. Established standardized methods for determining biodegradation under laboratory conditions apply to substance concentrations, which are much higherthan those expected in reality. Against this background, the laboratory scale sewage treatment plant (LSSTP), as described by the Organisation for Economic Cooperation and Development (OECD) Guideline No. 303A, was modified to construct a lossless system, which allows laboratory testing at realistic concentrations. To verify the experimental setup, the antibiotics benzylpenicillin, ceftriaxone, and trimethoprim were tested at low concentrations (microg/L) using 14C-labeled compounds. The results show that approximately 25% of benzylpenicillin was mineralized, whereas ceftriaxone and trimethoprim were not mineralized at all. Due to the high total recoveries of added radioactivity (> or =95%) and the fact that the findings comply with available literature data, the lossless operation of the test system could be proved. Consequently, the modified LSSTP is a suitable tool to determine more realistic biodegradation data required for the exposure assessment within the scope of an ERA for pharmaceuticals.