Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4 mPa s) showed an incomplete drug release within 24 h (<50%). Increasing production temperatures resulted in a lower drug release rate. Substituting part of the EC fraction by HPMC (HPMC/EC-ratio: 20/50 and 35/35) resulted in faster and constant drug release rates. Formulations containing 50% HPMC had a complete and first-order drug release

profile with drug release controlled via the combination of diffusion and swelling/erosion. Faster drug release rates were observed for higher viscosity grades of EC (Mw > 20 mPa s) and HPMC (4000 and 10,000 mPa s). Tablet porosity was low Selleckchem GSK2399872A (<4%). Differential scanning calorimetry (DSC) and X-ray powder diffraction studies (X-RD) showed that solid dispersions were formed during processing. Using thermogravimetrical analysis (TGA) and gel-permeation chromatography BAY 73-4506 mw no degradation of drug and matrix polymer was observed. The surface morphology was investigated with the aid of scanning electron microscopy (SEM) showing an influence of the process temperature. Raman spectroscopy demonstrated that the drug is distributed in the entire

matrix, however, some drug clusters were identified. (c) 2008 Elsevier B.V. All rights reserved.”
“Spontaneous deamination of cytosine to uracil in DNA is a ubiquitous source of C -> T mutations, but occurs with a half life of similar to 50 000 years. In contrast, cytosine within sunlight induced cyclobutane dipyrimidine dimers (CPD’s), deaminate

within hours to days. Methylation of C increases the frequency of CPD formation at PyCG sites which correlate with C -> T mutation hotspots in skin cancers. MeCP2 binds to (m)CG sites and acts as a transcriptional regulator and chromatin modifier affecting thousands of genes, but its effect on CPD formation and deamination is unknown. We report that the methyl CpG binding domain of MeCP2 (MBD) greatly enhances C=(m)C CPD formation at a TC(m)CG site in duplex DNA and binds with equal or better affinity to the CPD-containing duplex compared Pexidartinib mouse with the undamaged duplex. In comparison, MBD does not enhance T=(m)C CPD formation at a TT(m)CG site, but instead increases CPD formation at the adjacent TT site. MBD was also found to completely suppress deamination of the T=(m)CG CPD, suggesting that MeCP2 may have the capability to both suppress UV mutagenesis at Py(m)CpG sites as well as enhance it.”
“Background: Excessive airway mucus secretion is a remarkable trait of asthma. Mucus overproduction mainly resulted from an increase in goblet cell numbers, which causes considerable damage to health. However, effective therapeutic treatments are still lacking for mucus hypersecretion. Human calcium-activated chloride channel 1 (hCLCA1) has been identified to be predominantly responsible for mucus hypersecretion.