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To date, silicone gel and silicone occlusive plates are the most useful and effective treatment options for hypertrophic scars (surgical and traumatic). Use of silicone sheeting has also been demonstrated to be effective in the treatment of minor keloids in association with corticosteroid intralesional infiltration. In our practice, we encountered four problems: maceration, rashes, pruritus and infection. Not all patients are able to tolerate the cushion, especially children, and certain anatomical regions as the face and the upper chest are not easy to dress for obvious social, psychological and aesthetic reasons. In other anatomical regions, it is also difficult to obtain adequate compression and occlusion of the scar. To overcome such problems of applying silicone gel sheeting, we tested the use of liquid silicone gel (LSG) in the treatment of 18 linear hypertrophic scars (HS group) and 12 minor keloids (KS group) as an alternative to silicone gel sheeting or cushion. Objective parameters (volume, thickness and colour) and subjective symptoms such as pain and pruritus were examined. Evaluations were made when the therapy started and after 30, 90 and 180 days of follow-up. After 90 days of treatment with silicone gel alone (two applications daily), HS group showed a significant improvement in terms of volume decrease, reduced inflammation and redness and improved elasticity. In conclusion, on the basis of our clinical data, we find LSG to be a useful method to overcome the difficulties of applying silicone gel sheeting on irregular surface. To date, silicone gel and silicone occlusive plates are the most useful and effective treatment options for hypertrophic scars (surgical and traumatic). Use of silicone sheeting has also been demonstrated to be effective in the treatment of minor keloids in association with corticosteroid intralesional infiltration. In our practice, we encountered four problems: maceration, rashes, pruritus and infection. Not all patients are able to tolerate the cushion, especially children, and certain anatomical regions as the face and the upper chest are not easy to dress for obvious social, psychological and aesthetic reasons. In other anatomical regions, it is also difficult to obtain adequate compression and occlusion of the scar. To overcome such problems of applying silicone gel sheeting, we tested the use of liquid silicone gel (LSG) in the treatment of 18 linear hypertrophic scars (HS group) and 12 minor keloids (KS group) as an alternative to silicone gel sheeting or cushion. Objective parameters (volume, thickness and colour) and subjective symptoms such as pain and pruritus were examined. Evaluations were made when the therapy started and after 30, 90 and 180 days of follow-up. After 90 days of treatment with silicone gel alone (two applications daily), HS group showed a significant improvement in terms of volume decrease, reduced inflammation and redness and improved elasticity. In conclusion, on the basis of our clinical data, we find LSG to be a useful method to overcome the difficulties of applying silicone gel sheeting on irregular surface.

Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. Increasing evidence has shown that aggregation of amyloid β (Aβ) and oxidative stress are strictly interconnected, and their modulation might have a positive and synergic effect in contrasting AD-related impairments. Herein, a new and efficient fragment-based approach towards tyrosol phosphodiester derivatives (TPDs) has been developed starting from suitable tyrosol building blocks and exploiting the well-established phosphoramidite chemistry. The antioxidant activity of new TPDs has been tested as well as their ability to inhibit Aβ protein aggregation. In addition, their metal chelating ability has been evaluated as a possible strategy to develop new natural-based entities for the prevention or therapy of AD. Interestingly, TPDs containing a catechol moiety have demonstrated highly promising activity in inhibiting the aggregation of Aβ40 and a strong ability to chelate biometals such as CuII and ZnII .

Curcumin is a bioactive natural compound with a wide range of pharmacological properties, including antitumor activity; however, its clinical application has been limited because of its low solubility, stability, and bioavailability. In this study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics of curcumin in good purity and yield. The non-effective findings in pancreatic cancer cells switched to strong growth inhibition and cell death efficacy for PC3 prostate cancer cells, and mimic 9, in which tyrosol (TYR) and homovanillyl alcohol (HVA) units were linked by a phosphodiester bond, was quite effective not only in cell growth inhibition but also in causing strong cell death under the study conditions and treatments that were not effective in PANC1 cells. The results got more exciting when we also consider the findings in SW480 human colorectal carcinoma cell line, where the growth inhibitor effects were more in line with that of the PC3 cells, but the lack of cell death effect was more in line with the PANC1 cells.

Recently, many studies highlighted the consistent finding of irbesartan in effluents from wastewater treatment plants (WWTPs) and in some rivers and lakes in both Europe and North America, suggesting that no N80% can be removed by specific treatments. The present investigation attempts to study the chemical fate of irbesartan in a simulated chlorination step, mimicking the conditions of a WWTP. A total of six disinfection by-products were identified, five were completely new, and separated on a C-18 column by employing a gradient HPLC method. Initially, a complete mass fragmentation pathway of the drug was established with the help of MS/ TOF, and subsequently, the disinfection by-products were subjected to MS/TOF mass studies to obtain their mass and fragment pattern. The MS results helped to assign tentative structures to the disinfection products, which were verified through 1D and 2D NMR experiments. The chemical structures of the new compounds have been justified by a proposed mechanism of formation. A preliminary ecotoxicity assessment with the crus- tacean Daphnia magna showed that some of the identified by-products were up to 12-times more toxic than irbesartan.

The self-assembling of the amyloid β (Aβ) peptide into neurotoxic aggregates is considered a central event in the pathogenesis of Alzheimer’s disease (AD). Based on the “amyloid hypothesis”, many efforts have been devoted to designing molecules able to halt disease progression by inhibiting Aβ self-assembly. Here, we combine biophysical (ThT assays, TEM and AFM imaging), biochemical (WB and ESI-MS), and computational (all-atom molecular dynamics) techniques to investigate the capacity of four optically pure components of the natural product silymarin (silybin A, silybin B, 2,3-dehydrosilybin A, 2,3-dehydrosilybin B) to inhibit Aβ aggregation. Despite TEM analysis demonstrating that all the four investigated flavonoids prevent the formation of mature fibrils, ThT assays, WB and AFM investigations showed that only silybin B was able to halt the growth of small-sized protofibrils thus promoting the formation of large, amorphous aggregates. Molecular dynamics (MD) simulations indicated that silybin B interacts mainly with the C-terminal hydrophobic segment 35MVGGVV40 of Aβ40. Consequently to silybin B binding, the peptide conformation remains predominantly unstructured along all the simulations. By contrast, silybin A interacts preferentially with the segments 17LVFF20 and 27NKGAII32 of Aβ40 which shows a high tendency to form bend, turn, and β-sheet conformation in and around these two domains. Both 2,3-dehydrosilybin enantiomers bind preferentially the segment 17LVFF20 but lead to the formation of different small-sized, ThT-positive Aβ aggregates. Finally, in vivo studies in a transgenic Caenorhabditis elegans strain expressing human Aβ indicated that silybin B is the most effective of the four compounds in counteracting Aβ proteotoxicity. This study underscores the pivotal role of stereochemistry in determining the neuroprotective potential of silybins and points to silybin B as a promising lead compound for further development in anti-AD therapeutics.

A new and preparative oxidation of silibinin has been developed to give access to two different silibinin derivatives known for their enhanced antioxidant properties. Conventional heating methods were compared with results obtained from microwave (MW) heating. The base-catalysed oxidation of silibinin under MW heating is a very efficient method for the preparation of 2,3-dehydrosilybin and a related silybin rearrangement product. This latter compound shows enhanced radical scavenging properties. Optimised conditions were used to prepare 2,3-dehydrosilybins A and B from optically pure silybins A and B. An efficient, preparative purification method was also developed to enable isolation of different products in high purity. (C) 2013 Elsevier Ltd. All rights reserved.