ABSTRACT
In this work, the production and characterization of electrospun scaffolds of the copolymer α,ß-poly(N-2-hydroxyethyl)-DL-aspartamide-graft-polylactic acid (PHEA-g-PLA), proposed for a potential topical release of Ibuprofen (IBU), are reported. The drug has been chemically linked to PHEA-g-PLA and/or physically mixed to the copolymer before electrospinning. Degradation studies have been performed as a function of time in Dulbecco phosphate buffer solution pH 7.4, for both unloaded and drug-loaded scaffolds. By using an appropriate ratio between drug physically blended to the copolymer and drug-copolymer conjugate, a useful control of its release can be obtained. MTS assay on human dermal fibroblasts cultured onto these scaffolds, showed the absence of toxicity as well as their ability to allow cell adhesion.
Subject(s)
Analgesics, Non-Narcotic/administration & dosage , Aspartic Acid/analogs & derivatives , Drug Carriers/chemistry , Ibuprofen/administration & dosage , Polyesters/chemistry , Tissue Scaffolds/chemistry , Administration, Topical , Biocompatible Materials/chemistry , Cell Adhesion , Cell Line , Cell Survival , Dermis/cytology , Fibroblasts/cytology , HumansABSTRACT
A hyaluronic acid derivative bearing pendant L-benzoyl-cysteine portions (with a derivatization degree equal to 10 mol.%) was synthesized by linking N,N'-dibenzoyl-L-cystine to the polysaccharide and then reducing its disulfide bridge to thiol groups. The formation of pi-pi stacking interactions between the benzoyl moieties was studied by fluorescence spectroscopy as a function of polymer concentration and oxidation time. The efficiency of oxidation of thiol groups to disulfide bridges occurring in phosphate buffer pH 7.4, was determined by colorimetric assays. The hydrogel formed by means of oxidative crosslinking has shown the presence of fibrillar aggregates as detected by light and scanning electron microscopy. Human derm fibroblasts were encapsulated into hydrogel-forming solution, and their ability to proliferate was tested during 3 days of culture.
Subject(s)
Cross-Linking Reagents/chemistry , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Cell Proliferation , Cell Survival , Cystine/chemistry , Disulfides/chemistry , Fibroblasts/metabolism , Humans , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Materials Testing , Microscopy, Electron, Scanning/methods , Oxygen/chemistry , Phosphates/chemistry , Polymers/chemistry , Spectroscopy, Fourier Transform Infrared , Time FactorsABSTRACT
PURPOSE: To assess the efficacy of low mechanical index (MI) real time grey scale contrast-enhanced US (CEUS) in the differentiation of breast lesions in comparison to Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: 50 lesions previously detected at mammography or conventional US were evaluated by means of CEUS and MRI. Contrast-enhanced examinations were performed with a dedicated equipment (Esatune, Esaote, Genoa, Italy), before and after injection of 4.8 ml of Sonovue (Bracco, Milan, Italy). MRI was conducted with a 1.5 T equipment (Siemens Vision Plus, Erlangen, Germany) with bilateral dedicated superficial coil, on T2w STIR and 3D Flash T1w before and 1, 2, 3, 4, 5 minutes after the administration of contrast agent (Gd-DTPA, 1.5 ml/kg). Wash-in and wash-out curves were assessed for both procedures. A specific sonographic quantification software (Qontrast, Bracco, Milan, Italy), based on pixel by pixel signal intensity over time, was used to obtain contrast-enhanced sonographic perfusion maps for each lesion. Mc Nemar test was then calculated. RESULTS: 24 invasive ductal carcinomas, 18 fibroadenomas, 4 fibro-cystic dysplasias, 1 mucinous carcinoma, 1 invasive ducto-lobular carcinoma, 1 intraductal florid papillomatosis and 1 phylloides tumour were diagnosed. Contrast-enhanced sonographic patterns correlated well with those provided by MRI. Sensitivity, specificity, and accuracy of US were: 69.2 %, 66.7 %, and 68 %, respectively. According to the different contrast enhancement patterns and the resulting perfusion maps, all the malignant lesions and 9 out of 12 benign lesions were correctly diagnosed, thus resulting in 87.5 % of specificity and 100 % of sensitivity. Regarding the specificity, there is no difference between US and CEUS with McNemar (p = 0.18). Regarding sensitivity, the difference between contrast-enhanced US and US is significant as calculated with McNemar test (p = 0.013). The three lesions which were incorrectly classified as malignant were two hypervascularised fibroadenomas in young women and a phylloides tumour. CONCLUSION: CEUS seems to be a reliable method to differentiate breast lesions, since it provides typical enhancement patterns. Contrast sonographic perfusion curves correlate well with MRI wash in--wash out curves.
Subject(s)
Breast Diseases/diagnostic imaging , Breast Diseases/diagnosis , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/diagnostic imaging , Contrast Media , Diagnosis, Differential , Female , Fibroadenoma/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/methods , Male , Middle Aged , Sensitivity and Specificity , Ultrasonography/methodsABSTRACT
The synthetic copolypeptide (Lys33, Leu67)100-Orn20, modeled on some general features of the histone sequences, has been found to supercoil the DNA double helix, wrapping it into a micelle, as a result of cohesive interactions between the polypeptide hydrophobic moieties. X-ray low-angle diffraction of complexes between the polypeptide and DNA is characterized by maxima at 50, 32, and 23 A, reminiscent of the chromatin pattern. The existence of a nucleosome-like structure along the DNA is suggested by gel electrophoresis analysis of DNA fragments after micrococcal nuclease digestion, showing the presence of a fragment of about 100 basepairs (bp) long. Topological experiments on the complexes with supercoiled as well as relaxed circular DNA by two-dimensional gel electrophoresis show the presence of left-handed superhelical turns. The results are in agreement with an intrinsic propensity of B-DNA to writhe into left-handed supercoils.
