Polyenylphosphatidylcholines as bioactive excipient in tablets for the treatment of liver fibrosis.

Liver fibrosis is a condition characterized by the accumulation of extracellular matrix (ECM) arising from the myofibroblastic transdifferentiation of hepatic stellate cells (HSCs) occurring as the natural response to liver damage. To date, no pharmacological treatments have been specifically approved for liver fibrosis. We recently reported a beneficial effect of polyenylphosphatidylcholines (PPCs)-rich formulations in reverting fibrogenic features of HSCs. However, unsaturated phospholipids' properties pose a constant challenge to the development of tablets as preferred patient-centric dosage form. Profiting from the advantageous physical properties of the PPCs-rich Soluthin® S 80 M, we developed a tablet formulation incorporating 70% w/w of this bioactive lipid. Tablets were characterized via X-ray powder diffraction, thermogravimetry, and Raman confocal imaging, and passed the major compendial requirements. To mimic physiological absorption after oral intake, phospholipids extracted from tablets were reconstituted as protein-free chylomicron (PFC)-like emulsions and tested on the fibrogenic human HSC line LX-2 and on primary cirrhotic rat hepatic stellate cells (PRHSC). Lipids extracted from tablets and reconstituted in buffer or as PFC-like emulsions exerted the same antifibrotic effect on both activated LX-2 and PRHSCs as observed with plain S 80 M liposomes, showing that the manufacturing process did not interfere with the bioactivity of PPCs

Liver resection vs radiofrequency ablation in single hepatocellular carcinoma of posterosuperior segments in elderly patients

Background: Liver resection and radiofrequency ablation are considered curative options for hepatocellular carcinoma. The choice between these techniques is still controversial especially in cases of hepatocellular carcinoma affecting posterosuperior segments in elderly patients. Aim: To compare post-operative outcomes between liver resection and radiofrequency ablation in elderly with single hepatocellular carcinoma located in posterosuperior segments. Methods: A retrospective multicentric study was performed enrolling 77 patients age ≥ 70-years-old with single hepatocellular carcinoma (≤ 30 mm), located in posterosuperior segments (4a, 7, 8). Patients were divided into liver resection and radiofrequency ablation groups and preoperative, peri-operative and long-term outcomes were retrospectively analyzed and compared using a 1:1 propensity score matching. Results: After propensity score matching, twenty-six patients were included in each group. Operative time and overall postoperative complications were higher in the resection group compared to the ablation group (165 min vs 20 min, P < 0.01; 54% vs 19% P = 0.02 respectively). A median hospital stay was significantly longer in the resection group than in the ablation group (7.5 d vs 3 d, P < 0.01). Ninety-day mortality was comparable between the two groups. There were no significant differences between resection and ablation group in terms of overall survival and disease free survival at 1, 3, and 5 years. Conclusion: Radiofrequency ablation in posterosuperior segments in elderly is safe and feasible and ensures a short hospital stay, better quality of life and does not modify the overall and disease-free survival

Simple Determination of 1-Deoxynojirimycin in a New Dietary Supplement by Liquid Chromatography

A simple and fast chromatographic method using ultraviolet diode-array detector (UV-DAD) was developed for the high performance liquid chromatography determination of the content of 1-deoxynojirimycin (DNJ) in a new dietary supplement in the form of granules for oral solution preparation. The derivatization reaction was carried out at room temperature for 15 min at pH 7. The reaction reached completeness at a reagent to analyte molar ratio of about 60. The chromatographic separations were performed on a C18 Phenomenex Synergi Fusion stainless steel column (250 mm 7 4.6 mm; 4 \ub5m) with detection at \u3bb = 254 nm. The mobile phase consisted of triethylammonium (TEA) phosphate buffer (0.05 M; pH 3) and acetonitrile under gradient conditions at a flow-rate ramping from 1 to 1.2 mL/min. The validation parameters (linearity, sensitivity, accuracy, precision, specificity and stability) were satisfactory. Intra-day precision (relative standard deviation, RSD) was 64 2.23% for peak area and retention time without significant differences between intra- and inter-day data. Recovery studies gave good results (93.59%; n = 15) with a RSD of 2.64%. The developed method is suitable for the quality control of DNJ in raw material and industrial products. The method can be applied in any analytical laboratory and does not require sophisticated instrumentation

Exploring the interplay of mucin with biologically-relevant amorphous magnesium-calcium phosphate nanoparticles

Hypothesis: It has been recently shown that, in our organism, the secretions of Ca2+, Mg2+ and phosphate ions lead to the precipitation of amorphous magnesium-calcium phosphate nanoparticles (AMCPs) in the small intestine, where the glycoprotein mucin is one of the most abundant proteins, being the main com- ponent of the mucus hydrogel layer covering gut epithelium. Since AMCPs precipitate in vivo in a mucin- rich environment, we aim at studying the effect of this glycoprotein on the formation and features of endogenous-like AMCPs. Experiments: AMCPs were synthesized from aqueous solution in the presence of different concentrations of mucin, and the obtained particles were characterised in terms of crystallinity, composition and mor- phology. Solid State NMR investigation was also performed in order to assess the interplay between mucin and AMCPs at a sub-nanometric level. Finding: Results show that AMCPs form in the presence of mucin and the glycoprotein is efficiently incor- porated in the amorphous particles. NMR indicates the existence of interactions between AMCPs and mucin, revealing how AMCPs in mucin-hybrid nanoparticles affect the features of both proteic and oligosaccharidic portions of the glycoprotein. Considering that the primary function of mucin is the pro- tection of the intestine from pathogens, we speculate that the nature of the interaction between AMCPs and mucin described in the present work might be relevant to the immune system, suggesting a novel type of scenario which could be investigated by combining physico-chemical and biomedical approaches