Modification of the detrimental effect of TNF-α on human endothelial progenitor cells by fasudil and Y27632.

Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor-α (TNF-α) reduced their number and biological activity. Yet, signal transduction events linked to TNF-α action are still poorly understood. To address this issue, we examined the possible effect of fasudil and Y27632, two inhibitors of Rho kinase pathway, which is involved in endothelial dysfunction, atherosclerosis, and in- flammation. Results demonstrated that incubation with fasudil starting from 50 µM but not Y27632 determined a dose-dependent improvement of EPC number during exposure to TNF-α (P < 0.05 vs. TNF-α alone). Analysis of the signal transduction pathway activated by TNF-α revealed that the increased expression of p-p38 was not significantly altered by fasudil. Instead, fasudil blocked the TNF-α induced phosphorylation of Erk1/2 (P < 0.05 vs. TNF-α) as well as the inhibitor of Erk1/2-specific phosphorylated form, i.e., PD98059 (P < 0.05 vs. TNF-α). These results were confirmed by analysis of these kinases by confocal microscopy. Finally, 2D-DIGE and MALDI-TOF/TOF analysis of EPCs treated with fasudil revealed increased expression levels of an actin-related protein and an adenylyl cyclase associated protein and decreased expression levels of proteins related to radical scavenger and nucleotide metabolism. These findings suggest that fasudil positively affects EPC number and that other major signals might take part to this complex pathway.

Novel poly(HEMA-co-METAC)/alginate semi-interpenetrating hydrogels for biomedical applications: synthesis and characterization.

Novel p(HEMA-co-METAC)/alginate semi-interpenetrating hydrogels (semi-IPNs) were developed in the attempt to improve poly(hydroxyethylmethacrylate) biological response, extending its applications in the biomedical field. Materials with different alginate contents were synthesized by copolymerization of 2-hydroxyethylmethacrylate and 2-methacryloxy ethyltrimethyl ammonium chloride monomers in the presence of aqueous solutions of alginate and characterized with respect to p(HEMA-co-METAC) synthesized in the presence of water. Swelling studies in water revealed high values of water uptake (>100%) with marked differences in the swelling degree at increasing polysaccharide content. The effect of ionic strength and of pH on the swelling behavior of hydrogels was also investigated. Higher ionic strengths resulted in a minor swelling degree accordingly with hydrogels polyelectrolyte nature. The introduction of the natural ionizable polysaccharide into the network made the semi-IPNs swelling depending on pH values of the solutions. A biological characterization was performed in terms of protein absorption on hydrogel surfaces, cytotoxicity (ISO 10993-5) and cell adhesion and proliferation studies using both murine 3T3 and human fibroblasts. Hydrogels proved noncytotoxic; moreover, semi-IPN surfaces allowed cell attachment and proliferation, thus supporting their potential biomedical use.

Renal diseases in John Allen's 'Synopsis Universae Medicinae Practicae...'.

John Allen, a British physician of the eighteenth century, deserves being remembered for a series of inventions, but most importantly -- from a 'medical' point of view -- for his highly praised manuscript, the 'Universae Medicinae Practicae,sive Doctissimorum Virorum de Morbis Eorumque Causis ac Remediis Judicia', which long served as a text-book for medical students of the time, and also as a reference book for practitioners throughout European countries, for several decades after its original first publication. It contains the opinions ('Sententiae') of the most celebrated authors of all ages, from Hippocrates, Galen and Avicenna up to Allen's contemporaries, concerning a wide number of diseases, their causes, signs, symptoms, and therapeutical remedies where available. The present paper deals mostly with parts of the Synopsis concerning renal diseases and related clinical signs.

Response of intestinal cells and macrophages to an orally administered cellulose-PEG based polymer as a potential treatment for intractable edemas.

The elimination of water from the body represents a fundamental therapeutic goal in those diseases in which oedemas occur. Aim of this work is the design of a material able to absorb large amount of water to be used, by oral administration, in those cases in which resistance to diuretics appears. Sorption and mechanical properties of the cellulose based superabsorbent hydrogel acting as a water elimination system have been modulated through the insertion of molecular spacers between the crosslinks. Starting polymers are the sodium salt of carboxymethylcellulose (CMCNa), a polyelectrolyte cellulose derivative, and the hydroxyethylcellulose (HEC), a non-polyelectrolyte derivative. Polyethyleneglycol (PEG) with various molecular weights, has been linked by its free ends at two divinylsulfone (DVS) crosslinker molecules, in order to increase the average distance between two crosslinking sites and thus acting as spacer. Both the effect of concentration and molecular weight of the spacer resulted to significantly affect the hydrogel final sorption properties and thus the efficiency of the body water elimination system. Biocompatibility studies have been performed to test the hydrogel compatibility with respect to intestinal and macrophages cell lines. To investigate the effects of intestinal cells conditioned media after the contact with the gel on macrophages nitric oxide release tests have been carried out.