Process of pyroplastic shaping for special-purpose porcelain stoneware tiles

A novel technique to manufacture special-purpose tiles (i.e. trim pieces, steps, skirting boards, etc.) has been recently developed on the basis of a pyroplastic shaping of porcelain stoneware tiles. This innovative process involves a second firing, peaking at temperatures close to those of sintering, whose effect was investigated by comparing industrially-manufactured tiles before and after pyroplastic shaping. Characterization by XRF, XRPD, SEM and standard testing (ISO 10545) put in evidence that pyroplastic bending induced little changes in the water absorption and bulk density values, as in phase composition. Limited variations occurring to closed porosity, mechanical strength and microstructure do not significantly affect the overall technological performance of the special-purpose tiles, which is substantially the same of the original porcelain stoneware tiles. A detailed microstructural characterization was performed for the first time on porcelain stoneware tiles: coarse grains (>10 ?m) represent 10-15% of total volume, while fine-grained crystals, dispersed in the glassy phase, amount from 30% to 65% of the viscous matrix. The pyroplastic behaviour was found to depend in a complex way on such microstructural and compositional features, which deeply affect the effective viscosity of the matrix

Experimental Pharmacology of Glucosamine Sulfate

Several clinical studies demonstrated that glucosamine sulfate (GS) is effective in controlling osteoarthritis (OA), showing a structure-modifying action. However, little is known about the molecular mechanism(s) by which GS exerts such action and about the effects of GS at a tissue level on osteoarthritic cartilage and other joint structures. Here we provide mechanistic evidence suggesting that in vitro GS attenuates NF-κB activation at concentrations in the range of those observed after GS administration to volunteers and patients, thus strengthening previous findings. Furthermore, we describe the effects of GS at a tissue level on the progression of the disease in a relevant model of spontaneous OA, the STR/ort mouse. In this model, the administration of GS at human corresponding doses was associated with a significant decrease of OA scores. Histomorphometry showed that the lesion surface was also significantly decreased, while the number of viable chondrocytes within the matrix was significantly increased. GS improved the course of OA in the STR/Ort mouse, by delaying cartilage breakdown as assessed histologically and histomorphometrically

Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction.

We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor

Pharmacological characterisation of CR6086, a potent prostaglandin E2 receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug

Abstract Background Prostaglandin E2 (PGE2) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). Methods CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively. In immune cells, IL-6 and vascular endothelial growth factor (VEGF) expression were analysed by RT-PCR, and IL-23 and IL-17 release were measured by enzyme-linked immunosorbent assay (ELISA). In collagen-induced arthritis (CIA) models, rats or mice were immunised with bovine collagen type II. Drugs were administered orally (etanercept and methotrexate intraperitoneally) starting at disease onset. Arthritis progression was evaluated by oedema, clinical score and histopathology. Anti-collagen II immunoglobulin G antibodies were measured by ELISA. Results CR6086 showed selectivity and high affinity for the human EP4 receptor (K i = 16.6 nM) and functioned as a pure antagonist (half-maximal inhibitory concentration, 22 nM) on PGE2-stimulated cAMP production. In models of human immune cells in culture, CR6086 reduced key cytokine players of RA (IL-6 and VEGF expression in macrophages, IL-23 release from dendritic cells, IL-17 release from Th17 cells). In the CIA model of RA in rats and mice, CR6086 significantly improved all features of arthritis: severity, histology, inflammation and pain. In rats, CR6086 was better than the selective cyclooxygenase-2 inhibitor rofecoxib and at least as effective as the Janus kinase inhibitor tofacitinib. In mice, CR6086 and the biologic DMARD etanercept were highly effective, whereas the non-steroidal anti-inflammatory drug naproxen was ineffective. Importantly, in a study of CR6086/methotrexate, combined treatment greatly improved the effect of a fully immunosuppressive dose of methotrexate. Conclusions CR6086 is a novel, potent EP4 antagonist showing favourable immunomodulatory properties, striking DMARD effects in rodents, and anti-inflammatory activity targeted to immune-mediated inflammatory diseases and distinct from the general effects of cyclooxygenase inhibitors. These results support the clinical development of CR6086, both as a stand-alone DMARD and as a combination therapy with methotrexate. The proof-of-concept trial in patients with RA is ongoing

Additional file 4: of Pharmacological characterisation of CR6086, a potent prostaglandin E2 receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug

Data table showing the effect of repeated administration of CR6086, MTX and their combination in arthritic mice (CIA model). Arthritic CIA mice, recruited upon arthritis onset, were treated with test drugs for 16 days. CR6086 was administered orally once daily, whereas MTX was administered intraperitoneally every third day. Clinical score (a) and paw swelling in millimetres (b) were reported as median (IQR) and mean (SD), respectively. (DOCX 45 kb

Additional file 3: of Pharmacological characterisation of CR6086, a potent prostaglandin E2 receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug

Data table showing cytokine serum concentrations (pg/ml) of samples determined from 3-PLEX (MSD) in CIA mice. Arthritis was induced in mice by intradermal injection of bovine type II collagen. Upon onset, animals were recruited and randomised into experimental groups. Oral treatments with drugs were administered daily and lasted 10 days. At the end of the study, sera were isolated for determination of indicated cytokines by multiplex analysis on the MSD platform (Artialis, Liège, Belgium). Data represent mean ¹ SEM of the number of animals per group: N = 8 (sham, vehicle, 30 mg/kg CR6086), 6 (60 mg/kg CR6086) and 7 (60 mg/kg naproxen). (DOCX 40 kb