Strength-limiting damage and its mitigation in CAD-CAM zirconia-reinforced lithium-silicate ceramics machined in a fully crystallized state.

OBJECTIVES: The objective was to explore how clinically relevant machining process and heat treatment influence damage accumulation and strength degradation in lithium silicate-based glass ceramics machined in the fully crystallized state. METHODS: A commercial zirconia-reinforced lithium silicate (ZLS) glass ceramic with a fully developed microstructure (Celtra® Duo) was studied. Disk-shaped specimens (nominal 10 mm diameter and 1 mm thickness) were fabricated either using a CAD-CAM process, creating a clinically relevant dental restoration surface, or were sectioned from water-jet cut cylindrical blocks with their critical surfaces consistently polished. Bi-axial flexure strength (BFS) was determined in a ball-on-ring configuration, and fractographic analysis was performed on failed specimens. XRD, AFM and SEM measurements were conducted before and after heat treatment. For each sample group, BFS was correlated with surface roughness. A two-way ANOVA and post-hoc Tukey tests were used to determine differences in BFS between machining and heat treatment groups (ɑ = 0.05). RESULTS: A two-way ANOVA demonstrated that BFS was influenced by fabrication route (p < 0.01) with CAD-CAM specimens exhibiting significantly lower mean BFS. A factorial interaction was observed between heat treatment and machining route (p < 0.01), where a significant strengthening effect of post-manufacture heat treatment was noted for CAD-CAM specimens but not sectioned and polished samples. CAD-CAM specimens exhibited sub-surface lateral cracks alongside radial cracks near fracture origin which were not observed for polished specimens. BFS did not correlate with surface roughness for polished specimens, and no change in microstructure was detectable by XRD following heat treatment. SIGNIFICANCE: The mechanical properties of the ZLS ceramic material studied were highly sensitive to the initial surface defect integral associated with manufacturing route and order of operations. CAD-CAM manufacturing procedures result in significant strength-limiting damage which is likely to influence restoration performance; however, this can be partially mitigated by post-machining heat treatment

Cardiac Glycosides Ouabain and Digoxin Interfere with the Regulation of Glutamate Transporter GLAST in Astrocytes Cultured from Neonatal Rat Brain

Glutamate transport (GluT) in brain is mediated chiefly by two transporters GLT and GLAST, both driven by ionic gradients generated by (Na+, K+)-dependent ATPase (Na+/K+-ATPase). GLAST is located in astrocytes and its function is regulated by translocations from cytoplasm to plasma membrane in the presence of GluT substrates. The phenomenon is blocked by a naturally occurring toxin rottlerin. We have recently suggested that rottlerin acts by inhibiting Na+/K+-ATPase. We now report that Na+/K+-ATPase inhibitors digoxin and ouabain also blocked the redistribution of GLAST in cultured astrocytes, however, neither of the compounds caused detectable inhibition of ATPase activity in cell-free astrocyte homogenates (rottlerin inhibited app. 80% of Pi production from ATP in the astrocyte homogenates, IC50 = 25 μM). Therefore, while we may not have established a direct link between GLAST regulation and Na+/K+-ATPase activity we have shown that both ouabain and digoxin can interfere with GluT transport and therefore should be considered potentially neurotoxic

Potential use of recombinant human interleukin-6 in clinical oncology

Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was shown in vitro and in the preclinical setting. Various studies show that doses up to 10 mu g/kg/d rhIL-6 before and after chemotherapy are tolerable and the most frequent side-effects encountered consist of flu-like symptoms. Furthermore, a consistent decrease in hemoglobin was reported during rhIL-6 treatment. This was probably due to hemodilution, although a change in ferrokinetics, may also at least partly, explain the anemia. An evident increase of platelets has been observed in various studies, After chemotherapy, rhIL-6 seemed to hasten platelet recovery, without affecting platelet nadir. Preliminary data from studies investigating the value of rhIL-6 as an anti-tumor agent in renal cell carcinoma and melanoma reported low response rates, between 8 and 14%. The results of rhIL-6 in ameliorating chemotherapy induced bone-marrow depression and especially thrombocytopenia, are promising and merit further phase III studies

Potential use of recombinant human interleukin-6 in clinical oncology

Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was shown in vitro and in the preclinical setting. Various studies show that doses up to 10 mu g/kg/d rhIL-6 before and after chemotherapy are tolerable and the most frequent side-effects encountered consist of flu-like symptoms. Furthermore, a consistent decrease in hemoglobin was reported during rhIL-6 treatment. This was probably due to hemodilution, although a change in ferrokinetics, may also at least partly, explain the anemia. An evident increase of platelets has been observed in various studies, After chemotherapy, rhIL-6 seemed to hasten platelet recovery, without affecting platelet nadir. Preliminary data from studies investigating the value of rhIL-6 as an anti-tumor agent in renal cell carcinoma and melanoma reported low response rates, between 8 and 14%. The results of rhIL-6 in ameliorating chemotherapy induced bone-marrow depression and especially thrombocytopenia, are promising and merit further phase III studies