\n\nThirty (>= 75 years, gender M9/F21) and 20 (<= 60 years, gender M20/F0) patients scheduled to undergo cardiac surgery. A standard anesthesia with fentanyl as an opioid was used. Fentanyl plasma concentrations were measured at the end of surgery and 2 h later. After tracheal extubation, when the pain intensity was at least moderate, blood samples for fentanyl and oxycodone plasma concentration measurements were taken. Thereafter, oxycodone hydrochloride 0.05 mg/kg i.v. was administered. After 15 selleck screening library and 45 min, pain intensity, sedation and oxycodone plasma concentration were determined. This test protocol was repeated twice.\n\nThe elderly had a higher plasma
concentration of fentanyl at the end of surgery than younger patients (5.7 +/- 2.2 vs. 3.8 +/- 1.2 ng/ml, P=0.001). The plasma concentrations of oxycodone were comparable between the groups. The interval between the second and the third oxycodone dose was longer in the elderly patients (P=0.036). Pain intensity on the verbal rating scale was lower at the 45-min assessment
point after all three oxycodone test doses (P=0.008) and sedation scores were significantly higher after the third dose in the elderly patients (P=0.035).\n\nIn elderly patients, the plasma concentration of fentanyl was higher but plasma levels of oxycodone were at a similar level compared with middle-aged patients. However, the elderly small molecule library screening patients had less pain and were more sedated after doses of oxycodone.”
“Asthma is characterised by antigen-mediated mast cell degranulation resulting Selleckchem AZD6244 in secretion of inflammatory mediators. Protein phosphatase 2A (PP2A) is a serine/threonine protein
phosphatase composed of a catalytic (PP2A-C) subunit together with a core scaffold (PP2A-A) subunit and a variable, regulatory (PP2A-B) subunit. Previous studies utilising pharmacological inhibition of protein phosphatases have suggested a positive regulatory role for PP2A in mast cell degranulation. In support of this we find that a high okadaic acid concentration (1 mu M) inhibits mast cell degranulation. Strikingly, we now show that a low concentration of okadaic acid (0.1 mu M) has the opposite effect, resulting in enhanced degranulation. Selective downregulation of the PP2A-C alpha subunit by short hairpin RNA also enhanced degranulation of RBL-2H3 mast cells, suggesting that the primary role of PP2A is to negatively regulate degranulation. PP2A-B subunits are responsible for substrate specificity, and carboxymethylation of the PP2A-C subunit alters B subunit binding. We show here that carboxymethylation of PP2A-C is dynamically altered during degranulation and inhibition of methylation decreases degranulation. Moreover downregulation of the PP2A-B alpha subunit resulted in decreased MK2 phosphorylation and degranulation, whilst downregulation of the PP2A-B’delta subunit enhanced p38 MAPK phosphorylation and degranulation.