The treatment groups (n = 5 in each group) had the tourniquet applied for one hour, followed by one hour of reperfusion at 10 degrees C (cold) alone, at 10 degrees C with nitric oxide synthase inhibitor, at 10 degrees selleck chemicals C with heme oxygenase inhibitor, at 10 degrees C with a combination of inhibitors, at 34 degrees C (warm) alone, at 34 degrees C with a heme oxygenase inducer, at 34 degrees C with a nitric oxide synthase inducer, or at 34 degrees C with a combination of inducers.
Results: Rats in the sham group did not show a significant increase in microvascular permeability. Rats in the warm ischemia/reperfusion
group displayed significant increases in microvascular permeability, as did the rats that received inhibitors of heme oxygenase and nitric oxide synthase at 10 degrees C. No significant increase in microvascular permeability was observed in the animals in the cold ischemia/reperfusion group or in animals that received inducers of heme oxygenase and nitric oxide synthase at 34 degrees C.
Conclusions: Local hypothermia protects skeletal muscle from increased microvascular
permeability following ischemia-reperfusion injury. This protective effect is also seen with the induction of the nitric oxide synthase and heme oxygenase systems at physiologic temperature. We also have shown that the protective effects of hypothermia are blocked by giving heme oxygenase and nitric oxide
synthase inhibitors while AG-881 in vivo keeping the muscle hypothermic. These findings demonstrate that heme oxygenase and nitric oxide synthase play a combined role in ischemia-reperfusion injury, suggesting this website possible pathways for clinical intervention to modulate injury seen following trauma, tourniquet use, vascular surgery, and microvascular surgery.”
“Depsipeptide (FK228), a histone deacetylase inhibitor, was recently approved for use in cutaneous T-cell lymphoma. Roxithromycin (RXM) is a macrolide antibiotic that can induce apoptosis of some T-cell lines. In this study, we investigated whether combination of FK228 and RXM had a synergistic inhibitory effect on cell survival of various lymphoma cells and which signaling pathway was affected by the drugs in the presence or absence of chemokines, which were reported to inhibit apoptosis of some tumor cells. FK228 and RXM additively decreased the number of HUT-78, Ki-JK and EL-4 lymphoma cells at doses over 50nmol/L and 50mol/L, respectively. These drugs inhibited phosphorylation of Akt and extracellular signal-regulated kinase (ERK) of EL-4 cells in a dose-dependent manner. Significant association between ERK phosphorylation and cell number or annexin V+ cells suggested that the ERK pathway may be critical for survival of EL-4 cells. Combination of 10 or 50nmol/L of FK228 and 10mol/L of RXM decreased cell number of HUT78 and EL-4 compared to a single use of each drug.