Curcumin inhibits NFkappaB mediated radioprotection and modulate apoptosis related genes in human neuroblastoma cells

Curcumin has been shown to exhibit growth inhibitory effects and induce apoptosis in a broad range of tumors. Accordingly, we investigated the radiosensitizing effects of curcumin in human neuroblastoma cells. SK-N-MC cells exposed to either 2 Gy alone, or pretreated with curcumin (100 nM) or NFkappaB inhibitor peptide SN50 (50 nM) and exposed to 2 Gy were harvested after 48 h. Radioresistance was measured using clonogenic and MTT assay, NFkappaB DNA-binding activity using electrophoretic mobility shift assay, and apoptosis using Annexin V-FITC staining. Pathway (apoptosis) specific microarrays were used to measure gene expression and validated using QPCR. Radiation markedly enhanced the NFkappaB DNA-binding activity. Pre-treating the cells either with curcumin or SN50 significantly suppressed the radiation induced NFkappaB. Also, curcumin or SN50 pretreatment enhanced the radiation induced inhibition of cell survival. Microarray analysis revealed that curcumin enhanced the radiation induced activation of caspases, other pro-apoptotic and death effector molecules and, inhibit anti-apoptotic/survival molecules. In addition, curcumin markedly suppressed the radiation induced TNF super family genes. These results suggest that curcumin is a potent radiosensitizer and may act by overcoming the effects of radiation-induced NFkappaB mediated pro-survival gene expression in neuroblastoma.     

Outcomes from low versus high-flow cardiopulmonary resuscitation in a swine model of cardiac arrest

Background

Return of spontaneous circulation (ROSC) is improved by greater vital organ blood flow during cardiopulmonary resuscitation (CPR). We tested the hypothesis that myocardial flow above the threshold needed for ROSC may be associated with greater vital organ injury and worse outcome.

Methods

Aortic and right atrial pressures were measured with micromanometers in 27 swine. After 10 minutes of untreated ventricular fibrillation, chest compression was performed with an automatic, load-distributing band. Animals were randomly assigned to receive flows just sufficient for ROSC (low flow: target coronary perfusion pressure = 12 mm Hg) or well above the minimally effective level (high flow: coronary perfusion pressure = 30 mm Hg). Myocardial flow was measured with microspheres, defibrillation was performed after 3.5 minutes of CPR, and ejection fraction was measured with echocardiography.

Results

Return of spontaneous circulation was achieved by 9 of 9 animals in the high-flow group and 15 of 18 in the low-flow group. All animals in the high-flow group defibrillated initially into a perfusing rhythm, whereas 12 of 15 animals achieving ROSC in the low-flow group defibrillated initially into pulseless electrical activity (P < .05, Fisher exact test). Compared with animals in the low-flow group, animals in the high-flow group had shorter resuscitation times, higher mean aortic pressures at ROSC, and higher ejection fractions at 2 hours post-ROSC (all P < .05).

Conclusion

High-flow CPR significantly improved arrest hemodynamics, rates of ROSC, and post-ROSC indicators of myocardial status, all indicating less injury with higher flows. No evidence of organ injury from vital organ blood flow substantially above the threshold for ROSC was found.     

Evidence for eosinophil degranulation in acute appendicitis

Finding of increased numbers of eosinophils in the muscle in cases of acute appendicitis has led to the hypothesis that it may have an allergic origin. This study aimed to measure the eosinophil degranulation resulting in a rise in the serum of eosinophil granule proteins that would be expected in such cases. The levels of serum eosinophil cationic protein (ECP) measured by chemiluminescence assay in acute appendicitis were compared, with those of appropriate controls. Mean (95% CI) serum ECP (microg/L) levels were: acute appendicitis 45.3 (27.7-63.0); normal appendix 22.7 (16.0-29.3); asthma 24.2 (4.6-43.8); and healthy volunteers 13.2 (8.3-18.1). In cases of acute appendicitis, there is an inverse relationship between duration of symptoms and serum ECP. However, this was not statistically significant. Significant local eosinophil activation and degranulation occurs in acute appendicitis, enough to cause a rise in serum levels of eosinophil chemotactic protein.