Comparative analysis of the effects of opioids in angiogenesis.

BACKGROUND: Angiogenesis, the formation of blood vessel from pre-existing ones, plays an important role in many pathophysiological diseases, such as cancer. Opioids are often used in clinic for the management of chronic pain in cancer patients at terminal phases. Here, we investigated and compared the effects and mechanisms of four opioids on angiogenesis. METHODS: We performed angiogenesis assays on human umbilical vein endothelial cells (HUVEC) that represent an in vitro model to assess the toxicity of drugs to endothelium. RESULTS: Morphine and oxycodone at 0.1 µM to 100 µM dose-dependently increased endothelial cell tube formation and proliferation. We observed the same in endothelial cells exposed to fentanyl at 0.1 µM to 10 µM but there was a gradual loss of stimulation by fentanyl at 100 µM and 1000 µM. Morphine and fentanyl reduced endothelial cell apoptosis-induced by serum withdrawal whereas oxycodone did not display anti-apoptotic effect, via decreasing Bax level. Oxycodone at the same concentrations was less potent than morphine and fentanyl. Different from other three opioids, codeine at all tested concentrations did not affect endothelial cell tube formation, proliferation and survival. Mechanism studies demonstrated that opioids acted on endothelial cells via µ-opioid receptor-independent pathway. Although we observed the increased phosphorylation of mitogen-activated protein kinase (MAPK) in cells exposed to morphine, fentanyl and oxycodone, the rescue studies demonstrated that the stimulatory effects of morphine but not fentanyl nor oxycodone were reversed by a specific MAPK inhibitor. CONCLUSION: Our work demonstrates the differential effects and mechanisms of opioids on angiogenesis.

Numerical study on rupture process of fiber-reinforced composites.

INTRODUCTION: This study aims to investigate the strength characteristics of fiber composites under uniaxial tensile stress. METHODS: A tensile failure finite element model based on fracture mechanics was built for fiber composites. The principal stress concentration-release-transfer evolution and the crack propagation of the composites under the conditions of equal single fiber width, unequal quantity, and equal total fiber width and unequal quantity were discussed. RESULTS: The tensile strength of the composites increased with fiber quantity when the width of each single fiber was equal. CONCLUSIONS: The tensile strength of the composites increased with fiber quantity when the total width of the composite fiber was equal.