ABSTRACT
A chronic low-level inflammation contributes to the pathogenesis of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in Western countries. The loss of central vision results from attenuated maintenance of photoreceptors due to the degeneration of retinal pigment epithelium (RPE) cells beneath the photoreceptor layer. It has been proposed that pathologic inflammation initiated in RPE cells could be regulated by the activation of type 2 cannabinoid receptors (CB2). Here, we have analysed the effect of CB2 activation on cellular survival and inflammation in human RPE cells. RPE cells were treated with the selective CB2 agonist JWH-133 in the presence or absence of the oxidative stressor 4-hydroxynonenal. Thereafter, cellular viability as well as the release of pro-inflammatory cytokines and potential underlying signalling pathways were analysed. Our results show that JWH-133 led to increased intracellular Ca2+ levels, suggesting that RPE cells are capable of responding to a CB2 agonist. JWH-133 could not prevent oxidative stress-induced cell death. Instead, 10 µM JWH-133 increased cell death and the release of proinflammatory cytokines in an ERK1/2-dependent manner. In contrast to previous findings, CB2 activation increased, rather than reduced inflammation in RPE cells.
Subject(s)
Inflammation/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Receptor, Cannabinoid, CB2/metabolism , Retinal Pigment Epithelium/metabolism , Cannabinoids/pharmacology , Cell Death/drug effects , Cell Line , Humans , Macular Degeneration/metabolism , Oxidative Stress/drug effects , Receptor, Cannabinoid, CB2/agonists , Signal Transduction/drug effectsABSTRACT
The performance of recently introduced Surgical Stress Index (SSI), based on heart rate and photoplethysmography, was estimated during sevoflurane-fentanyl and isoflurane-fentanyl anesthesia during surgical procedures. Forty ASA I-III patients were enrolled. Anesthesia was induced with fentanyl 2 mug kg(-1) and thiopentone 3-5 mg kg(-1). Tracheal intubation was performed 5 minutes after fentanyl bolus. Patients were randomly allocated to receive sevoflurane (n = 20) or isoflurane (n = 20) in 30% oxygen/air. State entropy was kept at 40-60, target being 50. During surgery, fentanyl boluses 1.5 mug kg(-1) were given at 30-40-minute intervals. SSI increased significantly after intubation. During surgery, the decrease of SSI after fentanyl boluses was similar in sevoflurane and isoflurane groups but SSI values were higher in sevoflurane than in isoflurane group. Tracheal intubation, skin incision, and surgical stimuli increased SSI from baseline, indicating that nociceptive stimuli increase SSI. Fentanyl boluses during surgery decreased SSI, indicating that increasing analgesia decreases SSI.
