The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.
The results indicate that the volatile anesthetic isoflurane produces a second window of preconditioning against myocardial ischemia and reperfusion injury. Furthermore, COX-2 is an important mediator of isoflurane-induced delayed preconditioning.
Background: Reactive oxygen species (ROS) contribute to myocardial protection during ischemic preconditioning, but the role of the ROS in protection against ischemic injury produced by volatile anesthetics has only recently been explored. We tested the hypothesis that ROS mediate isoflurane-induced preconditioning in vivo.Methods: Pentobarbital-anesthetized rabbits were instrumented for measurement of hemodynamics and were subjected to a 30 min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive vehicle (0.9% saline), or the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptopropionyl glycine (2-MPG; 1 mg · kg ؊1 · min
Nausea and vomiting is one of the most frequently reported patient complaints following anesthesia (1, 2). This phenomenon, known as postoperative nausea and vomiting (PONV) is of greater concern to patients than postoperative pain (3). PONV occurs in approximately 30% of all patients undergoing generalized anesthesia (4). PONV can result in several post-surgical complications including discomfort or pain, fluid and electrolyte imbalances, surgical wound dehiscence, hemorrhage, and aspiration pneumonia (4). PONV has four main risk factors including : female gender, history of PONV Abstract : Purpose : Post-operative nausea and vomiting (PONV) remains the most frequently reported patient complaint after anesthesia. Aprepitant is the first neurokinin-1(NK1) receptor antagonism available for use as an antiemetic. We investigated whether aprepitant can effectively decrease PONV in patients undergoing laparoscopic gynecological surgery. Methods : Sixty four patients receiving general anesthesia for laparoscopic gynecological surgery were randomly assigned to either receive a preoperative dose of 80 mg aprepitant or no drug. Efficacy was assessed in 2 and 24 hours after surgery. Primary and secondary endpoints were analyzed for the time intervals 0-2 hours (acute phase) and 2-24 hours (delayed phase). Vomiting, nausea, use of rescue anti-emetic, and visual analog scale (VAS) were assessed. Nausea was assessed on a 4-point scale, from 0 to 3. Results : Sixty patients participated in the study. At acute phase, PONV was present in both control and NK1 group and were 63% % and 43% % respectively. The severity of nausea was much less in the NK1 group. PONV prevalence at delayed phase was present in control but absent in NK1 group 27% % vs. 0% %, respectively. The amount of pain medication used by patients in the NK1 group was significantly less for diclofenac and pentazocine suggesting increase pain tolerance. Conclusions : Neurokinin-1 receptor antagonism effectively lowered PONV increased pain tolerance, and expedited recovery in patients undergoing laparoscopic gynecological surgery. J. Med. Invest. 58 : 246-251, August, 2011
ORIGINAL
Neurokinin
These results show that isoflurane impairs insulin secretion and glucose utilization. The mechanism of action responsible for these effects may involve a decrease in glucose-induced inhibition of adenosine triphosphate-sensitive potassium channel activity in pancreatic beta cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.