IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCß3 during Airway Inflammation.

Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC gene expression via the inhibition of Gαq-induced Ca(2+) signaling. IL-1ra inhibited IL-1α protein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1α secretion were both mediated by PLCß3. A dominant-negative mutation in the PDZ-binding domain of PLCß3 inhibited ATP/P2Y2-induced IL-1ra and IL-1α secretion. IL-1α in the presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2 complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through inhibition of IL-1α secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.

Effect of Propofol on microRNA Expression Profile in Adipocyte-Derived Adult Stem Cells.

MicroRNA (miRNA) pathways have been implicated in stem cell regulation. This study investigated the molecular effects of propofol on adipocyte stem cells (ASCs) by analyzing RNA expression arrays. Human ASCs were isolated by use of a liposuction procedure. ASCs were treated with saline, 50 µM propofol, or 100 µM propofol in culture media for 3 hours. After the isolation of total RNA, the expression of 76 miRNAs was evaluated with peptide nucleic acid-miRNA array analysis through denaturation and hybridization processes. Treatment with 50 µM propofol resulted in significant down-regulation of expression of 18 miRNAs and upregulation of expression of 25 miRNAs; 100 µM propofol resulted in significant downregulation of expression of 14 miRNAs and upregulation of expression of 29 miRNAs. The lowest expression was seen for miR-204, which was 0.07-fold with 50 µM propofol and 0.18-fold with 100 µM propofol. The highest expression was seen for miR-208b, which was 11.23-fold with 50 µM propofol and 11.20-fold with 100 µM propofol. Expression patterns of miRNAs were not significantly different between 50 µM and 100 µM propofol treatment. The results of this study suggest that propofol is involved in altering the miRNA expression level in human ASCs. Additional research is necessary to establish the functional effect of miRNA alteration by propofol.

Usefulness of intraoperative real-time three-dimensional transesophageal echocardiography in preprocedural evaluation of cortriatriatum -a case report-.

Cortriatriatum is a rare congenital cardiac disorder with fibromuscular band (diaphragm) dividing the left atrium (LA) into the proximal and distal parts. Surgical correction of cortriatriatum requires full preoperative evaluation of the structural anomalies including the LA diaphragm and their pathophysiology. In the present case, a 44 year-old lady diagnosed as cortriatriatum underwent surgical correction. Intraoperative three-dimensional transesophageal echocardiography provided detailed information regarding the shape and extent of the LA diaphragm, which had been partially evaluated by preoperative two-dimensional transthoracic and transesophageal echocardiography, and facilitated the intraoperative patient management and surgical decision making.

The effect of dexmedetomidine on the adjuvant propofol requirement and intraoperative hemodynamics during remifentanil-based anesthesia.

BACKGROUND: The effects of dexmedetomidine on the propofol-sparing effect and intraoperative hemodynamics during remifentanil-based propofol-supplemented anesthesia have not been well investigated. METHODS: Twenty patients undergoing breast surgery were randomly allocated to receive dexmedetomidine (group DEX) or placebo (group C). In the DEX group, dexmedetomidine was loaded (1 µg/kg) before anesthesia induction and was infused (0.6 µg/kg/h) during surgery. Anesthesia was induced with a target-controlled infusion (TCI) of propofol (effect site concentration, Ce; 3 µg/ml) and remifentanil (plasma concentration, Cp, 10 ng/ml). The Ce of TCI-propofol was adjusted to a bispectral index of 45-55, and Cp of TCI-remifentanil was fixed at 10 ng/ml in both groups. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at baseline (T-control), after the loading of study drugs (T-loading), 3 min after anesthesia induction (T-induction), tracheal intubation (T-trachea), incision (T-incision), 30 min after incision (T-incision30), and at tracheal extubation (T-extubation). MAP% and HR% (MAP and HR vs. T-control) were determined and the propofol infusion rate was calculated. RESULTS: The propofol infusion rate was significantly lower in the DEX group than in group C (63.9 ± 16.2 vs. 96.4 ± 10.0 µg/kg/min, respectively; P < 0.001). The changes in MAP% at T-induction, T-trachea and T-incision in group DEX (-10.0 ± 3.9%, -9.4 ± 4.6% and -11.2 ± 6.3%, respectively) were significantly less than those in group C (-27.6 ± 13.9%, -21.7 ± 17.1%, and -25.1 ± 14.1%; P < 0.05, respectively). CONCLUSIONS: Dexmedetomidine reduced the propofol requirement for remifentanil-based anesthesia while producing more stable intraoperative hemodynamics.

Intraoperative transesophageal echocardiographic imaging of double valve repair for aortic and mitral stenosis.

An intraoperative echocardiographic evaluation to determine the feasibility and adequacy of the valve repair procedure is crucial for a successful repair. However, aortic valve repair in severe aortic stenosis (AS) is very limited and, consequently, its intraoperative echocardiographic evaluation has not been described well. Here, we describe an intraoperative transesophageal echocardiographic evaluation of a double-valve repair procedure for a patient with severe AS, moderate aortic insufficiency, and severe mitral stenosis.