Aqueous extract of Chrysanthemum morifolium Ramat. inhibits RANKL-induced osteoclast differentiation by suppressing the c-fos/NFATc1 pathway.

OBJECTIVE: The flower of chrysanthemum, used worldwide as a medicinal and edible product, has shown various bioactivities, such as anti-inflammatory, antioxidant, anti-tumorigenic, and hepatoprotective activities, as well as cardiovascular protection. However, the effect of Chrysanthemum morifolium Ramat. on the regulation of osteoclast differentiation has not yet been reported. In this study, we aimed to investigate the inhibitory effect of Chrysanthemum morifolium Ramat. water extract (CME) on RANKL-induced osteoclast differentiation in mouse bone marrow-derived macrophages (BMMs). STUDY DESIGN: Bone marrow-derived macrophages (BMMs) isolated from the C57BL/6 J mice. The viability of BMMs was detected with MTT assays. Inhibitory effects of CME on osteoclast differentiation and bone resorption was measured by TRAP staining and Pit assay. Osteoclast differentiation-associated gene expression were assessed by Real-time quantitative polymerase chain reaction. Intracellular signaling molecules was assessed by western blot. RESULTS: CME significantly inhibited osteoclast differentiation in BMMs without cytotoxicity, besides inhibiting MAPK/c-fos and PLCγ2/CREB activation. The inhibitory effects of CME on differentiation-related signaling molecules resulted in significant repression of NFATc1 expression, which is a key transcription factor in osteoclast differentiation, fusion, and activation. CONCLUSION: Our results confirmed the inhibition of RANKL-induced PLCγ2/CREB/c-fos/NFATc1 activation by CME during osteoclast differentiation. The findings collectively suggested CME as a traditional therapeutic agent for osteoporosis, RA, and periodontitis.

Validity and reliability of the Korean version of the Quality of Recovery-15 questionnaire.

BACKGROUND: The quality of recovery-40 questionnaire (QoR-40) has been widely used to assess quality of recovery after surgery, but it is too lengthy for clinical use. The short form of QoR-40, QoR-15, has been validated in many languages; however, an official Korean version of the QoR-15 (QoR-15K) has not yet been established. This study aimed to develop and validate QoR-15K. METHODS: Based on the previously-validated Korean QoR-40, we selected 15 items; the QoR-15K was patterned on the original QoR-15. We analyzed 210 subjects who had been scheduled for elective surgery under general anesthesia. The patients completed the questionnaire before surgery and on postoperative days one and two. The validity, reliability, and responsiveness of the QoR-15K were evaluated. RESULTS: We obtained excellent convergent validity on visual analog scale for recovery (ρ = 0.882, P < 0.001). The duration of anesthesia, post-anesthesia care unit, and overall hospital stay with the QoR-15K showed a significant negative correlation (ρ = -0.183, -0.151, and -0.185, respectively). Cronbach's α was 0.909. Cohen's effect size and standardized response mean were 0.819 and 0.721. The recruitment and completion rate were 92.9% and 100%, respectively. We based the above calculations on the results obtained on the first day following surgery. CONCLUSIONS: The validity and reliability of the QoR-15K are comparable to those of the English version. The QoR-15K would be a good instrument to assess the quality of recovery in Korean patients after surgery.

Comparison Between Preoperative and Intraoperative Administration of Nefopam for Acute and Chronic Postoperative Pain in Colon Cancer Patients: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: The present study was designed as a prospective, randomized, double-blind clinical trial to evaluate the effects of preoperatively administered nefopam on postoperative acute hyperalgesia and the long-term painful sequelae compared to intraoperative administration. METHODS: One hundred and fifty patients undergoing elective laparoscopic colectomy were enrolled. Group 1 (post-incisional nefopam) patients received saline at 30 min before skin incision followed by intraoperative administration of 20 mg nefopam at 1 h after incision. Group 2 (pre-incisional nefopam) patients were administered 20 mg nefopam before skin incision and received saline after skin incision. At postoperative 2, 6, 24, 48, and 72 h, fentanyl consumption and pain intensities at rest and during deep breathing were evaluated by visual analog scale (VAS). The incidence of the long-term painful sequelae after surgery was evaluated more than one year after surgery. RESULTS: Cumulative fentanyl consumption during postoperative 72 h was similar between Group 1 and Group 2 (1534 ± 698 µg, 95% CI 1367-1702 µg vs. 1442 ± 721 µg, 95% CI 1266-1618 µg, P = 0.197). VAS pain scores at rest were comparable between the two groups, but VAS scores during deep breathing were significantly lower in Group 2 than in Group 1. Six and five patients complained of mild pain (pain rating 1) at the surgical site in Group 1 and 2, respectively. CONCLUSIONS: Preoperatively administered nefopam reduced exertional pain compared to intraoperative administration although postoperative analgesic consumption was similar between two groups. It may be helpful to conduct early ambulation and deep breathing during the acute postoperative period in patients undergoing intestinal surgery. Trial registration No: KCT0001656.

Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia.

BACKGROUND: We previously reported that microvesicles (MVs) released by human mesenchymal stem cells (MSC) were as effective as the cells themselves in both Escherichia coli lipopolysaccharide and live bacteria-induced acute lung injury (ALI) mice models. However, it remained unclear whether the biological effect of MSC MV can be applied to human ALI. METHODS: In the current study, we tested the therapeutic effects of MSC MVs in a well-established ex vivo perfused human model of bacterial pneumonia. Using human donor lungs not used for transplantation, we instilled E. coli bacteria intrabronchially and, 1 hour later, administered MSC MVs into the perfusate as therapy. RESULTS: After 6 hours, instillation of E. coli bacteria caused influx of inflammatory cells, which resulted in significant inflammation, lung protein permeability and pulmonary oedema formation. Administration of MSC MV significantly increased alveolar fluid clearance and reduced protein permeability and numerically lowered the bacterial load in the injured alveolus. The beneficial effect on bacterial killing was more pronounced with pretreatment of MSCs with a Toll-like receptor 3 agonist, polyinosinic:polycytidylic acid (Poly (I:C)), prior to the isolation of MVs. Isolated human alveolar macrophages had increased antimicrobial activity with MSC MV treatment in vitro as well. Although oxygenation and lung compliance levels were similar between injury and treatment groups, administration of MSC MVs numerically decreased median pulmonary artery pressure at 6 hours. CONCLUSIONS: In summary, MSC MVs increased alveolar fluid clearance and reduced lung protein permeability, and pretreatment with Poly (I:C) enhanced the antimicrobial activity of MVs in an ex vivo perfused human lung with severe bacteria pneumonia.

Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases.

INTRODUCTION: Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. AREAS COVERED: The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. EXPERT OPINION: While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification.

The changes of endotracheal tube cuff pressure by the position changes from supine to prone and the flexion and extension of head.

BACKGROUND: The proper cuff pressure is important to prevent complications related to the endotracheal tube (ETT). We evaluated the change in ETT cuff pressure by changing the position from supine to prone without head movement. METHODS: Fifty-five patients were enrolled and scheduled for lumbar spine surgery. Neutral angle, which was the angle on the mandibular angle between the neck midline and mandibular inferior border, was measured. The initial neutral pressure of the ETT cuff was measured, and the cuff pressure was subsequently adjusted to 26 cmH2O. Flexed or extended angles and cuff pressure were measured in both supine and prone positions, when the patient's head was flexed or extended. Initial neutral pressure in prone was compared with adjusted neutral pressure (26 cmH2O) in supine. Flexed and extended pressure were compared with adjusted neutral pressure in supine or prone, respectively. RESULTS: There were no differences between supine and prone position for neutral, flexed, and extended angles. The initial neutral pressure increased after changing position from supine to prone (26.0 vs. 31.5 ± 5.9 cmH2O, P < 0.001). Flexed and extended pressure in supine were increased to 38.7 ± 6.7 (P < 0.001) and 26.7 ± 4.7 cmH2O (not statistically significant) than the adjusted neutral pressure. Flexed and extended pressure in prone were increased to 40.5 ± 8.8 (P < 0.001) and 29.9 ± 8.7 cmH2O (P = 0.002) than the adjusted neutral pressure. CONCLUSIONS: The position change from supine to prone without head movement can cause a change in ETT cuff pressure.

Cartoon distraction alleviates anxiety in children during induction of anesthesia.

BACKGROUND: We performed this study to determine the beneficial effects of viewing an animated cartoon and playing with a favorite toy on preoperative anxiety in children aged 3 to 7 years in the operating room before anesthesia induction. METHODS: One hundred thirty children aged 3 to 7 years with ASA physical status I or II were enrolled. Subjects were randomly assigned to 1 of 3 groups: group 1 (control), group 2 (toy), and group 3 (animated cartoon). The children in group 2 were asked to bring their favorite toy and were allowed to play with it until anesthesia induction. The children in group 3 watched their selected animated cartoon until anesthesia induction. Children's preoperative anxiety was determined by the modified Yale Preoperative Anxiety Scale (mYPAS) and parent-recorded anxiety Visual Analog Scale (VAS) the night before surgery, in the preanesthetic holding room, and just before anesthesia induction. RESULTS: In the preanesthetic holding room, the group 2 mYPAS and parent-recorded anxiety VAS scores were significantly lower than those of groups 1 and 3 (mYPAS: P = 0.007; parent-recorded anxiety VAS: P = 0.02). In the operating room, the children in group 3 had the lowest mYPAS and parent-recorded anxiety VAS scores among the 3 groups (mYPAS: P < 0.001; parent-recorded anxiety VAS: P < 0.001). In group 3, the mYPAS and parent-recorded anxiety VAS scores of only 3 and 5 children were increased in the operating room compared with their scores in the preanesthetic holding room, whereas the anxiety scores of 32 and 34 children in group 1 and 25 and 32 children in group 2 had increased (P < 0.001). The number of children whose scores indicated no anxiety (mYPAS score <30) in the operating room was 3 (7%), 9 (23%), and 18 (43%) in groups 1, 2, and 3, respectively (P < 0.001). CONCLUSIONS: Allowing the viewing of animated cartoons by pediatric surgical patients is a very effective method to alleviate preoperative anxiety. Our study suggests that this intervention is an inexpensive, easy to administer, and comprehensive method for anxiety reduction in the pediatric surgical population.

The willingness of patients to pay for intravenous patient-controlled analgesia in Korea.

BACKGROUND: The use of intravenous patient-controlled analgesia (IV-PCA) has been increasing because it has advantages such as improved pain relief, greater patient satisfaction, and fewer postoperative complications. However, current research has not considered the patients' thoughts about IV-PCA's cost-effectiveness. The purpose of this study was to investigate the willingness to pay (WTP) for IV-PCA and the relationship between patients' characteristics and WTP in Korea. METHODS: We enrolled 400 adult patients who were scheduled for elective surgery. The patient was requested to indicate a series of predefined amounts of money (Korean won; 30,000/50,000/100,000/150,000/200,000/300,000/500,000). We also recorded patient characteristics, such as age, sex, type of surgery, IV-PCA history, education level, the person responsible for medical expenses, type of insurance, net annual income, and residential area. Three days after surgery, we asked about the degree of satisfaction and the WTP for IV-PCA. RESULTS: For IV-PCA, the median WTP was 100,000 won (25-75%; 50,000-200,000 won: US$1 = W1078.04; July 19, 2011) before surgery. All patients' characteristics were not related to preoperative WTP for IV-PCA, whereas the increase in WTP after surgery showed a tendency correlated to higher IV-PCA satisfaction. CONCLUSIONS: The median WTP was 100,000 won. The satisfaction of IV-PCA increased patients' WTP after surgery, but the WTP may be independent of patient characteristics in Korea.

Reliability of assessment of nasal flow rate for nostril selection during nasotracheal intubation.

STUDY OBJECTIVE: To evaluate the reliability of assessments of nasal flow rate for improved nostril selection for nasotracheal intubation. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 118 ASA physical status 1 and 2 patients, aged 18-65 years, scheduled for elective maxillofacial and oral surgery requiring nasotracheal intubation. INTERVENTIONS: Patients were randomized to the left or right nostril groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV(1)) through the mouth and each nostril were measured before anesthesia induction. MEASUREMENTS: The relationship between the rate of airflow through the selected nostril and frequency of epistaxis and navigability of the nasotracheal tube were evaluated. MAIN RESULTS: There were no significant differences in the frequency of epistaxis and degree of navigability of the tracheal tube between the left and right nostril groups. In both nostril groups, patients who suffered epistaxis showed significantly less FEV(1) and FEV(1)/FVC values than did patients without epistaxis (P < 0.05). In addition, in both groups patients who passed the tube easily showed significantly higher FEV(1) and FEV(1)/FVC values than did patients who passed the tube with resistance or failed tube passage (P < 0.05). CONCLUSION: Measurement of nasal flow rate is a useful clinical method for choosing a nostril for nasotracheal intubation.