Hyun Jeong Kwak

Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction.

Background: Metformin exhibits anti-inflammatory effects. Results: In murine macrophages, metformin induces activating transcription factor-3 (ATF-3) in parallel with protective effects against LPS-induced inflammation. Conclusion: Anti-inflammatory action of metformin is at least partly mediated via ATF-3 induction. Significance: This finding provides a new perspective on metformin action and novel therapeutic means of treating inflammation-related diseases, i.e. ATF-3 modulation. Metformin, a well known antidiabetic agent that improves peripheral insulin sensitivity, also elicits anti-inflammatory actions, but its mechanism is unclear. Here, we investigated the mechanism responsible for the anti-inflammatory effect of metformin action in lipopolysaccharide (LPS)-stimulated murine macrophages. Metformin inhibited LPS-induced production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a concentration-dependent manner and in parallel induction of activating transcription factor-3 (ATF-3), a transcription factor and member of the cAMP-responsive element-binding protein family. ATF-3 knockdown abolished the inhibitory effects of metformin on LPS-induced proinflammatory cytokine production accompanied with reversal of metformin-induced suppression of mitogen-activated protein kinase (MAPK) phosphorylation. Conversely, AMP-activated protein kinase (AMPK) phosphorylation and NF-κB suppression by metformin were unaffected by ATF-3 knockdown. ChIP-PCR analysis revealed that LPS-induced NF-κB enrichments on the promoters of IL-6 and TNF-α were replaced by ATF-3 upon metformin treatment. AMPK knockdown blunted all the effects of metformin (ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation), suggesting that AMPK activation by metformin is required for and precedes ATF-3 induction. Oral administration of metformin to either mice with LPS-induced endotoxemia or ob/ob mice lowered the plasma and tissue levels of TNF-α and IL-6 and increased ATF-3 expression in spleen and lungs. These results suggest that metformin exhibits anti-inflammatory action in macrophages at least in part via pathways involving AMPK activation and ATF-3 induction.

The Effect of a Sequential Compression Device on Hemodynamics in Arthroscopic Shoulder Surgery Using Beach-Chair Position

PURPOSE This study investigated the effect of intermittent compression by a sequential compression device (SCD) on the incidence of hypotension and other hemodynamic variables in the beach-chair position. METHODS Fifty healthy patients undergoing elective shoulder arthroscopy under general anesthesia were randomly assigned to either the control group (n = 25) or SCD group (n = 25). A standardized protocol for pre-hydration and anesthetic technique was followed. Hemodynamic variables were measured before (pre-induction values) and 5 minutes after the induction of anesthesia in the supine position (baseline values) and 1, 3, and 5 minutes after the patient was raised to a 70 degrees sitting position. The incidence of hypotension was recorded and treated with ephedrine. RESULTS The incidence of hypotension was significantly higher in the control group (16 of 25) than that in the SCD group (7 of 25) (P = .022; odds ratio, 0.219; 95% confidence interval, 0.066 to 0.723). Between the groups, mean arterial pressure, cardiac index, and stroke volume index were significantly higher in the SCD group compared with values in the control group at 1 minute after patients were raised to a 70 degrees sitting position (P = .035, P = .046, and P = .011, respectively). CONCLUSIONS This study showed that the use of an SCD could reduce the incidence of hypotension from 64% to 28% and supports hemodynamic variables such as mean arterial pressure and stroke volume index when patients were changed from the supine to the beach-chair position in those undergoing shoulder arthroscopy. LEVEL OF EVIDENCE Level I, therapeutic randomized controlled trial.

Prevention of rocuronium-induced withdrawal movement in children: a comparison of remifentanil with alfentanil.

Background:  This study was designed to compare the efficacy of remifentanil and alfentanil without the venous occlusion technique in preventing the withdrawal response associated with rocuronium injection in children.

The effect of pressure-controlled ventilation on pulmonary mechanics in the prone position during posterior lumbar spine surgery: a comparison with volume-controlled ventilation.

Background: When an anesthetized patient is turned to the prone position using the Wilson frame, dynamic compliance (Cdyn) decreases and peak airway pressure (Ppeak) increases. As pressure-controlled ventilation (PCV) decreases the Ppeak, this prospective, randomized study was designed to compare the effect of PCV and volume-controlled ventilation (VCV) on lung mechanics in the prone position using the Wilson frame during posterior lumbar spine surgery. Methods: Forty patients scheduled for posterior lumbar spine surgery were randomly allocated to receive mechanical ventilation using either the VCV (n=20) or PCV (n=20) mode. Respiratory variables (including Ppeak and Cdyn) and oxygenation parameters were recorded at the supine position (Tsupine) and 30 minutes after prone positioning (Tprone). Results: During the study period, tidal volume, minute volume, end-tidal carbon dioxide tension, and positive end-expiratory pressure were comparable between the 2 groups. The Ppeak in the PCV group was lower than that in the VCV group throughout the study period (P=0.007 and 0.003 at Tsupine and Tprone, respectively) and was increased at Tprone compared with Tsupine in both groups. Cdyn was decreased from Tsupine to Tprone in both groups. However, the Cdyn in the PCV group was higher than that in the VCV group during the study period. The arterial oxygen tension was comparable between the 2 groups during the study period. Conclusions: PCV provides lower Ppeak compared with VCV when the ventilator is set to deliver the same tidal volume and variable respiratory rate to maintain a constant end-tidal carbon dioxide tension in patients undergoing posterior lumbar spine surgery in the prone position using the Wilson frame.

The effect of oral and IV ramosetron on postoperative nausea and vomiting in patients undergoing gynecological laparoscopy with total intravenous anesthesia

PurposeRamosetron can be administered orally as well as intravenously. We investigated the effect of oral ramosetron on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopy.MethodsOne hundred and twenty women were allocated randomly to one of three groups (n = 40 in each) to receive saline (control), 0.1 mg oral ramosetron (PO), or 0.3 mg IV ramosetron (IV). Total intravenous anesthesia (TIVA) with propofol and remifentanil was used in all patients.ResultsThe incidence of complete response (no PONV, no rescue) in the control, IV, and PO groups was: 65%, 90%, and 87.5%, respectively, during the first 1 h; and 67.5%, 87.5%, and 80%, respectively, during 1 to 24 h.ConclusionThe effect of oral ramosetron 0.1 mg was comparable to that of IV ramosetron 0.3 mg on the prevention of PONV in women undergoing gynecological laparoscopy with TIVA. Both the oral and IV forms were effective at preventing PONV during the first 1 h after surgery.

Bortezomib attenuates palmitic acid-induced ER stress, inflammation and insulin resistance in myotubes via AMPK dependent mechanism

Bortezomib is an anti-cancer agent that induces ER stress by inhibiting proteasomal degradation. However, the effects of bortezomib appear to be dependent on its concentration and cellular context. Since ER stress is closely related to type 2 diabetes, the authors examined the effects of bortezomib on palmitic acid (PA)-induced ER stress in C2C12 murine myotubes. At low concentrations (<20nM), bortezomib protected myotubes from PA (750μM)-induced ER stress and inflammation. Either tunicamycin or thapsigargin-induced ER stress was also reduced by bortezomib. In addition, reduced glucose uptake and Akt phosphorylation induced by PA were prevented by co-treating bortezomib (10nM) both in the presence or absence of insulin. These protective effects of bortezomib were found to be associated with reduced JNK phosphorylation. Furthermore, bortezomib-induced AMPK phosphorylation, and the protective effects of bortezomib were diminished by AMPK knockdown, suggesting that AMPK activation underlies the effects of bortezomib. The in vivo administration of bortezomib at nontoxic levels (at 50 or 200μg/kg, i.p.) twice weekly for 5weeks to ob/ob mice improved insulin resistance, increased AMPK phosphorylation, reduced ER stress marker levels, and JNK inhibition in skeletal muscle. The study shows that bortezomib reduces ER stress, inflammation, and insulin resistance in vitro and in vivo, and suggests that bortezomib has novel applications for the treatment of metabolic disorders.

The preventative effect of ramosetron on postoperative nausea and vomiting after total thyroidectomy

Background Postoperative nausea and vomiting (PONV) frequently develops in patients undergoing thyroidectomy, and propofol-based total intravenous anesthesia (TIVA) has been reported to reduce the incidence of PONV. The present study was undertaken to compare the effects of ramosetron on PONV in women following total thyroidectomy under TIVA. Methods One hundred and thirty women scheduled for thyroidectomy were allocated to either a control group (n = 65) or a ramosetron group (n = 65). Propofol in combination with remifentanil was used for TIVA in all patients. 2 ml of either intravenous saline (control group) or 0.3 mg of ramosetron (ramosetron group) were administered at the end of the surgery. Fentanyl-based patient-controlled analgesia was implemented for 48 h after surgery in all patients. The incidences and severities of PONV, pain scores, administrations of rescue antiemetics, and the side effects of the antiemetics were documented during the first 48 h after surgery. Results The incidences of complete response (no PONV, no rescue) in the control and ramosetron groups were 71% and 88%, respectively, during the first 6 h (P = 0.029), 85% and 94% during the next 6 to 24 h period (P = 0.155), and 97% and 95% during the last 24 to 48 h period (P = 1.00). During the first 6 h, the severity of nausea and the use of rescue antiemetic medication were significantly lower in the ramosetron group. Conclusions Ramosetron was found to be effective at reducing the incidence and severity of postoperative nausea in women that underwent total thyroidectomy with propofol-based TIVA, especially during the first 6 hours postoperatively.

The effect of warmed inspired gases on body temperature during arthroscopic shoulder surgery under general anesthesia

Background Perioperative hypothermia can develop easily during shoulder arthroscopy, because cold irrigation can directly influence core body temperature. The authors investigated whether active warming and humidification of inspired gases reduces falls in core body temperature and allows redistribution of body heat in patients undergoing arthroscopic shoulder surgery under general anesthesia. Methods Patients scheduled for arthroscopic shoulder surgery were randomly assigned to receive either room temperature inspired gases using a conventional respiratory circuit (the control group, n = 20) or inspired gases humidified and heated using a humidified and electrically heated circuit (HHC) (the heated group, n = 20). Results Core temperatures were significantly lower in both groups from 30 min after anesthesia induction, but were significantly higher in the heated group than in the control group from 75 to 120 min after anesthesia induction. Conclusions In this study the use of a humidified and electrically heated circuit did not prevent core temperature falling during arthroscopic shoulder surgery, but it was found to decrease reductions in core temperature from 75 min after anesthesia induction.

Comparative study of pressure- and volume-controlled ventilation on stroke volume variation as a predictor of fluid responsiveness in patients undergoing major abdominal surgery.

PURPOSE We hypothesized that the 2 ventilation modes might have a different influence on the stroke volume variation (SVV). This study investigated the effect of the ventilation modes on SVV as a predictor of fluid responsiveness during major abdominal surgery. MATERIALS AND METHODS Sixty patients were randomly allocated to volume-controlled ventilation (VCV, n = 30) or pressure-controlled ventilation (PCV, n = 30) modes. After the induction of anesthesia, hemodynamic variables and SVV were measured before and after volume expansion (VE) with colloid solution of 10 mL/kg. The ability of SVV to predict the fluid responsiveness was tested by calculation of the area under a receiver operating characteristic curve for an increase in stroke volume index of at least 15% after VE. RESULTS There were 10 and 16 responders in the VCV and PCV groups, respectively. The area under a receiver operating characteristic curve (95% confidence interval) for SVV before VE was 0.723 (0.538-0.907) and 0.799 (0.625-0.973) in the VCV and PCV groups, respectively. The optimal threshold value of SVV was 11% and 14% in the VCV and PCV groups, respectively. CONCLUSIONS Stroke volume variation can predict fluid responsiveness during both VCV and PCV modes. However, the optimal threshold values of SVV may differ according to the ventilation modes.

PRACTICAL SYNTHESIS OF ETHYL CIS-4-AMINO-3-METHOXY-1-PIPERIDINE CARBOXYLATE, A KEY INTERMEDIATE OF CISAPRIDE

A practical synthesis of ethyl cis-4-amino-3-methoxy-1-piperidinecarboxylate 1, a key intermediate of cisapride as a potent gastrointestinal stimulant, has been accomplished from 1-methyl-1,2,3,6-tetrahydropyridine 2 via an efficient formation of cis-fused oxazolidinopiperidine 7.