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To assess the effects of various concentrations of dexmedetomidine on the human blood coagulation profile using rotational thromboelastometry (ROTEM). Venous blood samples were collected from 11 healthy volunteers and divided into four specimen bottles; dexmedetomidine was added to attain final sample concentrations of 0, 0.5, 1.0, and 1.5 ng/mL. ROTEM was performed on each study sample. The concentration of dexmedetomidine increased, and the ROTEM values showed a hypercoagulable state. The change in clotting time (CT) for INTEM was larger in samples with a dexmedetomidine concentration of 1.5 ng/mL (− 34%) than in the 0.5 ng/mL samples (− 16%) (P = 0.010). The change in clot formation time (CFT) for INTEM was greater in 1.5 ng/mL samples (− 16%) than in 0.5 ng/mL samples (− 4%) (P = 0.004). A greater decrease in CT for EXTEM was identified in the 1.0 ng/mL and 1.5 ng/mL samples (− 36% and − 37%, respectively) than in the 0.5 ng/mL samples (− 12%) (P = 0.003 for both categories). The change in CFT for EXTEM was greater in the 1.0 ng/mL and 1.5 ng/mL samples (− 11% and − 13%, respectively) than in the 0.5 ng/mL samples (− 4%) (P = 0.006 and P = 0.001, respectively). A bigger change in maximum clot firmness (MCF) for EXTEM was observed in the 1.5 ng/mL samples (4%) than in the 0.5 ng/mL samples (0%) (P = 0.002). The change in MCF for FIBTEM was greater in the 1.5 ng/mL samples (19%) than in the 0.5 ng/mL samples (5%) (P = 0.001). All coagulation pathways showed a hypercoagulable state as the concentration of dexmedetomidine increased. Nevertheless, most of the values of ROTEM were maintained within the reference ranges. Clinical Trial NCT04269278.

Background: When an imbalance occurs between the demand and capacity for protein folding, unfolded proteins accumulate in the endoplasmic reticulum (ER) lumen and activate the unfolded protein response (UPR). In addition, unfolded proteins are cleared from the ER lumen for ubiquitination and subsequent cytosolic proteasomal degradation, which is termed as the ER-associated degradation (ERAD) pathway. This study focused on changes in the UPR and ERAD pathways induced by the repeated inhalation anesthetic exposure in Caenorhabditis elegans. Methods: Depending on repeated isoflurane exposure, C. elegans was classified into the control or isoflurane group. To evaluate the expression of a specific gene, RNA was extracted from adult worms in each group and real-time polymerase chain reaction was performed. Ubiquitinated protein levels were measured using western blotting, and behavioral changes were evaluated by chemotaxis assay using various mutant strains. Results: Isoflurane upregulated the expression of ire-1 and pek-1 whereas the expression of atf-6 was unaffected. The expression of both sel-1 and sel-11 was decreased by isoflurane exposure, possibly indicating the inhibition of retro-translocation. The expression of cdc-48.1 and cdc-48.2 was decreased and higher ubiquitinated protein levels were observed in the isoflurane group than in the control, suggesting that deubiquitination and degradation of misfolded proteins were interrupted. The chemotaxis indices of ire-1, pek-1, sel-1, and sel-11 mutants decreased significantly compared to N2, and they were not suppressed further even after the repeated isoflurane exposure. Conclusion: Repeated isoflurane exposure caused significant ER stress in C. elegans. Following the increase in UPR, the ERAD pathway was disrupted by repeated isoflurane exposure and ubiquitinated proteins was accumulated subsequently. UPR and ERAD pathways are potential modifiable neuroprotection targets against anesthesia-induced neurotoxicity.

BACKGROUND We investigated the effect of irrigation fluid on coagulation according to the hemodilution level using rotational thromboelastometry (ROTEM). METHODS Venous blood was taken from 12 healthy volunteers and divided into four specimen tubes that were diluted to various levels (0%, 10%, 20%, and 40%) using an irrigation fluid composed of 2.7% sorbitol and 0.54% mannitol. RESULTS Significant prolongation of clotting time was observed in the 40% diluted sample using both INTEM (P = 0.009) and EXTEM (P = 0.001) assays. However, the clot formation time was prolonged significantly in the 10%, 20%, and 40% diluted samples using both INTEM (P < 0.001) and EXTEM (P = 0.002, P < 0.001, and P < 0.001, respectively) assays. A significant decrease of α-angle of INTEM and EXTEM were observed in the 10% (P < 0.001), 20% (P < 0.001 and P = 0.001, respectively), and 40% (P < 0.001) groups compared with the 0% dilution group. The maximum clot firmness (MCF) of INTEM decreased significantly in the 20% (P < 0.001) and 40% (P < 0.001) diluted samples. In the MCF of EXTEM and FIBTEM assays, 10% (P = 0.009 and P = 0.015, respectively), 20% (P = 0.001), and 40% (P < 0.001) samples showed a significant decrease compared with the 0% sample. Nevertheless, most of the ROTEM values were within the reference range, except the 40% sample. CONCLUSIONS Blood became hypocoagulable when it was diluted in vitro with a fluid composed of 2.7% sorbitol and 0.54% mannitol.

Background and objectivesData is insufficient to determine whether perioperative statin use increases or decreases postoperative pain. This study aimed to investigate the association between perioperative statin use and pain outcomes after total knee arthroplasty performed under spinal anesthesia.MethodsThis is a retrospective, observational study based on medical records from a tertiary hospital between January 2005 and October 2017. Medical records of patients who underwent elective total knee arthroplasty under spinal anesthesia as inpatients were analyzed. Pain outcomes were compared through postoperative day (POD) 3 in patients who were taking statins perioperatively versus patients who were not taking statins.ResultsA total of 1088 propensity-matched participants were included in the final analysis (544 patients in the statin group and 544 patients in the non-statin group). The total morphine equivalent consumption through POD 3 was higher in the statin group than in the non-statin group (mean (SD), statin group: 525.4 (119.7) vs non-statin group: 495.3 (115.3), 95% CI of the difference: 15.9 to 44.4, pConclusionsPerioperative statin use is associated with a significant increase in postoperative opioid consumption after total knee arthroplasty performed under spinal anesthesia; however, this increase was so marginal that its clinical importance remains controversial.

Neurotoxic effects of local anesthetics (LAs) on developing motor neurons have not been documented. We investigated the neurotoxic effects of LAs on developing motor neurons in terms of cell viability, cytotoxicity, reactive oxygen species (ROS), and apoptosis. Embryonic spinal cord motor neurons were isolated from Sprague-Dawley rat fetuses and exposed to one of the three LAs—lidocaine, bupivacaine, or ropivacaine—at concentrations of 1, 10, 100, or 1000 µM. The exposure duration was set to 1 or 24 h. The neurotoxic effects of LAs were determined by evaluating the following: cell viability, cytotoxicity, ROS production, and apoptosis. In the 1-h exposure group, the motor neurons exposed to lidocaine and bupivacaine had reduced cell viability and increased cytotoxicity, ROS, and apoptosis in a concentration-dependent manner. Lidocaine showed the highest toxicity, followed by bupivacaine. In the 24-h exposure group, all three LAs showed significant effects (decreased cell viability and increased cytotoxicity, ROS, and apoptosis) on the motor neurons in a concentration-dependent manner. The neurotoxic effects of lidocaine were greater than those of bupivacaine and ropivacaine. Ropivacaine appeared to have the least effect on motor neurons. This study identified the neurotoxic effects of lidocaine and bupivacaine on developing spinal cord motor neurons.

Ultrasound-guided erector spinae plane block (ESPB), a recent regional analgesic technique, has been used to manage acute pain after surgery. The aim of this meta-analysis is to identify the benefits of ESPB in patients undergoing laparoscopic cholecystectomy (LC). The authors searched PubMed, EMBASE, CENTRAL, CINAHL, and Web of Science to identify all randomized controlled trials (RCTs) evaluating the effects of ESPB on postoperative pain after LC. Primary outcome was defined as 24 h cumulative opioid consumption. Secondary outcomes were pain scores and the incidence of postoperative nausea and vomiting (PONV). We estimated mean differences (MD) and odds ratio (OR) using a random-effects model. A total of 8 RCTs, including 442 patients, were included in the final analysis. Postoperative opioid consumption was significantly lower in the ESPB group than in the control group (MD &minus, 4.72, 95% CI &minus, 6.00 to &minus, 3.44, p &lt, 0.001). Compared with the control group, the ESPB group also showed significantly lower pain scores and incidence of PONV. A separate analysis of RCTs comparing ESPB with oblique subcostal transversus abdominis plane (OSTAP) block showed that the analgesic efficacy of ESPB was similar to that of OSTAP block. The results of this meta-analysis demonstrated that ESPB may provide effective postoperative analgesia in patients undergoing LC.

Background: Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the effects of TXA on the activity of glutamate transporter type 3 (excitatory amino acid transporter 3; EAAT3), which is the main neuronal glutamate transporter type. Methods: EAAT3 was expressed in Xenopus laevis oocytes through mRNA injection. Oocytes were incubated with diluted tranexamic acid for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 M L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (C). Results were presented as mean  SEM.Results: TXA (30 to 1,000 M) significantly decreased EAAT3 activity. Our kinetic study showed that Vmax was significantly decreased in the TXA group compared with the control group (1.1  0.1 vs. 1.4  0.1 C, n = 18–23, P = 0.043), but the Km did not significantly change (12.7  3.9 M for TXA vs. 12.8  3.8 for control, n = 18–23, P = 0.986).Conclusions: Our results suggest that TXA attenuates EAAT3 activity, which may explain its proconvulsant effect.

Postoperative delirium (PD) remains an issue in cardiac surgery despite the constant efforts to reduce its incidence. In this retrospective study, the incidence of PD was evaluated in patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) according to different primary anesthetic agents: sevoflurane and dexmedetomidine- versus propofol-based anesthesia. A total of 534 patients who underwent heart-valve surgery or coronary artery bypass graft surgery with CPB between January 2012 and August 2017 were divided into 2 groups according to the main anesthetic agent: sevoflurane with dexmedetomidine (sevo-dex group, n = 340) and propofol (propofol group, n = 194). The incidence of PD was evaluated as the primary outcome. Patient-, surgery-, and anesthesia-related factors and postoperative complications were investigated as secondary outcomes. To reduce the risk of confounding effects between the 2 groups, 194 patients were selected from the sevo-dex group after propensity-score matching. After propensity-score matching, the incidence of PD was not significantly different between the sevo-dex (6.2%) and propofol (10.8%) groups (P = .136). In comparisons of the incidence of each type of PD, only hyperactive PD occurred significantly less frequently in the sevo-dex group (P = .021). Older age, lower preoperative albumin levels, and emergency surgery were significant risk factors for PD. The overall incidence of PD after cardiac surgery with CPB did not differ between patients receiving sevoflurane and dexmedetomidine-based versus propofol-based anesthesia. Only hyperactive PD occurred less frequently in patients receiving sevoflurane and dexmedetomidine-based anesthesia.

Background This study was designed to compare the hemodynamic changes in response to direct laryngoscopy with using the McCoy or Macintosh blade. Methods Seventy seven patients were randomly allocated into two groups. The induction of anesthesia was done with target controlled infusion of propofol (5 microgram/ml) and remifentanil (3 ng/ml) and vecuronium 0.1 mg/kg was also given. The vocal cords were visualized with either the McCoy or the Macintosh laryngoscope blade, and then tracheal intubation was performed. The heart rate and blood pressure were measured just before induction, at intubation and at 1, 3 and 5 minutes after intubation. Results There were no significant differences in the blood pressure and heart rate responses to tracheal intubation with using the McCoy or Macintosh blade. But, in the Macintosh groups, the blood pressure at 1 and 3 minutes and the heart rate at 1 minute after intubation were increased significantly compared with the preintubation values. Also, in the McCoy groups, the blood pressure and heart rate at 1 minute after intubation were significantly higher than the preintubation values. Conclusions The McCoy and the Macintosh blade show similar changes in heart rate and blood pressure after tracheal intuba tion.

Objective: Systemic absorption of irrigation fluid can lead to a disturbed coagulation cascade. We compared the changes in hemostatic properties on using nonelectrolyte solution in monopolar hysteroscopic surgery (HS) with that on using isotonic saline in bipolar HS via rotational thromboelastometry (ROTEM) analysis. Methods: A total of 54 patients were randomized into 2 groups: 1 group underwent monopolar HS using a mixture of 2.7% sorbitol and 0.54% mannitol (the HSMP group), whereas the other group underwent bipolar HS using 0.9% isotonic saline (the HSBP group). The effects of these 2 methods on coagulation were assessed via pre and postoperative laboratory tests, including estimation of the international normalized ratio of prothrombin time and activated partial thromboplastin time and ROTEM analysis. In addition, the hemoglobin, hematocrit, and electrolyte levels and the platelet count were analyzed. Results: Patient characteristics, volume of irrigation fluid absorbed, and type of procedure were comparable between the 2 groups. There were no significant differences in the pre and postoperative values of ROTEM parameters between the 2 groups. Most postoperative ROTEM parameters, as compared with preoperative values, changed in both groups; clot formation time was prolonged, and the α-angle and maximum clot firmness were decreased. All ROTEM parameters were maintained within the normal range. Hematological parameters, including hemoglobin and hematocrit levels and platelet count, were significantly decreased postoperatively in both groups compared to the preoperative values. No pre and postoperative hematological and hemostatic parameters were significantly different between the 2 groups. Conclusion: Irrigation fluid absorbed in healthy women during HS caused hypocoagulable changes in the blood, irrespective of the irrigant type, and no significant differences between HS using monopolar and bipolar electrodes were demonstrated.

This study explores the technical merits of carbon encapsulation via an electrical wire explosion method to enhance the peroxymonosulfate activation performance of metals. Reflecting the nature of core-shell structures, the outer carbon layers hampered the reductive conversion of peroxymonosulfate to sulfate radicals by the inner metal cores, whereas the metal cores increased the overall electrical conductivity as a pivotal factor in non-radical activation. Hence, the impact of carbon wrapping hinged on the peroxymonosulfate reduction capability of the metals, i.e., kinetic retardation in organic degradation with reactive Cu, Fe, and Ni-Fe, but acceleration with unreactive Ni. Further, composite fabrication switched the major degradative pathway from radical-induced oxidation to mediated electron transfer, as determined from the effects of methanol and chloride, formaldehyde and bromate formation yields, reactivity toward multiple organics, and electron paramagnetic resonance spectral features. The protective carbon shells enabled pH-insensitive peroxymonosulfate activation, prevented metal ion leaching, and alleviated catalyst deactivation.

The use of lidocaine in spinal anesthesia may increase the risk of transient neurological symptoms (TNS) according to previous meta-analyses. However, the previous meta-analyses lacked data on some other local anesthetics and thus, more evaluations are still needed to compare the effect of lidocaine on the development of TNS. The objective of this study was to compare the risk of TNS according to lidocaine versus other local anesthetics in patients undergoing spinal anesthesia. A total of 39 randomized controlled trials with 4733 patients were analyzed. The incidence of TNS was 10.8% in the lidocaine group and was 2.2% in the control groups (risk ratio (RR) 4.12, 95% confidence interval (CI) 3.13 to 5.43, p &lt, 0.001). In subgroup analysis, lidocaine increased the incidence of TNS compared with other local anesthetics except mepivacaine, ropivacaine or sameridine. The risk of TNS was higher in the hyperbaric (p &lt, 0.001) or isobaric lidocaine (p &lt, 0.001) group compared with the control group, but there were no differences found between the two groups when hypobaric lidocaine was administered (p = 1.00). This study confirmed that lidocaine for spinal anesthesia still causes TNS more frequently than most other local anesthetics, especially when hyperbaric or isobaric lidocaine was used.

Background The relationship between statin use and incidence of postoperative delirium (POD) is controversial. We investigated the association between perioperative statin use and occurrence of delirium after total knee arthroplasty (TKA) under spinal anesthesia. Methods We retrospectively reviewed the electronic medical records of patients who underwent TKA under spinal anesthesia at single tertiary care hospital between January 2005 and October 2017. POD incidence was recorded for patients who received statins continuously from 1 month before surgery until discharge and for patients who did not receive any statins. Univariable and multivariable logistic regression analyses were conducted to investigate an association between occurrence of POD and perioperative statin use. Results In total, 6,020 procedures were included, and 992 (16.4%) were associated with perioperative statin use. POD was confirmed for 304 (5.0%) procedures. The statin group showed a 1.7% significant lower incidence ( P =0.017) of POD (35/992, 3.5%) than the no-statin group (1,420/5,028, 5.4%). In multivariable logistic regression analysis, the POD incidence in the statin group was 34% lower than that in the no statin group [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.45–0.97; P = 0.036] Moreover, the POD incidence was decreased by 37% (OR, 0.63; 95% CI, 0.40–0.99; P = 0.047), and 79% (OR, 0.21; 95% CI, 0.05-0.88; P = 0.033) respectively, when atorvastatin and simvastatin were administered. Conclusions Continuous perioperative statin use may be associated with a significantly lower risk of delirium after TKA under spinal anesthesia; simvastatin was the most effective statin for POD prevention.

Background: The use of sedatives (propofol or dexmedetomidine) is common in total knee arthroplasty (TKA) or total hip arthroplasty (THA) under spinal anesthesia. Although propofol and dexmedetomidine have been reported to decrease the risk of acute kidney injury (AKI) after cardiac surgery, their effects on AKI incidence after TKA or THA are still unknown. The purpose of this study was to investigate the associations between sedative dosage (propofol and dexmedetomidine) and AKI incidence after TKA or THA under spinal anesthesia. Methods: This retrospective observational study analyzed medical records of adult patients aged 18 years or older who underwent unilateral TKA or THA under spinal anesthesia at a single tertiary care hospital between January 2007 and June 2018. Data were analyzed using univariable and multivariable logistic regression analyses. Results: A total of 5,663 patients were included in the analysis (TKA: 3,570, 63.0%; THA: 2,093, 37.0%), and 147 patients (2.6%) developed AKI in postoperative days 0–3. Multivariable logistic regression analysis showed that propofol dosage (odds ratio: 0.99, 95% confidence interval: 0.94, 1.05; P=0.839) and dexmedetomidine dosage (odds ratio: 0.95, 95% confidence interval: 0.84, 1.09; P=0.461) were not significantly associated with AKI incidence. Conclusions: This study demonstrated no significant association between sedative uses (propofol, dexmedetomidine) and AKI incidence after THA or TKA under spinal anesthesia, and use of such sedatives does not require extreme caution.

Owing to the beneficial health effects on human cardiovascular system, soybeans and soy-related products have been a focus of intensive research. Soy isoflavones are known to be primarily responsible for the soy-related biological effects including anti-platelet activity but its in vivo relevancy has not been fully verified. Here we compared the role of adenosine, an active ingredient abundant in black soybean (BB) extract, in the anti-platelet effects of BB, to that of soy isoflavones. At the concentrations existing in BB, isoflavones such as genistein and daidzein could not attenuate collagen-induced platelet aggregation, however, adenosine significantly inhibited platelet aggregation with an equivalent potency to BB, suggesting that adenosine may be the major bioactive component. Consistently, the anti-aggregatory effects of BB disappeared after treatment of adenosine receptor antagonists. The effects of BB are mediated by adenosine through intracellular cAMP and subsequent attenuation of calcium mobilization. Of note, adenosine and BB significantly reduced platelet fibrinogen binding and platelet adhesion, other critical events for platelet activation, which were not affected by isoflavones. Taken together, we demonstrated that adenosine might be the major active ingredient for BB-induced anti-platelet activity, which will shed new light on the roles of adenosine as a bioactive compound in soybeans and soy-related food.

Background: The transversus abdominis plane block is recently described peripheral block to providing analgesia to the anterior abdominal wall. The goal of this study is to evaluate the analgesic efficacy of the ultrasound-guided transversus abdominis plane block (US-TAP block) in patients undergoing gynecologic surgery via a transverse lower abdominal skin incision. Methods: Thirty-two patients undergoing gynecologic surgery were randomized to undergo standard care such as PCA, or to receive additional US-TAP block with standard care. After general anesthesia induction, a bilateral USTAP block was performed using 0.375% ropivacaine 20 ml on each side. Postoperative demand of rescue analgesics in PACU and ward were recorded. Each patient was assessed postoperatively by a blinded investigator in the postanesthesia care unit (PACU) and at 2, 6, 10, 24, 48 hr postoperatively to investigate pain, drowsiness, nausea and itch. Results: The US-TAP block reduced pain intensity compared to standard care in the PACU (5.2 ± 3.1 vs 8.4 ± 1.3) and at 2, 24 postoperative hours (3.0 ± 2.4 vs 5.2 ± 2.4, 0.9 ± 1.5 vs 2.2 ± 1.9). Fentanyl requirements in PACU was reduced (20.3 ± 20.9 vs 62.5 ± 35.4 μg, P < 0.05). In ward, pethidine requirements was reduced (21.9 ± 28.7 vs 56.3 ± 34.8 mg, P < 0.05). Conclusions: The US-TAP block with standard care provide more effective analgesia after gynecologic surgery via a transverse lower abdominal skin incision. (Korean J Anesthesiol 2011; 61: 413-418)

This study examined the effect of different proteolytic enzymes on the production of cheese whey protein (CWP) hydrolysates with low antigenicity. Four enzyme combinations (1:1) trypsin + papain W-40 (TP), trypsin + neutrase 1.5 (TN), papain W-40 + protease S (PP) and papain W-40 + neutrase 1.5 (PN) were added at the rate of 1% of the CWP and it was incubated for 15, 30, 60, 90, 120 and 180min at 50 ◦ C. CWP hydrolysis and its non-protein nitrogen concentrations were higher with TP and TN compared with PP and PN at all incubation times. The SDS-PAGE revealed complete removal of α-lactalbumin (α-LA) and β-lactoglobulin (β-LG) from hydrolysates produced by trypsin-containing enzyme mixtures. Reverse-phase HPLC analysis ascertained the CWP hydrolysis and SDS-PAGE results. The lowest antigenicity in CWP hydrolysates was observed with the use of trypsin-containing enzyme mixtures compared with other enzyme combinations. Present results suggested that TP and TN combinations were the most effective for CWP hydrolysis for the removal of β-LG from CWP. Further research is warranted to identify the peptides in CWP hydrolysates produced with these enzyme combinations that may help enhance the utilisation of whey protein in human food.  2007 Society of Chemical Industry

Background Hydroxyethyl starch (HES) solutions are used as plasma expanders for correcting hypovolemia, but can lead to impaired coagulation. We evaluated the changes in hematological and hemostatic profiles with three types of HES. Methods Patients were randomized to receive volume replacement with 10% pentastarch 260/0.45 in 0.9% saline (Group-PEN, n = 25), 6% tetrastarch 130/0.4 in 0.9% saline (Group-TETS, n = 25), or 6% tetrastarch 130/0.4 in a balanced electrolyte solution (Group-TETB, n = 25). Coagulation was assessed using rotational thromboelastometry (ROTEM®) and other laboratory tests were performed, including measurements of hematological and hemostatic parameters and electrolytes. Results Post-operative ROTEM® parameters changed toward hypocoagulable states in all groups. The post-operative parameters of EXTEM and FIBTEM were more impaired in Group-PEN than in Group-TETB. The percentage change in INTEM clot formation time (P = 0.004) and α-angle (P = 0.003) were smaller in Group-TETS and Group-TETB than in Group-PEN. The percentage change in the FIBTEM maximum clot firmness was greatest in Group-PEN (P = 0.011). The international normalized ratio of prothrombin time (P < 0.001) and the activated partial thromboplastin time (P < 0.001) were significantly prolonged in Group-PEN compared to those of Group-TETB. Conclusions The 6% HES 130/0.4 in a balanced electrolyte solution seemed to have less of an impact on blood coagulation than the 10% HES 260/0.45. No differences in hemostatic profile were observed between the balanced electrolyte and saline-based 6% HES 130/0.4.

The adverse effects of spinal anesthesia (SA) include arterial hypotension and bradycardia. The aim of this study was to compare the effects of 2 type 3 serotonin receptor antagonists in SA-induced adverse effects. Specifically, we assessed whether ramosetron was more effective than ondansetron in reducing SA-induced decreases in blood pressure (BP) and heart rate (HR).A total of 117 patients undergoing orthopedic surgery and receiving SA were intravenously administered 0.3 mg of ramosetron (n = 39, group R), 4 mg of ondansetron (n = 39, group O4), or 8 mg of ondansetron (n = 39, group O8). Systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), HR, and the lowest SBP, DBP, MBP, and HR values were measured preoperatively (baseline) and intraoperatively. The incidence of postoperative nausea and vomiting, the need for rescue antiemetics, the amount of patient-controlled analgesia consumption, and pain score in the first 48 hours after surgery were determined.Baseline values did not significantly differ among the 3 groups. After SA, SBP, DBP, MBP, and HR were lower than their baseline values in all 3 groups. The differences between the baseline and the lowest values were significantly less in group R than in groups O4 and O8 with respect to SBP (P0.001), DBP (P = 0.001), and MBP (P0.001) less in group R than in group O4 with respect to HR (P = 0.032). Intergroup differences were not significant for postoperative nausea and vomiting, the need for rescue antiemetics, patient-controlled analgesia consumption, or pain score.The administration of ramosetron (0.3 mg) significantly attenuated the SA-induced decrease in BP compared with 4 or 8 mg of ondansetron and HR compared with 4 mg of ondansetron.

It is well known that c-kit is related to pigmentation as well as to the oncology target protein. The objective of this study was to discover a skin-whitening agent that regulates c-kit activity. We have developed a high-throughput screening system using recombinant human c-kit protein. Approximately 10,000 synthetic compounds were screened for their effect on c-kit activity. Phenyl-imidazole sulfonamide derivatives showed inhibitory activity on c-kit phosphorylation in vitro. The effects of one derivative, [4-t-butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03), on stem-cell factor (SCF)/c-kit cellular signaling in 501mel human melanoma cells were examined further. Pretreatment of 501mel cells with ISCK03 inhibited SCF-induced c-kit phosphorylation dose dependently. ISCK03 also inhibited p44/42 ERK mitogen-activated protein kinase (MAPK) phosphorylation, which is known to be involved in SCF/c-kit downstream signaling. However ISCK03 did not inhibit hepatocyte growth factor (HGF)-induced phosphorylation of p44/42 ERK proteins. To determine the in vivo potency of ISCK03, it was orally administered to depilated C57BL/6 mice. Interestingly, oral administration of ISCK03 induced the dose-dependent depigmentation of newly regrown hair, and this was reversed with cessation of ISCK03 treatment. Finally, to investigate whether the inhibitory effect of ISCK03 on SCF/c-kit signaling abolished UV-induced pigmentation, ISCK03 was applied to UV-induced pigmented spots on brownish guinea pig skin. The topical application of ISCK03 promoted the depigmentation of UV-induced hyperpigmented spots. Fontana-Masson staining analysis showed epidermal melanin was diminished in spots treated with ISCK03. These results indicate that phenyl-imidazole sulfonamide derivatives are potent c-kit inhibitors and might be used as skin-whitening agents.

Background: Tracheal intubation stimulates the sympathetic nervous system, resulting in hypertension, tachycardia and sometimes critical complications, especially in patients with underlying hypertension, cardiovascular disease or cerebrovascular disease. In this study, we sprayed 4% lidocaine into the trachea before intubation, and observed the hemodynamic changes after tracheal intubation. Methods: We randomly allocated 87 patients, whose ASA physical status was I or II, into three groups. The 4% topical lidocaine was sprayed before intubation at the following specific times: just before intubation (group 0), or 1 minute (group 1) and 2 minutes before intubation (group 2). For maintenance of anesthesia, TIVA (total intravenous anesthesia; propofol-remifentanil infusion with orchestra Ⓡ ) was used. We observed hemodynamic changes between the groups just after the intubation, as well as 1, 3 and 5 minutes after the intubation. Hemodynamic changes were also monitored in the same group. Results: When the patients arrived at the operating room, we found no significant difference in heart rate and ar- terial pressure between the groups. However, heart rate after intubation in group 1 was significantly lower than group 0. The diastolic and mean arterial pressure just after intubation were lower in group 1 and 2 than in group 0. Conclusions: Spraying lidocaine 1 or 2 minutes before intubation was more effective than spraying it just before intubation for reducing hypertensive responses after intubation.

Abstract 5103 Background Iron overload by repeated transfusions induced organ toxicity including liver, heart. We investigated hematologic manifestations and cytokines or hematopoietic growth factors in murine secondary hemochromatosis. Materials and methods We established murine secondary hemochromatosis model using 6 week-old male C57/BL6 (H-2b) with iron dextran. Mice (n=10∼12) were intraperitoneally injected with 10 mg of iron dextran for 2 or 4 weeks. We divided five groups: control (PBS injection), iron 100mg, iron 200mg, iron 200mg with deferasirox (DFX) 300mg, and only DFX 300mg. We examined hematocrit, platelet counts and plasma iron concentration (PIC) in peripheral blood, and liver iron contents (LIC) by atomic absorption spectrophotometer. We evaluated colony forming capacity from bone marrow according to experimental group. For cytokines and hematopoietic growth factors, we performed real-time PCR for IL-1b, iNOS, IFN-g, TNF-a, TGF-b, SCF, TPO, GM-CSF, and IL-11 in bone marrow. We compared each values of relative ratio with b-actin. Results There was no difference of hematocrit among experimental groups. The platelet counts were significantly decreased in iron 200mg among groups (P0.05). However, SCF was shown diminished expressions for treated mice compared with control (P=0.02). The levels of TPO were increased in hemochromatosis, and decreased after administration of DFX (P=0.05). The GM-CSF was observed significantly lower in iron 200mg, iron 200mg plus DFX, DFX than control and iron 100mg (P Conclusions Our results suggested that iron overload might affect hematopiesis and these findings were due to effects of hematopoietic growth factors including SCF, TPO, GM-CSF, not inhibitory cytokines. Also, we need further study for DFX in hematopoiesis. Disclosures No relevant conflicts of interest to declare.

BACKGROUND The addition of remifentanil during propofol TCI (target controlled infusion) attenuates the hemodynamic changes induced by endotracheal intubation. This study examined the optimal effect-site concentration of remifentanil to minimize the cardiovascular changes to endotracheal intubation in elderly patients. METHODS Fifty ASA 1 or 2 elderly patients scheduled for elective surgery under general anesthesia were assigned randomly to one of two groups according to the effect-site concentration of remifentanil. Each group was administered 4 microgram/ml of propofol TCI with 1 ng/ml (group R1) or 3 ng/ml (group R3) of remifentanil. The heart rate (HR), systolic (SAP), mean (MAP) and diastolic arterial pressure (DAP) were measured at pre-induction, before and after endotracheal intubation. RESULTS After intubation, the HR, SAP, MAP and DAP increased significantly in the two groups compared with the pre-intubation values. However, the HR, SAP, MAP and DAP for group R3 were lower than group R1 for 5 min after intubation. CONCLUSIONS In elderly patients administered 4 microg/ml of propofol TCI, we suggest that the optimal effect-site concentration of remifentanil to minimize the cardiovascular changes to endotracheal intubation is 3 ng/ml rather than 1 ng/ml.