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Background Serine synthetic pathway plays an essential role in the development and function of the nervous system. This study investigated whether the serine synthetic pathway was affected by repeated volatile anesthetic exposure using C. elegans and its relationship with anesthesia-induced neurotoxicity. Methods Synchronized worms were divided into two groups: the control and isoflurane groups. Worms in the isoflurane group were exposed to isoflurane for 1 h at each larval stage. The chemotaxis index was evaluated when they reached the young adult-stage in both groups. Also, RNA was extracted from the young adult-worms, and the expressions of C31C9.2, F26H9.5, and Y62E10 A.13 were evaluated using real-time polymerase chain reaction in both groups. At the same time, the l -serine level was measured. After phosphoserine phosphatase inhibitor – glycerophosphorylcholine (GPC) – and l -serine were treated, the change of chemotaxis index was determined. Results In young adult worms exposed to isoflurane, the genetic expressions of C31C9.2, F26H9.5, and Y62E10 A.13 were decreased, and a significant decrease was shown in Y62E10 A.13. The serine level in worms was also lower in the isoflurane group than in the control group (5.13 ± 1.44 vs. 7.65 ± 0.81 pM, n = 5 in each group, p = 0.009). Exposure to GPC reduced the chemotaxis index to a similar degree as repeated isoflurane exposure (52.9% in GPC group vs 58.7% in the isoflurane group). The chemotaxis index (61.1%) was not decreased by repeated isoflurane anesthesia in GPC-treated worms. In this condition, the l -serine level was low similarly in both groups (5.22 ± 1.19 vs. 4.90 ± 1.36 pM, n = 5 in each group, p = 0.702). When l -serine was supplied to C. elegans, the deteriorated chemotaxis index by isoflurane exposure recovered (78.1% in the control group vs. 75.5% in the isoflurane group, p = 0.465). Conclusion Serine synthetic pathway was negatively affected in C. elegans by repeated isoflurane exposure. Y62E10 A.13, which corresponds to phosphoserine phosphatase, was mostly influenced, followed by low l -serine level. Supplementation with l -serine could restore the chemotaxis index.

This study was conducted to evaluate the effect of scalp blocks using levobupivacaine on recovery profiles including postoperative pain, patient-controlled analgesia (PCA) consumption, postoperative nausea and vomiting (PONV), and other adverse events in patients undergoing frontoparietal craniotomy for aneurysm clipping.Fifty-two patients scheduled for elective frontoparietal craniotomy for unruptured aneurysm clipping were enrolled. After surgery, scalp blocks were performed using normal saline (group C, n = 26) or 0.75% levobupivacaine (group L, n = 26). Postoperative pain scores and PCA consumption were recorded for 72 hours after recovery of consciousness. The time from patient recovery to the first use of PCA drug and rescue analgesics, the requirement for vasoactive agents, and adverse effects related to PCA and local anesthetics also were recorded.Postoperative pain scores and PCA consumption in group L were lower than in group C (P.05). The time intervals from patient recovery to the first use of PCA drug (P.001) and rescue analgesics (P = .038) was longer in group L than in group C. Additionally, less antihypertensive agent was required (P = .017), and PONV occurred less frequently (P = .039) in group L than in group C.Scalp blocks with 0.75% levobupivacaine improved recovery profiles in that it effectively lowered postoperative pain and PCA consumption without severe adverse events and also reduced the requirement for a postoperative antihypertensive agent and the incidence of PONV in patients who underwent frontoparietal craniotomy for aneurysm clipping.

Catheter-related bladder discomfort (CRBD) secondary to intraoperative catheterization of urinary bladder is one of the most distressing symptoms during recovery from anaesthesia. Butylscopolamine, a peripheral antimuscarinic agent, is effective for relieving the pain, which is because of smooth muscle contraction. The aim of this study was to assess the efficacy and safety profiles of butylscopolamine in treating CRBD after urological surgeries.Adult male patients undergoing urological surgery requiring urinary bladder catheterization intraoperatively were enrolled. Induction and maintenance of anaesthesia were standardized. Patients were randomized into two groups after complaining of CRBD in the post-anaesthesia care unit. The control group (n=29) received normal saline and the butylscopolamine group (n=28) was administered butylscopolamine 20 mg i.v. The severity of CRBD, postoperative pain, and adverse effects were assessed at baseline, 20 min, 1, 2, and 6 h after administration of the study drug.The severity of CRBD observed in the butylscopolamine group was significantly lower than that of the control group at 1, 2, and 6 h after administration of the study drug [59 (12), 50 (16), 40 (21) in the control group vs 41 (22), 32 (25), 23 (18) in the butylscopolamine group, P0.01]. Rescue analgesics were required less in the butylscopolamine group than in the control group (P=0.001). Adverse events were comparable between the two groups.Butylscopolamine 20 mg administered i.v. after complaining CRBD during recovery reduced both the severity of CRBD and the need for rescue analgesics without adverse effects in patients undergoing urologic surgeries.

Progesterone is an important sex hormone for pregnancy and also has neuroprotective and anticonvulsant effects. It is well-known that full-term parturients become more susceptible to volatile anesthetics. Glutamate transporters are important for preventing neurotoxicity and anesthetic action in the central nervous system. We investigated the effects of progesterone on the activity of glutamate transporter type 3 (EAAT3), the major neuronal EAAT. EAAT3 was expressed in Xenopus laevis oocytes by injecting its mRNA. Oocytes were incubated with diluted progesterone for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 μM L-glutamate. Progesterone (1–100 nM) significantly increased EAAT3 activity in a dose-dependent manner. Our kinetic study showed that the V max was increased in the progesterone group compared with that in the control group (2.7±0.2 vs. 3.6±0.2 μC for control group vs. progesterone group; n =18–23; P K m was unaltered (46.7±10.2 μM vs. 55.9±10.5 μM for control group vs. progesterone group; n =18–23; P >0.05). P horbol-12-myristate-13-acetate, a protein kinase C (PKC) activator, did not change progesterone-enhanced EAAT3 activity. Inhibitors of PKC or phosphatidylinositol 3-kinase (PI3K) abolished the progesterone-induced increases in EAAT3 activity. Our results suggest that progesterone enhances EAAT3 activity and that PKC and PI3K are involved in mediating these effects. These effects of progesterone may contribute to its anticonvulsant and anesthesia-related properties.

This study aimed to evaluate the effect of riluzole on the activity of excitatory amino acid transporter type 3 (EAAT3), a neuronal glutamate transporter, and to investigate the role of protein kinase C (PKC) in this effect. EAAT3 expression was induced in Xenopus oocytes by injecting EAAT3 mRNA. Using the two-electrode voltage clamping method, membrane currents were recorded before, during, and after applying l-glutamate (30 μM) in the absence and presence of prior incubation with riluzole (0.3-100 μM). To study the effect of PKC on the riluzole-induced change in EAAT3 activity, oocytes were preincubated with 100 μM phorbol-12-myristate-13-acetate (PMA), a PKC activator, or PKC inhibitors (2 µM staurosporine and 100 µM chelerythrine) before the recording. Responses were quantified by integrating current traces and are reported in microCoulombs (μC). Riluzole reduced EAAT3 activity in a concentration-dependent manner (0.3-100 μM). Treatment of oocytes with PMA significantly increased the baseline and riluzole-reduced EAAT activity (P0.05). In addition, treatment of oocytes with PKC inhibitors reduced basal transporter currents, but did not show a further significant decrease in the riluzole-reduced EAAT3 activity. These results suggest that riluzole reduces EAAT3 activity through PKC inhibition.

Caffeine has been known to trigger seizures, however, the precise mechanism about the proconvulsive effect of caffeine remains unclear. Glutamate transporters play an important role to maintain the homeostasis of glutamate concentration in the brain tissue. Especially, dysfunction of excitatory amino acid transporter type 3 (EAAT3) can lead to seizures. We investigated the effects of caffeine on the activity of EAAT3 and the involvement of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K). Rat EAAT3 was expressed in Xenopus oocytes by injecting EAAT3 mRNA. l- Glutamate (30 μM)-induced inward currents were recorded via the two-electrode voltage clamp method. Caffeine decreased EAAT3 activity in a dose-dependent manner. Caffeine (30 μM for 3 min) significantly reduced V max , but did not alter K m value of EAAT3 for glutamate. When preincubated oocytes with phorbol-12-myristate-13-acetate (PMA, a PKC activator) were exposed to caffeine, PMA-induced increase in EAAT3 activity was abolished. Two PKC inhibitors (chelerythrine and staurosporine) significantly reduced basal EAAT3 activity. Whereas, there were no significant differences among the PKC inhibitors, caffeine, and PKC inhibitors + caffeine groups. In similarly fashion, wortmannin (a PI3K inhibitor) significantly decreased EAAT3 activity, however no statistical differences were observed among the wortmannin, caffeine, and wortmannin + caffeine groups. Our results demonstrate that caffeine attenuates EAAT3 activity and this reducing effect of caffeine seems to be mediated by PKC and PI3K.

Laryngoscopy and tracheal intubation (LTI) after induction of general anesthesia often cause hypertension and tachycardia. Labetalol and nicardipine have been used to prevent and treat acute cardiovascular responses to LTI.The goal of this study was to compare the preventive and therapeutic effects of labetalol 0.4 mg/kg IV and nicardipine 20 μg/kg IV on hypertensive responses to LTI during induction of general anesthesia.Patients undergoing general anesthesia were randomly allocated to 4 groups. In part I (prevention), 80 patients were randomized to receive either 0.4 mg/kg of labetalol (n = 40) or 20 μg/kg of nicardipine (n = 40) 4 minutes before LTI. In part II (treatment), patients were randomized to receive 0.4 mg/kg of labetalol (n = 40) or 20 μg/kg of nicardipine (n = 40) after LTI if hypertension occurred. The number of additional study drug doses required by patients with hypertension (parts I and II) and time to return to normotension (part II) were recorded. Mean arterial pressure and heart rate were monitored, and rate-pressure product was calculated. Adverse events were also monitored.A total of 130 patients (72 patients in part I and 58 patients in part II) were included in the analysis. In parts I and II, the number of patients who required additional doses of the study drug because of persistent hypertension was lower in the nicardipine groups than in the labetalol groups (P0.05). Mean arterial pressure was lower and heart rate was significantly higher over time in the nicardipine groups compared with the labetalol groups (P0.05) in parts I and II. In part II, time to return to normotension was shorter in the nicardipine treatment group than in the labetalol treatment group (61 [21] vs 130 [46] seconds; P = 0.01). No statistical differences were observed in the incidence of adverse events except for tachycardia in part I (2 cases in the labetalol prevention group vs 18 cases in the nicardipine prevention group; P = 0.01).Patients who received nicardipine were less likely to require additional doses for either the prevention or treatment of hypertensive responses to LTI and responded to the study drug more rapidly than patients who received labetalol for the treatment of hypertensive responses to LTI. However, labetalol was associated with a lower incidence of tachycardia and less of an increase in rate-pressure product when used for the prevention of hypertension during LTI.

Background Patients undergoing general anesthesia for laparoscopic cholecystectomy have a high risk of postoperative nausea and vomiting (PONV) with incidences up to 75%. Ramosetron, a serotonin subtype 3 (5-HT 3 ) antagonist, has been shown to be effective as an antiemetic after chemotherapy and surgery. Consensus guidelines recommend a combination of antiemetic therapies in high-risk groups. Until now, no published data have been available on the use of combination oral plus intravenous ramosetron. Objective The goal of this prospective, randomized, double-blind study was to compare the efficacy and tolerability of intravenous, oral, and the combination of oral and intravenous ramosetron for PONV prophylaxis in patients undergoing laparoscopic cholecystectomy. Methods Patients scheduled for laparoscopic cholecystectomy were double-randomly allocated to 1 of 3 groups. Patients were randomly allocated to receive either 0.3 mg of intravenous ramosetron (group A), 0.1 mg of oral ramosetron (group B), or the combination of 0.1 mg of oral ramosetron and 0.3 mg of intravenous ramosetron (group C). All patients received standardized balanced anesthesia with desflurane and remifentanil. Postoperative nausea, retching, vomiting, pain, and adverse effects were assessed at 0 to 2, 2 to 24, and 24 to 48 hours after surgery. Results A total of 124 Korean patients (67 women, 57 men; age range, 25–65 years) were randomized to 1 of 3 study groups (42 in group A [mean age, 49.8 years], 41 in group B [mean age, 47.4 years], and 41 in group C [mean age, 48.9 years]). No statistical differences were observed among the 3 groups with regard to patient characteristics and information on surgery and anesthesia. During postoperative period 0 to 2 hours, complete response occurred in 31 (74%) patients in group A, 27 (66%) in group B, and 37 (90%) in group C. During the postoperative period of 2 to 24 hours, complete response was observed in 36 (86%), 33 (80%), and 40 (98%) patients in groups A, B, and C, respectively; there was a statistically significant difference in group C compared with group A or group B. During the postoperative period of 0 to 48 hours, incidences of rescue antiemetic use were 13 (31%), 14 (34%), and 3 (7%) in groups A, B and C, respectively. Common adverse effects (headache, dizziness, and drowsiness) were observed, but there was no significant difference in the incidences of adverse effects among the 3 groups ( P > 0.05). Conclusions The combination of 0.1-mg oral and 0.3-mg intravenous ramosetron was more effective than either 0.3-mg intravenous ramosetron or 0.1-mg oral ramosetron alone for the prophylaxis of nausea and vomiting after laparoscopic cholecystectomy during the first 24 hours after surgery. In addition, differences did not reach the level of statistical significance between 0.1 mg of oral ramosetron and 0.3 mg of intravenous ramosetron for the prevention of PONV in this patient population. Oral, intravenous, and combined oral and intravenous ramosetron appears well tolerated in the population studied. ClinicalTrials.gov identifier: NCT 01041183.

Glucocorticoids can increase the extracellular concentrations of glutamate, the major excitatory neurotransmitter. We investigated the effects of corticosterone on the activity of a glutamate transporter, excitatory amino acid carrier 1 (EAAC1; also called excitatory amino acid transporter type 3 [EAAT3]), and the roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in regulating these effects. Rat EAAC1 was expressed in Xenopus oocytes by injecting mRNA. L-Glutamate (30 μM)-induced membrane currents were measured using the two-electrode voltage clamp technique. Exposure of these oocytes to corticosterone (0.01-1 μM) for 72 h decreased EAAC1 activity in a dose-dependent fashion, and this inhibition was incubation time-dependent. Corticosterone (0.01 μM for 72 h) significantly decreased the V(max), but not the K(m), of EAAC1 for glutamate. Furthermore, pretreatment of oocytes with staurosporine, a PKC inhibitor, significantly decreased EAAC1 activity (1.00±0.06 to 0.70±0.05 μC; P

To determine the effect-site target concentration (C(et)) of remifentanil that provides optimal conditions for patients and operators during cataract surgery during monitored anesthesia care using a target controlled infusion (TCI) of propofol and remifentanil.Prospective, randomized, double-blinded study.Operating room and postoperative recovery area of a university-affiliated hospital.66 adult, ASA physical status I, II, and III patients undergoing cataract surgery.Group I received C(et) of remifentanil 0.5 ng/mL; Group 2 received C(et) of remifentanil one ng/mL; and Group 3 received C(et) of remifentanil 1.5 ng/mL. After giving TCI propofol (C(et); one μg/mL)-remifentanil, an ophthalmologist administered topical anesthesia.Intraoperative hemodynamics, pain scores, sedation scores, patient satisfaction scores, and operators' satisfaction scores regarding surgical conditions were recorded. No statistical differences in heart rate or mean blood pressure were detected among the three groups during surgery. Pain scores (Group 1: 31.9 ± 17.9 vs. Group 2: 11.8 ± 7.7 and Group 3: 11.8 ± 7.7; P0.05) were higher and patient satisfaction scores (Group 1: 4.7 ± 0.8 vs. Group 2: 5.4 ± 0.4 and Group 3: 5.5 ± 0.4; P0.05) were lower in Group 1 than Groups 2 and 3. On the other hand, surgeon satisfaction was lowest in Group 3 (Group 3: 2.9 ± 1.3 vs. Group 1: 4.7 ± 0.4 and Group 2: 4.6 ± 0.7; P0.05) due to ocular movement.C(et) values of remifentanil and propofol of one ng/mL and one μg/mL, respectively, appear to provide optimal conditions for patients and operators during cataract surgery using monitored anesthesia care with TCI.