Quantitative assessment of gait bradykinesia in Parkinson's disease using a portable gait rhythmogram.

To quantify gait bradykinesia during daily activity in patients with Parkinson's disease (PD), we measured movement-induced accelerations over more than 24h in 50 patients with PD and 17 age-matched normal controls, using a new device, the portable gait rhythmogram. Acceleration values induced by various movements, averaged each 10 min, exhibited a gamma distribution. The mean value of the distribution curve was used as an index of the "amount of overall movement per 24h". Characteristic changes were observed in both the gait cycle and gait acceleration. During hypokinesia, the gait cycle became either faster or slower. A number of patients with marked akinesia/bradykinesia showed a reduced and narrow range of gait acceleration, i.e., a range of floor reaction forces. The results suggest that assessment of the combination of changes in gait cycle and gait acceleration can quantitatively define the severity of gait bradykinesia.

Ketamine inhibits endotoxin-induced inositol 1,4,5-triphosphate in rat ventricular cardiomyocytes.

OBJECTIVE: To investigate the effect of ketamine on endotoxin modulation of inositol 1,4,5-triphosphate (IP3) formation in cardiomyocytes. DESIGN: A prospective observational cell culture study. SETTING: A research laboratory in the University of Hirosaki School of Medicine. MATERIALS: Neonatal rat cardiomyocytes. INTERVENTION: We investigated bradykinin-induced IP3 production in the presence of lipopolysaccharide (LPS) and the effect of ketamine on the LPS modulation of IP3 formation. The LPS modulation of IP3 formation was measured in the presence of BM13177 (a thromboxane A2 (TXA2) receptor inhibitor) or GDPbetaS (a GTP-binding protein inhibitor). U46619 (a TXA2 agonist)-induced IP3 production was measured in the presence of ketamine, and the ketamine modulation of U46619-induced IP3 production was measured in the presence of W7 (a Ca2+ releasing agent) and verapamil (a Ca2+ channel blocker). RESULTS: One micromole ketamine significantly attenuated the LPS-induced IP3 production from 763.8+/-34.6 to 461.6+/-65.1 pmol mg protein(-1). Ten micromoles of BM13177 or 1 mM GDPbetaS significantly blocked LPS modulation of bradykinin-induced IP3 production from 786.0+/-33.8 to 218.6+/-21.6 and 226.8+/-25.4 pmol mg protein(-1). One micromole of ketamine significantly decreased U46619-induced IP3 production from 857.3+/-45.0 to 632.9+/-64.5 pmol mg(-1) protein. The ketamine inhibition of U46619-induced IP3 production was enhanced by W7 and inhibited by verapamil. CONCLUSION: Ketamine decreased LPS-induced IP3 formation and the ketamine inhibition was associated with inhibition of the TXA2-IP3 sequence. Inhibition of TXA2 by ketamine was associated with a decrease in intracellular Ca2+.

Protein identification by peptide mass fingerprinting and peptide sequence tagging with alternating scans of nano-liquid chromatography/infrared multiphoton dissociation Fourier transform ion cyclotron resonance mass spectrometry.

We have developed a method for protein identification with peptide mass fingerprinting and sequence tagging using nano liquid chromatography (LC)/Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). To achieve greater sensitivity, a nanoelectrospray (nano-ES) needle packed with reversed-phase medium was used and connected to the nano-ES ion source of the FTICR mass spectrometer. To obtain peptide sequence tag information, infrared multiphoton dissociation (IRMPD) was carried out in nano-LC/FTICR-MS analysis. The analysis involves alternating nano-ES/FTICR-MS and nano-ES/IRMPD-FTICR-MS scans during a single LC run, which provides sets of parent and fragment ion masses of the proteolytic digest. The utility of this alternating-scan nano-LC/IRMPD-FTICR-MS approach was evaluated by using bovine serum albumin as a standard protein. We applied this approach to the protein identification of rat liver diacetyl-reducing enzyme. It was demonstrated that this enzyme was correctly identified as 3-alpha-hydroxysteroid dehydrogenase by the alternating-scan nano-LC/IRMPD-FTICR-MS approach with accurate peptide mass fingerprinting and peptide sequence tagging.

A comparison of anesthetic quality in propofol-spinal anesthesia and propofol-fentanyl anesthesia for total knee arthroplasty in elderly patients.

STUDY OBJECTIVE: To compare propofol plus spinal anesthesia during spontaneous ventilation using the Laryngeal Mask Airway and propofol plus fentanyl anesthesia during mechanical ventilation with an endotracheal tube on quality of recovery after anesthesia. DESIGN: Prospective, randomized study. SETTING: Hirosaki National Hospital. PATIENTS: 150 patients (aged > 70 years) undergoing total knee arthroplasty. INTERVENTIONS: Patients were divided randomly into two groups, to receive spontaneous ventilation with a Laryngeal Mask Airway during propofol-spinal anesthesia, or to receive propofol-fentanyl anesthesia with mechanical ventilation via endotracheal tube. MEASUREMENTS: Quality of anesthesia recovery such as nausea, vomiting, headache, pain throat, hoarse voice, back pain, dizziness, feeling comfortable, dreaming, recovery times in recovery of anesthesia, recovery times, postoperative pain, confusion, was assessed. MAIN RESULTS: The frequency of postoperative pain throat, hoarse voice, and nausea was significantly lower in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group. The time to extubation, emergence, response to commands, and orientation were significantly faster (p < 0.001) in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group. The frequency of postoperative confusion occurring in the propofol-spinal anesthesia group during the first 24 hours was significantly lower than that of the propofol-fentanyl anesthesia group (p = 0.03). CONCLUSIONS: Propofol-spinal anesthesia provided better and faster recovery than did propofol-fentanyl anesthesia for elderly patients undergoing total knee arthroplasty.

Increased postoperative pain scores in chronic depression patients who take antidepressants.

STUDY OBJECTIVE: To investigate postoperative pain and current perception thresholds in chronic depression in patients who are treated with antidepressants. DESIGN: Prospective, randomized study. SETTING: Hakodate Watanabe Hospital and Hirosaki National Hospital. PATIENTS: 30 patients with major depression and 30 control patients who underwent abdominal surgery with general anesthesia. INTERVENTIONS: Postoperative pain scores via visual analog scale (0-100), current perception thresholds at 5, 250, and 2000 Hz. MEASUREMENTS AND MAIN RESULTS: Postoperative pain scores of depressed patients at 8 and 16 hours after the end of anesthesia were 36.2 +/- 10.4 and 33.4 +/- 8.5, which were significantly higher than 25.2 +/- 9.3 and 22.7 +/- 8.5 scores of the control patients. Current perception thresholds at 5 Hz, 250 Hz, and 2000 Hz in depressed patients were 38.2 +/- 6.7, 76.1 +/- 11.3, and 190.8 +/- 19.2, respectively. There were no significant differences between the depressed patients and control patients in current perception thresholds at 5 Hz, 250 Hz, and 2000 Hz. We found that visual analog scale scores in depressed patients at 8 and 16 hours after the end of anesthesia correlated with the Hamilton Depression Scale scores before operation. CONCLUSIONS: The degree of postoperative pain in depressed patients who take antidepressants depends on their depressive state.

Anesthesia with ketamine, propofol, and fentanyl decreases the frequency of postoperative psychosis emergence and confusion in schizophrenic patients.

STUDY OBJECTIVE: To investigate whether total IV anesthesia with ketamine, propofol, and fentanyl affects the frequency of postoperative psychosis emergence or confusion in schizophrenic patients. DESIGN: Prospective, controlled study. SETTING: Hirosaki National Hospital and Hakodate Watanabe Hospital. PATIENTS: 76 ASA physical status I and II schizophrenic patients taking chronic antipsychotic drugs and schedule for orthopedic surgery of extremities. INTERVENTIONS: In Group A (n = 38) patients, anesthesia was maintained with sevoflurane, nitrous oxide, and fentanyl. In Group B (n = 38) patients, anesthesia was maintained with ketamine, propofol, and fentanyl. MEASUREMENTS AND MAIN RESULTS: The frequency of psychosis emergence or confusion (54%) in Group A during the first 48 hours after surgery was significantly higher than the 30% figure in Group B. CONCLUSION: Ketamine, when combined with propofol and fentanyl, is an appropriate anesthetic drug for schizophrenic patients.

Postoperative confusion in schizophrenic patients is affected by interleukin-6.

STUDY OBJECTIVE: To investigate whether epidural analgesia with local anesthetics affects postoperative confusion in schizophrenic patients or the relationships between cortisol or interleukin-6 (IL-6) and postoperative confusion. DESIGN: Prospective, randomized study. SETTING: Hakodate Watanabe Hospital and Hirosaki National Hospital. PATIENTS: 105 patients who were scheduled to undergo abdominal surgery with general anesthesia. INTERVENTIONS: The schizophrenic patients were rendomly divided into two groups: patients in Group A received epidural anesthesia and patients in Group B did not receive epidural anesthesia. MEASUREMENTS AND MAIN RESULTS: Postoperative confusion during the first 48 hours after the end of operation occurred in 7 of 33 patients (21%) in Group A and 10 of 33 patients (30%) in Group B. There were no significant differences in the frequency of postoperative confusion between Groups A and B. Plasma cortisol concentrations in schizophrenic patients in Group A were significantly lower 15 minutes after incision and the end of surgery than those levels of patients in Group B; however, there was no significant difference between groups in plasma cortisol concentrations after anesthesia. Plasma IL-6 concentrations (51.7 +/- 22.0 and 31.4 +/- 8.2 pg mL(-1)) in patients with postoperative confusion at the end of surgery and 24 hours after surgery were significantly higher than those levels (34.4 +/- 16.2 and 16.9 +/- 7.7 pg mL(-1)) in patients without postoperative confusion. CONCLUSIONS: Epidural anesthesia does not significantly decrease the frequency of postoperative confusion in schizophrenic patients. Plasma IL-6 concentrations at the end of the operation and 24 hours after surgery in schizophrenic patients with postoperative confusion were significantly higher than those concentrations in patients without postoperative confusion.

[A case of severe bradycardia and AV block during administration of propofol].

A 69-yr-old man underwent emergency laparotomy. He was in endotoxic shock. Preoperative evaluation including a full blood count, chest X-ray and ECG were normal. Body temperature was 37.4 degrees C. Preoperative arterial pressure was 140/80 mmHg and heart rate 65 bpm. Anesthesia was induced with ketamine 100 mg, propofol 20 mg, fentanyl 50 micrograms and vecuronium 4 mg and maintained with propofol 4 mg.kg-1.hr-1 and fentanyl. Soon after opening the abdominal peritoneum, severe bradycardia (< 20 bpm) occurred, but it was effectively treated by ephedrine 16 mg. After that, surgery was performed uneventfully. In the intensive care unit (ICU), the patient developed four episodes of severe atrioventricular (AV) block after stimulation of the trachea by suction drainage under sedation with propofol, although there was no AV block during sedation with ketamine and propofol. After stopping propofol, the AV block was no longer observed. He was discharged from the ICU on the 12th postoperative day. Postoperative Holter ECG and echocardiography showed no abnormalities. It is likely that stimulation of the trachea triggered vagovagal reflex and propofol prolonged AV conduction, causing the AV block.

[A successfully treated case of aspiration pneumonia with adult respiratory distress syndrome and shock].

Right hip replacement was scheduled for a 74-year-old man who was treated with morphine for cancer pain. As the patient developed dyspnea and hypoxia after anesthesia, he was intubated and kept under mechanical ventilation. A diagnosis of aspiration pneumonia with adult respiratory distress syndrome was made based on the detection of gall obtained from the endotracheal tube. A chest X-ray showed pulmonary edema. He was treated with positive pressure ventilation and inotropic support. As he developed severe shock 10 hours after the intubation, he was treated with 20 mg.kg-1 of methylprednisolone for 3 days. The steroid therapy was successful and he was extubated on the 6th postoperative day and was discharged from the ICU on the 7th postoperative day. High-dose pulse methylprednisolone therapy resulted in a remarkable clinical improvement. Corticosteroids rescue treatment is effective for such a severe case of aspiration pneumonia with shock when the treatment is done in the early phase of the pneumonia.

How far do the complaints of patients with Parkinson's disease reflect motor fluctuation? Quantitative analysis using a portable gait rhythmogram.

In advanced-stage Parkinson's disease (PD), motor fluctuation is a frequent and disabling problem. Assessment of motor fluctuation depends on patient's subjective self-statement. We examined whether the subjective fluctuation matched the objective motor fluctuation defined by gait disorders. Using a new device, the portable gait rhythmogram, we recorded gait cadence and acceleration continuously over the 24-hour period in 54 patients with PD and 17 normal controls, for the quantitative evaluation of motor fluctuation. The patients were asked to estimate motor fluctuation every hour. In 44 of 54 patients, changes in the cadence were associated with simultaneous changes in acceleration. We examined the subjective fluctuation in these 44 patients who were confirmed to have motor fluctuation. Nineteen (82.7%) of 23 patients who felt no fluctuation showed distinct gait disorders. During off time, they walked with marked short or bradykinetic stepping. No matching changes were observed in either the cadence or acceleration in 11 (52.4%) of 21 patients who perceived motor fluctuation. No synchronization was noted in 30 (68.2%) of the 44 patients, between the times of subjectively assessed motor fluctuation and those of quantitative analysis of gait disorder. This discrepancy suggests that the objective continuous recording of the cadence and acceleration is necessary to understand motor fluctuation.

Deficits in scaling of gait force and cycle in parkinsonian gait identified by long-term monitoring of acceleration with the portable gait rhythmogram.

To examine the range of gait acceleration and cycle in daily walking of patients with Parkinson's disease (PD), we compared the gait of 40 patients with PD and 17 normal controls by using a newly developed long-term monitoring device that extracts gait-related accelerations from overall movements-related accelerations. The range of change in gait acceleration, relative to the control, was less than 75% in 12 patients. The range of change in gait cycle was less than 75% in 8 patients. The range of changes in both parameters was less than 75% in 4 patients. The results suggest narrow changes in gait parameters in PD.

Postoperative interleukin-6 and cortisol concentrations in elderly patients with postoperative confusion.

OBJECTIVE: To investigate changes in plasma interleukin (IL)-6, cortisol or noradrenaline concentrations after surgery in elderly patients with postoperative confusion. METHODS: We studied 80 patients aged 70-90 years undergoing abdominal surgery and measured plasma IL-6, cortisol or noradrenaline concentrations before surgery, at the end of surgery, and 24 and 48 h after surgery. RESULTS: Plasma IL-6 concentrations in elderly patients with postoperative confusion were 83.2 +/- 30.5, 49.3 +/- 14.1 and 42.9 +/- 19.4 pg.ml(-1) at the end of surgery, and 24 and 48 h after surgery, respectively, being significantly higher than in elderly patients without postoperative confusion (58.0 +/- 37.5, 36.1 +/- 20.0 and 28.2 +/- 16.7 pg.ml(-1)). Plasma cortisol concentrations in elderly patients with postoperative confusion (42.2 +/- 7.8, 38.3 +/- 8.3 and 33.1 +/- 8.4 microg.dl(-1) at the end of surgery, and 24 and 48 h after surgery, respectively) were significantly higher than in elderly patients without postoperative confusion (32.9 +/- 6.7, 30.4 +/- 8.6 and 25.6 +/- 6.5 microg.dl(-1), respectively). There were no significant differences in plasma norepinephrine concentrations at all sampling points between elderly patients with and without postoperative confusion. However, plasma IL-6 and cortisol concentrations were related in elderly patients with postoperative confusion (at the end of surgery and 24 and 48 h after surgery). However, there was no relationship between plasma IL-6 and cortisol concentrations 24 and 48 h after surgery in elderly patients without postoperative confusion. CONCLUSION: Elderly patients with postoperative confusion had increased plasma IL-6 and cortisol concentrations. The interaction between IL-6 and cortisol after surgery is associated with developing postoperative confusion in the elderly patients.

Determination of sites citrullinated by peptidylarginine deiminase using 18O stable isotope labeling and mass spectrometry.

Peptidylarginine deiminase (PADI) is an enzyme which catalyzes conversion of arginine residues into citrulline residues in proteins. Citrullination is known to be related to autoimmune diseases including rheumatoid arthritis. Previous work in this laboratory succeeded in identifying citrullinated sites of human fibrinogen by mass spectrometry, but discrimination between citrullination and deamidation of asparagines and glutamine required time-consuming and labor-intensive inspection of tandem mass spectra. In this work a stable isotope is utilized to improve on a previous method for the determination of citrullinated sites by mass spectrometry. Since an oxygen atom is incorporated into the citrulline residue from H(2)O in citrullination by PADI, peptides citrullinated in 50% H(2)(18)O would show a characteristic isotope distribution different from natural abundance, and thus determination of citrullinated sites is expected to be much easier. To verify the utility of this new method, the sites of citrullination of human fibrinogen by human PADI4 were investigated using 50% H(2)(18)O. Compared with the previous method, this new method identified citrullinated sites more easily and effectively, while both the determined citrullinated sites and protein sequence coverage were unaltered.

Comparison of enzymatic properties between hPADI2 and hPADI4.

In the sera of rheumatoid arthritis (RA) patients, autoantibodies directed to citrullinated proteins are found with high specificity for RA. Peptidylarginine deiminases (PADIs) are enzymes responsible for protein citrullination. Among many isoforms of PADIs, only PADI4 has been identified as an RA-susceptibility gene. To understand the mechanisms of the initiation and progression of RA, we compared the properties of two PADIs, human PADI2 and human PADI4, which are present in the synovial tissues of RA patients. We confirmed their precise distribution in the RA synovium and compared the stability, Ca2+ dependency, optimal pH range, and substrate specificity. Small but significant differences were found in the above-mentioned properties between hPADI2 and hPADI4. Using LC/MS/MS analysis, we identified the sequences in human fibrinogen indicating that hPADI2 and hPADI4 citrullinate in different manners. Our results indicate that hPADI2 and hPADI4 have different roles under physiological and pathological conditions. Further studies are needed for the better understanding of the role of hPADIs in the initiation and progression of RA.

Purification through Zeno-like measurements.

A series of frequent measurements on a quantum system (Zeno-like measurements) is shown to result in the "purification" of another quantum system in interaction with the former. Even though the measurements are performed on the former system, their effect drives the latter into a pure state, irrespectively of its initial (mixed) state, provided certain conditions are satisfied.

Chronic treatment with antipsychotics enhances intraoperative core hypothermia.

UNLABELLED: Antipsychotics can induce hypothermia, but intraoperative temperature regulation in schizophrenic patients taking antipsychotics remains unclear. We investigated intraoperative temperature regulation and postoperative shivering in chronic schizophrenic patients receiving antipsychotics. We studied 30 schizophrenic patients and 30 control patients who underwent orthopedic surgery. Tympanic membrane temperatures (35.7 degrees C +/- 0.5 degrees C, 35.6 degrees C +/- 0.5 degrees C, 35.6 degrees C +/- 0.4 degrees C, 35.5 degrees C +/- 0.4 degrees C, 35.4 degrees C +/- 0.5 degrees C, and 35.4 degrees C +/- 0.3 degrees C) 15, 30, 45, 60, 75, and 90 min, respectively, after induction in schizophrenic patients were significantly (P < 0.001) lower than those (36.5 degrees C +/- 0.5 degrees C, 36.4 degrees C +/- 0.5 degrees C, 36.3 degrees C +/- 0.4 degrees C, 36.2 degrees C +/- 0.5 degrees C, 36.2 degrees C +/- 0.4 degrees C, and 36.1 degrees C +/- 0.4 degrees C) in control patients. Mean skin temperatures (31.1 degrees C +/- 0.4 degrees C [P = 0.008], 31.1 degrees C +/- 0.3 degrees C [P = 0.007], and 31.1 degrees C +/- 0.2 degrees C [P = 0.006]) 60, 75, and 90 min, respectively, after induction in schizophrenic patients were significantly lower than those (31.5 degrees C +/- 0.3 degrees C, 31.5 degrees C +/- 0.3 degrees C, and 31.5 degrees C +/- 0.3 degrees C) in control patients. Four of 30 schizophrenic patients and 7 of 30 control patients developed postanesthesia shivering. There were no significant differences within 1 h after tracheal extubation in tympanic membrane temperatures between patients who shivered and those who did not shiver. In conclusion, chronic schizophrenic patients were more hypothermic during anesthesia. The incidence of postanesthesia shivering was not significantly increased. IMPLICATIONS: Antipsychotics inhibit autonomic thermoregulation. This is caused by decreased heat production, increased heat loss, and impaired central action at the hypothalamus. Thus, schizophrenic patients receiving antipsychotics may have impaired intraoperative temperature regulation.

Chronic treatment with antidepressants decreases intraoperative core hypothermia.

UNLABELLED: We investigated temperature regulation during anesthesia and postoperative shivering in chronically depressed patients given antidepressant drugs. We studied 35 depressed patients and 35 control patients who underwent orthopedic surgery. Tympanic membrane temperatures 60, 75, and 90 min after induction in the depression group were significantly (P < 0.05) higher than those of the control group. There were no significant differences in mean skin temperature between the depression and the control groups. Eight of 35 patients in the depression group and 2 of 35 patients in the control group developed postanesthetic shivering. The incidence of shivering in the depression group was significantly more frequent than that in the control group (P = 0.04). The tympanic membrane temperature of the patients treated with clomipramine tended to be higher than that of the patients treated with maprotiline. In conclusion, intraoperative core hypothermia in chronically depressed patients was decreased. However, the incidence of shivering in depressed patients was significantly more frequent. IMPLICATIONS: Thermoregulation in chronically depressed patients is often altered. The alteration of body temperature is affected by depression itself and by antidepressants. General anesthesia has an influence on thermoregulatory control. However, temperature regulation during anesthesia in chronically depressed patients remains unclear.

Atrial natriuretic peptide increases glucose uptake during hypoxia in cardiomyocytes.

The action of atrial natriuretic peptide on glucose uptake during hypoxia was investigated in neonatal cardiomyocytes. When the cultures were exposed to 100 n and 1 and 10 micro M of atrial natriuretic peptide for 60 min, hypoxia-induced glucose uptake significantly increased from 20.4 +/- 1.2 to 28.2 +/- 3.1, 31.6 +/- 2.7, and 30.1 +/- 2.8 pmol/h/mg protein, respectively, although atrial natriuretic peptide alone did not significantly affect the basal glucose uptake in normoxic condition. The atrial natriuretic peptide-stimulated glucose uptake during hypoxia was significantly decreased by 100 n of genistein and tyrphostin A-23 (a tyrosine kinase inhibitor) from 31.6 +/- 2.7 to 22.8 +/- 2.4 and 23.8 +/- 2.7 pmol/h/mg protein. U73122 100 n, which is a phospholipase C antagonist, significantly inhibited the atrial natriuretic peptide-induced glucose uptake under hypoxic conditions from 31.6 +/- 2.7 to 13.6 +/- 1.9 pmol/h/mg protein. However, the atrial natriuretic peptide-induced glucose uptake did not involve elevation of intracellular Ca and phosphatidylinositol (PI)3 kinase. It was concluded that the atrial natriuretic peptide-stimulated glucose uptake during hypoxia acts through a phospholipase C-tyrosine kinase pathway.

Antidepressant treatment for chronic depressed patients should not be discontinued prior to anesthesia.

PURPOSE: To investigate whether antidepressants administered to patients for chronic depression patients should be continued or discontinued before anesthesia. RESULTS: We studied 80 depressed patients who were scheduled to undergo orthopedic surgery under general anesthesia. The patients were divided randomly into two groups; patients in Group A (n=40) continued antidepressants before surgery and patients in Group B (n=40) discontinued antidepressants 72 hr before surgery. Two (5%) out of 40 patients in Group A and eight (20%) out of 40 patients in Group B had deterioration of depressive symptoms (P=0.04). Delirium or confusion during the perioperative course occurred in five patients (13%) in Group A and in 12 (30%) in Group B (P=0.05). There were no significant differences in incidence (5 vs 6%) of hypotension and arrhythmias during anesthesia between the two groups. CONCLUSION: Antidepressants administered to depressed patients should be continued before anesthesia. Discontinuation of antidepressants did not increase the incidence of hypotension and arrhythmias during anesthesia, but increased symptoms of depression and delirium or confusion.

Sevoflurane increases glucose transport in skeletal muscle cells.

UNLABELLED: Sevoflurane activates phospholipase C and protein kinase C, leading to an increase in intracellular Ca(2+) concentration, which modulates glucose transport. We studied in vitro the effect of sevoflurane on the uptake of 2-deoxyglucose in rat skeletal muscle cells and the mechanism that modulates the glucose transport. Sevoflurane 0.8, 1.2, and 2.0 mM significantly increased glucose uptake from 13.1 +/- 1.2 pmol. h(-1). mg protein(-1) to 22.6 +/- 1.4, 32.1 +/- 1.8, and 37.4 +/-2.7 pmol. h(-1). mg protein(-1), respectively. Tyrphostin A-23 (a highly selective tyrosine kinase inhibitor) 1 and 10 nM significantly decreased the sevoflurane-stimulated glucose uptake from 32.1 +/- 1.8 to 25.8 +/- 1.1 and 15.2 +/- 1.7 pmol. h(-1). mg protein(-1), respectively. Genistein (a selective tyrosine kinase inhibitor) 1 and 10 nM also significantly decreased the sevoflurane- stimulated glucose uptake from 32.1 +/- 1.8 to 25.7 +/- 1.5 and 15.2 +/- 1.4 pmol. h(-1). mg protein(-1), respectively. The sevoflurane-stimulated glucose uptake was decreased by 100 nM and 1 microM TMB-8 (an intracellular Ca(2+) antagonist), from 32.1 +/- 1.8 pmol. h(-1). mg protein(-1) to 25.6 +/- 3.3 and 20.3 +/- 1.6 pmol. h(-1). mg protein(-1), respectively. Staurosporine (a protein kinase C antagonist) 100 nM significantly decreased sevoflurane-stimulated glucose uptake to 26.1 +/- 1.5 pmol. h(-1). mg protein(-1). We conclude that sevoflurane increases glucose uptake in skeletal muscle cells and that the sevoflurane-stimulated glucose uptake was associated with tyrosine kinase, protein kinase C, and intracellular Ca(2+). IMPLICATIONS: Sevoflurane anesthesia has an inhibitory effect on insulin secretion. Glucose concentrations in plasma do not significantly change during sevoflurane anesthesia. Plasma glucose concentrations are affected by intracellular glucose metabolism. However, glucose transport into cells during sevoflurane anesthesia remains unclear.