Pharmacy services at the Tokyo 2020 Olympic and Paralympic Games: perspectives of the pharmacy workforce.

OBJECTIVES: To evaluate the awareness of the volunteer pharmacy workforce of medication use and their satisfaction with the pharmacy services of the Tokyo 2020 Olympic and Paralympic Games from a pharmacist's perspective. METHODS: A questionnaire was developed from related articles in published peer-reviewed journals and modified prior to distribution to the whole population of pharmacists serving at the Tokyo 2020 Olympic and Paralympic Games. Validity tests were conducted based on expert opinions and Cronbach's alpha (0.79). The questionnaire consisted of demographics (11 questions), knowledge of medication use in sports (8 questions) and satisfaction on the provision of the service (5 questions). Responses using a 5-point-Likert scale, from strongly agree (5) to strongly disagree (1), and two free text questions were analysed with descriptive statistics. RESULTS: The response rate was 86% (n=32/37). Overall, the pharmacists reported a high awareness of medication use. Specifically, questions on the prohibited list of medications (mean 4.0±SD 0.7), COVID-19 policy (3.8±0.9), use of alternative non-prohibited medications (3.6±1.0) and therapeutic use exemptions (3.5±0.9). Moreover, they rated high satisfaction with the pharmacy service they provided. However, rates were ≤3 for knowledge of the International Olympic Committee Needle Policy (2.6±1.0), Medication Importation Declaration (2.9±1.0) and communication skills (3.0±1.0). CONCLUSION: Pharmacists were confident and satisfied with the pharmacy service at the games. The study confirms the importance of prior training and education. Game-specific policies and strategies to improve communication skills should be included in the pharmacy education for future Games.

Conformational transition induced in the aspartate:alanine antiporter by L-Ala binding.

An aspartate:alanine antiporter (AspT) from the lactic acid bacterium Tetragenococcus halophilus catalyzes the electrogenic aspartate1-:alanine0 exchange reaction. Our previous kinetic analyses of transport reactions mediated by AspT in reconstituted liposomes suggested that, although the substrate transport reactions are physiologically coupled, the putative binding sites of L-aspartate (-Asp) and L-alanine (-Ala) are independently located on AspT. By using the fluorescent probe Oregon Green maleimide (OGM), which reacts specifically with cysteine, we also found that the presence of L-Asp changes the conformation of AspT. In this study, we conducted an OGM labeling assay in the presence of L-Ala. The labeling efficiency of single cysteine mutants (G62C and P79C) in transmembrane helix 3 of the AspT showed novel patterns depending on the presence of L-Ala or analogs. A concentration-dependent shift of AspT from the conformation in the presence of one substrate to that specific to the substrate added subsequently (L-Ala or L-Asp) was observed. Moreover, size-exclusion-chromatography-based thermostability assays indicated that the thermal stability of AspT in the presence of L-Ala differed from that in the presence of L-Asp. From these results, we concluded that L-Ala binding yields a conformation different from the apo or L-Asp binding conformations.

Oligomeric state of the aspartate:alanine transporter from Tetragenococcus halophilus.

The aspartate:alanine exchanger family of membrane transporters includes industrially important transporters such as succinate exporter and glutamate exporter. No high-resolution structure is available from this family so far, and the transport mechanism of these transporters also remains unclear. In the present study, we focus on the oligomeric status of the aspartate:alanine antiporter (AspT) of Tetragenococcus halophilus, which is the prototype of this family. To investigate the oligomeric structure of AspT, we established a system that produces high yields of highly purified AspT and determined the oligomeric structure of AspT by analysis with size exclusion chromatography coupled with multi-angle light scattering and blue native PAGE and by comparison of the wild-type AspT with a single-cysteine mutant that forms spontaneous inter-molecular thiol crosslinking. All the results consistently support the notion that AspT is a homodimer in solutions and in membranes.

Reconsidering Sports Pharmacists and Anti-Doping Education as the World Celebrates the Olympic and Paralympic Games.

The Tokyo Olympic and Paralympic Games in 2021 presented an opportunity for pharmacists to recognize the uniqueness of sports pharmacy as a developing field and to understand the importance of anti-doping education among patient-athletes. Patient-athletes make up a distinct patient population, and pharmacists are well positioned to support athletes' therapeutic decisions. Pharmacists need to be able to search for and interpret drug information to take care of this special population appropriately. The purpose of this commentary is to facilitate a discussion on what changes or reinforcement might help train pharmacists to become equipped with adequate knowledge and skills to support safe use of drugs among patient-athletes. While effective resources and tools have become more widely available, pharmacists' awareness of and training in the field of sports pharmacy continue to be needed. No matter where they practice, pharmacists should be ready to promote "the spirit of sport" and defend the importance of "clean" sport for their patient-athletes.

Job satisfaction and intention to remain on the job among Japanese nursing assistants.

Objective: To establish work environments that prevent Japanese nursing assistants from leaving their jobs, we investigated the associations between their job satisfaction levels and intentions to remain on their jobs. Materials and Methods: We distributed anonymous self-administered questionnaires to Japanese female nursing assistants in 30 different hospitals. Regarding job satisfaction, we investigated various items relevant to both intrinsic facets (e.g., gaining various experiences) and extrinsic facets (e.g., salary), and conducted factor analyses of those items. Standardized partial regression coefficients were then calculated using multiple regression analyses. Intention to remain on the job was the dependent variable for this study. The factor scores calculated by the factor analyses of job satisfaction and respondents' characteristics were the independent variables. Since multicollinearity occurred, we utilized two types of statistical models. After questionnaires with one or more missing values were excluded, 618 questionnaires were analyzed. Results: Using factor analyses, we discovered six factors related to job satisfaction among nursing assistants: "Intrinsic motivation", "Salary", "Relationships among nursing assistants", "Registered nurses' attitudes", "Fatigue reduction", and "Opportunities for vocational skills". In statistical model 1, "Intrinsic motivation", "Salary", "Fatigue reduction", "Age", "Employment status", and "Certified care worker status" were significantly associated with "Intention to remain on the job". In statistical model 2, "Salary", "Registered nurses' attitudes", "Fatigue reduction", "Opportunities for vocational skills", "Age", and "Employment status" were significantly associated with "Intention to remain on the job". Conclusion: "Intrinsic motivation" and "Opportunities for vocational skills" are included in intrinsic facets. To prevent nursing assistants from leaving their jobs, raising only their extrinsic job satisfaction levels is insufficient. Because nursing assistants have not received formal nursing education, they cannot take pride in having the same skills and expertise as registered nurses. However, hospital managers must respect their feelings and establish an appropriate working environment.

Knockout of Ceramide Kinase Aggravates Pathological and Lethal Responses in Mice with Experimental Colitis.

Sphingolipids and their metabolic enzymes are implicated in ulcerative colitis. Ceramide kinase (CerK) catalyzes the phosphorylation of ceramide to ceramide-1-phosphate (C1P). Previous studies showed the activation of CerK by the pro-inflammatory cytokine interleukin-1ß, the C1P-induced up-regulation of prostanoids exerting protective effects against colitis, and the C1P-induced down-regulation of the pro-inflammatory cytokine tumor necrosis factor-α. In order to elucidate CerK/C1P functions in colitis, we examined the severity of dextran sodium sulfate (DSS)-induced colitis in wild-type (WT) and CerK deletion (CerK(-/-)) mice. Lethal responses were observed in C57BL/6 mice treated with DSS in dose- and time-dependent manners. The depletion of CerK enhanced DSS-induced lethal responses without affecting the onset of these responses. In colons from mice treated with 2.5% DSS for 10 d, epithelial damage was significantly enhanced by the depletion of CerK by day 5, whereas decreases in occluding and E-cadherin levels were similar in both mice. On day 5, the DSS treatment increased spleen weights and colonic levels of cyclooxygenase-2, but not cytosolic phospholipase A2α, and induced a contractile dysfunction in the colons of both mice. The DSS-induced increase in the damage activity index score between days 5 and 10 was slightly enhanced and the decrease in this score from day 10 was slower in CerK(-/-) mice than in WT mice. On day 7 after the DSS treatment, spleen weights slightly decreased and increased in WT and CerK(-/-) mice, respectively. These results indicate that the depletion of CerK enhances the pathology of colitis and lethal responses in DSS-treated mice.

Yoga stretching for improving salivary immune function and mental stress in middle-aged and older adults.

Protection against age-related immune suppression is important in elderly individuals. This study determined the effect of yoga on mucosal immune function and mental stress. Saliva samples were collected from 23 adult women (age: 60.4 ± 10.4 years) before and after 90 minutes of yoga stretching or rest to measure secretory immunoglobulin A (SIgA), cortisol, and testosterone. The SIgA concentration and secretion rate were significantly higher after yoga than before (p < .05). The cortisol concentration and secretion rate were lower and testosterone secretion rate higher after yoga (p < .05). Yoga stretching can reduce stress and enhance mucosal immune function in elderly women.

Significant Heterogeneity and Slow Dynamics of the Unfolded Ubiquitin Detected by the Line Confocal Method of Single-Molecule Fluorescence Spectroscopy.

The conformation and dynamics of the unfolded state of ubiquitin doubly labeled regiospecifically with Alexa488 and Alexa647 were investigated using single-molecule fluorescence spectroscopy. The line confocal fluorescence detection system combined with the rapid sample flow enabled the characterization of unfolded proteins at the improved structural and temporal resolutions compared to the conventional single-molecule methods. In the initial stage of the current investigation, however, the single-molecule Förster resonance energy transfer (sm-FRET) data of the labeled ubiquitin were flawed by artifacts caused by the adsorption of samples to the surfaces of the fused-silica flow chip and the sample delivery system. The covalent coating of 2-methacryloyloxyethyl phosphorylcholine polymer to the flow chip surface was found to suppress the artifacts. The sm-FRET measurements based on the coated flow chip demonstrated that the histogram of the sm-FRET efficiencies of ubiquitin at the native condition were narrowly distributed, which is comparable to the probability density function (PDF) expected from the shot noise, demonstrating the structural homogeneity of the native state. In contrast, the histogram of the sm-FRET efficiencies of the unfolded ubiquitin obtained at a time resolution of 100 µs was distributed significantly more broadly than the PDF expected from the shot noise, demonstrating the heterogeneity of the unfolded state conformation. The variety of the sm-FRET efficiencies of the unfolded state remained even after evaluating the moving average of traces with a window size of 1 ms, suggesting that conformational averaging of the heterogeneous conformations mostly occurs in the time domain slower than 1 ms. Local structural heterogeneity around the labeled fluorophores was inferred as the cause of the structural heterogeneity. The heterogeneity and slow dynamics revealed by the line confocal tracking of sm-FRET might be common properties of the unfolded proteins.

R76 in transmembrane domain 3 of the aspartate:alanine transporter AspT is involved in substrate transport.

The L-aspartate:L-alanine antiporter of Tetragenococcus halophilus (AspT) possesses an arginine residue (R76) within the GxxxG motif in the central part of transmembrane domain 3 (TM3)-a residue that has been estimated to transport function. In this study, we carried out amino acid substitutions of R76 and used proteoliposome reconstitution for analyzing the transport function of each substitution. Both l-aspartate and l-alanine transport assays showed that R76K has higher activity than the AspT-WT (R76), whereas R76D and R76E have lower activity than the AspT-WT. These results suggest that R76 is involved in AspT substrate transport.

Characterization of Motor Neuron Prostaglandin E2 EP3 Receptor Isoform in a Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with adult onset, characterized by progressive loss of motor neurons. Prostaglandin E2 (PGE2), a lipid mediator, exerts its biological functions by binding to four subtypes of E-prostanoid (EP1-4). Among them, EP3 has been shown to have multiple isoforms, EP3α, EP3ß, and EP3γ, produced by alternative splicing. Since PGE2 has been shown to have important pathophysiological roles in ALS, experiments were performed to identify EP3 receptor isoform(s) in spinal motor neurons of wild-type (WT) and ALS model (G93A) mice. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of adult mice demonstrated expression of EP3α and EP3γ mRNAs in the lumbar spinal cord, whereas EP3ß mRNA was barely detectable. Laser capture microdissection was used to dissect out motor neurons from frozen samples of lumbar spinal cord in these mice for analysis by real-time PCR. We found that expression of EP3γ mRNA was predominant in these neurons, whereas EP3α and EP3ß mRNAs were undetectable. At the early symptomatic stage, the mRNA expression profiles of these splice isoforms in G93A motor neurons were comparable to those in neurons from WT mice. These results suggest that the PGE2-to-EP3 signaling pathway is mediated mainly by the EP3γ isoform in the motor neurons of mice, and that modulation of the EP3γ isoform in motor neurons may be a promising new therapeutic approach for ALS.

[Effectiveness of Sacral Intervertebral Epidural Block for Umbilical Hernia Repair in Children].

BACKGROUND: Effectiveness of sacral intervertebral epidural block (S 2-3 block) for umbilical hernia repair has not been clarified. METHOD: We investigate 24 children, undergoing umbilical hernia repair; mean age of 3 years (age range: 20-65 months). Under general anesthesia, epidural block was performed at S 2-3 interspace with 1 ml x kg(-1) ropivacaine (0.2%) at injecting rate of 1 ml x sec(-1) followed by 0.25 ml x kg(-1) normal saline. RESULTS: In all cases, neither systolic blood pressure nor heart rate increased > 15% from those just before the block. Postoperative analgesics were given in 6 patients (25%) rectally. Mean time between the block and the administration of analgesic was 10.5 hours. CONCLUSIONS: S 2-3 block can be effective for postoperative pain in umbilical hernia repair.

A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins.

Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. A transporter protein synthesized with the cell-free system could be functionally reconstituted into a lipid bilayer. In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins.

[The use of dexmedetomidine and Airwayscope in airway management of a child with Cornelia de Lange syndrome].

We report anesthetic management of a 22-month-old child with Cornelia de Lange syndrome scheduled for palatoplasty because of cleft palate. Micrognathia and short neck of the patient suggested difficult airway management. For anesthetic induction, 1 microg x kg(-1) dexmedetomidine was loaded intravenously, followed by infusion at a rate of 0.7 microg x kg(-1) x hr(-1) with incremental inhalation of sevoflurane. During the induction, spontaneous breathing was maintained. By laryngoscopy with Machintosh blade after intravenous propofol for the purpose of laryngeal reflex inhibition, only the tip of epiglottis was seen. Then, after another intravenous propofol, laryngoscopy was performed with Airwayscope, which enabled operators to see the glottis. Then, a RAE endotracheal tube (ID 4.5 mm) was inserted. During the Airwayscope operation, pharyngeal reflex, laryngeal reflex and saliva increase were inhibited resulting in good view of the larynx and the lowest Spo2 was 94% temporarily. After intubation, anesthesia was maintained with sevoflurane, remifentanil and fentanyl. Dexmedetomidine infusion was also useful to maintain adequate spontaneous breathing and to achieve awaking before extubation.

Effects of High-Intensity Endurance Exercise on Epidermal Barriers against Microbial Invasion.

For athletes, preventing infectious disease on skin is important. Examination measurement of epidermal barriers could provide valuable information on the risk of skin infections. The aim of this study was to determine the effects of high-intensity endurance exercise on epidermal barriers. Six healthy adult males (age; 22.3 ± 1.6 years) performed bicycle exercise at 75%HRmax for 60 min from 18:30 to 19:30. Skin surface samples were measured 18:30 (pre), 19:30 (post), 20:30 (60 min), and 21:30 (120 min). Secretory immunoglobulin A (SIgA) and human ß-defensin 2 (HBD-2) concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). SIgA concentration at pre was significantly higher than at post, 60 min and 120 min (p < 0.05). HBD-2 concentration at post and 120 min was significantly higher than at pre (p < 0. 05). Moisture content of the stratum corneum was significantly higher at post than at pre, 60 min, and 120 min (p < 0.05). On the chest, moisture content of the stratum corneum was significantly lower at 120 min than at pre (p < 0.05). The number of staphylococci was significantly higher at post than at pre (p < 0.05), and tended to be higher at 60 min than at pre on the chest (p = 0. 08). High-intensity endurance exercise might depress the immune barrier and physical barrier and enhance the risk of skin infection. On the other hand, the biochemical barrier increases after exercise, and our findings suggest that this barrier might supplement the compromised function of other skin barriers. Key pointsThe immune barrier and physical barrier might be depressed and the risk of skin infection might be enhanced by high-intensity endurance exercise.The biochemical barrier increases after high-intensity endurance exercise and might supplement the compromised function of other skin barriers.We recommend that athletes maintain their skin surface in good condition, for example, by showering immediately after sports activities and using moisturizers.

[Assessment of intraoperative hemodynamics, infusion volume, urinary output and dose of circulatory drugs in general anesthesia with transversus abdominis plane block for cholecystectomy].

We retrospectively reviewed intraoperative hemodynamics, infusion volume, urinary output and dose of circulatory drugs in patients undergoing cholecystectomy in 3 types of anesthesia group: General anesthesia (GA group), general anesthesia with epidural anesthesia (EPI group) and general anesthesia with transversus abdominis plane (TAP) block (TAPB group). TAP block was performed using ultrasound-guided subcostal method and 20-30 ml of ropivacaine (0.2-0.3%) was injected to TAP bilaterally. Though, the blood pressure in TAPB group was lower than that in GA group, the degree of low blood pressure was smaller than that in EPI group. Less changes in intraoperative blood pressure, infusion volume and dose of phenylephrine in TAPB group compared to those in EPI group can be the advantage of TAP block alternative to epidural anesthesia.

Effects of yoga exercise on salivary beta-defensin 2.

PURPOSE: Yoga stretching can be done comfortably and easily by beginners and older adults to compensate for lack of exercise or poor health maintenance. The aim of this study was to determine the effect of yoga stretching on mucosal immune functions, primarily human ß-defensin 2 (HBD-2) in saliva. METHODS: Fifteen healthy adults (age, 60.4 ± 8.0 years) participated in the study. Participants rested for 90 min on the first day and performed yoga for 90 min on the second day. Measurements were carried out before and after rest or yoga. Saliva samples were collected by chewing a sterile cotton at a frequency of 60 cycles per min. Salivary HBD-2 concentration was measured using an enzyme-linked immunosorbent assay. RESULTS: HBD-2 concentration after yoga stretching (165.4 ± 127.1 pg/mL) was significantly higher than that before yoga stretching (84.1 ± 63.4 pg/mL; p < 0.01). HBD-2 expression rate after yoga stretching (232.8 ± 192.9 pg/min) was significantly higher than that before yoga stretching (110.7 ± 96.8 pg/min; p < 0.01). HBD-2 concentration (p < 0.05) and HBD-2 expression rate (p < 0.01) at post on the second day (yoga) was significantly higher than that on the first day (rest). POMS score of anger-hostility was lower after yoga than before. CONCLUSIONS: Yoga stretching for 90 min can increase salivary HBD-2 expression in older adults. Therefore, yoga stretching might be useful for older adults and athletes to maintain their health.

[Anesthetic management of an emergency open-heart surgery for entrapment of a circular mapping catheter by chordae tendineae with mitral valve damage undergoing atrial fibrillation ablation].

The entrapment of a circular mapping catheter by chordae tendineae during catheter ablation is a very rare but serious complication requiring, in some cases, surgical treatment. We report a case that required open heart surgery for catheter removal and mitral valve repair. A 79-year-old man underwent catheter ablation for paroxysmal atrial fibrillation in other hospital. During the operation, he moved accidentally, despite circular mapping catheter was in the left atrium. The circular mapping catheter was uncontrolable due to resistance interfering with catheter removal, and the patient was brought to our hospital for open heart surgery to remove catheter. General anesthesia was induced and maintained with midazolam, fentanyl. Transesophageal echocardiography was performed to monitor catheter position and mitral valve condition. Transesophageal echocardiography revealed that circular catheter tip was located adjacent to the posterior mitral leaflet and the presence of moderate mitral valve regurgitation. Circular catheter tip was entraped by chordae tendineae and caused posterior mitral leaflet damage. Intracardiac foreign body removal and posterior mitral leaflet repair were completed uneventfully under cardiopulmonary bypass. The postoperative course was uneventful. It is expected that catheter ablation for atrial fibrillation will increase in number. This rare complication of catheter ablation may become a threat to cardiologist, cardiac surgeon and anesthesiologist.

Altered secretory immunoglobulin A on skin surface after intensive exercise.

The aim of this study was to determine the effects of high-intensity endurance exercise on skin immunity by estimating secretory immunoglobulin A (SIgA) and staphylococci on skin surface. Seven healthy adult men (age, 22.3 ± 2.0 years) performed bicycle exercise at 75% HRmax for 60 minutes from 2030 to 2130 hours. Secretory immunoglobulin A was obtained from 1 ml extraction liquids stirred with the microtube homogenizer in the open end of a polypropylene tube for 60 seconds. Secretory immunoglobulin A concentrations were measured using enzyme-linked immunosorbent assay. Staphylococci were harvested by pressed agar-based media against skin surface. Skin surface samples were collected from the chest and the forearm on the first day at 2030 hours (before rest, A1), 2130 hours (after rest, A2), and 2230 hours (after showering, A3); the next morning at 0700 hours (A4); on the second day at 2030 hours (before exercise, B1), 2130 hours (after exercise, B2), and 2230 hours (after showering, B3); and the next morning at 0700 hours (B4). Secretory immunoglobulin A concentration on the forearm was significantly lower at B2 (p < 0.05) and B3 (p < 0.05) than that at B1 and that on the chest at B1 tended to be higher compared with B2 (p = 0.084) and B3 (p = 0.075). The number of staphylococci was significantly higher at B2 than that at B1 (p < 0.01) and B4 (p < 0.01) on the forearm. We conclude that high-intensity endurance exercise might depress immune function and enhance infectious risk on skin surface. Coaches should encourage their athletes to take a shower and change into clean clothes immediately after sports activities and athletes should maintain a clean skin surface to decrease the infectious risk on skin surface.

[Anesthetic hazards in an undiagnosed case of retroperitoneal paraganglioma].

We report a patient with undiagnosed retroperitoneal paraganglioma who developed an intraoperative hypertensive crisis. A 64-year-old female was scheduled for right partial mastectomy and removal of an abdominal mass, preoperatively diagnosed as a small intestine GIST. Surgery was performed under general anesthesia combined with epidural anesthesia with close monitoring. Immediately after the surgical manipulation of the abdominal mass, her systolic blood pressure rose to over 200 mmHg. This hypertensive crisis was managed with nicardipine and alprostadil combined with increased infusion rate of remifentanil and propofol. Thereafter, the patient was hemodynamically stable and the postoperative course was uneventful. Pathological examination identified the tumor as extraadrenal paraganglioma. The possibility of paraganglioma should be considered even in asymptomatic abdominal mass, and adequate precautions are required in such cases.

[Low doses of ketamine have no effect on bispectral index during stable propofol-remifentanil anesthesia].

BACKGROUND: Ketamine is associated with an increase in the bispectral index (BIS) values that can lead to an overdose of hypnotic agents. We investigated the effect of ketamine on BIS values during general anesthesia with a target-controlled infusion (TCI) of propofol and infusion of remifentanil. METHODS: Forty-five ASA I or II patients undergoing gynecological surgery were included in this study. After 5 min of steady-state anesthesia (BIS at 35-45) without surgical stimulation, patients received either a bolus administration of ketamine 0.2 mg x kg(-1) (LK group) or ketamine 0.5 mg x kg(-1) (HK group). Patients in the control group received no intervention. BIS values were recorded every minute until 15 min after ketamine administration. RESULTS: After ketamine administration, BIS value in HK group increased significantly compared with that at baseline. There were no significant changes for BIS values in LK group and control group over time. BIS values in HK group were significantly higher than those in the LK group and control group after ketamine injection. BIS values were not statistically different between LK group and control group. CONCLUSIONS: Under stable propofol and remifentanil anesthesia, a small dose of ketamine did not increase the BIS value over the next 15 min.