Comparison of Gastric Emptying Time after the Ingestion of Whisky with Isocalorically Adjusted Glucose Solution.

Previous studies have shown that the liquid gastric emptying mainly depended on energy content, regardless of compositional differences. But the gastric emptying of alcoholic beverages remains unclear. Therefore, we performed the present study to compare gastric emptying times between whisky mixed with water and glucose solution with uniform energy contents and volumes. As a crossover study, 10 healthy male volunteers ingested one of 3 test solutions with a uniform volume of 150 ml, i.e., whisky with water-containing whisky 30 ml (67 kcal), sugar water containing glucose 16.8 g (67 kcal), and water (0 kcal), and the gastric emptying time of each beverage was then assessed by ultrasound measurements of the gastric antral cross-sectional area. The gastric emptying pattern of whisky with water was faster than that of isocaloric sugar water, but slower than that of water. Each antral cross-sectional area 20, 30, and 40 min after the ingestion of sugar water was significantly larger than that of whisky with water. Antral cross-sectional areas 10 and 20 min after the ingestion of water were significantly smaller than those of whisky with water. In conclusion, the gastric emptying time of whisky would be faster than that of isocaloric glucose solution and slower than that of water. Unlike the other beverages, the gastric emptying time of alcohol drinks does not purely depend on the energy content because alcohol itself has no calorie before absorption. This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000034443).

Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT-5): 52-week results from a randomized, open-label, phase III clinical trial.

AIMS: To investigate the safety and tolerability of 5 and 10 mg dapagliflozin added to insulin therapy over 52 weeks in Japanese patients with inadequately controlled type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This randomized, open-label, parallel-group, multicentre phase III clinical trial was conducted from October 26, 2015 to June 15, 2017. The primary endpoint was the occurrence of adverse events such as hypoglycaemia and diabetic ketoacidosis. Secondary endpoints included changes in glycaemic parameters, total daily insulin dosage and body weight over time. The efficacy of dapagliflozin in patients stratified by body mass index (BMI) <25.0 and ≥25.0 kg/m2 was evaluated in a subgroup analysis. RESULTS: In total, 151 patients received 5 mg (n = 76) or 10 mg (n = 75) dapagliflozin once daily for 52 weeks. Adverse events were observed in 88.2% and 73.3% of patients in the 5 and 10 mg dapagliflozin groups, respectively. Severe hypoglycaemia was reported in 2.6% (n = 2) and 6.7% (n = 5) of patients, and diabetic ketoacidosis in 2.6% (n = 2) and 1.3% (n = 1) of patients in the 5 and 10 mg dapagliflozin groups, respectively. The adjusted mean (95% confidence interval) changes in glycated haemoglobin at week 52 were -0.33% (-0.50, -0.15) and -0.36% (-0.53, -0.18) in the 5 and 10 mg dapagliflozin groups, respectively. There were no differences in efficacy parameters when stratified by BMI. CONCLUSIONS: This study demonstrated the long-term safety and tolerability of dapagliflozin added to insulin therapy in Japanese patients with inadequately controlled T1DM.

What is the manner of gastric emptying after ingestion of liquids with differences in the volume under uniform glucose-based energy content?

BACKGROUND & AIMS: We previously demonstrated that the gastric emptying rate of liquids chiefly depended on the total amount of calories (energy content) in a uniform volume. The aim of the present study was to examine the effects of different volumes of liquids with a uniform energy content on gastric emptying. METHODS: Three types of test solutions were prepared with a uniform amount of calories (200 kcal provided by glucose) and step-wise increments in volume (200 ml, 400 ml, and 600 ml). The gastric volume of each solution was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by 8 healthy volunteers. RESULTS: The mean gastric volume decreased exponentially to nearly 0 ml 70 min after ingestion in the 200 ml group, 90 min in the 400 ml group, and 100 min in the 600 ml group. Each gastric emptying curve converged with identical slopes on the graph when the points at which the gastric emptying curves of the 200 ml and 400 ml groups reached the zero point on the Y-axis (mean gastric volume) were shifted toward 110 min on the X-axis (time scale). CONCLUSIONS: The volume of liquid ingested with a uniform glucose-based energy content is a critical determinant of liquid gastric emptying. The gastric emptying time may be predicted following the ingestion of an isocaloric liquid with any volume over a predefined range once a gastric emptying curve following the ingestion of a liquid has been plotted on a graph. TRIAL REGISTRY NUMBER: UMIN000014930.

A case of unexpectedly difficult intubation caused by a large asymptomatic choanal polyp.

We report a case of unexpectedly difficult intubation in a patient with a huge but asymptomatic choanal polyp. A 77-year-old man with invasive bladder cancer was scheduled for total cystectomy under general anesthesia. However, tracheal intubation with a Macintosh laryngoscope proved impossible due to obstruction by a large oropharyngeal tumor. Using a video laryngoscope, intubation was successfully achieved. Choanal polyps are not uncommon, but large choanal polyps reaching the oropharynx appear relatively rare. Anesthesia and airway management for large oropharyngeal tumor has not been sufficiently discussed.

Effect of electroconvulsive stimulation on messenger RNA expression in the prefrontal cortex in a rat pain model.

Previous reports have shown that electroconvulsive therapy (ECT) is efficacious in the treatment of neuropathic pain; however, its mechanism of action remains unclear. The present study aimed to understand these mechanisms by investigating the alterations in the expression of neuropeptide Y (NPY) and interleukin-1ß (IL-1ß) in the prefrontal cortex. A rat model of neuropathic pain produced by chronic constrictive injury of the sciatic nerve was used, and mechanical and thermal hyperalgesia were evaluated starting 2 days after the injury. Using a pulse generator, ECT was administered to the rodents for 6 days from days 7-12 after the injury. Thermal and mechanical stimulation were administered to assess pain thresholds. Quantitative polymerase chain reaction, used to measure gene expression levels in the prefrontal cortex, showed that NPY and IL-1ß gene expression levels in the prefrontal cortex increased following the injury. The present results indicate that these gene expression level variations may be associated with the mechanisms underlying the effect of ECT in treating neuropathic pain.

[A Case of Differential Lung Ventilation Using a Double-lumen Endotracheal Tube for Tracheostomy Prior to Lung Surgery in a Patient with Congenital Laryngeal Web].

A 71-year-old male with left lung cancer was scheduled for endoscopic lung surgery under general anesthesia. During a preoperative examination, the patient had hoarseness and was diagnosed with congenital laryngeal web. Differential lung ventilation was needed throughout the surgery, but the opening orifice of the laryngeal web was estimated to be too small for intubation. Therefore, we performed a tracheostomy one week before surgery, for which a double-lumen endotracheal tube was used during differential lung ventilation. Under general anesthesia, the lung surgery was successfully completed, and the patient did not have any postoperative complications.

Gastric tube insertion under direct vision using the King Vision™ video laryngoscope: a randomized, prospective, clinical trial.

BACKGROUND: The frequency of malpositioning of gastric tubes in the trachea has been reported to be 0.3-15%, which may cause severe complications, such as pneumonia, if not detected promptly. If a gastric tube can be guided into the esophagus under direct vision with a video laryngoscope, misplacement of the gastric tube into the trachea can be avoided. We compared gastric tube insertion under direct vision using a video laryngoscope with the conventional method of blind insertion. METHODS: We enrolled 60 patients who required a transnasal gastric tube to facilitate elective abdominal surgery under general anesthesia. The participants were recruited consecutively into one of two groups, a group of 30 patients in whom a gastric tube was inserted using a King Vision™ video laryngoscope (KV group), and a group of 30 patients who underwent conventional blind insertion of the gastric tube (Blind group). The success rate, the time taken to insert the gastric tube, and the incidence of complications were compared. RESULTS: In the KV group, the time required for gastric tube placement was 52.5 ± 17.1 seconds, with a success rate of 100%. Slight oral hemorrhage occurred in two participants and slight epistaxis in one participant. In the Blind group, the time required for gastric tube placement was 65.9 ± 39.9 seconds, with a success rate of 90% (27 out of 30 patients). Slight oral hemorrhage occurred in two participants, slight epistaxis occurred in two participants, and tracheal malposition occurred in one participant but was detected promptly and corrected using the video laryngoscope. There were no significant differences in the time required for placing the gastric tube, the success rate, or the incidence of complications between the groups. CONCLUSIONS: Gastric tube insertion using a King Vision video laryngoscope was straightforward, and was particularly useful for detecting and correcting tracheal malpositioning. TRIAL REGISTRY NUMBER: UMIN000011014.

Gastric emptying of a carbohydrate-electrolyte solution in healthy volunteers depends on osmotically active particles.

BACKGROUND: Preoperative ingestion of only clear fluids until 2 hours before induction of anesthesia is a common preoperative fasting regimen. Gastric emptying times, however, vary among clear fluids. We therefore investigated the gastric emptying of 2 clear glucose-electrolyte drinks. METHOD: A 2-way crossover study was performed in 10 healthy volunteers. After fasting, the volunteers drank 500 mL of either OS-1(®), an oral rehydration solution, or Pocari Sweat(®), a popular sports drink, over 3 minutes in a standing position. Magnetic resonance imaging was performed before, immediately after, and 30 minutes after the drinking of each test fluid. The difference in gastric emptying between OS-1(®) and Pocari Sweat(®) was evaluated by comparing gastric fluid volume, flow rate, and residual ratio. We also compared the flow rates of sodium, potassium, carbohydrates, and osmotically active particles in the 2 test fluids. RESULTS: Gastric fluid volume 30 minutes after drinking was significantly smaller for OS-1(®) (76.0 ± 57.0 mL) than for Pocari Sweat(®) (158.1 ± 73.5 mL, p<0.01), although the volumes did not differ before or immediately after drinking. The flow rate was significantly faster for OS-1(®) (10.66 ± 3.34 mL) than for Pocari Sweat(®) (8.68 ± 3.02 mL/min, p<0.05), and the residual ratio was significantly smaller for OS-1(®) (21 ± 14% than for Pocari Sweat(®) (41 ± 19%, p<0.01). The flow rates of sodium, potassium, and glucose differed significantly between OS-1(®) and Pocari Sweat(®), whereas the flow rate of osmotically active particles did not. CONCLUSIONS: Gastric emptying is significantly faster for OS-1(®) than for Pocari Sweat(®).

Continuous infusion of dexmedetomidine improves renal ischemia-reperfusion injury in rat kidney.

BACKGROUND: Dexmedetomidine has shown beneficial effects in several inflammatory models, including ischemia-reperfusion injury (IRI). This study investigated whether the continuous infusion of dexmedetomidine could improve renal IRI in rats. METHODS: Rats were subjected to either a sham operation and given pentobarbital (10 mg/kg/h; n=6) or were subjected to 45 minutes of renal ischemia and anesthetized with pentobarbital (10 mg/kg/h; n=6), dexmedetomidine (10 or 20 µg/kg/h; both n=6), or both pentobarbital (10 mg/kg/h) and dexmedetomidine (1.0 µg/kg/h; n=6) for 6 hours of reperfusion. Blood urea nitrogen and serum creatinine were measured 6 hours after reperfusion. Gene expression mediated by inflammatory systems in the kidney was measured with the real-time reverse-transcriptase polymerase chain reaction. RESULTS: Treatment with 10 or 20 µg/kg/h of dexmedetomidine reduced renal dysfunction. The increases in the messenger RNA expression of interleukin-6, intercellular adhesion molecule 1, and inducible nitric oxide synthase caused by renal IRI were suppressed. Under In rats under pentobarbital anesthesia, 1.0 µg/kg/h of dexmedetomidine also improved renal dysfunction after renal IRI. CONCLUSION: The present study demonstrates that continuous infusion of dexmedetomidine improves renal IRI. Moreover, with pentobarbital anesthesia, a dose of dexmedetomidine lower than the sedative dose also improves renal IRI.

The miRNA and mRNA changes in rat hippocampi after chronic constriction injury.

OBJECTIVE: We elaborated the rat hippocampi in order to assess for central nervous system changes following a peripheral neuropathic injury. DESIGN, SETTING, SUBJECTS: We examined the gene changes in the hippocampi of chronic constriction injury (CCI) rats with TaqMan® low-density array analysis (TLDA) and quantitative real-time polymerase chain reaction (qRT-PCR) of miR-125b, -132, and messenger RNAs (mRNAs) of neuropeptide Y, brain-derived neural factor, N-methyl-D-aspartate glutamate 2A receptor, gamma-aminobutyric acid A a1 receptor, gamma-aminobutyric acid A b1 receptor, gamma-aminobutyric acid B b2 receptor, serotonin 1A receptor, serotonin 2A receptor, serotonin 2C receptor, and serotonin 3A receptor on days 0, 7, and 15 after surgery. INTERVENTIONS: None. OUTCOME MEASURES: Two behavioral tests (thermal and mechanical stimulation tests) were performed three times at 5-minute intervals to assess pain thresholds. MicroRNA (miRNA) changes were examined by TLDA. mRNA changes were examined by qRT-PCR. Statistical significance was determined by Tukey-Kramer's method and paired t-test. RESULTS: All rats showed mechanical and thermal hypersensitivity on the ipsilateral side. Out of 373 miRNAs analyzed, 237 were expressed, and 51 changed their expressions after CCI. By TLDA, cluster analysis found obvious miRNA changes on day 7 that tended to recover by day 15. For miR-125b, the relative expression decreased to 0.70 ± 0.30 at day 7 and recovered to 1.65 ± 0.19 at day 15. The miR-132 relative expressions were 0.69 ± 0.30 and 0.70 ± 0.15, respectively. The mRNA changes followed the miRNA changes. CONCLUSIONS: Our results showed that the peripheral nerve injury altered rat hippocampal miRNA.

microRNA changes in the dorsal horn of the spinal cord of rats with chronic constriction injury: A TaqMan® Low Density Array study.

Elucidation of the mechanisms underlying neuropathic pain is expected to aid in the discovery and selection of effective therapeutic methods. Currently, microRNA (miRNA) is thought to play an important role in the development and maintenance of the nervous system. We, therefore, hypothesized that miRNAs are involved in neuropathic pain, and investigated this possibility by analyzing miRNA expression in the dorsal horn of the spinal cord in a chronic constriction injury (CCI) rat model using the TaqMan® Low Density Array (TLDA). Neuropathic pain model rats were produced by CCI induced by ligation of the sciatic nerve. The miRNA expression in the dorsal horn of the spinal cord was analyzed in Day 0 rats, with no sciatic nerve ligation or sham operation, Day 7 rats, examined 7 days after sciatic nerve ligation or sham operation, and Day 14 rats, examined 14 days after sciatic nerve ligation or sham operation using TLDA. In this study, 111 miRNAs were significantly regulated in CCI rats in both the Day 7 and Day 14 groups compared with sham rats in both groups. Of these 111, there were 75 miRNAs (67.6%) that had been analyzed in previous reports and 36 miRNAs (32.4%) related to the development of tumors of the nervous system and neurodegenerative diseases. Certain miRNAs were reported to be related to neuropathic pain; miR-500, -221 and -21. The expression levels of a large number of miRNAs in the dorsal horn of the spinal cord in CCI rats changed. These results provide a step toward elucidation of the mechanisms underlying neuropathic pain.

Proteomic analysis of rat brains in a model of neuropathic pain following exposure to electroconvulsive stimulation.

Some reports have shown that electroconvulsive shock therapy is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. This study analyzes changes in protein expression in the brainstems of neuropathic pain model rats with or without electroconvulsive stimulation (ECS). A neuropathic pain model rat is produced by chronic constrictive injury (CCI) of the sciatic nerve. An ECS was administered to rodents once daily for 6 days after the CCI operation. After ECS, the latency to withdrawal from thermal stimulation was significantly increased. The expression of several proteins was changed after CCI. Ten proteins that increased after CCI then had decreased expression levels (close to control) after ECS, and 8 proteins that decreased after CCI then had increased expression levels (close to control) after ECS. In conclusion, ECS improved thermal hypersensitivity in a rat CCI model. Proteomic analysis showed that altered expression levels of proteins in the brainstem of CCI model rats returned to close to control levels after ECS, including many proteins associated with pain. This trend suggests an association of ECS with improved hypersensitivity, and these results may help elucidate the mechanism of this effect.

Changes in neuropeptide Y gene expression in the spinal cord of chronic constrictive injury model rats after electroconvulsive stimulation.

Some reports have shown that electroconvulsive shock therapy (ECT) is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. We have previously shown that electroconvulsive shock (ECS) improved thermal hypersensitivity in chronic constrictive injury (CCI) model rats and simultaneously elevated the neuropeptide Y (NPY) expression in the brain of these rats. In this study, we examined changes in the expression of NPY in the spinal cord of a CCI model. The rat model of CCI was established by ligating the left sciatic nerve. ECS was administered to the rats once daily for six days on days 7-12 after the operation using an electrical stimulator. RT-PCR was used to measure NPY mRNA expression in both the right and left L5 dorsal spinal cords on the 14th day after the operation. NPY gene expression was decreased in the dorsal spinal cords after ECS; however, no differences in NPY expression were observed between the right and left side of dorsal spinal cords, suggesting that the effect of changes in NPY expression after ECS on the improvement of neuropathic pain is not directly related to the spinal cord, but mainly to the upper central nerves.

A case of cancer pain management by long-term intrathecal PCA.

Titration of oral or intravenous medication is the preferred method of pain management for most patients with cancer pain. However, some patients experience insufficient pain relief or considerable adverse effects from systemic opioids. For these reasons, the control of severe cancer pain continues to present a variety of challenges to clinicians. We report our experience of successfully managing cancer pain in a patient by means of long-term intrathecal administration of morphine, bupivacaine, and racemic ketamine via a patient-controlled delivery system. This therapy reduced the patient's nausea, vomiting, and somnolence, led to early hospital discharge, and increased her level of daily activity. There were no signs of motor paralysis, psychomimetic alteration, neurological dysfunction, or infection related to the intrathecal route during treatment. Intrathecal therapy is an effective treatment in terminally ill patients.

An amino acid substitution in PBP-3 in Haemophilus influenzae associate with the invasion to bronchial epithelial cells.

Haemophilus influenzae is a common pathogen of respiratory infections. We examined whether beta-lactamase-negative ampicillin-resistant (BLNAR) strains that are known to have ampicillin resistance due to a substitution of amino acid of penicillin binding protein (PBP)-3, differ from beta-lactamase-negative ampicillin-susceptible strains with regard to invasion of bronchial epithelium. After 3h incubation of each of 34 beta-lactamase-negative ampicillin-susceptible and 57 BLNAR strains in the presence of BEAS-2B cells, a human bronchial epithelium cell line, extracellular bacteria were killed using gentamicin and intracellular bacteria numbered. All nine strains in which the efficiency of invasion was 1% or higher were BLNAR strains. The rate of invasion was significantly greater in strains with PBP-3 amino acid substitution (Met377 to Ile, Ser385 to Thr, Leu389 to Phe, and Asn526 to Lys) (n=34) than in those with no amino acid substitution. Electron microscopy showed that high invasive BLNAR strains were observed in cytoplasm of BEAS-2B cell layer. The injured cells were 9.44+/-1.76% among attaching cells examined by trypan blue staining after 6h. These data may suggest that the amino acid substitution of the PBP in BLNAR strains may at least partly play roles in macropinocytosis, leading to the invasion and injury to epithelial cells.

Electroconvulsive stimulation (ECS) increases the expression of neuropeptide Y (NPY) in rat brains in a model of neuropathic pain: a quantitative real-time polymerase chain reaction (RT-PCR) study.

OBJECTIVES: Electroconvulsive shock therapy (ECT) has been widely used as an effective and established treatment for refractory depression and schizophrenia. Some reports have shown that ECT is also effective for treating refractory neuropathic pain. DESIGN: In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from day 2 after surgery. An electroconvulsive shock (ECS) was administered to rodents once daily for 6 days on days 7-12 after CCI operation using a pulse generator. Thermal and mechanical stimulation tests were performed to assess pain thresholds. Real-time polymerase chain reaction was used to measure the gene expression levels for 5HT(1A)R, 5HT(2A)R, neuropeptide Y (NPY), and GABAA(alpha1)R in the brain. RESULTS: After ECS, the latency to withdrawal from thermal stimulation was significantly increased; however, pain withdrawal thresholds in response to mechanical stimulation were not significantly changed. Expression ratios of NPY were significantly greater after ECS. CONCLUSION: Symptoms of neuropathic pain improved and expression of NPY in the brain was increased in CCI model rats after ECS, suggesting that changes in the expression of NPY in the brain may be related to the mechanism of action of ECT in treating neuropathic pain.

High incidence of meropenem resistance among alpha-hemolytic streptococci in children with cancer.

BACKGROUND: Infections caused by antibiotics-resistant Gram-positive bacteria have been reported from many pediatric hematology-oncology centers. METHODS: The susceptibility profiles to meropenem, piperacillin, and vancomycin among oral flora isolates of alpha-hemolytic streptococci (AHS) obtained from six children with cancer who received several empirical therapies (ET) against febrile neutropenia, were investigated. RESULTS: Meropenem minimum inhibitory concentration (MIC) of AHS isolated from ET patients was 2.167 +/- 0.258 microg/mL (mean +/- SD), which was significantly higher than the MIC of AHS isolated from control groups. Intriguingly, AHS isolated approximately 6 months after hospital discharge indicated recovery of susceptibility to meropenem. CONCLUSIONS: AHS isolates from neutropenic children with cancer should be checked for antibiotic susceptibility, even against carbapenems.

Postoperative intensive care unit drug fever caused by dexmedetomidine.

Dexmedetomidine hydrochloride is a potent, highly selective alpha-2 adrenergic receptor agonist, broadly used as a sedative drug in intensive care units. We describe the case of a 59-yr-old patient who experienced drug fever caused by dexmedetomidine hydrochloride. The patient was transferred to the intensive care unit with an abdominal aortic aneurysm rupture. After initiation of sedation with dexmedetomidine hydrochloride, he developed pyrexia of more than 39 degrees C. This symptom improved rapidly 7 h after stopping dexmedetomidine hydrochloride. Other possible causes (such as infection) were sequentially eliminated.

[Nationwide susceptibility surveillance of ciprofloxacin and various parenteral antimicrobials against bacteria isolated from patients with severe infections--third ciproxan injection special survey (2005)].

We conducted 3 nationwide surveillance studies between 2001 and 2005 at 39 participating institutions throughout Japan according to the special survey plan to investigate susceptibility to ciprofloxacin (CPFX) and various parenteral antimicrobials using clinical isolates from patients with severe infection during the reexamination period of parenteral CPFX. Results of the first special survey (2001) were already reported in this journal. The current third special survey (2005) was conducted at 34 participating institutions throughout Japan to determine susceptibility to CPFX and 22 various parenteral antimicrobials with the use of the microdilution method with respect to 1696 strains isolated and identified from various clinical specimens between January and June 2005. The results of CPFX in this survey were compared with those in the first and second special surveys. The minimum inhibitory concentration of CPFX at which 90% of isolates were susceptible (MIC90) ranged from < or =0.063 to 2 microg/mL for methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella spp., Citrobacter freundii, Enterobacter spp., Proteus spp., Serratia marcescens, and Acinetobacter baumannii, revealing no marked change from results of the first and second surveys. However, the CPFX-susceptibility rate of Escherichia coli decreased in the second and third surveys compared to that in the first survey. For Morganella morganii and Pseudomonas aeruginosa, the MIC90 of CPFX tended to increase with time. The CPFX-susceptibility rates calculated from the pneumonia breakpoint were 85.2% for P. aeruginosa and 67.9% for Stenotrophomonas maltophilia. With the exception of these 2 species, major causative organisms of respiratory tract infection had susceptibility rates as high as 90% or more for CPFX, which were similar to results of the first and second special surveys. These susceptibility rates for CPFX were similar to the rates for cefozopran and imipenem. These values generally indicated favorable CPFX susceptibility testing results of major bacteria and the potent antimicrobial activity of CPFX particularly against Gram-negative bacteria. Further surveillance is required regarding the trend in susceptibility of E. coli, M. morganii, and P. aeruginosa, which tended to become less susceptible with time.

The effects of dexmedetomidine on human neutrophil apoptosis.

The purpose of the present study was to evaluate the effect of dexmedetomidine, used as a sedative in the intensive care unit, on human neutrophil apoptosis and superoxide production in vitro. Neutrophils from healthy volunteers were incubated in different concentrations of dexmedetomidine (1, 10 and 100 ng/mL). Apoptosis was assessed by Hoechst 33342 staining, caspase activities and loss of mitochondrial transmembrane potential (MTP). Superoxide production was determined by the WST-1 assay. After 24 h of incubation, dexmedetomidine accelerated neutrophil apoptosis in a dose-dependent manner and 100 microM yohimbine did not inhibit the apoptosis. Treatment with 100 ng/mL of dexmedetomidine significantly enhanced the activation of caspases-3/7, -8 and -9, and also markedly increased the number of neutrophils with decreased MTP. At 24 h, the suppression of superoxide production was dependent on dexmedetomidine concentrations. However, a clinically relevant concentration (1 ng/mL) of dexmedetomidine did not affect neutrophil apoptosis and superoxide production. These results suggest that high doses of dexmedetomidine induce apoptosis without alpha(2)-adrenoceptors stimulus and inhibit superoxide production after long-term incubation. The mechanisms of dexmedetomidine-induced apoptosis are associated with the caspase cascade and loss of MTP.