The effect of repeated isoflurane exposure on serine synthesis pathway during the developmental period in Caenorhabditis elegans.

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.

Predictive Value of Intraoperative Thromboelastometry for the Risk of Perioperative Excessive Blood Loss in Infants and Children Undergoing Congenital Cardiac Surgery: A Retrospective Analysis.

OBJECTIVE: Laboratory hemostatic variables and parameters of rotational thromboelastometry (ROTEM) were evaluated for their ability to predict perioperative excessive blood loss (PEBL) after congenital cardiac surgery. DESIGN: Retrospective and observational. SETTING: Single, large university hospital. PARTICIPANTS: The study comprised 119 children younger than 10 years old undergoing congenital cardiac surgery with cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: Intraoperative excessive blood loss was defined as estimated blood loss≥50% of estimated blood volume (EBV). Postoperative excessive blood loss was defined as measured postoperative chest tube and Jackson-Pratt drainage≥30% of EBV over 12 hours or≥50% of EBV over 24 hours in the intensive care unit. PEBL was defined as either intraoperative or postoperative excessive blood loss. External temogram (EXTEM) and fibrinogen temogram (FIBTEM) were analyzed before and after CPB with ROTEM and laboratory hemostatic variables. Multivariate logistic regression was performed. Incidence of PEBL was 19.3% (n = 23). Independent risk factors for PEBL were CPB time>120 minutes, post-CPB FIBTEM alpha-angle, clot firmness after 10 minutes<5 mm, post-CPB EXTEM alpha-angle, clot firmness after 10 minutes<30 mm, and post-CPB EXTEM maximal lysis>20%. Laboratory hemostatic variables were not significant in multivariate analysis. The risk prediction model was developed from the results of multivariate analysis. The area under the receiver operating characteristic curve was 0.94 (95% confidence interval: 0.90-0.99). CONCLUSIONS: Post-CPB ROTEM may be useful for predicting both intraoperative and postoperative excessive blood loss in congenital cardiac surgery. This study provided an accurate prediction model for PEBL and supported intraoperative transfusion guidance using post-CPB FIBTEM-A10 and EXTEM-A10.

Effect of a new heated and humidified breathing circuit with a fluid-warming device on intraoperative core temperature: a prospective randomized study.

BACKGROUND: The effect of the Mega Acer kit(@), a new heated and humidified breathing circuit (HHBC) containing a fluid-warming device, was investigated on intraoperative core temperature (T c). METHODS: A total of 102 patients undergoing elective craniotomies were randomly divided into three groups based on the breathing circuit used: a conventional breathing circuit (group C, n = 34), a Fisher & Paykel HHBC (group F, n = 34), and the Mega (group M, n = 34). From baseline to the end of the surgery, T c and infusion fluid temperature (T f) were recorded at 15-min intervals. If T c became lower than 35.5 °C, a forced-air warmer was used. RESULTS: Baseline temperatures were 36.7 ± 0.3, 36.6 ± 0.2, and 36.6 ± 0.2 °C in groups C, M, and F, respectively. T c at the end of surgery dropped from baseline values by 1.0 ± 0.4, 0.5 ± 0.5, and 0.8 ± 0.5 °C in groups C, M, and F, respectively. From 60 min of post-induction to the end of surgery, T c was higher in group M than group C (p < 0.05). From 105 min of post-induction to the end of surgery, T c was higher in group M than group F (p < 0.05). The number of patients receiving forced-air warmer and total forced-air warmer using time were significantly lower in group M than groups C and F (p < 0.05). T f was higher in group M than groups C and F throughout the study period (31.0 ± 1.0 vs. 23.5 ± 0.5 and 24.0 ± 0.4 °C; p < 0.01). CONCLUSIONS: The Mega significantly reduced the drop in intraoperative T c by delivering warm fluids, compared with the other breathing circuits tested. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01831843.

Hemodynamic effects of topical lidocaine on the laryngoscope blade and trachea during endotracheal intubation: a prospective, double-blind, randomized study.

PURPOSE: Minimizing hemodynamic changes during the peri-intubation period is a concern for anesthesiologists. We investigated the effect of lidocaine sprayed on the laryngoscope blade and trachea on hemodynamics during direct laryngoscopic intubation. METHODS: Seventy-two patients were randomly allocated to one of four groups: 10% lidocaine was sprayed either on the laryngoscope blade (group L), on the trachea (group V), or on the laryngoscope blade and the trachea (group LV). No lidocaine was used in group C. Anesthesia was induced in all patients with remifentanil (effect site concentration: 4.0 ng/ml) and propofol (effect site concentration 4.0 µg/ml) continuous infusion using a target control infusion (TCI) device. Mean arterial pressure (MAP) and heart rate (HR) were recorded during the peri-intubation period. RESULTS: Changes in MAP and HR over time were markedly different among the four groups (P < 0.05). MAP at 1 min post-intubation was significantly lower in groups L, V, and LV than in group C (86.1 ± 12.7, 85.3 ± 12.6, and 83.7 ± 13.1 vs. 106.3 ± 22.9 mmHg, P < 0.01). Maximum MAP values were lower in groups L and LV than in group C (P < 0.05). HRs at 1, 2, and 3 min post-intubation were lower in group LV than in group C (70.4 ± 9.0 vs. 84.2 ± 15.3; 64.0 ± 8.1 vs. 79.2 ± 15.4; 61.6 ± 8.3 vs. 77.2 ± 14.5 beats/min, P < 0.01, respectively). CONCLUSIONS: Lidocaine sprayed on the laryngoscope blade and/or trachea reduced the hemodynamic response to laryngoscopic intubation during the post-intubation period following anesthetic induction with remifentanil and propofol using a TCI device.

Effect of tracheostomy timing on clinical outcome in neurosurgical patients: early versus late tracheostomy.

BACKGROUND: The optimal timing of tracheostomy in neurosurgical patients is not well established. This retrospective study was conducted to determine the effect of the timing of tracheostomy on clinical outcome in mechanically ventilated neurosurgical patients admitted to the surgical intensive care unit (ICU). METHODS: A total of 125 neurosurgical patients, who underwent tracheostomy and had total mechanical ventilation (MV) duration of ≥7 days from October 2007 to December 2011, were enrolled. Patients were divided into 2 groups based on the timing of tracheostomy. Tracheostomy was performed within 10 days of MV in the early group (group E, n=39), whereas in the late group, it was performed after 10 days of MV (group L, n=86). The ICU and in-hospital mortality rates, total duration of MV, length of stay (LOS) in the ICU, hospital LOS, and incidence of ventilator-associated pneumonia (VAP) were compared between both the groups. RESULTS: The total MV duration and ICU LOS were significantly longer in group L than E (21.5±15.5 vs. 11.4±5.6 d, P<0.001; 31.1±18.2 vs. 19.9±10.6 d, P<0.001). The incidence of VAP before tracheostomy was higher in group L than group E (44 vs. 23%, P<0.05). No significant difference was found in the ICU and in-hospital mortality rates and hospital LOS between the groups. CONCLUSIONS: Early tracheostomy reduced the MV duration, ICU LOS, and incidence of VAP in critically ill neurosurgical patients. However, early tracheostomy did not reduce either the ICU or hospital mortality.

Suppression of autophagy and activation of glycogen synthase kinase 3beta facilitate the aggregate formation of tau.

Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer's disease. GSK3ß has been reported to play a major role in the NFT formation of tau. Dysfunction of autophagy might facilitate the aggregate formation of tau. The present study examined the role of GSK3ß-mediated phosphorylation of tau species on their autophagic degradation. We transfected wild type tau (T4), caspase-3-cleaved tau at Asp421 (T4C3), or pseudophosphorylated tau at Ser396/Ser404 (T4-2EC) in the presence of active or enzyme-inactive GSK3ß. Trehalose and 3-methyladenine (3-MA) were used to enhance or inhibit autophagic activity, respectively. All tau species showed increased accumulation with 3-MA treatment whereas reduced with trehalose, indicating that tau undergoes autophagic degradation. However, T4C3 and T4-2EC showed abundant formation of oligomers than T4. Active GSK3ß in the presence of 3-MA resulted in significantly increased formation of insoluble tau aggregates. These results indicate that GSK3ß-mediated phosphorylation and compromised autophagic activity significantly contribute to tau aggregation.

Phenotypic landscape of a bacterial cell.

The explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs.