Effects of Neostigmine and Sugammadex on QT Interval and QT Dispersion

Dispersion of QT dispersion(QTD)in 12-lead electrocardiogram is a useful index for assessment of ventricular arrhythmia risk and cardiovascular event. To determine the effects of reversal of nondepolarizing neuromuscular blockade on cardiovascular event, we evaluated the QT interval QTD after reversal of the neuromuscular blockade by neostigmine or sugammadex.After obtaining the approval of the ethics committee of Dokkyo Medical University Hospital, 40 patients with ASA physical status I or II were allocated to following two groups. Patients in the groups N(n=16)and S(n=15)received combination of neostigmine(40?μg/kg)and atropine(20?μg/kg)or sugammadex(2?mg/kg)as a reversal of neuromuscular blockade after the operation under 1% sevoflurane anesthesia, respectively. The RR interval, QT interval(QT), corrected QT interval(QTc), QT dispersion and corrected QT dispersion(QTcD)were consecutively recorded using computerized measurement before and after administration of reversal agents in both groups.RR interval in the group N significantly decreased 1-4?min after reversal of the neuromuscular blockade, but not in the group S. However, in the groups N and S, QT interval, QTc interval, QTD and QTcD were not changed after reversal of the neuromuscular blockade. Moreover, there was no significant difference between both groups in QT interval, QTc interval, QTD and QTcD during the study.Our results suggest that neither neostigmine nor sugammadex may increase the risk of ventricular arrhythmia and cardiovascular events in reversal of the neuromuscular blockade under sevoflurane anesthesia

Peripheral circadian rhythms in the liver and white adipose tissue of mice are attenuated by constant light and restored by time-restricted feeding.

Disturbance of circadian rhythms underlies various metabolic diseases. Constant light exposure (LL) is known to disrupt both central and peripheral circadian rhythms. Here, we attempted to determine whether the effects of LL are different between various peripheral tissues and whether time-restricted feeding restores the circadian rhythms especially in white adipose tissue (WAT). Six-week-old mice were subjected to three feeding regimes: ad libitum feeding under light/dark phase (LD), ad libitum feeding under LL cycle, and restricted feeding at night-time under LL cycle with a normal chow. After 3 weeks, we compared body weight, food intake, plasma levels of lipids and glucose, and the expression patterns of the clock genes and the genes involved in lipid metabolism in the liver and WAT. The mice kept under LL with or without time-restricted feeding were 5.2% heavier (p<0.001, n = 16) than the mice kept under LD even though the food intakes of the two groups were the same. Food intake occurred mostly in the dark phase. LL disrupted this pattern, causing disruptions in circadian rhythms of plasma levels of triglycerides (TG) and glucose. Time-restricted feeding partially restored the rhythms. LL eliminated the circadian rhythms of the expression of the clock genes as well as most of the genes involved in lipid metabolism in both liver and WAT. More notably, LL markedly decreased not only the amplitude but also the average levels of the expression of the genes in the liver, but not in the WAT, suggesting that transcription in the liver is sensitive to constant light exposure. Time-restricted feeding restored the circadian rhythms of most of the genes to various degrees in both liver and WAT. In conclusion, LL disrupted the peripheral circadian rhythms more severely in liver than in WAT. Time-restricted feeding restored the circadian rhythms in both tissues

Esterification of 4β-hydroxycholesterol and other oxysterols in human plasma occurs independently of LCAT

The acyltransferase LCAT mediates FA esterification of plasma cholesterol. In vitro studies have shown that LCAT also FA-esterifies several oxysterols, but in vivo evidence is lacking. Here, we measured both free and FA-esterified forms of sterols in 206 healthy volunteers and 8 individuals with genetic LCAT deficiency, including familial LCAT deficiency (FLD) and fish eye disease (FED). In the healthy volunteers, the mean values of the ester-to-total molar ratios of the following sterols varied: 4β-hydroxycholesterol (4βHC), 0.38; 5,6α-epoxycholesterol (5,6αEC), 0.46; 5,6β-epoxycholesterol (5,6βEC), 0.51; cholesterol, 0.70; cholestane-3β,5α,6β-triol (CT), 0.70; 7-ketocholesterol (7KC), 0.75; 24S-hydroxycholesterol (24SHC), 0.80; 25-hydroxycholesterol (25HC), 0.81; 27-hydroxycholesterol (27HC), 0.86; 7α-hydroxycholesterol (7αHC), 0.89. In the individuals with LCAT deficiency, the plasma levels of the FA-esterified forms of cholesterol, 5,6αEC, 5,6βEC, CT, 7αHC, 7KC, 24SHC, 25HC, and 27HC were significantly lower than those in the healthy volunteers. The individuals with FLD had significantly lower FA-esterified forms of 7αHC, 24SHC, and 27HC than those with FED. Of note, even in the three FLD individuals with negligible plasma cholesteryl ester, substantial amounts of the FA-esterified forms of 4βHC, 5,6αEC, 7αHC, 7KC and 27HC were present. We conclude that LCAT has a major role in the FA esterification of many plasma oxysterols, but contributes little to the FA esterification of 4βHC. Substantial FA esterification of 4βHC, 5,6αEC, 7αHC, 7KC and 27HC is independent of LCAT

Disilaruthena- and Ferracyclic Complexes Containing Isocyanide Ligands as Effective Catalysts for Hydrogenation of Unfunctionalized Sterically Hindered Alkenes

Disilaferra- and disilaruthenacyclic complexes containing mesityl isocyanide as a ligand, <b>3′</b> and <b>4′</b>, were synthesized and characterized by spectroscopy and crystallography. Both <b>3′</b> and <b>4′</b> showed excellent catalytic activity for the hydrogenation of alkenes. Compared with iron and ruthenium carbonyl analogues, <b>1′</b> and <b>2′</b>, the isocyanide complexes <b>3′</b> and <b>4′</b> were more robust under the hydrogenation conditions, and were still active even at higher temperatures (∼80 °C) under high hydrogen pressure (∼20 atm). The iron complex <b>3′</b> exhibited the highest catalytic activity toward hydrogenation of mono-, di-, tri-, and tetrasubstituted alkenes among currently reported iron catalysts. Ruthenium complex <b>4′</b> catalyzed hydrogenation under very mild conditions, such as room temperature and 1 atm of H₂. The remarkably high catalytic activity of <b>4′</b> for hydrogenation of unfunctionalized tetrasubstituted alkenes was especially notable, because it was comparable to the activity of iridium complexes reported by Crabtree and Pfaltz, which are catalysts with the highest activity in the literature. DFT calculations suggested two plausible catalytic cycles, both of which involved activation of H₂ assisted by the metal–silicon bond through σ-bond metathesis of late transition metals (oxidative hydrogen migration). The linear structure of MCNC (ipso carbon of the mesityl group) played an essential role in the efficient hydrogenation of sterically hindered tetrasubstituted alkenes

Disilaruthena- and Ferracyclic Complexes Containing Isocyanide Ligands as Effective Catalysts for Hydrogenation of Unfunctionalized Sterically Hindered Alkenes

Disilaferra- and disilaruthenacyclic complexes containing mesityl isocyanide as a ligand, <b>3′</b> and <b>4′</b>, were synthesized and characterized by spectroscopy and crystallography. Both <b>3′</b> and <b>4′</b> showed excellent catalytic activity for the hydrogenation of alkenes. Compared with iron and ruthenium carbonyl analogues, <b>1′</b> and <b>2′</b>, the isocyanide complexes <b>3′</b> and <b>4′</b> were more robust under the hydrogenation conditions, and were still active even at higher temperatures (∼80 °C) under high hydrogen pressure (∼20 atm). The iron complex <b>3′</b> exhibited the highest catalytic activity toward hydrogenation of mono-, di-, tri-, and tetrasubstituted alkenes among currently reported iron catalysts. Ruthenium complex <b>4′</b> catalyzed hydrogenation under very mild conditions, such as room temperature and 1 atm of H₂. The remarkably high catalytic activity of <b>4′</b> for hydrogenation of unfunctionalized tetrasubstituted alkenes was especially notable, because it was comparable to the activity of iridium complexes reported by Crabtree and Pfaltz, which are catalysts with the highest activity in the literature. DFT calculations suggested two plausible catalytic cycles, both of which involved activation of H₂ assisted by the metal–silicon bond through σ-bond metathesis of late transition metals (oxidative hydrogen migration). The linear structure of MCNC (ipso carbon of the mesityl group) played an essential role in the efficient hydrogenation of sterically hindered tetrasubstituted alkenes

MRS-measured glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice

To assess if magnetic resonance spectroscopy (MRS)-measured Glutamate (Glu) and GABA reflect excitatory and inhibitory neural activities, respectively, we conducted MRS measurements along with two-photon mesoscopic imagingof calcium signals in excitatory and inhibitory neurons of living, unanesthetized mice. For monitoring stimulus-driven activations of a brain region, MRS signals and mesoscopic neural activities were measured during two consecutivesessions of 15-min prolonged sensory stimulations. In the first session, putative excitatory neuronal activities were increased, while inhibitory neuronal activities remained at the baseline level. In the second half, while excitatory neuronal activities remained elevated, inhibitory neuronal activities were significantly enhanced. We assessed regionalneurochemical statuses by measuring MRS signals, which were overall in accordance with the neural activities, and neuronal activities and neurochemical statuses in a mouse model of Dravet syndrome under resting condition.Mesoscopic assessments showed that activities of inhibitory neurons in the cortex were diminished relative to wildtype mice in contrast to spared activities of excitatory neurons. Consistent with these observations, the Dravet modelexhibited lower concentrations of GABA than wild-type controls. Collectively, the current investigations demonstrate that MRS-measured Glu and GABA can reflect spontaneous and stimulated activities of neurons producing and releasingthese neurotransmitters in an awake condition

Synergistic Effect of Motivation for the Elderly and Support for Going Out II: Measures to Induce Elderly Men to Go Out

Background: The second demonstration experiment of supporting elderly people going out with the Choisoko system was conducted. The first study showed that for women, friends, shopping, convenience, and events are factors that have the potential to be effective motivational factors for encouraging these women to go out. On the other hand, these factors did not lead to any behavioral change in men. Since there are approximately 15 million men over the age of 65 in Japan, behavioral changes in the entire elderly population will not occur without guidance for elderly men to go out. Methods: Sixteen elderly men and forty-seven elderly women participated. Interestingly, men are far more passionate about games than women. Therefore, we hypothesized that a preference for games could be a hint as to how we might encourage older men to go out. Then, a second demonstration experiment was conducted, and we analyzed the relationship between six game preferences and the frequency of going out. Results: Among gaming preferences, men with gaming preferences such as Philanthropists, Achievers, and Free Spirits showed a tendency to go out. Conclusions: These stimuli may have the potential to be factors that may encourage elderly men to go out