Effects of intravenous bolus injection of emulsified isoflurane on QTc interval of healthy volunteers in Pharmacokinetics study.

Emulsified isoflurane is a novel intravenous anesthetic, which is a lipid emulsion of isoflurane. As some drugs have a QTc-prolongation effect which can increase a risk of arrhythmia, this study was to evaluate the effects of emulsified isoflurane on the QTc interval. This was a single-center, randomized, single-blind, non-comparative study. Subjects were randomly allocated to receive an intravenous bolus injection of 22.63, 38.26, or 49.73 mg/kg emulsified isoflurane, respectively. Standard 12-lead electrocardiograms were recorded before administration and at 28 timepoints after administration. Blood samples and the end-tidal isoflurane concentrations were collected for pharmacokinetic analysis. The primary target variable was the QTcF change from baseline at each time point. A two-sided 90% confidence interval (CI) was calculated for a QTcF change from baseline at each timepoint. The maximal 90% CIs of the mean QTcF from the baseline for 22.63, 38.26 and 49.73mg/kg emulsified isoflurane were 2.52-21.18 ms, 15.66-35.90 ms, and 17.65-40.71 ms, respectively. Non-significant relationship was observed between QTcF and the plasma concentration (or the end-tidal isoflurane concentration). Single intravenous dose of emulsified isoflurane of the anticipated therapeutic dose or supra-therapeutic doses was associated with a potential dose-dependent and non-concentration-related QTc-prolongation effect.

Calcium-sensing receptor regulates stomatal closure through hydrogen peroxide and nitric oxide in response to extracellular calcium in Arabidopsis.

The Arabidopsis calcium-sensing receptor CAS is a crucial regulator of extracellular calcium-induced stomatal closure. Free cytosolic Ca(2+) (Ca(2+)(i)) increases in response to a high extracellular calcium (Ca(2+)(o)) level through a CAS signalling pathway and finally leads to stomatal closure. Multidisciplinary approaches including histochemical, pharmacological, fluorescent, electrochemical, and molecular biological methods were used to discuss the relationship of hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) signalling in the CAS signalling pathway in guard cells in response to Ca(2+)(o). Here it is shown that Ca(2+)(o) could induce H(2)O(2) and NO production from guard cells but only H(2)O(2) from chloroplasts, leading to stomatal closure. In addition, the CASas mutant, the atrbohD/F double mutant, and the Atnoa1 mutant were all insensitive to Ca(2+)(o)-stimulated stomatal closure, as well as H(2)O(2) and NO elevation in the case of CASas. Furthermore, it was found that the antioxidant system might function as a mediator in Ca(2+)(o) and H(2)O(2) signalling in guard cells. The results suggest a hypothetical model whereby Ca(2+)(o) induces H(2)O(2) and NO accumulation in guard cells through the CAS signalling pathway, which further triggers Ca(2+)(i) transients and finally stomatal closure. The possible cross-talk of Ca(2+)(o) and abscisic acid signalling as well as the antioxidant system are discussed.

[Effect of single doses of HX0507 on QTc intervals in healthy people: a phase I safety and tolerability study].

OBJECTIVE: To assess the effect of HX0507 on QTc interval in healthy people in a phase I safety and tolerability study. METHODS: Eighty healthy people were randomly assigned to one of the 13 dosage groups. Standard 12-lead ECGs data were collected before and after HX0507, a water soluble prodrug of propofol, was given intravenously to the participants (at 33 time points). The QT interval values were corrected for heart rate using Fridericia's formula (QTcF = QT/RR(0.33)) and Bazett's formula (QTcB=QT/RR(0.5)). The primary target variable was baseline-adjusted changes in QTcF (deltaQTcF). RESULTS: Prolongation of QT interval was induced by HX0507 administered at an anticipated clinical dosage (3 mg/kg) or at a stronger dosage (8 mg/kg) and above. The mean deltaQTcF ranged from 5.61 ms to 32.24 ms, with an upper limit of 90% CI ranging from 10.30 ms to 53.90 ms. There was a linear correlation between HX0507 dosage and its effect on QT interval. Eight types of ECG-related adverse events were detected in 32 subjects. CONCLUSION: Single administration of HX0507 induces dose-related QT prolongation.

Influence of early fluid overload on bronchopulmonary dysplasia in very low-birth-weight infants.

Objective: This study aimed to determine the influence of fluid overload on bronchopulmonary dysplasia (BPD) in very low-birth-weight infants (VLBWI) within 1 week after birth. Methods: This was a retrospective case control study conducted in the Jingzhou Central Hospital. The clinical data of VLBWI (with a birth weight [BW] < 1,500 g and 26 weeks ≤ gestational age [GA] < 32 weeks) who were admitted to the neonatal intensive care unit of this hospital from January 2016 to December 2021 were analyzed retrospectively. A total of 157 cases were enrolled and divided into a BPD group (n = 60) and a non-BPD group (n = 97) according to whether BPD was present. The general condition, fluid intake, and fluid overload of the two groups of neonates within 1 week after birth were compared. The logistic regression was used to assess the association between infant characteristics and BPD. The ROC curve was used to assess how well the 7 day cumulative fluid overload predicted BPD, and to identify an optimal cut off for prediction. Results: The comparison of the patients' general condition revealed that the neonates in the BPD group had a younger GA, lower BW, lower 5-min Apgar score, longer duration of invasive mechanical ventilation, and higher incidence of intrauterine infections and administration of surfactants (P < 0.05). The differences in the other indicators were not statistically significant between the two groups. The logistic regression analysis revealed that a younger GA, the presence of intrauterine infection, and a 7-day cumulative fluid overload were the risk factors for the development of BPD. A ROC curve was plotted with the 7-day cumulative fluid overload as the test variable and BPD as the status variable. The area under the curve was 0.75 (95% confidence interval: 0.664-0.826, P = 0.042), with a sensitivity of 76.7% and a specificity of 70.1%, corresponding to a 7-day cumulative fluid overload of 36.2%. Conclusion: A younger GA, the presence of intrauterine infection, and a 7-day cumulative fluid overload were risk factors for the development of BPD. A 7 day cumulative fluid overload threshold of 36.2% best predicted the development of BPD.