Understanding the Molecular Mechanism of Anesthesia: Effect of General Anesthetics and Structurally Similar Non-Anesthetics on the Properties of Lipid Membranes.
作者: Zsófia B Rózsa ; György Hantal ; Milán Szőri ; Balázs Fábián ; Pál Jedlovszky
General anesthesia can be caused by various, chemically very different molecules, while several other molecules, many of which are structurally rather similar to them, do not exhibit anesthetic effects at all. To understand the origin of this difference and shed some light on the molecular mechanism of general anesthesia, we report here molecular dynamics simulations of the neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing the anesthetics diethyl ether and chloroform and the structurally similar non-anesthetics n-pentane and carbon tetrachloride, respectively. To also account for the pressure reversal of anesthesia, these simulations are performed both at 1 bar and at 600 bar. Our results indicate that all solutes considered prefer to stay both in the middle of the membrane and close to the boundary of the hydrocarbon domain, at the vicinity of the crowded region of the polar headgroups. However, this latter preference is considerably stronger for the (weakly polar) anesthetics than for the (apolar) non-anesthetics. Anesthetics staying in this outer preferred position increase the lateral separation between the lipid molecules, giving rise to a decrease of the lateral density. The lower lateral density leads to an increased mobility of the DPPC molecules, a decreased order of their tails, an increase of the free volume around this outer preferred position, and a decrease of the lateral pressure at the hydrocarbon side of the apolar/polar interface, a change that might well be in a causal relation with the occurrence of the anesthetic effect. All these changes are clearly reverted by the increase of pressure. Furthermore, non-anesthetics occur in this outer preferred position in a considerably smaller concentration and hence either induce such changes in a much weaker form or do not induce them at all.
2022-12-01·Food science and biotechnology
Determination of alcohols in various fermented food matrices using gas chromatography-flame ionization detector for halal certification
作者: Kim, Yuri ; Shim, You-Shin ; Lee, Kwang-Geun
In this study, an analytical method for the determination of alcohols by gas chromatography-flame ionization detection was applied to fermented foods. The limit of detection and limit of quantitation were 0.79 and 2.40 mg/kg for methanol, 0.55 and 1.66 mg/kg for ethanol, 0.51 and 1.56 mg/kg for n-propanol, 0.35 and 1.05 mg/kg for n-butanol, and 0.38 and 1.16 mg/kg for n-pentanol, respectively. The recoveries from the matrices of gochujang, soy sauce, and kimchi were 93.80-102.03%, 93.27-99.69% and 89.06-102.17%, respectively, and the corresponding intra- and inter-day relative standard deviations were below 5.33%, 5.35% and 4.10%. In 95 fermented foods, ethanol showed the highest mean, median and maximum values among the five alcohols. The detection rate of ethanol was 86.3% among all samples and 100% in gochujang and gochujang-based sauces. A total of 22 samples had an alcohol content above 0.5%, of which 16 were gochujang.
2022-10-07·World journal of urology
Efficacy of TAC-302 for patients with detrusor underactivity and overactive bladder: a randomized, double-blind, placebo-controlled phase 2 study.
This multicenter, randomized, double-blind, placebo-controlled phase 2 study evaluated the efficacy and safety of TAC-302, a novel drug that restores neurite outgrowth, in patients with detrusor underactivity (DU) and overactive bladder (OAB).
After 2-4 weeks of observation, patients were randomized 2:1 to receive oral TAC-302 200 mg or placebo twice daily for 12 weeks. The primary endpoint was detrusor contraction strength, estimated by bladder contractility index (BCI) for males and projected isovolumetric pressure 1 (PIP1) for females. Secondary endpoints included changes in bladder voiding efficiency (BVE) and safety.
Seventy-six patients were included (TAC-302, n = 52; placebo, n = 24). The mean (standard deviation [SD]) BCI for males was 64.6 (16.6) at baseline and 75.2 (21.1) at week 12 (p < 0.001) with TAC-302 (n = 27), and 61.3 (16.6) and 60.5 (16.7) (p = 0.82) with placebo (n = 11). The respective mean (SD) PIP1 for females was 18.8 (6.6) and 29.4 (9.4) (p < 0.001) with TAC-302 (n = 15), and 20.6 (7.5) and 25.5 (9.6) (p = 0.14) with placebo (n = 7). TAC-302 significantly increased BCI in males and BVE in both sexes. TAC-302 efficacy on OAB was not clearly shown. The incidences of adverse events (AEs), serious AEs, and AEs leading to dose interruption were similar between groups; no adverse drug reactions occurred.
Considering the significant effects on BCI in males and BVE in both sexes, TAC-302 may benefit patients with DU.