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1 The mode of action of reactive oxygen intermediates in cysosolic Ca 2+ movements of cultured porcine aortic endothelial cells exposed to xanthine/xanthine oxidase (X/XO) was investigated. 2 Cytosolic Ca 2+ movements provoked by X/XO consisted of an initial Ca 2+ release from thapsigargin-sensitive intracellular Ca 2+ stores and a sustained Ca 2+ in¯ux through cell-membrane Ca 2+ channels. The Ca 2+ movements from both sources were inhibited by catalase, cell-membrane permeable iron chelators (o-phenanthroline and deferoxamine), a . OH scavenger (5,5-dimethyl-1-pyrroline-N-oxide), or an anion channel blocker (disodium 4, 4'-diisothiocyano-2, 2'-stilbenedisulphonic acid), suggesting that . O 2 7 in¯ux through anion channels was responsible for the Ca 2+ movements, in which . OH generation catalyzed by intracellular transition metals (i.e., Haber-Weiss cycle) was involved.3 After an initial Ca 2+ elevation provoked by X/XO, cytosolic Ca 2+ concentration decreased to a level higher than basal levels. Removal of X/XO slightly enhanced the Ca 2+ decrease. Extracellular addition of sulphydryl (SH)-reducing agents, dithiothreitol or glutathione, after the removal of X/ XO accelerated the decrement. A Ca 2+ channel blocker, Ni 2+ , abolished the sustained increase in Ca 2+ , suggesting that Ca 2+ in¯ux through cell-membrane Ca 2+ channels was extracellularly regulated by the redox state of SH-groups. 4 The X/XO-provoked change in cellular respiration was inhibited by Ni 2+ or dithiothreitol as well as inhibitors of Haber-Weiss cycle, suggesting that Ca 2+ in¯ux was responsible for . OH-mediated cytotoxicity. We concluded that intracellular . OH generation was involved in the Ca 2+ movements in endothelial cells exposed to X/XO. Cytosolic Ca 2+ elevation was partly responsible for the oxidants-mediated cytotoxicity.

A new phenomenon of decalcification of the cement concrete structure and dissolution of bitumen in bituminous pavement is described, caused by the surfactants included in the windshield washer fluid of automobiles. Decalcification occurs in cement concrete samples in the laboratory even at low concentrations of surfactant of 25 ppm. Recently, foam with fine bubbles have been observed in the water on pavement just after rain worldwide. The decalcification reaction was identified as an ion exchange reaction between the calcium ions Ca2+ in the concrete and Na+ in the surfactants using the electron spectroscopy for chemical analysis (ESCA) method. Bitumen was also found in the decalcified cement concrete, from which the Ca component had dissolved out gradually with time.

Aims: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs.Main methods: An in vivo model of I/R injury was tested in control, mTOR +/+ , and mTOR +/-. Mice were randomly assigned to receive BCAAs, rapamycin, or BCAAs + rapamycin. Furthermore, isolated cardiomyocytes were subjected to simulated ischemia and cell death was quantified.Biochemical and mitochondrial swelling assays were also performed. Key findings: Mice treated with BCAAs had a significant reduction in infarct size as a percentage of the area at risk compared to controls (34.1 ± 3.9% vs. 44.7 ± 2.6%, P = 0.001), whereas mice treated with the mTOR inhibitor rapamycin were not protected by BCAA administration (42.2 ± 6.5%, vs. control, P = 0.015). This protection was not detected in our hetero knockout mice of mTOR. Western blot analysis revealed no change in AKT signaling whereas activation of mTOR was identified. Furthermore, BCAAs prevented swelling which was reversed by the addition of rapamycin. In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this 4 BCAA-induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001).Significance: BCAA treatment exhibits a protective effect in myocardial I/R injury and that mTOR plays an important role in this preconditioning effect.

Opioid inhibition of nociceptive stimuli varies in individuals and is difficult to titrate. We have reported the vascular stiffness value (K) as a standard monitor to quantify sympathetic response with high accuracy. On the contrary, among individuals, a considerable variation in the rate of change in K for constant pain has been observed. In this study, we proposed a new index, the minimum stimulus intensity value that evoked the response on K (MECK: Minimum Evoked Current of K), and evaluated its accuracy in predicting sympathetic response to nociceptive stimuli under constant opioid administration. Thirty patients undergoing open surgery under general anesthesia were included. After anesthetic induction, remifentanil was administered at a constant concentration of 2 ng/ml at the effect site followed by tetanus stimulation. MECK was defined as the minimal current needed to produce a change in K. MECK significantly (P < 0.001) correlated with the rate of change of systolic blood pressure during skin incision (ROCBP). Bland–Altman plot analysis using the predicted ROCBP calculated from MECK and the measured ROCBP showed that the prediction equation for ROCBP was highly accurate. This study showed the potential of MECK to predict blood pressure change during surgical incision under opioid analgesia.Clinical trial registration Registry: University hospital medical information network; Registration number: UMIN000041816; Principal investigator's name: Satoshi Kamiya; Date of registration: July 9th, 2019.

Background Remimazolam is a novel short-acting benzodiazepine characterized by metabolism independent from organ function. We report intraoperative MEP responses of two patients who underwent spine surgery under general anesthesia using remimazolam. Case presentation In case 1, MEP monitoring was successfully performed with the use of a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/kg/min. In case 2, an increasing dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals. In both cases, remimazolam was titrated to maintain the values of entropy electroencephalogram (EEG) monitoring at 40–60. Conclusions General anesthesia using remimazolam and remifentanil can be a valuable alternative for spine surgery with MEP monitoring by EEG to assess the optimal dose.

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In clinical practice, subjective pain evaluations, e.g., the visual analogue scale and the numeric rating scale, are generally employed, but these are limited in terms of their ability to detect inaccurate reports, and are unsuitable for use in anesthetized patients or those with dementia. We focused on the peripheral sympathetic nerve activity that responds to pain, and propose a method for evaluating pain sensation, including intensity, sharpness, and dullness, using the arterial stiffness index. In the experiment, electrocardiogram, blood pressure, and photoplethysmograms were obtained, and an arterial viscoelastic model was applied to estimate arterial stiffness. The relationships among the stiffness index, self-reported pain sensation, and electrocutaneous stimuli were examined and modelled. The relationship between the stiffness index and pain sensation could be modelled using a sigmoid function with high determination coefficients, where R2 ≥ 0.88, p < 0.01 for intensity, R2 ≥ 0.89, p < 0.01 for sharpness, and R2 ≥ 0.84, p < 0.01 for dullness when the stimuli could appropriately evoke dull pain.