Antioxidant Activity and Oxidation Products of 1,2,3,4- Tetrahydroquinoxalines in Peroxyl Radical Scavenging Reactions, Part I

This paper studies the antioxidant activity of 1,2,3,4-tetrahydroquinolines, 3,4-dihydro-2H-benzo[1,4]thiazines and 1,2,3,4-tetrahydroquinoxalines in the inhibition of the peroxidation of tetralin induced by an azo initiator. Neither 1,2,3,4- tetrahydroquinoline nor 3,4-dihydro-2H-benzo[1,4]thiazine alone acted as an antioxidant, but when they have an electron-donating group at the para position to the NH group, they act as potent antioxidants. On the other hand, 1,2,3,4- tetrahydroquinoxaline on its own showed good antioxidant activity. However, 1,2,3,4-tetrahydroquinoxalines with methyl and methoxy groups in the phenyl ring have reactivities similar to or less than that of unsubstituted 1,2,3,4-tetrahydroquinoxaline. The induction periods of 1,2,3,4-tetrahydroquinoxalines with an alkyl group or phenyl group at the 2-position were all longer than the value for the unsubstituted 1,2,3,4-tetrahydroquinoxaline, except for a compound with a t-butyl group. The oxidation of 1,2,3,4-tetrahydroquinoxalines by peroxyl radicals generated from an azo initiator in tetralin or benzene yields quinoxalines and a dimer product of quinoxalines, 6-(1,2,3,4-tetrahydroquinoxalin-1-yl)-quinoxaline

Characteristics of Ozone Jet Generated by Dielectric-Barrier Discharge

科研費報告書収録論文(課題番号:17206016/研究代表者:西山秀哉/プラズマ流動システムのマルチスケール統合化による最適制御)77

Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Is the change of percutaneous oxygen pressure available to judge the effects of brachial plexus block?

  BACKGROUND: To know the objective methods of the effects of the brachial plexus block, we studied the changes in percutaneous oxygen pressure (tcPO2) with the hypothesis that tcPO2 increases significantly on the blocked arm in comparison with the non-blocked arm, a phenomenon which is connected with vasodilation following the brachial plexus block. METHODS: Fifteen patients scheduled for upper extremity surgery, aged 20 to 70 years, with ASA physical status I or II were included. Before anaesthesia, the electrodes used to measure tcPO2 were put on the radial side of the forearm and upper arm of both the right and left sides (a total of 4 electrodes). Oxygen at 6 L min-1 was administered by a facial mask. Once midazolam 1–2 mg and fentanyl 50 μg had been administered intravenously, a propofol infusion was started at a dose of 2 mg kg-1 h-1. The interscalene block was performed by means of a nerve stimulator, using 20 mL of 1% lidocaine solution combined with 20 mL of 0.75% ropivacaine solution. TcPO2 was measured just before the block and 30 minutes after the block. RESULTS: TcPO2 in both forearm and upper arm significantly increased after the block in both sides namely, blocked and non-blocked. No difference was observed in tcPO2 between the blocked side and non-blocked side. CONCLUSION: Changes of tcPO2 are not useful in order to assess the effects of the interscalene block under oxygen administration.  BACKGROUND: To know the objective methods of the effects of the brachial plexus block, we studied the changes in percutaneous oxygen pressure (tcPO2) with the hypothesis that tcPO2 increases significantly on the blocked arm in comparison with the non-blocked arm, a phenomenon which is connected with vasodilation following the brachial plexus block. METHODS: Fifteen patients scheduled for upper extremity surgery, aged 20 to 70 years, with ASA physical status I or II were included. Before anaesthesia, the electrodes used to measure tcPO2 were put on the radial side of the forearm and upper arm of both the right and left sides (a total of 4 electrodes). Oxygen at 6 L min-1 was administered by a facial mask. Once midazolam 1–2 mg and fentanyl 50 μg had been administered intravenously, a propofol infusion was started at a dose of 2 mg kg-1 h-1. The interscalene block was performed by means of a nerve stimulator, using 20 mL of 1% lidocaine solution combined with 20 mL of 0.75% ropivacaine solution. TcPO2 was measured just before the block and 30 minutes after the block. RESULTS: TcPO2 in both forearm and upper arm significantly increased after the block in both sides namely, blocked and non-blocked. No difference was observed in tcPO2 between the blocked side and non-blocked side. CONCLUSION: Changes of tcPO2 are not useful in order to assess the effects of the interscalene block under oxygen administration

Changes in heart rate variability during anaesthesia induction using sevoflurane or isoflurane with nitrous oxide

  BACKGROUND: The purpose of this study was to compare cardiac sympathetic and parasympathetic balance using heart rate variability (HRV) during induction of anaesthesia between sevoflurane and isoflurane in combination with nitrous oxide. METHODS: 40 individuals aged from 30 to 60 years, scheduled for general anaesthesia were equally divided into sevoflurane or isoflurane groups. After 100% oxygen inhalation for a few minutes, anaesthesia was induced with nitrous oxide 3 L min-1, oxygen 3 L min-1 and sevoflurane or isoflurane. Sevoflurane or isoflurane concentration was increased by 0.5% every 2 to 3 breaths until 5% was attained for sevoflurane, or 3% for isoflurane. Vecuronium was administered to facilitate tracheal intubation. After intubation, sevoflurane was set to 2% while isoflurane was set to 1% with nitrous oxide with oxygen (1:1) for 5 min. RESULTS: Both sevoflurane and isoflurane provoked a decrease in blood pressure, total power, the low frequency component (LF), and high frequency component (HF) of HRV. Although the heart rate increased during isoflurane anaesthesia, it decreased under sevoflurane. The power of LF and HF also decreased in both groups. LF was higher in the isoflurane group while HF was higher in the sevoflurane group. The LF/HF ratio increased transiently in the isoflurane group, but decreased in the sevoflurane group. CONCLUSION: Anaesthesia induction with isoflurane-nitrous oxide transiently increased cardiac sympathetic activity, while sevoflurane-nitrous oxide decreased both cardiac sympathetic and parasympathetic activities. The balance of cardiac parasympathetic/sympathetic activity was higher in sevoflurane anaesthesia.    BACKGROUND: The purpose of this study was to compare cardiac sympathetic and parasympathetic balance using heart rate variability (HRV) during induction of anaesthesia between sevoflurane and isoflurane in combination with nitrous oxide. METHODS: 40 individuals aged from 30 to 60 years, scheduled for general anaesthesia were equally divided into sevoflurane or isoflurane groups. After 100% oxygen inhalation for a few minutes, anaesthesia was induced with nitrous oxide 3 L min-1, oxygen 3 L min-1 and sevoflurane or isoflurane. Sevoflurane or isoflurane concentration was increased by 0.5% every 2 to 3 breaths until 5% was attained for sevoflurane, or 3% for isoflurane. Vecuronium was administered to facilitate tracheal intubation. After intubation, sevoflurane was set to 2% while isoflurane was set to 1% with nitrous oxide with oxygen (1:1) for 5 min. RESULTS: Both sevoflurane and isoflurane provoked a decrease in blood pressure, total power, the low frequency component (LF), and high frequency component (HF) of HRV. Although the heart rate increased during isoflurane anaesthesia, it decreased under sevoflurane. The power of LF and HF also decreased in both groups. LF was higher in the isoflurane group while HF was higher in the sevoflurane group. The LF/HF ratio increased transiently in the isoflurane group, but decreased in the sevoflurane group. CONCLUSION: Anaesthesia induction with isoflurane-nitrous oxide transiently increased cardiac sympathetic activity, while sevoflurane-nitrous oxide decreased both cardiac sympathetic and parasympathetic activities. The balance of cardiac parasympathetic/sympathetic activity was higher in sevoflurane anaesthesia

Ketamine infusion was effective for severe pain of Non-Hodgkin lymphoma

A 52 years old man with a Non-Hodgkin lymphoma had severe pain at right buttock and lower leg. Sustained-release tablet of morphine 90 mg/day, intravenous morphine 40 mg/day, granisetron 9 mg/day, metoclopramide 30 mg/day, domperidone suppository 60 mg/day, intravenous hydroxyzine 25 mg/day, and haloperidol 20 mg/day did not decrease pain and side effects. Intravenous ketamine 10 mg in 15 min was quite effective for analgesia. Then infusion of ketamine started with 7 mg/h and increased to 10 mg/h with morphine 20 mg/day, which could control pain well with no side effects until his death. Keywords: Ketamine, Morphine, Cancer pain, Termina

Effects of repeat exposure to inhalation anesthetics on liver and renal function

Background: Cross hypersensitivity to inhalation anesthetics has not been studied. The aim of this study was to investigate it by comparing liver and renal function after repeated anesthesia with sevoflurane and isoflurane retrospectively. Materials and Methods: The adult patients who received general anesthesia twice within the interval of 14 days to 1 year were retrospectively analyzed. Those who received sevoflurane anesthesia twice (SS group, 53 cases), isoflurane anesthesia twice (II group, 31 cases), sevoflurane followed by isoflurane anesthesia (SI group, 29 cases), isoflurane followed by sevoflurane anesthesia (IS group, 35 cases), and propofol-fentanyl anesthesia twice (PP group, 58 cases) were enrolled. Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (Bil), gamma-glutamyl transpeptidase (γ-GTP), blood urea nitrogen (BUN), and creatinine (Cr) measured 1-3, 5-8, and 12-16 days after surgery were investigated. Results: In the IS group, the number of the patients with abnormal values of ALT and γ-GTP 5-8 days after surgery were significantly smaller at second anesthesia compared to the first anesthesia. The number of the patients with abnormal values of AST, ALT, and γ-GTP were significantly larger in the II group than the SS and PP groups. The number of patients who had higher values in each parameter at second anesthesia compared to the first anesthesia was not different among the groups. Conclusions: Sevoflurane and isoflurane might have no cross hypersensitivity. Both anesthetics might not have any additional risks to increase liver and renal damage by second anesthesia