Differential, histochemical and immunohistochemical changes in rat hepatocytes after isoflurane or sevoflurane exposure.

Differential, histochemical and immunohistochemical changes were observed in hepatocytes from immediately to 7 days after isoflurane or sevoflurane exposure (at H 0 to on Day 7) to study the process of development and recovery in anesthetic-induced hepatic injury. A total of 570 7-week-old male Sprague-Dawley rats with or without phenobarbital treatment were exposed to isoflurane or sevoflurane in 100%, 21%, or 10% oxygen, or to 10% oxygen alone for 2h. In phenobarbital-treated rats, hepatocytes both with and without anesthetic exposure markedly changed in 10% oxygen at H 0. Glycogen and ribosomal ribonucleic acid (rRNA) disappeared at H 0 and at H 6, respectively, and at H 6, AST levels in the blood rose. From H 6 to Day 1, necrosis developed more markedly and widely in zone 3 hepatocytes exposed to anesthetics in 10% oxygen than in those exposed to oxygen alone. All degenerated tissues had returned to normal levels by day 7. Recovery of the hepatolobular structure may be attributed to rearrangement of remaining hepatocytes in the portal vein area. Both the disappearance of glycogen and rRNA and the increase in blood AST levels after exposure to isoflurane or sevoflurane are considered to be factors contributing to the induction of necrosis around the central vein. The grade of isoflurane-induced hepatic injury was found to be significantly higher than that of sevoflurane.</p

乳癌縮小手術患者の術式選択時の情報提供のための回復過程の比較

乳癌患者が術式選択を行う場合の情報提供の資料とすることを目的に，乳房温存術（温存術）・胸筋温存乳房切除術（切除術）を受け，術後回復状態を３カ月間縦断的に観察しえたケース３９例において，温存術群（２１例）と切除術群（１８例）の２群にわけ，その２群間の比較を肩関節可動域・握力・創部ドレーン抜去日・胸部の疼痛と日常生活動作で行った．その結果，肩関節可動域は，切除術群・温存術群ともに，前方挙上，後方挙上・側方挙上のすべてにおいて統計的に有意差を認めなかった．しかし，術後１週目には温存術・切除術ともに肩関節可動域は一番低下し，その後３カ月をかけ徐々に回復する経過をたどった．一方，握力は，切除術群の２週目に有意に低下し，切除術は上肢筋力に関して手術侵襲の影響がみられた．術式別の創部ドレーン抜去日および日常生活動作においては，有意差はなかった．術後４週目の創部の動作時の疼痛が，切除術群に比べ温存術群においては「ある」と回答したものが多く，放射線療法による影響が考えられた．乳癌術前患者の術式選択に際しては，単に生存率のみの情報だけでなく，２つの術式には術後の肩関節可動域の制限の程度には差がないこと，温存術に比べ侵襲の比較的大きい切除術では術後２週目に握力の低下を認めること，放射線療法をおこなう温存術では創部の動作時の疼痛の認める例があることなどの，術式により回復のプロセスの違いがある点も情報提示し，対象者のライフスタイルに合わせた術式選択が可能となるよう支援していくことが重要であると考える．The present study was undertaken to collect data to be utilized for informed choice of operative procedure by patients with breast cancer. The subjects of this study were 39 patients who were followed for 3 months after breast-conserving surgery (the breast conserving group, 21 cases) or pectoral muscle-conserving mastectomy (the mastectomy group, 18 cases). The shoulder joint ROM (range of motion), grip, length of time until withdrawal of the drain, chest pain and activity of daily living (ADL) were compared between the two groups. There was no significant difference in shoulder joint ROM in any direction (anterior, posterior or lateral elevation of the joint) between the breast conserving group and the mastectomy group. In both groups, the shoulder joint ROM was minimal one week after surgery and later recovered gradually over 3 months. Grip was significantly lower in the mastectomy group two weeks after surgery, as compared to the breast-conserving group, suggesting influence of operative stress on the arm muscle strength in the mastectomy group. In terms of the ADL and the length of time from surgery to withdrawal of the drain, there was no significant difference between the two groups. Four weeks after surgery, a higher percentage of patients in the mastectomy group answered to have pain during motion of the surgical wound, as compared to the breast-conserving group, probably reflecting the influence of radiotherapy. These results suggest that when providing information to patients with breast cancer to allow selection of an operative procedure, information should be provided not only concerning expected survival rates, but also about similarities and differences in postoperative recovery between the two procedures, including for example the following information :（1）the degree of restriction of shoulder joint ROM does not differ between the two procedures ; （2）grip may decrease two weeks after pectoral muscle-conserving mastectomy which is more invasive than breast-conserving surgery ; and（3）pain during motion of the wound is sometimes complained after breast-conserving surgery which is combined with radiotherapy. It seems essential to help individual patients select a procedure tailored to their life style on the basis of these pieces of information

乳癌縮小手術患者の肩関節可動域の回復遅延に関わる要因の分析

本研究は，乳癌で胸筋切除を伴わない縮小手術を受けた患者の肩関節の可動域の回復遅延ケースにおける，回復遅延に関わる要因を明らかにし，術後の機能回復訓練時の患者指導に活かすことを目的とした．対象は乳房温存術や胸筋温存乳房切除術を受けた乳癌術後患者３９名で，機能回復訓練を術後１２週間縦断的に観察しえたケースにおいて，肩関節可動域の回復状態を良好群と遅延群の２群にわけ，その２群間の比較を，肩関節可動域や疼痛・日常生活動作から観察した．その結果，遅延群ケースから肩関節可動域の回復に関わる主要因として，創部の動作時の疼痛が考えられ，２つめの要因としてこの動作時の疼痛の発生により術後必要とされる運動を行わないことで，さらに回復を遅延させていることが考えられた．よって，動作時の疼痛を訴え，肩関節可動域の回復の遅れを認める例には，機能回復訓練状態の観察と術後１２週目までの継続的な運動の必要性の指導のほかに，肩関節可動域訓練を看護師が患者とともに一緒に行うという確実な実施が，肩関節の可動域の回復遅延の予防となると考えられた．The present study was undertaken to identify factors responsible for delay in recovery of the shoulder joint ROM (range of motion) after minimally invasive surgery for breast cancer (i.e., surgery not involving pectoral muscle excision), with the goal of facilitating better postoperative rehabilitation. The subjects of this study were 39 patients who were followed during 12 weeks of functional rehabilitation after breast-conserving surgery or pectoral muscle-conserving surgery for breast cancer. They were divided into the good recovery group and the delayed recovery group according to the smoothness in recovery of shoulder joint ROM. Shoulder joint ROM, pain and activity of daily living (ADL) were compared between these two groups. Analysis of the data from the delayed recovery group allowed us to identify the pain during movement of the surgical wound as a leading factor affecting the recovery of shoulder joint ROM. Failure to practice exercise after surgery due to pain during motion of the wound was identified as the second leading cause for delayed recovery. These results suggest that in cases where postoperative recovery in should joint ROM is delayed, recovery may be facilitated by monitoring the progress of rehabilitation, advising the patient to continue exercise until day 12 after surgery and guiding the patient to practice shoulder joint ROM training with the help of the nurse

Prospective association of soft drink consumption with depressive symptoms.

OBJECTIVE: Consumption of soft drinks has become a serious public health issue worldwide. However, prospective evidence is limited regarding the relationship between soft drink consumption and depression, especially in Asia. The aim of this study was to investigate the prospective association between soft drink consumption and the development of depressive symptoms. METHODS: We evaluated an occupational cohort of 935 adults in Japan (2012-2016), who were free from depressive symptoms at baseline and attended a 3-y follow-up assessment. Soft drink consumption was assessed using a self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multivariate logistic regression analysis controlling for sociodemographic, lifestyle, dietary, and occupational covariates. RESULTS: Over the 3-y study period, 16.9% (158 cases) of the study participants reported depressive symptoms. Higher soft drink consumption was associated with higher odds of depressive symptoms. The multivariable-adjusted OR was 1.91 (95% CI, 1.11-3.29; Ptrend = 0.015) when comparing soft drink consumption of ≥4 cups/wk with consumption of <1 cup/wk. CONCLUSION: The present results suggested that greater consumption of soft drinks would increase the likelihood of exhibiting depressive symptoms.This study was supported by JSPS KAKENHI Grant Numbers 25293146, 25702006, Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus (15ek0210021h0002) from the Japan Agency for Medical Research and Development, and the Industrial Health Foundation. F.I. was funded by the Medical Research Council Epidemiology Unit, United Kingdom (MC_UU_12015/5)

Impaired CD4⁺ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination

高齢者のT細胞応答は立ち上がりが遅く収束は早い --新型コロナワクチン接種機会を活用した免疫応答の個人差・年齢差の解明--. 京都大学プレスリリース. 2023-01-13.T-Cell Responses in the Elderly Rise Slowly and Contract Quickly --Learning About Individual and Age Differences in Immune Response From COVID-19 Vaccinations--. 京都大学プレスリリース. 2023-01-13.Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥65 years) had fewer vaccine-induced spike-specific CD4⁺ T cells including CXCR3⁺ circulating follicular helper T cells and the TH1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after the second dose, compared with younger adults. Moreover, spike-specific TH1 cells in older adults expressed higher levels of programmed cell death protein 1, a negative regulator of T cell activation, which was associated with low spike-specific CD8⁺ T cell responses. Thus, an inefficient CD4⁺ T cell response after the first dose may reduce the production of helper T cytokines, even after the second dose, thereby lowering humoral and cellular immunity and reducing systemic reactogenicity. Therefore, enhancing CD4⁺ T cell response following the first dose is key to improving vaccine efficacy in older adults

An NLR paralog Pit2 generated from tandem duplication of Pit1 fine-tunes Pit1 localization and function

NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication

Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84

食事性肥満から肝炎発症に関わる制御因子の同定 --中鎖脂肪酸油による予防・GPR84標的NASH治療薬の可能性--. 京都大学プレスリリース. 2023-01-18.Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein–coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity. Under high-fat diet (HFD) conditions, GPR84-deficient mice exhibited nonalcoholic steatohepatitis (NASH) and the progression of hepatic fibrosis but not steatosis. With markedly increased hepatic MCFA levels under HFD, GPR84 suppressed lipotoxicity-induced macrophage overactivation. Thus, GPR84 is an immunomodulating receptor that suppresses excessive dietary fat intake–induced toxicity by sensing increases in MCFAs. Additionally, administering MCTs, MCFAs (C10:0 or C12:0, but not C8:0), or GPR84 agonists effectively improved NASH in mouse models. Therefore, exogenous GPR84 stimulation is a potential strategy for treating NASH