Branched-chain amino acids-induced cardiac protection against ischemia/reperfusion injury

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 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.This work was supported by JSPS KAKENHI, Japan [grant number 19K09353]

開腹婦人科手術での術後鎮痛における硬膜外間欠投与の有効性

Background. It is well known that the programmed intermittent epidural bolus (PIEB) technique effectively provides epidural anesthesia in labor. This randomized double-blind trial compared the postoperative analgesic efficacy of PIEB with that of continuous epidural infusion (CEI) in patients undergoing gynecological surgery under combined general-epidural anesthesia. Methods. Patients undergoing open gynecological surgery under combined general-epidural anesthesia were randomized at a 1 : 1 ratio to receive PIEB or CEI. In the PIEB group, the pump delivered 4mL ropivacaine 0.2% plus fentanyl 2 g/mL every hour. In the CEI group, the pump delivered the same solution at a rate of 4 mL/h. In both groups, additional 4mL boluses of ropivacaine 0.2% plus fentanyl 2 g/mL were provided, when necessary, by patient-controlled epidural analgesia after surgery. The primary outcome was the total ropivacaine dose 40 hours after surgery. The secondary outcomes were the number of PCEA boluses and postoperative pain (evaluated on an 11-point numerical rating scale) 3, 24, and 48 hours after surgery. Results. In total, 57 patients were randomized ( = 28 and 29 in the PIEB and CEI groups, resp.). The two groups differ significantly in terms of the total ropivacaine dose 40 hours after surgery (mean (standard deviation): 155.38 (4.55) versus 159.73 (7.87) mL, = 0.016). Compared to the CEI group, the PIEB group had significantly lower numerical rating scale scores 3 hours (median [lower–upper quartiles]: 0 [0–0.5] versus 3 [0–5.5], = 0.002), 24 hours (1 [0–2] versus 3 [1–4], = 0.003), and 48 hours (1 [0–2] versus 2 [2–3.5], = 0.002) after surgery. Conclusion. PIEB was better than CEI in terms of providing postoperative analgesia after open gynecological surgery under combined general-epidural anesthesia

PONV after intraarticular anesthesia

Study Objective : the incidence of postoperative nausea and vomiting (PONV) following single-injection intraarticular anesthesia was compared to that following continuous epidural anesthesia. Design : Prospective, double-blind, randomized study. Setting : University-affiliated teaching hospital. Patients : Forty-eight patients finally participated in this study, and each group contained twenty-four patients. Interventions : Patients scheduled to undergo lower limb surgery under general anesthesia were randomly allocated into two groups, to receive either single-injection intraarticular or continuous epidural anesthesia for postoperative analgesia. Measurements : The incidence and severity of PONV, complete response rates (i.e., no vomiting or rescue antiemetic use), and pain scores were recorded 2, 24, and 48 h postoperatively. Main results : No significant differences between groups were observed in the incidence and severity of PONV, rescue antiemetic use, or complete response rate at any of the time points, but only the use of rescue analgesics was significantly less in continuous epidural anesthesia group during the 2-24h postoperative period (P=0.04). Conclusion : While the use of single-injection intraarticular anesthesia following lower limb surgery did not prevent PONV more than continuous epidural anesthesia in this study, the intraarticular technique still provides greater simplicity, safety, and cost-effectiveness

Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model

Background: Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods: In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results: Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice. Conclusions: Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice

Continuous blood glucose monitoring during pediatric cardiopulmonary bypass

The purpose of this study was to assess the accuracy and efficacy of a continuous blood glucose monitoring system (artificial endocrine pancreas; STG-22, Nikkiso, Co., Ltd., Tokyo, Japan) during pediatric cardiopulmonary bypass. Sixteen pediatric patients scheduled to undergo cardiovascular surgery with cardiopulmonary bypass (6 for atrial septal defects, 8 for ventricular septal defects and 2 for others, age: 7 months to 13 years, body weight 6.4-55.4 kg) were enrolled. The glucose sensor line of the artificial endocrine pancreas was connected to the venous side of the cardiopulmonary bypass circuit and used for continuous blood glucose monitoring. We obtained 66 samples for blood gas assessment from the cardiopulmonary bypass circuit, and i-STAT (Abbott, East Windsor, NJ, USA) was used for conventional blood glucose assessment. Data were analyzed with simple linear regression analysis using the Bland and Altman approach. After cardiopulmonary bypass was started and the aortic artery clamped, the blood glucose level rose markedly to around 300 mg/dl. Blood sampling via the venous side of the cardiopulmonary bypass circuit showed that continuous blood glucose monitoring was stable and reliable even during pediatric cardiovascular surgery with cardiopulmonary bypass. A close correlation (R = 0.97) was observed between continuous glucose measurement and conventional intermittent glucose measurements. The results of this continuous blood glucose monitoring system for cardiopulmonary bypass during pediatric cardiovascular surgery were highly reliable

Successful treatment of mixed (mainly cancer) pain by tramadol preparations

The patient, a 70-year-old Japanese woman diagnosed with parotid gland cancer, underwent wide excision and reconstruction (facial nerve ablation, nerve transposition). At 1 month after the surgery, she was brought to our hospital’s pain medicine department because her postoperative pain and cancer-related pain were poorly controlled. She had already been prescribed a tramadol (37.5 mg)/acetaminophen (325 mg) combination tablet (5 tablets/day). However, in addition to the continuous pain in her face and lower limbs, she was troubled by a trigeminal neuralgia-like prominence ache. Because this pain could not be controlled by an increase to eight combination tablets per day, we switched her medication to a tramadol capsule. At 11 months post-surgery, we then switched her medication to an orally disintegrating tramadol tablet to improve medication adherence of the drug. From 14 months post-surgery, the patient also used a sustained-release tramadol preparation, and she was then able to sleep well. Her current regimen is an orally disintegrating sustainedrelease tablet combination (total 300 mg tramadol) per day, and she achieved sufficient pain relief. Because tramadol is not classified as a medical narcotic drug, it widely available and was shown here to be extremely useful for the treatment of our patient’s mixed (mainly cancer) pain

Novel Prophylactic Vaccine Using a Prime-Boost Method and Hemagglutinating Virus of Japan-Envelope against Tuberculosis

Objective. Mycobacterium tuberculosis infection is a major global threat to human health. The only tuberculosis (TB) vaccine currently available is bacillus Calmette-Guérin (BCG), although it has no efficacy in adults. Therefore, the development of a novel vaccine against TB for adults is desired. Method. A novel TB vaccine expressing mycobacterial heat shock protein 65 (HSP65) and interleukin-12 (IL-12) delivered by the hemagglutinating virus of Japan- (HVJ)- envelope was evaluated against TB infection in mice. Bacterial load reductions and histopathological assessments were used to determine efficacy. Results. Vaccination by BCG prime with IgHSP65+murine IL-12/HVJ-envelope boost resulted in significant protective efficacy (>10, 000-fold versus BCG alone) against TB infection in the lungs of mice. In addition to bacterial loads, significant protective efficacy was demonstrated by histopathological analysis of the lungs. Furthermore, the vaccine increased the number of T cells secreting IFN-γ. Conclusion. This vaccine showed extremely significant protection against TB in a mouse model, consistent with results from a similar paper on cynomolgus monkeys. The results suggest that further development of the vaccine for eventual testing in clinical trials may be warranted

Cシ ノ トクテイ コウレイシャ ニトッテ ケンコウジョウ ノ アンシン トハ

高齢化が進む東北地方のB県C市の特定高齢者にとって"健康上の安心"を構成する要素は何か記述することを目的に、13名の協力者に対し半構成的インタビューを行ない質的に分析した。その結果、安心を構成する要素の中核カテゴリーとして【つながっている】、大カテゴリーとして《人生を認め合える》《今現在のつながりが残っている》《自分の体をやりくりできる》が抽出された。C市の高齢者が健康上安心して生活できるためには、互いに人生を認め合い共に過ごしてきた仲間がいることとそこから生まれた自尊感情が基盤となり、そのつながりに支えられ、更に今現在もそのつながりが残っていることが必要であった。現在のつながりは人や情報、行きたい場所の存在と移動手段などであるが、それらのつながりに支えられて、自分のからだをやりくりできるという自己効力感の存在が認められ、それらが特定高齢者の安心を支えていた。特定高齢者の自己効力感に働きかけ、自尊感情を尊重しながら、活動や参加という場や手段の提供により人や情報とのつながりを維持していくという視点は、ICFの健康の概念である「生活機能-身体状況だけでなく活動・参加-で生きる全体をとらえる」ことに通じていることが明らかになり、これからの高齢者支援の重要な視点として再確認された。The purpose of this study is to identify some factors that make the "tokutei" elderly people living in C city feel secure about their health. Based on interviews with thirteen "tokutei" elders, three major caregories were found as well as a core category that constitutes their secure feeling of "being related to someone or something." Besides these categories, the study also shows that the "tokutei" elderly people have self&#8209;efficacy in their health management. As the notion of ICF suggests, the feeling of "being related" and selfefficacy will bring the elders confidence in their health management. Therefore, these findings should be taken into account when we try to build a support system for the "tokutei" elderly people