Search

Bone loss and bone-related disease are associated with the deregulation of osteoclast function, and therefore agents that affect osteoclastogenesis have attracted attention. The purpose of the present study was to discover modified kavalactone analogs as potential anti-osteoclastogenic agents. We assessed the effect of 26 analogs on osteoclast differentiation in vitro. The most potent compound, (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22), suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of RAW264 cells with IC50 values of 4.3 µM. A partial structure-activity relationship study revealed the importance of fluorine and its position within the 5,6-dehydrokawain skeleton. The results of a pit formation assay suggested that compound 22 prevents osteoclastic bone resorption by inhibiting osteoclastogenesis. Moreover, compound 22 downregulated mRNA expression levels of RANKL-induced nuclear factor of activated T cells c1 (NFATc1) and osteoclastogenesis-related genes. These results suggest that (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one scaffold could lead to the identification of new anti-resorptive agents.

Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1β, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPS-stimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/β2-glycoprotein I (oxLDL/β2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr−/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1β) and hepatic (TNF-α, IL-1α, IL-1β) pro-inflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis., Food science; Food analysis; Rice bran extract (RBE); Functional food; Phytochemicals; Atherosclerosis; Oxidative stress; Inflammation; Antioxidant; Anti-inflammation; Oxidized lipoprotein (oxLDL).

As a Japanese folk medicine, Tithonia diversifolia is used for cardiovascular disease prevention and health maintenance. We isolated T. diversifolia-derived orizabin based on the nitric oxide production inhibitory effect. This study aimed to consider orizabin as a novel functional compound with anti-atherosclerotic activity. Orizabin significantly inhibited the adhesion of THP-1 cells to human umbilical vein endothelial cells (HUVECs) and suppressed the mRNA expression of adhesion molecules in HUVECs. In Phorbol 12-myristate 13-acetate stimulated THP-1 cells, orizabin suppressed macrophage differentiation, CD36 expression (1% at 10 μM), and NFκB transcriptional activity. Furthermore, orizabin suppressed oxidized low-density lipoprotein (oxLDL) uptake in macrophages and the Akt phosphorylation. On the contrary, we revealed that phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) mRNA and protein expression were promoted significantly by orizabin (mRNA, 270-fold at 10 μM). Our study presented the possibility that T. diversifolia-derived orizabin is novel anti-atherosclerotic compound via the suppression of Akt phosphorylation, and T. diversifolia may be effective as a new crop for vascular health maintenance. PRACTICAL APPLICATIONS: In this study, the differentiation of monocytes was suppressed without any toxicity, it was obvious in the image, and the oxLDL uptake in monocytes was clearly suppressed by orizabin. Our findings presented that T. diversifolia-derived compound orizabin specifically contributes to the promotion of PTEN expression and suppression of Akt signal in cells, and acts to suppress inflammation by suppression of NFκB transcriptional activity. As a component derived from food, it has a strong function and can be used to maintain the health for blood vessels. It is also a finding that deserves to expand production currently being carried out on a small scale. Furthermore, the promoting effect of PTEN known as a cancer suppressor in orizabin may result in further use for pharmaceuticals research. Orizabin can be safely used as a food-derived compound for maintaining human health.

An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity. Among the potential analogs we synthesized, (E)-6-(4-Ethylstyryl)-4-methoxy-2H-pyran-2-one (14) and (E)-6-(4-Butylstyryl)-4-methoxy-2H-pyran-2-one (21) both significantly up-regulated Runx2 and Osterix mRNA expression at 10µM. These osteogenic activities could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast differentiation of RAW264 cells. These results indicated that novel 5,6-dehydrokawain analogs not only increase osteogenic activity but also inhibit osteoclast differentiation, and could be potential lead compounds for the development of anti-osteoporosis agents.

Intrapulmonary or intracardiac thrombosis is a rare but catastrophic event following complex cardiothoracic surgery. Although there have been multiple cases reported in the literature, the causes of these events are largely unknown. In this retrospective review, we attempt to identify risk factors and propose possible mechanisms of thromboses after cardiopulmonary bypass (CPB).A literature search was conducted using the MEDLINE and EMBASE with these keywords: (intra)pulmonary thrombosis, pulmonary embolism, pulmonary infarction, lung embolism, (intra)cardiac thrombosis, cardiac thrombi, in combination with CPB, extracorporeal membrane oxygenation, deep hypothermic circulatory arrest, or cardiac surgery. Putative risk factors were compiled from reported cases.We identified 34 cases of massive intrapulmonary and/or intracardiac thromboses. All but 2 cases (94.1%) were fatal. Clinical presentations were systemic hypotension and/or pulmonary hypertension, right ventricular failure, and cardiogenic shock in 32 (94.1%) cases. The timing was immediate (10 min) following hemostatic intervention in 16 cases (47.1%), within 45 min in 8 cases (23.5%), and not reported in the rest. Putative risk factors included antifibrinolytic use (88.2%), congestive heart failure (55.9%), prolonged CPB use (2 h) (41.1%), and low activated clotting time (400 s) after initial heparinization (20.6%). The administration of tissue plasminogen activator in 5 cases was ineffective.Massive thrombosis following cardiac surgery is a highly lethal event with limited treatment options. Particular attention should be paid to the status of thrombin regulatory proteins before protamine and other hemostatic interventions in patients undergoing complex cardiac surgery with antifibrinolytic agents.

Antifibrinolytic agents have been prophylactically administered to patients undergoing cardiopulmonary bypass (CPB) to reduce postoperative bleeding due to plasmin-mediated coagulation disturbances. After the recent market withdrawal of aprotinin, a potent bovine-derived plasmin inhibitor, two lysine analogs, epsilon-aminocaproic acid and tranexamic acid are currently available for clinical use. Although the use of aprotinin recently raised major concerns about postoperative thrombosis and organ dysfunctions, there is a paucity of information on the potential complications related to lysine analogs. Using the available preclinical and clinical data, we present current perspectives on the hemostatic mechanism and potential harms of antifbirnolytic therapy related to cardiac surgery. Fibrin formation is the critical step for hemostasis at the site of vascular injury, and localized fibrinolytic activity counterbalances excess fibrin formation which might result in vascular occlusion. Inhibition of the endogenous fibrinolytic system may be associated with thrombotic complications in susceptible organs. It is thus important to understand CPB-related changes in endogenous fibrinolytic proteins (e.g., tissue plasminogen activator (tPA), plasminogen) and antifibrinolytic proteins (e.g., alpha(2)-antiplasmin).

Apicoaortic bypass (AAB), or apicoaortic conduit insertion, is a conventional surgical method that has been regaining attention due to the aging population and the increasing number of repeat surgeries. The indication for the procedure has been extended as an alternative for aortic stenosis when the usual sternotomy or aortic clamping is considered to be difficult, e.g., in patients with severe calcification of the ascending aorta (porcelain aorta), or in patients with a patent coronary artery bypass graft located adjacent to the posterior surface of the sternum. Herein, we report our recent anesthetic management of three patients undergoing AAB. Once the apicoaortic conduit is inserted, blood from the left ventricle is ejected via two routes, the narrowed native aortic valve and the apicoaortic conduit. Thus, it is necessary to elucidate any change in blood flow after the withdrawal of the extracorporeal circulation, by using intraoperative transesophageal echocardiography. Furthermore, if a rigid apical connector is not used, anastomosis of the cardiac apex and conduit is conducted under ventricular fibrillation without the infusion of cardioplegic solution; thus, patients are deemed likely to suffer increased myocardial damage. As a rigid apical connector was not used in the three present patients, the administraction of adequate catecholamines was needed for the withdrawal of the extracorporeal circulation. In addition, because those undergoing AAB often have extremely poor cardiac reserve preoperatively owing to the administration of adequate catecholamines was needed for the withdrawal of the extracorporeal circulation. In the three present patients, anesthetic management was successful, and there were no intraoperative or immediate postoperative complications.

術中経食道心エコー (IOTEE) は心臓大血管手術において必要不可欠な診断機器としてだけではなく, 心臓大血管手術麻酔の管理においても大変有用性の高いモニターであり, 拡張機能を含めたリアルタイムでの心機能や心室内容量の評価が可能である. 従来, 左心室容量の評価に肺動脈カテーテルが利用されていたが, その解析や治療方法の選択にばらつきが多いため, 近年, IOTEEが心臓大血管麻酔管理における血行動態モニターとして日常的に利用されるようになった. さらに, IOTEEの情報を心臓外科医と共有することで, 体外循環離脱時の薬剤の適切な選択や麻酔管理の戦略に応用することも可能である. IOTEEは比較的安全な機器ではあるが, 適切に使用することがIOTEEに関連する合併症の防止には肝要である. IOTEEの技術や知識を効率的に蓄積し, 実践できるようなトレーニングシステムを構築し, 客観的な評価を通して, 心臓外科医や集中治療医とこれらの情報を共有すれば, 循環器疾患に対する包括的な理解とともに, 心臓大血管手術患者に対する周術期管理の質をさらに向上させることができると考えられる.

This uncontrolled intervention study explored the effects of sauna bathing utilizing residual heat from charcoal kilns (charcoal kiln saunas) on psychological states. Forty-five volunteers (24 males and 21 females; mean age 51.9 years (S.D. 15.7) visiting a bamboo charcoal kiln in Japan participated in the study. They completed a shortened version of the Profile of Mood States (POMS) and State-Trait Anxiety Inventory (STAI) before and after charcoal kiln sauna bathing in order to determine mood and anxiety states. Six factors relating to mood were measured using the POMS: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor, Fatigue, and Confusion. The two anxiety concepts of state anxiety and trait anxiety were also measured. Changes in psychological states before and after sauna bathing were then determined. All mood scales and both manifest anxiety measures were improved after sauna bathing. Charcoal kiln sauna bathing appears to improve mood and decrease anxiety. It is a limitation of this study that this was a descriptive prospective and an uncontrolled intervention study. Further investigation of the improvement of trait anxiety is required.

非体外循環下冠動脈バイパス術(off-pump coronary-artery bypass grafting, off-pump CABG)術後に原因不明の強い全身性炎症を示し多臓器障害を呈したが,大量のコルチコステロイド投与により劇的に改善した症例を経験したので報告する。症例は72歳男性,既往症は高血圧,59歳時にCABG,70歳時に腹部大動脈瘤に対して人工血管置換術を受けた。今回増悪する狭心症に対してoff-pump CABGを受けたが,術後3日目より高熱,白血球増多,CRP高値を呈し,ショック,腎不全,高ビリルビン血症を合併した。アレルギー性疾患,感染症は否定的であった。術後12日目に,炎症の治療目的で,メチルプレドニゾロン500mgを3日間投与したところ,発熱,高炎症,多臓器障害は速やかに改善した。メチルプレドニゾロンの投与期間は25日間,その後,術後42日目に無事転棟となった。敗血症,ARDSなどの重症患者に対する高用量ステロイド投与による予後改善は現在否定されているが,今回のように全身性炎症状態のみが病態をなしている場合には有効でありうると考えた。

Purpose. The study was done to determine the characteristics and prevalence of myocardial ischemia with inverted T waves after noncardiac surgery. Methods. A list of patients who developed electrocardiogram (ECG) T-wave inversion associated with wall-motion abnormalities observed by transthoracic echocardiography (TTE) following noncardiac surgery was generated from the intensive care unit (ICU) medical records database between January 1, 1995, and December 31, 2000. The hospital records of these patients were analyzed retrospectively. Results. Among 4219 patients (2187 men and 2032 women) who were admitted to the ICU after noncardiac surgery, 13 developed myocardial ischemia with inverted T waves postoperatively. All of the patients were middle-aged or elderly women with no history of coronary artery disease; nine of them had undergone intraabdominal surgery. Characteristic ECG findings included inverted T waves in the left precordial leads, which subsequently became prominent with QT prolongation. In all of these patients, wall-motion abnormalities were observed on the anterior wall, but these resolved within 60 days of the episode. Myocardial ischemia was asymptomatic, with neither hemodynamic changes nor adverse cardiac events. Conclusion. Newly developed giant negative T waves with QT prolongation in the ECG may indicate myocardial stunning, but do not in themselves imply a poor prognosis. The marked preponderance of middle-aged and elderly women with this type of myocardial ischemia remains to be explained.

パラチオンを服毒した慢性透析患者において,持続的血液透析(continuous venovenous hemodialysis,CVVHD)下におけるpralidoxime(2-PAM)薬物動態を検討しえた。症例は67歳の男性で,週3回の血液透析を受けていた。自殺企図にてパラチオン15mlを服毒し,アトロピン,2-PAMを併用した心肺蘇生に成功の後,ICUに収容した。筋攣縮や縮瞳などの症状の改善を目安にCVVHD施行下で2-PAM0.1g・hr-1を約20時間持続投与し,血中ならびに透析廃液中の2-PAM濃度を経時的に測定してCVVHDによる排泄と薬物動態を検討した。その結果,持続投与中の血中濃度は22～23mg・ml-1と高値であり,CVVHDによるクリアランスは約8.1ml・min-1と極めて小さく,半減期が健常人の1.1時間に比べ40時間と著明に延長することが判明した。有機リン中毒に対しCVVHD施行下で2-PAMを投与する場合,体外排泄の遅延による過剰投与に十分注意する必要があると考えられた。

Transesophageal echocardiography is an invaluable hemodynamic monitoring modality. Extended and anatomically based evaluation of cardiac function with transesophageal echocardiography is essential to prompt and accurate decision-making in anesthetic management during cardiac surgery. Fractional shortening and fractional area changes are indices widely used to assess the global systolic performance of the left ventricle. Monitoring regional function using semi-quantitative scoring has been demonstrated to be a more sensitive indicator of myocardial ischemia. Assessment of left ventricular diastolic function should be performed in a systematic way, measuring transmitral flow, pulmonary venous flow, transmitral color M-mode flow propagation velocity, and mitral annulus tissue Doppler imaging. The unique anatomical features of the right ventricle make echocardiographic evaluation complicated and therefore less frequently employed. Right ventricular fractional area change, tricuspid annular plane systolic excursion, maximal systolic tricuspid annular velocity with tissue Doppler imaging, and myocardial performance index are indices successfully incorporated into intraoperative right ventricular assessment. Left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve may develop after cardiac procedures. Transesophageal echocardiography plays a central role in prevention as well as diagnosis of systolic anterior motion. Transesophageal echocardiography is extremely useful not only for detecting and locating intracardiac air, but also for guiding and evaluating the procedures to remove air. Air is likely to persist in the right and left superior pulmonary vein, left ventricular apex, left atrium, right coronary sinus of Valsalva, and ascending aorta. Accurate evaluation of cardiac function depends on performing TEE examination properly and obtaining optimal images.

An epidemiological survey on anorexia nervosa was performed in Japanese hospitals in 1985 and 1992 using a questionnaire. The reported number of patients with anorexia nervosa was 2391 from 732 institutions. From these data, the total number of anorexia nervosa patients treated in 1985 in Japanese hospitals was estimated to be about 3500–4500. In 1992, the reported number of patients with AN was 2247. The total number of AN patients treated in 1992 was estimated to be about 4500–4600, which is a little higher than that in 1985 (3500–4500). The prevalence was 3.6–4.5 per 100000 among the general population, 6.3–9.7 per 10 5 among the female population, and 25.2–30.7 per 10 5 among the 13–29 year-old female population.

Junior high school lshikawa prefecture Fukui prefecture Nagoya city Kyoto prefecture Sanin district Semor high school Sapporo city Tokyo metropolis lshikawa prefecture b ukui prefecture Nagoya city Aichl prefecture (countryside) Kyoto prcfccture (public schools) Kyoto prcfccturc (public schools) Kyoto prefccturc (prwatc schools) Ohita prcfccturc Mirushima et al. 21 153 Miruno et al. 12179 Tomita et al. 13762 Nakai et al. 5005 Ohreki et al. 18040 Nakagawa 13009 Suematsu et al. I 799 Mi7ushima et al 15250 Mwuno ct al. I2674 Tomita et al I I 084 Tomita et al. 73 553