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Bone tissue engineering has been developed using a combination of mesenchymal stem cells (MSCs) and calcium phosphate–based scaffolds. However, these complexes cannot regenerate large jawbone defects. To overcome this limitation of MSCs and ceramic scaffolds, a novel bone regeneration technology must be developed using cells possessing high bone forming ability and a scaffold that provides space for vertical bone augmentation. To approach this problem in our study, we developed alveolar bone–derived immature osteoblast–like cells (HAOBs), which have the bone regenerative capacity to correct a large bone defect when used as a grafting material in combination with polylactic acid fibers that organize the 3D structure and increase the strength of the scaffold material (3DPL). HAOB-3DPL constructs could not regenerate bone via xenogeneic transplantation in a micromini pig alveolar bone defect model. However, the autogenic transplantation of mouse calvaria–derived immature osteoblast–like cells (MCOBs) isolated using the identical protocol for HAOBs and mixed with 3DPL scaffolds successfully regenerated the bone in a large jawbone defect mouse model, compared to the 3DPL scaffold alone. Nanoindentation analysis indicated that the regenerated bone had a similar micromechanical strength to native bone. In addition, this MCOB-3DPL regenerated bone possesses osseointegration ability wherein a direct structural connection is established with the titanium implant surface. Hence, a complex formed between a 3DPL scaffold and immature osteoblast–like cells such as MCOBs represents a novel bone tissue engineering approach that enables the formation of vertical bone with the micromechanical properties required to treat large bone defects.

We examined whether orally administered octacosanol, a long-chain aliphatic saturated alcohol, improves the features of high fructose-induced metabolic syndrome in rats. Five-week-old rats were fed a high fructose diet containing 60% fructose for 3 weeks. Then, the high fructose fed rats received a daily single oral administration of octacosanol (10 or 100 mg/kg body weight) with high fructose feeding for one week. Three- or four-week high fructose feeding increased insulin resistance, serum insulin, triglyceride, total cholesterol, free fatty acids, uric acid, and lipid peroxide concentrations, and hepatic triglyceride and cholesterol contents significantly and decreased serum high-density lipoprotein cholesterol and adiponectin concentrations significantly but did not affect blood pressure and hepatic lipid peroxide and reduced glutathione contents. Four-week high fructose feeding decreased hepatic ascorbic acid content significantly. Oral administration of octacosanol (10 or 50 mg/kg body weight) to high fructose-fed rats for the last 1-week fructose diet feeding attenuated these changes except serum insulin level and insulin resistance significantly and increased hepatic reduced glutathione content significantly. The higher dose of Oct decreased hepatic lipid peroxide content significantly. These results indicate that orally administered octacosanol improves dyslipidemia, hyperuricemia, hypoadiponectinemia, and oxidative stress associated with the features of high fructose-induced metabolic syndrome rats.

Hemorrhage arising from the coronary sinus is very rare and can be lethal. It has historically been treated surgically. The present patient had coronary sinus rupture secondary to esophageal cancer and an abscess in the pericardium. Due to her poor general status, this patient was contraindicated for surgery and underwent endovascular therapy. The hemorrhage was treated by stent graft deployment and the patient was temporarily discharged. Two months later, CT showed that the stent graft was occluded by thrombosis. The patient died without hemorrhage 2.5 months thereafter.

In the present study, we examined the effect of high fructose-induced metabolic syndrome (MetS) on tissue vitamin E and lipid peroxide (LPO) levels in rats. Feeding of a diet containing 60% fructose (HFD) to Wistar rats for 2, 4, and 6 wk caused week-dependent increases in HOMA-IR score and serum insulin, triglyceride, total cholesterol, and free fatty acid concentrations. Each week HFD feeding increased serum vitamin E concentration. Six-week HFD feeding reduced vitamin E status (the serum ratio of vitamin E/triglyceride+total cholesterol). Four- and 6-wk HFD feeding increased serum LPO concentration. Two-week HFD feeding increased liver, heart, kidney, and skeletal muscle (SM) vitamin E contents and decreased white adipose tissue (WAT) vitamin E content. Four- and 6-wk HFD feeding further reduced WAT vitamin E content without affecting the increased kidney and SM vitamin E contents. Six-week HFD feeding reduced the increased liver and heart vitamin E contents below the level of non-HFD feeding. Four-week HFD feeding increased heart and WAT LPO contents. Six-week HFD feeding increased liver LPO content and further increased heart and WAT LPO contents. Kidney and SM LPO contents remained unchanged. These results indicate that HFD-rats with early MetS have increased liver, kidney, heart, and SM vitamin E contents and decreased WAT vitamin E content under unchanged tissue LPO content and vitamin E status, while HFD-fed rats with progressed MetS have both decreased liver, heart, and WAT vitamin E contents under increased tissue LPO content and disrupted vitamin E status.

To evaluate the radiopacity of contrast-loaded superabsorbent polymer microspheres (SAP-MS) under X-ray imaging. SAP-MS were suspended in contrast material (iodixanol) and the diameter change was assessed. The diameter of contrast-loaded SAP-MS in saline was measured sequentially. Radiography of the contrast-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio and visibility by multiple reader scoring. Under digital subtraction angiography, contrast-loaded SAP-MS were injected into a flow model. The flow speed was 1–10 cm/s, and images were acquired at 1–7.5 frames per second using a pulse width of 10–85 ms. Images were assessed by multiple reader scoring. The diameter of SAP-MS increased to 4.0–5.0 times its original size for approximately 15 min. The diameter of contrast-loaded SAP-MS in saline further increased by 10–30% within several minutes and returned to the previous size. Radiopacity and visibility of contrast-loaded SAP-MS decreased in 30 min after mixing with saline. Visibility was better with slow flow speed and narrow pulse width. For effective observation, contrast-loaded SAP-MS should be kept in non-diluted contrast material until use. The conditions of slower flow and use of a narrow pulse width are recommended.

This study aimed to assess the diagnostic accuracy of computed tomography (CT) and time-resolved magnetic resonance angiography (TR-MRA) for patency after coil embolization of pulmonary arteriovenous malformations (PAVMs) and identify factors affecting patency. Data from the records of 205 patients with 378 untreated PAVMs were retrospectively analyzed. Differences in proportional reduction of the sac or draining vein on CT between occluded and patent PAVMs were examined, and receiver operating characteristic analysis was performed to assess the accuracy of CT using digital subtraction angiography (DSA) as the definitive diagnostic modality. The accuracy of TR-MRA was also assessed in comparison to DSA. Potential factors affecting patency, including sex, age, number of PAVMs, location of PAVMs, type of PAVM, and location of embolization, were evaluated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CT were 82%, 81%, 77%, 85%, and 82%, respectively, when the reduction rate threshold was set to 55%, which led to the highest diagnostic accuracy. The sensitivity, specificity, PPV, NPV, and accuracy of TR-MRA were 89%, 95%, 89%, 95%, and 93%, respectively. On both univariable and multivariable analyses, embolization of the distal position to the last normal branch of the pulmonary artery was a factor that significantly affected the prevention of patency. TR-MRA appears to be an appropriate method for follow-up examinations due to its high accuracy for the diagnosis of patency after coil embolization of PAVMs. The location of embolization is a factor affecting patency. • Diagnosis of patency after coil embolization for pulmonary arteriovenous malformations (PAVMs) is important because a patent PAVM can lead to neurologic complications. • The diagnostic accuracies of CT with a cutoff value of 55% and TR-MRA were 82% and 93%, respectively. • The positioning of the coils relative to the sac and the last normal branch of the artery was significant for preventing PAVM patency.

Distribution of radiation by C-arm cone-beam computed tomography (CBCT) in the angiographic suite and effectiveness of protection devices were assessed. CBCT image of a human phantom was obtained by a rotation of 220 degrees during 8 seconds of exposure. One hundred and twelve dosimeters were placed at different positions around the beam entry site, and color maps of dose distributions were drawn for horizontal and vertical planes. The measurements showed the highest radiation dose over 600 μGy by a single CBCT image acquisition at a distance of 60 cm from the beam entry site and a height of 90 cm from the floor. The color maps demonstrated the dose distribution to be more intense at the bilateral directions of the phantom. With the use of a ceiling-mounted transparent lead-acryl screen and a table-suspended lead curtain, the doses were reduced by 45–92 % at a direction of 210 degrees and a distance of 120 cm.

Purpose To assess the safety and effectiveness of polidocanol sclerotherapy combined with transarterial embolization using a liquid adhesive agent (n-butyl cyanoacrylate, NBCA) for treatment of extracranial arteriovenous malformations (AVMs). Materials and Methods Twenty-three patients with symptomatic AVMs in the head and neck (6), upper (7) and lower extremity (10) with a mean age of 42 years (range 4–74) treated with polidocanol sclerotherapy were retrospectively assessed. AVMs were classified according to the angiographic morphology of the nidus. There were 2 type I, 6 type II, 6 type IIIa and 9 type IIIb. Arterial embolization using NBCA was performed to reduce arterial flow before sclerotherapy. Polidocanol mixed with contrast material or carbon dioxide was delivered by percutaneous direct puncture. Results Treatment was successfully performed in all patients. In the mean follow-up period of 38 months, symptoms resolved or improved in 20/23 patients (87.0%). AVMs were devascularized 100% in 2 patients, 76–99% in 13, 50–75% in 7 and

To determine the incidence and risk factors of renal dysfunction after abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). The study consisted of 227 patients treated with EVAR and 90 with TEVAR for aortic aneurysms. Parameters, including patients’ background factors, preoperative renal function, contrast dose and aortic wall irregularity on CT images were assessed in relation to postoperative renal dysfunction. Deterioration of renal function was observed in 33 of 218 patients (15.1%) after EVAR and in 7 of 79 (8.9%) patients after TEVAR. Hemodialysis was required in one patient after EVAR. In EVAR, renal dysfunction correlated with age (p = 0.034) and occlusion of accessory renal artery (p = 0.0001). In TEVAR, renal dysfunction correlated with age (p = 0.021), contrast dose (p = 0.042) and irregularity of the descending aortic wall (p = 0.023). In a multiple regression analysis, postoperative renal dysfunction was correlated with occlusion of accessory renal artery (p = 0.0003) after EVAR, and age (p = 0.02), contrast dose (p = 0.026) and irregularity of the descending aortic wall (p = 0.042) after TEVAR. Occlusion of accessory renal artery in EVAR, and age, contrast dose and irregularity of the descending aortic wall in TEVAR were considered to be predictors of postoperative renal dysfunction.

本研究は就職後6ヶ月目の新人看護師の離職願望に影響する要因を明らかにし、離職防止対策への示唆を得ることを目的とする。2012年9月に3都府県の新人看護師に質問紙調査を実施し268名を分析対象とした。離職願望を従属変数、基本属性、コーピング特性、ストレッサー、ストレス反応、ストレス緩衝因子を独立変数とする2項ロジスティック回帰分析を行った。対象者の平均年齢は24.9歳であった。看護師離職願望と病院離職願望のどちらもとも「処理可能感」と負の関連、「職場の対人関係でのストレス」、「疲労感」と正の関連があった。看護師離職願望は「有意味感」と負の関連があり、病院離職願望は「仕事のコントロール」と負の関連があった。新人看護師が離職することなく職業を継続するための支援として、新人看護師がチームの一員として受け入れられ、スタッフと良好な人間関係が確立され、自己の実践能力が有効であると感じることが重要である。, Aims ： This study clarifies how novice nurses’ desire to quit their jobs six months after being hired is correlated with sense of coherence (SOC), coping, stressors, stress response, and stress buffer to suggest measures for preventing such turnover.Methods ： Data were collected in September 2012. Self-administered questionnaires were distributed to 268 novices. Logistic regression analysis was performed using “quit being a nurse” and “leave my hospital” as dependent variables and basic attributes, SOC, coping, stressors, stress response, and stress buffer as independent variables.Results ： 268 participants’ mean age was 24.9 years. Novices thought of quitting nursing accounted for 64.2％; 51.5％ of resigning from the hospital. The factors correlated with “quit being a nurse” included “meaningfulness,” “manageability,” “stress in interpersonal relationships in the workplace,” and “feeling of fatigue.” Moreover, factors correlated with “leave my hospital” included “manageability,” “stress in interpersonal relationships in the workplace,” “feeling of fatigue,” and “degree of control in your job.” Discussion : To provide support for newly graduated nurses to continue in the profession without quitting, it is important for the newly graduated nurse to be accepted as a member of the team, for good human relations to be established, and for practical abilities to be enabled, with supervisors providing concrete, practical support to this end.

We have developed a method to calculate a secret key rate of a continuous-variable quantum-key-distribution scheme using four coherent states and postselection for a general model of Gaussian attacks. We assume that the transmission line and detection process are described by a pair of Gaussian channels. In our analysis, while the loss and noise on the transmission line are induced by an eavesdropper, Eve, who can replace the transmission line with a lossless and noiseless optical fiber, she is assumed inaccessible to the detection process. By separating the transmission noise and detection noise, we can always extract a larger key compared with the case that all loss and noises are induced by an eavesdropper's interference. An asymptotic key rate against collective Gaussian attacks can be determined numerically for the given channels' parameters. The improvement of the key rates turns out to be more significant for the reverse-reconciliation scheme., 9 pages, 4 figures

To evaluate the embolic effect and the safety of transarterial embolization (TAE) using n-butyl-2-cyanoacrylate (NBCA) in a prospective multicenter trial. This study was an open-label, multicenter, phase II trial. The inclusion criteria were (1) active bleeding or pseudoaneurysm, (2) true aneurysm, (3) arteriovenous malformation (except cerebral lesion), (4) arteriovenous fistula, or (5) need for arterial distribution before transarterial treatment. Selective TAE with NBCA diluted 2–10 times was performed. The primary endpoint was the success rate of embolization with a per-patient analysis based on the angiographic findings. Secondary endpoints were safety, evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) version 4, and the success rate of embolization with a per-vessel calculation. Sixty-five patients were initially enrolled, but due to protocol violation in two patients, efficacy was ultimately analyzed in 63 patients (103 vessels) and safety was analyzed in 64 patients. The success rate per patient was 98.4% (62/63; 95% confidence interval (CI), 91.5–100.00), and the success rate per vessel was 99.0% (102/103; 95% CI, 94.7–100.0). Adverse events of grade 3 or above based on CTCAE version 4 occurred in 22/64 patients (34.4%). Twelve intraoperative or postoperative adverse events grade 3 or above, which may have been related to embolization using NBCA, occurred in 11/64 patients (17.2%). Three patients died after embolization using NBCA, but their deaths were unrelated to TAE. In this prospective multicenter clinical trial, the efficacy of TAE using NBCA was 98.4% and adverse events were clinically acceptable. Level 3b.

The story “Ginga-Tetsudo-No-Yoru (Night on the Milky Way Train)” is a very famous literary work and is said to be one of the masterpieces of Kenji Miyazawa (hereinafter, Kenji). By many critics its theme has been discussed from various viewpoints, including the similarity to the Orpheus myth, the birth of a poet who has returned through the death world, the corpus of Kenjiʼs literature inquiring the fundamental way of life, and the religious allegory of Kenjiʼ s world view. This work has ʻthe Early Form (the third version)ʼ other than ʻthe Last Form (the fourth version).ʼ The former, which is known little, seems to reflect Kenjiʼs religious view more than the latter. In this essay, the meaning of the change from the ʻthe Early Formʼ to ʻthe Last Formʼ is considered first. By many critics this has also been disputed from various viewpoints such as the disappearance of the most important point in ʻthe Early Form,ʼ the emphasis on the solitude of Giovanni, the main character of this work, the subsistence of the ethical motif, the emphasis on the austerities as Bodhisattva, and so on. The writer remarks that the reason of its change is due to Kenjiʼs view of searching after the point of contact between religion and science and time passing after the death of Kenjiʼs sister, Toshiko. Second, what Kenji intended to tell through this work is viewed. Even if a person does not personify the religious truth, he can live peacefully by relating to the deep layer of his psyche, ʻTamashii (soul),ʼ and getting the support from it. Last, it is illustrated that the mental condition of Giovanni, reached through the voyage is deeply related to that of the client at the end of his psychotherapy. And the writer states that the significance of psychotherapy lies in the therapistʼs accompanying his client to let him follow the mental process similar to that of Giovanni.

This study was designed to assess the safety and effectiveness of ethanolamine oleate (EO) sclerotherapy combined with transarterial embolization using a liquid adhesive agent (n-butyl cyanoacrylate, NBCA) for treatment of extracranial arteriovenous malformations (AVMs).Twenty-four patients with symptomatic AVMs in the head and neck (n = 15), extremity (n = 5), and trunk (n = 4) with a mean age of 44 years (range, 18-78) treated with EO sclerotherapy were retrospectively assessed. AVMs were classified according to the angiographic morphology of the nidus. There were 7 type II (arteriolovenous fistulae), 6 type IIIa (arteriolovenulous fistulae with nondilated fistula), and 11 type IIIb (arteriolovenulous fistulae with dilated fistula). Transarterial embolization using NBCA was performed to reduce arterial flow before sclerotherapy. EO mixed with contrast material was delivered by percutaneous direct puncture or by catheterization into the draining vein under balloon occlusion.Three (13%) of 24 patients were cured, 17 (71%) had partial remission, and 4 (16%) no remission. Treatment was considered effective (cure and partial remission) in 20 patients (83%). Four patients (16%) experienced transient minor complications, including self-healing skin ulcer (n = 3) and localized deep venous thrombosis (n = 1). There were no major complications.EO sclerotherapy combined with transarterial embolization using NBCA is safe and effective for treating extracranial AVMs with an acceptable risk of minor complications.

We examined whether water-immersion restraint stress (WIRS) disrupts nonenzymatic antioxidant defense systems through ascorbic acid depletion in the adrenal gland of rats. Rats were exposed to WIRS for 0.5, 1.5, 3 or 6 h. WIRS increased serum adrenocorticotropic hormone, corticosterone and glucose concentrations and adrenal corticosterone content at each time point. WIRS increased adrenal lipid peroxide content at 3 and 6 h, and the increase was twofold higher than the unstressed level at 6 h. WIRS decreased adrenal ascorbic acid content at each time point, and the decrease reached one-third of the unstressed level at 6 h. WIRS increased adrenal reduced glutathione content at 0.5 and 6 h but reduced that content to half of the unstressed level at 6 h. WIRS increased adrenal α-tocopherol content at 1.5 h but returned that content to the unstressed level thereafter. When rats with 6 h of WIRS was orally preadministered with l-ascorbic acid (250 mg/kg), WIRS-induced changes in adrenal lipid peroxide, ascorbic acid and reduced glutathione contents were attenuated without any change in stress response. These results indicate that WIRS disrupts nonenzymatic antioxidant defense systems through rapid and continuous ascorbic acid depletion in the adrenal gland of rats.

In this study, we examined whether melatonin improves metabolic syndrome induced by high fructose intake in male Wistar rats. Feeding of a diet containing 60% fructose (HFD) for 4 or 6 wk caused increased serum insulin, triglyceride, total cholesterol, free fatty acids, uric acid, leptin, and lipid peroxide concentrations as well as hepatic triglyceride and cholesterol concentrations, and relative intra-abdominal fat and liver weights. The 4- or 6-wk HFD feeding reduced serum high-density lipoprotein cholesterol and adiponectin concentrations. The 6-wk HFD feeding increased serum tumor necrosis factor-α concentration and hepatic lipid peroxide concentration and lowered hepatic reduced glutathione concentration. Daily intraperitoneal administration of melatonin (1 or 10 mg/kg body weight), starting at 4-wk HFD feeding, attenuated these changes at 6-wk HFD feeding more effectively at its higher dose than at its lower dose. In an oral glucose tolerance test, rats with 4- or 6-wk HFD feeding showed higher serum insulin response curve and normal serum glucose response curve when compared with the corresponding animals that received the control diet. The 4- or 6-wk HFD feeding caused insulin resistance, judging from the scores of HOMR-IR and QUICKI, which are indices of insulin resistance. The daily administered melatonin (1 or 10 mg/kg body weight) ameliorated the higher serum insulin response curve in the oral glucose tolerance test and insulin resistance at 6-wk HFD feeding more effectively at its higher dose than at its lower dose. These results indicate that melatonin improves metabolic syndrome induced by high fructose intake in rats.

Angiotensin II receptor blocker (ARB) as a first-line drug for hypertension in diabetes often fails to control blood pressure adequately. The objective of the study was to evaluate the effect of amlodipine combined therapy on home blood pressure (HBP) useful for management of hypertension.A total of 263 type 2 diabetes with hypertension refractory to standard dose of ARB were randomized to increased ARB regimen (n=132) or amlodipine combination regimen (n=131). The primary endpoint was change in morning HBP at 1 year. The combination regimen significantly lowered morning HBP than the increased ARB regimen (158.2/82.5 mmHg in the combination regimen, 157.3/84.4 mmHg in the increased ARB regimen, at baseline; 142.7/76.3 vs. 155.0/83.1 mmHg, respectively, P0.001 for both, at 8 weeks; 139.6/74.6 vs. 149.1/78.1 mmHg, respectively, P0.001 for systolic and P=0.010 for diastolic, at 1 year). The combination regimen showed significantly higher rates of achieving target morning HBP at 8 weeks (11.3% vs. 2.7%, P=0.015). In the combination regimen, estimated glomerular filtration rate declined slower, and carotid intima-media thickness decreased in contrast to the increased ARB regimen.In type 2 diabetes patients with hypertension refractory to standard dose of ARB, the amlodipine combination regimen provides superior antihypertensive effect on HBP to the increased ARB regimen, and beneficial effects on reducing risks of cardiovascular events.

Bone marrow derived human mesenchymal stem cells (hMSCs) have attracted great interest from both bench and clinical researchers because of their pluripotency and ease of expansion ex vivo. However, these cells do finally reach a senescent stage and lose their multipotent potential. Proliferation of these cells is limited up to the time of their senescence, which limits their supply, and they may accumulate chromosomal changes through ex vivo culturing. The safe, rapid expansion of hMSCs is critical for their clinical application. Chromosomal aberration is known as one of the hallmarks of human cancer, and therefore it is important to understand the chromosomal stability and variability of ex vivo expanded hMSCs before they are used widely in clinical applications. In this study, we examined the effects of culturing under ambient (20%) or physiologic (5%) O2 concentrations on the rate of cell proliferation and on the spontaneous transformation of hMSCs in primary culture and after expansion, because it has been reported that culturing under hypoxic conditions accelerates the propagation of hMSCs. Bone marrow samples were collected from 40 patients involved in clinical research. We found that hypoxic conditions promote cell proliferation more favourably than normoxic conditions. Chromosomal aberrations, including structural instability or aneuploidy, were detected in significantly earlier passages under hypoxic conditions than under normoxic culture conditions, suggesting that amplification of hMSCs in a low-oxygen environment facilitated chromosomal instability. Furthermore, smoothed hazard-function modelling of chromosomal aberrations showed increased hazard after the fourth passage under both sets of culture conditions, and showed a tendency to increase the detection rate of primary karyotypic abnormalities among donors aged 60 years and over. In conclusion, we propose that the continuous monitoring of hMSCs will be required before they are used in therapeutic applications in the clinic, especially when cells are cultured under hypoxic conditions.

Background Randomized trials have established statins as an agent for prevention of coronary heart disease (CHD). The purpose of this study was to assess the hypothesis that standard-dose statin therapy has a beneficial effect in normocholesterolemic diabetic patients with CHD. Methods and results A prospective, randomized, open, blinded-endpoint trial was conducted from 2002 to 2004 at 55 hospitals in Japan to evaluate the effect of statins on subsequent cardiovascular events. A total number of 1,016 CHD patients (301 patients with type 2 diabetes mellitus [DM] and 715 non-DM patients) with serum total cholesterol levels of 180-240 mg/dl were randomly divided into non-statin and statin treatments. Clinical parameters were comparable between DM and non-DM groups. Serum low-density lipoprotein (LDL)-cholesterol levels were equally decreased after statin treatment in the 2 groups. Statin treatment improved prognosis in both the DM and non-DM groups; however, the number needed to treat (NNT) and relative risk reduction (RRR) were remarkable especially in the DM group (NNT=8, RRR=67%) compared with the non-DM group (NNT=30, RRR=24%). Conclusions Standard-dose statin therapy provides incremental clinical benefits in DM patients with normal cholesterol levels compared with non-DM patients. The data suggest that DM patients may enjoy the pleiotropic effects of statins, independent of the LDL-cholesterol lowering effects of these agents.

We examined whether octacosanol, the main component of policosanol, attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride (CCl(4)). In rats intoxicated with CCl(4) (1 ml/kg, i.p.), the activities of serum transaminases increased 6 h after intoxication and further increased at 24 h. In the liver of CCl(4)-intoxicated rats, increases in lipid peroxide (LPO) concentration and myeloperoxidase activity and decreases in superoxixde dismutase activity and reduced glutathione (GSH) concentration occurred 6 h after intoxication and these changes were enhanced with an increase in xanthine oxidase activity and a decrease in catalase activity at 24 h. Octacosanol (10, 50 or 100 mg/kg) administered orally to CCl(4)-intoxicated rats at 6 h after intoxication attenuated the increased activities of serum transaminases and the increased hepatic myeloperoxidase and xanthine oxidase activities and LPO concentration and the decreased hepatic superoxide dismutase and catalase activities and GSH concentration found at 24 h after intoxication dose-dependently. Octacosanol (50 or 100 mg/kg) administered to untreated rats decreased the hepatic LPO concentration and increased the hepatic GSH concentration. These results indicate that octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in CCl(4)-intoxicated rats.

Liver injury with cholestasis appeared 24 h, but not 12 h, after treatment of rats with alpha-naphthylisotiocyanate (ANIT) (75 mg/kg, i.p.). Serum total, free, and estrified cholesterol levels were unchanged at 12 h after ANIT treatment but increases in serum total and free cholesterol levels occurred at 24 h. Melatonin (100 mg/kg, p.o.) administered at 12 h after ANIT treatment significantly attenuated these increases at 24 h after the treatment. Thus, melatonin attenuates the disruption of serum cholesterol status with liver injury formation in rats treated with ANIT.

We examined how oxidative stress and cell damage develop in the liver of rats subjected to water-immersion stress (WIRS). In rats subjected to WIRS for 1.5, 3 or 6 h, serum alanine aminotransferase and aspartate aminotransferase activities increased time-dependently. In the liver tissue, vacuolization and apoptosis occurred at 1.5 h of WIRS and vacuolization further developed without further appearance of apoptosis at 3 h or 6 h. Serum lipid peroxide (LPO) and NOx (nitrite/nitrate) concentrations increased at 3 h of WIRS and these increases were enhanced at 6 h. In liver tissue, increases in LPO and NOx concentrations and myeloperoxidase activity and decreases in ascorbic acid and reduced glutathione concentrations and superoxide dismutase activity occurred at 3 h of WIRS and these changes were enhanced at 6 h, although vitamin E concentration and xanthine oxidase activity were unchanged. These results indicate that oxidative stress in the liver of rats with WIRS develops after the appearance of cell damage in the tissue, and suggests that oxidative stress is caused through disruption of the antioxidant defense system and increases in NO generation and neutrophil infiltration in the liver, which may contribute to the progression of cell damage in the tissue.

Background Statins are widely used to reduce blood levels of low-density lipoprotein-cholesterol (LDL-C). Each statin has unique pharmacokinetic properties; lipophilicity is one such property and relates to tissue selectivity. Methods and Results The Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) trial evaluated the effect of discretional statin treatment initiated within 96 h after onset of acute myocardial infarction (AMI) in Japanese patients. To clarify whether statin lipophilicity affects prognosis, a post hoc analysis of the MUSASHI-AMI database was performed. Patients who were assigned to receive statin were separated into 2 groups according to the lipophilicity of the statins they were administered: lipophilic statins (atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) or hydrophilic statins (pravastatin; HS group; n=110). There was no difference in baseline LDL-C concentrations between the 2 groups. Although LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069), acute coronary syndrome events tended to occur less frequently (3.6% vs 9.9%; p=0.0530) and the incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS than LS groups. Conclusions In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events. (Circ J 2007; 71: 1348 - 1353)

We examined whether xanthine oxidase (XO)-derived reactive oxygen species (ROS) contribute to the development of D-galactosamine (D-GaIN)-induced liver injury in rats. In rats treated with D-GaIN (500 mg/kg), liver injury appeared 6 h after treatment and developed until 24 h. Hepatic XO and myeloperoxidase activities increased 12 and 6 h, respectively, after D-GalN treatment and continued to increase until 24 h. D-GalN-treated rats had increased hepatic lipid peroxide (LPO) content and decreased hepatic reduced glutathione (GSH) and ascorbic acid contents and superoxide dismutase (SOD), catalase and Se-glutathione peroxidase (Se-GSHpx) activities at 24 h, but not 6 h, after treatment. Allopurinol (10, 25 or 50 mg/kg) administered at 6 h after D-GalN treatment attenuated not only the advanced liver injury and increased hepatic XO activity but also all other changes observed at 24 h after the treatment dose-dependently. These results suggest that XO-derived ROS contribute to the development of D-GaIN-induced liver injury in rats.

To evaluate the results of uterine artery embolization (UAE) for symptomatic uterine leiomyoma by use of porous gelatin particles (PGP) in comparison with conventional hand-cut gelatin sponge particles. One hundred and fifteen consecutive patients who had undergone UAE were retrospectively assessed. The first 64 patients were treated with hand-cut gelatin sponge and the last 51 with PGP. Extent of infarction, volume reduction of the dominant leiomyoma on magnetic resonance (MR) imaging, and change in symptoms were assessed. UAE was successfully performed for all patients. No major complications were observed. MR images one month after UAE showed that the mean extent of infarction of the dominant leiomyoma was 97 % for patients treated with PGP and 96 % for those treated with hand-cut gelatin sponge. Volume reductions of the dominant leiomyoma after 3, 6, 12, and 24 months were, respectively, 45, 56, 62, and 66 % for use of PGP and 45, 57, 63, and 68 % for use of hand-cut gelatin sponge. Symptoms including heavy menstrual bleeding, heavy menstrual pain, and abdominal heaviness had improved by 95–100 % at 12 months. There was no difference between the two groups. UAE with PGP is safe, and as effective as conventional gelatin sponge particles.

We examined whether Saikokeishito extract (TJ-10), a traditional Japanese herbal medicine, exerts a therapeutic effect on alpha-naphthylisothiocyanate (ANIT)-induced liver injury in rats through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. In rats treated once with ANIT (75 mg/kg, i.p.), liver injury with cholestasis occurred 24 h after treatment and progressed at 48 h. When ANIT-treated rats orally received TJ-10 (0.26, 1.3 or 2.6 g/kg) at 24 h after the treatment, progressive liver injury with cholestasis was significantly attenuated at 48 h after the treatment at the dose of 1.3 or 2.6 g/kg. At 24 h after ANIT treatment, increases in hepatic lipid peroxide and reduced glutathione contents and myeloperoxidase activity occurred with decreases in hepatic superoxide dismutase and glutathione reductase activities. At 48 h after ANIT treatment, these changes except for reduced glutathione were enhanced with decreases in catalase, Se-glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. TJ-10 (1.3 or 2.6 g/kg) post-administered to ANIT-treated rats attenuated these changes found at 48 h after the treatment significantly. These results indicate that TJ-10 exerts a therapeutic effect on ANIT-induced liver injury in rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue.

Statins have been shown to prevent coronary artery disease and to preserve left ventricular function in dilated cardiomyopathy. We hypothesized that early use of statins would decrease cardiovascular events, including heart failure in patients with acute myocardial infarction (AMI). To examine the effect of statins in Japanese patients with AMI, a prospective, randomized, open-label trial was conducted in 486 patients with normal total cholesterol levels. Patients were randomly assigned to receive any available statin (n = 241) within 96 hours of AMI onset or no statin (n = 245) and were followed for up to 24 months. The primary end point was a composite of cardiovascular death, nonfatal AMI, recurrent symptomatic myocardial ischemia, congestive heart failure, and stroke. Event rate for the primary end point was lower in the statin group than in the nonstatin group (6.1% vs 11.4%, p = 0.0433). The statin group had a lower risk of congestive heart failure and symptomatic myocardial ischemia (p = 0.0154 and 0.0264, respectively). In conclusion, early lipid-lowering therapy with statins decreases recurrent cardiovascular events, in particular, congestive heart failure.

Until the idea of the “health promotion” was advocated by the Ottawa charter in 1986, the purpose of health care was only seen as the improvement of an individual's health. Up to that time, social environmental factors and the processes involved in carrying out health projects and physical fitness promotion — its practice, evaluation, public participation and so on — had not been appreciated. In keeping with the basic concept of health promotion, and with the effort of individuals, it is essential to establish public policy for the support of health care. This implies that specialist groups, including administration, must respond to the demands of health care and physical fitness promotion. Furthermore, we can say that health care and physical fitness promotion must be carried out with regard for social policy. However, the ideals of health promotion have not been achieved so far. We examined the actual status of Health Japan 21 health promotion in two surveys, a basic survey in October 2003 and the main examination in October 2004. All local governments were examined in order to propose a community system for promoting life function and social participation for the elderly. We analyzed and assessed the questionnaire including 1) the planning and practice of Health Japan 21 strategies (a concrete assessment of the status of each of the nine items and of the details of each sub-item of plans in administrative divisions, government-designated major cities, special districts, and cities, towns, and villages); 2) the level of recognition of public participation in and opinion of projects, during execution and evaluation, and the level of cooperation with civilian organizations; 3) ways of spreading awareness of projects; 4) project evaluations (intermediate evaluation); and 5) the importance of and prospects for the future of health care Health Japan 21 projects. It is thought that research into these factors will become a reference point for an intermediate evaluation of Health Japan 21, and will help solve various problems facing health improvement in our country.

Introduction Inflammation is a key process in atherosclerotic formation. Structural changes in the carotid arterial wall including detection of focal plaques are measured as the intima-media thickness (IMT) providing an index of atheroma. Coronary arterial plaques may be considered as vascular structural changes. Distensibility of the arteries can be assessed by functional changes in pulse wave velocity (PWV) providing an index of sclerosis. Adiponectin has potential antiatherosclerotic properties. We hypothesized that adiponectin was associated with atherosclerotic vascular changes involved in inflammation. Materials and methods We enrolled 142 patients with coronary artery disease (CAD) and 108 control patients, matched for age, sex, and body mass index (BMI) with CAD patients. We investigated the relationship between adiponectin, C-reactive protein (CRP), and atherosclerotic vascular changes. Results CRP ( p =0.0009), high-density lipoprotein cholesterol (HDL-C; p =0.02), and IMTmax ( p =0.02) were determinants of adiponectin independent of glucose intolerance ( p =0.0001), BMI ( p =0.002), and CAD ( p =0.03), all of which have been significantly associated with adiponectin ( r =0.38). Adiponectin was not correlated with PWV. CRP, glucose intolerance, and HDL-C that correlated with adiponectin were inversely correlated with IMTmax and CAD. CRP was negatively correlated with HDL-C ( r =−0.24, p =0.0002) and positively correlated with glucose intolerance ( r =0.15, p =0.01). Conclusions Adiponectin has a close relationship with CRP, IMTmax, CAD, HDL-C, and other established risk factors. CRP, glucose intolerance, and HDL-C are common mediators between adiponectin and atheromatous vascular changes, which are contrary to each other. The exacerbation of atherogenesis may be involved in a decrease of adiponectin through abnormal glyco- and lipid-metabolism by promoting inflammation.

The preventive effect of teprenone (6,10,14,18-teramethyl-5,9,13,17-nonadecatetaene-2-one), an anti-ulcer drug, on acute gastric mucosal lesion progression was examined in rats with a single intraperitoneal (i.p.) injection of compound 48/80 (0.75 mg/kg). Teprenone (20, 100 or 200 mg/kg), which was orally administered 0.5 h after compound 48/80 treatment at which time gastric mucosal lesions appeared, prevented gastric mucosal lesion development at 3 h after the treatment dose-dependently. Gastric mucosal tissues of compound 48/80-treated rats showed increases in myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreases in Se-glutathione peroxidase activity and hexosamine and vitamin E contents at 3 h after the treatment. Post-administered teprenone attenuated all these changes dose-dependently. These results indicate that teprenone prevents acute gastric mucosal lesion progression in compound 48/80-treated rats possibly by suppressing gastric mucus depletion, neutrophil infiltration and oxidative stress in the gastric mucosal tissue.

We reported that melatonin prevents the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rats possibly by attenuating enhanced lipid peroxidation and reduced glutathione depletion. Herein, we examined the effect of melatonin on the changes in hepatic reactive oxygen species (ROS) metabolism in rats with a single intraperitoneal injection of CCl4 (1.6 g/kg body weight); the intent was to clarify the therapeutic mechanism of the indoleamine on CCl4-induced acute liver injury. Rats with and without CCl4 treatment received a single oral dose of melatonin (10, 50 or 100 mg/kg body weight) 6 hr after CCl4 treatment. Hepatic concentrations of ascorbic acid (ASC) and vitamin E (VE) and hepatic activities of superoxide dismutase (SOD), catalase (CAT), Se-glutathione peroxidase (Se-GSH-Px), glutathione reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PDH), and xanthine oxidase (XO) were determined 6 and 24 hr after CCl4 treatment. The liver of CCl4-treated rats showed reductions in ASC concentrations, and SOD activity and an increase in G-6-PDH activity at 6 hr after treatment and further decreases in ACS concentrations and SOD activity and also further increase in G-6-PDH activity in addition to decreases in CAT and GSSG-R activities and increases in VE concentrations and XO activity at 24 hr after treatment. Melatonin attenuated the reductions in hepatic ASC concentrations and SOD, CAT and GSSG-R activities and the increase in hepatic XO activity in a dose-dependent manner without affecting either hepatic Se-GSH-Px activity or the increased hepatic VE concentration and G-6-PDH activity at 24 hr after CCl4 treatment. No dose of melatonin influenced hepatic ACS and VE concentrations and SOD, CAT, Se-GSH-Px, G-6-PDH, and XO activities in CCl4-untreated rats. These results indicate that melatonin postadministered at pharmacological doses prevents the disruption of hepatic ROS metabolism associated with ASC, SOD, CAT, GSSG-R, and XO, in addition to reduced glutathione, in CCl4-treated rats.

It is known that o-, m- and p-cresols exert a toxic effect on rat liver cells. However, there is little information on the mechanism for the hepatotoxicity of cresols. We, therefore, investigated the effects of o-, m-, and p-cresols on the bioenergetic system using isolated rat liver mitochondria. When o-, m- or p-cresol was added to liver mitochondria with glutamate or succinate at concentrations of 0.3 to 6.0 mumol/mg protein, each cresol isomer reduced the rate of state 3 respiration dose-dependently. Three cresol isomers at 6.0 mumol/mg protein each inhibited state 3 respiration in liver mitochondria with glutamate or succinate by about 60 or 20%, respectively. The three isomers affected NAD- and succinate-linked respirations in liver mitochondria, by which the respiratory control ratio was dose-dependently attenuated. The inhibitory effects of o-, m- and p-cresols on the NAD-linked respiration were stronger than those on the succinate-linked respiration. However, three cresol isomers had little effect on the P/O ratio in liver mitochondria with glutamate or succinate. Three cresol isomers at 15 mumol/mg protein each induced the swelling in the absence of Ca2+ in medium and accelerated the swelling of liver mitochondria in the presence of Ca2+ in medium. These results indicate that o-, m- and p-cresols inhibit liver mitochondrial respiration and induce or accelerate the swelling of liver mitochondria, and suggest that liver mitochondria may be one of the targets for the hepatotoxic actions of cresols.

The protective effects of betamipron (BP, N-benzoyl-beta-alanine) against nephrotoxicity induced by repeated cisplatin injections were examined. The ratio of the kidney weight to body weight and the lipid peroxide level after treatment with cisplatin plus BP tended to be larger and lower than those after treatment with cisplatin plus alkaline solution, respectively. The blood urea nitrogen, serum creatinine and glutathione levels in the animals treated with cisplatin plus BP differed significantly from those in the animals treated with cisplatin plus alkaline solution. Furthermore, the mechanism of the preventive effects of BP was analyzed for cisplatin-induced nephrotoxicity. The concentration of cisplatin in the renal cortex significantly decreased with concomitant BP. BP inhibited the uptake of cisplatin into the renal cortex in a competitive manner in the same way as an anionic transport inhibitor, probenecid. The treatment with BP appears to be useful for the renal toxicity induced by repeated cisplatin administration.

The protective effects of betamipron (BP, N-benzoyl-beta-alanine) on the nephrotoxicity of cisplatin were examined as indicated by body weight gain, ratio of kidney weight to body weight, blood urea nitrogen and serum creatinine levels in tumor-bearing rats. The results showed clearly that administration of BP 1 h after cisplatin treatment affords protection against the nephrotoxicity of cisplatin. Furthermore, the addition of BP to cisplatin had no apparent effect on the efficacy of cisplatin against Walker 256 carcinosarcoma cells in rats. In addition, no observed significant difference in plasma cisplatin concentration between cisplatin with alkaline solution and cisplatin with BP may be partly attributed to the decrease in the cisplatin exsorption to the intestine and its excretion to bile, and to an increase in cisplatin excretion to the urine.

The toxic effect of rubroskyrin, a modified bis-anthraquinone pigment fromPenicillium islandicum Sopp, on mitochondrial respiration has been studied by using isolated rat liver mitochondria, comparing with those of luteoskyrin and rugulosin which are well knownislandicum toxins. It was found that rubroskyrin exerted an uncoupling effect on mitochondrial respiration, abating the respiratory control ratio (RCR) by a dose dependent manner (UD50: 10 μM) and markedly depressed state 3 respiration at high concentrations, whereas such respiration-impairing effects of luteoskyrin and rugulosin were not detected at the concentrations tested (max. 35 μM). The involvement of redox-reaction was not detected in the uncoupling effect of the quinone pigment, rubroskyrin.Spectroscopic study at various pHs revealed that rubroskyrin possessed a pK value within the range of physiological pH, suggesting that rubroskyrin is a weak acid-type uncoupler capable of conducting protons across mitochondrial inner membrane.

Prophylactic effects of N-benzoyl-beta-alanine (betamipron, BP), one of a series of N-acyl amino acids, were examined against cisplatin-induced nephrotoxicity. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with an i.p. BP dose given at various times and various doses. Rats were sacrificed 5 days after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Preliminary results suggest that treatment with BP is an effective means of protection against cisplatin-induced nephrotoxicity. Combination with BP reduced the weight loss following treatment with cisplatin. The ratios of the kidney and liver weights to the body weight in the animals treated with cisplatin followed later with BP are significantly different (p0.05) from those in the animals that received only cisplatin. The BUN and serum Cr levels in the animals treated with cisplatin followed from -1 to 4 hr, and from -4 to 4 hr later with 250 mg/kg BP dose and followed 1 hr later with from 250 to 1000 mg/kg, and from 250 to 2000 mg/kg BP doses differed significantly (p0.05) from those in the animals that received only cisplatin. Histological analysis of the kidneys confirmed the protective effect of BP.

The protective effects of N-benzoyl amino acids (NAAs) and piperacillin (PIP), anionic transport inhibitors, against the nephrotoxicity of cisplatin were examined in rats. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with i.p. NAAs or PIP. Rats were sacrificed on day 5 after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Treatments with NAAs were an effective means of protection against cisplatin-induced nephrotoxicity. The combination of cisplatin with NAAs containing a short and straight chain significantly suppressed (p < 0.05) the changes in body, kidney and liver weights, BUN and serum Cr. Further, betamipron (BP) at a 2000 mg/kg dose showed no apparent effect on the body, kidney and liver weights, BUN and serum Cr levels in rats. The combination of cisplatin with PIP caused a loss in body weight. The protective effects of PIP against cisplatin toxicity are inferior to those of BP when compared at 250 mg/kg doses.

BACKGROUND: In people with chronic illnesses, self-management education can reduce anxiety and depression. Those benefits, however, decay over time. Efforts have been made to prevent or minimize that "decay of impact", but they have not been based on information about the decay's characteristics, and they have failed. Here we show how the decay's basic characteristics (prevalence, timing, and magnitude) can be quantified. Regarding anxiety and depression, we also report the prevalence, timing, and magnitude of the decay. METHODS: Adults with various chronic conditions participated in a self-management educational program (n = 369). Data were collected with the Hospital Anxiety and Depression Scale four times over one year. Using within-person effect sizes, we defined decay of impact as a decline of ≥0.5 standard deviations after improvement by at least the same amount. We also interpret the results using previously-set criteria for non-cases, possible cases, and probable cases. RESULTS: Prevalence: On anxiety, decay occurred in 19% of the participants (70/369), and on depression it occurred in 24% (90/369). Timing: In about one third of those with decay, it began 3 months after the baseline measurement (6 weeks after the educational program ended). Magnitude: The median magnitudes of decay on anxiety and on depression were both 4 points, which was about 1 standard deviation. Early in the follow-up year, many participants with decay moved into less severe clinical categories (e.g., becoming non-cases). Later, many of them moved into more severe categories (e.g., becoming probable cases). CONCLUSIONS: Decay of impact can be identified and quantified from within-person effect sizes. This decay occurs in about one fifth or more of this program's participants. It can start soon after the program ends, and it is large enough to be clinically important. These findings can be used to plan interventions aimed at preventing or minimizing the decay of impact.

We examined whether water-immersion restraint stress (WIRS) disrupts nonenzymatic antioxidant defense systems through ascorbic acid depletion in the adrenal gland of rats. Rats were exposed to WIRS for 0.5, 1.5, 3 or 6 h. WIRS increased serum adrenocorticotropic hormone, corticosterone and glucose concentrations and adrenal corticosterone content at each time point. WIRS increased adrenal lipid peroxide content at 3 and 6 h, and the increase was twofold higher than the unstressed level at 6 h. WIRS decreased adrenal ascorbic acid content at each time point, and the decrease reached one-third of the unstressed level at 6 h. WIRS increased adrenal reduced glutathione content at 0.5 and 6 h but reduced that content to half of the unstressed level at 6 h. WIRS increased adrenal α-tocopherol content at 1.5 h but returned that content to the unstressed level thereafter. When rats with 6 h of WIRS was orally preadministered with l-ascorbic acid (250 mg/kg), WIRS-induced changes in adrenal lipid peroxide, ascorbic acid and reduced glutathione contents were attenuated without any change in stress response. These results indicate that WIRS disrupts nonenzymatic antioxidant defense systems through rapid and continuous ascorbic acid depletion in the adrenal gland of rats.