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Biomedical subjects

Kenji Toba

Publications and source records attributed to Kenji Toba.

At least 19 recordsLinked to original sources
PubMed2006

Potent free radical scavenger, edaravone, suppresses oxidative stress-induced endothelial damage and early atherosclerosis.

OBJECTIVE: Effects of potent free radical scavenger, edaravone, on oxidative stress-induced endothelial damage and early atherosclerosis were investigated using animal models and cultured cells. METHODS AND RESULTS: Endothelial apoptosis was induced by 5-min intra-arterial exposure of a rat carotid artery with 0.01 mmol/L H(2)O(2). Edaravone treatment (10mg/kg i.p.) for 3 days suppressed endothelial apoptosis, as evaluated by chromatin staining of en face specimens at 24h, by approximately 40%. Similarly, edaravone dose-dependently inhibited H(2)O(2)-induce apoptosis of cultured endothelial cells in parallel with the inhibition of 8-isoprostane formation, 4-hydroxy-2-nonenal (4-HNE) accumulation and VCAM-1 expression. Next, apolipoprotein-E knockout mice were fed a high-cholesterol diet for 4 weeks with edaravone (10mg/kg i.p.) or vehicle treatment. Edaravone treatment decreased atherosclerotic lesions in the aortic sinus (0.18+/-0.01 to 0.09+/-0.01 mm(2), P<0.001) and descending aorta (5.09+/-0.86 to 1.75+/-0.41 mm(2), P<0.05), as evaluated by oil red O staining without influence on plasma lipid concentrations or blood pressure. Dihydroethidium labeling and cytochrome c reduction assay showed that superoxide anions in the aorta were suppressed by edaravone. Also, plasma 8-isoprostane concentrations and aortic nitrotyrosine, 4-HNE and VCAM-1 contents were decreased by edaravone treatment. CONCLUSIONS: These results suggest that edaravone may be a useful therapeutic tool for early atherosclerosis, pending the clinical efficacy.

Aldehydes↗
PubMed2006

Autopsy case of Dubin-Johnson syndrome with pneumonia and abetalipoproteinemia-like lipid profile.

We report the autopsy of a 79-year-old Japanese woman with Dubin-Johnson syndrome accompanied by pneumonia, an abetalipoproteinemia-like lipid profile and acanthocytosis. On admission, physical examination of the patient revealed malnutrition. Blood tests revealed marked inflammatory changes and mild liver dysfunction. Chest X-ray indicated bilateral pneumonia. Total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were 89 mg/dL, 5 mg/dL and 6 mg/dL, respectively. Peripheral blood smears revealed numerous acanthocytes. Despite the administration of antibiotics and nutritional support, the patient died. Autopsy revealed a black liver, atrophy of fat tissue on the mesentery, and pneumonia with bilateral pleural effusion. We believe that the abetalipoproteinemia-like lipid profiles in this case were caused by malnutrition and the inflammatory changes rather than the direct effects of Dubin-Johnson syndrome. We base this conclusion on the following three findings: 1) the patient's lipid profile before hospitalization was in the normal range, 2) her serum LDL cholesterol and triglyceride levels gradually increased after nutritional support began, and 3) blood tests revealed marked inflammatory changes (C-reactive protein 9.0 mg/dL; interleukin-6 16.4 pg/mL). This case provides important information that enhances our understanding of lipid metabolism under conditions of malnutrition and inflammation.

Abetalipoproteinemia↗
PubMed2005

Angiotensin converting enzyme inhibitor attenuates oxidative stress-induced endothelial cell apoptosis via p38 MAP kinase inhibition.

BACKGROUND: The effects of angiotensin converting enzyme (ACE) inhibitors on oxidative stress-induced apoptosis of endothelial cells and the intracellular signaling were investigated. METHODS: Cultured endothelial cells derived from a bovine carotid artery were treated with H2O2 or TNF-alpha to induce apoptosis. Apoptosis was evaluated by DNA fragmentation and cell viability, p38 MAP kinase activity by Western blotting, and oxidative stress by formation of 8-isoprostane. The effects of ACE inhibitors were examined by adding them into the medium throughout the experiments. RESULTS: Apoptosis was attenuated by ACE inhibitors, temocapril and captopril, in a dose-dependent manner (1-100 micromol/l). H2O2 (0.2 mmol/l for 1.5 h) or TNF-alpha (10 ng/ml for 72 h) treatment stimulated the activities of p38 MAP kinase. Temocapril and captopril decreased the activity of p38 MAP kinase as well as 8-isoprostane formation induced by H2O2. A p38 MAP kinase inhibitor, SB203580, partially inhibited the effect of temocapril on apoptosis. CONCLUSIONS: These results suggest that ACE inhibitors protect endothelial cells from oxidative stress-induced apoptosis, and that p38 MAP kinase plays a critical role in the process.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Renin-angiotensin system modulates oxidative stress-induced endothelial cell apoptosis in rats.

The role of the renin-angiotensin system in oxidative stress-induced apoptosis of endothelial cells (ECs) was investigated using a rat model and cultured ECs. EC apoptosis was induced by 5-minute intra-arterial treatment of a rat carotid artery with 0.01 mmol/L H2O2 and was evaluated at 24 hours by chromatin staining of en face specimens with Hoechst 33342. Although activity of angiotensin-converting enzyme in arterial homogenates was not increased, administration of an angiotensin-converting enzyme inhibitor temocapril for 3 days before H2O2 treatment inhibited EC apoptosis, followed by reduced neointimal formation 2 weeks later. Also, an angiotensin II type 1 (AT1) receptor blocker (olmesartan) inhibited EC apoptosis, whereas angiotensin II administration accelerated apoptosis independently of blood pressure. Next, cultured ECs derived from a bovine carotid artery were treated with H2O2 to induce apoptosis, as evaluated by DNA fragmentation. Combination of angiotensin II and H2O2 dose-dependently increased EC apoptosis and 8-isoprostane formation, a marker of oxidative stress. Conversely, temocapril and olmesartan reduced apoptosis and 8-isoprostane formation induced by H2O2, suggesting that endogenous angiotensin II interacts with H2O2 to elevate oxidative stress levels and EC apoptosis. Neither an AT2 receptor blocker, PD123319, affected H2O2-induced apoptosis, nor a NO synthase inhibitor, NG-nitro-L-arginine methyl ester, influenced the effect of temocapril on apoptosis in cell culture experiments. These results suggest that AT1 receptor signaling augments EC apoptosis in the process of oxidative stress-induced vascular injury.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Impact of blood pressure variability on cardiovascular events in elderly patients with hypertension.

Blood pressure variability is one of the characteristic features of hypertension in the elderly. However, its clinical significance remains to be determined. We therefore examined the impact of blood pressure variability on the development of cardiovascular events in elderly hypertensive patients. A total of 106 consecutive hypertensive patients aged more than 60 years old (mean age, 73.9 +/- 8.1 years old; male, 54%), all of whom underwent 24-h ambulatory blood pressure monitoring, were followed up (median, 34 months; range, 3-60 months). During the follow-up period, 39 cardiovascular events were observed, including 14 cases of cerebral infarction and 7 cases of acute myocardial infarction. The coefficient of variation (CV) of 24-h systolic blood pressure (SBP) values was used as an index of blood pressure variability. The patients showed a mean CV value of 10.6%, and were divided into two groups according to this mean value as a cut-off point: a high CV group (n = 46) and a low CV group (n = 60). Although baseline clinical characteristics were similar in the two groups, Kaplan-Meier plots for event-free survival revealed that the rate of cardiovascular events was significantly higher in high CV group than in low CV group (p < 0.05). Cox's proportional hazards analysis showed that increased blood pressure variability (a high CV value of 24-h SBP) was an independent predictive variable for cardiovascular events. The CV value of daytime SBP and the SD value of both 24-h SBP and daytime SBP also had positive correlations with the onset of cardiovascular events. These results suggest that increased blood pressure variability may be an independent risk factor for cardiovascular events in elderly hypertensive patients.

Aged↗
PubMed2005

[Characteristics and limitation of portable bedside swallowing test in elderly with dementia: comparison between the repetitive saliva swallowing test and the simple swallowing provocation test].

Several bedside portable swallowing tests have been advocated for screening for dysphagia. However, the clinical usefulness and limitation of these tests have not been examined in elderly patients with dementia. We performed the repetitive saliva swallowing test (RSST) and the simple swallowing provocation test (SSPT) in 37 elderly inpatients (81.8 +/- 1.2 years old). Simultaneously, cognitive and verbal communication ability were assessed by the Hasegawa Dementia Scale revised version (HDSR) and the Mini-Communication Test (MCT). RSST was completed only in 22 patients (59%), whereas SSPT was successfully completed in all cases. Scores of HDSR and MCT were significantly lower in patients who were unable to cooperate with RSST compared to successful examinees (HDSR: 7 +/- 1 vs 15 +/- 3, p < 0.0; MCT: 47 +/- 8 vs 81 +/- 5, p < 0.01). Dysphagia was detected in 14 patients (64%) by RSST and 5 (14%) by SSPT. Patients with dysphagia showed significantly lower cognitive function (p < 0.05) and verbal communication ability (p < 0.05). In conclusion, RSST is more sensitive to detect dysphagia in elderly patients; however, compliance with RSST is strongly influenced by the patient's cognitive function and verbal communication ability. Comprehensive geriatric assessment will help to choose an alternative test for dysphagia such as SSPT which is more specific test for aspiration pneumonia.

Aged↗
PubMed2005

[Development of a portable fall risk index for elderly people living in the community].

AIM: To develop a portable risk index for falls. METHODS: Risk factors were chosen from previously established factors then we added several environmental factors to the risk index; previous falls in the last 12 month, trippig or stumbling, inability to ascend or descend stairs without help, decreased walking speed, inability to cross a road within the green signal interval, inability to walk 1km without a break, inability to stand on one leg for 5 seconds (eyes open), using a cane, inability to wring out a towel, dizziness or faintness, stooped or rounded back, knee joint pain, visual disturbance, hearing disturbance, cognitive decline, fear of falling, receiving 5 or more prescribed drugs, sensation of darkness at home, obstacles inside, barrier on the carpet or floor, using steps daily at home, steep slopes around home. SUBJECTS: The questionnaire sheet was completed by 2,439 community-dwelling elderly subjects (76.3 +/- 7.4 years old). The frequency of each items of fall risk index was compared between fallers (history of fall within one year) and non-fallers. Multiple regression analysis was performed to identify independent risk factors for previous falls. RESULTS: Except barrier, step use and steep slope around home, all items in the fall risk index were more frequent in fallers. Multivariate analysis revealed that tripping or stumbling, inability to cross a road within the green signal interval, dizziness or faintness, obstacles inside, inability to wring out a towel, cane use and knee joint pain were independent risk factors for previous falls. These 7 selected items were further analyzed as predictors. The maximum sum of sensitivity and specificity was reached at the cut-off point of 2/3 (sensitivity 0.65, specificity 0.72) by receiver operating curve. CONCLUSION: Portable fall risk index is useful for clinical settings to identify high-risk subjects.

Accidental Falls↗
PubMed2005

[A prospective comparison of day care and freely chosen occupational therapy for elderly patients with dementia].

Since the introduction of long-term care insurance, day care services have become popular throughout Japan and many kinds of behavioral approaches have been used. Although there have been many reports on the non-pharmacological effects on cognitive function, case control studies to evaluate the effect of day care services are insufficient Furthermore, no study has compared the advantages of different behavioral therapies for elderly subjects with loss of cognitive function. To clarify these issues, we compared the changes in activities of daily living, cognitive function and vitality/depression among 78 subjects receiving different day care services. Community dwelling subjects using day care (day care group: n = 29, 80+/-7.3 years old) showed an improvement in abnormal behavior (DBD scale; before 8.5+/-2.1, after 3.2+/-1.3, p<0.05). Vitality and volition measured by the Vitality Index were significantly preserved in the day care group compared with community dwelling subjects without day care services (n = 11, 78.6+/-9.4 y.o.). Comparing the effect of three different behavioral therapies (physical fitness, cooking and gardening), there was no difference in changes in cognitive function or in other comprehensive measurements among the groups. On the other hand, different responses to various therapies were observed among subjects. To determine the advantage of various non-pharmacological therapies for dementia, geriatricians need to perform prospective case-control studies with a large number of subjects, using comprehensive geriatric assessment as the art of a geriatrician.

Activities of Daily Living↗
PubMed2004

Interrelationship between non-invasive measurements of atherosclerosis: flow-mediated dilation of brachial artery, carotid intima-media thickness and pulse wave velocity.

Flow-mediated dilation (FMD) of the brachial artery, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) have been shown to be good surrogate markers of clinical atherosclerosis. We determined the interrelation between these measurements, and examined whether their combination would be of clinical significance. One hundred and thirty-five consecutive subjects (79 women/56 men) were enrolled, including 110 patients with risk factors for atherosclerosis, and 33 patients with atherosclerotic disease such as coronary heart disease, stroke or arteriosclerosis obliterans. IMT and plaque formation of the carotid artery and FMD of the brachial artery were assessed using ultrasonography. Brachial-ankle PWV (baPWV) was measured using an automated device (form ABI/PWV, Colin). Age, FMD, IMT and PWV were significantly correlated with each other. Multivariate analysis revealed an independent correlation between the parameters except for FMD, and all four parameters were independently correlated with each other in subjects <70 years. Next, we classified the subjects by tertile according to the values of FMD, IMT and PWV. Each of the worst tertiles was associated with a higher prevalence of atherosclerotic disease and carotid plaques compared to the other tertiles. Moreover, subjects with the worst tertiles of all three measurements had a markedly higher prevalence of atherosclerotic disease and carotid plaques. These results suggest that FMD, IMT and PWV are related to each other, but the combination of these measurements will be of stronger clinical relevance.

Aged↗