[Show abstract][Hide abstract] ABSTRACT: Sirtuin 1 (SIRT1), a member of the silent information regulator 2 in mammals, has recently been found to be involved in age-related diseases, such as cancer, metabolic diseases, cardiovascular disease, neurodegenerative diseases, osteoporosis and chronic obstructive pulmonary disease (COPD), mainly through deacetylation of substrates such as p53, forkhead box class O, peroxisome proliferator activated receptor gamma co-activator 1alpha, and nuclear factor-kappaB. It is widely reported that SIRT1 can promote not only carcinogenesis but also metastasis and insulin resistance, andhave beneficial effects in metabolic diseases, mediate high-density lipoprotein synthesis and regulate endothelial nitric oxide to protect against cardiovascular disease, have a cardioprotective role in heart failure, protect against neurodegenerative pathological changes, promote osteoblast differentiation, and also play a pivotal role as an anti-inflammatory mediator in COPD. However, there are controversial results suggesting that SIRT1 has an effect in protecting against DNA damage and accumulation of mutations, and preventing tumorigenesis. In addition, a high level of SIRT1 can induce cardiomyopathy and even heart failure. This article reviews recent developments relating to these issues.
Geriatrics & Gerontology International 04/2009; 9(1):7-15.
[Show abstract][Hide abstract] ABSTRACT: The object of this study was to examine blood pressure (BP) variability due to postural change in elderly hypertensive patients. The subjects studied were 154 elderly inpatients in a hospital for the elderly (48 male and 106 female; median age: 82 years), consisting of age- and sex-matched bedridden (n=39) and non-bedridden (n=39) normotensive controls and bedridden (n=38) and non-bedridden (n=38) hypertensive patients. BP and pulse rate (PR) were measured in the supine position, then again after a 2-min, 45 deg head-up tilt with the legs horizontal. The decrease in systolic BP (SBP) on tilting in the bedridden hypertensive group (median: -10 mmHg; range: -32 to 9 mmHg) was significantly (p<0.008) greater than those in the other three groups. Monotherapy with azeinidipine, a long-acting calcium channel blocker, for 3 months not only significantly reduced the basal BP and PR of hypertensive patients in the two groups, but also significantly (p<0.05) attenuated the tilt-induced decrease in the SBP to -3 mmHg (-19 to 25 mmHg) and enhanced the change in PR from -1 bpm (-10 to 7 bpm) to 1 bpm (-4 to 23 bpm) in the bedridden hypertensive group. Our findings indicate that tilt-induced decrease in SBP is a rather common phenomenon in bedridden elderly hypertensive patients, and that treatment with azelnidipine attenuates tilt-induced decrease in SBP, probably through an improvement of baroreceptor sensitivity.
Hypertension Research 01/2007; 29(12):943-9. · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sarcomatoid transformation was observed in 4.5% of autopsied cases of intrahepatic cholangiocarcinoma. Here, we report a case of intrahepatic sarcomatoid cholangiocarcinoma with round cell feature, extremely rare variant. An 87-year-old man was incidentally found to have a tumor in the left lobe of the liver by abdominal computed tomography scans. The patient was clinically diagnosed to have intrahepatic cholangiocarcinoma and received palliative care without specific treatment. He died of hepatic insufficiency 3 months after the diagnosis. The autopsied liver specimens showed a reddish gray tumor of 4.0x2.8 cm in size. Histologically, the tumor was centrally hemorrhagic and necrotic and was composed of tubular adenocarcinoma and a round cell component, which has an eccentrically located nucleus and eosinophilic cytoplasm without mucin production. Immunohistochemically, the adenocarcinoma cells expressed cytokeratin 19 and beta-catenin in their cytoplasm, with E-cadherin and CD44s at the plasma membrane. In the round cells, cytokeratin 19 and vimentin was detected in their cytoplasm and CD44s at the plasma membrane. E-cadherin immunoreactivity was weakly present in their cytoplasm and beta-catenin was negative. Loss or reduction of the E-cadherin and beta-catenin expressions and overexpression of CD44s in the round cells are suggested to be contributed to the high propensity for lymphatic permeation and poor prognosis.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 12/2006; 449(5):585-90. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. Blood flows of the forearms and legs were measured by strain-gauge plethysmography. The vasodilatory response to the release of compression of the forearms and thighs at 200 mmHg or 20 mmHg more than systolic blood pressure for 5 min and to sublingual administration of nitroglycerin (0.3 mg) was assessed. The maximum reactive hyperemic flow in 35 legs with arteriosclerosis obliterans was significantly (p < 0.001) decreased compared to the value in legs in the control hypertensive subjects. Moreover, maximum reactive hyperemic flow in the forearms of patients with arteriosclerosis obliterans was significantly (p = 0.002) decreased compared to that in the control subjects. Blood pressure was similarly decreased by treatment with temocapril or amlodipine. Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.
Hypertension Research 10/2006; 29(9):655-63. · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 98-year-old woman was admitted to our hospital complaining of anorexia, epigastralgia, and vomiting. An elastic hard tumor was palpable in her epigastric region. CT and US examination revealed a huge cystic lesion adjacent to the left lobe of the liver and the stomach. Her serum levels of CEA (13.6 ng/ml), CA19-9 (95 U/ml) and CA125 (99 U/ml) were high. She suffered from aspiration pneumonia on the 10th day of admission, which progressed to acute respiratory distress syndrome. On the 20th day of admission, the epigastric tumor suddenly disappeared. She passed away on the 31st day due to respiratory failure. Autopsy revealed that she had a ruptured pancreatic anaplastic mucinous cystadenocarcinoma. To the best of our knowledge, this is the oldest reported case of ruptured pancreatic cystadenocarcinoma in the world.
Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 04/2006; 43(2):246-51.
[Show abstract][Hide abstract] ABSTRACT: We have reported that use of angiotensin I-converting enzyme (ACE) inhibitor, which is a class of antihypertensive agent that induces cough, is an independent factor in reducing risk of pneumonia among elderly inpatients. Insertion/deletion (I/D) polymorphism of the ACE gene (ACE) has been associated with the risk of pneumonia in elderly individuals. However, the ability of ACE inhibitors to reduce pneumonia-related morbidity in individuals with the ACE polymorphism is unclear. Therefore we determined the association of ACE inhibitor use and ACE genotypes with reduction of pneumonia risk in the Japanese elderly population.
We conducted a hospital-based, retrospective, case-control study to evaluate the effect of an ACE inhibitor and ACE polymorphism on incidence of pneumonia. Case subjects were pneumonia patients (N = 105) >or=65 years of age, during an 8-month period of a nonwinter season. Control subjects (n = 420) were elderly patients who were frequency matched to the case subjects by age (within +/- 2 years) and gender. Data were collected on medication with the ACE inhibitor temocapril and on known risk factors for pneumonia. The significances of differences for the risk factors were analyzed using univariate and multivariate comparisons of the case and control subjects.
After adjustment for potential confounders by multiple logistic regression analysis, the odds ratio (OR) estimates for pneumonia were 0.458 (95% confidential interval [CI]: 0.230 to 0.909, P = .026) for ACE inhibitor use. Conditional logistic regression analysis according to ACE genotypes revealed significant reduction of pneumonia risk by use of temocapril compared with that in nonhypertensive individuals (ie, the reference group) in those with ACE ID + II (OR: 0. 416, 95% CI: 0.177 to 0.976, P = .044), but not in those with ACE DD (OR: 0.706, 95% CI: 0.198 to 2.518, P = .592).
These results suggest that use of an ACE inhibitor is beneficial for reducing risk of pneumonia, particularly in individuals with the ACE genotypes ID + II.
American Journal of Hypertension 10/2005; 18(10):1353-9. · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Electromagnetic field (EMF) radiation has been found to induce arteriolar dilatation, but the mechanism of action remains largely unknown. This study investigated the effect of EMF radiation on the production of endothelin-1 (ET-1), a potent vasoconstrictor, by cultured endothelial cells. EMF radiation reduced ET-1 basal levels in human umbilical vein and microvascular endothelial cells, but failed to reduce ET-1 basal levels in bovine and human aortic endothelial cells. EMF radiation significantly inhibited thrombin-stimulated ET-1 production in all four endothelial cell types in a dose-dependent manner. EMF radiation significantly inhibited thrombin-induced endothelin-1 mRNA expression in all four cell types. The inhibitory effect of EMF radiation on ET-1 production was abolished by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (10(-3) mol/1). These results demonstrate that EMF radiation modulates ET-1 production in cultured vascular endothelial cells and the inhibitory effect of EMF radiation is, at least partly, mediated through a nitric oxide-related pathway.
The Journal of international medical research 09/2005; 33(5):545-54. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quetiapine, which is a new atypical antipsychotic agent, was administered at low doses (25–50 mg/day) for psychotic symptoms in eight elderly patients with physical illnesses. Delirium and hallucination were alleviated by the administration of low doses of quetiapine, and the cause–effect relationship between the administration and alleviation of symptoms was evident, particularly in one patient with delirium, because delirium was alleviated after administration began, was exacerbated after discontinuation of quetiapine, and was alleviated again after administration was resumed. Little improvement was observed in delusions or mood disorders. None of the patients showed exacerbation of physical symptoms or abnormalities in clinical laboratory tests. The results of this study suggest that quetiapine might be effective in reducing delirium and hallucination that often accompany physical illness in elderly people and could be used without adverse effects.
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is an important problem that should be solved in the 21st century. Prior to treatment, a simple and easy diagnostic method using biological markers should be available. As a method to attain this goal, we detected and determined tau protein in oral mucosal epithelium.
Oral epithelium was exfoliated from 34 patients with AD or 29 patients with vascular dementia, and 33 young and 34 age-matched controls. Western blot was performed for determining the molecular weight of oral tau protein. The tau protein level was determined with an enzyme-linked immunosorbent assay (ELISA) kit for cerebrospinal fluid (CSF). CSF tau was also measured and compared with oral tau.
Western blot analysis using an anti-non-phosphorylated tau-protein antibody showed two bands, one at 65 Kd and the other at 110 Kd. The tau-protein level in oral epithelia showed a significant positive correlation with those in the CSF (p <.05). The patients with AD had significantly higher levels of tau protein than the patients with vascular dementia and the controls (p <.01). AD patients with a younger age at onset of the study showed a higher level of the tau protein than the patients with later age at onset (p <.05).
Like other nonneural tissues, oral epithelium contains small tau and big tau. The tau protein in oral epithelium reflects the pathological changes, as does the CSF tau. Individuals who develop AD may have had high levels of the tau protein in oral mucosal epithelium since early childhood. The tau-protein level in oral epithelia could be helpful in diagnosing AD.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 01/2002; 57(1):M64-70. · 4.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Arotinolol hydrochloride with alpha-and beta-receptor blocking action, developed in Japan, is mainly used for the treatment of hypertension. The study population consisted of 42 outpatients with essential hypertension with a blood pressure greater or equal to 160/96 mmHg. 10 men and 32 women, with a mean age of 77.5 year. The patients received 10 mg arotinolol hydrochloride daily for 24 weeks which was taken orally twice a day. We evaluated the changes of blood pressure, heart rate and chief complaints of patients before and every 4 weeks during treatment and the renal function before, 12 weeks after and 24 weeks after, the administration of arotinolol hydrochloride. Blood pressure and heart rate decreased significantly after 4 weeks of treatment with arotinolol hydrochloride (p < 0.05). However, no significant changes were found in blood urea nitrogen, serum creatinine, serum albumin, beta2-microglobuline, NAG or creatinine clearance during the 24 weeks of treatment. These results indicate that arotinolol hydrochloride has antihypertensive effects without renal dysfunction in elderly patients with essential hypertension.
Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 08/1999; 36(8):542-6.