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Biomedical subjects

Nobuyuki Ura

Publications and source records attributed to Nobuyuki Ura.

At least 19 recordsLinked to original sources
PubMed2006

Bradykinin release and inactivation in brain of rats submitted to an experimental model of Alzheimer's disease.

The kallikrein-kinin system is involved in a variety of physiological and pathological processes. Components of this system, identified in rat and human brains, can be altered in neurodegenerative processes such as Alzheimer's disease. Here, we studied kinin release and its inactivation in rats submitted to chronic cerebroventricular infusion of beta-amyloid (Abeta) peptide. Neurodegeneration was confirmed by histological analysis of brain samples. In cerebrospinal fluid of animals infused with Abeta, bradykinin concentration was increased, as determined by radioimmunoassay. However, in the brain of Abeta group, we only detected the tripeptide Arg-Pro-Pro, purified by reversed-phase chromatography and characterized by liquid chromatography-electrospray ionization mass spectrometry. This fragment of bradykinin indicated the possible participation of kinin-processing enzymes in the brain such as a prolyl oligopeptidase.

Alzheimer Disease↗
PubMed2006

Mechanisms of insulin resistance in hypertensive rats.

Insulin resistance and hyperinsulinemia are common findings in patients with essential hypertension. Recent evidence indicates that these impairments in glucose metabolism may play a role not only in the development of type 2 diabetes, but also in the onset and persistence of hypertension, dyslipidemia, and abdominal obesity. The accumulation of these risk factors constitutes a high-risk group of cardiovascular diseases, the so-called metabolic syndrome. Insulin resistance has also been reported in several animal models for hypertension, including the spontaneously hypertensive rat (SHR) and the fructose-fed rat (FFR). SHRs and FFRs have been employed in many studies to investigate the mechanisms and pathophysiology of insulin resistance and hypertension, but the precise mechanism of insulin resistance remains to be clarified. In this review, the possible mechanisms of insulin resistance in SHRs and FFRs are summarized.

Adiponectin↗
PubMed2006

Assessment of left ventricular ejection fraction using long-axis systolic function is independent of image quality: a study of tissue Doppler imaging and m-mode echocardiography.

BACKGROUND: Quantitative assessment of left ventricular ejection fraction (LVEF) is technically difficult in patients with poor image quality (IQ). Mitral annulus velocity assessed by pulsed tissue Doppler imaging (TDI) and mitral annulus motion assessed by M-mode echocardiography has been shown to correlate with LVEF. Furthermore, mitral annulus sites are easy to identify even in patients with poor IQ. The purpose of this study was to determine whether these methods are useful for estimating LVEF in patients with poor IQ. METHODS: One hundred ten patients underwent TDI and M-mode echocardiography simultaneously. Mitral annulus velocity and mitral annulus motion were obtained from each of the four mitral annulus sites. Mean mitral annular peak systolic velocities (Sm) and mean mitral annular motions (MAM) were calculated by averaging at each site. IQ was defined according to a previous report. RESULTS: Both Sm and MAM were successfully measured in all patients. Mean Sm and mean MAM correlated with LVEF. These correlations were observed not only in patients with good IQ (p < 0.001, r = 0.61 for mean Sm; p < 0.001, r = 0.61 for mean MAM) or fair IQ (p < 0.001, r = 0.58 for mean Sm; p < 0.001, r = 0.68 for mean MAM) but also in patients with poor IQ (p < 0.05, r = 0.42 for mean Sm, p < 0.001, r = 0.61 for mean MAM). Using optimal cutoff values of mean Sm and mean MAM in each IQ group, sensitivity and specificity for identifying LVEF < 50% were comparable among three IQ groups. CONCLUSIONS: Assessment of long-axis systolic function by TDI and M-mode echocardiography enables estimation of LVEF even in patients with poor IQ.

Aged↗
PubMed2006

Long-term outcome of implanted cardioverter defibrillators in survivors of out-of-hospital cardiac arrest of cardiac origin.

BACKGROUND: Little is known about the long-term outcome of implantable cardioverter defibrillator (ICD) therapy in survivors of out-of-hospital cardiac arrest (OHCA). METHODS AND RESULTS: The frequency of lethal ventricular arrhythmias and whether ICD implantation can prevent recurrence of cardiac arrest were examined. Long-term (24.4+/-11.9 months) outcome was examined in 23 patients with OHCA who were treated with an ICD (OHCA group) and 35 patients without OHCA (non-OHCA group) who were treated with an ICD. Patients in both groups had same clinical backgrounds; however, those in the OHCA group showed a significantly lower incidence of induced ventricular arrhythmias (71%) than the non-OHCA group (96%). In the follow-up period, patients in the OHCA group had almost the same incidence of ICD discharge (30%) as patients in the non-OHCA group (40%). The rate of recurrence of ventricular fibrillation in the OHCA patients was 13%, and it was difficult to estimate the rate by induced ventricular arrhythmia. CONCLUSION: The results suggest that ICD implantation for survivors of OHCA with favorable neurological recovery might be effective for preventing recurrence of cardiac arrest.

Adolescent↗
PubMed2006

Persistent insulin-sensitizing effects of sarpogrelate hydrochloride, a serotonin 2A receptor antagonist, in patients with peripheral arterial disease.

BACKGROUND: There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). METHODS AND RESULTS: Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300 mg/day) in 24 patients (19 men, 76+/-9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0+/-10.3 vs 9.2+/-2.0 microU/ml, p=0.03) and HOMA-R (4.30+/-2.83 vs 2.40+/-0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11+/-4.13 vs 9.64+/-4.37 microg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p<0.001, r=-0.441). CONCLUSIONS: Sarpogrelate has a persistent insulin-sensitizing effect through adiponectin modification and might be beneficial for anti-atherosclerotic therapy, at least, in non-diabetic and non-medicated diabetic patients with PAD.

Adiponectin↗
PubMed2006

The role of bradykinin B1 receptor on cardiac remodeling in stroke-prone spontaneously hypertensive rats (SHR-SP).

An angiotensin-converting enzyme inhibitor (ACE-I) reduces cardiac remodeling and a bradykinin B2 receptor (B2R) antagonist partially abolishes this ACE-I effect. However, bradykinin has two different types of receptor, the B1 receptor (B1R) and B2R. Although B1R is induced under several pathological conditions, including hypertension, the role of cardiac B1R in hypertension is not clear. We therefore investigated the role of cardiac B1R in stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto (WKY) rats. The B1R mRNA expression level in the heart was significantly higher in SHR-SP than in WKY rats. Chronic infusion of a B1R antagonist for 4 weeks significantly elevated blood pressure and left-ventricular weight of SHR-SP. Morphological analysis indicated that cardiomyocyte size and cardiac fibrosis significantly increased after administration of the B1R antagonist. The phosphorylation of mitogen-activated protein (MAP) kinases, including ERK, p38, and JNK, was significantly increased in the hearts of SHR-SP rats receiving the B1R antagonist. The TGF-beta1 expression level was significantly increased in SHR-SP rats treated with the B1R antagonist compared to that in WKY rats. The B1R antagonist significantly increased phosphorylation of Thr495 in endothelial nitric oxide synthase (eNOS), which is an inhibitory site of eNOS. These results suggest that the role of B1R in the heart may be attenuation of cardiac remodeling via inhibition of the expression of MAP kinases and TGF-beta1 through an increase in eNOS activity in a hypertensive condition.

Animals↗
PubMed2006

[TNF-alpha].

Explore the source record for details and available documents.

Adipocytes↗
PubMed2005

Strain rate imaging for noninvasive functional quantification of the left atrium: comparative studies in controls and patients with atrial fibrillation.

Strain rate (SR) imaging enables quantitative measurement of left ventricular (LV) function independent of cardiac translation. However, whether SR imaging is applicable for detection of left atrial (LA) dysfunction remains unknown. The purpose of this study was to assess the feasibility of measuring LA function by SR imaging, focusing on the effects of aging and LA dilatation during atrial fibrillation (AF). Echocardiographic evaluation including SR imaging was performed in 50 controls (29 males and 21 females; mean age, 41 +/- 14 years) and in 27 patients with AF (15 males and 12 females; mean age, 62 +/- 12 years; 8 with persistent AF and 19 with paroxysmal AF) from 3 apical views and analyzed off-line. Peak SR was measured at each LA segment (septum, lateral, posterior, anterior, and inferior), and mean peak systolic SR (SR-LAs), early diastolic SR (SR-LAe), and late diastolic SR (SR-LAa) were calculated by averaging the results for each segment. LA dimension, peak mitral and pulmonary velocities at late diastole, LA fractional shortening, and atrial filling fraction were calculated as parameters of LA function. Normal values for mean SR-LAs, SR-LAe, and SR-LAa were 3.4 +/- 1.0 s -1 , -3.9 +/- 1.7 s -1 , and -3.1 +/- 1.0 s -1 , respectively, and they were successfully measured in more than 95% of the LA segments. In controls, both mean SR-LAs and mean SR-LAe correlated with age, LA dimension, and early to late diastolic mitral flow velocity ratio. Conversely, mean SR-LAa did not show significant correlation with age or parameters of LA function. In AF patients, mean SR-LAs was correlated inversely with age. The mean SR-LAs was significantly lower in persistent AF patients than in age-matched controls (1.7 +/- 0.8 vs 2.9 +/- 0.9 s -1 ; P < .01). Based on our findings, we conclude that noninvasive quantification of LA function using SR imaging enables evaluation of LA dysfunction due to aging and LA dilatation.

Adult↗
PubMed2005

Early defibrillation and circulatory support can provide better long-term outcomes through favorable neurological recovery in patients with out-of-hospital cardiac arrest of cardiac origin.

BACKGROUND: Early defibrillation and cardiopulmonary bypass have been postulated to be a promising intervention against out-of-hospital cardiac arrest (OHCA); however, little is known about the long-term prognosis. The effects of early recovery of circulation (ROC) on neurological recovery and the long-term outcome in patients with OHCA were examined. METHODS AND RESULTS: Functional recovery and long-term (22.0+/-15.3 months) outcome were examined in 100 patients with definite diagnosis of OHCA. Spontaneous circulation recovered in 79% of the patients (using on-site counter shock in 20% of the patients). Cardiopulmonary bypass was performed in 38 of the OHCA patients. The total survival and favorable neurological recovery rates were 40% and 25%, respectively. The patients with favorable recovery obtained early ROC (28.2+/-16.0 min). Receiver-operating characteristic analysis showed that a period of less than 35 min for ROC was the optimal period for achieving a favorable recovery, with sensitivity of 68% and specificity of 73%. The patients with a prior history of heart failure or reduced left ventricular ejection fraction exhibited more frequent, exacerbated heart failure and ventricular arrhythmias. CONCLUSIONS: Early ROC using on-site counter shock or cardiopulmonary bypass might result in better long-term outcome in patients with OHCA of cardiac origin.

Adult↗
PubMed2005

Low adiponectin level in young normotensive men with a family history of essential hypertension.

Circulating level of adiponectin, an adipocyte-derived protein, is reduced in states of insulin resistance such as obesity and type 2 diabetes. We have previously shown that hypoadiponectinemia is related to insulin resistance in essential hypertension. Recent studies have shown that normotensive subjects with a positive family history of essential hypertension (FH+) have decreased insulin sensitivity compared to subjects with a negative family history of essential hypertension (FH-). We here examined the association between adiponectin concentration and insulin sensitivity in FH+ and FH-. Thirty young, non-obese and normotensive men without a family history of diabetes mellitus were enrolled. A total of 15 subjects were FH+, and the remaining 15 subjects were FH-. Insulin sensitivity index (ISI) was evaluated by the euglycemic hyperinsulinemic glucose clamp technique. Concentrations of adiponectin and other metabolic variables were measured. The FH+ group had significantly lower levels of ISI and adiponectin than did the FH- group. In all of the subjects, ISI was positively correlated with adiponectin concentration and high-density lipoprotein (HDL) cholesterol level and was negatively correlated with insulin level. Adiponectin concentration was the only independent determinant of ISI in a multiple regression analysis. Our results showed that adiponectin level was significantly decreased and that this was accompanied by reduced insulin sensitivity in young, nonobese and normotensive men with a family history of essential hypertension. Phenotype of reduced adiponectin level as an earlier penetrance may be especially useful in genetic analyses of insulin resistance and essential hypertension.

Adiponectin↗
PubMed2005

Olmesartan ameliorates insulin sensitivity by modulating tumor necrosis factor-alpha and cyclic AMP in skeletal muscle.

We have reported that tumor necrosis factor (TNF)-alpha in skeletal muscle is one of the determinants of insulin resistance and that the renin-angiotensin system may be related to the regulation of TNF-a in skeletal muscle. Recent studies have suggested the involvement of cyclic adenosine monophosphate (cAMP) in the regulation of TNF-a in vascular smooth muscle cells or monocytes. The aim of this study was to determine the relationship between cAMP and TNF-a in skeletal muscle in connection with the renin-angiotensin system. Six-week-old male Sprague-Dawley rats were fed either normal rat chow or fructose-rich chow for 6 weeks. For the last 2 weeks of a 6-week period, the rats were treated with a vehicle or with an angiotensin II type 1 receptor antagonist (olmesartan medoxomil, 0.1 mg/kg/day). TNF-alpha levels in the soleus muscle were significantly higher and cAMP levels in the soleus muscle were significantly lower in fructose-fed rats than in control rats. Olmesartan increased cAMP and reduced TNF-a simultaneously in fructose-fed rats. There was a significant negative correlation between levels of cAMP and TNF-alpha. Moreover, a cAMP analogue reduced TNF-a levels in the soleus muscle. These results indicate that the increase in TNF-alpha via suppression of cAMP may affect the induction of insulin resistance. In addition, the facts that olmesartan increased cAMP and decreased TNF-alpha suggest that a part of the TNF-alpha regulation by angiotensin II might consist of modulation of cAMP through Gi protein activation in skeletal muscle.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit.

Liddle's syndrome is an autosomal dominant form of salt-sensitive hypertension and has been shown to be caused by missense or frameshift mutations in the amiloride-sensitive epithelial sodium channel (ENaC), which is composed of three subunits: alpha, beta, and gamma. All disease mutations either remove or alter amino acids of the target proline-rich PPPxY sequence (PY motif) of beta- or gamma-ENaC and result in increased channel activity. In this report, we present a family with Liddle's syndrome whose abnormality is caused by a novel missense mutation, P616R, in the PY motif of the betaENaC. Functional studies using the P616R mutant expressed in Xenopus oocytes showed an approximately 6-fold increase in the amiloride-sensitive sodium channel activity compared with that of the wild type. These findings provide additional clinical evidence that a conserved PY motif is critically important for the regulation of ENaC activity.

Adult↗