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Review The combination therapy of hypertension to prevent cardiovascular events (COPE) trial: rationale and design. 2005
Ogihara T, Matsuzaki M, Matsuoka H, Shimamoto K, Shimada K, Rakugi H, Umemoto S, Kamiya A, Suzuki N, Kumagai H, Ohashi Y, Takishita S, Abe K, Saruta T, Anonymous00352. · Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. · Hypertens Res. · Pubmed #16138563 No free full text.
Abstract: A number of major clinical trials have demonstrated the clinical benefits of lowering blood pressure and have indicated that a majority of patients with hypertension will require more than one drug to achieve optimal blood pressure control. However, there is little data showing which antihypertensive combination best protects patients from cardiovascular events and which best achieves the target blood pressure with the fewest adverse events. The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial is the first large-scale investigator-initiated multicenter study with a prospective, randomized, open, blinded endpoint evaluation (PROBE) design to directly compare cardiovascular mortality and morbidity, incidence of adverse drug reaction, and degree of blood pressure reduction in Japanese hypertensive patients for a combination of angiotensin receptor blockers, beta-blockers or thiazide diuretics in addition to a calcium antagonist, benidipine hydrochloride, with a response-dependent dose titration scheme. The COPE trial is being conducted with the cooperation of more than 100 centers and clinics in Japan and involves 3,000 patients, who will be followed for 3 years. Eligible patients are being enrolled from May 2003 until May 2006. Results from the COPE trial should provide new evidence for selecting optimal combination therapies for hypertensive patients.
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Article Cardioprotective effects of pitavastatin on cardiac performance and remodeling in failing rat hearts. 2009
Kobayashi N, Takeshima H, Fukushima H, Koguchi W, Mamada Y, Hirata H, Machida Y, Shinoda M, Suzuki N, Yokotsuka F, Tabei K, Matsuoka H. · Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine, Mibu, Japan. · Am J Hypertens. · Pubmed #19039310 No free full text.
Abstract: BACKGROUND: Activation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling by statins increases the activity of endothelial nitric oxide synthase (eNOS). We investigate whether statins (pitavastatin) improve cardiac function and remodeling via eNOS production associated with the PI3K-Akt signaling pathway, Rho-kinase (ROCK) pathway, and the development of oxidative stress in Dahl salt-sensitive (DS) hypertensive rats with heart failure (DSHF). METHODS: Pitavastatin (3 mg/kg per day), or pitavastatin plus specific PI3K inhibitor, wortmannin (1 mg/kg per day), or wortmannin alone were administered from the age of 11-18 weeks. Age-matched male Dahl salt-resistant (DR) rats served as a control group. RESULTS: Decreased end-systolic elastance (Ees) and percent fractional shortening (%FS) in failing rats was significantly ameliorated by pitavastatin, but not pitavastatin plus wortmannin or wortmannin alone. Upregulation of eNOS and Akt phosphorylation by pitavastatin was suppressed by pitavastatin plus wortmannin or wortmannin alone. Pitavastatin effectively inhibited the vascular lesion formation such as medial thickness and perivascular fibrosis, but not pitavastatin plus wortmannin or wortmannin alone. Activated RhoA and myosin light chain phosphorylation and RhoA, ROCK expression was inhibited by pitavastatin or a specific ROCK inhibitor, Y-27632, and downregulated eNOS expression and Akt phosphorylation was ameliorated by Y-27632. Increased expression of NAD(P)H oxidase subunits and activated p65 nuclear factor (NF)-kappaB, p44/p42 extracellular signal-regulated kinases and its downstream effector p90 ribosomal S6 kinase phosphorylation in failing rat hearts was inhibited by pitavastatin. CONCLUSIONS: These findings suggest that pitavastatin may improve cardiac function and remodeling via eNOS production associated with the PI3K-Akt signaling pathway, the ROCK pathway and oxidative stress.
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Article Vessel shrinkage as a sign of atherosclerosis progression in type 2 diabetes: a serial intravascular ultrasound analysis. free! 2009
Jiménez-Quevedo P, Suzuki N, Corros C, Ferrer C, Angiolillo DJ, Alfonso F, Hernández-Antolín R, Bañuelos C, Escaned J, Fernández C, Costa M, Macaya C, Bass T, Sabaté M. · Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain. · Diabetes. · Pubmed #18829988 links to free full text
Abstract: OBJECTIVE: The aim of this study was to determine the natural history of vascular remodeling of atherosclerotic plaques in patients with type 2 diabetes and the predictors of vessel shrinkage. RESEARCH DESIGN AND METHODS: In this serial intracoronary ultrasound (IVUS) study, 237 coronary segments from 45 patients enrolled in the DIABETES I, II, and III trials were included. Quantitative volumetric IVUS analyses (motorized pullbacks at 0.5 mm/s) were performed in the same coronary segment after the index procedure and at the 9-month follow-up. Nontreated mild lesions (angiographic stenosis <25%) with > or =0.5 mm plaque thickening and length of > or =5 mm assessed by IVUS were included. Vessel shrinkage was defined as a Deltaexternal elastic membrane area/Deltaplaque area < 0. Statistical adjustment by multiple segments and multiple lesions per patient was performed. RESULTS: Vessel shrinkage was identified in 37.1% of segments and was associated with a significant decrease in lumen area at 9 months (vessel shrinkage, 10 +/- 4 mm(2) vs. non-vessel shrinkage, 11 +/- 4 mm(2); P = 0.04). Independent predictors of vessel shrinkage were insulin requirements (odds ratio 4.6 [95% CI 1.40-15.10]; P = 0.01), glycated hemoglobin (1.5 [1.05-2.10]; P = 0.02), apolipoprotein B (0.96 [0.94-0.98]; P < 0.001), hypertension (3.7 [1.40-10.30]; P = 0.009), number of diseased vessels (5.6 [2.50-12.50]; P < 0.001), and prior revascularization (17.5 [6.50-46.90]; P < 0.001). CONCLUSIONS: This serial IVUS study suggests that progression of coronary artery disease in patients with type 2 diabetes may be mainly attributed to vessel shrinkage. Besides, vessel shrinkage is influenced by insulin requirements and metabolic control and is associated with more advanced coronary atherosclerosis.
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Article Low prevalence of metabolic syndrome and its components in rural Japan. free! 2008
Morimoto A, Nishimura R, Suzuki N, Matsudaira T, Taki K, Tsujino D, Miyashita Y, Ebara F, Ishikawa S, Tajima N. · Department of Internal Medicine, Division of Diabetes, Metabolism and Endocrinology, Jikei University School of Medicine, Tokyo, Japan. · Tohoku J Exp Med. · Pubmed #18719340 links to free full text
Abstract: Tsunan, Niigata is a non-westernized rural Japanese town, known for heavy snowfalls and as a rice-producing area, whose inhabitants have a long life expectancy. We investigated the prevalence of obesity, metabolic syndrome (MetS) and its components in Tsunan. A total of 1,155 men and women, 40-69 years of age were recruited from participants in the 2005 public-health program in Tsunan. Obesity was defined as body-mass index (BMI) >or= 25 kg/m(2). MetS was defined as BMI >or= 25 kg/m(2) as well as at least two of the following three items: (1) high glycosylated hemoglobin (HbA1c >or= 5.5%); (2) high blood pressure (HBP: systolic blood pressure >or= 130 mmHg or diastolic blood pressure >or= 85 mmHg), and (3) low high-density lipoprotein cholesterol (HDL-C < 40 mg/dL). If an individual was diagnosed with diabetes, hypertension, or dyslipidemia, each item was recorded as a positive finding. The prevalence of MetS and its components among Tsunan inhabitants were compared to the results of the 2005 Japanese nationwide survey. The prevalence of MetS was 4.6% in males and 4.2% in females. The prevalence of obesity, high HbA1c, HBP, and low HDL-C were 22.1/22.2%, 13.4/16.4%, 46.6/40.0%, and 9.2/3.9% in males/females, respectively. All values were significantly lower than the national results, except for the rate of female obesity. The lower prevalence of MetS and its components in Tsunan may be due to the consumption of traditional Japanese food, which is still commonly eaten there, and the higher levels of regular physical activity of farmers.
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Article Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. 2008
Kobayashi N, Ohno T, Yoshida K, Fukushima H, Mamada Y, Nomura M, Hirata H, Machida Y, Shinoda M, Suzuki N, Matsuoka H. · Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan. · Am J Hypertens. · Pubmed #18437150 No free full text.
Abstract: BACKGROUND: Recently, some investigators have shown that telmisartan, an angiotensin II (Ang II)-receptor blocker (ARB), is a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We investigate whether telmisartan improves cardiovascular remodeling associated with the production of endothelial nitric oxide synthase (eNOS) through PPAR-gamma, inhibits the Rho-kinase pathway, and suppresses oxidative stress in Dahl salt-sensitive (DS) hypertensive rats. METHODS: Telmisartan (1 mg/kg per day) or telmisartan plus PPAR-gamma inhibitor, GW9662 (1 mg/kg per day) was administered from the age of 6-11 weeks. Age-matched male Dahl salt-resistant (DR) rats served as a control group. RESULTS: The levels of eNOS and PPAR-gamma expression, and eNOS phosphorylation were significantly lower in DS rats than in DR rats. Chronic telmisartan treatment in DS rats significantly increased these parameters, but not telmisartan plus GW9662. Telmisartan effectively inhibited the vascular lesion formation such as medial thickness and perivascular fibrosis, but not telmisartan plus GW9662. Moreover, upregulated RhoA protein, Rho-kinase mRNA, and myosin light-chain phosphorylation in DS rats was decreased by telmisartan to a similar degree as observed after treatment with Y-27632, a selective Rho-kinase inhibitor. In addition, NAD(P)H oxidase p22phox, p47phox, gp91phox expression, and mitogen-activated protein kinase and its downstream effector p70 S6 kinase phosphorylation in DS rats was also inhibited by telmisartan. CONCLUSIONS: These results suggest that the cardioprotective mechanism of telmisartan may be partly due to improvement of endothelial function associated with PPAR-gamma-eNOS, oxidative stress, and Rho-kinase pathway.
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Article Monitoring treatment with cyclosporine microemulsion in myasthenia gravis. 2008
Utsugisawa K, Nagane Y, Suzuki S, Suzuki N. · Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan. · Eur J Neurol. · Pubmed #18410372 No free full text.
Abstract: PURPOSE: To examine whether the monitoring of cyclosporine (CsA) blood concentrations is of benefit in CsA microemulsion pre-concentrate (MEPC) therapy for myasthenia gravis (MG). METHODS: We measured CsA blood concentrations both 2 h after administration (C2) and immediately before administration (C0) and examined associations with changes to clinical parameters in 20 MG patients treated with CsA MEPC in an unblinded, 6-month prospective open trial. RESULTS: Initial dose of CsA MEPC (4.7 +/- 0.5 mg/kg/day) provided both high C2 levels and safe C0 levels. Disease severity, daily dose of prednisolone, acetylcholine receptor-antibody titre levels and levels of interleukin-2 production by peripheral blood mononuclear cells were significantly reduced following treatment with CsA MEPC. A significant correlation existed between C2 levels following the initial dose and clinical improvement in responder MG patients. C0 levels were significantly higher in patients who exhibited increased serum creatinine or hypertension compared with patients free from side effects. Body mass index of individual patients was significantly correlated with C0 level, and may thus offer a useful marker to predict C0 levels. DISCUSSION: CsA MEPC was effective at suppressing symptoms and T-cell-dependent pathogenesis of MG, and monitoring of C2 and C0 levels can be useful to estimate efficacy and safety of the drug.
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Article Has laparoscopic bariatric surgery been accepted in Japan? The experience of a single surgeon. 2008
Kasama K, Tagaya N, Kanahira E, Umezawa A, Kurosaki T, Oshiro T, Ishikawa M, Negishi Y, Kurokawa Y, Suzuki N, Kakihara Y, Taketsuka S, Horie K, Nakazato T, Kikkawa E, Kabasawa S, Fukuda Y, Sonoda K. · Minimally Invasive Surgery Center, Yotsuya Medical Cube, 2-7-7 Niban-cho, Chiyoda-ku, Tokyo, 102-0084, Japan. · Obes Surg. · Pubmed #18398667 No free full text.
Abstract: BACKGROUND: Obesity is steadily increasing in Asia due to factors such as a lack of exercise, adoption of a more Western diet, changing lifestyles, environments, or stresses. Even in Japan, this tendency is notable, and metabolic syndrome has become widely recognized. However, bariatric surgery is still uncommon in Japan. There are no adequate data regarding the experience and outcome of bariatric surgery in Asia. Here, we report on the current status of morbid obesity and the outcomes of bariatric surgery by a single surgeon in Japan. METHODS: Between February 2002 and January 2008, we have performed laparoscopic bariatric surgery for morbid obesity in 178 cases. They consisted of laparoscopic Roux-en-Y gastric bypass (LRYGBP) in 105 cases, laparoscopic sleeve gastrectomy (LSG) in 26 cases, laparoscopic sleeve gastrectomy with duodenal jejunal bypass (LSG/DJB) in 14 cases, laparoscopic adjustable gastric banding (LAGB) in 13 cases, and laparoscopic biliopancreatic diversion with duodenal switch in one case under the same protocol of follow up. The first author of this paper performed all procedures. RESULTS: One hundred and thirty-eight patients with a follow-up of over 3 months after surgery were enrolled. LRYGBP accounted for 72% of all bariatric procedures. The reduction of weight and body mass index (BMI) in LRYGBP and LSG showed similar results. These outcomes were superior to those of LAGB. Percentage of excess BMI loss (%EBMIL) of LRYGBP showed greater reductions at follow-ups 6, 9, 12, and 18 months after surgery compared to that of LRYGBP and LAGB. All procedures resulted in over 50% of %EBMIL after 18 months of follow-up. There was no postoperative mortality within 30 days after surgery. Preoperative comorbidity including diabetes mellitus, hypertension, and hyperlipidemia were resolved or improved after surgery in most patients. CONCLUSION: In bariatric surgery, LRYGBP is the most effective treatment for morbid obesity, while LAGB has a low risk of postoperative complications. LSG is also a safe procedure for supermorbidly obese patients. We expect that bariatric surgery will be a common procedure for patients with morbid obesity in Japan.
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Article Aldosterone-stimulated SGK1 activity mediates profibrotic signaling in the mesangium. free! 2008
Terada Y, Kuwana H, Kobayashi T, Okado T, Suzuki N, Yoshimoto T, Hirata Y, Sasaki S. · Department of Blood Purification and Nephrology, Tokyo Medical and Dental University, 5-45, Yushima 1-chome, Bunkyo-ku, Tokyo 113-8519, Japan. · J Am Soc Nephrol. · Pubmed #18184857 links to free full text
Abstract: Several recent reports support the hypothesis that aldosterone contributes to the progression of renal injury. Mineralocorticoids increase the expression of serum- and glucocorticoid-inducible protein kinase 1 (SGK1), which is upregulated in several fibrotic diseases. It was hypothesized that SGK1 may mediate the effects of aldosterone on glomerular fibrosis and inflammation. In primary cultures of rat mesangial cells, aldosterone stimulated the expression, phosphorylation, and kinase activity of SGK1, as well as SGK1-dependent NF-kappaB activity. Furthermore, aldosterone augmented the promoter activity and protein expression of intercellular adhesion molecule-1 (ICAM-1), which modulates the inflammatory response, and the profibrotic cytokine connective tissue growth factor (CTGF) in an SGK1- and NF-kappaB-dependent manner. Similar to the in vitro results, uninephrectomized rats that were treated with aldosterone demonstrated increased glomerular expression of SGK1, ICAM-1, and CTGF proteins than untreated rats; these changes were accompanied by hypertension, glomerulosclerosis, and inflammation. In conclusion, these findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via the activation of SGK1 and NF-kappaB, effects that may contribute to the progression of aldosterone-induced mesangial fibrosis and inflammation.
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Article Possible beneficial effects of health counseling, given less frequently than ordinary, on blood pressure. free! 2007
Moriguchi J, Takeda K, Suzuki N, Ezaki T, Miyazaki T, Itoh H, Ohashi F, Ikeda M. · Kyoto Industrial Health Association (Uji Office), Uji, Japan. · Ind Health. · Pubmed #17878628 links to free full text
Abstract: This study was initiated to investigate the effects of health counseling under Total Health Promotion Plan (THP). The study populations consisted of 1,655 working men who had an initial THP-based counseling and a follow-up 3 yr later (the THP group; the counseling was given on a once-three year basis), and 1,655 age- and body mass index (BMI)-matched controls (working men who had no health counseling; the control group). In the THP group, systolic blood pressure (SBP) and the prevalence of excessive alcohol drinking were decreased, and nutritional score was improved, although BMI was increased. In contrast, SBP, BMI and the ratio of excessive drinkers were all increased in the controls. Multiple regression analysis of the THP group showed that the reduction in SBP was positively associated with the increase in maximal oxygen consumption (VO(2max)) and physical activity scores, as well as the decrease in BMI. In sub-group analyses of the THP group, VO(2max) and physical activity scores were increased, and BMI did not change in the sub-group with marked BP decrease. In the sub-group with marked BP increase, however, BMI was increased, and VO(2max) was decreased. The ratio of excessive drinkers was reduced only in the sub-group with marked BP decrease. The obese-hypertensive subjects in the THP group showed decreases in BMI and BP, and increases in VO(2max). Thus, these results appeared to suggest that health counseling given even at a low frequency of once in three years prevented the age-associated increase in BP through improvement of physical endurance, decrease in alcohol intake and reduction in body weight.
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Article Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension: the possible role of local renin-angiotensin system. free! 2007
Hirono Y, Yoshimoto T, Suzuki N, Sugiyama T, Sakurada M, Takai S, Kobayashi N, Shichiri M, Hirata Y. · Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. · Endocrinology. · Pubmed #17218415 links to free full text
Abstract: Recently, aldosterone has been shown to activate local renin-angiotensin system in vitro. To elucidate the potential role of local renin-angiotensin system in aldosterone-induced cardiovascular injury, we investigated the effects of selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL), angiotensin (Ang) II type 1 receptor antagonist candesartan (ARB), and superoxide dismutase mimetic tempol (TEM) on the development of hypertension, vascular injury, oxidative stress, and inflammatory-related gene expression in aldosterone-treated hypertensive rats. The increased systolic blood pressure and vascular inflammatory changes were attenuated by cotreatment either with EPL, ARB, or TEM. Aldosterone increased angiotensin-converting enzyme expression in the aortic tissue; its effects were blocked by EPL but not by ARB or TEM. Aldosterone also increased Ang II contents in the aortic tissue in the presence of low circulating Ang II concentrations. Aldosterone induced expression of various inflammatory-related genes, whose effects were abolished by EPL, whereas the inhibitory effects of ARB and TEM varied depending on the gene. Aldosterone caused greater accumulation of the oxidant stress marker 4-hydroxy-2-neonenal in the endothelium; its effect was abolished by EPL, ARB, or TEM. Aldosterone increased mRNA levels of reduced nicotinamide adenine dinucleotide phosphate oxidase components; their effect was abolished by EPL, whereas ARB and TEM decreased only the p47phox mRNA level but not that of p22phox or gp91phox. The present findings suggest that the Ang II-dependent pathway resulting from vascular angiotensin-converting enzyme up-regulation and Ang II-independent pathway are both involved in the underlying mechanisms resulting in the development of hypertension, vascular inflammation, and oxidative stress induced by aldosterone.
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Article Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice. free! 2006
Satoh K, Kagaya Y, Nakano M, Ito Y, Ohta J, Tada H, Karibe A, Minegishi N, Suzuki N, Yamamoto M, Ono M, Watanabe J, Shirato K, Ishii N, Sugamura K, Shimokawa H. · Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. · Circulation. · Pubmed #16534010 links to free full text
Abstract: BACKGROUND: Recent studies have suggested that endogenous erythropoietin (Epo) plays an important role in the mobilization of bone marrow-derived endothelial progenitor cells (EPCs). However, it remains to be elucidated whether the Epo system exerts protective effects on pulmonary hypertension (PH), a fatal disorder encountered in cardiovascular medicine. METHODS AND RESULTS: A mouse model of hypoxia-induced PH was used for study. We evaluated right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in mice lacking the Epo receptor (EpoR) in nonerythroid lineages (EpoR(-/-) rescued mice) after 3 weeks of exposure to hypoxia. Those mice lack EpoR in the cardiovascular system but not in the hematopoietic system. The development of PH and pulmonary vascular remodeling were accelerated in EpoR(-/-) rescued mice compared with wild-type mice. The mobilization of EPCs and their recruitment to the pulmonary endothelium were significantly impaired in EpoR(-/-) rescued mice. By contrast, reconstitution of the bone marrow with wild-type bone marrow cells ameliorated PH in the EpoR(-/-) rescued mice. Hypoxia enhanced the expression of EpoR on pulmonary endothelial cells in wild-type but not EpoR(-/-) rescued mice. Finally, hypoxia activated endothelial nitric oxide synthase in the lungs in wild-type mice but not in EpoR(-/-) rescued mice. CONCLUSIONS: These results indicate that the endogenous Epo/EpoR system plays an important role in the recruitment of EPCs and prevents the development of PH during chronic hypoxia in mice in vivo, suggesting the therapeutic importance of the system for the treatment of PH.
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Article Kidney stone disease and risk factors for coronary heart disease. 2005
Hamano S, Nakatsu H, Suzuki N, Tomioka S, Tanaka M, Murakami S. · Department of Urology, Asahi General Hospital, Asahi-city, Chiba, Japan. · Int J Urol. · Pubmed #16323977 No free full text.
Abstract: BACKGROUND: We conducted a case-control study to examine the impact of coronal heart disease (CHD) risk factors on calcium oxalate (CaOX) stone formation. METHODS: Variables included body mass index (BMI), current alcohol use, smoking habit, hypertension, hypercholesterolemia, diabetes mellitus, and hyperuricemia. Data suf fi cient for analysis were obtained for 181 CaOX stone formers and 187 controls. RESULTS: Seven of 181 stone formers (3.9%) had a history of CHD compared with none of 187 control subjects (P = 0.007). In univariate logistic regression analysis, smoking habit (OR 4.41, 95% CI 2.85-6.84, P < 0.0001), hypertension (OR 4.24, 95% CI 2.61-6.91, P < 0.0001), hypercholesterolemia (OR 3.03, 95% CI 1.77-5.20, P < 0.0001) and BMI (OR 1.10, 95% CI 1.04-1.17, P = 0.007) reached statistical signi fi cance. In a multivariate logistic regression analysis, smoking habit (OR 4.29, 95% CI 2.68-6.86, P < 0.0001), hypertension (OR 3.57, 95% CI 2.11-6.07, P < 0.0001), and hypercholesterolemia (OR 2.74, 95% CI 1.51-5.00, P = 0.001) reached statistical signi fi cance, while BMI (OR 1.06, 95% CI 0.99-1.12, P = 0.09) did not. CONCLUSIONS: CaOX stone formers are signi fi cantly associated with several CHD risk factors, including smoking habit, hypertension, hypercholesterolemia, and obesity.
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Article Enhanced erythropoiesis mediated by activation of the renin-angiotensin system via angiotensin II type 1a receptor. free! 2005
Kato H, Ishida J, Imagawa S, Saito T, Suzuki N, Matsuoka T, Sugaya T, Tanimoto K, Yokoo T, Ohneda O, Sugiyama F, Yagami K, Fujita T, Yamamoto M, Nangaku M, Fukamizu A. · Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki, Japan. · FASEB J. · Pubmed #16223784 links to free full text
Abstract: Although clinical and experimental studies have long suggested a role for the renin-angiotensin system (RAS) in the regulation of erythropoiesis, the molecular basis of this role has not been well understood. We report here that transgenic mice carrying both the human renin and human angiotensinogen genes displayed persistent erythrocytosis as well as hypertension. To identify the receptor molecule responsible for this phenotype, we introduced both transgenes into the AT1a receptor null background and found that the hematocrit level in the compound mice was restored to the normal level. Angiotensin II has been shown to influence erythropoiesis by two means, up-regulation of erythropoietin levels and direct stimulation of erythroid progenitor cells. Thus, we conducted bone marrow transplantation experiments and clarified that AT1a receptors on bone marrow-derived cells were dispensable for RAS-dependent erythrocytosis. Plasma erythropoietin levels and kidney erythropoietin mRNA expression in the double transgenic mice were significantly increased compared with those of the wild-type control, while the elevated plasma erythropoietin levels were significantly attenuated in the compound mice. These results provide clear genetic evidence that activated RAS enhances erythropoiesis through the AT1a receptor of kidney cells and that this effect is mediated by the elevation of plasma erythropoietin levels in vivo.
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Article Antioxidant activity and angiotensin I-converting enzyme inhibition by enzymatic hydrolysates from bee bread. 2005
Nagai T, Nagashima T, Suzuki N, Inoue R. · Department of Food Science and Technology, Tokyo University of Agriculture, Hokkaido 0992493, Japan. · Z Naturforsch C. · Pubmed #15787258 No free full text.
Abstract: Enzymatic hydrolysates were prepared from bee bread using three proteases. The antioxidant properties of these hydrolysates were measured using four different methods. These had remarkable antioxidant activity similar or superior to that of 1 mM alpha-tocopherol. They also had high scavenging activities against active oxygen species as the superoxide anion radical and hydroxyl radicals. Moreover, they showed angiotensin I-converting enzyme inhibitory activities and the activities were similar to those from various fermented foods such as fish sauce, sake, vinegar, cheese, miso, and natto. The present studies reveal that enzymatic hydrolysates from bee bread are of benefit not only for the materials of health food diets, but also for in patients undergoing various diseases such as cancer, cardiovascular diseases, diabetes, and hypertension.
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Article [Anesthetic management for removal of pheochromocytoma in a patient after repair of tetralogy of Fallot] 2004
Yano T, Maruta T, Kawano T, Hamakawa T, Suzuki N, Takasaki M. · Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, Miyazaki 889-1692. · Masui. · Pubmed #15587179 No free full text.
Abstract: A 45-year-old woman after repair of tetralogy of Fallot at the age of 19, was admitted to the hospital for treatment of paroxysmal hypertension. She was diagnosed with pheochromocytoma of the left adrenal gland, and was scheduled for removal of pheochromocytoma. She received doxazosin for preoperative preparation. Anesthesia was induced with propofol and vecuronium, and maintained with intermittent fentanyl and sevoflurane in nitrous oxide and oxygen. Before induction of anesthesia, magnesium sulfate 40 mg x kg(-1) was injected, and followed by continuous infusion of 40 mg x kg(-1) x hr(-1) until the removal of pheochromocytoma. Under neuromuscular monitoring, vecuronium was administered prudently. Cardiac output was continuously monitored with pulmonary arterial catheter and transesophageal aortic blood flow monitor. Blood pressure and heart rate were stable even though the tumor was handled, and no additional vasodilator therapy was needed. After surgery, prolonged neuromuscular blockade caused by magnesium sulfate was not observed. We consider that successful management was feasible by administration of magnesium sulfate and preoperative administration of alpha1 blocker, under adequate perioperative monitoring.
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Article An infant with systemic hypertension, renal artery stenosis, and neuroblastoma. 2004
Shinohara M, Shitara T, Hatakeyama SI, Suzuki N, Maruyama K, Kobayashi T, Tsuchida Y. · Division of Cardiology, Gunma Children's Medical Center, Gunma, Japan. · J Pediatr Surg. · Pubmed #14694383 No free full text.
Abstract: A newborn girl with neuroblastoma presented with hypertension (blood pressure 200/140 mm Hg). The concentration of active renin in the ipsilateral renal vein was exceedingly high compared with those in the other venous systems, and angiography results showed narrowing of the contralateral 2 renal arteries. The tumor regressed in size after chemotherapy, but the blood pressure remained high. Percutaneous transluminal angioplasty (PTA) for the left renal arteries was performed twice, the first one at 5 months of age, which achieved some success in the recovery of impaired kidney function. At 8 months of age, she underwent radical resection of the neuroblastoma and removal of the right kidney, and the blood pressure promptly returned to normal postoperatively. The current patient represents the second youngest, well-documented case of renovascular hypertension with neuroblastoma in early infancy.
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Article Intrahepatic biliary cysts in biliary atresia in the era of liver transplantation. 2003
Takahashi A, Tsuchida Y, Suzuki N, Kuroiwa M, Murai H, Toki F, Nomoto K, Kuwano H. · Department of Surgery, Gunma Children's Medical Center, and dagger Department of Surgery I, Gunma University School of Medicine, Gunma, Japan. · J Pediatr Gastroenterol Nutr. · Pubmed #12717083 No free full text.
Abstract: OBJECTIVES: The development of intrahepatic biliary cysts (IBC) after Kasai operation in patients with biliary atresia (BA) is recognized as an important problem; however, management strategy for IBC has not been clarified, particularly in the light of the increased use of liver transplantation. METHODS: Forty consecutive BA patients underwent hepatic portoenterostomy during 18 years from 1983 to 2000. We compared the clinical course and prognosis of the patients who developed IBC with those who did not. RESULTS: Seven of the 40 patients developed IBC. Three patients had type A (non-communicating cyst) and three patients had type C (multiple cystic dilation) IBC, and the remaining patients had type B (communicating cyst). Of the 7 patients, one patient underwent successful internal intestinal drainage, and one patient died of complications at the time of internal intestinal drainage. Three patients underwent liver transplantation due to either hepato-pulmonary syndrome (one case) or liver failure (two cases). One patient with IBC with liver failure was judged to require transplant, but was found to have pulmonary hypertension and was thus not a candidate. The remaining patient has survived without jaundice for 21 months postoperatively. Two of 21 patients with good initial bile drainage and without IBC underwent liver transplantation. The percentage of patients undergoing transplant was significantly higher in the group with IBC than in the group without IBC (P < 0.05). CONCLUSIONS: IBC was associated with worsening liver function. Previously, IBC was treated using internal/external drainage, or the patients were observed without treatment, with limited success. We now consider it reasonable to carry out liver transplantation in patients with long-standing IBC.
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Article [Clinical evaluation of the cause of left ventricular dysfunction in type 2 diabetes without significant cardiac disease] 2002
Mori H, Hazama M, Sakamoto T, Yamaguchi T, Suzuki N, Moriya M, Ueda Y, Yano K. · Department of Cardiology, Japanese Red Cross Nagasaki Genbaku Hospital, Morimachi 3-15, Nagasaki, Nagasaki 852-8511. · J Cardiol. · Pubmed #12420669 No free full text.
Abstract: OBJECTIVES: The relationship between left ventricular dysfunction and hypertension or proteinuria was evaluated in type 2 diabetic patients without significant cardiac disease to investigate the cause of diabetic cardiac dysfunction. METHODS: Twenty-one patients with type 2 diabetes mellitus (mean age 63.8 +/- 7.4 years) underwent left ventriculography and Doppler echocardiography to calculate the ejection fraction and E/A ratio (E/A). RESULTS: Thirteen patients had hypertension (61.9%) and six patients had proteinuria (28.6%). The E/A was 0.82 +/- 0.21 in all patients. The E/A in patients with hypertension or proteinuria was significantly less than in those without these diseases (0.74 +/- 0.18 vs 0.97 +/- 0.18, p = 0.011; 0.65 +/- 0.10 vs 0.89 +/- 0.20, p = 0.010, respectively). The ejection fraction was 73.3 +/- 7.2% in all patients. The ejection fraction in patients with proteinuria was significantly less than in those without proteinuria (67.6 +/- 10.0% vs 75.5 +/- 4.4%, p = 0.019), but there was no significant difference in ejection fraction between patients with and without hypertension. The duration of diabetes was significantly related to the ejection fraction (r = -0.436, p = 0.048) but not to the E/A. CONCLUSIONS: In patients with type 2 diabetes without significant cardiac disease, left ventricular diastolic function may be related to both hypertension and proteinuria and left ventricular systolic function may be related to proteinuria and duration of diabetes. Therefore, in addition to hypertension, complications of nephropathy or long duration of diabetes may be related to the cause of the diabetic cardiac dysfunction.
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Article Laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl. 2002
Tagaya N, Suzuki N, Furihata T, Kubota K. · Second Department of Surgery, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. · Surg Endosc. · Pubmed #11961657 No free full text.
Abstract: We describe the successful laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl. A 47-year-old man with hypertension and diabetes mellitus was found to have an abdominal mass beside the aorta. The tumor was diagnosed as a functional paraganglioma by diagnostic imaging and biochemical tests. We then performed a transperitoneal laparoscopic resection for removal. After freeing the left ureter, resecting the inferior mesenteric artery, and dividing the small blood vessels, the tumor was isolated and found to be preserved in its capsule. It was retrieved in a bag through an enlarged incision. The operation time was 450 min and blood loss was 410 ml. The postoperative course was uneventful and there has been no local recurrence or distant metastasis during the 18-month follow-up period. Laparoscopic resection of functional extraadrenal paragangliomas is technically feasible and safe if adequate pre- and intraoperative medical management and a careful, steady surgical technique are used.
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Retraction Serial quantitative coronary analyses for the evaluation of one-year change in saphenous vein grafts. 2008
Suzuki N, Kozuma K, Ueno Y, Nagaoka K, Kyono H, Ishikawa S, Watanabe H, Yokoyama N, Takeshita S, Isshiki T. · Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. · Ann Thorac Surg. · Pubmed #18222257 No free full text.
Abstract: BACKGROUND: A paucity of data exists with respect to changes in whole saphenous vein grafts (SVGs) despite accelerated atherosclerosis within grafted saphenous vein conduits. In the present study, we evaluated the one-year change in SVGs by means of quantitative coronary analysis. METHODS: This study enrolled consecutive 52 patients with 109 SVGs, who underwent coronary artery bypass graft surgery successfully. A follow-up study was performed in 33 patients with 65 SVGs after one year because 16 SVGs were obstructed (baseline, 8; follow-up period, 8), and 15 patients with 28 SVGs dropped out within one year. RESULTS: Both minimal and mean lumen diameters decreased significantly (3.17 +/- 0.64 mm vs 2.41 +/- 0.57 mm, p < 0.001; 3.70 +/- 0.69 mm vs 2.92 +/- 0.70 mm, p < 0.001; respectively). Graft length also decreased significantly (107.1 +/- 25.8 vs 100.6 +/- 25.2 mm, p < 0.001). The graft shortening rate (graft shortening length/baseline graft length x 100) was greater than 5% in 33 vessels (51%) and greater than 10% in 23 vessels (35%). Coronary risk factors (smoking, diabetes mellitus, hypertension, dyslipidemia) did not reveal significant relationship with late loss of minimal and mean lumen diameters. CONCLUSIONS: The present study showed a considerable and uniform lumen loss of SVGs after one year, irrespective of coronary risk factors. Graft length shortening was seen more than elongation.
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