Ikagaku Co.

Kyoto, Japan

Ikagaku Co.

Kyoto, Japan
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Wada H.,National Hospital Organization Kyoto Medical Center | Ura S.,National Hospital Organization Kyoto Medical Center | Satoh-Asahara N.,National Hospital Organization Kyoto Medical Center | Kitaoka S.,National Hospital Organization Kyoto Medical Center | And 11 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2012

Aim: While smoking cessation (SC) leads to a reduction of cardiovascular events, atherogenic biomarkers specifically connected with cigarette smoking and SC are unknown. Circulating levels of oxidatively modified low-density-lipoprotein (LDL) are associated with a high risk of cardiovascular diseases. Recently, two novel, oxidatively modified LDL markers, serum amyloid A-LDL (SAA-LDL) and α1-antitrypsin-LDL (AT-LDL), were identified; however, the significance of SAA-LDL and AT-LDL as cardiovascular risk markers is unknown. Methods: We carried out a cross-sectional study involving 243 patients, and determined serum levels of SAA-LDL and AT-LDL. Results: Both serum levels of SAA-LDL and AT-LDL were significantly increased in current compared to non-current smokers. Stepwise regression analysis revealed that the current smoking status and duration of smoking were strong independent determinants of the AT-LDL level. In contrast, high-sensitivity C-reactive protein was the strongest determinant of the SAA-LDL level. In multiple logistic regression analysis, the current smoking status was most closely associated with the AT-LDL level. Successful SC employing a 12-week program significantly increased the body mass index and serum levels of obesity-related markers. Notably, successful SC significantly decreased levels of AT-LDL, but not those of SAA-LDL. Conclusions: The present study provides the first evidence for the distinct characteristics of two novel, oxidatively modified LDL markers, SAA-LDL and AT-LDL. In contrast to SAA-LDL, an inflammatory marker, AT-LDL serves as a marker of smoking-specific oxidative stress. These findings warrant further investigations to clarify if AT-LDL provides a key link between smoking and cardiovascular diseases.


Kotani K.,National Hospital Organization Kyoto Medical Center | Kotani K.,Jichi Medical University | Kotani K.,U.S. National Institutes of Health | Sakane N.,National Hospital Organization Kyoto Medical Center | And 6 more authors.
Clinica Chimica Acta | Year: 2012

Background: Oxidized high-density lipoprotein (oxHDL) has reduced capacity for cholesterol efflux and some of other anti-atherogenic properties of HDL, but the role of oxHDL in the pathogenesis of cardiometabolic disease has not been fully demonstrated. This study investigated the association of oxHDL with plasma glucose (PG) and the other atherosclerotic risk variables in non-diabetic dyslipidemic subjects. Methods: Conventional atherosclerotic markers and LDL particle size (LDL-PS), as determined by gel electrophoresis, were measured in 155 non-diabetic subjects (mean age of 57. years) with dyslipidemia. Serum oxHDL levels were quantified using an antibody against oxidized human apoA-I in a sandwich ELISA format. Results: Multiple regression analysis adjusted for possible confounders revealed that HDL-cholesterol was independently, significantly and positively correlated with LDL-PS and oxHDL. By multiple regression analysis, oxHDL was independently, significantly and positively correlated with fasting PG (. β=. 0.19, P=. 0.01). Subjects in the highest PG tertile group had approximately 30% higher oxHDL levels than the lowest PG tertile group. Conclusions: These results suggest that high PG levels may contribute to the HDL oxidation, irrespective of HDL-cholesterol levels, even in non-diabetic subjects with dyslipidemia, and that the measurement of oxHDL may be a useful marker of dysfunctional HDL. © 2012 Elsevier B.V.


Honda H.,Showa University | Ueda M.,Ikagaku Co. | Kojima S.,Ikagaku Co. | Mashiba S.,Ikagaku Co. | And 4 more authors.
Atherosclerosis | Year: 2012

Background and objectives: Here, we assessed the impact of oxidized high-density lipoprotein (oxHDL), dysfunctional HDL, on mortality and cardiovascular disease (CVD) events in prevalent HD patients and compared oxHDL to interleukin-6 (IL-6), a strong predictor of CVD events in HD patients. Design, setting, participants, and measurements: This prospective study examined a cohort of prevalent HD patients (n=412). Blood samples were obtained at baseline to measure lipids, high-sensitive C-reactive protein (hsCRP), IL-6, oxidized low-density lipoprotein, N-terminal pro B-type natriuretic peptide, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase, adiponectin, and oxHDL. Carotid intima-media thickness (CIMT) was assessed at baseline and 3-year follow-up. Nutritional status was assessed by subjective global assessment (SGA), body mass index, and geriatric nutritional risk index (GNRI). After the baseline assessment, study patients were prospectively followed up (mean observational period, 40 months). Results: At baseline, patients with high oxHDL had a worse nutritional state and higher HDL-cholesterol (HDL-chol), ICAM-1, and adiponectin levels and a higher oxHDL/HDL-chol ratio than low oxHDL patients. A combination of high oxHDL and high IL-6 was significantly associated with increased CIMT at baseline and a larger increase in CIMT at 3-year follow-up. High oxHDL did not predict all-cause mortality; however, it was significantly associated with CVD-related mortality and composite CVD events, particularly with concomitant high IL-6. These associations were confirmed in multivariate Cox hazard models adjusted with confounding variables. Conclusions: High oxHDL, particularly with concomitant high IL-6, may be associated with an increased risk of CVD events and CVD-related mortality in prevalent HD patients. © 2011 Elsevier Ireland Ltd.


Honda H.,Showa University | Ueda M.,Ikagaku Co. | Kojima S.,Ikagaku Co. | Mashiba S.,Ikagaku Co. | And 11 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010

Background and objectives: Oxidized HDL (oxHDL) may behave as proinflammatory HDL because of reduced anti-inflammatory capacity and is considered a risk factor for mortality in patients on maintenance hemodialysis (MHD). The study presented here assessed the effect of oxHDL on protein-energy wasting (PEW) in MHD patients. Design, setting, participants, & measurements: This prospective study examined a cohort of MHD patients (n = 176) who were not taking lipid-lowering drugs. Blood samples were obtained to measure albumin, lipids, high-sensitivity C-reactive protein (hsCRP), oxidized LDL (oxLDL), and oxHDL. PEW was assessed by subjective global assessment (SGA) and geriatric nutritional risk index (GNRI). Measurements and assessment of nutritional status were followed up 1 year later. Results: OxHDL was significantly increased in patients with PEW at baseline. High oxHDL and high hsCRP were significantly associated with PEW, and receiver operating characteristic curves for oxHDL and hsCRP showed statistically similar accuracy for predicting SGA-positive status. According to multivariate regression models, high oxHDL had a significant influence on PEW in patients, particularly those with high hsCRP. Decreased changes in GNRI and high prevalence of SGA-positive status at 1 year were more common in patients with high oxHDL at baseline and 1 year later than in patients with low oxHDL at both time points. Conclusions: A high oxHDL state may be associated with PEW estimated by GNRI and SGA, particularly concomitant with inflammation in MHD patients. Copyright © 2010 by the American Society of Nephrology.


Ueno H.,University of Miyazaki | Saitoh Y.,University of Miyazaki | Mizuta M.,University of Miyazaki | Shiiya T.,University of Miyazaki | And 4 more authors.
Obesity Research and Clinical Practice | Year: 2011

Objective: The benefits of fenofibrate, a peroxisome proliferator-activated receptor α agonist, against cardiovascular risk factors have been established. To clarify the underlying mechanisms of these benefits, we examined the effects of fenofibrate on insulin resistance, hypertension, inflammation, oxidative stress and coagulation markers in patients with metabolic syndrome. Methods: Eleven Japanese patients with metabolic syndrome underwent physical examinations and blood tests before and after treatment with fenofibrate 200 mg daily for 8 weeks. Results: Fenofibrate significantly decreased systolic blood pressure, pulse wave velocity, serum insulin, insulin resistance (calculated from the homeostasis model assessment), total cholesterol, triglyceride, remnant-like particles cholesterol, uric acid, D-dimer, fibrinogen, serum amyloid A/low-density lipoprotein (LDL) and apoA1/LDL levels. It also significantly increased levels of high molecular weight adiponectin, thrombomodulin and high-density lipoprotein cholesterol in these patients. Plasminogen activator inhibitor-1, C-reactive protein, fasting plasma glucose and thrombin-antithrombin complex levels did not change. Limitation: Small sample size. Conclusion: Short-term fenofibrate administration not only improved lipid profiles, but also ameliorated insulin resistance, hypertension and oxidative stress markers in patients with metabolic syndrome, suggesting that fenofibrate can decrease the risk of arteriosclerosis through various pathways. © 2011 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.


PubMed | University of Miyazaki and Ikagaku Co.
Type: Journal Article | Journal: Obesity research & clinical practice | Year: 2013

The benefits of fenofibrate, a peroxisome proliferator-activated receptor agonist, against cardiovascular risk factors have been established. To clarify the underlying mechanisms of these benefits, we examined the effects of fenofibrate on insulin resistance, hypertension, inflammation, oxidative stress and coagulation markers in patients with metabolic syndrome.Eleven Japanese patients with metabolic syndrome underwent physical examinations and blood tests before and after treatment with fenofibrate 200 mg daily for 8 weeks.Fenofibrate significantly decreased systolic blood pressure, pulse wave velocity, serum insulin, insulin resistance (calculated from the homeostasis model assessment), total cholesterol, triglyceride, remnant-like particles cholesterol, uric acid, D-dimer, fibrinogen, serum amyloid A/low-density lipoprotein (LDL) and apoA1/LDL levels. It also significantly increased levels of high molecular weight adiponectin, thrombomodulin and high-density lipoprotein cholesterol in these patients. Plasminogen activator inhibitor-1, C-reactive protein, fasting plasma glucose and thrombin-antithrombin complex levels did not change.Small sample size.Short-term fenofibrate administration not only improved lipid profiles, but also ameliorated insulin resistance, hypertension and oxidative stress markers in patients with metabolic syndrome, suggesting that fenofibrate can decrease the risk of arteriosclerosis through various pathways.


Honda H.,Showa University | Hirano T.,Showa University | Ueda M.,Ikagaku Co. | Kojima S.,Ikagaku Co. | And 4 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2016

Aim: Chronic kidney disease (CKD. may lead to reduced concentrations of high-density lipoprotein (HDL. and its subfractions (HDL2 and HDL3), and damage them via inflammation and oxidative stress. The present study aimed to determine the contribution of such changes to cardiovascular disease (CVD. in patients with CKD. Methods: The levels of total cholesterol, low-density lipoprotein cholesterol, HDL-C, HDL2, HDL3, apolipoproteins, malondialdehyde-modified LDL (MDA-LDL), oxidized (ox. HDL, oxHDL2, and oxHDL3 were measured in blood samples from patients with CKD (stages 2 –5, n = 86. who were not on dialysis and from patients undergoing hemodialysis (CKD stage 5D, n =25). The patients were followed up for 28 ± 9 months after baseline examinations and CVD events were recorded. Result: The levels of HDL3 and ApoA1 in HDL3 fraction decreased according to CKD severity, whereas those of HDL2 and ApoA1 in HDL2 fraction did not differ. The levels of oxHDL were similar across CKD stages. The levels of oxHDL3 and MDA-LDL were decreased, whereas those of oxHDL2 increased according to CKD severity. Multivariate analyses using the Cox proportional hazards model selected high levels of oxHDL and its subfractions, and those adjusted with HDL-C and HDL subfractions or ApoA1 in HDL fractions respectively, compared with HDL-C and HDL subfractions or ApoA1 in HDL fractions alone as independent risk factors for CVD events. Conclusion: The levels of HDL subfractions and their oxidized subfraction particles differed among patients with CKD. The increasing levels of oxHDL subfractions might cause a high frequency of CVD events in such patients. © 2016, Japan Atherosclerosis Society. All rights reserved.


Okura T.,Ehime University | Jotoku M.,Ehime University | Irita J.,Ehime University | Enomoto D.,Ehime University | And 10 more authors.
Clinical and Experimental Nephrology | Year: 2010

Background: Serum cystatin C is not only a marker of renal function but also acts as an independent risk factor for cardiovascular damage, heart failure, and death. It is known that the initiation and progression of these cardiovascular events contributes to renal dysfunction and chronic inflammation. In this study, we investigated the relationship between cystatin C and proinflammatory cytokines. Methods: Eighty-eight patients with essential hypertension participated in the study, which involved measuring proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C reactive protein (CRP). Results: Positive correlations were detected between cystatin C and estimated glomerular filtration rate (eGFR) (r = -0.503, p < 0.001), systolic blood pressure (r = -0.246, p = 0.034), and pulse pressure (r = -0.295, p = 0.010). In contrast, serum creatinine correlated only with eGFR (r = -0.755, p < 0.001) and eGFR correlated only with age (r = -0.339, p = 0.001) and not with the other clinical parameters, whereas cystatin C also correlated with log natural (ln) IL-6 (r = -0.247, p = 0.033) and ln TNF-α (r = -0.405, p < 0.001) but not with CRP (r = -0.188, p = 0.108). In contrast, plasma creatinine and eGFR did not correlate with any of these proinflammatory cytokines. Stepwise regression analysis showed that ln TNF-α, eGFR and pulse pressure were independent determinants of serum cystatin C concentration. Conclusion: This study showed that cystatin C is a marker of inflammation as well as renal function. © 2010 Japanese Society of Nephrology.


Okura T.,Ehime University | Kurata M.,Ehime University | Irita J.,Ehime University | Enomoto D.,Ehime University | And 8 more authors.
Journal of Nephrology | Year: 2010

Aim: In patients with essential hypertension (EHT), the intrarenal resistance index (RI) has been shown to be related to the severity of target organ damage (TOD). Cystatin C is has been reported to be related to TOD in EHT. The aim of the present study was to clarify whether the RI predicts future renal function assessed by cystatin C levels in EHT. Methods: One-hundred and twelve patients participated. RI and cystatin C were measured at baseline, and 12 months later, cystatin C was measured again. Results: The patients were divided into 2 groups according to RI value: the low RI group (RI<0.7) and the high RI group (RI≥0.7). After 12 months, cystatin C levels were significantly elevated in the high RI group, whereas the levels remained unchanged in the low RI group. Stepwise regression analysis using the baseline values of RI, age, pulse pressure, HbA1c, cystatin C, log-transformed (ln) C-reactive protein and ln urinary albumin/creatinine as covariates, showed baseline RI was the only independent determinant of the time-related changes in cystatin C levels. Conclusion: This finding suggests that the renal RI may be a marker of future renal dysfunction in EHT. © 2010 Società Italiana di Nefrologia.

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