動脈硬化と予防医学

Although the average life span of the Japanese has lengthened to a great extent, health expectancy is very important issue for the promotion of public health. Management of vascular health can improve the health expectancy in subjects with lifestyle-related diseases including metabolic syndrome（MetS）. Since the development of atherosclerotic lesion formation is often found in patients with MetS, early detection of vascular dysfunction is essential to prevent cardiovascular diseases. We clinically use several medical equipment including ultrasound examination of carotid arteries, brachial-ankle pulse wave velocity（baPWV）, flow-mediated dilation（FMD）for non-invasive assessment of vascular function in patients with MetS. These vascular function analyses are very useful to plan and modify pharmacological intervention in each patient with MetS. In addition, diet therapy such as sodium restriction（less than６．０g／day）and exercise therapy with appropriate intensity are needed to maintain vascular function in patients with MetS

Basic and Clinical Science, and Clinical Practice for Prevention of Lifestyle-related Diseases

Heparin cofactor II（HCII）, a serine protease inhibitor inactivates thrombin action via formation of complex with dermatan sulfate. Since accelerated thrombin action via activation of its receptor contributes development of cardiovascular diseases and insulin resistance, we studied and demonstrated that low plasma HCII activities were associated with exaggerated atherosclerosis, cardiovascular remodeling and hyperglycemia with insulin resistance in both of humans and mice. These results suggested that plasma HCII activity might be a predictive biomarker and novel therapeutic target for the prevention and treatment of lifestyle-related diseases. Although metabolic disorders including diabetes, hypertension, dyslipidemia are thought to be major clinical problems in the public health, number of this clinical field specialist is not enough to treat those patients in local areas of Tokushima prefecture. In ２０１５, the Department of Community Medicine and Metabolic Disorders was established to practice patients-based medicine, to advance the cultivation of clinical human resources, to educate medical students and to make social contribution in Anan area of Tokushima prefecture. We are going to promote clinical support linkage between Tokushima University Hospital and Anan Clinical Center

コウシケッショウ ドウミャク コウカ ト メタボリック シンドローム

The cardiovascular disease has been increasingly recognized over the last decade. The metabolic syndrome is associated with increased risk for development of dyslipidemia leading to atherosclerosis. In addition to healthy lifestyle promotion, treatment of atherogenic dyslipidemia using lipid lowering agents such as fibrates and statins is useful. In fact, bezafibrate reduces the incidence of myocardial infarction in patients with metabolic syndrome during long-term follow-up. Early detection of atherosclerosis including endothelial dysfunction is very important strategy for preventing cardiovascular events in patients with metabolic syndrome. We attempt to establish multiphasic health testing system（Anti-Aging Medical Center : AAMC）using recently-developed devices for medical diagnosis in Tokushima University Hospital

Transforming Growth Factor-β1 as a Common Target Molecule for Development of Cardiovascular Diseases, Renal Insufficiency and Metabolic Syndrome

Transforming growth factor-β1 (TGF-β1) is a polypeptide member of the transforming growth factor β superfamily of cytokines. It is a secreted protein that performs many cellular functions including control of cell growth, cell proliferation, cell differentiation and apoptosis. In the cardiovascular system, TGF-β1 plays pivotal roles in the pathogenesis of hypertension, restenosis after percutaneous coronary intervention, atherosclerosis, cardiac hypertrophy and heart failure. In addition, TGF-β1 has been shown to be increased in adipose tissue of obese subjects with insulin resistance. Furthermore, TGF-β1 is a potent initiator of proliferation of renal mesangial cells leading to chronic kidney disease. Some currently available agents can manipulate TGF-β1 expression leading to amelioration of cardiovascular diseases. Thus, an understanding of interactions between chronic kidney disease and metabolic syndrome and the development of cardiovascular diseases is an important issue, and attention should be given to TGF-β1 as a crucial factor for regulation and modulation of those pathological conditions

Interactions between CKD and MetS and the Development of CVD

Metabolic syndrome (MetS) consists of a combination of metabolic disorders, including increased abdominal circumference, hyperglycemia, elevated blood pressure, and lipid disorders. MetS is now widely accepted as a crucial risk factor for the development of cardiovascular disease (CVD) and mortality. In addition, persistent proteinuria indicating chronic kidney disease (CKD) is well known as a powerful risk factor for the progression of end-stage renal disease and CVD. In recent years, patients with CKD and MetS appear to be increasing along with increasing incidence of CVD in industrial countries

A recyclable hydrophobic anchor-tagged asymmetric amino thiourea catalyst

A novel recyclable thiourea-based, asymmetric organocatalyst containing a hydrophobic anchor has been developed. The chemical nature of the hydrophobic anchor contributes to the desirable characteristics of the recyclable catalyst. The hydrophobic anchor-tagged thiourea catalyst is highly soluble in less polar solvents compatible to the amino thiourea catalyst-mediated asymmetric reactions, but sparingly soluble in polar solvents used for recycle process. This asymmetric catalyst delivers a catalytic performance comparable to that of a parent catalyst and can be readily recycled from reactions

ORAL HEALTH AND SELF-EFFICACY

Background : Bidirectional relationships exist between diabetes and periodontal disease. Fostering timely oral health assessments of patients with diabetes, the modified diabetes oral health assessment tool (M-DiOHATⓒ) for nurses was studied. The DiOHATⓒ has four factors, namely oral health conditions, oral hygiene behaviors, perception and knowledge, and health record sharing. It was modified as the M-DiOHATⓒ scale. To change people's health behaviors, “efficacy beliefs" and “outcome expectancies" are important. However, no studies have been reported that addressed efficacy beliefs and outcome expectancies of oral health conditions and behaviors of patients with diabetes. Objective : To clarify the oral health conditions and behaviors of patients with diabetes using the M-DiOHATⓒ, and to describe their associations with the Self-Efficacy Scale for Self-Care (SESS)/the Outcome Expectancy Scale for Self-Care (OESS). Methods : Twenty-eight patients with diabetes participated in the study. Their personal characteristics were determined from the items of self-efficacy for brushing of the teeth (SE-B), self-efficacy for dental consultations (SE-DC), OESS that are comprised of three factors, namely, the social outcome expectancy (OE-Social), oral outcome expectancy (OE-Oral), and self-evaluative outcome expectancy (OE-Self), and the M-DiOHATⓒ. Results : Forty-three percent of patients had retained their expected number of present teeth, and 68% of them had dental problems. The scores of health record sharing were low, and patients who were under 65 years old had fewer “expected number of present teeth," and lower SE-B/oral health conditions scores than those patients aged over 65 years. The scores of oral hygiene behaviors were significantly correlated with the SE-B scores, SE-DC, OE-Oral, and OE-Self. However, the oral health conditions showed no correlation with SE-B, SE-DC, OESS. Conclusion : The findings suggest that nursing interventions to promote SE-B, SE-DC, and OESS could be effective in enhancing patients' oral hygiene behaviors. However, severity of patients' periodontal disease require different types of dental self-efficacy procedures

Insulin receptor cleavage induced by estrogen impairs insulin signaling

Introduction: Soluble insulin receptor (sIR), which is the ectodomain of insulin receptor (IR), is present in human plasma. Plasma sIR levels are positively correlated with blood glucose levels and negatively correlated with insulin sensitivity. An in vitro model of IR cleavage shows that extracellular calpain 2 directly cleaves IR, which generates sIR, and sequential cleavage of the IRβ subunit by γ-secretase impairs insulin signaling in a glucose concentration-dependent manner. Nevertheless, sIR levels vary among subjects with normal glucose levels. Research design and methods: We examined sIR levels of pregnant women throughout gestation. Using an in vitro model, we also investigated the molecular mechanisms of IR cleavage induced by estradiol. Results: In pregnant women, sIR levels were positively correlated with estrogen levels and significantly increased at late pregnancy independent of glucose levels. Using an in vitro model, estrogen elicited IR cleavage and impaired cellular insulin signaling. Estradiol-induced IR cleavage was inhibited by targeting of calpain 2 and γ-secretase. Estrogen exerted these biological effects via G protein-coupled estrogen receptor, and its selective ligand upregulated calpain 2 expression and promoted exosome secretion, which significantly increased extracellular calpain 2. Simultaneous stimulation of estrogen and high glucose levels had a synergic effect on IR cleavage. Metformin prevented calpain 2 release in exosomes and restored insulin signaling impaired by estrogen. Conclusions: Estradiol-induced IR cleavage causes cellular insulin resistance, and its molecular mechanisms are shared with those by high glucose levels. sIR levels at late pregnancy are significantly elevated along with estrogen levels. Therefore, estradiol-induced IR cleavage is preserved in pregnant women and could be part of the etiology of insulin resistance in gestational diabetes mellitus and overt diabetes during pregnancy

Urinary adiponectin in DKD

Aims: Since diabetes-associated kidney complication changes from diabetic nephropathy to diabetic kidney disease (DKD), more suitable biomarkers than urinary albumin are required. It has been hypothesized that urinary adiponectin (u-ADPN) is associated with the progression of DKD. We therefore evaluated the effectiveness of u-ADPN in predicting the decline of the renal function in patients with diabetes prior to end-stage renal disease. Methods: An ultrasensitive immune complex transfer enzyme immunoassay (ICT-EIA) was used to measure total and high molecular weight (HMW) adiponectin separately. We evaluated the relationships between the creatinine-adjusted urinary total-ADPN and HMW-ADPN, albumin (UACR) and liver-type fatty acid binding protein (L-FABP) at baseline and the 2-year change of the estimated glomerular filtration rate (ΔeGFR). Results: This 2-year prospective observational study included 201 patients with diabetes. These patients were divided into three groups according to their ΔeGFR: ≤-10 ml/min/1.73m2, >-10 and ≤0 ml/min/1.73m2, and >0 ml/min/1.73m2. Jonckheere-Terpstra test showed that lower ΔeGFR was associated with higher u-HMW-ADPN (p = 0.045). In logistic regression analysis, u-HMW-ADPN was associated with ΔeGFR after adjusted age, sex, and basal eGFR. Conclusion: Urinary HMW-ADPN could predict a declining renal function in patients with diabetes