Live two-way video versus face-to-face treatment for depression, anxiety, and obsessive-compulsive disorder: A 24-week randomized controlled trial.

AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.

The relationship between masticatory performance and intakes of foods and nutrients in Japanese male workers: A cross-sectional study.

BACKGROUND: Although many studies have been conducted on the relationship between masticatory performance and nutrient ingestion in the elderly, few large-scale studies have been carried out using relatively young individuals. OBJECTIVES: The objective of this study was to clarify the association between the masticatory performance evaluated by the gummy-jelly test, not by visual examination, and nutrient ingestion state based on the brief self-administered diet history questionnaire (BDHQ). METHODS: This was a cross-sectional survey of 540 male workers. Somatometry, blood pressure measurement, blood test and medical interview were performed as a periodic health check-up. In the dental check-up, an oral examination, gummy-jelly test (glucosensor) and survey of ingested food and nutrients using BDHQ were performed. The participants were classified into two groups with low and normal values of masticatory performance. Participants with a score on the gummy-jelly test below 150 mg/dL or 150 mg/dL or higher were included in the low and normal groups, respectively. RESULTS: Two hundred and forty-eight participants (45.8%) had low masticatory performance, and 292 (53.2%) had normal masticatory performance. The intakes of some minerals and vitamins, such as calcium, vitamin D, vitamin B2 , small fish with bones and non-oily fish, were significantly lower in the low masticatory group than in the normal group. In contrast, the intake of sugar for coffee and tea and that of chicken were significantly higher in the low masticatory group than in the normal group. CONCLUSION: This study suggested that low masticatory performance can affect nutrient intake, which may cause non-communicable diseases.

Endothelium-Dependent Hyperpolarization (EDH) in Diabetes: Mechanistic Insights and Therapeutic Implications.

Diabetes mellitus is one of the major risk factors for cardiovascular disease and is an important health issue worldwide. Long-term diabetes causes endothelial dysfunction, which in turn leads to diabetic vascular complications. Endothelium-derived nitric oxide is a major vasodilator in large-size vessels, and the hyperpolarization of vascular smooth muscle cells mediated by the endothelium plays a central role in agonist-mediated and flow-mediated vasodilation in resistance-size vessels. Although the mechanisms underlying diabetic vascular complications are multifactorial and complex, impairment of endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells would contribute at least partly to the initiation and progression of microvascular complications of diabetes. In this review, we present the current knowledge about the pathophysiology and underlying mechanisms of impaired EDH in diabetes in animals and humans. We also discuss potential therapeutic approaches aimed at the prevention and restoration of EDH in diabetes.

Metyrapone-responsive ectopic ACTH-secreting pheochromocytoma with a vicious cycle via a glucocorticoid-driven positive-feedback mechanism.

In ectopic ACTH-secreting pheochromocytoma, combined ACTH-driven hypercortisolemia and hypercatecholaminemia are serious conditions, which can be fatal if not diagnosed and managed appropriately, especially when glucocorticoid-driven positive feedback is suggested with a high ACTH/cortisol ratio. A 46-year-old man presented with headache, rapid weight loss, hyperhidrosis, severe hypertension and hyperglycemia without typical Cushingoid appearance. Endocrinological examinations demonstrated elevated plasma and urine catecholamines, serum cortisol and plasma ACTH. Moreover, his ACTH/cortisol ratio and catecholamine levels were extremely high, suggesting catecholamine-dominant ACTH-secreting pheochromocytoma. Computed tomography revealed a large right adrenal tumor. 18F-FDG positron emission tomography showed uptake in the area of the adrenal tumor, while 123I-metaiodobenzylguanidine scintigraphy showed no accumulation. His plasma ACTH level paradoxically became elevated after a dexamethasone suppression test. After metyrapone administration, not only serum cortisol but also plasma ACTH levels were exponentially decreased almost in parallel, suggesting a glucocorticoid-driven positive-feedback regulation in this rapidly exacerbated ectopic ACTH-producing pheochromocytoma. Interestingly enough, plasma catecholamine levels were also decreased by metyrapone, although they remained extremely high. He became severely dehydrated due to hypoadrenalism requiring hydrocortisone supplementation. His clinical signs and symptoms were improved, and right adrenalectomy was performed uneventfully, resulting in complete remission of pheochromocytoma and Cushing's syndrome. A glucocorticoid-driven positive-feedback regulation in this ectopic ACTH-secreting pheochromocytoma created a vicious cycle with rapid exacerbation of both hypercortisolemia and hypercatecholaminemia with extremely elevated plasma ACTH level. Metyrapone was clinically effective to stop this vicious cycle; nonetheless, great care must be taken to avoid hypoadrenalism especially when hypercatecholaminemia remained.

Role of renin-angiotensin aldosterone system on short-term blood pressure variability in hypertensive patients.

The relationship between the renin-angiotensin aldosterone system and short-term blood pressure variability has not been well elucidated. Here, we investigated whether blood pressure variability determined by ambulatory blood pressure monitoring differed among patients with primary aldosteronism (PA), renovascular hypertension (RVHT), and essential hypertension (EHT). We examined 25 patients with PA, 28 patients with RVHT, and 18 patients with EHT. Ambulatory blood pressure monitoring was conducted in all patients. Short-term blood pressure variability was evaluated by calculating the standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) of 24-h, daytime, and nighttime blood pressure values. Day-night differences in blood pressure were also determined. The mean 24-h systolic blood pressure (SBP) and the mean diastolic blood pressure (DBP) in the PA and RVHT groups were found to be comparable to those in the EHT group. The SD, the CV, nor the ARV of the 24-h, daytime, and nighttime blood pressures showed any significant differences among the three groups. The day-night differences in blood pressure were comparable among the three groups. The short-term blood pressure variabilities evaluated by ambulatory blood pressure monitoring were comparable among the patients with EHT, RVHT, and PA. The results suggest that the renin-angiotensin aldosterone system may contribute little to short-term blood pressure variability in individuals with hypertension.

Impact of obstructive sleep apnea on blood pressure and cardiovascular risk factors in Japanese men: A cross-sectional study in work-site group.

It has been shown that obstructive sleep apnea (OSA) is related to hypertension and cardiovascular disease; however, the prevalence of OSA in general population and the impact of it on blood pressure especially in Japan has not been well determined. We have conducted a screening test for OSA from 2003 to 2011. In addition, a cross-sectional analysis was performed in 2012 to determine the association of OSA and cardiovascular risk factors in Japanese men (18-69 years of age; mean age, 44.4 ± 0.2). The study group consisted of 2208 male employees, and OSA was evaluated by using the 4% oxygen desaturation index and apnea-hypopnea index (AHI). The prevalence of mild-to-moderate (5≤AHI<30) and severe (AHI≥30) OSA in the studied subjects were 7.1%, and 6.1%, respectively. Among the 135 severe OSA subjects, 105 (77.8%) had been treated with continuous positive airway pressure. Both systolic and diastolic blood pressures (DBP) were significantly increased in the subjects with severe OSA compared with those without OSA. These associations in DBP remained observed after adjustment for age, body mass index (BMI), estimated glomerular filtration rate, HbA1c, current alcohol intake, current smoking habits, and OSA treatment. DBP in severe OSA subjects were significantly increased in 1807 subjects who were not treated for hypertension or OSA. However, the levels of blood pressures were not decreased by OSA treatment. These results suggest that the prevalence of OSA is relatively high in middle-aged Japanese men and that blood pressures were elevated in the subjects with severe OSA.

Endothelium-Dependent Hyperpolarization (EDH) in Hypertension: The Role of Endothelial Ion Channels.

Upon stimulation with agonists and shear stress, the vascular endothelium of different vessels selectively releases several vasodilator factors such as nitric oxide and prostacyclin. In addition, vascular endothelial cells of many vessels regulate the contractility of the vascular smooth muscle cells through the generation of endothelium-dependent hyperpolarization (EDH). There is a general consensus that the opening of small- and intermediate-conductance Ca2+-activated K⁺ channels (SKCa and IKCa) is the initial mechanistic step for the generation of EDH. In animal models and humans, EDH and EDH-mediated relaxations are impaired during hypertension, and anti-hypertensive treatments restore such impairments. However, the underlying mechanisms of reduced EDH and its improvement by lowering blood pressure are poorly understood. Emerging evidence suggests that alterations of endothelial ion channels such as SKCa channels, inward rectifier K⁺ channels, Ca2+-activated Cl- channels, and transient receptor potential vanilloid type 4 channels contribute to the impaired EDH during hypertension. In this review, we attempt to summarize the accumulating evidence regarding the pathophysiological role of endothelial ion channels, focusing on their relationship with EDH during hypertension.

[THE CAUSES OF ACUTE COUGH: A SINGLE-CENTER STUDY IN JAPAN].

BACKGROUND: Cough is the most frequent presenting complaint in clinics, and is classified into the following three groups: acute, subacute and chronic. The major causes of acute cough are infectious diseases, however, few observations on acute cough have been reported. METHODS: We retrospectively assessed the causes of acute cough among patients who had visited the respiratory clinic of our hospital because of acute cough from September 2014 to August 2015. RESULTS: Of 374 patients (195 females, mean age 60.3 years) who visited the clinic complaining of cough, 129 patients (63 females, mean age 61.5 years) suffered from acute cough. All acute cases were stratified into two groups based on the presence (n=43) or absence (n=86) of abnormal findings on the chest X-ray. The main causes of acute cough with abnormal findings were pneumonia (46.5%), interstitial pneumonia (18.6%) and lung cancer (16.3%). The main causes of acute cough without abnormal findings were respiratory tract infection (39.5%), post infectious cough (18.6%) and bronchial asthma (17.4%). Acute cough was the primary complaint in 29.5% and 19.6% of all patients diagnosed with bronchial asthma and cough variant asthma, respectively. CONCLUSION: Non-infectious diseases including asthma as well as infectious diseases could be the causes in acute cough without abnormal findings on the chest X-ray.

Trends in blood pressure control and medication use during 20 years in a hypertension clinic in Japan.

Guidelines for the management of hypertension have recommended strict control of blood pressure to help prevent cardiovascular disease. The aim of the present study was to evaluate the current status of blood pressure control and trends over the past two decades. Four hundred patients treated for hypertension at Kyushu University Hospital were included in the present study. Blood pressure levels and prescribed antihypertensive drugs were examined in 2011. The average blood pressure was 129/74 mmHg, and the number of prescribed antihypertensive drugs was 2.2. Angiotensin II receptor antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics, alpha-blockers, and beta-blockers were prescribed in 66%, 5%, 78%, 21%, 12%, and 27% of the cases, respectively. Systolic blood pressure was significantly higher, and diastolic blood pressure was significantly lower in patients aged 80 years or older compared with the younger patients (<80 and ≥80 years, 128/75 mmHg and 133/68 mmHg, respectively). The number of prescribed antihypertensive drugs was similar between the two groups. Sixty-five patients were continuously treated for 20 years. The average blood pressure of these patients significantly decreased from 142/87 mmHg in 1991 to 128/71 mmHg in 2011, accompanied with an increase in the number of antihypertensive drugs from 1.6 in 1991 to 2.7 in 2011. These findings suggest that the revised guidelines for the management of hypertension may have contributed to increased awareness and better management of blood pressure levels.

Energy metabolism and nutritional status in hospitalized patients with lung cancer.

This study aimed to investigate the energy metabolism of patients with lung cancer and the relationship between energy metabolism and proinflammatory cytokines. Twenty-eight patients with lung cancer and 18 healthy controls were enrolled in this study. The nutritional status upon admission was analyzed using nutritional screening tools and laboratory tests. The resting energy expenditure and respiratory quotient were measured using indirect calorimetry, and the predicted resting energy expenditure was calculated using the Harris-Benedict equation. Energy expenditure was increased in patients with advanced stage disease, and there were positive correlations between measured resting energy expenditure/body weight and interleukin-6 levels and between measured resting energy expenditure/predicted resting energy expenditure and interleukin-6 levels. There were significant relationships between body mass index and plasma leptin or acylated ghrelin levels. However, the level of appetite controlling hormones did not affect dietary intake. There was a negative correlation between plasma interleukin-6 levels and dietary intake, suggesting that interleukin-6 plays a role in reducing dietary intake. These results indicate that energy expenditure changes significantly with lung cancer stage and that plasma interleukin-6 levels affect energy metabolism and dietary intake. Thus, nutritional management that considers the changes in energy metabolism is important in patients with lung cancer.

Mice heterozygous for the xanthine oxidoreductase gene facilitate lipid accumulation in adipocytes.

OBJECTIVE: Xanthine oxidoreductase (XOR) catalyzes the production of uric acid with concomitant generation of reactive oxygen species. XOR has been shown to regulate adipogenesis through the control of peroxisome proliferator-activated receptor γ, but its role in adipose tissue remains unclear. The aim of this study was to examine the role of XOR in adipose tissue using XOR genetically modified mice. APPROACH AND RESULTS: Experiments were performed using 2-, 4-, and 18-month-old XOR heterozygous mice (XOR(+/-)) and their wild-type littermates to evaluate the physiological role of XOR as the mice aged. Stromal vascular fraction cells were prepared from epididymal white adipose tissue in 2-month-old XOR mice to assess adipogenesis. At 18 months, XOR(+/)- mice had significantly higher body weight, higher systolic blood pressure, and higher incidence of insulin resistance compared with wild-type mice. At 4 months, blood glucose and the expressions of CCAAT enhancer-binding protein ß, peroxisome proliferator-activated receptor γ, monocyte chemoattractant protein-1, and tumor necrosis factor α mRNA in epididymal white adipose tissue were significantly higher in XOR(+/-) than in wild-type mice. Furthermore, histological analysis of epididymal white adipose tissue in XOR(+/-) mice revealed that adipocyte size and the F4/80-positive macrophage count were increased. Experiments with a high-fat diet exhibited that body weight gain was also significantly higher in XOR(+/-) than in wild-type mice. In stromal vascular fraction cells derived from XOR(+/-) mice, the levels of peroxisome proliferator-activated receptor γ, fatty acid-binding protein 4, and CCAAT enhancer-binding protein α mRNA were upregulated, and oxidative stress levels were elevated during differentiation into adipocytes. CONCLUSIONS: These results suggest that the reduction in XOR gene expression in mice augments lipid accumulation in adipocytes, accompanied by an increase in oxidative stress, and induces obesity with insulin resistance in older age.

Relative contributions of emphysema and airway remodelling to airflow limitation in COPD: Consistent results from two cohorts.

BACKGROUND AND OBJECTIVE: The relative contributions of emphysema and airway remodelling to airflow limitation remain unclear in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the relative contributions of emphysema and airway wall thickness measured by quantitative computed tomography (CT) to the prediction of airflow limitation in two separate COPD cohorts. METHODS: Pulmonary function tests and whole-lung CT were performed in 250 male smokers with COPD, including 167 from University Medical Center at Ho Chi Minh City, Vietnam, and 83 from Shiga University of Medical Science Hospital, Japan. The same CT analysis software was used to measure the percentage of low attenuation volume (%LAV) at the threshold of -950 Hounsfield units and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10). The standardized coefficients in multiple linear regressions were used to evaluate the relative contributions of %LAV and Pi10 to predictions of FEV1 /FVC and FEV1 % predicted. RESULTS: Both %LAV and Pi10 independently predicted either forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) or FEV1 % predicted (P ≤ 0.001 for all standardized coefficients). However, the absolute values of the standardized coefficients were 2-3 times higher for %LAV than for Pi10 in all prediction models. The results were consistent in the two COPD cohorts. CONCLUSIONS: %LAV predicts both FEV1 /FVC and FEV1 better than Pi10 in patients with COPD. Thus, emphysema may make a greater contribution to airflow limitation than airway remodelling in COPD.

Medication adherence and associated factors in newly diagnosed hypertensive patients in Japan: the LIFE study.

Hypertension is the leading cardiovascular risk factor worldwide. However, in Japan, only 30% of patients have their blood pressure controlled under 140/90 mmHg, and nonadherence to antihypertensives is thought to be a reason for the poor control of hypertension. We therefore sought to assess the adherence to hypertension treatment and to evaluate factors influencing patients' adherence in a large, representative sample of the Japanese population. To this end, we analyzed claims data from the LIFE Study database, which includes 112 506 Japanese adults with newly diagnosed hypertension. Medication adherence was measured for a year postdiagnosis using the proportion of days covered (PDC) method. Factors associated with adherence to antihypertensives were also assessed. Among the total 112 506 hypertensive patients, the nonadherence rate (PDC ≤ 80%) for antihypertensives during the first year after initiation of the treatment was 26.2%. Younger age [31-35 years: odds ratio (OR), 0.15; 95% confidence interval (95% CI), 0.12-0.19 compared with 71-74-year-old patients], male gender, monotherapy, and diuretics use [OR, 0.87; 95% CI, 0.82-0.91 compared with angiotensin II receptor blockers (ARBs)] were associated with poor adherence in the present study. Cancer comorbidity (OR, 0.84; 95% CI, 0.79-0.91 compared with no comorbidity), prescription at a hospital, and living in a medium-sized to regional city were also associated with poor adherence. Our present findings showing the current status of adherence to antihypertensive medications and its associated factors using claims data in Japan should help to improve adherence to antihypertensives and blood pressure control.

Sleep-related breathing disorder in a Japanese occupational population and its association with hypertension-stratified analysis by obesity status.

Sleep-related breathing disorder (SRBD) causes hypertension, and obesity has been highly associated with SRBD, which has become a serious health problem in young and middle-aged Japanese males. However, the relation between SRBD and hypertension considering the effects of obesity remains unknown. In this cross-sectional study, we examined the relationship between SRBD and hypertension, with consideration for the effects of obesity, in Japanese occupational population. Using 3% oxygen desaturation index (3%ODI) obtained by simplified polysomnography (PSG), participants were classified into low (0 ≤ 3%ODI < 5), medium (5 ≤ 3%ODI < 15), and high (15 ≤ 3%ODI) 3%ODI groups. We excluded employees who had not undergone medical examination with simplified PSG in the same year from 2012 to 2018. Logistic regression analysis was performed to calculate odds ratios for having hypertension according to 3%ODI levels. In total, 2532 employees were included. Among them, 25% and 4% were categorized into the medium and high 3%ODI groups, respectively. The odds ratio for hypertension increased significantly with higher 3%ODI levels after adjustment for age, sex, alcohol drinking status and smoking status (p for trend < 0.0001). However, further adjustment for obesity status (body mass index ≥ 25 kg/m2) attenuated the associations. When we performed the stratified analysis by obesity status, the odds ratio for hypertension increased significantly with higher 3%ODI only for non-obese individuals, with significant interaction (p for interaction = 0.014). Higher 3%ODI was significantly associated with higher prevalence of hypertension especially in non-obese participants, suggesting the importance of vigilance for the presence of SRBD even in non-obese individuals. We investigated the association between SRBD and hypertension considering the effects of obesity, which would suggest the need to keep in mind the presence of SRBD even in non-obese individuals.

Activities of daily living dependency and disease-specific mortality during 12-year follow-up in an 80-year-old population.

BACKGROUND AND AIMS: Although total mortality is likely to be higher in elderly individuals with frailty or impaired activities of daily living (ADL), little is known about the relationships between disease-specific mortality and ADL dependency in the elderly. Therefore, we examined whether 12-year disease-specific mortality may be associated with ADL dependency in an 80-year-old population. METHODS: In 1998, of 1,282 community-dwelling residents of Japan's Fukuoka Prefecture, 824 (64.3 %) (309 males and 515 females) participated, the remaining 458 subjects did not participate, and their deaths and causes of death were followed up for 12 years after the baseline examination. ADL dependency was determined according to the guidelines for disabled elderly from the Health, Labor, and Welfare Ministry of Japan, and ADL dependency was measured only at baseline. RESULTS: During the 12-year follow-up, 506 died, 276 did not die, and 42 were lost. Of the 506 who died, 128 died due to cardiovascular disease, 96 to respiratory tract disease, 87 to cancer, and 51 to senility. The subjects were classified into three groups as follows: ADL-1 (independent group, n = 600), ADL-2 (almost-independent group, n = 113), and ADL-3 (dependent group, n = 93).Total-cause mortality was 2.8 times higher in ADL-3 subjects, respiratory disease mortality was 4.1 times higher in ADL-3 subjects, and senility mortality was 5.7 times higher in ADL-3 subjects than in ADL-1 subjects, after adjusting for various confounding factors. There was no association between mortality due to cancer or cardiovascular disease and ADL dependency. CONCLUSIONS: We found an independent association between ADL dependency and mortality due to all causes, respiratory disease or senility, but no association with mortality due to cancer or cardiovascular disease. These findings suggest that improving ADL dependency may reduce all mortality and mortality due to respiratory disease or senility.

Effects of the superoxide dismutase mimetic tempol on impaired endothelium-dependent and endothelium-independent relaxations in type II diabetic rats.

Endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization and relaxation, and endothelium-independent relaxations to the nitric oxide donor sodium nitroprusside and the adenosine 5'-triphosphate (ATP)-sensitive K(+)-channel opener levcromakalim were both impaired in mesenteric arteries of type II diabetic Goto-Kakizaki rats. The treatment with the superoxide dismutase mimetic tempol or its combination with the angiotensin II type 1 receptor blocker candesartan failed to improve EDHF-mediated responses, although both treatments partially improved endothelium-independent relaxations. These findings suggest that increased oxidative stress may in part account for the impaired endothelium-independent relaxations in diabetes, while it does not play a major role in the impaired EDHF-mediated responses.

Triglyceride, an Independent Risk Factor for New-Onset Hypertension: A Perspective.

Hypertension is the most important risk factor for cardiovascular disease worldwide. Although the pathogenesis of hypertension is complex and multifactorial, obesity-related hypertension has become a major focus of attention because of the continued increase in the prevalence of overweight and obesity. Several mechanisms have been suggested to underlie obesity-related hypertension, including an increase in sympathetic nervous system activity, an upregulation of the renin-angiotensinaldosterone system, alterations in adipose-derived cytokines, and an augmentation of insulin resistance. Emerging evidence from observational studies (including those using Mendelian randomization) suggests that the presence of high triglycerides, which is a common comorbidity in obesity, is an independent risk factor for new-onset hypertension. However, little is known about the mechanisms underlying triglyceride-associated hypertension. We summarize the existing clinical evidence that has demonstrated the adverse effect of triglycerides on blood pressure, and we then discuss possible underlying mechanisms based on the evidence from animal and human studies, with a particular focus on the roles of endothelial function, white blood cells, i.e., lymphocytes, and pulse rate.

Association of body mass index with glomerular filtration rate in Japanese: a cross-sectional study in work-site population.

It has been shown that aging and hypertension are important risk factors to promote renal damage. However, little data are available on the effect of obesity on the progression of renal damage, especially in young and middle-aged individuals. The aim of this study was to determine the association between body mass index (BMI) and renal function evaluated by estimated glomerular filtration rate (eGFR) in Japanese men. We studied the cross-sectional association of BMI with eGFR in 3872 Japanese men in a work-site population (18-64 y; mean age 42.1 ± 0.2 y). Estimated glomerular filtration rate was calculated by a novel equation for Japanese men. Estimated glomerular filtration rate was negatively correlated with age, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), and BMI. We performed multiple regression analysis, controlling for factors, such as SBP, low-density lipoprotein-cholesterol, gamma-glutamyl transpeptidase, age, HbA1c, and uric acid. The association between age and eGFR was highly statistically significant. In addition, BMI was still significantly associated with eGFR independently of SBP. Moreover, mean eGFR, which was adjusted for age, SBP, HbA1c, serum uric acid, and gamma-glutamyl transpeptidase, decreased from 88.9 mL/min/1.73 m(2) in the first quartile of BMI to 87.5 mL/min/1.73 m(2) in the second, 86.9 mL/min/1.73 m(2) in the third, and 85.9 mL/min/1.73 m(2) in the fourth quartile (test for trend, P < .0001). These results show that a close relationship is present between obesity and decreased eGFR in Japanese men. Keeping appropriate body weight, in addition to appropriate blood pressure, in young and middle age may be important to prevent renal damage in older age.

Chloride Ions, Vascular Function and Hypertension.

Blood pressure is determined by cardiac output and systemic vascular resistance, and mediators that induce vasoconstriction will increase systemic vascular resistance and thus elevate blood pressure. While peripheral vascular resistance reflects a complex interaction of multiple factors, vascular ion channels and transporters play important roles in the regulation of vascular tone by modulating the membrane potential of vascular cells. In vascular smooth muscle cells, chloride ions (Cl-) are a type of anions accumulated by anion exchangers and the anion-proton cotransporter system, and efflux of Cl- through Cl- channels depolarizes the membrane and thereby triggers vasoconstriction. Among these Cl- regulatory pathways, emerging evidence suggests that upregulation of the Ca2+-activated Cl- channel TMEM16A in the vasculature contributes to the increased vascular contractility and elevated blood pressure in hypertension. A robust accumulation of intracellular Cl- in vascular smooth muscle cells through the increased activity of Na+-K+-2Cl- cotransporter 1 (NKCC1) during hypertension has also been reported. Thus, the enhanced activity of both TMEM16A and NKCC1 could act additively and sequentially to increase vascular contractility and hence blood pressure in hypertension. In this review, we discuss recent findings regarding the role of Cl- in the regulation of vascular tone and arterial blood pressure and its association with hypertension, with a particular focus on TMEM16A and NKCC1.

Non-linear relationship between hyperpolarisation and relaxation enables long distance propagation of vasodilatation.

Blood flow is adjusted to tissue demand through rapidly ascending vasodilatations resulting from conduction of hyperpolarisation through vascular gap junctions. We investigated how these dilatations can spread without attenuation if mediated by an electrical signal. Cremaster muscle arterioles were studied in vivo by simultaneously measuring membrane potential and vessel diameter. Focal application of acetylcholine elicited hyperpolarisations which decayed passively with distance from the local site,while dilatation spread upstream without attenuation. Analysis of simultaneous recordings at the local site revealed that hyperpolarisation and dilatation were only linearly related over a restricted voltage range to a threshold potential, beyond which dilatation was maximal. Experimental data could be simulated in a computational model with electrotonic decay of hyperpolarisation but imposition of this threshold. The model was tested by reducing the amplitude of the local hyperpolarisation which led to entry into the linear range closer to the local site and decay of dilatation. Serial section electron microscopy and light dye treatment confirmed that the spread of dilatation occurred through the endothelium and that the two cell layers were tightly coupled. Generality of the mechanism was demonstrated by applying the model to the attenuated propagation of dilatation found in larger arteries.We conclude that long distance spread of locally initiated dilatations is not due to a regenerative electrical phenomenon, but rather a restricted linear relationship between voltage and vessel tone, which minimises the impact of electrotonic decay of voltage. Disease-related alterations in endothelial coupling or ion channel expression could therefore decrease the ability to adjust blood flow to meet metabolic demand.