Search

Reducing salt and increasing potassium intake are recommended lifestyle modifications for patients with hypertension. The estimated 24-h urinary salt excretion value from spot urine using Tanaka's formula and the salt check-sheet scores, questionnaire-based scores of salt intake, are practical indices of daily salt intake. However, few studies have evaluated salt intake with these methods in hypertensive outpatients. We examined salt and potassium intake with the spot urine method and the salt check-sheet scores of hypertensive outpatients in a multi-facility, real-world setting and examined whether the salt or potassium intake evaluated with these methods related to inadequate blood pressure control. Hypertensive outpatients from 12 medical facilities in the Okinawa prefecture were enrolled from November 2011 to April 2014 (n = 1559, mean age 63.9 years, 46% women). The mean blood pressure, urinary salt excretion value, urinary potassium excretion value, and total score on the salt check-sheet were 129/75 mmHg, 8.7 g/day, 1.6 g/day, and 10.4 points, respectively. The urinary salt excretion value and total score on the salt check-sheet but not urinary potassium excretion value were associated with inadequate blood pressure control (≥140/90 mmHg). Higher body mass index, estimated glomerular filtration rate, urinary potassium excretion value, total score on the salt check-sheet, and presence of inadequate blood pressure control were associated with high urinary salt excretion (≥10.2 g/day). In conclusion, hypertensive outpatients with high urinary salt excretion values estimated using Tanaka's formula or with high scores on the salt check sheet may be candidates for more intensive salt reduction guidance.

Although numerous studies have confirmed the beneficial effects of pharmacological therapy for arterial stiffness and endothelial dysfunction, which are predictors/therapeutic targets for cardiovascular diseases, only a few overall quantitative evaluations of MRAs (mineralocorticoid receptor antagonists) exist. We searched PubMed and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) for randomized trials evaluating MRA effects on arterial stiffness measured by pulse wave velocity (PWV) or augmentation index and endothelial function measured by flow-mediated dilation. Data from the included trials were pooled by using random-effects meta-analysis of the weighted mean difference (MD) between the comparator groups. The primary outcome was the MD of PWV. In 11 trials including 515 patients, the MRA treatment reduced the PWV when compared with control (MD, −0.75 m/s [95% CI, −1.12 to −0.39], P P =0.705 for heterogeneity). The effects of MRA on PWV were independent of blood pressure reduction related to the treatment according to meta-regression analysis. The MRA treatment reduced the augmentation index compared with control in 5 trials including 283 patients (MD, −6.74% [95% CI, −10.26 to −3.21], P =0.0002) and increased the flow-mediated dilation in 11 trials including 570 patients (MD, 1.18% [95% CI, 0.14 to 2.23], P =0.03). In conclusion, the current meta-analysis demonstrates the beneficial effects of MRA on PWV, augmentation index, and flow-mediated dilation.

OBJECTIVES We aimed to determine if the ankle--brachial index (ABI) increased with age as a result of increased arterial stiffness and wave reflection, and whether this was associated with left ventricular hypertrophy (LVH). METHODS An observational cross-sectional study was conducted in 13 396 participants aged 19-89 years who attended a health check-up. Brachial and ankle blood pressures were measured by an automatic oscillometric method. Electrocardiography-determined LVH (ECG-LVH) was defined by computer-interpreted Minnesota codes using resting 12-leads ECG. RESULTS The mean age of the participants was 53 years (54% women). The prevalence of ECG-LVH was 13%; this was the lowest in participants with normal blood pressure and increased with an increase in the hypertension grade. The ABI was higher in participants with ECG-LVH than in those without (1.13± 0.07 vs. 1.15 ± 0.07, P

Herein, we describe a rare case of Corynebacterium jeikeium endocarditis that silently progressed in a 65-year-old man undergoing hemodialysis. Because routine monthly blood examination revealed high C-reactive protein levels, blood cultures were collected, although he had no symptom and was afebrile. After 2 days, a Gram-positive rod was detected in one set of the blood culture. Furthermore, transthoracic echocardiography revealed new aortic regurgitation (AR) and vegetations, and, therefore, infective endocarditis was suspected. Transesophageal echocardiography showed vegetations with a maximum diameter of 8 mm on his aortic valve, with some valve destruction. C. jeikeium was identified in three sets of blood cultures. Administration of daptomycin was started because he had vancomycin allergy. Judging from the high risk of embolization due to vegetations, emergency aortic valve replacement was performed on the second day. C. jeikeium was detected in a resected cardiac valve specimen and blood. This case emphasizes that physicians should always consider the possibility of infective endocarditis even in hemodialysis patients without any symptoms.

Bone marrow-derived cells exert anti-inflammatory actions and can migrate into the brain. However, their role in the development of neurogenic hypertension remains unclear. A hyperactive renin–angiotensin system and inflammation in the brain are mechanisms that contribute to angiotensin II-initiated neurogenic hypertension. We hypothesized that bone marrow-derived cells in the brain attenuate the overactive brain renin–angiotensin system and inflammation, thereby reducing neurogenic hypertension. We cultured plastic-adherent bone marrow-derived cells for 3 weeks. Seven days after initiation of vehicle or angiotensin II infusions, the rats underwent intracerebroventricular administration of either serum-free medium or autologous bone marrow-derived cells (106 cells). After 23 days of infusion, the mean arterial pressure was recorded, and the sympathetic tone was evaluated. Rats infused with angiotensin II demonstrated significant increases in the resting mean arterial pressure and the peak depressor response to ganglionic blockade (vehicle vs. angiotensin II infusion, 119 ± 4 vs. 178 ± 6 mmHg and −34 ± 6 vs. −74 ± 5 mmHg, respectively). Intracerebroventricularly administered bone marrow-derived cells attenuated the angiotensin II-mediated increases in the resting mean arterial pressure and peak depressor response (142 ± 11 and −52 ± 4 mmHg, respectively). The cells also reduced the angiotensin II-induced increases in angiotensin II type 1 receptor and transforming growth factor-β expression in the brain. In conclusion, bone marrow-derived cells in the brain may have a protective role against the development of angiotensin II-induced neurogenic hypertension by modulating angiotensin II type 1 receptor expression and inflammatory processes.

Systolic blood pressure (SBP) and arterial stiffness are closely related and may behave reciprocally as cause or effect, interacting in a vicious cycle. Both SBP and arterial stiffness increase with age in populations in most developed countries. However, the age-related increase in SBP appears to be absent in indigenous populations, partially because of their lifelong low-sodium and high-potassium diets, whereas age-related arterial stiffening in these populations remains to be determined. We performed a field survey of the indigenous population of Soroba, a small village located in the central highlands of Papua, Indonesia. Blood pressure levels and brachial-ankle pulse wave velocity (baPWV) were measured using an automatic device. A total of 125 native Papuans 16-75 years of age (59% women) were included in this study. SBP and pulse pressure were not correlated with age. However, diastolic and mean arterial pressure levels increased with age. The prevalence of hypertension was 5% (n = 6; all women), and baPWV significantly increased with age. Compared with participants 45 years of age and older, those younger than 45 years had a higher body mass index (BMI) and spot urine sodium-to-potassium ratio but lower baPWV; however, SBP was not different between these age groups. Multivariate linear regression analysis revealed that SBP was independently associated with baPWV, sex and BMI but not with age; baPWV was independently associated with SBP, age, BMI, sex and heart rate. SBP and baPWV were closely related, but the age-related changes in these measurements differed in this highland Papuan population.

Inflammation is a feature of lung injury and plays a critical role in pulmonary vascular remodeling. Bone marrow-derived cells (BMCs) have anti-inflammatory properties and favor macrophage differentiation into an alternatively activated regulatory M2 profile. We investigated the effect of autologous BMCs on monocrotaline-induced pulmonary vessel remodeling and lung inflammation in rats, by direct administration into lungs via the airway.BMCs were isolated and plastic-adherent cells were cultured for 3 weeks. 1 week following monocrotaline (60 mg/kg) treatment, fluorescently labeled autologous BMCs (1 × 10Monocrotaline increased pulmonary vessel wall thickness, perivascular infiltration, alveolar septal thickening, and inflammatory cell infiltration including T lymphocytes and monocytes/macrophages in alveolar areas, and also increased mRNA expression of inflammatory-related cytokines including IL-10 in the lung. Intratracheal administration of autologous BMCs prevented pulmonary vessel wall thickening and perivascular infiltration, and increased CD163-positive M2-like macrophages in perivascular areas. BMC administration inhibited the thickening of alveolar septa and reduced monocrotaline-induced inflammatory cell infiltration in lung parenchyma compared with monocrotaline-vehicle-treated-rats. Furthermore, BMCs administration increased expression of CD163-positive cells in perivascular areas and maintained the increased mRNA expression of IL-10.Intratracheal administration of autologous BMCs prevented monocrotaline-induced pulmonary vessel remodeling and lung inflammation, at least in part, through induction of alternatively activated macrophages and regulation of the local lung environment toward resolving inflammation.

Background Age-related increase in systolic pressure is known to be absent in indigenous Papuan populations, partially because of their life-long low-sodium and high-potassium diets. Purpose The aim of this study was to investigate the age-related change in left ventricular (LV) systolic and diastolic function and the relationship with arterial hemodynamics among the indigenous Papuan highland people. Methods Indices of arterial hemodynamics were measured using oscillometric brachial cuff-based sphygmomanometer (Mobil-O-Graph). Brachial-ankle pulse wave velocity (baPWV) was measured using a semiautomatic device (form ABI/baPWV). LV systolic and diastolic function was evaluated by 2-dimensional echocardiography and tissue-Doppler imaging using Vivid iq. Results A total of 81 native Papuans (median age 42 years, 47% women) were enrolled in this study. None of the subjects took any medicines, particularly antihypertensive drugs. All participants presented in sinus rhythm. With ageing, LV mass index remained unchanged, and LV ejection fraction increased, but mildly reduced (40–50%) in 3 participants. Transmitral E-wave velocity slightly decrease but the change was not significant. Transmitral A-wave velocity markedly increased (ρ=0.60, P Conclusion LV systolic function was preserved in indigenous Papuan populations; however, LV diastolic function decreased with ageing. Age-related arterial stiffening, not wave reflection, was inversely related to LV diastolic function.

A significant relationship has been established between central hemodynamics and renal microvascular damage. We hypothesized that the increase in the ankle-brachial index (ABI) with age is due to increased arterial stiffness and wave reflection and is thus associated with the pathogenesis of the renal small artery in patients with chronic kidney disease (CKD). We recruited 122 patients with CKD (stages 1–5) who underwent renal biopsy and ABI measurements between 2010 and 2013. Renal small artery intimal thickening (SA-IT) severity was assessed by semiquantitative grading. The median age was 47 years, with a range of 15–86 years (47% women). The median estimated glomerular filtration rate (eGFR) was 62 mL/min/1.73 m2. Compared with patients with the lowest 1–3 SA-IT index quartile, those with the highest quartile of the SA-IT index were older in age had higher mean arterial pressure, ABI, brachial-ankle pulse wave velocity, and lower eGFR. ABI was positively associated with SA-IT severity and inversely associated with eGFR. Multivariate logistic regression analyses showed that ABI was significantly associated with the highest quartile of the SA-IT index (odds ratio per SD increase in ABI, 1.83; 95% confidence interval, 1.08–3.26) and low eGFR (

Objectives Arterial stiffness is associated with longitudinal increases in blood pressure and hypertension development. A screened cohort was used to test whether increases in the ankle-brachial index (ABI) with age occur as a result of increasing arterial stiffness and wave reflection and is associated with hypertension incidence. Methods We analysed the data of 1344 participants without hypertension at baseline who underwent ABI measurements at least twice with an interval of at least 36 months. Participants with abnormal ABI values were excluded. Results The median age of participants was 51 years (55% women). The ABI was lowest for participants younger than 40 years and increased with age. At the time of the follow-up visit (median follow-up period, 47 months), 224 (17%) participants had developed hypertension. Multiple linear regression analysis revealed that baseline ABI was positively and independently associated with the yearly change in brachial SBP and hypertension incidence. Compared with participants with a normal ABI (1.00-1.19), the adjusted odds ratio for hypertension incidence was significantly higher for participants with a high-normal ABI (1.20-1.39) before and after multivariate adjustment for conventional risk factors (odds ratio, 2.17, 95% confidence interval 1.20-3.95). Addition of ABI to a model containing conventional risk factors did not improve the c-statistics but the net reclassification index of ABI was 0.17 (95% confidence index 0.01-0.37) for hypertension incidence. Conclusion Baseline ABI was positively and independently associated with the yearly change in SBP and hypertension incidence.

BACKGROUND The temporal change in ankle-brachial index (ABI) in the general population, especially in those aged

This paper investigates relationships between the ADL evaluations of convalescent stroke patients in rehabilitation and their physical activity amounts measured by an accelerometer. A previous study performed a correlation analysis between the activity amount and two FIM items (i.e., motor FIM and cognitive FIM), which is one of the ADL evaluations, and showed the existence of a significant correlation between both of them. In this paper, we performed a correlation analysis and also did a multidimensional PCA (MPCA) of data matrix and tensors, respectively, constructed from more detailed FIM items than above. As the results of the correlation analysis, we showed that the correlation coefficients of the activity amount of walking when compared the motor and cognitive FIM were relatively large, and that the similar tendency to the result of the previous study was obtained. By considering the detailed FIM items, we noticed that correlation coefficients of the locomotion subscale of FIM compared with the walking calories and the number of walking steps were the largest. Furthermore, from the results of performing MPCA, we found several pairs of principal component scores with higher correlation coefficients. The above-mentioned results suggest that the use of accelerometer is considered to be effective in grasping patients’ FIM scores.

Background: Adults 80 years and older are the fastest-growing segment of the Japanese population and face a high risk of cognitive decline. There are some evidences connecting hypertension to cognitive decline. In mid-life hypertension is known to have influence the cognitive decline in older age. However, a few study have examined the association between hypertension or vascular stiffness and cognitive function among elderly over 80 years old. We analyzed the associations between vascular stiffness and cognitive function among relatively healthy community-dwelling non-demented oldest old. Method: Data came from the Keys to Optimal Cognitive Aging (KOCOA) study; an ongoing cohort of relatively healthy volunteers aged over 80 years old, living in Okinawa, Japan. In 2017, 105 non-demented (Clinical Dementia Rating < 1) subjects completed three kinds of examination for vascular function (75 % female, mean age (SD) 84.0 (3.0)). We categorized subjects into low and high cognitive function groups using Montreal Cognitive Assessment (MoCA) (25/26 as a cutpoint). Logistic regression models were used to examine the association between cognitive and vascular functions. Results: Narrower pulse pressure, an indicator of lower arterial stiffness, was associated with better cognitive function among subjects, after adjusting for gender, age, and education (p≦0.05), although systolic and diastolic blood pressure were not. Conclusion: Our findings suggest that narrower pulse pressure is related with cognitive preservation. The present study supports the hypothesis that lower arterial stiffness is related with better cognitive function even among the oldest old.

The multi-dimensional principal component analysis (MPCA), which is an extension of the well-known principal component analysis (PCA), is proposed to reduce the dimension and to extract the feature of the multi-dimensional data. We have analyzed the rehabilitation data, which is known as the Functional Independence Measure (FIM), routinely measured from inpatients of a hospital by using MPCA. This time, we implemented the MPCA program by the statistical software R, and carried out the analysis of that data with changed configuration from the previous works in the environment of the R statistical system. From the results, the usefulness and the effectiveness of MPCA analysis in the R environment are confirmed.

Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv) APA in a conscious, unrestrained state after pretreatment with (i) vehicle, (ii) 80 μg of telmisartan, an Ang II type-1 (AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg). Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg). In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response.

OBJECTIVES Arterial stiffness is associated with the pathogenesis of cerebral microbleeds (CMBs). The ankle-brachial index (ABI) is used to predict arterial stiffness. We hypothesized that the increase in ABI with age occurs as a result of increasing arterial stiffness and wave reflection, and is thus associated with target organ damage. The aim of this study was to investigate the relationship between ABI, brachial-ankle pulse wave velocity (baPWV), and CMBs. METHODS We recruited 990 cardiovascular disease-free and stroke-free participants [median age 53 (24-86) years, 531 were woman] who underwent brain MRI, ABI, and baPWV at a health checkup. RESULTS The prevalence of CMBs was 4%. Both ABI (1.14 vs. 1.10) and baPWV (17.29 vs. 14.68 m/s) were higher in participants with CMBs than those without. Cutoff values of ABI and baPWV for the presence of CMBs were 1.12 and 16.07 m/s, respectively. Multivariate logistic regression analysis showed that ABI at least 1.12 [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.30-5.37, P

Objectives:Increaseing dose of angintensin receptor inhibitors (ARB) could augument blood pressure (BP) lowering effect in the hypertensive patients with ARB and diuretics, while it may cause hyperuricemia. Dosigng up losartan which has urate lowering effect may augment BP lowering effect without hy

Cardiac involvement is a rare complication with thromboangiitis obliterans (TAO). We report a 29-year-old man with TAO accompanied with non-ischemic dilated cardiomyopathy. He had no history of heart disease, but echocardiogram demonstrated diffuse hypokinesis and dilated left ventricle. Coronary angiography revealed no organic stenotic lesion. For limb salvage, he was treated with granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cell (PBMNC) implantation on his right leg. Not only ischemic leg symptoms, but also plasma level of BNP and ^I-metaiodobenzylguanidine scintigraphic parameters improved after 24 weeks. G-CSF-mobilized PBMNC implantation could be an effective approach to treating non-ischemic cardiomyopathy., 論文

Hyperuricemia may promote the progression of hypertension and renal dysfunction. However, the effects of hyperuricemia treatment on blood pressure and renal function in adult hypertensive patients with hyperuricemia remain unclear. A total of 137 hypertensive patients with hyperuricemia (96 men and 41 women; mean age of 67 years) who recently started taking xanthine oxidase inhibitors (allopurinol or febuxostat) as outpatients were recruited. Serum uric acid level, estimated glomerular filtration rate (eGFR, ml min(-1) per 1.73 m(2)) and blood pressure (mm Hg) were retrospectively compared immediately before and shortly after starting treatment with xanthine oxidase inhibitors. The mean blood pressure and the eGFR immediately before starting treatment were 128/71 mm Hg and 44.6 ml min(-1) per 1.73 m(2), respectively. Although the eGFR decreased from 46.6 to 44.6 ml min(-1) per 1.73 m(2) before starting treatment with xanthine oxidase inhibitors, it increased to 46.2 ml min(-1) per 1.73 m(2) (P=0.001, compared with immediately before treatment) without any significant changes in blood pressure after the administration of xanthine oxidase inhibitors. Multiple regression analysis revealed that the increase in eGFR after starting xanthine oxidase inhibitor treatment positively correlated with the changes in systolic blood pressure and negatively correlated with the changes in uric acid levels and the use of renin-angiotensin system inhibitors. These results suggest that xanthine oxidase inhibitors may delay the progression of renal dysfunction in adult hypertensive patients with hyperuricemia.

Nature Communications 5, Article number: 3950 10.1038/ncomms4950 (2014); Published May272014; Updated September302015 During the analysis of additional data, the authors identified errors in the original Article. The first relates to the presentation of sinking particle flux data in Fig. 2c, which was mistakenly plotted in reference to a previous dataset, rather than Supplementary Data 1. The corrected version of Fig. 2 appears below. The second error concerns the miscalculation of the Particulate Organic Nitrogen (PON) and Carbon (POC) fluxes presented in Supplementary Data 1 and Fig. 3b,c. During the flux calculation process, we mistakenly used the weight of analysed subsamples rather than aliquot samples, which resulted in an underestimation of the mole fluxes of PON and POC in the published Article. Two new columns, detailing the correctly calculated fluxes, have been added to Supplementary Data 1, while the corrected version of Fig. 3 appears below. As a consequence of these corrections, the Article text in the Results section requires further revisions: the description of the POC and PON fluxes in the Results section should cite the revised values 926.9 and 94.0 μmol-Nm−2 per day, rather than 124.5 and 12.6 μmol-Nm−2 per day; and the comparison of observed and modelled should state that modelled fluxes better reflect trap data at the shallower, rather than the deeper site as was originally stated. Finally, an additional typographical correction must be applied to the text in the Results scetion. The sixth sentence should refer to ‘November 2010', rather than ‘November 2011'. We sincerely apologise for these errors and the corresponding confusion. We assure the reader that these corrections in no way alter the conclusions in the published article. Figure 2 Figure 3

The time evolution of the Indian Ocean warm pool, studied using a global high-resolution general circulation model, shows strong seasonality. The warm pool has the largest spatial extent during April–May, and least in December. The spatio-temporal variability of its surface area is tightly coupled to incoming solar radiation, except during the summer monsoon (June–September) when Ekman dynamics dominate. The vertical extension of the warm pool, on the other hand, appears to be controlled by the equatorial currents. The heat budget of the warm pool shows that the local heat storage is entirely accounted for by the surface heat flux and advection (horizontal and vertical) in all the three regions, viz. northern, equatorial and southern, considered in the study. Surface heat flux has a dominant role in determining the local heat storage and SST in the northern region, while advection plays an important role in equatorial region. In the southern region both surface heat flux as well as advection are equally important in regulating the local heat storage and SST.

Background Implantation of bone marrow mononuclear cells, including endothelial progenitor cells, into ischemic limbs has been shown to improve collateral vessel formation. In the present study the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization was investigated in patients with severe peripheral arterial disease. Methods and results Six cases were enrolled: 5 of thromboangitis obliterans and 1 of arteriosclerosis obliterans. Following administration of G-CSF (10 microg . kg(-1) . day(-1)), PBMNCs were harvested and injected intramuscularly (5 legs and 1 arm) for 2 days for the patients with ischemia of the legs. No serious adverse events related to G-CSF administration, harvest or implantation were observed during this study period. Improvement in the ankle - brachial pressure index (ABI: >0.1) was seen in 4 patients at 4 weeks and ischemic ulcers improved in 3 of 3 patients. The mean maximum walking distance significantly increased from 203 m to 559 m (p=0.031) at 4 weeks and was sustained for 24 weeks. Significant improvement was seen in physiological functioning subscale of Short Form-36. Conclusion Implantation of PBMNCs collected after G-CSF administration could be an alternative to therapeutic angioplasty in patients with severe peripheral arterial disease.

The Luzon Strait transport (LST) from the Pacific into the South China Sea (SCS) is examined using results from a high-resolution ocean general circulation model. The LST from the model has a mean value of 2.4 Sv (Sv ( 106 m3 s 21) and reaches its seasonal maximum (6.1 Sv westward) in winter and seasonal minimum (0.9 Sv eastward) in summer. Both the annual mean and seasonal variation of LST compare favorably with earlier observations. On an interannual time scale, LST tends to be higher during El Nino years and lower during La Nina years, with its maximum (minimum) leading the mature phase of El Nino (La Nina) by 1 month. The interannual variation of LST appears to be oppositely phased with the Kuroshio transport east of Luzon, indicating a possible nonlinear hysteresis of the Kuroshio as a driving mechanism of LST. For the annual average, water leaving the SCS in the south is of higher temperature than that with LST, thus producing a cooling advection in the upper 405 m equivalent to a surface heat flux of 2 19 Wm 22. Most of this cooling advection is balanced by the atmospheric heating (17 W m22). From late spring to early fall, surface heat flux is the primary heating process; only a small part of the heat content change can be explained by heat advection. But, in winter, heat advection seems to be the only important process responsible for the cooling in the upper layer of the SCS. The interannual variation of the upper-layer heat content has a strong signature of ENSO, cooling in the development of El Nino and warming in the development of La Nina. An oceanic connection is revealed, in which LST seems to be a key process conveying the impact of the Pacific ENSO into the SCS.

OBJECTIVES We hypothesized that ankle-brachial index (ABI) increased with age as a result of arterial stiffness, and decreased when flow-limiting atherosclerotic stenosis occurred in the lower limbs. As arterial stiffness is associated with proteinuria, we investigated the relationship between ABI and prevalence of proteinuria. METHODS A cross-sectional study of ABI and proteinuria with 13,193 participants aged 21-89 years (53% women) from health checkups between July 2003 and March 2010 was conducted. ABI was measured using the automatic oscillometric method, and stratified into four groups: ABI ≤ 0.9 (low); 0.9 < ABI

Nitric oxide-generating vasodilators inhibit vascular smooth muscle cell proliferation. To elucidate the mechanism underlying this process, we investigated the effect of S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide-releasing agent, on the smooth muscle cell cycle. When G0 cells were stimulated with fetal bovine serum and basic fibroblast growth factor, DNA synthesis assessed by [3H]thymidine incorporation started about 15 h later. SNAP dose-dependently inhibited this incorporation, and this effect was maximal at 100 μM. This inhibition was attenuated when SNAP was added after 9-12 h. SNAP inhibited the activity of cyclin-dependent kinase 2 (Cdk2) and phosphorylation of the retinoblastoma protein, both of which usually increased from about 9 h, whereas it did not inhibit the activities of cyclin D-associated kinase(s), Cdk4, and Cdk6, which normally increased from 0-3 h. Although SNAP reduced the mRNA levels of cyclins E and A, it neither reduced their protein levels nor impaired their association with Cdk2. SNAP did not reduce the mRNA levels of cyclins G, C, and D1, Cdk2, Cdk4, and Cdk5, which were normally elevated from 0-3 h. The mRNA and protein levels of the Cdk inhibitor p21 were high in the early G1 phase, peaking at 3 h and then rapidly decreasing after 6 h. In the presence of SNAP, however, p21 expression was enhanced, and moreover, the later decrease disappeared. SNAP also increased the amount of Cdk2-associated p21. These results suggested that nitric oxide inhibits the G1/S transition by inhibiting Cdk2-mediated phosphorylation of the retinoblastoma protein and that p21 induction is involved in the Cdk2 inhibition.

The effects of N-benzyl-D-glucaminedithiocarbamate (BGD), N-benzyl-D-galactamine dithiocarbamate (BGalD), N-p-methylbenzyl-D-glucamine dithiocarbamate (MeBGD), penicillamine (D-PEN), triethylenetetramine·2HCl (Trien), on the excretion and the distribution of copper were compared in male LEC rats (5 weeks). Rats were injected intraperitoneally with chelating agents (2 mmol/kg) every other day for 10 d. The hepatic copper content after treatment with BGD and MeBGD decreased more than that with D-PEN and Trien. Those treatment with dithiocarbamates did not redistribute copper to kidneys and brain. BGD, BGalD and MeBGD all significantly enhanced the biliary excretion of copper, zinc and iron.

The role of protein kinase C (PKC) in vascular endothelial cell proliferation was investigated using human umbilical vein endothelial cells released from the G1/S border. Phorbol 12-myristate 13-acetate (PMA) caused G2 arrest because 1) when added to G2 cells, PMA inhibited subsequent cell division; 2) these growth-arrested cells did not show morphological features of mitotic cells; and 3) PMA did not interrupt mitosis in cells released from nocodazole-induced M phase arrest. 1-Oleoyl-2-acetyl-sn-glycerol (OAG) added repeatedly from G2 also inhibited mitosis. The activation of cdc2 kinase around the G2/M transition was suppressed by PMA and OAG. Although cdc2 was expressed in the presence of PMA, dephosphorylation of its tyrosine residue was inhibited by PMA. In parallel, the expression of cdc25B was suppressed by PMA. The total and the cdc2-associated amount of cyclin B were both reduced by PMA. These data suggested that the PKC pathway negatively regulates the G2/M transition and that the inhibition of cdc2 kinase by the reduction in the levels of cdc25B and cyclin B may contribute to this effect.

Escherichia coli cells (ATCC-9637) grew well in the artificial sea water (ASW) containing yeast extract (1%), but the cell growth was repressed with increasing concentration of ASW; complete inhibition was observed in 2.5-fold strength ASW (×2.5 ASW). However, if the cells had been previously incubated with the normal concentration of ASW for a short time (30min), they exhibited salt-tolerance and grew well even in the high salinity medium (×2.5 ASW). This induction of salt-tolerance was dependent on both the concentration of ASW and the suitable organic solutes such as yeast extract. The salt-tolerance was maintained for up to 2 weeks when cell were suspended in ASW, but not in distilled water. NaCl as an osmolyte, and Mg2+/Ca2+ were suggested to be important for the maintenance of the salt-tolerance.

Age-related change of ankle-brachial index (ABI) within the general population, especially40 years, has not been determined in large population studies. We evaluated the value of the ABI by age- and sex-related differences in a screened cohort.The ABI was examined in 13,211 participants (aged 21-89 years) in a health evaluation programme. The mean ABI was lower in women than in men at all ages. The ABI was lowest at40 years, and increased with age; the maximum was at 60-69 years in both sexes. In participants40 years, 186 (22%) of women and 108 (9.8%) of men had a borderline ABI (0.9-1.0). The prevalence of an ABI ≤0.9 in men increased with age, and sharply rose to 3.3% at ≥70 years. Conversely, women demonstrated a J-curve relationship, where the prevalence of an ABI ≤0.9 was lowest at 60-69 years (0.2%), and increased at40 (0.9%) and ≥70 years (1.6%). The prevalence of atherosclerotic risk factors was higher in participants with an ABI ≤0.9 than those with an ABI0.9 in men, both ≤60 and60 years, and in women60 years. In women ≤60 years, however, the prevalence of atherosclerotic risk factors in participants with an ABI0.9 was as small as those with an ABI ≤0.9.The ABI increased with age until 60-69 years, and was lower in women than in men. It is unlikely that a low ABI in younger healthy women always indicate that existence of arterial stenosis.

Escherichia coli cells exhibited osmotolerance and grew well even in hyperosmotic medium containing 1.2M NaCl (or 2.0M sorbitol) if they had been previously exposed to moderate osmotic stress for a short time (30min). Untreated cells showed repressed growth. This acquirement of osmotolerance against hyperosmolarity was dependent on the concentration of the osmoticum in the osmotic stress conditioning. The most effective conditioning occurred when almost the same moderate osmolarity of electrolytes (about 0.4-0.6M NaCl or KCl) and non-electrolytes (about 0.8-1.2M sorbitol or sucrose) was used as osmoticum. The acquired osmotolerance could be inhibited markedly by chloramphenicol or rifampicin, but not by nalidixic acid. Experiments with 35S-methionine incorporation suggest that the synthesis of several proteins might be related to the acquiring of osmotolerance.

A 33-year-old woman was referred from an outside dialysis clinic to our hospital because of severe abdominal pain during hemodialysis. She had been on chronic hemodialysis for the past 11 years due to chronic glomerulonephritis. Nafamostat mesilate was used as an anticoagulant for hemodialysis, because it was during her menstrual period with hypermenorrhea. On admission, she had no abdominal pain or gynecological abnormalities. On the second day, she had similar abdominal pain during hemodialysis with nafamostat mesilate in our dialysis unit. The abdominal pain disappeared within 60 minutes after discontinuing the hemodialysis. We re-started dialysis using heparin instead of nafamostat mesilate and she had no symptoms. The titer of total immunoglobulin E was high. The drug lymphocyte stimulation test was positive for nafamostat mesilate and antigen specific immunoglobulin E to nafamostat mesilate was highly positive in her blood. Although an allergic reaction to nafamostat mesilate is a rare complication, it should be one of the differential diagnoses of abdominal pain occurring during hemodialysis.

Activity of proline uptake in Escherichia coli CSH4 was inhibited in the presence of 1 M NaCl, while it was recovered if the cells were incubated at 30 degrees C for 1 h in a moderate salinity stress (MSS) solution which consists of Davis minimal medium with 5 mM proline and 0.5 M NaCl. Then, an attempt was made to examine whether MSS treatment is also effective on the activity restoration of proline uptake and growth under high salinity for E. coli CSH4 mutants with different combinations of proP, putA, putP, and proU which are related to the transport and metabolization of proline. After MSS treatment, proline uptake was vigorously occurred for the mutants with proline transporter gene proP but not for its deficient ones. For the expression of proline uptake activities of these mutant strains after MSS treatment, PO(4)(3-) in MSS solution is more important than K(+). No growth of strain CSH4 and its mutants without MSS treatment was observed, when cultured in high osmotic medium G (0.8 M NaCl) consisting of 1 mM glycine betaine and Davis minimal medium without potassium phosphate supplemented. After MSS treatment, however, mutant strains lacking proP showed sufficient growth in medium G. Cell growth of proP(+) strains was recognized if MSS treatment was performed in the absence of proline. In conclusion, growth of mutant strains under high-salinity medium G depended on their amount of proline accumulated during MSS treatment, in which K(+) and PO(4)(3-) might play a key role to guarantee their sufficient growth.

Objective Circulating endothelial progenitor cells (EPCs) play a critical role in maintaining the integrity of vascular vessels. The number of EPCs inversely correlates with the number of atherosclerotic risk factors. Although nonpharmacological treatment represents the first approach to the primary prevention of atherosclerotic diseases, little is known about the effects of diet on EPCs. We investigated the effect of a dietary intervention with vegetables that are commonly eaten in Okinawa on the number of EPCs. Methods and results Forty-five healthy young women were employed and randomized to a dietary intervention group (n = 24) or a control group (n = 21). Subjects in the intervention group received typical Okinawan vegetables through home-parcel delivery for 2 weeks. After the dietary intervention, urinary potassium and magnesium excretion increased only in the intervention group and changes were greater than in the control group (p = 0.007, 0.010, respectively). The consumption of total vegetables correlated with changes in both urinary potassium and magnesium excretion. Serum folic acid increased and plasma homocysteine decreased in both groups but the change was significant only in the intervention group. The EPCs number significantly increased in the intervention group but did not in the control group. An inverse correlation was observed between EPC number and plasma homocysteine level (r = −0.272, p = 0.016). Changes in the EPC number inversely correlated with changes in both serum total cholesterol and low-density lipoprotein cholesterol level (r = −0.555, p = 0.0002; r = −0.626, p Conclusions The consumption of vegetables increased the number of circulating EPCs; this change might be associated with a homocysteine-lowering effect.

Beneficial effects of thiazolidinediones, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, on cardiovascular injuries have been reported. However, the effects of these agonists on left ventricular (LV) hypertrophy have not been clarified. To investigate whether pioglitazone improves LV hypertrophy, we used 32-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) that had been treated or not treated with pioglitazone (10 mg/kg/day) for 8 weeks, and Wistar Kyoto rats (WKY). We evaluated LV geometry by echocardiography; myocyte hypertrophy, tissue fibrosis, and appearance of myofibroblasts by histological examination; mRNA expression by real-time polymerase chain reaction (PCR); protein expression by Western blot; activities of matrix metalloproteinase (MMP) by zymography; and production of reactive oxygen species (ROS) by electron spin resonance spectroscopy or thiobarbituric acid reactive substances (TBARS). SHR-SP showed concentric hypertrophy of the LV, but WKY did not. The myocyte diameter, fraction of tissue fibrosis, and number of myofibroblasts were greater in SHR-SP. mRNA expressions of collagen type I and type III, tissue growth factor (TGF)-beta1, and brain natriuretic peptide (BNP); protein expression of connective tissue growth factor (CTGF); activities of MMP2 and MMP9; and ROS were increased in SHR-SP. Pioglitazone did not decrease blood pressure, but partially normalized LV geometry in addition to decreasing myocyte diameter, interstitial fibrosis and number of myofibroblasts; mRNA levels of collagen type I and BNP; MMP2 activity; and protein level of CTGF. However, the mRNA level of collagen type III and TGF-beta1, MMP9 activity, and ROS production were not improved. In conclusion, pioglitazone reversed the concentric LV remodeling independently from blood pressure or oxidative stress in chronic hypertension.

Background: A decreased number of endothelial progenitor cells (EPCs) as well as anemia have been reported to be associated with cardiovascular disease. Maintenance hemodialysis (MHD) patients who require higher doses of recombinant human erythropoietin (rHuEPO) have higher cardiovascular mortality. However, it has not been examined whether there is correlation between the numbers of CD34+ cells, including EPCs and erythroid progenitor cells, and the dose of rHuEPO in MHD patients. Methods: We measured the number of circulating CD34+ cells by flow cytometry and examined the clinical characteristics in 35 MHD patients (50% male). Results: A significant negative correlation was discovered between the number of circulating CD34+ cells and the dose of rHuEPO (r = –0.441, p = 0.013). We performed multivariate regression analysis to determine whether the number of CD34+ cells was associated with age, gender, diabetes, serum albumin, C-reactive protein, ferritin, statin, and dose of rHuEPO. The dose of rHuEPO, diabetes, and statin were independent predictors of the number of circulating CD34+ cells. A reciprocal analysis that divided these patients into two groups according to mean value of CD34+ cells also demonstrated the significant relationship between rHuEPO dose level and the number of CD34+ cells. Conclusion: These findings suggested that the requirement of a higher dose of rHuEPO to maintain target hemoglobin was associated with a decrease in the number of CD34+ cells. This relationship may be partly responsible for the higher cardiovascular mortality of this group among MHD patients.

We report a 64-year-old man who complained of headache without chest pain at the onset of acute myocardial infarction (AMI). He had no history of chest pain or headache. Severe headache in this case was the first symptom of AMI. The headache was reproduced during stress test. During the angioplasty procedure, he also complained of headache without vasospastic change in the coronary artery. These findings suggest that the headache which accompanied AMI or myocardial ischemia in this case was due to referred pain rather than a generalized vasospastic disorder.

The respiratory activity of Escherichia coli K-12 was inhibited by high NaCl concentrations. The addition of compatible solutes such as proline and ectoine led to the recovery of the respiration of E. coli K-12 inhibited by 1 M NaCl to a similar extent as did the addition of glycine betaine. Glucose, an exogenous substrate for the stimulation of respiratory activity, was not taken up by the cells in the presence of 1 M NaCl, but active uptake of glucose was observed following the addition of compatible solutes. As a result, we obtained a good correlation between respiratory activities and glucose uptake rates, suggesting that the glucose uptake activity inhibited by high NaCl concentrations was facilitated by these solutes. The addition of proline did not lead to cell proliferation in the minimal medium containing 1 M NaCl, although the cells took up proline quite efficiently under high osmolarity. On the other hand, cell growth occurred after a lag time in the medium containing glycine betaine or ectoine in place of proline. Similar actions of the compatible solutes mentioned above were observed for E. coli ATCC 9637.

The Jak/STAT pathway is activated following stimulation of the type I angiotensin II receptor. To examine whether this pathway is shared among other G-protein-coupled receptors, we studied the linkage between the alpha(1) adrenergic receptor and this pathway. The alpha(1) agonist phenylephrine induced tyrosine phosphorylation of Jak2, Tyk2, and STAT1 in vascular smooth muscle cells. The phosphorylation of Jak2 was prevented by the alpha(1) receptor antagonists prazosin and chloroethylclonidine, but not by WB4101, and that of STAT1 was inhibited by prazosin and the Jak2 inhibitor AG490. After stimulation with phenylephrine, Jak2 and STAT1 were found to associate with alpha(1B) receptor. Phenylephrine stimulated the DNA binding activity of STAT1. Protein synthesis promoted by phenylephrine was inhibited by prazosin, AG490, and the introduction of a decoy oligonucleotide for STAT1. These results suggested that alpha(1) receptor is linked to the Jak/STAT pathway and that this pathway mediates alpha(1) agonist-induced smooth muscle hypertrophy.