A novel route for aspartame production by combining enzymatic and chemical reactions for industrial use.

Here, we report a novel industrial aspartame production route, involving the enzymatic production of α-l-aspartyl-l-phenylalanine ß-methylester from l-aspartic acid dimethylester and l-phenylalanine by α-amino acid ester acyl transferase. The route also involves the chemical transformation of α-l-aspartyl-l-phenylalanine ß-methylester to α-l-aspartyl-l-phenylalanine methylester hydrochloride (aspartame hydrochloride) in an aqueous solution with methanol and HCl, followed by HCl removal to form aspartame.

Blood pressure control status and relationship between salt intake and lifestyle including diet in hypertensive outpatients treated at a general hospital.

The purpose of the present study was to investigate blood pressure (BP) control and salt intake in hypertensive outpatients treated at a general hospital and to examine the relationship between their lifestyles and amount of salt intake. Subjects comprised 429 hypertensive patients (206 males, 223 females, and average age of 71 ± 11 years). We estimated 24-hour salt excretion using spot urine samples and assessed lifestyle using a self-description questionnaire. Average clinic BP and the number of antihypertensive drugs were 132 ± 11/73 ± 8 mmHg and 1.8 ± 0.9, respectively. In all subjects, average estimated salt intake was 9.2 ± 2.8 g/day and the rate of achievement of the estimated salt intake of <6 g/day was 11.2%. In patients with chronic kidney disease or cardiovascular disease, these values were 8.6 ± 2.6 g/day and 15.5%, and 9.1 ± 3.3 g/day and 18.2%, respectively. Estimated salt intake was lower in patients living alone than in those with a family. In a multivariate analysis, estimated salt intake correlated positively with body mass index and negatively with age. Among patients with an excessive salt intake (≥10 g/day), 75.2% answered that they made an effort to reduce their salt intake. The amount of food and processed food consumption correlated with estimated salt intake. In conclusion, the rate of achievement of salt restriction was low in hypertensive patients treated at a general hospital. It may be important to provide data on actual salt intake and guide salt restriction in the individual management of hypertension.

Intraoperative blood pressure changes during cemented versus uncemented bipolar hemiarthroplasty for displaced femoral neck fracture: a multi-center cohort study : The effect of bone cement for bipolar hemiarthroplasty in elderly patients.

INTRODUCTION: The purpose of this study was to compare the cemented bipolar hemiarthroplasty with uncemented about the change of intraoperative blood pressure and the incidence of major complications in elderly patients with femoral neck fracture. MATERIALS AND METHODS: This multiple center prospective cohort study included only patients with acute displaced femoral neck fracture (Garden stage III or IV). All patients were treated with cemented or uncemented bipolar hemiarthroplasty using modified Hardinge or Watson-Jones approach in the lateral decubitus position. Baseline data, medical history, type of anesthesia, FiO2 value, the number of vasopressor using during operation, femoral component, intraoperative blood pressure, SaO2, and major complications were evaluated. RESULTS: Of 164 patients (45 males and 119 females), 86 underwent cemented and 78 underwent uncemented bipolar hemiarthroplasty. Baseline medical histories were similar in both groups. In both the cemented and uncemented groups, intraoperative systolic blood pressure significantly decreased during cementing or rasping (106.3 and 103.6 mmHg) and after femoral component insertion (103.3 and 99.1 mmHg) compared to before rasping (120.7 and 116.4 mmHg) (p < 0.0001, respectively). Donaldson's grade seemed more favorable in uncemented group than in cemented group during cementing or rasping, during stem insertion; however, no patients experienced the lethal complication in both groups. CONCLUSIONS: Intraoperative blood pressure did not change during cemented and uncemented bipolar hemiarthrplasty for displaced femoral neck fracture. If the standard modern cement technique was performed during operation, bone cement is a safe and acceptable for elderly patients who have a lot of medical histories.

Predictive factors for acetabular labral lesions in osteoarthritis of the hip with radial magnetic resonance imaging--a cross-sectional study.

OBJECTIVES: To document the reliability of Abe's classification and to clarify the predictive factors for acetabular labral lesions in osteoarthritis of the hip with radial magnetic resonance (MR) imaging. METHODS: Reliability trial for the classification of acetabular labral lesion was performed by six orthopedic surgeons, grading 20 radial MR images in a blinded fashion at an interval of 4-5 weeks. Radial MR images of 275 hips in 263 patients were prospectively analyzed to determine the relationship between acetabular labral lesions, their distribution, age, and the acetabular coverage. RESULTS: Cohen's quadratic weighted kappa of inter-observer reliability was 0.784 for the grade and 0.812 for the shape category. The weighted kappa of intra-observer reliability was 0.852 for the grade and 0.90 for the shape category. Multiple regression analysis revealed that both the grade and the shape were associated with age, acetabular coverage, and location of the labrum. CONCLUSIONS: Abe's classification of labral lesions was reliable for both the grade and shape categories. Aging, acetabular dysplasia, and the anterosuperior portion would be predictive factors for degeneration of the acetabular labrum using radial MR imaging.

Enzymatic production of L-alanyl-L-glutamine by recombinant E. coli expressing α-amino acid ester acyltransferase from Sphingobacterium siyangensis.

An enzymatic production method for synthesizing L-alanyl-L-glutamine (Ala-Gln) from L-alanine methyl ester hydrochloride (AlaOMe) and L-glutamine (Gln) was developed in this study. The cultivation conditions for an Escherichia coli strain overexpressing α-amino acid ester acyltransferase from Sphingobacterium siyangensis AJ 2458 (SAET) and reaction conditions for Ala-Gln production were optimized. A high cell density culture broth prepared by fed-batch cultivation showed 440 units/mL of Ala-Gln-producing activity. In addition, an Ala-Gln-producing reaction using intact E. coli cells overexpressing SAET under optimum conditions was conducted. A total Ala-Gln yield of 69.7 g/L was produced in 40 min. The molar yield was 67% against both AlaOMe and Gln.

Screening of α-amino acid ester acyl transferase variant with improved activity by combining rational and random mutagenesis.

Random and rational mutagenesis of an α-amino acid ester acyl transferase from Sphingobacterium siyangensis AJ2458 (SAET) was conducted to examine the production of aspartame, an α-l-aspartyl-l-phenylalanine methyl ester. We previously reported aspartame production via combination of enzymatic and chemical methods. However, the productivity of the aspartame intermediate by SAET was approximately one-fifth that of l-alanyl-l-glutamine (Ala-Gln), whose production method has already been established. Here, to improve the enzymatic activity of SAET, we performed random mutagenesis in the gene encoding SAET and obtained 10 mutations that elevated the enzymatic activity (1.2- to 1.7-fold increase) relative to that of wild-type SAET. To further improve the activity, we performed mutagenesis to optimize the combination of the obtained mutations and finally selected one SAET variant with 10 amino acid substitutions (M35-4 SAET). An Escherichia coli strain overexpressing M35-4 SAET displayed a 5.7-fold higher activity than that of the wild-type SAET, which was almost equal to that of Ala-Gln by an E. coli strain overexpressing wild-type SAET. The Vmax value of M35-4 SAET was 2.0-fold greater, and its thermostability was higher than those of wild-type SAET. These results suggest that the obtained SAET variants contribute to improvement in aspartame production.

Gene cloning and characterization of α-amino acid ester acyl transferase in Empedobacter brevis ATCC14234 and Sphingobacterium siyangensis AJ2458.

The gene encoding α-amino acid ester acyl transferase (AET), the enzyme that catalyzes the peptide-forming reaction from amino acid methyl esters and amino acids, was cloned from Empedobacter brevis ATCC14234 and Sphingobacterium siyangensis AJ2458 and expressed in Escherichia coli. This is the first report on the aet gene. It encodes a polypeptide composed of 616 (ATCC14234) and 619 (AJ2458) amino acids residues. The V(max) values of these recombinant enzymes during the catalysis of L-alanyl-L-glutamine formation from L-alanine methylester and L-glutamine were 1,010 U/mg (ATCC14234) and 1,154 U/mg (AJ2458). An amino acid sequence similarity search revealed 35% (ATCC14234) and 36% (AJ2458) identity with an α-amino acid ester hydrolase from Acetobacter pasteurianus, which contains an active-site serine in the consensus serine enzyme motif, GxSYxG. In the deduced amino acid sequences of AET from both bacteria, the GxSYxG motif was conserved, suggesting that AET is a serine enzyme.

Improvement of blood pressure control in a hypertension clinic in Japan: a 15-year follow-up study.

Many guidelines recommended strict blood pressure (BP) control to prevent cardiovascular events. However, BP control in a substantial majority of hypertensives remains to be insufficient. We have determined the trends of BP control of the same patients during 15 years in a hypertension clinic. One hundred three patients (age 32-91, mean 68 +/- 11 years in 2006), who were followed at our hypertension clinic between 1991-2006, were retrospectively investigated. We compared the clinical characteristics of the patients in 2006 to those in 1991, 1996, and 2001, using the averaged BP determined at two occasions of each year for our analysis. The average BP decreased from 144 +/- 17/87 +/- 10 mmHg to 132 +/- 12/75 +/- 10 mmHg (p < 0.01) during the 15 years between 1991 and 2006. When good BP control was defined as < 140/90 mmHg, the rate of patients with good BP control increased from 35% in 1991 to 45% in 1996, to 54% in 2001 (p < 0.01 vs. 1991), and to 72% in 2006 (p < 0.01 vs. 1991). The number of anti-hypertensive drugs used in 2006 significantly increased compared to those in 1991, 1996, and 2001. More specifically, the use of diuretics and alpha-blockers increased significantly during this period. Results suggest that BP control improved in the 15 years studied, and the increased use of the anti-hypertensive drugs, as well as the increased awareness of the importance of strict BP control, seems to have contributed to improve the BP control.

Sensibility Assessment For User Interface And Training Program Of An Upper-Limb Rehabilitation Robot, D-SEMUL.

Upper-limb rehabilitation training for hemiplegic patients has been primarily conducted by human therapists, and, hence, their use of training methods and conditions strongly depends on their expertise. The force control and motion sensing functions of rehabilitation robots are expected to be used for the qualitative training/assessment in the next-generation computerized rehabilitation. In this study, we developed a desktop rehabilitation robot for upper limbs (D-SEMUL). In addition, we also assessed the usability of its user interface and the affinity (acceptance) of the training program with a questionnaire for elderly hemiplegic/non-hemiplegic participants (nine hemiplegic, five males and four females and seven non-hemiplegic, two males and five females). The results indicated that the touchscreen is acceptable for the user interface, and the background music used significantly affects the affinity of the program.

The influence of bone cement and American Society of Anesthesiologists (ASA) class on cardiovascular status during bipolar hemiarthroplasty for displaced femoral-neck fracture: A multicenter, prospective, case-control study.

BACKGROUND: Little is known about how bone cement and American Society of Anesthesiologists (ASA) classification influence the cardiovascular system in elderly patients with femoral-neck fractures treated with cemented hemiarthroplasty. Therefore, we performed a case-control study to investigate these questions and compared the following:≥ASA III with≤ASA II patients who underwent cemented hemiarthroplasty; and cemented with cementless hemiarthroplasty in≥ASA III patients. HYPOTHESIS: ASA classification influences the cardiovascular system during cemented hemiarthroplasty and bone cement influences intraoperative blood pressure [IBP] in patients rated≥ASA III. MATERIALS AND METHODS: This multicenter, prospective study included patients with acute displaced femoral-neck fractures. Baseline data, medical history, anesthesia, FiO2, vasopressor use, femoral component, IBP, SpO2, and complications were evaluated. Of 200 patients, 100 were cemented (mean age, 77±10 years), and 100 were cementless (mean age, 78±9 years). Cemented hemiarthroplasty employed a third-generation technique (plugging, irrigating, drying and filling the canal with cement under pressurization). RESULTS: Systolic blood pressure (SBP) decreased significantly during cementing, versus pre-rasping in≤ASA II patients (from 117.9±24.5 [range, 65-199] to 106.9±20.3 [range, 59-172]; p=0.007), in≥ASA III patients (from 129.5±21.0 [range, 90-169] to 110.4±17.9 [range, 79-157]; p=0.006), and post-stem-insertion, versus pre-rasping in≤ASA II patients (from 117.9±24.5 [range, 65-199] to 103.9±20.7 [range, 53-178]; p=0.0004), and in≥ASA III patients (from 129.5±21.0 [range, 90-169] to 111.2±24.6 [range, 70-156]; p=0.009). In≥ASA III patients, SBP decreased significantly during cementing or rasping, versus pre-rasping in cemented patients (from 129.5±21.0 [range, 90-169] to 110.4±17.9 [range, 79-157]; p=0.006), in cementless patients (from 115.0±17.7 [range, 85-150] to 100.7±15.7 [range, 75-142]; p=0.004), and post-stem-insertion, versus pre-rasping in cemented patients (from 129.5±21.0 [range, 90-169] to 111.2±SD [range]; p=0.009), and in cementless patients (from 115.0±17.7 [range, 85-150] to 89.4±17.5 [range, 58-140]; p<0.0001). There were no lethal complications. CONCLUSIONS: This study indicate a similar hemodynamic change intraoperatively between≤ASA II patients and≥ASA III patients in the cemented group, and between patients with cemented and cementless hemiarthroplasty in the≥ASA III patients. With modern hemiarthroplasty techniques, bone cement might be as safe as cementless techniques in elderly,≥ASA III patients. LEVEL OF EVIDENCE: III, multicenter case-control cohort study.

Novel ankle orthosis with elastomer-embedded flexible joint.

In this study, we propose a new ankle orthosis with elastomer-embedded flexible joints (EEFJ), composed of C-shaped springs and 3D-printed circular elastomer. This orthosis was designed to reduce burden on the tibialis anterior muscle (TA) and to achieve clearance between the tip of the toe and the ground. Fabrication method, strength testing, and gait analysis were conducted. According to the results of strength testing, the combination of the C-spring with 0.3 mm and 0.5 mm thickness and the elastomer with 30% and 60% filling density performs a supporting torque of 0.7-2.3 Nm to plantarflexion. In contrast, torques in the other directions were relatively small. According to the results of gait experiments in seven healthy young subjects, the proposed orthosis successfully reduced activation of TA on initial contact and in the swing phase, and range of motion on initial contact.

Ankle-foot orthosis using elastomer-embedded flexible joint.

We proposed a new ankle-foot orthosis using elastomer-embedded flexible joints (EEFJ), composed of C-shaped springs and 3D-printed circular elastomer. This orthosis was designed to reduce burden on the tibialis anterior muscle (TA) and to achieve clearance between the tip of the toe and the ground. Strength testing, and gait analysis were conducted for the orthosis. According to the results of strength testing, the combination of the C-spring with 0.3 mm and 0.5 mm thickness and the elastomer with 30% and 60% filling density performs a supporting torque of 0.7-2.3 Nm to plantarflexion. In contrast, torques in the other directions were relatively small. According to the results of gait experiments in seven healthy young subjects, the proposed orthosis successfully reduced the TA activation on initial contact and in the swing phase, and range of motion on initial contact.

Upper limb training/assessment program using passive force controllable rehabilitation system.

Upper limb rehabilitation training for Hemiplegie patients has been conducted mainly by human therapists. Training methods and conditions depend strongly on their experience because of the wide range of individual differences between patients. The force control and sensing functions of rehabilitation robots are expected to be used for the qualitative assessment of next-generation computational rehabilitation. In this study, we developed a simple exercise machine for upper limbs (SEMUL) using an electro-rheological fluid brake, as a safe brake-type robotic rehabilitation system. We also developed a new upper limb training/assessment program, called "WIPE," for the SEMUL. Furthermore, we conducted clinical tests on twelve subjects (six each for the SEMUL training and for general training). We adopted the ABA design methodology for the clinical research tests. The motor functions of upper limbs were assessed using five clinical scores: Fugl-Meyer Assessment (FMA), Brunnstrome recovery stage, Simple Test for Evaluating Hand Function (STEF), Stroke Impairment Assessment Set (SIAS), and Motor Activity Log. Improvements of the FMA, STEF, and SIAS in the SEMUL training groups were found to be higher than those in the general training groups.

Spinal anesthesia increases the risk of venous thromboembolism in total arthroplasty: Secondary analysis of a J-PSVT cohort study on anesthesia.

Clinical guidance on the choice of anesthetic modality vis-à-vis the risk of perioperative venous thromboembolism (VTE) is largely lacking because of a paucity of recent evidence. A comparative effect of general anesthesia and neuraxial blockade on the perioperative incidence of VTE has not been well-investigated.We compared the effects of different types of anesthetic modalities on the risk of VTE after total hip arthroplasty (THA) and total knee arthroplasty (TKA).This is a secondary analysis of the Japanese Study of Prevention and Actual Situation of Venous Thromboembolism after Total Arthroplasty (J-PSVT). Data pertaining to a total of 2162 patients who underwent THA and TKA at 34 hospitals were included in this analysis. We compared the different anesthetic modalities with respect to the incidence of VTE. The composite end-point was asymptomatic/symptomatic deep vein thrombosis detected using scheduled bilateral ultrasonography up to postoperative day (POD) 10 and fatal/non-fatal pulmonary embolism up to POD 10.The study groups were as follows: general anesthesia (n = 646), combined epidural/general anesthesia (n = 1004), epidural anesthesia (n = 87), and spinal anesthesia (n = 425). On multivariate analysis, only spinal anesthesia was associated with a significant increase in the risk of VTE as compared with that associated with general anesthesia. Propensity score-matched analysis for "combined epidural/general anesthesia group" versus "spinal anesthesia group" demonstrated a 48% higher incidence of VTE (relative risk = 1.48, 95% confidence interval [CI] 1.18-1.85) in the latter.Spinal anesthesia was associated with a higher risk of postoperative VTE, as compared with that associated with combined epidural/general anesthesia, in patients undergoing total arthroplasty.

Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system.

Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mg/kg/day), or a combination of hydralazine (30 mg/kg/day) and hydrochlorothiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant antihypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and angiotensin II type 1 receptor activation are involved in the up-regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension.

Validity of the JNC VI recommendations for the management of hypertension in a general population of Japanese elderly: the Hisayama study.

BACKGROUND: It is not known whether the treatment recommendations presented in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure are applicable to the Japanese elderly population. METHODS: We followed up 588 cardiovascular disease-free residents of a Japanese community who were 60 years or older from November 1, 1961, through October 31, 1993. Treated hypertensive patients were excluded from the analysis. During this period, CVD occurred in 179 subjects. The incidences were estimated by the pooling of repeated observations method. RESULTS: The age- and sex-adjusted incidences of cardiovascular disease significantly increased with elevated blood pressure levels. The hazard ratio for stage 3 hypertension was 5.34 (95% confidence interval, 2.66-10.71; P<.001) compared with optimal blood pressure after adjustment for other covariates. Among subjects aged 60 to 79 years, the incidences for stages 1 through 3 hypertension were significantly higher than for those with optimal and normal blood pressure. In comparison, among those 80 years or older, the incidence was significantly higher only in patients with stage 3 hypertension. We further estimated the incidences according to the risk stratification system. In the younger elderly subjects, the incidences increased with rising blood pressure levels in each risk stratum. Similar relationships were not observed among the older elderly subjects. CONCLUSIONS: Our findings demonstrate that the recommendations of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were potentially applicable to the Japanese elderly subjects 79 years or younger. Based on our findings, however, hypertension might not be a risk factor for cardiovascular disease among very old hypertensive patients with advanced atherosclerosis.

Central cardiovascular action of urotensin II in conscious rats.

OBJECTIVE: To examine the central cardiovascular action of urotensin II in conscious rats. METHODS: Intracerebroventricular (ICV) injections of urotensin II (1 and 10 nmol) were carried out in conscious Wistar rats. The effects of intravenous (i.v.) urotensin II (10 nmol) were also determined. RESULTS: The ICV injection of urotensin II at a dose of 1 nmol did not alter the arterial pressure or heart rate significantly, while 10 nmol urotensin II increased the arterial pressure and heart rate. The mean arterial pressure at 5 min of ICV urotensin II was 121 +/- 4 mmHg, which was significantly higher than that obtained by ICV injection of artificial cerebrospinal fluid (107 +/- 3 mmHg, P <0.05). In addition, significant increases in heart rate were observed 5-15 min after ICV urotensin II. Pre-treatment with pentolinium (5 mg/kg, i.v.) significantly attenuated the increases in mean arterial pressure (20 +/- 3 versus 8 +/- 2 mmHg, P <0.01) and heart rate (78 +/- 18 versus 7 +/- 5 beats/min, P <0.05) induced by ICV urotensin II. On the other hand, i.v. injection of urotensin II (10 nmol) elicited a depressor response associated with tachycardia; mean arterial pressure 5 min after injection was significantly lower in the urotensin II-injected rats (89 +/- 5 mmHg) than in the control rats (102 +/- 2 mmHg, P <0.05), and the heart rate was significantly higher in the former (402 +/- 11 versus 360 +/- 9 beats/min, respectively, P <0.05). CONCLUSIONS: Central urotensin II produces pressor and tachycardic responses through sympathetic activation, while peripheral urotensin II exerts a vasodilation-mediated depressor response in conscious rats.

Angiotensin II receptor antagonist improves age-related endothelial dysfunction.

BACKGROUND: We previously demonstrated that the angiotensin converting enzyme (ACE) inhibitor, enalapril, prevents the age-related impairment of endothelium-dependent hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF). OBJECTIVE: To test whether angiotensin II type 1 (AT1) receptor antagonists would also improve age-related endothelial dysfunction. METHODS: Normotensive Wistar-Kyoto (WKY) rats were treated for 3 months with either the AT1 receptor antagonist, candesartan cilexetil (3.5 mg/kg per day; candesartan group), or the ACE inhibitor, enalapril (20 mg/kg per day; enalapril group), from 9 to 12 months of age. Untreated 12-month-old WKY rats (old group) served as controls (n = 7-12). RESULTS: The two treatments decreased systolic blood pressure comparably. EDHF-mediated hyperpolarization in response to acetylcholine (ACh; 10(-5) mol/l) in the presence of norepinephrine in mesenteric arteries was improved in both the candesartan and enalapril groups to a similar extent compared with the old group (candesartan group, -24 +/- 3 mV; enalapril group, -21 +/- 2 mV; old group, -13 +/- 2 mV). EDHF-mediated relaxation was similarly improved in the candesartan and enalapril groups (maximum relaxation: candesartan group, 70 +/- 7%; enalapril group, 63 +/- 8%; old group, 33 +/- 9%). Hyperpolarization and relaxation responses to levcromakalim, an ATP-sensitive K+-channel opener, were similar in all groups. CONCLUSIONS: These findings suggest that the AT1 receptor antagonist is as effective as the ACE inhibitor in improving the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats. Thus AT1 receptor antagonists might serve as novel tools with which to prevent endothelial dysfunction associated with aging.

Alcohol reduces insulin-hypertension relationship in a general population: the Hisayama study.

Insulin resistance may be a factor in the etiology of hypertension, and habitual alcohol intake may modify this relationship. We prospectively examined this hypothesis in 1,133 nonhypertensive, nondiabetic Japanese subjects, aged 40-79 years. Alcohol drinkers were more frequent among men than women at baseline (57.7 vs. 8.2%). The age-adjusted incidence of hypertension significantly increased with the elevating baseline insulin levels in women (P =.003 for trend), but not in men. The age- and sex-adjusted insulin levels and insulin resistance index decreased with elevating alcohol intake, while fasting glucose levels remained unchanged, suggesting that alcohol improves insulin sensitivity. Among nondrinkers, the age-adjusted incidence of hypertension significantly increased with elevating insulin tertiles in both sexes (P =.048 and.002 for trend in men and women, respectively), but not among drinkers. Our findings suggest a close association between insulin resistance and the incidence of hypertension in Japanese. However, alcohol modified and reduced this relationship.

Reproducibility of blood pressure variation in older ambulatory and bedridden subjects.

OBJECTIVES: We investigated the influence of ambulation on the reproducibility of circadian blood pressure variation in older nursing home residents. DESIGN: Ambulatory blood pressure monitoring was performed twice in 37 older nursing home residents. SETTING: Nursing home in Japan. PARTICIPANTS: Subjects included 18 ambulatory nursing home residents who had no limitation on physical activity and 19 bedridden residents who did not participate in physical activity. MEASUREMENTS: Twenty-four-hour, daytime, and nighttime blood pressure levels and their variability. RESULTS: The 24-hour and daytime variability of systolic blood pressure (SBP) was significantly greater in ambulatory than in bedridden subjects, whereas nighttime variability was similar. Significant correlations in SBP averaged for the whole day, daytime, and nighttime were observed between the two examinations in ambulatory (r =.80-.83) and bedridden (r =.83-.91) subjects, but the variabilities of SBP for the whole day and during the daytime of the first measurement were correlated with those of the second measurement in bedridden (r =.67 and r =.47, respectively) but not in ambulatory (r =.39 and r =.28, respectively) subjects. Significant correlations were found between the nocturnal SBP changes at two occasions in both ambulatory (r =.50) and bedridden (r =.51) subjects, but the dipper versus nondipper profiles, defined as reduction in SBP of greater than 10% versus not, showed low reproducibility in ambulatory subjects; five ambulatory (28%) and one bedridden (5%) subjects showed divergent profiles between the two examinations. CONCLUSIONS: The reproducibility of blood pressure variation in nursing home residents is influenced by ambulation.