Management of Blood Pressure in Patients with Glaucoma.

PubMed

Levine, Russell M; Yang, Alina; Brahma, Venkatesh; Martone, James F

2017-09-19

Ocular perfusion pressure (OPP) is defined as the difference between BP and intraocular pressure (IOP). With low BP comes low OPP and resultant ischemic damage to the optic nerve, leading to glaucoma progression. The purpose of this article is to review the literature on BP as it relates to glaucoma and to create a forum of discussion between ophthalmologists and internal medicine specialists. Both high and low BP has been linked glaucoma. Low BP is particularly associated with glaucoma progression in normal-tension glaucoma (NTG) patients. Patients who have low nighttime BP readings are at highest risk of progression of their glaucoma. Internal medicine specialists and ophthalmologists should consider the relationship between BP and glaucoma when treating patients with concomitant disease. Too-low nighttime BP should be avoided. Ambulatory blood pressure monitoring is a useful tool to identify patients at greatest risk for progression.

Effects of myofascial release after high-intensity exercise: a randomized clinical trial.

PubMed

Arroyo-Morales, Manuel; Olea, Nicolas; Martinez, Manuel; Moreno-Lorenzo, Carmen; Díaz-Rodríguez, Lourdes; Hidalgo-Lozano, Amparo

2008-03-01

The usefulness of massage as a recovery method after high-intensity exercise has yet to be established. We aimed to investigate the effects of whole-body massage on heart rate variability (HRV) and blood pressure (BP) after repeated high-intensity cycling exercise under controlled and standardized pretest conditions. The study included 62 healthy active individuals. After baseline measurements, the subjects performed standardized warm-up exercises followed by three 30-second Wingate tests. After completing the exercise protocol, the subjects were randomly assigned to a massage (myofascial release) or placebo (sham treatment with disconnected ultrasound and magnetotherapy equipment) group for a 40-minute recovery period. Holter recording and BP measurements were taken after exercise protocol and after the intervention. After the exercise protocol, both groups showed a significant decrease in normal-to-normal interval, HRV index, diastolic BP (P > .001), and low-frequency domain values (P = .006). After the recovery period, HRV index (P = .42) and high-frequency (HF) (P = .94) values were similar to baseline levels in the massage group, whereas the HRV index tended (P = .05) to be lower and the HF was significantly (P < .01) lower vs baseline values in the placebo group, which also showed a tendency (P = .06) for HF to be lower than after the exercise. Likewise, diastolic BP returned to baseline levels in the massage group (P = .45) but remained lower in the placebo group (P = .02). Myofascial release massage favors the recovery of HRV and diastolic BP after high-intensity exercise (3 Wingate tests) to preexercise levels.

Estimation of the Blood Pressure Response With Exercise Stress Testing.

PubMed

Fitzgerald, Benjamin T; Ballard, Emma L; Scalia, Gregory M

2018-04-20

The blood pressure response to exercise has been described as a significant increase in systolic BP (sBP) with a smaller change in diastolic BP (dBP). This has been documented in small numbers, in healthy young men or in ethnic populations. This study examines these changes in low to intermediate risk of myocardial ischaemia in men and women over a wide age range. Consecutive patients having stress echocardiography were analysed. Ischaemic tests were excluded. Manual BP was estimated before and during standard Bruce protocol treadmill testing. Patient age, sex, body mass index (BMI), and resting and peak exercise BP were recorded. 3200 patients (mean age 58±12years) were included with 1123 (35%) females, and 2077 males, age range 18 to 93 years. Systolic BP increased from 125±17mmHg to 176±23mmHg. The change in sBP (ΔsBP) was 51mmHg (95% CI 51,52). The ΔdBP was 1mmHg (95% CI 1, 1), from 77 to 78mmHg, p<0.001). The upper limit of normal peak exercise sBP (determined by the 90th percentile) was 210mmHg in males and 200mmHg in females. The upper limit of normal ΔsBP was 80mmHg in males and 70mmHg in females. The lower limit of normal ΔsBP was 30mmHg in males and 20mmHg in females. In this large cohort, sBP increased significantly with exercise. Males had on average higher values than females. Similar changes were seen with the ΔsBP. The upper limit of normal for peak exercise sBP and ΔsBP are reported by age and gender. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

PubMed

Combe, Roy; Mudgett, John; El Fertak, Lahcen; Champy, Marie-France; Ayme-Dietrich, Estelle; Petit-Demoulière, Benoit; Sorg, Tania; Herault, Yann; Madwed, Jeffrey B; Monassier, Laurent

2016-01-01

Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies. The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry). In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges. Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.

Medically supervised water-only fasting in the treatment of borderline hypertension.

PubMed

Goldhamer, Alan C; Lisle, Douglas J; Sultana, Peter; Anderson, Scott V; Parpia, Banoo; Hughes, Barry; Campbell, T Colin

2002-10-01

Hypertension-related diseases are the leading causes of morbidity and mortality in industrially developed societies. Surprisingly, 68% of all mortality attributed to high blood pressure (BP) occurs with systolic BP between 120 and 140 mm Hg and diastolic BP below 90 mm Hg. Dietary and lifestyle modifications are effective in the treatment of borderline hypertension. One such lifestyle intervention is the use of medically supervised water-only fasting as a safe and effective means of normalizing BP and initiating health-promoting behavioral changes. Sixty-eight (68) consecutive patients with borderline hypertension with systolic BP in excess of 119 mm Hg and diastolic BP less than 91 mm Hg were treated in an inpatient setting under medical supervision. The treatment program consisted of a short prefasting period (approximately 1-2 days on average) during which food consumption was limited to fruits and vegetables followed by medically supervised water-only fasting (approximately 13.6 days on average). Fasting was followed by a refeeding period (approximately 6.0 days on average). The refeeding program consisted of a low-fat, low-sodium, plant-based, vegan diet. Approximately 82% of the subjects achieved BP at or below 120/80 mm Hg by the end of the treatment program. The mean BP reduction was 20/7 mm Hg, with the greatest decrease being observed for subjects with the highest baseline BP. A linear regression of BP decrease against baseline BP showed that the estimated BP below which no further decrease would be expected was 96.0/67.0 mm Hg at the end of the fast and 99.2/67.3 mm Hg at the end of refeeding. These levels are in agreement with other estimates of the BP below which stroke events are eliminated, thus suggesting that these levels could be regarded as the "ideal" BP values. Medically supervised water-only fasting appears to be a safe and effective means of normalizing BP and may assist in motivating health-promoting diet and lifestyle changes.

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

PubMed

Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

2018-01-23

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc expression, increased cell proliferation and repressed apoptosis. Conclusions: NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP may be a new therapeutic strategy for ESCC patients.

Neuronal Suppressor of Cytokine Signaling 3: Role in Modulating Chronic Metabolic and Cardiovascular Effects of Leptin.

PubMed

do Carmo, Jussara M; da Silva, Alexandre A; Freeman, John Nathan; Wang, Zhen; Moak, Sydney P; Hankins, Michael W; Drummond, Heather A; Hall, John E

2018-06-01

We determined whether deficiency of neuronal SOCS3 (suppressor of cytokine signaling 3)-a potential negative regulator of leptin signaling-amplifies the chronic effects of leptin on food intake, energy expenditure, glucose, and blood pressure (BP) and protects against adverse cardiometabolic effects of obesity. BP and heart rate were recorded by telemetry, and oxygen consumption (VO 2 ) was monitored in 22-week-old mice with nervous system SOCS3 deficiency (SOCS3-Nestin-Cre) and control mice (SOCS3 flox/flox ) fed normal or high-fat-high-fructose diet from 6 to 22 weeks of age. Compared with controls, SOCS3-Nestin-Cre mice had lower plasma glucose (124±7 versus 146±10 mg/dL), consumed less food (3.0±0.4 versus 3.6±0.2 g/d), and had similar VO 2 (77±6 versus 73±3 mL/kg per minute) and BP (103±3 versus 107±3 mm Hg) but higher heart rate (666±15 versus 602±17 bpm). In mice fed the normal diet, leptin infusion for 7 days caused similar reductions in food intake (2.3±0.1 versus 2.4±0.2 g) but greater increases in BP (15±3 versus 7±2 mm Hg) in SOCS3-Nestin-Cre compared with controls. Leptin reduced blood glucose concentrations in both groups. Male or female SOCS3-Nestin-Cre fed high-fat-high-fructose diet exhibited less weight gain, body fat, and liver steatosis and greater energy expenditure and heart rate compared with controls. Female SOCS3-Nestin-Cre mice fed high-fat-high-fructose diet had higher BP compared with controls. Thus, neuronal SOCS3 seems to play an important role in cardiometabolic regulation because neuronal SOCS3 deficiency reduced body weight and food intake while amplifying leptin's effects on appetite and BP and attenuating the adverse metabolic effects of high-fat-high-fructose diet. © 2018 American Heart Association, Inc.

Fermented Soy Product Intake Is Inversely Associated with the Development of High Blood Pressure: The Japan Public Health Center-Based Prospective Study.

PubMed

Nozue, Miho; Shimazu, Taichi; Sasazuki, Shizuka; Charvat, Hadrien; Mori, Nagisa; Mutoh, Michihiro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Inoue, Manami; Kokubo, Yoshihiro; Yamagishi, Kazumasa; Iso, Hiroyasu; Tsugane, Shoichiro

2017-09-01

Background: Randomized controlled studies have investigated the short-term effect of soy product intake on blood pressure (BP) in normotensive people. To our knowledge, no prospective studies exist on the effect of habitual intake of fermented soy products, separate from total soy products, on BP in the general population. Objective: We examined the association between the habitual intake of soy products, including fermented soy products, and the development of high BP during a 5-y period among participants in a population-based prospective cohort study in Japan. Methods: The study included normotensive participants aged 40-69 y at baseline (926 men and 3239 women) who completed 2 questionnaires and whose BP was measured at the baseline survey between 1993 and 1994 and the 5-y follow-up in the Japan Public Health Center-Based Prospective Study Cohort II. The intake of soy products was assessed with a food-frequency questionnaire. High BP was defined as systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥85 mm Hg, or antihypertensive medication use. ORs and 95% CIs of high BP by frequency of soy products (miso, natto, and tofu) consumption, intake of total and fermented soy products, and intake of isoflavones from total and fermented soy products were estimated with the use of multiple logistic regression analysis. Results: Multivariable-adjusted ORs of high BP for the highest compared with the lowest tertile of total and fermented soy product intake were 1.03 (95% CI: 0.84, 1.25; P -trend = 0.786) and 0.72 (95% CI: 0.56, 0.92; P -trend = 0.009), respectively. The frequency of nonfermented soy product (tofu) intake was not associated with the development of high BP ( P -trend = 0.597). Conclusions: The intake of fermented soy products, but not total or nonfermented soy products, was inversely associated with developing high BP in men and women with normal BP. © 2017 American Society for Nutrition.

Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC.

PubMed

Wang, Xia; Wang, Yadi; Wang, Yue; Cheng, Jian; Wang, Yanyun; Ha, Minwen

2013-01-25

Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3'-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival. Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3'-UTR 1494 bp (-6 bp/-6 bp) genotype and the rest had TS gene 3'-UTR 1494 bp (-6 bp/+6 bp). There was no TS 3'-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3'-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (-6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (-6 bp/+6 bp). This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3'-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized therapy in lung adenocarcinoma.

PARENTAL AND SIBLING MIGRATION AND HIGH BLOOD PRESSURE AMONG RURAL CHILDREN IN CHINA.

PubMed

Wen, Ming; Li, Kelin

2016-01-01

This study examines the associations between parental and sibling rural-to-urban migration and blood pressure (BP) of rural left-behind children (LBC) in rural China. Analysis was based on the 2000, 2004, 2006 and 2009 waves of longitudinal data from the China Health and Nutrition Survey, which is an ongoing prospective survey covering nine provinces with an individual-level response rate of 88%. Blood pressure levels were measured by trained examiners at three consecutive times on the same visit and the means of three measurements were used as the final BP values. An ordinal BP measure was then created using a recently validated age-sex-specified distribution for Chinese children and adolescents, distinguishing normal BP, pre-hypertension and hypertension. Random effect modelling was performed. Different migration circumstances play different roles in LBC's BP with mother-only and both-parent migration being particularly detrimental and father-only and sibling-only migration either having no association or a negative association with LBC's BP levels or odds of high BP. In conclusion, the link between family migration and left-behind children's blood pressure is complex, and depends on who is the person out-migrating.

The interplay of exercise heart rate and blood pressure as a predictor of coronary artery disease and arterial hypertension.

PubMed

Michaelides, Andreas P; Liakos, Charalampos I; Vyssoulis, Gregory P; Chatzistamatiou, Evangelos I; Markou, Maria I; Tzamou, Vanessa; Stefanadis, Christodoulos I

2013-03-01

Delayed blood pressure (BP) and heart rate (HR) decline at recovery post-exercise are independent predictors of incident coronary artery disease (CAD). Delayed BP recovery and exaggerated BP response to exercise are independent predictors of future arterial hypertension (AH). This study sought to examine whether the combination of two exercise parameters provides additional prognostic value than each variable alone. A total of 830 non-CAD patients (374 normotensive) were followed for new-onset CAD and/or AH for 5 years after diagnostic exercise testing (ET). At the end of follow-up, patients without overt CAD underwent a second ET. Stress imaging modalities and coronary angiography, where appropriate, ruled out CAD. New-onset CAD was detected in 110 participants (13.3%) whereas AH was detected in 41 former normotensives (11.0%). The adjusted (for confounders) relative risk (RR) of CAD in abnormal BP and HR recovery patients was 1.95 (95% confidence interval [CI], 1.28-2.98; P=.011) compared with delayed BP and normal HR recovery patients and 1.71 (95% CI, 1.08-2.75; P=.014) compared with normal BP and delayed HR recovery patients. The adjusted RR of AH in normotensives with abnormal BP recovery and response was 2.18 (95% CI, 1.03-4.72; P=.047) compared with delayed BP recovery and normal BP response patients and 2.48 (95% CI, 1.14-4.97; P=.038) compared with normal BP recovery and exaggerated BP response individuals. In conclusion, the combination of two independent exercise predictors is an even stronger CAD/AH predictor than its components. © 2012 Wiley Periodicals, Inc.

Exercise Hypertension.

PubMed

Schultz, Martin G; Sharman, James E

2014-05-01

Irrespective of apparent 'normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a 'hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory 'masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs.

PubMed

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = -19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

PubMed Central

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

Objective To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. Methods In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. Results 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average −4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = −19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Conclusion Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. PMID:27454447

Casual blood pressure and neurocognitive function in children with chronic kidney disease: a report of the children with chronic kidney disease cohort study.

PubMed

Lande, Marc B; Gerson, Arlene C; Hooper, Stephen R; Cox, Christopher; Matheson, Matt; Mendley, Susan R; Gipson, Debbie S; Wong, Cynthia; Warady, Bradley A; Furth, Susan L; Flynn, Joseph T

2011-08-01

Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55). Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.

Prevalence of overweight and central obesity and their relationship with blood pressure among college students in Shandong, China.

PubMed

Zhang, Ying-Xiu; Wang, Shu-Rong; Zhao, Jin-Shan; Chu, Zun-Hua

2016-08-01

BMI and waist circumference (WC) are the two most common anthropometric measurements for general obesity and central obesity. The present study examined the distributions of BMI and WC and their relationship with blood pressure (BP) among college students in Shandong, China. A total of 5838 college students (2915 men and 2923 women) aged 19-22 years participated in the study. Height, weight, WC, and BP of all participants were measured, and BMI and waist-to-height ratio were calculated. The BMI cutoffs recommended by the Working Group on Obesity in China were used to define underweight, normal weight, and overweight. Central obesity was defined as waist-to-height ratio of at least 0.5. High BP was defined as systolic blood pressure of at least 140 mmHg and/or diastolic blood pressure of at least 90 mmHg. All individuals were classified into four groups (Q1-Q4) according to the quartiles of BMI and WC, and the BP level, and the prevalence of high BP among the four groups was compared. The prevalences of overweight, central obesity, and high BP were 22.74, 7.85, and 8.79% for men and 8.42, 3.02, and 1.92% for women, respectively; these figures were all significantly higher in men than in women (P<0.01). In both men and women, overweight and central obesity are associated with elevated BP. College students with high BMI and high WC might have an increased risk of elevated BP. These findings emphasize the importance of the prevention of overweight and obesity to prevent future-related problems such as hypertension in young individuals.

Exaggerated exercise blood pressure response in middle-aged men as a predictor of future blood pressure: a 10-year follow-up.

PubMed

Ito, Katsuyuki; Iwane, Masataka; Miyai, Nobuyuki; Uchikawa, Yukiko; Mugitani, Koichi; Mohara, Osamu; Shiba, Mitsuru; Arita, Mikio

The prognostic value of an exaggerated exercise systolic blood pressure response (EESBPR) remains controversial. This study was designed to assess whether an EESBPR is associated with the predictor of future blood pressure. From an initial population of 1,534 male-subjects with normal BP or no medication who underwent ergometric exercise, 733 subjects (mean age: 41 years old) at baseline to follow-up BP after an average of 10 years were selected. A 12-min exercise tolerance test with three phases of estimated load from predictive maximum oxygen intake was performed at baseline, and exercise BP was measured. Exercise BP response was classified by three group: Low group (G) (exercise SBP < 180 mmHg), Middle G (exercise BP:180-199 mmHg), High G (exercise BP:200 mmHg ≦). BP after 10 years in Low G was 123 ± 12/79 ± 7 mmHg, in Middle G:127 ± 13/81 ± 8 mmHg, in High G :134 ± 15/84 ± 10 mmHg. Compared with in Low G, BP after 10 years in High G significantly increased (p < 0.05). Multiple regression analysis was carried out to clarify the relationship of exercise SBP at baseline to BP after 10 years. In multivariate-adjusted models, the relationship of SBP at follow-up was stronger to exercise SBP (β = 0.271, P < 0.001) than to resting SBP (β = 0.148, P < 0.001). Maximum oxygen intake (β = -0.193, P = 0.003) and resting SBP correlated with SBP after 10 years. In middle-aged men, exercise SBP would be a stronger predictor of future SBP, DBP rather than BP at rest. In optimal of classification of BP (SBP < 120 mmHg), exercise BP response was clearly associated with BP after 10 years.

Changes in Central Aortic Pressure Levels, Wave Components and Determinants Associated with High Peripheral Blood Pressure States in Childhood: Analysis of Hypertensive Phenotype.

PubMed

García-Espinosa, Victoria; Curcio, Santiago; Marotta, Marco; Castro, Juan M; Arana, Maite; Peluso, Gonzalo; Chiesa, Pedro; Giachetto, Gustavo; Bia, Daniel; Zócalo, Yanina

2016-10-01

The aims were to determine whether children's high peripheral blood pressure states (HBP) are associated with increased central aortic blood pressure (BP) and to characterize hemodynamic and vascular changes associated with HBP in terms of changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR) and net and relative contributions of reflected waves to the aortic pulse amplitude. We included 154 subjects (mean age 11; range 4-16 years) assigned to one of two groups: normal peripheral BP (NBP, n = 101), defined as systolic and diastolic BP < 90th percentile, or high BP (HBP, n = 53), defined as average systolic and/or diastolic BP levels ≥90th percentile (curves for sex, age and body height). The HBP group included children with hypertensive and pre-hypertensive BP levels. After a first analysis, groups were compared excluding obese and dyslipidemic children. Peripheral and central aortic BP, PWV and pulse wave-derived parameters (augmentation index, forward and backward wave components' amplitude) were measured using gold-standard techniques, applanation tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). Independent of the presence of dyslipidemia and/or obesity, aortic systolic and pulse BP were higher in HBP than in NBP children. The increase in central BP could not be explained by an increase in the relative contribution of reflections to the aortic pressure wave, higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP would be explained by an increase in the amplitude of both incident and reflected wave components.

Blood pressure in head‐injured patients

PubMed Central

Mitchell, Patrick; Gregson, Barbara A; Piper, Ian; Citerio, Giuseppe; Mendelow, A David; Chambers, Iain R

2007-01-01

Objective To determine the statistical characteristics of blood pressure (BP) readings from a large number of head‐injured patients. Methods The BrainIT group has collected high time‐resolution physiological and clinical data from head‐injured patients who require intracranial pressure (ICP) monitoring. The statistical features of this dataset of BP measurements with time resolution of 1 min from 200 patients is examined. The distributions of BP measurements and their relationship with simultaneous ICP measurements are described. Results The distributions of mean, systolic and diastolic readings are close to normal with modest skewing towards higher values. There is a trend towards an increase in blood pressure with advancing age, but this is not significant. Simultaneous blood pressure and ICP values suggest a triphasic relationship with a BP rising at 0.28 mm Hg/mm Hg of ICP, for ICP up to 32 mm Hg, and 0.9 mm Hg/mm Hg of ICP for ICP from 33 to 55 mm Hg, and falling sharply with rising ICP for ICP >55 mm Hg. Conclusions Patients with head injury appear to have a near normal distribution of blood pressure readings that are skewed towards higher values. The relationship between BP and ICP may be triphasic. PMID:17138594

Clinical study on the factors affecting the post-partum recovery of patients with hypertensive pregnancy disorders at a Chinese hospital.

PubMed

Wei, Jun; Wang, Yan; Xu, Jiayuan; Zhang, Chunfang; Zhou, Helen; Liu, Guoli

2017-03-01

The aim of this study was to investigate the post-partum recovery of blood pressure (BP) in women with hypertensive disorders of pregnancy (HDP) and to evaluate HDP risk factors. A total of 124 patients with gestational hypertension (n = 63) or pre-eclampsia (n = 61) who gave birth at Peking University People's Hospital between January and December 2013 were included in this study. The recorded clinical and laboratory parameters included the patients' general information, maternal pre-pregnancy body mass index, gestational weight gain, gestational age at onset and delivery, delivery mode and time taken for BP to return to normal level. Logistic regression analysis was performed to evaluate the influence of various risk factors on post-partum BP recovery. The mean interval for BP normalization was 24.1 ± 22.8 days (median, 7 days). Forty-six percent of the patients recovered from hypertension within three days, and 75% recovered within six weeks of delivery. About 90% of the patients required 60 days for BP to normalize after delivery. After adjusting for confounding factors, post-partum recovery from hypertension was found to be influenced by hypertension severity, maternal serum albumin level, a family history of hypertension and gestational week at delivery. The BP of the majority of the patients with gestational hypertension or pre-eclampsia returned to normal within 60 days of delivery. Hypertension severity, maternal serum albumin level, a family history of family hypertension and gestational week at delivery influenced the time required for BP normalization. © 2016 Japan Society of Obstetrics and Gynecology.

Exercise Hypertension

PubMed Central

Schultz, Martin G.; Sharman, James E.

2014-01-01

Irrespective of apparent ‘normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a ‘hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory ‘masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE. PMID:26587435

[Obesity in schoolchildren from Merida, Venezuela: association with cardiovascular risk factors].

PubMed

Paoli, Mariela; Uzcátegui, Lilia; Zerpa, Yajaira; Gómez-Pérez, Roald; Camacho, Nolis; Molina, Zarela; Cichetti, Rosanna; Vallarroel, Vanessa; Fargier, Andrea; Arata-Bellabarba, Gabriela

2009-05-01

To investigate the prevalence of obesity and associated cardiovascular risk factors in schoolchildren in our city, given the influence of these factors on the development of atherosclerosis. We studied a representative sample of second grade students composed of 370 children aged 7.82+/-0.62 years (47.8% girls and 52.2% boys); 52.4% were from public schools and 47.6% were from private schools. Surveys were performed and anthropometric measurements, blood pressure (BP) values and glucose and lipid profiles in capillary blood were determined. A total of 9.7% (36 schoolchildren) were obese and 13.8% were overweight. There were no differences according to sex or school system. Abdominal obesity was observed in 69.4% (p<0.0001), normal-high BP (90-97th percentile) in 27.8% (p<0.0001), dyslipidemia in 66.7% (p<0.05) and metabolic syndrome in 38.9% (p<0.0001) of the obese children compared with 1.3%, 5.1%, 48.9% and 0.4% of the children with normal weight, respectively. No association was found between fasting hyperglycemia and obesity. There were no cases of hypertension or diabetes mellitus. The risk (odds ratio) for normal-high BP, dyslipidemia, abdominal obesity and metabolic syndrome was 6.3, 2.2, 60.9, and 70.2 times higher in obese children than in non-obese children, respectively. A positive and significant correlation was found between waist circumference and body mass index with BP and the atherogenic indexes triglycerides/high-density lipoprotein cholesterol (HDL-C), total cholesterol/HDL-C and low-density lipoprotein cholesterol/HDL-C (p=0.0001). Compared with cities in other countries, the city of Mérida, Venezuela, has an intermediate prevalence of overweight and obesity in schoolchildren. The high frequency of cardiovascular risk factors in the obese and its positive correlation with adiposity highlights the need to implement population-based strategies for its prevention in childhood.

Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

PubMed

Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

2017-05-01

The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Disruption in the relationship between blood pressure and salty taste thresholds among overweight and obese children

PubMed Central

Bobowski, Nuala K.

2015-01-01

Background Prevalence of high blood pressure (BP) among American children has increased over the past two decades, due in part to increasing rates of obesity and excessive dietary salt intake. Objective We tested the hypotheses that the relationships among BP, salty taste sensitivity, and salt intake differ between normal-weight and overweight/obese children. Design In an observational study, sodium chloride (NaCl) and monosodium glutamate (MSG) taste detection thresholds were measured using the Monell two-alternative, forced-choice, paired-comparison tracking method. Weight and BP were measured, and salt intake was determined by 24-hour dietary recall. Participants/Setting Eight- to 14-year-olds (N=97; 52% overweight or obese) from the Philadelphia area completed anthropometrics and BP measurements; 97% completed one or both thresholds. Seventy-six percent provided valid dietary recall data. Testing was completed between December 2011 and August 2012. Main outcome measures NaCl and MSG detection thresholds, BP, and dietary salt intake. Statistical analyses Outcome measures were compared between normal-weight and overweight/obese children with t-tests. Relationships among outcome measures within groups were examined with Pearson correlations, and multiple regression analysis was used to examine the relationship between BP and thresholds, controlling for age, BMI-Z score, and dietary salt intake. Results Salt and MSG thresholds were positively correlated (r(71)=0.30, p=0.01) and did not differ between body-weight groups (p>0.20). Controlling for age, BMI-Z score, and salt intake, systolic BP was associated with NaCl thresholds among normal-weight children (p=0.01), but not among overweight/obese children. All children consumed excess salt (>8 g/day). Grain and meat products were the primary source of dietary sodium. Conclusions The apparent disruption in the relationship between salty taste response and BP among overweight/obese children suggests the relationship may be influenced by body weight. Further research is warranted to explore this relationship as a potential measure to prevent development of hypertension. PMID:25843808

Low dietary sodium intake is associated with enhanced vascular endothelial function in middle-aged and older adults with elevated systolic blood pressure

PubMed Central

Jablonski, Kristen L.; Gates, Phillip E.; Pierce, Gary L.; Seals, Douglas R.

2012-01-01

Background Age and increasing systolic blood pressure (BP) are associated with vascular endothelial dysfunction, but the factors involved are incompletely understood. We tested the hypothesis that vascular endothelial function is related to dietary sodium intake among middle-aged and older adults (MA and O) with elevated systolic BP. Methods Data were analyzed on 25 otherwise healthy adults aged 48–73 years with high normal systolic BP or stage I systolic hypertension (130–159 mmHg). Self-reported sodium intake was <100 mmol/d in 12 (7 M) subjects (low sodium, 73 ± 6 mmol/d) and between 100 and 200 mmol/d in 13 (9 M) subjects (normal sodium, 144 ± 6 mmol/d). Results Groups did not differ in other dietary factors, age, body weight and composition, BP, metabolic risk factors, physical activity and maximal aerobic capacity. Plasma concentrations of norepinephrine, endothelin-1, oxidized low-density lipoproteins (LDL), antioxidant status and inflammatory markers did not differ between groups. Brachial artery flow-mediated dilation (FMD) was 42% (mm Δ) to 52% (% Δ) higher in the low versus normal sodium group (p <0.05). In all subjects, brachial artery FMD was inversely related to dietary sodium intake (FMD mm Δr =−0.40, p <0.05; %Δr =−0.53, p <0.01). Brachial artery FMD was not related to any other variable. In contrast, endothelium-independent dilation did not differ between groups (p ≥ 0.24) and was not related to sodium intake in the overall group (p ≥ 0.29). Conclusions Low sodium intake is associated with enhanced brachial artery FMD in MA and O with elevated systolic BP. These results suggest that dietary sodium restriction may be an effective intervention for improving vascular endothelial function in this high-risk group. PMID:19723834

The distinct temperament profiles of bipolar I, bipolar II and unipolar patients.

PubMed

Akiskal, Hagop S; Kilzieh, Nael; Maser, Jack D; Clayton, Paula J; Schettler, Pamela J; Traci Shea, M; Endicott, Jean; Scheftner, William; Hirschfeld, Robert M A; Keller, Martin B

2006-05-01

Despite a plethora of studies, controversies abound on whether the long-term traits of unipolar and bipolar patients could be differentiated by temperament and whether these traits, in turn, could be distinguished from subthreshold affective symptomatology. 98 bipolar I (BP-I), 64 bipolar II (BP-II), and 251 unipolar major depressive disorder (UP-MDD) patients all when recovered from discrete affective episodes) and 617 relatives, spouses or acquaintances without lifetime RDC diagnoses (the comparison group, CG) were administered a battery of 17 self-rated personality scales chosen for theoretical relevance to mood disorders. Subsamples of each of the four groups also received the General Behavior Inventory (GBI). Of the 436 personality items, 103 that significantly distinguished the three patient groups were subjected to principal components analysis, yielding four factors which reflect the temperamental dimensions of "Mood Lability", "Energy-Assertiveness," "Sensitivity-Brooding," and "Social Anxiety." Most BP-I described themselves as near normal in emotional stability and extroversion; BP-II emerged as labile in mood, energetic and assertive, yet sensitive and brooding; MDD were socially timid, sensitive and brooding. Gender and age did not have marked influence on these overall profiles. Within the MDD group, those with baseline dysthymia were the most pathological (i.e., high in neuroticism, insecurity and introversion). Selected GBI items measuring hypomania and biphasic mood changes were endorsed significantly more often by BP-II. Finally, it is relevant to highlight a methodologic finding about the precision these derived temperament factors brought to the UP-BP differentiation. Unlike BP-I who were low on neuroticism, both BP-II and UP scored high on this measure: yet, in the case of BP-II high neuroticism was largely due to mood lability, in UP it reflected subdepressive traits. We used self-rated personality measures, a possible limitation generic to the paper-and-pencil personality literature. It is therefore likely that BP-I may have over-rated their "sanguinity"; or should one consider such self-report as a reliable reflection of one's temperament? One can raise similar unanswerable questions about "depressiveness" and "mood lability." As contrasted to CG and published norms, the postmorbid self-described "usual" personality is 1) sanguine among many, but not all, BP-I; 2) labile or cyclothymic among BP-II; and 3) subanxious and subdepressive among UP. It is further noteworthy that with the exception of BP-II, the temperament scores of BP-I and MDD were within one SD from published norms. Rather than being pathological, these attributes are best conceived as subclinical temperamental variants of the normal, thereby supporting the notion of continuity between interepisodic and episodic phases of affective disorders. These findings overall are in line with Kraepelin's views and contrary to the DSM-IV formulation of axis-II constructs as being pathological and sharply demarcated from affective episodes.

DYZ1 copy number variation, Y chromosome polymorphism and early recurrent spontaneous abortion/early embryo growth arrest.

PubMed

Yan, Junhao; Fan, Lingling; Zhao, Yueran; You, Li; Wang, Laicheng; Zhao, Han; Li, Yuan; Chen, Zi-Jiang

2011-12-01

To find the association between recurrent spontaneous abortion (RSA)/early embryo growth arrest and Y chromosome polymorphism. Peripheral blood samples of the male patients of big Y chromosome, small Y chromosome and other male patients whose partners suffered from unexplained RSA/early embryo growth arrest were collected. PCR and real-time fluorescent quantitative PCR were used to test the deletion and the copy number variation of DYZ1 region in Y chromosome of the patients. A total of 79 big Y chromosome patients (48 of whose partners suffered from RSA or early embryo growth arrest), 7 small Y chromosome patients, 106 other male patients whose partners had suffered from unexplained RSA or early embryo growth arrest, and 100 normal male controls were enrolled. There was no fraction deletion of DYZ1 detected both in big Y patients and in normal men. Of RSA patients, 1 case showed deletion of 266bp from the gene locus 25-290bp, and 2 cases showed deletion of 773bp from 1347 to 2119bp. Of only 7 small Y chromosome patients, 2 cases showed deletion of 266bp from 25 to 290bp, and 4 cases showed deletion of 773bp from 1347 to 2119bp and 275bp from 3128 to 3420bp. The mean of DYZ1 copies was 3900 in normal control men; the mean in big Y patients was 5571, in RSA patients was 2655, and in small Y patients was 1059. All of the others were significantly different (P<0.01) compared with normal control men, which meant that DYZ1 copy number in normal control men was less than that of big Y chromosome patients, and was more than that of unexplained early RSA patients and small Y patients. The integrity and copy number variation of DYZ1 are closely related to the Y chromosome length under microscope. The cause of RSA/early embryo growth arrest in some couples may be the increase (big Y patients) or decrease of DYZ1 copy number in the husbands' Y chromosome. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of cilnidipine on normal to marginally elevated urine albumin-creatinine ratio in asymptomatic non-diabetic hypertensive patients: an exponential decay curve analysis.

PubMed

Nakatsu, Takaaki; Toyonaga, Shinji; Mashima, Keiichi; Yuki, Yoko; Nishitani, Aya; Ogawa, Hiroko; Miyoshi, Toru; Hirohata, Satoshi; Izumi, Reishi; Kusachi, Shozo

2010-01-01

High-normal urinary albumin excretion has been reported to have clinical significance with respect to progression of proteinuria and hypertension. We analysed the effect of cilnidipine (10 mg/day) on morning systolic blood pressure (SBP) and urine albumin-creatinine ratio (UACR) in 16 non-diabetic hypertensive patients with a normal to marginally elevated UACR (mean +/- SD 29.4 +/- 21.7; range 7.5-72.9 mg/g creatinine). Sequential home BP and UACR data were fitted to a simple exponential function as follows: where y is SBP (mmHg) or UACR (mg/g creatinine); alpha is the extent of the SBP (mmHg)- or UACR (mg/g creatinine)-lowering effect; beta (days) is the time-constant for SBP or UACR decrease; t is the number of days after the start of cilnidipine administration; and gamma is the finally stabilized SBP (mmHg) or UACR (mg/g creatinine). Mean +/- SD morning SBP and UACR decreased by 20.4 +/- 11.4 mmHg and 15.2 +/- 13.1 mg/g creatinine, respectively, as determined by coefficient alpha. The mean +/- SD time-constant for UACR decrease was significantly longer than that for BP decrease (43.5 +/- 22.9 vs 15.4 +/- 7.1 days). UACR reduction correlated with pre-treatment UACR values (correlation coefficient [R] = 0.88, p < 0.01) but not with BP decrease. The present study demonstrated that cilnidipine reduced UACR in hypertensive patients with normal to marginally elevated UACR independent of its BP-lowering effect.

Casual Blood Pressure and Neurocognitive Function in Children with Chronic Kidney Disease: A Report of the Children with Chronic Kidney Disease Cohort Study

PubMed Central

Gerson, Arlene C.; Hooper, Stephen R.; Cox, Christopher; Matheson, Matt; Mendley, Susan R.; Gipson, Debbie S.; Wong, Cynthia; Warady, Bradley A.; Furth, Susan L.; Flynn, Joseph T.

2011-01-01

Summary Background and objectives Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. Design, setting, participants, & measurements This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. Results Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90th percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95th percentile BP) correlated inversely with Performance IQ score (systolic, r = −0.13, P = 0.01; diastolic, r = −0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = −3.7, 95% confidence interval [CI]: −7.3 to −0.06; systolic BP index, β = −1.16 to 95% CI: −2.1, −0.21; diastolic BP index, β = −1.17, 95% CI: −1.8 to −0.55). Conclusions Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD. PMID:21700829

Dietary Sodium Restriction and Association with Urinary Marinobufagenin, Blood Pressure, and Aortic Stiffness

PubMed Central

Fedorova, Olga V.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; Fleenor, Bradley S.; Lakatta, Edward G.; Bagrov, Alexei Y.; Seals, Douglas R.

2013-01-01

Summary Background and objectives Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading. Design, setting, participants, & measurements The hypothesis was that dietary sodium restriction performed in middle-aged/older adults (eight men and three women; 60±2 years) with moderately elevated systolic BP (139±2/83±2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium (77±9 mmol/d) and 5 weeks of a normal-sodium (144±7 mmol/d) diet. Results Urinary marinobufagenin excretion (weekly measurements; 25.4±1.8 versus 30.7±2.1 pmol/kg per day), systolic BP (127±3 versus 138±5 mmHg), and aortic pulse-wave velocity (700±40 versus 843±36 cm/s) were lower during the low- versus normal-sodium condition (all P<0.05). Across all weeks, marinobufagenin excretion was related with systolic BP (slope=0.61, P<0.001) and sodium excretion (slope=0.46, P<0.001). These associations persisted during the normal- but not the low-sodium condition (both P<0.005). Marinobufagenin excretion also was associated with aortic pulse-wave velocity (slope=0.70, P=0.02) and endothelial cell expression of NAD(P)H oxidase-p47phox (slope=0.64, P=0.006). Conclusions These results show, for the first time in humans, that dietary sodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-sodium diets. PMID:23929930

Black phosphorus as a saturable absorber for generating mode-locked fiber laser in normal dispersion regime

NASA Astrophysics Data System (ADS)

Latiff, A. A.; Rusdi, M. F. M.; Hisyam, M. B.; Ahmad, H.; Harun, S. W.

2016-11-01

This paper reports a few-layer black phosphorus (BP) as a saturable absorber (SA) or phase-locker in generating modelocked pulses from a double-clad ytterbium-doped fiber laser (YDFL). We mechanically exfoliated the BP flakes from BP crystal through a scotch tape, and repeatedly press until the flakes thin and spread homogenously. Then, a piece of BP tape was inserted in the cavity between two fiber connectors end facet. Under 810 mW to 1320 mW pump power, stable mode-locked operation at 1085 nm with a repetition rate of 13.4 MHz is successfully achieved in normal dispersion regime. Before mode-locked operation disappears above maximum pump, the output power and pulse energy is about 80 mW and 6 nJ, respectively. This mode-locked laser produces peak power of 0.74 kW. Our work may validates BP SA as a phase-locker related to two-dimensional nanomaterials and pulsed generation in normal dispersion regime.

CacyBP/SIP promotes the proliferation of colon cancer cells

PubMed Central

Chen, Xiong; Wang, Jun; Lu, Yuanyuan; Zhang, Faming; Liu, Zhengxiong; Lei, Ting; Fan, Daiming

2017-01-01

CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium. CacyBP/SIP promoted the cell proliferation of colon cancer cells under both basal and gastrin stimulated conditions as shown by knockdown studies. Gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27kip1 protein. The gastrin induced reduction in p27kip1 was prevented when cells were treated with the proteasome inhibitor MG132. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27kip1. PMID:28196083

Complex engagement of DNA damage response pathways in human cancer and in lung tumor progression.

PubMed

Nuciforo, Paolo Giovanni; Luise, Chiara; Capra, Maria; Pelosi, Giuseppe; d'Adda di Fagagna, Fabrizio

2007-10-01

Tumor initiation and progression provide a multitude of occasions for the generation of DNA damage and the consequent activation of the DNA damage response (DDR) pathway. DDR signaling involves the engagement of key factors such as ATM, CHK2, 53BP1 and the phosphorylation of histone H2AX (gamma-H2AX). The systematic study of DDR in human tumors and normal tissues by high-throughput tissue microarrays revealed that ATM and gamma-H2AX were engaged in cancer but the extent of their activation was strongly affected by the organ and cell type involved, whereas 53BP1 loss was the most consistent feature among the tumor studied. Unexpectedly, we also observed activated DDR markers in morphologically normal tissues, also in association with inflammation. Analysis of the dynamic engagement of DDR along the different stages of lung tumorigenesis showed that 53BP1 loss occurs early at the transition from normal to dysplastic change whereas the activated forms of ATM and CHK2, but not gamma-H2AX, initially accumulate in pre-invasive lesions and are then lost during tumor progression. In individual lung tumors, the activation of ATM, CHK2 and the presence of 53BP1 were consistently correlated, whereas gamma-H2AX did not correlate with activated ATM. Finally, the study of associations between critical clinicopathological parameters and activated DDR factors highlighted a statistically meaningful correlation between reduced local tumor extension and the phosphorylation of ATM, CHK2 and the presence of 53BP1, whereas no significant correlations with parameters such as survival or relapse of early-stage lung carcinomas were found.

Ring-shaped pulse oximeter and its application: measurement of SpO2 and blood pressure during sleep and during flight.

PubMed

Kishimoto, Aya; Tochikubo, Osamu; Ohshige, Kenji; Yanaga, Akihiko

2005-01-01

Respiratory and cardiovascular functions show circadian and day-to-day changes. We have developed a wireless ring-shaped pulse oximeter in collaboration with MC Medical Inc. and Advanced Medical Inc. We investigated the accuracy of this pulse oximeter and its application in daily life. Percutaneous arterial oxygen saturation (SpO2) of 47 volunteers was measured simultaneously with the ring-shaped pulse oximeter and a standard pulse oximeter. A total of 103 volunteers underwent measurement of SpO2 for 24 hr, and 11 healthy volunteers underwent measurement of SpO2 and blood pressure (BP) during flight. SpO2 and heart rate (HR) were measured and recorded every 20 sec, cabin barometric pressure and cabin oxygen concentration equivalent to sea level were measured minute-to-minute, and BP was measured every 3 min with a portable BP recorder during each flight. The SpO2 values measured with the ring-shaped pulse oximeter were similar to those measured with the standard method. The mean SpO2 during sleep was significantly lower in the group with high-normal BP or mild hypertension than in the group with normal BP. During flight, the mean change in SpO2 was -2.4 +/- 1.7% during nose-up flight, and 2.1 +/- 2.6% during nose-down flight. There was a significant correlation between change in SpO2 and change in systolic BP during nose-up flight. The wireless ring-shaped pulse oximeter was useful for investigating changes in SpO2 and its effect on BP in daily life during sleep and during air travel.

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS)

NASA Technical Reports Server (NTRS)

Low, P. A.; Novak, V.; Spies, J. M.; Novak, P.; Petty, G. W.

1999-01-01

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Stress management and dietary counseling in hypertensive patients: a pilot study of additional effect.

PubMed

Katsarou, Alexia L; Vryonis, Marios M; Protogerou, Athanassios D; Alexopoulos, Evangelos C; Achimastos, Apostolos; Papadogiannis, Dimitrios; Chrousos, George P; Darviri, Christina

2014-01-01

In Western societies, cardiovascular (CV) disease is the primary cause of mortality, and high blood pressure (BP) is the main reversible factor leading to CV disease. Dietary habits and psychosocial stress contribute to the establishment of hypertension, while its role in the control of high BP is currently examined. In this study, we examined the effect and feasibility of a combined intervention of dietary education and stress management on the control of hypertension. A randomized, controlled pilot study was designed to evaluate the effect of combined education on stress management techniques and dietary habits (Mediterranean diet principle) on office BP after eight weeks. Of the 45 randomized subjects, 36 were included in the final analysis (control group = 20 (age: 67 ± 12 years, 31.8%, males) and intervention group = 16 (age: 62 ± 12 years, 47%, males)). CV disease risk factors (except smoking), BP, dietary habits, perceived stress and physical activity (all assessed with validated questionnaires) were similar between the two groups at baseline. After eight weeks, office BP (systolic and diastolic) and perceived stress were significantly reduced, whereas the adherence in Mediterranean diet principle was significantly increased, but only in the intervention group. A combined intervention of stress management techniques and Mediterranean diet education seems to be beneficial for BP reduction. Such interventions could possibly serve as a complementary treatment along with drug therapy or in the early treatment of high normal BP. A call to action for designing epidemiological studies and evaluating the efficacy of such non-pharmacological treatment strategies is therefore warranted.

Impaired baroreflex sensitivity, carotid stiffness, and exaggerated exercise blood pressure: a community-based analysis from the Paris Prospective Study III.

PubMed

Sharman, James E; Boutouyrie, Pierre; Perier, Marie-Cécile; Thomas, Frédérique; Guibout, Catherine; Khettab, Hakim; Pannier, Bruno; Laurent, Stéphane; Jouven, Xavier; Empana, Jean-Philippe

2018-02-14

People with exaggerated exercise blood pressure (BP) have adverse cardiovascular outcomes. Mechanisms are unknown but could be explained through impaired neural baroreflex sensitivity (BRS) and/or large artery stiffness. This study aimed to determine the associations of carotid BRS and carotid stiffness with exaggerated exercise BP. Blood pressure was recorded at rest and following an exercise step-test among 8976 adults aged 50 to 75 years from the Paris Prospective Study III. Resting carotid BRS (low frequency gain, from carotid distension rate, and heart rate) and stiffness were measured by high-precision echotracking. A systolic BP threshold of ≥ 150 mmHg defined exaggerated exercise BP and ≥140/90 mmHg defined resting hypertension (±antihypertensive treatment). Participants with exaggerated exercise BP had significantly lower BRS [median (Q1; Q3) 0.10 (0.06; 0.16) vs. 0.12 (0.08; 0.19) (ms2/mm) 2×108; P < 0.001] but higher stiffness [mean ± standard deviation (SD); 7.34 ± 1.37 vs. 6.76 ± 1.25 m/s; P < 0.001) compared to those with non-exaggerated exercise BP. However, only lower BRS (per 1SD decrement) was associated with exaggerated exercise BP among people without hypertension at rest {specifically among those with optimal BP; odds ratio (OR) 1.16 [95% confidence intervals (95% CI) 1.01; 1.33], P = 0.04 and high-normal BP; OR, 1.19 (95% CI 1.07; 1.32), P = 0.001} after adjustment for age, sex, body mass index, smoking, alcohol, total cholesterol, high-density lipoprotein cholesterol, resting heart rate, and antihypertensive medications. Impaired BRS, but not carotid stiffness, is independently associated with exaggerated exercise BP even among those with well controlled resting BP. This indicates a potential pathway from depressed neural baroreflex function to abnormal exercise BP and clinical outcomes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

PubMed

Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

2016-02-01

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

Tunneling in BP-MoS2 heterostructure

NASA Astrophysics Data System (ADS)

Liu, Xiaochi; Qu, Deshun; Kim, Changsik; Ahmed, Faisal; Yoo, Won Jong

Tunnel field effect transistor (TFET) is considered to be a leading option for achieving SS <60 mV/dec. In this work, black phosphorus (BP) and molybdenum disulfide (MoS2) heterojunction devices are fabricated. We find that thin BP flake and MoS2 form normal p-n junctions, tunneling phenomena can be observed when BP thickness increases to certain level. PEO:CsClO4 is applied on the surface of the device together with a side gate electrode patterned together with source and drain electrodes. The Fermi level of MoS2 on top of BP layer can be modulated by the side gating, and this enables to vary the MoS2-BP tunnel diode property from off-state to on-state. Since tunneling is the working mechanism of MoS2-BP junction, and PEO:CsClO4\\ possesses ultra high dielectric constant and small equivalent oxide thickness (EOT), a low SS of 55 mV/dec is obtained from MoS2-BP TFET. This work was supported by the Global Research Laboratory and Global Frontier R&D Programs at the Center for Hybrid Interface Materials, both funded by the Ministry of Science, ICT & Future Planning via the National Research Foundation of Korea (NRF).

Association of Neck Circumference and Obesity with Blood Pressure among Adolescents in Urban and Rural Population in North Tamil Nadu.

PubMed

Rajagopalan, Archana; Balaji, Nisha

2017-01-01

Since a few studies exist on the association of neck circumference (NC) and obesity with blood pressure (BP) among adolescents in India, we found it highly relevant to measure the NC and body mass index (BMI) using them as indicators of upper body subcutaneous fat and obesity and relate them to BP in a rural and urban adolescent population in North Tamil Nadu. This is a community-based cross-sectional study of descriptive design where 500 students from urban and rural areas were selected, and their BMI, NC, and BP were measured using standardized instruments. Among urban and rural population high and normal NC positively correlated with BMI, systolic BP (SBP) and diastolic BP (DBP), indicating that the data clearly reflects increase in BMI, SBP, and DBP values with increase in NC or vice versa. The correlation was statistically significant ( P < 0.001) significantly higher BMI ( P < 0.01), SBP ( P < 0.05), and NC ( P < 0.001) was observed in urban population than rural. DBP was not significantly different in rural and urban population. 95 th percentile values are significantly higher than rest in both urban and rural population. Only the 95 th percentile values correlate and reflect similar changes in BMI, SBP, and DBP. Our studies indicate a strong association of elevation in BP with high NC and increase in BMI. Overweight and obesity were positively correlated with increase in SBP and DBP.

Relationship between hot flashes and ambulatory blood pressure: the Hilo women's health study.

PubMed

Brown, Daniel E; Sievert, Lynnette L; Morrison, Lynn A; Rahberg, Nichole; Reza, Angela

2011-01-01

To examine ambulatory blood pressure (BP) differences between women who report hot flashes (HFs) and those who do not, and to observe whether an objectively measured HF is associated with transient changes in BP. HFs have been associated with elevated BP, but studies have not examined the relationship between objectively measured HFs and blood pressure during normal daily activities. A sample of 202 women in Hilo, Hawaii, aged 45 to 55 years, were asked to fill out a questionnaire that included demographic information and an inventory of symptoms. The women underwent simultaneous 24-hour monitoring of ambulatory BP and HFs, at the same time keeping a diary that included mood and HF reports. No significant difference was present in mean BP between women who reported having an HF during the last 2 weeks and those who did not. When measurements controlled for negative mood reports and posture, there was a highly significant elevation in Z scores of systolic BP when a measured, objective HF occurred within 10 minutes before a BP reading, and a significant elevation of Z scores of diastolic BP when a subjectively reported HF occurred within 10 minutes after a BP reading. These results suggest that objectively measured HFs precede transient elevations of systolic BP, but it is unclear if there is a causal relationship. These results also suggest that women experience subjective HFs within 10 minutes after a transient increase in diastolic BP. Again, the causal relationship is not understood.

Antecedent rest may not be necessary for automated office blood pressure at lower treatment targets.

PubMed

Colella, Tracey J F; Tahsinul, Anam; Gatto, Hannah; Oh, Paul; Myers, Martin G

2018-06-14

In SPRINT (Systolic Blood Pressure Intervention Trial), use of the Omron 907XL blood pressure (BP) monitor set at 5 minutes of antecedent rest to record BP produced an automated office BP value 7/6 mm Hg lower than awake ambulatory BP at 27 months. The authors studied the impact on automated office BP of setting the Omron 907XL to 0 minutes instead of 5 minutes of rest in patients with readings in the lower normal BP range, similar to on-treatment BP in the SPRINT intensive therapy group. Patients (n = 100) in cardiac rehabilitation were randomized to three BP readings at 1-minute intervals using an Omron 907XL BP device set for 5 or 0 minutes of antecedent rest. Mean (±standard deviation) automated office BP (mm Hg) after 5 minutes of rest (120.2 ± 14.6/66.9 ± 8.6 mm Hg) was lower (P < .001/P < .01) than without rest (124.2 ± 16.4/67.9 ± 9.1 mm Hg). When target BP is in the lower normal range, automated office BP recorded without antecedent rest using an Omron 907XL device should be higher and closer to the awake ambulatory BP, compared with readings taken after 5 minutes of rest. ©2018 Wiley Periodicals, Inc.

Association of masked hypertension and left ventricular remodeling with the hypertensive response to exercise.

PubMed

Sharman, James E; Hare, James L; Thomas, Scott; Davies, Justin E; Leano, Rodel; Jenkins, Carly; Marwick, Thomas H

2011-08-01

A hypertensive response to exercise (HRE; defined as normal clinic blood pressure (BP) and exercise systolic BP (SBP) ≥210 mm Hg in men or ≥190 mm Hg in women, or diastolic BP (DBP) ≥105 mm Hg) independently predicts mortality. The mechanisms remain unclear but may be related to masked hypertension. This study aimed to assess the prevalence of masked hypertension and its association with cardiovascular risk factors, including left ventricular (LV) mass, in patients with a HRE. Comprehensive clinical and echocardiographic evaluation (including central BP, aortic pulse wave velocity by tonometry) and 24-h ambulatory BP monitoring (ABPM) were performed in 72 untreated patients with HRE (aged 54 ± 9 years; 60% male; free from coronary artery disease confirmed by exercise stress echocardiography). Masked hypertension was defined according to guidelines as daytime ABPM ≥135/85 mm Hg and clinic BP <140/90 mm Hg. Masked hypertension was present in 42 patients (58%). These patients had higher LV mass index (41.5 ± 8.7 g/m(2.7) vs. 35.9 ± 8.5 g/m(2.7); P = 0.01), LV relative wall thickness (RWT; 0.42 ± 0.09 vs. 0.37 ± 0.06; P = 0.004) and exercise SBP (222 ± 17 mm Hg vs. 212 ± 14 mm Hg; P = 0.01), but no significant difference in aortic pulse wave velocity or central pulse pressure (P > 0.05 for both). The strongest independent determinant of LV mass index was the presence of masked hypertension (unstandardized β = 5.6; P = 0.007), which was also independently related to LV RWT (unstandardized β = 0.04; P = 0.03). Masked hypertension is highly prevalent in HRE patients with a normal resting office BP and is associated with increased LV mass index and RWT. Clinicians should consider measuring ABPM or home BP in HRE patients.

Sodium intake and cardiac sympatho-vagal balance in young men with high blood pressure.

PubMed

Tochikubo, Osamu; Nishijima, Kiyoko

2004-06-01

We have previously reported that a high sodium intake increases sleep-time blood pressure (BP) in young men. However, there are cases in which this relation does not apply. To account for them, we investigated the relation between sodium intake and cardiac sympatho-vagal balance (SVB) in young men with high BP. Sodium intake was estimated from the amount of urinary sodium excretion over 1 week. Twenty-four-hour (24-h) urinary sodium excretion (Salt24), 24-h ambulatory BP and ECG were obtained on the last day of the observation period. As an index of sodium intake, the expression In(Salt24/Cr24) (Cr24, 24-h urinary creatinine excretion) was used. From power-spectral analysis of ECG-RR intervals during sleep, we obtained the LF/HF ratio between the low-frequency component (LF) and the high frequency component (HF) and used it as an index of SVB. The subjects were male medical students divided into a normal BP group (N-group; n=103) and a high BP group (H-group; n=26, 24-h BP>125/75 mmHg). Mean In(Salt24/Cr24) and LF/HF in the H-group were significantly higher than those in the N-group (LF/HF: 1.86+/-0.44 [SD] vs. 1.37+/-0.30, p<0.001). The calculated discriminant function (D) for the H-group and N-group was D=1.6x + 5y - 11, where x is In(Salt24/Cr24) and y is LF/HF. This formula (D) resulted in high discriminant predictive accuracy (82%) between the groups. If D=0 (the value of the cut-off line determining separation of the groups), the relation y=-0.32x + 2.2 (negative relation between y and x) was obtained. These results suggest that excessive sodium intake in combination with accentuated SVB (LF/HF) increases BP in young men.

A New Cuffless Device for Measuring Blood Pressure: A Real-Life Validation Study.

PubMed

Schoot, Tessa S; Weenk, Mariska; van de Belt, Tom H; Engelen, Lucien J L P G; van Goor, Harry; Bredie, Sebastian J H

2016-05-05

Cuffless blood pressure (BP) monitoring devices, based on pulse transit time, are being developed as an easy-to-use, more convenient, fast, and relatively cheap alternative to conventional BP measuring devices based on cuff occlusion. Thereby they may provide a great alternative to BP self-measurement. The objective of our study was to evaluate the performance of the first release of the Checkme Health Monitor (Viatom Technology), a cuffless BP monitor, in a real-life setting. Furthermore, we wanted to investigate whether the posture of the volunteer and the position of the device relative to the heart level would influence its outcomes. Study volunteers fell into 3 BP ranges: high (>160 mmHg), normal (130-160 mmHg), and low (<130 mmHg). All requirements for test environment, observer qualification, volunteer recruitment, and BP measurements were met according to the European Society of Hypertension International Protocol (ESH-IP) for the validation of BP measurement devices. After calibrating the Checkme device, we measured systolic BP with Checkme and a validated, oscillometric reference BP monitor (RM). Measurements were performed in randomized order both in supine and in sitting position, and with Checkme at and above heart level. We recruited 52 volunteers, of whom we excluded 15 (12 due to calibration failure with Checkme, 3 due to a variety of reasons). The remaining 37 volunteers were divided into low (n=14), medium (n=13), and high (n=10) BP ranges. There were 18 men and 19 women, with a mean age of 54.1 (SD 14.5) years, and mean recruitment systolic BP of 141.7 (SD 24.7) mmHg. BP results obtained by RM and Checkme correlated well. In the supine position, the difference between the RM and Checkme was >5 mmHg in 17 of 37 volunteers (46%), of whom 9 of 37 (24%) had a difference >10 mmHg and 5 of 37 (14%) had a difference >15 mmHg. BP obtained with Checkme correlated well with RM BP, particularly in the position (supine) in which the device was calibrated. These preliminary results are promising for conducting further research on cuffless BP measurement in the clinical and outpatient settings.

3-Bromopyruvate: targets and outcomes.

PubMed

Shoshan, Maria C

2012-02-01

The pyruvate mimetic 3-bromopyruvate (3-BP) is generally presented as an inhibitor of glycolysis and has shown remarkable efficacy in not only preventing tumor growth, but even eradicating existant tumors in animal studies. We here review reported molecular targets of 3-BP and suggest that the very range of possible targets, which pertain to the altered energy metabolism of tumor cells, contributes both to the efficacy and the tumor specificity of the drug. Its in vivo efficacy is suggested to be due to a combination of glycolytic and mitochondrial targets, as well as to secondary effects affecting the tumor microenvironment. The cytotoxicity of 3-BP is less due to pyruvate mimicry than to alkylation of, e.g., key thiols. Alkylation of DNA/RNA has not been reported. More research is warranted to better understand the pharmacokinetics of 3-BP, and its potential toxic effects to normal cells, in particular those that are highly ATP-/mitochondrion-dependent.

High Prevalence of Hypertension in a Danish Population Telemedical Home Measurement of Blood Pressure in Citizens Aged 55–64 Years in Holstebro County

PubMed Central

Lauritzen, Torsten; Bech, Jesper Nørgaard; Pedersen, Erling Bjerregaard

2016-01-01

BACKGROUND Home blood pressure (HBP) is prognostically superior to office BP (OBP) and similar to ambulatory BP measurements. We determined the prevalence of hypertension using HBP with telemedical data transmission in the municipality of Holstebro, Denmark (57,000 citizens). METHODS Using the Civil Registration System, we invited citizens aged 55–64 years to have their OBP and HBP measured using telemedical data transmission. Elevated OBP was defined as ≥140/90mm Hg. HBP was measured 3 times daily on 3 consecutive days with 3 measurements on each occasion. HBP was the mean of all measurements on day 1 and 3, and hypertension was defined as ≥135/85mm Hg. RESULTS We included 3,102 citizens who had performed at least 12 HBP measurements during day 2 and 3. Group 1: (n = 1,464, 47%) had both normal OBP and HBP. Group 2: (n = 838, 27%) had both elevated OBP and HBP indicating persistent hypertension. Group 3: (n = 560, 18%) had elevated OBP and normal HBP indicating white coat hypertension (WCH). Group 4: (n = 240, 8%) had normal OBP and elevated HBP indicating masked hypertension (MH). Thus, 1,078 (35%, groups 2 and 4) were untreated or insufficiently treated. Awareness of hypertension was registered in 950 patients (31%) and of these 49% had a normal HBP. CONCLUSIONS This is the first large-scale study to eliminate completely reporting bias by using telemedical transmission of BP data. One third of citizens in the age group 55–64 years had an abnormally high HBP, and one fourth either had WCH or MH. CLINICAL TRIALS REGISTRATION ClinicalTrials.gov identification number: NCT02355392 PMID:26208671

High Prevalence of Hypertension in a Danish Population Telemedical Home Measurement of Blood Pressure in Citizens Aged 55-64 Years in Holstebro County.

PubMed

Hoffmann-Petersen, Nikolai; Lauritzen, Torsten; Bech, Jesper Nørgaard; Pedersen, Erling Bjerregaard

2016-04-01

Home blood pressure (HBP) is prognostically superior to office BP (OBP) and similar to ambulatory BP measurements. We determined the prevalence of hypertension using HBP with telemedical data transmission in the municipality of Holstebro, Denmark (57,000 citizens). Using the Civil Registration System, we invited citizens aged 55-64 years to have their OBP and HBP measured using telemedical data transmission. Elevated OBP was defined as ≥140/90mm Hg. HBP was measured 3 times daily on 3 consecutive days with 3 measurements on each occasion. HBP was the mean of all measurements on day 1 and 3, and hypertension was defined as ≥135/85mm Hg. We included 3,102 citizens who had performed at least 12 HBP measurements during day 2 and 3. Group 1: (n = 1,464, 47%) had both normal OBP and HBP. Group 2: (n = 838, 27%) had both elevated OBP and HBP indicating persistent hypertension. Group 3: (n = 560, 18%) had elevated OBP and normal HBP indicating white coat hypertension (WCH). Group 4: (n = 240, 8%) had normal OBP and elevated HBP indicating masked hypertension (MH). Thus, 1,078 (35%, groups 2 and 4) were untreated or insufficiently treated. Awareness of hypertension was registered in 950 patients (31%) and of these 49% had a normal HBP. This is the first large-scale study to eliminate completely reporting bias by using telemedical transmission of BP data. One third of citizens in the age group 55-64 years had an abnormally high HBP, and one fourth either had WCH or MH. ClinicalTrials.gov identification number: NCT02355392. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Elevated Blood Pressure and Obesity in Childhood: A Cross-Sectional Evaluation of 4,609 Schoolchildren

PubMed Central

Rosaneli, Caroline Filla; Baena, Cristina Pellegrio; Auler, Flavia; Nakashima, Alika Terumi Arasaki; Netto-Oliveira, Edna Regina; Oliveira, Amauri Bássoli; Guarita-Souza, Luiz César; Olandoski, Marcia; Faria-Neto, José Rocha

2014-01-01

Background: The incidence of obesity in children is increasing worldwide, primarily in urbanized, high-income countries, and hypertension development is a detrimental effect of this phenomenon. Objective: In this cross-sectional study, we evaluated the prevalence of excess weight and its association with high blood pressure (BP) in schoolchildren. Methods: Here 4,609 male and female children, aged 6 to 11 years, from 24 public and private schools in Maringa, Brazil, were evaluated. Nutritional status was assessed by body mass index (BMI) according to cutoff points adjusted for sex and age. Blood pressure (BP) levels above 90th percentile for gender, age and height percentile were considered elevated. Results: The prevalence of excess weight among the schoolchildren was 24.5%; 16.9% were overweight, and 7.6% were obese. Sex and socioeconomic characteristics were not associated with elevated BP. In all age groups, systolic and diastolic BP correlated with BMI and waist and hip measurements, but not with waist-hip ratio. The prevalence of elevated BP was 11.2% in eutrophic children, 20.6% in overweight children [odds ratio (OR), 1.99; 95% confidence interval (CI), 1.61-2.45], and 39.7% in obese children (OR, 5.4; 95% CI, 4.23-6.89). Conclusion: Obese and overweight children had a higher prevalence of elevated BP than normal-weight children. Our data confirm that the growing worldwide epidemic of excess weight and elevated BP in schoolchildren may also be ongoing in Brazil. PMID:25076178

Elevated blood pressure and obesity in childhood: a cross-sectional evaluation of 4,609 schoolchildren.

PubMed

Rosaneli, Caroline Filla; Baena, Cristina Pellegrio; Auler, Flavia; Nakashima, Alika Terumi Arasaki; Netto-Oliveira, Edna Regina; Oliveira, Amauri Bássoli; Guarita-Souza, Luiz César; Olandoski, Marcia; Faria-Neto, José Rocha

2014-09-01

The incidence of obesity in children is increasing worldwide, primarily in urbanized, high-income countries, and hypertension development is a detrimental effect of this phenomenon. In this cross-sectional study, we evaluated the prevalence of excess weight and its association with high blood pressure (BP) in schoolchildren. Here 4,609 male and female children, aged 6 to 11 years, from 24 public and private schools in Maringa, Brazil, were evaluated. Nutritional status was assessed by body mass index (BMI) according to cutoff points adjusted for sex and age. Blood pressure (BP) levels above 90th percentile for gender, age and height percentile were considered elevated. The prevalence of excess weight among the schoolchildren was 24.5%; 16.9% were overweight, and 7.6% were obese. Sex and socioeconomic characteristics were not associated with elevated BP. In all age groups, systolic and diastolic BP correlated with BMI and waist and hip measurements, but not with waist-hip ratio. The prevalence of elevated BP was 11.2% in eutrophic children, 20.6% in overweight children [odds ratio (OR), 1.99; 95% confidence interval (CI), 1.61-2.45], and 39.7% in obese children (OR, 5.4; 95% CI, 4.23-6.89). Obese and overweight children had a higher prevalence of elevated BP than normal-weight children. Our data confirm that the growing worldwide epidemic of excess weight and elevated BP in schoolchildren may also be ongoing in Brazil.

A translational study "case report" on the small molecule "energy blocker" 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside.

PubMed

Ko, Y H; Verhoeven, H A; Lee, M J; Corbin, D J; Vogl, T J; Pedersen, P L

2012-02-01

The small alkylating molecule, 3-bromopyruvate (3BP), is a potent and specific anticancer agent. 3BP is different in its action from most currently available chemo-drugs. Thus, 3BP targets cancer cells' energy metabolism, both its high glycolysis ("Warburg Effect") and mitochondrial oxidative phosphorylation. This inhibits/ blocks total energy production leading to a depletion of energy reserves. Moreover, 3BP as an "Energy Blocker", is very rapid in killing such cells. This is in sharp contrast to most commonly used anticancer agents that usually take longer to show a noticeable effect. In addition, 3BP at its effective concentrations that kill cancer cells has little or no effect on normal cells. Therefore, 3BP can be considered a member, perhaps one of the first, of a new class of anticancer agents. Following 3BP's discovery as a novel anticancer agent in vitro in the Year 2000 (Published in Ko et al. Can Lett 173:83-91, 2001), and also as a highly effective and rapid anticancer agent in vivo shortly thereafter (Ko et al. Biochem Biophys Res Commun 324:269-275, 2004), its efficacy as a potent anticancer agent in humans was demonstrated. Here, based on translational research, we report results of a case study in a young adult cancer patient with fibrolamellar hepatocellular carcinoma. Thus, a bench side discovery in the Department of Biological Chemistry at Johns Hopkins University, School of Medicine was taken effectively to bedside treatment at Johann Wolfgang Goethe University Frankfurt/Main Hospital, Germany. The results obtained hold promise for 3BP as a future cancer therapeutic without apparent cyto-toxicity when formulated properly.

The impact of non-dipper circadian rhythm of blood pressure on left ventricular hypertrophy in patients with non-dialysis chronic kidney disease.

PubMed

Che, Xiajing; Mou, Shan; Zhang, Weiming; Zhang, Minfang; Gu, Leyi; Yan, Yucheng; Ying, Hua; Hu, Chunhua; Qian, Jiaqi; Ni, Zhaohui

2017-04-01

Objective The aim of this study was to investigate the correlation between non-dipper circadian rhythm of blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). Methods and results All 257 patients with stage 1 to 5 CKD were enrolled in the study and classified into a CKD1-3 group and a CKD4-5 group according to renal function. The parameters and circadian rhythm of BP were measured by a GE Marquette Tonoport V Eng dynamic sphygmomanometer, and cardiac structure was examined by echocardiography. The incidence of abnormal circadian BP rhythm (non-dipper rhythm) was quite high (75.4% in all enrolled patients and 71.3% in the patients with normal BP levels) in CKD patients and increased with the deterioration of renal function. Changes of cardiac structure such as LVH in patients with non-dipper BP were more distinct than in patients with dipper BP. The development of left ventricular mass index (LVMI) correlated positively with the incidence of non-dipper BP rhythm. Multiple regression analysis showed that 24-h systolic BP (β = 0.417, P < 0.01), triglycerides (TG) (β = -0.132, P = 0.007), Hb (β = -0.394, P = 0.016) and gender (β = 0.158, P = 0.039) were independent risk factors of LVMI. Conclusions The incidence of non-dipper circadian rhythm of blood pressure was quite high in CKD patients and increased with the deterioration of renal function. Non-dipper circadian rhythm of BP is closely related with LVMI.

Knowledge of hypertension and its management among hypertensive patients on chronic medicines at primary health care public sector facilities in South Africa; findings and implications.

PubMed

Rampamba, Enos M; Meyer, Johanna C; Helberg, Elvera; Godman, Brian

2017-08-01

There are high growing prevalence rates of hypertension in South Africa. Consequently, there is a need to assess knowledge and management among hypertensive patients receiving chronic medication from primary health care (PHC) facilities in South Africa as a basis for improving future management. This is important as South Africa seeks to improve its management of chronic diseases. Descriptive, quantitative study amongst chronic hypertensive patients in the chronic disease programme. Patients were interviewed face-to-face by trained pharmacists using a structured questionnaire. Data analysis included descriptive and inferential statistics. Half (53.7%) of the patients had uncontrolled blood pressure (BP). Less than a third of patients (27.7%) knew what hypertension is, the meaning of recorded BP numbers (4.5%), and what normal BP should be (19.9%). All patients who knew the meaning of BP numbers had formal education (p = 0.047). Only 15.6% of the 56.0% patients, who received hypertension information, received it on antihypertensive medicines specifically. The majority of the patients lacked hypertension specific knowledge and only half had controlled BP. Interventions to improve the control of high BP should be targeted at closing knowledge gaps as part of the current chronic treatment initiatives in South Africa to ensure the benefits of increased access to care are realized.

Transport of 3-bromopyruvate across the human erythrocyte membrane.

PubMed

Sadowska-Bartosz, Izabela; Soszyński, Mirosław; Ułaszewski, Stanisław; Ko, Young; Bartosz, Grzegorz

2014-06-01

3-Bromopyruvic acid (3-BP) is a promising anticancer compound because it is a strong inhibitor of glycolytic enzymes, especially glyceraldehyde 3-phosphate dehydrogenase. The Warburg effect means that malignant cells are much more dependent on glycolysis than normal cells. Potential complications of anticancer therapy with 3-BP are side effects due to its interaction with normal cells, especially erythrocytes. Transport into cells is critical for 3-BP to have intracellular effects. The aim of our study was the kinetic characterization of 3-BP transport into human erythrocytes. 3-BP uptake by erythrocytes was linear within the first 3 min and pH-dependent. The transport rate decreased with increasing pH in the range of 6.0-8.0. The Km and Vm values for 3-BP transport were 0.89 mM and 0.94 mmol/(l cells x min), respectively. The transport was inhibited competitively by pyruvate and significantly inhibited by DIDS, SITS, and 1-cyano-4-hydroxycinnamic acid. Flavonoids also inhibited 3-BP transport: the most potent inhibition was found for luteolin and quercetin.

The energy blockers 3-bromopyruvate and lonidamine: effects on bioenergetics of brain mitochondria.

PubMed

Macchioni, Lara; Davidescu, Magdalena; Roberti, Rita; Corazzi, Lanfranco

2014-10-01

Tumor cells favor abnormal energy production via aerobic glycolysis and show resistance to apoptosis, suggesting the involvement of mitochondrial dysfunction. The differences between normal and cancer cells in their energy metabolism provide a biochemical basis for developing new therapeutic strategies. The energy blocker 3-bromopyruvate (3BP) can eradicate liver cancer in animals without associated toxicity, and is a potent anticancer towards glioblastoma cells. Since mitochondria are 3BP targets, in this work the effects of 3BP on the bioenergetics of normal rat brain mitochondria were investigated in vitro, in comparison with the anticancer agent lonidamine (LND). Whereas LND impaired oxygen consumption dependent on any complex of the respiratory chain, 3BP was inhibitory to malate/pyruvate and succinate (Complexes I and II), but preserved respiration from glycerol-3-phosphate and ascorbate (Complex IV). Accordingly, although electron flow along the respiratory chain and ATP levels were decreased by 3BP in malate/pyruvate- and succinate-fed mitochondria, they were not significantly influenced from glycerol-3-phosphate- or ascorbate-fed mitochondria. LND produced a decrease in electron flow from all substrates tested. No ROS were produced from any substrate, with the exception of 3BP-induced H(2)O(2) release from succinate, which suggests an antimycin-like action of 3BP as an inhibitor of Complex III. We can conclude that 3BP does not abolish completely respiration and ATP synthesis in brain mitochondria, and has a limited effect on ROS production, confirming that this drug may have limited harmful effects on normal cells.

Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans.

PubMed

Diaz, K M; Veerabhadrappa, P; Kashem, M A; Thakkar, S R; Feairheller, D L; Sturgeon, K M; Ling, C; Williamson, S T; Kretzschmar, J; Lee, H; Grimm, H; Babbitt, D M; Vin, C; Fan, X; Crabbe, D L; Brown, M D

2013-11-01

The purpose of this study was to investigate the association of visit-to-visit and 24-h blood pressure (BP) variability with markers of endothelial injury and vascular function. We recruited 72 African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. Office BP was measured at three visits and 24-h ambulatory BP monitoring was conducted to measure visit-to-visit and 24-h BP variability, respectively. The 5-min time-course of brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were assessed as measures of endothelial and smooth muscle function. Fasted blood samples were analyzed for circulating endothelial microparticles (EMPs). Significantly lower CD31+CD42- EMPs were found in participants with high visit-to-visit systolic blood pressure (SBP) variability or high 24-h diastolic blood pressure (DBP) variability. Participants with high visit-to-visit DBP variability had significantly lower flow-mediated dilation and higher nitroglycerin-mediated dilation at multiple time-points. When analyzed as continuous variables, 24-h mean arterial pressure variability was inversely associated with CD62+ EMPs; visit-to-visit DBP variability was inversely associated with flow-mediated dilation normalized by smooth muscle function and was positively associated with nitroglycerin-mediated dilation; and 24-h DBP variability was positively associated with nitroglycerin-mediated dilation. All associations were independent of age, gender, body mass index and mean BP. In conclusion, in this cohort of African Americans visit-to-visit and 24-h BP variability were associated with measures of endothelial injury, endothelial function and smooth muscle function. These results suggest that BP variability may influence the pathogenesis of CV disease, in part, through influences on vascular health.

Symmetric ambulatory arterial stiffness index and 24-h pulse pressure in HIV infection: results of a nationwide cross-sectional study.

PubMed

Schillaci, Giuseppe; Maggi, Paolo; Madeddu, Giordano; Pucci, Giacomo; Mazzotta, Elena; Penco, Giovanni; Orofino, Giancarlo; Menzaghi, Barbara; Rusconi, Stefano; Carenzi, Laura; Celesia, Benedetto M; Martinelli, Canio; Bonfanti, Paolo; De Socio, Giuseppe Vittorio

2013-03-01

HIV infection has been associated with increased cardiovascular risk. Twenty-four-hour ambulatory blood pressure (BP) is a more accurate and prognostically relevant measure of an individual's BP load than office BP, and the ambulatory BP-derived ambulatory arterial stiffness index (AASI) and symmetric AASI (s-AASI) are established cardiovascular risk factors. In the setting of the HIV and HYpertension (HIV-HY) study, an Italian nationwide survey on high BP in HIV infection, 100 HIV-infected patients with high-normal BP or untreated hypertension (72% men, age 48 ± 10 years, BP 142/91 ± 12/7 mmHg) and 325 HIV-negative individuals with comparable age, sex distribution, and office BP (68% men, age 48 ± 10 years, BP 141/90 ± 11/8 mmHg) underwent 24-h ambulatory BP monitoring. Despite having similar office BP, HIV-infected individuals had higher 24-h SBP (130.6 ± 14 vs. 126.4 ± 10 mmHg) and pulse pressure (49.1 ± 9 vs. 45.9 ± 7 mmHg, both P < 0.001), and a lower day-night reduction of mean arterial pressure (14.3 ± 9 vs. 16.3 ± 7%, P = 0.025). Both s-AASI and AASI were significantly higher in HIV patients (s-AASI, 0.22 ± 0.18 vs. 0.11 ± 0.15; AASI, 0.46 ± 0.22 vs. 0.29 ± 0.17; both P <0.001). In a multivariate regression, s-AASI was independently predicted by HIV infection (β = 0.252, P <0.001), age, female sex, and 24-h SBP. In HIV patients, s-AASI had an inverse relation with CD4 cell count (Spearman's ρ -0.24, P = 0.027). Individuals with HIV infection and borderline or definite hypertension have higher symmetric AASI and 24-h systolic and pulse pressures than HIV-uninfected controls matched by office BP. High ambulatory BP may play a role in the HIV-related increase in cardiovascular risk.

Relationship of Office and Ambulatory Blood Pressure With Left Ventricular Global Longitudinal Strain.

PubMed

Sera, Fusako; Jin, Zhezhen; Russo, Cesare; Lee, Edward S; Schwartz, Joseph E; Rundek, Tatjana; Elkind, Mitchell S V; Homma, Shunichi; Sacco, Ralph L; Di Tullio, Marco R

2016-11-01

Left ventricular (LV) global longitudinal strain (GLS) is an early indicator of subclinical cardiac dysfunction, even when LV ejection fraction (LVEF) is normal, and is an independent predictor of cardiovascular events. Ambulatory blood pressure (BP) is a better predictor of cardiovascular events, including heart failure, than office BP. We investigated the association of office and ambulatory BP measurements with subclinical LV systolic dysfunction in a community-based cohort with normal LVEF. Two-dimensional speckle-tracking echocardiography and 24-hour ambulatory BP monitoring were performed in 577 participants (mean age 70±9 years; 60% women) with LVEF ≥50% from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. Univariable and multivariable linear regression analyses were used to assess the associations of BP measures with GLS. Higher ambulatory and office BP values were consistently associated with impaired GLS. After adjustment for pertinent covariates (age, sex, race/ethnicity, body mass index, diabetes mellitus, coronary artery disease, LV mass index, and antihypertensive medication), office diastolic BP and ambulatory systolic and diastolic BPs (24-hour, daytime and nighttime) were independently associated with GLS (P = 0.003 for office DBP, P ≤ 0.001 for all ambulatory BPs). When ambulatory and office BP values were included in the same model, all ambulatory BP measures remained significantly associated with GLS (all P < 0.01), whereas office BP values were not. Ambulatory BP values are significantly associated with impaired GLS and the association is stronger than for office BP. Ambulatory BP monitoring might have a role in the risk stratification of hypertensive patients for early LV dysfunction.

Longitudinal cognitive trajectories and associated clinical variables in youth with bipolar disorder.

PubMed

Frías, Álvaro; Dickstein, Daniel P; Merranko, John; Gill, Mary Kay; Goldstein, Tina R; Goldstein, Benjamin I; Hower, Heather; Yen, Shirley; Hafeman, Danella M; Liao, Fangzi; Diler, Rasim; Axelson, David; Strober, Michael; Hunt, Jeffrey I; Ryan, Neal D; Keller, Martin B; Birmaher, Boris

2017-06-01

There is substantial interest in delineating the course of cognitive functioning in bipolar (BP) youth. However, there are no longitudinal studies aimed at defining subgroups of BP youth based on their distinctive cognitive trajectories and their associated clinical variables. Cognitive functioning was measured in 135 participants from the Course and Outcome of BP Youth (COBY) study using several subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Youth were prospectively evaluated three times on average every 13.75 months over 2.5 years. Clinical and functional outcomes were assessed using the Longitudinal Interval Follow-Up Evaluation (LIFE). Latent class growth analysis identified three longitudinal patterns of cognitive functioning based on a general cognitive index: class 1, "persistently high" (N=21; 15.6%); class 2, "persistently moderate" (N=82; 60.74%); and class 3, "persistently low" (N=32; 23.7%). All classes showed normal cognitive functioning when compared with the CANTAB normative data. After adjustment for confounders, youth from class 3 had a significantly greater percentage of time with overall, manic, and depressive syndromal symptoms than youth in the other two classes. Also, after adjustment for confounders, youth from class 3 had significantly poorer global, academic, and social functioning than youth from class 1. BP youth showed normal overall cognitive functioning that remained stable during the follow-up within each class. However, 24% of BP youth showed poorer cognitive functioning than the other BP youth. This subgroup had poorer mood course and functioning, and may benefit from cognitive remediation and early management with evidence-based pharmacological treatments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sources of Dietary Protein in Relation to Blood Pressure in a General Dutch Population

PubMed Central

Altorf - van der Kuil, Wieke; Engberink, Mariëlle F.; Vedder, Moniek M.; Boer, Jolanda M. A.; Verschuren, W. M. Monique; Geleijnse, Johanna M.

2012-01-01

Background Little is known about the relation of different dietary protein types with blood pressure (BP). We examined whether intake of total, plant, animal, dairy, meat, and grain protein was related to BP in a cross sectional cohort of 20,820 Dutch adults, aged 20–65 y and not using antihypertensive medication. Design Mean BP levels were calculated in quintiles of energy-adjusted protein with adjustment for age, sex, BMI, education, smoking, and intake of energy, alcohol, and other nutrients including protein from other sources. In addition, mean BP difference after substitution of 3 en% carbohydrates or MUFA with protein was calculated. Results Total protein and animal protein were not associated with BP (ptrend = 0.62 and 0.71 respectively), both at the expense of carbohydrates and MUFA. Systolic BP was 1.8 mmHg lower (ptrend<0.01) in the highest (>36 g/d) than in the lowest (<27 g/d) quintile of plant protein. This inverse association was present both at the expense of carbohydrates and MUFA and more pronounced in individuals with untreated hypertension (−3.6 mmHg) than in those with normal (+0.1 mmHg) or prehypertensive BP (−0.3 mmHg; pinteraction<0.01). Meat and grain protein were not related to BP. Dairy protein was directly associated with systolic BP (+1.6 mmHg, ptrend<0.01), but not with diastolic BP (ptrend = 0.24). Conclusions Total protein and animal protein were not associated with BP in this general untreated Dutch population. Plant protein may be beneficial to BP, especially in people with elevated BP. However, because high intake of plant protein may be a marker of a healthy diet and lifestyle in general, confirmation from randomized controlled trials is warranted. PMID:22347387

Risks for Hypertension among Undiagnosed African American Mothers and Daughters

PubMed Central

Taylor, Jacquelyn Y.

2009-01-01

Introduction This study examines risks for high blood pressure (BP) among undiagnosed African American (AA) mothers and daughters, because AA children are at risk for hypertension due to familial influences. Method This study was cross-sectional in design and included 70 AA mother and daughter participants from the Detroit metropolitan area. Results BP readings clinically diagnostic of hypertension were found for mothers (25.7%) and daughters (54.3%), although they were undiagnosed. Many participants with BP readings in pre-hypertension or hypertension categories were overweight or obese (mothers, 90.9%; daughters, 50.2%). Fewer underweight or normal weight mothers (25.0%) and daughters (64.3%) had BP readings indicative of hypertension. Lower diastolic BP was associated with higher body mass index (BMI) among mothers (r = −.34, p = .045). Higher systolic blood pressure was positively related to potassium consumption among daughters and total AAs (r = .55, p = .005 and r = .41, p = .003 respectively). Discussion Early screening for hypertension is needed to improve health among AAs. Health providers should use American Academy of Pediatrics (AAP) guidelines for determining hypertension in children. Research on familial and environment influences on BP among children is recommended to determine early risk for hypertension development. PMID:19875025

Assessing Specific Oligonucleotides and Small Molecule Antibiotics for the Ability to Inhibit the CRD-BP-CD44 RNA Interaction

PubMed Central

Thomsen, Dana; Lee, Chow H.

2014-01-01

Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3′UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862–3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862–3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions. PMID:24622399

Assessing specific oligonucleotides and small molecule antibiotics for the ability to inhibit the CRD-BP-CD44 RNA interaction.

PubMed

King, Dustin T; Barnes, Mark; Thomsen, Dana; Lee, Chow H

2014-01-01

Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3'UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862-3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862-3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions.

A study of the CCG polymorphism in the IT15 cDNA in the Scottish Huntington`s disease and normal populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barron, L.H.; Rae, A.; Brock, D.J.H.

1994-09-01

The CCG rich sequence immediately 3{prime} to the CAG repeat that is expanded in Huntington`s disease (HD) has recently been shown to be polymorphic with at least 5 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 200 Scottish HD families and have found very strong evidence for almost complete disequilibrium in this population. For all the families phase was unambiguously determined and 196 were shown to have a CCG repeat allele of 176 bp cosegregating with the HD chromosome. This observation is significantly different to the normal populationmore » distribution where 31% of people have an allele of 185 bp. This overrepresentation of the 176 bp allele is also seen in the normal population on chromosomes with greater than 26 CAG repeats. The DNA sequence across the CAG and CCG repeats has been obtained for the four HD patients that do not have a 176 bp CCG repeat size and will be presented. We present strong evidence of genetic heterogeneity in the Scottish HD population making it very unlikely that there is a founder effect in the Scottish HD population. These data suggest that we may have identified a region of the IT15 gene that is critical in the mechanism of Huntington`s disease CAG expansion.« less

Body fat and blood pressure: comparison of blood pressure measurements in Chinese children with different body fat levels.

PubMed

Ma, Jun; Wang, Zhiqiang; Dong, Bin; Song, Yi; Hu, Peijin; Zhang, Bing

2012-11-14

Children in China are experiencing a rapid increase in the prevalence of obesity, which is associated with hypertension. To compare the effect of body fat on blood pressure (BP) with that of the normal physical growth, we compared BP levels in Chinese children with different body fat levels. In the present population-based study, 13 972 children in the highest-skinfold-thickness-quartile group were individually matched to 13 972 children in the lowest-skinfold-thickness-quartile group by height and weight. Similarly, 5103 children in the highest-waist-circumference-quartile group were matched to the same number of children in the lowest-waist-circumference-quartile group. The high- and low-fat groups had similar height and weight but the high-fat group had significantly higher skinfold and waist circumference measurements. The differences in systolic BP (SBP) between the high- and low-skinfold-thickness groups were small: 0·01 (95 % CI -0·41, 0·44) mmHg in boys and 0·20 (95 % CI -0·15, 0·54) mmHg in girls. The differences in diastolic BP (DBP) were also small (0·39 and 0·38 mmHg for boys and girls, respectively) but were statistically significant. The differences in both SBP and DBP between the high- and low-waist-circumference groups were small but not statistically significant. For a given body size as measured by height and weight, relative body fat had little impact on BP levels in these children. Fat mass and lean mass may have a similar quantitative impact on BP in healthy-weight children.

Baroreflex Sensitivity Decreases During 90-Day Bed Rest

NASA Technical Reports Server (NTRS)

Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

2008-01-01

Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

Temperament and character profiles in bipolar I, bipolar II and major depressive disorder: Impact over illness course, comorbidity pattern and psychopathological features of depression.

PubMed

Zaninotto, Leonardo; Souery, Daniel; Calati, Raffaella; Di Nicola, Marco; Montgomery, Stuart; Kasper, Siegfried; Zohar, Joseph; Mendlewicz, Julien; Robert Cloninger, C; Serretti, Alessandro; Janiri, Luigi

2015-09-15

Studies comparing temperament and character traits between patients with mood disorders and healthy individuals have yielded variable results. The Temperament and Character Inventory (TCI) was administered to 101 bipolar I (BP-I), 96 bipolar II (BP-II), 123 major depressive disorder (MDD) patients, and 125 HS. A series of generalized linear models were performed in order to: (a) compare the TCI dimensions across groups; (b) test any effect of the TCI dimensions on clinical features of mood disorders; and (c) detect any association between TCI dimensions and the psychopathological features of a major depressive episode. Demographic and clinical variables were also included in the models as independent variables. Higher Harm Avoidance was found in BP-II and MDD, but not in BP-I. Higher Self-Transcendence was found in BP-I. Our models also showed higher Self-Directedness in HS, either vs MDD or BP-II. No association was found between any TCI dimension and the severity of symptoms. Conversely, a positive association was found between Harm Avoidance and the overall burden of depressive episodes during lifetime. The cross-sectional design and the heterogeneity of the sample may be the main limitations of our study. In general, our sample seems to support the view of a similar profile of temperament and character between MDD and BP-II, characterized by high Harm Avoidance and low Self-Directedness. In contrast, patients with BP-I only exhibit high Self-Transcendence, having a near-normal profile in terms of Harm Avoidance or Self-Directedness. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of 1,25-dihydroxyvitamin D3 on plasma concentrations of calcium-binding protein in normal and rachitic (vitamin D-dependent rickets type I) pigs.

PubMed

Maunder, E M; Pillay, A V; Care, A D

1987-10-01

An i.v. injection of calcitriol (1,25-(OH)2D3) had no effect within 2.5 h on plasma concentrations of calbindin-D9K (vitamin D-induced calcium-binding protein; CaBP) in hypocalcaemic pigs with inherited vitamin D-dependent rickets type I or in their normocalcaemic siblings or half-siblings. Three days later the plasma concentration of CaBP had doubled in the hypocalcaemic pigs, but was unaltered in the normocalcaemic siblings and half-siblings. Following daily i.v. injections of 1,25-(OH)2D3 for a further 5 days (days 4-8) plasma concentrations of CaBP increased in both the hypocalcaemic (days 4-8) and normocalcaemic (day 8) pigs, the effect being more rapid and greater in the hypocalcaemic 1,25-(OH)2D3-deficient animals. An i.v. injection of 1,25-(OH)2D3 to pure Yucatan pigs also had no effect on plasma concentrations of CaBP within 1.5 h, but in the following 1 h there was some indication of an increase in plasma CaBP levels. In contrast to the normal pigs, insulin-induced hypoglycaemia did not lead to a peak in plasma CaBP concentrations in the hypocalcaemic pigs. There was also no change in the plasma concentrations of 1,25-(OH)2D3 associated with the peak in plasma CaBP following insulin-induced hypoglycaemia in normocalcaemic pigs. These results suggest that changes in plasma concentrations of 1,25-(OH)2D3 are not directly involved in mediating the increase in plasma CaBP which follows hypoglycaemia induced by insulin in normal pigs, although 1,25-(OH)2D3 probably plays a permissive role.

[2013 Ambulatory blood pressure monitoring recommendations for the diagnosis of adult hypertension, assessment of cardiovascular and other hypertension-associated risk, and attainment of therapeutic goals (summary). Joint recommendations from the International Society for Chronobiology (ISC), American Association of Medical Chronobiology and Chronotherapeutics (AAMCC), Spanish Society of Applied Chronobiology, Chronotherapy, and Vascular Risk (SECAC), Spanish Society of Atherosclerosis (SEA), and Romanian Society of Internal Medicine (RSIM)].

PubMed

Hermida, Ramón C; Smolensky, Michael H; Ayala, Diana E; Portaluppi, Francesco; Crespo, Juan J; Fabbian, Fabio; Haus, Erhard; Manfredini, Roberto; Mojón, Artemio; Moyá, Ana; Piñeiro, Luis; Ríos, María T; Otero, Alfonso; Balan, Horia; Fernández, José R

2013-01-01

Correlation between systolic (SBP) and diastolic (DBP) blood pressure (BP) level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is much greater for ambulatory BP monitoring (ABPM) than daytime office measurements. The 2013 ABPM guidelines specified herein are based on ABPM patient outcomes studies and constitute a substantial revision of current knowledge. The asleep SBP mean and sleep-time relative SBP decline are the most significant predictors of CVD events, both individually as well as jointly when combined with other ABPM-derived prognostic markers. Thus, they should be preferably used to diagnose hypertension and assess CVD and other associated risks. Progressive decrease by therapeutic intervention in the asleep BP mean is the most significant predictor of CVD event-free interval. The 24 h BP mean is not recommended to diagnose hypertension because it disregards the more valuable clinical information pertaining to the features of the 24 h BP pattern. Persons with the same 24 h BP mean may display radically different 24 h BP patterns, ranging from extreme-dipper to riser types, representative of markedly different risk states. Classification of individuals by comparing office with either the 24 h or awake BP mean as "masked normotensives" (elevated clinic BP but normal ABPM), which should replace the terms of "isolated office" or "white-coat hypertension", and "masked hypertensives" (normal clinic BP but elevated ABPM) is misleading and should be avoided because it disregards the clinical significance of the asleep BP mean. Outcome-based ABPM reference thresholds for men, which in the absence of compelling clinical conditions are 135/85 mmHg for the awake and 120/70 mmHg for the asleep SBP/DBP means, are lower by 10/5 mmHg for SBP/DBP in uncomplicated, low-CVD risk, women and lower by 15/10 mmHg for SBP/DBP in male and female high-risk patients, e.g., with diabetes, chronic kidney disease (CKD), and/or past CVD events. In the adult population, the combined prevalence of masked normotension and masked hypertension is >35%. Moreover, >20% of "normotensive" adults have a non-dipper BP profile and, thus, are at relatively high CVD risk. Clinic BP measurements, even if supplemented with home self-measurements, are unable to quantify 24 h BP patterning and asleep BP level, resulting in potential misclassification of up to 50% of all evaluated adults. ABPM should be viewed as the new gold standard to diagnose true hypertension, accurately assess consequent tissue/organ, maternal/fetal, and CVD risk, and individualize hypertension chronotherapy. ABPM should be a priority for persons likely to have a blunted nighttime BP decline and elevated CVD risk, i.e., those who are elderly and obese, those with secondary or resistant hypertension, and those diagnosed with diabetes, CKD, metabolic syndrome, and sleep disorders. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

Prevalence of hypertension and circadian blood pressure variations in patients with obstructive sleep apnoea-hypopnoea syndrome.

PubMed

Wang, Yan; Li, Caili; Feng, Liting; Feng, Jing; Cao, Jie; Chen, Baoyuan

2014-06-01

To investigate the prevalence of hypertension and circadian blood pressure (BP) variations in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Patients referred to a sleep clinic underwent polysomnography with measurement of BP at four time points. They were classified into four groups (control, and mild, moderate or severe sleep apnoea) using the apnoea-hypopnoea index (AHI). Circadian variation was assessed using night-time to daytime mean BP (R(N/D)) and morning to evening mean BP (R(M/E)) ratios. Hypertension was significantly more common in patients with OSAHS (50.5%) than in controls (30.4%). AHI was positively correlated with hypertension after controlling for related confounders. Mean BP values at all four time points rose with increasing AHI. The increase in night-time and morning values was more pronounced than the increase in daytime and evening values in patients with OSAHS, resulting in loss of the normal BP diurnal rhythm. The R(N/D) and R(M/E) ratios increased with increasing AHI. Daytime BP was significantly correlated with AHI and the lowest oxygen saturation value. OSAHS was shown to be an independent risk factor for hypertension. It was also associated with loss of the normal BP diurnal rhythm. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A New Cuffless Device for Measuring Blood Pressure: A Real-Life Validation Study

PubMed Central

Schoot, Tessa S; Weenk, Mariska; van de Belt, Tom H; Engelen, Lucien JLPG; van Goor, Harry

2016-01-01

Background Cuffless blood pressure (BP) monitoring devices, based on pulse transit time, are being developed as an easy-to-use, more convenient, fast, and relatively cheap alternative to conventional BP measuring devices based on cuff occlusion. Thereby they may provide a great alternative to BP self-measurement. Objective The objective of our study was to evaluate the performance of the first release of the Checkme Health Monitor (Viatom Technology), a cuffless BP monitor, in a real-life setting. Furthermore, we wanted to investigate whether the posture of the volunteer and the position of the device relative to the heart level would influence its outcomes. Methods Study volunteers fell into 3 BP ranges: high (>160 mmHg), normal (130–160 mmHg), and low (<130 mmHg). All requirements for test environment, observer qualification, volunteer recruitment, and BP measurements were met according to the European Society of Hypertension International Protocol (ESH-IP) for the validation of BP measurement devices. After calibrating the Checkme device, we measured systolic BP with Checkme and a validated, oscillometric reference BP monitor (RM). Measurements were performed in randomized order both in supine and in sitting position, and with Checkme at and above heart level. Results We recruited 52 volunteers, of whom we excluded 15 (12 due to calibration failure with Checkme, 3 due to a variety of reasons). The remaining 37 volunteers were divided into low (n=14), medium (n=13), and high (n=10) BP ranges. There were 18 men and 19 women, with a mean age of 54.1 (SD 14.5) years, and mean recruitment systolic BP of 141.7 (SD 24.7) mmHg. BP results obtained by RM and Checkme correlated well. In the supine position, the difference between the RM and Checkme was >5 mmHg in 17 of 37 volunteers (46%), of whom 9 of 37 (24%) had a difference >10 mmHg and 5 of 37 (14%) had a difference >15 mmHg. Conclusions BP obtained with Checkme correlated well with RM BP, particularly in the position (supine) in which the device was calibrated. These preliminary results are promising for conducting further research on cuffless BP measurement in the clinical and outpatient settings. PMID:27150527

Altered cardiovascular reactivity and osmoregulation during hyperosmotic stress in adult rats developmentally exposed to polybrominated diphenyl ethers (PBDEs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, Ashini; Coburn, Cary G.; Watson-Siriboe, Abena

2011-10-15

Polybrominated diphenyl ethers (PBDEs) and the structurally similar chemicals polychlorinated biphenyls (PCBs) disrupt the function of multiple endocrine systems. PCBs and PBDEs disrupt the secretion of vasopressin (VP) from the hypothalamus during osmotic activation. Since the peripheral and central vasopressinergic axes are critical for osmotic and cardiovascular regulation, we examined whether perinatal PBDE exposure could impact these functions during physiological activation. Rats were perinatally dosed with a commercial PBDE mixture, DE-71. Dams were given 0 (corn oil control), 1.7 (low dose) or 30.6 mg/kg/day (high dose) in corn oil from gestational day (GD) 6 through postnatal day (PND) 21 bymore » oral gavage. In the male offspring exposed to high dose PBDE plasma thyroxine and triiodothyronine levels were reduced at PND 21 and recovered to control levels by PND 60 when thyroid stimulating hormone levels were elevated. At 14-18 months of age, cardiovascular responses were measured in four groups of rats: Normal (Oil, normosmotic condition), Hyper (Oil, hyperosmotic stress), Hyper PBDE low (1.7 mg/kg/day DE-71 perinatally, hyperosmotic stress), and Hyper PBDE high (30.6 mg/kg/day DE-71 perinatally, hyperosmotic stress). Systolic blood pressure (BP), diastolic BP, and heart rate (HR) were determined using tail cuff sphygmomanometry and normalized to pretreatment values (baseline) measured under basal conditions. Hyperosmotic treatment yielded significant changes in systolic BP in PBDE exposed rats only. Hyper PBDE low and high dose rats showed 36.1 and 64.7% greater systolic BP responses at 3 h post hyperosmotic injection relative to pretreatment baseline, respectively. No treatment effects were measured for diastolic BP and HR. Hyper and Hyper PBDE rats showed increased mean plasma osmolality values by 45 min after injection relative to normosmotic controls. In contrast to Hyper rats, Hyper PBDE (high) rats showed a further increase in mean plasma osmolality at 3 h (358.3 {+-} 12.4 mOsm/L) relative to 45 min post hyperosmotic injection (325.1 {+-} 11.4 mOsm/L). Impaired osmoregulation in PBDE-treated animals could not be attributed to decreased levels of plasma vasopressin. Our findings suggest that developmental exposure to PBDEs may disrupt cardiovascular reactivity and osmoregulatory responses to physiological activation in late adulthood. - Highlights: > We examined whether PBDE exposure could impact osmotic and cardiovascular regulation. > Hyperosmotic treatment yielded significant changes in systolic BP in PBDE exposed rats only. > PBDEs may disrupt cardiovascular and osmoregulatory responses to physiological activation.« less

The Relation between Hot Flashes and Ambulatory Blood Pressure: The Hilo Women’s Health Study

PubMed Central

Brown, Daniel E.; Sievert, Lynnette L.; Morrison, Lynn A.; Rahberg, Nichole; Reza, Angela

2011-01-01

Objectives Hot flashes (HFs) have been associated with elevated blood pressure, but studies have not examined the relationship between objectively measured HFs and blood pressure during normal daily activities. The objectives of this study are to examine ambulatory blood pressure (BP) differences between women who report HFs and those who do not, and to observe whether an objectively measured HF is associated with transient changes in BP. Methods A sample of 202 women in Hilo, Hawaii aged 45–55 years were asked to fill out a questionnaire that included demographic information and an inventory of symptoms. The women underwent simultaneous 24-hour monitoring of ambulatory BP and HFs, while keeping a diary that included mood and HF reports. Results No significant difference was present in mean BP between women who reported having a HF during the past 2 weeks and those who did not. When measurements controlled for negative mood reports and posture, there was a highly significant elevation in Z scores of systolic BP when a measured, objective HF occurred within 10 minutes preceding a BP reading, and a significant elevation of Z scores of diastolic BP when a subjectively reported HF occurred within 10 minutes after a BP reading. Conclusions These results suggest that objectively measured HFs precede transient elevations of systolic BP, but it is unclear if there is a causal relationship. These results also suggest that women experience subjective HFs within 10 minutes after a transient increase in diastolic BP. Again, the causal relationship is not understood. PMID:21183716

RAAS polymorphisms alter the acute blood pressure response to aerobic exercise among men with hypertension.

PubMed

Blanchard, Bruce E; Tsongalis, Gregory J; Guidry, Margaux A; LaBelle, Lisa A; Poulin, Michelle; Taylor, Amy L; Maresh, Carl M; Devaney, Joseph; Thompson, Paul D; Pescatello, Linda S

2006-05-01

Limited evidence suggests renin-angiotensin-aldosterone system (RAAS) polymorphisms alter the blood pressure (BP) response to aerobic exercise training. We examined if RAAS polymorphisms influenced postexercise hypotension in men with high normal to Stage 1 hypertension. Forty-seven men (44.2+/-1.4 years, 145.1+/-1.6/85.5+/-1.1 mmHg) randomly completed three experiments: seated rest (control) and two cycle exercise bouts at 40% (LITE) and 60% (MOD) of maximal oxygen consumption. Ambulating BP was measured for 14 h after each experiment. RAAS polymorphisms associated with hypertension (i.e. angiotensin converting I enzyme, ACE I/D; angiotensin II type 1 receptor, AT1R A/C; and intron 2 of aldosterone synthase, Int2 W/C) were analyzed using polymerase chain reaction and restriction enzyme digestion. Repeated measure ANOVA tested if BP differed between experimental conditions by RAAS genotypes. Compared to men with 0-2 variant alleles, men with > or =3 combined RAAS variant alleles had lower average systolic BP (SBP) (P=0.030) and lower average diastolic BP (DBP) (P=0.009) for 14 h only after LITE. In contrast, average BP was not different for MOD and control between RAAS variant allele groups over this time period (P> or =0.05). LITE reduced BP in men with > or =3 variant RAAS alleles for 14 h, whereas MOD had no influence on BP in these men. In order to optimally prescribe exercise for its BP lowering benefits in those with hypertension, additional knowledge of how genetic variation affects the BP response to exercise is needed.

A comparison of recovered bipolar patients, healthy relatives of bipolar probands, and normal controls using the short TEMPS-A.

PubMed

Mendlowicz, Mauro V; Jean-Louis, Girardin; Kelsoe, John R; Akiskal, Hagop S

2005-03-01

To investigate the presence of temperament dysregulation in healthy relatives of bipolar probands (RBP), a population at high risk for developing mood disorders, by comparing them with clinically recovered bipolar patients (BP) and normal controls (NC). 52 RBP and 23 BP were originally recruited for a multicenter genetic study in bipolar disorders. NC (n=102) were also recruited by newspaper advertisement, radio and television announcements, flyers, newsletters, or word of mouth. All volunteers were asked to complete the TEMPS-A Scale, a self-report questionnaire designed to measure temperamental variations in psychiatric patients and healthy volunteers. In scoring temperaments, we relied upon the short validated version of the TEMPS-A [J. Affect. Disord. (2004)], from which traits with loadings <0.035 had been deleted. To examine differences in temperament dimensions among the three groups, a MANCOVA model was constructed using diagnostic group as the fixed factor (BP vs. RBP vs. NC); effects of age and gender were adjusted as covariates. MANCOVA showed overall group effect on the dependent variables (Hotelling's F5,175=6.64, p<0.001). Four dependent variables (dysthymic, cyclothymic, irritable, and anxious temperaments) showed significant between-group differences. RBP showed lower cyclothymic temperament scores than BP, but higher scores than NC. BP and RBP showed higher anxious temperament scores than NC. Hyperthymic scores were significantly highest in the NC. In view of the small cell sizes, bipolar I vs. bipolar II subanalyses could not be conducted. Methodologic strengths of the present analyses is that the BP group had clinically recovered, and we used the validated short version of the TEMPS-A for the present analyses. Our findings suggest that some clinically healthy relatives of bipolar probands exhibit a subclinical cyclothymic instability in mood, interest, self-confidence, sleep, and/or energy as well as anxiety proneness that is not observed among normal controls. These traits may represent vulnerability markers and could presumably be used to identify individuals at high risk for developing bipolar spectrum disorders, or specific clinical subtypes (e.g., bipolar I, bipolar II) within this spectrum. This is a conceptual perspective with many unanswered questions. Resolution of these questions will require innovative definitions of phenotypes to be included in the analyses of the temperament subscales in different populations. The temperament subscales themselves need to be calibrated properly, to find out which traits or specific combinations of trains are most promising. More extensive and complex quantitative trait analyses of these temperaments in a much expanded sample are reported elsewhere in this issue [J. Affect. Disord. (2004)].

Increased masked hypertension prevalence in patients with obesity.

PubMed

Özkan, Selçuk; Ata, Naim; Yavuz, Bunyamin

2018-02-08

Masked hypertension is associated with an increased risk for cardiovascular conditions. The aim of the study was to evaluate the relationship obesity parameters, including body weight, waist circumference, and body mass index. The study group consisted of 251 consecutive outpatient subjects without overt hypertension. Subjects were classified according to BMI. After a complete medical history and laboratory examination, patients' height, weight, waist circumference heart rate, and office blood pressure were recorded. All subjects underwent ambulatory blood pressure monitoring. Masked hypertension is defined as normal office blood pressure measurement and high ambulatory blood pressure level. Baseline characteristics in patients and controls were similar. Prevalence of Masked hypertension was significantly higher in patients with obesity than controls (30.9% vs 5.7%, p < 0.001). Body mass index (33.2 ± 4.3 vs 25.1 ± 2.7 p < 0.001), waist circumference (98.5 ± 11.7 vs 86.8 ± 8.8, p < 0.001), and weight (86.5 ± 11.8 vs. 69 ± 9.1, p < 0.001) in patients with obesity were significantly higher than in patients with normal weight. Office Systolic BP (121.8 ± 4.4 vs 120.5 ± 4.78, p = 0.035), ambulatory daytime systolic BP (128.8 ± 8.9 vs 124.5 ± 7.4, p < 0.001), ambulatory daytime diastolic BP (73.9 ± 9.5 vs 71.5 ± 7.0, p = 0.019), ambulatory night-time systolic BP in patients with obesity was significantly higher than in patients with normal weight. This study demonstrated that masked hypertension prevalence is higher in patients with obesity than control patients. It can be suggested that predefining obesity might be helpful in early detection of masked hypertension.

Association of blood glucose level and hypertension in Elderly Chinese Subjects: a community based study.

PubMed

Yan, Qun; Sun, Dongmei; Li, Xu; Chen, Guoliang; Zheng, Qinghu; Li, Lun; Gu, Chenhong; Feng, Bo

2016-07-13

There is a scarcity of epidemiological researches examining the relationship between blood pressure (BP) and glucose level among older adults. The objective of the current study was to investigate the association of high BP and glucose level in elderly Chinese. A cross-sectional study of a population of 2092 Chinese individuals aged over 65 years was conducted. Multiple logistic analysis was used to explore the association between hypertension and hyperglycemia. Independent risk factors for systolic and diastolic BP were analyzed using stepwise linear regression. Subjects in impaired fasting glucose group (IFG) (n = 144) and diabetes (n = 346), as compared with normal fasting glucose (NFG) (n = 1277), had a significant higher risk for hypertension, with odds ratios (ORs) of 1.81 (95 % CI, 1.39-2.35) (P = 0.000) and 1.40 (95 % CI, 1.09-1.80) (P = 0.009), respectively. Higher fasting plasma glucose (FPG) levels in the normal range were still significantly associated with a higher prevalence of hypertension in both genders, with ORs of 1.24 (95 % CI, 0.85-1.80), R (2) = 0.114, P = 0.023 in men and 1.61 (95 % CI, 1.12-2.30), R (2) = 0.082, P = 0.010 in women, respectively, when compared with lower FPG. Linear regression analysis revealed FPG was an independent factor of systolic and diastolic BP. Our findings suggest that hyperglycemia as well as higher FPG within the normal range is associated with a higher prevalence of hypertension independent of other cardiovascular risk factors in elderly Chinese. Further studies are needed to explore the relationship between hyperglycemia and hypertension in a longitudinal setting.

Mitochondria: 3-bromopyruvate vs. mitochondria? A small molecule that attacks tumors by targeting their bioenergetic diversity.

PubMed

Galina, Antonio

2014-09-01

Enhanced glycolysis, the classic bioenergetic phenotype of cancer cells was described by Otto Warburg approximately 90 years ago. However, the Warburg hypothesis does not necessarily imply mitochondrial dysfunction. The alkyl-halogen, 3-bromopyruvate (3BP), would not be expected to have selective targets for cancer therapy due to its high potential reactivity toward many SH side groups. Contrary to predictions, 3BP interferes with glycolysis and oxidative phosphorylation in cancer cells without side effects in normal tissues. The mitochondrial hexokinase II has been claimed as the main target. This "Organelle in focus" article presents a historical view of the use of 3BP in biochemistry and its effects on ATP-producing pathways of cancer cells. I will discuss how the alkylated enzymes contribute to the cooperative collapse of mitochondria and apoptosis. Perspectives for targeting 3BP to bioenergetics enzymes for cancer treatment will be considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation and management of patients referred to a tertiary-level hypertension clinic in Cape Town, South Africa.

PubMed

Moosa, M S; Kuttschreuter, L S; Rayner, B L

2016-07-04

Hypertension remains a global health burden, with a high incidence of long-term morbidity and mortality. To evaluate blood pressure (BP) control, factors associated with poor BP control, target organ damage (TOD), white-coat hypertension, treatment-resistant hypertension and secondary hypertension in patients referred to a tertiary-level hypertension clinic. This was a prospective case-control study of patients referred for specialist hypertension management. Patient parameters recorded included age, gender, body mass index, uric acid, cholesterol, screening BP, follow-up BP, TOD and medications. We also recorded causes of secondary hypertension. Net BP change and the percentage achieving target BP were calculated in all patients followed up. A total of 175 patients were sampled (72 males and 103 females, mean age 46.5 years). Of the patients 16.6% had a normal screening BP; 62.9% of patients were followed up, and 43.6% of these achieved BP control. After intervention, there was a net drop of 13.2 mmHg (range 7.9 - 18.4) in systolic BP and of 3.8 mmHg (4.4 - 12.0) in diastolic BP. Of all the patients, 12.6% had resistant hypertension, 49.1% had evidence of left ventricular hypertrophy and 18.3% had microalbuminuria; 13.1% of the patients were diagnosed with secondary hypertension. Specialist intervention was useful in identifying patients with white-coat and secondary hypertension, as well as in improving hypertension control in patients with apparent treatment-resistant hypertension. However, a significant percentage of patients did not reach target BP, and further efforts are required to identify the underlying causes for this.

The effect of acute maximal exercise on postexercise hemodynamics and central arterial stiffness in obese and normal-weight individuals.

PubMed

Bunsawat, Kanokwan; Ranadive, Sushant M; Lane-Cordova, Abbi D; Yan, Huimin; Kappus, Rebecca M; Fernhall, Bo; Baynard, Tracy

2017-04-01

Central arterial stiffness is associated with incident hypertension and negative cardiovascular outcomes. Obese individuals have higher central blood pressure (BP) and central arterial stiffness than their normal-weight counterparts, but it is unclear whether obesity also affects hemodynamics and central arterial stiffness after maximal exercise. We evaluated central hemodynamics and arterial stiffness during recovery from acute maximal aerobic exercise in obese and normal-weight individuals. Forty-six normal-weight and twenty-one obese individuals underwent measurements of central BP and central arterial stiffness at rest and 15 and 30 min following acute maximal exercise. Central BP and normalized augmentation index (AIx@75) were derived from radial artery applanation tonometry, and central arterial stiffness was obtained via carotid-femoral pulse wave velocity (cPWV) and corrected for central mean arterial pressure (cPWV/cMAP). Central arterial stiffness increased in obese individuals but decreased in normal-weight individuals following acute maximal exercise, after adjusting for fitness. Obese individuals also exhibited an overall higher central BP ( P  <   0.05), with no exercise effect. The increase in heart rate was greater in obese versus normal-weight individuals following exercise ( P  <   0.05), but there was no group differences or exercise effect for AIx@75 In conclusion, obese (but not normal-weight) individuals increased central arterial stiffness following acute maximal exercise. An assessment of arterial stiffness response to acute exercise may serve as a useful detection tool for subclinical vascular dysfunction. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Non-linear models for the detection of impaired cerebral blood flow autoregulation.

PubMed

Chacón, Max; Jara, José Luis; Miranda, Rodrigo; Katsogridakis, Emmanuel; Panerai, Ronney B

2018-01-01

The ability to discriminate between normal and impaired dynamic cerebral autoregulation (CA), based on measurements of spontaneous fluctuations in arterial blood pressure (BP) and cerebral blood flow (CBF), has considerable clinical relevance. We studied 45 normal subjects at rest and under hypercapnia induced by breathing a mixture of carbon dioxide and air. Non-linear models with BP as input and CBF velocity (CBFV) as output, were implemented with support vector machines (SVM) using separate recordings for learning and validation. Dynamic SVM implementations used either moving average or autoregressive structures. The efficiency of dynamic CA was estimated from the model's derived CBFV response to a step change in BP as an autoregulation index for both linear and non-linear models. Non-linear models with recurrences (autoregressive) showed the best results, with CA indexes of 5.9 ± 1.5 in normocapnia, and 2.5 ± 1.2 for hypercapnia with an area under the receiver-operator curve of 0.955. The high performance achieved by non-linear SVM models to detect deterioration of dynamic CA should encourage further assessment of its applicability to clinical conditions where CA might be impaired.

Non-linear models for the detection of impaired cerebral blood flow autoregulation

PubMed Central

Miranda, Rodrigo; Katsogridakis, Emmanuel

2018-01-01

The ability to discriminate between normal and impaired dynamic cerebral autoregulation (CA), based on measurements of spontaneous fluctuations in arterial blood pressure (BP) and cerebral blood flow (CBF), has considerable clinical relevance. We studied 45 normal subjects at rest and under hypercapnia induced by breathing a mixture of carbon dioxide and air. Non-linear models with BP as input and CBF velocity (CBFV) as output, were implemented with support vector machines (SVM) using separate recordings for learning and validation. Dynamic SVM implementations used either moving average or autoregressive structures. The efficiency of dynamic CA was estimated from the model’s derived CBFV response to a step change in BP as an autoregulation index for both linear and non-linear models. Non-linear models with recurrences (autoregressive) showed the best results, with CA indexes of 5.9 ± 1.5 in normocapnia, and 2.5 ± 1.2 for hypercapnia with an area under the receiver-operator curve of 0.955. The high performance achieved by non-linear SVM models to detect deterioration of dynamic CA should encourage further assessment of its applicability to clinical conditions where CA might be impaired. PMID:29381724

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

PubMed

Di Biase, M A; Zalesky, A; O'keefe, G; Laskaris, L; Baune, B T; Weickert, C S; Olver, J; McGorry, P D; Amminger, G P; Nelson, B; Scott, A M; Hickie, I; Banati, R; Turkheimer, F; Yaqub, M; Everall, I P; Pantelis, C; Cropley, V

2017-08-29

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [ 11 C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide ( 11 C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BP ND ) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BP ND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BP ND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BP ND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BP ND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11 C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11 C-(R)-PK11195 BP ND .

Complete genome sequence of a novel aquareovirus that infects the endangered fountain darter, Etheostoma fonticola

USGS Publications Warehouse

Iwanowicz, Luke R.; Iwanowicz, Deborah; Adams, Cynthia; Lewis, Teresa D.; Brandt, Thomas M.; Cornman, Robert S.; Sanders, Lakyn R.

2016-01-01

Here, we report the complete genome of a novel aquareovirus isolated from clinically normal fountain darters, Etheostoma fonticola, inhabiting the San Marcos River, Texas, USA. The complete genome consists of 23,958 bp consisting of 11 segments that range from 783 bp (S11) to 3,866 bp (S1).

Complete Genome Sequence of a Novel Aquareovirus That Infects the Endangered Fountain Darter, Etheostoma fonticola

PubMed Central

Adams, Cynthia R.; Lewis, Teresa D.; Brandt, Thomas M.; Sanders, Lakyn

2016-01-01

Here, we report the complete genome of a novel aquareovirus isolated from clinically normal fountain darters, Etheostoma fonticola, inhabiting the San Marcos River, Texas, USA. The complete genome consists of 23,958 bp consisting of 11 segments that range from 783 bp (S11) to 3,866 bp (S1). PMID:28007856

Association Mapping of the High-Grade Myopia MYP3 Locus Reveals Novel Candidates UHRF1BP1L, PTPRR, and PPFIA2

PubMed Central

Hawthorne, Felicia; Feng, Sheng; Metlapally, Ravikanth; Li, Yi-Ju; Tran-Viet, Khanh-Nhat; Guggenheim, Jeremy A.; Malecaze, Francois; Calvas, Patrick; Rosenberg, Thomas; Mackey, David A.; Venturini, Cristina; Hysi, Pirro G.; Hammond, Christopher J.; Young, Terri L.

2013-01-01

Purpose. Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21–23 by four independent linkage studies. Methods. We performed a genetic association study of the MYP3 locus in a family-based high-grade myopia cohort (n = 82) by genotyping 768 single-nucleotide polymorphisms (SNPs) within the linkage region. Qualitative testing for high-grade myopia (sphere ≤ −5 D affected, > −0.5 D unaffected) and quantitative testing on the average dioptric sphere were performed. Results. Several genetic markers were nominally significantly associated with high-grade myopia in qualitative testing, including rs3803036, a missense mutation in PTPRR (P = 9.1 × 10−4) and rs4764971, an intronic SNP in UHRF1BP1L (P = 6.1 × 10−4). Quantitative testing determined statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10−6); rs7134216, in the 3′ untranslated region (UTR) of DEPDC4 (P = 5.4 × 10−7); and rs17306116, an intronic SNP within PPFIA2 (P < 9 × 10−4). Independently conducted whole genome expression array analyses identified protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR). Conclusions. In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs4764971, was validated for quantitative association, and SNPs within PTPRR (quantitative) and PPFIA2 (qualitative and quantitative) approached significance. Three genes identified by our association study and supported by ocular expression and/or replication, UHRF1BP1L, PTPRR, and PPFIA2, are novel candidates for myopic development within the MYP3 locus that should be further studied. PMID:23422819

Noninvasive beat-to-beat finger arterial pressure monitoring during orthostasis: a comprehensive review of normal and abnormal responses at different ages.

PubMed

van Wijnen, V K; Finucane, C; Harms, M P M; Nolan, H; Freeman, R L; Westerhof, B E; Kenny, R A; Ter Maaten, J C; Wieling, W

2017-12-01

Over the past 30 years, noninvasive beat-to-beat blood pressure (BP) monitoring has provided great insight into cardiovascular autonomic regulation during standing. Although traditional sphygmomanometric measurement of BP may be sufficient for detection of sustained orthostatic hypotension, it fails to capture the complexity of the underlying dynamic BP and heart rate responses. With the emerging use of noninvasive beat-to-beat BP monitoring for the assessment of orthostatic BP control in clinical and population studies, various definitions for abnormal orthostatic BP patterns have been used. Here, age-related changes in cardiovascular control in healthy subjects will be reviewed to define the spectrum of the most important abnormal orthostatic BP patterns within the first 180 s of standing. Abnormal orthostatic BP responses can be defined as initial orthostatic hypotension (a transient systolic BP fall of >40 mmHg within 15 s of standing), delayed BP recovery (an inability of systolic BP to recover to a value of >20 mmHg below baseline at 30 s after standing) and sustained orthostatic hypotension (a sustained decline in systolic BP of ≥20 mmHg occurring 60-180 s after standing). In the evaluation of patients with light-headedness, pre(syncope), (unexplained) falls or suspected autonomic dysfunction, it is essential to distinguish between normal cardiovascular autonomic regulation and these abnormal orthostatic BP responses. The prevalence, clinical relevance and underlying pathophysiological mechanisms of these patterns differ significantly across the lifespan. Initial orthostatic hypotension is important for identifying causes of syncope in younger adults, whereas delayed BP recovery and sustained orthostatic hypotension are essential for evaluating the risk of falls in older adults. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes.

PubMed

Kim, Hyoung-June; Lee, Eunyoung; Lee, Moonyoung; Ahn, Sungjin; Kim, Jungmin; Liu, Jingjing; Jin, Sun Hee; Ha, Jaehyoun; Bae, Il Hong; Lee, Tae Ryong; Noh, Minsoo

2018-01-01

Benzophenone-3 (BP-3), which is extensively used in organic sunscreen, has phototoxic potential in human skin. Phosphodiesterase 4B (PDE4B) has a well-established role in inflammatory responses in immune cells. Currently, it is unknown if PDE4B is associated with BP-3-induced phototoxicity in normal human keratinocytes (NHKs). We found that BP-3 significantly increased PDE4B expression in ultraviolet B (UVB)-irradiated NHKs. Notably, BP-8, a sunscreen agent that shares the 2-hydroxy-4-methoxyphenyl methanone moiety with BP-3, also upregulated PDE4B expression in NHKs. Upon UVB irradiation, BP-3 upregulated the expression of pro-inflammatory factors, such as prostaglandin endoperoxide synthase 2, tumor necrosis factor α, interleukin 8, and S100A7, and downregulated the level of cornified envelope associated proteins, which are important in the development of the epidermal permeability barrier. The additive effects of UVB-activated BP-3 on the expression of both pro-inflammatory mediators and cornified envelope associated proteins were antagonized by treatment with the PDE4 inhibitor rolipram. The BP-3 and UVB co-stimulation-induced PDE4B upregulation and its association with the upregulation of pro-inflammatory mediators and the downregulation of epidermal differentiation markers were confirmed in a reconstituted three dimensional human epidermis model. Therefore, PDE4B has a role in the mechanism of BP-3-induced phototoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

The relationship of depression with the level of blood pressure in population-based Kangbuk Samsung Health Study.

PubMed

Park, Sung Keun; Jung, Ju Young; Ryoo, Jae-Hong; Oh, Chang-Mo; Lee, Jae-Hon; Pan, Zihang; Mansur, Rodrigo B; Shekotikhina, Margarita; McIntyre, Roger S; Choi, Joong-Myung

2018-05-01

There has been increasing evidence about psychosomatic relationship between mood disorder and blood pressure (BP). However, the degree to which BP categories are associated with depression has been less well described. Thus, this study was to investigate the association of depression with BP categories. A total of 90,643 men and 68,933 women were enrolled in this study. They were stratified into four groups (normal, prehypertension, newly diagnosed hypertension, and recognized hypertension) according to the BP levels and the history of hypertension. Center for Epidemiological Studies-Depression was used to evaluate the depressive symptom, and the degree of depression was evaluated by the cutoff of Center for Epidemiological Studies-Depression (mild: 16-20, moderate: 21-24, severe: ≥25). The multivariate logistic regression was used in calculating odds ratios for depression according to the four BP categories, with adjustment for multiple confounding factors. Subgroup analysis was conducted by gender and age. The adjusted odds ratios for depression tended to decrease from normal to newly diagnosed hypertension, but significantly increased in recognized hypertension (normal: reference, prehypertension: 0.85 [0.80-0.91], newly diagnosed hypertension: 0.75 [0.65-0.86], recognized hypertension: 1.11 [1.03-1.20]). Subgroup analysis also indicated the similar pattern of relationship, which was more prominent in male and middle-aged subgroup than any other subgroups. Depression was inversely associated with elevated BP. However, recognized hypertension had the increased likelihood of depression in male and young age group. These findings suggest that the association between depression and BP may be moderated by the chronicity of hypertension in men and young individuals. Copyright © 2018 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Complex segregation analysis of blood pressure and heart rate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

PubMed

An, P; Rice, T; Pérusse, L; Borecki, I B; Gagnon, J; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-05-01

Complex segregation analysis of baseline resting blood pressure (BP) and heart rate (HR) and their responses to training (post-training minus baseline) were performed in a sample of 482 individuals from 99 white families who participated in the HERITAGE Family Study. Resting BP and HR were measured at baseline and after a 20-week training program. Baseline resting BP and HR were age-adjusted and age-BMI-adjusted, and the responses to training were age-adjusted and age-baseline-adjusted, within four gender-by-generation groups. This study also analyzed the responses to training in two subsets of families: (1) the so-called "high" subsample, 45 families (216 individuals) with at least one member whose baseline resting BP is in the high end of the normal BP range (the upper 95th percentile: systolic BP [SBP] > or = 135 or diastolic BP [DBP] > or = 80 mm Hg); and (2) the so-called "nonhigh" subsample, the 54 remaining families (266 individuals). Baseline resting SBP was influenced by a multifactorial component (23%), which was independent of body mass index (BMI). Baseline resting DBP was influenced by a putative recessive locus, which accounted for 31% of the variance. In addition to the major gene effect, which may impact BMI as well, baseline resting DBP was also influenced by a multifactorial component (29%). Baseline resting HR was influenced by a putative dominant locus independent of BMI, which accounted for 31% of the variance. For the responses to training, no familiality was found in the whole sample or in the nonhigh subsample. However, in the high subsample, resting SBP response to training was influenced by a putative recessive locus, which accounted for 44% of the variance. No familiality was found for resting DBP response to training. Resting HR response to training was influenced by a major effect (accounting for 35% of the variance), with an ambiguous transmission from parents to offspring.

Blood Pressure Control in Hypertensive Patients, Cardiovascular Risk Profile and the Prevalence of Masked Uncontrolled Hypertension (MUCH).

PubMed

Naser, Nabil; Dzubur, Alen; Durak, Azra; Kulic, Mehmed; Naser, Nura

2016-07-27

The term masked hypertension (MH) should be used for untreated individuals who have normal office blood pressure but elevated ambulatory blood pressure. For treated patients, this condition should be termed masked uncontrolled hypertension (MUCH). Masked uncontrolled hypertension (MUCH) has gone unrecognized because few studies have used 24-h ABPM to determine the prevalence of suboptimal BP control in seemingly well-treated patients, and there are few such studies in large cohorts of treated patients attending usual clinical practice. This is important because masked hypertension is associated with a high risk of cardiovascular events. This study was conducted to obtain more information about the association between hypertension and other CV risk factors, about office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients, also to define the prevalence and characteristics of masked uncontrolled hypertension (MUCH) among treated hypertensive patients in routine clinical practice. In this study 2514 male and female patients were included during a period of 5 years follow up. All patients have ambulatory blood pressure monitoring (ABPM) for at least 24h. We identified patients with treated and controlled BP according to current international guidelines (clinic BP, 140/90mmHg). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Masked uncontrolled hypertension (MUCH) was diagnosed in these patients if despite controlled clinic BP, the mean 24-h ABPM average remained elevated (24-h systolic BP ≥130mmHg and/or 24-h diastolic BP ≥80mmHg). Patients had a mean age of 60.2+10 years, and the majority of them (94.6%) were followed by specialist physicians. Average clinic BP was 150.4+16/89.9+12 mmHg. About 70% of patients displayed a very high-risk profile. Ambulatory blood pressure monitoring (ABPM) was performed in all recruited patients for at least 24h. Despite the combined medical treatment (78% of the patients), clinic control (<140/90 mmHg) was achieved in only 26.2% of patients, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 32.7%. From 2514 patients with treated BP, we identified 803 with treated and controlled office BP control (<140/90 mmHg), of whom 258 patients (32.1%) had MUCH according to 24-h ABPM criteria (mean age 57.2 years, 54.7% men). The prevalence of MUCH was slightly higher in males, patients with borderline clinic and office BP (130-139/80-89 mmHg), and patients at high cardiovascular risk (smokers, diabetes, obesity). Masked uncontrolled hypertension (MUCH) was most often due to poor control of nocturnal BP, with the proportion of patients in whom MUCH was solely attributable to an elevated nocturnal BP almost double that solely attributable to daytime BP elevation (22.3 vs. 10.1%, P 0.001). The prevalence of masked suboptimal BP control in patients with treated and well-controlled clinic BP is high. The characteristics of patients with MUCH (male, longer duration of hypertension, obesity, smoking history, and diabetes) indicate that this is a higher-risk group with most to gain from improved BP.

Complete Genome Sequence of a Novel Aquareovirus That Infects the Endangered Fountain Darter, Etheostoma fonticola.

PubMed

Iwanowicz, Luke R; Iwanowicz, Deborah D; Adams, Cynthia R; Lewis, Teresa D; Brandt, Thomas M; Cornman, Robert S; Sanders, Lakyn

2016-12-22

Here, we report the complete genome of a novel aquareovirus isolated from clinically normal fountain darters, Etheostoma fonticola, inhabiting the San Marcos River, Texas, USA. The complete genome consists of 23,958 bp consisting of 11 segments that range from 783 bp (S11) to 3,866 bp (S1). Copyright © 2016 Iwanowicz et al.

4E-BP is a target of the GCN2–ATF4 pathway during Drosophila development and aging

PubMed Central

Park, Jung-Eun; Zeng, Xiaomei

2017-01-01

Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation–activated kinase GCN2 mediates this response in part by phosphorylating eIF2α. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids. The 4E-BP intron contains ATF4-binding sites that not only respond to stress but also show inherent ATF4 activity during normal development. Analysis of the newly synthesized proteome through metabolic labeling combined with click chemistry shows that certain stress-responsive proteins are resistant to inhibition by 4E-BP, and gcn2 mutant flies have reduced levels of stress-responsive protein synthesis. These results indicate that GCN2 and ATF4 are important regulators of 4E-BP transcription during normal development and aging. PMID:27979906

Effects of 12-week brisk walking training on exercise blood pressure in elderly patients with essential hypertension: a pilot study.

PubMed

He, L I; Wei, Wang Ren; Can, Zhao

2018-01-24

Essential hypertension (EP) is characterized by blood pressure (BP) elevations, which often lead to target organ damage and cardiovascular illness. The following study investigates whether aerobic exercise programs with different intensities could reduce the magnitude of BP rise. Patients with essential hypertension were recruited from the Baoshan Community Health Service Center. A total of 46 patients were finally selected and randomly assigned into two groups: control group (CON) included patients who did not participate in exercise intervention training; treatment group (TRG) included patients who participated in 12-week brisk walking training (60-min of brisk walking, three times a week for a total of 12 weeks). 3-minute step tests of low and high intensity were conducted pre- and post-intervention. To compare the effects of exercise intervention, 23 subjects with normal blood pressure (NBP) who did not participate in 12-week brisk walking training, were recruited. After 12 weeks of brisk walking, SBP of TRG during resting, low and high-intensity exercise was significantly reduced by 8.3mmHg, 15.6mmHg, and 22.6mmHg, respectively; while HR of TRG's during resting, low and high intensity was significantly reduced by 3.6beats/minute, 8.7beats/minute and 11.3beats/minute, respectively. Meanwhile, after 12 weeks of brisk walking, TRG's steps per day, [Formula: see text]o 2max , moderate physical activity time and physical activity energy expenditure significantly increased by 6000 steps, 2.4 ml/kg/m, 40 minutes and 113 kcal, respectively. At the same time, TRG's body fat rate and sedentary time significantly reduced by 2% and 60 minutes per day. Brisk walking can reduce the magnitude of BP rise during exercise of different intensities and may be reduced the risk of acute cardiovascular incidents in elderly patients with essential hypertension. EP: Essential hypertension; BP: blood pressure; CON: control group; TRG: treatment group; NBP: normal blood pressure; PA: physical activity.

Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle.

PubMed

Copeland, O'Neal; Sadayappan, Sakthivel; Messer, Andrew E; Steinen, Ger J M; van der Velden, Jolanda; Marston, Steven B

2010-12-01

A unique feature of MyBP-C in cardiac muscle is that it has multiple phosphorylation sites. MyBP-C phosphorylation, predominantly by PKA, plays an essential role in modulating contractility as part of the cellular response to β-adrenergic stimulation. In vitro studies indicate MyBP-C can be phosphorylated at Serine 273, 282, 302 and 307 (mouse sequence) but little is known about the level of MyBP-C phosphorylation or the sites phosphorylated in heart muscle. Since current methodologies are limited in specificity and are not quantitative we have investigated the use of phosphate affinity SDS-PAGE together with a total anti MyBP-C antibody and a range of phosphorylation site-specific antibodies for the main sites (Ser-273, -282 and -302). With these newly developed methods we have been able to make a detailed quantitative analysis of MyBP-C phosphorylation in heart tissue in situ. We have found that MyBP-C is highly phosphorylated in non-failing human (donor) heart or mouse heart; tris and tetra-phosphorylated species predominate and less than 10% of MyBP-C is unphosphorylated (0, 9.3 ± 1%: 1P, 13.4 ± 2.7%: 2P, 10.5 ± 3.3%: 3P, 28.7 ± 3.7%: 4P, 36.4 ± 2.7%, n=21). Total phosphorylation was 2.7 ± 0.07 mol Pi/mol MyBP-C. In contrast in failing heart and in myectomy samples from HCM patients the majority of MyBP-C was unphosphorylated. Total phosphorylation levels were 23% of normal in failing heart myofibrils (0, 60.1 ± 2.8%: 1P, 27.8 ± 2.8%: 2P, 4.8 ± 2.0%: 3P, 3.7 ± 1.2%: 4P, 2.8 ± 1.3%, n=19) and 39% of normal in myectomy samples. The site-specific antibodies showed a distinctive distribution pattern of phosphorylation sites in the multiple phosphorylation level species. We found that phosphorylated Ser-273, Ser-282 and Ser-302 were all present in the 4P band of MyBP-C but none of them were significant in the 1P band, indicating that there must be at least one other site of MyBP-C phosphorylation in human heart. The pattern of phosphorylation at the three sites was not random, but indicated positive and negative interactions between the three sites. Phosphorylation at Ser-282 was not proportional to the number of sites available. The 2P band contained 302 but not 273; the 3P band contained 273 but not 302. Copyright © 2010 Elsevier Ltd. All rights reserved.

Impact of high fat/high salt diet on myocardial oxidative stress.

PubMed

Mayyas, Fadia; Alzoubi, Karem H; Al-Taleb, Zahraa

2017-01-01

High fat high salt diet contributes to oxidative stress and cardiac diseases. To determine the impact of moderately high fat diet (HFD), high salt (HS) or their combination on blood pressure (Bp) and myocardial oxidants/antioxidants. Sprague Dawley rats were assigned into four groups; conventional diet (control, 5% fat, 0.5% NaCl), HFD (25% fat, 0.5% NaCl), HS (5% fat, 8% NaCl), or combined diet (HFD+HS) for 10 weeks. Bp and cardiac oxidants and antioxidants were measured. HFD, HS, and their combination didn't cause obesity or dyslipidemia. Both HS and combined diets resulted in an increase in the heart/body weight ratio accompanied by an increase in Bp. No changes were observed in levels of the glutathione (GSH) system or superoxide dismutase (SOD) activities. However, a significant decrease in TBARS levels was observed in the HFD and the combined diet with a parallel increase in catalase activity in all groups. Relative to HFD, the combined diet was associated with increases in GSH reductase/peroxidase and SOD activities. The lack of changes in the GSH system, the decrease in TBARS, and the increase in catalase activity suggest that normal hearts adapt compensatory mechanisms to prevent oxidative damage in response to HFD/and or HS.

Calcium metabolism and cardiovascular function after spaceflight

NASA Technical Reports Server (NTRS)

Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric;

Significance of White-Coat Hypertension in Older Persons With Isolated Systolic Hypertension

PubMed Central

Franklin, Stanley S.; Thijs, Lutgarde; Hansen, Tine W.; Li, Yan; Boggia, José; Kikuya, Masahiro; Björklund-Bodegård, Kristina; Ohkubo, Takayoshi; Jeppesen, Jørgen; Torp-Pedersen, Christian; Dolan, Eamon; Kuznetsova, Tatiana; Stolarz-Skrzypek, Katarzyna; Tikhonoff, Valérie; Malyutina, Sofia; Casiglia, Edoardo; Nikitin, Yuri; Lind, Lars; Sandoya, Edgardo; Kawecka-Jaszcz, Kalina; Imai, Yutaka; Wang, Jiguang; Ibsen, Hans; O’Brien, Eoin; Staessen, Jan A.

2013-01-01

The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes database who had daytime ambulatory blood pressure (BP; ABP) and conventional BP (CBP) measurements. After excluding persons with diastolic hypertension by CBP (≥90 mm Hg) or by daytime ABP (≥85 mm Hg), a history of cardiovascular disease, and persons <18 years of age, the present analysis totaled 7295 persons, of whom 1593 had isolated systolic hypertension. During a median follow-up of 10.6 years, there was a total of 655 fatal and nonfatal cardiovascular events. The analyses were stratified by treatment status. In untreated subjects, those with white-coat hypertension (CBP ≥140/<90 mm Hg and ABP <135/<85 mm Hg) and subjects with normal BP (CBP <140/<90 mm Hg and ABP <135/<85 mm Hg) were at similar risk (adjusted hazard rate: 1.17 [95% CI: 0.87–1.57]; P=0.29). Furthermore, in treated subjects with isolated systolic hypertension, the cardiovascular risk was similar in elevated conventional and normal daytime systolic BP as compared with those with normal conventional and normal daytime BPs (adjusted hazard rate: 1.10 [95% CI: 0.79–1.53]; P=0.57). However, both treated isolated systolic hypertension subjects with white-coat hypertension (adjusted hazard rate: 2.00; [95% CI: 1.43–2.79]; P<0.0001) and treated subjects with normal BP (adjusted hazard rate: 1.98 [95% CI: 1.49–2.62]; P<0.0001) were at higher risk as compared with untreated normotensive subjects. In conclusion, subjects with sustained hypertension who have their ABP normalized on antihypertensive therapy but with residual white-coat effect by CBP measurement have an entity that we have termed, “treated normalized hypertension.” Therefore, one should be cautious in applying the term “white-coat hypertension” to persons receiving antihypertensive treatment. PMID:22252396

Significance of white-coat hypertension in older persons with isolated systolic hypertension: a meta-analysis using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes population.

PubMed

Franklin, Stanley S; Thijs, Lutgarde; Hansen, Tine W; Li, Yan; Boggia, José; Kikuya, Masahiro; Björklund-Bodegård, Kristina; Ohkubo, Takayoshi; Jeppesen, Jørgen; Torp-Pedersen, Christian; Dolan, Eamon; Kuznetsova, Tatiana; Stolarz-Skrzypek, Katarzyna; Tikhonoff, Valérie; Malyutina, Sofia; Casiglia, Edoardo; Nikitin, Yuri; Lind, Lars; Sandoya, Edgardo; Kawecka-Jaszcz, Kalina; Imai, Yutaka; Wang, Jiguang; Ibsen, Hans; O'Brien, Eoin; Staessen, Jan A

2012-03-01

The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes database who had daytime ambulatory blood pressure (BP; ABP) and conventional BP (CBP) measurements. After excluding persons with diastolic hypertension by CBP (≥90 mm Hg) or by daytime ABP (≥85 mm Hg), a history of cardiovascular disease, and persons <18 years of age, the present analysis totaled 7295 persons, of whom 1593 had isolated systolic hypertension. During a median follow-up of 10.6 years, there was a total of 655 fatal and nonfatal cardiovascular events. The analyses were stratified by treatment status. In untreated subjects, those with white-coat hypertension (CBP ≥140/<90 mm Hg and ABP <135/<85 mm Hg) and subjects with normal BP (CBP <140/<90 mm Hg and ABP <135/<85 mm Hg) were at similar risk (adjusted hazard rate: 1.17 [95% CI: 0.87-1.57]; P=0.29). Furthermore, in treated subjects with isolated systolic hypertension, the cardiovascular risk was similar in elevated conventional and normal daytime systolic BP as compared with those with normal conventional and normal daytime BPs (adjusted hazard rate: 1.10 [95% CI: 0.79-1.53]; P=0.57). However, both treated isolated systolic hypertension subjects with white-coat hypertension (adjusted hazard rate: 2.00; [95% CI: 1.43-2.79]; P<0.0001) and treated subjects with normal BP (adjusted hazard rate: 1.98 [95% CI: 1.49-2.62]; P<0.0001) were at higher risk as compared with untreated normotensive subjects. In conclusion, subjects with sustained hypertension who have their ABP normalized on antihypertensive therapy but with residual white-coat effect by CBP measurement have an entity that we have termed, "treated normalized hypertension." Therefore, one should be cautious in applying the term "white-coat hypertension" to persons receiving antihypertensive treatment.

Exaggerated blood pressure response to exercise in athletes: dysmetabolism or altered autonomic nervous system modulation?

PubMed

Turmel, Julie; Bougault, Valérie; Boulet, Louis-Philippe; Poirier, Paul

2012-10-01

The importance of exercise-induced exaggerated blood pressure (BP) response in endurance athletes is not known. To assess the hemodynamic parameters and metabolic profile in athletes with an exaggerated BP response to exercise. Forty-four endurance athletes underwent a maximal exercise test, a 24-h ambulatory blood pressure monitoring, a 24-h Holter assessment, and sampling of blood on two occasions: (a) during intense training and (b) following 3 weeks without training. During the training period, 11 athletes showed an exaggerated BP response to exercise, whereas seven of these 11 athletes also showed an exaggerated BP response during the resting period. Elevation in systolic BP was greater in athletes with an exaggerated BP response than athletes with a normal BP response to exercise (resting: 84 ± 22 vs. 60 ± 18 mmHg, P = 0.02; training: 100 ± 21 vs. 70 ± 18 mmHg, P = 0.004). During the training period, athletes with an exaggerated BP response to exercise showed higher systolic BP values on 24-h ambulatory blood pressure monitoring (136 ± 15 vs. 118 ± 8 mmHg, P = 0.02). During the resting period, athletes with an exaggerated BP response to exercise had lower apolipoprotein-A1 (1.3 ± 0.1 vs. 1.5 ± 0.2 g/l, P = 0.009), and higher SDNN (259 ± 47 vs. 209 ± 52 ms, P = 0.03) and pNN50 (0.4 ± 0.1 vs. 0.3 ± 0.1%, P = 0.05). These observations may represent the first sign of a slight metabolic disturbance associated with vascular wall abnormalities, although the parameters remain within normal values.

Impact of Whole Body Cryotherapy at -110 °C on Subjects with Arterial Hypertension.

PubMed

Missmann, M; Himsl, M; Mur, E; Ulmer, H; Marschang, P

2016-02-01

Whole body cryotherapy (WBC) in a cryo-chamber as a medical treatment was first established in Japan in the 1980s, later in Central Europe, and is now becoming more popular also in the United States. The exposure to extreme, non-physiological environmental conditions in a cryo-chamber at -110 °C may exceed the normal adaption capacity. The aim of this study was to investigate the effects of WBC on blood pressure (BP) readings in adult subjects with rheumatic disorders and normal or moderately elevated BP. A sample of 23 subjects (8 female, 15 male) which were recruited according to their pathology between the age of 35 and 69 years undergoing 21 WBC applications was divided into three groups: a group of subjects with anti-hypertensive therapy, a group of subjects with mild arterial hypertension without medical treatment, and a normotensive control-group. A total of 483 BP readings were taken immediately before and after each WBC application. The systolic and diastolic BP were recorded, and the mean arterial pressure, and the amplitude of BP were calculated. A statistically significant rise of BP after WBC was found in the whole sample and in the normotensive group. Over the course of time, no significant change of BP behavior was observed, except for normotensive subjects, who showed a wider range in their systolic BP values. Generally accepted exclusion criteria were applied, and in our sample group WBC was safe with respect to unwanted BP alterations for adult subjects under 70 years-regardless of a pre-existing untreated mild or pharmacologically treated arterial hypertension. Greater changes of BP values might infrequently occur, so an individual monitoring of subjects is necessary.

Trajectories of Childhood Blood Pressure and Adult Left Ventricular Hypertrophy: The Bogalusa Heart Study.

PubMed

Zhang, Tao; Li, Shengxu; Bazzano, Lydia; He, Jiang; Whelton, Paul; Chen, Wei

2018-07-01

This longitudinal study aims to characterize longitudinal blood pressure (BP) trajectories from childhood and examine the impact of level-independent childhood BP trajectories on adult left ventricular hypertrophy (LVH) and remodeling patterns. The longitudinal cohort consisted of 1154 adults (787 whites and 367 blacks) who had repeated measurements of BP 4 to 15 times from childhood (4-19 years) to adulthood (20-51 years) and assessment of echocardiographic LV dimensions in adulthood. Model-estimated levels and linear slopes of BP at childhood age points were calculated in 1-year intervals using the growth curve parameters and their first derivatives, respectively. Linear and nonlinear curve parameters of BP showed significant race and sex differences from age 15 years onwards. Adults with LVH had higher long-term BP levels than adults with normal LVM in race-sex groups. Linear and nonlinear slope parameters of BP differed consistently and significantly between LVH and normal groups. Associations of level-independent linear slopes of systolic BP with adult LVH were significantly inverse (odds ratio=0.75-0.82; P =0.001-0.015) in preadolescent children of 4 to 9 years but significantly positive (odds ratio=1.29-1.46; P =0.001-0.008) in adolescents of 13 to 19 years, adjusting for covariates. These associations were consistent across race-sex groups. Of note, the association of childhood BP linear slopes with concentric LVH was significantly stronger than that with eccentric LVH during the adolescence period of 12 to 19 years. These observations indicate that the impact of BP trajectories on adult LVH and geometric patterns originates in childhood. Adolescence is a crucial period for the development of LVH in later life, which has implications for early prevention. © 2018 American Heart Association, Inc.

Effect of obesity on cardiovascular disease risk factors in African American women.

PubMed

Henry-Okafor, Queen; Cowan, Patricia A; Wicks, Mona N; Rice, Muriel; Husch, Donna S; Khoo, Michelle S C

2012-04-01

Obesity is a growing health care concern with implications for cardiovascular disease (CVD). Obesity and CVD morbidity and mortality are highly prevalent among African American women. This pilot study examined the association between obesity and the traditional and emerging CVD risk factors in a sample of African American women. Participants comprised 48 women (27 obese, 21 normal weight) aged 18-45. with no known history of CVD. The women completed demographic and 7-day physical activity recall questionnaires. Height and weight were used to determine body mass index (BMI). Hypertension risk was assessed using the average of two resting blood pressure (BP) measurements. Lipid profile, blood glucose, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule-1 (sICAM-1), and E-selectin (eSel) levels were assessed using fasting blood samples. Laboratory findings were interpreted using the American Diabetes Association (ADA) and Adult Treatment Panel (ATP) III reference guidelines as well as manufacturers' reference ranges for the novel CVD risk factors. The most common traditional risk factors were physical inactivity (72.9%), positive family history of CVD (58.3%), and obesity (56.3%). Obese individuals had elevated systolic BP (p = .0002), diastolic BP (p = .0007) and HDL-cholesterol (p = .01), triglyceride (p = .02), hs-CRP (p = .002), and fibrinogen (p = .01), when compared with normal-weight women. The findings suggest an association between obesity and higher prevalence of both traditional and emerging CVD risk factors in young African American women.

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

PubMed Central

McBride, Shawna M.; Culver, Bruce; Flynn, Francis W.

2008-01-01

This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6–8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors. PMID:18614766

Ambulatory Blood Pressure Monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults.

PubMed

Hermida, Ramón C; Smolensky, Michael H; Ayala, Diana E; Portaluppi, Francesco

2015-01-01

New information has become available since the ISC, AAMCC, and SECAC released their first extensive guidedelines to improve the diagnosis and treatment of adult arterial hypertension. A critical assessment of evidence and a comparison of what international guidelines now propose are the basis for the following statements, which update the recommendations first issued in 2013. Office blood pressure (BP) measurements should no longer be considered to be the "gold standard" for the diagnosis of hypertension and assessment of cardiovascular risk. Relying on office BP, even when supplemented with at-home wake-time self-measurements, to identify high-risk individuals, disregarding circadian BP patterning and asleep BP level, leads to potential misclassification of 50% of all evaluated persons. Accordingly, ambulatory BP monitoring is the recommended reference standard for the diagnosis of true hypertension and accurate assessment of cardiovascular risk in all adults ≥18 yrs of age, regardless of whether office BP is normal or elevated. Asleep systolic BP mean is the most significant independent predictor of cardiovascular events. The sleep-time relative SBP decline adds prognostic value to the statistical model that already includes the asleep systolic BP mean and corrected for relevant confounding variables. Accordingly, the asleep systolic BP mean is the recommended protocol to diagnose hypertension, assess cardiovascular risk, and predict cardiovascular event-free interval. In men, and in the absence of compelling clinical conditions, reference thresholds for diagnosing hypertension are 120/70 mmHg for the asleep systolic/diastolic BP means derived from ambulatory BP monitoring. However, in women, in the absence of complicating co-morbidities, the same thresholds are lower by 10/5 mmHg, i.e., 110/65 mmHg for the asleep means. In high-risk patients, including those diagnosed with diabetes or chronic kidney disease, and/or those having experienced past cardiovascular events, the thresholds are even lower by 15/10 mmHg, i.e., 105/60 mmHg. Bedtime treatment with the full daily dose of ≥1 hypertension medications is recommended as a cost-effective means to improve the management of hypertension and reduce hypertension-associated risk. Bedtime treatment entailing the full daily dose of ≥1 conventional hypertension medications must be the therapeutic regimen of choice for the elderly and those with diabetes, resistant and secondary hypertension, chronic kidney disease, obstructive sleep apnea, and medical history of past cardiovascular events, among others, given their documented high prevalence of sleep-time hypertension.

An affordable cuff-less blood pressure estimation solution.

PubMed

Jain, Monika; Kumar, Niranjan; Deb, Sujay

2016-08-01

This paper presents a cuff-less hypertension pre-screening device that non-invasively monitors the Blood Pressure (BP) and Heart Rate (HR) continuously. The proposed device simultaneously records two clinically significant and highly correlated biomedical signals, viz., Electrocardiogram (ECG) and Photoplethysmogram (PPG). The device provides a common data acquisition platform that can interface with PC/laptop, Smart phone/tablet and Raspberry-pi etc. The hardware stores and processes the recorded ECG and PPG in order to extract the real-time BP and HR using kernel regression approach. The BP and HR estimation error is measured in terms of normalized mean square error, Error Standard Deviation (ESD) and Mean Absolute Error (MAE), with respect to a clinically proven digital BP monitor (OMRON HBP1300). The computed error falls under the maximum standard allowable error mentioned by Association for the Advancement of Medical Instrumentation; MAE <; 5 mmHg and ESD <; 8mmHg. The results are validated using two-tailed dependent sample t-test also. The proposed device is a portable low-cost home and clinic bases solution for continuous health monitoring.

[Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients].

PubMed

Liu, Bao-guo; Li, Zhi-ying; Du, Ming

2006-10-01

To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients. Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01). JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid.

Changing the "Normal Range" for Blood Pressure from 140/90 to 130/Any Improves Risk Assessment.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2015-01-01

Objective .- Redefine the "normal" reference range for blood pressure from <140/90 to one that more effectively identifies individuals with increased mortality risk. Method .- Data from the recently published 2014 CRL blood pressure study was used. It includes 2,472,706 life insurance applicants tested by Clinical Reference Laboratory from 1993 to 2007 with follow-up for vital status using the September 2011 Social Security Death Master File. Various upper limits of blood pressure (BP in mm Hg) were evaluated to determine if any was superior to the current, commonly used limit of 140/90 in identifying individuals with increased mortality risk. Results .- An alternative reference range using a systolic BP (SBP) <130 with any diastolic BP (DBP) included 84% of life insurance applicants. It had a lower mortality rate and narrower range of relative risk than <140/90, including 89% as many applicants but only 68% as many deaths. This pattern of lives and deaths was consistent across age and sex. Conclusion .- Switching to a "normal" reference range of SBP <130 offers superior risk assessment relative to using BP <140/90 while still including a sufficient percentage of the population.

Effect of nitroglycerin administration on cardio-ankle vascular index.

PubMed

Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

2016-01-01

The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey-Kramer test was used for post hoc comparisons. In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (-1.4±0.7 vs -1.4±0.9, -1.1±0.7 vs -1.4±1.0, -0.8±0.7 vs -1.2±1.0, and -0.5±0.7 vs -1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes (normal controls vs CAD; -3±7 vs -10±11, -3±5 vs -10±11, -3±6 vs -13±10, and -1±6 vs -11±10 mmHg, respectively). ΔDiastolic BP in the normal controls was significantly higher than in the CAD patients at 5 and 10 minutes (normal controls vs CAD; -8±6 vs -4±4 and -9±4 vs -6±5 mmHg, respectively). After NTG administration, the stiffness of the arteries from the origin of the aorta to the ankle as measured by CAVI decreased in both the normal controls and CAD patients, indicating that the response of arterial smooth muscle cells to nitric oxide is preserved even in CAD patients under medication.

Quantitation of normal CFTR mRNA in CF patients with splice-site mutations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Z.; Olsen, J.C.; Silverman, L.M.

Previously we identified two mutations in introns of the CFTR gene associated with partially active splice sites and unusual clinical phenotypes. One mutation in intron 19 (3849+10 kb C to T) is common in CF patients with normal sweat chloride values; an 84 bp sequence from intron 19, which contains a stop codon, is inserted between exon 19 and exon 20 in most nasal CFTR transcripts. The other mutation in intron 14B (2789+5 G to A) is associated with elevated sweat chloride levels, but mild pulmonary disease; exon 14B (38 bp) is spliced out of most nasal CFTR transcipts. Themore » remaining CFTR cDNA sequences, other than the 84 bp insertion of exon 14B deletion, are identical to the published sequence. To correlate genotype and phenotype, we used quantitative RT-PCR to determine the levels of normally-spliced CFTR mRNA in nasal epithelia from these patients. CFTR cDNA was amplified (25 cycles) by using primers specific for normally-spliced species, {gamma}-actin cDNA was amplified as a standard.« less

Oncogenic NRAS, Required for Pathogenesis of Embryonic Rhabdomyosarcoma, Relies upon the HMGA2–IGF2BP2 Pathway

PubMed Central

Li, Zhizhong; Zhang, Yunyu; Ramanujan, Krishnan; Ma, Yan; Kirsch, David G.; Glass, David J.

2013-01-01

Embryonic rhabdomyosarcoma (ERMS) is the most common soft-tissue tumor in children. Here, we report the identification of the minor groove DNA-binding factor high mobility group AT-hook 2 (HMGA2) as a driver of ERMS development. HMGA2 was highly expressed in normal myoblasts and ERMS cells, where its expression was essential to maintain cell proliferation, survival in vitro, and tumor outgrowth in vivo. Mechanistic investigations revealed that upregulation of the insulin–like growth factor (IGF) mRNA-binding protein IGF2BP2 was critical for HMGA2 action. In particular, IGF2BP2 was essential for mRNA and protein stability of NRAS, a frequently mutated gene in ERMS. shRNA-mediated attenuation of NRAS or pharmacologic inhibition of the MAP-ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) effector pathway showed that NRAS and NRAS-mediated signaling was required for tumor maintenance. Taken together, these findings implicate the HMGA2–IGFBP2–NRAS signaling pathway as a critical oncogenic driver in ERMS. PMID:23536553

Red cell distribution width and hypertensive response to exercise in patients with type 2 diabetes mellitus.

PubMed

Kucukdurmaz, Zekeriya; Karavelioglu, Yusuf; Karapinar, Hekim; Sancakdar, Enver; Deveci, Koksal; Gul, Ibrahim; Yilmaz, Ahmet

2014-01-01

There is no study about hypertensive response to exercise (HRE), which is a marker of unborn hypertension (HT), and red cell distribution width (RDW) association, in diabetic normotensive patients. So, we aimed to investigate any correlation among RDW and HRE in normotensive type 2 diabetic patients. Consecutive type 2 diabetic patients without history of HT and with normal blood pressure (BP) on ambulatory BP monitoring were included to the study. We divided the patients into two groups depending on their peak systolic BP on exercise; HRE (Group 1) or normal response to exercise (Group 2). Data of 75 diabetic patients (51.9 ± 9.7) were analyzed (31 male (48%)). Their mean RDW was 13.11 ± 0.46. Patients with HRE were significantly older than patients without HRE. Smoking was more frequent in Group 2. Gender distribution and body mass index were similar between the groups. Else hemoglobin, hematocrit, red blood cell count and RDW values were not significantly different. Office systolic BP and diastolic BP, daytime and 24-h systolic BP were significantly higher in Group 1 but heart rate was similar between the groups. This study revealed that RDW do not differ between diabetic normotensive patients with HRE or not.

Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement

PubMed Central

Bhatt, Hemal; Siddiqui, Mohammed; Judd, Eric; Oparil, Suzanne; Calhoun, David

2016-01-01

Background The prevalence of pseudoresistant hypertension (HTN) due to inaccurate BP measurement remains unknown. Methods Triage BP measurements and measurements obtained at the same clinic visit by trained physicians were compared in consecutive adult patients referred for uncontrolled resistant HTN (RHTN). Triage BP measurements were taken by the clinic staff during normal intake procedures. BP measurements were obtained by trained physicians using the BpTRU device. The prevalence of uncontrolled RHTN and differences in BP measurements were compared. Results Of 130 patients with uncontrolled RHTN, 33.1% (n=43) were falsely identified as having uncontrolled RHTN based on triage BP measurements. The median (IQR) of differences in systolic BP between pseudoresistant and true resistant groups were 23 (17 – 33) mm Hg and 13 (6 – 21) mm Hg, respectively (P=0.0001). The median (IQR) of differences in diastolic BP between the two groups were 12 (7 – 18) mm Hg and 8 (4 – 11) mm Hg, respectively (P=0.001). Conclusion Triage BP technique overestimated the prevalence of uncontrolled RHTN in approximately 33% of the patients emphasizing the importance of obtaining accurate BP measurements. PMID:27129931

Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue.

PubMed Central

Nagle, R. B.; Hao, J.; Knox, J. D.; Dalkin, B. L.; Clark, V.; Cress, A. E.

1995-01-01

The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin-gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778688

Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese.

PubMed

He, Jiang; Kelly, Tanika N; Zhao, Qi; Li, Hongfan; Huang, Jianfeng; Wang, Laiyuan; Jaquish, Cashell E; Sung, Yun Ju; Shimmin, Lawrence C; Lu, Fanghong; Mu, Jianjun; Hu, Dongsheng; Ji, Xu; Shen, Chong; Guo, Dongshuang; Ma, Jixiang; Wang, Renping; Shen, Jinjin; Li, Shengxu; Chen, Jing; Mei, Hao; Chen, Chung-Shiuan; Chen, Shufeng; Chen, Jichun; Li, Jianxin; Cao, Jie; Lu, Xiangfeng; Wu, Xigui; Rice, Treva K; Gu, C Charles; Schwander, Karen; Hamm, L Lee; Liu, Depei; Rao, Dabeeru C; Hixson, James E; Gu, Dongfeng

2013-12-01

Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals' BP responses to dietary intervention and cold pressor test. We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 (P=7.29 × 10(-9)), CDCA7 (P=3.57 × 10(-8)), PIBF1 (P=1.78 × 10(-9)), ARL4C (P=1.86 × 10(-8)), IRAK1BP1 (P=1.44 × 10(-10)), SALL1 (P=7.01 × 10(-13)), TRPM8 (P=2.68 × 10(-8)), and FBXL13 (P=3.74 × 10(-9)). There was a strong dose-response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively (P=0.0003 for trend). Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.

Genome-Wide Association Study Identifies Eight Novel Loci Associated with Blood Pressure Responses to Interventions in Han Chinese

PubMed Central

He, Jiang; Kelly, Tanika N.; Zhao, Qi; Li, Hongfan; Huang, Jianfeng; Wang, Laiyuan; Jaquish, Cashell E.; Sung, Yun Ju; Shimmin, Lawrence C.; Lu, Fanghong; Mu, Jianjun; Hu, Dongsheng; Ji, Xu; Shen, Chong; Guo, Dongshuang; Ma, Jixiang; Wang, Renping; Shen, Jinjin; Li, Shengxu; Chen, Jing; Mei, Hao; Chen, Chung-Shiuan; Chen, Shufeng; Chen, Jichun; Li, Jianxin; Cao, Jie; Lu, Xiangfeng; Wu, Xigui; Rice, Treva K.; Gu, C. Charles; Schwander, Karen; Hamm, L. Lee; Liu, Depei; Rao, Dabeeru C.; Hixson, James E.; Gu, Dongfeng

2014-01-01

Background Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test (CPT) vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and CPT. Methods and Results We conducted a genome-wide association study of BP responses in 1,881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/day), a 7-day high-sodium (307.8 mmol/day), and a 7-day high-sodium plus potassium-supplementation (60 mmol/day). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified eight novel loci for BP phenotypes, which physically mapped in or near PRMT6 (P=7.29×10−9), CDCA7 (P=3.57×10−8), PIBF1 (P=1.78×10−9), ARL4C (P=1.86×10−8), IRAK1BP1 (P=1.44×10−10), SALL1 (P=7.01×10−13), TRPM8 (P=2.68×10−8), and FBXL13 (P=3.74×10−9). There was a strong dose-response relationship between the number of risk alleles of these independent SNPs and the risk of developing hypertension over 7.5-year follow-up in the study participants. Compared to those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively (P=0.0003 for trend). Conclusions Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and CPT. The effect size of these novel loci on BP phenotypes are much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline. PMID:24165912

Nesfatin-1 and Vitamin D levels may be associated with systolic and diastolic blood pressure values and hearth rate in polycystic ovary syndrome.

PubMed

Sahin, Figen Kir; Sahin, Serap Baydur; Ural, Ulku Mete; Cure, Medine Cumhur; Senturk, Senol; Tekin, Yesim Bayoglu; Balik, Gulsah; Cure, Erkan; Yuce, Suleyman; Kirbas, Aynur

2015-07-09

Obesity, insulin resistance (IR), inflammation, and hyperandrogenism may lead to polycystic ovary syndrome (PCOS) and hypertension. Nesfatin-1 (N1) may be related to IR, obesity, and hypertension. Furthermore, a vitamin D (VD) deficiency is associated with hypertension and PCOS. We aimed to investigate N1 and VD levels in PCOS that have an effect on systolic and diastolic blood pressure (BP) and heart rate (HR).This study included 54 patients with PCOS and 48 age-body mass index (BMI)-matched healthy controls. PCOS was diagnosed according to clinical practice guidelines. Ferriman-Gallwey scores (FGS) were calculated, while N1, VD, and other hormonal and biochemical parameters were measured for all subjects. Systolic and diastolic BP was measured as well. HR was calculated using an electrocardiogram.The levels of N1 (p < 0.001), high-sensitivity C-reactive protein (hs-CRP) (p = 0.036), homeostasis model assessment as an index of insulin resistance (HOMA-IR) (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) BP and HR (p < 0.001) in the PCOS group were significantly higher than in the control group. However, the VD levels of the PCOS group were lower than the control group (p = 0.004). N1 had a strong positive correlation with BMI, HOMA-IR, hs-CRP, luteinizing hormone, systolic and diastolic BP, and HR. VD levels were negatively correlated with HOMA-IR and luteinizing hormone.Elevated N1 and decreased VD levels may be related to the presence of high-normal BP or hypertension in PCOS subjects.  N1 level may be associated with an increased BP due to its relation to inflammation and IR.

Depressor effect of the young leaves of Polygonum hydropiper Linn. in high-salt induced hypertensive mice.

PubMed

Devarajan, Sankar; Yahiro, Eiji; Uehara, Yoshinari; Kuroda, Rieko; Hirano, Yoshio; Nagata, Kaori; Miura, Shinichiro; Saku, Keijiro; Urata, Hidenori

2018-06-01

A novel chymase inhibitor has been reported to have depressor effect in salt-induced hypertension. Therefore, we examined the hypothesis that chymase inhibitory dried young leaves of Polygonum hydropiper (PPH) or young leaves extract of Polygonum hydropiper (PHE) could reduce salt-induced hypertension. In this study, 8-wk old wild-type mice were allocated into three experiments and experiment I included groups, I- normal water drinking, II- high salt (2% NaCl) water (HSW) drinking, and III- HSW plus PPH (500 mg kg -1 , orally) for 12-wk. Blood pressure (BP) and heart rate (HR) were measured at baseline and weekly up to wk-12. In experiment II, mice were given HSW for 12-wk followed by 8-wk treatment with PPH plus HSW (62.5, 125, 250 and 500 mg kg -1 for groups I, II, III and IV, respectively). BP and HR were measured at baseline and monthly until wk-12, following weekly for 8-wk. Experiment III comprised of four groups of mice for 12-wk HSW and 8-wk treatment with PHE plus HSW (2.5, 5, 10 and 20 mg kg -1 for groups I-IV, respectively). BP and HR were measured at baseline and monthly up to wk-12, following weekly for 8-wk. Significant reduction in BP and HR were observed in mice treated with PPH (500 mg kg -1 ) compared to HSW control. PPH reduced BP and HR dose dependently in hypertensive mice and the higher dose showed maximum reduction. PHE at its maximum dose (20 mg kg -1 ) significantly suppressed BP and HR. Over all, we found that the young leaves of Polygonum hydropiper suppressed salt-induced hypertension. Copyright © 2018. Published by Elsevier Masson SAS.

Delayed systolic blood pressure recovery following exercise as a mechanism of masked uncontrolled hypertension in chronic kidney disease.

PubMed

Agarwal, Rajiv; Pappas, Maria K

2017-10-01

Among people treated for hypertension, the presence of elevated blood pressure (BP) out of the clinic but normal BP in the clinic is called masked uncontrolled hypertension (MUCH). What causes MUCH remains unknown. The purpose of this study was to answer the question of whether patients with MUCH have an increased hemodynamic reactivity to exercise and delayed hemodynamic recovery following exercise. Four groups were compared: controlled hypertension (CH, n = 58), MUCH (n = 34) and uncontrolled hypertension (UCH, n = 12), all of which had chronic kidney disease (CKD), and a group of healthy normal volunteers who did not have hypertension or CKD (n = 16). All participants underwent assessment of 24-h ambulatory BP monitoring, BP measurement during a graded symptom-limited exercise using a cycle ergometer and BP recovery over 7 min following exercise. Exercise-induced increase in systolic BP was similar among the four groups. When compared with healthy controls, recovery of systolic BP following termination of exercise was blunted among the CKD groups in unadjusted (P < 0.0001) and adjusted (P < 0.001) models. During recovery, the healthy control group had 5.9% decline in systolic BP per minute. In contrast, MUCH had only 3.3% per minute reduction and the UCH group had 0.3% reduction per minute. A test of linear trend was significant (P = 0.002, adjusted model). Because there was no impairment in the heart rate recovery among groups, we speculate that the parasympathetic pathway appears intact among treated hypertensives with CKD. However, the failure to withdraw sympathetic tone upon termination of exercise causes ongoing vasoconstriction and delayed systolic BP recovery providing a biological basis for MUCH. Delayed recovery from exercise-induced hypertension in those with poorly controlled BP provides potentially a new target to assure round-the-clock BP control. Published by Oxford University Press on behalf of ERA-EDTA 2016. This work is written by US Government employees and is in the public domain in the US.

The Relationship Between Cognitive Functioning and the JNC-8 Guidelines for Hypertension in Older Adults

PubMed Central

Hajjar, Ihab M.; Dunn, Callie B.; Levey, Allan I.; Wharton, Whitney

2017-01-01

Background: Guidelines for hypertension treatment by the Eighth Joint National Committee (JNC-8) in 2014 recommended a target systolic blood pressure (BP) of <150/<90 mmHg in persons older than 60 years, in contrast to the 2003 JNC-7 recommendations of systolic BP <140 mmHg. This study evaluated the implications of raising the BP target on cognitive functioning and conversion from normal cognition to mild cognitive impairment (MCI). Methods: This was a longitudinal study of individuals older than 60 years enrolled in the NIH-NIA Alzheimer’s Disease Centers. All had normal cognition at baseline. 453 participants were taking BP medications and had readings of <140/<90 mmHg at four annual visits (reference group). Two other groups consisted of participants with either systolic BP of 140–149 mmHg (n = 112) or ≥150 mmHg (n = 280) on three or four annual visits. Results: Compared with the reference and the 140–149 mmHg groups, those with BP ≥150 mmHg exhibited poorer cognitive status by Year 4 on the Mini-Mental State Exam, and they had a higher risk of conversion to MCI. The 140–149 mmHg exhibited poorer performance than the reference group on domains assessing attention and executive functioning. In contrast, their performance was not significantly different from those with BP ≥150 mmHg. Conclusions: Persons with BP ≥150 mmHg show a faster global cognitive decline and transition to MCI than those with lower BP readings. However, the poor cognitive performance in the attention and executive functioning domains for the 140–149 mmHg group indicates the need for further research evaluating the newer recommended cutoff. PMID:27678289

Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin.

PubMed

Liu, Kang; Lin, Fang-Tsyr; Graves, Joshua D; Lee, Yu-Ju; Lin, Weei-Chin

2017-05-09

Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress. The effect on ATR response caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR-activating function during replication stress, TopBP1 interacts with Treslin in a Cdk-dependent manner to initiate DNA replication during normal growth. We find that mutp53 also interferes with TopBP1 replication function. Several contact, but not conformational, mutp53s enhance the interaction between TopBP1 and Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor. Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA replication: ( i ) Both contact and conformational mutp53s can bind TopBP1 and attenuate the checkpoint response to replication stress, and ( ii ) during normal growth, contact (but not conformational) mutp53s can override the Cdk2 requirement to promote replication by facilitating the TopBP1/Treslin interaction.

Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET.

PubMed

Wong, Dean F; Brasić, James R; Singer, Harvey S; Schretlen, David J; Kuwabara, Hiroto; Zhou, Yun; Nandi, Ayon; Maris, Marika A; Alexander, Mohab; Ye, Weiguo; Rousset, Olivier; Kumar, Anil; Szabo, Zsolt; Gjedde, Albert; Grace, Anthony A

2008-05-01

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DA(rel)) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DA rel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D(2)-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DA rel and 5-HT2A BP, when compared with TS-OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DA rel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DA rel, suggest a condition of increased phasic DA rel modulated by low 5-HT in concomitant OCD.

Experimental selective elevation of renal medullary blood flow in hypertensive rats: evidence against short-term hypotensive effect.

PubMed

Bądzyńska, B; Sadowski, J

2012-08-01

Renal medullary blood flow (MBF) can be selectively increased by intrarenal or systemic infusion of bradykinin (Bk) in anaesthetized normotensive rats. We reproduced this effect in a number of rat models of arterial hypertension and examined whether increased perfusion of the renal medulla can cause a short-term decrease in blood pressure (BP) that is not mediated by increased renal excretion and depletion of body fluids. In uninephrectomized Sprague-Dawley rats, BP was elevated to approx. 145 mmHg by acute i.v. infusion of noradrenaline (NA) or angiotensin II (Ang II) (groups 1, 2), 2-week exposure to high-salt diet (3), high-salt diet + chronic low-dose infusion of Ang II using osmotic minipumps (4) or chronic high-dose Ang II infusion on normal diet (5). Uninephrectomized spontaneous hypertensive rats (SHR) were also examined (6,7). To selectively increase medullary perfusion, in anaesthetized rats, bradykinin was infused during 30-75 min into the renal medullary interstitium or intravenously. Bradykinin increased outer- and inner-medullary blood flow (laser-Doppler fluxes) by 10-20% in groups (1, 2), by 30-50% in groups (3, 4, 5) and approx. 20% in SHR (6, 7). The concurrent increase in total renal blood flow (Transonic probe) was < 3%. A minor (<3%) decrease in BP was seen only in rats acutely rendered hypertensive by NA or Ang II infusions; however, the decreases in BP and increases in medullary perfusion were not correlated. Thus, there was no evidence that in hypertensive rats, substantial selective increases in medullary perfusion can cause a short-term decrease in BP. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Is increased uric acid a risk factor or a defensive response? The Campania Salute Network.

PubMed

Mancusi, C; Izzo, R; Ferrara, L A; Rozza, F; Losi, M A; Canciello, G; Pepe, M; de Luca, N; Trimarco, B; de Simone, G

2018-05-04

Circulating uric acid (UA) is positively associated with body mass index (BMI), blood glucose, blood pressure (BP), markers of inflammation, and altered lipid profile. UA has also anti-oxidative properties which might be beneficial for cardiovascular (CV) system. It is still debated whether or not UA is independently associated with increased CV morbidity and/or mortality. We studied prognostic impact of UA in 8833 hypertensive adults (mean age 53 ± 12 yrs, 3857 women) from the Campania Salute Network, without prevalent CV disease and more than stage 3 CKD. We calculated standardized UA Z-score, adjusted for age, sex, glomerular filtration rate, and BMI. Low and high UA and UA Z-score quartiles were compared to the 2 middle quartiles assumed to be "normal". Prevalence of obesity and diabetes was higher in low and high than in normal UA Z-score group (all p < 0.001). Systolic BP, left ventricular mass, carotid intima thickness were significantly higher and ejection fraction was reduced in the presence of high UA Z-score (all p < 0.001). Over 33-months average follow-up, incident major CV end-points (MACE) were not significantly different among low, normal and high UA or UA Z-score. In the latter analysis, however, incident MACE tended to be more frequent in the low than the high UA Z-score. Despite the results of multivariable analyses, the effect of less aggressive therapy in low UA Z-score cannot be excluded with certainty. In treated hypertensive patients, high levels of UA normalized for major biological determinants do not independently predict CV outcome. CLINICALTRIALS. NCT02211365. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Effects of acute dietary nitrate supplementation on aortic blood pressure and aortic augmentation index in young and older adults.

PubMed

Hughes, William E; Ueda, Kenichi; Treichler, David P; Casey, Darren P

2016-09-30

Aging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults. Noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 ± 4 years, n = 14; older: 64 ± 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. Nitrate consumption increased plasma nitrite in both groups 60-180 min following beetroot consumption (P < 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P < 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, -4.3 to -8.8%, P < 0.05), whereas aortic AIx remained unchanged in the older adults. Taken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes.

PubMed

Gaillard, María Emilia; Bottero, Daniela; Errea, Agustina; Ormazábal, Maximiliano; Zurita, M Eugenia; Moreno, Griselda; Rumbo, Martin; Castuma, Celina; Bartel, Erika; Flores, Dario; van der Ley, Peter; van der Ark, Arno; F Hozbor, Daniela

2014-02-12

Despite high vaccination coverage rates, pertussis continues to be a global concern, with increased incidence widely noted. The current pertussis epidemiologic situation has been mainly attributed to waning immunity and pathogen adaptation. To improve the disease control, a new generation of vaccines capable to overcome those weaknesses associated to the current vaccines need to be developed. Previously we have demonstrated that the outer membrane vesicles obtained from the recombinant Bordetella pertussis strain expressing PagL enzyme (OMVs(BpPagL)) are good vaccine candidates to protect against pertussis. In this work the OMVs(BpPagL) formulated with diphtheria and tetanus toxoids (Tdap(OMVsBpPagL)) was used to evaluate its capacity to offer protection against Argentinean clinical isolates and to induce long-term immunity. To these aims BALB/c mice were immunized with Tdap(OMVsBpPagL) and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of Tdap(OMVsBpPagL) were performed. With the normalized doses of both vaccines we observed that Tdap(OMVsBpPagL) protected against the clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Regarding long-term immunity we observed that the Tdap(OMVsBpPagL) protective capacity against the recommended WHO reference strain persisted at least 9 months. In agreement with these results Tdap(OMVsBpPagL) induced Th1 and Th2 immune response. In contrast, commercial Tdap induced Th2 but weak Th1 responses. All results presented here showed that Tdap(OMVsBpPagL) is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of bee products on pentylenetetrazole-induced seizures in the rat.

PubMed

Zárraga-Galindo, N; Vergara-Aragón, P; Rosales-Meléndez, S; Ibarra-Guerrero, P; Domínguez-Marrufo, L E; Oviedo-García, R E; Hernández-Ramírez, H; Hernández-Téllez, B; López-Martínez, I E; Sánchez-Cervantes, I; Vázquez-García, M; Santiago, J

2011-01-01

Bee products (BP) have been used for centuries as a diet complement with claimed curative properties. The aim of this study was to determine whether oral administration of BP prevented behavioral, histological, and biochemical alterations, caused by pentylenetetrazole (PTZ)-induced kindling in rats. Male Wistar rats were employed to evaluate seizure latency, number and duration, performance in the open field test, histological alterations and mortality following BP administration. Oral administration of BP at two doses, 30 and 60 mg/kg/day, significantly lengthened latency of both clonic and tonic PTZ-induced seizures, decreased the duration and frequency of seizures and reduced mortality. In the Open Field test, BP treated groups showed increases in the number of crossed squares and rearing counts, and on optimal dose, decreases in fecal boli. Histological analysis showed in PTZ (50 and 80 mg/kg) kindling rats, lungs with inflammatory peribronchiolar, and perialveolar infiltrates. In the liver, mild losses of trabeculae, multi-vesiculated hepatocytes (steatosis) and inflammatory infiltrates in hepatic parenchyma were observed. Interestingly, in the heart, fibers were markedly separated. In testis, stratified epithelium of seminal tubules lost its normal structure, tubules had epithelium loss, spermatids were absent, and spermatogonia and Leydig cells diminished. In PTZ kindling rats treated with BP, the lungs had no inflammatory infiltrates, although the heart showed some inflammatory infiltrates. Remaining structures had normal characteristics. These results, suggest that BP can protect rats from effects of PTZ-induced kindling.

Novel and differential accumulation of mitochondrial DNA deletions in Swedish and vietnamese patients with colorectal cancer.

PubMed

Dimberg, Jan; Hong, Thai Trinh; Skarstedt, Marita; Löfgren, Sture; Zar, Niklas; Matussek, Andreas

2014-01-01

Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and aging. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in colorectal cancer (CRC). In the present study, we aimed to evaluate the frequency of mtDNA 4977 bp deletion in CRC tissues and its association with clinical factors. We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 105 Swedish and 88 Vietnamese patients with CRC using polymerase chain reaction (PCR) assays. The mtDNA 4977 bp deletion was shown to be significantly more frequent in normal tissues in comparison with paired cancer tissues in both Swedish and Vietnamese patients. The 4977 bp common deletion was significantly more frequent in cancer tissues of the Vietnamese patients compared to the Swedish patients, and in Vietnamese cancer tissues, the 4977 bp deletion was significantly over represented in those with localized disease compared to those with disseminated disease. Moreover, we detected nine novel mtDNA deletions and found a significantly higher rate of these in CRC tissues in Swedish in comparison to Vietnamese patients. The mtDNA 4977 bp deletion seems to have an impact on the clinical outcome of CRC in Vietnamese patients, that the Swedish patients accumulate more of the detected novel deletions in CRC tissue compared to Vietnamese patients probably indicates divergent mechanisms in colorectal carcinogenesis.

Children and Adolescent Obesity Associates with Pressure-Dependent and Age-Related Increase in Carotid and Femoral Arteries' Stiffness and Not in Brachial Artery, Indicative of Nonintrinsic Arterial Wall Alteration

PubMed Central

García-Espinosa, Victoria; Curcio, Santiago; Castro, Juan Manuel; Arana, Maite; Giachetto, Gustavo; Chiesa, Pedro; Zócalo, Yanina

2016-01-01

Aim. To analyze if childhood obesity associates with changes in elastic, transitional, and/or muscular arteries' stiffness. Methods. 221 subjects (4–15 years, 92 females) were assigned to normal weight (NW, n = 137) or obesity (OB, n = 84) groups, considering their body mass index z-score. Age groups were defined: 4–8; 8–12; 12–15 years old. Carotid, femoral, and brachial artery local stiffness was determined through systodiastolic pressure-diameter and stress-strain relationships. To this end, arterial diameter and peripheral and aortic blood pressure (BP) levels and waveforms were recorded. Carotid-femoral, femoropedal, and carotid-radial pulse wave velocities were determined to evaluate aortic, lower-limb, and upper-limb regional arterial stiffness, respectively. Correlation analysis between stiffness parameters and BP was done. Results. Compared to NW, OB subjects showed higher peripheral and central BP and carotid and femoral stiffness, reaching statistical significance in subjects aged 12 and older. Arterial stiffness differences disappeared when levels were normalized for BP. There were no differences in intrinsic arterial wall stiffness (elastic modulus), BP stiffness relationships, and regional stiffness parameters. Conclusion. OB associates with BP-dependent and age-related increase in carotid and femoral (but not brachial) stiffness. Stiffness changes would not be explained by intrinsic arterial wall alterations but could be associated with the higher BP levels observed in obese children. PMID:27066273

Elevated blood pressure at the first measurement predicts cardiovascular disease independently from the subsequent second reading in men, but not in women.

PubMed

Makita, Shinji; Tanaka, Fumitaka; Onoda, Toshiyuki; Ohsawa, Masaki; Tanno, Kozo; Omama, Shinichi; Yoshida, Yuki; Ishibashi, Yasuhiro; Segawa, Toshie; Takahashi, Tomohiro; Satoh, Kenyu; Itai, Kazuyoshi; Sakata, Kiyomi; Ohta, Mutsuko; Kuribayashi, Toru; Ogasawara, Kuniaki; Ogawa, Akira; Okayama, Akira; Nakamura, Motoyuki

2015-01-01

There have been no investigations concerning the association of each blood pressure (BP) reading with future cardiovascular disease (CVD) when multiple measurements are taken on one occasion. This community-based, prospective cohort study (n = 23 344, mean age = 62.4 years) investigated the associations between the BP obtained from the first and second of two consecutive measurements on one occasion and future cardiovascular events in men and women. During the mean follow-up of 5.5 years, 624 CVD events were identified. On the Cox regression analysis of age- and BP-adjusted models, the increased CVD risk of a hypertensive first measurement (systolic BP ≥ 140 mmHg) was independent from the second measurement in men. Even in subjects without a hypertensive second measurement, the CVD risk of the hypertensive first measurement was increased in men. In women, despite a hypertensive first measurement, subjects with a systolic BP < 130 mmHg on the second measurement showed a significantly reduced risk for CVD compared with subjects who retained a hypertensive level during the two measurements. An elevated BP on the first measurement should not be disregarded for CVD risk estimation in men, even if the second BP moves to the normal range. In women, elevated BP on the first measurement may have relatively less meaning for CVD prediction if the second BP shifts to a normal range.

Ratio of mBDNF to proBDNF for Differential Diagnosis of Major Depressive Disorder and Bipolar Depression.

PubMed

Zhao, Guoqing; Zhang, Chen; Chen, Jun; Su, Yousong; Zhou, Rubai; Wang, Fan; Xia, Weiping; Huang, Jia; Wang, Zuowei; Hu, Yingyan; Cao, Lan; Guo, Xiaoyun; Yuan, Chengmei; Wang, Yong; Yi, Zhenghui; Lu, Weihong; Wu, Yan; Wu, Zhiguo; Hong, Wu; Peng, Daihui; Fang, Yiru

2017-09-01

There is a high rate of misdiagnosis between major depressive disorder (MDD) and bipolar disorder (BD) in clinical practice. Our previous work provided suggestive evidence for brain-derived neurotrophic factor (BDNF) in differentiating BD from MDD. In this study, we aimed to investigate the role of mature BDNF (mBDNF) and its precursor (proBDNF) in distinguishing bipolar depression (BP) from MDD during acute depressive episode. A total of 105 participants, including 44 healthy controls, 37 MDD patients and 24 BP patients, were recruited. Enzyme-linked immunosorbent assay kits were applied to measure plasma mBDNF levels and proBDNF levels of all participants. Plasma mBDNF levels were significantly decreased in BP group than those in MDD group (P = 0.001) and healthy controls (P = 0.002). Significantly higher ratio of mBDNF to proBDNF (M/P) at baseline was showed in MDD group than those in BP group as well as in healthy controls (P = 0.000 and P = 0.000, respectively). The optimal model for discriminating BP was the M/P ratio (area under the ROC curve = 0.858, 95 % CI 0.753-0.963). Furthermore, the M/P ratio was restored to normal levels after antidepressants treatment in MDD group. In summary, our data demonstrated that both plasma mBDNF levels and M/P ratio were lower in BP compared with MDD. These findings further support M/P ratio as a potential differential diagnostic biomarker for BP among patients in depressive episodes.

[24-Hour blood pressure profile in patients with mild and moderate arterial hypertension and sleep apnea/hypopnea].

PubMed

Zelveian, P A; Oshchepkova, E V; Buniatian, M S; Badikov, D N; Rogoza, A N

2001-01-01

To evaluate 24-hour blood pressure (BP) profile in arterial hypertension (AH) patients (pts) with desaturation signs of sleep apnea/hypopnea syndrome (SAHS). We investigated 61 pts (44 males and 17 females) aged between 23-70 (52 +/- 2) years with mild to moderate AH. BP monitoring was performed with multisensor system TM-2425 (A&D, Japan). We assessed the following parameters: mean 24-h, awake, sleep systolic (S), diastolic (D) and pulse (P) BPs, systolic and diastolic BP loads ("normalized area under the curve"--NAUC). A normal circadian rhythm of BP was defined when nocturnal fall of SBP was > 10% and < 20%. The morning rise of BP we assessed by speed of increase of mean BP from 4 a.m. to 12 a.m. The nocturnal monitoring of arterial oxygen saturation(SaO2) was performed with pulseoximeter "NONIN 8500M" (USA). The analysis of the results was performed with the original program ARM-SaO2". The presence of SAHS was confirmed when the number of 4% desaturations were greater than 15 per hour or in the presence of group episodes of 4% desaturation below 90%. In 19 pts we revealed desaturation signs of SAHS. The comparison group included pts without SAHS (n = 42). We compared the groups regarding 24-h BP profile parameters. SAHS group had the following parameters significantly higher: mean 24-h (151.7 +/- 4.5 vs 142.9 +/- 2.4 mm Hg, p < 0.07) and sleep SBPs (142.8 +/- 5.1 vs 132.7 +/- 2.6 mm Hg, p < 0.05); mean 24-h (65.2 +/- 2.6 vs 55.9 +/- 1.9 mm Hg, p < 0.008), daytime (65.6 +/- 2.7 vs 56.6 +/- 2.0 mm Hg, p < 0.01) and sleep PBPs (64.1 +/- 2.7 vs 53.1 +/- 1.9 mm Hg, p < 0.002); 24-h (20.1 +/- 3.8 vs 12.6 +/- 1.8 mm Hg, p < 0.05) and sleep NAUC of SBP (24.6 +/- 4.4 vs 15.3 +/- 2.2 mm Hg, p < 0.03). In the group with SAHS were significantly higher the frequency of abnormal circadian rhythm of SBP (84 vs 57%, p < 0.05) and the speed of morning rise of mean BP (23.3 +/- 5.9 vs 8.5 +/- 2.8 mm Hg/h, p < 0.01). Our results suggest that pts with desaturation signs of SAHS are characterized by unfavourable changes in 24-h BP profile parameters, first of all owning to sleep systolic and pulse blood pressures with alteration of circadian rhythm and high speed of morning rise of BP.

Effect of nitroglycerin administration on cardio-ankle vascular index

PubMed Central

Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

2016-01-01

Purpose The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). Subjects and methods The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey–Kramer test was used for post hoc comparisons. Results In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (−1.4±0.7 vs −1.4±0.9, −1.1±0.7 vs −1.4±1.0, −0.8±0.7 vs −1.2±1.0, and −0.5±0.7 vs −1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes (normal controls vs CAD; −3±7 vs −10±11, −3±5 vs −10±11, −3±6 vs −13±10, and −1±6 vs −11±10 mmHg, respectively). ΔDiastolic BP in the normal controls was significantly higher than in the CAD patients at 5 and 10 minutes (normal controls vs CAD; −8±6 vs −4±4 and −9±4 vs −6±5 mmHg, respectively). Conclusion After NTG administration, the stiffness of the arteries from the origin of the aorta to the ankle as measured by CAVI decreased in both the normal controls and CAD patients, indicating that the response of arterial smooth muscle cells to nitric oxide is preserved even in CAD patients under medication. PMID:27536126

An Examination of the Behavioral and Neuropsychological Correlates of Three ADHD Candidate Gene Polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40bp VNTR) in Hyperactive and Normal Children Followed to Adulthood

PubMed Central

Barkley, Russell A.; Smith, Karen M.; Fischer, Mariellen; Navia, Bradford

2008-01-01

Several candidate gene polymorphisms have been implicated in attention deficit hyperactivity disorder (ADHD), including DAT1 40bp VNTR, DRD4 7+, and DBH TaqI A2 alleles. We used the Milwaukee longitudinal study of hyperactive (N=122) and normal (N=67) children to compare participants with and without these respective polymorphisms on ADHD-related behavioral ratings at childhood, 8 years later in adolescence, and 13+ years later into young adulthood. Neuropsychological tests were given at the adolescent and young adulthood follow-up. No differences were found between the DRD4-7+ and 7- repeat polymorphism. The DBH TaqI A2 allele, when homozygous, was associated with being more hyperactive in childhood, having more pervasive behavior problems at adolescence, and earning less money on a Card Playing Task in adulthood. At adolescence, poorer test scores were also found only in the hyperactive group with homozygous for this allele. The DAT1 40bp VNTR heterozygous 9/10 repeat, however, differed from the 10/10 repeat pair in many respects, having greater ADHD and externalizing symptoms at all three follow-ups, more cross-situational behavioral problems at both childhood and adolescence, poorer mother-teen relations at adolescence, and lower class rankings in high school. Participants with the 9/10 pair in the control group also had lower work performance, a lower grade point average in high school, greater teacher rated externalizing symptoms at adolescence, and greater omission errors on a continuous performance test in adulthood. The DAT1 40bp VNTR 9/10 polymorphism pairing appears to be reliably associated with greater symptoms of ADHD and externalizing behavior from childhood to adulthood, and with family, educational, and occupational impairments. We also present a contrary view on the appropriate endophenotypes for use in behavioral genetic research on ADHD. PMID:16741944

Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome.

PubMed

van Bon, B W M; Mefford, H C; Menten, B; Koolen, D A; Sharp, A J; Nillesen, W M; Innis, J W; de Ravel, T J L; Mercer, C L; Fichera, M; Stewart, H; Connell, L E; Ounap, K; Lachlan, K; Castle, B; Van der Aa, N; van Ravenswaaij, C; Nobrega, M A; Serra-Juhé, C; Simonic, I; de Leeuw, N; Pfundt, R; Bongers, E M; Baker, C; Finnemore, P; Huang, S; Maloney, V K; Crolla, J A; van Kalmthout, M; Elia, M; Vandeweyer, G; Fryns, J P; Janssens, S; Foulds, N; Reitano, S; Smith, K; Parkel, S; Loeys, B; Woods, C G; Oostra, A; Speleman, F; Pereira, A C; Kurg, A; Willatt, L; Knight, S J L; Vermeesch, J R; Romano, C; Barber, J C; Mortier, G; Pérez-Jurado, L A; Kooy, F; Brunner, H G; Eichler, E E; Kleefstra, T; de Vries, B B A

2009-08-01

Recurrent 15q13.3 microdeletions were recently identified with identical proximal (BP4) and distal (BP5) breakpoints and associated with mild to moderate mental retardation and epilepsy. To assess further the clinical implications of this novel 15q13.3 microdeletion syndrome, 18 new probands with a deletion were molecularly and clinically characterised. In addition, we evaluated the characteristics of a family with a more proximal deletion between BP3 and BP4. Finally, four patients with a duplication in the BP3-BP4-BP5 region were included in this study to ascertain the clinical significance of duplications in this region. The 15q13.3 microdeletion in our series was associated with a highly variable intra- and inter-familial phenotype. At least 11 of the 18 deletions identified were inherited. Moreover, 7 of 10 siblings from four different families also had this deletion: one had a mild developmental delay, four had only learning problems during childhood, but functioned well in daily life as adults, whereas the other two had no learning problems at all. In contrast to previous findings, seizures were not a common feature in our series (only 2 of 17 living probands). Three patients with deletions had cardiac defects and deletion of the KLF13 gene, located in the critical region, may contribute to these abnormalities. The limited data from the single family with the more proximal BP3-BP4 deletion suggest this deletion may have little clinical significance. Patients with duplications of the BP3-BP4-BP5 region did not share a recognisable phenotype, but psychiatric disease was noted in 2 of 4 patients. Overall, our findings broaden the phenotypic spectrum associated with 15q13.3 deletions and suggest that, in some individuals, deletion of 15q13.3 is not sufficient to cause disease. The existence of microdeletion syndromes, associated with an unpredictable and variable phenotypic outcome, will pose the clinician with diagnostic difficulties and challenge the commonly used paradigm in the diagnostic setting that aberrations inherited from a phenotypically normal parent are usually without clinical consequences.

Trait anxiety mimics age-related cardiovascular autonomic modulation in young adults.

PubMed

Sanchez-Gonzalez, M A; Guzik, P; May, R W; Koutnik, A P; Hughes, R; Muniz, S; Kabbaj, M; Fincham, F D

2015-04-01

Anxiety produces maladaptive cardiovascular changes and accelerates biological aging. We evaluated cardiovascular reactivity in young and middle-aged individuals with varying anxiety scores to test the hypothesis that anxiety mimics cardiovascular aging by influencing cardiovascular autonomic modulation. The State-Trait Anxiety Inventory was used to classify healthy young individuals (20-29 years) into high (YHA, n=22;10 men) and low (YLA, n=21;10 men) anxiety, and to identify middle-aged individuals (50-60 years) with low anxiety (MLA, n=22;11 men). Heart rate, blood pressure (BP) and their variability (HRV and BPV, respectively) and baroreflex function were analyzed from beat-to-beat finger BP and electrocardiogram recordings collected during 5-min baseline, 6-min speech task (ST) and 3-min post ST recovery. Analyses of covariance showed significant differences (P<0.05) at baseline for HRV, BPV and barorelfex, and low-frequency power of systolic BP variability (LFSBP) was lower, whereas baroreflex and high frequency (HF) normalized units were higher in the YLA compared with YHA and MLA groups. Compared with YLA, YHA and MLA displayed attenuated vagal withdraw response (HF) to ST. BP and LFSBP responses to ST in YHA and MLA were higher compared with the YLA group. These findings suggest that anxiety could be linked to cardiovascular aging as it attenuates cardiac reactivity and exaggerates vascular responses to stress.

Pharmacodynamic and pharmacokinetic studies and prostatic tissue distribution of fosfomycin tromethamine in bacterial prostatitis or normal rats.

PubMed

Fan, L; Shang, X; Zhu, J; Ma, B; Zhang, Q

2018-05-02

In this study, we assessed the therapeutic effects of fosfomycin tromethamine (FT) in a bacterial prostatitis (BP) rat model. The BP model was induced by Escherichia coli and was demonstrated after 7 days microbiologically and histologically. Then, 25 BP rats selected were randomly divided into five treatment groups: model group, positive group, FT-3 day group, FT-7 day group and FT-14 day group. Ventral lobes of prostate from all animals were removed, and the serum samples were collected at the end of the experiments. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in FT-treatment groups compared with the model group, indicating that FT against prostatic infection induced by E. coli showed good antibacterial effects. Moreover, plasma pharmacokinetics and prostatic distribution of fosfomycin were studied and compared in BP and normal rats. The concentrations of fosfomycin in samples were analysed by liquid chromatography-tandem mass spectrometry. There were no differences in plasma pharmacokinetic parameters between two groups. But significantly higher penetration of fosfomycin into prostatic tissues was found in BP rats. We therefore suggested that FT had a good therapeutic effect on BP and it might be used in curing masculine reproductive system diseases. © 2018 Blackwell Verlag GmbH.

Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway

PubMed Central

Arad, Shiri; Le, Phuong T.; Bustin, Michael; Rosen, Clifford J.; Gabet, Yankel

2015-01-01

Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3−/− mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3−/− mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3−/− bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3−/− mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components. PMID:26402843

Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway.

PubMed

Garfinkel, Benjamin P; Arad, Shiri; Le, Phuong T; Bustin, Michael; Rosen, Clifford J; Gabet, Yankel; Orly, Joseph

2015-12-01

Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3(-/-) mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3(-/-) mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3(-/-) bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3(-/-) mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components.

Variable Penetrance of the 15q11.2 BP1-BP2 Microduplication in a Family with Cognitive and Language Impairment

PubMed Central

Benítez-Burraco, Antonio; Barcos-Martínez, Montserrat; Espejo-Portero, Isabel; Jiménez-Romero, Salud

2017-01-01

The 15q11.2 BP1-BP2 region is found duplicated or deleted in people with cognitive, language, and behavioral impairment. We report on a family (a father and 3 male twin siblings) that presents with a duplication of the 15q11.2 BP1-BP2 region and a variable phenotype: the father and the fraternal twin are normal carriers, whereas the monozygotic twins exhibit severe language and cognitive delay as well as behavioral disturbances. The genes located within the duplicated region are involved in brain development and function, and some of them are related to language processing. The probands' phenotype may result from changes in the expression level of some of these genes important for cognitive development. PMID:28588435

Fabrication and characterization of buckypapers for use in air sampling

NASA Astrophysics Data System (ADS)

Oh, Jonghwa

Occupational exposure to volatile organic compounds (VOCs) is a concern from a public health perspective. In many industrial activities, workers' exposure to VOCs can be sufficiently high to induce adverse health effects, so their monitoring is necessary. In exposure assessment, post sampling extraction and quantification are the typical analytical procedures. Recently, our group developed the photothermal desorption (PTD) technique in which a pulse of light thermally desorbs an analyte directly from a sorbent. Advantages of this technique are; it is solvent free, repeated analysis is possible, sorbents are reusable, and no high cost of equipment is required. PTD overcomes almost all drawbacks of current extraction methods. This study was aimed to develop and test a new sorbent which will efficiently work with PTD. Single-walled carbon nanotubes (SWNTs) were examined as potential sorbents because of their high surface area, great thermal conductivity, and efficient light absorption. SWNTs were fabricated into a self-supporting form (i.e., buckypaper (BP)) which will preserve its physical integrity under normal working conditions. Largely two types of SWNTs were used, arc discharge (AD) and high-pressure carbon monoxide (HiPco), and different fabrication methods were examined. Upon fabrication, their adsorption properties were characterized in terms of Brunauer, Emmett, and Teller (BET) surface area, pore size, and toluene adsorption capacity. HiPco BP and methanol-cleaned AD BP (suspended/rinsed with methanol) were the top two materials, showing the highest surface area (649 and 387 m²/g, respectively) and adsorption capacity (106 and 46 mg/g, respectively) with relatively small mean pore diameter (7.7 and 8.8 nm, respectively). To further improve the adsorption properties, specific heat treatment conditions for each type of BPs were employed. After initial treatments only HiPco BP and acetone-cleaned AD BP (suspended/rinsed with acetone) were selected for further investigations based on obtained surface area (933 and 970 m²/g, respectively) and physical integrity. These two BPs were then examined for PTD and the AD BP showed higher recovery rate (0.016 - 0.431 %) at all energy levels examined (1.84 - 7.37 J). The AD BP has been shown to be an efficient sorbent for toluene and possibly a good candidate for PTD.

The First Report of a 290-bp Deletion in β-Globin Gene in the South of Iran

PubMed Central

Hamid, Mohammad; Nejad, Ladan Dawoody; Shariati, Gholamreza; Galehdari, Hamid; Saberi, Alihossein; Mohammadi-Anaei, Marziye

2017-01-01

Background: β-thalassemia is one of the most widespread diseases in the world, including Iran. In this study, we reported, for the first time, a 290-bp β-globin gene deletion in the south of Iran. Methods: Four individuals from three unrelated families with Arabic ethnic background were studied in Khuzestan Province. Red blood cell indices and hemoglobin analysis were carried out according to the standard methods. Genomic DNA was obtained from peripheral blood cells by salting out procedures. β-globin gene amplification, multiplex ligation-dependent probe amplification (MLPA), and DNA sequencing were performed. Results: The PCR followed by sequencing and MLPA test of the β-globin gene confirmed the presence of a 290-bp deletion in the heterozygous form, along with -88C>A mutation. All the individuals had elevated hemoglobin A2 and normal fetal hemoglobin levels. Conclusions: This mutation causes β0-thalassemia and can be highly useful for prenatal diagnosis in compound heterozygous condition with different β-globin gene mutations. PMID:26948378

DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy.

PubMed

Kinashi, Yuko; Yokomizo, Natsuya; Takahashi, Sentaro

2017-04-01

To use the 53BP1 foci assay to detect DNA double-strand breaks induced by fractionated neutron beam irradiation of normal cells. The Kyoto University Research Reactor heavy-water facility and gamma-ray irradiation system were used as experimental radiation sources. After fixation of Chinese Hamster Ovary cells with 3.6% formalin, immunofluorescence staining was performed. Number and size of foci were analyzed using ImageJ software. Fractionated neutron irradiation induced 25% fewer 53BP1 foci than single irradiation at the same dose. By contrast, gamma irradiation induced 30% fewer 53BP1 foci than single irradiation at the same dose. Fractionated neutron irradiation induced larger foci than gamma irradiation, raising the possibility that persistent unrepaired DNA damage was amplified due to the high linear energy transfer component in the neutron beam. Unrepaired cluster DNA damage was more prevalent after fractionated neutron irradiation than after gamma irradiation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Blood Pressure Gradients and Cardiovascular Risk Factors in Urban and Rural Populations in Abia State South Eastern Nigeria Using the WHO STEPwise Approach

PubMed Central

Okpechi, Ikechi Gareth; Chukwuonye, Innocent Ijezie; Tiffin, Nicki; Madukwe, Okechukwu Ojoemelam; Onyeonoro, Ugochukwu Uchenna; Umeizudike, Theophilus Ifeanyichukwu; Ogah, Okechukwu Samuel

2013-01-01

Background Developing countries of sub-Saharan Africa (SSA) face a double burden of non-communicable diseases (NCDs) and communicable diseases. As high blood pressure (BP) is a common global cardiovascular (CV) disorder associated with high morbidity and mortality, the relationship between gradients of BP and other CV risk factors was assessed in Abia State, Nigeria. Methods Using the WHO STEPwise approach to surveillance of chronic disease risk factors, we conducted a population-based cross-sectional survey in Abia state, Nigeria from August 2011 to March 2012. Data collected at various steps included: demographic and behavioral risk factors (Step 1); BP and anthropometric measurements (Step 2), and fasting blood cholesterol and glucose (Step 3). Results Of the 2983 subjects with complete data for analysis, 52.1% were females and 53.2% were rural dwellers. Overall, the distribution of selected CV disease risk factors was diabetes (3.6%), hypertension (31.4%), cigarette smoking (13.3%), use of smokeless tobacco (4.8%), physical inactivity (64.2%) and being overweight or obese (33.7%). Presence of hypertension, excessive intake of alcohol, smoking (cigarette and smokeless tobacco) and physical inactivity occurred more frequently in males than in females (p<0.05); while low income, lack of any formal education and use of smokeless tobacco were seen more frequently in rural dwellers than in those living in urban areas (p<0.05). The frequency of selected CV risk factors increased as BP was graded from optimal, normal to hypertension; and high BP correlated with age, gender, smokeless tobacco, overweight or obesity, annual income and level of education. Conclusion Given the high prevalence of hypertension in this part of Nigeria, there is an urgent need to focus on the reduction of preventable CV risk factors we have observed to be associated with hypertension, in order to effectively reduce the burden of NCDs in Africa. PMID:24039932

Blood pressure gradients and cardiovascular risk factors in urban and rural populations in Abia State South Eastern Nigeria using the WHO STEPwise approach.

PubMed

Okpechi, Ikechi Gareth; Chukwuonye, Innocent Ijezie; Tiffin, Nicki; Madukwe, Okechukwu Ojoemelam; Onyeonoro, Ugochukwu Uchenna; Umeizudike, Theophilus Ifeanyichukwu; Ogah, Okechukwu Samuel

2013-01-01

Developing countries of sub-Saharan Africa (SSA) face a double burden of non-communicable diseases (NCDs) and communicable diseases. As high blood pressure (BP) is a common global cardiovascular (CV) disorder associated with high morbidity and mortality, the relationship between gradients of BP and other CV risk factors was assessed in Abia State, Nigeria. Using the WHO STEPwise approach to surveillance of chronic disease risk factors, we conducted a population-based cross-sectional survey in Abia state, Nigeria from August 2011 to March 2012. Data collected at various steps included: demographic and behavioral risk factors (Step 1); BP and anthropometric measurements (Step 2), and fasting blood cholesterol and glucose (Step 3). Of the 2983 subjects with complete data for analysis, 52.1% were females and 53.2% were rural dwellers. Overall, the distribution of selected CV disease risk factors was diabetes (3.6%), hypertension (31.4%), cigarette smoking (13.3%), use of smokeless tobacco (4.8%), physical inactivity (64.2%) and being overweight or obese (33.7%). Presence of hypertension, excessive intake of alcohol, smoking (cigarette and smokeless tobacco) and physical inactivity occurred more frequently in males than in females (p<0.05); while low income, lack of any formal education and use of smokeless tobacco were seen more frequently in rural dwellers than in those living in urban areas (p<0.05). The frequency of selected CV risk factors increased as BP was graded from optimal, normal to hypertension; and high BP correlated with age, gender, smokeless tobacco, overweight or obesity, annual income and level of education. Given the high prevalence of hypertension in this part of Nigeria, there is an urgent need to focus on the reduction of preventable CV risk factors we have observed to be associated with hypertension, in order to effectively reduce the burden of NCDs in Africa.

Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus.

PubMed

Viazzi, Francesca; Piscitelli, Pamela; Ceriello, Antonio; Fioretto, Paola; Giorda, Carlo; Guida, Pietro; Russo, Giuseppina; De Cosmo, Salvatore; Pontremoli, Roberto

2017-09-22

Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice. Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction ≥30% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P <0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% ( P =0.036) greater risk of developing the renal end points. ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Valuation of Normal Range of Ankle Systolic Blood Pressure in Subjects with Normal Arm Systolic Blood Pressure.

PubMed

Gong, Yi; Cao, Kai-wu; Xu, Jin-song; Li, Ju-xiang; Hong, Kui; Cheng, Xiao-shu; Su, Hai

2015-01-01

This study aimed to establish a normal range for ankle systolic blood pressure (SBP). A total of 948 subjects who had normal brachial SBP (90-139 mmHg) at investigation were enrolled. Supine BP of four limbs was simultaneously measured using four automatic BP measurement devices. The ankle-arm difference (An-a) on SBP of both sides was calculated. Two methods were used for establishing normal range of ankle SBP: the 99% method was decided on the 99% reference range of actual ankle BP, and the An-a method was the sum of An-a and the low or up limits of normal arm SBP (90-139 mmHg). Whether in the right or left side, the ankle SBP was significantly higher than the arm SBP (right: 137.1 ± 16.9 vs 119.7 ± 11.4 mmHg, P<0.05). Based on the 99% method, the normal range of ankle SBP was 94~181 mmHg for the total population, 84~166 mmHg for the young (18-44 y), 107~176 mmHg for the middle-aged(45-59 y) and 113~179 mmHg for the elderly (≥ 60 y) group. As the An-a on SBP was 13 mmHg in the young group and 20 mmHg in both middle-aged and elderly groups, the normal range of ankle SBP on the An-a method was 103-153 mmHg for young and 110-160 mmHg for middle-elderly subjects. A primary reference for normal ankle SBP was suggested as 100-165 mmHg in the young and 110-170 mmHg in the middle-elderly subjects.

Autoregulation of cerebral blood flow in orthostatic hypotension

NASA Technical Reports Server (NTRS)

Novak, V.; Novak, P.; Spies, J. M.; Low, P. A.

1998-01-01

BACKGROUND AND PURPOSE: We sought to evaluate cerebral autoregulation in patients with orthostatic hypotension (OH). METHODS: We studied 21 patients (aged 52 to 78 years) with neurogenic OH during 80 degrees head-up tilt. Blood flow velocities (BFV) from the middle cerebral artery were continuously monitored with transcranial Doppler sonography, as were heart rate, blood pressure (BP), cardiac output, stroke volume, CO2, total peripheral resistance, and cerebrovascular resistance. RESULTS: All OH patients had lower BP (P<.0001), BFV_diastolic (P<.05), CVR (P<.007), and TPR (P<.02) during head-up tilt than control subjects. In control subjects, no correlations between BFV and BP were found during head-up tilt, suggesting normal autoregulation. OH patients could be separated into those with normal or expanded autoregulation (OH_NA; n=16) and those with autoregulatory failure (OH_AF; n=5). The OH_NA group showed either no correlation between BFV and BP (n=8) or had a positive BFV/BP correlation (R2>.75) but with a flat slope. An expansion of the "autoregulated" range was seen in some patients. The OH_AF group was characterized by a profound fall in BFV in response to a small reduction in BP (mean deltaBP <40 mm Hg; R2>.75). CONCLUSIONS: The most common patterns of cerebral response to OH are autoregulatory failure with a flat flow-pressure relationship or intact autoregulation with an expanded autoregulated range. The least common pattern is autoregulatory failure with a steep flow-pressure relationship. Patients with patterns 1 and 2 have an enhanced capacity to cope with OH, while those with pattern 3 have reduced capacity.

Respiratory modulation of oscillometric cuff pressure pulses and Korotkoff sounds during clinical blood pressure measurement in healthy adults.

PubMed

Chen, Diliang; Chen, Fei; Murray, Alan; Zheng, Dingchang

2016-05-10

Accurate blood pressure (BP) measurement depends on the reliability of oscillometric cuff pressure pulses (OscP) and Korotkoff sounds (KorS) for automated oscillometric and manual techniques. It has been widely accepted that respiration is one of the main factors affecting BP measurement. However, little is known about how respiration affects the signals from which BP measurement is obtained. The aim was to quantify the modulation effect of respiration on oscillometric pulses and KorS during clinical BP measurement. Systolic and diastolic BPs were measured manually from 40 healthy subjects (from 23 to 65 years old) under normal and regular deep breathing. The following signals were digitally recorded during linear cuff deflation: chest motion from a magnetometer to obtain reference respiration, cuff pressure from an electronic pressure sensor to derive OscP, and KorS from a digital stethoscope. The effects of respiration on both OscP and KorS were determined from changes in their amplitude associated with respiration between systole and diastole. These changes were normalized to the mean signal amplitude of OscP and KorS to derive the respiratory modulation depth. Reference respiration frequency, and the frequencies derived from the amplitude modulation of OscP and KorS were also calculated and compared. Respiratory modulation depth was 14 and 40 % for OscP and KorS respectively under normal breathing condition, with significant increases (both p < 0.05) to 16 and 49 % with deeper breathing. There was no statistically significant difference between the reference respiration frequency and those derived from the oscillometric and Korotkoff signals (both p > 0.05) during deep breathing, and for the oscillometric signal during normal breathing (p > 0.05). Our study confirmed and quantified the respiratory modulation effect on the oscillometric pulses and KorS during clinical BP measurement, with increased modulation depth under regular deeper breathing.

The Relationship Between Cognitive Functioning and the JNC-8 Guidelines for Hypertension in Older Adults.

PubMed

Goldstein, Felicia C; Hajjar, Ihab M; Dunn, Callie B; Levey, Allan I; Wharton, Whitney

2017-01-01

Guidelines for hypertension treatment by the Eighth Joint National Committee (JNC-8) in 2014 recommended a target systolic blood pressure (BP) of <150/<90 mmHg in persons older than 60 years, in contrast to the 2003 JNC-7 recommendations of systolic BP <140 mmHg. This study evaluated the implications of raising the BP target on cognitive functioning and conversion from normal cognition to mild cognitive impairment (MCI). This was a longitudinal study of individuals older than 60 years enrolled in the NIH-NIA Alzheimer's Disease Centers. All had normal cognition at baseline. 453 participants were taking BP medications and had readings of <140/<90 mmHg at four annual visits (reference group). Two other groups consisted of participants with either systolic BP of 140-149 mmHg (n = 112) or ≥150 mmHg (n = 280) on three or four annual visits. Compared with the reference and the 140-149 mmHg groups, those with BP ≥150 mmHg exhibited poorer cognitive status by Year 4 on the Mini-Mental State Exam, and they had a higher risk of conversion to MCI. The 140-149 mmHg exhibited poorer performance than the reference group on domains assessing attention and executive functioning. In contrast, their performance was not significantly different from those with BP ≥150 mmHg. Persons with BP ≥150 mmHg show a faster global cognitive decline and transition to MCI than those with lower BP readings. However, the poor cognitive performance in the attention and executive functioning domains for the 140-149 mmHg group indicates the need for further research evaluating the newer recommended cutoff. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identifying allelic loss and homozygous deletions in pancreatic cancer without matched normals using high-density single-nucleotide polymorphism arrays.

PubMed

Calhoun, Eric S; Hucl, Tomas; Gallmeier, Eike; West, Kristen M; Arking, Dan E; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Chakravarti, Aravinda; Hruban, Ralph H; Kern, Scott E

2006-08-15

Recent advances in oligonucleotide arrays and whole-genome complexity reduction data analysis now permit the evaluation of tens of thousands of single-nucleotide polymorphisms simultaneously for a genome-wide analysis of allelic status. Using these arrays, we created high-resolution allelotype maps of 26 pancreatic cancer cell lines. The areas of heterozygosity implicitly served to reveal regions of allelic loss. The array-derived maps were verified by a panel of 317 microsatellite markers used in a subset of seven samples, showing a 97.1% concordance between heterozygous calls. Three matched tumor/normal pairs were used to estimate the false-negative and potential false-positive rates for identifying loss of heterozygosity: 3.6 regions (average minimal region of loss, 720,228 bp) and 2.3 regions (average heterozygous gap distance, 4,434,994 bp) per genome, respectively. Genomic fractional allelic loss calculations showed that cumulative levels of allelic loss ranged widely from 17.1% to 79.9% of the haploid genome length. Regional increases in "NoCall" frequencies combined with copy number loss estimates were used to identify 41 homozygous deletions (19 first reports), implicating an additional 13 regions disrupted in pancreatic cancer. Unexpectedly, 23 of these occurred in just two lines (BxPc3 and MiaPaCa2), suggesting the existence of at least two subclasses of chromosomal instability (CIN) patterns, distinguished here by allelic loss and copy number changes (original CIN) and those also highly enriched in the genomic "holes" of homozygous deletions (holey CIN). This study provides previously unavailable high-resolution allelotype and deletion breakpoint maps in widely shared pancreatic cancer cell lines and effectively eliminates the need for matched normal tissue to define informative loci.

Circadian pattern of blood pressure in normal pregnancy and preeclampsia.

PubMed

Gupta, Hem Prabha; Singh, R K; Singh, Urmila; Mehrotra, Seema; Verma, N S; Baranwal, Neelam

2011-08-01

AIMS #ENTITYSTARTX00026; To find out the circadian pattern of blood pressure in normotensive pregnant women and in women with preeclampsia. A cross-sectional prospective observational case control study. Blood pressure was sampled in thirty-five normotensive pregnant women (control) and thirty five preeclamptic women (study group) by using non-invasive automatic ambulatory blood pressure monitoring machine for 72 h. Blood pressure (BP) was not constant over 24 h period and it oscillated from time to time in control group. BP was maximum during early part of afternoon. However, in preeclampsia besides quantitative increase in BP, circadian BP oscillations were less pronounced and in around 50% subjects BP was maximum during evening and night hours. Both systolic and diastolic BP showed definite reproducible circadian pattern in both preeclamptic and normotensive pregnant women. This pattern both quantitatively and qualitatively was different in preeclamptic women. Standardized 24 h BP monitoring allows quantitative and qualitative evaluation of hypertensive status and is important for timing and dosing of antihypertensive medications.

Assessment of Knowledge of Critical Cardiovascular Risk Indicators among College Students: Does Stage of Education Matter?

PubMed Central

Sarpong, Daniel F.; Curry, India Y.; Williams, Melinda

2017-01-01

The health risk of college students in the United States (US) is on the rise, with a significant increase in the prevalence of cardiovascular risk factors. Cardiovascular disease is the leading cause of death in the US, costing approximately $475.3 billion yearly. The goals of this “Know Your Numbers” study were to: (1) estimate the awareness of college students of their critical health numbers (CHN); and (2) compare a college of pharmacy entry class (IP1) with second semester non-commuter freshman college students (FCS) in knowing their numbers. A cross-sectional 15-item pre-test survey was conducted among a convenience sample of IP1 and FCS. All statistical tests were performed at α = 0.05. Awareness of their: cholesterol (7%), blood pressure (BP) (35%), glucose (8%), and body mass index (BMI) (42%) were low. The IP1, compared to FCS, were more knowledgeable of: (1) their BP (46% vs. 28%, p = 0.01); (2) BP normal range (74% vs. 63%, p = 0.02); and (3) BMI normal range (39% vs. 23%, p = 0.04). The IP1s maintained a healthier diet than the FCS (64% vs. 36%, p < 0.0001). Awareness of knowing CHN was very low. Knowledge of one’s CHN was significantly associated with knowledge of normal reference values for BP, glucose, and BMI. PMID:28257080

High dietary phosphate intake induces hypertension and augments exercise pressor reflex function in rats.

PubMed

Mizuno, Masaki; Mitchell, Jere H; Crawford, Scott; Huang, Chou-Long; Maalouf, Naim; Hu, Ming-Chang; Moe, Orson W; Smith, Scott A; Vongpatanasin, Wanpen

2016-07-01

An increasing number of studies have linked high dietary phosphate (Pi) intake to hypertension. It is well established that the rise in sympathetic nerve activity (SNA) and blood pressure (BP) during physical exertion is exaggerated in many forms of hypertension, which are primarily mediated by an overactive skeletal muscle exercise pressor reflex (EPR). However, it remains unknown whether high dietary Pi intake potentiates the EPR-mediated SNA and BP response to exercise. Accordingly, we measured renal SNA (RSNA) and mean BP (MBP) in normotensive Sprague-Dawley rats fed a normal Pi diet (0.6%, n = 13) or high Pi diet (1.2%, n = 13) for 3 mo. As previously reported, we found that resting BP was significantly increased by 1.2% Pi diet in both conscious and anesthetized animals. Activation of the EPR by electrically induced hindlimb contraction triggered greater increases in ΔRSNA and ΔMBP in the 1.2% compared with 0.6% Pi group (126 ± 25 vs. 42 ± 9%; 44 ± 5 vs. 14 ± 2 mmHg, respectively, P < 0.01). Activation of the muscle mechanoreflex, a component of the EPR, by passively stretching hindlimb muscle also evoked greater increases in ΔRSNA and ΔMBP in the 1.2% compared with 0.6% Pi group (109 ± 27 vs. 24 ± 7%, 38 ± 7 vs. 8 ± 2 mmHg, respectively, P < 0.01). A similar response was produced by hindlimb intra-arterial capsaicin administration to stimulate the metaboreflex arm of the EPR. Thus, our data demonstrate a novel action of dietary Pi loading in augmenting EPR function through overactivation of both the muscle mechanoreflex and metaboreflex. Copyright © 2016 the American Physiological Society.

Let-7b Regulates Myoblast Proliferation by Inhibiting IGF2BP3 Expression in Dwarf and Normal Chicken

PubMed Central

Lin, Shumao; Luo, Wen; Ye, Yaqiong; Bekele, Endashaw J.; Nie, Qinghua; Li, Yugu; Zhang, Xiquan

2017-01-01

The sex-linked dwarf chicken is caused by the mutation of growth hormone receptor (GHR) gene and characterized by shorter shanks, lower body weight, smaller muscle fiber diameter and fewer muscle fiber number. However, the precise regulatory pathways that lead to the inhibition of skeletal muscle growth in dwarf chickens still remain unclear. Here we found a let-7b mediated pathway might play important role in the regulation of dwarf chicken skeletal muscle growth. Let-7b has higher expression in the skeletal muscle of dwarf chicken than in normal chicken, and the expression of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which is a translational activator of IGF2, showed opposite expression trend to let-7b. In vitro cellular assays validated that let-7b directly inhibits IGF2BP3 expression through binding to its 3′UTR region, and the protein level but not mRNA level of IGF2 would be reduced in let-7b overexpressed chicken myoblast. Let-7b can inhibit cell proliferation and induce cell cycle arrest in chicken myoblast through let-7b-IGF2BP3-IGF2 signaling pathway. Additionally, let-7b can also regulate skeletal muscle growth through let-7b-GHR-GHR downstream genes pathway, but this pathway is non-existent in dwarf chicken because of the deletion mutation of GHR 3′UTR. Notably, as the loss binding site of GHR for let-7b, let-7b has enhanced its binding and inhibition on IGF2BP3 in dwarf myoblast, suggesting that the miRNA can balance its inhibiting effect through dynamic regulate its binding to target genes. Collectively, these results not only indicate that let-7b can inhibit skeletal muscle growth through let-7b-IGF2BP3-IGF2 signaling pathway, but also show that let-7b regulates myoblast proliferation by inhibiting IGF2BP3 expression in dwarf and normal chickens. PMID:28736533

Functional Status Modifies the Association of Blood Pressure with Death in Elders: Health and Retirement Study.

PubMed

Wu, Chenkai; Smit, Ellen; Peralta, Carmen A; Sarathy, Harini; Odden, Michelle C

2017-07-01

To examine whether grip strength, gait speed, and the combination of the two physical functioning measures modified the association of systolic BP (SBP) and diastolic BP (DBP) with mortality. Nationally representative cohort study. Health and Retirement Study. 7,492 U.S. adults aged ≥65 years. Grip strength was measured by a hand dynamometer and classified as normal (≥16 kg for female; ≥26 kg for male) and weak. Gait speed was assessed over a 98.5-inch walk and classified as non-slow (≥0.60 m/s for female; ≥0.52 m/s for male) and slow. Over an average follow-up time of 6.0 years, 1,870 (25.0%) participants died. After adjustment for socio-demographic, behavioral, and clinical measures, elevated SBP (≥150 mmHg) and DBP (≥90 mmHg) was associated with a 24% (95% CI, 7-43%) and 25% (95% CI, 5-49%) higher mortality among participants with normal grip strength. In contrast, elevated SBP and DBP was associated with a 6% (95% CI, 31 to -27%) and a 16% (95% CI, 46 to -26%) lower mortality among those with weak grip strength (P-values of interactions: both=.07). The inverse relations between BP with death were most pronounced among slow walkers with weak grip strength. The HRs of elevated SBP and DBP for death was 0.85 (95% CI, 0.56-1.29) and 0.53 (95% CI, 0.30-0.96), respectively, and was substantially different from non-slow walkers with normal grip strength (HR = 1.24 and 1.15, respectively; P-values of interactions: both <.001). Therefore, associations of BP with death varied modestly by gait speed. Grip strength modified the association of BP with death. Combination of grip strength and gait speed has incremental value for modifying the association of BP with death. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Prevalence, Determinants, and Clinical Significance of Masked Hypertension in a Population-Based Sample of African Americans: The Jackson Heart Study.

PubMed

Diaz, Keith M; Veerabhadrappa, Praveen; Brown, Michael D; Whited, Matthew C; Dubbert, Patricia M; Hickson, DeMarc A

2015-07-01

The disproportionate rates of cardiovascular disease in African Americans may, in part, be due to suboptimal assessment of blood pressure (BP) with clinic BP measurements alone. To date, however, the prevalence of masked hypertension in African Americans has not been fully delineated. The purpose of this study was to evaluate masked hypertension prevalence in a large population-based sample of African Americans and examine its determinants and association with indices of target organ damage (TOD). Clinic and 24-hour ambulatory BP monitoring were conducted in 972 African Americans enrolled in the Jackson Heart Study. Common carotid artery intima-media thickness, left ventricular mass index, and the urinary albumin:creatinine excretion ratio were evaluated as indices of TOD. Masked hypertension prevalence was 25.9% in the overall sample and 34.4% in participants with normal clinic BP. All indices of TOD were significantly higher in masked hypertensives compared to sustained normotensives and were similar between masked hypertensives and sustained hypertensives. Male gender, smoking, diabetes, and antihypertensive medication use were independent determinants of masked hypertension in multivariate analyses. In this population-based cohort of African Americans, approximately one-third of participants with presumably normal clinic BP had masked hypertension when BP was assessed in their daily environment. Masked hypertension was accompanied by a greater degree of TOD in this cohort. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High risk blood pressure and obesity increase the risk for left ventricular hypertrophy in African-American adolescents.

PubMed

Falkner, Bonita; DeLoach, Stephanie; Keith, Scott W; Gidding, Samuel S

2013-01-01

To examine the relative effects of high blood pressure (HBP) and obesity on left ventricular mass (LVM) among African-American adolescents; and if metabolic or inflammatory factors contribute to LVM. Using a 2 × 2 design, African-American adolescents were stratified by body mass index percentile (body mass index <95th percentile = non-obese; ≥ 95th percentile = obese) and average blood pressure (BP) (normal BP <120/80 mm Hg; HBP ≥ 120/80). Glucose, insulin, insulin resistance, lipids, and inflammatory cytokines were measured. From echocardiography measures of LVM, calculated LVM index (LVMI) ≥ 95th percentile defined left ventricular hypertrophy (LVH). Data included 301 adolescents (48% female), mean age 16.2 years, 51% obese, and 29% HBP. LVMI was highest among adolescents with both obesity and HBP. The multiplicative interaction of obesity and HBP on LVH was not significant (OR = 2.35, P = .20) but the independent additive associations of obesity and HBP with log-odds of LVH were significant; obesity OR = 3.26, P < .001; HBP OR = 2.92, P < .001. Metabolic and inflammatory risk factors were associated with obesity, but had no independent association with LVMI. Compared with those with average systolic BP (SBP) <75th percentile, adolescents with SBP from the 75th percentile to 90th percentile had higher LVMI (33.2 vs 38.7 g/m(2.7), P < .001) and greater LVH (18% vs 43%, P < .001), independent of obesity. Prevalence of LVH is highest among African-American adolescents with average BP ≥ 120/80 mm Hg and obesity. There also is an independent association of LVMI with BP, beginning at the 75th SBP percentile. Copyright © 2013 Mosby, Inc. All rights reserved.

Blood Pressure Variability and Cognitive Function Among Older African Americans: Introducing a New Blood Pressure Variability Measure.

PubMed

Tsang, Siny; Sperling, Scott A; Park, Moon Ho; Helenius, Ira M; Williams, Ishan C; Manning, Carol

2017-09-01

Although blood pressure (BP) variability has been reported to be associated with cognitive impairment, whether this relationship affects African Americans has been unclear. We sought correlations between systolic and diastolic BP variability and cognitive function in community-dwelling older African Americans, and introduced a new BP variability measure that can be applied to BP data collected in clinical practice. We assessed cognitive function in 94 cognitively normal older African Americans using the Mini-Mental State Examination (MMSE) and the Computer Assessment of Mild Cognitive Impairment (CAMCI). We used BP measurements taken at the patients' three most recent primary care clinic visits to generate three traditional BP variability indices, range, standard deviation, and coefficient of variation, plus a new index, random slope, which accounts for unequal BP measurement intervals within and across patients. MMSE scores did not correlate with any of the BP variability indices. Patients with greater diastolic BP variability were less accurate on the CAMCI verbal memory and incidental memory tasks. Results were similar across the four BP variability indices. In a sample of cognitively intact older African American adults, BP variability did not correlate with global cognitive function, as measured by the MMSE. However, higher diastolic BP variability correlated with poorer verbal and incidental memory. By accounting for differences in BP measurement intervals, our new BP variability index may help alert primary care physicians to patients at particular risk for cognitive decline.

High risk for obesity in children with a subtype of developmental coordination disorder.

PubMed

Zhu, Yi-Ching; Cairney, John; Li, Yao-Chuen; Chen, Wei-Ying; Chen, Fu-Chen; Wu, Sheng K

2014-07-01

The purpose of this study was to compare the prevalence of overweight and obesity in typically developing (TD) children, children with developmental coordination disorder (DCD) and balance problems (DCD-BP), and children with DCD without balance problems (DCD-NBP). Two thousand and fifty-seven children (1095 boys, 962 girls) ages 9-12 years were recruited from 18 elementary schools in Taiwan. The Movement Assessment Battery for Children was used to assess motor coordination ability. International cut-off points for body mass index were used to classify participants into the following groups: normal-weight, overweight or obese. Compared with TD children, children in the DCD-BP group were more than twice as likely to be obese (OR=2.28; 95% CI=1.41-3.68). DCD-BP children were also more likely to be obese compared to DCD-NBP children (OR=1.79; 95% CI=1.02-3.16). Boys in the DCD-BP group were more likely to be obese when compared to DCD-BP girls (OR=3.12; 95% CI=1.28-7.57). Similarly, DCD-NBP boys were more likely to be obese when compared to DCD-NBP girls (OR=2.67; 95% CI=1.21-5.89). Children with both DCD and BP were significantly more likely to be obese when compared to TD and DCD-NBP children. From an intervention perspective, the inclusion of regular physical activity, including activities that encourage development of both balance and energy expenditure, may be required to prevent obesity in this population. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection of DNA Double Strand Breaks by γH2AX Does Not Result in 53bp1 Recruitment in Mouse Retinal Tissues

PubMed Central

Müller, Brigitte; Ellinwood, N. M.; Lorenz, Birgit; Stieger, Knut

2018-01-01

Gene editing is an attractive potential treatment of inherited retinopathies. However, it often relies on endogenous DNA repair. Retinal DNA repair is incompletely characterized in humans and animal models. We investigated recruitment of the double stranded break (DSB) repair complex of γH2AX and 53bp1 in both developing and mature mouse neuroretinas. We evaluated the immunofluorescent retinal expression of these proteins during development (P07-P30) in normal and retinal degeneration models, as well as in potassium bromate induced DSB repair in normal adult (3 months) retinal explants. The two murine retinopathy models used had different mutations in Pde6b: the severe rd1 and the milder rd10 models. Compared to normal adult retina, we found increased numbers of γH2AX positive foci in all retinal neurons of the developing retina in both model and control retinas, as well as in wild type untreated retinal explant cultures. In contrast, the 53bp1 staining of the retina differed both in amount and character between cell types at all ages and in all model systems. There was strong pan nuclear staining in ganglion, amacrine, and horizontal cells, and cone photoreceptors, which was attenuated. Rod photoreceptors did not stain unequivocally. In all samples, 53bp1 stained foci only rarely occurred. Co-localization of 53bp1 and γH2AX staining was a very rare event (< 1% of γH2AX foci in the ONL and < 3% in the INL), suggesting the potential for alternate DSB sensing and repair proteins in the murine retina. At a minimum, murine retinal DSB repair does not appear to follow canonical pathways, and our findings suggests further investigation is warranted. PMID:29765300

Dietary sodium restriction restores nocturnal reduction of blood pressure in patients with primary aldosteronism.

PubMed

Takakuwa, Hiroshi; Shimizu, Kazuaki; Izumiya, Yoshiaki; Kato, Tamayo; Nakaya, Izaya; Yokoyama, Hitoshi; Kobayashi, Ken-ichi; Ise, Takuyuki

2002-09-01

The purpose of this study was to elucidate the effects of dietary sodium restriction on diurnal blood pressure (BP) variation in primary aldosteronism. We studied the diurnal variation in the systemic hemodynamic indices and in baroreflex sensitivity (BRS). In 13 subjects with aldosterone-producing adenomas (2 males; mean age, 39+/-2 years), intra-arterial pressure was monitored telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers were defined as those with a nocturnal reduction in systolic BP (SBP) of less than 10% of daytime SBP. Ten subjects showed a non-dipper pattern. Six of these "non-dippers" underwent repetitive hemodynamic studies on the last day of a 1-week low salt diet regimen (NaCl 2-4 g/day). Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. BRS was calculated every 30 min as delta pulse interval/delta SBP on spontaneous variations. Nocturnal reduction of SBP was 4.1% on the normal salt diet. With sodium restriction, urinary sodium excretion decreased from 187+/-8 to 46+/-8 mmol/day, and body weight decreased from 57.9+/-2.1 to 56.6+/-1.9 kg. Night-time BP significantly decreased with dietary modification from 154+/-7/88+/-4 to 140+/-6/78+/-4 mmHg, whereas daytime BP was unaltered. With sodium restriction, cardiac index and stroke index decreased throughout the day. No significant difference was seen in either daytime or nighttime BRS between the two diets. We conclude that the non-dipper pattern is common in patients with an aldosterone-producing adenoma on a normal salt intake, and under such conditions, volume expansion appears to play a major role in the impairment of nocturnal BP reduction.

Frequency of cystathionine beta-synthase 844INS68 polymorphism in Southern Iran.

PubMed

Senemar, Sara; Doroudchi, Mehrnoosh; Pezeshki, Abdul Mohammad; Bazrgar, Masood; Torab-Jahromi, Ardeshir; Ghaderi, Abbas

2009-02-01

Iranian population with an Indo-European origin is one of the oldest populations in the world. Historical evidence suggests the close similarity in the origin of Iranian, European and north Indian population. However, there are few anthropological and genetic evidences on this subject. This study, which is the first report from Iran, was performed to investigate the genetic origin of Iranian population using a polymorphism in Cystathionine beta synthase (CBS) gene known as 844INS68bp in this respect, genomic DNA was extracted from the whole blood of 480 healthy normal blood donors referred to Fars Blood Transfusion Center, using a salting out method. The fragment containing 844INS68bp was amplified, the normal fragment was 174 bp and the fragment containing the insertion was 242 bp in length. Results indicated that 418 (87.08%) out of 480 individuals had a normal (N/N) genotype, 59 (12.29%) individuals were heterozygote (N/I) and 3 (0.63%) had homozygote a mutated genotype (I/I). The total frequency of 844INS68bp allele was found 6.8% which is similar to with the reported in White Caucasians. Comparison of the genotype of this study with the polymorphism in other populations revealed that Southern Iranian population has a great similarity with other Caucasians populations' especially South Italy and North America while differed from East Asian and African populations. These results are in agreement with the result of other studied polymorphisms. Therefore, despite the great admixture of Iranian population with the neighboring non-Caucasian populations during the time, Iranian population still share a genetic background with other Caucasian populations.

Ambulatory blood pressure and arterial stiffness in individuals with type 1 diabetes.

PubMed

Lithovius, Raija; Gordin, Daniel; Forsblom, Carol; Saraheimo, Markku; Harjutsalo, Valma; Groop, Per-Henrik

2018-05-24

This study aimed to assess the use of ambulatory BP monitoring (ABPM) to identify the presence of masked, nocturnal and white-coat hypertension in individuals with type 1 diabetes, patterns that could not be detected by regular office-based BP monitoring alone. We also analysed associations between BP patterns and arterial stiffness in order to identify individuals at cardiovascular risk. This substudy included 140 individuals with type 1 diabetes from the Helsinki metropolitan area, who attended the Finnish Diabetic Nephropathy Study (FinnDiane) Centre in Helsinki between January 2013 and August 2017. Twenty-four hour ABPM and pulse wave analysis were performed simultaneously using a validated non-invasive brachial oscillometric device (Mobil-O-Graph). Definitions of hypertension were based on the European Society of Hypertension guidelines. Masked hypertension was defined as normal office BP (BP obtained using a standardised automated BP device) but elevated 24 h ABPM, and white-coat hypertension as elevated office BP but normal 24 h ABPM. A total of 38% of individuals were normotensive and 33% had sustained hypertension, while 23% had masked and 6% had white-coat hypertension. About half of the cohort had increased absolute levels of night-time BP, half of whom were untreated. In the ambulatory setting, central BP and pulse wave velocity (PWV) were higher in participants with masked hypertension than in those with normotension (p ≤ 0.001). In a multivariable linear regression model adjusted for age, sex, BMI, antihypertensive treatment and eGFR, masked hypertension was independently associated with higher 24 h PWV (β 0.50 [95% CI 0.34, 0.66]), but not with PWV obtained during resting conditions (adjusted β 0.28 [95% CI -0.53, 1.10]), using normotension as the reference group. ABPM analysis revealed that one-quarter of the participants with type 1 diabetes had masked hypertension; these individuals would not have been detected by office BP alone. Moreover, arterial stiffness was increased in individuals with masked hypertension. These findings support the use of ABPM to identify individuals at risk of cardiovascular disease.

Cerebral morphology and dopamine D2/D3 receptor distribution in humans: a combined [18F]fallypride and voxel-based morphometry study.

PubMed

Woodward, Neil D; Zald, David H; Ding, Zhaohua; Riccardi, Patrizia; Ansari, M Sib; Baldwin, Ronald M; Cowan, Ronald L; Li, Rui; Kessler, Robert M

2009-05-15

The relationship between cerebral morphology and the expression of dopamine receptors has not been extensively studied in humans. Elucidation of such relationships may have important methodological implications for clinical studies of dopamine receptor ligand binding differences between control and patient groups. The association between cerebral morphology and dopamine receptor distribution was examined in 45 healthy subjects who completed T1-weighted structural MRI and PET scanning with the D(2)/D(3) ligand [(18)F]fallypride. Optimized voxel-based morphometry was used to create grey matter volume and density images. Grey matter volume and density images were correlated with binding potential (BP(ND)) images on a voxel-by-voxel basis using the Biological Parametric Mapping toolbox. Associations between cerebral morphology and BP(ND) were also examined for selected regions-of-interest (ROIs) after spatial normalization. Voxel-wise analyses indicated that grey matter volume and density positively correlated with BP(ND) throughout the midbrain, including the substantia nigra. Positive correlations were observed in medial cortical areas, including anterior cingulate and medial prefrontal cortex, and circumscribed regions of the temporal, frontal, and parietal lobes. ROI analyses revealed significant positive correlations between BP(ND) and cerebral morphology in the caudate, thalamus, and amygdala. Few negative correlations between morphology and BP(ND) were observed. Overall, grey matter density appeared more strongly correlated with BP(ND) than grey matter volume. Cerebral morphology, particularly grey matter density, correlates with [(18)F]fallypride BP(ND) in a regionally specific manner. Clinical studies comparing dopamine receptor availability between clinical and control groups may benefit by accounting for potential differences in cerebral morphology that exist even after spatial normalization.

Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm.

PubMed

Bouchlariotou, Sofia; Liakopoulos, Vassilios; Giannopoulou, Myrto; Arampatzis, Spyridon; Eleftheriadis, Theodoros; Mertens, Peter R; Zintzaras, Elias; Messinis, Ioannis E; Stefanidis, Ioannis

2014-08-01

Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, p<0.001) levels. Adjustment for circadian BP rhythm status ascribed this finding exclusively to non-dippers (p<0.01). Two months after delivery, in 11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.

Interleukin (IL)-18 Binding Protein Deficiency Disrupts Natural Killer Cell Maturation and Diminishes Circulating IL-18

PubMed Central

Harms, Robert Z.; Creer, Austin J.; Lorenzo-Arteaga, Kristina M.; Ostlund, Katie R.; Sarvetnick, Nora E.

2017-01-01

The cytokine interleukin (IL)-18 is a crucial amplifier of natural killer (NK) cell function. IL-18 signaling is regulated by the inhibitory effects of IL-18 binding protein (IL-18BP). Using mice deficient in IL-18BP (IL-18BPKO), we investigated the impact of mismanaged IL-18 signaling on NK cells. We found an overall reduced abundance of splenic NK cells in the absence of IL-18BP. Closer examination of NK cell subsets in spleen and bone marrow using CD27 and CD11b expression revealed that immature NK cells were increased in abundance, while the mature population of NK cells was reduced. Also, NK cells were polarized to greater production of TNF-α, while dedicated IFN-γ producers were reduced. A novel subset of IL-18 receptor α− NK cells contributed to the expansion of immature NK cells in IL-18BPKO mice. Splenocytes cultured with IL-18 resulted in alterations similar to those observed in IL-18BP deficiency. NK cell changes were associated with significantly reduced levels of circulating plasma IL-18. However, IL-18BPKO mice exhibited normal weight gain and responded to LPS challenge with a >10-fold increase in IFN-γ compared to wild type. Finally, we identified that the source of splenic IL-18BP was among dendritic cells/macrophage localized to the T cell-rich regions of the spleen. Our results demonstrate that IL-18BP is required for normal NK cell abundance and function and also contributes to maintaining steady-state levels of circulating IL-18. Thus, IL-18BP appears to have functions suggestive of a carrier protein, not just an inhibitor. PMID:28900426

Simultaneous blood pressure measurement in both arms in hypertensive and nonhypertensive adult patients.

PubMed

Fonseca-Reyes, Salvador; Forsyth-MacQuarrie, Avril M; García de Alba-García, Javier Eduardo

2012-08-01

When blood pressure (BP) is taken for the first time, it should be measured in both arms; follow-up measurements should be taken in the arm with the highest BP. However, in clinical practice, this recommendation is rarely followed. Identify the degree of differences in BP between the right and the left arm in individuals with normal and high BP. We measured BP in 111 hypertensive and 80 normotensive patients in both arms at the same time using identical Omron HEM 725 CIC automatic sphygmomanometers. The devices were then switched to the other arm and another set of readings was taken. The absolute and relative difference in BP between arms was calculated from the average of these two readings. We categorized differences as at least 5, at least 10, and at least 20 mmHg for systolic blood pressure/diastolic blood pressure (SBP/DBP). The BP was higher in the right arm, with no statistical significance. The relative differences were also not significant: SBP 1.1±7.1 and DBP 0.21±5.0. However, the absolute differences were significant at an individual level, with a systolic difference of 5.4±4.8 mmHg and a diastolic difference of 3.9 ±3.2 mmHg. The percentages of absolute SBP/DBP differences more than 5 mmHg (21.4%/20.4%) and more than 10 mmHg (15.7%/4.7%) were considerable. The range of arm differences was clinically significant; in hypertensives, the SBP/DBP was -13.2 to +15/-9.2 to +9.6 mmHg and in nonhypertensives it was -12.9 to +15.6/-9.7 to +10.1 mmHg. Although on average there was no clinically significant relative difference between arms, absolute differences at an individual level were often clinically significant. Failure to determine interarm BP differences will lead to erroneous clinical decisions.

Nonspecific ST-T changes associated with unsatisfactory blood pressure control among adults with hypertension in China: Evidence from the CSPTT study.

PubMed

Bao, Huihui; Cai, Huaxiu; Zhao, Yan; Huang, Xiao; Fan, Fangfang; Zhang, Chunyan; Li, Juxiang; Chen, Jing; Hong, Kui; Li, Ping; Wu, Yanqing; Wu, Qinhua; Wang, Binyan; Xu, Xiping; Li, Yigang; Huo, Yong; Cheng, Xiaoshu

2017-03-01

Nonspecific ST-segment and T-wave (ST-T) changes represent one of the most prevalent electrocardiographic abnormalities in hypertensive patients. However, a limited number of studies have investigated the association between nonspecific ST-T changes and unsatisfactory blood pressure (BP) control in adults with hypertension.The study population comprised 15,038 hypertensive patients, who were selected from 20,702 participants in the China Stroke Primary Prevention Trial. The subjects were examined with electrocardiogram test at the initial visit in order to monitor baseline heart activity. According to the results of the electrocardiogram (defined by Minnesota coding), the subjects were divided into 2 groups: ST-T abnormal and ST-T normal. Unsatisfactory BP control was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg following antihypertensive treatment during the 4.5-year follow-up period. Multivariate analysis was used to analyze the association between nonspecific ST-T abnormalities and unsatisfactory BP control.Nonspecific ST-T changes were common in hypertensive adults (approximately 8.5% in the study), and more prevalent in women (10.3%) and diabetic patients (13.9%). The unsatisfactory BP control rate was high in the total population (47.0%), notably in the ST-T abnormal group (55.5%). The nonspecific ST-T abnormal group exhibited a significantly greater rate of unsatisfactory BP control (odds ratio [OR] 1.20, 95% confidence interval [CI] [1.06, 1.36], P = 0.005]), independent of traditional risk factors, as demonstrated by multivariate regression analysis. Notable differences were further observed in male subjects (OR 1.51, 95% CI [1.17, 1.94], P = 0.002) and in patients with comorbid diabetes (OR 1.47, 95% CI [1.04, 2.07], P = 0.029).Greater rates of unsatisfactory BP control in hypertensive patients with electrocardiographic nonspecific ST-T abnormalities were observed, notably in the subcategories of the male subjects and the diabetic patients.

Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay.

PubMed

Burnside, Rachel D; Pasion, Romela; Mikhail, Fady M; Carroll, Andrew J; Robin, Nathaniel H; Youngs, Erin L; Gadi, Inder K; Keitges, Elizabeth; Jaswaney, Vikram L; Papenhausen, Peter R; Potluri, Venkateswara R; Risheg, Hiba; Rush, Brooke; Smith, Janice L; Schwartz, Stuart; Tepperberg, James H; Butler, Merlin G

2011-10-01

The proximal long arm of chromosome 15 has segmental duplications located at breakpoints BP1-BP5 that mediate the generation of NAHR-related microdeletions and microduplications. The classical Prader-Willi/Angelman syndrome deletion is flanked by either of the proximal BP1 or BP2 breakpoints and the distal BP3 breakpoint. The larger Type I deletions are flanked by BP1 and BP3 in both Prader-Willi and Angelman syndrome subjects. Those with this deletion are reported to have a more severe phenotype than individuals with either Type II deletions (BP2-BP3) or uniparental disomy 15. The BP1-BP2 region spans approximately 500 kb and contains four evolutionarily conserved genes that are not imprinted. Reports of mutations or disturbed expression of these genes appear to impact behavioral and neurological function in affected individuals. Recently, reports of deletions and duplications flanked by BP1 and BP2 suggest an association with speech and motor delays, behavioral problems, seizures, and autism. We present a large cohort of subjects with copy number alteration of BP1 to BP2 with common phenotypic features. These include autism, developmental delay, motor and language delays, and behavioral problems, which were present in both cytogenetic groups. Parental studies demonstrated phenotypically normal carriers in several instances, and mildly affected carriers in others, complicating phenotypic association and/or causality. Possible explanations for these results include reduced penetrance, altered gene dosage on a particular genetic background, or a susceptibility region as reported for other areas of the genome implicated in autism and behavior disturbances.

Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia

PubMed Central

Southcombe, J H; Redman, C W G; Sargent, I L; Granne, I

2015-01-01

Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother. PMID:25693732

Effect of diurnal temperature range on cardiovascular markers in the elderly in Seoul, Korea

NASA Astrophysics Data System (ADS)

Lim, Youn-Hee; Kim, Ho; Kim, Jin Hee; Bae, Sanghyuk; Hong, Yun-Chul

2013-07-01

While diurnal temperature range (DTR) has been found to be a risk factor for mortality, evaluation of the underlying mechanisms involved in this association are lacking. To explain the association between DTR and health effects, we investigated how cardiovascular markers responded to DTR. Data was obtained from 560 participants who regularly attended a community elderly welfare center located in Seoul, Korea. Data collection was conducted a total of five times over a 3-year period beginning in August, 2008. We examined systolic and diastolic blood pressure (BP), heart rate (HR), and heart rate variability (HRV). Mixed-effects models and generalized additive mixed models were used to assess the relationship of DTR with BP, HR, and HRV. BP was not associated significantly with rapid temperature changes during the day. While HR was associated linearly with increments of DTR, the relationship between DTR and HRV showed nonlinear associations, or the presence of a cutoff around median DTR. At the cutoff level of DTR determined by an inflection point in the graph, standard deviation of normal-to-normal intervals (SDNN) and root mean square successive difference (RMSSD) were peaked, whereas the low frequency:high frequency (LF:HF) ratio was elevated with decreasing DTR below the cutoff level. The study demonstrated that HR increases with increasing temperature range during the day, and that HRV is reduced at small or large DTR, which suggests minimal cardiovascular stress around the median level of temperature range during the day.

Renal function in type 2 diabetes with rosiglitazone, metformin, and glyburide monotherapy.

PubMed

Lachin, John M; Viberti, Giancarlo; Zinman, Bernard; Haffner, Steven M; Aftring, R Paul; Paul, Gitanjali; Kravitz, Barbara G; Herman, William H; Holman, Rury R; Kahn, Steven E

2011-05-01

In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups. A total of 4351 recently diagnosed, drug-naïve patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR ≥30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m(2)). Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators. Copyright © 2011 by the American Society of Nephrology

Cerebral pressure–flow relationship in lowlanders and natives at high altitude

PubMed Central

Smirl, Jonathan D; Lucas, Samuel J E; Lewis, Nia C S; duManior, Gregory R; Smith, Kurt J; Bakker, Akke; Basnyat, Aperna S; Ainslie, Philip N

2014-01-01

We investigated if dynamic cerebral pressure–flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO2 normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m. Testing sessions involved resting spontaneous and driven (squat–stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.10 Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure–flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure–flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure–flow relationship (in both frequency and time domains) is unaltered at 5,050 m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP. PMID:24169852

Cerebral pressure-flow relationship in lowlanders and natives at high altitude.

PubMed

Smirl, Jonathan D; Lucas, Samuel J E; Lewis, Nia C S; duManoir, Gregory R; Dumanior, Gregory R; Smith, Kurt J; Bakker, Akke; Basnyat, Aperna S; Ainslie, Philip N

2014-02-01

We investigated if dynamic cerebral pressure-flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO2 normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m. Testing sessions involved resting spontaneous and driven (squat-stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.10 Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure-flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure-flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure-flow relationship (in both frequency and time domains) is unaltered at 5,050 m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP.

A cross-sectional analysis of the effects of residential greenness on blood pressure in 10-year old children: results from the GINIplus and LISAplus studies

PubMed Central

2014-01-01

Background According to Ulrich’s psychoevolutionary theory, contact with green environments mitigates stress by activating the parasympathetic system, (specifically, by decreasing blood pressure (BP)). Experimental studies have confirmed this biological effect. However, greenness effects on BP have not yet been explored using an observational study design. We assessed whether surrounding residential greenness is associated with BP in 10 year-old German children. Methods Systolic and diastolic BPs were assessed in 10 year-old children residing in the Munich and Wesel study areas of the German GINIplus and LISAplus birth cohorts. Complete exposure, outcome and covariate data were available for 2,078 children. Residential surrounding greenness was defined as the mean of Normalized Difference Vegetation Index (NDVI) values, derived from Landsat 5 TM satellite images, in circular 500-m buffers around current home addresses of participants. Generalized additive models assessed pooled and area-specific associations between BP and residential greenness categorized into area-specific tertiles. Results In the pooled adjusted model, the systolic BP of children living at residences with low and moderate greenness was 0.90 ± 0.50 mmHg (p-value = 0.073) and 1.23 ± 0.50 mmHg (p-value = 0.014) higher, respectively, than the systolic BP of children living in areas of high greenness. Similarly, the diastolic BP of children living in areas with low and moderate greenness was 0.80 ± 0.38 mmHg (p-value = 0.033) and 0.96 ± 0.38 mmHg (p-value = 0.011) higher, respectively, than children living in areas with high greenness. These associations were not influenced by environmental stressors (temperature, air pollution, noise annoyance, altitude and urbanisation level). When stratified by study area, associations were significant among children residing in the urbanised Munich area but null for those in the rural Wesel area. Conclusions Lower residential greenness was positively associated with higher BP in 10 year-old children living in an urbanised area. Further studies varying in participants’ age, geographical area and urbanisation level are required. PMID:24886243

Orthostatic Hypotension: Mechanisms, Causes, Management

PubMed Central

Tomalia, Victoria A.

2015-01-01

Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP control fails. Such regulation depends on the baroreflexes, normal blood volume, and defenses against excessive venous pooling. OH is common in the elderly and is associated with an increase in mortality rate. There are many causes of OH. Aging coupled with diseases such as diabetes and Parkinson's disease results in a prevalence of 10-30% in the elderly. These conditions cause baroreflex failure with resulting combination of OH, supine hypertension, and loss of diurnal variation of BP. The treatment of OH is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension. The practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension. It is possible to achieve these goals with a combination of fludrocortisone, a pressor agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers. We provide a pragmatic guide on patient education and the patient-orientated approach to the moment to moment management of OH. PMID:26174784

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring.

PubMed

Ramos, Débora R; Costa, Nauilo L; Jang, Karen L L; Oliveira, Ivone B; da Silva, Alexandre A; Heimann, Joel C; Furukawa, Luzia N S

2012-05-22

The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.16% NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA, ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. Copyright © 2012 Elsevier Inc. All rights reserved.

[Dectection of G3BP and CD44v6 in the tissues of laryngeal squamous cell carcinoma and their clinical significance].

PubMed

Luo, Dahu; Lou, Weihua

2017-07-01

Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry. Thereafter, we compared the positive expression rates of G3BP and CD44v6 between in cancer tissues and in normal tissues, analyzed the correlations between the expressions of G3BP, CD44v6 and the laryngeal squamous cell carcinoma features as well as their correlations with microvessel density (MVD) that was determined by FVIIIAg immunohistochemistry. Results Western blotting showed that the expressions of G3BP and CD44v6 proteins in the laryngeal squamous cell carcinoma were higher than those in the paracancerous tissues. Immunohistochemistry showed that compared with the paracancerous tissues, G3BP, CD44v6 and VEGF-A expressions (the positive rates are 58.9%, 53.6%, 46.4%, respectively) were higher in cancer tissues. The positive rates of G3BP and CD44v6 in cancer tissues were related with the clinical stage, recurrence or metastasis, and lymph node metastasis of laryngeal squamous cell carcinoma, but had nothing to do with patients' age and tumor size. Pearson correlation analysis showed the expressions of both G3BP and CD44v6 were positively correlated with VEGF-A (r=0.741, r=0.756). MVD values were significantly higher in the G3BP and CD44v6 positive cases than in paracancerous tissues, but there was no difference in MVD between those without G3BP and CD44v6 positive expressions and the paracancerous tissues. Conclusion The positive expression rates of G3BP and CD44v6 in laryngeal squamous cell carcinoma tissues are very high, and they have a close relationship with the clinical prognosis. They may raise the VEGF-A expression so as to promote angiogenesis, and then accelerate the development of the laryngeal squamous cell carcinoma.

Sleep, insomnia, and hypertension: current findings and future directions.

PubMed

Thomas, S Justin; Calhoun, David

2017-02-01

Blood pressure (BP) varies over 24 hours. During normal sleep, BP typically decreases by 10% or more. Research suggests that disordered sleep, particularly sleep deprivation and obstructive sleep apnea, is associated with increased BP and risk of hypertension. Less is known about the relationship between insomnia and hypertension. Population-based studies have reported an association between insomnia symptoms and both prevalent and incident hypertension, particularly in the context of short sleep duration. Furthermore, a number of mechanisms have been proposed to explain the relationship between insomnia and hypertension. However, few studies have examined these proposed mechanisms, and even fewer clinical trials have been conducted to determine if improved sleep improves BP and/or reverses a nondipping BP pattern. Methodological concerns, particularly with respect to the diagnosis of insomnia, no doubt impact the strength of any observed association. Additionally, a large majority of studies have only examined the association between insomnia symptoms and clinic BP. Therefore, future research needs to focus on careful consideration of the diagnostic criteria for insomnia, as well as inclusion of either home BP or ambulatory BP monitoring. Finally, clinical trials aimed at improving the quality of sleep should be conducted to determine if improved sleep impacts 24-hour BP. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Epigenetic analysis of bovine parthenogenetic embryonic fibroblasts.

PubMed

Kaneda, Masahiro; Takahashi, Masashi; Yamanaka, Ken-Ichi; Saito, Koji; Taniguchi, Masanori; Akagi, Satoshi; Watanabe, Shinya; Nagai, Takashi

2017-08-19

Although more than 100 imprinted genes have already been identified in the mouse and human genomes, little is known about genomic imprinting in cattle. For a better understanding of these genes in cattle, parthenogenetically activated bovine blastocysts were transferred to recipient cows to obtain parthenotes, and fibroblasts derived from a Day 40 (Day 0 being the day of parthenogenetic activation) parthenogenetic embryo (BpEFs) were successfully obtained. Bovine embryonic fibroblasts (BEFs) were also isolated from a normal fertilized embryo obtained from an artificially inseminated cow. The expression of imprinted genes was analyzed by RT-PCR. Paternally expressed genes (PEGs) in mouse (viz., IGF2, PEG3, ZAC1, NDN, DLK1, SGCE, and PEG10) were expressed in BEFs, but not in BpEFs, suggesting that these genes are also imprinted in cattle. However, other PEGs in mouse (viz., IMPACT, MAGEL2, SNRPN, and PEG1/MEST) were expressed in both BEFs and BpEFs. These genes may not be imprinted in BEFs. The expression of seven maternally expressed genes in mouse was also analyzed, and only CDKN1C was not expressed in BpEFs. The DNA methylation patterns of repetitive elements (Satellite I, Satellite II, alpha-satellite, and Art2) were not different between the BEFs and BpEFs; however, the differentially methylated region (DMR) of paternally methylated H19 was hypomethylated, whereas those of maternally methylated PEG3 and PEG10 were hypermethylated in BpEFs, as expected. The methylation of the SNRPN DMR was not different between the BEFs and BpEFs, in accordance with the SNRPN expression levels in both cell types. The XIST gene, which is essential for X chromosome inactivation in females, was expressed in BpEFs, whereas its DMR was half-methylated, suggesting that X chromosome inactivation is normal in these cells. Microarray analysis was also applied to identify novel PEGs that should be expressed only in BEFs but not in BpEFs. More than 300 PEG candidate genes, including IGF2, PEG3, and PEG10, were obtained. These results illustrate the epigenetic characteristic of bovine parthenogenetic embryos and contribute to the identification of novel imprinted genes in cattle.

An online spaced-education game among clinicians improves their patients' time to blood pressure control: a randomized controlled trial.

PubMed

Kerfoot, B Price; Turchin, Alexander; Breydo, Eugene; Gagnon, David; Conlin, Paul R

2014-05-01

Many patients with high blood pressure (BP) do not have antihypertensive medications appropriately intensified at clinician visits. We investigated whether an online spaced-education (SE) game among primary care clinicians can decrease time to BP target among their hypertensive patients. A 2-arm randomized trial was conducted over 52 weeks among primary care clinicians at 8 hospitals. Educational content consisted of 32 validated multiple-choice questions with explanations on hypertension management. Providers were randomized into 2 groups: SE clinicians were enrolled in the game, whereas control clinicians received identical educational content in an online posting. SE game clinicians were e-mailed 1 question every 3 days. Adaptive game mechanics resent questions in 12 or 24 days if answered incorrectly or correctly, respectively. Clinicians retired questions by answering each correctly twice consecutively. Posting of relative performance among peers fostered competition. Primary outcome measure was time to BP target (<140/90 mm Hg). One hundred eleven clinicians enrolled. The SE game was completed by 87% of clinicians (48/55), whereas 84% of control clinicians (47/56) read the online posting. In multivariable analysis of 17 866 hypertensive periods among 14 336 patients, the hazard ratio for time to BP target in the SE game cohort was 1.043 (95% confidence interval, 1.007-1.081; P=0.018). The number of hypertensive episodes needed to treat to normalize one additional patient's BP was 67.8. The number of clinicians needed to teach to achieve this was 0.43. An online SE game among clinicians generated a modest but significant reduction in the time to BP target among their hypertensive patients. http://www.clinicaltrials.gov. Unique identifier: NCT00904007. © 2014 American Heart Association, Inc.

Association between exercise intensity and renal blood flow evaluated using ultrasound echo.

PubMed

Kawakami, Shotaro; Yasuno, Tetsuhiko; Matsuda, Takuro; Fujimi, Kanta; Ito, Ai; Yoshimura, Saki; Uehara, Yoshinari; Tanaka, Hiroaki; Saito, Takao; Higaki, Yasuki

2018-03-10

High-intensity exercise reduces renal blood flow (RBF) and may transiently exacerbate renal dysfunction. RBF has previously been measured invasively by administration of an indicator material; however, non-invasive measurement is now possible with technological innovations. This study examined variations in RBF at different exercise intensities using ultrasound echo. Eight healthy men with normal renal function (eGFR cys 114 ± 19 mL/min/1.73 m 2 ) participated in this study. Using a bicycle ergometer, participants underwent an incremental exercise test using a ramp protocol (20 W/min) until exhaustion in Study 1 and the lactate acid breaking point (LaBP) was calculated. Participants underwent a multi-stage test at exercise intensities of 60, 80, 100, 120, and 140% LaBP in Study 2. RBF was measured by ultrasound echo at rest and 5 min after exercise in Study 1 and at rest and immediately after each exercise in Study 2. To determine the mechanisms behind RBF decline, a catheter was placed into the antecubital vein to study vasoconstriction dynamics. RBF after maximum exercise decreased by 51% in Study 1. In Study 2, RBF showed no significant decrease until 80% LaBP, and showed a significant decrease (31%) at 100% LaBP compared with at rest (p < 0.01). The sympathetic nervous system may be involved in this reduction in RBF. RBF showed no significant decrease until 80% LaBP, and decreased with an increase in blood lactate. Reduction in RBF with exercise above the intensity at LaBP was due to decreased cross-sectional area rather than time-averaged flow velocity.

A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment.

PubMed

Gaburro, Stefano; Stiedl, Oliver; Giusti, Pietro; Sartori, Simone B; Landgraf, Rainer; Singewald, Nicolas

2011-11-01

Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

Evaluation of factors associated with severe and frequent back pain in high school athletes.

PubMed

Noll, Matias; Silveira, Erika Aparecida; Avelar, Ivan Silveira de

2017-01-01

Several studies have shown that half of all young athletes experience back pain (BP). However, high intensity and frequency of BP may be harmful, and the factors associated with BP severity have not been investigated in detail. Here, we investigated the factors associated with a high intensity and high frequency of BP in high school athletes. We included 251 athletes (173 boys and 78 girls [14-20 years old]) in this cross-sectional study. The dependent variables were a high frequency and high intensity of BP, and the independent variables were demographic, socioeconomic, psychosocial, hereditary, anthropometric, behavioural, and postural factors and the level of exercise. The effect measure is presented as prevalence ratio (PR) with 95% confidence interval (CI). Of 251 athletes, 104 reported BP; thus, only these athletes were included in the present analysis. Results of multivariable analysis showed an association between high BP intensity and time spent using a computer (PR: 1.15, CI: 1.01-1.33), posture while writing (PR: 1.41, CI: 1.27-1.58), and posture while using a computer (PR: 1.39, CI: 1.26-1.54). Multivariable analysis also revealed an association of high BP frequency with studying in bed (PR: 1.19, CI: 1.01-1.40) and the method of carrying a backpack (PR: 1.19, CI: 1.01-1.40). In conclusion, we found that behavioural and postural factors are associated with a high intensity and frequency of BP. To the best of our knowledge, this study is the first to compare different intensities and frequencies of BP, and our results may help physicians and coaches to better understand BP in high school athletes.

Evaluation of factors associated with severe and frequent back pain in high school athletes

PubMed Central

Noll, Matias; Silveira, Erika Aparecida; de Avelar, Ivan Silveira

2017-01-01

Several studies have shown that half of all young athletes experience back pain (BP). However, high intensity and frequency of BP may be harmful, and the factors associated with BP severity have not been investigated in detail. Here, we investigated the factors associated with a high intensity and high frequency of BP in high school athletes. We included 251 athletes (173 boys and 78 girls [14–20 years old]) in this cross-sectional study. The dependent variables were a high frequency and high intensity of BP, and the independent variables were demographic, socioeconomic, psychosocial, hereditary, anthropometric, behavioural, and postural factors and the level of exercise. The effect measure is presented as prevalence ratio (PR) with 95% confidence interval (CI). Of 251 athletes, 104 reported BP; thus, only these athletes were included in the present analysis. Results of multivariable analysis showed an association between high BP intensity and time spent using a computer (PR: 1.15, CI: 1.01–1.33), posture while writing (PR: 1.41, CI: 1.27–1.58), and posture while using a computer (PR: 1.39, CI: 1.26–1.54). Multivariable analysis also revealed an association of high BP frequency with studying in bed (PR: 1.19, CI: 1.01–1.40) and the method of carrying a backpack (PR: 1.19, CI: 1.01–1.40). In conclusion, we found that behavioural and postural factors are associated with a high intensity and frequency of BP. To the best of our knowledge, this study is the first to compare different intensities and frequencies of BP, and our results may help physicians and coaches to better understand BP in high school athletes. PMID:28222141

Epicardial adipose tissue volume a diagnostic study for independent predicting disorder of circadian rhythm of blood pressure in patients with essential hypertension.

PubMed

Zhou, L; Deng, Y; Gong, J; Chen, X; Zhang, Q; Wang, J

2016-05-30

The aim of the study was to determine whether epicardial adipose tissue volume (EATV), a new cardiometabolic risk factor, is associated with circadian changes of blood pressure (BP) in patients with newly diagnosed essential hypertension. Ninety patients with newly diagnosed essential hypertension underwent ambulatory blood pressure monitoring for 24 h. EATV was measured using cardiac computed tomography. These patients were categorized into three groups according to their BP patterns (group 1, n=46, dipper hypertension, also called normal pattern; group 2, n=24, non-dipper hypertension; group 3, n=20, anti-dipper hypertension; group 2 and 3 are also called abnormal pattern). Data were collected retrospectively and compared between hypertensive patients with normal pattern and abnormal pattern. The normal pattern hypertensive patient had significant lower mean EATV and BP ((EATV, 91.3±29.4 cm3) than those of abnormal pattern patients including group 2 (EATV, 116.2±31.06cm3, <0.01) and group 3 (EATV, 124.8±28.5cm3, P<0.01). Mean systolic BP over 24 h (BPs24) and mean diastolic BP over 24 h (BPd24) of group 1 (BPs24, 135.7 ± 12.6 mmHg; BPd24, 83.6 ± 10.6 mmHg) were significantly lower than those of group 2 (BPs24, 150.1± 17.6 mmHg, P<0.01; BPd24, 93.2 ± 16.5 mmHg, P<0.01) and group 3 (BPs24, 154.1 ± 16.6mmHg, P<0.01; BPd24, 93.8 ± 17.5 mmHg; P<0.01). Bivariate correlation analysis showed that correlation coefficient of EATV with abnormal blood pressure mode was 0.500 (p<0.001), partial correlation coefficient after adjustment for waist circumference and body mass index was 0.469 (p<0.001). When multivariate backward logistic regression analysis was performed to assess the correlation of BP pattern with EAT volume, it showed that the prevalence of abnormal BP pattern (non-dipper and anti-dipper BP pattern) increased by 1.54 times after adjusting for age and gender per additional 10 cm3 of EAT volume. Receiver operating characteristic curve for EAT alone indicated that the cutoff value of 95.17cm3 had the best performance in predicting abnormal BP pattern with a sensitivity of 75.0% and a specificity of 72.7%. EATV was elevated in newly diagnosed and untreated patients with non-dipper hypertension and anti-dipper hypertension. EATV measured by cardiac computed tomography can be used to indicate the increased risk of circadian rhythm of blood pressure.

Blood pressure load does not add to ambulatory blood pressure level for cardiovascular risk stratification.

PubMed

Li, Yan; Thijs, Lutgarde; Boggia, José; Asayama, Kei; Hansen, Tine W; Kikuya, Masahiro; Björklund-Bodegård, Kristina; Ohkubo, Takayoshi; Jeppesen, Jørgen; Torp-Pedersen, Christian; Dolan, Eamon; Kuznetsova, Tatiana; Stolarz-Skrzypek, Katarzyna; Tikhonoff, Valérie; Malyutina, Sofia; Casiglia, Edoardo; Nikitin, Yuri; Lind, Lars; Sandoya, Edgardo; Kawecka-Jaszcz, Kalina; Filipovsky, Jan; Imai, Yutaka; Ibsen, Hans; O'Brien, Eoin; Wang, Jiguang; Staessen, Jan A

2014-05-01

Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP load as percentage (%) of systolic/diastolic readings ≥135/≥85 mm Hg and ≥120/≥70 mm Hg during day and night, respectively, or as the area under the BP curve (mm Hg×h) using the same ceiling values. During a period of 10.7 years (median), 1284 participants died and 1109 experienced a fatal or nonfatal cardiovascular end point. In multivariable-adjusted models, the risk of cardiovascular complications gradually increased across deciles of BP level and load (P<0.001), but BP load did not substantially refine risk prediction based on 24-hour systolic or diastolic BP level (generalized R(2) statistic ≤0.294%; net reclassification improvement ≤0.28%; integrated discrimination improvement ≤0.001%). Systolic/diastolic BP load of 40.0/42.3% or 91.8/73.6 mm Hg×h conferred a 10-year risk of a composite cardiovascular end point similar to a 24-hour systolic/diastolic BP of 130/80 mm Hg. In analyses dichotomized according to these thresholds, increased BP load did not refine risk prediction in the whole study population (R(2)≤0.051) or in untreated participants with 24-hour ambulatory normotension (R(2)≤0.034). In conclusion, BP load does not improve risk stratification based on 24-hour BP level. This also applies to subjects with normal 24-hour BP for whom BP load was proposed to be particularly useful in risk stratification.

Blood pressure and endothelial function in healthy, pregnant women after acute and daily consumption of flavanol-rich chocolate: a pilot, randomized controlled trial.

PubMed

Mogollon, Jaime Andres; Bujold, Emmanuel; Lemieux, Simone; Bourdages, Mélodie; Blanchet, Claudine; Bazinet, Laurent; Couillard, Charles; Noël, Martin; Dodin, Sylvie

2013-04-08

Several randomized clinical trials (RCTs) indicate that flavanol-rich chocolate has beneficial effects on flow-mediated dilation (FMD) and blood pressure (BP). However, no RCTs have evaluated these outcomes in pregnant women. The objective of this 2-group, parallel, double-blind RCT was to examine the effects of flavanol-rich chocolate on FMD and BP in pregnant women with normal BP. Forty-four healthy, pregnant women were randomized to the high-flavanol (n = 23) or low-flavanol (n = 21) chocolate consumption for 12 weeks. At randomization (0, 60, 120 and 180 min after a single 40-g dose of chocolate), 6 and 12 weeks after daily 20-g chocolate intake, we evaluated plasma concentrations of flavanols and theobromine, as well as the FMD and BP. Plasma epicatechin was significantly increased (p < 0.001) 180 min after the consumption of 40-g high-flavanol chocolate compared to low-flavanol chocolate. Theobromine concentrations were significantly higher 180 min and 12 weeks after the intake of experimental chocolate or low-flavanol chocolate (p < 0.001). FMD was not different between the 2 groups at all pre-defined time periods. No other significant within-group or between-group changes were observed. These results confirm the feasibility of a large-scale RCT comparing daily consumption of flavanol-rich chocolate to an equivalent placebo during pregnancy and demonstrate higher plasma epicatechin and theobromine concentration in the intervention group after acute ingestion ClinicalTrials.gov Identifier: NCT01659060.

Exercise training for blood pressure: a systematic review and meta-analysis.

PubMed

Cornelissen, Veronique A; Smart, Neil A

2013-02-01

We conducted meta-analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure (BP) in adults. The aims were to quantify and compare BP changes for each training modality and identify patient subgroups exhibiting the largest BP changes. Randomized controlled trials lasting ≥4 weeks investigating the effects of exercise on BP in healthy adults (age ≥18 years) and published in a peer-reviewed journal up to February 2012 were included. Random effects models were used for analyses, with data reported as weighted means and 95% confidence interval. We included 93 trials, involving 105 endurance, 29 dynamic resistance, 14 combined, and 5 isometric resistance groups, totaling 5223 participants (3401 exercise and 1822 control). Systolic BP (SBP) was reduced after endurance (-3.5 mm Hg [confidence limits -4.6 to -2.3]), dynamic resistance (-1.8 mm Hg [-3.7 to -0.011]), and isometric resistance (-10.9 mm Hg [-14.5 to -7.4]) but not after combined training. Reductions in diastolic BP (DBP) were observed after endurance (-2.5 mm Hg [-3.2 to -1.7]), dynamic resistance (-3.2 mm Hg [-4.5 to -2.0]), isometric resistance (-6.2 mm Hg [-10.3 to -2.0]), and combined (-2.2 mm Hg [-3.9 to -0.48]) training. BP reductions after endurance training were greater (P<0.0001) in 26 study groups of hypertensive subjects (-8.3 [-10.7 to -6.0]/-5.2 [-6.8 to -3.4] mm Hg) than in 50 groups of prehypertensive subjects (-2.1 [-3.3 to -0.83]/-1.7 [-2.7 to -0.68]) and 29 groups of subjects with normal BP levels (-0.75 [-2.2 to +0.69]/-1.1 [-2.2 to -0.068]). BP reductions after dynamic resistance training were largest for prehypertensive participants (-4.0 [-7.4 to -0.5]/-3.8 [-5.7 to -1.9] mm Hg) compared with patients with hypertension or normal BP. Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP. Data from a small number of isometric resistance training studies suggest this form of training has the potential for the largest reductions in SBP.

Associations of Baroreflex Sensitivity, Heart Rate Variability, and Initial Orthostatic Hypotension with Prenatal and Recent Postnatal Methylmercury Exposure in the Seychelles Child Development Study at Age 19 Years

PubMed Central

Périard, Daniel; Beqiraj, Bujar; Hayoz, Daniel; Viswanathan, Bharathi; Evans, Katie; Thurston, Sally W.; Davidson, Philip W.; Myers, Gary J.; Bovet, Pascal

2015-01-01

Background: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. Methods: Subjects in theSeychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects’ hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. Results: Prenatal MeHg exposures were similar in boys and girls (6.7 ± 4.3, 6.7 ± 3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2 ± 5.8 vs 7.9 ± 4.3 ng/g, p = 0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8 ± 7 ms/mm Hg, PNN50: 24.9 ± 6.8%, rMSSD: 68 ± 22, LF/HF: 0.61 ± 0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop >40 mm Hg, but only 5.3% reported dizziness or had syncope. Prenatal and recent postnatal MeHg levels, overall, were not associated with BRS, E/I ratio, PNN50, rMSSD, LF/HF ratio, Max30/Min15 ratio, and IOH. Conclusions: This study provides no support for the hypothesis that prenatal or recent postnatal MeHg exposure from fish consumption is associated with impaired autonomic heart rate control. PMID:25807149

Associations of baroreflex sensitivity, heart rate variability, and initial orthostatic hypotension with prenatal and recent postnatal methylmercury exposure in the Seychelles Child Development Study at age 19 years.

PubMed

Périard, Daniel; Beqiraj, Bujar; Hayoz, Daniel; Viswanathan, Bharathi; Evans, Katie; Thurston, Sally W; Davidson, Philip W; Myers, Gary J; Bovet, Pascal

2015-03-23

A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. Subjects in the Seychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects' hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. Prenatal MeHg exposures were similar in boys and girls (6.7±4.3, 6.7±3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2±5.8 vs 7.9±4.3 ng/g, p=0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8±7 ms/mm Hg, PNN50: 24.9±6.8%, rMSSD: 68±22, LF/HF: 0.61±0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop>40 mm Hg, but only 5.3% reported dizziness or had syncope. Prenatal and recent postnatal MeHg levels, overall, were not associated with BRS, E/I ratio, PNN50, rMSSD, LF/HF ratio, Max30/Min15 ratio, and IOH. This study provides no support for the hypothesis that prenatal or recent postnatal MeHg exposure from fish consumption is associated with impaired autonomic heart rate control.

Arterial α2-Na+ pump expression influences blood pressure: lessons from novel, genetically engineered smooth muscle-specific α2 mice.

PubMed

Chen, Ling; Song, Hong; Wang, Youhua; Lee, Jane C; Kotlikoff, Michael I; Pritchard, Tracy J; Paul, Richard J; Zhang, Jin; Blaustein, Mordecai P

2015-09-01

Arterial myocytes express α1-catalytic subunit isoform Na(+) pumps (75-80% of total), which are ouabain resistant in rodents, and high ouabain affinity α2-Na(+) pumps. Mice with globally reduced α2-pumps (but not α1-pumps), mice with mutant ouabain-resistant α2-pumps, and mice with a smooth muscle (SM)-specific α2-transgene (α2 (SM-Tg)) that induces overexpression all have altered blood pressure (BP) phenotypes. We generated α2 (SM-DN) mice with SM-specific α2 (not α1) reduction (>50%) using nonfunctional dominant negative (DN) α2. We compared α2 (SM-DN) and α2 (SM-Tg) mice to controls to determine how arterial SM α2-pumps affect vasoconstriction and BP. α2 (SM-DN) mice had elevated basal mean BP (mean BP by telemetry: 117 ± 4 vs. 106 ± 1 mmHg, n = 7/7, P < 0.01) and enhanced BP responses to chronic ANG II infusion (240 ng·kg(-1)·min(-1)) and high (6%) NaCl. Several arterial Ca(2+) transporters, including Na(+)/Ca(2+) exchanger 1 (NCX1) and sarcoplasmic reticulum and plasma membrane Ca(2+) pumps [sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and plasma membrane Ca(2+)-ATPase 1 (PMCA1)], were also reduced (>50%). α2 (SM-DN) mouse isolated small arteries had reduced myogenic reactivity, perhaps because of reduced Ca(2+) transporter expression. In contrast, α2 (SM-Tg) mouse aortas overexpressed α2 (>2-fold), NCX1, SERCA2, and PMCA1 (43). α2 (SM-Tg) mice had reduced basal mean BP (104 ± 1 vs. 109 ± 2 mmHg, n = 15/9, P < 0.02) and attenuated BP responses to chronic ANG II (300-400 ng·kg(-1)·min(-1)) with or without 2% NaCl but normal myogenic reactivity. NCX1 expression was inversely related to basal BP in SM-α2 engineered mice but was directly related in SM-NCX1 engineered mice. NCX1, which usually mediates arterial Ca(2+) entry, and α2-Na(+) pumps colocalize at plasma membrane-sarcoplasmic reticulum junctions and functionally couple via the local Na(+) gradient to help regulate cell Ca(2+). Altered Ca(2+) transporter expression in SM-α2 engineered mice apparently compensates to minimize Ca(2+) overload (α2 (SM-DN)) or depletion (α2 (SM-Tg)) and attenuate BP changes. In contrast, Ca(2+) transporter upregulation, observed in many rodent hypertension models, should enhance Ca(2+) entry and signaling and contribute significantly to BP elevation. Copyright © 2015 the American Physiological Society.

Impact of Different Normality Thresholds for 24-hour ABPM at the Primary Health Care Level.

PubMed

Grezzana, Guilherme Brasil; Moraes, David William; Stein, Airton Tetelbon; Pellanda, Lucia Campos

2017-02-01

Hypertension is an important risk factor for cardiovascular outcomes. Primary health care (PHC) physicians should be prepared to act appropriately in the prevention of cardiovascular risk factors. However, the rates of patients with control of blood pressure (BP) remain low. The impact of the reclassification of high BP by 24-hour ambulatory BP monitoring (ABPM) can lead to different medical decisions in PHC. To evaluate the agreement between the BP measured by a conventional method by PHC physicians and by 24-hour ABPM, considering different BP normal thresholds for the 24-hour ABPM according to the V Brazilian ABPM Guidelines and the European Society of Hypertension Guidelines. A cross-sectional study including 569 hypertensive patients. The BP was initially measured by the PHC physicians and, later, by 24-hour ABPM. The BP measurements were obtained independently between the two methods. The therapeutic targets for the conventional BP followed the guidelines by the Eighth Joint National Committee (JNC 8), the V ABPM Brazilian Guidelines, and the 2013 European Hypertension Guidelines. There was an accuracy of 54.8% (95% confidence interval [95%CI] 0.51 - 0.58%) for the BP measured with the conventional method when compared with the 24-hour ABPM, with a sensitivity of 85% (95%CI 80.8 - 88.6%), specificity of 31.9% (95%CI 28.7 - 34.7%), and kappa value of 0.155, when considering the European Hypertension Guidelines. When using more stringent thresholds to characterize the BP as "normal" by ABPM, the accuracy was 45% (95%CI 0.41 - 0.47%) for conventional measurement when compared with 24-hour ABPM, with a sensitivity of 86.7% (95%CI 0.81 - 0.91%), specificity of 29% (95%CI 0.26 - 0.30%), and kappa value of 0.103. The BP measurements obtained by PHC physicians showed low accuracy when compared with those obtained by 24-hour ABPM, regardless of the threshold set by the different guidelines. A hipertensão arterial sistêmica é um fator de risco importante para desfechos cardiovasculares. Médicos da atenção primária à saúde (APS) devem estar preparados para atuar adequadamente na prevenção de fatores de risco cardiovascular. No entanto, as taxas de pacientes com pressão arterial (PA) controlada continuam baixas. O impacto da reclassificação do diagnóstico de hipertensão pela utilização da monitorização ambulatorial da PA (MAPA) de 24 horas pode levar a diferentes decisões médicas na APS. Avaliar a concordância entre as PAs medidas por método convencional por médicos da APS e por MAPA de 24 horas, considerando diferentes limiares de normalidade para a MAPA de 24 horas de acordo com as recomendações da V Diretriz Brasileira de MAPA e da Diretriz da Sociedade Europeia de Hipertensão. Estudo transversal com 569 pacientes hipertensos. A PA foi medida inicialmente por médicos da APS e, posteriormente, pela MAPA de 24 horas. As medidas foram obtidas de forma independente entre os dois métodos. Os alvos terapêuticos para a PA convencional seguiram as orientações do Eighth Joint National Committee (JNC 8), das V Diretrizes Brasileiras de MAPA e das Diretrizes Europeias de Hipertensão de 2013. Foi observada uma acurácia de 54,8% (intervalo de confiança de 95% [IC95%] 0,51 - 0,58%) para a PA aferida de forma convencional quando comparada à obtida com a MAPA de 24 horas, além de uma sensibilidade de 85% (IC95% 80,8 - 88,6%), especificidade de 31,9% (IC95% 28,7 - 34,7%) e kappa de 0,155, quando consideradas as Diretrizes Europeias de Hipertensão. Quando utilizados limiares mais rígidos para caracterizar a PA como "normal" pela MAPA, foi identificada uma acurácia de 45% (IC95% 0,41 - 0,47%) pela medida convencional quando comparada à obtida pela MAPA de 24 horas, além de uma sensibilidade de 86,7% (IC95% 0,81 - 0,91%), especificidade de 29% (IC95% 0,26 - 0,30%) e kappa de 0,103. As medidas de PA avaliadas pelos médicos da APS apresentaram baixa acurácia quando comparadas às medidas pela MAPA de 24 horas, independente do limiar utilizado pelas diferentes diretrizes.

Carotid artery intima-media thickness and distensibility in children and adolescents: reference values and role of body dimensions.

PubMed

Doyon, Anke; Kracht, Daniela; Bayazit, Aysun K; Deveci, Murat; Duzova, Ali; Krmar, Rafael T; Litwin, Mieczyslaw; Niemirska, Anna; Oguz, Berna; Schmidt, Bernhard M W; Sözeri, Betul; Querfeld, Uwe; Melk, Anette; Schaefer, Franz; Wühl, Elke

2013-09-01

Carotid intima-media thickness (cIMT) and carotid artery distensibility are reliable screening methods for vascular alterations and the assessment of cardiovascular risk in adult and pediatric cohorts. We sought to establish an international reference data set for the childhood and adolescence period and explore the impact of developmental changes in body dimensions and blood pressure (BP) on carotid wall thickness and elasticity. cIMT, the distensibility coefficient, the incremental modulus of elasticity, and the stiffness index β were assessed in 1155 children aged 6 to 18 years and sex-specific reference charts normalized to age or height were constructed from 1051 nonobese and nonhypertensive children. The role of body dimensions, BP, and family history, as well as the association between cIMT and distensibility, was investigated. cIMT increased and distensibility decreased with age, height, body mass index, and BP. A significant sex difference was apparent from the age of 15 years. Age- and height-normalized cIMT and distensibility values differed in children who are short or tall for their age. By stepwise multivariate analysis, standardized systolic BP and body mass index were independently positively associated with cIMT SD scores (SDS). Systolic BP SDS independently predicted all distensibility measures. Distensibility coefficient SDS was negatively and β SDS positively associated with cIMT SDS, whereas incremental modulus of elasticity was independent of cIMT. Morphological and functional aspects of the common carotid artery are particularly influenced by age, body dimensions, and BP. The reference charts established in this study allow to accurately compare vascular phenotypes of children with chronic conditions with those of healthy children.

Intake of low sodium salt substitute for 3years attenuates the increase in blood pressure in a rural population of North China - A randomized controlled trial.

PubMed

Zhou, Bo; Webster, Jacqui; Fu, Ling-Yu; Wang, Hai-Long; Wu, Xiao-Mei; Wang, Wen-Li; Shi, Jing-Pu

2016-07-15

Lowering salt intake is one of the successful and cost-effective methods to reduce blood pressure (BP). In this randomized controlled study, we investigated the effects of a 3-year substitution of table salt with a low-sodium salt substitute in a rural population of North China. Subjects from 200 families residing in five villages in Liaoning, North China were registered in this study and randomly divided into two groups: normal salt (100% sodium chloride) and low salt substitute (65% NaCl, 25% KCl, 10% MgSO4). We compared the effects of the low-sodium salt substitute and normal salt on differences in BP from baseline to various follow-up time points during this 3-year study period. We also examined several factors that may affect the long-term changes in BP. Hypertension was defined per World Health Organization guidelines as BP≥140/90mmHg. The low sodium substitute significantly reduced the increase in both systolic and diastolic BP compared with the regular salt (P=0.000). Also, the population aged 40-70years showed most beneficial response to the salt substitute compared with those aged <40 or >70years. The low salt substitute had similar beneficial effects in both males and females. In addition, the salt type consumed and body mass index significantly affected the change in BP. Use of the salt substitute significantly reduces the increase in BP over a long term, and thus, the salt substitute can be used as a replacement for regular salt in the daily diet to prevent/diminish the incidence of hypertension. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The HK2 Dependent "Warburg Effect" and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate.

PubMed

Lis, Paweł; Dyląg, Mariusz; Niedźwiecka, Katarzyna; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

2016-12-15

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the "Warburg" and "Crabtree" effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the "Warburg effect" and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the "Warburg effect", and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the "Warburg effect", i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as "multiple myeloma". Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development.

Nocturnal and Circadian Rhythm of Blood Pressure Is Associated with Renal Structure Damage and Function in Patients with IgAN.

PubMed

Lin, Lirong; Zhang, Huhai; Yang, Jurong; Zhang, Jianguo; Li, Kailong; Huo, Bengang; Dai, Huanzi; Zhang, Weiwei; Yang, Jie; Tan, Wei; He, Yani

2016-01-01

Abnormal circadian rhythm of blood pressure (BP) is closely related to target organ damage in hypertension. However, the association between abnormal circadian rhythm of BP and renal injury is not clear. We investigated whether renal injury is associated with nocturnal BP and circadian rhythm of BP in Chinese IgAN patients. Clinic and 24 h ambulatory BP monitoring data were obtained from 330 Chinese IgAN patients with mean 24 h BP < 130/80 and mean daytime BP < 135/85 mmHg. Renal histopathological injury was determined according to the Oxford classification of IgAN. Among the 330 IgAN subjects, 35.8% suffered from nocturnal hypertension, 61.5% had abnormal circadian BP, and 27% had nocturnal hypertension with a nondipping pattern. Compared with nocturnal normotensive patients, patients with nocturnal hypertension had significantly higher levels of blood cystatin C, blood uric acid, and lower estimated glomerular filtration rate (eGFR), and significantly a higher mean renal tissue injury score. The nondipping hypertensive group had significantly higher nocturnal diastolic and systolic BP, blood uric acid, and glomerulosclerosis rates, whereas eGFR was lower. In nondipping hypertensive patients, urinary sodium excretion and renal tissue injury scores were significantly higher than dipping patients. Nocturnal hypertension and abnormal circadian BP correlated with renal tissue injury, renal interstitial fibrosis, and aortic arch atherosclerosis. Abnormal circadian rhythm of BP and nocturnal hypertension are common clinical manifestations in Chinese IgAN patients with normal mean 24 h BP. Abnormal circadian BP and nocturnal hypertension may accelerate IgAN progression by inducing renal dysfunction and histopathological damage. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Renal Function in Type 2 Diabetes with Rosiglitazone, Metformin, and Glyburide Monotherapy

PubMed Central

Viberti, Giancarlo; Zinman, Bernard; Haffner, Steven M.; Aftring, R. Paul; Paul, Gitanjali; Kravitz, Barbara G.; Herman, William H.; Holman, Rury R.; Kahn, Steven E.

2011-01-01

Summary Background and objectives In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups. Design, setting, participants, & measurements A total of 4351 recently diagnosed, drug-naïve patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. Results The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR ≥30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m2). Conclusions Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators. PMID:21454723

Increased frequency of angiotensin-converting enzyme DD genotype in Saudi overweight and obese patients.

PubMed

El-Hazmi, Mohsen Af; Warsy, Arjumand S

2003-01-01

Several studies have been carried out to investigate the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) in obese and normal weight individuals, often with contradictory results in different populatios. In some studies, the DD genotype occurs at a high frequency in obesity, while in others no association has been demonstrated. Since obesity and overweight are of frequent occurrence in the Saudi population, we initiated this study to investigate the I/D polymorphism of ACE in obese, overweight and normal weight Saudis. The study group included 457 Saudi males and females. The height and weight were measured and body mass index (BMI) was calculated. Based on the BMI value, the total study population was classified as normal, overweight and obese. A total of 117 obese (BMI >30 (kg/m(2))), 185 overweight (BMI=25-29.9 (kg/m(2))) and 155 normal weight individuals (BMI< (kg/m (2)) were enrolled. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used to study the ACE polymorphism. For the deletion (D) form, a 190 bp and for the insertion (I) form, 490 bp DNA fragment were obtained on 2% agarose gel electrophoresis. The frequency of DD genotype was 76.9% in the obese, and 73.5% in the overweight individuals, compared to 19.66% and 24.86% of the ID genotype in the obese and overweight, respectively. Among the normal weight individuals, the frequency was significantly lower for DD and higher for the ID genotype, i.e., 58.7% for DD and 40% for ID. The allele frequencies in the obese were 0.867 and 0.133 for the D and I alleles, respectively. While in the overweight, the frequencies were 0.859 and 0.141 for these alleles, respectively, compared to 0.787 and 0.213 in the normal weight individuals. The DD genotype and D allele occur at a high frequency in Saudi overweight and obese individuals, and may have some role in fat accumulation by affecting metabolic pathways of fat, thus leading to the development of overweight and obesity.

Impaired systolic blood pressure recovery directly after standing predicts mortality in older falls clinic patients.

PubMed

Lagro, Joep; Schoon, Yvonne; Heerts, Inger; Meel-van den Abeelen, Aisha S S; Schalk, Bianca; Wieling, Wouter; Olde Rikkert, Marcel G M; Claassen, Jurgen A H R

2014-04-01

Normally, standing up causes a blood pressure (BP) drop within 15 seconds, followed by recovery to baseline driven by BP control mechanisms. The prognostic value of this initial BP drop, but also of the recovery hereafter, is unknown. The aim of this study was to examine the prognostic value of these BP characteristics in response to standing. In a retrospective cohort study of 238 consecutive patients visiting our falls outpatient clinic, we examined the relation between all-cause mortality and BP decline and recovery directly after active standing up with Cox proportional hazards analyses. Of 238 patients (mean age 78.4 ± 7.8 years), during a median follow-up of 21.0 months, 36 (15%) patients died. Neither absolute nor relative (%) initial BP drop after standing predicted mortality. In contrast, the magnitude of BP recovery 40-60 seconds after standing was associated with mortality, even after adjustment for age, comorbidity, and other baseline characteristics. When systolic BP had recovered to less than 80% of prestanding baseline after 60 seconds of standing, this was a powerful independent predictor of mortality (hazard ratio: 3.00; 95% confidence interval 1.17-7.68). Failure to recover from BP decline in the first minute after active standing up is associated with excess mortality in falls clinic patients. A recovery of systolic BP to less than 80% of baseline after 60 seconds may be used as an easily available cardiovascular marker for increased mortality risk in older falls clinic patients.

Acute effects of violent video-game playing on blood pressure and appetite perception in normal-weight young men: a randomized controlled trial.

PubMed

Siervo, M; Sabatini, S; Fewtrell, M S; Wells, J C K

2013-12-01

Watching television and playing video game being seated represent sedentary behaviours and increase the risk of weight gain and hypertension. We investigated the acute effects of violent and non-violent video-game playing on blood pressure (BP), appetite perception and food preferences. Forty-eight young, normal-weight men (age: 23.1±1.9 years; body mass index: 22.5±1.9 kg/m(2)) participated in a three-arm, randomized trial. Subjects played a violent video game, a competitive, non-violent video game or watched TV for 1 h. Measurements of BP, stress and appetite perception were recorded before a standardized meal (∼300 kcal) and then repeated every 15 min throughout the intervention. Violent video-game playing was associated with a significant increase in diastolic BP (Δ±s.d.=+7.5±5.8 mm Hg; P=0.04) compared with the other two groups. Subjects playing violent video games felt less full (P=0.02) and reported a tendency towards sweet food consumption. Video games involving violence appear to be associated with significant effects on BP and appetite perceptions compared with non-violent gaming or watching TV.

[Effect of blood lipid on the change of brachial-ankle pulse wave velocity among prehypertensive population].

PubMed

Wang, Lin; Shuai, Ping; Liu, Yuping; Cheng, Youfu; Yang, Hua; Li, Tingxin; Gong, Lirong; Ren, Jiaojiao; Wang, Hongjia

2014-09-01

To explore the effect of blood lipid and lipoprotein ratios on the change of brachial-ankle pulse wave velocity (baPWV) among prehypertensive subjects. 11 611 subjects with normal blood pressure (BP) were divided into two groups, which was one with optimal blood pressure (BP<120/80 mmHg) and the other with prehypertension (BP:120-139/80-89 mmHg). Height, weight, baPWV, fasting blood-glucose, TC, TG, LDL-C and HDL-C were detected. The abnormal rate of baPWV in prehypertension group was obviously higher than that in the optimal blood pressure group. For optimal blood pressure group, the abnormality of TG, TC, LDL-C, TC/HDL-C as well as LDL-C/HDL-C, caused the increase of baPWV significantly (P < 0.001). For prehypertensive group, the abnormality of TC and LDL-C caused the significant increase of baPWV (P < 0.001). Results from logistic regression analysis showed that except for age, BMI and fasting blood-glucose, TC/HDL-C increasing was the independent risk factor in optimal blood pressure group, while TG increasing was for the prehypertension group. With different normal BP level, both abnormality of blood lipid and lipoprotein ratio were the independent risk factors for baPWV increasing.

The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside.

PubMed

Azevedo-Silva, J; Queirós, O; Baltazar, F; Ułaszewski, S; Goffeau, A; Ko, Y H; Pedersen, P L; Preto, A; Casal, M

2016-08-01

At the beginning of the twenty-first century, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues. The altered metabolism of cancers, an essential hallmark for their progression, also became their Achilles heel by facilitating 3BP's selective entry and specific targeting. Treatment with 3BP has been administered in several cancer type models both in vitro and in vivo, either alone or in combination with other anticancer therapeutic approaches. These studies clearly demonstrate 3BP's broad action against multiple cancer types. Clinical trials using 3BP are needed to further support its anticancer efficacy against multiple cancer types thus making it available to more than 30 million patients living with cancer worldwide. This review discusses current knowledge about 3BP related to cancer and discusses also the possibility of its use in future clinical applications as it relates to safety and treatment issues.

Therapeutic Approach to Hypertension Urgencies and Emergencies in the Emergency Room.

PubMed

Maloberti, Alessandro; Cassano, Giulio; Capsoni, Nicolò; Gheda, Silvia; Magni, Gloria; Azin, Giulia Maria; Zacchino, Massimo; Rossi, Adriano; Campanella, Carlo; Beretta, Andrea Luigi Roberto; Bellone, Andrea; Giannattasio, Cristina

2018-05-18

Hypertensive urgencies-emergencies are important and common events. They are defined as a severe elevation in BP, higher than 180/120 mmHg, associated or not with the evidence of new or worsening organ damage for emergencies and urgencies respectively. Anamnestic information, physical examination and instrumental evaluation determine the following management that could need oral (for urgencies) or intravenous (for emergencies) anti-hypertensives drugs. The choice of the specific drugs depend on the underlying causes of the crisis, patient's demographics, cardiovascular risk and comorbidities. For emergencies a maximum BP reduction of 20-25% within the first hour and then to 160/110-100 over next 2-6 h, is considered appropriate with a further gradual decrease over the next 24-48 h to reach normal BP levels. In the case of hypertensive urgencies, a gradual lowering of BP over 24-48 h with an oral medication is the best approach and an aggressive BP lowering should be avoided. Subsequent management with particular attention on chronic BP values control is important as the right treatment of the acute phase.

Home blood pressure monitoring. Current knowledge and directions for future research.

PubMed

Reims, H; Fossum, E; Kjeldsen, S E; Julius, S

2001-01-01

Home blood pressure (BP) monitoring has become popular in clinical practice and several automated devices for home BP measurement are now recommendable. Home BP is generally lower than clinic BP, and similar to daytime ambulatory BP. Home BP measurement eliminates the white coat effect and provides a high number of readings, and it is considered more accurate and reproducible than clinic BP. It can improve the sensitivity and statistical power of clinical drug trials and may have a higher prognostic value than clinic BP. Home monitoring may improve compliance and BP control, and reduce costs of hypertension management. Diagnostic thresholds and treatment target values for home BP remain to be established by longitudinal studies. Until then, home BP monitoring is to be considered a supplement. However, high home BP may support or confirm the diagnosis made in the doctor's office, and low home BP may warrant ambulatory BP monitoring. During long-term follow-up, home BP monitoring provides an opportunity for close attention to BP levels and variations. The first international guidelines have established a consensus document with recommendations, including a proposal of preliminary diagnostic thresholds, but further research is needed to define the precise role of home BP monitoring in clinical practice.

Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial.

PubMed

Teo, Koon K; Pfeffer, Marc; Mancia, Giuseppe; O'Donnell, Martin; Dagenais, Gilles; Diaz, Rafael; Dans, Antonio; Liu, Lisheng; Bosch, Jackie; Joseph, Philip; Copland, Ingrid; Jung, Hyejung; Pogue, Janice; Yusuf, Salim

2014-07-01

We studied the unclear question whether blood pressure (BP) lowering reduces cardiovascular disease (CVD) in elderly individuals with systolic BP <160 mm Hg. We initiated a randomized placebo-controlled stratified 2 × 2 factorial clinical trial evaluating the effects of BP lowering in 11 000 elderly individuals with systolic blood pressure (SBP) between 130 and 159 mm Hg, for 5 years. Following 5-week active run-in, participants were randomized to aliskiren (300 mg) or placebo, and to an additional antihypertensive [hydrochlorothiazide (25 mg) or amlodipine (5 mg)], or their respective placeboes. Study was terminated by sponsor after 1759 subjects (age 72.1 ± 5.2 years, 88% receiving at least one antihypertensive) were randomized and followed for 0.6 year. Study drugs were well tolerated with few serious adverse events during run-in and after randomization, with no significant differences between treatment groups. By design, three levels of BP reductions were achieved, adjusted mean BP reductions of 3.5/1.7 mm Hg (P < 0.001) by aliskiren, 6.8/3.3 mm Hg (P < 0.001) by hydrochlorothiazide or amlodipine, and 10.3/5.0 mm Hg (P < 0.001) by double therapy compared with placebo. Twenty-five major CVD events occurred. Non-significant trends towards fewer CVD events with greater BP reductions are evident: hazard ratios (HR) 0.82 [95% confidence interval (CI): 0.37-1.81] for 3.5 mm Hg SBP reduction; HR 0.45 (95% CI: 0.19-1.04) for 6.8 mm Hg; and HR 0.25 (0.05-1.18) for 10.3 mm Hg reduction for primary composite of CV death, MI, stroke, or significant heart failure. Sizeable reductions in BP, with potential for substantial CVD reduction, can be safely achieved using combinations of BP drugs in the elderly with normal high and Stage 1 hypertension. NCT01259297. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Polymorphism at the 3'-UTR of the thymidylate synthase gene: A potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao Zhongxing; Liu Hongji; Swisher, Stephen G.

2006-03-01

Purpose: To test the hypothesis that TS3'UTR polymorphisms predict outcomes in 146 Caucasian patients with esophageal adenocarcinoma treated with preoperative 5-fluorouracil-based chemoradiation. Methods and Materials: DNA was extracted from hematoxylin-and-eosin stained histologic slides of normal esophageal or gastric mucosa sections from paraffin blocks of esophagectomy specimens. Genotypes of the TS3'UTR polymorphism were determined by polymerase chain reaction for a 6-bp insertion. The genotype groups (0bp/0bp, 6bp/0bp, and 6bp/6bp) were compared for clinical features and overall survival, recurrence-free-survival, locoregional control (LRC), and distant metastasis control. Multivariable Cox regression analyses were performed to find independent predictors for the stated outcomes. Results: Theremore » was a trend of association between 6bp/6bp genotype and a decreased risk of local regional recurrence (hazards ratio = 0.211, 95% confidence interval = 0.041-1.095, p = 0.06) compared with other genotypes. There was a trend that patients with 6bp/6bp genotype had a higher 3-year probability of LRC compared with patients with the other two genotypes combined (p = 0.07); however, the difference was not statistically significant. Conclusions: The null hypotheses were not rejected in this study, probably owing to small sample size or the single gene examined. Prospective studies with adequate statistical power analyzing a family of genes involved in the 5-fluorouracil metabolism are needed to assess genetic determinants of treatment-related outcomes in esophageal adenocarcinoma.« less

Cloud-based BP system integrated with CPOE improves self-management of the hypertensive patients: A randomized controlled trial.

PubMed

Lee, Peisan; Liu, Ju-Chi; Hsieh, Ming-Hsiung; Hao, Wen-Rui; Tseng, Yuan-Teng; Liu, Shuen-Hsin; Lin, Yung-Kuo; Sung, Li-Chin; Huang, Jen-Hung; Yang, Hung-Yu; Ye, Jong-Shiuan; Zheng, He-Shun; Hsu, Min-Huei; Syed-Abdul, Shabbir; Lu, Richard; Nguyen, Phung-Anh; Iqbal, Usman; Huang, Chih-Wei; Jian, Wen-Shan; Li, Yu-Chuan Jack

2016-08-01

Less than 50% of patients with hypertensive disease manage to maintain their blood pressure (BP) within normal levels. The aim of this study is to evaluate whether cloud BP system integrated with computerized physician order entry (CPOE) can improve BP management as compared with traditional care. A randomized controlled trial done on a random sample of 382 adults recruited from 786 patients who had been diagnosed with hypertension and receiving treatment for hypertension in two district hospitals in the north of Taiwan. Physicians had access to cloud BP data from CPOE. Neither patients nor physicians were blinded to group assignment. The study was conducted over a period of seven months. At baseline, the enrollees were 50% male with a mean (SD) age of 58.18 (10.83) years. The mean sitting BP of both arms was no different. The proportion of patients with BP control at two, four and six months was significantly greater in the intervention group than in the control group. The average capture rates of blood pressure in the intervention group were also significantly higher than the control group in all three check-points. Cloud-based BP system integrated with CPOE at the point of care achieved better BP control compared to traditional care. This system does not require any technical skills and is therefore suitable for every age group. The praise and assurance to the patients from the physicians after reviewing the Cloud BP records positively reinforced both BP measuring and medication adherence behaviors. Copyright © 2016. Published by Elsevier Ireland Ltd.

Impact of a social marketing media campaign on public awareness of hypertension.

PubMed

Petrella, Robert J; Speechley, Mark; Kleinstiver, Peter W; Ruddy, Terry

2005-02-01

Barriers to high blood pressure (BP) awareness and control are exacerbated by poor knowledge of the consequences and uncertainty regarding how to and who should direct care. We developed a social marketing hypertension awareness program to determine baseline awareness, knowledge, and treatment behavior, and then studied the impact of a targeted, media intervention among randomly surveyed adults at risk in a representative urban community compared to a control community immediately and 6 months after the intervention. The program consisted of three random-digit telephone surveys conducted in two mid-sized Ontario cities to determine high BP awareness, knowledge, and treatment behavior. Using baseline knowledge and attitudes toward high BP in both communities, a social marketing awareness strategy and mass media intervention campaign incorporating television, radio, print, direct to patient, and interactive techniques was developed and implemented in the test city only. Both test and control cities were resurveyed immediately after and at 6 months post-media intervention to detect change and decay. A sample of 6873 men and women more than 35 years old who were aware of their high BP demonstrated a high prevalence of high BP in the general population ( approximately 34% in both communities). At baseline this population had poor knowledge of their own BP numbers and poor understanding of the diseases related to high BP. Although few considered high BP a health concern, they had good understanding of lifestyle interventions for high BP prevention and control. The number of the respondents who claimed to have high BP increased immediately after intervention in the test city (38%; P < .02), whereas the number of respondents who were treated and uncontrolled decreased (P < .05) compared to control. There was a significant increase in patients' knowledge of consequences and in their perception that they were most responsible for high BP control in the test city (P < .005) compared to control. At 6 months, no further changes were observed in those claiming to have high BP in either city, whereas decay to baseline in those treated but not controlled and those claiming responsibility for their BP control was observed in the test city. No changes were observed in the control city accept for an increase from baseline to 6 months in the percentage claiming to be treated but uncontrolled. We were unable to determine whether the increase in number treated but uncontrolled was due to a higher treatment rate, similar treatment rate but more patients being uncontrolled, or a combination of these scenarios. High BP is very prevalent in adults and knowledge of lifestyle options for management is encouraging. In the short-term, although our media awareness program increased the number of respondents claiming to have high BP and patient self-efficacy for BP control, this was not maintained. We did not change knowledge of consequences or importantly, the health importance of BP control among those at risk. Hence, in addition to a mass media campaign, attention should be focused on dissemination of awareness knowledge information through medical professionals at the point of care.

Time Trends of High Blood Pressure Prevalence, Awareness and Control in the Italian General Population : Surveys of the National Institute of Health.

PubMed

Di Lonardo, Anna; Donfrancesco, Chiara; Palmieri, Luigi; Vanuzzo, Diego; Giampaoli, Simona

2017-06-01

High blood pressure (BP) is a major risk factor for cardiovascular disease. The urgency of the problem was underlined by the World Health Organization (WHO) Global Action Plan for the prevention and control of noncommunicable diseases, which recommends a 25% relative reduction in the prevalence of raised BP by 2020. A surveillance system represents a useful tool to monitor BP in the general population. Since 1980s, the National Institute of Health has conducted several surveys of the adult general population, measuring cardiovascular risk factors by standardized procedures and methods. To describe mean BP levels and high BP prevalence from 1978 to 2012 by sex and quinquennia of age. Data were derived from the following three studies: (i) Risk Factors and Life Expectancy (RIFLE), conducted between 1978 and 2002 in 13 Italian regions (>70,000 persons); (ii) Osservatorio Epidemiologico Cardiovascolare (OEC), conducted between 1998-2002 in the general population from all Italian regions (>9000 persons); and (iii) Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey (OEC/HES), conducted between 2008-2012 in the general population from all Italian regions (>9000 persons). A significant decrease in mean systolic and diastolic BP levels and prevalence of high BP from 1978 to 2012 was observed both in men and women. BP and high BP increased by age classes in all considered periods. BP awareness and control also improved. Our data suggest that BP control could be achieved by 2020, as recommended by WHO.

Decreased IGF-1 concentration during the first trimester of pregnancy in women with normal somatotroph function.

PubMed

Persechini, Marie-Laure; Gennero, Isabelle; Grunenwald, Solange; Vezzosi, Delphine; Bennet, Antoine; Caron, Philippe

2015-08-01

A decrease of insulin-like growth factor-I levels (IGF-I) has been reported during the first trimester of pregnancy in women with acromegaly before the secretion of placental growth hormone (GH) progressively increases IGF-1 concentration. To evaluate variations of concentrations of IGF-1, insulin-like growth factor (IGF)-binding protein-3 (IGF-BP3) and GH during the first trimester of pregnancy in women with normal somatotroph function. Sixteen women (median age 31 years) with as who were followed for benign thyroid disorders (n = 15) or prolactin-secreting microadenoma (n = 1) were evaluated before and in the first trimester of pregnancy. Serum concentrations of GH, IGF-1, IGF-BP3, TSH and estradiol (E2) were measured before and in the first trimester (5.4 ± 2.2 weeks of gestation). Before pregnancy, somatotroph and thyroid functions (median TSH 1.2 mU/L) were normal in all women. At the first trimester IGF-1 levels decreased significantly (before = 210 ng/mL, first trimester = 145 ng/mL, p < 0.001) with no significant change in GH (before = 1.5 ng/mL, first trimester = 0.84 ng/mL) or IGF-BP3 levels (before = 2.3 ng/mL, first trimester = 2.2 ng/mL), while estradiol levels increased significantly (before = 46.5 pg/100 mL, first trimester = 448.5 pg/100 mL, p < 0.001). In women with normal somatotroph function, IGF-1 levels decrease in the first trimester of pregnancy without changes in GH or IGF-BP3 levels. These results confirm liver resistance to GH as a consequence of the physiological increase of estrogens during the first trimester.

U-Healthcare Center Service in Busan City, South Korea: An Empirical Analysis and the Results of 1 Year of Service.

PubMed

Bravo Santisteban, Ramiro D; Youm, Sekyoung; Park, Seung-Hun

2015-10-01

Studies have demonstrated that technological innovation is vital for prosperous economies, and greater technological innovation leads to improved public health indicators. The South Korean government has implemented policies to provide city services using information communication technologies, and ubiquitous healthcare (u-healthcare) wellness is one of these. This article presents the effects of using a u-healthcare center model that proves self-healthcare monitoring can work for the general population. The u-healthcare center has provided service to the public since April 2013. It is equipped with medical devices that evaluate physiological parameters such as weight, body mass index (BMI), blood pressure (BP), pulse rate (PR), and body fat (BF). This article focuses on the analysis of BMI, BP, PR, and BF parameters. Health test results from 12,766 voluntary patients of the u-healthcare center were analyzed during a 1-year period. The four health parameters from each of the four seasons were analyzed and compared, showing statistically significant seasonal differences. A Duncan's post hoc analysis showed that BMI did not differ between spring and summer, whereas BP differed throughout all seasons. Participation of females was higher compared with males, and men's average BMI was statistically higher than that of the women. Some additional significant findings for all participants were as follows: 48.8% scored normal in BMI, 31.7% scored normal-controlled in BP, 90.7% scored normal in PR, and 24.8% scored normal in BF. A survey showed that 96.4% found the u-healthcare center to be generally helpful, and 95.7% responded that they would recommend it. Implementation of u-healthcare projects provides a new public service toward evaluating health parameters, providing historical health information access, promoting self-monitoring, and motivating users to be more aware of their own health status.

High Index Values of Enzyme-Linked Immunosorbent Assay for BP180 at Baseline Predict Relapse in Patients With Bullous Pemphigoid

PubMed Central

Koga, Hiroshi; Teye, Kwesi; Ishii, Norito; Ohata, Chika; Nakama, Takekuni

2018-01-01

Bullous pemphigoid (BP) presenting with erythema plaques and tense blisters is the most frequent autoimmune bullous disease. Immunologically, BP is characterized by the presence of circulating anti-epidermal basement membrane zone (BMZ) antibodies. The autoantigens in BMZs targeted by patient's antibodies are mainly BP180 (type XVII collagen) and BP230. Previous reports have indicated that IgG to the immunodominant region of BP180 in BP, 16th non-collagenous domain (NC16A), and anti-BP180NC16A IgE are related to disease activity. In the cytokine profile, serum levels of IL-6, TNF-α, IL-15, and CCL18 were associated with the severity or activity of the disease. Blood eosinophilia is seen frequently, especially in severe cases. These biomarkers are helpful to evaluate efficacy of treatment and disease severity. Due to the high frequency of disease relapse, prediction of relapse at initiation of treatment (baseline) must be beneficial for clinicians. Therefore, we evaluated biomarkers anti-BP180 IgG (BP180 ELISA), anti-BP230 IgG (BP230 ELISA), peripheral eosinophils, and serum IgE at baseline between BP patients with (n = 16) and without (n = 31) relapse. We found significantly higher index values of BP180 ELISA in the relapse group, whereas no significant difference was found in BP230 ELISA, peripheral eosinophils, and serum IgE. This study indicated that a high index value of BP180 ELISA (cutoff value, 53.09 U/mL; sensitivity, 81.3%; specificity, 48.4%) at baseline may predict relapse in patients with BP. This may help clinicians treating BP patients in decision-making regarding duration and intensity of treatment. PMID:29868591

High Salt Intake Increases Blood Pressure in Normal Rats: Putative Role of 20-HETE and No Evidence on Changes in Renal Vascular Reactivity

PubMed Central

Walkowska, A.; Kuczeriszka, M.; Sadowski, J.; Olszyński, K.H.; Dobrowolski, L.; Červenka, L.; Hammock, B.D.; Kompanowska-Jezierska, E.

2015-01-01

Background/Aims High salt (HS) intake may elevate blood pressure (BP), also in animals without genetic salt sensitivity. The development of salt-dependent hypertension could be mediated by endogenous vasoactive agents; here we examined the role of vasodilator epoxyeicosatrienoic acids (EETs) and vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). Methods In conscious Wistar rats on HS diet systolic BP (SBP) was examined after chronic elevation of EETs using 4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB), a blocker of soluble epoxide hydrolase, or after inhibition of 20-HETE with 1-aminobenzotriazole (ABT). Thereafter, in acute experiments the responses of renal artery blood flow (Transonic probe) and renal regional perfusion (laser-Doppler) to intrarenal acetylcholine (ACh) or norepinephrine were determined. Results HS diet increased urinary 20-HETE excretion. The SBP increase was not reduced by c-AUCB but prevented by ABT until day 5 of HS exposure. Renal vasomotor responses to ACh or norepinephrine were similar on standard and HS diet. ABT but not c-AUCB abolished the responses to ACh. Conclusions 20-HETE seems to mediate the early-phase HS diet-induced BP increase while EETs are not engaged in the process. Since HS exposure did not alter renal vasodilator responses to Ach, endothelial dysfunction is not a critical factor in the mechanism of salt-induced blood pressure elevation. PMID:26067851

Association of low blood pressure with suicidal ideation: a cross-sectional study of 10,708 adults with normal or low blood pressure in Korea.

PubMed

Joung, Kyung-In; Cho, Sung-Il

2018-03-01

Whether constitutional low blood pressure (BP) causes substantive health problems has been controversial, and subjects with hypotension exhibit a range of symptoms, from mild typical conditions such as tiredness and dizziness to more specific psychological conditions and even cognitive disorders. This study investigated whether low BP is associated with suicidal ideation in the general population. Four years of data from the 2010-2013 Korean National Health and Nutrition Examination Survey were used. Among the 23,163 participants, aged 19-101 years, 10,708 with normal or low BP were included in the analysis of the association between low BP and suicidal ideation. The criterion used for low BP was systolic BP (SBP) < 100 mmHg, and in comparative analyses, the criteria used for low BP were SBP < 110, < 95, and < 90 mmHg. The association of prehypertension or hypertension with suicidal ideation was also examined. Suicidal ideation was assessed by a questionnaire. Compared with the normotensive reference group, the odds ratios (ORs) for suicidal ideation were significantly higher in the three hypotensive groups after adjusting for sex, age, body mass index, total cholesterol level, household income, educational level, marital status, current smoking status, alcohol intake, and the interaction between sex and age (OR = 1.29, 95% confidence interval [CI], 1.08 to 1.55; OR = 1.44, 95% CI, 1.14 to 1.82; and OR = 1.71, 95% CI, 1.11 to 2.62 for SBP < 100, SBP < 95, and SBP < 90 mmHg, respectively). Adding the clinical morbidities of diabetes mellitus, stroke, myocardial infarction/angina pectoris, and depression as covariates had little effect on the strength of the associations (OR = 1.25, 95% CI, 1.04 to 1.50; OR = 1.43, 95% CI, 1.13 to 1.81; and OR = 1.74, 95% CI, 1.14 to 2.68 for SBP < 100, < 95, and < 90 mmHg, respectively). Low SBP showed an association with suicidal ideation in the general Korean population. The association was significant for low BP, defined as a SBP < 100 mmHg, and the strength of the association increased as the criteria for low BP increased in strictness.

Neurogenic orthostatic hypotension - management update and role of droxidopa.

PubMed

Vijayan, Joy; Sharma, Vijay K

2015-01-01

Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy.

Neurogenic orthostatic hypotension – management update and role of droxidopa

PubMed Central

Vijayan, Joy; Sharma, Vijay K

2015-01-01

Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy. PMID:26089676

Association of perioperative blood pressure with long-term survival in rectal cancer patients.

PubMed

Yu, Hui-Chuan; Luo, Yan-Xin; Peng, Hui; Wang, Xiao-Lin; Yang, Zi-Huan; Huang, Mei-Jin; Kang, Liang; Wang, Lei; Wang, Jian-Ping

2016-04-11

Several studies suggested that hypertension is positively related to cancer incidence and mortality. In this study, we investigated the association between perioperative blood pressure (BP) and long-term survival outcomes in patients with rectal cancer. This study included a cohort of 358 patients with stages I-III rectal cancer who underwent a curative resection between June 2007 and June 2011. Both pre- and postoperative BPs were measured, by which patients were grouped (low BP: <120/80 mmHg; high BP: ≥120/80 mmHg). The survival outcomes were compared between these two groups. The primary endpoints were disease-free survival (DFS) and cancer-specific survival (CSS). Univariate analysis showed that patients with high preoperative systolic BP had lower 3-year DFS (67.2% vs. 82.1%, P = 0.041) and CSS rates (81.9% vs. 94.8%, P = 0.003) than patients with low preoperative systolic BP, and the associations remained significant in the Cox multivariate analysis, with the adjusted hazard ratios equal to 1.97 [95% confidence interval (CI) = 1.08-3.60, P = 0.028] and 2.85 (95% CI = 1.00-8.25, P = 0.050), respectively. Similarly, in postoperative evaluation, patients with high systolic BP had significantly lower 3-year CSS rates than those with low systolic BP (78.3% vs. 88.9%, P = 0.032) in univariate analysis. Moreover, high pre- and/or postoperative systolic BP presented as risk factors for CSS in the subgroups of patients who did not have a history of hypertension, with and/or without perioperative administration of antihypertensive drugs. High preoperative systolic BP was an independent risk factor for both CSS and DFS rates, and high postoperative systolic BP was significantly associated with a low CSS rate in rectal cancer patients. Additionally, our results suggest that rectal cancer patients may get survival benefit from BP control in perioperative care. However, further studies should be conducted to determine the association between BP and CSS and targets of BP control.

X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene.

PubMed

Christie, P T; Harding, B; Nesbit, M A; Whyte, M P; Thakker, R V

2001-08-01

X-linked hypophosphatemia is commonly caused by mutations of the coding region of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). However, such PHEX mutations are not detected in approximately one third of X-linked hypophosphatemia patients who may harbor defects in the noncoding or intronic regions. We have therefore investigated 11 unrelated X-linked hypophosphatemia patients in whom coding region mutations had been excluded, for intronic mutations that may lead to mRNA splicing abnormalities, by the use of lymphoblastoid RNA and RT-PCRs. One X-linked hypophosphatemia patient was found to have 3 abnormally large transcripts, resulting from 51-bp, 100-bp, and 170-bp insertions, all of which would lead to missense peptides and premature termination codons. The origin of these transcripts was a mutation (g to t) at position +1268 of intron 7, which resulted in the occurrence of a high quality novel donor splice site (ggaagg to gtaagg). Splicing between this novel donor splice site and 3 preexisting, but normally silent, acceptor splice sites within intron 7 resulted in the occurrences of the 3 pseudoexons. This represents the first report of PHEX pseudoexons and reveals further the diversity of genetic abnormalities causing X-linked hypophosphatemia.

Pathophysiology of salt sensitivity hypertension.

PubMed

Ando, Katsuyuki; Fujita, Toshiro

2012-06-01

Dietary salt intake is the most important factor contributing to hypertension, but the salt susceptibility of blood pressure (BP) is different in individual subjects. Although the pathogenesis of salt-sensitive hypertension is heterogeneous, it is mainly attributable to an impaired renal capacity to excrete sodium (Na(+) ). We recently identified two novel mechanisms that impair renal Na(+) -excreting function and result in an increase in BP. First, mineralocorticoid receptor (MR) activation in the kidney, which facilitates distal Na(+) reabsorption through epithelial Na(+) channel activation, causes salt-sensitive hypertension. This mechanism exists not only in models of high-aldosterone hypertension as seen in conditions of obesity or metabolic syndrome, but also in normal- or low-aldosterone type of salt-sensitive hypertension. In the latter, Rac1 activation by salt excess causes MR stimulation. Second, renospecific sympathoactivation may cause an increase in BP under conditions of salt excess. Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, resulting in salt-dependent hypertension. Abnormalities identified in these two pathways of Na(+) reabsorption in the distal nephron may present therapeutic targets for the treatment of salt-sensitive hypertension.

Paleomagnetic investigation of late Quaternary sediments of south San Francisco Bay, California

USGS Publications Warehouse

Hillhouse, John W.

1977-01-01

Paleomagnetic inclinations of the Late Quaternary sediments of South San Francisco Bay were determined from bore hole samples collected near Dumbarton Bridge. The sediments consist of estuarine muds and nonmarine sand deposits, floored by bedrock of the Mesozoic Franciscan Formation. - Beneath Dumbarton Bridge the entire sedimentary fill is normally polarized; therefore, the fill postdates the Brunhes-Matayama polarity reversal (700,000 y. B.P.). Magnetic time lines such as the Mono Lake excursion (24,000 y. B.P.) and the reversed Blake event (110,000 y B.P.) were not found in this bore hole. In addition to Holocene and modern deposits of San Francisco Bay, an older estuarine unit occurs in the stratigraphic section. The older unit was deposited during a period of high sea level, tentatively correlated with the Sangamon interglacial period. Because evidence of the Blake event is not present in the older estuarine unit, the proposed age of this unit could not be confirmed. Although the Holocene estuarine deposits of South San Francisco Bay carry stable remanent magnetization, a reliable record of geomagnetic secular variation could not be recovered because the water-saturated sdiment was deformed by drilling.

Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

DTIC Science & Technology

2014-03-01

in BRCA1, which is required for homologous recombination, or in any of the Fanconi anaemia complementation group ( FANC ) genes , which excise DNA...The Brca1 gene is required for DNA repair by homologous recombination and normal embryonic development. The protein 53BP1 promotes ligation and...in the right panel. Key Research Accomplishments • Deletion of the DNA damage response gene RIF1 mimics 53BP1 deficiency with respect to

Blood pressure and endothelial function in healthy, pregnant women after acute and daily consumption of flavanol-rich chocolate: a pilot, randomized controlled trial

PubMed Central

2013-01-01

Background Several randomized clinical trials (RCTs) indicate that flavanol-rich chocolate has beneficial effects on flow-mediated dilation (FMD) and blood pressure (BP). However, no RCTs have evaluated these outcomes in pregnant women. The objective of this 2-group, parallel, double-blind RCT was to examine the effects of flavanol-rich chocolate on FMD and BP in pregnant women with normal BP. Methods Forty-four healthy, pregnant women were randomized to the high-flavanol (n = 23) or low-flavanol (n = 21) chocolate consumption for 12 weeks. At randomization (0, 60, 120 and 180 min after a single 40-g dose of chocolate), 6 and 12 weeks after daily 20-g chocolate intake, we evaluated plasma concentrations of flavanols and theobromine, as well as the FMD and BP. Results Plasma epicatechin was significantly increased (p < 0.001) 180 min after the consumption of 40-g high-flavanol chocolate compared to low-flavanol chocolate. Theobromine concentrations were significantly higher 180 min and 12 weeks after the intake of experimental chocolate or low-flavanol chocolate (p < 0.001). FMD was not different between the 2 groups at all pre-defined time periods. No other significant within-group or between-group changes were observed. Conclusion These results confirm the feasibility of a large-scale RCT comparing daily consumption of flavanol-rich chocolate to an equivalent placebo during pregnancy and demonstrate higher plasma epicatechin and theobromine concentration in the intervention group after acute ingestion Trial registration ClinicalTrials.gov Identifier: NCT01659060 PMID:23565841

Cloning and expression analysis of a HSP70 gene from Pacific abalone (Haliotis discus hannai).

PubMed

Cheng, Peizhou; Liu, Xiao; Zhang, Guofan; He, Jianguo

2007-01-01

Heat shock protein 70 (HSP70), the primary member of HSPs that are responsive of thermal stress, is found in all multicellular organisms and functions mostly as molecular chaperon. The inducible HSP70 cDNA cloned from Pacific abalone (Haliotis discus hannai) using rapid amplification of cDNA ends (RACE), was highly homologous to other HSP70 genes. The full-length cDNA of the Pacific abalone HSP70 was 2631bp, consisting of a 5'-terminal untranslated region (UTR) of 90bp, a 3'-terminal UTR of 573bp with a canonical polyadenylation signal sequence AATAAA and a poly (A) tail, and an open reading frame of 1968bp. The HSP70 cDNA encoded a polypeptide of 655 amino acids with an ATPase domain of 382 amino acids, the substrate peptide binding domain of 161 amino acids and a C-terminus domain of 112 amino acids. The temporal expression of HSP70 was measured by semi-quantitative RT-PCR after heat shock and bacterial challenge. Challenge of Pacific abalone with heat shock or the pathogenic bacteria Vibrio anguillarum resulted in a dramatic increase in the expression of HSP70 mRNA level in muscle, followed by a recovery to normal level after 96h. Unlike the muscle, the levels of HSP70 expression in gills reached the top at 12h and maintained a relatively high level compared with the control after thermal and bacterial challenge. The upregulated mRNA expression of HSP70 in the abalone following heat shock and infection response indicates that the HSP70 gene is inducible and involved in immune response.

The Role of 24-hour Ambulatory Blood Pressure Monitoring in Hypertensive Patients with Normal-tension Glaucoma.

PubMed

Marjanović, Ivan; Marjanović, Marija; Stojanov, Vesna; Hentova-Senćanić, Paraskeva; Marković, Vujica; Božić, Marija; Vukčević-Milošević, Gordana

2015-01-01

Extreme dippers are patients with a nocturnal fall of blood pressure (BP) of more than 20%, dippers have normal diurnal rhythm and decrease of BP of 10-15%, while patients with a nocturnal BP fall of less than 10% are considered to be non-dippers. The aim of this study was to compare 24-hour ambulatory BP monitoring results of normal-tension glaucoma (NTG) patients with NTG suspects, as well as to determine whether NTG patients are more prone to daytime/nighttime systemic arterial BP and heart rate oscillations in comparison to NTG suspects. This was a prospective, cross-sectional and observational study of 57 hypertensive patients (39 female and 18 male), all examined at the Eye and the Cardiology Clinic, Clinical Center of Serbia in Belgrade, between November 2011 and March 2012. Before 24-hour ambulatory BP monitoring, complete ophthalmological examination was performed (intraocular pressure was measured with both Goldmann applanation and dynamic contour tonometer, as well as with computerized perimetry and Heidelberg retinal tomography). There was no statistically significant difference between NTG patients and NTG suspects both in systolic daytime (131.86-141.81 mmHg, SD=±l 4.92 vs. 129.67-141.83 mmHg, SD=±l3; p=0.53) and nighttime measurements (117.1-129.7 mmHg, SD=±l 8.96 vs. 112.11-127.59 mmHg, SD=±16.53; p=0.53) as well as diastolic daytime (74.55-80.37 mmHg, SD=±8.72 vs. 75.19-82.41 mmHg, SD=±7.72; p=0.58) and nighttime measurements (65.66-71.48 mmHg, SD=±8.73 vs. 67.12-73.78 mmHg, SD=±7.1 1; p=0.34). There was no statistically significant difference between NTG patients and NTG suspects in heart rate during the day (72.73-76.36 beats per minute [bpm], SD=±5.44 vs. 72.15-76.45 bpm, SD=±4.59; p=0.43) nor during the night (64.4-71.9 bpm, SD=±6.74 vs. 68.02-72.48 bpm, SD=±4.76; p=0.11). No statistically significant difference was found between NTG patients and NTG suspects in regard to their systolic and diastolic BP measured both during daytime and nighttime. NTG patients had fall (both systolic and diastolic) than NTG suspects.

The non-diuretic hypotensive effects of thiazides are enhanced during volume depletion states

PubMed Central

Alshahrani, Saeed; Rapoport, Robert M.; Zahedi, Kamyar; Jiang, Min; Nieman, Michelle; Barone, Sharon; Meredith, Andrea L.; Lorenz, John N.; Rubinstein, Jack

2017-01-01

Thiazide derivatives including Hydrochlorothiazide (HCTZ) represent the most common treatment of mild to moderate hypertension. Thiazides initially enhance diuresis via inhibition of the kidney Na+-Cl- Cotransporter (NCC). However, chronic volume depletion and diuresis are minimal while lowered blood pressure (BP) is maintained on thiazides. Thus, a vasodilator action of thiazides is proposed, likely via Ca2+-activated K+ (BK) channels in vascular smooth muscles. This study ascertains the role of volume depletion induced by salt restriction or salt wasting in NCC KO mice on the non-diuretic hypotensive action of HCTZ. HCTZ (20mg/kg s.c.) lowered BP in 1) NCC KO on a salt restricted diet but not with normal diet; 2) in volume depleted but not in volume resuscitated pendrin/NCC dKO mice; the BP reduction occurs without any enhancement in salt excretion or reduction in cardiac output. HCTZ still lowered BP following treatment of NCC KO on salt restricted diet with paxilline (8 mg/kg, i.p.), a BK channel blocker, and in BK KO and BK/NCC dKO mice on salt restricted diet. In aortic rings from NCC KO mice on normal and low salt diet, HCTZ did not alter and minimally decreased maximal phenylephrine contraction, respectively, while contractile sensitivity remained unchanged. These results demonstrate 1) the non-diuretic hypotensive effects of thiazides are augmented with volume depletion and 2) that the BP reduction is likely the result of HCTZ inhibition of vasoconstriction through a pathway dependent on factors present in vivo, is unrelated to BK channel activation, and involves processes associated with intravascular volume depletion. PMID:28719636

Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Hewitt, L Arthur; Rowse, Gerald J; White, William B

2016-10-01

The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. The BP profile of droxidopa in neurogenic orthostatic hypotension patients (n = 18) was investigated using ambulatory BP monitoring. Following dose optimization and a washout period, 24-hour "off-drug" data were collected. "On-drug" assessment was conducted after 4-5 weeks of droxidopa treatment (mean dose, 444 mg, three times daily). Ambulatory monitoring off drug revealed that 90% of patients already had abnormalities in the circadian BP profile and did not meet criteria for normal nocturnal BP dipping. On treatment, both overall mean 24-hour systolic and diastolic BPs were higher compared to off drug (137/81 mm Hg vs. 129/76 mm Hg; P = .017/.002). Mean daytime systolic BP was significantly higher with droxidopa (8.4 ± 3.1 mm Hg; P = .014). Although nocturnal BP was not significantly higher on droxidopa versus off treatment (P = .122), increases in nocturnal (supine) BP ≥10 mm Hg were observed in four cases (22%). Severe supine systolic hypertensive readings at night (>200 mm Hg) were captured in one case and only while on treatment. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Exercise Training for Blood Pressure: A Systematic Review and Meta‐analysis

PubMed Central

Cornelissen, Veronique A.; Smart, Neil A.

2013-01-01

Background We conducted meta‐analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure (BP) in adults. The aims were to quantify and compare BP changes for each training modality and identify patient subgroups exhibiting the largest BP changes. Methods and Results Randomized controlled trials lasting ≥4 weeks investigating the effects of exercise on BP in healthy adults (age ≥18 years) and published in a peer‐reviewed journal up to February 2012 were included. Random effects models were used for analyses, with data reported as weighted means and 95% confidence interval. We included 93 trials, involving 105 endurance, 29 dynamic resistance, 14 combined, and 5 isometric resistance groups, totaling 5223 participants (3401 exercise and 1822 control). Systolic BP (SBP) was reduced after endurance (−3.5 mm Hg [confidence limits −4.6 to −2.3]), dynamic resistance (−1.8 mm Hg [−3.7 to −0.011]), and isometric resistance (−10.9 mm Hg [−14.5 to −7.4]) but not after combined training. Reductions in diastolic BP (DBP) were observed after endurance (−2.5 mm Hg [−3.2 to −1.7]), dynamic resistance (−3.2 mm Hg [−4.5 to −2.0]), isometric resistance (−6.2 mm Hg [−10.3 to −2.0]), and combined (−2.2 mm Hg [−3.9 to −0.48]) training. BP reductions after endurance training were greater (P<0.0001) in 26 study groups of hypertensive subjects (−8.3 [−10.7 to −6.0]/−5.2 [−6.8 to −3.4] mm Hg) than in 50 groups of prehypertensive subjects (−2.1 [−3.3 to −0.83]/−1.7 [−2.7 to −0.68]) and 29 groups of subjects with normal BP levels (−0.75 [−2.2 to +0.69]/−1.1 [−2.2 to −0.068]). BP reductions after dynamic resistance training were largest for prehypertensive participants (−4.0 [−7.4 to −0.5]/−3.8 [−5.7 to −1.9] mm Hg) compared with patients with hypertension or normal BP. Conclusion Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP. Data from a small number of isometric resistance training studies suggest this form of training has the potential for the largest reductions in SBP. PMID:23525435

Stimulatory effects of curcumin and quercetin on posttranslational modifications of p53 during lung carcinogenesis.

PubMed

Zhang, P; Zhang, Xy

2018-06-01

Lung cancer is responsible for increase in mortality due to cancer-related deaths, and new approaches are being explored for the betterment of the situation. In the present study, chemopreventive efficacy of curcumin and quercetin was investigated against benzo(a)pyrene (BP)-induced lung carcinogenesis. The mice were segregated into five groups, which included normal control, BP-treated, BP + curcumin-treated, BP + quercetin-treated, and BP + curcumin + quercetin-treated groups. The morphological and histological analyses of tumor nodules confirmed lung carcinogenesis22 weeks after weeks single intraperitoneal injection of BP at a dose of 100 mg/kg body weight to mice. Curcumin and quercetin when administered individually as well as in combination significantly elevated the expression of acetylated-p53, which was otherwise depressed due to BP treatment. Also, both the phytochemicals significantly reduced the BP-inflicted increased levels of phosphorylated-p53. Furthermore, observed increase in the number of apoptotic cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), assay and increased activities of caspase 3 and 9 confirmed the induction of apoptosis by curcumin and quercetin. Moreover, the histological slides also showed noticeable improvement in the histoarchitecture of lungs by phytochemicals. The present study concludes that prophylactic treatment with curcumin and quercetin induces apoptosis in the lungs by modulation of p53 posttranslational modifications.

Enhancing the estimation of blood pressure using pulse arrival time and two confounding factors.

PubMed

Baek, Hyun Jae; Kim, Ko Keun; Kim, Jung Soo; Lee, Boreom; Park, Kwang Suk

2010-02-01

A new method of blood pressure (BP) estimation using multiple regression with pulse arrival time (PAT) and two confounding factors was evaluated in clinical and unconstrained monitoring situations. For the first analysis with clinical data, electrocardiogram (ECG), photoplethysmogram (PPG) and invasive BP signals were obtained by a conventional patient monitoring device during surgery. In the second analysis, ECG, PPG and non-invasive BP were measured using systems developed to obtain data under conditions in which the subject was not constrained. To enhance the performance of BP estimation methods, heart rate (HR) and arterial stiffness were considered as confounding factors in regression analysis. The PAT and HR were easily extracted from ECG and PPG signals. For arterial stiffness, the duration from the maximum derivative point to the maximum of the dicrotic notch in the PPG signal, a parameter called TDB, was employed. In two experiments that normally cause BP variation, the correlation between measured BP and the estimated BP was investigated. Multiple-regression analysis with the two confounding factors improved correlation coefficients for diastolic blood pressure and systolic blood pressure to acceptable confidence levels, compared to existing methods that consider PAT only. In addition, reproducibility for the proposed method was determined using constructed test sets. Our results demonstrate that non-invasive, non-intrusive BP estimation can be obtained using methods that can be applied in both clinical and daily healthcare situations.

Diuretics prescribing in chronic kidney disease patients: physician assessment versus bioimpedence spectroscopy.

PubMed

Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

2017-06-01

The relationship between hypertension and fluid overload in pre-dialysis CKD patients need to be elucidated. Current study aimed to find relationship between fluid overload and hypertension along with prescribed diuretic therapy using bioimpedance spectroscopy (BIS). A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by BIS. A total of 312 CKD patients with mean eGFR 24.5 ± 11.2 ml/min/1.73 m 2 were enrolled. Based on OH value ≥7 %, 135 (43.3 %) patients were hypervolemic while euvolemia was observed in 177 (56.7 %) patients. Patients were categorized in different regions of hydration reference plot (HRP) generated by BIS i.e., 5.1 % in region-N (normal BP and fluid status), 20.5 % in region I (hypertensive with severe fluid overload), 29.5 % in region I-II (hypertensive with mild fluid overload), 22 % in region II (hypertensive with normohydration), 10.2 % in region III (underhydration with normal/low BP) and 12.5 % in region IV (normal BP with severe fluid overload). A total of 144 (46 %) patients received diuretics on basis of physician assessment of BP and edema. Maximum diuretics 100 (69.4 %) were prescribed in patients belonging to regions I and I-II of HRP. Interestingly, a similar number of diuretic prescriptions were observed in region II (13 %) and region IV (12 %). Surprisingly, 7 (4.9 %) of patients in region III who were neither hypervolemic nor hypertensive were also prescribed with diuretics. BIS can aid clinicians to categorize CKD patients on basis of their fluid status and provide individualized pharmacotherapy to manage hypertensive CKD patients.

Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10.

PubMed

Giacalone, B; D'Auria, L; Bonifati, C; Ferraro, C; Riccardi, E; Mussi, A; D'Agosto, G; Cordiali-Fei, P; Ameglio, F

1998-08-01

This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF-beta1 in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations (P<0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no significant TGF-beta1 variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity (r=0.64, P=0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts (r=0.80, P<0.001) and antibodies directed against the basement membrane zone (r=0.65, P<0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at the local level (keratinocyte is known to produce IL-7 and the latter is known to be down-regulated by IL-10, and in other models also by TGF-beta1 and IL-4, whose levels are elevated in BP BFs) as opposed to an increased peripheral release of the same modulator. The IL-7 reduction may have a biological relevance in controlling a chronic, progressive disease.

Day/Night Variability in Blood Pressure: Influence of Posture and Physical Activity

PubMed Central

2013-01-01

BACKGROUND Blood pressure (BP) is highest during the day and lowest at night. Absence of this rhythm is a predictor of cardiovascular morbidity and mortality. Contributions of changes in posture and physical activity to the 24-hour day/night rhythm in BP are not well understood. We hypothesized that postural changes and physical activity contribute substantially to the day/night rhythm in BP. METHODS Fourteen healthy, sedentary, nonobese, normotensive men (aged 19–50 years) each completed an ambulatory and a bed rest condition during which BP was measured every 30–60 minutes for 24 hours. When ambulatory, subjects followed their usual routines without restrictions to capture the “normal” condition. During bed rest, subjects were constantly confined to bed in a 6-degree head-down position; therefore posture was constant, and physical activity was minimized. Two subjects were excluded from analysis because of irregular sleep timing. RESULTS The systolic and diastolic BP reduction during the sleep period was similar in ambulatory (−11±2mmHg/−8±1mmHg) and bed rest conditions (−8±3mmHg/−4±2mmHg; P = 0.38/P = 0.12). The morning surge in diastolic BP was attenuated during bed rest (P = 0.001), and there was a statistical trend for the same effect in systolic BP (P = 0.06). CONCLUSIONS A substantial proportion of the 24-hour BP rhythm remained during bed rest, indicating that typical daily changes in posture and/or physical activity do not entirely explain 24-hour BP variation under normal ambulatory conditions. However, the morning BP increase was attenuated during bed rest, suggesting that the adoption of an upright posture and/or physical activity in the morning contributes to the morning BP surge. PMID:23535155

Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

PubMed

de Graauw, E; Sitaru, C; Horn, M; Borradori, L; Yousefi, S; Simon, H-U; Simon, D

2017-07-01

Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab') 2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P < 0.0001) or eosinophil extracellular trap (EET) formation (P = 0.048). Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blood Pressure in Adolescence, Adipokines and Inflammation in Young Adults. The Rio de Janeiro Study

PubMed Central

Campana, Erika Maria Gonçalves; Brandão, Andréa Araujo; Pozzan, Roberto; Magalhães, Maria Eliane Campos; Fonseca, Flávia Lopes; Pizzi, Oswaldo Luiz; de Freitas, Elizabete Viana; Brandão, Ayrton Pires

2014-01-01

Background The impact of blood pressure (BP) during adolescence on other cardiovascular risk factors in young adults is important for the primary prevention. Objective To evaluate BP, anthropometric indexes, metabolic and inflammatory profiles in young individuals stratified by their BP behavior recorded for 18 years. Methods A total of 116 individuals, of whom 63 were males, from the Rio de Janeiro study (follow-up of 17.76 ± 1.63 years), were assessed at two moments: A1 (12.40 ± 1.49 years) and A2 (30.09 ± 2.01 years). The 116 individuals were divided into two groups: GN (n = 71), of participants with normal BP at A1; and GH (n = 45), of those with abnormal BP at A1. BP, weight, height and body mass index (BMI) were measured at A1 and A2. At A2, abdominal circumference (AC) and laboratory, metabolic and inflammatory variables were included. Results 1) No difference was observed between the groups as regards age and gender; 2) At A2, GH showed higher mean weight, BMI, BP, insulin, HOMA-IR (p < 0.001), leptin (p < 0.02), apolipoprotein B100 and A1 (p < 0.02), apolipoprotein B100 / apolipoprotein A1 ratio (p < 0.010); and higher prevalences of overweight/obesity (p < 0.001), of increased AC (p < 0.001) and of hypertension (p < 0.02); 3) No difference was observed between the groups as regards the inflammatory variables; 4) There was a positive correlation of BP at A1 with BP, BMI, insulin, leptin and HOMA-IR at A2 (p < 0.05). Conclusion BP in adolescence was associated with higher values of BP, and anthropometric and metabolic variables in young adulthood, but not with inflammatory variables. PMID:24263778

Cardioprotective effects of SGLT2 inhibitors are possibly associated with normalization of the circadian rhythm of blood pressure.

PubMed

Rahman, Asadur; Hitomi, Hirofumi; Nishiyama, Akira

2017-06-01

Improvement in cardiovascular (CV) morbidity and mortality in the EMPA-REG OUTCOME study provides new insight into the therapeutic use of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. Although SGLT2 inhibitors have several pleiotropic effects, the underlying mechanism responsible for their cardioprotective effects remains undetermined. In this regard, the absence of a nocturnal fall in blood pressure (BP), that is, non-dipping BP, is a common phenomenon in type 2 diabetes and has a crucial role in the pathogenesis of CV morbidity and mortality. In most clinical trials, SGLT2 inhibitors reduce both systolic BP (~3-5 mm Hg) and diastolic BP (~2 mm Hg) in patients with type 2 diabetes. In addition, recent clinical and animal studies have revealed that SGLT2 inhibitors enable the change in BP circadian rhythm from a non-dipper to a dipper type, which is possibly associated with the improvement in CV outcomes in patients with type 2 diabetes. In this review, recent data on the effect of SGLT2 inhibitors on the circadian rhythm of BP will be summarized. The possible underlying mechanisms responsible for the SGLT2 inhibitor-induced improvement in the circadian rhythm of BP will also be discussed.

[Spironolactone in patients with resistant hypertension].

PubMed

Rodilla, Enrique; Costa, José A; Pérez-Lahiguera, Francisco; González, Carmen; Pascual, José M

2008-10-04

The aim of the study was to assess the effect of adding spironolactone to hypertensive resistant (HTR) patients and characterize those who respond effectively. Observational retrospective study on outpatients with HTR (being treated with at least 3 drugs at full doses, one of these being a diuretic) not achieving blood pressure (BP) goals, with normal creatinine values (< 1.6 mg/dl for males and < 1.4 mg/dl in women). A total of 95 patients (70% male), average (standard deviation) age of 66 (12) years (40% diabetics), were treated with spironolactone during 4 months (range: 2-13). Mean systolic and diastolic BP fell from 170/86 (20/14) mmHg, by 29/12 mmHg (95% confidence interval [CI], 25 to 33/10 to 14 mmHg; p = 0.001). At the end of follow-up, 38% of all patients achieved the goal of BP control. Initial systolic BP < 165 mmHg (odds ratio [OR] = 3,97; 95% CI, 1.52-10.37; p = 0.005), and diabetes (OR = 0.33; 95% CI, 0.13-0.86; p = 0.02) were the only independent factors related to BP control in a logistic regression analysis. The addition of spironolactone effectively lowers BP in patients with HTR treated with 3 drugs. BP control is more difficult to achieve in diabetics.

Passivation of black phosphorus saturable absorbers for reliable pulse formation of fiber lasers

NASA Astrophysics Data System (ADS)

Na, Dongsoo; Park, Kichul; Park, Ki-Hwan; Song, Yong-Won

2017-11-01

Black phosphorus (BP) has attracted increasing attention due to its unique electrical properties. In addition, the outstanding optical nonlinearity of BP has been demonstrated in various ways. Its functionality as a saturable absorber, in particular, has been validated in demonstrations of passive mode-locked lasers. However, normally, the performance of BP is degraded eventually by both thermal and chemical damage in ambient conditions. The passivation of BP is the critical issue to guarantee a stable performance of the optical devices. We quantitatively characterized the mode-locked lasers operated by BP saturable absorbers with diversified passivation materials such as polydimethylsiloxane (PDMS) or Al2O3, considering the atomic structure of the materials, and therefore the hydro-permeability of the passivation layers. Unlike the BP layers without passivation, we demonstrated that the Al2O3-passivated BP layer was protected from the surface oxidation reaction in the long-term, and the PDMS-passivated one had a short-term blocking effect. The quantitative analysis showed that the time-dependent characteristics of the pulsed laser without passivation were changed with respect to the pulse duration, spectral width, and time-bandwidth product displaying 550 fs, 2.8 nm, and 0.406, respectively. With passivation, the changes were limited to <43 fs, <0.3 nm, and <0.012, respectively.

Maternal blood pressure and heart rate response to pelvic floor muscle training during pregnancy.

PubMed

Ferreira, Cristine H; Naldoni, Luciane M V; Ribeiro, Juliana Dos Santos; Meirelles, Maria Cristina C C; Cavalli, Ricardo de Carvalho; Bø, Kari

2014-07-01

To assess whether maternal blood pressure (BP) and heart rate (HR) change significantly in response to pelvic floor muscle training during pregnancy. Longitudinal exploratory study with repeated measurements. Twenty-seven nulliparous healthy women of mean age 23.3 years (range 18-36) and mean body mass index 23.4 (range 23.1-29.5). Individual supervised pelvic floor muscle training from gestational week 20 till 36 with assessment of BP and HR at gestational weeks 20, 24, 28, 32 and 36. Systolic and diastolic BP was measured before and after each training session and HR was monitored during each session. Pelvic floor muscle training did not change BP. 77% (n = 21) of participants exceeded 70% of estimated maximum HR during at least one session. The time for exceeding 70% of estimated maximum HR was between 2.2 and 3.2 % of the total exercise session. Increases in BP and HR from gestational weeks 20 till 36 were within normal limits for pregnant women. Pelvic floor muscle training in nulliparous sedentary pregnant women does not increase BP. It significantly increases HR during the exercise sessions, but only for a limited period of time and with no negative long-term effect on BP or HR. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Passivation of black phosphorus saturable absorbers for reliable pulse formation of fiber lasers.

PubMed

Na, Dongsoo; Park, Kichul; Park, Ki-Hwan; Song, Yong-Won

2017-11-24

Black phosphorus (BP) has attracted increasing attention due to its unique electrical properties. In addition, the outstanding optical nonlinearity of BP has been demonstrated in various ways. Its functionality as a saturable absorber, in particular, has been validated in demonstrations of passive mode-locked lasers. However, normally, the performance of BP is degraded eventually by both thermal and chemical damage in ambient conditions. The passivation of BP is the critical issue to guarantee a stable performance of the optical devices. We quantitatively characterized the mode-locked lasers operated by BP saturable absorbers with diversified passivation materials such as polydimethylsiloxane (PDMS) or Al 2 O 3 , considering the atomic structure of the materials, and therefore the hydro-permeability of the passivation layers. Unlike the BP layers without passivation, we demonstrated that the Al 2 O 3 -passivated BP layer was protected from the surface oxidation reaction in the long-term, and the PDMS-passivated one had a short-term blocking effect. The quantitative analysis showed that the time-dependent characteristics of the pulsed laser without passivation were changed with respect to the pulse duration, spectral width, and time-bandwidth product displaying 550 fs, 2.8 nm, and 0.406, respectively. With passivation, the changes were limited to <43 fs, <0.3 nm, and <0.012, respectively.

Stable high-power saturable absorber based on polymer-black-phosphorus films

NASA Astrophysics Data System (ADS)

Mao, Dong; Li, Mingkun; Cui, Xiaoqi; Zhang, Wending; Lu, Hua; Song, Kun; Zhao, Jianlin

2018-01-01

Black phosphorus (BP), a rising two-dimensional material with a layer-number-dependent direct bandgap of 0.3-1.5 eV, is very interesting for optoelectronics applications from near- to mid-infrared wavebands. In the atmosphere, few-layer BP tends to be oxidized or degenerated during interacting with lasers. Here, we fabricate few-layer BP nanosheets based on a liquid exfoliation method using N-methylpyrrolidone as the dispersion liquid. By incorporating BP nanosheets with polymers (polyvinyl alcohol or high-melting-point polyimide), two flexible filmy BP saturable absorbers are fabricated to realize passive mode locking in erbium-doped fiber lasers. The polymer-BP saturable absorber, especially the polyimide-BP saturable absorber, can prevent the oxidation or water-induced etching under high-power laser illuminations, providing a promising candidate for Q-switchers, mode lockers, and light modulators.

Voxel-Based Morphometry ALE meta-analysis of Bipolar Disorder

NASA Astrophysics Data System (ADS)

Magana, Omar; Laird, Robert

2012-03-01

A meta-analysis was performed independently to view the changes in gray matter (GM) on patients with Bipolar disorder (BP). The meta-analysis was conducted on a Talairach Space using GingerALE to determine the voxels and their permutation. In order to achieve the data acquisition, published experiments and similar research studies were uploaded onto the online Voxel-Based Morphometry database (VBM). By doing so, coordinates of activation locations were extracted from Bipolar disorder related journals utilizing Sleuth. Once the coordinates of given experiments were selected and imported to GingerALE, a Gaussian was performed on all foci points to create the concentration points of GM on BP patients. The results included volume reductions and variations of GM between Normal Healthy controls and Patients with Bipolar disorder. A significant amount of GM clusters were obtained in Normal Healthy controls over BP patients on the right precentral gyrus, right anterior cingulate, and the left inferior frontal gyrus. In future research, more published journals could be uploaded onto the database and another VBM meta-analysis could be performed including more activation coordinates or a variation of age groups.

A Highly Aromatic and Sulfonated Ionomer for High Elastic Modulus Ionic Polymer Membrane Micro-Actuators

DTIC Science & Technology

2012-05-01

fluorophenyl)sulfone (DPA-PS:BP) is investigated for ionic polymer actuators. The uniqueness of DPA-PS:BP is that it can have a high ionic liquid (IL... ionic liquid Q M Zhang, Gokhan Hatipoglu, Yang Liu, Ran Zhao, Mitra Yoonessi, Dean M Tigelaar, Srinivas Tadigadapa Virginia Polytechnic Institute...DPA-PS:BP) is investigated for ionic polymer actuators. The uniqueness of DPA-PS:BP is that it can have a high ionic liquid (IL) uptake and

The white-coat effect is unrelated to the difference between clinic and daytime blood pressure and is associated with greater reactivity to public speaking.

PubMed

Palatini, Paolo; Palomba, Daniela; Bertolo, Olivo; Minghetti, Rita; Longo, Daniele; Sarlo, Michela; Pessina, Achille C

2003-03-01

To compare the blood pressure (BP) response to doctor's visit with the BP reaction to a psycho-social challenge and with the difference between clinic and daytime BP (DeltaC-D). We studied 64 young stage-1 hypertensive subjects and 33 normotensive controls. Relationship between direct and surrogate measure of white-coat effect (WCE) and assessment of BP response to public speaking in subjects with normal or increased reaction to BP measurement. The responses to BP measurement by a doctor and to public speaking were assessed with beat-to-beat Finapres recording. DeltaC-D was calculated on the basis of two BP monitorings and used as a surrogate measure of WCE. BP and heart rate changes elicited by the visit were unrelated to DeltaC-D and were correlated to the changes caused by the speech test [P <0.001 for systolic BP (SBP), P = 0.01 for diastolic BP (DBP), and P <0.001 for heart rate]. Hypertensive subjects with SBP response to doctor's visit above the median (hyper-reactive) showed increased reactivity also to public speaking (61 +/- 15 mmHg), while those with BP response below the median (normo-reactive) had a response to the psycho-social challenge (40 +/- 21 mmHg, 0.001 versus hyper-reactive) similar to that of the normotensive controls (38 +/- 17 mmHg). Epinephrine urinary output was greater in the hyper-reactive than the normo-reactive subjects (23 versus 12 microg/24 h, = 0.01). The SBP response to public speaking was greater in the hypertensive subjects with higher systolic daytime BP than in those with lower daytime BP (55.3 +/- 20.9 versus 45.1 +/- 20.6 mmHg, = 0.046). Subjects with increased WCE have an exaggerated response also to psycho-social stimuli. Average daytime BP, which incorporates the BP reactions to many psycho-social triggers can, thus, not be taken as the basal BP of an individual. This helps explain why DeltaC-D does not reflect the true WCE.

Large magnetoresistance and Hall effect in paramagnetic black phosphorus synthesized from red phosphorus

NASA Astrophysics Data System (ADS)

Jiang, X. H.; Xiong, F.; Zhang, X. W.; Hua, Z. H.; Wang, Z. H.; Yang, S. G.

2018-05-01

Black phosphorus (BP) is an important material, which can be used in the fabrication of phosphorene. In this manuscript, a systematic study was described on the high-pressure synthesis of BP from red phosphorus. For physical characterization, the bulk BP was synthesized under the high pressure of 1.6 GPa and high temperature of 700 °C for 2 h. X-ray diffraction and Raman studies illustrated the formation of high-quality pure phase pleomorphic BP. A nonlinear Hall effect was observed in the BP sample. Magnetoresistance (MR) in the bulk BP reached 90% at 40 K, and positive-to-negative crossover in MR was measured. A paramagnetic feature was found in the prepared bulk BP, and the MR results were attributed to the combination of the effect of classical resistor network and magnetic polaron. The conduction tensors were analyzed by a two-band model to determine the carrier concentration and mobility at several temperatures.

Late Glacial and Holocene Fire History From Radiocarbon Dating of Charcoal in Valley-Bottom Sediments in Small Watersheds of the Oregon Coast Range

NASA Astrophysics Data System (ADS)

Lancaster, S. T.; Frueh, W. T.

2011-12-01

A large number (N = 351) of radiocarbon dates of charcoal from valley-bottom sediments in headwater valleys of the southern Oregon Coast Range provides the basis for a new index of fire frequency during the past 17,000 years in this steep landscape covered by dense coniferous forest. Study areas were chosen for their relative lack of recent forest disturbance by harvest or fire, and sampling of stream banks and terrace risers was random, weighted by deposit volume and bank or riser area. This sampling methodology was designed to characterize sediment residence times within valley-bottom storage, and the overall shape of the calibrated age distribution is therefore assumed representative of the dependence of charcoal preservation probability on calibrated age. A proxy record of fire history in the study areas is obtained by fitting a gamma distribution to the weighted mean calibrated charcoal ages by the method of moments; calculating the relative difference between the fit and the normalized histogram, with 50-year bin-widths, of charcoal ages; and smoothing that relative difference with a gaussian distribution, the standard deviation of which is at least two bin-widths and inversely proportional to the value of the fit distribution at larger ages. The calibrated charcoal age mean and variance of 1900 yrs BP and 7.39 x 106 yr2, respectively, yield shape and scale parameters of the fit gamma distribution of 0.490 and 3880 yrs, respectively. This heavy-tailed distribution indicates that probabilities of charcoal evacuation are not simply proportional to relative volume of encasing sediment deposits but, rather, decrease with deposit age. The smoothed proxy record of relative fire frequency has a global maximum at 7700 BP and prominent local maxima at 600 BP and 5700 BP, in order of decreasing magnitude; a global minimum at 4500 BP and local minimum at 1800 BP roughly bracket a period of fluctuating but relatively low fire frequency during the period 5000-1500 BP. Although resolution in the late glacial to early Holocene is limited, the record shows a high relative fire frequency during the late glacial before dipping 10,000-9000 BP. The 7700 BP maximum and 1800 BP minimum are consistent with another fire history from lake sediments northeast of our sites in the Oregon Coast Range. Other features appear to contradict that record but to support of climate change inferences based on other climate proxies.

Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats

NASA Technical Reports Server (NTRS)

Rousseau, D.; Helies-Toussaint, C.; Raederstorff, D.; Moreau, D.; Grynberg, A.

2001-01-01

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.

Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex

PubMed Central

Elbediwy, Ahmed; Zihni, Ceniz; Terry, Stephen J.; Clark, Peter

2012-01-01

Epithelial cell–cell adhesion and morphogenesis require dynamic control of actin-driven membrane remodeling. The Rho guanosine triphosphatase (GTPase) Cdc42 regulates sequential molecular processes during cell–cell junction formation; hence, mechanisms must exist that inactivate Cdc42 in a temporally and spatially controlled manner. In this paper, we identify SH3BP1, a GTPase-activating protein for Cdc42 and Rac, as a regulator of junction assembly and epithelial morphogenesis using a functional small interfering ribonucleic acid screen. Depletion of SH3BP1 resulted in loss of spatial control of Cdc42 activity, stalled membrane remodeling, and enhanced growth of filopodia. SH3BP1 formed a complex with JACOP/paracingulin, a junctional adaptor, and CD2AP, a scaffolding protein; both were required for normal Cdc42 signaling and junction formation. The filamentous actin–capping protein CapZ also associated with the SH3BP1 complex and was required for control of actin remodeling. Epithelial junction formation and morphogenesis thus require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics. PMID:22891260

Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats.

PubMed

Rousseau, D; Héliès-Toussaint, C; Raederstorff, D; Moreau, D; Grynberg, A

2001-09-01

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.

Occupational burnout and empathy influence blood pressure control in primary care physicians.

PubMed

Yuguero, Oriol; Marsal, Josep Ramon; Esquerda, Montserrat; Soler-González, Jorge

2017-05-12

Good physician-patient communication can favor the adoption of healthy lifestyle habits, which is essential in high blood pressure (BP) management. More empathic physicians tend to have lower burnout and better communication skills. We analyzed the association between burnout and empathy among primary care physicians and nurses and investigated the influence on BP control performance. Descriptive study conducted in 2014 investigating burnout and empathy levels in 267 primary care physicians and nurses and BP control data for 301,657 patients under their care. We administered the Maslach Burnout Inventory and the Jefferson Scale of Physician Empathy and defined good BP control as a systolic BP <130 mmHg. Low burnout and high empathy were observed in 58.8% and 33.7% of practitioners, respectively. Burnout and empathy were significantly negatively associated (p < 0.009). Practitioners with high empathy and low burnout had significantly better BP control and performance than those with low empathy and high burnout (p < 0.05). Low burnout and high empathy were significantly associated with improved BP control and performance, possibly in relation to better physician/nurse-patient communication.

Mechanisms of Resistance to Chemotherapies Targeting BRCA-Mutant Breast Cancer

DTIC Science & Technology

2016-12-01

such as 53BP1, restored normal HR activity in BRCA1 deficient cells and rendered these cells resistant to chemotherapeutic agents. Under the aegis...NHEJ (defined as NHEJ conducted during S phase which typically results in genome instability). We found that the anti-resection activities of 53BP1...for the recruitment of the PALB2/BRCA2 complex that may be dependent on the ubiquitin ligase activity of RNF168. Specifically, we are interested in

History of biochemical pregnancy was associated with the subsequent reproductive failure among women with recurrent spontaneous abortion.

PubMed

Maesawa, Yoko; Yamada, Hideto; Deguchi, Masashi; Ebina, Yasuhiko

2015-04-01

The aim of this study was to evaluate whether the presence of history of biochemical pregnancy (BP) was associated with clinical characteristics and the subsequent pregnancy outcome among women with recurrent spontaneous abortion (RSA). One-hundred and seventy-five RSA women with two or more clinical pregnancy losses were enrolled. The clinical characteristics were compared between 164 women with history of 0-1 BP (Group A) and 11 women with two or more BP (Group B). The frequency of previous pregnancy loss and history of in vitro fertilization and embryo transfer in Group B was higher than that in Group A; while frequency of secondary RSA in Group B was lower than Group A. The subsequent pregnancy outcome was assessed prospectively; and live-birth rate in Group A (72.9%) was higher (p < 0.05) than that in Group B (41.7%). The incidence of reproductive failure (58.3%, p < 0.05) and spontaneous abortion with normal chromosome (25.0%, p = 0.050) in Group B was higher than those (27.1 and 5.9%, respectively) in Group A. RSA women with two or more BP had higher risk of reproductive failure and spontaneous abortion with normal chromosome together with lower chance of live-birth. The results of the present study involve important information and are helpful for clinical practitioners.

Room temperature ferromagnetism in transition metal-doped black phosphorous

NASA Astrophysics Data System (ADS)

Jiang, Xiaohong; Zhang, Xinwei; Xiong, Fang; Hua, Zhenghe; Wang, Zhihe; Yang, Shaoguang

2018-05-01

High pressure high temperature synthesis of transition metal (TM = V, Cr, Mn, Fe, Co, Ni, and Cu) doped black phosphorus (BP) was performed. Room temperature ferromagnetism was observed in Cr and Mn doped BP samples. X-ray diffraction and Raman measurements revealed pure phase BP without any impurity. Transport measurements showed us semiconducting character in 5 at. % doped BP samples Cr5%P95% and Mn5%P95%. The magnetoresistance (MR) studies presented positive MR in the relatively high temperature range and negative MR in the low temperature range. Compared to that of pure BP, the maximum MR was enhanced in Cr5%P95%. However, paramagnetism was observed in V, Fe, Co, Ni, and Cu doped BP samples.

Associations of Blood Pressure with Body Composition among Afro-Caribbean Children in Barbados

PubMed Central

Gaskin, Pamela S.; Hall, Ryan V.; Chami, Peter; St. John, Margaret A.; Gaskin, David A.; Molaodi, Oarabile R.; Harding, Seeromanie

2015-01-01

Despite complex presentation of adult hypertension and a concomitant obesity epidemic, little is known about overweight in relation to blood pressure among Caribbean children. We examined blood pressure in relation to body size in a cross-sectional study of 573 Barbadian children aged 9–10 years (2010-2011).The United States normative blood pressure percentiles were used to identify children with high (≥ 95th percentile) or high normal blood pressure (90th – 95th percentile). The World Health Organization body mass index cut-off points were used to assess weight status. Major findings Thirty percent of children were overweight/obese. Percentage fat mass differed between girls (20.4%) and boys (17.72%) (p< 0.05). Mean systolic blood pressure among girls was 106.11 (95% CI 105.05, 107.17) mmHg and 105.23 (104.09, 106.38) for boys. The percentages with high or high-normal mean systolic blood pressurewere14.38% (10.47, 18.29) for girls and 8.08% (4.74, 11.41) for boys. Height and body mass index were independent correlates of systolic and diastolic blood pressure. Mean systolic blood pressure was related to lean mass but not fat mass, while diastolic blood pressure was associated with fat mass index and overweight. Principal conclusion One third of 9-10 year old children in Barbados were overweight/obese and 12% had elevated mean systolic blood pressure. BP was related to body size. These findings signal potential adverse trends in weight gain and BP trends for children growing up in the context of a country that has recently undergone rapid economic transition. PMID:25815726

The C8-binding protein of human erythrocytes: interaction with the components of the complement-attack phase.

PubMed Central

Schönermark, S; Filsinger, S; Berger, B; Hänsch, G M

1988-01-01

C8-binding protein is an intrinsic membrane protein of the human erythrocyte. It inhibits the complement (C5b-9)-mediated lysis in a species-restricting manner. In the present study we incorporated C8bp, isolated from human erythrocytes, into sheep erythrocytes (SRBC). SRBC, normally sensitive to lysis by human C5b-9, became insensitive to lysis. Furthermore, we found that C8bp is incorporated into the membrane-attack complex C5b-9, most probably by interacting with C8, since C8bp has an affinity for C8, particularly for the C8 alpha-gamma-subunit. Antibodies to C8bp react with the C8 alpha-subunits and with C9, pointing to the possibility of a partial homology between these proteins. Images Figure 4 Figure 6 Figure 7 PMID:3366469

Recurrent 15q11.2 BP1-BP2 microdeletions and microduplications in the etiology of neurodevelopmental disorders.

PubMed

Picinelli, Chiara; Lintas, Carla; Piras, Ignazio Stefano; Gabriele, Stefano; Sacco, Roberto; Brogna, Claudia; Persico, Antonio Maria

2016-12-01

Rare and common CNVs can contribute to the etiology of neurodevelopmental disorders. One of the recurrent genomic aberrations associated with these phenotypes and proposed as a susceptibility locus is the 15q11.2 BP1-BP2 CNV encompassing TUBGCP5, CYFIP1, NIPA2, and NIPA1. Characterizing by array-CGH a cohort of 243 families with various neurodevelopmental disorders, we identified five patients carrying the 15q11.2 duplication and one carrying the deletion. All CNVs were confirmed by qPCR and were inherited, except for one duplication where parents were not available. The phenotypic spectrum of CNV carriers was broad but mainly neurodevelopmental, in line with all four genes being implicated in axonal growth and neural connectivity. Phenotypically normal and mildly affected carriers complicate the interpretation of this aberration. This variability may be due to reduced penetrance or altered gene dosage on a particular genetic background. We evaluated the expression levels of the four genes in peripheral blood RNA and found the expected reduction in the deleted case, while duplicated carriers displayed high interindividual variability. These data suggest that differential expression of these genes could partially account for differences in clinical phenotypes, especially among duplication carriers. Furthermore, urinary Mg 2+ levels appear negatively correlated with NIPA2 gene copy number, suggesting they could potentially represent a useful biomarker, whose reliability will need replication in larger samples. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Characterization of ribulose-1, 5-bisphosphate carboxylase/oxygenase and transcriptional analysis of its related genes in Saccharina japonica (Laminariales, Phaeophyta)

NASA Astrophysics Data System (ADS)

Shao, Zhanru; Liu, Fuli; Li, Qiuying; Yao, Jianting; Duan, Delin

2014-03-01

Saccharina japonica is a common macroalga in sublittoral communities of cold seawater environments, and consequently may have highly efficient ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) activity for carbon assimilation. In our study, we cloned the full-length Rubisco gene from S. japonica ( SJ-rbc). It contained an open reading frame for a large subunit gene ( SJ — rbcL) of 1 467 bp, a small subunit gene ( SJ-rbcS) of 420 bp, and a SJ-rbcL/S intergenic spacer of 269 bp. The deduced peptides of SJ-rbcL and SJ-rbcS were 488 and 139 amino acids with theoretical molecular weights and isoelectric points of 53.97 kDa, 5.81 and 15.84 kDa, 4.71, respectively. After induction with 1 mmol/L isopropyl- β-D-thiogalactopyranoside for 5 h and purification by Ni2+ affinity chromatography, electrophoresis and western blot detection demonstrated successful expression of the 55 kDa SJ-rbcL protein. Real-time quantitative PCR showed that the mRNA levels of SJ-rbcL in gametophytes increased when transferred into normal growth conditions and exhibited diurnal variations: increased expression during the day but suppressed expression at night. This observation implied that Rubisco played a role in normal gametophytic growth and development. In juvenile sporophytes, mRNA levels of SJ-rbcL, carbonic anhydrase, Calvin-Benson-Bassham cycle-related enzyme, and chloroplast light-harvesting protein were remarkably increased under continuous light irradiance. Similarly, expression of these genes was up-regulated under blue light irradiance at 350 μmol/(m2·s). Our results indicate that long-term white light and short-term blue light irradiance enhances juvenile sporophytic growth by synergistic effects of various photosynthetic elements.

High CO2 concentration as an inductor agent to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories.

PubMed

Ruiz, Cristina; Pla, Maria; Company, Nuri; Riudavets, Jordi; Nadal, Anna

2016-03-01

Cationic α-helical antimicrobial peptides such as BP100 are of increasing interest for developing novel phytosanitary or therapeutic agents and products with industrial applications. Biotechnological production of these peptides in plants can be severely impaired due to the toxicity exerted on the host by high-level expression. This can be overcome by using inducible promoters with extremely low activity throughout plant development, although the yields are limited. We examined the use of modified atmospheres using the increased levels of [CO2], commonly used in the food industry, as the inductor agent to biotechnologically produce phytotoxic compounds with higher yields. Here we show that 30% [CO2] triggered a profound transcriptional response in rice leaves, including a change in the energy provision from photosynthesis to glycolysis, and the activation of stress defense mechanisms. Five genes with central roles in up-regulated pathways were initially selected and their promoters successfully used to drive the expression of phytotoxic BP100 in genetically modified (GM) rice. GM plants had a normal phenotype on development and seed production in non-induction conditions. Treatment with 30 % [CO2] led to recombinant peptide accumulation of up to 1 % total soluble protein when the Os.hb2 promoter was used. This is within the range of biotechnological production of other peptides in plants. Using BP100 as a proof-of-concept we demonstrate that very high [CO2] can be considered an economically viable strategy to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories.

Syntheses and evaluation of 68 Ga- and 153 Sm-labeled DOTA-conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases.

PubMed

Chakraborty, Sudipta; Goswami, Dibakar; Chakravarty, Rubel; Mohammed, Sahiralam Khan; Sarma, Haladhar Deb; Dash, Ashutosh

2018-05-05

This article reports the syntheses and evaluation of 68 Ga- and 153 Sm-complexes of a new DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-conjugated geminal bisphosphonate, DOTA-Bn-SCN-BP, for their potential uses in the early detection of skeletal metastases by imaging and palliation of pain arising from skeletal metastases, respectively. The conjugate was synthesized in high purity following an easily adaptable three-step reaction scheme. Gallium-68- and 153 Sm-complexes were prepared in high yield (>98%) and showed excellent in vitro stability in phosphate-buffered saline (PBS) and human serum. Both the complexes showed high affinity for hydroxyapatite particles in in vitro binding study. In biodistribution studies carried out in normal Wistar rats, both the complexes exhibited rapid skeletal accumulation with almost no retention in any other major organ. The newly synthesized molecule DOTA-Bn-SCN-BP would therefore be a promising targeting ligand for the development of radiopharmaceuticals for both imaging skeletal metastases and palliation of pain arising out of it in patients with cancer when radiolabeled with 68 Ga and 153 Sm, respectively. A systematic comparative evaluation, however, showed that there was no significant improvement of skeletal accumulation of the 153 Sm-DOTA-Bn-SCN-BP complex over 153 Sm-DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid) as the later itself demonstrated optimal properties required for an agent for bone pain palliation. © 2018 John Wiley & Sons A/S.

Self-measurement of blood pressure in arterial hypertension--preliminary results from the AMPA study.

PubMed

Maldonado, João; Pereira, Telmo

2009-01-01

The clinical usefulness of home blood pressure monitoring (HBPM) is still uncertain, and is currently a major topic of scientific debate. Some studies have stressed its potential role in the clinical decision-making process, but there have been few prospective studies addressing this subject. The AMPA study is intended to contribute to this debate, exploring the potential usefulness of this methodology in the clinical setting of arterial hypertension using a prospective, observational and multicenter design. The study included 685 hypertensive patients (346 female), with a mean age of 54.2 +/- 11.1 years (range: 17-86 years). All patients were being followed in primary care centers by their family doctors, and were being treated for arterial hypertension and other comorbidities. Forty-seven patients were smokers (6%), 90 (13%) had a personal history of cardiovascular disease, 42 (6%) were diabetic, 255 (37%) had dyslipidemia, and 31 (5%) were both diabetic and dyslipidemic. Blood pressure (BP) was measured in the brachial artery with a validated automatic blood pressure measurement device (Colson MAM BP 3AA1-2; Colson, Paris). This device has solid state memory (sufficient for 60 measurements) and an adaptable printer. A cuff appropriate for the arm size of each patient was used. All patients were instructed on how to operate the device correctly and how to perform the measurements in compliance with the study protocol. BP was always measured after a 5-minute resting period in a seated position. The protocol consisted of an HBP program over a period of five working days. Each day the patient performed six BP measurements in two different periods: three in the morning (between 6 and 10 am) and three in the evening (between 6 and 10 pm). Other clinical and anthropometric data were also collected. The HBP reference values adopted were 135 mmHg for systolic and 85 mmHg for diastolic BP. Analysis of BP behavior over time demonstrated a significant white-coat effect, with regression to the mean of BP levels after the first day of the HBP program. As a consequence, the first day values were excluded in determining mean HBP. This behavior was independent of gender, and was more pronounced in diabetic patients. Analysis of diagnostic concordance between office BP and HBP showed discrepancies in 27.4% of the patients. This prompted a change in diagnosis based on HBP values, with 133 patients (19.4%) presenting uncontrolled office BP levels but normal HBP values, while 55 patients (8%) had elevated HBP in contrast to normal office BP. These first results of the AMPA study illustrate the superiority of HBP compared with office BP in the evaluation of hypertensive patients. HBP provides a better characterization of each patient's BP profile, and hence may help improve therapeutic and clinical decisions. Confirmation of the potential of HBP monitoring will be addressed in a prospective analysis (6-year follow-up) of the AMPA study in the near future.

100 or 30 years after Janeway or Bartter, Healthwatch helps avoid 'flying blind'.

PubMed

Cornélissen, Germaine; Halberg, Franz; Bakken, Earl; Singh, Ram B; Otsuka, Kuniaki; Tomlinson, Brian; Delcourt, Alain; Toussaint, Guy; Bathina, Srilakshmi; Schwartzkopff, Othild; Wang, Zhengrong; Tarquini, Roberto; Perfetto, Federico; Pantaleoni, Giancarlo; Jozsa, Rita; Delmore, Patrick A; Nolley, Ellis

2004-10-01

Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with 'non-dipping'). A non-parametric approach consisting of a computer comparison of the subject's profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention).

Blood pressure at age 60-65 versus age 70-75 and vascular dementia: a population based observational study.

PubMed

Peng, Mingkai; Chen, Guanmin; Tang, Karen L; Quan, Hude; Smith, Eric E; Faris, Peter; Hachinski, Vladimir; Campbell, Norm R C

2017-10-27

Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD. This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values. After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60-65 cohort with the risk of developing VaD (hazard ratio [HR] 1.53 (95% confidence interval: 1.04, 2.25) for prehypertension, 1.90 (1.30, 2.78) for stage 1 hypertension, and 2.19 (1.48, 3.26) for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60-65 cohort and age 70-75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD. High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.

Relation of Dietary Sodium (Salt) to Blood Pressure and Its Possible Modulation by Other Dietary Factors: The INTERMAP Study.

PubMed

Stamler, Jeremiah; Chan, Queenie; Daviglus, Martha L; Dyer, Alan R; Van Horn, Linda; Garside, Daniel B; Miura, Katsuyuki; Wu, Yangfeng; Ueshima, Hirotsugu; Zhao, Liancheng; Elliott, Paul

2018-04-01

Available data indicate that dietary sodium (as salt) relates directly to blood pressure (BP). Most of these findings are from studies lacking dietary data; hence, it is unclear whether this sodium-BP relationship is modulated by other dietary factors. With control for multiple nondietary factors, but not body mass index, there were direct relations to BP of 24-hour urinary sodium excretion and the urinary sodium/potassium ratio among 4680 men and women 40 to 59 years of age (17 population samples in China, Japan, United Kingdom, and United States) in the INTERMAP (International Study on Macro/Micronutrients and Blood Pressure), and among its 2195 American participants, for example, 2 SD higher 24-hour urinary sodium excretion (118.7 mmol) associated with systolic BP 3.7 mm Hg higher. These sodium-BP relations persisted with control for 13 macronutrients, 12 vitamins, 7 minerals, and 18 amino acids, for both sex, older and younger, blacks, Hispanics, whites, and socioeconomic strata. With control for body mass index, sodium-BP-but not sodium/potassium-BP-relations were attenuated. Normal weight and obese participants manifested significant positive relations to BP of urinary sodium; relations were weaker for overweight people. At lower but not higher levels of 24-hour sodium excretion, potassium intake blunted the sodium-BP relation. The adverse association of dietary sodium with BP is minimally attenuated by other dietary constituents; these findings underscore the importance of reducing salt intake for the prevention and control of prehypertension and hypertension. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005271. © 2018 American Heart Association, Inc.

Blood Pressure Control and Cardiovascular Outcomes in Normal, Overweight, and Obese Hypertensives Treated with Three Different Anti-Hypertensives in ALLHAT

PubMed Central

Reisin, Efrain; Graves, John; Yamal, Jose-Miguel; Barzilay, Joshua I; Pressel, Sara; Einhorn, Paula T.; Dart, Richard A.; Retta, Tamrat M.; Saklayen, Mohammad G.; Davis, Barry R

2017-01-01

Objective Epidemiologically there is a strong relationship between body mass index (BMI) and blood pressure (BP) levels. We prospectively examined randomization to first-step chlorthalidone, a thiazide-type diuretic; amlodipine, a calcium-channel blocker; and lisinopril, an angiotensin-converting-enzyme inhibitor, on BP control and cardiovascular outcomes in a hypertensive cohort stratified by baseline BMI (normal weight [BMI<25], overweight [BMI=25–29·9], and obese [BMI≥30]). Methods 33,357 hypertensive participants, age ≥55 years were followed for an average of 4·9 years in a randomized, double-blind, practice-based Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), for primary outcome of fatal coronary heart disease (CHD) or nonfatal myocardial infarction and secondary outcomes of stroke, heart failure, combined cardiovascular disease, mortality, and renal failure. Results Of participants, 37·9% were overweight and 42·1% were obese at randomization. For each medication, BP control (<140/90 mmHg) was equivalent in each BMI stratum. At year five, 66·1%, 66·5%, and 65·1% of normal weight, overweight, and obese participants, respectively, were controlled. Those randomized to chlorthalidone had highest BP control (67·2%, 68·3%, and 68·4%, respectively) and lisinopril the lowest (60·4%, 63·2%, and 59·6%, respectively) in each BMI stratum. A significant interaction (p=0·004) suggests a lower CHD risk in the obese for lisinopril vs. chlorthalidone (hazard ratio [HR]=0·85, 95% confidence interval [CI]=[0·74–0·98]) and a significant interaction (p=0·011) suggests a higher risk of end-stage renal disease for amlodipine vs. chlorthalidone in obese participants (HR [95% CI]=1·49[1·06–2·08]). However, these results were not consistent among other outcomes. Conclusions BMI status does not modify the effects of antihypertensive medications on BP control or cardiovascular disease outcomes. PMID:24842697

The human luteinizing hormone receptor gene promoter: activation by Sp1 and Sp3 and inhibitory regulation.

PubMed

Geng, Y; Tsai-Morris, C H; Zhang, Y; Dufau, M L

1999-09-24

To understand the transcriptional mechanism(s) of human LH receptor (LHR) gene expression, we have identified the dominant functional cis-elements that regulate the activity of the promoter domain (-1 to -176 bp from ATG). Mutagenesis demonstrated that the promoter activity was dependent on two Sp1 domains (-79 bp, -120 bp) in a transformed normal placental cell (PLC) and the choriocarcinoma JAR cell. Both elements interacted with endogenous Sp1 and Sp3 factors but not with Sp2 or Sp4. In Drosophila SL2 cells, the promoter was activated by either Sp1 or Sp3. An ERE half-site (EREhs) at -174 bp was inhibitory (by 100%), but was unresponsive to estradiol and did not bind the estrogen receptor or orphan receptors ERR1 and SF-1. The 5' upstream sequence (-177 to -2056 bp) inhibited promoter activity in PLC by 60%, but only minimally in JAR cells. Activation of the human LHR promoter through Sp1/3 factors is negatively regulated through EREhs and upstream sequences to exert control of gene expression. Copyright 1999 Academic Press.

Calmodulin and calmodulin-binding proteins in cystic fibrosis and normal human fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tallant, E.A.; Wallace, R.W.

1986-05-01

The authors have investigated the possibility that a lesion in a calmodulin (CaM)-dependent regulatory mechanism may be involved in cystic fibrosis (CF). The level of CaM, CaM-binding proteins (CaM-BP) and a CaM-dependent phosphatase (CaM-Ptase) have been compared in cultured fibroblasts from CF patients versus age- and sex-matched control subjects. The CaM concentration, measured by radioimmunoassay, ranged from 0.20 to 0.76 ..mu..g/mg protein (n=8); there was no significant difference in the average CaM concentration from CF patients vs controls. Using Western blotting techniques with /sup 125/I-CaM, they detected at least ten distinct CaM-BPs in fibroblasts with molecular weights ranging from 230Kmore » to 37K; the only consistent difference between control and CF cell lines was in a 46.5K CaM-BP, which was depressed in all three CF samples. The 46.5 K CaM-BP was found only in the particulate fraction. A 59K CaM-BP was identified as a CaM-Ptase by its crossreactivity with an antibody against a brain CaM-Ptase. There was no significant difference in CaM-Ptase activity or in the amount of the phosphatase as determined by radioimmunoassay in CF vs. normal samples (n=8). Thus, the level of CaM as well as its various enzymes and proteins do not appear to be altered in CF fibroblasts except for a CaM-BP of 46.5K, the identity of which is currently being investigated.« less

Application of artificial neural network model combined with four biomarkers in auxiliary diagnosis of lung cancer.

PubMed

Duan, Xiaoran; Yang, Yongli; Tan, Shanjuan; Wang, Sihua; Feng, Xiaolei; Cui, Liuxin; Feng, Feifei; Yu, Songcheng; Wang, Wei; Wu, Yongjun

2017-08-01

The purpose of the study was to explore the application of artificial neural network model in the auxiliary diagnosis of lung cancer and compare the effects of back-propagation (BP) neural network with Fisher discrimination model for lung cancer screening by the combined detections of four biomarkers of p16, RASSF1A and FHIT gene promoter methylation levels and the relative telomere length. Real-time quantitative methylation-specific PCR was used to detect the levels of three-gene promoter methylation, and real-time PCR method was applied to determine the relative telomere length. BP neural network and Fisher discrimination analysis were used to establish the discrimination diagnosis model. The levels of three-gene promoter methylation in patients with lung cancer were significantly higher than those of the normal controls. The values of Z(P) in two groups were 2.641 (0.008), 2.075 (0.038) and 3.044 (0.002), respectively. The relative telomere lengths of patients with lung cancer (0.93 ± 0.32) were significantly lower than those of the normal controls (1.16 ± 0.57), t = 4.072, P < 0.001. The areas under the ROC curve (AUC) and 95 % CI of prediction set from Fisher discrimination analysis and BP neural network were 0.670 (0.569-0.761) and 0.760 (0.664-0.840). The AUC of BP neural network was higher than that of Fisher discrimination analysis, and Z(P) was 0.76. Four biomarkers are associated with lung cancer. BP neural network model for the prediction of lung cancer is better than Fisher discrimination analysis, and it can provide an excellent and intelligent diagnosis tool for lung cancer.

Prevalence, Clinical Presentation, and Differential Diagnosis of Pediatric Bipolar Disorder

PubMed Central

Goldstein, Benjamin I.; Birmaher, Boris

2016-01-01

Background Over the past 20 years, the evidence regarding pediatric bipolar disorder (BP) has increased substantially. As a result, recent concerns have focused primarily on prevalence and differential diagnosis. Method Selective review of the literature. Results BP as defined by rigorously applying diagnostic criteria has been observed among children and especially adolescents in numerous countries. In contrast to increasing diagnoses in clinical settings, prevalence in epidemiologic studies has not recently changed. BP-spectrum conditions among youth are highly impairing and confer high risk for conversion to BP-I and BP-II. Compared to adults, youth with BP have more mixed symptoms, more changes in mood polarity, are more often symptomatic and seem to have worse prognosis. The course, clinical characteristics, and comorbidities of BP among children and adolescents are in many ways otherwise similar to those of adults with BP. Nonetheless, many youth with BP receive no treatment and most do not receive BP-specific treatment. Conclusion Despite increased evidence supporting the validity of pediatric BP, discrepancies between clinical and epidemiologic findings suggest that diagnostic misapplication may be common. Simultaneously, low rates of treatment of youth with BP suggest that withholding of BP diagnoses may also be common. Clinicians should apply diagnostic criteria rigorously in order to optimize diagnostic accuracy and ensure appropriate treatment. PMID:22652925

Serum levels of Mac-2 binding protein increase with cardiovascular risk and reflect silent atherosclerosis.

PubMed

Sugiura, Tomonori; Dohi, Yasuaki; Takase, Hiroyuki; Yamashita, Sumiyo; Murai, Shunsuke; Tsuzuki, Yuji; Ogawa, Shintaro; Tanaka, Yasuhito; Ohte, Nobuyuki

2016-08-01

Mac-2 binding protein (M2BP) was reported to be a useful biomarker for liver fibrosis and malignant tumors. We hypothesized that expression of M2BP might also change in the process of atherosclerosis. This study included subjects who visited our hospital for a physical checkup. The M2BP levels in subjects with hypertension, dyslipidemia, or abnormal glucose metabolism were higher than those in subjects without such risk factors. Moreover, the M2BP levels were associated with severity of cardiovascular risk. Subdivision of M2BP levels into quartiles revealed that M2BP was significantly associated with reactive oxygen metabolites, central systolic blood pressure, and radial augmentation index (AI). Logistic regression analysis with the endpoint of high radial AI (above mean value) showed that high radial AI was independently associated with high M2BP. Although the spectrum was narrow as compared to that in cases of hepatic fibrosis, serum M2BP may reflect silent atherosclerosis in apparently healthy subjects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identification of a 467 bp Promoter of Maize Phosphatidylinositol Synthase Gene (ZmPIS) Which Confers High-Level Gene Expression and Salinity or Osmotic Stress Inducibility in Transgenic Tobacco

PubMed Central

Zhang, Hongli; Hou, Jiajia; Jiang, Pingping; Qi, Shoumei; Xu, Changzheng; He, Qiuxia; Ding, Zhaohua; Wang, Zhiwu; Zhang, Kewei; Li, Kunpeng

2016-01-01

Salinity and drought often affect plant growth and crop yields. Cloning and identification of salinity and drought stress inducible promoters is of great significance for their use in the genetic improvement of crop resistance. Previous studies showed that phosphatidylinositol synthase is involved in plant salinity and drought stress responses but its promoter has not been characterized by far. In the study, the promoter (pZmPIS, 1834 bp upstream region of the translation initiation site) was isolated from maize genome. To functionally validate the promoter, eight 5′ deletion fragments of pZmPIS in different lengths were fused to GUS to produce pZmPIS::GUS constructs and transformed into tobacco, namely PZ1–PZ8. The transcription activity and expression pattern obviously changed when the promoter was truncated. Previous studies have demonstrated that NaCl and PEG treatments are usually used to simulate salinity and drought treatments. The results showed that PZ1–PZ7 can respond well upon NaCl and PEG treatments, while PZ8 not. PZ7 (467 bp) displayed the highest transcription activity in all tissues of transgenic tobacco amongst 5′ deleted promoter fragments, which corresponds to about 20 and 50% of CaMV35S under normal and NaCl or PEG treatment, respectively. This implied that PZ7 is the core region of pZmPIS which confers high-level gene expression and NaCl or PEG inducible nature. The 113 bp segment between PZ7 and PZ8 (-467 to -355 bp) was considered as the key sequence for ZmPIS responding to NaCl or PEG treatment. GUS transient assay in tobacco leaves showed that this segment was sufficient for the NaCl or PEG stress response. Bioinformatic analysis revealed that the 113 bp sequence may contain new elements that are crucial for ZmPIS response to NaCl or PEG stress. These results promote our understanding on transcriptional regulation mechanism of ZmPIS and the characterized PZ7 promoter fragment would be an ideal candidate for the overexpression of drought and salinity responsive gene to improve crop resistance. PMID:26870063

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

PubMed

Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Comparison of Efficacy and Safety of Azilsartan and Olmesartan in Patients With Essential Hypertension.

PubMed

Shiga, Yuhei; Miura, Shin-Ichiro; Motozato, Kota; Norimatsu, Kenji; Yano, Masaya; Hitaka, Yuka; Adachi, Sen; Kuwano, Takashi; Inoue, Ken; Inoue, Asao; Fujisawa, Kazuaki; Shirotani, Tetsuro; Kusumoto, Takaaki; Ideishi, Munehito; Saku, Keijiro

2017-05-31

Many patients still have high blood pressure (BP) after treatment with angiotensin II type 1 (AT 1 ) receptor blockers (ARBs). We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective randomized clinical trial. Sixty-four hypertensive patients who were treated with ARBs other than azilsartan and olmesartan were enrolled in this study. We randomly assigned patients to changeover from their prior ARBs to either azilsartan or olmesartan, and followed the patients for 3 months. Systolic BP (SBP) in the azilsartan group was significantly decreased at 3 months, and diastolic BP (DBP) and pulse rate (PR) in the olmesartan group showed significant reductions after 3 months. There were no significant differences in ΔSBP, ΔDBP, or ΔPR (Δ = the value at 3 months minus the value at 0 months) between the groups. Serum levels of creatinine (Cr), uric acid (UA), and potassium (K) in the azilsartan group significantly increased after 3 months. While the changes in Cr, UA, and K were within the respective normal ranges, ΔSBP was positively associated with ΔCr in the azilsartan group. In conclusion, there was no difference in the depressor effects of azilsartan and olmesartan, and there were no serious changes in biochemical parameters with azilsartan and olmesartan.

Flexible Black-Phosphorus Nanoflake/Carbon Nanotube Composite Paper for High-Performance All-Solid-State Supercapacitors.

PubMed

Yang, Bingchao; Hao, Chunxue; Wen, Fusheng; Wang, Bochong; Mu, Congpu; Xiang, Jianyong; Li, Lei; Xu, Bo; Zhao, Zhisheng; Liu, Zhongyuan; Tian, Yongjun

2017-12-27

We proposed a simple route for fabrication of the flexible BP nanoflake/carbon nanotube (CNT) composite paper as flexible electrodes in all-solid-state supercapacitors. The highly conductive CNTs not only play a role as active materials but also increase conductivity of the hybrid electrode, enhance electrolyte shuttling and prevent the restacking between BP nanoflakes. The fabricated flexible all-solid-state supercapacitor (ASSP) device at the mass proportion of BP/CNTs 1:4 was found to deliver the highest volumetric capacitance of up to 41.1 F/cm 3 at 0.005 V/s, superior to the ASSP based on the bare graphene or BP. The BP/CNTs (1:4) device delivers a rapid charging/discharging up to 500 V/s, which exhibits the characteristic of a high power density of 821.62 W/cm 3 , while having outstanding mechanical flexibility and high cycling stability over 10 000 cycles (91.5% capacitance retained). Moreover the BP/CNTs (1:4) ASSP device still retains large volumetric capacitance (35.7 F/cm 3 at the scan rate of 0.005 V/s) even after 11 months. In addition, the ASSP of BP/CNTs (1:4) exhibits high energy density of 5.71 mWh/cm 3 and high power density of 821.62 W/cm 3 . As indicated in our work, the strategy of assembling stacked-layer composites films will open up novel possibility for realizing BP and CNTs in new-concept thin-film energy storage devices.

The preparation of BP single crystals by high pressure flux method

NASA Technical Reports Server (NTRS)

Kumashiro, Y.; Misawa, S.; Gonda, S.

1984-01-01

Single crystals of BP, a III-V compound semiconductor, were obtained by the high pressure flux method. Cu3P and Ni12P5 powders were used as the flux, and mixed with BP powder. Two kinds of mixtures were prepared: (1) 1.8g (BP) + 35 G (Cu3P) and (2) 1.7 g (BP) + 25 g (Ni12P5). They were compressed into pellets, heated at 1300 C for 24 h in an induction furnace under a pressure of 1 MPa using Ar-P2 gas, and slowly cooled to room temperature. In case (1), BP single crystals grew along the (III) plane, and in case (2) they grew as an aggregate of crystallites. The cathodoluminescence spectra of the synthetic BP crystals showed peaks near 680 nm (1.82 eV) for case (1), and 500 nm (2.47 eV) for case (2). By using the high pressure flux method conventional sized crystals were obtained in a relatively short time.

Blood pressure and arterial stiffness in obese children and adolescents.

PubMed

Hvidt, Kristian Nebelin

2015-03-01

Obesity, elevated blood pressure (BP) and arterial stiffness are risk factors for cardiovascular disease. A strong relationship exists between obesity and elevated BP in both children and adults. Obesity and elevated BP in childhood track into adult life increasing the risk of cardiovascular disease in adulthood. Ambulatory BP is the most precise measure to evaluate the BP burden, whereas carotid-femoral pulse wave velocity (cfPWV) is regarded as the gold standard for evaluating arterial (i.e. aortic) stiffness. These measures might contribute to a better understanding of obesity's adverse impact on the cardiovascular system, and ultimately a better prevention and treatment of childhood obesity. The overall aim of the present PhD thesis is to investigate arterial stiffness and 24-hour BP in obese children and adolescents, and evaluate whether these measures are influenced by weight reduction. The present PhD thesis is based on four scientific papers.  In a cross-sectional design, 104 severe obese children and adolescents with an age of 10-18 years were recruited when newly referred to the Children's Obesity Clinic, Holbæk University Hospital, and compared to 50 normal weighted age and gender matched control individuals. Ambulatory BP was measured, and cfPWV was investigated in two ways in respect to the distance measure of aorta; the previously recommended length - the so called subtracted distance, and the currently recommended length - the direct distance. In a longitudinal design, the obese patients were re-investigated after one-year of lifestyle intervention at the Children's Obesity Clinic in purpose of reducing the degree of obesity. In the cross-sectional design, the obese group had higher measures of obesity, while matched for age, gender and height, when compared to the control group. In the longitudinal design, 74% of the 72 followed up obese patients experienced a significant weight reduction. CfPWV was dependent on the method used to measure the length of the aorta. The subtracted distance was not consistent in its relation to height in the obese and the control group. Opposite, the direct distance was consistent in its relation to height in the two groups. Therefore, cfPWV using the direct distance (cfPWV-direct) was regarded as the appropriate measure of arterial stiffness. CfPWV-direct was reduced in the obese group after adjustment for known confounders. In the longitudinal design, weight reduction across one year did not have an impact on cfPWV-direct in the obese patients. In fact, cfPWV-direct was higher at follow-up, which was explained by the increased age and partly by changes in BP and heart rate. The obese group had a relatively higher night- than day-time BP when compared to the control group. The obesity-related elevated night-time BP was independent of arterial stiffness and insulin resistance. Although night-time systolic BP was related to arterial stiffness and tended to be related to insulin resistance, insulin resistance and arterial stiffness were not related. In the longitudinal design, changes in anthropometric obesity measures across one year were associated with changes in 24-hour, day- and night-time BP, and consistent when evaluated in standardised values that accounted for growth. No association was found between changes in anthropometric obesity measures and changes in clinic BP. In conclusion, the results suggest that obesity in children is not "yet" associated with structural changes in aorta when evaluated with the appropriate new method of cfPWV. In this respect, weight reduction did not have an impact on arterial stiffness. The ambulatory BP, namely the night-time BP, was elevated in the obese patients, whereas changes in anthropometric obesity measures were related to changes in ambulatory BP but not to changes in clinic BP. In perspective, it is reassuring that weight changes are accompanied with a change in 24-hour BP as ambulatory BP is the most precise measure to evaluate the BP burden, and it emphasises the use of 24-hour ambulatory BP measurements in children and adolescents. It is important to recognise, that obese children who recover their normal weight before adulthood will have a similar cardiovascular risk as those who were never obese. Hence, early treatment and prevention of childhood obesity is important because it may prevent irreversible damage to the cardiovascular system.

American College of Sports Medicine position stand. Exercise and hypertension.

PubMed

Pescatello, Linda S; Franklin, Barry A; Fagard, Robert; Farquhar, William B; Kelley, George A; Ray, Chester A

2004-03-01

Hypertension (HTN), one of the most common medical disorders, is associated with an increased incidence of all-cause and cardiovascular disease (CVD) mortality. Lifestyle modifications are advocated for the prevention, treatment, and control of HTN, with exercise being an integral component. Exercise programs that primarily involve endurance activities prevent the development of HTN and lower blood pressure (BP) in adults with normal BP and those with HTN. The BP lowering effects of exercise are most pronounced in people with HTN who engage in endurance exercise with BP decreasing approximately 5-7 mm HG after an isolated exercise session (acute) or following exercise training (chronic). Moreover, BP is reduced for up to 22 h after an endurance exercise bout (e.g.postexercise hypotension), with greatest decreases among those with highest baseline BP. The proposed mechanisms for the BP lowering effects of exercise include neurohumoral, vascular, and structural adaptations. Decreases in catecholamines and total peripheral resistance, improved insulin sensitivity, and alterations in vasodilators and vasoconstrictors are some of the postulated explanations for the antihypertensive effects of exercise. Emerging data suggest genetic links to the BP reductions associated with acute and chronic exercise. Nonetheless, definitive conclusions regarding the mechanisms for the BP reductions following endurance exercise cannot be made at this time. Individuals with controlled HTN and no CVD or renal complications may participated in an exercise program or competitive athletics, but should be evaluated, treated and monitored closely. Preliminary peak or symptom-limited exercise testing may be warranted, especially for men over 45 and women over 55 yr planning a vigorous exercise program (i.e. > or = 60% VO2R, oxygen uptake reserve). In the interim, while formal evaluation and management are taking place, it is reasonable for the majority of patients to begin moderate intensity exercise (40-<60% VO2R) such as walking. When pharmacological therapy is indicated in physically active people it should be, ideally: a) lower BP at rest and during exertion; b) decrease total peripheral resistance; and, c) not adversely affect exercise capacity. For these reasons, angiotensin converting enzyme (ACE) inhibitors (or angiotensin II receptor blockers in case of ACE inhibitor intolerance) and calcium channel blockers are currently the drugs of choice for recreational exercisers and athletes who have HTN. Exercise remains a cornerstone therapy for the primary prevention, treatment, and control of HTN. The optimal training frequency, intensity, time, and type (FITT) need to be better defined to optimize the BP lowering capacities of exercise, particularly in children, women, older adults, and certain ethnic groups. based upon the current evidence, the following exercise prescription is recommended for those with high BP: Frequency: on most, preferably all, days of the week. Intensity: moderate-intensity (40-<60% VO2R). Time: > or = 30 min of continuous or accumulated physical activity per day. Type: primarily endurance physical activity supplemented by resistance exercise.

Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study.

PubMed

El Sayed, Salah Mohamed; Mohamed, Walaa Gamal; Seddik, Minnat-Allah Hassan; Ahmed, Al-Shimaa Ahmed; Mahmoud, Asmaa Gamal; Amer, Wael Hassan; Helmy Nabo, Manal Mohamed; Hamed, Ahmed Roshdi; Ahmed, Nagwa Sayed; Abd-Allah, Ali Abdel-Rahman

2014-07-01

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.

Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study

PubMed Central

El Sayed, Salah Mohamed; Mohamed, Walaa Gamal; Seddik, Minnat-Allah Hassan; Ahmed, Al-Shimaa Ahmed; Mahmoud, Asmaa Gamal; Amer, Wael Hassan; Helmy Nabo, Manal Mohamed; Hamed, Ahmed Roshdi; Ahmed, Nagwa Sayed; Abd-Allah, Ali Abdel-Rahman

2014-01-01

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects. PMID:24636230

Low job control is associated with higher diastolic blood pressure in men with mildly elevated blood pressure: the Rosai Karoshi study.

PubMed

Hattori, Tomomi; Munakata, Masanori

2015-01-01

Job strain is a risk factor for hypertension, but it is not fully understood if components of job strain, or job demand or job control per se could be related to blood pressure (BP), and if so, whether the relationship differs between normotension and mildly elevated BP. We examined resting BP, and job stress components in 113 Japanese male hospital clerks (38.1 ± 4.4 yr). Subjects were classified into normotensive (NT) (<130/85 mmHg, n=83) and mildly elevated BP (ME) (≥130/85 mmHg) groups. Diastolic BP (DBP) showed a significant interaction between group and job control level (p=0.013). Subjects with low job control demonstrated higher DBP than those with high job control (89.1 ± 2.1 vs. 82.3 ± 2.3 mmHg, p=0.042) in ME group even after adjustments for covariates while DBP did not differ between low and high job control subjects in NT group. Systolic BP (SBP) did not differ between high and low job control subjects in both groups. Neither SBP nor DBP differed between high and low demand groups in either group. Among job strain components, job control may be independently related to BP in Japanese male workers with mildly elevated BP.

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

NASA Technical Reports Server (NTRS)

Iwasaki, K. I.; Zhang, R.; Zuckerman, J. H.; Pawelczyk, J. A.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

2000-01-01

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP.

PubMed

Pagan, Julia K; Arnold, Jeremy; Hanchard, Kim J; Kumar, Raman; Bruno, Tiziana; Jones, Mathew J K; Richard, Derek J; Forrest, Alistair; Spurdle, Amanda; Verdin, Eric; Crossley, Merlin; Fanciulli, Maurizio; Chenevix-Trench, Georgia; Young, David B; Khanna, Kum Kum

2007-05-18

Corepressors play a crucial role in negative gene regulation and are defective in several diseases. BCoR is a corepressor for the BCL6 repressor protein. Here we describe and functionally characterize BCoR-L1, a homolog of BCoR. When tethered to a heterologous promoter, BCoR-L1 is capable of strong repression. Like other corepressors, BCoR-L1 associates with histone deacetylase (HDAC) activity. Specifically, BCoR-L1 coprecipitates with the Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its role as a transcriptional repressor. BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Abrogation of the CtBP binding site within BCoR-L1 partially relieves BCoR-L1-mediated transcriptional repression. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay. The inhibition of BCoR-L1 expression by RNA-mediated interference results in derepression of E-cadherin in cells that do not normally express E-cadherin, indicating that BCoR-L1 contributes to the repression of an authentic endogenous CtBP target.

[Features of daily rhythm of arterial pressure in patients with primary arterial hypertension and neurogenic syncope conditions].

PubMed

Musaeva, Z A; Oknin, V Iu; Khapaev, B A; Fedotova, A V; Veĭn, A M

2002-01-01

A comparative analysis of parameters of systemic BP in patients with primary arterial hypotension (PAH) and in patients with neurogenic syncopes (NS) in the cycle sleep-awake. Blood pressure was investigated in 20 patients with PAH aged 16-44 years and 18 patients with NS aged 16-49 years. 24-h ambulatory monitoring of BP was made on the monitor ABPM-02/M (Meditech, Hungary). Rhythm indices of BP in NS patients corresponded to age normal criteria. 24-h arrhythmia of BP in PAH patients manifests with excessive drop of diastolic BP in sleep (55% patients were overdippers). PAH and NS patients differ maximally by hypotonic load in sleep: 1.0 +/- 0.7% in NS vs 15.4 +/- 3.2% in PAH. Hypotonia episodes in awake PAH patients were registered at each 4th-5th measurement of BP, in NS patients--at each 11th-13th. Heart rate in awake PAH patients is higher than in healthy subjects. Hypotonic load in sleep carries the highest differentially-diagnostic importance. This makes more perspective examinations of such patients in the cycle sleep-awake. The changes observed in PAH patients evidence for activation of cerebral sympathico-adrenal systems participating in baroreflex regulation.

Aspartate Decarboxylase is Required for a Normal Pupa Pigmentation Pattern in the Silkworm, Bombyx mori.

PubMed

Dai, Fangyin; Qiao, Liang; Cao, Cun; Liu, Xiaofan; Tong, Xiaoling; He, Songzhen; Hu, Hai; Zhang, Li; Wu, Songyuan; Tan, Duan; Xiang, Zhonghuai; Lu, Cheng

2015-06-16

The pigmentation pattern of Lepidoptera varies greatly in different development stages. To date, the effects of key genes in the melanin metabolism pathway on larval and adult body color are distinct, yet the effects on pupal pigmentation remains unclear. In the silkworm, Bombyx mori, the black pupa (bp) mutant is only specifically melanized at the pupal stage. Using positional cloning, we found that a mutation in the Aspartate decarboxylase gene (BmADC) is causative in the bp mutant. In the bp mutant, a SINE-like transposon with a length of 493 bp was detected ~2.2 kb upstream of the transcriptional start site of BmADC. This insertion causes a sharp reduction in BmADC transcript levels in bp mutants, leading to deficiency of β-alanine and N-β-alanyl dopamine (NBAD), but accumulation of dopamine. Following injection of β-alanine into bp mutants, the color pattern was reverted that of the wild-type silkworms. Additionally, melanic pupae resulting from knock-down of BmADC in the wild-type strain were obtained. These findings show that BmADC plays a crucial role in melanin metabolism and in the pigmentation pattern of the silkworm pupal stage. Finally, this study contributes to a better understanding of pupa pigmentation patterns in Lepidoptera.

Aspartate Decarboxylase is Required for a Normal Pupa Pigmentation Pattern in the Silkworm, Bombyx mori

PubMed Central

Dai, Fangyin; Qiao, Liang; Cao, Cun; Liu, Xiaofan; Tong, Xiaoling; He, Songzhen; Hu, Hai; Zhang, Li; Wu, Songyuan; Tan, Duan; Xiang, Zhonghuai; Lu, Cheng

2015-01-01

The pigmentation pattern of Lepidoptera varies greatly in different development stages. To date, the effects of key genes in the melanin metabolism pathway on larval and adult body color are distinct, yet the effects on pupal pigmentation remains unclear. In the silkworm, Bombyx mori, the black pupa (bp) mutant is only specifically melanized at the pupal stage. Using positional cloning, we found that a mutation in the Aspartate decarboxylase gene (BmADC) is causative in the bp mutant. In the bp mutant, a SINE-like transposon with a length of 493 bp was detected ~2.2 kb upstream of the transcriptional start site of BmADC. This insertion causes a sharp reduction in BmADC transcript levels in bp mutants, leading to deficiency of β-alanine and N-β-alanyl dopamine (NBAD), but accumulation of dopamine. Following injection of β-alanine into bp mutants, the color pattern was reverted that of the wild-type silkworms. Additionally, melanic pupae resulting from knock-down of BmADC in the wild-type strain were obtained. These findings show that BmADC plays a crucial role in melanin metabolism and in the pigmentation pattern of the silkworm pupal stage. Finally, this study contributes to a better understanding of pupa pigmentation patterns in Lepidoptera. PMID:26077025

A prospective study on pulse wave velocity (PWV) and response to anti-hypertensive treatments: PWV determines BP control.

PubMed

Zheng, Meili; Huo, Yong; Wang, Xiaobin; Xu, Xin; Qin, Xianhui; Tang, Genfu; Xing, Houxun; Fan, Fangfang; Li, Jianping; Zhang, Yan; Wang, Binyan; Xu, Xiping; Yang, Xinchun; Chen, Yundai; Qian, Geng

2015-01-15

Recent data indicate that hypertension is not well controlled in many populations throughout the world. The factors that influence individual response to anti-hypertensive treatment need to be clarified. Pulse wave velocity (PWV), as a marker of arterial stiffness, has been demonstrated to have important relationships with BP progression; however, little information is available on the role of PWV in blood pressure (BP) control. We aimed to assess BP control during the run-in treatment period in the China Stroke Primary Prevention Trial (CSPPT). These analyses included a total of 3056 treated hypertensive subjects (age: 59.6±7.5years, male/female 1339/1717) with PWV measured at baseline. The average BP at enrollment was 166/95mmHg, and declined to 141/85mmHg after short-term antihypertensive treatment (a median follow-up of 20days). There was an inverse relationship between PWV level and BP reduction during the treatment, most notably for systolic BP (with estimated coefficients of -9.01 (P<0.001) for the top quartile, as compared to the bottom quartile). The association did not differ significantly by gender or types of antihypertensive drugs. Factors related to smaller BP decline were low baseline BP, high baseline PWV, high body mass index, high creatinine, use of fewer types of antihypertensive drug, high heart rate (only for SBP), high homocysteine and low age (only for DBP). PWV appears to be an independent determinant of individual response to anti-hypertensive treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Serum creatinine levels are significantly influenced by renal size in the normal pediatric population.

PubMed

Di Zazzo, Giacomo; Stringini, Gilda; Matteucci, Maria Chiara; Muraca, Maurizio; Malena, Saverio; Emma, Francesco

2011-01-01

Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children. A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender. When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements. These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship.

Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the beta-globin gene in the Thai population.

PubMed

Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Brittenham, Gary; Looareesuwan, Sornchai; Clark, Andrew G; Tokunaga, Katsushi

2005-01-01

A binding site for the repressor protein BP1, which contains a tandem (AT)x(T)y repeat, is located approximately 530 bp 5' to the human beta-globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)9(T)5 allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)x(T)y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; beta26Glu-->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)9(T)5 and (AT)7(T)7 alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)9(T)5 allele, which can explain why the betaE chain is inefficiently synthesized compared to the normal betaA chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)9(T)5 repeat on the HbE chromosome. In addition, a novel (AC)n polymorphism adjacent to the (AT)x(T)y repeat (i.e., (AC)3(AT)7(T)5) was found through the variation screening in this study.

Deficiency of uridine monophosphate synthase (DUMPS) and X-chromosome deletion in fetal mummification in cattle.

PubMed

Ghanem, Mohamed Elshabrawy; Nakao, Toshihiko; Nishibori, Masahide

2006-01-01

Ten mummified fetuses were tested for the deficiency of uridine monophosphate synthase (DUMPS), which is known to contribute to the embryonic and fetal mortality in cattle. Genomic DNAs of the mummified fetuses were extracted from tissue samples collected from the mummies and were amplified by GenomiPhi DNA amplification kit. UMPS gene of the mummies was amplified by polymerase chain reaction (PCR) with DUMPS primers. Out of ten mummies examined, two fetuses were heterozygous (carriers) for DUMPS as indicated by the presences of three bands of 89, 53 and 36 bp. Estimated stage of gestation when the death occurred in the two mummies was 3.5 and 2.5 months, respectively. The other fetuses exhibited only two bands of 53 and 36 bp on the polyacrylamide gel indicated that they were normal. On the other hand, all the mummies were sexed using AMX/Y primers. Specific regions of Y and X chromosomes were amplified by PCR using AMX/Y. The expected 280 bp fragment in the female sample and the 280 and 217 bp in the male sample were observed. Nine mummies had a normal X and Y chromosome bands; however, the other mummified fetus exhibited only Y chromosome band, while the constitutive X chromosome fragment was missing. The estimated stage of gestation when the death occurred in this mummified fetus was 100 days. This might be the first report of DUMPS and X-chromosome deletion at the amelogenin gene in bovine-mummified fetuses in Japan.

Fragment Length of Circulating Tumor DNA.

PubMed

Underhill, Hunter R; Kitzman, Jacob O; Hellwig, Sabine; Welker, Noah C; Daza, Riza; Baker, Daniel N; Gligorich, Keith M; Rostomily, Robert C; Bronner, Mary P; Shendure, Jay

2016-07-01

Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.

Changes in ventricular function during emotional stress and cold exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiess, M.C.; Moore, R.A.; Dimsdale, J.

1984-01-01

Patients with cardiac disease frequently develop symptoms with emotional stress or cold exposure. To investigate the effects of these stresses in normal subjects, an ambulatory ventricular function monitor (VEST) (previously reported to measure EFs which correlate well with gamma camera measurements) was employed to record sequential 2 minute time activity curves from the left ventricles of 6 healthy men (ages 19-24) during a control period and during a 30 minute stress interview with a psychiatrist. Four of the subjects were also monitored in a cold room (1/sup 0/C) for 20 min. In addition to the left ventricular time-activity curve, heartmore » rate (HR), and BP (cuff) were recorded. All subjects had increases in HR, BP and EF during the stress interview. Cold, however, produced decreases in HR and EF and an increase in BP. The results (mean +- SD) are tabulated. End-systolic and end-diastolic counts and hence volume decreased during the interview and increased during cold exposure. The results suggest that (1) ambulatory changes in ventricular function can be measured with the VEST, and (2) significant changes in cardiovascular physiology are seen in normal subjects during a stress interview and exposure to cold.« less

Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy

PubMed Central

Sivakumar, Siddharth S.; Namath, Amalia G.; Tuxhorn, Ingrid E.; Lewis, Stephen J.

2016-01-01

We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy. PMID:26888110

High blood pressure and cognitive decline in mild cognitive impairment.

PubMed

Goldstein, Felicia C; Levey, Allan I; Steenland, N Kyle

2013-01-01

To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains. Prospective longitudinal cohort. Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers. One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits. Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score. Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score. Hypertension is associated with faster cognitive decline in persons at risk for dementia. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

High Blood Pressure and Cognitive Decline in Mild Cognitive Impairment

PubMed Central

Goldstein, Felicia C.; Levey, Allan I.; Steenland, N. Kyle

2013-01-01

Objectives To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains. Design Prospective longitudinal cohort. Setting Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers. Participants One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits. Measurements Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score. Results Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score. Conclusion Hypertension is associated with faster cognitive decline in persons at risk for dementia. PMID:23301925

Nanoscopy reveals surface-metallic black phosphorus

DOE PAGES

Abate, Yohannes; Gamage, Sampath; Li, Zhen; ...

2016-10-21

Black phosphorus (BP) is an emerging two-dimensional material with intriguing physical properties. It is highly anisotropic and highly tunable by means of both the number of monolayers and surface doping. Here, we experimentally investigate and theoretically interpret the near-field properties of a-few-atomic-monolayer nanoflakes of BP. We discover near-field patterns of bright outside fringes and a high surface polarizability of nanofilm BP consistent with its surface-metallic, plasmonic behavior at mid-infrared frequencies <1176 cm -1. We conclude that these fringes are caused by the formation of a highly polarizable layer at the BP surface. This layer has a thickness of ~1 nmmore » and exhibits plasmonic behavior. We estimate that it contains free carriers in a concentration of n≈1.1 × 10 20 cm -3. Surface plasmonic behavior is observed for 10–40 nm BP thicknesses but absent for a 4-nm BP thickness. This discovery opens up a new field of research and potential applications in nanoelectronics, plasmonics and optoelectronics.« less

Molecular analysis of two phytohemagglutinin genes and their expression in Phaseolus vulgaris cv. Pinto, a lectin-deficient cultivar of the bean.

PubMed

Voelker, T A; Staswick, P; Chrispeels, M J

1986-12-01

Phytohemagglutinin (PHA), the seed lectin of the common bean, Phaseolus vulgaris, is encoded by two highly homologous, tandemly linked genes, dlec1 and dlec2, which are coordinately expressed at high levels in developing cotyledons. Their respective transcripts translate into closely related polypeptides, PHA-E and PHA-L, constituents of the tetrameric lectin which accumulates at high levels in developing seeds. In the bean cultivar Pinto UI111, PHA-E is not detectable, and PHA-L accumulates at very reduced levels. To investigate the cause of the Pinto phenotype, we cloned and sequenced the two PHA genes of Pinto, called Pdlec1 and Pdlec2, and determined the abundance of their respective mRNAs in developing cotyledons. Both genes are more than 90% homologous to the normal PHA genes found in other cultivars. Pdlec1 carries a 1-bp frameshift mutation close to the 5' end of its coding sequence. Only very truncated polypeptides could be made from its mRNA. The gene Pdlec2 encodes a polypeptide, which resembles PHA-L and its predicted amino acid sequence agrees with the available Pinto PHA amino acid sequence data. Analysis of the mRNA of developing cotyledons revealed that the Pdlec1 message is reduced 600-fold, and Pdlec2 mRNA is reduced 20-fold with respect to mRNA levels in normal cultivars. A comparison of the sequences which are upstream from the coding sequence shows that Pdlec2 has a 100-bp deletion compared to the other genes (dlec1, dlec2 and Pdlec1). This deletion which contains a large tandem repeat may be responsible for the low level of expression of Pdlec2. The very low expression of Pdlec1 is as yet unexplained.

Serum growth hormone (GH)-binding protein/receptor: an important determinant of GH responsiveness.

PubMed

Martha, P M; Reiter, E O; Dávila, N; Shaw, M A; Holcombe, J H; Baumann, G

1992-12-01

Individual growth rates (or responses to GH therapy) and adult heights vary over a wide range. The reasons for this variation are poorly understood. Based on the reciprocal relationship between GH production and serum GH-binding protein/receptor (GH-BP), we hypothesized that genetic growth potential was achieved by a specific combination of GH-BP/receptor and GH production in each individual. To address the question whether GH production regulates GH-BP, or vice versa, we studied GH-deficient children, where one of the parameters, GH exposure, could be controlled through exogenous administration. Forty-three untreated prepubertal GH-deficient children were studied before and after 6 and 12 months of GH replacement therapy (0.18 mg/kg.week). Growth velocity, height, bone age, weight and their respective Z scores, serum GH-BP, and serum insulin-like growth factor I (IGF-I) were measured at each time point. The patients responded with significant increases in serum IGF-I, age-adjusted growth velocity, and height (P < 10(-6) for all). Before therapy, GH-BP correlated directly with chronologic and bone age (P < 10(-4), but not with either growth velocity or IGF-I. In contrast, GH-BP correlated strongly with the response to therapy whether assessed as the incremental change in IGF-I (P < 10(-6)) or as the increase in growth velocity (P approximately 0.003). GH treatment had no consistent effect on GH-BP/receptor levels. These findings support the concept that the GH-BP/receptor endowment is characteristic for an individual and plays a pivotal role in somatic growth. The GH-BP/receptor system and its ontogeny appears relatively independent of regulation by GH. Differences in individual GH-BP/GH receptor complement account for some of the variability in the response to GH, and GH-BP levels may serve as a predictor for the degree of response. The reciprocal relationship between GH production and GH-BP in normal subjects probably results from adjustment of GH secretion to accommodate the prevailing GH-BP/receptor environment.

Home blood pressure predicts stroke incidence among older adults with impaired physical function: the Ohasama study.

PubMed

Murakami, Keiko; Asayama, Kei; Satoh, Michihiro; Hosaka, Miki; Matsuda, Ayako; Inoue, Ryusuke; Tsubota-Utsugi, Megumi; Murakami, Takahisa; Nomura, Kyoko; Kikuya, Masahiro; Metoki, Hirohito; Imai, Yutaka; Ohkubo, Takayoshi

2017-12-01

Several observational studies have found modifying effects of functional status on the association between conventional office blood pressure (BP) and adverse outcomes. We aimed to examine whether the association between higher BP and stroke was attenuated or inverted among older adults with impaired function using self-measured home BP measurements. We followed 501 Japanese community-dwelling adults aged at least 60 years (mean age, 68.6 years) with no history of stroke. Multivariate-adjusted hazard ratios for 1-SD increase in home BP and office BP measurements were calculated by the Cox proportional hazards model. Functional status was assessed by self-reported physical function. During a median follow-up of 11.5 years, first strokes were observed in 47 participants. Higher home SBP, but not office SBP, was significantly associated with increased risk of stroke among both 349 participants with normal physical function and 152 participants with impaired physical function [hazard ratio (95% confidence interval) per 14.4-mmHg increase: 1.74 (1.12-2.69) and 1.77 (1.06-2.94), respectively], with no significant interaction for physical function (P = 0.56). Higher home DBP, but not office DBP, was also significantly associated with increased risk of stroke (P ≤ 0.029) irrespective of physical function (all P > 0.05 for interaction). Neither home BP nor office BP was significantly associated with all-cause mortality irrespective of physical function. Higher home BP was associated with increased risk of stroke even among those with impaired physical function. Measurements of home BP would be useful for stroke prevention, even after physical function decline.

Synthesis of novel benzodioxane midst piperazine moiety decorated chitosan silver nanoparticle against biohazard pathogens and as potential anti-inflammatory candidate: A molecular docking studies.

PubMed

Karthik, C S; Manukumar, H M; Ananda, A P; Nagashree, S; Rakesh, K P; Mallesha, L; Qin, Hua-Li; Umesha, S; Mallu, P; Krishnamurthy, N B

2018-03-01

Nanoparticles (NPs) are currently being investigated along with the use of biodegradable polymer containing active agents in many areas of medicine for targeted applications. The present study was aimed to synthesize novel compound Benzodioxane midst piperazine (BP) and characterization of a BP decorated chitosan silver nanoparticles (BP*C@AgNPs) and shown effective against hazardous pathogens, and also having anti-inflammatory property. It was further evaluated for molecular docking proofs, and toxicity. The BP*C@AgNPs had spherical shape with size of 36.6nm with wide biocidal activity against hazardous Gram-positive and Gram-negative bacteria with excellent inhibition at 100μg/mL for S. aureus (10.08±0.05mm ZOI), and E. coli (10.03±0.04mm ZOI) compared to antibiotic Streptomycin. The anti-inflammatory activity exhibited IC 50 value of 71.61±1.05μg/mL for BP*C@AgNPs compared to indomethacin (IC 50 =40.15±1.21μg/mL). Also, the docking study of BP showed excellent score for COX1 and DNA gyrase. This in silico study confirmed the achieved efficacy of BP, with less toxicity against normal PMBCs in vitro and in vivo studies. This study concludes that, the novel synthesized BP*C@AgNPs had excellent biocidal property and as anti-inflammatory candidate revealed by docking studies, it confirms BP*C@AgNPs for first-class therapeutic applications in the area of medicinal nanotechnology for the coming days. Copyright © 2017 Elsevier B.V. All rights reserved.

Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

PubMed

Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

2012-10-01

The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Orientation of Myosin Binding Protein C in the Cardiac Muscle Sarcomere Determined by Domain-Specific Immuno-EM

PubMed Central

Lee, Kyounghwan; Harris, Samantha P.; Sadayappan, Sakthivel; Craig, Roger

2014-01-01

Myosin binding protein-C is a thick filament protein of vertebrate striated muscle. The cardiac isoform (cMyBP-C) is essential for normal cardiac function, and mutations in cMyBP-C cause cardiac muscle disease. The rod-shaped molecule is composed primarily of 11 immunoglobulin- or fibronectin-like domains, and is located at 9 sites, 43 nm apart, in each half of the A-band. To understand how cMyBP-C functions, it is important to know its structural organization in the sarcomere, as this will affect its ability to interact with other sarcomeric proteins. Several models have been proposed, in which cMyBP-C wraps around, extends radially from, or runs axially along the thick filament. Our goal was to define cMyBP-C orientation by determining the relative axial positions of different cMyBP-C domains. Immuno-electron microscopy was performed using mouse cardiac myofibrils labeled with antibodies specific to the N- and C-terminal domains and to the middle of cMyBP-C. Antibodies to all regions of the molecule, except the C-terminus, labeled at the same nine axial positions in each half A-band, consistent with a circumferential and/or radial rather than an axial orientation of the bulk of the molecule. The C-terminal antibody stripes were slightly displaced axially, demonstrating an axial orientation of the C-terminal 3 domains, with the C-terminus closer to the M-line. These results, combined with previous studies, suggest that the C-terminal domains of cMyBP-C run along the thick filament surface, while the N-terminus extends towards neighboring thin filaments. This organization provides a structural framework for understanding cMyBP-C’s modulation of cardiac muscle contraction. PMID:25451032

Exaggerated blood pressure response to exercise--a new portent of masked hypertension.

PubMed

Kayrak, Mehmet; Bacaksiz, Ahmet; Vatankulu, Mehmet Akif; Ayhan, Selim S; Kaya, Zeynettin; Ari, Hatem; Sonmez, Osman; Gok, Hasan

2010-01-01

Masked hypertension (MHT) is a popular entity with increased risk of developing sustained hypertension, heart attack, stroke, and death. Subjects have normal blood pressure (BP) at office but elevated values at night so it is difficult to diagnose. Exaggerated blood pressure response to exercise (EBPR) is also a predictor of future hypertension. To investigate the relationship between these two entities, we evaluated 61 normotensive subjects with EBPR. The subjects underwent 24-h ambulatory blood pressure monitoring (ABPM). The prevalence of masked hypertension among subjects with EBPR was 41%. Body mass index (BMI), non-high density lipoprotein (HDL) cholesterol, diastolic blood pressure (DBP) at peak exercise and recovery, nondipping DBP pattern, and elevated early morning average BPs were associated with masked hypertension. In multivariate logistic regression analysis, the DBP measured at peak exercise was detected as an independent predictor of MHT in subjects with EBPR. Subjects with abnormally elevated BP during exercise are prone to MHT, necessitate medical assessment and close follow-up for hypertension.

Type-controlled nanodevices based on encapsulated few-layer black phosphorus for quantum transport

NASA Astrophysics Data System (ADS)

Long, Gen; Xu, Shuigang; Shen, Junying; Hou, Jianqiang; Wu, Zefei; Han, Tianyi; Lin, Jiangxiazi; Wong, Wing Ki; Cai, Yuan; Lortz, Rolf; Wang, Ning

2016-09-01

We demonstrate that encapsulation of atomically thin black phosphorus (BP) by hexagonal boron nitride (h-BN) sheets is very effective for minimizing the interface impurities induced during fabrication of BP channel material for quantum transport nanodevices. Highly stable BP nanodevices with ultrahigh mobility and controllable types are realized through depositing appropriate metal electrodes after conducting a selective etching to the BP encapsulation structure. Chromium and titanium are suitable metal electrodes for BP channels to control the transition from a p-type unipolar property to ambipolar characteristic because of different work functions. Record-high mobilities of 6000 cm2 V-1 s-1 and 8400 cm2 V-1 s-1 are respectively obtained for electrons and holes at cryogenic temperatures. High-mobility BP devices enable the investigation of quantum oscillations with an indistinguishable Zeeman effect in laboratory magnetic field.

Post-partum recovery course in patients with gestational hypertension and pre-eclampsia.

PubMed

Mikami, Yukiko; Takagi, Kenjiro; Itaya, Yukiko; Ono, Yoshihisa; Matsumura, Hideyoshi; Takai, Yasushi; Seki, Hiroyuki

2014-04-01

We examined the post-partum recovery course in patients with pre-eclampsia (PE) and gestational hypertension (GH) and evaluated the associated factors. In a retrospective review of 145 patients with GH or PE who gave birth between 1 January 2008 and 30 October 2011 at our institution, there were 125 PE and 20 GH cases. Data collected included the gestational age at initial examination and delivery, delivery mode, time for normalization of blood pressure (BP), and time until resolution of proteinuria in PE patients. Comparisons were made between singleton and multiple pregnancies, onset (early, <32 weeks; late, ≥ 32 weeks) and fetal growth restriction in singleton pregnancies. The mean interval for normalization of BP was 41.8 ± 29.4 days (median, 31.5). The mean interval for resolution of proteinuria was 30.0 ± 39.6 days (median, 27.0). Ninety percent of patients required 77 and 60 days to recover from hypertension and proteinuria, respectively. The time for BP normalization was longer in the early-onset group. The time for resolution of proteinuria was not affected by any factor examined. A post-partum observation period of 12 weeks is acceptable for differentiating PE and GH from chronic hypertension or renal disease. GH severity did not affect the recovery period, but proteinuria severity did. Onset time was a factor influencing the recovery from PE and GH. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

[Field observation on the effect of low-sodium and high-potassium salt substitute on blood pressure in the rural community-based population in China].

PubMed

Zhang, Gao-hui; Ma, Ji-xiang; Guo, Xiao-lei; Dong, Jing; Chen, Xi; Zhang, Ji-yu; Su, Jun-ying; Tang, Jun-li; Xu, Ai-qiang

2011-09-01

To investigate the effect of commercial low-sodium and high-potassium salt substitutes on blood pressure in the rural community-based population in China. We conducted a quasi-experiment on 411 adults, who were 30 to 60 years of age, in 2 rural communities from Laiwu city in Shandong province of China on data from blood pressure screening. The subjects were divided into 2 groups: high blood pressure (HBP) and non-HBP (NHBP). Both groups and their family members took a low-sodium and high-potassium salt substitute for 3 months to replace the normal salt in their bodies. Blood pressure (BP) and 24-hour urinary sodium and potassium were measured regularly in the 2 groups. There was a continuously decreasing trend for BP at the end of the first month. Three months later, the mean BP decreased by 7.4 mm Hg (1 mm Hg = 0.133 kPa, t = 10.096, P = 0.000) for SBP and 3.8 mm Hg (t = 8.017, P = 0.000) for DBP in the HBP group, when compared to a 1.2 mm Hg (t = 2.507, P = 0.007) decrease on SBP and 1.0 mm Hg (t = 2.987, P = 0.002) on DBP in the NHBP group. The mean urinary sodium had a decrease of 15.5 mmol/24 h (t = 1.803, P = 0.037), but the urinary potassium increased by 4.2 mmol/24 h (t' = 2.132, P = 0.018). The result of urinary sodium appeared to be as follows: potassium ratio (Na(+)/K(+)) decreased by 1.2 (t = 2.786, P = 0.003) in the HBP group. However, in NHBP group, the mean urinary sodium decreased by 1.7 mmol/24 h (t = 0.211, P = 0.417) and urinary potassium increased by 3.7 mmol/24 h (t' = 2.207, P = 0.015), together with the decrease of Na(+)/K(+) by 0.7 (t = 1.818, P = 0.036). Results from our study clearly demonstrated that the intake of low-sodium and high-potassium salt substitute could effectively reduce the BP with good compliance among adults in the rural community-based population in China. This was an effective but non-medical method to prevent and control the high blood pressure.

The role of body mass in the response to growth hormone therapy.

PubMed

Martha, P M; Reiter, E O; Dávila, N; Shaw, M A; Holcombe, J H; Baumann, G

1992-12-01

Obesity is associated with normal or increased growth despite diminished GH secretion compared to lean children. The mechanism by which adequate growth is maintained in the presence of low GH levels is unknown, but is possibly mediated at the GH receptor level. To probe this hypothesis, we examined the relationship between GH responsivity, body mass index (BMI) and plasma GH-binding protein (GH-BP)/receptor level in 43 GH-deficient children during treatment with a fixed dose of GH (0.18 mg/kg.week). Before treatment, BMI [expressed as standard deviation score (SDS) for age (BMI-SDS)] did not correlate with either growth velocity or serum insulin-like growth factor-I (IGF-I). In contrast, after 12 months of GH therapy BMI-SDS correlated directly with plasma IGF-I (P < 10(-5)) and growth velocity (P < 10(-3)). These findings parallel those obtained for GH-BP vs. the response to GH, suggesting that BMI and GH-BP are covariants. The interrelationships among BMI, GH-BP, and response to GH were further probed by multiple regression analysis. Partial correlation coefficients vs. response to GH were consistently stronger for GH-BP than for BMI-SDS, indicating that GH-BP is the dominant factor between these two covariants in determining responsiveness to GH. The data suggest a primary role for GH-BP/receptor levels in determining GH action, with secondary but significant effects of nutrition and degree of adiposity. The latter may be mediated through the impact of nutrition and body mass on GH-BP/receptor levels.

Mutations in ARL2BP, Encoding ADP-Ribosylation-Factor-Like 2 Binding Protein, Cause Autosomal-Recessive Retinitis Pigmentosa

PubMed Central

Davidson, Alice E.; Schwarz, Nele; Zelinger, Lina; Stern-Schneider, Gabriele; Shoemark, Amelia; Spitzbarth, Benjamin; Gross, Menachem; Laxer, Uri; Sosna, Jacob; Sergouniotis, Panagiotis I.; Waseem, Naushin H.; Wilson, Robert; Kahn, Richard A.; Plagnol, Vincent; Wolfrum, Uwe; Banin, Eyal; Hardcastle, Alison J.; Cheetham, Michael E.; Sharon, Dror; Webster, Andrew R.

2013-01-01

Retinitis pigmentosa (RP) is a genetically heterogeneous retinal degeneration characterized by photoreceptor death, which results in visual failure. Here, we used a combination of homozygosity mapping and exome sequencing to identify mutations in ARL2BP, which encodes an effector protein of the small GTPases ARL2 and ARL3, as causative for autosomal-recessive RP (RP66). In a family affected by RP and situs inversus, a homozygous, splice-acceptor mutation, c.101−1G>C, which alters pre-mRNA splicing of ARLBP2 in blood RNA, was identified. In another family, a homozygous c.134T>G (p.Met45Arg) mutation was identified. In the mouse retina, ARL2BP localized to the basal body and cilium-associated centriole of photoreceptors and the periciliary extension of the inner segment. Depletion of ARL2BP caused cilia shortening. Moreover, depletion of ARL2, but not ARL3, caused displacement of ARL2BP from the basal body, suggesting that ARL2 is vital for recruiting or anchoring ARL2BP at the base of the cilium. This hypothesis is supported by the finding that the p.Met45Arg amino acid substitution reduced binding to ARL2 and caused the loss of ARL2BP localization at the basal body in ciliated nasal epithelial cells. These data demonstrate a role for ARL2BP and ARL2 in primary cilia function and that this role is essential for normal photoreceptor maintenance and function. PMID:23849777

Blood pressure and hypertension in athletes: a systematic review.

PubMed

Berge, H M; Isern, C B; Berge, E

2015-06-01

Hypertension is reported to be the most prevalent risk factor for cardiovascular disease in elite athletes. We aimed to review blood pressure (BP) and prevalence of hypertension in different elite athletes, and study whether there was an association between high BP and left ventricular hypertrophy (LVH). A systematic review of studies reporting BP in athletes using search strategies developed for PubMed and EMBASE, including only studies with ≥100 participants. We collected data on BP, prevalence of hypertension, LVH and methods of BP measurement. Of 3723 records identified, 51 met the inclusion criteria. These included men and women (n=138,390), aged mostly between 18 and 40 years, from varied sports disciplines. Mean systolic BP varied from 109±11 to 138±7 mm Hg and mean diastolic BP from 57±12 to 92±10 mm Hg. Strength-trained athletes had higher BP than endurance-trained athletes (131.3±5.3/77.3±1.4 vs 118.6±2.8/71.8±1.2 mm Hg, p<0.05), and there was a trend towards a higher BP in athletes training ≥10 h compared with others (121.8±3.8/73.8±2.5 vs 117.6±3.3/66.8±6.9, p=0.058), but overall there was no significant difference in BP between athletes and controls. The prevalence of hypertension varied from 0% to 83%. Some studies showed an association between high BP and LVH. Measurement methods were poorly standardised. BP and prevalence of hypertension in athletes varied considerably partly because of variations in methodology, but type and intensity of training may contribute towards higher BP. High BP may be associated with LVH. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cardiovascular and renal manifestations of glutathione depletion induced by buthionine sulfoximine.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Pérez-Abud, Rocío; Vargas Tendero, Pablo; Baca, Yolanda; Wangensteen, Rosemary

2012-06-01

Oxidative stress contributes to the development of several cardiovascular diseases, including diabetes, renal insufficiency, and arterial hypertension. Animal studies have evidenced the association between higher blood pressure (BP) and increased oxidative stress, and treatment with antioxidants has been shown to reduce BP, while BP reduction due to antihypertensive drugs is associated with reduced oxidative stress. In 2000, it was first reported that oxidative stress and arterial hypertension were produced in normal Sprague-Dawley rats by oral administration of buthionine sulfoximine (BSO), which induces glutathione (GSH) depletion, indicating that oxidative stress may induce hypertension. The contribution of several potential pathogenic factors has been evaluated in the BSO rat model, the prototype of oxidative stress-induced hypertension, including vascular reactivity, endothelium-derived factors, renin-angiotensin system activity, TXA(2)-PGH(2) production, sodium sensitivity, renal dopamine-induced natriuresis, and sympathetic tone. This review summarizes the main factors implicated in the pathogenesis of BSO-induced hypertension and the alterations associated with GSH depletion that are related to renal function or BP control.

Possible role for increased C4b-binding-protein level in acquired protein S deficiency in type I diabetes.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Marchi, E; Barbanti, M; Lefebvre, P

1990-04-01

In this study, total protein S (PS) immunological levels, free-PS and C4b-binding-protein (C4bBP) concentrations, and PS functional activity were investigated in insulin-dependent (type I) diabetic patients and compared with nondiabetic subjects. Mean total PS antigen concentration was not different between diabetic patients and nondiabetic subjects, whereas free-PS levels and PS functional activity were significantly reduced in diabetic patients. C4bBP was increased in diabetic patients and correlated with HbA1 levels. This study shows that type I diabetic patients have depressed free PS and PS activity despite the presence of normal total PS concentration and suggests that this phenomenon is probably linked to the increase of circulating C4bBP.

The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells.

PubMed

Chen, W L; Luo, D F; Gao, C; Ding, Y; Wang, S Y

2015-07-01

The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+ cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P < 0.0001). Moreover, FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs =0.317, P=0.006), hemoglobin levels (rs = 0.210, P = 0.049), and percentage of peripheral blood blasts (rs = 0.256, P = 0.027), but inversely correlated with hemoglobin levels in the control group (rs = -0.391, P < 0.0001). AML patients with high CD34+ expression showed significantly higher FAMLF-CS expression than those with low CD34+ expression (P = 0.041). Our results showed that FAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.

Characteristics of depression among offspring at high and low familial risk of bipolar disorder.

PubMed

Diler, Rasim Somer; Goldstein, Tina R; Hafeman, Danella; Rooks, Brian Thomas; Sakolsky, Dara; Goldstein, Benjamin I; Monk, Kelly; Hickey, Mary Beth; Axelson, David; Iyengar, Satish; Birmaher, Boris

2017-08-01

Having a parent with bipolar disorder (BP) is a very strong risk factor for developing BP. Similarly, depression among youth is a clinical risk factor for subsequent BP. We evaluated whether mood symptomatology in depressed youth is different between those at high and low familial risk to develop BP. The most severe major depressive episode in BP offspring (N=61) and community control offspring (N=20) was evaluated using expanded depression and mania rating scales derived from the Schedule for Affective Disorders and Schizophrenia for Children Present Version. The results were adjusted for any between-group significant demographic differences and for multiple comparisons. The severity of depressive symptoms and the percentage of offspring with severe depressive symptoms, especially atypical depressive features, were significantly higher in the depressed offspring of BP parents compared to the depressed controls (P s <.05). The depressive symptoms were helpful to identify a high-risk group (e.g., odds ratio [OR] for hypersomnia: 22.4, 95% confidence interval [CI]: 1.3-404, P=.04). In addition, there were significantly more depressed offspring of BP parents with subsyndromal manic symptoms than controls (52.5% vs 20%, OR: 4.2, 95% CI: 1.2-14.7, P<.01). Depressed BP offspring had more severe depression including atypical depressive symptoms, and were more likely to have subsyndromal mixed manic symptoms than depressed control offspring. Prospective studies to evaluate whether these youth are at high risk to develop BP are warranted. If replicated, the results of this study have important clinical (e.g., treatment of depression in depressed offspring of BP parents) and research implications. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke.

PubMed

Mustanoja, Satu; Putaala, Jukka; Gordin, Daniel; Tulkki, Lauri; Aarnio, Karoliina; Pirinen, Jani; Surakka, Ida; Sinisalo, Juha; Lehto, Mika; Tatlisumak, Turgut

2016-06-01

High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7-13.2). Patients with a recurrent stroke (n=142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (P<0.001) and 24-h SBP, diastolic BP, and mean arterial pressure compared with patients without the recurrent stroke. Patients with SBP ≥160 mm Hg compared with those with SBP <160 mm Hg had significantly more recurrent strokes (hazard ratio 3.3 [95% confidence interval, 2.05-4.55]; P<0.001) occurring earlier (13.9 years [13.0-14.6] versus 16.2 [15.8-16.6]; P<0.001) within the follow-up period. In multivariable analyses, higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure were independently associated with the risk of recurrent stroke, while the 24-hour BP levels were not. In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes. © 2016 American Heart Association, Inc.

Low job control is associated with higher diastolic blood pressure in men with mildly elevated blood pressure: the Rosai Karoshi study

PubMed Central

HATTORI, Tomomi; MUNAKATA, Masanori

2015-01-01

Job strain is a risk factor for hypertension, but it is not fully understood if components of job strain, or job demand or job control per se could be related to blood pressure (BP), and if so, whether the relationship differs between normotension and mildly elevated BP. We examined resting BP, and job stress components in 113 Japanese male hospital clerks (38.1 ± 4.4 yr). Subjects were classified into normotensive (NT) (<130/85 mmHg, n=83) and mildly elevated BP (ME) (≥130/85 mmHg) groups. Diastolic BP (DBP) showed a significant interaction between group and job control level (p=0.013). Subjects with low job control demonstrated higher DBP than those with high job control (89.1 ± 2.1 vs. 82.3 ± 2.3 mmHg, p=0.042) in ME group even after adjustments for covariates while DBP did not differ between low and high job control subjects in NT group. Systolic BP (SBP) did not differ between high and low job control subjects in both groups. Neither SBP nor DBP differed between high and low demand groups in either group. Among job strain components, job control may be independently related to BP in Japanese male workers with mildly elevated BP. PMID:25914072

Benzophenone-type UV filters in surface waters: An assessment of profiles and ecological risks in Shanghai, China.

PubMed

Wu, Ming-Hong; Xie, Deng-Guo; Xu, Gang; Sun, Rui; Xia, Xiao-Yu; Liu, Wen-Long; Tang, Liang

2017-07-01

Benzophenone-type UV filters (BP-UV filters) are frequently introduced into aquatic environment from several sources. The occurrence and fate of select BP-UV filters and their metabolites were investigated in this study. All target compounds were detected in water samples, except for 2, 3, 4-trihydroxybenzophenone (2, 3, 4-OH-BP). The concentration reached up 131ngL -1 for 5-benzoyl-4-hydroxy-2-ethoxybenzenesulfonic acid (BP-4), 30.0ngL -1 for 2-hydroxy-4-methoxybenzophenone (BP-3), and mean value of 158ngL -1 for benzophenone (BP). Concentrations of BP-UV filters were not related to recreational waters but with high population frequencies. In addition, five BP-UV filters, namely 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2,3,4-OH-BP, 2,4-dihydroxybenzophenone (BP-1), 4-hydroxybenzophenone (4-OH-BP) and BP were investigated for probable sources, and found that they originate from BP-3 metabolism. There is a similar source for BP-3, BP-4, BP-1, 4-OH-BP and BP. Environmental risk assessment (ERA) showed that risk quotients (RQs) of BP-4, BP-3 and BP were 2.7, 0.8 and 0.5, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

The mitochondrial genome of the quiet-calling katydids, Xizicus fascipes (Orthoptera: Tettigoniidae: Meconematinae).

PubMed

Yang, Ming Ru; Zhou, Zhi Jun; Chang, Yan Lin; Zhao, Le Hong

2012-08-01

To help determine whether the typical arthropod arrangement was a synapomorphy for the whole Tettigoniidae, we sequenced the mitochondrial genome (mitogenome) of the quiet-calling katydids, Xizicus fascipes (Orthoptera: Tettigoniidae: Meconematinae). The 16,166-bp nucleotide sequences of X. fascipes mitogenome contains the typical gene content, gene order, base composition, and codon usage found in arthropod mitogenomes. As a whole, the X. fascipes mitogenome contains a lower A+T content (70.2%) found in the complete orthopteran mitogenomes determined to date. All protein-coding genes started with a typical ATN codon. Ten of the 13 protein-coding genes have a complete termination codon, but the remaining three genes (COIII, ND5 and ND4) terminate with incomplete T. All tRNAs have the typical clover-leaf structure of mitogenome tRNA, except for tRNA(Ser(AGN)), in which lengthened anticodon stem (9 bp) with a bulged nuleotide in the middle, an unusual T-stem (6 bp in constrast to the normal 5 bp), a mini DHU arm (2 bp) and no connector nucleotides. In the A+T-rich region, two (TA)n conserved blocks that were previously described in Ensifera and two 150-bp tandem repeats plus a partial copy of the composed at 61 bp of the beginning were present. Phylogenetic analysis found: i) the monophyly of Conocephalinae was interrupted by Elimaea cheni from Phaneropterinae; and ii) Meconematinae was the most basal group among these five subfamilies.

Self-reported creativity in bipolar disorder: prevalence, types and associated outcomes in mania versus hypomania.

PubMed

McCraw, Stacey; Parker, Gordon; Fletcher, Kathryn; Friend, Paul

2013-12-01

Bipolar (BP) disorder has been linked to creativity following investigation of prominent artists and controlled trials of creativity in BP disorder patients. However, it is unclear whether creativity is differentially expressed across the BP I and BP II subtypes. 219 patients (aged 19-63 years) diagnosed with BP disorder by clinical interview and DSM-IV criteria were asked whether they tended to be more creative during hypo/manic episodes, and answered five questions about personality styles associated with creativity. Qualitative analyses were performed on a smaller subset of 69 BP patients (n=19 BP I, n=50 BP II) who provided written responses of the types of creative activities engaged in when hypo/manic and any perceived advantages or disadvantages of their creative pursuits. 82% of BP patients affirmed being creative when hypo/manic, with comparable results for the BP I and BP II subtypes (84% and 81% respectively). Both BP subtypes engaged mostly in writing, painting, work or business ideas and 'other' forms of art; however BP II patients were more likely to draw and be musical. Both subgroups reported the consequences of feeling good, being productive or quitting their project. BP I patients were more likely to overspend during their creative highs while BP II patients were more likely to experience improved focus and clarity. BP patients affirming creative highs were significantly more likely to report creative personality styles more generally outside of a mood episode. BP patients' self-reported creative activities were not retrospectively judged for quality or originality and so may reflect common creative abilities rather than exceptional quality. The impact of depressive episodes on creativity was not assessed. Uneven sample sizes in the BP I and BP II subgroups may have compromised statistical power. Creativity during hypo/manic episodes was extremely common in both BP subtypes. While some nuances in activity type and outcomes were observed, no significant creative phenotype specific to BP I or BP II disorder emerged. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.

Measurement of carotid blood pressure and local pulse wave velocity changes during cuff induced hyperemia.

PubMed

Nabeel, P M; Karthik, Srinivasa; Joseph, Jayaraj; Sivaprakasam, Mohanasankar

2017-07-01

We present a prototype design of dual element photoplethysmograph (PPG) probe along with associated measurement system for carotid local pulse wave velocity (PWV) evaluation in a non-invasive and continuous manner. The PPG probe consists of two identical sensing modules placed 23 mm apart. Simultaneously measured blood pulse waveforms from these arterial sites were processed and the pulse transit time delay was resolved using the developed application-specific software. The ability of developed PPG probe and associated measurement system to detect acute changes in carotid local PWV due to blood pressure (BP) variations was experimentally validated by an in-vivo study. Intra-subject carotid BP elevation was achieved by an upper arm cuff based occlusion, which offered a controlled way of local PWV escalation. The elevated carotid BP values were also recorded by a calibrated pressure tonometer prior to the study, and was used as a reference. A significant increment (1.0 - 2.6 m/s) in local PWV was observed and was proportional to the BP increment induced by the occlusive reactive hyperemia. Study results demonstrated the feasibility of real-time signal acquisition and reliable local PWV evaluation under normal and elevated BP conditions using the developed measurement system.

Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans

NASA Technical Reports Server (NTRS)

Zhang, Rong; Iwasaki, Kenichi; Zuckerman, Julie H.; Behbehani, Khosrow; Crandall, Craig G.; Levine, Benjamin D.; Blomqvist, C. G. (Principal Investigator)

2002-01-01

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (< 0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.

Association between Blood Pressure Responses to Cold Pressor Test and Dietary Sodium Intervention in the Chinese Population

PubMed Central

Chen, Jing; Gu, Dongfeng; Jaquish, Cashell E.; Chen, Chung-Shiuan; Rao, DC; Liu, Depei; Hixson, James E.; Hamm, L. Lee; Gu, C. Charles; Whelton, Paul K.; He, Jiang

2008-01-01

Background Blood pressure (BP) responses to the cold pressor test (CPT) and to dietary sodium intake might be related to the risk of hypertension. We examined the association between BP responses to the CPT and to dietary sodium and potassium interventions. Methods The CPT and dietary intervention were conducted among 1,906 study participants in rural China. The dietary intervention included three 7-day periods of low-sodium-feeding (51.3 mmol/day), high-sodium-feeding (307.8 mmol/day), and high-sodium-feeding plus potassium-supplementation (60 mmol/day). A total of 9 BP measurements were obtained during the 3-day baseline observation and the last 3 days of each intervention using a random-zero sphygmomanometer. Results BP response to the CPT was significantly associated with BP changes during the sodium and potassium interventions (all p<0.0001). Compared to the lowest quartile of BP response to the CPT, systolic BP changes (95% confident interval) for the top 3 quartiles, respectively, were −2.02 (−2.87, −1.16), −3.17 (−4.05, −2.28), and −5.98 (−6.89, −5.08) mm Hg during the low-sodium intervention. Corresponding systolic BP changes during the high-sodium intervention were 0.40 (−0.36, 1.16), 0.44 (−0.35, 1.22), and 2.30 (1.50, 3.10) mm Hg, and during the potassium-supplementation were −0.26 (−0.99, 0.46), −0.95 (−1.70, −0.20), and −1.59 (−2.36, −0.83) mm Hg, respectively. Conclusions These results indicated that BP response to the CPT was associated with salt-sensitivity and potassium-sensitivity. Furthermore, a low-sodium or high-potassium diet might be more effective to lower BP among individuals with high responses to the CPT. PMID:18779460

Feasibility and antihypertensive effect of replacing regular salt with mineral salt -rich in magnesium and potassium- in subjects with mildly elevated blood pressure

PubMed Central

2011-01-01

Background High salt intake is linked to hypertension whereas a restriction of dietary salt lowers blood pressure (BP). Substituting potassium and/or magnesium salts for sodium chloride (NaCl) may enhance the feasibility of salt restriction and lower blood pressure beyond the sodium reduction alone. The aim of this study was to determine the feasibility and effect on blood pressure of replacing NaCl (Regular salt) with a novel mineral salt [50% sodium chloride and rich in potassium chloride (25%), magnesium ammonium potassium chloride, hydrate (25%)] (Smart Salt). Methods A randomized, double-blind, placebo-controlled study was conducted with an intervention period of 8-weeks in subjects (n = 45) with systolic (S)BP 130-159 mmHg and/or diastolic (D)BP 85-99 mmHg. During the intervention period, subjects consumed processed foods salted with either NaCl or Smart Salt. The primary endpoint was the change in SBP. Secondary endpoints were changes in DBP, daily urine excretion of sodium (24-h dU-Na), potassium (dU-K) and magnesium (dU-Mg). Results 24-h dU-Na decreased significantly in the Smart Salt group (-29.8 mmol; p = 0.012) and remained unchanged in the control group: resulting in a 3.3 g difference in NaCl intake between the groups. Replacement of NaCl with Smart Salt resulted in a significant reduction in SBP over 8 weeks (-7.5 mmHg; p = 0.016). SBP increased (+3.8 mmHg, p = 0.072) slightly in the Regular salt group. The difference in the change of SBP between study groups was significant (p < 0.002). Conclusions The substitution of Smart Salt for Regular salt in subjects with high normal or mildly elevated BP resulted in a significant reduction in their daily sodium intake as well as a reduction in SBP. Trial Registration ISRCTN: ISRCTN01739816 PMID:21888642

Back-Projection Cortical Potential Imaging: Theory and Results.

PubMed

Haor, Dror; Shavit, Reuven; Shapiro, Moshe; Geva, Amir B

2017-07-01

Electroencephalography (EEG) is the single brain monitoring technique that is non-invasive, portable, passive, exhibits high-temporal resolution, and gives a directmeasurement of the scalp electrical potential. Amajor disadvantage of the EEG is its low-spatial resolution, which is the result of the low-conductive skull that "smears" the currents coming from within the brain. Recording brain activity with both high temporal and spatial resolution is crucial for the localization of confined brain activations and the study of brainmechanismfunctionality, whichis then followed by diagnosis of brain-related diseases. In this paper, a new cortical potential imaging (CPI) method is presented. The new method gives an estimation of the electrical activity on the cortex surface and thus removes the "smearing effect" caused by the skull. The scalp potentials are back-projected CPI (BP-CPI) onto the cortex surface by building a well-posed problem to the Laplace equation that is solved by means of the finite elements method on a realistic head model. A unique solution to the CPI problem is obtained by introducing a cortical normal current estimation technique. The technique is based on the same mechanism used in the well-known surface Laplacian calculation, followed by a scalp-cortex back-projection routine. The BP-CPI passed four stages of validation, including validation on spherical and realistic head models, probabilistic analysis (Monte Carlo simulation), and noise sensitivity tests. In addition, the BP-CPI was compared with the minimum norm estimate CPI approach and found superior for multi-source cortical potential distributions with very good estimation results (CC >0.97) on a realistic head model in the regions of interest, for two representative cases. The BP-CPI can be easily incorporated in different monitoring tools and help researchers by maintaining an accurate estimation for the cortical potential of ongoing or event-related potentials in order to have better neurological inferences from the EEG.

Neotectonic and seismic activity in the Armorican and Cornubian Massifs: Regional stress field with glacio-isostatic influence?

NASA Astrophysics Data System (ADS)

Van Vliet-Lanoë, B.; Bonnet, S.; Hallegouët, B.; Laurent, M.

1997-09-01

In Brittany and SW England, evidence for low magnitude Quaternary seismicity can be found in sand pit exposures and beach sections. Deformation is especially well seen in alluvial and estuarine complexes resting on Late Pliocene sands or thick saprolite. The deformations are shallow, dominantly hydroplastic (high water-table) and led to overconsolidated sands, silts or clays. They reveal normal loading at micro (millimetric) and macro (decametric) scales as controlled by the local rheological properties of the sediments, by strikeslip faults associated with positive flower structures, folding, and intraformational water expulsion or hill slope sliding with reverse microfaulting. All the sites where these features occur, are in the vicinity of presumed active faults or steep slopes in highly fractured Proterozoic basement rocks indicating a possible shear zone. In most cases, these features are not associated with synsedimentary deformation, as strong superficial red soils are generally reworked by them. All these features are reworked by microfaulting after overconsolidation. Additional periglacial phenomena are superimposed on them and are often confused with them. Deformation occurred after the development of Holstenian peats (isotopic stage 11,400 ka BP) at Crozon (Brittany), after 317 ka BP (beginning of isotopic stage 9) in the Vilaine estuary, and in most other sites before the last rubified pedogenesis in the Middle Pleistocene (presumed isotopic stage 9). These dates correspond to the same episode that gave rise to the last main reactivation of the fossil cliff around 300 ka BP and to local uplift. One or several seismic clusters have taken place, probably due to delayed crustal rebound after a major glacial event (stage 10) and to rapid loading resulting from younger ice sheet growth (stage 8). Similar events occurred in late stage 7 and late stage 5. These events might have locally amplified the crustal deformation of the old Brittany and Cornubian Hercynian massifs resulting from a regional stress field especially from 400 ka to 200 ka BP. Stratigraphical, geodynamical and paleoclimatological implications are discussed.

Early-Mid Holocene climatic variations in Tasmania, Australia: multi-proxy records in a stalagmite from Lynds Cave

NASA Astrophysics Data System (ADS)

Xia, Qikai; Zhao, Jian-xin; Collerson, K. D.

2001-12-01

Mass spectrometric uranium-series dating and C-O isotopic analysis of a stalagmite from Lynds Cave, northern Tasmania, Australia provide a high-resolution record of regional climate change between 5100 and 9200 yr before present (BP). Combined δ18O, δ13C, growth rate, initial 234U/238U and physical property (color, transparency and porosity) records allow recognition of seven climatic stages: Stage I (>9080 yr BP) - a relatively dry period at the beginning of stalagmite growth evidenced by elevated 234U/238U; Stage II (9080-8600 yr BP) - a period of unstable climate characterized by high-frequency variability in temperature and bio-productivity; Stage III (8600-8000 yr BP) - a period of stable and moderate precipitation and stable and high bio-productivity, with a continuously rising temperature; Stage IV (8000-7400 yr BP) - the warmest period with high evaporation and low effective precipitation (rainfall less evaporation); Stage V (7400-7000 yr BP) - the wettest period with highest stalagmite growth and enhanced but unstable bio-productivity; Stage VI (7000-6600 yr BP) - a period with a significantly reduced precipitation and bio-productivity without noticeable change in temperature; Stage VII (6600-5100 yr BP) - a period of lowest temperature and precipitation marking a significant climatic deterioration. Overall, the records suggest that the warmest climate occurred between 8000 and 7400 yr BP, followed by a wettest period between 7400 and 7000 yr BP. These are broadly correlated with the so-called 'Mid Holocene optimum' previously proposed using pollen and lake level records. However, the timing and resolution of the speleothem record from Lynds Cave are significantly higher than in both the pollen and lake level records. This allows us to correlate the abrupt change in physical property, δ18O, δ13C, growth rate, and initial 234U/238U of the stalagmite at ˜8000 yr BP with a global climatic event at Early-Mid Holocene transition.

Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity).

PubMed

Nierenberg, Jovia L; Li, Changwei; He, Jiang; Gu, Dongfeng; Chen, Jichun; Lu, Xiangfeng; Li, Jianxin; Wu, Xigui; Gu, C Charles; Hixson, James E; Rao, Dabeeru C; Kelly, Tanika N

2017-12-01

We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome-wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9× at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS ( P =2.7×10 -8 , 9.8×10 -8 , and 6.4×10 -6 , respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention ( P =1.4×10 -3 , 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions ( P =0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension. © 2017 American Heart Association, Inc.

Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy

PubMed Central

Gong, Zimu; Medeiros, L. Jeffrey; Cortes, Jorge E.; Chen, Zi; Zheng, Lan; Li, Yan; Bai, Shi; Lin, Pei; Miranda, Roberto N.; Jorgensen, Jeffrey L.; McDonnell, Timothy J.; Wang, Wei; Kantarjian, Hagop M.

2017-01-01

The high fatality of patients with blast phase (BP) chronic myeloid leukemia (CML) necessitates identification of high-risk (HR) patients to prevent onset of BP. Here, we investigated the risk of BP based on additional chromosomal abnormality (ACA) profiles in a cohort of 2326 CML patients treated with tyrosine kinase inhibitors (TKIs). We examined the time intervals from initial diagnosis to ACA emergence (interval 1), from ACA emergence to onset of BP (interval 2), and survival after onset of BP (interval 3). Based on BP risk associated with each ACA, patients were stratified into intermediate-1, intermediate-2, and HR groups, with a median duration of interval 2 of unreached, 19.2 months, and 1.9 months, respectively. There was no difference in durations of intervals 1 or 3 among 3 groups. Including patients without ACAs who formed the standard-risk group, the overall 5-year cumulative probability of BP was 9.8%, 28.0%, 41.7%, and 67.4% for these 4 groups, respectively. The pre-BP disease course in those who developed BP was similar regardless of cytogenetic alterations, and 84.4% of BP patients developed BP within the first 5 years of diagnosis. In summary, interval 2 is the predominant determinant of BP risk and patient outcome. By prolonging the duration of interval 2, TKI therapy mitigates BP risk associated with low-risk ACAs or no ACAs but does not alter the natural course of CML with HR ACAs. Thus, we have identified a group of patients who have HR of BP and may benefit from timely alternative treatment to prevent onset of BP. PMID:29296906

3-Bromopyruvate: a novel antifungal agent against the human pathogen Cryptococcus neoformans.

PubMed

Dyląg, Mariusz; Lis, Paweł; Niedźwiecka, Katarzyna; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

2013-05-03

We have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. The human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C. neoformans correlated with high intracellular accumulation of 3-BP and also with low levels of intracellular ATP and glutathione. Weak cytotoxicity towards mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug Resistance) network in the yeast Saccharomyces cerevisiae, are other properties of 3-BP that makes it a novel promising anticryptococcal drug. Copyright © 2013 Elsevier Inc. All rights reserved.

Blood pressure, magnesium and other mineral balance in two rat models of salt-sensitive, induced hypertension: effects of a non-peptide angiotensin II receptor type 1 antagonist.

PubMed

Rondón, Lusliany Josefina; Marcano, Eunice; Rodríguez, Fátima; del Castillo, Jesús Rafael

2014-01-01

The renin-angiotensin system is critically involved in regulating arterial blood pressure (BP). Inappropriate angiotensin type-1 receptor activation by angiotensin-II (Ang-II) is related to increased arterial BP. Mg has a role in BP; it can affect cardiac electrical activity, myocardial contractility, and vascular tone. To evaluate the relationship between high BP induced by a high sodium (Na) diet and Mg, and other mineral balances, two experimental rat models of salt-sensitive, induced-hypertension were used: Ang-II infused and Dahl salt-sensitive (SS) rats. We found that: 1) Ang-II infusion progressively increased BP, which was accompanied by hypomagnesuria and signs of secondary hyperaldosteronism; 2) an additive effect between Ang-II and a high Na load may have an effect on strontium (Sr), zinc (Zn) and copper (Cu) balances; 3) Dahl SS rats fed a high Na diet had a slow pressor response, accompanied by altered Mg, Na, potassium (K), and phosphate (P) balances; and 4) losartan prevented BP increases induced by Ang II-NaCl, but did not modify mineral balances. In Dahl SS rats, losartan attenuated high BP and ameliorated magnesemia, Na and K balances. Mg metabolism maybe considered a possible defect in this strain of rat that may contribute to hypertension.

Estimated GFR and the Effect of Intensive Blood Pressure Lowering After Acute Intracerebral Hemorrhage.

PubMed

Zheng, Danni; Sato, Shoichiro; Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Cao, Yongjun; Chalmers, John; Anderson, Craig S

2016-07-01

The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP<140mmHg) or contemporaneous guideline-based (target SBP<180mmHg) BP management. 2,823 patients from 144 clinical hospitals in 21 countries. Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60mL/min/1.73m(2), respectively). The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P=0.5 for homogeneity). Generalizability issues arising from a clinical trial population. Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Prevalence of Hypertension in Children with Early-Stage ADPKD.

PubMed

Massella, Laura; Mekahli, Djalila; Paripović, Dušan; Prikhodina, Larisa; Godefroid, Nathalie; Niemirska, Anna; Ağbaş, Ayşe; Kalicka, Karolina; Jankauskiene, Augustina; Mizerska-Wasiak, Malgorzata; Afonso, Alberto Caldas; Salomon, Rémi; Deschênes, Georges; Ariceta, Gema; Özçakar, Z Birsin; Teixeira, Ana; Duzova, Ali; Harambat, Jérôme; Seeman, Tomáš; Hrčková, Gabriela; Lungu, Adrian Catalin; Papizh, Svetlana; Peco-Antic, Amira; De Rechter, Stéphanie; Giordano, Ugo; Kirchner, Marietta; Lutz, Teresa; Schaefer, Franz; Devuyst, Olivier; Wühl, Elke; Emma, Francesco

2018-04-19

Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited. Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected. Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P =0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P =0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P =0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P =0.10). These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages. Copyright © 2018 by the American Society of Nephrology.

Norrie disease pedigree carrying the novel mutation C65Y, predicted to disrupt the cystine knot growth factor motif, analyzed by RasI restriction digestion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strasberg, P.M.; Liede, H.A.; Stein, T.

1994-09-01

Norrie disease (MIM 310600; ND) is an X-linked (Xp11.2-11.3) neurodevelopmental disorder characterized by congenital blindness, retinal dysplasia with pseudoglioma formation, and often associated with progressive mental retardation and deafness. The ND gene, comprised of 3 exons, codes for an evolutionarily conserved protein of 133 amino acids. We have analyzed 8 pedigrees segregating Norrie disease. Although microdeletions have been detected in several typical ND patients, Southern blot analysis with probes L1.28, MAO-A, MAO-B, TIMP-3.9X, pTak8, and M27{beta} failed to detect such deletions in these 8 ND pedigrees. With the cloning of the ND gene, PCR analysis of all 3 exons likewisemore » did not reveal any insertions or deletions. SSCP analysis ({sup 35}S-dNTP PCR) on PCR products of exon 3 showed a band shift for 1 patient. Repeat `cold` SSCP on minigels (3 inches x 4 inches) followed by liver staining was confirmatory. Direct sequencing revealed a G{r_arrow}A transition at nucleotide 610 corresponding to amino acid 65, changing Cys to Tyr. The mutation created an RsaI site, such that the uncut, normal, and mutant PCR products (using the same PCR primers) were 297 bp, 243 and 54 bp, and 177, 72 and 54 bp respectively. Affected males in the relevant pedigree had restricted PCR products of 177, 72 and 54 bp, carrier mothers 243, 177, 72, and 54 bp, and normals, including 30 unrelated individuals, 243 and 54 bp. Recent evidence indicates that the ND gene has a C-terminal domain homologous to that of TGF{beta}, thus identifying it as putative peptide growth factor, providing a monogenic disease model for the family of cystine knot growth factors. This is the first report of a mutation in Cys 2, critical for crosslinking to Cys 5 forming a disulphide bridge which holds the cystine knot growth factor tertiary structure together.« less

Race and sex differences in cardiovascular α-adrenergic and β-adrenergic receptor responsiveness in men and women with high blood pressure

PubMed Central

Sherwood, Andrew; Hill, LaBarron K.; Blumenthal, James A.; Johnson, Kristy S.; Hinderliter, Alan L.

2018-01-01

Objective Hypertension is associated with unfavorable changes in adrenergic receptor responsiveness, but the relationship of race and sex to adrenergic receptor responsiveness in the development of cardiovascular disease is unclear. This study examined α-adrenergic and β-adrenergic receptor responsiveness in African-American and white men and women with untreated high blood pressure (BP) (HBP) and with normal BP. Methods and results The study sample comprised 161 African-American and white men and women in the age range 25–45 years. Isoproterenol, a nonselective β-adrenergic receptor agonist, was administered intravenously to determine the bolus dose required to increase heart rate by 25 bpm, an index of β-adrenergic receptor responsiveness. Similarly, phenylephrine, an α1-adrenergic receptor agonist, was administered to determine the bolus dose required to increase BP by 25 mmHg, an index of vascular α1-adrenergic receptor responsiveness. HBP (P <0.01), male sex (P =0.04), and higher BMI (P <0.01) were all associated with reduced β-adrenergic receptor responsiveness, with a similar trend observed for African-American race (P =0.07). Conversely, α1-adrenergic receptor responsiveness was increased in association with HBP (P <0.01), female sex (P <0.01), and African-American race (P <0.01). Conclusion In the early stages of hypertension, cardiovascular β-adrenergic receptors demonstrate blunted responsiveness, whereas conversely α1-adrenergic receptors exhibit increased responsiveness. This pattern of receptor changes is especially evident in men and African-Americans, is exacerbated by obesity, and may contribute to the development of cardiovascular disease. PMID:28306633

The relationship of body mass index and blood pressure in Iranian children <7 years old.

PubMed

Ataei, Neamatollah; Hosseini, Mostafa; Iranmanesh, Mohammad

2009-10-01

The objective of this study was to evaluate the association between the body mass index (BMI), in healthy young children with their blood pressure (BP). The study included 3186 healthy children aged 1-6 years who were studied between March 2004 and March 2007 in different kindergartens and health centers in Tehran. Each child was classified on the basis of age- and sex-specific BMI percentile as normal weight (BMI <85th percentile), at risk for overweight (BMI >85th and <95th percentile), or overweight (BMI > or =95th percentile). Systolic BP (SBP) and diastolic BP (DBP) was compared among age-sex-BMI groups. Among children aged below 7 years in kindergartens and health centers in Tehran, 7.2% were at risk of overweight and 12.2% were overweight. These proportions were similar for boys and girls and were as follows: 6.9%, 13.9% and 7.5%, 10.5%, respectively. Analysis of variance showed that mean SBP significantly increased according to age (p < 0.0001) and BMI group (p = 0.001). Analysis of variance also showed that mean DBP significantly increased as age increased (p < 0.0001), but no significant difference was found between boys and girls in different age and BMI groups (p = 0.37). Our survey identified a high prevalence of overweight that was associated with elevated SBP among preschool-aged children in Iran. The effect of higher BMI on mean SBP is present in childhood and can be used as a predictor of high SBP even in children as young as 1-6 years.

Is tinnitus an early voice of masked hypertension? High masked hypertension rate in patients with tinnitus.

PubMed

Gun, Taylan; Özkan, Selçuk; Yavuz, Bunyamin

2018-04-23

Tinnitus is hearing a sound without any external acoustic stimulus. There are some clues of hypertension can cause tinnitus in different ways. The aim of the study was to evaluate the relationship between tinnitus and masked hypertension including echocardiographic parameters and severity of tinnitus. This study included 88 patients with tinnitus of at least 3 months duration and 85 age and gender-matched control subjects. Tinnitus severity index was used to classify the patients with tinnitus. After a complete medical history, all subjects underwent routine laboratory examination, office blood pressure measurement, hearing tests and ambulatory blood pressure monitoring. Masked hypertension is defined as normal office blood pressure measurement and high ambulatory blood pressure level. Baseline characteristics in patients and controls were similar. Prevalence of masked hypertension was significantly higher in patients with tinnitus than controls (18.2% vs 3.5%, p = 0.002). Office diastolic BP (76 ± 8.1 vs. 72.74 ± 8.68, p = 0.01), ambulatory 24-H diastolic BP (70.2 ± 9.6 vs. 66.9 ± 6.1, p = 0.07) and ambulatory daytime diastolic BP (73.7 ± 9.5 vs. 71.1 ± 6.2, p = 0.03) was significantly higher in patients with tinnitus than control group. Tinnitus severity index in patients without masked hypertension was 0 and tinnitus severity index in patients with masked hypertension were 2 (1-5). This study demonstrated that masked hypertension must be kept in mind if there is a complaint of tinnitus without any other obvious reason.

BP180 Is Critical in the Autoimmunity of Bullous Pemphigoid

PubMed Central

Liu, Yale; Li, Liang; Xia, Yumin

2017-01-01

Bullous pemphigoid (BP) is by far the most common autoimmune blistering dermatosis that mainly occurs in the elderly. The BP180 is a transmembrane glycoprotein, which is highly immunodominant in BP. The structure and location of BP180 indicate that it is a significant autoantigen and plays a key role in blister formation. Autoantibodies from BP patients react with BP180, which leads to its degradation and this has been regarded as the central event in BP pathogenesis. The consequent blister formation involves the activation of complement-dependent or -independent signals, as well as inflammatory pathways induced by BP180/anti-BP180 autoantibody interaction. As a multi-epitope molecule, BP180 can cause dermal–epidermal separation via combining each epitope with specific immunoglobulin, which also facilitates blister formation. In addition, some inflammatory factors can directly deplete BP180, thereby leading to fragility of the dermal–epidermal junction and blister formation. This review summarizes recent investigations on the role of BP180 in BP pathogenesis to determine the potential targets for the treatment of patients with BP. PMID:29276517

Association between somatotypes and blood pressure in an adult Chuvasha population.

PubMed

Kalichman, Leonid; Livshits, Gregory; Kobyliansky, Eugene

2004-01-01

The relationship between blood pressure (BP) and anthropometrical characteristics has been indeed examined extensively, but only a few studies have investigated any connection of somatotypes to BP. to evaluate the association between BP and various anthropometrical characteristics, including components of somatotypes (using the methods of Heath and Carter and of Deriabin). The study sample comprised 783 males aged 18-89 years and 720 females aged 18-90 years, all residents of the Chuvasha, Russian Federation. We used multiple regression, Pearson's and canonical correlation analyses. Significant correlations (r = 0.19-0.28, p < 0.05) were obtained between BP and anthropometric characteristics associated with body compositions and somatotypes. The most impressive were the canonical correlations between BP and somatotype components derived according to Heath and Carter (0.275), and according to Deriabin's (0.333) method. Different body types were highly significantly (P < 0.001) associated with systolic and diastolic BP. Individuals of robust physique (with high endomorphy and mesomorphy) showed high mean values of systolic and diastolic BP, whereas the smallest persons had the lowest BP values. These findings suggest the existence of common physiological paths in the development of body physique and blood pressure regulation and may possibly be indicative of the involvement of pleiotropic genetic and/or epigenetic mechanisms in this regulation.

SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway

PubMed Central

Tao, Yiming; Hu, Kuan; Tan, Fengbo; Zhang, Sai; Zhou, Ming; Luo, Jia; Wang, Zhiming

2016-01-01

SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target WAVE2 is required for cell motility. The present study shows SH3BP1 expression patterns in human HCC tissues and cell lines were examined. The regulation of SH3BP1 on HCC cell migration and invasion related to Rac1-WAVE2 signaling was characterized using in vitro and in vivo models. SH3BP1 overexpressed in HCC tissues and highly metastatic HCC cells was significantly associated vascular invasion (VI). SH3BP1 promoted VEGF secretion via Rac1-WAVE2 signaling, so as to exert an augmentation on cell invasion and microvessel formation. In three study cohorts with a total of 516 HCC patients, high SH3BP1 expression combined with high microvessel density (MVD) was confirmed as a powerful independent predictor of HCC prognosis in both training cohorts and validation cohort. Being an important angiogenic factor of HCC through Rac1-WAVE2 signaling, SH3BP1 promotes tumor invasion and microvessel formation contributing to HCC metastasis and recurrence. SH3BP1 is a novel WAVE2 regulator, a prognostic marker and a potential therapeutic target of HCC. PMID:26933917

SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway.

PubMed

Tao, Yiming; Hu, Kuan; Tan, Fengbo; Zhang, Sai; Zhou, Ming; Luo, Jia; Wang, Zhiming

2016-04-05

SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target WAVE2 is required for cell motility. The present study shows SH3BP1 expression patterns in human HCC tissues and cell lines were examined. The regulation of SH3BP1 on HCC cell migration and invasion related to Rac1-WAVE2 signaling was characterized using in vitro and in vivo models. SH3BP1 overexpressed in HCC tissues and highly metastatic HCC cells was significantly associated vascular invasion (VI). SH3BP1 promoted VEGF secretion via Rac1-WAVE2 signaling, so as to exert an augmentation on cell invasion and microvessel formation. In three study cohorts with a total of 516 HCC patients, high SH3BP1 expression combined with high microvessel density (MVD) was confirmed as a powerful independent predictor of HCC prognosis in both training cohorts and validation cohort. Being an important angiogenic factor of HCC through Rac1-WAVE2 signaling, SH3BP1 promotes tumor invasion and microvessel formation contributing to HCC metastasis and recurrence. SH3BP1 is a novel WAVE2 regulator, a prognostic marker and a potential therapeutic target of HCC.

Phase transition thermodynamics of bisphenols.

PubMed

Costa, José C S; Dávalos, Juan Z; Santos, Luís M N B F

2014-10-16

Herein we have studied, presented, and analyzed the phase equilibria thermodynamics of a bisphenols (BP-A, BP-E, BP-F, BP-AP, and BP-S) series. In particular, the heat capacities, melting temperatures, and vapor pressures at different temperatures as well as the standard enthalpies, entropies, and Gibbs energies of phase transition (fusion and sublimation) were experimentally determined. Also, we have presented the phase diagrams of each bisphenol derivative and investigated the key parameters related to the thermodynamic stability of the condensed phases. When all the bisphenol derivatives are compared at the same conditions, solids BP-AP and BP-S present lower volatilities (higher Gibbs energy of sublimation) and high melting temperatures due to the higher stability of their solid phases. Solids BP-A and BP-F present similar stabilities, whereas BP-E is more volatile. The introduction of -CH3 groups in BP-F (giving BP-E and BP-A) leads an entropic differentiation in the solid phase, whereas in the isotropic liquids the enthalpic and entropic differentiations are negligible.

Population heterogeneity in trajectories of midlife blood pressure

PubMed Central

Wills, Andrew K; Lawlor, Debbie A; Muniz-Terrera, Graciela; Matthews, Fiona; Cooper, Rachel; Ghosh, Arjun K; Kuh, Diana; Hardy, Rebecca

2012-01-01

Background We investigated whether there are subgroups with different underlying (latent) trajectories of midlife systolic blood pressure (BP), diastolic BP and pulse pressure in a UK cohort. Methods Data are from 1840 men and 1819 women with BP measured at age 36, 43 and 53years. We used unconditional growth mixture models to test for the presence of latent trajectory classes. Extracted classes were described in terms of a number of known lifetime risk factors, and linked to the risk of undiagnosed angina (Rose questionnaire) at age 53 years. Results In both sexes for systolic BP, diastolic BP and pulse pressure, there was a large “normative” class (>90% of the sample) characterized by gentle annual increases (eg an increase in male systolic BP of 0.9mmHg/year [95% confidence interval = 0.9 to1.0]), with a smaller class for whom the rate of increase was high (e.g. an increase in male systolic BP of 3.1mmHg/year [2.8 to3.4]). In women there was an additional class for whom BP was high at age 36 and remained high. Persons in the “normative” classes were, on average, heavier at birth and taller at age 7 years, had a lower midlife body mass index, and were less likely to be on antihypertensive medication compared with those in other classes. Among those with no diagnosed cardiovascular disease, those in the classes with more strongly increasing systolic BP and pulse pressure were at greatest risk of angina. Conclusion Our study suggests that in midlife the majority of the population have a gentle underlying increase in BP, but that there also exists an important subgroup in whom BP increases much more markedly. These classes may be useful for identifying those most at risk of cardiovascular disease. PMID:22249241

Elevated blood pressure in cytochrome P4501A1 knockout mice is associated with reduced vasodilation to omega − 3 polyunsaturated fatty acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agbor, Larry N.; Walsh, Mary T.; Boberg, Jason R.

In vitro cytochrome P4501A1 (CYP1A1) metabolizes omega − 3 polyunsaturated fatty acids (n − 3 PUFAs); eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily to 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP), respectively. These metabolites have been shown to mediate vasodilation via increases in nitric oxide (NO) and activation of potassium channels. We hypothesized that genetic deletion of CYP1A1 would reduce vasodilatory responses to n − 3 PUFAs, but not the metabolites, and increase blood pressure (BP) due to decreases in NO. We assessed BP by radiotelemetry in CYP1A1 wildtype (WT) and knockout (KO) mice ± NO synthase (NOS) inhibitor.more » We also assessed vasodilation to acetylcholine (ACh), EPA, DHA, 17,18-EEQ and 19,20-EDP in aorta and mesenteric arterioles. Further, we assessed vasodilation to an NO donor and to DHA ± inhibitors of potassium channels. CYP1A1 KO mice were hypertensive, compared to WT, (mean BP in mm Hg, WT 103 ± 1, KO 116 ± 1, n = 5/genotype, p < 0.05), and exhibited a reduced heart rate (beats per minute, WT 575 ± 5; KO 530 ± 7; p < 0.05). However, BP responses to NOS inhibition and vasorelaxation responses to ACh and an NO donor were normal in CYP1A1 KO mice, suggesting that NO bioavailability was not reduced. In contrast, CYP1A1 KO mice exhibited significantly attenuated vasorelaxation responses to EPA and DHA in both the aorta and mesenteric arterioles, but normal vasorelaxation responses to the CYP1A1 metabolites, 17,18-EEQ and 19,20-EDP, and normal responses to potassium channel inhibition. Taken together these data suggest that CYP1A1 metabolizes n − 3 PUFAs to vasodilators in vivo and the loss of these vasodilators may lead to increases in BP. -- Highlights: ► CYP1A1 KO mice are hypertensive. ► CYP1A1 KO mice exhibit reduced vasodilation responses to n-3 PUFAs. ► Constitutive CYP1A1 expression regulates blood pressure and vascular function.« less

D-amino acid oxidase gene therapy sensitizes glioma cells to the antiglycolytic effect of 3-bromopyruvate.

PubMed

El Sayed, S M; Abou El-Magd, R M; Shishido, Y; Chung, S P; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

2012-01-01

Glioma tumors are refractory to conventional treatment. Glioblastoma multiforme is the most aggressive type of primary brain tumors in humans. In this study, we introduce oxidative stress-energy depletion (OSED) therapy as a new suggested treatment for glioblastoma. OSED utilizes D-amino acid oxidase (DAO), which is a promising therapeutic protein that induces oxidative stress and apoptosis through generating hydrogen peroxide (H2O2). OSED combines DAO with 3-bromopyruvate (3BP), a hexokinase II (HK II) inhibitor that interferes with Warburg effect, a metabolic alteration of most tumor cells that is characterized by enhanced aerobic glycolysis. Our data revealed that 3BP induced depletion of energetic capabilities of glioma cells. 3BP induced H2O2 production as a novel mechanism of its action. C6 glioma transfected with DAO and treated with D-serine together with 3BP-sensitized glioma cells to 3BP and decreased markedly proliferation, clonogenic power and viability in a three-dimensional tumor model with lesser effect on normal astrocytes. DAO gene therapy using atelocollagen as an in vivo transfection agent proved effective in a glioma tumor model in Sprague-Dawley (SD) rats, especially after combination with 3BP. OSED treatment was safe and tolerable in SD rats. OSED therapy may be a promising therapeutic modality for glioma.

Alteration of Cyclic-AMP Response Element Binding Protein in the Postmortem Brain of Subjects with Bipolar Disorder and Schizophrenia

PubMed Central

Ren, Xinguo; Rizavi, Hooriyah S.; Khan, Mansoor A.; Bhaumik, Runa; Dwivedi, Yogesh; Pandey, Ghanshyam N.

2013-01-01

Background Abnormalities of cyclic-AMP (cAMP) response element binding protein (CREB) function has been suggested in bipolar (BP) illness and schizophrenia (SZ), based on both indirect and direct evidence. To further elucidate the role of CREB in these disorders, we studied CREB expression and function in two brain areas implicated in these disorders, i.e., dorsolateral prefrontal cortex (DLPFC) and cingulate gyrus (CG). Methods We determined CREB protein expression using Western blot technique, CRE-DNA binding using gel shift assay, and mRNA expression using real-time RT-polymerase chain reaction (qPCR) in DLPFC and CG of the postmortem brain of BP (n = 19), SZ (n = 20), and normal control (NC, n = 20) subjects. Results We observed that CREB protein and mRNA expression and CRE-DNA binding activity were significantly decreased in the nuclear fraction of DLPFC and CG obtained from BP subjects compared with NC subjects. However, the protein and mRNA expression and CRE-DNA binding in SZ subjects was significantly decreased in CG, but not in DLPFC, compared with NC. Conclusion These studies thus indicate region-specific abnormalities of CREB expression and function in both BP and SZ. They suggest that abnormalities of CREB in CG may be associated with both BP and SZ, but its abnormality in DLPFC is specific to BP illness. PMID:24148789

Tribological behavior of polytetrafluoroethylene coating reinforced with black phosphorus nanoparticles

NASA Astrophysics Data System (ADS)

Peng, Shiguang; Guo, Yue; Xie, Guoxin; Luo, Jianbin

2018-05-01

This study compares the tribological performance of polytetrafluoroethylene (PTFE) thin film coating reinforced with black phosphorus (BP) or ball-milled graphite (BMG) nanoparticles, so as to elucidate their mechanism of action under reciprocating sliding test conditions. PTFE coatings with 0.5 wt.% BMG (BMG/PTFE) and 0.5 wt.% BP (BP/PTFE) were prepared on GCr15 bearing steel disk by using a spin coater. The friction and wear tests were carried out by using the ball-on-disk tribometer under a normal load of 1 N (contact pressure: 780 MPa), a frequency of 2 Hz, and 4.2 mm sliding displacement amplitude. The surface roughness, wear volume and surface morphology of the coatings were characterized by the three-dimensional white light, and Energy Dispersive X-ray Detector (EDX) analysis coupled with environmental scanning electron microscope (ESEM). It is found that BP/PTFE coating has better anti-wear and anti-friction performances than those of pure PTFE or BMG/PTFE coating. The coating with BP nanoparticles shows excellent tribological properties with the wear volume decreased from 3.52 × 106 μm3 to 1.64 × 106 μm3 and the coefficient of friction (COF) decreased from 0.117 to 0.046. More importantly, the BP layer probably expands and absorbs much energy due to its negative Poisson's ratio phenomenon under reciprocating sliding, and effectively reducing furrow and adhesive wear.

Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification

PubMed Central

Castro, Juan M.; García-Espinosa, Victoria; Curcio, Santiago; Arana, Maite; Chiesa, Pedro; Giachetto, Gustavo; Zócalo, Yanina; Bia, Daniel

2016-01-01

The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5–15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV. PMID:26881081

Total Antioxidant Status in Type 2 Diabetic Patients in Palestine.

PubMed

Kharroubi, Akram T; Darwish, Hisham M; Akkawi, Mutaz A; Ashareef, Abdelkareem A; Almasri, Zaher A; Bader, Khaldoun A; Khammash, Umaiyeh M

2015-01-01

The objective of this study was to compare the level of total antioxidant status (TAS) in type 2 diabetic and normal Palestinian subjects as well as the major factors influencing TAS levels. A sample of convenience composed of 212 type 2 diabetic and 208 normal subjects above the age of 40 were recruited. Only 9.8% of the subjects had normal body mass index (BMI) levels (<25), 29% were overweight (≥25 to <30), and 61.2% were obese (≥30). The mean levels of TAS were significantly higher in diabetic compared to control subjects (2.18 versus 1.84 mM Trolox, P = 0.001) and in hypertensive subjects compared to subjects with normal blood pressure (BP). Mean TAS levels were higher in obese compared to nonobese subjects (2.12 versus 1.85 mM Trolox, P = 0.001). Mean TAS levels were similarly higher in subjects with high fasting plasma glucose (FPG) compared to normal FPG (2.19 versus 1.90 mM Trolox) and high HbA1c (≥6.5%) compared to HbA1c < 6.5% (2.14 versus 1.91 mM Trolox). Multivariate analysis revealed that only diabetic status (P = 0.032) and the level of education (P = 0.036) were significantly associated with TAS. In conclusion diabetic patients had 18.5% increase in TAS levels compared to control subjects.

SU-F-T-48: Clinical Implementation of Brachytherapy Planning System for COMS Eye Plaques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferreira, C; Islam, M; Ahmad, S

Purpose: To commission the Brachytherapy Planning (BP) system (Varian, Palo Alto, CA) for the Collaborative Ocular Melanoma Study (COMS) eye plaques by evaluating dose differences against original plans from Nucletron Planning System (NPS). Methods: NPS system is the primary planning software for COMS-plaques at our facility; however, Brachytherapy Planning 11.0.47 (Varian Medical Systems) is used for secondary check and for seed placement configurations not originally commissioned. Dose comparisons of BP and NPS plans were performed for prescription of 8500 cGy at 5 mm depth and doses to normal structures: opposite retina, inner sclera, macula, optic disk and lens. Plans weremore » calculated for Iodine-125 seeds (OncoSeeds, Model 6711) using COMS-plaques of 10, 12, 14, 16, 18 and 20 mm diameters. An in-house program based on inverse-square was utilized to calculate point doses for comparison as well. Results: The highest dose difference between BP and NPS was 3.7% for the prescription point for all plaques. Doses for BP were higher than doses reported by NPS for all points. The largest percent differences for apex, opposite retina, inner sclera, macula, optic disk, and lens were 3.2%, 0.9%, 13.5%, 20.5%, 15.7% and 2.2%, respectively. The dose calculated by the in-house program was 1.3% higher at the prescription point, and were as high as 42.1%, for points away from the plaque (i.e. opposite retina) when compared to NPS. Conclusion: Doses to the tumor, lens, retina, and optic nerve are paramount for a successful treatment and vision preservation. Both systems are based on TG-43 calculations and assume water medium tissue homogeneity (ρe=1, water medium). Variations seen may result from the different task group versions and/or mathematical algorithms of the software. BP was commissioned to serve as a backup system and it also enables dose calculation in cases where seeds don’t follow conventional placement configuration.« less

Integrating a Smartphone-Based Self-Management System into Usual Care of Advanced CKD.

PubMed

Ong, Stephanie W; Jassal, Sarbjit V; Miller, Judith A; Porter, Eveline C; Cafazzo, Joseph A; Seto, Emily; Thorpe, Kevin E; Logan, Alexander G

2016-06-06

Patient self-management has been shown to improve health outcomes. We developed a smartphone-based system to boost self-care by patients with CKD and integrated its use into usual CKD care. We determined its acceptability and examined changes in several clinical parameters. We recruited patients with stage 4 or 5 CKD attending outpatient renal clinics who responded to a general information newsletter about this 6-month proof-of-principle study. The smartphone application targeted four behavioral elements: monitoring BP, medication management, symptom assessment, and tracking laboratory results. Prebuilt customizable algorithms provided real-time personalized patient feedback and alerts to providers when predefined treatment thresholds were crossed or critical changes occurred. Those who died or started RRT within the first 2 months were replaced. Only participants followed for 6 months after recruitment were included in assessing changes in clinical measures. In total, 47 patients (26 men; mean age =59 years old; 33% were ≥65 years old) were enrolled; 60% had never used a smartphone. User adherence was high (>80% performed ≥80% of recommended assessments) and sustained. The mean reductions in home BP readings between baseline and exit were statistically significant (systolic BP, -3.4 mmHg; 95% confidence interval, -5.0 to -1.8 and diastolic BP, -2.1 mmHg; 95% confidence interval, -2.9 to -1.2); 27% with normal clinic BP readings had newly identified masked hypertension. One hundred twenty-seven medication discrepancies were identified; 59% were medication errors that required an intervention to prevent harm. In exit interviews, patients indicated feeling more confident and in control of their condition; clinicians perceived patients to be better informed and more engaged. Integrating a smartphone-based self-management system into usual care of patients with advanced CKD proved feasible and acceptable, and it appeared to be clinically useful. The results provide a strong rationale for a randomized, controlled trial. Copyright © 2016 by the American Society of Nephrology.

Evaluation of the Use of Home Blood Pressure Measurement Using Mobile Phone-Assisted Technology: The iVitality Proof-of-Principle Study.

PubMed

Wijsman, Liselotte W; Richard, Edo; Cachucho, Ricardo; de Craen, Anton Jm; Jongstra, Susan; Mooijaart, Simon P

2016-06-13

Mobile phone-assisted technologies provide the opportunity to optimize the feasibility of long-term blood pressure (BP) monitoring at home, with the potential of large-scale data collection. In this proof-of-principle study, we evaluated the feasibility of home BP monitoring using mobile phone-assisted technology, by investigating (1) the association between study center and home BP measurements; (2) adherence to reminders on the mobile phone to perform home BP measurements; and (3) referrals, treatment consequences and BP reduction after a raised home BP was diagnosed. We used iVitality, a research platform that comprises a Website, a mobile phone-based app, and health sensors, to measure BP and several other health characteristics during a 6-month period. BP was measured twice at baseline at the study center. Home BP was measured on 4 days during the first week, and thereafter, at semimonthly or monthly intervals, for which participants received reminders on their mobile phone. In the monthly protocol, measurements were performed during 2 consecutive days. In the semimonthly protocol, BP was measured at 1 day. We included 151 participants (mean age [standard deviation] 57.3 [5.3] years). BP measured at the study center was systematically higher when compared with home BP measurements (mean difference systolic BP [standard error] 8.72 [1.08] and diastolic BP 5.81 [0.68] mm Hg, respectively). Correlation of study center and home measurements of BP was high (R=0.72 for systolic BP and 0.72 for diastolic BP, both P<.001). Adherence was better in participants measuring semimonthly (71.4%) compared with participants performing monthly measurements (64.3%, P=.008). During the study, 41 (27.2%) participants were referred to their general practitioner because of a high BP. Referred participants had a decrease in their BP during follow-up (mean difference final and initial [standard error] -5.29 [1.92] for systolic BP and -2.93 [1.08] for diastolic BP, both P<.05). Mobile phone-assisted technology is a reliable and promising method with good adherence to measure BP at home during a 6-month period. This provides a possibility for implementation in large-scale studies and can potentially contribute to BP reduction.

[The state of carotid arteries in young men with arterial hypertension].

PubMed

Safarova, A F; Iurtaeva, V R; Kotovskaia, Iu V; Kobalava, Zh D

2012-01-01

To study elastic properties of carotid arteries in young men with arterial hypertension (AH). We examined men aged 18-25 years (mean 21.1+/-0.14 years): 36 with normal blood pressure (BP), 123 with stable and 51 with unstable AH. Parameters studied comprised intima-media thickness (IMT) of carotid arteries, their M-mode measured maximal systolic and minimal diastolic diameters (Ds and Dd), stiffness of common carotid artery (CCA) wall determined on the basis of analysis of elasticity and distensibility coefficients (CC and DC), Peterson's and Young's modules of elasticity (Ep and E), and index of flow deformation (CS). Compared with young men with normal BP and unstable AH patients with stable AH had abnormal elastic properties of CCA and increased IMT. Stable AH in young men is associated with signs of remodeling of CCA walls and increase of their rigidity.

Antispasmodic, bronchodilator, vasorelaxant and cardiosuppressant effects of Buxus papillosa.

PubMed

Khan, Arif-Ullah; Ali, Shamsher; Gilani, Anwarul-Hassan; Ahmed, Manzoor; Choudhary, Muhammad Iqbal

2017-01-18

The present research was carried out to investigate pharmacological properties of Buxus papillosa C.K. Schneid. (Buxaceae). Buxus papillosa extracts of leaves (BpL), stem (BpS), roots (BpR) and BpL fractions: hexane (BpL-H), aqueous (BpL-A) also plant constituent, cyclomicrobuxine effect were studied in jejunum, atria, aorta and tracheal preparations from rabbit and guine-peg. Ca ++ antagonistic effect of BpS, BpR, BpL-H, BpL-A and cyclomicrobuxine were conclusively suggested, when spontaneous contractions of rabbit jejunal preparation was relaxed along with subsequent relaxation of potassium chloride (80 mM) induced contractions. Ca ++ antagonistic effect was further confirmed, when a prominent right shift like that of verapamil was observed in Ca ++ concentration-response curves, drawn in a tissue pretreated with BpL (0.3-1.0 mg/mL). In rabbit tracheal tissues BpL, BpS, BpR, BpL-H and BpL-A produced a prominent relaxation in contractions induced by potassium chloride (80 mM) and carbachol (1 μm). When tested in rabbit aortic rings, BpL, BpS, BpR, BpL-H and BpL-A showed concentration-dependent (0.1-3.0 mg/mL) vasorelaxant effect against phenylephrine (1 μM) and high K + -induced contractions. In isolated guinea-pig right atria, BpL, BpS, BpR, BpL-H and BpL-A suppressed atrial force of spontaneous contractions, with BpL-A being most potent. Our results reveal that Buxus papillosa possesses gut, airways and cardiovascular inhibitory actions.

Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter?

PubMed

Adair, Linda S; Martorell, Reynaldo; Stein, Aryeh D; Hallal, Pedro C; Sachdev, Harshpal S; Prabhakaran, Dorairaj; Wills, Andrew K; Norris, Shane A; Dahly, Darren L; Lee, Nanette R; Victora, Cesar G

2009-05-01

Promoting catch-up growth in malnourished children has health benefits, but recent evidence suggests that accelerated child weight gain increases adult chronic disease risk. We aimed to determine how birth weight (BW) and weight gain to midchildhood relate to blood pressure (BP) in young adults. We pooled data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa. We used conditional weight (CW), a residual of current weight regressed on prior weights, to represent deviations from expected weight gain from 0 to 12, 12 to 24, 24 to 48 mo, and 48 mo to adulthood. Adult BP and risk of prehypertension or hypertension (P/HTN) were modeled before and after adjustment for adult body mass index (BMI) and height. Interactions of CWs with small size-for-gestational age (SGA) at birth were tested. Higher CWs were associated with increased BP and odds of P/HTN, with coefficients proportional to the contribution of each CW to adult BMI. Adjusted for adult height and BMI, no child CW was associated with adult BP, but 1 SD of BW was related to a 0.5-mm Hg lower systolic BP and a 9% lower odds of P/HTN. BW and CW associations with systolic BP and P/HTN were not different between adults born SGA and those with normal BW, but higher CW at 48 mo was associated with higher diastolic BP in those born SGA. Greater weight gain at any age relates to elevated adult BP, but faster weight gains in infancy and young childhood do not pose a higher risk than do gains at other ages.

Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter?123

PubMed Central

Martorell, Reynaldo; Stein, Aryeh D; Hallal, Pedro C; Sachdev, Harshpal S; Prabhakaran, Dorairaj; Wills, Andrew K; Norris, Shane A; Dahly, Darren L; Lee, Nanette R; Victora, Cesar G

2009-01-01

Background: Promoting catch-up growth in malnourished children has health benefits, but recent evidence suggests that accelerated child weight gain increases adult chronic disease risk. Objective: We aimed to determine how birth weight (BW) and weight gain to midchildhood relate to blood pressure (BP) in young adults. Design: We pooled data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa. We used conditional weight (CW), a residual of current weight regressed on prior weights, to represent deviations from expected weight gain from 0 to 12, 12 to 24, 24 to 48 mo, and 48 mo to adulthood. Adult BP and risk of prehypertension or hypertension (P/HTN) were modeled before and after adjustment for adult body mass index (BMI) and height. Interactions of CWs with small size-for-gestational age (SGA) at birth were tested. Results: Higher CWs were associated with increased BP and odds of P/HTN, with coefficients proportional to the contribution of each CW to adult BMI. Adjusted for adult height and BMI, no child CW was associated with adult BP, but 1 SD of BW was related to a 0.5-mm Hg lower systolic BP and a 9% lower odds of P/HTN. BW and CW associations with systolic BP and P/HTN were not different between adults born SGA and those with normal BW, but higher CW at 48 mo was associated with higher diastolic BP in those born SGA. Conclusions: Greater weight gain at any age relates to elevated adult BP, but faster weight gains in infancy and young childhood do not pose a higher risk than do gains at other ages. PMID:19297457

NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

PubMed

Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

2016-08-01

Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

The algorithm study for using the back propagation neural network in CT image segmentation

NASA Astrophysics Data System (ADS)

Zhang, Peng; Liu, Jie; Chen, Chen; Li, Ying Qi

2017-01-01

Back propagation neural network(BP neural network) is a type of multi-layer feed forward network which spread positively, while the error spread backwardly. Since BP network has advantages in learning and storing the mapping between a large number of input and output layers without complex mathematical equations to describe the mapping relationship, it is most widely used. BP can iteratively compute the weight coefficients and thresholds of the network based on the training and back propagation of samples, which can minimize the error sum of squares of the network. Since the boundary of the computed tomography (CT) heart images is usually discontinuous, and it exist large changes in the volume and boundary of heart images, The conventional segmentation such as region growing and watershed algorithm can't achieve satisfactory results. Meanwhile, there are large differences between the diastolic and systolic images. The conventional methods can't accurately classify the two cases. In this paper, we introduced BP to handle the segmentation of heart images. We segmented a large amount of CT images artificially to obtain the samples, and the BP network was trained based on these samples. To acquire the appropriate BP network for the segmentation of heart images, we normalized the heart images, and extract the gray-level information of the heart. Then the boundary of the images was input into the network to compare the differences between the theoretical output and the actual output, and we reinput the errors into the BP network to modify the weight coefficients of layers. Through a large amount of training, the BP network tend to be stable, and the weight coefficients of layers can be determined, which means the relationship between the CT images and the boundary of heart.

Independent influences of excessive body weight and elevated blood pressure from childhood on left ventricular geometric remodeling in adulthood.

PubMed

Yan, Yinkun; Liu, Junting; Wang, Liang; Hou, Dongqing; Zhao, Xiaoyuan; Cheng, Hong; Mi, Jie

2017-09-15

Obesity and hypertension are two risk factors of left ventricular hypertrophy (LVH) in adults. We aimed to examine the impacts of body weight and blood pressure (BP) from childhood on adult LV geometric remodeling. The study cohort consisted of 1256 adults aged 27-42years who had 2-10 measurements of body mass index (BMI) and BP from childhood in 1987 to adulthood in 2010. We calculated the cumulative and incremental values of BMI and BP from childhood to adulthood. In adulthood, four LV geometric patterns were defined based on the values of left ventricular mass index (g/m 2.7 ) and relative wall thickness: normal geometry, concentric remodeling (CR), eccentric hypertrophy (EH) and concentric hypertrophy (CH). The prevalence of abnormal LV geometric patterns in adults was 26.4% for CR, 2.0% for EH and 2.5% for CH. For childhood values, systolic BP (Odds Ratio [OR]=1.26, 95% confidence interval [CI]=1.08-1.47) but not BMI (OR=1.06, 95%CI=0.93-1.18) was associated with adult CR, whereas BMI (OR=3.53, 95%CI=2.09-5.98) but not systolic BP (OR=1.04, 95%CI=0.65-1.66) was associated with adult EH. Both childhood BMI (OR=2.69, 95%CI=1.77-4.09) and systolic BP (OR=1.64, 95%CI=1.07-2.51) were independently associated with adult CH. For adulthood, cumulative and incremental values, BMI and systolic BP were independently associated with adult CR, EH and CH. Excessive body weight and elevated BP from childhood have independent influences on the development of adult LV geometric remodeling. Copyright © 2017 Elsevier B.V. All rights reserved.

Fragment Length of Circulating Tumor DNA

PubMed Central

Underhill, Hunter R.; Kitzman, Jacob O.; Hellwig, Sabine; Welker, Noah C.; Daza, Riza; Gligorich, Keith M.; Rostomily, Robert C.; Shendure, Jay

2016-01-01

Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134–144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132–145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA. PMID:27428049

Lower cognitive performance in 81-year-old men with greater nocturnal blood pressure dipping

PubMed Central

Axelsson, Johan; Reinprecht, Faina; Siennicki-Lantz, Arkadiusz; Elmståhl, Sölve

2008-01-01

Abnormal day-to-night blood pressure (BP) pattern have been found to be associated with cerebrovascular damage, yet studies of the elderly 80 years of age and above, for whom the risk pattern may be different due to ageing and age-associated diseases, are lacking. Ninety-seven 81-year-old men underwent ambulatory BP monitoring and were given six cognitive tests, 79 of the men completing the cognitive test battery. The odds ratio (OR) for performing one standard deviation below the mean on any cognitive test was calculated using a forward stepwise logistic regression model, confounding factors being controlled for. Groups defined in terms of day-to-night changes in BP were compared in this respect. Cognitive performance was lower (OR 3.6; P = 0.017) in the group usually described as dippers (10%–20% nocturnal drop in systolic BP [SBP]) as compared with nondippers (<10% drop). The tertile with the greatest SBP fall (10.6%–19.8%, a range considered as normal among middle aged) showed lowest cognitive performance (OR 4.7; P = 0.008) as compared with the middle tertile (5.1%–10.5% drop). The mean nocturnal fall in SBP was 7.4%, significantly greater in those with lower rather than higher cognitive performance. A nocturnal drop in SBP of ≥10% was associated with lower cognitive performance in these elderly men. The limits to normal dipping appear to be shifted in the direction of a lesser drop in the very elderly. PMID:20428409

A Case for Less Intensive Blood Pressure Control: It Matters to Achieve Target Blood Pressure Early and Sustained Below 140/90mmHg.

PubMed

Mariampillai, Julian E; Eskås, Per Anders; Heimark, Sondre; Kjeldsen, Sverre E; Narkiewicz, Krzysztof; Mancia, Giuseppe

Although high blood pressure (BP) is the leading risk factors for cardiovascular (CV) disease, the optimal BP treatment target in order to reduce CV risk is unclear in the aftermath of the SPRINT study. The aim of this review is to assess large, randomized, and controlled trials on BP targets, as well as review selected observational analyses from other large randomized BP trials in order to evaluate the benefit of intense vs. standard BP control. None of the studies, except SPRINT, favored intense BP treatment. Some of the studies suggested favorable effects of lowering treatment target in patients with diabetes or high risk of stroke. In SPRINT, a new BP measurement method was introduced, and the results must be interpreted in light of this. The results of the observational analyses indicated the best preventive effect when achieving early and sustained BP control rather than low targets. In conclusion, today's guidelines' recommended treatment target of <140/90mmHg seems sufficient for most patients. Early and sustained BP control should be the main focus. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive Hypertension

PubMed Central

Herrera, Victoria L. M.; Pasion, Khristine A.; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications. PMID:22912817

Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

PubMed

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein in GABAergic Interneurons in the Prefrontal Cortex

PubMed Central

Ketchesin, Kyle D.; Huang, Nicholas S.; Seasholtz, Audrey F.

2017-01-01

Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized. In the current study, we sought to determine the cell type-specific expression of CRH-BP in the PFC to begin to define the neural circuits in which this key regulator is acting. To characterize the expression of CRH-BP in excitatory and/or inhibitory neurons, we utilized dual in situ hybridization to examine the cellular colocalization of CRH-BP mRNA with vesicular glutamate transporter (VGLUT) or glutamic acid decarboxylase (GAD) mRNA in different subregions of the PFC. We show that CRH-BP is expressed predominantly in GABAergic interneurons of the PFC, as revealed by the high degree of colocalization (>85%) between CRH-BP and GAD. To further characterize the expression of CRH-BP in this heterogenous group of inhibitory neurons, we examined the colocalization of CRH-BP with various molecular markers of GABAergic interneurons, including parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP) and cholecystokinin (CCK). We demonstrate that CRH-BP is colocalized predominantly with SST in the PFC, with lower levels of colocalization in PV- and CCK-expressing neurons. Our results provide a more comprehensive characterization of the cell type-specific expression of CRH-BP and begin to define its potential role within circuits of the PFC. These results will serve as the basis for future in vivo studies to manipulate CRH-BP in a cell type-specific manner to better understand its role in stress-related psychiatric disorders, including anxiety, depression and addiction. PMID:29066956

Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid

PubMed Central

Lee, Eui Hyung; Kim, Yeon Hee; Kim, Sinyoung; Kim, Song-ee

2012-01-01

Background Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease associated with autoantibodies against BP180 and BP230. Enzyme-linked immunosorbent assay (ELISA) is a sensitive tool for the detection of immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies. Objective The aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP. Methods We evaluated serum IgG levels of anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through retrospective review of the medical records, the clinical characteristics of BP including disease activity, duration, pruritus severity and peripheral blood eosinophil counts were assessed. Results The sensitivity of BP180 ELISA was 97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was 90.3%. BP180 ELISA scores showed strong associations with disease activity, pruritus severity, peripheral blood eosinophil counts, and disease duration, whereas BP230 ELISA scores did not. Conclusion BP180 and BP230 ELISAs are highly sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a sensitive tool for monitoring the disease activity of BP. PMID:22363155

Black Phosphorus-Zinc Oxide Nanomaterial Heterojunction for p-n Diode and Junction Field-Effect Transistor.

PubMed

Jeon, Pyo Jin; Lee, Young Tack; Lim, June Yeong; Kim, Jin Sung; Hwang, Do Kyung; Im, Seongil

2016-02-10

Black phosphorus (BP) nanosheet is two-dimensional (2D) semiconductor with distinct band gap and attracting recent attention from researches because it has some similarity to gapless 2D semiconductor graphene in the following two aspects: single element (P) for its composition and quite high mobilities depending on its fabrication conditions. Apart from several electronic applications reported with BP nanosheet, here we report for the first time BP nanosheet-ZnO nanowire 2D-1D heterojunction applications for p-n diodes and BP-gated junction field effect transistors (JFETs) with n-ZnO channel on glass. For these nanodevices, we take advantages of the mechanical flexibility of p-type conducting of BP and van der Waals junction interface between BP and ZnO. As a result, our BP-ZnO nanodimension p-n diode displays a high ON/OFF ratio of ∼10(4) in static rectification and shows kilohertz dynamic rectification as well while ZnO nanowire channel JFET operations are nicely demonstrated by BP gate switching in both electrostatics and kilohertz dynamics.

Identification and characterization of cryptic SHOX intragenic deletions in three Japanese patients with Léri-Weill dyschondrosteosis.

PubMed

Fukami, Maki; Dateki, Sumito; Kato, Fumiko; Hasegawa, Yukihiro; Mochizuki, Hiroshi; Horikawa, Reiko; Ogata, Tsutomu

2008-01-01

Although short-stature homeobox-containing gene (SHOX ) haploinsufficiency is responsible for Léri-Weill dyschondrosteosis (LWD), the molecular defect has not been identified in approximately 20% of Japanese LWD patients. Furthermore, although high prevalence of microdeletions affecting SHOX is primarily ascribed to the presence of repeat sequences such as Alu elements around SHOX, it remains to be determined whether microdeletions are actually mediated by repeat sequences. We performed multiple ligation probe amplification (MLPA) assay in six Japanese LWD patients with apparently normal SHOX, followed by fluorescent in situ hybridization (FISH) analysis and sequencing for polymerase chain reaction (PCR) products encompassing the deletion junctions in patients with abnormal MLPA patterns. Consequently, heterozygous intragenic deletions were identified in three cases, i.e., a 5,906-bp deletion involving exons 4-5 in case 1, a 5,594-bp deletion involving exons 4-6a in case 2, and a 50,199-bp deletion involving exons 4-6b in case 3. The deletion breakpoints of cases 1 and 2 were present in nonrepeat sequences, whereas those of case 3 resided within Alu elements. The results suggest that cryptic SHOX intragenic deletions account for a small fraction of LWD and that microdeletions affecting SHOX can be generated by repeat-sequence-mediated aberrant recombinations and by nonhomologous end joining.

Adults with initial metabolic syndrome have altered muscle deoxygenation during incremental exercise.

PubMed

Machado, Alessandro da Costa; Barbosa, Thales Coelho; Kluser Sales, Allan Robson; de Souza, Marcio Nogueira; da Nóbrega, Antonio Claudio Lucas; Silva, Bruno Moreira

2017-02-01

Reduced aerobic power is independently associated with metabolic syndrome (MetS) incidence and prevalence in adults. This study investigated whether muscle deoxygenation (proxy of microvascular O 2 extraction) during incremental exercise is altered in MetS and associated with reduced oxygen consumption ( V˙O 2peak ). Twelve men with initial MetS (no overt diseases and medication-naive; mean ± SD, age 38 ± 7 years) and 12 healthy controls (HCs) (34 ± 7 years) completed an incremental cycling test to exhaustion, in which pulmonary ventilation and gas exchange (metabolic analyzer), as well as vastus lateralis deoxygenation (near infrared spectroscopy), were measured. Subjects with MetS, in contrast to HCs, showed lower V˙O 2peak normalized to total lean mass, similar V˙O 2 response to exercise, and earlier break point (BP) in muscle deoxygenation. Consequently, deoxygenation slope from BP to peak exercise was greater. Furthermore, absolute V˙O 2peak was positively associated with BP in correlations adjusted for total lean mass. MetS, without overt diseases, altered kinetics of muscle deoxygenation during incremental exercise, particularly at high-intensity exercise. Therefore, the balance between utilization and delivery of O 2 within skeletal muscle is impaired early in MetS natural history, which may contribute to the reduction in aerobic power. © 2017 The Obesity Society.

Novel mutation in the 5' splice site of exon 4 of the TCOF1 gene in the patient with Treacher Collins syndrome.

PubMed

Marszalek, Bozena; Wisniewski, Slawomir A; Wojcicki, Piotr; Kobus, Kazimierz; Trzeciak, Wieslaw H

2003-12-01

Treacher Collins syndrome (TCS) is caused by mutations in the TCOF1 gene. This gene encodes a serine/alanine-rich protein called treacle. The structure of the entire TCOF1 gene was investigated in a patient with TCS. We detected a novel deletion (376delAAGGTGAGTGGGACTGCC) spanning 3 bp of exon 4 and 15 bp of the adjacent intronic sequence. This mutation causes premature termination of translation, resulting in a truncated protein devoid of nucleolar localization signal, and potential phosphorylation sites. Real-time PCR analysis showed different melting temperatures of the amplified fragment containing normal allele and that harboring the 18 bp deletion, thus providing a rapid screening assay for this and other deletions of the TCOF1 gene. Copyright 2003 Wiley-Liss, Inc.

Deceleration time of left ventricular outflow tract flow as a simple surrogate marker for central haemodynamics at rest and as well as during exercise.

PubMed

Cho, In-Jeong; Shim, Chi Young; Moon, Sun-Ha; Lee, Hyun-Jin; Hong, Geu-Ru; Chung, Namsik; Ha, Jong-Won

2017-05-01

The shape and duration of left ventricular outflow tract (LVOT) flow has not been applied to assess the central haemodynamics, although LVOT flow is confronted with afterload of arterial system during systole. The aim of this study was to evaluate whether the LVOT flow parameters are related with central systolic blood pressure (BP) and arterial compliance at rest and as well as during exercise. We studied 258 subjects (175 females, age 61 ± 11 years) with normal left ventricular (LV) systolic function who underwent supine bicycle stress echocardiography and arterial tonometry simultaneously at rest and at peak exercise. Deceleration time (DT) of LVOT flow and RR interval were measured and deceleration time corrected for heart rate (DTc) was calculated. Peripheral and central haemodynamic parameters including systolic and diastolic BP, and augmentation index at a heart rate of 75 (AIx@75) were assessed using radial artery tonometry. Carotid femoral pulse wave velocity (PWV) was measured. Deceleration time corrected for heart rate was independently associated with central systolic BP and AIx@75 at rest (P < 0.001 and 0.006). Similarly, it also showed significant independent correlations with central systolic BP and AIx@75 during peak exercise (P = 0.006 and P = 0.021). In addition, DTc which measured both at rest and at peak exercise demonstrated significant positive correlations with PWV, suggesting association of prolonged DTc with arterial stiffening (P = 0.023 and P = 0.005). Prolongation of LVOT flow DTc represents raised central systolic BP and increased arterial stiffness not only at rest but also during exercise. Therefore, central aortic pressures and arterial stiffness influence the DT of LVOT flow at rest as well as during exercise in individuals with normal LV systolic function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Regulation of COL1A1 expression in type I collagen producing tissues: identification of a 49 base pair region which is required for transgene expression in bone of transgenic mice

NASA Technical Reports Server (NTRS)

Bedalov, A.; Salvatori, R.; Dodig, M.; Kronenberg, M. S.; Kapural, B.; Bogdanovic, Z.; Kream, B. E.; Woody, C. O.; Clark, S. H.; Mack, K.;

The biogeophysical climatic impacts of anthropogenic land use change during the Holocene

NASA Astrophysics Data System (ADS)

Smith, M. Clare; Singarayer, Joy S.; Valdes, Paul J.; Kaplan, Jed O.; Branch, Nicholas P.

2016-04-01

The first agricultural societies were established around 10 ka BP and had spread across much of Europe and southern Asia by 5.5 ka BP with resultant anthropogenic deforestation for crop and pasture land. Various studies (e.g. Joos et al., 2004; Kaplan et al., 2011; Mitchell et al., 2013) have attempted to assess the biogeochemical implications for Holocene climate in terms of increased carbon dioxide and methane emissions. However, less work has been done to examine the biogeophysical impacts of this early land use change. In this study, global climate model simulations with Hadley Centre Coupled Model version 3 (HadCM3) were used to examine the biogeophysical effects of Holocene land cover change on climate, both globally and regionally, from the early Holocene (8 ka BP) to the early industrial era (1850 CE). Two experiments were performed with alternative descriptions of past vegetation: (i) one in which potential natural vegetation was simulated by Top-down Representation of Interactive Foliage and Flora Including Dynamics (TRIFFID) but without land use changes and (ii) one where the anthropogenic land use model Kaplan and Krumhardt 2010 (KK10; Kaplan et al., 2009, 2011) was used to set the HadCM3 crop regions. Snapshot simulations were run at 1000-year intervals to examine when the first signature of anthropogenic climate change can be detected both regionally, in the areas of land use change, and globally. Results from our model simulations indicate that in regions of early land disturbance such as Europe and south-east Asia detectable temperature changes, outside the normal range of variability, are encountered in the model as early as 7 ka BP in the June-July-August (JJA) season and throughout the entire annual cycle by 2-3 ka BP. Areas outside the regions of land disturbance are also affected, with virtually the whole globe experiencing significant temperature changes (predominantly cooling) by the early industrial period. The global annual mean temperature anomalies found in our single model simulations were -0.22 at 1850 CE, -0.11 at 2 ka BP, and -0.03 °C at 7 ka BP. Regionally, the largest temperature changes were in Europe with anomalies of -0.83 at 1850 CE, -0.58 at 2 ka BP, and -0.24 °C at 7 ka BP. Large-scale precipitation features such as the Indian monsoon, the Intertropical Convergence Zone (ITCZ), and the North Atlantic storm track are also impacted by local land use and remote teleconnections. We investigated how advection by surface winds, mean sea level pressure (MSLP) anomalies, and tropospheric stationary wave train disturbances in the mid- to high latitudes led to remote teleconnections.

Renovascular hypertension in spontaneous hypertensive rats: an experimental model of renal artery stenosis superimposed on essential hypertension.

PubMed

Rosenthal, T; Bass, A; Grossman, E; Shani, M; Griffel, B; Adar, R

1987-09-01

Renovascular hypertension superimposed on essential hypertension, a condition encountered in the elderly, was studied. An experimental animal model consisting of a two-kidney one-clip Goldblatt preparation in the spontaneous hypertensive (SHR) rat, that would simulate this condition, was designed. A 0.25 mm silver clip was placed on the left renal artery of SHR male rats. The same procedure performed on WKY rats served as control. All experiments were performed on low, normal, and rich sodium diet. Systolic blood pressure (BP) was measured by tail-cuff method. Plasma renin concentration (PRC) was determined before and after clipping of the renal artery. Results were as follows: Mean systolic BP increased significantly in clipped rats fed with normal and rich sodium diets. SHR showed an increase from 144 +/- 3 (mean + s.e.m.) to 168 +/- 3 mmHg, and WKY rats showed an increase from 120 +/- 2 to 139 +/- 5 mmHg. There was a two- to threefold rise in PRC. A low-salt diet given prior to clipping prevented the appearance of renovascular hypertension despite a significant rise in PRC. We concluded that renal artery narrowing plays a significant role in the rise of BP in the basically essential type of hypertension.

Left ventricular geometry in children and adolescents with primary hypertension

PubMed Central

Richey, Phyllis A.; DiSessa, Thomas G.; Somes, Grant W.; Alpert, Bruce S.; Jones, Deborah P.

2009-01-01

Objective Children with hypertension (HTN) are at increased risk for left ventricular hypertrophy (LVH). Increased LV mass by the process of remodeling in response to volume or pressure loading may be eccentric (increased LV diameter) or concentric (increased wall thickness). Our objective was to classify LV geometry among children with primary HTN and examine differences in ambulatory blood pressure (ABP). Study design Subjects aged 7-18 years with suspected HTN were enrolled in this cross-sectional study. ABP and LVM index (LVMI) and were measured within the same 24 hour period. LV geometry was classified as normal, concentric remodeling, concentric LVH or eccentric LVH. Results Children with LVH had significantly higher ambulatory systolic and diastolic BP levels and BMI z-score. Sixty-eight children had HTN based upon ABPM. Thirty-eight percent of the hypertensive subjects had LVH, with equal distribution in the concentric and eccentric groups. There were significant differences in the 24-hour diastolic BP (DBP) parameters when the eccentric LVH group was compared to the normal geometry and concentric LVH groups. Relative wall thickness was inversely associated with nighttime DBP parameters. These relationships persisted after controlling for BMI Z-score. Conclusions While the risk for LVH is associated with increased systolic BP and BMI Z-score, those with eccentric LVH had significantly higher DBP. PMID:19851297

Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation.

PubMed

Bai, S Y; Briggs, D I; Vickers, M H

2012-10-01

An adverse prenatal environment may induce long-term metabolic consequences, in particular hypertension and cardiovascular disease. A maternal low-protein (LP) diet is well known to result in increased blood pressure (BP) in offspring. Choline has been shown to have direct BP-reducing effects in humans and animals. It has been suggested that endogenous choline synthesis via phosphatidylcholine is constrained during maternal LP exposure. The present study investigates the effect of choline supplementation to mothers fed a LP diet during pregnancy on systolic BP (SBP) in offspring as measured by tail-cuff plethysmography. Wistar rats were assigned to one of three diets to be fed ad libitum throughout pregnancy: (1) control diet (CONT, 20% protein); (2) an LP diet (9% protein); and (3) LP supplemented with choline (LP + C). Dams were fed the CONT diet throughout lactation and offspring were fed the CONT diet from weaning for the remainder of the trial. At postnatal day 150, SBP and retroperitoneal fat mass was significantly increased in LP offspring compared with CONT animals and was normalized in LP + C offspring. Effects of LP + C reduction in SBP were similar in both males and females. Plasma choline and phosphatidylcholine concentrations were not different across treatment groups, but maternal choline supplementation resulted in a significant reduction in homocysteine concentrations in LP + C offspring compared with LP and CONT animals. The present trial shows for the first time that maternal supplementation with dietary choline during periods of LP exposure can normalize increased SBP and fat mass observed in offspring in later life.

Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for the management of blood pressure in CKD.

PubMed

Ruzicka, Marcel; Quinn, Robert R; McFarlane, Phil; Hemmelgarn, Brenda; Ramesh Prasad, G V; Feber, Janusz; Nesrallah, Gihad; MacKinnon, Martin; Tangri, Navdeep; McCormick, Brendan; Tobe, Sheldon; Blydt-Hansen, Tom D; Hiremath, Swapnil

2014-06-01

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) provides the structural and evidence base for the Canadian Society of Nephrology (CSN) commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 13 of the 21 KDIGO guideline statements. Specifically, we agreed that nonpharmacological interventions should play a significant role in the management of hypertension in patients with CKD. We also agreed that the approach to the management of hypertension in elderly patients with CKD should be individualized and take into account comorbid conditions to avoid adverse outcomes from excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is insufficient evidence to target a lower BP for nondiabetic CKD patients based on the presence and severity of albuminuria. The CSN Work Group concurs with the Canadian Hypertension Education Program (CHEP) recommendation of a target BP for all non-dialysis-dependent CKD patients without diabetes of ≤140 mm Hg systolic and ≤90 mm Hg diastolic. Similarly, it is our position that in diabetic patients with CKD and normal urinary albumin excretion, raising the threshold for treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs with the CHEP and the Canadian Diabetic Association recommendation for diabetic patients with CKD with or without albuminuria to continue to be treated to a BP target similar to that of the overall diabetes population, aiming for BP levels < 130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the absence of evidence for a lower BP target, the CSN Work Group concurs with the CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a kidney transplant. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Night/day ratios of ambulatory blood pressure among healthy adolescents: roles of race, socioeconomic status, and psychosocial factors.

PubMed

Burford, Tanisha I; Low, Carissa A; Matthews, Karen A

2013-10-01

Elevated nighttime blood pressure (BP) predicts hypertension and its complications in adulthood. This study aimed to assess the independent effects of race and family income on night/day BP among adolescents and to examine whether negative emotions, low positive resources, and unpleasant interactions during the day are also related. Healthy African American and Caucasian high school students (N = 239) wore an ambulatory BP monitor for 48 h, recorded quality of ongoing interpersonal interactions, and completed questionnaires. African Americans and those with lower family income had higher night/day BP ratios. African Americans reporting greater negative emotions, lower positive resources, and more unpleasant interactions had higher night/day BP ratios. Racial differences in night BP emerge by adolescence, independent of family income. African Americans, especially those high in negative emotions and low in positive resources, may be at higher relative risk for hypertension later in life in part due to elevated night BP.

Triangular Black Phosphorus Atomic Layers by Liquid Exfoliation.

PubMed

Seo, Soonjoo; Lee, Hyun Uk; Lee, Soon Chang; Kim, Yooseok; Kim, Hyeran; Bang, Junhyeok; Won, Jonghan; Kim, Youngjun; Park, Byoungnam; Lee, Jouhahn

2016-03-30

Few-layer black phosphorus (BP) is the most promising material among the two-dimensional materials due to its layered structure and the excellent semiconductor properties. Currently, thin BP atomic layers are obtained mostly by mechanical exfoliation of bulk BP, which limits applications in thin-film based electronics due to a scaling process. Here we report highly crystalline few-layer black phosphorus thin films produced by liquid exfoliation. We demonstrate that the liquid-exfoliated BP forms a triangular crystalline structure on SiO2/Si (001) and amorphous carbon. The highly crystalline BP layers are faceted with a preferred orientation of the (010) plane on the sharp edge, which is an energetically most favorable facet according to the density functional theory calculations. Our results can be useful in understanding the triangular BP structure for large-area applications in electronic devices using two-dimensional materials. The sensitivity and selectivity of liquid-exfoliated BP to gas vapor demonstrate great potential for practical applications as sensors.

Triangular Black Phosphorus Atomic Layers by Liquid Exfoliation

PubMed Central

Seo, Soonjoo; Lee, Hyun Uk; Lee, Soon Chang; Kim, Yooseok; Kim, Hyeran; Bang, Junhyeok; Won, Jonghan; Kim, Youngjun; Park, Byoungnam; Lee, Jouhahn

2016-01-01

Few-layer black phosphorus (BP) is the most promising material among the two-dimensional materials due to its layered structure and the excellent semiconductor properties. Currently, thin BP atomic layers are obtained mostly by mechanical exfoliation of bulk BP, which limits applications in thin-film based electronics due to a scaling process. Here we report highly crystalline few-layer black phosphorus thin films produced by liquid exfoliation. We demonstrate that the liquid-exfoliated BP forms a triangular crystalline structure on SiO2/Si (001) and amorphous carbon. The highly crystalline BP layers are faceted with a preferred orientation of the (010) plane on the sharp edge, which is an energetically most favorable facet according to the density functional theory calculations. Our results can be useful in understanding the triangular BP structure for large-area applications in electronic devices using two-dimensional materials. The sensitivity and selectivity of liquid-exfoliated BP to gas vapor demonstrate great potential for practical applications as sensors. PMID:27026070

Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice.

PubMed

Meyer, R A; Meyer, M H; Gray, R W; Bruns, M E

1987-02-01

X-linked hypophosphatemic (Hyp) mice are a model for human sex-linked vitamin D-resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2 vitamin D3, this hormone was continually infused via osmotic minipumps into 4-week-old normal and Hyp mice at 0, 17, 50 or 150 ng/kg/day. After 3 days, 45Ca and inorganic 32P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45Ca and 32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D-dependent calcium-binding protein (calbindin-D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of 45Ca and 32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal and Hyp mice and was found to be lower in 4-week-old Hyp mice than in 4-week-old normal mice (113 +/- 10 pM (n = 18) vs. 67 +/- 10 (n = 20), normal vs. Hyp, p less than .01), but unchanged at 13 weeks of age (77 +/- 13 (n = 13) vs. 70 +/- 15 (n = 15), NS). This observed difference in plasma 1,25(OH)2D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal-to-Hyp differences in intestinal absorption of 45Ca and duodenal and renal CaBP. It also explained 72 +/- 18% of the observed difference in 32P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4-week-old Hyp mice causes intestinal malabsorption of calcium and phosphate.

In situ SUMOylation analysis reveals a modulatory role of RanBP2 in the nuclear rim and PML bodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saitoh, Noriko; Uchimura, Yasuhiro; The 21st Century Center of Excellence, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811

2006-05-01

SUMO modification plays a critical role in a number of cellular functions including nucleocytoplasmic transport, gene expression, cell cycle and formation of subnuclear structures such as promyelocytic leukemia (PML) bodies. In order to identify the sites where SUMOylation takes place in the cell, we developed an in situ SUMOylation assay using a semi-intact cell system and subsequently combined it with siRNA-based knockdown of nucleoporin RanBP2, also known as Nup358, which is one of the known SUMO E3 proteins. With the in situ SUMOylation assay, we found that both nuclear rim and PML bodies, besides mitotic apparatuses, are major targets formore » active SUMOylation. The ability to analyze possible SUMO conjugation sites would be a valuable tool to investigate where SUMO E3-like activities and/or SUMO substrates exist in the cell. Specific knockdown of RanBP2 completely abolished SUMOylation along the nuclear rim and dislocated RanGAP1 from the nuclear pore complexes. Interestingly, the loss of RanBP2 markedly reduced the number of PML bodies, in contrast to other, normal-appearing nuclear compartments including the nuclear lamina, nucleolus and chromatin, suggesting a novel link between RanBP2 and PML bodies. SUMOylation facilitated by RanBP2 at the nuclear rim may be a key step for the formation of a particular subnuclear organization. Our data imply that SUMO E3 proteins like RanBP2 facilitate spatio-temporal SUMOylation for certain nuclear structure and function.« less

Gender differences in the relationship between blood pressure and body mass index during adolescence.

PubMed

Kawada, Noritaka; Nakanishi, Kaori; Ohama, Tohru; Nishida, Makoto; Yamauchi-Takihara, Keiko; Moriyama, Toshiki

2015-01-01

In adults, gender and obesity play significant roles in the regulation of blood pressure (BP). This study investigated the effects of gender and body mass index (BMI) on BP during adolescence. A cross-sectional and longitudinal study involving 6838 students under twenty years old (median, eighteen years old; male, 4624; female, 2214) at Osaka University visited the Healthcare Center for their matriculation health examination from April to May in the years 2008, 2009, and 2010, and re-visited the Healthcare Center for their student health examination from May to June in the years 2011, 2012, and 2013. Height, body weight, and BP were measured in students both on and 3 years after admission to Osaka University. On admission, the slope of the regression line for BMI and systolic BP (SBP) in non-underweight students was significantly different between genders. SBP and diastolic BP (DBP) increased in both genders during the observation period. Among male students who had a normal BMI on admission, those who had an increase in BMI of over 4% during the observation period showed a greater increase in SBP than those who had a change in BMI of -4% to 4%. On the other hand, female students showed no change in BP with the increase in BMI. The magnitude of BP elevation with increased BMI was associated with gender during adolescence. This may be a cause of the higher prevalence of hypertension in adult males. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Hemodynamics during Dialysis and Cognitive Performance

PubMed Central

Wolfgram, Dawn; Sunio, Lily; Vogt, Elisabeth; Smith, Heather M; Visotcky, Alexis; Laud, Purushottam; Whittle, Jeff

2015-01-01

Background/Aims Persons receiving hemodialysis (HD) are at increased risk of cognitive impairment (CI). Since blood pressure (BP) fluctuations during HD may affect cerebral perfusion – and subsequently cognitive function – we examined the relationship between dialytic BP fluctuation and cognitive outcomes. Methods We included HD patients without diagnosed dementia who were 50 years or older. Using established methods, we classified participants’ in CI categories (none to mild and moderate to severe) based on results of a neurocognitive battery. We collected demographic and laboratory data from dialysis unit records, as well as all BP measurements from 12 dialysis sessions. We tested the association between CI and BP fluctuation, adjusting for demographic and laboratory variables. Results Our study enrolled 39 patients; 25 had moderate to severe CI. The normal to mild CI group and the moderate to severe patients had similar degrees of BP fluctuation (average minimum SBP: 107.6 ± 18.7 vs 110.2 ± 18.6 mmHg, maximum drop in SBP: 32.6 ± 10.2 vs 35.4 ± 15.0 mmHg; proportion of sessions with SBP < 90 mmHg: 0.2 ± 0.3 vs 0.2 ± 0.3; average change in SBP, pre to post HD: 10.2 ± 12.4 vs 11.8 ± 16.4 mmHg, all p > 0.55). There was no association between BP variables and performance on individual cognitive tests. Multivariable analysis showed that older age and non-Caucasian race were associated with a reduction in cognitive scores. Conclusions There was no cross-sectional association between dialytic BP changes and cognitive performance. PMID:25103846

INtensive versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional DeclINe In The ElderlY (INFINITY)

PubMed Central

White, William B.; Marfatia, Ravi; Schmidt, Julia; Wakefield, Dorothy B.; Kaplan, Richard F.; Bohannon, Richard W.; Hall, Charles B.; Guttmann, Charles R.; Moscufo, Nicola; Fellows, Douglas; Wolfson, Leslie

2012-01-01

Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white-matter hyperintensities(WMH) on magnetic resonance imaging (MRI) canoccur in older hypertensive patients in as little as 2 years. We have designed a trial evaluating two levels of ambulatory BP control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease (>0.5% WMH fraction of intracranial volume) on functional outcomes. The study is a prospective randomized, open-label trial with blinded endpoints, inpatients ages 75 and older with elevated 24-h systolic BP (≥145 mmHg in the untreated state) who do not have unstable cardiovascular disease, heart failure or stroke. The primary and key secondary outcomes in the trial are: change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes indiffusion tensor imaging.Approximately 300 patients will be enrolled and 200 randomized to one of two levels of ambulatory BP control (intensive to achieve a goal 24-hour systolic BP of ≤ 130 mmHg or standard to achieve a goal 24-hour systolic BP of ≤ 145 mmHg) for a total of 36 months using similar antihypertensive regimens. The analytical approach provides 85% power to show a clinically meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups. The INFINITY trial is the first to guide antihypertensive therapy using ambulatory BP monitoring rather than clinic BP to reduce cerebrovascular disease. PMID:23453090

Maximizing PTH Anabolic Osteoporosis Therapy

DTIC Science & Technology

2015-09-01

SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c...normalization or endogenous controls and calculates fold 263 changes with P values. Gene expression data were normalized to five endogenous controls ( 18S ...adapters were ligated and the sample was size-fractionated (200-300 bp) on an agarose gel. After a final 294 PCR amplification step ( 18 cycles), the

A conscious rat model involving bradycardia and hypotension after oral administration: a toxicokinetical study of aconitine.

PubMed

Zhang, Panpan; Kong, Dezhi; Du, Qian; Zhao, Jing; Li, Qing; Zhang, Jianghua; Li, Tonghui; Ren, Leiming

2017-06-01

1. A model of aconitine-induced bradycardia and hypotension, which is similar to aconitine poisoning in humans, was constructed in conscious rats by oral administration. 2. Blood pressure (BP) and heart rate (HR) of Sprague-Dawley rats were measured using a volume pressure recording (VPR) system. The pharmacokinetics of toxic doses of aconitine and its metabolites were analyzed using UPLC-MS/MS. 3. The HR was significantly decreased by 29% at 2 h after oral administration of 200 μg/kg aconitine. When the dose was increased to 400 μg/kg, systolic BP and diastolic BP were significantly decreased by 11% and 12% at 2 h after the administration, except when bradycardia occurred at 2 h and 4 h. The drug concentration-time curve showed a double-peak phenomenon in rats administered a 400 μg/kg dose. The AUC 0-12 h value in the 400 μg/kg group significantly increased 0.8-fold compared to the 200 μg/kg group. Moreover, a high plasma concentration of 16-O-demethyaconitine was found in the rats that received two toxic doses. 4. In conclusion, bradycardia and hypotension are induced in conscious rats by a toxic dose of aconitine (400 μg/kg), and there was no significant difference in dose-normalized AUC 0-12 h values between oral administrations of 200 μg/kg and that of 400 μg/kg. However, the dose-normalized C max and AUC 0-12 h values in 200 μg/kg and 400 μg/kg groups were significantly smaller than those in 100 μg/kg group. The metabolites of aconitine, 16-O-demethyaconitine, and benzoylaconitine may also contribute to the hypotensive response.

mTOR signaling pathway in penile squamous cell carcinoma: pmTOR and peIF4E over expression correlate with aggressive tumor behavior.

PubMed

Ferrandiz-Pulido, Carla; Masferrer, Emili; Toll, Agustin; Hernandez-Losa, Javier; Mojal, Sergio; Pujol, Ramon M; Ramon y Cajal, Santiago; de Torres, Ines; Garcia-Patos, Vicente

2013-12-01

Penile squamous cell carcinoma is a rare neoplasm associated with a high risk of metastasis and morbidity. There are limited data on the role of the mTOR signaling pathway in penile squamous cell carcinoma carcinogenesis and tumor maintenance. We assessed a possible role for mTOR signaling pathway activation as a potential predictive biomarker of outcome and a therapeutic target for penile cancer. A cohort of 67 patients diagnosed with invasive penile squamous cell carcinoma from 1987 to 2010 who had known HPV status were selected for study. Tissue microarrays were constructed with 67 primary penile squamous cell carcinomas, matched normal tissues and 8 lymph node metastases. Immunohistochemical staining was performed for p53, pmTOR, pERK, p4E-BP1, eIF4E and peIF4E. Expression was evaluated using a semiquantitative H-score on a scale of 0 to 300. Expression of pmTOR, p4E-BP1, eIF4E and peIF4E was increased in penile tumors compared with matched adjacent normal tissues, indicating activation of the mTOR signaling pathway in penile tumorigenesis. Over expression of pmTOR, peIF4E and p53 was significantly associated with lymph node disease. peIF4E and p53 also correlated with a poor outcome, including recurrence, metastasis or disease specific death. In contrast, pERK and p4E-BP1 were associated with lower pT stages. pmTOR and intense p53 expression was associated with HPV negative tumors. Activation of mTOR signaling may contribute to penile squamous cell carcinoma progression and aggressive behavior. Targeting mTOR or its downstream signaling targets, such as peIF4E, may be a valid therapeutic strategy. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Mutations in the PCCA gene encoding the {alpha} subunit of propionyl-CoA carboxylase in patients with propionic acidemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campeau, E.; Leon-Del-Rio, A.; Gravel, R.A.

Propionic acidemia is a rare autosomal recessive disorder characterized by a deficiency of the mitochondrial biotin-dependent enzyme, propionyl-CoA carboxylase (PCC). PCC has the structure {alpha}{sub 4}{beta}{sub 4}, with the {alpha} subunit containing the biotin prosthetic group. This study is concerned with defining the spectrum of mutations occurring in the PCCA gene encoding the {alpha} subunit. Mutations were initially assigned to this gene through complementation experiments done after somatic fusion of patient fibroblasts. The analyses were performed on PCR-amplified reverse transcripts of fibroblast RNA. The mutations were identified by single strand conformational polymorphism analysis and direct sequencing of PCR products. Threemore » candidate disease-causing mutations and one DNA polymorphism were identified in the {alpha} subunit sequence in different patients: (1) a 3 bp deletion {triangle}CTG{sub 2058-2060}, which eliminates Cys687 near the biotin binding site (Lys669); (2) T{sub 611}{r_arrow}A which converts Met204 to Lys in a highly conserved region matching that of an ATP binding site; (3) An {approximately}50 bp deletion near the 3{prime} end of the cDNA which likely corresponds to the loss of an exon due to a splicing defect; and (4) a 3 bp insertion, +CAG{sub 2203}, located downstream of the stop codon, which is likely a DNA polymorphism. In order to determine the effect of the Cys687 deletion on the biotinylation of PCC, we expressed the mutation in a 67 amino acid C-terminal fragment of the PCC {alpha} subunit in E. coli in which biotinylation is directed by the bacterial biotin ligase. While the mutant peptide was expressed at about half-normal levels, the biotinylation of the peptide that was present was reduced to only {approximately}20% normal. We suggest, therefore, that the absence of PCC activity due to {triangle}Cys687 results at least in part from defective biotinylation of an unstable protein.« less

Physiological and psychological effects of forest therapy on middle-aged males with high-normal blood pressure.

PubMed

Ochiai, Hiroko; Ikei, Harumi; Song, Chorong; Kobayashi, Maiko; Takamatsu, Ako; Miura, Takashi; Kagawa, Takahide; Li, Qing; Kumeda, Shigeyoshi; Imai, Michiko; Miyazaki, Yoshifumi

2015-02-25

Time spent walking and relaxing in a forest environment ("forest bathing" or "forest therapy") has well demonstrated anti-stress effects in healthy adults, but benefits for ill or at-risk populations have not been reported. The present study assessed the physiological and psychological effects of forest therapy (relaxation and stress management activity in the forest) on middle-aged males with high-normal blood pressure. Blood pressure and several physiological and psychological indices of stress were measured the day before and approximately 2 h following forest therapy. Both pre- and post-treatment measures were conducted at the same time of day to avoid circadian influences. Systolic and diastolic blood pressure (BP), urinary adrenaline, and serum cortisol were all significantly lower than baseline following forest therapy (p<0.05). Subjects reported feeling significantly more "relaxed" and "natural" according to the Semantic Differential (SD) method. Profile of Mood State (POMS) negative mood subscale scores for "tension-anxiety," "confusion," and "anger-hostility," as well as the Total Mood Disturbance (TMD) score were significantly lower following forest therapy. These results highlight that forest is a promising treatment strategy to reduce blood pressure into the optimal range and possibly prevent progression to clinical hypertension in middle-aged males with high-normal blood pressure.

Black Phosphorus Flexible Thin Film Transistors at Gighertz Frequencies.

PubMed

Zhu, Weinan; Park, Saungeun; Yogeesh, Maruthi N; McNicholas, Kyle M; Bank, Seth R; Akinwande, Deji

2016-04-13

Black phosphorus (BP) has attracted rapidly growing attention for high speed and low power nanoelectronics owing to its compelling combination of tunable bandgap (0.3 to 2 eV) and high carrier mobility (up to ∼1000 cm(2)/V·s) at room temperature. In this work, we report the first radio frequency (RF) flexible top-gated (TG) BP thin-film transistors on highly bendable polyimide substrate for GHz nanoelectronic applications. Enhanced p-type charge transport with low-field mobility ∼233 cm(2)/V·s and current density of ∼100 μA/μm at VDS = -2 V were obtained from flexible BP transistor at a channel length L = 0.5 μm. Importantly, with optimized dielectric coating for air-stability during microfabrication, flexible BP RF transistors afforded intrinsic maximum oscillation frequency fMAX ∼ 14.5 GHz and unity current gain cutoff frequency fT ∼ 17.5 GHz at a channel length of 0.5 μm. Notably, the experimental fT achieved here is at least 45% higher than prior results on rigid substrate, which is attributed to the improved air-stability of fabricated BP devices. In addition, the high-frequency performance was investigated through mechanical bending test up to ∼1.5% tensile strain, which is ultimately limited by the inorganic dielectric film rather than the 2D material. Comparison of BP RF devices to other 2D semiconductors clearly indicates that BP offers the highest saturation velocity, an important metric for high-speed and RF flexible nanosystems.

Double Exposure to Adverse Psychosocial Work Factors and High Family Responsibilities as Related to Ambulatory Blood Pressure at Work: A 5-Year Prospective Study in Women With White-Collar Jobs.

PubMed

Gilbert-Ouimet, Mahée; Brisson, Chantal; Milot, Alain; Vézina, Michel

2017-06-01

Accumulating evidence shows that psychosocial work factors of the demand-control and effort-reward imbalance models may contribute to increase blood pressure (BP). Women are more likely to be exposed to these psychosocial factors than men. Moreover, women spend twice as much time per week performing family responsibilities than men. This study aimed to evaluate the longitudinal association of the double exposure to psychosocial work factors and high family responsibilities in women with BP for a 5-year follow-up. At baseline, the study sample was composed of 1215 working women. Psychosocial work factors were measured using validated scales. Family responsibilities were measured using items related to "the number of children and their age" and "housework and children care." Ambulatory BP measures were taken every 15 minutes during a working day. Associations between psychosocial measures and BP were examined using analyses of covariance. Women with a double exposure to effort-reward imbalance and high family responsibilities had significantly higher BP means than women not exposed to these factors at baseline (diastolic: +2.75 mm Hg), at 3-year follow-up (systolic: +2.22 mm Hg and diastolic: +2.55 mm Hg), and at 5-year follow-up (systolic: +2.94 mm Hg and diastolic: + 3.10 mm Hg). No adverse effect on BP was observed for the double exposure to the psychosocial work factors of the demand-control model and high family responsibilities. A double exposure to effort-reward imbalance at work and high family responsibilities might contribute to elevated ambulatory BP at work among women. BP elevations related to this double exposure may persist for several years.

Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles.

PubMed

Lee, Donna H; Riquier, Anne D M; Yang, Li E; Leong, Patrick K K; Maunsbach, Arvid B; McDonough, Alicia A

2009-04-01

When blood pressure (BP) is elevated above baseline, a pressure natriuresis-diuresis response ensues, critical to volume and BP homeostasis. Distal convoluted tubule Na(+)-Cl(-) cotransporter (NCC) is regulated by trafficking between the apical plasma membrane (APM) and subapical cytoplasmic vesicles (SCV). We aimed to determine whether NCC trafficking contributes to pressure diuresis by decreasing APM NCC or compensates for increased volume flow to the DCT by increasing APM NCC. BP was raised 50 mmHg (high BP) in rats by arterial constriction for 5 or 20-30 min, provoking a 10-fold diuresis at both times. Kidneys were excised, and NCC subcellular distribution was analyzed by 1) sorbitol density gradient fractionation and immunoblotting and 2) immunoelectron microscopy (immuno-EM). NCC distribution did not change after 5-min high BP. After 20-30 min of high BP, 20% of NCC redistributed from low-density, APM-enriched fractions to higher density, endosome-enriched fractions, and, by quantitative immuno-EM, pool size of APM NCC decreased 14% and SCV pool size increased. Because of the time lag of the response, we tested the hypothesis that internalization of NCC was secondary to the decrease in ANG II that accompanies high BP. Clamping ANG II at a nonpressor level by coinfusion of captopril (12 microg/min) and ANG II (20 ng.kg(-1).min(-1)) during 30-min high BP reduced diuresis to eightfold and prevented redistribution of NCC from APM- to SCV-enriched fractions. We conclude that DCT NCC may participate in pressure natriuresis-diuresis by retraction out of apical plasma membranes and that the retraction is, at least in part, driven by the fall in ANG II that accompanies acute hypertension.

The Nutritional Characteristics of the Hypotensive WASHOKU-modified DASH Diet: A Sub-analysis of the DASH-JUMP Study.

PubMed

Kawamura, Atsuko; Kajiya, Katsuko; Kishi, Hiroko; Inagaki, Junko; Mitarai, Makoto; Oda, Hiroshi; Umemoto, Seiji; Kobayashi, Sei

2018-01-01

We developed a WASHOKU-modified DASH diet named DASH-JUMP. We previously reported the hypotensive effect of the DASH-JUMP diet in Japanese participants with untreated high-normal Blood Pressure (BP) or stage 1 hypertension. We aim to introduce the DASH-JUMP diet worldwide as a new lifestyle medicine. Accordingly, we prospectively assessed the nutritional characteristics of the DASH-JUMP diet. Participants were treated with the DASH-JUMP diet for 2 months. Then, for 4 months after the intervention, they consumed their usual diets. We conducted a nutritional survey using the FFQg nutrient questionnaire at baseline and after 1, 2, 3, and 6 months. We received completed questionnaires from 55 participants (28 men and 27 women; mean age 54.2 ± 8.0 years) and analyzed them. The DASH-JUMP diet is rich in green-yellow vegetables, seaweed, milk, and mushrooms, while it has low contents of meat, eggs, confectionery, oils and fats, pickles, shellfish boiled in sweetened soy sauce, and fruits. Nutrients significantly associated with the observed change in systolic BP were niacin (P = 0.005) and carbohydrate (P = 0.033). The results of the FFQg questionnaire revealed that participants who had an increased BP at 1 month after ceasing the intervention had eating habits that broadly imitated the DASH-JUMP diet at 4 months after ceasing the intervention. Therefore, the systolic and diastolic BP values at 4 months after ceasing the intervention decreased significantly compared to those at baseline. The DASH-JUMP diet may represent a new lifestyle medicine for reducing hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Complete Mitochondrial Genome of Corizus tetraspilus (Hemiptera: Rhopalidae) and Phylogenetic Analysis of Pentatomomorpha

PubMed Central

Guo, Zhong-Long; Wang, Juan; Shen, Yu-Ying

2015-01-01

Insect mitochondrial genome (mitogenome) are the most extensively used genetic information for molecular evolution, phylogenetics and population genetics. Pentatomomorpha (>14,000 species) is the second largest infraorder of Heteroptera and of great economic importance. To better understand the diversity and phylogeny within Pentatomomorpha, we sequenced and annotated the complete mitogenome of Corizus tetraspilus (Hemiptera: Rhopalidae), an important pest of alfalfa in China. We analyzed the main features of the C. tetraspilus mitogenome, and provided a comparative analysis with four other Coreoidea species. Our results reveal that gene content, gene arrangement, nucleotide composition, codon usage, rRNA structures and sequences of mitochondrial transcription termination factor are conserved in Coreoidea. Comparative analysis shows that different protein-coding genes have been subject to different evolutionary rates correlated with the G+C content. All the transfer RNA genes found in Coreoidea have the typical clover leaf secondary structure, except for trnS1 (AGN) which lacks the dihydrouridine (DHU) arm and possesses a unusual anticodon stem (9 bp vs. the normal 5 bp). The control regions (CRs) among Coreoidea are highly variable in size, of which the CR of C. tetraspilus is the smallest (440 bp), making the C. tetraspilus mitogenome the smallest (14,989 bp) within all completely sequenced Coreoidea mitogenomes. No conserved motifs are found in the CRs of Coreoidea. In addition, the A+T content (60.68%) of the CR of C. tetraspilus is much lower than that of the entire mitogenome (74.88%), and is lowest among Coreoidea. Phylogenetic analyses based on mitogenomic data support the monophyly of each superfamily within Pentatomomorpha, and recognize a phylogenetic relationship of (Aradoidea + (Pentatomoidea + (Lygaeoidea + (Pyrrhocoroidea + Coreoidea)))). PMID:26042898

[Spanish Society of Hypertension position statement on the 2017 ACC/AHA hypertension guidelines].

PubMed

Gijón-Conde, T; Gorostidi, M; Camafort, M; Abad-Cardiel, M; Martín-Rioboo, E; Morales-Olivas, F; Vinyoles, E; Armario, P; Banegas, J R; Coca, A; de la Sierra, A; Martell-Claros, N; Redón, J; Ruilope, L M; Segura, J

2018-04-24

The American College of Cardiology (ACC) and the American Heart Association (AHA) have recently published their guidelines for the prevention, detection, evaluation, and management of hypertension in adults. The most controversial issue is the classification threshold at 130/80mmHg, which will allow a large number of patients to be diagnosed as hypertensive who were previously considered normotensive. Blood pressure (BP) is considered normal (<120mmHg systolic and <80mmHg diastolic), elevated (120-129 and <80mmHg), stage 1 (130-139 or 80-89mmHg), and stage 2 (≥140 or ≥90mmHg). Out-of-office BP measurements are recommended to confirm the diagnosis of hypertension and for titration of BP-lowering medication. In management, cardiovascular risk would be determinant since those with grade 1 hypertension and an estimated 10-year risk of atherosclerotic cardiovascular disease ≥10%, and those with cardiovascular disease, chronic kidney disease and/or diabetes will require pharmacological treatment, the rest being susceptible to non-pharmacological treatment up to the 140/90mmHg threshold. These recommendations would allow patients with level 1 hypertension and high atherosclerotic cardiovascular disease to benefit from pharmacological therapies and all patients could also benefit from improved non-pharmacological therapies. However, this approach should be cautious because inadequate BP measurement and/or lack of systematic atherosclerotic cardiovascular disease calculation could lead to overestimation in diagnosing hypertension and to overtreatment. Guidelines are recommendations, not impositions, and the management of hypertension should be individualized, based on clinical decisions, preferences of the patients, and an adequate balance between benefits and risks. Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.

Intraocular Pressure, Blood Pressure, and Retinal Blood Flow Autoregulation: A Mathematical Model to Clarify Their Relationship and Clinical Relevance

PubMed Central

Guidoboni, Giovanna; Harris, Alon; Cassani, Simone; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Tobe, Leslie; Egan, Patrick; Januleviciene, Ingrida; Park, Joshua

2014-01-01

Purpose. This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. Methods. A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. Results. The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. Conclusions. The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics. PMID:24876284

Intraocular pressure, blood pressure, and retinal blood flow autoregulation: a mathematical model to clarify their relationship and clinical relevance.

PubMed

Guidoboni, Giovanna; Harris, Alon; Cassani, Simone; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Tobe, Leslie; Egan, Patrick; Januleviciene, Ingrida; Park, Joshua

2014-05-29

This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Characterization of IntA, a Bidirectional Site-Specific Recombinase Required for Conjugative Transfer of the Symbiotic Plasmid of Rhizobium etli CFN42

PubMed Central

Hernández-Tamayo, Rogelio; Sohlenkamp, Christian; Puente, José Luis; Brom, Susana

2013-01-01

Site-specific recombination occurs at short specific sequences, mediated by the cognate recombinases. IntA is a recombinase from Rhizobium etli CFN42 and belongs to the tyrosine recombinase family. It allows cointegration of plasmid p42a and the symbiotic plasmid via site-specific recombination between attachment regions (attA and attD) located in each replicon. Cointegration is needed for conjugative transfer of the symbiotic plasmid. To characterize this system, two plasmids harboring the corresponding attachment sites and intA were constructed. Introduction of these plasmids into R. etli revealed IntA-dependent recombination events occurring at high frequency. Interestingly, IntA promotes not only integration, but also excision events, albeit at a lower frequency. Thus, R. etli IntA appears to be a bidirectional recombinase. IntA was purified and used to set up electrophoretic mobility shift assays with linear fragments containing attA and attD. IntA-dependent retarded complexes were observed only with fragments containing either attA or attD. Specific retarded complexes, as well as normal in vivo recombination abilities, were seen even in derivatives harboring only a minimal attachment region (comprising the 5-bp central region flanked by 9- to 11-bp inverted repeats). DNase I-footprinting assays with IntA revealed specific protection of these zones. Mutations that disrupt the integrity of the 9- to 11-bp inverted repeats abolish both specific binding and recombination ability, while mutations in the 5-bp central region severely reduce both binding and recombination. These results show that IntA is a bidirectional recombinase that binds to att regions without requiring neighboring sequences as enhancers of recombination. PMID:23935046

Real-Time Classification of Patients with Balance Disorders vs. Normal Subjects Using a Low-Cost Small Wireless Wearable Gait Sensor.

PubMed

Nukala, Bhargava Teja; Nakano, Taro; Rodriguez, Amanda; Tsay, Jerry; Lopez, Jerry; Nguyen, Tam Q; Zupancic, Steven; Lie, Donald Y C

2016-11-29

Gait analysis using wearable wireless sensors can be an economical, convenient and effective way to provide diagnostic and clinical information for various health-related issues. In this work, our custom designed low-cost wireless gait analysis sensor that contains a basic inertial measurement unit (IMU) was used to collect the gait data for four patients diagnosed with balance disorders and additionally three normal subjects, each performing the Dynamic Gait Index (DGI) tests while wearing the custom wireless gait analysis sensor (WGAS). The small WGAS includes a tri-axial accelerometer integrated circuit (IC), two gyroscopes ICs and a Texas Instruments (TI) MSP430 microcontroller and is worn by each subject at the T4 position during the DGI tests. The raw gait data are wirelessly transmitted from the WGAS to a near-by PC for real-time gait data collection and analysis. In order to perform successful classification of patients vs. normal subjects, we used several different classification algorithms, such as the back propagation artificial neural network (BP-ANN), support vector machine (SVM), k -nearest neighbors (KNN) and binary decision trees (BDT), based on features extracted from the raw gait data of the gyroscopes and accelerometers. When the range was used as the input feature, the overall classification accuracy obtained is 100% with BP-ANN, 98% with SVM, 96% with KNN and 94% using BDT. Similar high classification accuracy results were also achieved when the standard deviation or other values were used as input features to these classifiers. These results show that gait data collected from our very low-cost wearable wireless gait sensor can effectively differentiate patients with balance disorders from normal subjects in real time using various classifiers, the success of which may eventually lead to accurate and objective diagnosis of abnormal human gaits and their underlying etiologies in the future, as more patient data are being collected.

Multilevel Associations of Neighborhood Poverty, Crime, and Satisfaction With Blood Pressure in African-American Adults.

PubMed

Coulon, Sandra M; Wilson, Dawn K; Alia, Kassandra A; Van Horn, M Lee

2016-01-01

African-American adults experience the highest rates of elevated blood pressure (BP), and this disparity may be linked to socioeconomic and neighborhood-related disadvantage. Based on a bioecological stress-buffering framework, relations of poverty and neighborhood environmental perceptions with BP were assessed using multilevel regression in at-risk African-American adults. This cross-sectional study used baseline data that were collected in 2008 as part of the Positive Action for Today's Health (PATH) trial (N = 409), a community-based intervention to increase walking in low-income, high-crime neighborhoods. BP and perceived neighborhood crime and satisfaction were investigated as individual-level indicators of health and neighborhood environment. Census block groups (N = 22) served as geographic proxies for neighborhoods, and poverty was obtained using 2010 U.S. Census data, to characterize the neighborhood-level socioeconomic environment. There were no individual-level direct associations. Significant cross-product interactions demonstrated that with higher perceived crime, high satisfaction was associated with lower systolic (γ = 3.34) and diastolic (γ = -1.37) BP, but low satisfaction was associated with higher systolic (γ = 15.12) and diastolic (γ = 7.57) BP. Neighborhood-level poverty was associated with diastolic (γ = 11.48, SE = 4.08, P = 0.008) and systolic BP (γ = 12.79, SE = 6.33, P = 0.052). Variance in BP across block groups was low (intraclass correlation coefficients = 0.002-0.014) and there were no significant random effects. Results supported hypotheses, with greater neighborhood satisfaction linked to lower systolic and diastolic BP when perceived crime was high. Neighborhood poverty was also linked to higher systolic and diastolic BP. Prevention efforts should further investigate whether attending to issues of poverty and related neighborhood perceptions reduces high BP in at-risk African-American communities. © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2015. This work is written by (a) US Government employees(s) and is in the public domain in the US.

Multilevel Associations of Neighborhood Poverty, Crime, and Satisfaction With Blood Pressure in African-American Adults

PubMed Central

Wilson, Dawn K.; Alia, Kassandra A.; Van Horn, M. Lee

2016-01-01

BACKGROUND African-American adults experience the highest rates of elevated blood pressure (BP), and this disparity may be linked to socioeconomic and neighborhood-related disadvantage. Based on a bioecological stress-buffering framework, relations of poverty and neighborhood environmental perceptions with BP were assessed using multilevel regression in at-risk African-American adults. METHODS This cross-sectional study used baseline data that were collected in 2008 as part of the Positive Action for Today’s Health (PATH) trial (N = 409), a community-based intervention to increase walking in low-income, high-crime neighborhoods. BP and perceived neighborhood crime and satisfaction were investigated as individual-level indicators of health and neighborhood environment. Census block groups (N = 22) served as geographic proxies for neighborhoods, and poverty was obtained using 2010U.S. Census data, to characterize the neighborhood-level socioeconomic environment. RESULTS There were no individual-level direct associations. Significant cross–product interactions demonstrated that with higher perceived crime, high satisfaction was associated with lower systolic (γ = 3.34) and diastolic (γ = −1.37) BP, but low satisfaction was associated with higher systolic (γ = 15.12) and diastolic (γ = 7.57) BP. Neighborhood-level poverty was associated with diastolic (γ = 11.48, SE = 4.08, P = 0.008) and systolic BP (γ = 12.79, SE = 6.33, P = 0.052). Variance in BP across block groups was low (intraclass correlation coefficients = 0.002–0.014) and there were no significant random effects. CONCLUSIONS Results supported hypotheses, with greater neighborhood satisfaction linked to lower systolic and diastolic BP when perceived crime was high. Neighborhood poverty was also linked to higher systolic and diastolic BP. Prevention efforts should further investigate whether attending to issues of poverty and related neighborhood perceptions reduces high BP in at-risk African-American communities. PMID:25917562

Prevalence and clinical characteristics of isolated-office and true resistant hypertension determined by ambulatory blood pressure monitoring.

PubMed

Ríos, María T; Domínguez-Sardiña, Manuel; Ayala, Diana E; Gomara, Sonia; Sineiro, Elvira; Pousa, Lorenzo; Callejas, Pedro A; Fontao, María J; Fernández, José R; Hermida, Ramón C

2013-03-01

Hypertension is defined as resistant to treatment when a therapeutic plan including ≥3 hypertension medications failed to sufficiently lower systolic (SBP) and diastolic (DBP) blood pressures (BPs). Most individuals, including those under hypertension therapy, show a "white-coat" effect that could cause an overestimation of their real BP. The prevalence and clinical characteristics of "white-coat" or isolated-office resistant hypertension (RH) has always been evaluated by comparing clinic BP values with either daytime home BP measurements or the awake BP mean obtained from ambulatory monitoring (ABPM), therefore including patients with either normal or elevated asleep BP mean. Here, we investigated the impact of including asleep BP mean as a requirement for the definition of hypertension on the prevalence, clinical characteristics, and estimated cardiovascular (CVD) risk of isolated-office RH. This cross-sectional study evaluated 3042 patients treated with ≥3 hypertension medications and evaluated by 48-h ABPM (1707 men/1335 women), 64.2 ± 11.6 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 522 (17.2%) had true isolated-office RH (elevated clinic BP and controlled awake and asleep ambulatory BPs while treated with 3 hypertension medications), 260 (8.6%) had false isolated-office RH (elevated clinic BP, controlled awake SBP/DBP means, but elevated asleep SBP or DBP mean while treated with 3 hypertension medications), and the remaining 2260 (74.3%) had true RH (elevated awake or asleep SBP/DBP means while treated with 3 medications, or any patient treated with ≥4 medications). Patients with false, relative to those with true, isolated-office RH had higher prevalence of microalbuminuria and chronic kidney disease (CKD), significantly higher albumin/creatinine ratio (p < .001), significantly higher 48-h SBP/DBP means by 9.6/5.3 mm Hg (p < .001), significantly lower sleep-time relative SBP and DBP decline (p < .001), and significantly greater prevalence of a non-dipper BP profile (96.9% vs. 38.9%; p < .001). Additionally, the prevalence of the riser BP pattern, which is associated with highest CVD risk, was much greater, 40.4% vs. 5.0% (p < .001), among patients with false isolated-office RH. The estimated hazard ratio of CVD events, using a fully adjusted model including the significant confounding variables of sex, age, diabetes, chronic kidney disease, asleep SBP mean, and sleep-time relative SBP decline, was significantly greater for patients with false compared with those with true isolated-office RH (2.13 [95% confidence interval: 1.95-2.32]; p < .001). Patients with false isolated-office hypertension and true RH, however, were equivalent for the prevalence of obstructive sleep apnea, metabolic syndrome, obesity, diabetes, microalbuminuria, and chronic kidney disease, and they had an equivalent estimated hazard ratio of CVD events (1.04 [95% confidence interval: .97-1.12]; p = .265). Our findings document a significantly elevated prevalence of a blunted nighttime BP decline in patients here categorized as either false isolated-office RH and true RH, jointly accounting for 82.8% of the studied sample. Previous reports of much lower prevalence of true RH plus a nonsignificant increased CVD risk of this condition compared with isolated-office RH are misleading by disregarding asleep BP mean for classification. Our results further indicate that classification of RH patients into categories of isolated-office RH, masked RH, and true RH cannot be based on the comparison of clinic BP with either daytime home BP measurements or awake BP mean from ABPM, as so far customary in the available literature, totally disregarding the highly significant prognostic value of nighttime BP. Accordingly, ABPM should be regarded as a clinical requirement for proper diagnosis of true RH.

Rejection Sensitivity and Executive Control: Joint predictors of Borderline Personality features

PubMed Central

Ayduk, Özlem; Zayas, Vivian; Downey, Geraldine; Cole, Amy Blum; Shoda, Yuichi; Mischel, Walter

2008-01-01

Two studies tested the hypothesis that rejection sensitivity (RS) and executive control (EC) jointly predict borderline personality (BP) features. We expected high RS to be related to increased vulnerability for BP features specifically in people who also had difficulties in executive control (EC). Study 1 tested this hypothesis using a sample of college students (N = 379) whereas Study 2 (N = 104) was conducted using a community sample of adults. Both studies operationalized EC by a self-report measure. For a subsample in Study 2 (N = 80), ability to delay gratification at age 4 was also used as an early behavioral precursor of EC in adulthood. In both studies, high RS was associated with increased BP features among people low in self-reported EC. Among those high in self-reported EC, the relationship between RS and BP features was attenuated. Study 2 found parallel findings using preschool delay ability as a behavioral index of EC. These findings suggest that EC may protect high RS people against BP features. PMID:18496604

Overexpression of BpAP1 induces early flowering and produces dwarfism in Betula platyphylla × Betula pendula.

PubMed

Huang, Haijiao; Wang, Shan; Jiang, Jing; Liu, Guifeng; Li, Huiyu; Chen, Su; Xu, Huanwen

2014-08-01

The involvement of APETALA1 (AP1) in the flowering transition has been the focus of much research. Here, we produced Betula platyphylla × Betula pendula (birch) lines that overexpressed BpAP1 using Agrobacterium-mediated transformation; we obtained five independent 35S::BpAP1 transgenic lines. Polymerase chain reaction (PCR), Southern, northern and western analyses were used to identify the transformants. As determined by quantitative real-time PCR (qRT-PCR), BpAP1 expression in roots, shoots, leaves and terminal buds of 35S::BpAP1 transgenic lines was significantly higher than that in the wild type (WT, P < 0.01). The average height of 2-year-old 35S::BpAP1 plants was significantly lower (41.17%) than that of non-transgenic plants. In the 35S::BpAP1 lines, inflorescences emerged successively beginning 2 months after transplanting. In addition, the length-diameter ratio of fully developed male and female inflorescences were both significantly less than those of the WT (P < 0.05), i.e. the morphological characteristic was stubby. The male inflorescences emerged early, with empty, draped anthers, and pollen was rarely produced, whereas the female floret structure was not different from WT. The pistils developed normally and could accept pollen, leading to the production of hybrid progeny (F1 ). F1 plants completed flowering within only 1 year after sowing. We demonstrate that BpAP1 can be inherited through sexual reproduction. Overexpression of BpAP1 caused early flowering and dwarfism; these lines had an obviously shortened juvenile phase. These results greatly increase our understanding of the mechanisms underlying the flowering transition and enhance genetic studies of birch traits, and they open up new possibilities for the breeding of birch and other woody plants. © 2013 Scandinavian Plant Physiology Society.

Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.

PubMed

Fadl Elmula, Fadl Elmula M; Hoffmann, Pavel; Larstorp, Anne C; Fossum, Eigil; Brekke, Magne; Kjeldsen, Sverre E; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjaer, Vibeke N; Rostrup, Morten; Os, Ingrid; Stenehjem, Aud; Høieggen, Aud

2014-05-01

We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

Design and rationale for Home Blood Pressure Telemonitoring and Case Management to Control Hypertension (HyperLink): a cluster randomized trial.

PubMed

Margolis, Karen L; Kerby, Tessa J; Asche, Stephen E; Bergdall, Anna R; Maciosek, Michael V; O'Connor, Patrick J; Sperl-Hillen, JoAnn M

2012-07-01

Patients with high blood pressure (BP) visit a physician an average of 4 times or more per year in the U.S., yet BP is controlled in fewer than half. Practical, robust and sustainable models are needed to improve BP in patients with uncontrolled hypertension. The Home Blood Pressure Telemonitoring and Case Management to Control Hypertension study (HyperLink) is a cluster-randomized trial designed to determine whether an intervention that combines home BP telemonitoring with pharmacist case management improves BP control compared to usual care at 6 and 12 months in patients with uncontrolled hypertension. Secondary outcomes are maintenance of BP control at 18 months, patient satisfaction with their health care, and costs of care. HyperLink enrolled 450 hypertensive patients with uncontrolled BP from 16 primary care clinics. Eight clinics were randomized to provide usual care (UC) to their patients (n=222) and 8 were randomized to provide the telemonitoring intervention (TI) (n=228). TI patients received home BP telemonitors that internally store and electronically transmit BP data to a secure database. Pharmacist case managers adjust antihypertensive therapy based on the home BP data under a collaborative practice agreement with the clinics' primary care teams. The length of the intervention is 12 months, with follow-up to 18 months to determine the durability of the intervention. We will test in a real primary care setting whether combining BP telemonitoring and pharmacist case management can achieve and maintain high rates of BP control compared to usual care. Copyright © 2012 Elsevier Inc. All rights reserved.

Enhancing and optimizing electronic transport in biphenyl derivative single-molecule junctions attached to carbon nanotubes electrodes

NASA Astrophysics Data System (ADS)

Reis-Silva, J. C.; Ferreira, D. F. S.; Leal, J. F. P.; Pinheiro, F. A.; Del Nero, J.

2017-02-01

We investigate, by means of ab initio calculations based on non-equilibrium Green's function method coupled to density function theory, electronic transport in molecular junctions composed of biphenyl (BP) and biphenyl within (-2H+) defect (BP2D) molecules attached to metallic (9,0) carbon nanotubes. We demonstrate that the BP2D junction exhibits unprecedented electronic transport properties, and that its conductance can be up to three orders of magnitude higher than biphenyl single-molecule junctions. These findings are explained in terms of the non-planar molecular conformation of BP2D, and of the stronger electronic coupling between the BP2D molecule and the organic electrodes, which confers high stability to the junction. Our results suggest that BP2D attached to carbon nanotubes can be explored as an efficient and highly stable platform in single-molecule electronics with extraordinary transport properties.

Subepidermal Blistering Induced by Human Autoantibodies to BP180 Requires Innate Immune Players in a Humanized Bullous Pemphigoid Mouse Model

PubMed Central

Liu, Zhi; Sui, Wen; Zhao, Minglang; Li, Zhuowei; Li, Ning; Thresher, Randy; Giudice, George J.; Fairley, Janet A.; Sitaru, Cassian; Zillikens, Detlef; Ning, Gang; Marinkovich, Peter; Diaz, Luis A.

2008-01-01

Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease associated with subepidermal blistering and autoantibodies against BP180, a transmembrane collagen and major component of the hemidesmosome. Numerous inflammatory cells infiltrate the upper dermis in BP. IgG autoantibodies in BP fix complement and target multiple BP180 epitopes that are highly clustered within a non-collagen linker domain, termed NC16A. Anti-BP180 antibodies induce BP in mice. In this study, we generated a humanized mouse strain, in which the murine BP180NC14A is replaced with the homologous human BP180NC16A epitope cluster region. We show that the humanized NC16A (NC16A+/+) mice injected with anti-BP180NC16A autoantibodies develop BP-like subepidermal blisters. The F(ab′)2 fragments of pathogenic IgG fail to activate complement cascade and are no longer pathogenic. The NC16A+/+ mice pretreated with mast cell activation blocker or depleting of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players. PMID:18922680

Blood Pressure Response to Exercise and Cardiovascular Disease.

PubMed

Schultz, Martin G; La Gerche, Andre; Sharman, James E

2017-10-18

This review aimed to provide a clinical update on exercise blood pressure (BP) and its relationship to cardiovascular disease (CVD), outlining key determinants of abnormal exercise BP responses. We also highlight current evidence gaps that need addressing in order to optimise the relevance of exercise BP as clinical CVD risk factor. Abnormal exercise BP manifests as either exercise hypotension (low BP response) or as exaggerated exercise BP (high BP response). Exercise hypotension is an established sign of existing and likely severe CVD, but exaggerated exercise BP also carries elevated CVD risk due to its association with sub-clinical hypertension. Although exaggerated exercise BP is related to heightened CVD risk at any exercise intensity, recent data suggest that the BP response to submaximal intensity exercise holds greater prognostic and clinical significance than BP achieved at peak/maximal intensity exercise. Cardiorespiratory fitness is a strong modifier of the exercise BP response, and should be taken into consideration when assessing the association with CVD. Both exercise hypotension and exaggerated exercise BP serve as markers that should prompt evaluation for potential underlying CVD. However, the clinical utility of these markers is currently inhibited by the lack of consensus informing the definitions and thresholds for abnormalities in exercise BP.

Characterizing the DNA Damage Response by Cell Tracking Algorithms and Cell Features Classification Using High-Content Time-Lapse Analysis

PubMed Central

Georgescu, Walter; Osseiran, Alma; Rojec, Maria; Liu, Yueyong; Bombrun, Maxime; Tang, Jonathan; Costes, Sylvain V.

2015-01-01

Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation. PMID:26107175

Characterizing the DNA damage response by cell tracking algorithms and cell features classification using high-content time-lapse analysis

DOE PAGES

Georgescu, Walter; Osseiran, Alma; Rojec, Maria; ...

2015-06-24

Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were ablemore » to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm 2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Furthermore, such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation.« less

Temporal Lobe Toxicity Analysis After Proton Radiation Therapy for Skull Base Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pehlivan, Berrin; Ares, Carmen, E-mail: carmen.ares@psi.ch; Lomax, Antony J.

2012-08-01

Purpose: Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT. Methods and Materials: Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63-74 Gy). The dose-volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1,more » 2, and 3 cc of brain volume (D{sub 0.5}, D{sub 1}, D{sub 2}, D{sub 3}) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. Results: At a mean follow-up of 38 months (range, 14-92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 {+-} 5 Gy (RBE) for no toxicity to 74 {+-} 5 Gy (RBE) for Grade 1 and to 76 {+-} 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of {>=}64 Gy (RBE) D{sub 3}, {>=}68 Gy (RBE) D{sub 2}, {>=}72 Gy (RBE) D{sub 1}, and {>=}73 Gy (RBE) D{sub 0.5}, respectively (p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy. Conclusions: A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose-volume parameters investigated. Our findings support the importance of establishing an organ-at-risk maximally permissible dose for BP.« less

A cool eastern Pacific Ocean at the close of the Last Interglacial complex

USGS Publications Warehouse

Muhs, D.R.; Simmons, K.R.; Kennedy, G.L.; Ludwig, K. R.; Groves, L.T.

2006-01-01

New high-precision thermal ionization mass-spectrometric (TIMS) U-series ages of solitary corals (Balanophyllia elegans) from several marine terrace localities along the California and southern Oregon coasts date to the ???80,000 yr BP high stand of sea, correlative with marine isotope substage 5a, late in the last interglacial complex. Ages of multiple corals from localities north of Point An??o Nuevo (central California) and San Nicolas Island (southern California) suggest that this high sea stand could have lasted at least 8000 yr, from ???84,000 to ???76,000 yr BP. These ages overlap with those from marine deposits on tectonically stable Bermuda and tectonically emergent Barbados. Higher-elevation terraces at two California localities, in the Palos Verdes Hills and on San Nicolas Island, have corals with ages that range mostly from ???121,000 to ???116,000 yr BP, correlative with marine isotope substage 5e. These ages are similar to those reported for other terraces in southern California but are younger than some ages reported from Hawaii, Barbados and the Bahamas. Marine terrace faunas are excellent proxies for nearshore marine paleotemperatures during past high sea stands. Terraces on the Palos Verdes Hills and San Nicolas Island dated to the ???120,000 yr BP high sea stand have dominantly zoogeographically "neutral" species in exposed coastal localities, indicating nearshore waters similar to those of today. In contrast, ???80,000 yr BP, exposed coastal localities typically have molluscan faunas characterized by numerous extralimital northern species and a lack of extralimital southern species. These fossil assemblages are indicative of nearshore water temperatures that were cooler than modern temperatures at ???80,000 yr BP. Waters at least as warm as today's at ???120,000 yr BP and cooler than present at ???80,000 yr BP are in excellent agreement with marine alkenone records and coastal vegetation records derived from pollen data, from both southern and northern California. Decreased insolation or increased upwelling seem inadequate to explain the cool waters off the Pacific Coast from southern Oregon to southern California at ???80,000 yr BP. We propose that a stronger California Current (or at least one with a greater component of subarctic waters) may explain cooler-than-modern coastal waters during the ???80,000 yr BP high sea stand. ?? 2005 Elsevier Ltd. All rights reserved.

Relationship Between Blood Pressure Values, Depressive Symptoms, and Cardiovascular Outcomes in Patients With Cardiometabolic Disease.

PubMed

Jani, Bhautesh Dinesh; Cavanagh, Jonathan; Barry, Sarah J E; Der, Geoff; Sattar, Naveed; Mair, Frances S

2016-10-01

The authors studied the joint effect of blood pressure (BP) and depression on the risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35,537 patients with coronary heart disease, diabetes, or stroke underwent depression screening and BP measurement recorded concurrently. The authors used Cox's proportional hazards to calculate risk of major adverse cardiovascular event (MACE; myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with baseline BP and depression. A total of 11% (3939) had experienced a MACE within 4 years. Patients with very high systolic BP (160-240 mm Hg; hazard ratio, 1.28) and depression (hazard ratio, 1.22) at baseline had significantly higher adjusted risk. Depression had a significant interaction with systolic BP in risk prediction (P=.03). Patients with a combination of high systolic BP and depression at baseline had 83% higher adjusted risk of MACE, as compared with patients with reference systolic BP without depression. Patients with cardiometabolic disease and comorbid depression may benefit from closer monitoring of systolic BP. © 2016 The Authors. The Journal of Clinical Hypertension Published by Wiley Periodicals, Inc.

Low physical activity is a determinant for elevated blood pressure in high cardiovascular risk obstructive sleep apnea.

PubMed

Mendelson, Monique; Tamisier, Renaud; Laplaud, David; Dias-Domingos, Sonia; Baguet, Jean-Philippe; Moreau, Laurent; Koltes, Christian; Chavez, Léonidas; de Lamberterie, Gilles; Herengt, Frédéric; Levy, Patrick; Flore, Patrice; Pépin, Jean-Louis

2014-08-01

Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity, including hypertension. Beyond the severity of nocturnal hypoxia, other factors such as metabolic abnormalities but also sedentary behaviors and insufficient physical activity may contribute to elevated blood pressure (BP). To clarify the respective role of these factors as determinants of BP in OSA patients, we examined the relationship between BP and anthropometrics, severity of sleep apnea, and objectively measured physical activity and sedentary behaviors. Ninety-five adults presenting with OSA (apnea-hypopnea index > 10 events/h) and high cardiovascular risk (63.3 ± 8.8 y; body mass index: 29.9 ± 4.9 kg/m(2); apnea-hypopnea index: 41.3 ± 17.5/h; cardiovascular risk score: 13.5 ± 3.7%) were included. Physical activity and sedentary behaviors were objectively assessed by actigraphy, and self-measured home BP monitoring was measured. Logistic regression models adjusted for sex, age, and body mass index were built to identify the predictors of self-measured morning and evening BP. Physical activity was significantly related to obesity but not to the severity of sleep apnea or sleepiness. Sedentary behaviors were associated with self-measured morning and evening systolic BP (r = 0.32, P = .002; r = 0.29, P = .004). Steps per day were inversely associated with evening BP (r = -0.27, P = .01). Univariate analysis identified steps/d and time spent in vigorous physical activity as determinants for evening self-measured BP. In multivariate analysis, only steps/d were identified as a significant determinant of evening BP. Physical activity is the major determinant for evening BP in adults with OSA presenting high cardiovascular risk. Our results emphasize the need for lifestyle counseling programs in combination with CPAP to encourage regular physical activity in OSA subjects to obtain better BP control. (ClinicalTrials.gov registration NCT01226641.)

Identification of a differentially-expressed gene in fatty liver of overfeeding geese.

PubMed

Zhao, Ayong; Tang, Huachun; Lu, Sufang; He, Ruiguo

2007-09-01

In response to overfeeding, geese develop fatty liver. To understand the fattening mechanism, mRNA differential display reverse transcription PCR was used to study the gene expression differences between French Landes grey geese and Xupu white geese in conditions of overfeeding and normal feeding. One gene was found to be up-regulated in the fatty liver in both breeds, and it has a 1797 bp cDNA with 83% identity to chicken SELENBP1. The sequence analysis revealed that its open reading frame of 1413 bp encodes a protein of 471 amino acids, which contains a putative conserved domain of 56 kDa selenium binding protein with high homology to its homologues of chicken (95%), rat (86%), mouse (84%), human (86%), monkey (86%), dog (86%), and cattle (86%). The function of this protein has been briefly reviewed based on published information. In tissue expression analysis, the expression of geese SELENBP1 mRNA was found to be higher in liver or kidney than in other tested tissues. The results showed that overfeeding could increase the mRNA expression level of geese SELENBP1.

[The bereitschaftspotential. The concept and methodology for acquiring it].

PubMed

Conill, J

The movement of extension of the index finger in a stereotyped manner, not as a reaction to any external or internal stimulus, is preceded by EEG activity representing activity of the supplementary motor area of the motor cortex. By averaging retrograde EEG activity prior to movement, the Bereitschaftspotential (BP) may be obtained, using the German nomenclature of the earliest investigators who first described it and its components NS1 and NS2. We include a table with normal values obtained from a group of healthy persons. In our study we show the usefulness of off-line methodology with manual adjustment of the start of EMG activity to obtain better morphological definition and greater voltage of the BP. At the same time, continual acquisition with the trigger adjusted to a prefixed threshold (on-line methodology) means that a smaller BP is obtained, especially in persons with difficulty in the organization of this movement.

Comparison of the Gyro C1E3 and BioMedicus centrifugal pump performances during cardiopulmonary bypass.

PubMed

Nakazawa, T; Takami, Y; Makinouchi, K; Gay, J; Taylor, D; Ueyama, K; Ohashi, Y; Kawahito, K; Tayama, E; Glueck, J; Nosé, Y

1997-07-01

The compact eccentric inlet port (C1E3) centrifugal blood pump was developed as a cardiopulmonary bypass (CPB) pump. The C1E3 pump incorporated a sealless design with a blood stagnation free structure. The pump impeller was magnetically coupled to the driver magnet in a sealless manner. To develop an atraumatic and antithrombogenic centrifugal pump without a shaft seal junction, a double pivot bearing system was introduced. Recently, a mass production model of the C1E3 was fabricated and evaluated. The ratio of the normalized index of hemolysis (NIH) of the C1E3 was 0.007 g/ 100 L, in comparison to the NIH of the BP-80, 0.018 g/ 100 L, each in a CPB condition of 5 L/min against 325 mm Hg. Both pumps were compared in identical in vitro circuits. To further evaluate the pumps during cardiopulmonary bypass for reliability and function, 6 h of CPB was performed on each of 8 bovines using either the C1E3 or BP-80 centrifugal pump. The BP-80 and C1E3 provided pump flows of 50-60 ml/kg/min without incident. The hemodynamics were stable, and the hematology and biochemistry data were within normal ranges. There were no statistically significant differences between the 2 groups. Concerning the plasma free hemoglobin values, a mass production model of the C1E3 pump had the same hemolysis levels as the BP-80. Our preliminary studies reveal that the C1E3 pump is reliable. Also, the C1E3 will satisfy clinical requirements as a cardiopulmonary bypass pump.

Regression of albuminuria and hypertension and arrest of severe renal injury by a losartan-hydrochlorothiazide association in a model of very advanced nephropathy.

PubMed

Arias, Simone Costa Alarcon; Valente, Carla Perez; Machado, Flavia Gomes; Fanelli, Camilla; Origassa, Clarice Silvia Taemi; de Brito, Thales; Camara, Niels Olsen Saraiva; Malheiros, Denise Maria Avancini Costa; Zatz, Roberto; Fujihara, Clarice Kazue

2013-01-01

Treatments that effectively prevent chronic kidney disease (CKD) when initiated early often yield disappointing results when started at more advanced phases. We examined the long-term evolution of renal injury in the 5/6 nephrectomy model (Nx) and the effect of an association between an AT-1 receptor blocker, losartan (L), and hydrochlorothiazide (H), shown previously to be effective when started one month after Nx. Adult male Munich-Wistar rats underwent Nx, being divided into four groups: Nx+V, no treatment; Nx+L, receiving L monotherapy; Nx+LH, receiving the L+H association (LH), and Nx+AHHz, treated with the calcium channel blocker, amlodipine, the vascular relaxant, hydralazine, and H. This latter group served to assess the effect of lowering blood pressure (BP). Rats undergoing sham nephrectomy (S) were also studied. In a first protocol, treatments were initiated 60 days after Nx, when CKD is at a relatively early stage. In a second protocol, treatments were started 120 days after Nx, when glomerulosclerosis and interstitial fibrosis are already advanced. In both protocols, L treatment promoted only partial renoprotection, whereas LH brought BP, albuminuria, tubulointerstitial cell proliferation and plasma aldosterone below pretreatment levels, and completely detained progression of renal injury. Despite normalizing BP, the AHHz association failed to prevent renal damage, indicating that the renoprotective effect of LH was not due to a systemic hemodynamic action. These findings are inconsistent with the contention that thiazides are innocuous in advanced CKD. In Nx, LH promotes effective renoprotection even at advanced stages by mechanisms that may involve anti-inflammatory and intrarenal hemodynamic effects, but seem not to require BP normalization.

Efficacy and safety of nifedipine GITS in Asians with hypertension: results of a post-marketing surveillance study in China.

PubMed

Runlin, Gao; Junren, Zhu; Guozhang, Liu; Weizhong, Zhang; Tingjie, Zhang; Ningling, Sun; Landen, Harald

2007-01-01

This post-marketing surveillance study assessed the efficacy, safety and tolerability of treatment with nifedipine GITS (gastrointestinal therapeutic system) in hypertensive patients with different risk profiles under normal daily practice conditions in China. A total of 7395 patients were included in 564 outpatient clinics. Patients received 30mg or 60mg of nifedipine GITS, which could be up- and down-titrated if necessary. Efficacy, safety and tolerability data were collected at up to three follow-up visits. Patient documentation was completed using standardised and barcoded case report forms. Descriptive and explorative analyses of the data were performed. At endpoint, 93% of patients were receiving 30mg of nifedipine GITS and 7% were taking 60mg of nifedipine GITS. The mean observation period was 9 +/- 7 weeks. At endpoint, the mean BP reduction was 27.7/14.8mm Hg; 43% of patients had a systolic BP <140mm Hg, and 58% had a diastolic BP <90mm Hg. BP control as recommended by international guidelines was achieved in 43.5% of all patients. A total of 3163 patients (42.8%) received additional antihypertensive medication, of which ACE inhibitors were most commonly used (40.7%), followed by beta-adrenoceptor antagonists (25.8%).Twenty-nine patients (0.4%) experienced a total of 39 adverse events. Subjective physicians' assessments of efficacy, tolerability and patient acceptance of nifedipine GITS treatment returned ratings of 'very good' and 'good' in 91-95% of each category. Nifedipine GITS proved to be effective and well tolerated for the treatment of hypertension in 7395 Chinese patients under normal daily practice conditions. The results confirm the findings and experience of previously performed clinical studies.

The use of 15-point hypomanic checklist in differentiating bipolar I and bipolar II disorder from major depressive disorder.

PubMed

He, Hongbo; Xu, Guiyun; Sun, Bin; Ouyang, Huiyi; Dang, Yamei; Guo, Yangbo; Miao, Guodong; Rios, Catherine; Akiskal, Hagop S; Lin, Kangguang

2014-01-01

Individuals with bipolar disorder (BP) are often misdiagnosed with major depressive disorder (MDD). In this study, we developed a Chinese version of 15-point hypomania scale (HCL-15) in order to determine its sensitivity and specificity in the diagnosis of BP and BP-II in particular. A total of 623 individuals suffering a major depressive episode (MDE) were systematically interviewed with both Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Patient Edition, and HCL-15. A cutoff score of 8 or more in HCL-15 was suggested for BP. Of the 623 depressed patients, 115 (18.5%) actually required a diagnosis of BP-I, and another 159 (25.5%) could be more appropriately diagnosed with BP-II, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The sensitivity of 15-HCL in detection of BP-II was 0.78 and 0.46 for BP-I; the specificity was 0.9 and 0.69, respectively. The specificity of HCL-15 for BP versus MDD was as high as 0.93. Approximately 60%-80% of all questions in the HCL-15 questionnaire revealed positive responses from patients, while items 11 and 12, measuring the consumption of alcohol, coffee and cigarettes, demonstrated a low positive response rate. The HCL-15 assessment scale was fairly sensitive and highly specific for a BP-II diagnosis but not for a BP-I diagnosis. Some items in the HCL-15 symptom list need to be further modified to better fit Chinese culture and customs. The HCL-15 scale could be a useful tool in clinical practice for screening individuals with BP-II in order to avoid a misdiagnosis of MDD. Copyright © 2014 Elsevier Inc. All rights reserved.

A Preliminary Examination of the Role of Emotion Differentiation in the Relationship between Borderline Personality and Urges for Maladaptive Behaviors

PubMed Central

Dixon-Gordon, Katherine L.; Chapman, Alexander L.; Weiss, Nicole H.; Rosenthal, M. Zachary

2015-01-01

Background and Objectives Impulsive, maladaptive, and potentially self-damaging behaviors are a hallmark feature of borderline personality (BP) pathology. Difficulties with emotion regulation have been implicated in both BP pathology and maladaptive behaviors. One facet of emotion regulation that may be particularly important in the relation between BP pathology and urges for maladaptive behaviors is emotion differentiation. Methods Over one day, 84 participants high (n = 34) and low (n = 50) in BP pathology responded to questions regarding state emotions and urges to engage in maladaptive behaviors using handheld computers, in addition to a measure of emotion-related difficulties controlling impulsive behaviors. Results Results revealed that individuals high in BP pathology reported greater emotion-related impulsivity as well as daily urges to engage in maladaptive behaviors. However, the association between BP group and both baseline emotion-related impulsivity and daily urges for maladaptive behaviors was strongest among individuals who had low levels of positive emotion differentiation. Conversely, negative emotion differentiation did not significantly moderate the relationships between BP group and either emotion-related difficulties controlling impulsive behaviors or state urges for maladaptive behaviors. Limitations Limitations to the present study include the reliance upon an analogue sample and the relatively brief monitoring period. Conclusions Despite limitations, these results suggest that, among individuals with high BP pathology, the ability to differentiate between positive emotions may be a particularly important target in the reduction of maladaptive behaviors. PMID:25750478

Bisphosphonate associated osteonecrosis of the jaw.

PubMed

Khan, Aliya A; Sándor, George K B; Dore, Edward; Morrison, Archibald D; Alsahli, Mazen; Amin, Faizan; Peters, Edmund; Hanley, David A; Chaudry, Sultan R; Lentle, Brian; Dempster, David W; Glorieux, Francis H; Neville, Alan J; Talwar, Reena M; Clokie, Cameron M; Mardini, Majd Al; Paul, Terri; Khosla, Sundeep; Josse, Robert G; Sutherland, Susan; Lam, David K; Carmichael, Robert P; Blanas, Nick; Kendler, David; Petak, Steven; Ste-Marie, Louis Georges; Brown, Jacques; Evans, A Wayne; Rios, Lorena; Compston, Juliet E

2009-03-01

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Race and sex differences in cardiovascular α-adrenergic and β-adrenergic receptor responsiveness in men and women with high blood pressure.

PubMed

Sherwood, Andrew; Hill, LaBarron K; Blumenthal, James A; Johnson, Kristy S; Hinderliter, Alan L

2017-05-01

Hypertension is associated with unfavorable changes in adrenergic receptor responsiveness, but the relationship of race and sex to adrenergic receptor responsiveness in the development of cardiovascular disease is unclear. This study examined α-adrenergic and ß-adrenergic receptor responsiveness in African-American and white men and women with untreated high blood pressure (BP) (HBP) and with normal BP. The study sample comprised 161 African-American and white men and women in the age range 25-45 years. Isoproterenol, a nonselective ß-adrenergic receptor agonist, was administered intravenously to determine the bolus dose required to increase heart rate by 25 bpm, an index of β-adrenergic receptor responsiveness. Similarly, phenylephrine, an α1-adrenergic receptor agonist, was administered to determine the bolus dose required to increase BP by 25 mmHg, an index of vascular α1-adrenergic receptor responsiveness. HBP (P < 0.01), male sex (P = 0.04), and higher BMI (P < 0.01) were all associated with reduced β-adrenergic receptor responsiveness, with a similar trend observed for African-American race (P = 0.07). Conversely, α1-adrenergic receptor responsiveness was increased in association with HBP (P < 0.01), female sex (P < 0.01), and African-American race (P < 0.01). In the early stages of hypertension, cardiovascular β-adrenergic receptors demonstrate blunted responsiveness, whereas conversely α1-adrenergic receptors exhibit increased responsiveness. This pattern of receptor changes is especially evident in men and African-Americans, is exacerbated by obesity, and may contribute to the development of cardiovascular disease.

Distribution of subcutaneous fat and the relationship with blood pressure in obese children and adolescents in Shandong, China.

PubMed

Zhang, Ying-xiu; Wang, Shu-rong

2015-03-01

The association between elevated blood pressure (BP) and childhood obesity has been documented in several studies. However, the association between BP and body fat distribution in obese children remains poorly understood. We examined the distribution of subcutaneous fat and its association with BP in obese children and adolescents. Data for this study were obtained from a large cross-sectional survey of school children. A total of 38,873 students (19,485 boys and 19,388 girls) aged 7-17 years participated in this study. Height, weight, BP, subscapular and triceps skinfold thicknesses (SFT) of all subjects were measured. Obesity was defined by using body mass index (BMI) criteria recommended by the Working Group on Obesity in China. A total of 3,579 obese children and adolescents (2,367 boys and 1,212 girls) were examined. Most of the obese children and adolescents had high subcutaneous fat. However, a small number of the obese individuals had a lower SFT levels. Obese children and adolescents with high SFT and central distribution had higher BP levels than those with low SFT and peripheral distribution. Obese children and adolescents assessed by BMI might not necessarily have a high SFT level. The BP level of obese individuals is associated with the level and distribution pattern of SFT. Additional measurement of SFT is better than BMI alone to help identify high BP risks. © 2015 John Wiley & Sons Ltd.

Synergistic Effects of the Membrane Actions of Cecropin-Melittin Antimicrobial Hybrid Peptide BP100

PubMed Central

Ferre, Rafael; Melo, Manuel N.; Correia, Ana D.; Feliu, Lidia; Bardají, Eduard; Planas, Marta; Castanho, Miguel

2009-01-01

BP100 (KKLFKKILKYL-NH2) is a short cecropin A-melittin hybrid peptide, obtained through a combinatorial chemistry approach, which is highly effective in inhibiting both the in vitro and in vivo growth of economically important plant pathogenic Gram-negatives. The intrinsic Tyr fluorescence of BP100 was taken advantage of to study the peptide's binding affinity and damaging effect on phospholipid bilayers modeling the bacterial and mammalian cytoplasmic membranes. In vitro cytotoxic effects of this peptide were also studied on mammalian fibroblast cells. Results show a stronger selectivity of BP100 toward anionic bacterial membrane models as indicated by the high obtained partition constants, one order of magnitude greater than for the neutral mammalian membrane models. For the anionic systems, membrane saturation was observed at high peptide/lipid ratios and found to be related with BP100-induced vesicle permeabilization, membrane electroneutrality, and vesicle aggregation. Occurrence of BP100 translocation was unequivocally detected at both high and low peptide/lipid ratios using a novel and extremely simple method. Moreover, cytotoxicity against mammalian models was reached at a concentration considerably higher than the minimum inhibitory concentration. Our findings unravel the relationships among the closely coupled processes of charge neutralization, permeabilization, and translocation in the mechanism of action of antimicrobial peptides. PMID:19254540

Trends in prevalence, awareness, treatment and control of high blood pressure in the Seychelles between 1989 and 2013.

PubMed

Heiniger, Samuel; Viswanathan, Bharathi; Gedeon, Jude; Paccaud, Fred; Bovet, Pascal

2017-07-01

Limited data are available in the African region on trends in blood pressure (BP) and awareness, treatment and control rates. We examined trends in these indicators for a 25-year period in the Seychelles, a rapidly developing small island state in the African region. Population-based surveys of adults aged 25-64 years were performed in 1989, 1994, 2004 and 2013 using nearly identical methods for all surveys. BP was based on the average of the second and third readings. Data were age-standardized. Between 1989 and 2013, mean SBP decreased in older adults (but increased in younger adults) and mean DBP decreased in all age categories, despite a marked secular increase in mean BMI. At age 25-64 years, the proportions with BP at least 140/90 mmHg decreased from 44%/33% (men/women) in 1989 to 37%/22% in 2013. The proportions of persons aware of having high BP (among those with BP ≥ 140/90 or treatment) increased from 40%/63% (men/women) in 1989 to 65%/80% in 2013; the proportions under treatment (among aware) increased from 37%/49% to 64%/78%; and the proportions with controlled BP (among treated) increased from 10%/16% to 34%/61%. Awareness was associated with female sex, age, obesity and diabetes; treatment with age, obesity, low alcohol consumption and diabetes; and control with female sex, age and high socio-economic status. In 2013, the main classes of antihypertensive medications were used in similar proportions, and 64.5% received at least two medications. The prevalence of high BP (≥140/90 mmHg) decreased over time, which paralleled improved detection and control of hypertension. The identified associated factors should be considered when strengthening BP control programs.

Impact of long-term burden of excessive adiposity and elevated blood pressure from childhood on adulthood left ventricular remodeling patterns: the Bogalusa Heart Study.

PubMed

Lai, Chin-Chih; Sun, Dianjianyi; Cen, Ruiqi; Wang, Jian; Li, Shengxu; Fernandez-Alonso, Camilo; Chen, Wei; Srinivasan, Sathanur R; Berenson, Gerald S

2014-10-14

Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and LV hemodynamic variables. The aim of this study was to examine the impact of cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adulthood LVH and LV geometric remodeling patterns. This longitudinal study consisted of 1,061 adults, age 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood, with a mean follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined-normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH)-all on the basis of LV mass indexed for body height (m(2.7)) and relative wall thickness. Higher values of BMI and systolic and diastolic BP in childhood and adulthood, as well as total AUC and incremental AUC, were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP in childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not with CR. Importantly, all of these measures of BMI had a consistently and significantly greater influence on EH than did measures of BP. These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Various 30 and 69 bp deletion variants of the Epstein-Barr virus LMP1 may arise by homologous recombination in nasopharyngeal carcinoma of Tunisian patients.

PubMed

Hadhri-Guiga, Boutheina; Khabir, Abdel-Majid; Mokdad-Gargouri, Raja; Ghorbel, Abdel-Monem; Drira, Mohamed; Daoud, Jamel; Frikha, Mounir; Jlidi, Rachid; Gargouri, Ali

2006-01-01

Nasopharyngeal carcinoma (NPC) occurs with a striking geographic distribution, it is endemic in certain areas of Southeast Asia and North Africa. NPC is tightly linked to Epstein-Barr virus (EBV), however, only a small subset of EBV genes are expressed, among them the latent membrane protein 1 (LMP1). LMP1 is considered as the main EBV oncoprotein and its 30 bp deleted-variant has been reported to be more prevalent in biopsies of NPC. We have assessed the 30 bp deletion and the XhoI polymorphisms of the BNLF1 gene in 30 peripheral bloods of NPC patients and 62 nasopharyngeal biopsies, 42 being confirmed as undifferentiated nasopharyngeal carcinoma and 20 are normal nasopharyngeal epithelium cells. Our results show that 100% of individuals retained the XhoI restriction site. A rare NPC variant, having a 69 bp deletion in the C-terminus region of the BNLF1 gene, covering the 30 bp deletion, was found in two NPC biopsies. The deleted 30 and 69 bp deleted-variants are significantly (p = 0.006) more frequent in NPC (71.42%) than in control biopsies (52%). In peripheral blood of NPC patients, the deleted-variants (47%) are also lower than in tumor tissues (p = 0.0004), suggesting that the deletion could be associated with a risk of tumor genesis. Direct repeats, located at the extremities of the 30 and 69 bp deletions, should be involved in this process. We propose that other deletions could be found since another similar direct repeat is present at the vicinity of the former ones.

Submesoscale characteristics and transcription of a fatty acid elongase gene from a freshwater green microalgae, Myrmecia incisa Reisigl

NASA Astrophysics Data System (ADS)

Yu, Shuiyan; Liu, Shicheng; Li, Chunyang; Zhou, Zhigang

2011-01-01

Myrmecia incisa is a green coccoid freshwater microalgae, which is rich in arachidonic acid (ArA, C20: 4ω-6, δ5, 8, 11, 14), a long chain polyunsaturated fatty acid (PUFA), especially under nitrogen starvation stress. A cDNA library of M. incisa was constructed with λ phage vectors and a 545 nt expressed sequence tag (EST) was screened from this library as a putative elongase gene due to its 56% and 49% identity to Marchantia polymorpha L. and Ostreococcus tauri Courties et Chrétiennot-Dinet, respectively. Based upon this EST sequence, an elongase gene designated MiFAE was isolated from M. incisa via 5'/3' rapid amplification of cDNA ends (RACE). The cDNA sequence was 1 331 bp long and included a 33 bp 5'-untranslated region (UTR) and a 431 bp 3'-UTR with a typical poly-A tail. The 867 bp ORF encoded a predicted protein of 288 amino acids. This protein was characterized by a conserved histidine-rich box and a MYxYY motif that was present in other members of the elongase family. The genomic DNA sequence of MiFAE was found to be interrupted by three introns with splicing sites of Introns I (81 bp), II (81 bp), and III (67 bp) that conformed to the GT-AG rule. Quantitative real-time PCR showed that the transcription level of MiFAE in this microalga under nitrogen starvation was higher than that under normal condition. Prior to the ArA content accumulation, the transcription of MiFAE was enhanced, suggesting that it was possibly responsible for the ArA accumulation in this microalga cultured under nitrogen starvation conditions.

Hybrid Black Phosphorus/Zero-Dimensional Quantum Dot Phototransistors: Tunable Photodoping and Enhanced Photoresponsivity.

PubMed

Lee, A-Young; Ra, Hyun-Soo; Kwak, Do-Hyun; Jeong, Min-Hye; Park, Jeong-Hyun; Kang, Yeon-Su; Chae, Weon-Sik; Lee, Jong-Soo

2018-05-09

Recently, black phosphorus (BP) with direct band gap exhibited excellent potential for optoelectronic applications because of its high charge carrier mobility and low dark current as well as the variable band gap of 0.3-1.5 eV depending on the number of layers. However, few-layer BP-based phototransistors (photo-FETs) have been limited in sensitivity and wavelength selectivity. To overcome the drawback of these photo-FETs, we studied hybrid photo-FETs combined with the novel properties of the two materials between the channel and sensitizer layers. By combining a strong absorbance of a quantum dot (QD) layer and a two-dimensional layer material with high carrier mobility, the hybrid photo-FETs are expected to produce high-performance photodetectors that can effectively control the responsivity, detectivity, and response time. In this study, we demonstrate that the photogenerated carriers formed from QD sensitizer layers migrate to the BP transport layer with high charge mobility and not only improve the photodetector performance but also enhance the photodoping effect of the BP transport layer with an ambipolar characteristic by electrons transferred from n-type CdSe QDs or holes injected from p-type PbS QDs. The responsivity and detectivity of hybrid BP/0D photo-FETs exhibit 1.16 × 10 9 A W -1 and 7.53 × 10 16 Jones for the BP/CdSe QD photo-FET and 5.36 × 10 8 A W -1 and 1.89 × 10 16 Jones for the BP/PbS QD photo-FET, respectively. The photocurrent rise (τ rise ) and decay (τ decay ) times were τ rise = 0.406 s and τ decay = 0.815 s for BP/CdSe QD photo-FET and τ rise = 0.576 s and τ decay = 0.773 s for BP/PbS QD photo-FET, respectively.

Enhanced Performance of Field-Effect Transistors Based on Black Phosphorus Channels Reduced by Galvanic Corrosion of Al Overlayers.

PubMed

Lee, Sangik; Yoon, Chansoo; Lee, Ji Hye; Kim, Yeon Soo; Lee, Mi Jung; Kim, Wondong; Baik, Jaeyoon; Jia, Quanxi; Park, Bae Ho

2018-06-06

Two-dimensional (2D)-layered semiconducting materials with considerable band gaps are emerging as a new class of materials applicable to next-generation devices. Particularly, black phosphorus (BP) is considered to be very promising for next-generation 2D electrical and optical devices because of its high carrier mobility of 200-1000 cm 2 V -1 s -1 and large on/off ratio of 10 4 to 10 5 in field-effect transistors (FETs). However, its environmental instability in air requires fabrication processes in a glovebox filled with nitrogen or argon gas followed by encapsulation, passivation, and chemical functionalization of BP. Here, we report a new method for reduction of BP-channel devices fabricated without the use of a glovebox by galvanic corrosion of an Al overlayer. The reduction of BP induced by an anodic oxidation of Al overlayer is demonstrated through surface characterization of BP using atomic force microscopy, Raman spectroscopy, and X-ray photoemission spectroscopy along with electrical measurement of a BP-channel FET. After the deposition of an Al overlayer, the FET device shows a significantly enhanced performance, including restoration of ambipolar transport, high carrier mobility of 220 cm 2 V -1 s -1 , low subthreshold swing of 0.73 V/decade, and low interface trap density of 7.8 × 10 11 cm -2 eV -1 . These improvements are attributed to both the reduction of the BP channel and the formation of an Al 2 O 3 interfacial layer resulting in a high- k screening effect. Moreover, ambipolar behavior of our BP-channel FET device combined with charge-trap behavior can be utilized for implementing reconfigurable memory and neuromorphic computing applications. Our study offers a simple device fabrication process for BP-channel FETs with high performance using galvanic oxidation of Al overlayers.

Antihypertensive and cardioprotective effects of pumpkin seed oil.

PubMed

El-Mosallamy, Aliaa E M K; Sleem, Amany A; Abdel-Salam, Omar M E; Shaffie, Nermeen; Kenawy, Sanaa A

2012-02-01

Pumpkin seed oil is a natural product commonly used in folk medicine for treatment of prostatic hypertrophy. In the present study, the effects of treatment with pumpkin seed oil on hypertension induced by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg /kg/day) in rats were studied and compared with those of the calcium channel blocker amlodipine. Pumpkin seed oil (40 or 100 mg/kg), amlodipine (0.9 mg/kg), or vehicle (control) was given once daily orally for 6 weeks. Arterial blood pressure (BP), heart rate, electrocardiogram (ECG) changes, levels of serum nitric oxide (NO) (the concentrations of nitrite/nitrate), plasma malondialdehyde (MDA), blood glutathione, and erythrocytic superoxide dismutase activity were measured. Histopathological examination of heart and aorta was conducted as well. L-NAME administration resulted in a significant increase in BP starting from the second week. Pumpkin seed oil or amlodipine treatment significantly reduced the elevation in BP by L-NAME and normalized the L-NAME-induced ECG changes-namely, prolongation of the RR interval, increased P wave duration, and ST elevation. Both treatments significantly decreased the elevated levels of MDA and reversed the decreased levels of NO metabolites to near normal values compared with the L-NAME-treated group. Amlodipine also significantly increased blood glutathione content compared with normal (but not L-NAME-treated) rats. Pumpkin seed oil as well as amlodipine treatment protected against pathological alterations in heart and aorta induced by L-NAME. In conclusion, this study has shown that pumpkin seed oil exhibits an antihypertensive and cardioprotective effects through a mechanism that may involve generation of NO.

A novel deletion/insertion mutation in the mRNA transcribed from one {alpha}1(I) collagen allele in a family with dominant type III OI and germline mosaicism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, O.; Masters, C.; Lewis, M.B.

1994-09-01

In an 8-year-old girl and her father, both of whom have severe type III OI, we have previously used RNA/RNA hybrid analysis to demonstrate a mismatch in the region of {alpha}1(I) mRNA coding for aa 558-861. We used SSCP to further localize the abnormality to a subregion coding for aa 579-679. This region was subcloned and sequenced. Each patient`s cDNA has a deletion of the sequences coding for the last residue of exon 34, and all of exons 35 and 36 (aa 604-639), followed by an insertion of 156 nt from the 3{prime}-end of intron 36. PCR amplification of leukocytemore » DNA from the patients and the clinically normal paternal grandmother yielded two fragments: a 1007 bp fragment predicted from normal genomic sequences and a 445 bp fragment. Subcloning and sequencing of the shorter genomic PCR product confirmed the presence of a 565 bp genomic deletion from the end of exon 34 to the middle of intron 36. The abnormal protein is apparently synthesized and incorporated into helix. The inserted nucleotides are in frame with the collagenous sequence and contain no stop codons. They encode a 52 aa non-collagenous region. The fibroblast procollagen of the patients has both normal and electrophoretically delayed pro{alpha}(I) bands. The electrophoretically delayed procollagen is very sensitive to pepsin or trypsin digestion, as predicted by its non-collagenous sequence, and cannot be visualized as collagen. This unique OI collagen mutation is an excellent candidate for molecular targeting to {open_quotes}turn off{close_quotes} a dominant mutant allele.« less

Electrostatic Functionalization and Passivation of Water-Exfoliated Few-Layer Black Phosphorus by Poly Dimethyldiallyl Ammonium Chloride and Its Ultrafast Laser Application.

PubMed

Feng, Qingliang; Liu, Hongyan; Zhu, Meijie; Shang, Jing; Liu, Dan; Cui, Xiaoqi; Shen, Diqin; Kou, Liangzhi; Mao, Dong; Zheng, Jianbang; Li, Chun; Zhang, Jin; Xu, Hua; Zhao, Jianlin

2018-03-21

Few-layer black phosphorus (BP) which exhibits excellent optical and electronic properties, has great potential applications in nanodevices. However, BP inevitably suffers from the rapid degradation in ambient air because of the high reactivity of P atoms with oxygen and water, which greatly hinders its wide applications. Herein, we demonstrate the electrostatic functionalization as an effective way to simultaneously enhance the stability and dispersity of aqueous phase exfoliated few-layer BP. The poly dimethyldiallyl ammonium chloride (PDDA) is selected to spontaneously and uniformly adsorb on the surface of few-layer BP via electrostatic interaction. The positive charge-center of the N atom of PDDA, which passivates the lone-pair electrons of P, plays a critical role in stabilizing the BP. Meanwhile, the PDDA could serve as hydrophilic ligands to improve the dispersity of exfoliated BP in water. The thinner PDDA-BP nanosheets can stabilize in both air and water even after 15 days of exposure. Finally, the uniform PDDA-BP-polymer film was used as a saturable absorber to realize passive mode-locking operations in a fiber laser, delivering a train of ultrafast pulses with the duration of 1.2 ps at 1557.8 nm. This work provides a new way to obtain highly stable few-layer BP, which shows great promise in ultrafast optics application.

Graded replacement of maize grain with molassed sugar beet pulp modulated ruminal microbial community and fermentation profile in vitro.

PubMed

Münnich, Matthias; Khol-Parisini, Annabella; Klevenhusen, Fenja; Metzler-Zebeli, Barbara U; Zebeli, Qendrim

2018-02-01

Molassed sugar beet pulp (Bp) is a viable alternative to grains in cattle nutrition for reducing human edible energy input. Yet little is known about the effects of high inclusion rates of Bp on rumen microbiota. This study used an in vitro approach and the quantitative polymerase chain reaction technique to establish the effects of a graded replacement of maize grain (MG) by Bp on the ruminal microbial community, fermentation profile and nutrient degradation. Six different amounts of Bp (0-400 g kg -1 ), which replaced MG in the diet, were tested using the in vitro semi-continuous rumen simulation technique. The increased inclusion of Bp resulted in greater dietary content and degradation of neutral detergent fibre (P < 0.01). Further, Bp feeding enhanced (P < 0.01) the abundance of genus Prevotella and shifted (P < 0.01) the short-chain fatty acid patterns in favour of acetate and propionate and at the expense of butyrate. A total replacement of MG with Bp resulted in an increased daily methane production (P < 0.01). Results suggest positive effects of the replacement of MG by Bp especially in terms of stimulating ruminal acetate and propionate fermentation. However, high replacement rates of Bp resulted in lowered utilization of ammonia and higher ruminal methane production. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Systematic Testing of Belief-Propagation Estimates for Absolute Free Energies in Atomistic Peptides and Proteins.

PubMed

Donovan-Maiye, Rory M; Langmead, Christopher J; Zuckerman, Daniel M

2018-01-09

Motivated by the extremely high computing costs associated with estimates of free energies for biological systems using molecular simulations, we further the exploration of existing "belief propagation" (BP) algorithms for fixed-backbone peptide and protein systems. The precalculation of pairwise interactions among discretized libraries of side-chain conformations, along with representation of protein side chains as nodes in a graphical model, enables direct application of the BP approach, which requires only ∼1 s of single-processor run time after the precalculation stage. We use a "loopy BP" algorithm, which can be seen as an approximate generalization of the transfer-matrix approach to highly connected (i.e., loopy) graphs, and it has previously been applied to protein calculations. We examine the application of loopy BP to several peptides as well as the binding site of the T4 lysozyme L99A mutant. The present study reports on (i) the comparison of the approximate BP results with estimates from unbiased estimators based on the Amber99SB force field; (ii) investigation of the effects of varying library size on BP predictions; and (iii) a theoretical discussion of the discretization effects that can arise in BP calculations. The data suggest that, despite their approximate nature, BP free-energy estimates are highly accurate-indeed, they never fall outside confidence intervals from unbiased estimators for the systems where independent results could be obtained. Furthermore, we find that libraries of sufficiently fine discretization (which diminish library-size sensitivity) can be obtained with standard computing resources in most cases. Altogether, the extremely low computing times and accurate results suggest the BP approach warrants further study.

HIGH LEVEL OF PERSISTENCE OF PEDIATRIC BIPOLAR-I DISORDER FROM CHILDHOOD ONTO ADOLESCENT YEARS: A FOUR YEAR PROSPECTIVE LONGITUDINAL FOLLOW-UP STUDY

PubMed Central

Wozniak, Janet; Petty, Carter R.; Schreck, Meghan; Moses, Alana; Faraone, Stephen V.; Biederman, Joseph

2011-01-01

Objective To examine the longitudinal course of pediatric bipolar (BP)-I disorder in youth transitioning from childhood into adolescence. Methods We conducted a four-year prospective follow-up study of 78 youth with BP-I disorder 6-17 years old at ascertainment followed up into adolescent years (13.4±3.9 years). All subjects were comprehensively assessed with structured diagnostic interviews, neuropsychological testing, psychosocial, educational and treatment history assessments. BP disorder was considered persistent if subjects met full criteria for DSM-IV BP-I disorder at follow-up. Results Of 78 BP-I participating youth subjects, 57 (73.1%), continued to meet full diagnostic criteria for BP-I Disorder. Of those with a non-persistent course, only 6.4% (n=5) were euthymic (i.e., syndromatic and symptomatic remission) at the 4-year follow-up and were not receiving pharmacotherapy for the disorder. The other non-persistent cases either continued to have subthreshold BP-I disorder (n=5, 6.4%), met full (n=3, 3.8%) or subthreshold (n=1, 1.3%) criteria for major depression, or were euthymic but were treated for the disorder (n=7, 9.0%). Full persistence was associated with higher rates of major depression and disruptive behavior disorders at the follow-up assessment and higher use of stimulant medicines at the baseline assessment. Non-Peristent BP-I was also characterized by high levels of dysfunction and morbidity. Conclusions This four-year follow-up shows that the majority of BP-I disorder youth continue to experience persistent disorder into their mid and late adolescent years and its persistence is associated with high levels of morbidity and disability. Persistence of subsyndromal forms of bipolar disorder was also associated with dysfunction and morbidity. PMID:21683960

Psychosocial Factors Are Associated With Blood Pressure Progression Among African Americans in the Jackson Heart Study

PubMed Central

Sims, Mario; Higginbotham, John C.; Crowther, Martha R.; Wyatt, Sharon B.; Musani, Solomon K.; Payne, Thomas J.; Fox, Ervin R.; Parton, Jason M.

2016-01-01

BACKGROUND Research that examines the associations of psychosocial factors with incident hypertension among African Americans (AA) is limited. Using Jackson Heart Study (JHS) data, we examined associations of negative affect and stress with incident hypertension and blood pressure (BP) progression among AA. METHODS Our sample consisted of 1,656 normotensive participants at baseline (2000–2004) (mean age 47±12; 61% women). We investigated associations of negative affect (cynical distrust, anger-in, anger-out, and depressive symptoms) and stress (perceived stress, weekly stress inventory (WSI)-event, WSI-impact, and major life events) with BP progression (an increase by one BP stage as defined by JNC VII) and incident hypertension by examination 2 (2005–2008). Poisson regression analysis was utilized to examine the prevalence ratios (PRs; 95% confidence interval (CI)) of BP tracking and incident hypertension with psychosocial factors, adjusting for baseline age, sex, socioeconomic status (SES), and hypertension risk factors. RESULTS Fifty-six percentage of the sample (922 cases) had BP progression from 2005 to 2008. After adjustment for age, sex, and SES, a high anger-out score was associated with a 20% increased risk of BP progression compared to a low anger-out score (PR 1.20; 95% CI 1.05–1.36). High depressive symptoms score was associated with BP progression in the age, sex, and SES-adjusted model (PR 1.14; 95% CI 1.00–1.30). High WSI-event scores were associated with BP progression in the fully adjusted model (PR 1.21; 95% CI 1.04–1.40). We did not observe significant associations with any of the psychosocial measures and incident hypertension. CONCLUSIONS Psychosocial factors were associated with BP progression, with the strongest evidence for number of stressful events that occurred. PMID:26964661

Adjusting for treatment effects in studies of quantitative traits: antihypertensive therapy and systolic blood pressure.

PubMed

Tobin, Martin D; Sheehan, Nuala A; Scurrah, Katrina J; Burton, Paul R

2005-10-15

A population-based study of a quantitative trait may be seriously compromised when the trait is subject to the effects of a treatment. For example, in a typical study of quantitative blood pressure (BP) 15 per cent or more of middle-aged subjects may take antihypertensive treatment. Without appropriate correction, this can lead to substantial shrinkage in the estimated effect of aetiological determinants of scientific interest and a marked reduction in statistical power. Correction relies upon imputation, in treated subjects, of the underlying BP from the observed BP having invoked one or more assumptions about the bioclinical setting. There is a range of different assumptions that may be made, and a number of different analytical models that may be used. In this paper, we motivate an approach based on a censored normal regression model and compare it with a range of other methods that are currently used or advocated. We compare these methods in simulated data sets and assess the estimation bias and the loss of power that ensue when treatment effects are not appropriately addressed. We also apply the same methods to real data and demonstrate a pattern of behaviour that is consistent with that in the simulation studies. Although all approaches to analysis are necessarily approximations, we conclude that two of the adjustment methods appear to perform well across a range of realistic settings. These are: (1) the addition of a sensible constant to the observed BP in treated subjects; and (2) the censored normal regression model. A third, non-parametric, method based on averaging ordered residuals may also be advocated in some settings. On the other hand, three approaches that are used relatively commonly are fundamentally flawed and should not be used at all. These are: (i) ignoring the problem altogether and analysing observed BP in treated subjects as if it was underlying BP; (ii) fitting a conventional regression model with treatment as a binary covariate; and (iii) excluding treated subjects from the analysis. Given that the more effective methods are straightforward to implement, there is no argument for undertaking a flawed analysis that wastes power and results in excessive bias. Copyright (c) 2005 John Wiley & Sons, Ltd.

ELECTRONIC STRUCTURE AND LINEAR OPTICAL PROPERTIES OF MIXED ALKALI-METAL BOROPHOSPHATES (LiK2BP2O8, Li3K2BP4O14): A FIRST-PRINCIPLES STUDY

NASA Astrophysics Data System (ADS)

Zhang, Bei; Jing, Qun; Yang, Zhihua; Wang, Ying; Su, Xin; Pan, Shilie; Zhang, Jun

2013-07-01

LiK2BP2O8 and Li3K2BP4O14 are synthesized by high-temperature solution method with the same elements, while contain different fundamental building units. Li3K2BP4O14 is a novel P-O-P linking structure which gives a rare example of violation of Pauling's fourth rule. The electronic structures of LiK2BP2O8 and Li3K2BP4O14 are investigated by density functional calculations. Direct gaps of 5.038 eV (LiK2BP2O8) and 5.487 eV (Li3K2BP4O14) are obtained. By analyzing the density of states (DOS) of LiK2BP2O8 and Li3K2BP4O14, the P-O-P linking in fundamental building units of Li3K2BP4O14 crystal is proved theoretically. Based on the electronic properties, the linear optical information is captured.

Perfect 24-h management of hypertension: clinical relevance and perspectives.

PubMed

Kario, K

2017-04-01

Out-of-office blood pressure (BP) measured by home BP monitoring, or ambulatory BP monitoring, was demonstrated to be superior to office BP for the prediction of cardiovascular events. The J-HOP study of a nationwide Japanese cohort demonstrated that morning home BP is the best stroke predictor. In the prospective HONEST study of >21 000 hypertensives, on-treatment morning home BP was shown to be a strong predictor both of future coronary artery disease and stroke events. In subjects whose office BP was maintained at ⩾150 mm Hg, there was no increase in cardiovascular events when their morning systolic BP was well-controlled at <125 mm Hg. Since Asians show greater morning BP surges, it is particularly important for Asians to achieve 'perfect 24-hr BP control,' that is, the 24-h BP level, nocturnal BP dipping and BP variability including morning surge. The morning BP surge and the extremes of disrupted circadian rhythm (riser and extreme dipper patterns) are independent risks for stroke in hypertensives. A morning BP-guided approach is thus the first step toward perfect 24-h BP control, followed by the control of nocturnal hypertension. In the resonance hypothesis, the synergistic resonance of BP variability phenotypes would produce an extraordinary large 'dynamic BP surge' that can trigger a cardiovascular event, especially in high-risk patients with systemic hemodynamic atherothrombotic syndrome, a vicious cycle of exaggerated BP variability and vascular disease. In the future, information and communications technology and artificial intelligence technology with the innovation of wearable continuous surge BP monitoring will contribute to 'anticipation medicine' with the goal of zero cardiovascular events.

Molecular cloning and promoter analysis of squalene synthase and squalene epoxidase genes from Betula platyphylla.

PubMed

Zhang, Mengyan; Wang, Siyao; Yin, Jing; Li, Chunxiao; Zhan, Yaguang; Xiao, Jialei; Liang, Tian; Li, Xin

2016-09-01

Betula platyphylla is a rich repository of pharmacologically active secondary metabolites known as birch triterpenoids (TBP). Here, we cloned the squalene synthase (SS) and squalene epoxidase genetic (SE) sequences from B. platyphylla that encode the key enzymes that are involved in triterpenoid biosynthesis and analyzed the conserved domains and phylogenetics of their corresponding proteins. The full-length sequence of BpSS is 1588 bp with a poly-A tail, which contained an open reading frame (ORF) of 1241 bp that encoded a protein of 413 amino acids. Additionally, the BpSE full-length sequence of 2040 bp with a poly-A tail was also obtained, which contained an ORF of 1581 bp encoding a protein of 526 amino acids. Their organ-specific expression patterns in 4-week-old tissue culture seedlings of B. platyphylla were detected by real-time PCR and showed that they were all highly expressed in leaves, as compared to stem and root tissues. Additionaly, both BpSS and BpSE were enhanced following stimulation with ethephon and MeJA. The expression of BpSS was enhanced by ABA, whereas BpSE was not. The SA treatment did not affect the BpSS and BpSE transcripts notably. Using a genome walking approach, promoter sequences of 965 and 1193 bp, respectively, for BpSS and BpSE were isolated, and they revealed several key cis-regulatory elements known to be involved in the response to phytohormone and abiotic plant stress. We also found that the BpSS protein is localized in the cytoplasm. Opening reading frames of BpSS and BpSE were ligated into yeast expression plasmid pYES2 under control of GAL1 promoter and introduced into the yeast INVScl1 strain. The transformants were cultured for 12 h, the squalene content of galactose-induced BpSS expression yeast cells was 13.2 times of control (empty vector control yeast cells) by high-performance liquid chromatography (HPLC) test method. And, the squalene epoxidase activity of induced BpSE expression yeast cell was about 11.8 times of control. These indicated that we cloned birch BpSS and BpSE that were indeed involved in the synthesis of triteropenoids. This is the first report wherein SS and SE from B. platyphylla were cloned and may be of significant interest to understand the regulatory role of SS and SE in the triterpenoids biosynthesis of B. platyphylla. This is the first report wherein SS and SE from B. platyphylla were cloned and may be of significant interest to understand the regulatory role of SS and SE in the biosynthesis of birch triterpenoids.

Ten cases of severe oral lichen planus showing granular C3 deposition in oral mucosal basement membrane zone.

PubMed

Hashimoto, Takashi; Fukuda, Aoi; Himejima, Akio; Morita, Shosuke; Tsuruta, Daisuke; Koga, Hiroshi; Krol, Rafal P; Ishii, Norito

2015-01-01

Oral lichen planus (OLP) may show depositions of immunoglobulins and complement components in oral mucosal basement membrane zone (BMZ) in direct immunofluorescence, although these finding are not frequently seen. We collected and examined ten cases of severe OLP showing granular C3 deposition in BMZ. In addition to clinical, histopathological and direct immunofluorescence assessments, we performed various immune-serological tests, including indirect immunofluorescence of normal human skin and 1M NaCl-split skin, immunoblotting of normal human epidermal and dermal extracts, recombinant proteins of BP180 NC16a and C-terminal domains, concentrated culture supernatant of HaCaT cells and purified human laminin-332, and enzyme-linked immunosorbent assays for BP230 and BP180. Direct immunofluorescence showed C3 deposition in BMZ exclusively of granular pattern in 7 cases and of both granular and linear patterns in 3 cases. The 10 cases showed no positive reactivity for either IgG or IgA antibodies in any immuno-serological tests. Detailed analyses of clinical, histopathological and immunological findings revealed striking female prevalence, although other parameters were in general characteristic of OLP. Granular C3 deposition in oral BMZ may be one of the characteristic features of severe OLP, although mechanisms for C3 deposition and its pathogenic role in OLP are currently unknown.

Holocene pollen and sediment record from the tangle lakes area, central Alaska

USGS Publications Warehouse

Ager, Thomas A.; Sims, John D.

1981-01-01

Pollen and sediments have been analyzed from a 5.5 meter‐length core of lacustrine sediments from Tangle Lakes, in the Gulkana Upland south of the Alaska Range (63 ° 01 ‘ 46”; N. latitude, 146° 03 ‘ 48 “ W. longitude). Radiocarbon ages indicate that the core spans the last 4700 years. The core sediments are sandy silt and silty clay; the core shows distinct rhythmic laminations in the lower 398 cm. The laminae appear to be normally graded; peat fibers and macerated plant debris are more abundant near the tops of the laminae. Six volcanic‐ash layers are present in the upper 110 cm of the core.Present‐day vegetation of the Tangle Lakes area is mesic shrub tundra and open spruce woodland, with scattered patches of shrub willow (Salix), balsam poplar (P. balsamifera), spruce (Picea), paper birch (Betula papyrifera), and alder (Alnus). Pollen analysis of 27 core samples suggests that this vegetation type has persisted throughout the past 4700 years, except for an apparently substantial increase in Picea beginning about 3500 years B.P. Percentages of Picea pollen are very low (generally 1–3 percent) in the lower 2 meters of core (ca. 4700 to 3500 years B.P.), but rise to 13–18 percent in the upper 3.4 meters (ca. 3500 years B.P. to present). Previously reported data from this area indicate that Picea trees initially arrived in the Tangle Lakes area about 9100 years B.P., at least 2.5 to 3 thousand years after deglaciation of the region. The present investigation suggests that Picea trees became locally scarce or died out sometime after about 9000 years B.P. but before 4700 years B.P., then reinvaded the area about 3500 years B.P. If this extrapolated age for the Picea reinvasion is accurate it suggests that local expansion of the Picea population coincides with the onset of a Neoglacial interval of cooler, moister climate. This is an unexpected result, because intervals of cooler climate generally coincide with lowering of the altitudinal limit of trees. In this case, improved moisture conditions may have promoted spruce growth and reproduction in spite of somewhat cooler temperatures.Previous pollen records from Alaska suggest that Artemisia pollen contributed little to the pollen rain of most taiga and tundra sites during Holocene time. The pollen record from Tangle Lakes, however shows rather high percentages (7–13 percent) of Artemisia deposited during the approximate time interval 4700 to 3500 years B.P. Local habitats that have well‐drained soils derived from glacial deposits support patches of Artemisia telesii and other Artemisia species. These local habitats may account for the source of Artemisiapollen deposited in the Tangle Lakes area during Holocene time.

Variable range hopping electric and thermoelectric transport in anisotropic black phosphorus

DOE PAGES

Liu, Huili; Sung Choe, Hwan; Chen, Yabin; ...

2017-09-05

Black phosphorus (BP) is a layered semiconductor with a high mobility of up to ~1000 cm 2 V -1 s -1 and a narrow bandgap of ~0.3 eV, and shows potential applications in thermoelectrics. In stark contrast to most other layered materials, electrical and thermoelectric properties in the basal plane of BP are highly anisotropic. In order to elucidate the mechanism for such anisotropy, we fabricated BP nanoribbons (~100 nm thick) along the armchair and zigzag directions, and measured the transport properties. It is found that both the electrical conductivity and Seebeck co efficient increase with temperature, a behavior contradictorymore » to that of traditional semiconductors. The three-dimensional variable range hopping model is adopted to analyze this abnormal temperature dependency of electrical conductivity and Seebeck coefficient. Furthermore, the hopping transport of the BP nanoribbons, attributed to high density of trap states in the samples, provides a fundamental understanding of the anisotropic BP for potential thermoelectric applications.« less

Variable range hopping electric and thermoelectric transport in anisotropic black phosphorus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Huili; Sung Choe, Hwan; Chen, Yabin

Black phosphorus (BP) is a layered semiconductor with a high mobility of up to ~1000 cm 2 V -1 s -1 and a narrow bandgap of ~0.3 eV, and shows potential applications in thermoelectrics. In stark contrast to most other layered materials, electrical and thermoelectric properties in the basal plane of BP are highly anisotropic. In order to elucidate the mechanism for such anisotropy, we fabricated BP nanoribbons (~100 nm thick) along the armchair and zigzag directions, and measured the transport properties. It is found that both the electrical conductivity and Seebeck co efficient increase with temperature, a behavior contradictorymore » to that of traditional semiconductors. The three-dimensional variable range hopping model is adopted to analyze this abnormal temperature dependency of electrical conductivity and Seebeck coefficient. Furthermore, the hopping transport of the BP nanoribbons, attributed to high density of trap states in the samples, provides a fundamental understanding of the anisotropic BP for potential thermoelectric applications.« less

Biodegradable black phosphorus-based nanomaterials in biomedicine: theranostic applications.

PubMed

Wang, Zhen; Liu, Zhiming; Su, Chengkang; Yang, Biwen; Fei, Xixi; Li, Yi; Hou, Yuqing; Zhao, Henan; Guo, Yanxian; Zhuang, Zhengfei; Zhong, Huiqing; Guo, Zhouyi

2017-09-20

Ascribe to the unique two-dimensional planar nanostructure with exceptional physical and chemical properties, black phosphorous (BP) as the emerging inorganic two-dimensional nanomaterial with high biocompatibility and degradability has been becoming one of the most promising materials of great potentials in biomedicine. The exfoliated BP sheets possess ultra-high surface area available for valid bio-conjugation and molecular loading for chemotherapy. Utilizing the intrinsic near-infrared optical absorbance, BP-based photothermal therapy in vivo, photodynamic therapy and biomedical imaging has been realized, achieving unprecedented anti-tumor therapeutic efficacy in animal experiments. Additionally, the BP nanosheets can strongly react with oxygen and water, and finally degrade to non-toxic phosphate and phosphonate in the aqueous solution. This manuscript aimed to summarize the preliminary progresses on theranostic application of BP and its derivatives black phosphorus quantum dots (BPQDs), and discussed the prospects and the state-of-art unsolved critical issues of using BP-based material for theranostic applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

International differences in the links between obesity and physiological dysregulation: the United States, England, and Taiwan.

PubMed

Vasunilashorn, Sarinnapha; Kim, Jung Ki; Crimmins, Eileen M

2013-01-01

Excess weight has generally been associated with adverse health outcomes; however, the link between overweight and health outcomes may vary with socioeconomic, cultural, and epidemiological conditions. We examine associations of weight with indicators of biological risk in three nationally representative populations: the US National Health and Nutrition Examination Survey, the English Longitudinal Study of Ageing, and the Social Environment and Biomarkers of Aging Study in Taiwan. Indicators of biological risk were compared for obese (defined using body mass index (BMI) and waist circumference) and normal weight individuals aged 54+. Generally, obesity in England was associated with elevated risk for more markers examined; obese Americans also had elevated risks except that they did not have elevated blood pressure (BP). Including waist circumference in our consideration of BMI indicated different links between obesity and waist size across countries; we found higher physiological dysregulation among those with high waist but normal BMI compared to those with normal waist and normal BMI. Americans had the highest levels of biological risk in all weight/waist groups. Cross-country variation in biological risk associated with obesity may reflect differences in health behaviors, lifestyle, medication use, and culture.

International Differences in the Links between Obesity and Physiological Dysregulation: The United States, England, and Taiwan

PubMed Central

Vasunilashorn, Sarinnapha; Kim, Jung Ki; Crimmins, Eileen M.

2013-01-01

Excess weight has generally been associated with adverse health outcomes; however, the link between overweight and health outcomes may vary with socioeconomic, cultural, and epidemiological conditions. We examine associations of weight with indicators of biological risk in three nationally representative populations: the US National Health and Nutrition Examination Survey, the English Longitudinal Study of Ageing, and the Social Environment and Biomarkers of Aging Study in Taiwan. Indicators of biological risk were compared for obese (defined using body mass index (BMI) and waist circumference) and normal weight individuals aged 54+. Generally, obesity in England was associated with elevated risk for more markers examined; obese Americans also had elevated risks except that they did not have elevated blood pressure (BP). Including waist circumference in our consideration of BMI indicated different links between obesity and waist size across countries; we found higher physiological dysregulation among those with high waist but normal BMI compared to those with normal waist and normal BMI. Americans had the highest levels of biological risk in all weight/waist groups. Cross-country variation in biological risk associated with obesity may reflect differences in health behaviors, lifestyle, medication use, and culture. PMID:23781331

Synthesis, biophysical and functional studies of two BP100 analogues modified by a hydrophobic chain and a cyclic peptide.

PubMed

Carretero, Gustavo P B; Saraiva, Greice K V; Cauz, Ana C G; Rodrigues, Magali A; Kiyota, Sumika; Riske, Karin A; Dos Santos, Alcindo A; Pinatto-Botelho, Marcos F; Bemquerer, Marcelo P; Gueiros-Filho, Frederico J; Chaimovich, Hernan; Schreier, Shirley; Cuccovia, Iolanda M

2018-05-09

Antimicrobial peptides (AMPs) work as a primary defense against pathogenic microorganisms. BP100, (KKLFKKILKYL-NH 2 ), a rationally designed short, highly cationic AMP, acts against many bacteria, displaying low toxicity to eukaryotic cells. Previously we found that its mechanism of action depends on membrane surface charge and on peptide-to-lipid ratio. Here we present the synthesis of two BP100 analogs: BP100‑alanyl‑hexadecyl‑1‑amine (BP100-Ala-NH-C 16 H 33 ) and cyclo(1‑4)‑d‑Cys 1 , Ile 2 , Leu 3 , Cys 4 -BP100 (Cyclo(1‑4)‑cILC-BP100). We examined their binding to large unilamellar vesicles (LUV), conformational and functional properties, and compared with those of BP100. The analogs bound to membranes with higher affinity and a lesser dependence on electrostatic forces than BP100. In the presence of LUV, BP100 and BP100-Ala-NH-C 16 H 33 acquired α-helical conformation, while Cyclo(1‑4)‑cILC-BP100) was partly α-helical and partly β-turn. Taking in conjunction: 1. particle sizes and zeta potential, 2. effects on lipid flip-flop, 3. leakage of LUVs internal contents, and 4. optical microscopy of giant unilamellar vesicles, we concluded that at high concentrations, all three peptides acted by a carpet mechanism, while at low concentrations the peptides acted by disorganizing the lipid bilayer, probably causing membrane thinning. The higher activity and lesser membrane surface charge dependence of the analogs was probably due to their greater hydrophobicity. The MIC values of both analogs towards Gram-positive and Gram-negative bacteria were similar to those of BP100 but both analogues were more hemolytic. Confocal microscopy showed Gram-positive B. subtilis killing with concomitant extensive membrane damage suggestive of lipid clustering, or peptide-lipid aggregation. These results were in agreement with those found in model membranes. Copyright © 2018. Published by Elsevier B.V.

How do family physicians measure blood pressure in routine clinical practice? National survey of Canadian family physicians.

PubMed

Kaczorowski, Janusz; Myers, Martin G; Gelfer, Mark; Dawes, Martin; Mang, Eric J; Berg, Angelique; Grande, Claudio Del; Kljujic, Dragan

2017-03-01

To describe the techniques currently used by family physicians in Canada to measure blood pressure (BP) for screening for, diagnosing, and treating hypertension. A Web-based cross-sectional survey distributed by e-mail. Stratified random sample of family physicians in Canada. Family physician members of the College of Family Physicians of Canada with valid e-mail addresses. Physicians' self-reported routine methods for recording BP in their practices to screen for, diagnose, and manage hypertension. A total of 774 valid responses were received, for a response rate of 16.2%. Respondents were similar to nonrespondents except for underrepresentation of male physicians. Of 769 respondents, 417 (54.2%) indicated that they used manual office BP measurement with a mercury or aneroid device and stethoscope as the routine method to screen patients for high BP, while 42.9% (330 of 769) reported using automated office BP (AOBP) measurement. The method most frequently used to make a diagnosis of hypertension was AOBP measurement (31.1%, 240 of 771), followed by home BP measurement (22.4%, 173 of 771) and manual office BP measurement (21.4%, 165 of 771). Ambulatory BP monitoring (ABPM) was used for diagnosis by 14.4% (111 of 771) of respondents. The most frequently reported method for ongoing management was home BP monitoring (68.7%, 528 of 769), followed by manual office BP measurement (63.6%, 489 of 769) and AOBP measurement (59.2%, 455 of 769). More than three-quarters (77.8%, 598 of 769) of respondents indicated that ABPM was readily available for their patients. Canadian family physicians exhibit overall high use of electronic devices for BP measurement, However, more efforts are needed to encourage practitioners to follow current Canadian guidelines, which advocate the use of AOBP measurement for hypertension screening, ABPM and home BP measurement for making a diagnosis, and both AOBP and home BP monitoring for ongoing management. Copyright© the College of Family Physicians of Canada.

How do family physicians measure blood pressure in routine clinical practice?

PubMed Central

Kaczorowski, Janusz; Myers, Martin G.; Gelfer, Mark; Dawes, Martin; Mang, Eric J.; Berg, Angelique; Grande, Claudio Del; Kljujic, Dragan

2017-01-01

Abstract Objective To describe the techniques currently used by family physicians in Canada to measure blood pressure (BP) for screening for, diagnosing, and treating hypertension. Design A Web-based cross-sectional survey distributed by e-mail. Setting Stratified random sample of family physicians in Canada. Participants Family physician members of the College of Family Physicians of Canada with valid e-mail addresses. Main outcome measures Physicians’ self-reported routine methods for recording BP in their practices to screen for, diagnose, and manage hypertension. Results A total of 774 valid responses were received, for a response rate of 16.2%. Respondents were similar to nonrespondents except for underrepresentation of male physicians. Of 769 respondents, 417 (54.2%) indicated that they used manual office BP measurement with a mercury or aneroid device and stethoscope as the routine method to screen patients for high BP, while 42.9% (330 of 769) reported using automated office BP (AOBP) measurement. The method most frequently used to make a diagnosis of hypertension was AOBP measurement (31.1%, 240 of 771), followed by home BP measurement (22.4%, 173 of 771) and manual office BP measurement (21.4%, 165 of 771). Ambulatory BP monitoring (ABPM) was used for diagnosis by 14.4% (111 of 771) of respondents. The most frequently reported method for ongoing management was home BP monitoring (68.7%, 528 of 769), followed by manual office BP measurement (63.6%, 489 of 769) and AOBP measurement (59.2%, 455 of 769). More than three-quarters (77.8%, 598 of 769) of respondents indicated that ABPM was readily available for their patients. Conclusion Canadian family physicians exhibit overall high use of electronic devices for BP measurement, However, more efforts are needed to encourage practitioners to follow current Canadian guidelines, which advocate the use of AOBP measurement for hypertension screening, ABPM and home BP measurement for making a diagnosis, and both AOBP and home BP monitoring for ongoing management. PMID:28292817

Molecular analysis of two phytohemagglutinin genes and their expression in Phaseolus vulgaris cv. Pinto, a lectin-deficient cultivar of the bean

PubMed Central

Voelker, Toni A.; Staswick, Paul; Chrispeels, Maarten J.

1986-01-01

Phytohemagglutinin (PHA), the seed lectin of the common bean, Phaseolus vulgaris, is encoded by two highly homologous, tandemly linked genes, dlec1 and dlec2, which are coordinately expressed at high levels in developing cotyledons. Their respective transcripts translate into closely related polypeptides, PHA-E and PHA-L, constituents of the tetrameric lectin which accumulates at high levels in developing seeds. In the bean cultivar Pinto UI111, PHA-E is not detectable, and PHA-L accumulates at very reduced levels. To investigate the cause of the Pinto phenotype, we cloned and sequenced the two PHA genes of Pinto, called Pdlec1 and Pdlec2, and determined the abundance of their respective mRNAs in developing cotyledons. Both genes are more than 90% homologous to the normal PHA genes found in other cultivars. Pdlec1 carries a 1-bp frameshift mutation close to the 5' end of its coding sequence. Only very truncated polypeptides could be made from its mRNA. The gene Pdlec2 encodes a polypeptide, which resembles PHA-L and its predicted amino acid sequence agrees with the available Pinto PHA amino acid sequence data. Analysis of the mRNA of developing cotyledons revealed that the Pdlec1 message is reduced 600-fold, and Pdlec2 mRNA is reduced 20-fold with respect to mRNA levels in normal cultivars. A comparison of the sequences which are upstream from the coding sequence shows that Pdlec2 has a 100-bp deletion compared to the other genes (dlec1, dlec2 and Pdlec1). This deletion which contains a large tandem repeat may be responsible for the low level of expression of Pdlec2. The very low expression of Pdlec1 is as yet unexplained. ImagesFig. 5. PMID:16453730

Comparison of laboratory and ambulatory measures of central blood pressure and pulse wave reflection: hitting the target or missing the mark?

PubMed

Burns, Matthew J; Seed, Jeremy D; Incognito, Anthony V; Doherty, Connor J; Notay, Karambir; Millar, Philip J

2018-04-01

Prior studies demonstrating clinical significance of noninvasive estimates of central blood pressure (BP) and pulse wave reflection have relied primarily on discrete resting measures. The aim of this study was to compare central BP and pulse wave reflection measures sampled during a single resting laboratory visit against those obtained under ambulatory conditions. The secondary aim was to investigate the reproducibility of ambulatory central BP and pulse wave reflection measurements. Forty healthy participants (21 males; 24 ± 3 years) completed three measurements of brachial artery pulse wave analysis (Oscar 2 with SphygmoCor Inside) in the laboratory followed by 24 hours of ambulatory monitoring. Seventeen participants repeated the 24-hour ambulatory monitoring visit after at least 1 week. Ambulatory measures were divided into daytime (9 AM-9 PM), nighttime (1 AM-6 AM), and 24-hour periods. Compared with laboratory measurements, central systolic BP, augmentation pressure, and augmentation index (with and without heart rate normalization) were higher (all P < .01) during daytime and 24-hour periods but lower during the nighttime period (all P < .001). The drop in nighttime brachial systolic BP was larger than central systolic pressure (Δ -20 ± 6 vs. -15 ± 6 mm Hg; P < .0001). Repeat ambulatory measurements of central BP and pulse wave reflection displayed good-to-excellent intraclass correlation coefficients (r = 0.58-0.86; all P < .01), although measures of pulse wave reflection had higher coefficients of variation (14%-41%). The results highlight absolute differences in central BP and pulse wave reflection between discrete laboratory and ambulatory conditions. The use of ambulatory measures of central BP and pulse wave reflection warrant further investigation for clinical prognostic value. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Olmesartan/amlodipine: a review of its use in the management of hypertension

PubMed Central

Kreutz, R

2011-01-01

Combination therapy is an effective strategy to increase antihypertensive efficacy in those patients with poor blood pressure (BP) control. In order to achieve BP targets, at least 75% of patients may require combination therapy, and European guidelines advocate this approach, particularly in those patients with a high cardiovascular risk. Evidence from large, randomized controlled trials, and the European hypertension treatment guidelines is supportive of the use of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB). Fixed-dose combination formulations of olmesartan medoxomil, an ARB, and the CCB amlodipine are approved in several European countries for patients with essential hypertension. The olmesartan/amlodipine combination has demonstrated greater efficacy than its component monotherapies in reducing BP in patients with mild-to-severe hypertension. Significantly greater reductions in seated diastolic BP were observed between baseline and after eight weeks of treatment with olmesartan/amlodipine, compared with equivalent doses of olmesartan or amolodipine monotherapy (P < 0.001), in the factorial Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial. About 85% of the maximal BP reductions after the 8-week treatment period were already observed after two weeks. Uptitration as necessary, with or without hydrochlorothiazide, allowed the majority of patients to achieve BP control in a 44-week open-label extension treatment period to the COACH trial. The use of olmesartan/amlodipine allowed up to 54% of patients, with previously inadequate responses to amlodipine or olmesartan monotherapy, to achieve their BP goals. Data from post-registration studies using tight BP control and forced titration regimens have further demonstrated the high efficacy of olmesartan/amlodipine in achieving BP goal rates. Moreover, consistent reductions in BP were observed over the 24-hour dosing interval using ambulatory measurements. Olmesartan/amlodipine was generally well tolerated over the short- and long-term, with a lower frequency of peripheral edema with olmesartan/amlodipine 40/10 mg than with amlodipine 10 mg monotherapy. PMID:21490944

Zebrafish foxP2 Zinc Finger Nuclease Mutant Has Normal Axon Pathfinding

PubMed Central

Xing, Lingyan; Hoshijima, Kazuyuki; Grunwald, David J.; Fujimoto, Esther; Quist, Tyler S.; Sneddon, Jacob; Chien, Chi-Bin; Stevenson, Tamara J.; Bonkowsky, Joshua L.

2012-01-01

foxP2, a forkhead-domain transcription factor, is critical for speech and language development in humans, but its role in the establishment of CNS connectivity is unclear. While in vitro studies have identified axon guidance molecules as targets of foxP2 regulation, and cell culture assays suggest a role for foxP2 in neurite outgrowth, in vivo studies have been lacking regarding a role for foxP2 in axon pathfinding. We used a modified zinc finger nuclease methodology to generate mutations in the zebrafish foxP2 gene. Using PCR-based high resolution melt curve analysis (HRMA) of G0 founder animals, we screened and identified three mutants carrying nonsense mutations in the 2nd coding exon: a 17 base-pair (bp) deletion, an 8bp deletion, and a 4bp insertion. Sequence analysis of cDNA confirmed that these were frameshift mutations with predicted early protein truncations. Homozygous mutant fish were viable and fertile, with unchanged body morphology, and no apparent differences in CNS apoptosis, proliferation, or patterning at embryonic stages. There was a reduction in expression of the known foxP2 target gene cntnap2 that was rescued by injection of wild-type foxP2 transcript. When we examined axon pathfinding using a pan-axonal marker or transgenic lines, including a foxP2-neuron-specific enhancer, we did not observe any axon guidance errors. Our findings suggest that foxP2 is not necessary for axon pathfinding during development. PMID:22937139

Zebrafish foxP2 zinc finger nuclease mutant has normal axon pathfinding.

PubMed

Xing, Lingyan; Hoshijima, Kazuyuki; Grunwald, David J; Fujimoto, Esther; Quist, Tyler S; Sneddon, Jacob; Chien, Chi-Bin; Stevenson, Tamara J; Bonkowsky, Joshua L

2012-01-01

foxP2, a forkhead-domain transcription factor, is critical for speech and language development in humans, but its role in the establishment of CNS connectivity is unclear. While in vitro studies have identified axon guidance molecules as targets of foxP2 regulation, and cell culture assays suggest a role for foxP2 in neurite outgrowth, in vivo studies have been lacking regarding a role for foxP2 in axon pathfinding. We used a modified zinc finger nuclease methodology to generate mutations in the zebrafish foxP2 gene. Using PCR-based high resolution melt curve analysis (HRMA) of G0 founder animals, we screened and identified three mutants carrying nonsense mutations in the 2(nd) coding exon: a 17 base-pair (bp) deletion, an 8bp deletion, and a 4bp insertion. Sequence analysis of cDNA confirmed that these were frameshift mutations with predicted early protein truncations. Homozygous mutant fish were viable and fertile, with unchanged body morphology, and no apparent differences in CNS apoptosis, proliferation, or patterning at embryonic stages. There was a reduction in expression of the known foxP2 target gene cntnap2 that was rescued by injection of wild-type foxP2 transcript. When we examined axon pathfinding using a pan-axonal marker or transgenic lines, including a foxP2-neuron-specific enhancer, we did not observe any axon guidance errors. Our findings suggest that foxP2 is not necessary for axon pathfinding during development.

[Preventing cardiovascular diseases through a screening modelling applicable to wide population groups: results from the first phase of the project].

PubMed

Ferro, Antonio; Cinquetti, Sandro; Moro, Alessandro; Siddu, Andrea; Trimarchi, Antonino; Penon, Maria Gabriella; Pavan, Pierpaolo; Camillotto, Raffaella; Rossetto, Luca; Volpe, Valter; Zevrain, Simone; Brusaferro, Silvio

2014-01-01

evaluate, through active call, lifestyles of an asymptomatic population in order to identify hyperglycaemic subjects and/or high-blood pressure sufferers to dispatch to their GP to perform suitable checking, and subjects to invite to a cardiovascular disease prevention programme because of their lifestyles. between January 2009 and July 2012, all healthy residents in the Local Health Authority of Este (ULSS 17 Este) aged 45-59 years were invited to join a cardiovascular disease prevention programme. all participants were evaluated through an administered lifestyle questionnaire. Parameters such as blood pressure (BP), glycaemia, waist circumference and body mass index were collected and recorded. Participants also received counseling, informational materials on lifestyle and were invited to individual or group health promotion initiatives in relation to personal risk factors. among the invited, 55.5% (3,922/7,071) adhered. Women (58.8%) responded significantly better than men (51.9%) (p <0,01). Subjects without risks factors were 16.7%. Subjects with lifestyle risk factors but normal BP and glycaemia were 49.4%, while those adding altered values for BP and glycaemia were 25.2%. The 8.6% of the respondents were not eligible for the study. the preliminary results suggest that a preventive programme based on the citizens active call by the Department of Prevention could be an effective tool to identify asymptomatic individuals with unknown hypertension and/or hyperglycaemia and to offer lifestyle interventions to lower the risk of cardiovascular diseases.

Metabolism of UV-filter benzophenone-3 by rat and human liver microsomes and its effect on endocrine-disrupting activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, Yoko, E-mail: y-watanabe@nichiyaku.ac.jp; Nihon Pharmaceutical University, Komuro 10281, Ina-machi, Saitama 362-0806; Kojima, Hiroyuki

2015-01-15

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) is widely used as sunscreen for protection of human skin and hair from damage by ultraviolet (UV) radiation. In this study, we examined the metabolism of BP-3 by rat and human liver microsomes, and the estrogenic and anti-androgenic activities of the metabolites. When BP-3 was incubated with rat liver microsomes in the presence of NADPH, 2,4,5-trihydroxybenzophenone (2,4,5-triOH BP) and 3-hydroxylated BP-3 (3-OH BP-3) were newly identified as metabolites, together with previously detected metabolites 5-hydroxylated BP-3 (5-OH BP-3), a 4-desmethylated metabolite (2,4-diOH BP) and 2,3,4-trihydroxybenzophenone (2,3,4-triOH BP). In studies with recombinant rat cytochrome P450, 3-OH BP-3 and 2,4,5-triOHmore » BP were mainly formed by CYP1A1. BP-3 was also metabolized by human liver microsomes and CYP isoforms. In estrogen reporter (ER) assays using estrogen-responsive CHO cells, 2,4-diOH BP exhibited stronger estrogenic activity, 2,3,4-triOH BP exhibited similar activity, and 5-OH BP-3, 2,4,5-triOH BP and 3-OH BP-3 showed lower activity as compared to BP-3. Structural requirements for activity were investigated in a series of 14 BP-3 derivatives. When BP-3 was incubated with liver microsomes from untreated rats or phenobarbital-, 3-methylcholanthrene-, or acetone-treated rats in the presence of NADPH, estrogenic activity was increased. However, liver microsomes from dexamethasone-treated rats showed decreased estrogenic activity due to formation of inactive 5-OH BP-3 and reduced formation of active 2,4-diOH BP. Anti-androgenic activity of BP-3 was decreased after incubation with liver microsomes. - Highlights: • Metabolic modification of the endocrine-disrupting activity of BP-3 was examined. • 2,4,5-TriOH BP and 3-OH BP-3 were identified as new BP-3 metabolites. • 2,4-DiOH BP and 2,3,4-triOH BP exhibited high or similar estrogenic activities. • Estrogenic activity of BP-3 was enhanced by incubation with rat liver microsomes. • Structural requirements for the activities of BP-3 derivatives were demonstrated.« less

The J-shaped Curve for Blood Pressure and Cardiovascular Disease Risk: Historical Context and Recent Updates.

PubMed

Rahman, Faisal; McEvoy, John W

2017-08-01

The definition and treatment of hypertension have both changed dramatically over the last century, with recent trials suggesting benefit for lower blood pressure (BP) targets than ever before considered. However, tempering the enthusiasm for more intensive BP targets are long-held concerns that BP reduction below a certain threshold may pose dangers, the so-called "J-curve." In this review, we summarize the evidence for a J-curve in the treatment of hypertension. The Systolic Blood Pressure Intervention Trial (SPRINT) reported that achieving a systolic BP target of 120 mmHg reduces cardiovascular disease in high-risk individuals, supporting more intensive BP reduction. However, contemporary observational studies consistently demonstrate a BP J-curve, the threshold of which is often close to the SPRINT target. Studies also suggest that the BP level of this J-curve may vary based on patient characteristics, including age and comorbidities. There is also more compelling evidence for the specific presence of a J-curve between diastolic BP and coronary events, in contrast to conflicting evidence of a J-curve with systolic BP and cardiovascular disease more generally. There is increased risk of coronary events below a diastolic BP of 60-70 mmHg. In comparison, the presence of a systolic J-curve is less clear and some persons at high risk may actually benefit from systolic levels down to 120 mmHg. Therefore, we suggest a personalized approach to BP management considering individual risks, benefits, and preferences when choosing therapeutic targets. Further, well-designed studies are required to support our suggestions and to define J-curve thresholds more clearly.

Interdialysis blood pressure control by long haemodialysis sessions.

PubMed

Chazot, C; Charra, B; Laurent, G; Didier, C; Vo Van, C; Terrat, J C; Calemard, E; Vanel, T; Ruffet, M

1995-01-01

High blood pressure (BP) is a major factor contributing to the high incidence of cardiovascular morbidity and mortality in haemodialysis (HD) patients. According to predialysis casual BP measurements, long HD has been shown to provide good BP control. To confirm this result during the period between dialysis sessions, we performed ambulatory monitoring of BP in 91 non-selected HD patients (mean age, 58.7 (14.1) years; 14% incidence of nephrosclerosis and diabetes mellitus; treatment duration, 93.0 (77.2) months; 3 x 8 h/week, cuprophane, acetate buffer in 95% of the patients). Only one patient (1.1%) was receiving an antihypertensive medication. Ambulatory BP results were systolic (S) BP, 119.4 (19.9) mmHg; diastolic (D) BP, 70.6 (12.9) mmHg; mean (M) BP, 87.6 (13.9) mmHg. These values were significantly lower than the casual predialysis BP data and close to the reference values reported by Staessen et al. in a meta-analysis including 3476 normotensive subjects. The MBP was inversely correlated with the treatment duration, but not with interdialysis weight gain. The MBP increased significantly in the last part of the interdialysis period, and this rise was not correlated with the interdialysis weight gain. The nocturnal/diurnal ratios for SBP and DBP for the HD patients (0.97 and 0.92) were higher than the reference values reported by Staessen, (0.87 and 0.83), and argued against a nocturnal decrease in BP. We found that 52.1% of the patients had an abnormal nocturnal BP fall (MBP fall < 5%). This feature worsened during the second night of the interdialysis period.(ABSTRACT TRUNCATED AT 250 WORDS)

Trace Element Geochemistry as a Tool for the Reconstruction of Upwelling Patterns at 12oS off Peru since the Last Glacial Maximum (LGM)

NASA Astrophysics Data System (ADS)

Boening, P.; Brumsack, H.; Wolf, A.

2002-05-01

Laminated sediments (core 106KL), recovered during R/V Sonne cruise 147 from the Peruvian upper slope mud lens at 12oS, were analyzed for bulk parameters (TOC, TIC, TS) and opal as well as major and trace element composition by XRF and ICP-MS in 5 cm intervals. The composition of the terrigenous-detrital sediment fraction is comparable to average shale. The sediments exhibit slight increases in biogenic silica (diatoms) and carbonate contents (foraminifera) in varying layers. The experimentally determined opal contents correlate well with Si/Al ratios. High TOC and P contents are due to enhanced primary productivity, high sedimentation rates and corresponding organic matter preservation under a strong OMZ. We distinguish between three different groups of elements: 1.) trace elements involved in bio-cycling (e.g. Cd, Ag, Ni, Cu) are highly enriched in the sediments due to their association with plankton, high sedimentation rates (preventing remobilization from the sediments) and fixation as sulfides. 2.) redox-sensitive elements (e.g. Re, Mo) are significantly enriched probably due to reduction and precipitation under suboxic/anoxic conditions. Diffusion of these elements from the water column into sub/anoxic sediments seems to be the controlling factor, besides sulfide precipitation. An average Re/Mo ratio of 1.3 indicates anoxic sedimentary conditions. Most trace elements correlate well with the TOC content presumably documenting productivity events. 3.) Al, Zr and Y are well correlated, presumably representing sporadic high-energy fluvial input from the continent or enhanced current velocities. The three element groups were used to reconstruct the upwelling patterns off Lima since the LGM: TOC content and Al-normalized trace element patterns from the bio/redox-sensitive fractions represent the signal from the water column, whereas Al, Y and Zr reflect the terrigenous input. During the LGM (about 17 ky BP) the site was hardly affected by upwelling as the upwelling cell was located more basinward. As the sea level rose during the Late Glacial (17-10 ky BP) the upwelling cell shifted towards the coast. The Early Holocene (10-5 ky BP) is not documented likely because strong currents (presumably the Peru counter current) eroded the slope. In the Late Holocene the upwelling cell was established at the site. However, a higher terrrigenous proportion and lower input from the water column suggest a basinward shifting of the upwelling cell during the Second Neoglacial (2000-2700 BP). Stronger Element/Al and TOC variabilities indicate the influence of El Nino during the Late Holocene.

Definition of Cis-Acting Elements Regulating Expression of the Drosophila Melanogaster Ninae Opsin Gene by Oligonucleotide-Directed Mutagenesis

PubMed Central

Mismer, D.; Rubin, G. M.

1989-01-01

We have analyzed the cis-acting regulatory sequences of the Rh1 (ninaE) gene in Drosophila melanogaster by P-element-mediated germline transformation of indicator genes transcribed from mutant ninaE promoter sequences. We have previously shown that a 200-bp region extending from -120 to +67 relative to the transcription start site is sufficient to obtain eye-specific expression from the ninaE promoter. In the present study, 22 different 4-13-bp sequences in the -120/+67 promoter region were altered by oligonucleotide-directed mutagenesis. Several of these sequences were found to be required for proper promoter function; two of these are conserved in the promoter of the homologous gene isolated from the related species Drosophila virilis. Alteration of a conserved 9-bp sequence results in aberrant, low level expression in the body. Alteration of a separate 11-bp sequence, found in the promoter regions of several photoreceptor-specific genes of Drosophila, results in an approximately 15-fold reduction in promoter efficiency but without apparent alteration of tissue-specificity. A protein factor capable of interacting with this 11-bp sequence has been detected by DNaseI footprinting in embryonic nuclear extracts. Finally, we have further characterized two separable enhancer sequences previously shown to be required for normal levels of expression from this promoter. PMID:2521839

Impact of job and marital strain on ambulatory blood pressure results from the double exposure study.

PubMed

Tobe, Sheldon W; Kiss, Alexander; Szalai, John Paul; Perkins, Nancy; Tsigoulis, Michelle; Baker, Brian

2005-08-01

Psychosocial stressors such as job strain and marital stress have been associated with a sustained increase in blood pressure (BP). We evaluated whether job strain and marital cohesion were associated with ambulatory BP in workers with normal or untreated elevated BP using baseline data from the Double Exposure study. The study population included 248 male and female volunteers who were nonmedicated, employed, and living with a significant other, all for a minimum of 6 months. Blood pressure was measured with an ambulatory BP monitor and participants completed a diary that recorded time during work, spousal contact, and sleep. Job strain and marital cohesion were calculated from the Job Content Questionnaire and the Dyadic Adjustment Scale, respectively. Of the subjects, 54.4% were female with a mean age of 50.8 years (6.6, SD). In all, 21.3% reported job strain. Significant assocations were found between 24-h systolic BP (SBP) and alcohol consumption (P = .033), job strain (P = .007), male gender (P = .004), and age (P = .039) and was inversely associated with exercise (P = .037). An interaction between 24-h SBP, job strain, and marital cohesion was found such that greater marital cohesion was associated with lower SBP in subjects with job strain. Psychosocial factors may influence the development of early hypertension. This should be clarified by the cohort phase of the Double Exposure study.

The internal head protein Gp16 controls DNA ejection from the bacteriophage T7 virion.

PubMed

Struthers-Schlinke, J S; Robins, W P; Kemp, P; Molineux, I J

2000-08-04

A wild-type T7 virion ejects about 850 bp of the 40 kb genome into the bacterial cell by a transcription-independent process. Internalization of the remainder of the genome normally requires transcription. Inhibition of transcription-independent DNA translocation beyond the leading 850 bp is not absolute but the time taken by a population of phage genomes in overcoming the block averages about 20 minutes at 30 degrees C. There are additional blocks to transcription-independent translocation and less than 20 % of infecting DNA molecules completely penetrate the cell cytoplasm after four hours of infection. Mutant virions containing an altered gene 16 protein either prevent the blocks to transcription-independent DNA translocation or effect rapid release from blocking sites and allow the entire phage DNA molecule to enter the cell at a constant rate of about 75 bp per second. This rate is likely the same at which the leading 850 bp is ejected into the cell from a wild-type virion. All mutations fall into two clusters contained within 380 bp of the 4 kb gene 16, suggesting that a 127 residue segment of gp16 controls DNA ejection from the phage particle. We suggest that this segment of gp16 acts as a clamp to prevent transcription-independent DNA translocation. Copyright 2000 Academic Press.

An investigation into the association between HLA-G 14 bp insertion/deletion polymorphism and multiple sclerosis susceptibility.

PubMed

Mohammadi, Nabiallah; Adib, Minoo; Alsahebfosoul, Fereshteh; Kazemi, Mohammad; Etemadifar, Masoud

2016-01-15

Human Leukocyte Antigen G (HLA-G) gene polymorphism and expression rate have recently been suggested to have a potential role in susceptibility to Multiple Sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. The aim of this study was to investigate the association of the frequency of HLA-G gene 14 bp insertion/deletion polymorphism and its plasma level with MS susceptibility. In this study, the HLA-G gene from 212 patients and 210 healthy individuals was amplified using real time PCR and screened for the 14 bp insertion/deletion polymorphism. In addition, HLA-G plasma levels of the patients were measured and compared to normal controls by ELISA method. Our results revealed that 14 bp insertion in HLA-G could result in lower plasma HLA-G level of the subjects, regardless of their health status and vice versa. Additionally, significant correlation of HLA-G genotype and its plasma level with MS susceptibility was observed. In conclusion, not only HLA-G 14 bp insertion/deletion polymorphism could be associated with expression rate of the HLA-G gene and its plasma level, but also could be considered as a risk factor for susceptibility to MS in our study population. Copyright © 2015 Elsevier B.V. All rights reserved.

Association Between Serum Levels of Uric Acid and Blood Pressure Tracking in Childhood.

PubMed

Park, Bohyun; Lee, Hye Ah; Lee, Sung Hee; Park, Bo Mi; Park, Eun Ae; Kim, Hae Soon; Cho, Su Jin; Park, Hyesook

2017-07-01

Recent studies suggest that high levels of serum uric acid of very early life are a result of the in-utero environment and may lead to elevated blood pressure (BP) in adulthood. However, serum uric acid levels can change throughout life. We investigated the effect of serum uric acid levels in childhood on the BP tracking and analysed BP according to changes in serum uric acid levels in early life. A total of 449 children from the Ewha Birth and Growth Cohort study underwent at least 2 follow-up examinations. Data were collected across 3 check-up cycles. Serum uric acid levels, BP, and anthropometric characteristics were assessed at 3, 5, and 7 years of age. Children with a serum uric acid level higher than the median values had significantly increased systolic BP (SBP) and diastolic BP at 3 years of age. Baseline serum uric acid levels measured at 3 years of age, significantly affected subsequent BP in the sex and body mass index adjusted longitudinal data analysis (P < 0.05). Considering the changing pattern of serum uric acid over time, subjects with high uric acid levels at both 3 and 5 years of age had the highest SBP at 7 years of age. These findings suggest the importance of maintaining an adequate level of serum uric acids from the early life. Appropriate monitoring and intervention of uric acid levels in a high-risk group can reduce the risk of a future increased BP. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Transformation mechanism of benzophenone-4 in free chlorine promoted chlorination disinfection.

PubMed

Xiao, Ming; Wei, Dongbin; Yin, Junxia; Wei, Guohua; Du, Yuguo

2013-10-15

The UV-filter BP-4 (2-hydroxy-4-methoxybenzophenone-5-sulfonic acid) has been frequently observed in the environment, showing high potentials to invade drinking water, swimming water, or wastewater reclamation treatment systems. With the help of high performance liquid chromatography-high resolution mass spectrometry and nuclear magnetic resonance spectroscopy, 10 new products from free chlorine-promoted BP-4 disinfection have been disclosed and their possible transformation routes have been investigated. The first route is chlorine substitution of BP-4 and its transformation products, forming mono-, di-, and tri-chlorinated BP-4 analogs. The second is Baeyer-Villiger-Type oxidation, converting diphenyl ketone to phenyl ester derivatives. The third is ester hydrolysis, generating corresponding phenolic and benzoic products. The fourth is decarboxylation, replacing the carboxyl group by chloride in the benzoic-type intermediate. The fifth is desulfonation, degrading the sulfonic group through an alternative chlorine substitution on the benzene ring. Orthogonal experiments have been established to investigate the species transformed from BP-4 at different pH values and free available chlorine (FAC) dosages. The reaction pathways are strongly dependent on pH conditions, while an excessive amount of FAC eliminates BP-4 to the smaller molecules. The initial transformation of BP-4 in chlorination system follows pseudo-first-order kinetics, and its half-lives ranged from 7.48 s to 1.26 × 10(2) s. More importantly, we have observed that the FAC-treated BP-4 aqueous solution might increase the genotoxic potentials due to the generation of chlorinated disinfection by-products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Blood pressure cuffs as a vector for transmission of multi-resistant organisms: colonisation rates and effects of disinfection.

PubMed

Grewal, Harjeet; Varshney, Kavita; Thomas, Lee C; Kok, Jen; Shetty, Amith

2013-06-01

Blood pressure (BP) cuffs are potential vectors for transmission of multi-resistant organisms (MROs). The present study aims to determine MRO colonisation rates in BP cuffs from areas of high patient flow as an assessment of the quality of disinfection and infection control practices. BP cuffs in the ED, high dependency unit (HDU) and operating theatres (OT) were prospectively examined after routine disinfection procedures. Swabs collected from the inner and outer surfaces of BP cuffs during inter-patient intervals were plated onto replicate organism detection and counting, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) chromogenic agar plates to detect rates of bacterial, MRSA and VRE colonisation, respectively. High bacterial colonisation rates were detected in BP cuffs from all three areas. BP cuffs from OT were significantly less colonised compared with cuffs from HDU and ED; 76% versus 96% and 100% (P < 0.0001) for inner surfaces and 86% versus 98% and 100% (P < 0.0001) for outer surfaces, respectively. Equivalent or higher bacterial growth was observed on the inner surface compared with outer surface in 54%, 84% and 86% of BP cuffs from OT, HDU and ED, respectively. MRSA was detected in 3 of 150 (2%) swabs collected, but no VRE was detected. Although MRSA and VRE were infrequently isolated, current disinfection and infection control protocols need to be improved given the greater recovery of organisms from the inner compared with outer surfaces of BP cuffs. © 2013 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Cardiovascular Depression in Rats Exposed to Inhaled Particulate Matter and Ozone: Effects of Diet-Induced Metabolic Syndrome

PubMed Central

Allen, Katryn; Yang, Hui-yu; Nan, Bin; Morishita, Masako; Mukherjee, Bhramar; Dvonch, J. Timothy; Spino, Catherine; Fink, Gregory D.; Rajagopalan, Sanjay; Sun, Qinghua; Brook, Robert D.; Harkema, Jack R.

2013-01-01

Background: High ambient levels of ozone (O3) and fine particulate matter (PM2.5) are associated with cardiovascular morbidity and mortality, especially in people with preexisting cardiopulmonary diseases. Enhanced susceptibility to the toxicity of air pollutants may include individuals with metabolic syndrome (MetS). Objective: We tested the hypothesis that cardiovascular responses to O3 and PM2.5 will be enhanced in rats with diet-induced MetS. Methods: Male Sprague-Dawley rats were fed a high-fructose diet (HFrD) to induce MetS and then exposed to O3, concentrated ambient PM2.5, or the combination of O3 plus PM2.5 for 9 days. Data related to heart rate (HR), HR variability (HRV), and blood pressure (BP) were collected. Results: Consistent with MetS, HFrD rats were hypertensive and insulin resistant, and had elevated fasting levels of blood glucose and triglycerides. Decreases in HR and BP, which were found in all exposure groups, were greater and more persistent in HFrD rats compared with those fed a normal diet (ND). Coexposure to O3 plus PM2.5 induced acute drops in HR and BP in all rats, but only ND rats adapted after 2 days. HFrD rats had little exposure-related changes in HRV, whereas ND rats had increased HRV during O3 exposure, modest decreases with PM2.5, and dramatic decreases during O3 plus PM2.5 coexposures. Conclusions: Cardiovascular depression in O3- and PM2.5-exposed rats was enhanced and prolonged in rats with HFrD-induced MetS. These results in rodents suggest that people with MetS may be prone to similar exaggerated BP and HR responses to inhaled air pollutants. Citation: Wagner JG, Allen K, Yang HY, Nan B, Morishita M, Mukherjee B, Dvonch JT, Spino C, Fink GD, Rajagopalan S, Sun Q, Brook RD, Harkema JR. 2014. Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome. Environ Health Perspect 122:27–33; http://dx.doi.org/10.1289/ehp.1307085 PMID:24169565

Dose-rate effect was observed in T98G glioma cells following BNCT.

PubMed

Kinashi, Yuko; Okumura, Kakuji; Kubota, Yoshihisa; Kitajima, Erika; Okayasu, Ryuichi; Ono, Koji; Takahashi, Sentaro

2014-06-01

It is generally said that low LET radiation produce high dose-rate effect, on the other hand, no significant dose rate effect is observed in high LET radiation. Although high LET radiations are produced in BNCT, little is known about dose-rate effect of BNCT. T98G cells, which were tumor cells, were irradiated by neutron mixed beam with BPA. As normal tissue derived cells, Chinese hamster ovary (CHO-K1) cells and DNA double strand breaks (DNA-DSBs) repair deficient cells, xrs5 cells were irradiated by the neutrons (not including BPA). To DNA-DSBs analysis, T98G cells were stained immunochemically with 53BP1 antibody. The number of DNA-DSBs was determined by counting 53BP1 foci. There was no dose-rate effect in xrs5 cells. D0 difference between 4cGy/min and 20cGy/min irradiation were 0.5 and 5.9 at the neutron and gamma-ray irradiation for CHO-K1, and 0.3 at the neutron for T98G cells. D0 difference between 20cGy/min and 80cGy/min irradiation for T98G cells were 1.2 and 0.6 at neutron irradiation plus BPA and gamma-ray. The differences between neutron irradiations at the dose rate in T98G cells were supported by not only the cell viability but also 53BP1 foci assay at 24h following irradiation to monitor DNA-DSBs. Dose-rate effect of BNCT when T98G cells include 20ppm BPA was greater than that of gamma-ray irradiation. Moreover, Dose-rate effect of the neutron beam when CHO-K1 cells did not include BPA was less than that of gamma-ray irradiation These present results may suggest the importance of dose-rate effect for more efficient BNCT and the side effect reduction. © 2013 Published by Elsevier Ltd.

Effects of weather conditions on emergency ambulance calls for acute coronary syndromes

NASA Astrophysics Data System (ADS)

Vencloviene, Jone; Babarskiene, Ruta; Dobozinskas, Paulius; Siurkaite, Viktorija

2015-08-01

The aim of this study was to evaluate the relationship between weather conditions and daily emergency ambulance calls for acute coronary syndromes (ACS). The study included data on 3631 patients who called the ambulance for chest pain and were admitted to the department of cardiology as patients with ACS. We investigated the effect of daily air temperature ( T), barometric pressure (BP), relative humidity, and wind speed (WS) to detect the risk areas for low and high daily volume (DV) of emergency calls. We used the classification and regression tree method as well as cluster analysis. The clusters were created by applying the k-means cluster algorithm using the standardized daily weather variables. The analysis was performed separately during cold (October-April) and warm (May-September) seasons. During the cold period, the greatest DV was observed on days of low T during the 3-day sequence, on cold and windy days, and on days of low BP and high WS during the 3-day sequence; low DV was associated with high BP and decreased WS on the previous day. During June-September, a lower DV was associated with low BP, windless days, and high BP and low WS during the 3-day sequence. During the warm period, the greatest DV was associated with increased BP and changing WS during the 3-day sequence. These results suggest that daily T, BP, and WS on the day of the ambulance call and on the two previous days may be prognostic variables for the risk of ACS.

High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Wei; Department of Endocrinology, The People’s Hospital of Xindu, Xindu, Sichuang, 610500; Xu, Ling

Highlights: •The expression of SUMO1, SUMO2/3 under high glucose was obviously enhanced. •High glucose induced degradation of IκBα and activation of NF-κB pathway. •Sumoylation of IκBα in high glucose were significantly decreased. •The proteasome inhibitor MG132 could partially revert the degradation of IκBα. -- Abstract: The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation ofmore » inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p < 0.05). However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p < 0.05). The present results support the hypothesis that high glucose may activate NF-κB inflammatory signaling through IκBα sumoylation and ubiquitination.« less

Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen)

PubMed Central

Noe, Megan H.; Messingham, Kelly A.N.; Brandt, Debra S.; Andrews, Janet I.; Fairley, Janet A.

2016-01-01

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n = 299) and from non-pregnant controls (n = 134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p = 0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function. PMID:20471095

MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei.

PubMed

Kim, Hee-Sook; Park, Sung Hee; Günzl, Arthur; Cross, George A M

2013-01-01

Trypanosoma brucei variant surface glycoprotein (VSG) expression is a classic example of allelic exclusion. While the genome of T. brucei contains >2,000 VSG genes and VSG pseudogenes, only one allele is expressed at the surface of each infectious trypanosome and the others are repressed. Along with recombinatorial VSG switching, allelic exclusion provides a major host evasion mechanism for trypanosomes, a phenomenon known as antigenic variation. To extend our understanding of how trypanosomes escape host immunity by differential expression of VSGs, we attempted to identify genes that contribute to VSG silencing, by performing a loss-of-silencing screen in T. brucei using a transposon-mediated random insertional mutagenesis. One identified gene, which we initially named LOS1, encodes a T. brucei MCM-Binding Protein (TbMCM-BP). Here we show that TbMCM-BP is essential for viability of infectious bloodstream-form (BF) trypanosome and is required for proper cell-cycle progression. Tandem affinity purification of TbMCM-BP followed by mass spectrometry identified four subunits (MCM4-MCM7) of the T. brucei MCM complex, a replicative helicase, and MCM8, a subunit that is uniquely co-purified with TbMCM-BP. TbMCM-BP is required not only for repression of subtelomeric VSGs but also for silencing of life-cycle specific, insect-stage genes, procyclin and procyclin-associated genes (PAGs), that are normally repressed in BF trypanosomes and are transcribed by RNA polymerase I. Our study uncovers a functional link between chromosome maintenance and RNA pol I-mediated gene silencing in T. brucei.

Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats.

PubMed

Zicha, Josef; Dobesová, Zdenka; Kunes, Jaroslav

2006-12-01

Hypertension due to chronic inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine methyl ester (L-NAME) administration is characterized by both impaired NO-dependent vasodilation and enhanced sympathetic vasoconstriction. The aim of our study was to evaluate changes in the participation of major vasoactive systems in L-NAME-treated rats which were subjected to simultaneous antihypertensive (captopril) or antioxidant (N-acetylcysteine, NAC) treatment. Three-month-old Wistar males treated with L-NAME (60 mg/kg/day) for 5 weeks were compared to rats in which L-NAME treatment was combined with simultaneous chronic administration of captopril or NAC. Basal blood pressure (BP) and its acute responses to consecutive i.v. injections of captopril (10 mg/kg), pentolinium (5 mg/kg), L-NAME (30 mg/kg), tetraethylammonium (TEA, 16 mg/kg) and nitroprusside (NP, 20 microg/kg) were determined in conscious rats at the end of the study. The development of L-NAME hypertension was prevented by captopril treatment, whereas NAC treatment caused only a moderate BP reduction. Captopril treatment normalized the sympathetic BP component and significantly reduced residual BP (measured at full NP-induced vasodilation). In contrast, chronic NAC treatment did not modify the sympathetic BP component or residual BP, but significantly enhanced NO-dependent vasodilation. Neither captopril nor NAC treatment influenced the compensatory increase of TEA-sensitive vasodilation mediated by endothelium-derived hyperpolarizing factor in L-NAME-treated rats. Chronic captopril treatment prevented L-NAME hypertension by lowering of sympathetic tone, whereas chronic NAC treatment attenuated L-NAME hypertension by reduction in the vasodilator deficit due to enhanced NO-dependent vasodilation.

Experimental and numerical study of high order Stokes lines in Brillouin-erbium fiber laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Yijun; College of Physics Science and Engineering Technology, Yichun University, Yichun, Jiangxi Province 336000; Yao, Yong, E-mail: yaoyong@hit.edu.cn

2014-01-28

We experimentally study the dependences of high-order Stokes lines on the erbium-doped fiber (EDF) pump power P{sub EDF}, the Brillouin pump (BP) power P{sub BP}, and its working wavelength in a multiwavelength Brillouin erbium-doped fiber laser (MBEFL). By using the rate and propagation equations, and the coupled wave equations of stimulated Brillouin scattering, we establish a lumped model to describe the MBEFL. Numerical simulations show that the number of Stokes lines can be increased by decreasing the spacing between the BP wavelength and the EDF peak gain or P{sub BP} as long as it is larger than a critical valuemore » P{sub BP}{sup (cr)}=1.7 mW, or by increasing P{sub EDF} without reaching a saturation value P{sub EDF}{sup (cr)}=250 mW. However, when P{sub BP} and P{sub EDF} are varied beyond P{sub BP}{sup (cr)} and P{sub EDF}{sup (cr)}, respectively, the number of Stokes lines is reduced, accompanied by some self-lasing cavity modes. These results by numerical simulation are consistent with experimental observations from the MBEFL.« less

The Influence of Domestic Overload on the Association between Job Strain and Ambulatory Blood Pressure among Female Nursing Workers

PubMed Central

Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

2013-01-01

Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers. PMID:24287860

The influence of domestic overload on the association between job strain and ambulatory blood pressure among female nursing workers.

PubMed

Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

2013-11-27

Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers.

Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: a case control study.

PubMed

Wee, Bee S; Poh, Bee K; Bulgiba, Awang; Ismail, Mohd N; Ruzita, Abdul T; Hills, Andrew P

2011-05-18

With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic syndrome. However, for ethnicity, Indians were found to have higher odds (OR = 5.5; 95%CI 1.5, 20.5) compared to Malays, with Chinese children (OR = 0.3; 95%CI 0.0, 2.7) having the lowest odds. We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are required to prevent this problem from escalating.

Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: A case control study

PubMed Central

2011-01-01

Background With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. Methods A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Results Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic syndrome. However, for ethnicity, Indians were found to have higher odds (OR = 5.5; 95%CI 1.5, 20.5) compared to Malays, with Chinese children (OR = 0.3; 95%CI 0.0, 2.7) having the lowest odds. Conclusions We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are required to prevent this problem from escalating. PMID:21592367