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BACKGROUND: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses. METHODS: An open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis. RESULTS: We enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns. CONCLUSION: In patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients.
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Vacinas contra Hepatite B , Hepatite B , Adolescente , Adulto , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B/efeitos adversos , Humanos , Diálise Renal/efeitos adversosRESUMO
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Post-traumatic stress disorder (PTSD) is triggered by experiencing terrifying event(s) for which there is currently no objective test for a definitive diagnosis. We report a pilot study where two-dimensional (2D) neuro magnetic resonance spectroscopy (MRS), collected at 3 T in a clinical scanner with a 64-channel head coil, identifies neuro deregulation in the PTSD cohort. The control subjects (n = 10) were compared with PTSD participants with minimal co-morbidities (n = 10). The 2D MRS identified statistically significant increases in the total spectral region containing both free substrate fucose and fucosylated glycans of 31% (P = 0.0013), two of multiple fucosylated glycans (Fuc IV and VI) were elevated by 48% (P = 0.002), and 41% (P = 0.02), respectively, imidazole was increased by 12% (P = 0.002), and lipid saturation was increased by 12.5% (P = 0.009). This is the first evidence of fucosylated glycans, reported in animals to be involved in learning and memory, to be affected in humans with PTSD.
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Encéfalo/diagnóstico por imagem , Fucose/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Transtornos de Estresse Pós-Traumáticos/metabolismo , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: Tea consumption may improve endothelial function and blood pressure via increased bioavailability and bioactivity of nitric oxide. However, questions remain as to the impact of the common practice of adding milk. OBJECTIVE: To investigate the effect of regular consumption of black tea, with and without milk, on vascular function and blood pressure in healthy volunteers. DESIGN: A randomised, controlled, crossover study was performed in 17 healthy volunteers; 7 men and 10 women, mean age 22.4 ± 3.0 years. Participants received each of the following treatments in random order for 4 weeks, with no washout period in between, (i) hot water, (ii) black tea and (iii) black tea with milk. Vascular function was assessed using flow-mediated dilatation (FMD) of the brachial artery at the end of each treatment period. In addition, participants monitored their home blood pressure for the last 7 days of each treatment period. A blood and urine sample was also collected at the end of each treatment period. RESULTS: Black tea increased FMD compared to the hot water control group (1.00 ± 0.18%, P < 0.0001). Black tea with milk decreased FMD compared to both the hot water control (-0.64 ± 0.19%, P = 0.001) and black tea (-1.64 ± 0.19%, P < 0.0001). Compared with hot water, black tea did not alter blood pressure, while black tea with milk increased systolic (1.1 ± 0.5 mmHg, P = 0.03) and diastolic blood pressure (2.0 ± 0.5 mmHg, P < 0.0001). Black tea (-1.8 ± 0.5 bpm, P < 0.001) and black tea with milk (-1.8 ± 0.6 bpm, P < 0.001) lowered heart rate compared to hot water. No significant difference for plasma nitrate or nitrite was observed between treatment groups. CONCLUSIONS: The addition of milk to black tea alters the acute/short-term impact of regular tea consumption on vascular function and blood pressure in young healthy men and women. The exact mechanism for this affect remains unknown and longer-term trials to establish this effect in a range of populations are warranted.
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Artéria Braquial/fisiologia , Leite/metabolismo , Chá/metabolismo , Adulto , Animais , Pressão Sanguínea , Camellia sinensis/química , Camellia sinensis/metabolismo , Estudos Cross-Over , Feminino , Frequência Cardíaca , Humanos , Masculino , Vasodilatação , Adulto JovemRESUMO
BACKGROUND: Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids. OBJECTIVES: We determined whether the acute administration of increasing doses of a common quercetin glycoside (quercetin-3-O-glucoside) improves endothelial function and reduces BP in a dose-dependent manner. We also explored whether any effects were correlated with changes in plasma NO production. DESIGN: A randomized, controlled, crossover study was performed in 15 healthy volunteers who each completed 5 visits with a minimum washout period of 1 wk between testing days. Participants received each of the following 5 interventions in a random order: 1) 0, 2) 50, 3) 100, 4) 200, or 5) 400 mg quercetin-3-O-glucoside. Endothelial function and BP were assessed before and 60 min after intervention. A blood sample was taken before and 90 min after intervention for the analysis of plasma nitrate and nitrite as markers of NO production as well as of plasma quercetin metabolites. RESULTS: Although we observed a significant correlation between the dose of quercetin-3-O-glucoside and plasma concentrations of total quercetin (R(2) = 0.52, P < 0.001) and isorhamnetin (R(2) = 0.12, P = 0.005), we showed no improvements in endothelial function or BP and no changes in NO production after any dose. CONCLUSION: From these results, we conclude that there are no acute changes in BP or the NO-mediated endothelium-dependent relaxation of the brachial artery with doses of quercetin ranging from 50 to 400 mg in healthy men and women. This trial was registered at www.anzctr.org.au as ACTRN12615001338550.
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Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Vasodilatação/efeitos dos fármacos , Idoso , Artéria Braquial , Doenças Cardiovasculares/sangue , Estudos Cross-Over , Relação Dose-Resposta a Droga , Endotélio Vascular/fisiologia , Feminino , Flavonoides/sangue , Flavonoides/farmacologia , Glucosídeos , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Quercetina/sangue , Quercetina/farmacologia , Valores de ReferênciaRESUMO
An increase in nitrate intake can augment circulating nitrite and nitric oxide. This may lead to lower blood pressure and improved vascular function. Green leafy vegetables, such as spinach, are rich sources of nitrate. We aimed to assess the acute effects of a nitrate-rich meal containing spinach on arterial stiffness and blood pressure in healthy men and women. Twenty-six participants aged 38-69years were recruited to a randomized controlled cross-over trial. The acute effects of two energy-matched (2000kJ) meals, administered in random order, were compared. The meals were either high nitrate (220mg of nitrate derived from spinach [spinach]) or low nitrate [control]. Outcome measurements were performed pre-meal and at specific time points up to 210min post meal. Spinach resulted in an eightfold increase in salivary nitrite and a sevenfold increase in salivary nitrate concentrations from pre-meal (P<0.001) to 120min post meal. Spinach compared with control resulted in higher large artery elasticity index (P<0.001), and lower pulse pressure (P<0.001) and systolic blood pressure (P<0.001). Post meal carotid-femoral pulse wave velocity (P=0.07), augmentation index (P=0.63), small artery elasticity index (P=0.98) and diastolic blood pressure (P=0.13) were not significantly altered by spinach relative to control. Therefore, consumption of a nitrate-rich meal can lower systolic blood pressure and pulse pressure and increase large artery compliance acutely in healthy men and women. If sustained, these effects could contribute to better cardiovascular health.
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Pressão Sanguínea/efeitos dos fármacos , Nitratos/farmacologia , Rigidez Vascular/efeitos dos fármacos , Adulto , Idoso , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/administração & dosagem , Nitratos/análise , Óxido Nítrico/sangue , Nitritos/análise , Saliva/química , Spinacia oleracea/química , Rigidez Vascular/fisiologiaRESUMO
There is mounting evidence that specific dietary polyphenols can enhance vascular health by augmenting nitric oxide. Our aim was to investigate the acute effects of chlorogenic acid, an important dietary phenolic acid present in coffee (400 mg, equivalent to 2 cups of coffee), on nitric oxide status, endothelial function, and blood pressure. Healthy men and women (n = 23) were recruited to a randomized, double-blind, placebo-controlled, crossover trial. Chlorogenic acid resulted in significantly higher plasma concentrations of chlorogenic acid (P < 0.001). Relative to control, the mean post-treatment systolic blood pressure (-2.41 mmHg, 95% CI: -0.03, -4.78; P = 0.05) and diastolic blood pressure (-1.53 mmHg, 95% CI: -0.05, -3.01; P = 0.04) were significantly lower with chlorogenic acid. Markers of nitric oxide status (P > 0.10) and the measure of endothelial function (P = 0.60) were not significantly influenced. Chlorogenic acid can lower blood pressure acutely, an effect that, if sustained, would benefit cardiovascular health.
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Pressão Sanguínea/efeitos dos fármacos , Ácido Clorogênico/administração & dosagem , Endotélio Vascular/fisiologia , Óxido Nítrico/metabolismo , Adulto , Ácido Clorogênico/sangue , Café/química , Endotélio Vascular/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Humanos , MasculinoRESUMO
Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33 nmol/L, 26, 42; apple, 51 nmol/L, 40, 65; spinach, 86 nmol/L, 68, 110; apple+spinach, 69 nmol/L, 54, 88; P<0.01) and higher nitrite (control, 35 nmol/L, 27, 46; apple, 69 nmol/L, 53, 90; spinach, 99 nmol/L, 76, 129; apple+spinach, 80 nmol/L, 61, 104; P<0.01). Compared to control, all treatments resulted in higher flow-mediated dilatation (P<0.05) and lower pulse pressure (P<0.05), and apple and spinach resulted in lower systolic blood pressure (P<0.05). No significant effect was observed on diastolic blood pressure. The combination of apple and spinach did not result in additive effects on nitric oxide status, endothelial function, or blood pressure. In conclusion, flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status, enhance endothelial function, and lower blood pressure acutely, outcomes that may benefit cardiovascular health.
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Doenças Cardiovasculares/prevenção & controle , Endotélio Vascular/metabolismo , Flavonoides/metabolismo , Malus/metabolismo , Nitratos/metabolismo , Óxido Nítrico/biossíntese , Spinacia oleracea/metabolismo , Adulto , Pressão Sanguínea , Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/dietoterapia , Estudos Cross-Over , Feminino , Humanos , Masculino , Malus/química , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Nitritos/sangue , S-Nitrosotióis/análise , Spinacia oleracea/química , Sístole , Vasodilatação/fisiologiaRESUMO
BACKGROUND: Impaired endothelial function has been reported in hypertensive individuals. The extent to which such changes reflect the co-existence of other cardiovascular disease risk factors rather than an independent association with blood pressure remains uncertain. OBJECTIVE: To assess the relationship between brachial artery vasomotor function and ambulatory blood pressure in hypertensive individuals and normotensive controls. METHODS: We assessed 24-h ambulatory blood pressure and brachial artery endothelial and smooth muscle function in 155 patients with hypertension and 40 normotensive controls. The vasomotor functions were determined by ultrasonographic assessment of vasodilator responses to flow and sublingual glyceryl trinitrate, respectively. Patients with hypertension were categorized as either treated (n = 85) or untreated (n = 70), and further subdivided on the basis of either no or at least one other cardiovascular risk factor. These included hyperlipidaemia, smoking, diabetes or a previous coronary or cerebrovascular event. RESULTS: Age- and sex-adjusted flow-mediated and glyceryl trinitrate-mediated responses were not significantly different in hypertensive individuals with respect to treatment status or the presence of risk factors when compared with controls. However, when data from all 195 study participants were pooled, 24-h ambulatory systolic blood pressure was inversely related to flow-mediated response (P = 0.002), and both systolic and diastolic blood pressure were inversely related to glyceryl trinitrate response (P < 0.001 and P = 0.009, respectively). Observed relationships were largely unaltered after further adjustment for body mass index, antihypertensive treatment or the presence of other risk factors. CONCLUSIONS: The finding of a direct and inverse relationship between the level of ambulatory blood pressure and flow-mediated and glyceryl trinitrate responses is consistent with a direct influence of blood pressure on conduit vessel vascular function.
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Pressão Sanguínea/fisiologia , Artéria Braquial/fisiologia , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/efeitos dos fármacos , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Nitroglicerina , Valor Preditivo dos Testes , Fatores de Risco , Ultrassonografia , VasodilatadoresRESUMO
BACKGROUND: Regular light consumption of alcohol appears to reduce the risk of cardiovascular disease, whereas in heavier drinkers the opposite effect is seen. This biphasic relationship could partly be due to contrasting actions of low and high alcohol intake on endothelial function. OBJECTIVE: To determine whether reducing alcohol intake in moderate-to-heavy drinkers (40-110 g/day) would improve conduit artery endothelial function as assessed by post-ischaemic brachial artery flow-mediated dilatation (FMD). METHODS: In a two-way cross-over study, 16 healthy men either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake during sequential 4-week periods. At the end of each period of FMD and glyceryl trinitrate-induced brachial artery dilatation, blood pressure, plasma lipids, homocysteine and biomarkers of alcohol consumption (gamma-glutamyl transpeptidase) and endothelial function (E-selectin, von Willebrand factor, endothelin-1) were assessed. RESULTS: The participants reduced their alcohol intake from 72.4 to 7.9 g/day. This self-reported reduction in alcohol intake was corroborated by significant decreases in gamma-glutamyl transpeptidase (24%). The decrease in alcohol intake resulted in reductions in total cholesterol (5%), high-density lipoprotein cholesterol (17%), homocysteine (9%) and systolic and diastolic blood pressure [5 mmHg (P = 0.01) and 4 mmHg (P = 0.003), respectively]. There was no effect of alcohol on FMD (6.23 +/- 0.75% compared with 6.24 +/- 0.71%, P = NS), glyceryl trinitrate-induced vasodilatation, E-selectin, endothelin-1 and von Willebrand factor. CONCLUSION: Substantial reduction in alcohol intake in healthy moderate-to-heavy drinkers does not improve endothelial function as measured by post-ischaemic flow-mediated dilatation of the brachial artery or biomarkers of endothelial function.