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1.
J Hypertens ; 42(1): 23-49, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37712135

RESUMO

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Hipertensão , Humanos , Hipertensão/prevenção & controle , Hipertensão/complicações , Doenças Cardiovasculares/etiologia , Estilo de Vida , Pressão Sanguínea , Insuficiência Cardíaca/complicações
2.
Food Funct ; 14(22): 10232-10239, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37916919

RESUMO

Industrially generated trans-fats have been linked with cardiovascular disease (CVD) and have thus been replaced by interesterified (IE) fats, in foods. Interesterification rearranges fatty acids on the glycerol backbone of a triacylglycerol molecule. However, the impact of IE fat on health is unknown. We recently reported differences in lipid absorption kinetics between IE and rapeseed oil (RO). Here, we investigated the mechanisms underpinning IE fat digestion kinetics in the same muffins baked using an IE fat, non-IE fat [with the same fatty acid composition] and rapeseed oil (RO) under simulated conditions. IE and non-IE fats were largely solid in the gastric phase and strongly associated within the muffin matrix, whereas RO formed liquid droplets which separated from the matrix. No significant difference in lipolysis rates was detected between IE and non-IE fats. The lipolysis of the RO fat was slower, due to long-chain PUFAs. Interesterification itself did not affect digestibility, but the strong interaction between the hard fats and the muffin matrix resulted in extensive creaming of the matrix in the stomach, leading to delayed gastric emptying compared to the RO sample. The rate and extent of lipolysis were determined by the amount of fat available and the structure of the fat. This demonstrates the importance of the physical behaviour of the fats during digestion and provides a mechanistic understanding of the overall lipid digestion of IE fats, which relates to their physiological response.


Assuntos
Gorduras na Dieta , Ácidos Graxos , Óleo de Brassica napus , Triglicerídeos/química , Ácidos Graxos/química , Gorduras , Estômago
3.
Dev Psychol ; 59(5): 813-828, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36972093

RESUMO

Two experiments investigated perceived and physiological changes in anxiety in children (7-11 years; N = 222; 98 female) in a performance situation after they observed another child in a similar situation with a negative or neutral outcome. The sample's London, United Kingdom, school catchment areas ranged from low to high socioeconomic statuses with 31% to 49% of children from ethnic minority backgrounds. In Study 1, participants watched one of two films of a child playing a simple musical instrument (a kazoo). In one film, an audience of peers responds negatively to the performance. In the other film, the audience response was neutral. Participants were then filmed playing the instrument themselves and measures of perceived and actual heart rate were taken along with individual differences in trait social anxiety, anxiety sensitivity, and effortful control. To better understand findings from Study 1, Study 2 replicated Study 1 but added a manipulation check and measures of effortful control and self-reported anxiety. Multiple regression analyses found watching a negative performance film, compared with a neutral one, was associated with a blunted heart rate response for children with low effortful control (Study 1 and 2). These findings suggest that children who are low in effortful control may disengage during performance tasks if the situation's social threat is elevated. Hierarchical regression analyses found that, compared to the neutral film, the negative performance film elevated children's self-report anxiety (Study 2). Overall, the findings indicated that anxiety in performance situations can be elevated after observing peers' negative experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Etnicidade , Grupos Minoritários , Criança , Humanos , Feminino , Ansiedade , Transtornos de Ansiedade , Medo
4.
Nutrients ; 14(22)2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36432493

RESUMO

Anthocyanins have poor bioavailability, but the factors affecting this remain unclear. Uptake into cells could impact the bioavailability; therefore, understanding factors affecting anthocyanin uptake is pivotal to improve their bioavailability and reveal the mechanism for their uptake. This study aimed to investigate the effect of anthocyanin structure, pH and glucose on the uptake of anthocyanins by Caco-2 cells. Anthocyanin extract from strawberry and red grape at 10 or 20 µM was added to Caco-2 cells. Anthocyanin toxicity to the cells was firstly examined to ensure the same cell viability. The uptake was carried out at pH 7 and 6.5 to evaluate the effect of pH. Glucose (1 mM) was used to investigate its effect. The results show that anthocyanins toxicity was dependent on the concentration and length of exposure. Anthocyanin uptake was concentration-dependent and affected by their structures, in which cyanidin-3-glucoside uptake was higher than pelargonidin-3-glucoside. No metabolites from Caco-2 cell activity were detected. An increased uptake with a decrease in pH was observed, which may be linked to the increase in anthocyanins stability and may indicate the role of proton co-transporter. This also suggests that the jejunum would be the favourable section of small intestine for anthocyanin uptake. Reduced anthocyanin uptake in the presence of glucose suggested that facilitative glucose transporter could be involved in the uptake of anthocyanins by Caco-2 cells.


Assuntos
Antocianinas , Glucose , Humanos , Antocianinas/química , Células CACO-2 , Transporte Biológico , Concentração de Íons de Hidrogênio
5.
Int J Food Sci Nutr ; 73(8): 1091-1095, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36146949

RESUMO

The majority of university curricula for health professionals does not incorporate courses on human nutrition and its links with human and planetary health. This primarily applies to medical and pharmacy students, who have important counselling roles and are at the forefront of public health. To address this important issue, EIT Food recently launched an online course on nutrition, health, and sustainability. Learners were able to provide feedback on the course through an end-of-course survey and social interaction on the FutureLearn platform. The course was very well attended worldwide and received positive feedback from learners. A total of 3,858 students enrolled in the program, from >20 countries. Learners reported inadequate training on nutrition in their own curriculum and indicated they would use key insights from the course to inform their own practice. This report provides insights from the course, which could be used as guidance for future initiatives.


Assuntos
Currículo , Estado Nutricional , Humanos , Dieta , Inquéritos e Questionários , Pessoal de Saúde
6.
J Hypertens ; 40(9): 1758-1767, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35943103

RESUMO

BACKGROUND: Most comparisons of arterial stiffness between ethnic groups focus on pulse wave velocity. This study used the cardio-ankle vascular index (CAVI) in European compared to Japanese individuals to investigate how cardiovascular risk factors affect arterial aging across geographic regions. METHODS: Four hundred and ninety-four European and 1044 Japanese individuals underwent measurements of CAVI, blood pressure and information on cardiovascular risk factors. Both datasets included individuals with 0-5 cardiovascular risk factors. RESULTS: Average CAVI was higher in the Japanese than the European group in every age category, with significant differences up to 75 years for males and 85 for females. The correlation of CAVI with age, controlled for cardiovascular risk factors, was slightly higher in Japanese females (r = 0.594 vs. Europeans r = 0.542) but much higher in European males (r = 0.710 vs. Japanese r = 0.511). There was a significant correlation between CAVI and total cardiovascular risk factors in the Japanese (r = 0.141, P < 0.001) but not the European group. On linear regression, average CAVI was significantly dependent on age, sex, diabetes, BMI, SBP and geographic region. When divided into 'healthy' vs. 'high risk', the healthy group had a steeper correlation with age for Europeans (r = 0.644 vs. Japanese r = 0.472, Fisher's Z P < 0.001), whereas in the high-risk group, both geographic regions had similar correlations. CONCLUSION: Japanese patient groups had higher arterial stiffness than Europeans, as measured by CAVI, controlling for cardiovascular risk factors. Europeans had greater increases in arterial stiffness with age in healthy individuals, particularly for males. However, cardiovascular risk factors had a greater impact on the Japanese group.


Assuntos
Análise de Onda de Pulso , Rigidez Vascular , Envelhecimento , Tornozelo/irrigação sanguínea , Índice Tornozelo-Braço , Artérias , Pressão Sanguínea , Feminino , Humanos , Japão/epidemiologia , Masculino , Rigidez Vascular/fisiologia
7.
Microorganisms ; 11(1)2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36677347

RESUMO

Soil microbes play important roles in plant health and ecosystem functioning, however, they can often be disturbed or depleted in degraded lands. During seed-based revegetation of such sites there is often very low germination and seedling establishment success, with recruitment of beneficial microbes to the rhizosphere one potential contributor to this problem. Here we investigated whether Australian native plant species may benefit from planting seed encapsulated within extruded seed pellets amended with one of two microbe-rich products: a commercial vermicast extract biostimulant or a whole-soil inoculum from a healthy reference site of native vegetation. Two manipulative glasshouse trials assessing the performance of two Australian native plant species (Acacia parramattensis and Indigofera australis) were carried out in both unmodified field-collected soil (trial 1) and in the same soil reduced in nutrients and microbes (trial 2). Seedling emergence and growth were compared between pelleted and bare-seeded controls and analyzed alongside soil nutrient concentrations and culturable microbial community assessments. The addition of microbial amendments maintained, but did not improve upon, high levels of emergence in both plant species relative to unamended pellets. In trial 1, mean time to emergence of Acacia parramattensis seedlings was slightly shorter in both amended pellet types relative to the standard pellets, and in trial 2, whole-soil inoculum pellets showed significantly improved growth metrics. This work shows that there is potential for microbial amendments to positively affect native plant emergence and growth, however exact effects are dependent on the type of amendment, the plant species, and the characteristics of the planting site soil.

8.
Naturwissenschaften ; 108(6): 61, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797399

RESUMO

Nomadism is an advantageous life history strategy for specialised predators because it enables the predator to respond rapidly to changes in prey populations. The letter-winged kite (Elanus scriptus) is a nomadic nocturnal bird of prey endemic to arid and semi-arid zones of Australia. Letter-winged kites prey almost exclusively on nocturnal rodents and are often associated with rodent irruptions, but little is known about the ecology of letter-winged kites inside their core range. The Strzelecki Desert contains a known dingo-mediated predation refuge for native rodents. In this manuscript, we compare kite sightings, predator activity, and small mammal populations across survey sites in the Strzelecki Desert where dingoes were common and where dingoes were rare and use publicly available data from the Atlas of Living Australia (ALA) to assess trends in the occurrence of kites in the region. Ninety-five percent of ALA observations occurred in areas where dingoes were common. Similarly, all our observations of kites occurred where dingoes were common and during an extended population irruption of Notomys fuscus. Notomys fuscus was the most frequent item in the letter-winged kite diet at our study sites. We suggest that there is significant evidence that these sites in the Strzelecki Desert form part of the core range for the letter-winged kite whose use of this area is facilitated by a predation refuge for rodents mediated by the dingo. We conclude that predation refuges mediated by dingoes could be a factor driving the distributions of letter-winged kites and other predators of rodents, particularly nomadic predators.


Assuntos
Cadeia Alimentar , Comportamento Predatório , Animais , Dieta , Mamíferos , Murinae
9.
Br J Clin Pharmacol ; 87(12): 4726-4736, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33982797

RESUMO

AIMS: To test if 6 months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, vs. placebo/doxazosin, to control for blood pressure (BP). METHODS: A subgroup of participants in our double-blind, randomized-controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate-containing beetroot juice or placebo nitrate-depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima-media thickness (CIMT, mm) was performed at baseline, 3- and 6-months. Carotid local stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph) and carotid lumen area. Data were analysed by modified intention to treat and using mixed-model effect, adjusted for confounders. RESULTS: In total, 93 subjects had a baseline evaluation and 86% had follow-up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate-containing vs. placebo juice significantly lowered CIMT (-0.06 [95% confidence interval -0.12, -0.01], P = .034), an overall difference of ~8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (-0.34 [-0.62, -0.06]) however, no difference was detected vs. spironolactone (-0.15 [-0.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD. CONCLUSIONS: Our results show that 6 months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP-independent effect on carotid structure and function.


Assuntos
Aterosclerose , Beta vulgaris , Diabetes Mellitus Tipo 2 , Aterosclerose/tratamento farmacológico , Beta vulgaris/química , Pressão Sanguínea , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Humanos , Nitratos
10.
Am J Clin Nutr ; 113(5): 1221-1231, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33675343

RESUMO

BACKGROUND: Interesterified (IE) fats are widely used in place of trans fats; however, little is known about their metabolism. OBJECTIVES: To test the impact of a commonly consumed IE compared with a non-IE equivalent fat on in vivo postprandial and in vitro lipid metabolism, compared with a reference oil [rapeseed oil (RO)]. METHODS: A double-blinded, 3-phase crossover, randomized controlled trial was performed in healthy adults (n = 20) aged 45-75 y. Postprandial plasma triacylglycerol and lipoprotein responses (including stable isotope tracing) to a test meal (50 g fat) were evaluated over 8 h. The test fats were IE 80:20 palm stearin/palm kernel fat, an identical non-IE fat, and RO (control). In vitro, mechanisms of digestion were explored using a dynamic gastric model (DGM). RESULTS: Plasma triacylglycerol 8-h incremental area under the curves were lower following non-IE compared with RO [-1.7 mmol/L⋅h (95% CI: -3.3, -0.0)], but there were no differences between IE and RO or IE and non-IE. LDL particles were smaller following IE and non-IE compared with RO (P = 0.005). Extra extra large, extra large, and large VLDL particle concentrations were higher following IE and non-IE compared with RO at 6-8 h (P < 0.05). No differences in the appearance of [13C]palmitic acid in plasma triacylglycerol were observed between IE and non-IE fats. DGM revealed differences in phase separation of the IE and non-IE meals and delayed release of SFAs compared with RO. CONCLUSIONS: Interesterification did not modify fat digestion, postprandial lipemia, or lipid metabolism measured by stable isotope and DGM analysis. Despite the lower lipemia following the SFA-rich fats, increased proatherogenic large triacylglycerol-rich lipoprotein remnant and small LDL particles following the SFA-rich fats relative to RO adds a new postprandial dimension to the mechanistic evidence linking SFAs to cardiovascular disease risk.


Assuntos
Gorduras Insaturadas na Dieta/efeitos adversos , Gorduras Insaturadas na Dieta/análise , Ácidos Graxos Monoinsaturados/efeitos adversos , Lipoproteínas/sangue , Ácido Palmítico/efeitos adversos , Período Pós-Prandial , Idoso , Apolipoproteína B-48 , Aterosclerose/induzido quimicamente , Quilomícrons/química , Estudos Cross-Over , Gorduras Insaturadas na Dieta/administração & dosagem , Método Duplo-Cego , Ácidos Graxos Monoinsaturados/administração & dosagem , Feminino , Humanos , Hiperlipidemias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Ácido Palmítico/administração & dosagem , Ácido Palmítico/química , Triglicerídeos
11.
Ecology ; 102(4): e03301, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33565639

RESUMO

Herbivory is ubiquitous. Despite being a potential driver of plant distribution and performance, herbivory remains largely undocumented. Some early attempts have been made to review, globally, how much leaf area is removed through insect feeding. Kozlov et al., in one of the most comprehensive reviews regarding global patterns of herbivory, have compiled published studies regarding foliar removal and sampled data on global herbivory levels using a standardized protocol. However, in the review by Kozlov et al., only 15 sampling sites, comprising 33 plant species, were evaluated in tropical areas around the globe. In Brazil, which ranks first in terms of plant biodiversity, with a total of 46,097 species, almost half (43%) being endemic, a single data point was sampled, covering only two plant species. In an attempt to increase knowledge regarding herbivory in tropical plant species and to provide the raw data needed to test general hypotheses related to plant-herbivore interactions across large spatial scales, we proposed a joint, collaborative network to evaluate tropical herbivory. This network allowed us to update and expand the data on insect herbivory in tropical and temperate plant species. Our data set, collected with a standardized protocol, covers 45 sampling sites from nine countries and includes leaf herbivory measurements of 57,239 leaves from 209 species of vascular plants belonging to 65 families from tropical and temperate regions. They expand previous data sets by including a total of 32 sampling sites from tropical areas around the globe, comprising 152 species, 146 of them being sampled in Brazil. For temperate areas, it includes 13 sampling sites, comprising 59 species. Thus, when compared to the most recent comprehensive review of insect herbivory (Kozlov et al.), our data set has increased the base of available data for the tropical plants more than 460% (from 33 to 152 species) and the Brazilian sampling was increased 7,300% (from 2 to 146 species). Data on precise levels of herbivory are presented for more than 57,000 leaves worldwide. There are no copyright restrictions. Please cite this paper when using the current data in publications; the authors request to be informed how the data is used in the publications.

12.
Br J Clin Pharmacol ; 87(2): 577-587, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32520418

RESUMO

AIMS: Dietary nitrate from sources such as beetroot juice lowers blood pressure (BP) via the nitrate-nitrite-nitric oxide (NO) pathway. However, NO and nitrite are inactivated via reoxidation to nitrate, potentially limiting their activity. Cytochrome P450-3A4 inhibition with troleandomycin prevents nitrite re-oxidation to nitrate in rodent liver. Grapefruit juice contains the CYP3A4 inhibitor furanocoumarin. We therefore hypothesized that grapefruit juice would enhance BP-lowering with beetroot juice by maintaining circulating [nitrite]. METHODS: We performed a randomized, placebo-controlled, 7-hour crossover study in 11 healthy volunteers, attending on 3 occasions, receiving: a 70-mL shot of active beetroot juice (Beet-It) and either (i) 250 mL grapefruit juice (Active Beet+GFJ), or (ii) 250 mL water (Buxton, Active Beet+H2 O); or (iii) Placebo Beet+GFJ. RESULTS: The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJ vs Active Beet+H2 O (P = .02), and pulse pressure, PP (P = .0003). Peak mean differences in SBP and PP were seen at T = 5 hours: -3.3 mmHg (95% confidence interval [CI] -6.43 to -0.15) and at T = 2.5 hours: -4.2 mmHg (95% CI -0.3 to -8.2), respectively. Contrary to the hypothesis, plasma [nitrite] was lower with Active Beet+GFJ vs Active Beet+H2 O (P = .006), as was salivary nitrite production (P = .002) and saliva volume (-0.34 mL/min [95% CI -0.05 to -0.68]). The taste score of Beet+GFJ was 1.4/10 points higher than Beet+H2 O (P = .03). CONCLUSION: Grapefruit juice enhanced beetroot juice's effect on lowering SBP and PP despite decreasing plasma [nitrite]. Besides suggesting more complex mechanisms, there is potential for maximising the clinical benefit of dietary nitrate and targeting isolated systolic hypertension.


Assuntos
Beta vulgaris , Citrus paradisi , Pressão Sanguínea , Estudos Cross-Over , Suplementos Nutricionais , Sucos de Frutas e Vegetais , Nitratos
14.
Br J Clin Pharmacol ; 86(5): 891-902, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31833569

RESUMO

AIMS: To test if spironolactone or dietary nitrate from beetroot juice could reduce arterial stiffness as aortic pulse wave velocity (PWVart), a potential treatment target, independently of blood pressure. METHODS: Daily spironolactone (≤50 mg) vs doxazosin (control ≤16 mg) and 70 mL beetroot juice (Beet-It ≤11 mmol nitrate) vs nitrate-depleted juice (placebo; 0 mmol nitrate) were tested in people at risk or with type-2 diabetes using a double-blind, 6-month factorial trial. Vascular indices (baseline, 12, 24 weeks) were cardiac-ankle vascular index (CAVI), a nominally pressure-independent stiffness measure (primary outcome), PWVart secondary, central systolic pressure and augmentation. Analysis was intention-to-treat, adjusted for systolic pressure differences between trial arms. RESULTS: Spironolactone did not reduce stiffness, with evidence for reduced CAVI on doxazosin rather than spironolactone (mean difference [95% confidence interval]; 0.25 [-0.3, 0.5] units, P = .080), firmer for PWVart (0.37 [0.01, 0.7] m/s, P = .045). There was no difference in systolic pressure reduction between spironolactone and doxazosin (0.7 [-4.8, 3.3] mmHg, P = .7). Circulating nitrate and nitrite increased on active vs placebo juice, with central systolic pressure lowered -2.6 [-4.5, - 0.8] mmHg, P = .007 more on the active juice, but did not reduce CAVI, PWVart or peripheral pressure. Change in nitrate and nitrite concentrations were 1.5-fold [1.1-2.2] and 2.2-fold [1.3, 3.6] higher on spironolactone than on doxazosin respectively; both P < .05. CONCLUSION: Contrary to our hypothesis, in at-risk/type 2 diabetes patients, spironolactone did not reduce arterial stiffness, rather PWVart was lower on doxazosin. Dietary nitrate elevated plasma nitrite, selectively lowering central systolic pressure, observed previously for nitrite.


Assuntos
Beta vulgaris , Diabetes Mellitus Tipo 2 , Nitratos , Espironolactona , Rigidez Vascular , Adulto , Idoso , Pressão Sanguínea , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/uso terapêutico , Análise de Onda de Pulso , Espironolactona/uso terapêutico , Rigidez Vascular/efeitos dos fármacos
15.
Diabetologia ; 63(2): 313-323, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31732790

RESUMO

AIMS/HYPOTHESIS: Progressive decline in functional beta cell mass is central to the development of type 2 diabetes. Elevated serum levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) are associated with beta cell failure in type 2 diabetes and eNAMPT immuno-neutralisation improves glucose tolerance in mouse models of diabetes. Despite this, the effects of eNAMPT on functional beta cell mass are poorly elucidated, with some studies having separately reported beta cell-protective effects of eNAMPT. eNAMPT exists in structurally and functionally distinct monomeric and dimeric forms. Dimerisation is essential for the NAD-biosynthetic capacity of NAMPT. Monomeric eNAMPT does not possess NAD-biosynthetic capacity and may exert distinct NAD-independent effects. This study aimed to fully characterise the structure-functional effects of eNAMPT on pancreatic beta cell functional mass and to relate these to beta cell failure in type 2 diabetes. METHODS: CD-1 mice and serum from obese humans who were without diabetes, with impaired fasting glucose (IFG) or with type 2 diabetes (from the Body Fat, Surgery and Hormone [BodyFatS&H] study) or with or at risk of developing type 2 diabetes (from the VaSera trial) were used in this study. We generated recombinant wild-type and monomeric eNAMPT to explore the effects of eNAMPT on functional beta cell mass in isolated mouse and human islets. Beta cell function was determined by static and dynamic insulin secretion and intracellular calcium microfluorimetry. NAD-biosynthetic capacity of eNAMPT was assessed by colorimetric and fluorescent assays and by native mass spectrometry. Islet cell number was determined by immunohistochemical staining for insulin, glucagon and somatostatin, with islet apoptosis determined by caspase 3/7 activity. Markers of inflammation and beta cell identity were determined by quantitative reverse transcription PCR. Total, monomeric and dimeric eNAMPT and nicotinamide mononucleotide (NMN) were evaluated by ELISA, western blot and fluorometric assay using serum from non-diabetic, glucose intolerant and type 2 diabetic individuals. RESULTS: eNAMPT exerts bimodal and concentration- and structure-functional-dependent effects on beta cell functional mass. At low physiological concentrations (~1 ng/ml), as seen in serum from humans without diabetes, eNAMPT enhances beta cell function through NAD-dependent mechanisms, consistent with eNAMPT being present as a dimer. However, as eNAMPT concentrations rise to ~5 ng/ml, as in type 2 diabetes, eNAMPT begins to adopt a monomeric form and mediates beta cell dysfunction, reduced beta cell identity and number, increased alpha cell number and increased apoptosis, through NAD-independent proinflammatory mechanisms. CONCLUSIONS/INTERPRETATION: We have characterised a novel mechanism of beta cell dysfunction in type 2 diabetes. At low physiological levels, eNAMPT exists in dimer form and maintains beta cell function and identity through NAD-dependent mechanisms. However, as eNAMPT levels rise, as in type 2 diabetes, structure-functional changes occur resulting in marked elevation of monomeric eNAMPT, which induces a diabetic phenotype in pancreatic islets. Strategies to selectively target monomeric eNAMPT could represent promising therapeutic strategies for the treatment of type 2 diabetes.


Assuntos
Citocinas/sangue , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Nicotinamida Fosforribosiltransferase/sangue , Nicotinamida Fosforribosiltransferase/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Glucagon/sangue , Glucagon/metabolismo , Humanos , Immunoblotting , Secreção de Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Masculino , Espectrometria de Massas , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Somatostatina/sangue , Somatostatina/metabolismo , Relação Estrutura-Atividade
16.
J Gerontol A Biol Sci Med Sci ; 74(7): 967-976, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-30772905

RESUMO

Potential health benefits of blueberries may be due to vascular effects of anthocyanins that predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation. The effects were similar to those of wild blueberries containing similar amounts of anthocyanins, whereas control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month wild blueberry consumption increased flow-mediated dilation and lowered 24-hour ambulatory systolic blood pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 21 correlated with acute and chronic flow-mediated dilation improvements, respectively. Injection of these metabolites improved flow-mediated dilation in mice. Daily wild blueberry consumption led to differential expression (>1.2-fold) of 608 genes and 3 microRNAs, with Mir-181c showing a 13-fold increase in peripheral blood mononuclear cells. Patterns of 13 metabolites were independent predictors of gene expression changes and pathway enrichment analysis revealed significantly modulated biological processes involved in cell adhesion, migration, immune response, and cell differentiation. Our results identify anthocyanin metabolites as major mediators of vascular bioactivities of blueberries and changes of cellular gene programs. Trial registration: NCT025208.


Assuntos
Antocianinas/metabolismo , Mirtilos Azuis (Planta) , Doenças Cardiovasculares , Endotélio Vascular , Fitoterapia/métodos , Animais , Antocianinas/farmacologia , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Metabolômica/métodos , Modelos Animais , Nutrigenômica/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Br J Clin Pharmacol ; 85(1): 169-180, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30294825

RESUMO

AIMS: The aims of the present study were to explore whether a long-term intervention with dietary nitrate [(NO3- ), a potential tolerance-free source of beneficial vasoactive nitric oxide] and spironolactone (to oppose aldosterone's potential deleterious cardiovascular effects) improve cardiac structure/function, independently of blood pressure (BP), in patients with/at risk of type 2 diabetes (a population at risk of heart failure). METHODS: A subsample of participants in our double-blind, randomized, factorial-design intervention (VaSera) trial of active beetroot juice as a nitrate source (≤11.2 mmol) or placebo (nitrate depleted) beetroot juice, and either ≤50 mg spironolactone or ≤16 mg doxazosin (control), had transthoracic cardiac ultrasounds at baseline (n = 105), and at 3 months and 6 months (n = 87) after the start of the intervention. Analysis was by modified intent-to-treat. RESULTS: Nitrate-containing juice (n = 40) decreased left ventricular (LV) end-diastolic volume {-6.3 [95% confidence interval (CI) -11.1, -1.6] ml} and end-systolic volume [-3.2 (95% CI -5.9, -0.5) ml], and increased end-diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall thickness compared with doxazosin (n = 43) [-0.01 (95% CI -0.02, -0.00)]. Although spironolactone reduced LV mass index relative to baseline [-1.48 (95% CI -2.08, -0.88) g m-2.7 ], there was no difference vs. doxazosin [-0.85 (95% CI -1.76, 0.05) g m-2.7 ]. Spironolactone also decreased the E/A ratio [-0.12 (95% CI -0.19, -0.04)] and increased S' (a tissue-Doppler systolic function index) by 0.52 (95% CI 0.05, 1.0) cm s-1 . BP did not differ between the juices, or between the drugs. CONCLUSIONS: Six months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP-independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic-diastolic function, although confirmatory, were independent of BP.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Insuficiência Cardíaca/prevenção & controle , Coração/efeitos dos fármacos , Nitratos/administração & dosagem , Espironolactona/administração & dosagem , Adulto , Idoso , Beta vulgaris/química , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Doxazossina/administração & dosagem , Ecocardiografia , Feminino , Sucos de Frutas e Vegetais , Coração/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Análise de Onda de Pulso , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos
18.
J R Soc Interface ; 15(144)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29973403

RESUMO

Vegetation cover is fundamental in the formation and maintenance of geomorphological features in dune systems. In arid Australia, increased woody shrub cover has been linked to removal of the apex predator (Dingoes, Canis dingo) via subsequent trophic cascades. We ask whether this increase in shrubs can be linked to altered physical characteristics of the dunes. We used drone-based remote sensing to measure shrub density and construct three-dimensional models of dune morphology. Dunes had significantly different physical characteristics either side of the 'dingo-proof fence', inside which dingoes are systematically eradicated and shrub density is higher over vast spatial extents. Generalized additive models revealed that dunes with increased shrub density were higher, differently shaped and more variable in height profile. We propose that low shrub density induces aeolian and sedimentary processes that result in greater surface erosion and sediment transport, whereas high shrub density promotes dune stability. We speculate that increased vegetation cover acts to push dunes towards an alternate stable state, where climatic variation no longer has a significant effect on their morphodynamic state within the bi-stable state model. Our study provides evidence that anthropogenically induced trophic cascades can indirectly lead to large-scale changes in landscape geomorphology.


Assuntos
Canidae/fisiologia , Clima Desértico , Cadeia Alimentar , Modelos Biológicos , Animais , Austrália
19.
R Soc Open Sci ; 5(1): 171977, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29410877

RESUMO

Functional extinction of once abundant species has frequently preceded understanding of their ecological roles. Consequently, our understanding of ecosystems is prone to shifting baselines because it often relies on observations made on depauperate species assemblages. In Australian deserts, current paradigms are that ants are the dominant granivores, mammals are unimportant seed predators and that myrmecochory in many Australian shrubs is an adaptation to increase dispersal distance and direct seeds to favourable germination sites. Here, we ask whether these paradigms could be artefacts of mammal extinction. We take advantage of a predator-proof reserve within which locally extinct native mammals have been reintroduced to compare seed removal by ants and mammals. Using foraging trays that selectively excluded mammals and ants we show that a reintroduced mammal, the woylie (Bettongia penicillata) was at least as important as ants in the removal of seeds of two shrub species (Dodonaea viscosa and Acacia ligulata). Our results provide evidence that the dominance of ants as granivores and current understanding of the adaptive benefit of myrmecochory in arid Australia may be artefacts of the functional extinction of mammals. Our study shows how reversing functional extinction can provide the opportunity to rethink contemporary understanding of ecological processes.

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