bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUBTLE CORTISOL HYPERSECRETION IS ASSOCIATED WITH GLUCOSE HOMEOSTASIS AND INSULIN RESISTANCE IN NON-DIABETIC ESSENTIAL HYPERTENSIVE PATIENTS
Authors: Catena Cristiana , Da Porto Andrea , Colussi Gianluca , Bulfone Luca , Vivarelli Cinzia , Sechi Leonardo A. 
Published: April 2021

Abstract

Objective:
Patients with Cushing's syndrome (CS) and subclinical Cushing's syndrome (SCS) have a higher prevalence of cardiovascular complications than general population. Increased prevalence of impaired glucose tolerance has been reported in patients with SCS. Excess cortisol secretion can inhibit insulin secretion and impair insulin sensitivity and glucose uptake. We sought that a mild cortisol hypersecretion or an impairment in circadian cortisol rhythm might be associated with glucose homeostasis or insulin-resistance in essential hypertensive (EH) patients.

Design and method:
In 155 non-diabetic EH patients we measured fasting glucose and insulin, calculated the HOMA-index, performed an oral glucose tolerance test (OGTT), calculated the area under the curve for glucose (GAUC) and insulin (IAUC), glucose level at 2-h of OGTT (G120), plasma cortisol level at 8 AM, 5 PM and 11 PM, and after overnight suppression with 1 mg of dexamethasone (DST), 24-h free urinary cortisol and plasma ACTH.

Results:
GAUC and G120 were associated with both 11 PM and post-DST cortisol levels. Fasting insulin level, HOMA-index and IAUC were associated with post-DST cortisol level. These associations were independent of age, adiposity, plasma potassium and ACTH levels, alcohol intake and physical activity.

Conclusions:
In non-diabetic EH patients free of overt CS or SCS, glucose uptake and insulin resistance are associated with subtle cortisol hypersecretion.
THE EXTRACELLULAR ROLE OF REF-1 AS ANTI-INFLAMMATORY FUNCTION
Authors: Jeon Byeong Hwa , Lee Yu Ran , Jo Hee Kyoung , Lee Eun Ok 
Published: April 2021

Abstract

Objective:
Apurinic/apyrimidinic endonuclease/redox factor-1 (Ref-1), a multifunctional protein secreted from stimulated cells, has been identified as a new serological biomarker. Active secretion of Ref-1 in cultured medium occurs in response to intracellular acetylation in cultured human embryonic kidney cells. The presence of plasma Ref-1 in lipopolysaccharides (LPS)-induced endotoxemic rats has also been reported. Despite recent reports on the role of Ref-1 in inflammation, the biological function of secreted Ref-1 remains unknown, especially in vivo. This study aimed to evaluate the possible roles of secreted Ref-1 in lipopolysaccharide-induced systemic inflammation in vivo.

Design and method:
We generated a secretory Ref-1 adenoviral vector system, AdPPT-LS-Ref-1, by conjugation of preprotrypsin leading sequence (PPT-LS) with full-length Ref-1 sequences. Plasma Ref-1 or secreted Ref-1 levels were evaluated with sandwich ELISA.

Results:
TNF-alpha-induced vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells and lipopolysaccharide (LPS)-induced cyclooxygenase-2 in Raw264.7 cells was inhibited by secretory Ref-1, and this inhibitory effect was abrogated following neutralization of Ref-1 with anti-Ref-1 antibody. Plasma Ref-1 levels following administration of AdPPT-LS-Ref-1 (2 × 10^9 ifu, i.p.) for 24 h were substantially higher than those of Adgal (84.6 ± 7.2 ng/ml vs. 4.4 ± 1.5 ng/ml). Treatment with LPS (10 mg/kg, i.v. for 6 h) markedly increased VCAM-1 expression, cathepsin or myeloperoxidase activity, which were significantly suppressed by treatment with AdPPT-LS-Ref-1. Furthermore, LPS-induced cytokines, such as TNF-alpha, interleukin (IL)-1beta, IL-6, and monocyte chemoattractant protein 1, were significantly inhibited in AdPPT-LS-Ref-1-treated mice. However, LPS-induced myeloperoxidase activities were not suppressed by treatment with the redox mutant of secretory Ref-1, AdPPT-LS-Ref-1 (C65A/C93A), or wild-type AdRef-1.

Conclusions:
Collectively, these results suggest that secreted Ref-1 has anti-inflammatory properties and that its redox cysteine residue is associated with the anti-inflammatory activity in vivo. Furthermore, our findings indicate that secretory Ref-1 may be useful as a therapeutic biomolecule against systemic inflammation.
MITOCHONDRIAL ROS MEDIATE ENDOTHELIAL DYSFUNCTION INDUCED BY CHRONIC PARATHYROID HORMONE EXPOSURE
Authors: Iaccarino Guido , Gambardella Jessica , Fiordelisi Antonella , Prevete Nella , Sorriento Daniela 
Published: April 2021

Abstract

Objective:
Vitamin D deficiency contributes to cardiovascular risk (CVR), with hyperparathyroidism advocated as a putative mechanism. Indeed, mounting evidence supports the hypothesis that parathyroid hormone (PTH) impairs endothelial function, even though mechanisms are not fully elucidated. The present study was designed to verify in vitro the ability of sustained exposure to PTH to cause endothelial dysfunction, exploring the underlying mechanisms.

Design and method:
In bovine aortic endothelial cells (BAECs), we evaluated the effects of PTH exposure ([0,1 nM]-24 hours) on both endothelial response to vasodilators, such as bradykinin (Bk, [30 nM]) and acetylcholine (Ach [1 mM]), and angiogenic competence.

Results:
Pretreatment with PTH impaired endothelial response to Bk, but not to Ach, in terms of cytosolic calcium fluxes and NO production. In order to explore the underlying mechanisms, we assessed the production of total and mitochondrial ROS (respectively tROS and mROS) in response to PTH (at 1 and 3 hours). PTH increased ROS generation to an extent high enough to determine oxidation of Bk-receptor B2. Conversely, the oxidation levels oxidation of M1 and M3 Ach-receptors was not affected by PTH. A mROS selective scavenger (MitoTEMPO, [5 mM]) restored the endothelial responsiveness to Bk while the well known antioxidant properties of Vitamin D ([100 nM]) failed to counteract PTH-mediated oxidative stress. PTH determined mitochondrial calcium fluxes ([Ca2+]mt) and the inhibition of Mitochondrial Calcium Uniporter with inhibitor Ru360 [10 mM] reduced mROS production and prevented the following PTH-mediated endothelial dysfunction. Angiogenic competence was evaluated by tubular formations in Endothelial Matrigel Assay and showed a significant impairment in PTH-pretreated cells ([0,1 nM]-24 hours), despite the increase in VEGF transcriptional levels. VEGF-R2 oxidation occurred in response to PTH, suggesting that even the impairment of angiogenesis was due to ROS surge.

Conclusions:
These results indicate that PTH affects endothelial function through ROS production, driven by mitochondrial calcium overload. PTH-induced oxidative stress might act as signaling modifier, altering specific pathways (Bk and VEGF) and preserving others (Ach).
DAILY CONSUMPTION OF DIFFERENT FRUITS IS ASSOCIATED WITH LOWER SYSTOLIC HOME BLOOD PRESSURE IN POPULATION-BASED STUDY
Authors: Ström Edvin , Johansson Martina Ak , Engvall Jan , Östgren Carl Johan , Nystrom Fredrik H. , Wijkman Magnus 
Published: April 2021

Abstract

Objective:
Fruit consumption has in epidemiological studies been associated with lower blood pressure. We studied if home blood pressure was different when eating fruit daily compared to non-daily.

Design and method:
The study design was cross-sectional. Validated food frequency questionnaires and blood pressure monitors were used. The fruits asked for were bananas, apples and pears, citrus fruits including oranges and other fruit or berries. Dichotomisation was done into daily and non-daily fruit consumption. A subgroup analysis was performed regarding self-reported hypertension diagnosis at baseline. Means and differences were analysed with independent t-test.

Results:
In total there were 5057 participants (2531 men and 2526 women). Home blood pressure values were available in 5029 cases, with a mean of 120.8 ± 13.9 / 77.9 ± 8.7 mmHg. There were 1016 individuals in the population stating they had hypertension. Missing data on fruit consumption ranged from 18.0 % in the banana group to 28.1% in other fruit or berries in the total population. The proportion of individuals with valid values eating other fruit or berries daily was 18.9% (n = 686) and non-daily consumption at 81.1% (n = 2953).
The systolic blood pressure levels for the population were on average significantly lower when consuming fruit daily. The greatest difference was when eating other fruit or berries daily (n = 679), with 116.8 ± 13.3 mmHg compared to 120.5 ± 13.8 mmHg non-daily (n = 2940, p < 0.001). The largest difference in the material was found in those with hypertension diagnosis eating other fruit or berries daily (n = 119) with 123.9 ± 13.8 mmHg compared to non-daily (n = 585) 129.7 ± 12.0 mmHg (p < 0.001).

Conclusions:
Overall the blood pressure levels were lower in those consuming fruit daily. The largest difference in systolic blood pressure was when having hypertension and eating other fruit or berries daily compared to non-daily. Due to cross-sectional design, inference analysis is not possible. Further studies on the impact of different fruit consumption on home blood pressure seem warranted, particularly in patients with hypertension.
MAY MEASUREMENT MONTH 2019. AN ANALYSIS OF BLOOD PRESSURE SCREENING RESULTS IN CRETE, GREECE
Authors: Papanikolaou John A. Papadakis Kostas , Papakitsou Ioanna , Mavrikaki Vasiliki , Theodorakopoulou Fotini Psicharaki Vasiliki , Moschou Aikaterini , Vrentzos George 
Published: April 2021

Abstract

Objective:
Worldwide, there is a high level of ignorance about elevated blood pressure (BP), which contributes to the large percentage of underdiagnosed and untreated hypertensive subjects. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and acting as a stimulus to improving screening programs.

Design and method:
An opportunistic cross-sectional survey of volunteers aged = > 18 years was carried out in May 2019. Each adult individual underwent evaluation by 3 sitting BP measurements, a dedicated questionnaire regarding awareness of hypertension (HT) and control of it and other cardiovascular risk factors. Screenings sites in hospitals, shopping centres, workplaces, community centres, GP practices, and pharmacies were set up across the island of Crete as part of this initiative. HT was defined as SBP > 140mmHg and/or DBP > 90mmHg (average of 2nd and 3rd BP measurement) or previous HT diagnosis. BP control was defined as SBP/DBP < 140/90 mmHg in treated hypertensives.

Results:
During this survey, a total of 1612 participants [729 (45.2%) men] were screened for high BP and associated risk factors. Their median age was 57 (range: 18–93) years.
The prevalence of HT was 49.9% (57.9% in men and 43.4% in women; p < 0.001). Only 584 out of 805 hypertensives (72.5%) were treated. Among those on anti-hypertensive medication 70.0% were controlled.
Among hypertensive subjects, 13.7% did not have any other cardiovascular risk factor, 41.2% had dyslipidaemia, 25.8% were diabetics, 23.6% were smokers and 58.8% were obese.

Conclusions:
This study reveals that arterial hypertension prevalence continue to rise, with poor blood pressure control. There is an urgent need to conduct further national level screening campaigns to identify individuals with raised BP. This will ensure early detection and management of BP thereby reducing complications associated with it.
BLOOD PRESSURE CONTROL IN DIABETIC SUBJECTS: A NATIONWIDE EPIDEMIOLOGICAL SURVEY AMONG ITALIAN PHARMACIES CUSTOMERS
Authors: De Feo Martina , Del Pinto Rita , Grassi Davide , Ferri Claudio , Pagliacci Silvia 
Published: April 2021

Abstract

Objective:
The prevalence of hypertension is estimated at around 30% of the adult population in industrialized countries and is much higher in patients with diabetes mellitus. The global percentage of hypertensive individuals whose condition is treated and controlled is currently low. We analyzed data from a nationwide, cross-sectional epidemiological survey on pharmacies customers in order to have an overview of the prevalence and awareness of cardiovascular (CV) risk factors, with particular focus on hypertension and diabetes.

Design and method:
The survey was conducted in 3956 Italian pharmacies from 17 to 20 May 2018. Self-presenting participants were asked to answer a questionnaire on their clinical and demographic characteristics and lifestyle habits, and trained pharmacists measured their blood pressure (BP) according to guidelines. Prevalence of CV risk factors and hypertension rate/control according to the latest version of the European guidelines on hypertension was examined by diabetic status. Statistical analyses were performed using R (v3.5.1).

Results:
A total of 47217 subjects were enrolled in the project: 5695 diabetics and 41522 non-diabetics. Their characteristics are shown in Table 1.
Compared to non-diabetic patients, those with diabetes tended to be older, to declare a family/personal history of CV diseases/chronic kidney disease, to have prevalent/uncontrolled hypertension, dyslipidemia, higher mean systolic BP (135,96 ± 18,38 mmHg vs 128,32 ± 17,77 mmHg), and greater CV risk (p < 0.001). No significant differences in terms of salt intake, vegetable consumption, and smoking habits were recorded between the examined groups. Diabetic subjects with uncontrolled hypertension showed a lower propensity to physical activity (p = 0.016).

Conclusions:
Despite the limitations of the study design (selection bias, self-reported information, no data on medications and compliance, lack of generalizability), our results are substantially in line with the available literature, underlining that BP control is more challenging in diabetic patients, who normally present with a higher global CV risk. As lifestyle interventions (including dietary changes, weight loss, increased physical activity) appear effective both in lowering BP and reducing the incidence of diabetes, similar awareness-rising campaigns might be useful to promote CV health.
AWARENESS, TREATMENT AND CONTROL OF HYPERTENSION IN GREECE: THE EMENO NATIONAL EPIDEMIOLOGICAL STUDY
Authors: Stergiou George , Menti Ariadni , Kalpourtzi Natasa , Gavana Magdalini , Vantarakis Apostolos , Chlouverakis Gregory , Hadjichristodoulou Christos , Trypsianis Gregory , Voulgari Paraskevi , Alamanos Yannis , Karakosta Argiro , Touloumi Giota 
Published: April 2021

Objective:
The evidence on the epidemiology of hypertension in Greece is limited. The EMENO nationwide epidemiological study assessed the prevalence, awareness, treatment and control of hypertension in randomly selected adults in the general population in Greece.

Design and method:
EMENO applied a multi-stage stratified random sampling method involving 577 areas throughout Greece from May 2013 to June 2016. Participants were assessed at homes visits with standardized questionnaires, blood tests and 3 seated blood pressure (BP) measurements (validated upper-arm oscillometric device Microlife BPA100 Plus). Hypertension was defined as BP >=140/90 mmHg (average of 2nd-3rd measurement) and/or use of antihypertensive drugs). Post-stratification weights were applied in order to match the age/sex distribution to the general population in Greece based on census 2011. Non-response was adjusted by inverse probability weighting.

Results:
A total of 6,006 subjects were recruited and 4,699 with complete data were analysed (mean age 49.0 ± 18.5 [SD]) years, men 48.5%, BMI 28.1 ± 5.7 kg/m2). The prevalence of HT was 39.2% and was higher in men than women (42.4% vs. 36.1%, p < 0.001). Among hypertensive patients, 32.0% were unaware (men/women 39.7/23.7, p < 0.001), 2.7% aware untreated, 34.9% treated uncontrolled (men/women 31.8/38.2, p < 0.001) and 30.4% treated controlled (men/women 25.7/35.6, p < 0.001).

Conclusions:
More than one third of the adults in the general population in Greece have elevated BP. One third of them are undiagnosed and only 30.4% are controlled with treatment. Nationwide programs are needed to prevent hypertension and improve its awareness and control in Greece.
HYPERTENSION CHANGES THE ASSOCIATIONS BETWEEN HYPERURICEMIA AND OTHER CARDIOVASCULAR RISK FACTORS
Authors: Ruf Ruslan , Grinshtein Yuri , Shabalin Vladimir 
Published: April 2021

Objective:
The present study analyzed the interrelations of gender, hypertension, and associations between hyperuricemia and other cardiovascular risk factors.

Design and method:
Within the scope of the ESSE-RF study, we formed a randomized representative sample of 1603 inhabitants of Krasnoyarsk Krai aged 25–64. The protocol of the study provided the questionnaire, anthropometry, office blood pressure measurement, and biochemical blood analysis (lipids, glucose, creatinine, and uric acid).
We registered hyperuricemia at serum uric acid levels higher than 360 micromoles/l in females and 400 micromoles/l in males. At measured blood pressure 140/90 mm Hg or more, or if a person took antihypertensive medications, we registered hypertension.
Statistical calculations included descriptive statistics (the percentage of people having hypertension or hyperuricemia and 95% confidence intervals), chi-square to check group disparities for significance, and logistic regression to analyze the associations of hyperuricemia and other cardiovascular risk factors. We considered disparities and associations significant at p =<0.05.

Results:
We found 30.7% (28.4%; 33.0%) of the sample having hyperuricemia. It was more prevalent in males compared to females (49.9% (45.9%;53.9%) versus 18.2% (15.7%;20.7%); p < 0.001) and in hypertension compared to normal blood pressure (57.7% (53.3%;62.2%) versus 45.7% (42.7%;48.7%); p < 0.001).
Regression analysis found more factors associated with hyperuricemia in males compared to females. The table shows additional disparities between normal blood pressure and hypertension.

Conclusions:
Krasnoyarsk Krai population demonstrated the high prevalence of hyperuricemia and its association with several metabolic and nutritional factors, including dyslipidemia and renal dysfunction. Hypertension and gender changed the amount and structure of the factors associated with hyperuricemia.
ALTERED EXPRESSION OF LUNG EPITHELIAL ION AND FLUID TRANSPORTERS DURING PROGRESSION OF PULMONARY HYPERTENSION IN THE MONOCROTALINE MODEL
Authors: Zirova Katarina , Kmecova Zuzana , Veteskova Jana , Podzubanova Martina , Klimas Jan , Krenek Peter 
Published: April 2021

Objective:
Recent studies have evaluated a significant incidence of pleural effusions in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) co-diagnosed with isolated right-sided heart failure (RHF). Coincidence of pleural effusions and RHF in these patients significantly increased mortality rate during follow-up. However, mechanism of pleural effusions formation has not been fully explained. Therefore, we examined expression of lung epithelial ion and fluid transporters responsible for alveolar fluid clearance (AFC), which may contribute to lung fluid accumulation under pathological conditions and potentially formation of pleural effusions.

Design and method:
12-weeks old male Wistar rats were subcutaneously injected with monocrotaline (60 mg/kg, MCT) or vehicle (CON). The relative expression of AFC transporters: Na+/K+-ATPase alpha1, alpha2, beta1, beta3 subunits, epithelial sodium channel (ENaC) alpha, beta, gama subunits, cystic fibrosis transmembrane conductance regulator (CFTR) were determined by RT-qPCR 1, 2, 4 weeks after MCT application and also in end-stage disease (animals sacrificed after acute health deterioration, ∼ 4 weeks after MCT application) where pleural effusions were observed.

Results:
Increase in lung weight was observed from second week after MCT application and was more profound in end-stage disease (by 26 % compared to fourth week, p < 0.05). A downregulation of all three pore-forming subunits of ENaC was observed in end-stage disease, accompanied by downregulation of small beta3 subunit of Na+/K+-ATPase. Expression of catalytic alpha2 subunit of Na+/K+-ATPase gradually decreased with disease progression from first week after MCT (-80% in end-stage vs. CON, p < 0.05). On the other hand, we observed upregulation of CFTR (by 80%) and beta1 subunit of Na+/K+ATPase (by 79% vs. CON, p < 0.05) mainly in end-stage disease.

Conclusions:
Downregulation of lung epithelial ion and fluid transporters contributing to AFC is predominantly limited to higher stages of PH with a marked downregulation in end-stage. These expression alterations may contribute to overall lung weight increase observed in end-stage disease. However, observed early alpha2 subunit of Na+/K+-ATPase downregulation could participate on the pathogenesis of PH while upregulation of beta1 subunit and CFTR in end-stage disease could represent a compensatory mechanism.
EXOSOMAL MICRORNA-26A RESPONSE TO TGF-B1 STRESS IN HYPERTENSION
Authors: Martínez-Arroyo Olga , Ortega Ana , Perez-Hernandez Javier , Chaves Felipe J. , Redon Josep , Cortes Raquel 
Published: April 2021

Objective:
In a previous work we established an exosomal miRNA signature associated to urinary albumin excretion (UAE) in hypertension, which included microRNA (miRNA) miR-26a, and obtaining cell signaling (MAPK, calcium, p53), TGF-ß and VEGF pathways as the most regulated biological processes. The aim of this work was to validate the exosomal miR-26a changes and its potential association with TGF-ß in human podocytes.

Design and method:
This prospective study analysed the miR-26a levels in 52 hypertensive patients, 24 with UAE (162,8 ± 168.2 mg/g creatinine; mean age 52.7 ± 8.4 years) and 28 normoalbuminuric (mean age 54.5 ± 5.6 years). Exosomes were isolated by differential ultracentrifugation from urine and plasma and miRNA levels were calculated by qRT-PCR. Urinary levels of TGF-ß1 were quantified by ELISA. Finally, human podocytes cultures were stimulated with recombinant human TGF-ß1 at several concentrations (5 ng/mL, 10 ng/mL and 15 ng/mL) for up 24 h to assess miR-26a changes in exosomal and cellular fractions.

Results:
We found a decrease in the levels of miR-26-5p in plasma and urinary exosomes of patients con increased UAE (p < 0.05 and p < 0.01, respectively). In addition, miR-26a-5p correlated inversely with UAE levels, both in urinary and plasma exosomes (r = -0.49, p < 0.01; r = -0.53, p < 0.01). Our patients also showed a significant increase in urinary levels of TGF-ß1 (2-fold increase, p < 0.05) in hypertensive patients with UAE. Finally, we analysed the effect in vitro of TGF-ß1 stress. Significant changes in scaffolding of podocytes, such as an increase of vimentin levels, has been also observed. Finally, significant down-regulated miR-26a expression in exosomes from podocytes after TGF-ß1 stimulation (5 – 15 ng / mL): 2.23, 1.96 and 1.7-fold decrease, with p < 0.001 and p < 0.05, respectively. No significant changes were obtained at intracellular level.

Conclusions:
Our results show that miR-26a-5p is decreased in urinary and plasma exosomes of microalbuminuric patients. In addition, exosomal miR-26a podocyte release is associated with TGF-ß1 pathway, key molecule in the development and maintenance structure of the glomerular filtration barrier and fibrosis.