bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACCURATE ESTIMATION OF INDIVIDUAL SODIUM INTAKE WITH REPEATED SPOT URINE SAMPLING
Authors: Ginos Bigina , Vogt Liffert , Frings-Meuthen Petra , Heer Martina , Engberink Rik Olde 
Published: April 2021

Objective:
In clinical practice, individual sodium (Na+) intake is estimated by measuring Na+ excretion in one 24-h urine collection (UC), whereas long-term Na+ balance studies indicate that 7 consecutive 24-h UCs may be needed. In this study, we investigate whether the use of repeated spot UCs is an appropriate alternative for multiple 24-h UCs to estimate Na+ intake.

Design and method:
We performed a post-hoc analysis of a metabolic ward study in 8 healthy male adults who consumed a 7-d diet with a fixed amount of 200 mmol/d Na+. Urine was collected in 4 daily intervals (7–13 h, 13–19 h, 19–23 h and 23–7 h). After reaching steady state, we estimated Na+ intake by single and repeated 24-h UCs and repeated spot UCs, using the Kawasaki formula with measured 24-h urine creatinine excretion.

Results:
At day 5, mean 24-h Na+ excretion matched intake, indicating that steady state was achieved (Fig 1A). Mean absolute differences (δ) between measured Na+ intake and 3-d spot UC estimates were 18.8 (SD 14.6), 32.3 (SD 18.7), 74.6 (SD 30.0) and 28.2 (SD 19.8) mmol for interval 7–13 h, 13–19 h, 19–23 h and 23–7 h, respectively (Fig 1B). With the exception of samples collected between 19–23 h, Na+ intake estimates by 3-d spot UCs did not significantly differ from Na+ intake estimates by single (δ 29.8 mmol; SD 23.9) and three 24-h UCs (δ 22.9 mmol; SD 11.4).
Figure 1. (A) Mean 24-h Na+ excretion during 7-d diet. (B) Comparison of the performance of three consecutive spot UCs (blue), single 24-h UC (green) and three consecutive 24-h UCs (red) for estimating Na+ intake (200 mmol/d). Absolute differences (δ) between estimated and measured Na+ intake. Data are mean and SD.

Conclusions:
In this 7-d Na+ balance study, repeated spot UCs performed similar to a single and repeated 24-h UCs in estimating Na+ intake. Adequately powered studies need to confirm whether repeated spot UCs are an accurate and low burden alternative to 24-h UCs.
IMPACT EVALUATION OF SOUTH AFRICA'S MANDATORY SALT LEGISLATION
Authors: Charlton Karen , Kowal Paul , Ware Lisa , Schutte Alta , Corso Barbara , Minicuci Nadia 
Published: April 2021

Objective:
South Africa implemented legislation in June 2016 mandating maximum sodium (Na) levels in a range of processed foods. A pre-post impact evaluation was undertaken to assess whether the legislative approach reduced salt intake and blood pressure in South Africans.

Design and method:
Baseline sodium intake was assessed in a nested cohort of the WHO Study on global AGEing and adult health (WHO-SAGE) Wave 2 (W2; 2014–2015). From 4030 randomly selected households, 24 h urine samples were collected in a random subsample (n = 1200) for Na potassium (K), creatinine and iodine analysis, alongside blood pressure (BP) and anthropometric measures. Follow-up in Wave 3 (W3; 2018) included replacements in the case of non-compliance or loss to follow-up. Complete urine collections were determined as volume > 300 mL and creatinine excretion > = 4 mmol/day (women) or > = 6 mmol/day (men).

Results:
Median salt intake indicated a slight downward trend between W2 (median 6.6 (IQR 6.1) g salt/day; n = 408) and W3 (6.3 (5.4) g/day; n = 392); with borderline significance (P = 0.0924). Proportion meeting the salt target of < 5 g/day remained similar (33.3 vs 34.7%; P = 0.685). In n = 48 paired subjects with complete urine and survey data in both waves, a non significant downward trend in salt intake was observed (median 6.7 (4.3) to 6.1 (5.4) g/day); P = 0.644). Significant predictors for increased systolic BP pressure between W2 and W3 were hypertension status (p < 0.0001) and age (p = 0.002).

Conclusions:
Complexities of obtaining repeat measures in the same individuals over 3 years of follow-up prevents determination of the magnitude of change in salt intake. These first results of salt intake following implementation of South Africa's mandatory sodium legislation, using valid 24hr urinary Na concentrations in a national sample suggest that the phased approach whereby stricter Na levels were enforced from June 2019 is necessary to achieve predicted population salt reduction of 0.85 g salt/person.
INCREASED EXPRESSION OF EPITHELIAL SODIUM CHANNEL AFFECTS MECHANICAL PROPERTIES OF ENDOTHELIAL CELLS BY REORGANISING THE F-ACTIN CYTOSKELETON
Authors: Shah Vikash Kumar , Fronius Martin 
Published: April 2021

Objective:
Epithelial sodium channel (ENaC) in the kidney maintain body salt/water balance and regulate blood pressure. Recent finding suggests that endothelial cells express ENaC. Here elevated ENaC contributes to increased endothelial cell stiffness (ECS) that associates with endothelial dysfunction and hypertension. dysfunction and hypertension. However, the mechanism how ENaC influence ECS remains unknown. This study aims to investigate the potential role of ENaC subunits in mediating ECS by cytoskeletal changes. I hypothesize ENaC mediated ECS via an increased expression of F-actin. To challenge our hypothesis, ENaC protein expression was quantified by Western blot in human umbilical vein endothelial cells (HUVECs) treated with aldosterone under static condition (0 dyn/cm2) and under laminar shear stress (LSS, 10 dyn/cm2, 24 h). Atomic Force Microscopy (AFM) was used to measure cell stiffness and changes of F-actin were assessed by immunofluorescence microscopy. Under static condition, aldosterone significantly increased ?-, and ?-ENaC protein levels. On the other hand, under LSS conditions aldosterone increased ?-, and ?-ENaC protein levels. Also under static condition, a significantly increased Young's modulus was determined in both fixed and live HUVEC cells treated with aldosterone. Furthermore, the increased stiffness in aldosterone treated cells revealed increased F-actin levels. Overall, these findings indicate that aldosterone has different effects on ENaC subunit expression in HUVECs grown under static and LSS conditions. The increased ENaC expression does increase ECS. This seems to involve an increased F-actin expression as a major determinant of ECS. Therefore, this study may provide a new mechanism for ENaC-mediated ECS and blood pressure regulation.
SKIN MICROVASCULAR REACTIVITY AND SUBENDOCARDIAL VIABILITY RATIO IN RELATION TO LIPID PROFILE AND METABOLIC STATUS, IN PRIMARY HYPERTENSION: THE DOXAZOSIN RAMIPRIL STUDY
Authors: Jekell Andreas , Kalani Majid , Kahan Thomas 
Published: April 2021

Objective:
Skin and coronary microvascular dysfunction both relate to increased cardiovascular risk in type 2 diabetes and in the metabolic syndrome. Disturbances in microvascular function are multifactorial, and both low HDL-cholesterol (HDL-C) and glucose intolerance are important mediators. However, their importance in relation to microvascular function in primary hypertension is not well studied.

Design and method:
We included 71 patients with untreated hypertension (55 ± 13 years, 34% women) but no coronary artery disease, dyslipidaemia, or diabetes. Subendocardial viability ratio (SEVR) as a measure of coronary microcirculation was calculated by pulse wave analysis (SphygmoCor). Skin microvascular function was assessed by laser Doppler fluxmetry and local iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), and by maximum reactive hyperaemia by local heating. Glucose tolerance was estimated by the triglyceride (TG) glucose index (TyG, ln[fasting plasma glucose (mg/dL) x triglycerides (mg/dL)/2]), and by TG/HDL-C ratio.

Results:
Mean office BP was 154/93 mmHg, fasting LDL-C, HDL-C and TG 3.48 ± 0.92, 1.40 ± 0.40 and 1.16 ± 0.86 mmol/L, respectively. Mean glucose was 5.40 ± 0.55 mmol/L, TyG 6.74 ± 0.59, and median TG/HDL-C ratio 0.65 [0.43–1.18]. SEVR (mean 169 ± 29%) was inversely related to LDL (r = –0.25; P = 0.041), but not to HDL-C (r = –0.05; P = 0.69). SEVR did not relate to TyG or TG/HDL-C ratio. Ach peak flux increase (mean 483 ± 380%) was related to HDL-C (r = 0.28, P = 0.021), whereas SNP (679 ± 395%) and heat induced maximum reactive hyperaemia (906 ± 491%) peak flux increase did not. Ach peak flux increase tended to relate inversely to TyG (r = –0.22, P = 0.069) and to TG/HDL-C ratio (r = –0.19, P = 0.12), while responses to SNP and local heating did not.

Conclusions:
Different mechanisms mediate skin and coronary microvascular dysfunction. In the coronary microcirculation LDL-C was associated with endothelial dysfunction, suggesting atherosclerotic disease to be an important factor, whereas skin microvascular reactivity was reduced by dyslipidaemia with low HDL-C in combination with impaired glucose tolerance. Our results are, in consort with observations in type 2 diabetes and in the metabolic syndrome, and suggest that early signs of skin and coronary microvascular dysfunction can be detected in uncomplicated hypertension and predict different aspects of cardiovascular risk.
NAIL CAPILLARY DENSITY DURING POSTOCCLUSIVE REACTIVE HYPEREMIA AND VENOUS CONGESTION IS MORE IMPAIRED IN DIABETIC COMPARED TO NON-DIABETIC CKD PATIENTS
Authors: Schoina Maria , Loutradis Charalampos , Memmos Evangelos , Triantafillidou Eva , Pagkopoulou Eleni , Dimitroulas Theodoros , Garyfallos Alexandros , Papagianni Aikaterini , Sarafidis Pantelis 
Published: April 2021

Objective:
Alterations in endothelial function and capillary circulation have been associated with increased cardiovascular events and overall mortality. Both diabetes mellitus (DM) and chronic kidney disease (CKD) have been associated with microcirculatory damage. Nailfold video-capillaroscory can provide a thorough assessment of capillary density and microcirculation changes. This is the first study examining in comparison microcirculatory function parameters in diabetic and non-diabetic patients with CKD.

Design and method:
We included 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (eGFR: < 90 and > 15 mL/min/1.73m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia) and at the end of a 2-minute venous occlusion (congestion phase).

Results:
Baseline demographic, anthropometric and laboratory characteristics were similar between patients with and without diabetes in total and in CKD stages. Overall, no significant differences at baseline capillary density were observed between groups; however diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm2, p = 0.022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm2, p = 0.015). When stratified according to CKD stages, the between-group differences in parameters of interest were not significant in stages 2, 3a and 4. In stage 3b, capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline (31.1 ± 2.8 vs 33.4 ± 3.4 capillaries/mm2, p = 0.044), during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm2, p = 0.037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm2, p = 0.022).

Conclusions:
Capillary density during postocclusive reactive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory functional impairment in CKD. These differences are more prominent in CKD stage 3b, and less prominent in earlier and later stages.
SEVERE HYPOURICEMIA IMPAIRS ENDOTHELIUM-DEPENDENT VASODILATATION: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 3-WAY CROSSOVER STUDY
Authors: Benjamin De Becker , Martin Chaumont , Philippe Van De Borne 
Published: April 2021

Objective:
Assess UA depletion through xanthine oxidase inhibition with febuxostat (FX) and recombinant uricase (rasburicase, R) on endothelial function.

Design and method:
Microvascular function, blood pressure, renin-angiotensin system activity measured (n = 17).

Results:
Hypouricemia alters heating-induced hyperemia in the presence of nitric oxide synthase inhibition (figure). Blood pressure, angiotensin II (P < 0.03 versus FX) and aldosterone decreased (FX-R, P = 0.01).

Conclusions:
UA depletion alters heat-induced endothelium-dependent microvascular vasodilation.
RESISTANT HYPERTENSION AND METABOLIC SYNDROME –A TWO-WAY RELATIONSHIP
Authors: Manta E. , Tsioufis K. , Konstantinidis D. , Kouremeti M. , Iliakis P. , Papakonstantinou P. , Tatakis F. , Anastasiou A. , Dimitriadi M. , Mourtzoukou D. , Zamanis I. , Karaminas N. , Tousoulis D. 
Published: April 2021

Objective:
Resistant hypertension is often accompanied by sympathetic hyperactivity, arterial stiffness and metabolic syndrome. Moreover, the idea of metabolic syndrome increasing the effect of resistant hypertension in sympathetic nervous system and vascular wall is under examination. The aim of this study was to appraise the effect of the metabolic syndrome on sympathetic drive, as it was assessed by MSNA estimations, and arterial stiffness in patients with resistant hypertension.

Design and method:
We studied 34 patients with resistant hypertension (age: 57 ± 11 years, 22 males, office blood pressure (BP): 157/93 ± 13/11 mmHg, 24-hour BP: 138/83 ± 14/10 mmHg, under 3.2 ± 0.5 antihypertensive drugs) who underwent anthropometric measurements, blood examinations and transthoracic echocardiographic study, for assessment of the metabolic profile. In all participants, MSNA was evaluated based on established methodology (microneurography) and arterial stiffness on the basis of carotid to femoral pulse wave velocity (PWV). Metabolic syndrome was defined according to the Adult Treatment Panel III criteria.

Results:
Patients with resistant hypertension and metabolic syndrome (n = 14), compared to those without metabolic syndrome (n = 20) were characterized by higher levels of office systolic BP (166 ± 15 vs 151 ± 15 mmHg, p < 0.001), fasting glucose (132.7 ± 2.7 vs 94.7 ± 2.2 mg/dl, p < 0.05), waist circumference (109.1 ± 5.3 vs 94.8 ± 9.3 cm, p = 0.002), as well as left ventricular mass index (124.2 ± 16.2 vs 114.4 ± 16.2 g/m2, p = 0.001). Furthermore, metabolic syndrome patients exhibited greater levels of MSNA (84.8 ± 2.5 vs 74.2 ± 2.4 bursts per 100 heart beats, p < 0.001) and greater levels of carotid to femoral PWV (11.5 ± 0.8 vs 9.1 ± 1.3m/sec, p < 0.001). In all participants, sympathetic nerve traffic as assessed by resting MSNA was related to office systolic BP (r = 0.38, p < 0.05) and waist circumference (r = 0.33, p = 0.002), but there was no association with PWV values (p = NS).

Conclusions:
In patients with resistant hypertension, metabolic syndrome is associated with high MSNA and PWV levels. These results suggest thatthe presence of metabolic syndrome can exacerbate the setting of resistant hypertension, through sympathetic overdrive and vascular abnormalities, conditions that can be the subject of therapeutic interventions.
NOVEL ANTHROPOMETRIC INDICES WERE BETTER ASSOCIATED WITH HYPERTENSIVE TARGET ORGAN DAMAGES IN THE COMMUNITY-DWELLING ELDERLY CHINESE: THE NORTHERN SHANGHAI STUDY
Authors: Tang Jiamin , Zhao Song , Yu Shikai , Chi Chen , Ji Hongwei , Xiong Jing , Teliewubai Jiadela , Zhang Yi , Xu Yawei 
Published: April 2021

Objective:
Body mass index (BMI), the most commonly used body composition assessing indice, has recently been challenged by two novel anthropometric indices, a body shape index (ABSI) and body roundness index (BRI), in arterial stiffness predicting capacity[1,2]. The purpose of this study was to detect and compare the different predictive capacities of the four anthropometric indices (ABSI, BRI, waist-hip ratio (WHR) and BMI) in predicting hypertensive target organ damages (HTODs).

Design and method:
Overall, 3077 community-dwelling elderly Chinese (age > 65 years, 1329 men and 1748 women) in northern Shanghai were enrolled prospectively from June 2014 to August 2019. ABSI and BRI were calculated with validated formula. HTODs were defined as three levels: (1) left ventricular hypertrophy (LVH), (2) arterial stiffness (AS) and lower limb atherosclerosis (LLA), (3) micro-albuminuria (MAU). Multivariate linear and logistic regression were performed to detect the relations between anthropometric indices and HTODs.

Results:
Spearman correlation analysis revealed that all anthropometric indices were correlated with HTODs indices (all P < 0.001). In multivariate logistic regression models, compared to the lowest quartiles, participants with the highest quartiles of ABSI, BRI and WHR all exhibited a significantly higher risk of LVH, AS and MAU independent of confounders and BMI (all P for trend < 0.01). Results of receiver operator characteristic (ROC) analysis performed within the female subgroup demonstrated that BRI and WHR were the better anthropometric indices in predicting HTODs compared to BMI. However, similar trend disappeared in the male subgroup. Further comparison analysis about the predictive priorities in the female subgroup were tested with stepwise logistic regression, after all anthropometric indices were put into models, only BRI stayed and was significantly associated higher prevalence of LVH (OR = 1.42, 95%CI 1.30∼1.55) and LLA (OR = 1.48, 95%CI 1.23∼1.77) together with WHR stayed to predict higher risks of AS (OR = 1.30, 95%CI 1.18∼1.43) and MAU (OR = 1.48, 95%CI 1.28∼1.72, all P < 0.01).

Conclusions:
Novel anthropometric indices, especially BRI and WHR, compared to the conventional indice BMI, have the superior capacities in predicting HTODs in the elderly female Chinese population.
L-GLUTAMINE IMPROVES ADIPOSE FUNCTION AND AMELIORATES EXCESS HEPATIC LIPID IN ESTROGEN-PROGESTIN ORAL CONTRACEPTIVE-TREATED FEMALE RATS
Authors: Olaniyi Kehinde , Olatunji Lawrence 
Published: April 2021

Objective:
Adipose dysfunction and inflammation with or without hepatic defects underlie metabolic obesity. Glutamine (GLU) improves glucoregulation and metabolic indices but its effects on adipose function and hepatic lipid deposition in estrogen-progestin oral contraceptive (EPOC) users are unknown. We therefore hypothesized that GLUT supplementation would protect against adipose dysfunction and excess hepatic lipid influx and deposition in animals treated with EPOC by suppressing adenosine deaminase (ADA) activity and improving glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defense.

Design and method:
Female Wistar rats weighing between 150–180 g were allotted into control, GLUT, EPOC and EPOC + GLUT groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLUT (1 g/kg), EPOC containing 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel and EPOC plus GLUT respectively, daily for 8 weeks. Glucoregulatory parameters were determined by homeostatic model of assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI), while metabolically-induced obesity was determined using triglyceride-glucose index. Plasma and tissue biochemical analysis were estimated with enzyme-linked immunosorbent assay kits or fluorescence assay as appropriate

Results:
Results showed that the administration of EPOC caused glucose dysregulation and increased triglyceride-glucose index and visceral adiposity, but the body weight and liver weight were not affected. However, EPOC significantly decreased adipose lipid, G6PD and glutathione, and increased glycogen synthesis, ADA, XO, uric acid, lipid peroxidation, lactate production and Gamma-glutamyl transferase activity (GGT). On the other hand, EPOC significantly increased hepatic lipid, ADA, XO, uric acid, lipid peroxidation and lactate production, and decreased glycogen synthesis, G6PD and glutathione. Nevertheless, supplementation with glutamine attenuated these alterations.

Conclusions:
Collectively, the present results indicate that EPOC causes metabolically-induced obesity which is associated with adipose dysfunction and hepatic metabolic defection. The findings also suggest that glutamine confers metabo-protection with corresponding improvement in adipose and hepatic metabolic function by suppression of ADA activity and enhancement of G6PD-dependent antioxidant defense (Figure 1).
NICOTINE AVERTS CARDIORENAL DYSFUNCTION BY MITIGATING ESTROGEN-PROGESTIN-INDUCED IMPAIRED NA+/K+-ATPASE ACTIVITY AND TRIGLYCERIDE ACCUMULATION IN INSULIN RESISTANT FEMALE RATS
Authors: Michael Olugbenga , Areola Emmanuel , Dibia Chinaza , Adeyanju Oluwaseun , Olatunji Lawrence 
Published: April 2021

Objective:
Roughly fifty percent of premenopausal women who smoke cigarettes are also on hormonal contraceptives, especially oral estrogen-progestin therapy. Oral estrogen-progestin therapy has been reported to promote insulin resistance (IR), a major risk factor for the development of cardiometabolic dysfunction. Impaired Na+/K+ -ATPase activity has also been associated with cardiometabolic disturbances. The effects of nicotine on cardiorenal metabolic dysfunctions during estrogen-progestin therapy have not been fully elucidated. It is therefore hypothesized that nicotine would ameliorate IR that is accompanied by improved cardiorenal Na+/K+-ATPase activity, uric acid, oxidative stress and lipid accumulation in estrogen-progestin-treated rats.

Design and method:
Female Wistar rats (n = 6/group) aged 10 weeks were given (po) vehicle, nicotine (1.0 mg/kg) with or without estrogen-progestin steroids (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel) daily for 6 weeks. The insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR).

Results:
Data showed that estrogen-progestin treatment or nicotine exposure led to insulin resistance, hyperinsulinemia, increased cardiac and renal uric acid, malondialdehyde, triglyceride, glycogen synthase kinase-3, plasminogen activator inhibitor-1, alkaline phosphatase, aspartate transaminase, alanine transferase activity and reduced bilirubin. Estrogen-progestin treatment led to decreased cardiac Na+/K+-ATPase activity while nicotine did not alter the activity. Renal Na+/K+-ATPase activity was not altered by the treatment. However, these alterations were ameliorated by nicotine exposure plus estrogen-progestin treatment

Conclusions:
The results showed that oral nicotine enhanced cardiorenal Na+/K+-ATPase activity and suppressed lipid accumulation, oxidative stress, inflammation and thrombotic tendency in estrogen-progestin-induced insulin resistance. Therefore, the findings of the present study imply that oral nicotine may be cardiorenal protective especially during estrogen-progestin therapy.