bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEDICATION-FREE BLOOD PRESSURE (B.P.) MANAGEMENT IN INDIVIDUALS WITH PRE-HYPERTENSION OR STAGE 1 HYPERTENSION
Authors: Sachla Zacharo , Koursioumbas Georgios , Tsoutsouli Vasiliki , Paskalis Georgios-Charis , Christodoulou Emmanouil , Gkogkos Konstantinos 
Published: April 2021

Objective:
Hypertension is defined as systolic blood pressure (S.B.P.) > 140 mm Hg and/or diastolic blood pressure (D.B.P.).) > 90 mm Hg at rest. Further classification of hypertension generates 4 groups of patients. Those with normal high blood pressure (S.B.P. > 130–139 mm Hg and /or D.B.P. > 85–89 mm Hg) and with stage 1 hypertension (SAP > 140–159 mm Hg and / or D.A.P. > 90–99 mm Hg), form a special category in which, the implement of medication creates debatable and controversial opinions among health care professionals, due to borderline values and patients’ low compliance. We aim to evaluate the management of B.P. without medication in patients with high normal blood pressure or stage 1 hypertension.

Design and method:
180 individuals, 77 men (43%) and 103 women (57%), aged 40–70 years, without comorbidities except of dyslipidemia, were classified as pre-hypertensive or stage 1 hypertensive patients after measuring their B.P. three times a day for a week. Subsequently, they were weighed and recommended to follow hygienic-dietary measures such as Mediterranean diet, reduced sodium intake, weight loss and exercise with a daily walk of about 4 kilometers. After a period of 6 months, they were reevaluated with a new record of body weight and a special questionnaire regarding the observance of doctor's recommendations. Of the total sample, 122 (67%) were considered suitable for the study, 55 of which were men (45%).

Results:
122 (67%) were considered suitable for the study, 55 of which were men (45%). 83 of these patients (69%), 36 men and 47 women, presented regulation of their B.P. at normal levels. In addition, there was a significant reduction of LDL levels in half of the patients (35/68). Medication for hypertension was given to the remaining 39, approximately 1/3 of the initial patients.

Conclusions:
The adoption of hygienic-dietary measures contributes to regulation of B.P. and improvement of lipid status in a major proportion of patients with marginally high B.P or with stage 1 hypertension, avoiding the need for medication at least for some years, justifying the guidelines that insist in taking such measures.
CADASIL-CAUSING NOTCH3 MUTATION CONTRIBUTES TO THE DEVELOPMENT OF PULMONARY ARTERIAL HYPERTENSION IN MALES
Authors: Morris Hannah , Neves Karla , Montezano Augusto , Joutel Anne , Maclean Margaret , Touyz Rhian 
Published: April 2021

Objective:
Notch3 signalling has been associated with changes in the pulmonary vasculature leading to pulmonary arterial hypertension (PAH). Mice with the CADASIL-causing R169C Notch3 mutation (TgNotch3R169C) exhibit gain-of-function Notch3 signalling and develop peripheral vascular dysfunction and injury. Here we investigated whether the R169C mutation contributes to PAH development.

Design and method:
Briefly, 24-week male and female mice overexpressing either a WT or R169C mutant Notch3 gene were exposed to 2 weeks normoxia (N) or chronic hypobaric hypoxia (10% O2) (H). PAH was assessed by in vivo haemodynamic measurements, Fulton index analysis of right ventricle hypertrophy (RVH), and histological remodelling analysis by elastin staining of pulmonary arteries under 80 microns in diameter. Pulmonary artery wire myography was also performed.

Results:
RV systolic pressure increased in hypoxic animals vs normoxic (WT H 27.5 ± 1.0 vs WT N 22.8 ± 2.2mmHg); and was exacerbated only in male R169C hypoxic animals (R169C H 32.2 ± 1.1 mmHg vs R169C N 23.6 ± 1.4) (p < 0.05). Male R169C hypoxic animals also exhibited significant RV hypertrophy (H 0.26 ± 0.033 vs N 0.16 ± 0.012), p < 0.05. RVH was not significantly different between female groups. R169C pulmonary arteries from males were significantly hypercontractile to 5HT (Emax: R169C 142 ± 10% vs WT 92 ± 6%); an effect attenuated by ROCK inhibitor Fasudil (Emax: R169C ± Fas. 117 ± 20%). Female R169C arteries were not hypercontractile to 5HT (R169C 113.3 ± 11% vs WT 120.3 ± 8%) but Fasudil reduced contraction (Emax: R169C + Fas. 96.8 ± 10%). Notch3 effector gene Hes5, implicated in PAH, was significantly increased in male R169C lung (8.7 fold change vs WT) suggesting increased Notch3 activation. RhoA/ROCK activating Rho-guanine nucleotide exchange factors LARG and PDZ mRNA were upregulated in R169C lung (R169C 33.5 fold vs WT, R169C 18.7 fold vs WT respectively). These changes were not observed in lungs from female mice.

Conclusions:
Notch3 R169C mutation may contribute to PAH susceptibility and pulmonary vascular hypercontractility in males. ROCK signaling plays an important role in these processes.
MICROVASCULAR ANGINA IS ASSOCIATED WITH SYSTEMIC DYSFUNCTION OF PERIPHERAL RESISTANCE ARTERIES
Authors: Michielon Alberto , Lanza Oreste , Ingrasciotta Gesssica , Ferrera Armando , Cesario Vincenzo , Marino Gaetano , Ruscio Eleonora , Filice Monica , De Vita Antonio , Crea Filippo , Volpe Massimo , Lanza Gaetano A. , Savoia Carmine 
Published: April 2021

Objective:
Microvascular angina (MVA) is characterized by functional and structural alterations of resistance coronary arteries without any significant alterations of epicardial coronary arteries. Whether MVA patients present also dysfunction of peripheral resistance arteries is still a matter of debate. We sought to evaluate whether MVA is associated with parameters of systemic microvascular dysfunction.

Design and method:
Thirteen patients with MVA and 13 healthy control subjects were enrolled in this study. The diagnosis of MVA was based on the presence of typical symptoms of ischemic heart disease, evidence of myocardial ischemia on exercise stress testing and normal epicardial coronary arteries at angiography. Parameters of peripheral microvascualar alterations, arterial stiffness (Pulse Wave Velocity, PWV), and central blood pressure (cBP) and Subendocardial Viability Ratio (SEVR, and index of subendocardial microvascular dysfunction), were evaluated by applanation tonometry.

Results:
Patients and controls were similar with respect to metabolic parameters, BMI, and renal function.
MVA patients were on therapy with beta-blockers (50%), calcium channel blockers (37%), nitrates (12%), renin-angiotensin-blockers (44%), and statins (25%). MVA patients were slightly older than controls (63.6 ± 1.9 vs 53.1 ± 2.0 years, p < 0.05). Albeit in the normal range, peripheral (pSBP) and central (cSBP) systolic BP were significantly higher in MVA patients as compared to controls (pSBP:134.3 ± 2.9 vs 118.5 ± 3.5 mmHg, p < 0.002; and cSBP:124.8 ± 2.9 vs 109.7 ± 2.9 mmHg, p < 0.001). Diastolic BP was similarly preserved in both groups. SEVR, an index of subendocardial microvascular dysfunction, was lower in MVA patients as compared to controls (139.7 ± 4.1 vs 160.4 ± 8.5 %, p < 0.05). Augmentation index (AI), reflected (RPH), and forward (FPH) pulse height, all parameters of peripheral microvascular dysfunction, were also altered in MVA patients as compared to controls (AI:29.0 ± 1.0 vs 19.9 ± 2.4%, p < 0.003; RPH:22.3 ± 1.4 vs 15.3 ± 0.9 mmHg, p < 0.001; FPH:31.0 ± 1.4 vs 24.2 ± 1.4 mmHg p < 0.005). The index of aortic stiffness PWV was similar in both groups (7.20 ± 07 vs 6.6 ± 0.2 m/sec, NS).

Conclusions:
Patients with MVA on optimal anti-schemic therapy exhibit alterations of parameters of both subendocardial and peripheral microvascular dysfunction, suggesting that coronary microvascular dysfunction is part of a more generalized disorder also involving peripheral resistance arteries.
RELATION OF PERIAORTIC ADIPOSE TISSUE WITH PARAMETERS OF METABOLIC SYNDROME IN YOUNG PEOPLE WITH ABDOMINAL OBESITY
Authors: Zheleznova Ekaterina , Zhernakova Yu , Chazova I. , Blinova N. , Azimova M. , Shariya M. , Gorieva Sh 
Published: April 2021

Objective:
The main aim of study was to investigate the association between periaortic fat (PF) and metabolic parameters, subcutaneous (SF), visceral (VF), epicardial (EF) fat in patients with abdominal obesity (AO).

Design and method:
127 patients 18–45 y.o. (average age 38,4 ± 6,0) with AO (men (M) – 58,3%) were enrolled in study. Height, weight, BMI, waist circumference, blood tests (fast glucose (FG),glucose tolerance (GT), insulin, HOMA-IR, lipid profile) were measured. MS was defined as AO (cut-off of > 80 cm in women (W) and > 94 cm in M) plus > 1 sign: HDL < 1,30 (w)/1,04(m)mmol/l; triglycerides > 1,7mmol/l; FG > 5,6mmol/l; violation GT; BP > 140/90mmHg. SF, VF, PF, EF (range: -150 to -30 HU) was measured by computed tomography. We calculated ratio subcutaneous to visceral fat (RSV). 24 hour blood pressure monitoring was performed. We formed 2 groups: AO (AO plus 1 or less sing of MS) and MS.

Results:
Tab. 1. Correlations PF with sex r = 0,223 (p = 0,009), with BMI r = 0,347 (p = 0,000), with WC r = 0,525 (p = 0,000), with uric acid r = 0,425 (p = 0,000), FG r = 0,27 (p = 0,002), insulin level r = 0,40 (p = 0,000), with HOMA r = 0,41 (p = 0,000), TG r = 0,32 (p = 0,000), HDL r = -0,37 (p = 0,000), LDL r = 0,23 (p = 0,005), with VF r = 0,55 (p = 0,000), SF r = 0,31 (p = 0,000), EF r = 0,69 (p = 0,000), RSV r = -0,300 (p = 0,000) were found.

Conclusions:
PF are directly related to most of metabolically parameters. PF in people with abdominal obesity is involved in metabolic syndrome.
N-METHYL-D-ASPARTATE RECEPTOR INHIBITION PREVENTS GLUCOMETABOLIC DYSREGULATION AND CARDIAC INJURY IN NICOTINE-EXPOSED MALE RATS
Authors: Michael Olugbenga , Ojo Gideon , Olatunji Lawrence , Soladoye Ayodele 
Published: April 2021

Objective:
Since non-smoking nicotine exposure has been associated with cardiometabolic disorders and smoking cessation therapies are of great global and medical significance. N-methyl-D-aspartate receptor (NMDAR) activity has been implicated in diabetes. Although NMDAR is also expressed in cardiomyocytes, there is dearth of information on its activity on cardiometabolic dysfunctions and its associated mechanism yet to be fully elucidated. It is therefore hypothesized that NMDAR inhibition by low-dose ketamine would improve nicotine-induced glucometabolic deregulation and cardiac injury.

Design and method:
Male Wistar rats (n = 6/group) aged 10 weeks were given (p.o.) vehicle, nicotine (1.0 mg/kg) with or without ketamine (0.2 mg/kg) daily for 28 days. Oral glucose tolerance test was performed 24-hours to the end of the experiment. The insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR).

Results:
Data showed that nicotine exposure led to insulin resistance, hyperinsulinemia, elevated 1-hour postload glucose, glucose intolerance, triglyceride-glucose index. Likewise, plasma and cardiac uric acid, malondialdehyde, lactate, triglyceride (TG), TG/HDL-C, oxidized glutathione (GSSG) levels, creatinine kinase (CK), lactate dehydrogenase (LDH), adenosine deaminase (ADA), xanthine oxidase (XO) activities were increased in nicotine-exposed rats. On the other hand, plasma and cardiac nitric oxide level was reduced by nicotine exposure. However, ketamine treatment also led to elevated TG, LDH, lactate, CK activity, nitric oxide, and reduced TG/HDL-C, uric acid, MDA, GSSG levels, XO and ADA activities when compared to control. However, these nicotine-induced cardiometabolic disorders were ameliorated in ketamine-treated rats.

Conclusions:
The results demonstrated that low-dose ketamine prevents glucose dysregulation, plasma and cardiac TG, uric acid, lactate accumulation and suppressed ADA, XO and CK activities. Therefore, these findings imply that inhibition of NMDAR by low dose-ketamine improves glucometabolic regulation and ameliorates cardiac injury through ADA/XO/CK-dependent mechanisms.
OBESITY: A MAJOR PUBLIC HEALTH HAZARD AND LEADING CAUSE OF METABOLIC DISEASES
Authors: Arain Mudassar Iqbal 
Published: April 2021

Objective:
Obesity has become a major public health hazard and its prevalence continues to rise in Pakistan faster than ever. Obesity is major risk factor for many cardiovascular diseases. High cholesterol is a key factor for the development of type-II diabetes mellitus, dyslipidaemia, chronic kidney disease, and non-alcoholic fatty and liver disease. There is a linkage between serum cholesterol and triglyceride levels and atherosclerotic cardiovascular disease in type I and type II of hyperglycaemia. The relationship between obesity and type-II diabetes mellitus is multifaceted and closely intertwined with other co-morbidities present in obesity

Design and method:
An interventional study was designed for a period of six months among 300 patients selected via purposive sampling with 95% confidence interval using slovin's formula. All the interventions were performed as per standard guidelines later the same tests were carried out to assess the outcomes. Pre and post interventional Proforma/data analysis sheet were filled by the investigator and then the outcomes were compared.

Results:
Majority (25.5%) of the patients who participated in the study were in the age group 60–96 which shows an increase in obesity occurrence with advanced age. About 48% patients have had BMI more than 30 and about 29.5% have had BMI range of 25–29.9. most of the patients about 35.5% didn’t check their blood glucose level before intervention and 121(60.5%) patients have had high cholesterol level and 79 patients with high cholesterol had glucose level above 126 mg/dl.

Conclusions:
The study findings revealed that Patients’ attitude (treatment, diet intake, sleeping and exercise habits) mean scores, pre-counselling and post-counselling for patients were significantly different and had improved after our interventions. Post interventions results revealed that the patients upgraded their practice by intermittently checking their blood glucose level, control smoking habit and maintain their life styles.
OBESITY AND ELEVATED LEVELS OF VON WILLEBRAND FACTOR IN PATIENTS WITH HYPERTENSION AND EARLY CORONARY ATHEROSCLEROSIS
Authors: Urazgildeeva Soreiia , Shugurova Irina , Vasina Lubov , Muzalevskaya Maria , Baranova Elena , Shurygina Valeria , Gurevich Victor , Perepech Nikita 
Published: April 2021

Objective:
Obesity is one of the additional risk factors for early development of atherosclerosis and cardiovascular complications in patients with hypertension. Von Willebrand factor (vWF) is a plasma glycoprotein which plays an important role in the thrombogenesis. On the other hand it is considered as a marker of the endothelial dysfunction. The objective of our study was to assess the level of vWF in patients with hypertension and early manifestations of coronary atherosclerosis depending on the presence of obesity.

Design and method:
79 middle-age (49,88 ± 7,77) patients with hypertension and established coronary atherosclerosis (71 men and 8 women) were involved into study. According to the calculating body mass index (BMI), all subjects were divided into 2 groups: 22 obese people (BMI above 30 kg/m2) and 57 non-obese patients. In all patients we analyzed family history, smoking status, history of diabetes. The plasma lipid profile and vWF level were estimated using EIA kit (Uscn Life Science Inc., Cloud-Clone Corp., USA).

Results:
Both groups did not differ in the family history of cardiovascular disease, smoking status and diabetes. Though all patients received statins triglycerides levels were significantly higher in obese patients [95%CI: 1.50; 2.57] compared with patients in the other group [95% CI: 1.29; 1.70] (p < 0.05). Almost all but one obese patient had high levels of vWF [95% CI: 53.87; 72.38]. Among patients with a BMI below 30 kg/m2, normal values of vWF were detected in 21 patients [95% CI: 41.38; 52.76]. The groups significantly differed in the level of vWF, both when calculating the odds ratio (OR) using the Pearson chi-square criterion [OR: 5,6; p = 0.0035] and when comparing samples according to the Student's t-criterion (p < 0.005).

Conclusions:
Results of the study suggest enhanced endothelial dysfunction as one of the possible links between obesity and increased risk of cardiovascular complications in patients with hypertension.
COMPOUND 21 IMPROVES VASCULAR FUNTION IN THE THORACIC AORTA FROM OBESE MICE: IMPLICATION OF AT2, MAS AND B2 RECEPTORS
Authors: González-Blázquez Raquel , Gil-Ortega Marta , Alcalá Martín , Viana Marta , Unger Thomas , Steckelings Ulrike Muscha , Fernández-Alfonso Maria Soledad , Somoza Beatriz 
Published: April 2021

Objective:
The angiotensin AT2 Receptor (AT2R) is known to form heterodimers with either the Mas (MasR) or the bradykinin B2 receptor (B2R). Compound 21 (C21), a highly selective AT2R agonist, induces vascular relaxation through stimulation of nitric oxide (NO). Since AT2R is overexpressed in obese models, we hypothesize that C21 might prevent the development of vascular alterations associated with obesity. The aim of this study was to assess the effect of C21 on endothelial function in a model of diet-induced obesity and the potential crosstalk between AT2R, MasR and/or B2R in this response.

Design and method:
Eleven-week-old male C57BL6J mice (n = 20/group) were fed a standard (Chow) or a very high-fat diet (HF) for 6 weeks. Half of mice per group were simultaneously treated with C21 (1 mg/kg/day in drinking water, Chow-C21, HF-C21). Vascular reactivity experiments were performed in rings from thoracic aorta. NO production was determined in human endothelial cells (EA.hy926) using DAF-2DA (10-5 M).

Results:
Thoracic aortas from HF mice exhibited impaired relaxations to acetylcholine (Ach) compared to the Chow group. This alteration was prevented by treatment with C21 [Ach, ChowEmax = 85,6 ± 1,7%; HFEmax = 63,8 ± 3,0% vs HF-C21Emax = 86,0 ± 1,8%, P < 0.001]. In addition, NO availability calculated from the area under the Ach curve in presence and absence of L-NAME (NO synthase inhibitor) was significantly lower in HF mice and increased by C21 treatment [Chow = 237 arbitrary units (AU), HF = 168 AU vs HF-C21 = 239 AU; P < 0.001]. Aortic rings from HF mice exhibited stronger contractions to angiotensin II (Ang II, 10-9-10-6 M). PD123177 (AT2R antagonist, 10-7 M), A779 (MasR antagonist, 10-6 M) or HOE-140 (B2R antagonist, 10-7 M) significantly enhanced Ang II-induced contractions in Chow- but not in HF-rings. HF-C21 aortas exhibited similar responses to Chow rings. In EA.hy926 cells, C21 (10-6 M) significantly increased levels of phosphorylated eNOS and NO production. Both effects were abolished by PD123177, A779 or HOE-140, respectively.

Conclusions:
In conclusion, our data suggest that C21 improves endothelial dysfunction induced by HF-feeding due to an increase in endothelial NO availability via AT2R activation. In addition, both MasR and B2R are implicated in this response and seem necessary for mediating C21 effects.
L-GLUTAMINE SUPPLEMENTATION PROTECTS AGAINST DISRUPTED CARDIAC GLUTATHIONE ANTIOXIDANT DEFENSE AND POOR FETAL OUTCOME FOLLOWING LATE GESTATIONAL TESTOSTERONE EXPOSURE
Authors: Usman Taofeek , Layonu Naheemat , Oyediran Opeyemi , Olaiya Ajibola , Olabisi Adijat , Nurudeen Ramadan , Wahab Raseedat , Olatunji Lawrence 
Published: April 2021

Objective:
Gestational testosterone exposure has been linked with low birth weight and the development of cardiometabolic disorders in both the mother as well as offspring. Increase in circulating testosterone has been associated with pregnancy pathologies such as preeclampsia. L-glutamine supplementation in healthy humans has been shown to cause reduction in pro-inflammatory cytokines as well as improve the glutathione antioxidant defenses. However, the effect of L-glutamine on circulating and cardiac inflammation as well as glutathione antioxidant defenses in gestational testosterone-exposed animals is yet to be determined. This study therefore aimed to investigate the effect of L-glutamine supplementation on circulating and cardiac inflammation, oxidative stress, glutathione antioxidant defenses as well as fetal outcome following late gestational testosterone exposure.

Design and method:
Pregnant Wistar rats were allotted into four groups (n = 6) receiving vehicle (distilled water, p.o and olive oil, s.c), testosterone (0.5 mg/kg body weight s.c), L-glutamine (1 g/kg body weight p.o) or a combination of testosterone and L-glutamine between gestational days 15 and 19.

Results:
The findings of this study shows that late gestational testosterone exposure led to an increase in circulating and cardiac inflammatory (adenosine deaminase, xanthine oxidase, uric acid) and oxidative stress (lactate dehydrogenase, malondialdehyde) markers as well as a disruption in the circulating and cardiac glutathione antioxidant defenses (glutathione, glutathione peroxidase, glutathione disulfide and glucose-6-phosphate dehydrogenase) and fetal outcome (fetal weight and number of pups). However, supplementation with L-glutamine led to a reduction of the gestational testosterone-induced increase in circulatory and cardiac inflammatory and oxidative stress markers. L-glutamine supplementation also improved the testosterone-induced disrupted circulating and cardiac glutathione antioxidant defenses as well as the fetal outcome.

Conclusions:
The findings of this study demonstrate that supplementation with L-glutamine prevents disruption of the glutathione antioxidant defenses and poor fetal outcome associated with late gestational testosterone exposure. This was accompanied by an improvement in the inflammatory and oxidative stress profile of these animals.
ROLE OF NOVEL ECHOCARDIOGRAPHIC METHODS TO DETECT EARLY MYOCARDIAL DYSFUNCTION IN WOMEN WITH PREECLAMPSIA
Authors: Hristova-Tselova Krasimira , Marinov Rumen , Tselov Nikolay , Stamenov Georgi , Chacheva Kristina , Racheva Anelia 
Published: April 2021

Objective:
Normal pregnancy is associated with reversible changes in both systolic and diastolic mechanics, consistent with an increase in preload and decrease in afterload and systemic vascular resistance. The aim of the study is to evaluate left ventricular cardiac mechanics via speckle tracking echocardiography in a population of pregnant women with per partum cardiomyopathy and preeclampsia(PE) after invitro fertilization (IVF) during different stages of pregnancy.

Design and method:
The study population included 42 pregnant women with PE, after IVF, 10 of them with multiple pregnancy (46.5 ± 3 years) and 20 healthy nonpregnant women (33 ± 4years). 2D images were acquired (65 ± 7 frames/s) during the first, second and third trimester of the pregnancy, as well as up to two months post partum. The curves of longitudinal(GLS), circumferential(GCS), radial strain(GRS) and LVT /LVUR were extracted using a commercial software.

Results:
Peak LVT and LVUR increased significantly in the 3rd trimester in both pregnancy groups (13.48 ± 2.90°,13.12 ± 3.30°,16.83 ± 3.61°,P < 0.001; and -111.52 ± 23.54°/sec,-107.40 ± 26.58°/sec,-144.30 ± 45.14°/sec, P < 0.001; in the 1st, 2nd, and 3rd trimester, The pregnants with twins have the highest value for LVT and LVUR (p < 0.01),.An independent correlation was found between the change in LVT and LV end-systolic volume in 1st and 3rd trimester (r = 0,56). Peak LVUR at the 3rd trimester correlated significantly with LV end-diastolic volume. Multiple regression analysis indicates that only systolic blood pressure (r = 0.394, P = 0.005) was an independent predictor for increased LV torsion. Arterial hypertension (AH) and prevalence of preeclampsia (PE) are more often in IVF group. Longitudinal strain decreased significantly (p < 0.001) during 3th trimester in women with AH and PE. Global longitudinal strain measures of the LV were non-significantly different between the different groups in first and second trimester (GLS-20.6 ± 3,14 vs.-19,29 ± 2,17).

Conclusions:
LV twist and peak untwisting rate increase in the 3rd trimester and correlate with end-systolic and end-diastolic volume, respectively. Blood pressure and condition of multiple pregnancy are independently associated with increased torsion during pregnancy and may predict the new onset heart failure and perinatal cardiomyopathy. Global longitudinal strain is the main predictor of new onset peripartum cardiomyopathy