bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRE-DIABETES AND ASYMPTOMATIC HYPERTENSION-MEDIATED ORGAN DAMAGE IN PATIENTS WITH ARTERIAL HYPERTENSION AND OBESITY
Authors: Koval Sergiy , Mysnychenko Olga , Penkova Marina , Lytvynov Vadim , Lytvynova Olga 
Published: June 2023

Objective:
Patients with arterial hypertension (AH) and abdominal obesity (AO) are characterized by a high risk of developing type 2 diabetes mellitus, the addition of which significantly worsens the prognosis. One of the early disorders of carbohydrate metabolism, which has been subclinical for a long time and remains undiagnosed, is pre-diabetes. The aim of our study was to evaluate the frequency of pre-diabetes in patients with AH and AO and its relationship with asymptomatic hypertension-mediated organ damage (HMOD).

Design and method:
The survey included 87 patients (50 men) with essential AH of 2-3 degrees with AO of I-II degrees, aged 40 to 59 years. Patients were examined using standard clinical, laboratory and instrumental methods. Pre-diabetes was diagnosed in accordance with the recommendations of the European Society of Cardiology and the European Association for the Study of Diabetes (2019). Diagnosis of HMOD was also carried out in accordance with the recommendations of the European Society of Cardiology and the European Society of Hypertension (2018). Insulin resistance (IR) was determined by HOMA-IR.

Results:
The frequency of pre-diabetes among AH patients with AO in the whole group was 40.3%. A significant increase in the subgroup of patients with pre-diabetes compared with the subgroup of patients without pre-diabetes was found in the frequency of more severe AH of the 3rd degree (71.4% and 50.0%, P<0.05), more pronounced obesity-AO of the 2nd degree (68.6% and 32.7%, P<0.05), IR (88.6% and 40.4%, P<0.05) and dyslipidemia (94.3% and 76.9%, P<0.05). The subgroup of patients with pre-diabetes differed from the subgroup of patients without pre-diabetes by a significantly higher incidence of such HMOD as: left ventricular hypertrophy (97.1% and 75.0%, P<0.05), increased pulse pressure (48.6% and 25.0%, P<0.05) and microalbuminuria (42.9% and 23.1%, P<0.05).

Conclusions:
Pre-diabetes in AH patients with AO is associated not only with a significantly more severe course of hypertension and obesity, more pronounced metabolic disorders, but also with a higher incidence of asymptomatic HMOD such as heart, vascular, and kidney damage.
STUDY OF C-786T POLYMORPHISM IN THE NOS3 GENE IN THE DEVELOPMENT OF PREECLAMPSIA
Authors: Kurbanov Bakhodir 
Published: June 2023

Objective:
Given the importance of endogenous NO in maintaining normal endothelial function, it is possible that polymorphisms in the gene encoding the enzyme that synthesizes NO may contribute to the development of preeclampsia. The purpose of the work was to determine the role of the C-786T polymorphism in the NOS3 gene in the development of preeclampsia.

Design and method:
We conducted a study of 90 pregnant women in the II-III trimester, which were divided into two groups: The main group of 53 pregnant women with severe preeclampsia. Control group - 47 pregnant women with a physiological course of the gestational period. The age of the examined women ranged from 19 to 41 years. Samples of pregnant women served as the material for the study. We have identified gene polymorphism - C-786T in the NOS3 gene. Isolation of DNA from blood and PCR analysis were carried out using kits of reagents and test systems from Ampli Prime Ribo-prep. Statistical processing of the results was carried out using statistical programs EpiCalc 2000.

Results:
There was a trend towards the prevalence of the heterozygous C/T genotype in the group of patients with severe preeclampsia, where it was detected with a frequency of 39.5% (x2-2.23; p-0.15; RR-1.46; 95% CI: 0.54-3.91; OR -1.76.; 95% CI: 0.84-3.69), relative to 27.1% in the control group.
The T/T genotype was slightly more common – in 11.6% of cases it was detected among patients with severe preeclampsia (x2-1.08; p-0.30; RR-1.78; 95%CI:0.43-7.32; OR-1.88; 95%CI:0.57- 6.19), while in the control group - with a frequency of 6.5%.
The C/C genotype was found in 59.8% of patients with severe preeclampsia (x2-1.04; p-0.31; RR-0.81; 95% CI: 0.37-1.74; OR-0.62)
The T allele among patients with severe preeclampsia was detected in 31.4% of cases, which was statistically significantly higher (x2-4.38; p-0.04; RR-1.17; 95%CI:0.79-1.73; OR-1.82; 95%CI:1.04- 3.19) than in the control group.

Conclusions:
Thus, the results of our study allow us to conclude that the adverse genotypic variants of the C-786T polymorphism of the NOS3 gene (associated with vascular endothelial dysfunction) contribute significantly to the mechanism of preeclampsia.
DISTURBED ASSOCIATION BETWEEN PLACENTAL SODIUM CONTENT AND GLYCOSAMINOGLYCANS IN GESTATIONAL HYPERTENSION BUT NOT IN PRE-ECLAMPSIA
Authors: Oppelaar Marjet , Vriend Esther , Lens Laura , Wijland Martine , Salik Priyaashri , Berg Romy Van Den , Vaz Frédéric , Dijk Marie Van , Bugiani Marianna , Boer Marjon De , Pampus Mariëlle Van , Ganzevoort Wessel , Engberink Rik Olde , Born Bert -Jan Van Den , Vogt Liffert 
Published: June 2023

Objective:
Glycosaminoglycans (GAGs) facilitate tissue sodium accumulation which plays an important role in regulation of sodium homeostasis, water balance and blood pressure. During pregnancy, GAGs are also highly expressed in placental tissue. We studied placental sodium concentration and GAG content from normotensive and hypertensive pregnancies to explore a link between placental sodium and blood pressure during pregnancy.

Design and method:
We performed a prospective case-control study in singleton pregnancies with normal blood pressure (nBP, n = 22), gestational hypertension (GH, n = 12) and pre-eclampsia (PE, n = 10). Two full thickness placental biopsies (central [near umbilical cord insertion] and peripheral) were collected after delivery for analysis of placental electrolyte concentration (ICP-OES) and GAG content (UPLC-MS/MS). Linear associations were explored with a linear regression analysis with correction for gestational age, mode of delivery and treatment with antihypertensive drugs.

Results:
Placental sodium concentration in GH was 10.1% (p = 0.01) lower in central and 9.4% (p = 0.04) lower in peripheral biopsies compared to nBP. Total peripheral heparan sulfate (HS) expression was 32.3% lower in GH compared to nBP (p = 0.04). Also, di-sulfated HS as percentage of total HS was lower in peripheral biopsies of GH compared to nBP (11.0% [IQR 10.0-11.4] vs 12.3% [IQR 11.3-14.5], p = 0.02). In PE, placental GAG and sodium content were not significantly different from nBP. Placental sodium concentration was linearly associated with percentage of di-sulfated HS (Fig A), while in central biopsies it was negatively associated with systolic BP (Fig B).

Conclusions:
We show that GH is accompanied by lower placental sodium content when compared to pregnancies with normal blood pressure. Also, lower placental sodium content during pregnancy is associated with lower placental GAG content and higher BP. This indicates that placental sodium homeostasis might be involved in chronic maternal blood pressure regulation.
BLOOD GLUCOSE CONTROL DURING PREGNANCY IN GESTATIONAL DIABETES MELLITUS RESULTS IN A LOWER RISK OF PREGNANCY INDUCED HYPERTENSION (PIH) & BETTER MATERNAL-FETAL OUTCOMES
Authors: Jain Rajesh , Shoghli Mohammadreza , Seshiah Veeraswamy , Agarwal Shally , Tiwari Sadhna , Bhavatharini Natarajan , Saxena Pikee , Yadav Akshama , Kirubanidhi Vidyaa , Singh Mamta , Jain Rachna 
Published: June 2023

Objective:
In Gestational Diabetes Mellitus GDM, pregnancy-induced hypertension PIH and low birth weight of newborns <2.5 kg are major and significant causes of maternal and fetal morbidity & mortality in developing worlds with low resource settings. Can we reduce these risks by Controlling Blood sugar and resulting in better maternal-fetal outcomes?

Design and method:
A prospective cohort study was done for one year from October 1, 2013, to September
31, 2014, at 198 diabetic screening units as a part of the Project
approved by the Indian Government in Kanpur, state of Uttar Pradesh district. 57,108 pregnant
women were screened during their 24–28th weeks of pregnancy by impaired oral glucose test OGTT Single Test Procedure with 2 Hour Post Blood glucose 140 mg/dl after 75 gm of Glucose load irrespective of non-fasting approved by, Govt of India.
Maternal and perinatal outcomes were followed up in GDM who have controlled Blood glucose value postprandial 2 hours of <140 mg/dl and those with uncontrolled GDM Group with >140 mg/dl between 2013 and 2014 in public health facilities with low resource settings.

Results:
Out of the Total number of Gestational Diabetes Mellitus cases followed up in this study, 5043; out of them, 4589 GDM women's blood Glucose was mild to moderately controlled < 140 mg/dl throughout pregnancy by Medical Nutrition therapy MNT & Insulin use and 454 GDM blood Glucose were not the well-controlled groups for not following MNT strictly and low insulin use 1.1%
Pregnancy-induced hypertension PIH and low birth weight of newborns <2.5 kg are major significant causes of maternal and fetal morbidity & mortality in developing worlds with scarce resource settings. We found that Pregnancy Induced Hypertension in GDM cases with <140 mg/dl Control was 2.98% compared to 9.3% in Blood glucose >140 mg/dl GDM women; low birth weight was 15.6% in an uncontrolled group compared to 8.9% in the control group.

Conclusions:
Blood Glucose control, in public health facilities, may result in better outcomes, specially pregnancy-induced hypertension, and low birth weight risk, which contribute significantly to morbidity and mortality of mothers and infants with GDM
INHIBITION OF AT1 RECEPTOR PARTIALLY PREVENTS ENDOVASCULAR ETHANOL INJECTION INDUCED ACUTE PULMONARY HYPERTENSION AND SECONDARY PULMONARY ARTERY REMODELING
Authors: Shen Yuchen , Su Lixin , Fan Xindong , Wang Deming 
Published: June 2023

Objective:
Ethanol can induce acute pulmonary hypertension (APH) during endovascular sclerotherapy and embolization. We aimed to examine whether the inhibition of the AT1 receptor can prevent this pathological phenomenon and assess its related mechanisms.

Design and method:
A total of 40 male swine (age, approximately six months) were selected and performed with absolute ethanol endovascular injection (jugular vein). Saline was used as the negative control. Preventive administration of losartan was conducted orally for 3 consecutive days before operations. Pulmonary arterial pressure (PAP), femoral arterial pressure (FAP), and heart rate (HR) were monitored during procedures. Venous plasma and fresh pulmonary artery (PA) tissue of 32 swine were harvested immediately after the operation. The remaining eight swine were kept and sacrificed one-month after the operations, and PA tissues were harvested for paraffin embedding procedures. Protein level was detected by Western blotting and ELISA, whereas qRT-PCR was used in mRNA detection. H & E staining and immunohistochemistry (IHC) were conducted to evaluate histopathology.

Results:
Ethanol injection elevated PAP in all swine. The concentration of renin-angiotensin system (RAS) ligands was elevated in plasma (all P < 0.0001) but not in PA. The level of oxidative stress increased in both plasma and PA. MRNA level of AT1R (P < 0.01, 95% CI: 0.251 to 1.006), not AT2R increased in PA. Losartan failed to inhibit APH after all sessions of ethanol injection, and partially reversed the ethanol-induced PA remodeling (1. H & E staining presented abnormal morphology of PA; 2. CD31 IHC staining indicated the intimal hyperplasia; 3. a-SMA IHC staining suggested the pathomorphology of smooth muscle cells; 4. TNF-a IHC staining showed the infiltration of immune cells). The P38 MAPK was activated after ethanol injection and could be inhibited by losartan (P < 0.01, 95% CI: -0.391 to -0.164). Ethanol also promoted the translocation of the P40-PHOX/P47-PHOX/P67-PHOX complex and the activation of NOX, which was independent from RAS.

Conclusions:
Endovascular ethanol injection can induce AEPAP mainly by activating RAS and P38 MAPK signaling. Losartan can partially prevent AEPAP and vascular remodeling owing to the promotion of NOX activity by ethanol.
ANGIOTENSIN-(1-7) FORMATION UPON FLUID FLOW SHEAR STRESS IN HUMAN PODOCYTES
Authors: Kaiser-Graf Debora , Domenig Oliver , Poglitsch Marko , Kreutz Reinhold , Bolbrinker Juliane 
Published: June 2023

Objective:
Glomerular hyperfiltration associates with increased fluid flow shear stress (FFSS) on podocytes. This can lead to irreversible podocyte damage, which in turn negatively affects the permeability and integrity of the glomerular filtration barrier. AngiotensinII (AngII) is an important mediator in chronic kidney disease. The negative effects of AngII are at least partially opposed by the alternative signaling pathways within the renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-[1-7]) and the MAS1 receptor. This counteracting pathway may exert renoprotective effects and support anti-inflammatory processes. As the pathomechanisms and signaling pathways underlying podocyte damage induced by FFSS are not fully understood, our aim is to elucidate the potential renoprotective impact of the alternative RAS axis in human podocytes in the context of glomerular hyperfiltration.

Design and method:
Conditionally immortalized human podocytes (hPCs) were used for mechanistic studies. Cells seeded on collagen IV coated Culture Slips® were inserted in a Streamer® Shear Stress Device and exposed to FFSS of 1dyne/cm2 for 2h. Control cells were not exposed to FFSS. Afterwards, the formation rate of AngII to Ang-[1-7] was measured in whole cell lysates (1 experiment, n = 6 samples per condition) using spiked AngII as a substrate with and without addition of Z-Pro-Prolinal and MLN-4760. Additionally, gene expression analyses of the enzymes involved in Ang-[1-7] formation were performed.

Results:
Preliminary data show an increased AngII to Ang-[1-7] formation rate in hPCs following FFSS exposure compared to control. Ang-[1-7] formation under both conditions is reduced by addition of Z-Pro-Prolinal, whereas MLN-4760 has no effect. RNA-expression levels of prolylcarboxypeptidase and prolylendopeptidase are not significantly affected upon FFSS compared to control. In contrast, ACE2 is significantly upregulated by FFSS although expression levels are substantially lower under both conditions compared to prolylcarboxypeptidase and prolylendopeptidase.

Conclusions:
Our results suggest an elevated AngII to Ang-[1-7] formation rate upon FFSS in hPCs compared to no-flow control. Under both settings, Ang-[1-7] formation in hPCs seems to be mediated by prolylcarboxypeptidase and/or prolylendopeptidase but not ACE2. These results support further studies to confirm the potential role and mechanisms of Ang-[1-7] upregulation in response to glomerular hyperfiltration.
THE RENIN ANGIOTENSIN SYSTEM BLOCKADE DOES NOT SIGNIFICANTLY REDUCE THE RISK OF CARDIOVASCULAR EVENTS IN DIALYSIS PATIENTS: A META-ANALYSIS OF 5 RCTS
Authors: Georgianos Panagiotis , Tziatzios Georgios , Roumeliotis Stefanos , Georgianou Eleni , Vaios Vasilios , Liakopoulos Vassilios , Agarwal Rajiv 
Published: June 2023

Objective:
Angiotensin-converting-enzyme-inhibitors (ACEIs) and/or angiotensin-receptor-blockers (ARBs) are recommended by guidelines as first-line therapies for the management of hypertension in the general population. However, the cardioprotective benefit of these agents among patients on chronic dialysis remains uncertain. This meta-analysis aimed to explore the effect of ACEIs/ARBs on cardiovascular events in this high-risk patient population.

Design and method:
We searched Medline/PubMed and Cochrane database of clinical trials from inception through February 2022 to identify randomized controlled trials (RCTs) comparing the effect of ACEIs/ARBs relative to placebo or no add-on treatment in patients receiving dialysis. RCTs were eligible in quantitative data synthesis, if they were assessing fatal or non-fatal cardiovascular events as a primary efficacy endpoint.

Results:
We identified 5 RCTs including a total of 1,582 dialysis patients. As compared with placebo or no add-on treatment, the use of ACEIs/ARBs was not associated with a significantly lower risk of cardiovascular events [risk ratio (RR): 0.79; 95% confidence interval (CI): 0.57-1.11; I2 = 73%, P = 0.005]. Furthermore, there was no benefit of ACEIs/ARBs on cardiovascular mortality (RR: 0.82; 95% CI: 0.59-1.14; I2 = 6%, P = 0.37) and all-cause mortality (RR: 0.86; 95% CI: 0.64-1.15; I2 = 44%, P = 0.13). These results were consistent, when the included RCTs were stratified into subgroups according to the hypertension status and ethnicity of patients, sample size, duration of follow-up and method quality.

Conclusions:
The present meta-analysis showed that among patients on dialysis, the use of ACEIs/ARBs is not associated with a significantly lower risk of cardiovascular events and all-cause mortality as compared with placebo or no add-on treatment.
ALDOSTERONE IN POLYCYSTIC OVARY SYNDROME
Authors: Chaabouni Khansa , Issaoui Nader , Khanfir Fatma , Frikha Moez , Boudaouara Imene , Bouzid Imene , Eloud Zoubeir , Aloulou Dorra , Elleuch Aida , Ayadi Fatma 
Published: June 2023

Objective:
Aldosterone was involved in several metabolic disorders. Elevated levels were also reported in polycystic ovary syndrome (PCOS).

Objective:
to investigate aldosterone and metabolic abnormalities in PCOS at first discovery

Design and method:
we conducted a case-control study. First diagnosed PCOS patients were included with age and body mass index matched controls. Fasting blood samples were taken at the 3rd day of mezes. Aldosterone was assayed by ELISA DRG kit. The other parameters were dertemined by cobas 6000-Roche.

Results:
A total of 77 participants were enrolled: 41 PCOS and 35 controls. Aldosterone levels were significantly higher in PCOS. Median value in controls was 160ng/mL. We observed that 70% of aldosterone levels in PCOS were above this median value. Increased aldosterone levels were associated with elevated fasting glucose. Although, There was no significant difference in the prevalence of insulin-resistance, dyslipidemia, obesity, and metabolic syndrome between patients with different aldosterone levels distribution.

Conclusions:
Elevated aldosterone levels could be the primum movens activating carbohydrate metabolic alterations. Once elevated, aldosterone levels could give evidence of preclinic alterations at an early stage of PCOS.
MAGNESIUM: A BLOOD PRESSURE MODULATOR
Authors: Vernaglione Luigi , Balestra Cosima , Renzo Brigida Di , Flores Antonio , Schiavone Palmira , Capaccio Flavia , Covella Patrizia , Spinelli Alessandra , Mangiulli Marco , Leonardi Giuseppe , Recupero Michi , Giorgi Annarita De , Mariotti Amalia 
Published: June 2023

Objective:
Magnesium plays an important role at cardiac level as it affects myocardial metabolism, calcium homeostasis, tone and vascular peripherals resistances. Low serum magnesium levels are associated with an increased risk of coronary artery disease and arteriosclerosis.

Design and method:
We propose a case of a 57 y.o. male, non smoker hypertensive patient treated with sartans and potassium kanreonate. In the past medical history: biopsy-proven chronic gastropathy and revascularized ischemic heart disease. He arrived in ER for dizziness, nausea and severe hypertension. The patient presented psychomotor agitation, muscle pain and paraesthesia. Blood tests revealed hypocalcaemia, hypokalaemia, hypomagnesaemia. Electrolyte supplementation was performed with a significant improvement of clinical picture. Two months later, the patient is back to the ER for hypertensive crisis. So he is hospitalized in the Nephrology Unit to be studied.

Results:
Blood tests revealed: haemoglobin: 12.2 g/dl, serum creatinine: 0.6 mg/dL, serum potassium levels: 4 mEq/L, serum calcium levels: 9.1 mg/dL, and serum magnesium levels: 1.2 mg/dL. Abdominal echo resulted negative for acute lesions and the renal artery Doppler did not show stenosis. Plasma and urinary catecholamines were normal. During the hospitalization, due to severe symptoms, iv supplementation with Magnesium sulphate (1 fl IV/week) was performed with an increased of serum magnesium levels and progressive hemodynamic compensation. On the contrary, serum sodium and potassium levels and magnesuria were normal, rather than increased. The patient was discharged after performing genetic investigations for possible tubulopathy (in progress) and with a programmed outpatient follow-up in which we observed the normalization of blood pressure values with the same antihypertensive therapy, but with magnesium values rather normal.

Conclusions:
Blood pressure control is affected by serum magnesium levels .
HIGH SALT INTAKE DID NOT DIMINISH BENEFICIAL EFFECT OF RENAL DENERVATION ON BLOOD PRESSURE, KIDNEY FUNCTION AND METABOLIC PROFILE - CROATIAN REAL-LIFE STUDY
Authors: Begic Zvonimir , Jelakovic Ana , Basic Matija , Perkov Drazen , Lovric Mila , Prkacin Ingrid , Fodor Ljiljana , Kolaric Melanija , Sarac Antonela , Vrkic Tajana Zeljkovic , Dika Zivka , Stambuk Sandra Karanovic , Zivko Marijana , Josipovic Josipa , Kacinari Patricija , Abramovic Ivana , Jelakovic Bojan 
Published: June 2023

Objective:
Last trials clearly documented and confirmed the efficacy of renal denervation (RDN) on decrease of blood pressure (BP). Our aim was to analyze the effects of RDN beyond BP lowering in truly resistant hypertensive patients in real-life conditions.

Design and method:
Out of 31 truly resistant patients whose secondary forms of hypertension were ruled out and were enrolled into the Croatian Spyral RDN registry, 18(10 m, 8 w, average age 49.3) were eligible for analysis. Office BP, ABPM, central BP and PWV were measured with Omron M6, Mobilograph and Sphygmocor devices, respectively. Albuminuria and salt intake were determined from 24-h urine samples, eGFR using the CKD Epi equation. Sympathetic/parasympathetic activity was measured with an ANX-3.0 ANSAR device. All RDN procedures(Spyral Medtronic) were done by one physician (average number of ablation spots was 41/procedure). Patients were examined day before and that day, 1,3,6, and 12 months after the RDN. Reponse was drop of office systolic BP by 10 mmHg or more 6 months after RDN. There were no differences in the RDN procedure between responders and non-responders.

Results:
Office and ABPM values dropped the day after RDN and remained significantly lower at the end of the follow-up (6.5/-5.5 and -16.2/9 mmHg, respectively). The effect of RDN on BP was not abolished with high salt intake(15.5 g/day at the end of follow up). eGFR remained stable, and even slight improvement was observed at the end of follow-up(+8.4 ml/min/1.72m2); albuminuria significantly decreased (-115 mg/day). All metabolic parameters (lipids, uric acid) improved at the end of follow-up. LFa/RFa decreased the day after RDN and remained lower during the follow-up period. After RND central systolic BP and Aix decreased more in responders than in non-responders (-12.8 vs. -7.3; -7 vs. -2.6) while PP amplification was improved in responders (1.22 to 1.33) but decreased in non-responders (1.33 to 1.25).

Conclusions:
In real-life circumstances, BP significantly decreased after RDN despite large salt ingestion. eGFR and albuminuria improved as well as metabolic parameters at the end of follow-up and all of the beneficial changes run in parallel with observed decrease in sympathetic activity.