bluuebunny/crossref_metadata_2025_split huggingface dataset:
A RARE CASE OF PHEOCROMOCYTOMA IN PREGNANCY EXACERBATED BY METOCLOPRAMIDE
Authors: Negro Aurelio , Santi Rosaria , Verzicco Ignazio , Giunta Alessandro , Tedeschi Stefano , Graiani Gallia , Volpi Riccardo , Cabassi Aderville 
Published: April 2021

Objective:
Pheocromocytoma (PHEO) is a rare catecholamines secreting tumor presenting with variable clinical setting, mostly with headaches, sweating, palpitation and poor controlled arterial hypertension. In 85–90% of cases, tumors are of adrenal gland origin while in 10–15% are commonly located in paravertebral sympathetic plexus. The prevalence of PHEO in hypertensive patients ranges between 0.1 and 0.6%; PHEO is extremely rare during pregnancy with a prevalence of 1 in 54000 pregnancies thus, delayed diagnose may cause life-threatening situations. Accurate identification of PHEO during the antenatal period reduces the risk of mortality for mother and fetus.

Design and method:
We described a case of 33 years old pregnant woman with a one-year history of grade I hypertension.

Results:
The patient has been previously evaluated by endocrinologist for the onset of “striae rubrae” associated with illness, muscle pain, asthenia, anxiety, palpitations and weakness; lab tests were negative for hypercortisolism thus clinicians hypothesized a “functional syndrome”. However, during the 28th week of gestation she was admitted to the emergency room because of severe headache and severe arterial hypertension. CT brain scan was negative for acute events, lab tests showed mild hypokalemia and proteinuria. An in depth revaluation of the clinical history revealed a treatment with metoclopramide taken one week earlier.

Conclusions:
Metoclopramide can stimulate catecholamine- and granin-derived peptide secretion from PHEO cells through activation of serotonin type 4 (5-HT4) receptors and induced PHEO crisis. Thus, under suspicion of PHEO exacerbated by metoclopramide we performed lab tests resulted positive for catecholamines secretion while aldosterone and renin levels were normal.
Abdomen ultrasound and MRI showed oval lesion located in right adrenal gland confirming diagnosis of PHEO. We started treatment with alpha and beta blockers associated with calcium-antagonist; at 33th week, patient underwent a caesarean section and after seven weeks a videolaparoscopic right adrenalectomy, obtaining a normalization of blood pressure levels.
ASSESSING THE KNOWLEDGE, ATTITUDE AND AWARENESS OF ADULT HYPERTENSIVE PATIENTS REGARDING HYPERTENSION
Authors: Patil Vishal , Patil Mansi 
Published: April 2021

Objective:
The aim of this study was to assess the awareness, knowledge, attitude, and practice of hypertensive patients and its relation to demographic data in those attending the out-patient services.

Design and method:
The study included 400 patients between the age 18–60 years were recruited who were previously diagnosed with hypertension as per JNC 7 criteria and were on regular anti-hypertensives for at least 6 months, and did not have any known or previously diagnosed psychological problem. Data was collected using a 2-parts closed ended questionnaire using a 4-point Likert scale. Data was analysed using both descriptive and inferential statistics (student's t-test, Pearson correlation coefficient and Spearman correlation coefficient).

Results:
A significant relationship was established between knowledge score and age of the participants (p = 0.002), but not between age and awareness and attitude (p >; 0.05). A significant relation was observed between duration of hypertension and knowledge score (p < 0.05). There is a significant relationship between knowledge score and educational level (p < 0.05). There is a significant difference between men and women's awareness score (p < 0.005), but this difference is not seen in other aspects (knowledge, attitude) (p >; 0.05). Women's awareness score was more than men (p = 0.0007). Data analysis showed that there is significant relationship between awareness and knowledge (P = 0.003), awareness and attitude (P = 0.0001).

Conclusions:
The blood pressure of the participants was not controlled in spite of good awareness and attitude. The knowledge score was low and community based programs to improve knowledge should be initiated. Adequate training for home blood pressure measurement should be given to rule out incoorect blood pressure measurement practics. Also, other barriers like physician turn over, non-adherence to protocol, incorrect prescriptions need to be assessed.
WHAT ARE THE PREFERRED BLOOD PRESSURE MEASUREMENT METHODS BY DOCTORS TO DETECT, DIAGNOSE AND TREAT HYPERTENSION? A SURVEY STUDY IN A CHINESE POPULATION
Authors: Lee Kam Pui , Choi Ryan Chun Ming , Liu Licheng , Yip Benjamin Hon-Kei , Gao Ting , Wong Samuel Yeung-Sha 
Published: April 2021

Objective:
Hypertension(HT) is the most common chronic disease and is the leading cause of morbidity and mortality. Its detection, diagnosis and management depend heavily on accurate blood pressure(BP) measurement. It is recommended that the diagnosis of HT should be confirmed or assisted by out-of-office BP measurement, including ambulatory BP measurement(ABPM) and home BP measurement(HBPM). When office BP is used, automated BP measurement(AOBP), which automatically provides an average of 3–5 BP readings, is preferred. This study aimed to describe the BP measurement methods used by doctors working in primary care to detect, diagnose and treat hypertension.

Design and method:
This is a cross-sectional survey. All doctors registered in the “Primary Care Directory” were mailed a questionnaire, asking their preferred methods to detect, diagnose and treat hypertension. Furthermore, the number of BP readings they usually obtained on office BP or HBPM to diagnose or manage HT was asked.

Results:
Four hundred and forty-five doctors responded. Manual measurement by a mercury or aneroid devices was the commonest method to detect(63.1%), diagnose(56.4%), and manage(72.4%) HT. There was an underuse of ABPM and only 1.6% of doctors used ABPM to diagnose HT. 22.2% of doctors used HBPM to diagnose HT; and 56.8% of doctors used HBPM to manage HT. A quarter (26.7%) of participants only obtained one BP reading when they used office BP. Only 40% of participants obtained at least 12 BP readings when HBPM was used. Doctors who obtained specialist qualification in family medicine were more likely to use AOBP in clinics and to obtain enough office BP readings for diagnosis and management of HT.

Conclusions:
Doctors in primary care in Hong Kong prefer to use manual office BP, especially mercury or aneroid devices, to screen, diagnose and treat HT. There is an underuse of AOBP and out-of-office BP. Studies are needed to understand the underlying reasons and to minimize the gap between real-life clinical practice and scientific advances.
EFFECTIVENESS OF THE EASY HYPERTENSION CLINIC MODEL: A 3-YEAR OUTCOME FROM SRINAGARIND HOSPITAL, KHON KAEN UNIVERSITY, THAILAND
Authors: Kotruchin Praew , Mitsungnern Thapanawong , Im-Oun Supap 
Published: April 2021

Objective:
From the National Health Examination Survey, one-fourth of Thai population had hypertension (HTN) but more than half were unaware of their high blood pressure (BP). Furthermore, only one-third of treated HTN patients had their BP under control. Uncontrolled HTN is a major risk factor for cardiovascular events, especially in low and middle-income countries. Therefore, we aimed to determine the effectiveness of the EASY HTN clinic model in terms of BP outcome.

Design and method:
The EASY HTN clinic was established in the year 2013 with 3 goals; easy access, minimal resource use, and provide standard treatment. The EASY concept included “Encourage home BP monitoring (HBPM), Adequate health education, Stage of change behavioral theorY”. The clinic consists of a doctor who was responsible for medication adjustment, and a well-trained nurse who was responsible for health education, and reinforcing a BP goal and healthy lifestyles. The clinic was run 6 hours per session, 1 day per week. The first 30 minutes was for group health education, and a question/answer session modulated by the nurse. Every new case was health-educated individually. Treatment was according to standard HTN guidelines. Doctor's treatment time was 7–10 minutes per case, including HBPM check. The follow-up was scheduled every 4 weeks by online messaging and every 3 months at the clinic. The effectiveness of the clinic model in terms of BP control and complication rate from 1st January 2016 to 30th September 2018 were analyzed.

Results:
There were 269, 312, and 206 new patients in 2016,2017, and 2018, respectively. The BP control rate (<140/90 mmHg) was 56.7% in 2016 and increased to 63.7% and 80.8% in 2017 and 2018. Anti-HTN medication can be down-titrated safely in 15.2%, 11.8%, and 12.3% of patients in 2016, 2017, and 2018. There was 2% of patients who can sustainably stop anti-HTN medication for 2 years. Low rate of cardiovascular complications were observed (1.8%).

Conclusions:
The EASY HTN clinic model is effective for BP control. It may be a good model for the primary care clinic in Southeast Asia due to the minimal medical resources need.
CHANGES THE LEVELS OF ANGIOTENSIN 1-7 DEPENDING ON TREATMENT WITH BLOCKERS OF RENIN-ANGIOTENSIN SISTEM IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES
Authors: Koval S. , Yushko K. , Snihurska I. , Mysnychenko O. 
Published: April 2021

Objective:
The leading pathogenetic role in development of hypertension plays the renin-angiotensin system (RAS). The angiotensin 1–7 is the novel part of RAS, the metabolic product of angiotensin-II and the important protective cardiovascular factor. The aim of this study was to evaluate the effect of combined treatment with such blockers of RAS as angiotensin-II receptor blocker (ARB) olmesartan or angiotensin-converting enzyme inhibitor (ACEi) ramipril on the blood levels of angiotensin 1–7 in patients with hypertension and type 2 diabetes (T2D).

Design and method:
The study involved 76 patients with hypertension grades 2–3 and T2D (37 men and 39 women) aged 43 to 70. Depending on antihypertensive treatment, the patients randomized into two groups: patients treated with ARB olmesartan (20–40 mg/day) and calcium channel blocker lercanidipine (10–20 mg/day) (n = 38) and patients received ACEi ramipril (5–10 mg/day) with lercanidipine (10–20 mg/day) (n = 38). All patients treated with lipid-lowering therapy (atorvastatin 20–40 mg/day) and antidiabetic therapy (metformin 1000–2000 mg/day) additionally. The angiotensin 1–7 levels determined by ELISA at baseline and after 12 months of therapy.

Results:
Both groups did not differ significantly by angiotensin 1–7 levels at baseline. In the olmesartan group the levels of angiotensin 1–7 were 108,39(92,32;121,17) ng/l and in the ramipril group were 104,37(87,16;122,83) ng/l (p > 0,05). After 12 months from the start of the treatment in both groups there was powerful antihypertensive effect. Targeted blood pressure levels were reached in 84.2% of patients (n = 32) treated with olmesartan and in 81.6% of patients (n = 31) treated with ramipril (p > 0.05 - intergroup). In the end of the treatment the levels of angiotensin 1–7 were differed significantly only in patients treated with olmesartan - there was increasing in its concentration by 20.3% (from 108.39(92.32;121.17) ng/l to (130.43(124.42;138.37) ng/l, p < 0.01). In patients treated with ramipril the levels of angiotensin 1–7 were 112.09(104.3;115.33) ng/l, which were not significantly different from basal levels (p > 0.05).

Conclusions:
The using of ARB olmesartan, unlike ACEi ramipril, significantly increased angiotensin 1–7 blood levels in patients with hypertension and T2D. The increasing the levels of angiotensin 1–7 may have additional cardioprotective value of ARB olmesartan, which requires further study.
RAGE-MEDIATED CELLULAR SIGNALING IS TRIGGERED BY THE ALLOSTERIC ACTIVATION OF THE AT1 RECEPTOR
Authors: Yamamoto Koichi , Yokoyama Serina , Huang Yibin , Kawai Tatsuo , Rakugi Hiromi 
Published: April 2021

Objective:
We recently identified the physical interaction of a pattern recognition receptor (PRR), lectin-like oxidized LDL receptor with the GPCR, angiotensin II type 1 receptor (AT1) whereby oxLDL allosterically activates AT1. In this study, we investigated if AT1 physically interacts with another PRR, the receptor for AGE (RAGE), and ligands of RAGE could allosterically activate AT1.

Design and method:
We used normal rat kidney epithelial cells (NRK52E) to investigate the interaction of the endogenous receptors. We also generated five different genetically-engineered CHO cells to individually analyze the G protein and β-arrestin pathways of AT1 activation; CHO cells expressing human RAGE (CHO-RAGE), CHO cells expressing both hRAGE and hAT1 (CHO-RAGE-AT1), CHO cells expressing both hRAGE and mutated hAT1 with impaired ability to activate G protein, and CHO cells expressing both hLOX-1 and mutated hAT1 with impaired ability to activate β-arrestin

Results:
In NRK52E, AGE-BSA provoked the activation of MAP kinase (ERK) that was inhibited by ARB or siRNA of AT1 or RAGE. Activation of NfκB and Epithelial mesanchmal transition induced by AGE-BSA was inhibited by ARBs as well as RAGE inhibitor. In genetically engineered CHO-cells, in situ PLA assay and immunoprecipitation confirmed the physical interaction of AT1 and RAGE on cellular membrane. HMGB1, a RAGE ligand induced Gαi-dependent inhibition of cAMP production only in the presence of both RAGE and AT1 with intact G protein binding. The effect of HMGB1 on cAMP content was abolished by ARB as well as RAGE inhibitor. HMGB1 did not induce the accumulation of IP1, a downstream of Gαq signaling, in CHO cells expressing both AT1 and RAGE. Real-time imaging of cellular membrane revealed that RAGE induced endocytosis of LOX-1 that depends on the intact β-arrestin pathway of AT1, and the phenomenon was not inhibited by ARB.

Conclusions:
RAGE ligands mediates cellular signaling via a physical interaction between RAGE and AT1. The activation of AT1 by RAGE ligands is distinct from that by angiotensin II in terms of selective G protein activation and the effect of ARB on G protein pathway but not on β-arrestin pathway.
ASSOCIATION BETWEEN CARDIAC (PRO)RENIN RECEPTOR EXPRESSION AND MYOCARDIAL HYPERTROPHY IN HUMAN
Authors: Morimoto Satoshi , Morishima Noriko , Watanabe Daisuke , Kato Yoichiro , Sawada Tatsuo , Shibata Noriyuki , Ichihara Atsuhiro 
Published: April 2021

Objective:
The (pro)renin receptor [(P)RR] is expressed in vital organs throughout the body, with the highest expression level in the heart, and is thought to regulate the tissue renin-angiotensin system (RAS) through the non-proteolytic activation of prorenin. (P)RR is cleaved by processing enzymes to generate soluble (s)(P)RR, which is secreted into the extracellular space, and blood concentration of s(P)RR is considered to reflect the expression level of tissue RAS. Although it has been suggested that increased expression of (P)RR may be involved in cardiac pathophysiology in experimental studies, the significance of (P)RR expression in human heart remains unclear. Therefore, in the present studies, we investigated association between cardiac (P)RR expression and myocardial hypertrophy in human.

Design and method:
Study (1): We measured serum s(P)RR concentration and assessed the relationships between serum s(P)RR level and background factors including left ventricular mass index (LVMI) in 135 patients (57 males) of our department. Study (2): We performed immunostaining for (P)RR and atrial natriuretic peptide (ANP) and α-skeletal actin (SKA), markers for myocardial hypertrophy, in left ventricle specimens obtained from 13 autopsy cases. The expression level of (P)RR, ANP, or SKA and cardiomyocyte area were analyzed using an image processing software (ImageJ) and expression level of (P)RR was compared with cardiomyocyte area and expression level of ANP or SKA.

Results:
Study (1): The patients’ age was 57 (44–67) y.o., serum s(P)RR concentration was 22.8 (21.1–27.7) ng/ml, eGFR was 74.4 (59.4–91.2) ml/min/1.73 m2, and LVMI was 79 (66–90) g/ m2. Serum s(P)RR level was significantly positively correlated with LVMI (β = 0.238, p < 0.01) independent of other related factors. Study (2): (P)RR immunostaining was observed in cytoplasm of cardiomyocytes. The expression level of (P)RR was significantly positively correlated with cardiomyocyte area (ρ = 0.386, p < 0.001) and expression level of ANP (ρ = 0.782, p < 0.001) or SKA (ρ = 0.373, p < 0.001).

Conclusions:
These data suggested that cardiac (P)RR expression may be associated with myocardial hypertrophy in human. Further studies are needed to determine the underlying mechanism of this association.
BRAIN-PENETRATING AMINOPEPTIDASE A INHIBITORS FOR NEW TREATMENT OF HYPERTENSION AND HEART FAILURE
Authors: Llorens-Cortes Catherine , Hmazzou Reda , Boitard Solene , Marc Yannick , Keck Mathilde , Balavoine Fabrice , Roques Bernard 
Published: April 2021

Objective:
Brain renin-angiotensin system (RAS) hyperactivity is involved in the pathophysiology of hypertension and heart failure (HF). Angiotensin III/(AngIII), one of the main effector peptides of the brain RAS, exerts tonic stimulatory control over blood pressure/(BP) in hypertensive rats and plays a pivotal role in sympathetic hyperactivity and left ventricular/(LV) dysfunction in rats post-myocardial infarction/(MI). Thus, aminopeptidase A/(APA), the enzyme generating brain AngIII represents a potential therapeutic target for the treatment of these pathologies. Our aim was to evaluate the mode of action of firibastat, a brain-penetrating prodrug of the APA inhibitor, EC33, to reduce BP in hypertensive rats and prevent LV dysfunction in mice post-MI.

Design and method:
Firibastat and MLN4760, an angiotensin-converting enzyme2/(ACE2) inhibitor were administered by central route in hypertensive DOCA-salt rats and mean arterial BP (MABP) was recorded following insertion of a catheter into the femoral artery. Brain APA and ACE2 activities were measured 30 min post-treatment. Two days post-MI induced by the left anterior descending artery ligation, mice were randomized to receive during 4–8 weeks oral treatment with vehicle, firibastat (150 mg/kg) or the ACE inhibitor, enalapril (1 mg/kg). Cardiac function was evaluated by echocardiography

Results:
1-Firibastat, when given centrally in hypertensive rats, is immediately cleaved by brain reductases, generating EC33 which inhibits brain APA activity, blocks brain AngIII formation and decreases BP. At the same time, firibastat treatment increases the activity of brain ACE2, majoring the conversion of AngII to Ang1-7, which by acting on the Mas-receptor, participate to the firibastat-induced BP decrease.
2-Chronic firibastat treatment in mice post-MI normalizes brain APA activity (normalizing brain RAS activity) and prevents sympathetic hyperactivity. It reduced LV end-diastolic pressure, LV end-systolic diameter and volume, and increased LV ejection fraction. It decreased the expression of HF and fibrosis biomarkers. Firibastat treatment prevents cardiac dysfunction and attenuates cardiac hypertrophy and fibrosis.

Conclusions:
Following these data, firibastat was selected for clinical development. Phase IIa/IIb clinical trials provided pharmacological proof-of-principle of firibastat efficacy for decreasing BP in hypertensive patients. The ongoing phase II study/QUORUM will determine if firibastat treatment may constitute a new therapeutic approach for preventing HF post-MI.
THE RELATIONSHIP BETWEEN RESISTANT HYPERTENSION AND RENAL PROGNOSIS IN THE IN PATIENTS WITH CARDIOVASCULAR DISEASES AND CHRONIC KIDNEY DISEASE
Authors: Nakamura Satoko 
Published: April 2021

Objective:
In the patients having chronic kidney disease (CKD) and cardiovascular diseases (CVD), the control of the blood pressure (BP) is important to prevent complications and renal function aggravation. Treatment-resistant hypertension (RHT) is hypertension not to fall to suitable BP with the antihypertensive medications more than three. Therefore, in the inpatients, we examined a ratio of RHT and renal prognosis.

Design and method:
417 inpatients (274 men, 143 women, average age 73 ± 11 years old) having CKD and CVD were examined. We investigated BP, blood test, urinalysis and oral medicines at the admission and the discharge.

Results:
The ratio of RHT was 24.5 % at the admission, and 19.9 % at the discharge. We classified the patients into five groups using BP at the admission. A group (normal BP, n = 21): SBP < 130mmHg and DBP < 80mmHg without medications. B group (untreated hypertension, n = 46): SBP more than 130mmHg or DBP more than 80mmHg without medications. C group (controlled hypertension, n = 138): SBP < 130 mmHg and DBP < 80 mmHg with medications (one to three drugs). D group (uncontrolled hypertension, n = 110): SBP more than 130 mmHg or DBP more than 80 mmHg with medications (one or two drugs). RHT group (n = 102): SBP more than 130mmHg or DBP more than 80 mmHg with medications (more than three drugs). The blood pressure at admission was 128 ± 22/76 ± 15, 133 ± 22/84 ± 16, 129 ± 23/71 ± 15, 141 ± 25/77 ± 19 and 146 ± 29/72 ± 16, respectively. The number of the antihypertensive medications was 1.8 ± 1.1 (C group), 1.6 ± 1.1 (D group) and 3.1 ± 1.2 (RHT group). In the RHT group, eGFR and the hemoglobin level were significantly lower, and the complications (diabetes, hyperuricemia, angina, atherosclerosis of lower limbs) were frequent. The factors that participated in RHT at admission were eGFR, diabetes and dyslipidemia. eGFR at the admission have related to the renal function aggravation at the discharge.

Conclusions:
In the inpatients having CKD and CVD, RHT existed frequently. The factors concerning with RHT were the renal function and the aggregation of the lifestyle-relate diseases.
LEFT VENTRICULAR HYPERTROPHY REGRESSION DURING ANTIHYPERTENSIVE TREATMENT IN RESISTANT HYPERTENSION PATIENTS
Authors: Matova Olena , Mishchenko Larysa , Serbeniyk Katerina , Krot Olena 
Published: April 2021

Objective:
Objective: to determine the predictors of regression of left ventricular hypertrophy (LVH) in treated resistant hypertensive (RH) patients after 2.1 ± 0.1 years of follow-up.

Design and method:
We studied 51 patients with RH confirmed by the office and ambulatory blood pressure (BP) monitoring despite the use of 3 antihypertensive medications for at least 3 months. During 2 years-period patients had been treated to 12-week rotations of oral daily treatment with spironolactone, nebivolol, torsemide, eplerenone, moxonidine in addition to their baseline triple-combination. Then participants continued to receive the personal most effective fourth-line agent. Patients were divided into 2 groups: 17 patients had LV mass index (LVMI) which was increased or stayed stable after 2 years (1st group), 34 patients with a reduction of LVMI in 2 years (2nd group).

Results:
Initially there were no significant differences in sex, duration of hypertension, body mass index, office and average 24-h ambulatory BP between the 2 groups. Compared with the 1st group patients from the 2nd group had a higher prevalence of non-dippers (24.3 vs 65 %, P < 0.001, respectively) and larger baseline LVMI (127.3 ± 4.1 vs 147.8 ± 6.5 g/m2, P < 0.01, respectively). Patients with persistent LVH included more subjects with coronary artery disease, chronic kidney disease and had less baseline active renin concentration (all P < 0.05). After 2 years in both groups office and average 24-h BP levels have been reduced, but goal rates were achieved at 28.6 % patients of the 1st group and 44.1 % patients of the 2nd group (P < 0.05). Reduction in nighttime BP was greater in the 2nd group. Initial higher LVMI (β = 0.655; P < 0.0001), baseline 24-h urinary albumin excretion (β = - 0.475; P < 0.0001), active renin concentration (β = 0.442; P = 0.005) were predictors of δ LVMI in multivariate modeling.

Conclusions:
Regression of LVH is possible in patients with RH in case of BP control, especially at night. Baseline higher LVMI, an increase of active renin concentration, decline of urinary albumin excretion are factors that determine reversibility LVH.