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https://www.readbyqxmd.com/read/29792841/decarboxylation-of-ang-1-7-to-ala-1-ang-1-7-leads-to-significant-changes-in-pharmacodynamics
#1
Anja Tetzner, Maura Naughton, Kinga Gebolys, Jenny Eichhorst, Esther Sala, Óscar Villacañas, Thomas Walther
The heptapeptide angiotensin (Ang)-(1-7) is part of the beneficial arm of the renin-angiotensin system. Ang-(1-7) has cardiovascular protective effects, stimulates regeneration, and opposes the often detrimental effects of Ang II. We recently identified the G protein-coupled receptors Mas and MrgD as receptors for the heptapeptide. Ala1 -Ang-(1-7) (Alamandine), a decarboxylated form of Ang-(1-7), has similar vasorelaxant effects, but has been described to only stimulate MrgD. Therefore, this study aimed to characterise the consequences of the lack of the carboxyl group in amino acid 1 on intracellular signalling and to identify the receptor fingerprint for Ala1 -Ang-(1-7)...
May 21, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29792376/somatic-ace-regulates-self-renewal-of-mouse-spermatogonial-stem-cells-via-the-mapk-signaling-pathway
#2
Tingting Gao, Xin Zhao, Chenchen Liu, Binbin Shao, Xi Zhang, Kai Li, Jinyang Cai, Su Wang, Xiaoyan Huang
Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs...
May 24, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29792136/zinc-dependent-histone-deacetylase-inhibitors-in-cancer-therapeutics-recent-update
#3
Panagiotis I Georgianos, Maria Divani, Theodoros Eleftheriadis, Peter R Mertens, Vassilios Liakopoulos
BACKGROUND: Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensin-aldosterone-system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD...
May 23, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29791486/involvement-of-the-renin-angiotensin-system-in-the-progression-of-severe-hand-foot-and-mouth-disease
#4
Chao Zhang, Shuaiyin Chen, Guangyuan Zhou, Yuefei Jin, Rongguang Zhang, Haiyan Yang, Yuanlin Xi, Jingchao Ren, Guangcai Duan
BACKGROUND: Hand-foot-and-mouth disease (HFMD) is generally considered as a mild exanthematous disease to infants and young children worldwide. HFMD cases are usually mild and self-limiting but for few cases leads to complicated severe clinical outcomes, and even death. Previous studies have indicated that serum Ang II levels in patients with H7N9 infection were related to the severity of infection. However, the mechanisms underlying the pathogenesis of severe HFMD remain unclear. This study was undertaken to clarify the role of the renin-angiotensin system (RAS) in the progression of severe HFMD...
2018: PloS One
https://www.readbyqxmd.com/read/29791178/-rare-combination-of-turner-syndrome-and-congenital-adrenal-hyperplasia-with-21-hydroxylase-deficiency-case-report
#5
Ivana Ságová, Matej Stančík, Dušan Pavai, Daniela Kantárová, Anton Vaňuga, Peter Vaňuga
Combination of Turner syndrome (TS) and classic congenital adrenal hyperplasia (CAH) is rare. Globally, the incidence of CAH, autosomal recessive disorder caused by enzyme defect of steroidogenic pathway, is very low (1 : 10 000-16 000). 90 % of CAH cases are caused by 21-hydroxylase gene mutation (CYP21A2). Globally, the incidencie of Turner syndrome reaches 1 : 2 500. Phenotypically, females with TS may render wide spectrum of clinical features. Dominant symptoms are lowered terminal height and gonadal dysgenesia, ultimately leading to absence of puberty and infertility...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29790816/the-effect-of-elevated-%C3%AE-1-acid-glycoprotein-on-the-pharmacokinetics-of-tak-272-sco-272-an-orally-active-renin-inhibitor-in-rats
#6
Takuya Ebihara, Hisao Shimizu, Masami Yamamoto, Tomoaki Higuchi, Fumihiro Jinno, Yoshihiko Tagawa
1. The pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, was investigated in rats with subcutaneously injected turpentine oil, which was an inflammation animal model. 2. Following intravenous administration of TAK-272 to the turpentine-treated rats, the systemic clearance and volume of distribution decreased with the elevated plasma α1 -acid glycoprotein (AGP) levels. The elevated plasma AGP levels were negatively correlated with the plasma unbound fraction of TAK-272 in the rats. Although the AUCs of total TAK-272 in the turpentine-treated rats were higher than those in the control rats after intravenous and oral administration, those of unbound TAK-272, which seem to directly contribute to the pharmacological effect and safety, were nearly equal between the turpentine-treated and control rats in the respective dose routes...
May 23, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29790205/hyperkalaemia-in-diabetes-a-silent-risk-predicting-poor-outcomes
#7
F K Dojki, G L Bakris
Hyperkalaemia is traditionally defined as serum potassium levels >5.5 mmol/l and is associated with an elevated risk of adverse events and mortality. The renin angiotensin aldosterone system plays a pivotal role in potassium regulation [1,2], with aldosterone being a major regulator of potassium balance in the kidney.Potassium excretion and balance is primarily handled by the kidney (90%) and 10% by the colon [2]; thus, the risk of hyperkalaemia is linked to the following factors: level of kidney function; dietary potassium intake; concomitant diseases that affect potassium balance, such as diabetes; and use of medications that influence potassium excretion...
May 23, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29789689/postmenopausal-osteoporosis-is-associated-with-elevated-aldosterone-renin-ratio
#8
Xiaoyu Shu, Mei Mei, Linqiang Ma, Zhihong Wang, Shumin Yang, Jinbo Hu, Ying Song, Wenwen He, Ting Luo, Qingfeng Cheng, Yue Wang, Qianna Zhen, Qifu Li
Plasma aldosterone/renin ratio (ARR) is a useful method for primary aldosteronism (PA) screening. However some confounders, such as medications and dietary, affect plasma renin and aldosterone levels, resulting in false-negative or -positive plasma ARR. This study investigated the association between postmenopausal osteoporosis (PMO) and plasma ARR. Bone mineral density (BMD) was measured by dual-energy X-ray-absorptiometry (DXA) in 324 normotensive postmenopausal women. Based on clinical characteristics and BMD, 186 and 96 subjects were diagnosed as PMO and osteopenia respectively, and the remaining 42 subjects were grouped as normal BMD...
May 22, 2018: Journal of Human Hypertension
https://www.readbyqxmd.com/read/29788258/is-the-plasma-aldosterone-to-renin-ratio-associated-with-blood-pressure-response-to-treatment-in-general-practice
#9
Sabine C Käyser, Bianca W M Schalk, Wim J C de Grauw, Tjard R Schermer, Reinier P Akkermans, Jacques W M Lenders, Jaap Deinum, Marion C J Biermans
Background: Individualized antihypertensive treatment based on specific biomarkers such as renin may lead to more effective blood pressure control in patients with newly diagnosed essential hypertension. Recent studies suggested that the plasma aldosterone-to-renin ratio (ARR) may also be a candidate predictor for this purpose. Objective: To assess whether the ARR is associated with the blood pressure response to antihypertensive treatment in patients with newly diagnosed hypertension...
May 19, 2018: Family Practice
https://www.readbyqxmd.com/read/29786183/-hyperkalemia-as-a-limiting-factor-in-the-use-of-drugs-that-block-the-renin-angiotensin-aldosterone-system-raas
#10
Antonio Santoro, Marcora Mandreoli
Angiotensin-converting enzyme (ACE-I) inhibitors and ARBs have shown real efficacy in reducing blood pressure, proteinuria, in slowing the progression of chronic kidney disease (MRC) and in clinical improvement. in patients with heart failure, diabetes mellitus and ischemic heart disease. However, their use is limited by some side effects such as the increase in serum potassium (K), which can be particularly severe in patients with renal insufficiency. In the 23,000 patients followed by the PIRP project of the Emilia-Romagna Region, hyperkalaemia at the first visit (K> 5...
May 2018: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/29785962/age-related-blood-pressure-sensitivity-to-aldosterone-in-blacks-and-whites
#11
Wanzhu Tu, Ruohong Li, Vivek Bhalla, George J Eckert, J Howard Pratt
Aldosterone sensitivity, defined as the magnitude of the association of plasma aldosterone concentration with blood pressure (BP), seems to be a function of plasma volume. It increases as plasma renin activity decreases, and it is more significant in blacks but less so in whites. Age is a strong determinant of BP, and an increase in aldosterone sensitivity could contribute to the increase in BP. In the present study, we tested the hypothesis that aldosterone sensitivity increases with age. We used observational data collected from normotensive blacks and whites enrolled in a prospective cohort study...
May 21, 2018: Hypertension
https://www.readbyqxmd.com/read/29782633/macrothrombocytopenia-renal-dysfunction-and-nephrotic-syndrome-in-a-young-male-patient-a-case-report-of-myh9-related-disease
#12
Gabriela Sevignani, Giovana Memari Pavanelli, Sibele Sauzem Milano, Bianca Ramos Ferronato, Maria Aparecida Pachaly, Hae Ii Cheong, Mauricio de Carvalho, Fellype Carvalho Barreto
MYH9-related disease is an autosomal dominant disorder caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA on chromosome 22q12. It is characterized by congenital macrothrombocytopenia, bleeding tendency, hearing loss, and cataracts. Nephropathy occurs in approximately 30% of MYH9-related disease in a male patient carrier of a de novo missense mutation in exon 1 of the MYH9 gene [c.287C > T; p.Ser(TCG)96(TTG)Leu]. He presented all phenotypic manifestations of the disease, but cataracts...
May 17, 2018: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29782275/-specific-features-of-pharmacotherapy-of-patients-with-chronic-heart-failure-and-preserved-left-ventricular-ejection-fraction
#13
V N Larina, M V Leonova, I I Chukaeva, D G Karpenko
The review is devoted to pharmacotherapy of chronic heart failure (CHF) with preserved left ventricular ejection fraction. In this review we discuss data of meta-analyzes of randomized clinical trials and observational studies, as well as the indications for use of inhibitors of the renin-angiotensin-aldosterone system, β-blockers, and antagonists of mineralocorticoid receptors in these patients in current clinical guidelines. New approaches to therapy of CHF from the perspective of influence on myocardial fibrosis are considered in this review...
March 2018: Kardiologiia
https://www.readbyqxmd.com/read/29781840/cardiovascular-autonomic-profile-in-women-with-constitutional-hypotension
#14
Giris Jacob, Franca Barbic, Meytal Glago, Franca Dipaola, Alberto Porta, Raffaello Furlan
BACKGROUND: Constitutional hypotension (CHT) is defined as a SBP below 105 mmHg. As autonomic-related symptoms are frequently reported in CHT, these symptoms suggest that the cardiovascular autonomic control is perturbed in individuals with CHT. METHODS: We investigated the autonomic cardiovascular control of 15 women with CHT and 12 women with NBP (SBP >110 mmHg). We monitored BP and ECG for autonomic function test. Supine and head up tilt (HUT) spectral analysis of RR interval and BP variability, baroreflex sensitivity and plasma levels of plasma renin activity and aldosterone were determined...
May 16, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29781736/comparison-of-real-world-effectiveness-between-valsartan-and-non-ras-inhibitor-monotherapy-on-the-incidence-of-new-diabetes-in-chinese-hypertensive-patients-an-electronic-health-recording-system-based-study
#15
Tian Shen, Jiwei Wang, Yingjun Yu, Jinming Yu
This study aimed to compare the real-world effectiveness of valsartan and non renin-angiotensin system (non-RAS) agent monotherapy on the incidence of new on-set diabetes (NOD) in Chinese hypertensive patients. It was based on an electronic Health Recording System database from Minhang District of Shanghai. Hypertensive patients aged ≥18 years continuously taking either valsartan or non-RAS agent monotherapy for >12 months were included. Hazard ratios (HR) of NOD events were estimated using propensity score matching method and multivariate regression...
May 21, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29781721/current-prescription-status-of-antihypertensive-drugs-in-japanese-patients-with-hypertension-analysis-by-type-of-comorbidities
#16
Takayuki Ishida, Akinori Oh, Shinzo Hiroi, Yukio Shimasaki, Takuya Tsuchihashi
In 2014, the Japanese Society of Hypertension (JSH) issued revised guidelines for hypertension management. To assess adherence to the guidelines, this retrospective study evaluated the real-world status of antihypertensive drug prescribing for Japanese patients with hypertension, classified by comorbidity: diabetes mellitus, dyslipidemia, gout/hyperuricemia and renal diseases. Data on 59,867 hypertensive patients who received their first prescription for antihypertensive therapy between April 2014 and March 2015, were obtained from a medical insurance claims database for hospitals participating in the Diagnosis Procedure Combination/Per-Diem payment system...
May 21, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29781558/characteristics-of-high-and-low-risk-individuals-in-the-priority-study-urinary-proteomics-and-mineralocorticoid-receptor-antagonism-for-prevention-of-diabetic-nephropathy-in-type-2-diabetes
#17
N Tofte, M Lindhardt, K Adamova, J Beige, J W J Beulens, A L Birkenfeld, G Currie, C Delles, I Dimos, L Francová, M Frimodt-Møller, P Girman, R Göke, T Havrdova, A Kooy, H Mischak, G Navis, G Nijpels, M Noutsou, A Ortiz, A Parvanova, F Persson, P L Ruggenenti, F Rutters, I Rychlík, G Spasovski, M Speeckaert, M Trillini, H von der Leyen, P Rossing
AIM: To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high- or low-risk groups based on CKD273 score...
May 21, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29781322/the-impact-of-chronic-kidney-disease-on-medication-choice-and-pharmacologic-management-in-patients-with-heart-failure
#18
Syed Raza Shah, David E Winchester
In the past few years, medical community, including doctors, have become increasingly aware of the fact that chronic kidney disease (CK) and heart failure (HF) have common risk factors which impacts one another in terms of choice of therapy. Areas covered: Management of these two diseases has been a challenge for physicians. The treatment goals for HF patients in CK are very important. They serve as the end-point in using a specific treatment for management and treatment of CK patients hence, decreasing mortality rates...
May 21, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29779164/update-on-endothelin-receptor-antagonists-in-hypertension
#19
REVIEW
Michel Burnier
To review the most recent data on the development of endothelin receptor antagonists (ERAs) for the treatment of hypertension and the management of diabetic nephropathy RECENT FINDINGS: Recent reviews and meta-analyses of experimental and clinical data obtained with ERAs confirmed that endothelin receptor blockade is associated with significant decreases in blood pressure in essential hypertension but also in resistant hypertension. In addition, in patients with diabetic nephropathy, ERAs induce significant 30-40% decreases in albuminuria when administered on top of blockers of the renin-angiotensin system...
May 19, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29779118/change-in-kidney-function-after-unilateral-adrenalectomy-in-patients-with-primary-aldosteronism-identification-of-risk-factors-for-decreased-kidney-function
#20
Il Young Kim, In Seong Park, Min Jeong Kim, Miyeun Han, Harin Rhee, Eun Young Seong, Dong Won Lee, Soo Bong Lee, Ihm Soo Kwak, Sang Heon Song, Hyun Chul Chung
PURPOSE: Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA. METHODS: The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6 months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6 months postoperatively...
May 19, 2018: International Urology and Nephrology
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