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https://www.readbyqxmd.com/read/28636754/linagliptin-and-its-effects-on-hyperglycaemia-and-albuminuria-in-patients-with-type-2-diabetes-and-renal-dysfunction-the-randomized-marlina-t2d%C3%A2-trial
#1
P-H Groop, M E Cooper, V Perkovic, B Hocher, K Kanasaki, M Haneda, G Schernthaner, K Sharma, R C Stanton, R Toto, J Cescutti, M Gordat, T Meinicke, A Koitka-Weber, S Thiemann, M von Eynatten
AIMS: The MARLINA-T2D™ study (ClinicalTrials.gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. METHODS: 360 individuals with type 2 diabetes, HbA1c 6.5 - 10.0% (48 - 86 mmol/mol), estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m(2) , and urinary albumin-to-creatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks...
June 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28636532/a-novel-pan-nox-inhibitor-apx-115-protects-kidney-injury-in-streptozotocin-induced-diabetic-mice-possible-role-of-peroxisomal-and-mitochondrial-biogenesis
#2
Guideock Kwon, Md Jamal Uddin, Gayoung Lee, Songling Jiang, Ahreum Cho, Jung Hwa Lee, Sae Rom Lee, Yun Soo Bae, Sung Hwan Moon, Soo Jin Lee, Dae Ryong Cha, Hunjoo Ha
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are increasingly recognized as a key factor in inflammation and extracellular matrix accumulation in diabetic kidney disease. APX-115 (3-phenyl-1-(pyridin-2-yl)-4-propyl-1-5-hydroxypyrazol HCl) is a novel orally active pan-Nox inhibitor. The objective of this study was to compare the protective effect of APX-115 with a renin-angiotensin system inhibitor (losartan), the standard treatment against kidney injury in diabetic patients, on streptozotocin (STZ)-induced diabetic kidney injury...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636269/commentary-on-r-d-trends-away-from-general-medicine-cardiovascular-drugs-can-the-fda-help-reverse-the-trend
#3
R J Meyer
In the latter part of the 20th century, drug development in cardiovascular diseases (CVDs) was a paragon of "modern" therapeutics, bringing about a substantial number of effective, well-tolerated agents targeting some of the most prevalent diseases of the Western world. These drugs were often examples of rational drug development targeting specific pathophysiologic pathways previously elucidated through basic research (e.g., targeting of the renin-angiotensin system or the cholesterol synthesis pathway). The widespread adoption of these ground-breaking medications in practice and into medical guidelines undoubtedly played a role in the fall of morbidity and mortality from CVD in the United States in recent decades...
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28635327/within-visit-blood-pressure-variability-and-cardiovascular-risk-factors-in-hypertensive-patients-with-non-dialysis-chronic-kidney-disease
#4
Kengo Azushima, Hiromichi Wakui, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kohji Ohki, Sho Kinguchi, Kotaro Haruhara, Tetsuya Fujikawa, Yoshiyuki Toya, Satoshi Umemura, Kouichi Tamura
As there may be an association between within-visit blood pressure (BP) variability and cardiovascular disease (CVD), we investigated the clinical significance of this BP variability in non-dialysis chronic kidney disease (CKD) patients. MATERIALS AND METHODS: According to the median of coefficient of variation (CV) of three systolic BP (SBP) readings within a single visit, we divided hypertensive patients with stage G1-4 CKD already treated with antihypertensive therapy into the high SBP-CV group and the low SBP-CV group...
June 21, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28634582/cancer-stem-cells-in-moderately-differentiated-lip-squamous-cell-carcinoma-express-components-of-the-renin-angiotensin-system
#5
Rachna S Ram, Helen D Brasch, Jonathan C Dunne, Paul F Davis, Swee T Tan, Tinte Itinteang
AIM: We investigated the expression of the renin-angiotensin system (RAS) by cancer stem cell (CSC) subpopulations we have identified in moderately differentiated lip squamous cell carcinoma (MDLSCC). METHOD: Ten MDLSCC samples underwent 3,3-diaminobenzidine (DAB) and immunofluorescent immunohistochemical (IHC) staining for (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and receptor 2 (ATIIR2). NanoString analysis and Western blotting (WB) were performed on six MDLSCC samples for gene and protein expression, respectively...
2017: Frontiers in Surgery
https://www.readbyqxmd.com/read/28632449/prevalence-of-essential-hypertension-and-its-complications-among-chinese-population-at-high-altitude
#6
Le Yue, Zhiqing Fan, Lin Sun, Wei Feng, Jingjie Li
Yue Le, Zhiqing Fan, Lin Sun, Wei Feng, and Jingjie Li. Prevalence of essential hypertension and its complications among Chinese population at high altitude. High Alt Med Biol. 18:140-144, 2017. OBJECTIVES: This study examined the prevalence of essential hypertension (EH) and its complications among Chinese population at different altitude regions in Qinghai province. METHODS: This cross-sectional analysis used data from 2000 residents living in the area with two different latitudes for more than 20 years, using 1:1 pairing mode...
June 2017: High Altitude Medicine & Biology
https://www.readbyqxmd.com/read/28632190/soluble-pro-renin-receptor-and-obstructive-sleep-apnea-syndrome-oxidative-stress-in-brain
#7
REVIEW
Kazuhiro Takahashi, Koji Ohba, Kazuki Tajima, Tsuguo Nishijima, Shigeru Sakurai
(Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H⁺-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and urine. Elevated plasma s(P)RR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(P)RR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS)...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28629525/erythropoietin-regulation-by-angiotensin-ii
#8
Yong-Chul Kim, Ognoon Mungunsukh, Regina M Day
The renin-angiotensin system (RAS) is a key regulator of blood pressure and blood volume homeostasis. The RAS is primarily comprised of the precursor protein angiotensinogen and the two proteases, renin and angiotensin-converting enzyme (ACE). Angiotensin I (Ang I) is derived from angiotensinogen by renin, but appears to have no biological activity. In contrast, angiotensin II (Ang II) that has a variety of biological functions in the cells is converted from Ang I through removal of two-C-terminal residues by ACE...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28626963/exercise-training-modulates-the-hepatic-renin-angiotensin-system-in-fructose-fed-rats
#9
Eliete Dalla Corte Frantz, Renata Frauches Medeiros, Isabele Gomes Giori, Juliana Bittencourt Silveira Lima, Thais Bento-Bernardes, Thaiane Gadioli Gaique, Caroline Fernandes-Santos, Tiago Fernandes, Edilamar Menezes Oliveira, Carla Paulo Vieira, Carlos Adam Conte-Junior, Karen Jesus Oliveira, Antonio Claudio Lucas da Nóbrega
The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and if this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high fructose (HFr) and exercise high fructose (HFr-Ex) groups. Fructose-drinking rats received D-fructose (100 g L(-1) ). After two weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate-intensity for eight weeks (60 min day(-1) , four days/week)...
June 19, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28626916/unexpected-functions-of-angiotensin-converting-enzyme-beyond-its-enzymatic-activity
#10
REVIEW
Jean Martinez
Angiotensin converting enzyme (ACE) is a well-known enzyme, largely studied for its action on hypertension, as it produces angiotensin II from angiotensin I. This paper describes two original behaviours of ACE. We showed that ACE could hydrolyse gastrin, a neuropeptide from the gastrointestinal tract, releasing the C-terminal amidated dipeptide H-Asp-Phe-NH2 . This dipeptide is believed to be involved in the gastrin-induced acid secretion in the stomach. This hypothetic mechanism of action of gastrin resulted in a strategy to rationally design gastrin receptor antagonists...
June 19, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28626726/cancer-stem-cells-in-oral-cavity-squamous-cell-carcinoma-a-review
#11
REVIEW
Ranui Baillie, Swee T Tan, Tinte Itinteang
Cancer stem cells (CSCs) have been identified in oral cavity squamous cell carcinoma (OCSCC). CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells and cancer cells that drive tumor growth. Studies of many cancer types including OCSCC have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple CSC subtypes within OCSCC, making investigation reliant on the use of multiple markers...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28625483/silymarin-protects-against-renal-injury-through-normalization-of-lipid-metabolism-and-mitochondrial-biogenesis-in-high-fat-fed-mice
#12
Bin Feng, Ran Meng, Bin Huang, Yan Bi, Shanmei Shen, Dalong Zhu
Obesity is associated with an increased risk of chronic kidney diseases and the conventional treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors is not enough to prevent renal injury and prolong the progression of disease. Recently, silymarin has shown protective effects on renal tissue injury, but the underlying mechanisms remain elusive. The goal of this study was to investigate the potential capacity of silymarin to prevent renal injury during obesity induced by high fat diet (HFD) in mice...
June 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28624952/endocrine-functions-of-the-renal-interstitium
#13
REVIEW
Armin Kurtz
This review aims to summarize the knowledge about the sensor and endocrine response functions of resident interstitial cells of the kidney. By the production of renin, erythropoietin and arachidonate metabolites (medullipin) subsets of renal interstitial fibroblasts and pericytes in different kidney zones play a central role in salt, blood pressure and oxygen homeostasis of the body. Common to these endocrine functions is that their regulation mainly occurs by (de)recruitment of active cells.
June 17, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28624188/a-novel-single-strand-rnai-therapeutic-agent-targeting-the-pro-renin-receptor-suppresses-ocular-inflammation
#14
Atsuhiro Kanda, Erdal Tan Ishizuka, Atsushi Shibata, Takahiro Matsumoto, Hidekazu Toyofuku, Kousuke Noda, Kenichi Namba, Susumu Ishida
The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623899/renin-angiotensin-system-blockers-and-residual-kidney-function-loss-in-patients-initiating-peritoneal-dialysis-an-observational-cohort-study
#15
Jenny I Shen, Anjali B Saxena, Sitaram Vangala, Satvinder K Dhaliwal, Wolfgang C Winkelmayer
BACKGROUND: Although angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U...
June 17, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28620832/the-pro-renin-receptor-and-its-interaction-partners
#16
REVIEW
Jörg Peters
The prorenin receptor was originally discovered as a receptor that binds renin and prorenin, thereby inducing pro-fibrotic intracellular signal cascades. These effects are partially mediated in vitro by angiotensin (ANG) and partially independent of ANG. Consequently, inhibitors of the interaction between the prorenin and the (pro)renin receptor (PRR) were designed hoping that they may prevent fibrotic tissue damage, for instance, in the kidney. However, this concept was challenged by the fact that overexpression of the PRR was not harmful at all, whereas depletion of the PRR was lethal or markedly detrimental...
June 15, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28620011/dietary-restriction-but-not-angiotensin-ii-type-1-receptor-blockade-improves-dna-damage-related-vasodilator-dysfunction%C3%A2-in-rapidly-aging-ercc1-%C3%AE-mice
#17
Haiyan Wu, Bibi S van Thiel, Paula Katherine Bautista-Nino, Erwin Reiling, Matej Durik, Frank P J Leijten, Yanto Ridwan, Renata M C Brandt, Harry van Steeg, Martijn E T Dollé, Wilbert P Vermeij, Jan H J Hoeijmakers, Jeroen Essers, Ingrid van der Pluijm, A H Jan Danser, Anton J M Roks
DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1(∆/-) mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system ...
June 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28619367/the-vasoprotective-axes-of-the-renin-angiotensin-system-physiological-relevance-and-therapeutic-implications-in-cardiovascular-hypertensive-and-kidney-diseases
#18
REVIEW
Xiao C Li, Jianfeng Zhang, Jia L Zhuo
The renin-angiotensin system (RAS) is undisputedly one of the most prominent endocrine (tissue-to-tissue), paracrine (cell-to-cell) and intracrine (intracellular/nuclear) vasoactive systems in the physiological regulation of neural, cardiovascular, blood pressure, and kidney function. The importance of the RAS in the development and pathogenesis of cardiovascular, hypertensive and kidney diseases has now been firmly established in clinical trials and practice using renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, type 1 (AT1) angiotensin II (ANG II) receptor blockers (ARBs), or aldosterone receptor antagonists as major therapeutic drugs...
June 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28618007/an-exploratory-study-in-healthy-male-subjects-of-the-mechanism-of-mirabegron-induced-cardiovascular-effects
#19
Marcel van Gelderen, Matthias Stölzel, John Meijer, Virginie Kerbusch, Christiane Collins, Cees Korstanje
To explore the role of β1 -adrenoceptors (ARs) in the heart rate response to the selective β3 -adrenoceptor agonist mirabegron, 12 young male volunteers received single oral doses of the nonselective β1/2 -AR antagonist propranolol (160 mg), the selective β1 -AR antagonist bisoprolol (10 mg), or placebo on days 1 and 5 of each period in a 3-period crossover study. On day 5, dosing was followed by a supratherapeutic dose of mirabegron (200 mg). Vital signs, impedance cardiography, and plasma renin activity were collected...
June 15, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28615146/novel-insights-into-acute-kidney-injury-chronic-kidney-disease-continuum-and-the-role-of-renin-angiotensin-system
#20
REVIEW
Yu-Hsiang Chou, Tao-Min Huang, Tzong-Shinn Chu
Acute kidney injury (AKI) is an independent risk factor for chronic kidney disease (CKD). If injury is mild, a repair process can be adaptive and lead to complete renal recovery. However, severe injury will be accompanied by a maladaptive repair which usually leads to nephron loss, fibrosis, vascular rarefaction, and chronic inflammation. Although various mechanisms underlying AKI-CKD transition have been explored, no intervention has been proved effective to block the transition until very recently. A lack of consensus for monitoring renal function and defining renal recovery after AKI should be the reasons for the slow advance in the discovery of a timely pharmacologic treatment to block AKI-CKD transition...
June 11, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
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