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https://www.readbyqxmd.com/read/28647918/designing-future-clinical-trials-in-heart-failure-with-preserved-ejection-fraction-lessons-from-topcat
#1
REVIEW
Ravi B Patel, Sanjiv J Shah, Gregg C Fonarow, Javed Butler, Muthiah Vaduganathan
PURPOSE OF REVIEW: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. RECENT FINDINGS: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects...
June 24, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28645352/r%C3%A3-sistances-aux-hormones-st%C3%A3-ro%C3%A3-des-physiologie-et-pathologie-pathophysiology-of-steroid-resistance-syndrome
#2
N Ramos, M Lombès
Steroid resistance syndrome (mineralocorticoids, glucocorticoids, estrogens, androgens) is a rare clinical disorder, androgen insensitivity syndrome being the most commonly described. Resistance syndromes are characterized by elevated steroid hormone levels, secondary to an impaired signal transduction and a lack of negative feedback, without any specific clinical signs of steroid excess. In most cases, steroid hormone resistance is generally caused by steroid receptor mutations. Several nonsense and missense mutations or deletions have already been described for all steroid receptors, except for the progesterone receptor...
October 2016: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28637706/endothelial-mineralocorticoid-receptor-contributes-to-systolic-dysfunction-induced-by-pressure-overload-without-modulating-cardiac-hypertrophy-or-inflammation
#3
Ane M Salvador, M Elizabeth Moss, Mark Aronovitz, Kathleen B Mueller, Robert M Blanton, Iris Z Jaffe, Pilar Alcaide
Heart Failure (HF) is associated with increased circulating levels of aldosterone and systemic inflammation. Mineralocorticoid receptor (MR) antagonists block aldosterone action and decrease mortality in patients with congestive HF However, the molecular mechanisms underlying the therapeutic benefits of MR antagonists remain unclear. MR is expressed in all cell types in the heart, including the endothelial cells (EC), in which aldosterone induces the expression of intercellular adhesion molecule 1 (ICAM-1)...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28637490/lipoid-congenital-adrenal-hyperplasia-by-steroidogenic-acute-regulatory-protein-star-gene-mutation-in-an-italian-infant-an-uncommon-cause-of-adrenal-insufficiency
#4
Carla Bizzarri, Elisa Pisaneschi, Mafalda Mucciolo, Stefania Pedicelli, Daniela Galeazzi, Antonio Novelli, Marco Cappa
BACKGROUND: Lipoid congenital adrenal hyperplasia (CAH) (OMIM n. 201710) is the most severe form of congenital adrenal hyperplasia. It is characterized by severe adrenal and gonadal steroidogenesis impairment due to a defect in the conversion of cholesterol to pregnenolone. Affected infants experience salt loss, but glucocorticoid and mineralocorticoid replacement therapy enables long-term survival. Classic lipoid congenital adrenal hyperplasia is relatively common in Japan and Korea but extremely rare in Caucasian populations...
June 20, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28636485/mineralocorticoids-modulate-the-expression-of-the-beta-3-subunit-of-the-na-k-atpase-in-the-renal-collecting-duct
#5
Macarena Rojas, Pablo Díaz, Pablo León, Alexis A González, Magdalena González, Víctor Barrientos, Nikolay B Pestov, Rodrigo Alzamora, Luis Michea
Renal sodium reabsorption depends on the activity of the Na(+),K(+)-ATPase α/β heterodimer. Four α (α1-4) and three β (β1-3) subunit isoforms have been described. It is accepted that renal tubule cells express α1/β1 dimers. Aldosterone stimulates Na(+),K(+)-ATPase activity and may modulate α1/β1 expression. However, some studies suggest the presence of β3 in the kidney. We hypothesized that the β3 isoform of the Na(+),K(+)-ATPase is expressed in tubular cells of the distal nephron, and modulated by mineralocorticoids...
June 21, 2017: Channels
https://www.readbyqxmd.com/read/28634268/30-years-of-the-mineralocorticoid-receptor-mineralocorticoid-receptor-antagonists-60-years-of-research-and-development
#6
REVIEW
Peter Kolkhof, Lars Bärfacker
The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinical in vivo models, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward identifying a second generation of much more specific steroidal MRAs were all based on the initial 17-spirolactone construct...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28634267/30-years-of-the-mineralocorticoid-receptor-the-role-of-the-mineralocorticoid-receptor-in-the-vasculature
#7
REVIEW
Jennifer J DuPont, Iris Z Jaffe
Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28634266/30-years-of-the-mineralocorticoid-receptor-the-brain-mineralocorticoid-receptor-a-saga-in-three-episodes
#8
REVIEW
Marian Joëls, E Ronald de Kloet
In 1968, Bruce McEwen discovered that (3)H-corticosterone administered to adrenalectomised rats is retained in neurons of hippocampus rather than those of hypothalamus. This discovery signalled the expansion of endocrinology into the science of higher brain regions. With this in mind, our contribution highlights the saga of the brain mineralocorticoid receptor (MR) in three episodes. First, the precloning era dominated by the conundrum of two types of corticosterone-binding receptors in the brain, which led to the identification of the high-affinity corticosterone receptor as the 'promiscuous' MR cloned in 1987 by Jeff Arriza and Ron Evans in addition to the classical glucocorticoid receptor (GR)...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28634265/30-years-of-the-mineralocorticoid-receptor-coregulators-as-mediators-of-mineralocorticoid-receptor-signalling-diversity
#9
REVIEW
Peter J Fuller, Jun Yang, Morag J Young
The cloning of the mineralocorticoid receptor (MR) 30 years ago was the start of a new era of research into the regulatory processes of MR signalling at target genes in the distal nephron, and subsequently in many other tissues. Nuclear receptor (NR) signalling is modified by interactions with coregulatory proteins that serve to enhance or inhibit the gene transcriptional responses. Over 400 coregulatory proteins have been described for the NR super family, many with functional roles in signalling, cellular function, physiology and pathophysiology...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28634264/30-years-of-the-mineralocorticoid-receptor-the-scientific-impact-of-cloning-the-mineralocorticoid-receptor-30-years-on
#10
EDITORIAL
John W Funder, Maria-Christina Zennaro
No abstract text is available yet for this article.
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28634263/30-years-of-the-mineralocorticoid-receptor-short-reflections-on-the-discovery-of-the-mineralocorticoid-receptor
#11
EDITORIAL
Ronald M Evans
No abstract text is available yet for this article.
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28626824/atypical-chronic-central-serous-chorioretinopathy-with-cystoid-macular-edema-therapeutic-response-to-medical-and-laser-therapy
#12
Jiun L Do, Lisa C Olmos de Koo, Hossein Ameri
PURPOSE: To describe an atypical case of chronic central serous chorioretinopathy (CSCR). METHODS: A 58-year-old man with longstanding, bilateral visual impairment was self-referred for a second opinion. RESULTS: Findings by direct ophthalmoscopy, optical coherence tomography, fluorescein angiography, and fundus autofluorescence (FAF) were suggestive of atypical, chronic CSCR. Treatment with oral anti-mineralocorticoids resulted in moderate improvement, and photodynamic therapy (PDT) had minimal effect...
June 2017: Journal of Current Ophthalmology
https://www.readbyqxmd.com/read/28626417/spironolactone-as-an-adjunctive-treatment-in-neovascular-age-related-macular-degeneration
#13
Kapil G Kapoor, Jennifer Sim
Neovascular age-related macular degeneration (AMD) is a potentially sight-threatening condition. The current standard-of-care treatment regimen is serial intravitreal antivascular endothelial growth factor injections. While these typically have great success, they do carry exceptional treatment burden on the patient, cost burden due to their required frequency of use, and the risk of endophthalmitis, which can be devastating. This case report explores an alternative potential option as a treatment adjunct for neovascular AMD (nAMD), and identifies some of the overlap between nAMD and central serous chorioretionpathy...
May 2017: Case Reports in Ophthalmology
https://www.readbyqxmd.com/read/28624548/glucocorticoids-and-gut-bacteria-the-galf-hypothesis-in-the-metagenomic-era
#14
REVIEW
David J Morris, Jason M Ridlon
A new concept is emerging in biomedical sciences: the gut microbiota is a virtual 'organ' with endocrine function. Here, we explore the literature pertaining to the role of gut microbial metabolism of endogenous adrenocorticosteroids as a contributing factor in the etiology of essential hypertension. A body of literature demonstrates that bacterial products of glucocorticoid metabolism are absorbed into the portal circulation, and pass through the kidney before excretion into urine. Apparent Mineralocorticoid Excess (AME) syndrome patients were found to have congenital mutations resulting in non-functional renal 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) and severe hypertension often lethal in childhood...
June 14, 2017: Steroids
https://www.readbyqxmd.com/read/28623763/saturated-high-fat-feeding-independent-of-obesity-alters-hypothalamus-pituitary-adrenal-axis-function-but-not-anxiety-like-behaviour
#15
Cecile Hryhorczuk, Léa Décarie-Spain, Sandeep Sharma, Caroline Daneault, Christine Des Rosiers, Thierry Alquier, Stephanie Fulton
Overconsumption of dietary fat can elicit impairments in emotional processes and the response to stress. While excess dietary lipids have been shown to alter hypothalamus-pituitary-adrenal (HPA) axis function and promote anxiety-like behaviour, it is not known if such changes rely on elevated body weight and if these effects are specific to the type of dietary fat. The objective of this study was to investigate the effect of a saturated and a monounsaturated high-fat diet (HFD) on HPA axis function and anxiety-like behaviour in rats...
June 10, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28619768/liquorice-induced-hypokalaemia-in-patients-treated-with-yokukansan-preparations-identification-of-the-risk-factors-in-a-retrospective-cohort-study
#16
Saori Shimada, Tetsuaki Arai, Akira Tamaoka, Masato Homma
OBJECTIVE: To evaluate serum potassium levels and rates of hypokalaemia in patients treated with liquorice-containing Japanese traditional Kampo-medicines Yokukansan (YK) and Yokukansan-ka-chinpihange (YKCH). DESIGN: Retrospective cohort study. SETTING: Patients receiving YK preparations for dementia and other psychiatric disorders in the University of Tsukuba Hospital in Japan. PARTICIPANTS: 389 patients (male/female: 174/215, 68...
June 15, 2017: BMJ Open
https://www.readbyqxmd.com/read/28611666/mineralocorticoid-receptor-signaling-as-a-therapeutic-target-for-renal-and-cardiac-fibrosis
#17
REVIEW
Greg H Tesch, Morag J Young
Activation of the mineralocorticoid receptor (MR) plays important roles in both physiological and pathological events. Blockade of MR signaling with MR antagonists (MRAs) has been used clinically to treat kidney and cardiac disease associated with hypertension and other chronic diseases, resulting in suppression of fibrosis in these organs. However, the current use of steroidal MRAs has been limited by off target effects on other hormone receptors or adverse effects on kidney tubular function. In this review, we summarize recent insights into the profibrotic roles of MR signaling in kidney and cardiovascular disease...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28611594/overexpression-of-mineralocorticoid-receptors-in-the-mouse-forebrain-partly-alleviates-the-effects-of-chronic-early-life-stress-on-spatial-memory-neurogenesis-and-synaptic-function-in-the-dentate-gyrus
#18
Sofia Kanatsou, Henk Karst, Despoina Kortesidou, Rachelle A van den Akker, Jan den Blaauwen, Anjanette P Harris, Jonathan R Seckl, Harm J Krugers, Marian Joels
Evidence from human studies suggests that high expression of brain mineralocorticoid receptors (MR) may promote resilience against negative consequences of stress exposure, including childhood trauma. We examined, in mice, whether brain MR overexpression can alleviate the effects of chronic early life stress (ELS) on contextual memory formation under low and high stress conditions, and neurogenesis and synaptic function of dentate gyrus granular cells. Male mice were exposed to ELS by housing the dam with limited nesting and bedding material from postnatal day (PND) 2 to 9...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28589964/hpa-axis-genes-and-their-interaction-with-childhood-maltreatment-are-related-to-cortisol-levels-and-stress-related-phenotypes
#19
Lotte Gerritsen, Yuri Milaneschi, Christiaan Vinkers, Bert van Hemert, Laura van Velzen, Lianne Schmaal, Brenda Wjh Penninx
Stress responses are controlled by the hypothalamus pituitary adrenal (HPA)-axis and maladaptive stress responses are associated with the onset and maintenance of stress-related disorders such as major depressive disorder (MDD). Genes that play a role in the HPA-axis regulation may likely contribute to the relation between relevant neurobiological substrates and stress-related disorders. Therefore, we performed gene-wide analyses for 30 a-priori literature-based genes involved in HPA-axis regulation in 2014 subjects (34% male; mean age: 42...
June 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28587112/is-there-a-role-for-genomics-in-the-management-of-hypertension
#20
REVIEW
Jacopo Burrello, Silvia Monticone, Fabrizio Buffolo, Martina Tetti, Franco Veglio, Tracy A Williams, Paolo Mulatero
Hypertension (HTN) affects about 1 billion people worldwide and the lack of a single identifiable cause complicates its treatment. Blood pressure (BP) levels are influenced by environmental factors, but there is a strong genetic component. Linkage analysis has identified several genes involved in Mendelian forms of HTN and the associated pathophysiological mechanisms have been unravelled, leading to targeted therapies. The majority of these syndromes are due to gain-of-function or loss-of-functions mutations, resulting in an alteration of mineralocorticoid, glucocorticoid, or sympathetic pathways...
May 26, 2017: International Journal of Molecular Sciences
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