Molecular mechanisms of posaconazole- and itraconazole-induced pseudohyperaldosteronism and assessment of other systemically used azole antifungals

Publication date: Available online 23 January 2020Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Katharina R. Beck, Lucija Telisman, Chris J. van Koppen, George R. Thompson, Alex OdermattAbstractRecent reports described cases of severe hypertension and hypokalemia accompanied by low renin and aldosterone levels during antifungal therapy with posaconazole and itraconazole. These conditions represent characteristics of secondary endocrine hypertension caused by mineralocorticoid excess. Different mechanisms can cause mineralocorticoid excess, including inhibition of the adrenal steroidogenic enzymes CYP17A1 and CYP11B1, inhibition of the peripheral cortisol oxidizing enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) or direct activation of the mineralocorticoid receptor (MR). Compared to previous experiments revealing a threefold more potent inhibition of 11β-HSD2 by itraconazole than with posaconazole, the current study found sevenfold stronger CYP11B1 inhibition by posaconazole over itraconazole. Both compounds most potently inhibited CYP11B2. The major pharmacologically active itraconazole metabolite hydroxyitraconazole (OHI) resembled the effects of itraconazole but was considerably less active. Molecular modeling assessed the binding of posaconazole, itraconazole and OHI to 11β-HSD2 and the relevant CYP enzymes, and predicted important interactions not formed by the other systemically used azole antifungals, thus pro...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research

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Authors: El-Demiry NM, Maged AM, Gaafar HM, ElAnwary S, Shaltout A, Ibrahim S, El-Didy HM, Elsherbini MM Abstract Objective: To evaluate the diagnostic performance of Doppler sonography of umbilical artery (UA), fetal middle cerebral artery (MCA), ductus venosus (DV) &umbilical vein (UV) for prediction of adverse perinatal outcome.Material and Methods: A prospective cohort study conducted on 60 women diagnosed  with preeclampsia with severe features divided into two groups based on adverse perinatal outcome.Results: Statistically Significant differences were demonstrated UA PI (1.28 ± 0.23 vs. 0.96 ± 0.21, P
Source: Hypertension in Pregnancy - Category: OBGYN Tags: Hypertens Pregnancy Source Type: research
Publication date: Available online 25 February 2020Source: Indian Heart JournalAuthor(s): Priyanka Satish, Aditya Khetan, Shyamsundar Raithatha, Punam Bhende, Richard Josephson
Source: Indian Heart Journal - Category: Cardiology Source Type: research
Publication date: Available online 25 February 2020Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Su-Ying Cui, Yuan-Li Huang, Xiang-Yu Cui, Hui-Ling Zhao, Xiao Hu, Yu-Tong Liu, Yu Qin, Nurhumar Kurban, Yong-He Zhang
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research
Authors: Wyssmüller I, Schaal K, Wolf S, Zinkernagel M Abstract BACKGROUND: It has previously been shown that the process of anti-vascular endothelial growth factor (VEGF) injections can lead to a significant increase of blood pressure. The aim of this study was to investigate whether this blood pressure increase was reproducible with repeated anti-VEGF injections. PATIENTS AND METHODS: Patients with a systolic blood pressure of ≥ 180 mmHg during previous injections who were scheduled for further injections were asked to participate in this study. Systolic as well as diastolic blood pressu...
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Boutou AK, Pitsiou G Abstract Introduction: Pulmonary arterial hypertension (PAH) is still a chronic disorder characterized by high morbidity and mortality. Chronic thromboembolic pulmonary hypertension (CTEPH) is another form of pulmonary hypertension (PH) for which pulmonary endarterectomy (PEA) is the treatment of choice. However, not all patients are operable, while PH is often recurrent or persistent. Thus, for both disorders novel treatment options are urgently needed.Areas covered: This review describes the mechanism of action of riociguat, a soluble guanylate cyclase (sGC) stimulator, with a dual m...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
Conditions:   Open-Angle Glaucoma;   Ocular Hypertension Interventions:   Drug: Bimatoprost SR;   Drug: LUMIGAN Sponsor:   Allergan Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Pregnancy Induced Hypertension;   Pregnancy Related Intervention:   Sponsor:   University of Calgary Active, not recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
People with high blood pressure could reduce their risk of cardiovascular disease by adding this food to their diet. → Support PsyBlog for just $5 per month. Enables access to articles marked (M) and removes ads. → Explore PsyBlog's ebooks, all written by Dr Jeremy Dean: Accept Yourself: How to feel a profound sense of warmth and self-compassion The Anxiety Plan: 42 Strategies For Worry, Phobias, OCD and Panic Spark: 17 Steps That Will Boost Your Motivation For Anything Activate: How To Find Joy Again By Changing What You Do
Source: PsyBlog | Psychology Blog - Category: Psychiatry & Psychology Authors: Tags: Heart Disease Source Type: blogs
Okay, I'm not an epidemiologist or a virologist. But I do know something about those subjects, I'm a public health professor, and I am an expert in clinical communication and risk communication. So I'm going to offer some observations that I hope will help people keep this public health scare in proper perspective and maybe be of practical use.There are two important parameters we need to understand the risk caused by any communicable disease. I'm going to broadly say transmissibility, and the probability that exposure will lead to serious disease.We often see transmissibility represented as a single number, called R0 or &...
Source: Stayin' Alive - Category: American Health Source Type: blogs
This study was performed in Zhongshan Hospital, Fudan University, China. 803 patients with hypertension were consecutively recruited from 2012 to 2015. All participants underwent routine biochemical measurements, including plasma renin activity (PRA) and plasma aldosterone concentration (PAC). In all patients with a PAC higher than 10 ng/dl, a saline perfusion test was conducted, and a CT scan or adrenal venous sampling was also performed if needed. Receiver operating characteristic (ROC) analysis was conducted in all eGFR 
Source: International Journal of Endocrinology - Category: Endocrinology Tags: Int J Endocrinol Source Type: research
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