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https://www.readbyqxmd.com/read/28767678/pharmacoperone-rescue-of-vasopressin-2-receptor-mutants-reveals-unexpected-constitutive-activity-and-coupling-bias
#1
Jo Ann Janovick, Timothy P Spicer, Thomas D Bannister, Louis Scampavia, P Michael Conn
Pharmacoperones are small molecules that diffuse into cells and rescue misfolded, mistrafficked protein mutants, restoring their function. These substances act with high target specificity, serving as templates to fold (or refold) receptors, enzymes, ion channels or other proteins and enable them to pass the scrutiny of the cellular quality control system ("rescue"). In the present study we demonstrate that a rescued mutant (L83Q) of the vasopressin type 2 receptor (V2R), shows a strong bias for Gs coupling unlike the WT V2 receptor, which couples to both Gs and Gq/11...
2017: PloS One
https://www.readbyqxmd.com/read/28763054/an-improved-database-of-coastal-flooding-in-the-united-kingdom-from-1915-to-2016
#2
Ivan D Haigh, Ozgun Ozsoy, Matthew P Wadey, Robert J Nicholls, Shari L Gallop, Thomas Wahl, Jennifer M Brown
Coastal flooding caused by extreme sea levels can produce devastating and wide-ranging consequences. The 'SurgeWatch' v1.0 database systematically documents and assesses the consequences of historical coastal flood events around the UK. The original database was inevitably biased due to the inconsistent spatial and temporal coverage of sea-level observations utilised. Therefore, we present an improved version integrating a variety of 'soft' data such as journal papers, newspapers, weather reports, and social media...
August 1, 2017: Scientific Data
https://www.readbyqxmd.com/read/28754558/magnetic-resonance-t2-mapping-and-diffusion-weighted-imaging-for-early-detection-of-cystogenesis-and-response-to-therapy-in-a-mouse-model-of-polycystic-kidney-disease
#3
Mareike Franke, Bettina Baeßler, Jan Vechtel, Claudia Dafinger, Martin Höhne, Lori Borgal, Heike Göbel, Friederike Koerber, David Maintz, Thomas Benzing, Bernhard Schermer, Thorsten Persigehl
Polycystic kidney disease (PKD) is among the leading causes of end-stage renal disease. Increasing evidence exists that molecular therapeutic strategies targeted to cyst formation and growth might be more efficacious in early disease stages, highlighting the growing need for sensitive biomarkers. Here we apply quantitative magnetic resonance imaging techniques of T2 mapping and diffusion-weighted imaging in the jck mouse model for PKD using a clinical 3.0 T scanner. We tested whether kidney T2 values and the apparent diffusion coefficient (ADC) are superior to anatomical imaging parameters in the detection of early cystogenesis, as shown on macro- and histopathology...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28751997/corrigendum-to-management-challenges-in-a-child-with-chronic-hyponatremia-use-of-v2-receptor-antagonist
#4
Sowmya Krishnan, Swapna Deshpande, Ashwini Mallappa, Divya Gunda, Pascale Lane, Anu Vishwanath, Rene Y McNall-Knapp
[This corrects the article DOI: 10.1155/2017/3757423.].
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28751810/effectiveness-of-tolvaptan-monotherapy-and-low-dose-furosemide-tolvaptan-combination-therapy-for-hepatoprotection-and-diuresis-in-a-rat-cirrhotic-model
#5
Norikazu Tanabe, Taro Takami, Koichi Fujisawa, Toshihiko Matsumoto, Naoki Yamamoto, Isao Sakaida
Spironolactone and furosemide, which are used to treat ascites associated with decompensated cirrhosis, are ineffective in treating refractory ascites. Hence, combination therapy with tolvaptan, a vasopressin V2 receptor antagonist, has been approved in Japan. Tolvaptan monotherapy and combination therapy with furosemide inhibit fibrosis in cardiac remodeling; hence, we examined these therapies in a rat cirrhotic model, including their usefulness in inhibiting hepatic fibrosis. In the present study, we used a model of hepatic fibrosis induced by a choline-deficient l-amino-acid-defined diet + diethylnitrosamine...
July 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28725324/cardiorenal-syndrome-role-of-arginine-vasopressin-and-vaptans-in-heart-failure
#6
REVIEW
Poornima Vinod, Vinod Krishnappa, Abigail M Chauvin, Anshika Khare, Rupesh Raina
Heart and kidney failure continued to be of increasing prevalence in today's society, and their comorbidity has synergistic effect on the morbidity and mortality of patients. Cardiorenal syndrome (CRS) is a complex disease with multifactorial pathophysiology. Better understanding of this pathophysiological network is crucial for the successful intervention to prevent advancement of the disease process. One of the major factors in this process is neurohormonal activation, predominantly involving renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP)...
June 2017: Cardiology Research
https://www.readbyqxmd.com/read/28665450/predicting-mirna-targets-for-head-and-neck-squamous-cell-carcinoma-using-an-ensemble-method
#7
Hong Gao, Hui Jin, Guijun Li
BACKGROUND: This study aimed to uncover potential microRNA (miRNA) targets in head and neck squamous cell carcinoma (HNSCC) using an ensemble method which combined 3 different methods: Pearson's correlation coefficient (PCC), Lasso and a causal inference method (i.e., intervention calculus when the directed acyclic graph (DAG) is absent [IDA]), based on Borda count election. METHODS: The Borda count election method was used to integrate the top 100 predicted targets of each miRNA generated by individual methods...
June 19, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28654793/pure-total-flavonoids-from-citrus-improve-non-alcoholic-fatty-liver-disease-by-regulating-tlr-ccl-signaling-pathway-a-preliminary-high-throughput-omics-study
#8
Liyan Wu, Maoxiang Yan, Jianping Jiang, Beihui He, Wei Hong, Zhiyun Chen
OBJECTIVE: This study investigated the possible molecular mechanisms of pure total flavonoids from citrus (PTFC) for the treatment of non-alcoholic fatty liver disease (NAFLD) via toll-like receptor/C-C chemokine ligand (TLR/CCL) signaling pathways by monitoring the changes in gene expression profile in liver tissues induced by high-fat diet. METHODS: We performed systematical analyses on hepatic expression profiles of mRNAs in a high-fat diet (HFD)-induced steatotic animal model with or without PTFC treatment...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28649750/vasopressin-physiology-assessment-and-osmosensation
#9
L Bankir, D G Bichet, N G Morgenthaler
Vasopressin (AVP) plays a major role in the regulation of water and sodium homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. AVP secretion is stimulated by a rise in plasma osmolality, a decline in blood volume or stress. V1a receptors are expressed in vascular smooth muscle cells, but the role of vasopressin in blood pressure regulation is still a matter of debate. AVP may also play a role in some metabolic pathways, including gluconeogenesis, through its action on V1a receptors expressed in the liver...
June 25, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28637297/a-role-for-progesterone-regulated-sfrp4-expression-in-uterine-leiomyomas
#10
Meaghan A Delaney, Ying-Wooi Wan, Gyoung-Eun Kim, Chad J Creighton, Margaret G Taylor, Ramya Masand, Andrew Park, Cecilia Valdes, William Gibbons, Zhandong Liu, Matthew L Anderson
Context: Despite progesterone's key role in uterine smooth muscle tumorigenesis, the mechanisms by which it promotes the growth of uterine leiomyomas remain poorly understood. Objective: The aim of this study was to identify novel gene products mediating progesterone's effects in uterine leiomyomas. Design: Gene expression profiling was used to identify putative progesterone-regulated genes differentially expressed in uterine leiomyomas, which were then studied in vitro...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28615206/plasticity-and-epitope-exposure-of-the-hiv-1-envelope-trimer
#11
Rebecca L R Powell, Maxim Totrov, Vincenza Itri, Xiaomei Liu, Alisa Fox, Susan Zolla-Pazner
We recently showed that mutations in the HIV-1 Envelope (Env) destabilize the V3 loop, rendering neutralization-resistant viruses sensitive to V3-directed monoclonal antibodies (mAbs). Here we investigated the propagation of this effect on other Env epitopes, with special emphasis on V2 loop exposure. Wildtype JR-FL and 19 mutant JR-FL pseudoviruses were tested for neutralization sensitivity to 21 mAbs specific for epitopes in V2, the CD4 binding site (CD4bs), and the CD4-induced (CD4i) region. Certain glycan mutants, mutations in the gp120 hydrophobic core, and mutations in residues involved in intra-protomer interactions exposed epitopes in the V2i region (overlays the α4β7 integrin binding site) and the V3 crown, suggesting a general destabilization of the distal region of the trimer apex...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28614813/polycystic-kidney-disease-and-the-vasopressin-pathway
#12
Maatje D A van Gastel, Vicente E Torres
Vasopressin, also known as arginine vasopressin or antidiuretic hormone, plays a pivotal role in maintaining body homeostasis. Increased vasopressin concentrations, measured by its surrogate copeptin, have been associated with disease severity as well as disease progression in polycystic kidney disease (PKD), and in experimental studies vasopressin has been shown to directly regulate cyst growth. Blocking vasopressin effects on the kidney via the vasopressin V2-receptor and lower circulating vasopressin concentration are potential treatment opportunities that have been the subject of study in PKD in recent years...
2017: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/28599463/cancer-gene-panel-analysis-of-cultured-circulating-tumor-cells-and-primary-tumor-tissue-from-patients-with-breast-cancer
#13
Eunjoo Hwang, Ji-Hyun Uh, Hye Seon Lee, Cham Han Lee, Soo Jeong Lee, Sei Hyun Ahn, Byung Ho Son, Jong Won Lee, Jong Han Yu, Nak-Jung Kwon, Woo Chung Lee, Kap-Seok Yang, Sung Ho Choi, Myoung Shin Kim, Jinseon Lee, Byung Hee Jeon
Although numerous effective therapies have improved the survival rate of patients with breast cancer, a number of patients present with tumor recurrence and metastasis. A liquid biopsy of circulating tumor cells (CTC) is a non-invasive method to obtain tumor cells and may be used as substitute for a tumor tissue biopsy. The present study focuses on determining whether CTC culture is an optimal method of obtaining sufficient amounts of CTCs for molecular analysis. The current study demonstrates a method of isolating and culturing CTCs from patients with breast cancer and the construction of a molecular profile of cultured cells using the Ion AmpliSeq Cancer Gene Panel V2...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28577072/regulation-of-renal-na-k-cl-cotransporters-by-vasopressin
#14
REVIEW
Sebastian Bachmann, Kerim Mutig
Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28494541/-new-therapeutic-paradigm-and-concepts-for-patients-with-cirrhotic-refractory-ascites
#15
S Z Wang, H G Ding
The activation of renin-angiotensin-aldosterone-vasopressin system is a key factor in the formation of ascites due to splanchnic vasodilation in cirrhosis. In theory, aldosterone antagonists, contraction of blood vessels, vasopressin V2 receptor, and angiotensin receptor antagonists are important targets for the prevention and treatment of cirrhotic ascites. The 15%-20% of patients with cirrhotic ascites that show no response to at least one week's treatment with potent diuretics (spironolactone 160 mg/d combined with furosemide 80 mg/d) are considered to have refractory ascites...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28474366/population-pharmacokinetic-analysis-of-lanicemine-azd6765-an-nmda-channel-blocker-in-healthy-subjects-and-patients-with-major-depressive-disorder
#16
F Agbo, K H Bui, D Zhou
WHAT IS KNOWN AND OBJECTIVE: Lanicemine (AZD6765) is a low-trapping N-methyl-d-aspartate receptor channel blocker that has demonstrated antidepressant efficacy in three of four clinical studies. The aim of this study was to develop a population pharmacokinetic model describing the concentration vs time profile of intravenously administered lanicemine in healthy subjects and patients with major depressive disorder (MDD) and to use the model to evaluate the impact of demographic and clinical factors and concomitant medication on the pharmacokinetics of lanicemine...
May 4, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28455745/expanding-the-role-of-vasopressin-antagonism-in-polycystic-kidney-diseases-from-adults-to-children
#17
Peter Janssens, Caroline Weydert, Stephanie De Rechter, Karl Martin Wissing, Max Christoph Liebau, Djalila Mekahli
Polycystic kidney disease (PKD) encompasses a group of genetic disorders that are common causes of renal failure. The two classic forms of PKD are autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD). Despite their clinical differences, ARPKD and ADPKD share many similarities. Altered intracellular Ca(2+) and increased cyclic adenosine monophosphate (cAMP) concentrations have repetitively been described as central anomalies that may alter signaling pathways leading to cyst formation...
April 28, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28432473/vasopressin-and-vasopressin-antagonists-in-heart-failure
#18
Julie K Vishram-Nielsen, Finn Gustafsson
Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels of arginine vasopressin (AVP), a peptide hormone produced in the hypothalamus, play a role in development of hyponatremia, and AVP and its surrogate, copeptin, are related to changes in osmolality, hemodynamics, neuro-hormones as well as in overall outcome in HF patients...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28428148/plasma-ctdna-analysis-for-detection-of-the-egfr%C3%A2-t790m-mutation-in-patients-with-advanced-non-small%C3%A2-cell-lung-cancer
#19
Suzanne Jenkins, James C-H Yang, Suresh S Ramalingam, Karen Yu, Sabina Patel, Susie Weston, Rachel Hodge, Mireille Cantarini, Pasi A Jänne, Tetsuya Mitsudomi, Glenwood D Goss
INTRODUCTION: Tumor biopsies for detecting EGFR mutations in advanced NSCLC are invasive, costly, and not always feasible for patients with late-stage disease. The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease progression after previous EGFR tyrosine kinase inhibitor therapy was investigated to determine eligibility for osimertinib treatment. METHODS: Matched tumor tissue and plasma samples from patients screened for the AURA extension and AURA2 phase II studies were tested for EGFR mutations by using tissue- and plasma-based cobas EGFR mutation tests...
July 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28419717/ligand-recognition-properties-of-the-vasopressin-v2-receptor-studied-under-qsar-and-molecular-modeling-strategies
#20
Marlet Martínez-Archundia, Brenda Colín-Astudillo, L M Moreno-Vargas, G Ramírez-Galicia, R Garduño-Juárez, O Deeb, Martha C Contreras-Romo, A Quintanar-Stephano, Edgar Abarca-Rojano, José Correa-Basurto
The design of new drugs that target vasopressin 2 receptor (V2R) is of vital importance to develop new therapeutic alternatives to treat diseases such as heart failure, polycystic kidney disease, etc. To get structural insights related to V2R-ligand recognition, we have used a combined approach of docking, molecular dynamics simulations (MD) and quantitative structure-activity relationship (QSAR) to elucidate the detailed interaction of the V2R with 119 of its antagonists. The three-dimensional model of V2R was built by threading methods refining its structure through MD simulations upon which the 119 ligands were subjected to docking studies...
April 17, 2017: Chemical Biology & Drug Design
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