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https://www.readbyqxmd.com/read/28432473/vasopressin-and-vasopressin-antagonists-in-heart-failure
#1
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...
April 22, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28428148/plasma-ctdna-analysis-for-detection-of-the-egfr-t790m-mutation-in-patients-with-advanced-non-small-cell-lung-cancer
#2
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 epidermal growth factor receptor mutations (EGFRm) in advanced non-small cell lung cancer (NSCLC) are invasive, costly and not always feasible for patients with late-stage disease. The clinical utility of the cobas(®) EGFR Mutation Test v2 with plasma samples from patients with NSCLC at disease progression following previous EGFR-tyrosine kinase inhibitor (TKI) therapy was investigated to determine osimertinib treatment eligibility. METHODS: Matched tumor tissue and plasma samples from patients screened for AURA extension and AURA2 phase II studies were tested for EGFRm using tissue- and plasma-based cobas(®) EGFR Mutation Tests v2...
April 17, 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
#3
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
https://www.readbyqxmd.com/read/28416805/a-new-inhibitor-of-the-%C3%AE-arrestin-ap2-endocytic-complex-reveals-interplay-between-gpcr-internalization-and-signalling
#4
Alexandre Beautrait, Justine S Paradis, Brandon Zimmerman, Jenna Giubilaro, Ljiljana Nikolajev, Sylvain Armando, Hiroyuki Kobayashi, Lama Yamani, Yoon Namkung, Franziska M Heydenreich, Etienne Khoury, Martin Audet, Philippe P Roux, Dmitry B Veprintsev, Stéphane A Laporte, Michel Bouvier
In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28413470/identification-of-genes-associated-with-the-effect-of-inflammation-on-the-neurotransmission-of-vascular-smooth-muscle-cell
#5
Shujie Gan, Shenlong Qiu, Yiwen Feng, Yanping Zhang, Qin Qian, Zhong Wan, Jingdong Tang
Vascular smooth muscle cell (VSMC) accumulation and hypertrophy are common in vascular disorders, and inflammation has a crucial role in the development of these diseases. To investigate the effect of inflammation on the neurotransmission of VSMC, bioinformatic analysis was performed, following next generation sequencing. Genes of lipopolysaccharide (LPS)-treated A7r5 cells and phosphate-buffered saline (PBS)-treated A7r5 cells were sequenced via next generation sequencing, and each assay was repeated three times...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412033/antagonism-of-vasopressin-v2-receptor-improves-albuminuria-at-the-early-stage-of-diabetic-nephropathy-in-a-mouse-model-of-type-2-diabetes
#6
Ray El Boustany, Christopher Taveau, Catherine Chollet, Gilberto Velho, Lise Bankir, François Alhenc-Gelas, Ronan Roussel, Nadine Bouby
AIMS: Vasopressin is increased in diabetes and was shown to contribute to development of diabetic nephropathy through V2 receptor (V2R) activation in an experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains undocumented. This study addresses the issue in a mouse model of type 2 diabetes. METHODS: Male obese diabetic db/db mice were treated for 12weeks with a selective V2R antagonist (SR121463) and compared to non-treated db/db and non-diabetic db/m mice...
April 6, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28403013/vasopressin-and-diabetic-nephropathy
#7
Ronan Roussel, Gilberto Velho, Lise Bankir
PURPOSE OF REVIEW: The prevalence of diabetic kidney disease (DKD) is increasing worldwide. Despite major therapeutic advances in the last decades in DKD, the current standard of care let many people progress to severe stages. Vasopressin secretion is increased in diabetes, and its potential role in the onset and progression of DKD is being re-investigated. RECENT FINDINGS: Recently, observational studies evidenced an association between surrogates of vasopressin secretion (daily fluid intake or urine volume, and plasma copeptin concentration) and chronic kidney disease in the community, but also specifically in type 1 and in type 2 diabetes...
April 11, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28401776/molecular-characteristics-of-the-envelope-of-vertically-transmitted-hiv-1-strains-from-infants-with-hiv-infection
#8
Manickam Ashokkumar, Manohar Nesakumar, Cheedarla Narayanaiah, Vidya Vijayan Kk, Babu Hemalatha, Srikanth P Tripathy, Luke Elizabeth Hanna
Mother-to-child transmission of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV infected infants (< 2 years)...
April 12, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28379536/multicenter-open-label-extension-trial-to-evaluate-the-long-term-efficacy-and-safety-of-early-versus-delayed-treatment-with-tolvaptan-in-autosomal-dominant-polycystic-kidney-disease-the-tempo-4-4-trial
#9
Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Ron T Gansevoort, Ronald D Perrone, Ann Dandurand, John Ouyang, Frank S Czerwiec, Jaime D Blais
Background.: In TEMPO 3:4, the vasopressin V2 receptor antagonist tolvaptan slowed total kidney volume (TKV) growth and estimated glomerular filtration rate (eGFR) decline relative to placebo. Methods.: TEMPO 4:4 was designed to provide an additional 2 years of data on the long-term safety and efficacy of tolvaptan in subjects completing TEMPO 3:4. The objective was to assess the disease-modifying effects of tolvaptan on TKV and eGFR end-points including change from baseline over the combined duration of TEMPO 3:4 and TEMPO 4:4, and non-inferiority of slopes during TEMPO 4:4...
March 31, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28377483/vulvar-squamous-cell-carcinoma-vscc-as-two-diseases-hpv-status-identifies-distinct-mutational-profiles-including-oncogenic-fibroblast-growth-factor-receptor-3
#10
Johanne I Weberpals, Bryan Lo, Marc M Duciaume, Johanna N Spaans, Aisling A Clancy, Jim Dimitroulakos, Glenwood D Goss, Harman S Sekhon
PURPOSE: Patients with advanced or recurrent invasive vulvar squamous cell carcinoma (VSCC) have limited treatment options and a grave prognosis. Understanding the genomic landscape may facilitate the identification of new therapies and improve clinical outcomes. EXPERIMENTAL DESIGN: A retrospective chart review and molecular analysis of patients with VSCC from 2000-2016 was performed at the Ottawa Hospital Research Institute. The presence of oncogenic HPV was determined by nested PCR and amplified DNA was sequenced using the Ion AmpliSeq Cancer Hotspot v2 Panel...
April 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28326667/the-v2-receptor-antagonist-tolvaptan-raises-cytosolic-calcium-and-prevents-aqp2-trafficking-and-function-an-in-vitro-and-in-vivo-assessment
#11
Grazia Tamma, Annarita Di Mise, Marianna Ranieri, Ari Geller, Roberto Tamma, Alberta Zallone, Giovanna Valenti
Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney...
March 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28280053/copeptin-associates-with-cause-specific-mortality-in-patients-with-impaired-renal-function-results-from-the-luric-and-the-4d-study
#12
Vera Krane, Bernd Genser, Marcus E Kleber, Christiane Drechsler, Winfried März, Graciela Delgado, Bruno Allolio, Christoph Wanner, Wiebke Fenske
BACKGROUND: In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function. METHODS: Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients)...
March 9, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28279605/memory-alterations-and-white-matter-hyperintensities-in-elderly-patients-with-hypertension-the-adelahyde-2-study
#13
João Pedro Ferreira, Anna Kearney Schwartz, Ghassan Watfa, Lamiral Zohra, Jacques Felblinger, Jean-Marc Boivin, Serge Bracard, Gabriella Hossu, Antoine Verger, Laure Joly, Faiez Zannad, Patrick Rossignol, Athanase Benetos
OBJECTIVES: The longitudinal ADELAHYDE-2 study aims to identify the factors associated with cognitive impairment/decline and white matter hyperintensities burden. METHODS: Longitudinal single-center study comprising two visits separated by approximately 7 years. A total of 131 patients completed the two visits. The primary outcome was global memory composite scale, while the secondary outcome was white matter hyperintensities (WMH/Fazekas scale) load. RESULTS: Global memory at visit 2 (V2) was largely influenced by age, smoking status, glycated hemoglobin, and history of stroke already present at visit 1 (V1)...
May 1, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28274095/sphingosylphosphorylcholine-induces-thrombospondin-1-secretion-in-mcf10a-cells-via-erk2
#14
June Hee Kang, Hyun Ji Kim, Mi Kyung Park, Chang Hoon Lee
Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and Ca²⁺ signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28251822/tolvaptan-use-in-cancer-patients-with-hyponatremia-due-to-the-syndrome-of-inappropriate-antidiuretic-hormone-a-post-hoc-analysis-of-the-salt-1-and-salt-2-trials
#15
Richard J Gralla, Fatima Ahmad, Jaime D Blais, Joseph Chiodo, Wen Zhou, Linda A Glaser, Frank S Czerwiec
Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer-related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT-1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT-2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2-receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once-daily for 30 days...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28251326/the-effect-of-starvation-and-re-feeding-on-vasotocinergic-and-isotocinergic-pathways-in-immature-gilthead-sea-bream-sparus-aurata
#16
Arleta Krystyna Skrzynska, Magdalena Gozdowska, Ewa Kulczykowska, Gonzalo Martínez-Rodríguez, Juan Miguel Mancera, Juan Antonio Martos-Sitcha
This study describes the responses of the vasotocinergic and isotocinergic systems to food deprivation and re-feeding processes in immature gilthead sea bream (Sparus aurata). The animals were subjected to the following experimental treatments: (1) normal feeding (control), (2) food deprivation for 21 days; and (3) re-feeding for 7 days, beginning 14 days after starvation. The animals were sampled at 0, 7, 14 and 21 days from the beginning of the trial. The pituitary and plasma arginine vasotocin (AVT) and isotocin (IT) levels and the hypothalamic pro-vasotocin and pro-isotocin mRNA expression levels were measured...
March 1, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28241310/editing-vegfr2-blocks-vegf-induced-activation-of-akt-and-tube-formation
#17
Xionggao Huang, Guohong Zhou, Wenyi Wu, Gaoen Ma, Patricia A D'Amore, Shizuo Mukai, Hetian Lei
Purpose: Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in VEGF-induced angiogenesis. The goal of this project was to test the hypothesis that editing genomic VEGFR2 loci using the technology of clustered regularly interspaced palindromic repeats (CRISPR)-associated DNA endonuclease (Cas)9 in Streptococcus pyogenes (SpCas9) was able to block VEGF-induced activation of Akt and tube formation. Methods: Four 20 nucleotides for synthesizing single-guide RNAs based on human genomic VEGFR2 exon 3 loci were selected and cloned into a lentiCRISPR v2 vector, respectively...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28218410/pharmacokinetics-and-pharmacodynamics-of-tolvaptan-in-autosomal-dominant-polycystic-kidney-disease-phase-2-trials-for-dose-selection-in-the-pivotal-phase-3-trial
#18
Susan E Shoaf, Arlene B Chapman, Vicente E Torres, John Ouyang, Frank S Czerwiec
In the pivotal TEMPO 3:4 trial, the arginine vasopressin V2-receptor antagonist tolvaptan reduced the rate of kidney growth in patients with autosomal dominant polycystic kidney disease. Tolvaptan was initiated as daily morning/afternoon doses of 45/15 mg, and uptitrated weekly to 60/30 mg and 90/30 mg according to patient-reported tolerability. The current report describes 3 phase 2 trials in adult autosomal dominant polycystic kidney disease subjects that were the basis for the titrated split-dose regimen: a single ascending-dose trial (tolvaptan 15 to 120 mg; n = 11), a multiple split-dose trial (tolvaptan 15/15 mg, 30/0 mg, 30/15 mg, and 30/30 mg; n = 37), and an 8-week open-label safety and efficacy trial in 46 of the 48 subjects who participated in the prior 2 trials (tolvaptan 30/15 mg, 45/15 mg, 60/30 mg, and 90/30 mg)...
February 20, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28202885/tolvaptan-reduces-the-risk-of-worsening-renal-function-in-patients-with-acute-decompensated-heart-failure-and-preserved-left-ventricular-ejection-fraction%C3%A3-prospective-randomized-controlled-study
#19
Shunsuke Tamaki, Yoshihiro Sato, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tatsuhisa Ozaki, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Makoto Abe, Jun Nakamura, Masatake Fukunami
BACKGROUND: Although the mainstay of treatment for acute decompensated heart failure (ADHF) is decongestion by diuretic therapy, it is often associated with worsening renal function (WRF). The effect of tolvaptan, a selective V2 receptor antagonist, on WRF in ADHF patients with preserved left ventricular ejection fraction (LVEF) is unknown.Methods and Results:We enrolled 50 consecutive ADHF patients whose LVEF on admission was ≥45%. Patients were randomly assigned to either tolvaptan add-on (n=26) or conventional diuretic therapy (n=24)...
February 16, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28194370/peptide-agonists-of-vasopressin-v2-receptor-reduce-expression-of-neuroendocrine-markers-and-tumor-growth-in-human-lung-and-prostate-tumor-cells
#20
Marina Pifano, Juan Garona, Carla S Capobianco, Nazareno Gonzalez, Daniel F Alonso, Giselle V Ripoll
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects...
2017: Frontiers in Oncology
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