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https://www.readbyqxmd.com/read/29311539/tolvaptan-for-fluid-management-in-living-donor-liver-transplant-recipients
#1
Shunichi Imai, Masahiro Shinoda, Hideaki Obara, Minoru Kitago, Taizo Hibi, Yuta Abe, Hiroshi Yagi, Kentaro Matsubara, Hisanobu Higashi, Osamu Itano, Yuko Kitagawa
BACKGROUND Tolvaptan, an antagonist of the vasopressin V2 receptor is a novel oral diuretic that promotes water excretion selectively. We have used furosemide as a primary diuretic and added human atrial natriuretic peptide (hANP) if necessary for fluid management postoperatively in living-donor liver transplantation (LDLT) recipients. Recently we introduced tolvaptan and used both tolvaptan and furosemide as primary diuretics. MATERIAL AND METHODS Clinical outcomes were compared between LDLT recipients whose postoperative fluid management was performed before (control group, n=10) and after (tolvaptan group, n=16) introduction of tolvaptan...
January 9, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29310037/a-nationwide-registry-based-cohort-study-of-the-mammaprint-genomic-risk-classifier-in-invasive-breast-cancer
#2
Floris H Groenendijk, Agnes Jager, Fatima Cardoso, Carolien H M van Deurzen
AIM: To evaluate the use of the MammaPrint assay, a 70-gene risk signature for early breast cancers, and to correlate genomic risk stratification with individual clinicopathological parameters and clinical risk as assessed by Adjuvant! Online. METHODS: A Dutch Pathology Registry (PALGA)-based cohort study consisting of 1916 patients for which 1946 MammaPrint assay results were synoptically reported from 2013 to 2016. We could retrospectively assess clinical risk for 1146 tumors (58...
January 5, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29302194/in-vitro-binding-and-receptor-mediated-activity-of-terlipressin-at-vasopressin-receptors-v1-and-v2
#3
Khurram Jamil, Stephen Chris Pappas, Krishna R Devarakonda
Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V1) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys8]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg8]-vasopressin (AVP) at V1 and vasopressin-2 (V2) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V1 and V2 receptors were used in competitive binding assays to measure receptor-binding activity...
2018: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/29297709/utilization-and-budget-impact-of-tolvaptan-in-the-inpatient-setting-among-patients-with-heart-failure-and-hyponatremia
#4
Alpesh N Amin, Jesse D Ortendahl, Amanda L Harmon, Siddhesh A Kamat, Robert A Stellhorn, Sandra L Chase, Shirin V Sundar
OBJECTIVE: Assess characteristics of patients with heart failure (HF) and hyponatremia (HN) using tolvaptan, a selective vasopressin V2-receptor antagonist, for sodium correction, and estimate the budget impact of tolvaptan use in a hospital. METHODS: The Premier Hospital Database was analyzed to assess the utilization of tolvaptan, characteristics of users and non-users, and hospitalization costs among patients with HF and HN. Using these findings, a model was developed to estimate tolvaptan costs in proportion to total medical costs of managing patients with HF and HN, and the budget impact of tolvaptan use...
January 3, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29251736/pge2-ep1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#5
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29242281/fda-benefit-risk-assessment-of-osimertinib-for-the-treatment-of-metastatic-non-small-cell-lung-cancer-harboring-epidermal-growth-factor-receptor-t790m-mutation
#6
Lauretta Odogwu, Luckson Mathieu, Kirsten B Goldberg, Gideon M Blumenthal, Erin Larkins, Mallorie H Fiero, Lisa Rodriguez, Karen Bijwaard, Eunice Y Lee, Reena Philip, Ingrid Fan, Martha Donoghue, Patricia Keegan, Amy McKee, Richard Pazdur
On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive, non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression-free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open-label, randomized trial (AURA3)...
December 14, 2017: Oncologist
https://www.readbyqxmd.com/read/29215154/analysis-of-factors-predicting-the-response-to-tolvaptan-in-patients-with-liver-cirrhosis-and-hepatic-edema
#7
Masanori Atsukawa, Akihito Tsubota, Keizo Kato, Hiroshi Abe, Noritomo Shimada, Toru Asano, Tadashi Ikegami, Mai Koeda, Tomomi Okubo, Taeang Arai, Ai Nakagawa-Iwashita, Yuji Yoshida, Korenobu Hayama, Norio Itokawa, Chisa Kondo, Yoshimichi Chuganji, Yasushi Matsuzaki, Katsuhiko Iwakiri
BACKGROUND AND AIM: This study aimed to clarify the factors predictive of treatment response to tolvaptan (V2-receptor antagonist) for cirrhotic patients with hepatic edema in a real-world setting. METHODS: In this retrospective, multicenter study, tolvaptan was orally administered at a dose of 7.5 mg once a day. Patients with a decrease in body weight of 1.5 kg or greater from baseline were characterized as responders at day 7. RESULTS: Of 229 patients, 210 were subjected to this analysis...
December 7, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29204517/proteomic-analysis-of-aqp11-null-kidney-proximal-tubular-type-polycystic-kidney-disease
#8
Tatsuya Saito, Yasuko Tanaka, Yoshiyuki Morishita, Kenichi Ishibashi
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the mutation of polycystins (PC-1 or PC-2), in which cysts start from the collecting duct to extend to all nephron segments with eventual end stage renal failure. The cyst development is attenuated by a vasopressin V2 receptor antagonist tolvaptan which, however, will not affect proximal tubule cysts devoid of V2 receptor. Aquaporin-11 (AQP11) is expressed selectively in the proximal tubule of the kidney and AQP11-null kidneys have a disruptive PC-1 trafficking to the plasma membrane to develop polycystic kidneys...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29177155/novel-de-novo-avpr2-variant-in-a-patient-with-congenital-nephrogenic-diabetes-insipidus
#9
Shivani Joshi, Per Brandstrom, Niels Gregersen, Søren Rittig, Jane Hvarregaard Christensen
Early diagnosis and treatment of congenital nephrogenic diabetes insipidus (CNDI) are essential due to the risk of intellectual disability caused by repeated episodes of dehydration and rapid rehydration. Timely genetic testing for disease-causing variants in the arginine vasopressin receptor 2 (AVPR2) gene is possible in at-risk newborns with a known family history of X-linked CNDI. In this study, a Swedish male with no family history was diagnosed with CNDI at 6 months of age during an episode of gastroenteritis...
September 2017: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/29146141/the-myth-of-water-and-salt-from-aquaretics-to-tenapanor
#10
REVIEW
Luca Visconti, Valeria Cernaro, Sebastiano Calimeri, Antonio Lacquaniti, Francesca De Gregorio, Carlo Alberto Ricciardi, Viviana Lacava, Domenico Santoro, Michele Buemi
The impact of water intake has been studied in several renal diseases. For example, increasing water intake is useful to prevent primary and secondary nephrolithiasis. In autosomal dominant polycystic kidney disease, arginine vasopressin (AVP) is involved in the progression of the disease, and water intake could play a therapeutic role by inhibiting the synthesis of AVP, but its efficacy is still controversial. Conversely, the use of aquaretics, which are antagonists of AVP V2 receptors, results in the reduction of the increase rate of total kidney volume with a slower decline of glomerular filtration rate...
November 14, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/29145907/-autosomal-dominant-polycystic-kidney-disease-should-patients-young-adult-relatives-be-screened-or-not
#11
B J Kramers, M Storm, R T Gansevoort
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, with a global prevalence of 10 per 10,000. It is characterized by the formation of numerous cysts in both kidneys, and leads to renal function loss; the majority of patients will eventually need renal replacement therapy. It is possible to screen patients' presymptomatic family members from a young age, but this has not historically been recommended as until recently there were no treatment options. This year, the vasopressin V2 receptor antagonist tolvaptan was approved for prescription in ADPKD, to slow the rate of renal function decline...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29105594/tolvaptan-in-later-stage-autosomal-dominant-polycystic-kidney-disease
#12
RANDOMIZED CONTROLLED TRIAL
Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Ron T Gansevoort, Ronald D Perrone, Gary Koch, John Ouyang, Robert D McQuade, Jaime D Blais, Frank S Czerwiec, Olga Sergeyeva
BACKGROUND: In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODS: We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial...
November 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29044966/v1b-vasopressin-receptor-trafficking-and-signaling%C3%A2-role-of-arrestins-g-proteins-and-src-kinase
#13
Sanja Perkovska, Catherine Méjean, Mohammed Akli Ayoub, Juan Li, Floriane Hemery, Maithé Corbani, Nadine Laguette, Maria-Angeles Ventura, Hélène Orcel, Thierry Durroux, Bernard Mouillac, Christiane Mendre
The signaling pathway of G protein-coupled receptors (GPCRs) is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the vasopressin receptor V1b subtype (V1b R) trafficking and its impact on receptor signaling and regulation. For this purpose, we investigated the role of β-arrestins in receptor desensitization, internalization and recycling and attempted to dissect the V1b R-mediated MAP Kinase pathway. Using β-arrestin 1-2 KO-MEF cells, we demonstrated that both β-arrestin 1 and 2 play a fundamental role in internalization and recycling of V1b R with a rapid and transient V1b R-β-arrestin interaction in contrast to a slow and long-lasting β-arrestin recruitment of the V2 vasopressin receptor subtype (V2 R)...
October 16, 2017: Traffic
https://www.readbyqxmd.com/read/29033832/cyclotides-isolated-from-an-ipecac-root-extract-antagonize-the-corticotropin-releasing-factor-type-1-receptor
#14
Mohsen Fahradpour, Peter Keov, Carlotta Tognola, Estela Perez-Santamarina, Peter J McCormick, Alireza Ghassempour, Christian W Gruber
Cyclotides are plant derived, cystine-knot stabilized peptides characterized by their natural abundance, sequence variability and structural plasticity. They are abundantly expressed in Rubiaceae, Psychotrieae in particular. Previously the cyclotide kalata B7 was identified to modulate the human oxytocin and vasopressin G protein-coupled receptors (GPCRs), providing molecular validation of the plants' uterotonic properties and further establishing cyclotides as valuable source for GPCR ligand design. In this study we screened a cyclotide extract derived from the root powder of the South American medicinal plant ipecac (Carapichea ipecacuanha) for its GPCR modulating activity of the corticotropin-releasing factor type 1 receptor (CRF1R)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28978475/elicitation-of-neutralizing-antibodies-targeting-the-v2-apex-of-the-hiv-envelope-trimer-in-a-wild-type-animal-model
#15
James E Voss, Raiees Andrabi, Laura E McCoy, Natalia de Val, Roberta P Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N Khan, Fernando Garces, Laura K Pritchard, Richard T Wyatt, Andrew B Ward, Max Crispin, Ian A Wilson, Dennis R Burton
Recent efforts toward HIV vaccine development include the design of immunogens that can engage B cell receptors with the potential to affinity mature into broadly neutralizing antibodies (bnAbs). V2-apex bnAbs, which bind a protein-glycan region on HIV envelope glycoprotein (Env) trimer, are among the most broad and potent described. We show here that a rare "glycan hole" at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bnAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, we immunized wild-type rabbits with soluble trimers adapted from these Envs...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28973931/systems-level-identification-of-pka-dependent-signaling-in-epithelial-cells
#16
Kiyoshi Isobe, Hyun Jun Jung, Chin-Rang Yang, J'Neka Claxton, Pablo Sandoval, Maurice B Burg, Viswanathan Raghuram, Mark A Knepper
G protein stimulatory α-subunit (Gαs)-coupled heptahelical receptors regulate cell processes largely through activation of protein kinase A (PKA). To identify signaling processes downstream of PKA, we deleted both PKA catalytic subunits using CRISPR-Cas9, followed by a "multiomic" analysis in mouse kidney epithelial cells expressing the Gαs-coupled V2 vasopressin receptor. RNA-seq (sequencing)-based transcriptomics and SILAC (stable isotope labeling of amino acids in cell culture)-based quantitative proteomics revealed a complete loss of expression of the water-channel gene Aqp2 in PKA knockout cells...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28943585/the-outcome-of-cirrhotic-patients-with-ascites-is-improved-by-the-normalization-of-the-serum-sodium-level-by-tolvaptan
#17
Tomomi Kogiso, Mutsuki Kobayashi, Kuniko Yamamoto, Yuichi Ikarashi, Kazuhisa Kodama, Makiko Taniai, Nobuyuki Torii, Etsuko Hashimoto, Katsutoshi Tokushige
Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy. Methods This was a single-center retrospective study...
November 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28939971/pharmacological-chaperones-as-potential-therapeutic-strategies-for-misfolded-mutant-vasopressin-receptors
#18
Bernard Mouillac, Christiane Mendre
Pharmacological chaperones recently opened new possibilities in G protein-coupled receptor drug discovery. Even more interestingly, some unique ligands combine pharmacological chaperoning and biased agonism properties, boosting their therapeutic interest in many human diseases resulting from G protein-coupled receptor mutation and misfolding. These compounds displaying dual characteristics would constitute a perfect treatment for congenital Nephrogenic Diabetes Insipidus, a typical conformational disease. This X-linked genetic pathology is mostly associated with inactivating mutations of the renal arginine-vasopressin V2 receptor leading to misfolding and intracellular retention of the receptor, causing the inability of patients to concentrate their urine in response to the antidiuretic hormone...
September 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28924378/vasopressin-mediates-the-renal-damage-induced-by-limited-fructose-rehydration-in-recurrently-dehydrated-rats
#19
Fernando E García-Arroyo, Edilia Tapia, Mónica G Blas-Marron, Guillermo Gonzaga, Octaviano Silverio, Magdalena Cristóbal, Horacio Osorio, Abraham S Arellano-Buendía, Cecilia Zazueta, Omar Emiliano Aparicio-Trejo, Juan G Reyes-García, José Pedraza-Chaverri, Virgilia Soto, Carlos Roncal-Jiménez, Richard J Johnson, Laura G Sánchez-Lozada
Recurrent dehydration and heat stress cause chronic kidney damage in experimental animals. The injury is exacerbated by rehydration with fructose-containing beverages. Fructose may amplify dehydration-induced injury by directly stimulating vasopressin release and also by acting as a substrate for the aldose reductase-fructokinase pathway, as both of these systems are active during dehydration. The role of vasopressin in heat stress associated injury has not to date been explored. Here we show that the amplification of renal damage mediated by fructose in thermal dehydration is mediated by vasopressin...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28915250/multi-layered-mutation-in-hedgehog-related-genes-in-gorlin-syndrome-may-affect-the-phenotype
#20
Shoko Onodera, Akiko Saito, Daigo Hasegawa, Nana Morita, Katsuhito Watanabe, Takeshi Nomura, Takahiko Shibahara, Shinsuke Ohba, Akira Yamaguchi, Toshifumi Azuma
Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to a variety of disorders that are attributed largely to heterozygous germline patched1 (PTCH1) mutations. PTCH1 is a hedgehog (Hh) receptor as well as a repressor, mutation of which leads to constitutive activation of Hh pathway. Hh pathway encompasses a wide variety of cellular signaling cascades, which involve several molecules; however, no associated genotype-phenotype correlations have been reported...
2017: PloS One
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