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https://www.readbyqxmd.com/read/29146141/the-myth-of-water-and-salt-from-aquaretics-to-tenapanor
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
Tomomi Kogiso, Mutsuki Kobayashi, Kuniko Yamamoto, Yuichi Ikarashi, Kazuhisa Kodama, Makiko Taniai, Nobuyuki Torii, Etsuko Hashimoto, Katsutoshi Tokushige
Objectives 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...
September 25, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28939971/pharmacological-chaperones-as-potential-therapeutic-strategies-for-misfolded-mutant-vasopressin-receptors
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28905441/the-vasopressin-system-new-insights-for-patients-with-kidney-diseases-epidemiological-evidence-and-therapeutic-perspectives
#12
REVIEW
W F Clark, O Devuyst, R Roussel
People with chronic kidney disease (CKD) are at risk of severe outcomes, such as end-stage renal disease or cardiovascular disease, and CKD is a globally increasing health burden with a high personal and economic cost. Despite major progresses in prevention and therapeutics in last decades, research is still needed to reverse this epidemic trend. The regulation of water balance and the state of activation of the vasopressin system have emerged as factors tightly associated with kidney health, in the general population but also in specific conditions; among them, various stages of CKD, diabetes and autosomal dominant polycystic kidney disease (ADPKD)...
October 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28883824/natural-killer-nk-cell-education-differentially-influences-hiv-antibody-dependent-nk-cell-activation-and-antibody-dependent-cellular-cytotoxicity
#13
REVIEW
Nicole F Bernard, Zahra Kiani, Alexandra Tremblay-McLean, Sanket A Kant, Christopher E Leeks, Franck P Dupuy
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28854286/therapeutic-time-window-for-conivaptan-treatment-against-stroke-evoked-brain-edema-and-blood-brain-barrier-disruption-in-mice
#14
Emil Zeynalov, Susan M Jones, J Paul Elliott
BACKGROUND: Ischemic stroke is often complicated by brain edema, disruption of blood-brain barrier (BBB), and uncontrolled release of arginine-vasopressin (AVP). Conivaptan, a V1a and V2 receptor antagonist, reduces brain edema and minimizes damage to the blood-brain barrier after stroke. Most stroke patients do not receive treatment immediately after the onset of brain ischemia. Delays in therapy initiation may worsen stroke outcomes. Therefore, we designed a translational study to explore the therapeutic time window for conivaptan administration...
2017: PloS One
https://www.readbyqxmd.com/read/28815407/efficacy-and-safety-of-the-early-use-of-v2-receptor-antagonists-in-elderly-patients-with-decompensated-heart-failure
#15
Ryuichi Matsukawa, Toru Kubota, Masanori Okabe, Yusuke Yamamoto, Hiroshi Meno
We recently reported that the early initiation of tolvaptan in congestive heart failure shortened the hospital stay and reduced the rate of in-hospital death. However, whether or not these results apply to elderly patients with congestive heart failure is unclear. We performed a sub-analysis of our previous study. Among the 102 patients in that study, we retrospectively analyzed the elderly patients >75 years of age treated with tolvaptan. First, we analyzed the efficacy of early tolvaptan use in these patients...
August 16, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28767678/pharmacoperone-rescue-of-vasopressin-2-receptor-mutants-reveals-unexpected-constitutive-activity-and-coupling-bias
#16
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
#17
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
#18
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
#19
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
#20
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
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