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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28166521/rationale-and-design-of-a-clinical-trial-investigating-tolvaptan-safety-and-efficacy-in-autosomal-dominant-polycystic-kidney-disease
#4
Vicente E Torres, Olivier Devuyst, Arlene B Chapman, Ron T Gansevoort, Ronald D Perrone, John Ouyang, Jaime D Blais, Frank S Czerwiec, Olga Sergeyeva
BACKGROUND: In TEMPO 3:4, the vasopressin V2-receptor antagonist tolvaptan slowed kidney growth and function decline in autosomal dominant polycystic kidney disease (ADPKD) patients with relatively preserved kidney function. METHODS: Prospective, phase 3b, multi-center, randomized-withdrawal, placebo-controlled, double-blind trial of tolvaptan in ADPKD patients with late stage 2 to early stage 4 chronic kidney disease (CKD). The primary endpoint was estimated glomerular filtration rate (eGFR) change from pre-treatment baseline to post-treatment follow-up...
February 7, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28149654/management-challenges-in-a-child-with-chronic-hyponatremia-use-of-v2-receptor-antagonist
#5
Sowmya Krishnan, Swapna Deshpande, Ashwini Mallappa, Gunda Divya, Pascale Lane, Anu Vishwanath, Rene Y McNall-Knapp
Chronic hyponatremia is very rare in children and is often seen in the setting of congestive heart failure or liver failure in adults. Here, we report an 8-year-old child with hypothalamic glioma who presented with severe hyponatremia. Initial management consisted of fluid restriction. This was very difficult for the child to follow and the child developed bizarre drinking habits requiring intervention from child psychiatry. So therapy was initiated with low dose V2 receptor antagonist under close inpatient monitoring...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28134709/nephrogenic-diabetes-insipidus
#6
D Bockenhauer, Daniel G Bichet
PURPOSE OF REVIEW: In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite elevated concentrations of the antidiuretic hormone arginine-vasopressin. In congenital NDI, polyuria and polydipsia are present from birth and should be immediately recognized to avoid severe episodes of dehydration. Unfortunately, NDI is still often recognized late after a 'diagnostic odyssey' involving false leads and dangerous treatments.Once diagnosed, appropriate treatment can be started...
January 27, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28129709/profile-of-the-roche-cobas%C3%A2-egfr-mutation-test-v2-for-non-small-cell-lung-cancer
#7
Umberto Malapelle, Rafael Sirera, Eloísa Jantus-Lewintre, Pablo Reclusa, Silvia Calabuig-Fariñas, Ana Blasco, Pasquale Pisapia, Christian Rolfo, Carlos Camps
The discovery of driver mutations in non-small cell lung cancer (NSCLC) has led to the development of genome-based personalized medicine. Fifteen to 20% of adenocarcinomas harbor an epidermal growth factor receptor (EGFR) activating mutation associated with responses to EGFR tyrosine kinase inhibitors (TKIs). Individual laboratories' expertise and the availability of appropriate equipment are valuable assets in predictive molecular pathology, although the choice of methods should be determined by the nature of the samples to be tested and whether the detection of only well-characterized EGFR mutations or rather, of all detectable mutations, is required...
March 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28117000/vasopressin-and-related-peptides-potential-value-in-diagnosis-prognosis-and-treatment-of-clinical-disorders
#8
Ewa Szczepanska-Sadowska, Tymoteusz Zera, Piotr Sosnowski, Agnieszka Cudnoch-Jedrzejewska, Anna Puszko, Aleksandra Misicka
Vasopressin (AVP) and its receptors play a pivotal role in maintaining body homeostasis under physiological and pathophysiological conditions. As a consequence, the vasopressin system has emerged as an important target for both diagnostic and therapeutic applications in a number of medical conditions. Stoichiometric generation of AVP with copeptin, which is relatively accessible in the blood for measurements, makes copeptin a valuable surrogate of AVP. In this review, we present the regulation of release of AVP and activation of V1a, V1b, and V2 vasopressin receptors under physiological and pathological conditions...
January 19, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28116522/molecular-characterization-of-cd44-cd24-ck-cd45-cells-in-benign-and-malignant-breast-lesions
#9
Arnaud Da Cruz Paula, Catarina Leitão, Oriana Marques, Ana Margarida Rosa, Ana Helena Santos, Alexandra Rêma, Maria de Fátima Faria, Ana Rocha, José Luís Costa, Margarida Lima, Carlos Lopes
Breast cancer epithelial cells with the CD44(+)/CD24(-/low) phenotype possess tumor-initiating cells and epithelial-mesenchymal transition (EMT) capacity. Massive parallel sequencing can be an interesting approach to deepen the molecular characterization of these cells. We characterized CD44(+)/CD24(-)/cytokeratin(Ck)(+)/CD45(-) cells isolated through flow cytometry from 43 biopsy and 6 mastectomy samples harboring different benign and malignant breast lesions. The Ion Torrent Ampliseq Cancer Hotspot panel v2 (CHPv2) was used for the identification of somatic mutations in the DNA extracted from isolated CD44(+)/CD24(-)/Ck(+)/CD45(-) cells...
January 23, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28111410/who-needs-longer-tolvaptan-treatment
#10
Koichiro Kinugawa, Takayuki Inomata, Naoki Sato, Moriyoshi Yasuda, Toshiyuki Shimakawa, Kosuke Bando, Yasuhiko Fukuta
The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been approved for heart failure patients with volume overload in Japan. In this study (SMILE study), we investigated patient characteristics and effectiveness in both a 14 days and shorter treated group (14DS) and 15 days and longer treated group (15DL). The results showed that the patients in the 15DL group had low cardiac output with intensive diuretic administration (ie, diuretic resistance). The congestive symptoms were greatly improved within 14 days of treatment in both the 14DS and 15DL groups...
February 7, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28110691/is-insulin-growth-factor-1-the-future-for-treating-autism-spectrum-disorder-and-or-schizophrenia
#11
Rami Bou Khalil
To date, no curative psychopharmacologic treatment exists for the core symptoms of autism spectrum disorder (ASD) as well as for schizophrenia. Bumatenide is a specific antagonist of the first isoform of the Na-K-Cl cotransporter (NKCC1). It is usually used as a diuretic but may also promote a decrease in intraneuronal chloride ion concentration leading to hyperpolarization in neuronal membrane and subsequent decrease in neuronal hyperexcitability. This physiologic effect has been considered to be behind the relative efficacy of bumetanide in improving symptoms of ASD and, to a lesser extent, schizophrenia...
February 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28108651/roflumilast-and-aquaporin-2-regulation-in-rat-renal-inner-medullary-collecting-duct
#12
Ezigbobiara N Umejiego, Yanhua Wang, Mark A Knepper, Chung-Lin Chou
Roflumilast is a cyclic nucleotide phosphodiesterase inhibitor that is FDA-approved for treatment of chronic obstructive pulmonary disease. With a view toward possible use for treatment of patients with X-linked nephrogenic diabetes insipidus (NDI) due to hemizygous mutations in the V2 vasopressin receptor, this study sought to determine the effect of roflumilast on aquaporin-2 (AQP2) phosphorylation, AQP2 trafficking, and water permeability in the rat inner medullary collecting duct (IMCD). In the presence of the vasopressin analog dDAVP (0...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28065737/osmoregulatory-role-of-vasotocinergic-and-isotocinergic-systems-in-the-gilthead-sea-bream-sparus-aurata-l
#13
Juan Miguel Mancera, Gonzalo Martínez-Rodríguez, Arleta Krystyna Skrzynska, Juan Antonio Martos-Sitcha
Gilthead sea bream, Sparus aurata L., is an important fish species for the Mediterranean aquaculture and is considered a good model for studying the osmoregulatory process, due to its capacity to cope with great changes in environmental salinity (5-60‰). Our group studied the osmoregulatory role of different endocrine systems in this species, focusing on the vasotocinergic and isotocinergic systems over several years. For this purpose, the cDNAs coding for pro-vasotocin (pro-vt), pro-isotocin (pro-it), two arginine vasotocin (AVT) receptors (avtr v1a2- and v2-types) and one IT receptor (itr) were cloned...
January 5, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28055379/relationship-between-runx1-and-axin1-in-er-negative-versus-er-positive-breast-cancer
#14
Nyam-Osor Chimge, Sara Ahmed-Alnassar, Baruch Frenkel
RUNX1 plays opposing roles in breast cancer: a tumor suppressor in estrogen receptor-positive (ER(+)) disease and an oncogenic role in ER-negative (ER(-)) tumors. Potentially mediating the former, we have recently reported that RUNX1 prevents estrogen-driven suppression of the mRNA encoding the tumor suppressor AXIN1. Accordingly, AXIN1 protein expression was diminished upon RUNX1 silencing in ER(+) breast cancer cells and was positively correlated with AXIN1 protein expression across tumors with high levels of ER...
February 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28051801/utility-and-safety-of-tolvaptan-in-cirrhotic-patients-with-hyponatremia-a-prospective-cohort-study
#15
Ji-Dong Jia, Wen Xie, Hui-Guo Ding, Hua Mao, Hui Guo, Yonggang Li, Xiaojin Wang, Jie-Fei Wang, Wei Lu, Cheng-Zhong Li, Yimin Mao, Gui-Qiang Wang, Yue-Qiu Gao, Bangmao Wang, Qin Zhang, Yan Ge, Vincent Wai-Sun Wong
: Introduction and aim. Hyponatremia is common in patients with decompensated cirrhosis and is associated with increased mortality. Tolvaptan, a vasopressor V2 receptor antagonist, can increase free water excretion, but its efficacy and safety in cirrhotic patients remain unclear. MATERIAL AND METHODS: We studied the usage and safety of tolvaptan in cirrhotic patients in a real-life, non-randomized, multicenter prospective cohort study. Forty-nine cirrhotic patients with hyponatremia were treated with tolvaptan 15 mg daily, and 48 patients not treated with tolvaptan in the same period served as controls...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28025412/effects-of-17%C3%AE-estradiol-on-leptin-signaling-in-anterior-pituitary-of-ovariectomized-rats
#16
Chunhua Yin, Lumei Kang, Cong Lai, Jing Zhou, Bin Shi, Lei Zhang, Hongping Chen
Leptin is secreted predominantly by adipocytes and exerts its role mainly by interaction with the long form of leptin receptor (LEPR_V2). It has been identified that LEPR_V2 is widely distributed in various tissues, including the anterior pituitary. Cross-talk between leptin and estrogens has been indentified. Estrogen is known to modulate the tissue-specific expression of LEPR_V2 and leptin in ovariectomized (OVX) rats, a model of postmenopausal condition. Our previous data showed that 17β-estradiol (E2) up-regulated the expression of LEPR_V2 protein and mRNA in rat dorsal root ganglion (DRG) in an estrogen receptor alpha (ERα)-dependent manner...
December 26, 2016: Experimental Animals
https://www.readbyqxmd.com/read/28008190/central-diabetes-insipidus
#17
REVIEW
Hiroshi Arima, Yoshinori Azuma, Yoshiaki Morishita, Daisuke Hagiwara
Central diabetes insipidus (CDI), characterized by polyuria and polydipsia, is caused by deficiency of arginine vasopressin (AVP), an antidiuretic hormone which acts on V2 receptors in kidney to promote reabsorption of free water. CDI is classified into three subtypes; idiopathic, secondary and familial. A previous study suggests that infundibulo-neurohypophysitis might be an underlying cause of idiopathic CDI. Among secondary CDI, the tumors in the central nervous system such as craniopharyngioma and germ cell tumors are the most frequent causes...
December 2016: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/28003190/the-effects-of-exogenous-desmopressin-on-a-model-of-heat-stress-nephropathy-in-mice
#18
Carlos A Roncal-Jimenez, Tamara Milagres, Ana Andres-Hernando, Masanari Kuwabara, Thomas Jensen, Zhilin Song, Petter Bjornstad, Gabriela E Garcia, Yuka Sato, Laura-Gabriela Sanchez-Lozada, Miguel A Lanaspa, Richard J Johnson
BACKGROUND: Recurrent heat stress and dehydration have recently been shown experimentally to cause chronic kidney disease (CKD). One potential mediator may be vasopressin, acting via the type 2 vasopressin receptor (V2 receptor). We tested the hypothesis that desmopressin accelerates CKD in mice subjected to heat stress and recurrent dehydration. METHODS: Recurrent exposure to heat with limited water availability was performed in male mice over a 5 week period, with one group receiving desmopressin twice daily and the other group received vehicle...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27943449/investigation-and-comparison-of-the-binding-between-tolvaptan-and-pepsin-and-trypsin-multi-spectroscopic-approaches-and-molecular-docking
#19
Xiangling Ma, Jiawei He, Yanmei Huang, Ying Xiao, Qing Wang, Hui Li
Tolvaptan (TF), a selective arginine vasopressin V2 receptor antagonist, was approved by the Food and Drug Administration in 2009. This study mainly investigated the differences between the binding of TF with pepsin and trypsin by using a series of spectroscopy and molecular modeling methods. Thermodynamic parameters and molecular docking results suggested that the binding of TF to pepsin and trypsin were both spontaneous but driven by different forces. For pepsin, the binding was driven by hydrogen bonds and van der Waals forces; but for trypsin, it was driven by electrostatic forces and hydrophobic forces...
December 12, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27932956/hypothalamic-vasopressinergic-projections-innervate-central-amygdala-gabaergic-neurons-implications-for-anxiety-and-stress-coping
#20
Vito S Hernández, Oscar R Hernández, Miguel Perez de la Mora, María J Gómora, Kjell Fuxe, Lee E Eiden, Limei Zhang
The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA)...
2016: Frontiers in Neural Circuits
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