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M Barletta, S M Ostenkamp, A C Taylor, J Quandt, B D X Lascelles, K M Messenger
Buprenorphine is a partial μ agonist opioid used for analgesia in dogs. An extended-release formulation (ER-buprenorphine) has been shown to provide effective analgesia for 72 hr in rats and mice. Six healthy mongrel dogs were enrolled in a randomized, blinded crossover design to describe and compare the pharmacokinetics and pharmacodynamics of ER-buprenorphine administered subcutaneous at 0.2 mg/kg (ER-B) and commercially available buprenorphine for injection intravenously at 0.02 mg/kg (IV-B). After drug administration, serial blood samples were collected to measure plasma buprenorphine concentrations using liquid chromatography/mass spectrometry detection...
March 9, 2018: Journal of Veterinary Pharmacology and Therapeutics
Diming Xu, Maxim Avdeev, Peter D Battle, D H Ryan
Polycrystalline samples of Ln2 CoGe4 O12 (Ln = Gd, Tb, Dy, Ho or Er) and LnBCoGe4 O12 (B = Sc or Lu) have been prepared and characterised by a combination of magnetometry,155 Gd Mössbauer spectroscopy and, in the case of Tb2 CoGe4 O12 and TbScCoGe4 O12 , neutron diffraction. The holmium- and erbium-containing compositions remain paramagnetic down to 2 K, those containing dysprosium behave as spin glasses and the terbium and gadolinium-containing compounds show long-range magnetic order with transition temperatures below 4 K in all cases...
November 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Ibrahim M Abbass, Eleanor O Caplan, Daniel B Ng, Rita Kristy, Carol R Schermer, Pamela Bradt, Jenna M Collins, Wai Man Maria Chan, Brandon T Suehs
BACKGROUND: The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs. OBJECTIVE: To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients...
January 2017: Journal of Managed Care & Specialty Pharmacy
A Salazar, M Dueñas, F Fernandez-Palacin, I Failde
BACKGROUND: The aim is to know the factors related to the evolution of Health Related Quality of Life (HRQL) in Coronary Patients (CP) from a longitudinal perspective using an appropriate method that handles missing data adequately when the mechanism of missingness is uncertain. METHODS: Prospective study with repeated measures at baseline, 3 and 6months. 250 patients with acute myocardial infarction or unstable angina were studied. Sociodemographic and clinical data were collected at baseline...
November 15, 2016: International Journal of Cardiology
Steven Christensen, Ed Paluch, Shyamalie Jayawardena, Stephen Daniels, Suzanne Meeves
Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0...
May 2017: Clinical Pharmacology in Drug Development
Rohit B Sharma, Amy C O'Donnell, Rachel E Stamateris, Binh Ha, Karen M McCloskey, Paul R Reynolds, Peter Arvan, Laura C Alonso
Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic β cell number expands in response to an increase in insulin demand. Lineage tracing shows that new β cells are generated from proliferation of mature, differentiated β cells; however, the mechanism by which these mature cells sense systemic insulin demand and initiate a proliferative response remains unknown...
October 1, 2015: Journal of Clinical Investigation
Urška B Ogrinc, Sabina Senčar, Helena Lenasi
BACKGROUND AND OBJECTIVE: Urinary incontinence (UI) is a common disorder that affects women of various ages and impacts all aspects of life. Our aim was to evaluate the non-invasive erbium:yttrium-aluminum-garnet (Er:YAG) laser that exploits its thermal effect and has been used in reconstructive and rejuvenation surgery as a potential treatment strategy for stress UI (SUI) and mixed UI (MUI). STUDY DESIGN/MATERIALS AND METHODS: We included 175 women (aged 49.7 ± 10 years) with newly diagnosed SUI (66% of women) and MUI (34%), respectively...
November 2015: Lasers in Surgery and Medicine
Bruno M Simões, Ciara S O'Brien, Rachel Eyre, Andreia Silva, Ling Yu, Aida Sarmiento-Castro, Denis G Alférez, Kath Spence, Angélica Santiago-Gómez, Francesca Chemi, Ahmet Acar, Ashu Gandhi, Anthony Howell, Keith Brennan, Lisa Rydén, Stefania Catalano, Sebastiano Andó, Julia Gee, Ahmet Ucar, Andrew H Sims, Elisabetta Marangoni, Gillian Farnie, Göran Landberg, Sacha J Howell, Robert B Clarke
Breast cancers (BCs) typically express estrogen receptors (ERs) but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC) activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX) tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen and that a NOTCH4/HES/HEY gene signature predicts for a poor response/prognosis in 2 ER+ patient cohorts...
September 29, 2015: Cell Reports
Jianguo Zhao, Weijie Xu, Jason W Ross, Eric M Walters, Stephen P Butler, Jeff J Whyte, Lindsey Kelso, Mostafa Fatemi, Nicholas C Vanderslice, Keith Giroux, Lee D Spate, Melissa S Samuel, Cliff N Murphy, Kevin D Wells, Nick C Masiello, Randall S Prather, William H Velander
Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to <20% of the world's population. We used transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio...
September 21, 2015: Scientific Reports
Ju-Wen Zhang, Xiao-Min Kan, Bin-Qiu Liu, Guo-Cheng Liu, Ai-Xiang Tian, Xiu-Li Wang
Three series of copper-lanthanide/lanthanide coordination polymers (CPs) Ln(III) Cu(II) Cu(I) (bct)3 (H2 O)2 [Ln=La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6), Gd (7), Tb (8), Dy (9), Er (10), Yb (11), and Lu (12), H2 bct=2,5-bis(carboxymethylmercapto)-1,3,4-thiadiazole acid], Ln(III) Cu(I) (bct)2 [Ln=Ce (2 a), Pr (3 a), Nd (4 a), Sm (5 a), Eu (6 a), Gd (7 a), Tb (8 a), Dy (9 a), Er (10 a), Yb (11 a), and Lu (12 a)], and Ln(III) 2 (bct)3 (H2 O)5 [Ln=La (1 b), Ce (2 b), Pr (3 b), Nd (4 b), Sm (5 b), Eu (6 b), Gd (7 b), Tb (8 b), and Dy (9 b)] have been successfully constructed under hydrothermal conditions by modulating the reaction time...
November 2, 2015: Chemistry: a European Journal
B Ruggiero, B L Padwa, K M Christoph, S Zhou, J Glowacki
Vitamin D is crucial for mineral homeostasis and contributes to bone metabolism by inducing osteoblast differentiation of marrow stromal cells (MSCs). We recently reported that MSCs from adults demonstrate 1α-hydroxylase activity in vitro and express vitamin D-related genes; this raises a possible autocrine/paracrine role for D activation in pre-osteoblasts. In this studies, we tested the hypotheses that pediatric MSCs have 1α-hydroxylase activity and express vitamin D-related genes. With IRB approval, we isolated MSCs from discarded excess iliac marrow graft from 6 male and 6 female subjects (age 8-12 years) undergoing alveolar cleft repair...
November 2016: Journal of Steroid Biochemistry and Molecular Biology
Kelly A Hirko, Wendy Y Chen, Walter C Willett, Bernard A Rosner, Susan E Hankinson, Andrew H Beck, Rulla M Tamimi, A Heather Eliassen
Alcohol consumption is a consistent risk factor for breast cancer, although it is unclear whether the association varies by breast cancer molecular subtype. We investigated associations between cumulative average alcohol intake and risk of breast cancer by molecular subtype among 105,972 women in the prospective Nurses' Health Study cohort, followed from 1980 to 2006. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6, and epidermal growth factor status from immunostained tumor microarrays in combination with histologic grade...
March 1, 2016: International Journal of Cancer. Journal International du Cancer
Hanan S Elsarraj, Yan Hong, Kelli E Valdez, Whitney Michaels, Marcus Hook, William P Smith, Jeremy Chien, Jason I Herschkowitz, Melissa A Troester, Moriah Beck, Marc Inciardi, Jason Gatewood, Lisa May, Therese Cusick, Marilee McGinness, Lawrence Ricci, Fang Fan, Ossama Tawfik, Jeffrey R Marks, Jennifer R Knapp, Hung-Wen Yeh, Patricia Thomas, D R Carrasco, Timothy A Fields, Andrew K Godwin, Fariba Behbod
INTRODUCTION: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription...
September 17, 2015: Breast Cancer Research: BCR
Kimberley J Anderson, Aaron P Russell, Victoria C Foletta
The function of the stress-responsive N-myc downstream-regulated gene 2 (NDRG2) in the control of myoblast growth, and the amino acids contributing to its function, are not well characterized. Here, we investigated the effect of increased NDRG2 levels on the proliferation, differentiation and apoptosis in skeletal muscle cells under basal and stress conditions. NDRG2 overexpression increased C2C12 myoblast proliferation and the expression of positive cell cycle regulators, cdk2, cyclin B and cyclin D, and phosphorylation of Rb, while the serine/threonine-deficient NDRG2, 3A-NDRG2, had less effect...
2015: FEBS Open Bio
B E Mouthaan, M A van 't Klooster, D Keizer, G J Hebbink, F S S Leijten, C H Ferrier, M J A M van Putten, M Zijlmans, G J M Huiskamp
OBJECTIVE: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. METHODS: We used data from 12 refractory epilepsy patients...
February 2016: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Ilaria Cancarini, Vittorio Krogh, Claudia Agnoli, Sara Grioni, Giuseppe Matullo, Valeria Pala, Samuele Pedraglio, Paolo Contiero, Cristina Riva, Paola Muti, Sabina Sieri
BACKGROUND: Vitamins involved in one-carbon metabolism are hypothesized to influence breast cancer (BC) risk. However, epidemiologic studies that examined associations between B vitamin intake and BC risk have provided inconsistent results. We prospectively examined, in the Italian ORDET cohort, whether B vitamin consumption was associated with risk of BC and BC subtypes. METHODS: After a mean follow-up of 16.5 years, 391 BCs were diagnosed among 10,786 cohort women...
2015: PloS One
N Wagner, B Relja, J Menke, M Lehnert, I Marzi
INTRODUCTION: The influence of alcohol consumption on inflammatory state and outcome in patients suffering from traumatic brain injury (TBI) remains controversial. We analyzed effects of positive blood alcohol concentration (BAC) on inflammatory changes, in-hospital complications, and mortality in TBI-patients. METHODS: Patients with an Injury Severity Score (ISS)≥16 and Abbreviated Injury Scale of head (AIS-head)≥3 were enrolled upon arrival in the emergency room...
October 2015: Shock
Ali Pedram, Mahnaz Razandi, Bruce Blumberg, Ellis Robert Levin
Estrogen and estrogen receptor (ER)-α suppress visceral fat development through actions in several organs via unclear mechanisms that we sought to identify. Using mice that express only nuclear ER-α [nuclear-only ER-α (NOER) mice] or plasma membrane ER-α [membrane-only ER-α (MOER) mice], we found that 10-wk-old mice that lacked either receptor pool showed extensive abdominal visceral fat deposition and weight gain compared with wild-type (WT) mice. Differentiation of cultured bone marrow stem cells (BMSCs) into the adipocyte lineage was suppressed by 17-β-estradiol (E2) in WT female mice but not in NOER or MOER mice...
January 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Andreas Kehlberger, Ulrike Ritzmann, Denise Hinzke, Er-Jia Guo, Joel Cramer, Gerhard Jakob, Mehmet C Onbasli, Dong Hun Kim, Caroline A Ross, Matthias B Jungfleisch, Burkard Hillebrands, Ulrich Nowak, Mathias Kläui
We investigate the origin of the spin Seebeck effect in yttrium iron garnet (YIG) samples for film thicknesses from 20 nm to 50  μm at room temperature and 50 K. Our results reveal a characteristic increase of the longitudinal spin Seebeck effect amplitude with the thickness of the insulating ferrimagnetic YIG, which levels off at a critical thickness that increases with decreasing temperature. The observed behavior cannot be explained as an interface effect or by variations of the material parameters...
August 28, 2015: Physical Review Letters
Alexander B Lang, Arun T John Peter, Peter Walter, Benoît Kornmann
The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex tethers the endoplasmic reticulum and the mitochondria. It is thought to facilitate interorganelle lipid exchange and influence mitochondrial dynamics and mitochondrial DNA maintenance. Despite this important role, ERMES is not found in metazoans. Here, we identified single amino acid substitutions in Vps13 (vacuolar protein sorting 13), a large universally conserved eukaryotic protein, which suppress all measured phenotypic consequences of ERMES deficiency...
September 14, 2015: Journal of Cell Biology
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