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https://www.readbyqxmd.com/read/28650232/pharmacokinetics-of-cyclophosphamide-and-4-hydroxycyclophosphamide-in-cats-after-oral-intravenous-and-intraperitoneal-administration-of-cyclophosphamide
#1
Katherine A Stroda, Jacqueline D Murphy, Ryan J Hansen, Lisa Brownlee, Elizabeth A Atencio, Daniel L Gustafson, Susan E Lana
OBJECTIVE To characterize pharmacokinetics of cyclophosphamide and 4-hydoxycyclophosphamide (4-OHCP) in the plasma of healthy cats after oral, IV, and IP administration of cyclophosphamide. ANIMALS 6 healthy adult cats. PROCEDURES Cats were randomly assigned to receive cyclophosphamide (200 mg/m(2)) via each of 3 routes of administration (oral, IV, and IP); there was a 30-day washout period between successive treatments. Plasma samples were obtained at various time points for up to 8 hours after administration...
July 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28649790/safety-of-a-benazepril-and-pimobendan-combination-tablet-in-adult-healthy-dogs
#2
E A Kuntz, G Strehlau, J M Giraudel, J N King
The objective of the study was to investigate the safety of a combination tablet of benazepril and pimobendan, Fortekor PLUS(®) , in a randomized, blinded, parallel-group design study in healthy adult beagle dogs. The test article, Fortekor PLUS(®) tablets, was administered orally twice daily for 6 months at one, two, and four times the highest recommended dosage of 0.5 mg/kg benazepril hydrochloride/0.25 mg/kg pimobendan (four males and four females per group). An additional control group was sham-dosed...
June 26, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28649557/dusquetide-reduction-in-oral-mucositis-associated-with-enduring-ancillary-benefits-in-tumor-resolution-and-decreased-mortality-in-head-and-neck-cancer-patients
#3
Mahesh Kudrimoti, Amarinthia Curtis, Samar Azawi, Francis Worden, Sanford Katz, Douglas Adkins, Marcelo Bonomi, Zack Scott, Jenna Elder, Stephen T Sonis, Richard Straube, Oreola Donini
Innate immunity is a key component in the pathogenesis of oral mucositis, a universal toxicity of chemoradiation therapy (CRT). Dusquetide, a novel Innate Defense Regulator, has demonstrated both nonclinical and clinical efficacy in ameliorating severe oral mucositis (SOM). Long term follow-up studies from the Phase 2 clinical study evaluating dusquetide as a treatment for SOM in head and neck cancer (HNC) patients receiving CRT have now been completed. Extended analysis indicates that dusquetide therapy was well-tolerated and did not contribute to increased infection, tumor growth or mortality...
September 2017: Biotechnology Reports
https://www.readbyqxmd.com/read/28649379/is-transoral-robotic-surgery-a-safe-and-effective-multilevel-treatment-for-obstructive-sleep-apnoea-in-obese-patients-following-failure-of-conventional-treatment-s
#4
George Garas, Anthousa Kythreotou, Christos Georgalas, Asit Arora, Bhik Kotecha, Floyd C Holsinger, David G Grant, Neil Tolley
A best evidence topic was written according to a structured protocol. The question addressed was whether TransOral Robotic Surgery (TORS) is a safe and effective multilevel treatment for Obstructive Sleep Apnoea (OSA) in obese patients following failure of conventional treatment(s). A total of 39 papers were identified using the reported searches of which 5 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated...
July 2017: Annals of Medicine and Surgery
https://www.readbyqxmd.com/read/28649294/randomised-controlled-trial-of-a-baked-egg-intervention-in-young-children-allergic-to-raw-egg-but-not-baked-egg
#5
Merryn Netting, Michael Gold, Patrick Quinn, Adaweyah El-Merhibi, Irmeli Penttila, Maria Makrides
BACKGROUND: Consumption of baked egg by raw egg allergic children is associated with immune changes suggesting development of tolerance. However, causation has not been tested using a double blind randomized controlled trial (RCT). We aimed to compare clinical and immunological outcomes after baked egg (BE) consumption in young BE tolerant egg allergic children. METHODS: In a double blind RCT, BE tolerant egg allergic children consumed 10 g BE (1.3 g protein) 2 to 3 times per week for 6 months (n = 21 intervention group) or similar egg free baked goods (n = 22 control group) while maintaining an otherwise egg free diet...
2017: World Allergy Organization Journal
https://www.readbyqxmd.com/read/28648803/sorafenib-in-combination-with-transarterial-chemoembolisation-in-patients-with-unresectable-hepatocellular-carcinoma-tace-2-a-randomised-placebo-controlled-double-blind-phase-3-trial
#6
Tim Meyer, Richard Fox, Yuk Ting Ma, Paul J Ross, Martin W James, Richard Sturgess, Clive Stubbs, Deborah D Stocken, Lucy Wall, Anthony Watkinson, Nigel Hacking, T R Jeffry Evans, Peter Collins, Richard A Hubner, David Cunningham, John Neil Primrose, Philip J Johnson, Daniel H Palmer
BACKGROUND: Transarterial chemoembolisation (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma, while the multikinase inhibitor sorafenib improves survival in patients with advanced disease. We aimed to determine whether TACE with sorafenib improves progression-free survival versus TACE with placebo. METHODS: We did a multicentre, randomised, placebo-controlled, phase 3 trial (TACE 2) in 20 hospitals in the UK for patients with unresectable, liver-confined hepatocellular carcinoma...
June 22, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28648493/the-use-of-fructosamine-in-cystic-fibrosis-related-diabetes-cfrd-screening
#7
Grace Y Lam, Michelle Doll-Shankaruk, Jan Dayton, Karina Rodriguez-Capote, Trefor N Higgins, Dylan Thomas, Kimberley Mulchey, Maeve P Smith, Neil E Brown, Winnie M Leung, Mathew P Estey
OBJECTIVE: To determine whether serum fructosamine correlates with glycemic control and clinical outcomes in patients being screened for cystic fibrosis-related diabetes (CFRD). METHODS: Fructosamine and percent predicted forced expiratory volume in 1s (FEV1) were measured in patients undergoing a 2h oral glucose tolerance test (OGTT) for CFRD screening. Fractional serum fructosamine (FSF) was calculated as fructosamine/total protein. RESULTS: FSF exhibited a positive correlation with 2h OGTT results (r(2)=0...
June 22, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28648463/optimization-of-a-novel-series-of-potent-and-orally-bioavailable-gpr119-agonists
#8
Tomoaki Koshizawa, Toshiharu Morimoto, Gen Watanabe, Toshiaki Watanabe, Nao Yamasaki, Yoshikazu Sawada, Tomoaki Fukuda, Ayumu Okuda, Kimiyuki Shibuya, Tadaaki Ohgiya
We describe the discovery and optimization of a novel series of furo[3,2-d]pyrimidines as G protein-coupled receptor 119 agonists. Agonistic activity of 4 (EC50=129nM) was improved by replacing the intramolecular hydrogen bond between the fluorine atom and the aniline hydrogen in the head moiety with a covalent C-C bond to enhance conformational restriction, which consequently gave a lead compound 12 (EC50=53nM). Optimized compound 26, which was identified by the further optimization of 12, exhibited potent activity (EC50=42nM) with improved clearance in liver microsomes and induced a 33% reduction in blood glucose area under the curve at a dose of 10mg/kg in an oral glucose tolerance test in C57BL/6N mice...
June 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28648305/assessing-the-budget-impact-and-economic-outcomes-of-the-introduction-of-daclatasvir-asunaprevir-and-sofosbuvir-ledipasvir-for-the-treatment-of-chronic-hepatitis-c-virus-infection-in-japan
#9
Thomas Ward, Samantha Webster, Sari Mishina, Phil McEwan, Gail Wygant, Feng Wang
BACKGROUND: The advent of highly efficacious, well-tolerated, all-oral direct-acting antiviral regimens has revolutionized the standard of care for patients chronically infected with hepatitis C virus. As efficacy and safety rates converge, prescribers and payers need to consider value for money. OBJECTIVES: To evaluate the health economic value of daclatasvir + asunaprevir versus sofosbuvir/ledipasvir via a cost-effectiveness analysis, and determine the optimal treatment considering both costs and health outcomes in Japan...
May 2017: Value in Health Regional Issues
https://www.readbyqxmd.com/read/28647674/in-pregnancy-increased-maternal-stai-trait-stress-score-shows-decreased-insulin-sensitivity-and-increased-stress-hormones
#10
Georgios Valsamakis, Dimitrios C Papatheodorou, Nikolaos Chalarakis, N Nikolaos Vrachnis, Elpida J Sidiropoulou, Maria Manolikaki, Aimilia Mantzou, Alexandra Margeli, Ioannis Papassotiriou, George P Chrousos, George Mastorakos
INTRODUCTION: Chronic or acute stressors influence maternal and fetal Hypothalamus-Pituitary-Adrenal Axes (HPA) during pregnancy. In this study, the effect of maternal stress into maternal insulin sensitivity was investigated during pregnancy. MATERIALS AND METHODS: Eighty-two pregnant women [aged 27.1±2.5 (mean±SD) yrs; BMI=25±2.2kg/m(2)] had at the 2(nd) and 3(rd) trimesters anthropometry, fasting blood samples (cortisol, Corticotropin Releasing Hormone (CRH), active amylin, Interleukin (IL6)), Oral Glucose Tolerance Test (OGTT) for glucose and insulin, state-trait anxiety inventory (STAI) trait and state questionnaires (for stress assessment)...
June 13, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28647180/helianthus-tuberosus-jerusalem-artichoke-tubers-improve-glucose-tolerance-and-hepatic-lipid-profile-in-rats-fed-a-high-fat-diet
#11
Naoto Okada, Shinya Kobayashi, Kouta Moriyama, Kohsuke Miyataka, Shinji Abe, Chiemi Sato, Kazuyoshi Kawazoe
OBJECTIVES: To analyze the effects of feeding Helianthus tuberosus (HT) tubers on glucose tolerance and lipid profile in rats fed a high-fat diet (HFD). METHODS: A normal HFD or HFD including 10 w/w% HT tubers (HFD + HT) was fed to F334/Jcl rats. After 10 weeks, organ weights, glucose tolerance, and lipid profile were analyzed. RESULTS: The body weight, liver weight, and epidermal fat content in the HFD group were higher than those of the normal group, and similar to those of the HFD + HT group...
May 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28646676/multicenter-phase-2-study-of-combination-therapy-with-ruxolitinib-and-danazol-in-patients-with-myelofibrosis
#12
K Gowin, H Kosiorek, A Dueck, J Mascarenhas, R Hoffman, C Reeder, J Camoriano, R Tibes, K Gano, J Palmer, R Mesa
Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol...
June 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28646358/metabolomics-of-diabetes-in-pregnancy
#13
REVIEW
Carolyn F McCabe, Wei Perng
PURPOSE OF REVIEW: The purpose of this review is to describe ways in which metabolomics may enhance understanding of gestational diabetes mellitus (GDM) etiology and refine current diagnostic criteria. RECENT FINDINGS: Current clinical recommendations suggest screening for GDM between 24 and 28 of gestational weeks using an oral glucose tolerance test. Despite this consensus, there are discrepancies regarding the exact criteria for GDM diagnosis. Further, emerging evidence has unveiled heterogeneous physiological pathways underlying GDM-specifically, GDM with defective insulin secretion vs...
August 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#14
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28645296/myd88-dependent-pro-interleukin-1%C3%AE-induction-in-dendritic-cells-exposed-to-food-grade-synthetic-amorphous-silica
#15
Hans Christian Winkler, Julian Kornprobst, Peter Wick, Lea Maria von Moos, Ioannis Trantakis, Elisabeth Maria Schraner, Barbara Bathke, Hubertus Hochrein, Mark Suter, Hanspeter Naegeli
BACKGROUND: Dendritic cells (DCs) are specialized first-line sensors of foreign materials invading the organism. These sentinel cells rely on pattern recognition receptors such as Nod-like or Toll-like receptors (TLRs) to launch immune reactions against pathogens, but also to mediate tolerance to self-antigens and, in the intestinal milieu, to nutrients and commensals. Since inappropriate DC activation contributes to inflammatory diseases and immunopathologies, a key question in the evaluation of orally ingested nanomaterials is whether their contact with DCs in the intestinal mucosa disrupts this delicate homeostatic balance between pathogen defense and tolerance...
June 23, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28644771/biomarker-based-phase-ii-trial-of-savolitinib-in-patients-with-advanced-papillary-renal-cell-cancer
#16
Toni K Choueiri, Elizabeth Plimack, Hendrik-Tobias Arkenau, Eric Jonasch, Daniel Y C Heng, Thomas Powles, Melanie M Frigault, Edwin A Clark, Amir A Handzel, Humphrey Gardner, Shethah Morgan, Laurence Albiges, Sumanta Kumar Pal
Purpose Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status. Patients and Methods Patients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily...
June 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28644367/oral-cholic-acid-is-efficacious-and-well-tolerated-in-patients-with-bile-acid-synthesis-and-zellweger-spectrum-disorders
#17
James E Heubi, Kevin E Bove, Kenneth D R Setchell
BACKGROUND/AIMS: Patients with bile acid synthesis disorders (BASD) due to single enzyme defects (SED) or Zellweger spectrum disorders (ZSD) accumulate hepatotoxic atypical bile acids resulting in potentially fatal progressive liver disease. We evaluated the efficacy and safety of oral cholic acid in patients with BASD. METHODS: In this phase 3, open-label, single-arm, nonrandomized, noncomparative study conducted over 18 years, patients were administered cholic acid orally 10 to 15 mg/kg/day...
June 21, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28642713/benefits-of-substituting-sitting-with-standing-and-walking-in-free-living-conditions-for-cardiometabolic-risk-markers-cognition-and-mood-in-overweight-adults
#18
Bernard M F M Duvivier, Nicolaas C Schaper, Annemarie Koster, Linh van Kan, Harry P F Peters, Jos J Adam, Timo Giesbrecht, Esther Kornips, Martine Hulsbosch, Paul Willems, Matthijs K C Hesselink, Patrick Schrauwen, Hans H C M Savelberg
Background: We investigated whether substituting sitting with standing and self-perceived light walking in free-living conditions would improve cardiometabolic risk factors, mood, and cognition in overweight/obese adults. Methods: In a randomized, cross-over study, 24 (m/f: 13/11) sedentary overweight/obese participants (64 ± 7 years, BMI 29 ± 2 kg/m(2)) followed two activity regimens of each 4 days in free-living conditions: "Sit": sitting 13.5 h/day, standing 1.4 h/day, self-perceived light-intensity walking 0...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28641925/safety-pharmacokinetics-and-sialic-acid-production-after-oral-administration-of-n-acetylmannosamine-mannac-to-subjects-with-gne-myopathy
#19
Xin Xu, Amy Q Wang, Lea L Latham, Frank Celeste, Carla Ciccone, May Christine Malicdan, Barry Goldspiel, Pramod Terse, James Cradock, Nora Yang, Selwyn Yorke, John C McKew, William A Gahl, Marjan Huizing, Nuria Carrillo
GNE myopathy is a rare, autosomal recessive, inborn error of sialic acid metabolism, caused by mutations in GNE, the gene encoding UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase. The disease manifests as an adult-onset myopathy characterized by progressive skeletal muscle weakness and atrophy. There is no medical therapy available for this debilitating disease. Hyposialylation of muscle glycoproteins likely contributes to the pathophysiology of this disease. N-acetyl-D-mannosamine (ManNAc), an uncharged monosaccharide and the first committed precursor in the sialic acid biosynthetic pathway, is a therapeutic candidate that prevents muscle weakness in the mouse model of GNE myopathy...
April 26, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28641783/abnormal-levels-of-adipokines-in-adolescent-offspring-of-women-with-type-1-diabetes-results-from-the-epicom-study
#20
Zuzana Lohse, Birgitte Bytoft, Sine Knorr, Tine D Clausen, Rikke Beck Jensen, Henning Beck-Nielsen, Anne Pernille Hermann, Peter Oturai, Jan Frystyk, Peter Damm, Claus H Gravholt, Kurt Højlund, Dorte M Jensen
AIMS/HYPOTHESIS: To investigate long-term consequences of diabetes during pregnancy, we determined adiponectin and leptin levels in adolescents born by women with type 1 diabetic (T1D) or non-diabetic mothers, and determined associations between adiponectin and leptin levels in adolescence and the magnitude of intrauterine hyperglycemia. RESEARCH DESIGN AND METHODS: We measured serum adiponectin and leptin and calculated leptin to adiponectin ratio (LAR) in 271 offspring of T1D women (index offspring) (13-20years), and 297 matched control offspring...
July 2017: Metabolism: Clinical and Experimental
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