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https://www.readbyqxmd.com/read/28213955/the-skin-barrier-function-gene-spink5-is-associated-with-challenge-proven-ige-mediated-food-allergy-in-infants
#1
Sarah E Ashley, Hern-Tze Tina Tan, Peter Vuillermin, Shyamali C Dharmage, Mimi L K Tang, Jennifer Koplin, Lyle C Gurrin, Adrian Lowe, Caroline Lodge, Anne-Louise Ponsonby, John Molloy, Pamela Martin, Melanie C Matheson, Richard Saffery, Katrina J Allen, Justine A Ellis, David Martino
BACKGROUND: A defective skin barrier is hypothesised to be an important route of sensitisation to dietary antigens, and may lead to food allergy in some children. Missense mutations in the Serine peptidase inhibitor kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE mediated food allergy. METHOD: We genotyped 71 'tag' single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kilobases (kb) including SPINK5 (~61kb) in n=722 (n=367 food allergic, n=199 food sensitised, tolerant and n=156 non-food allergic controls) 12-month infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge (OFC)...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28213862/apremilast-a-review-in-psoriasis-and-psoriatic-arthritis
#2
Gillian M Keating
Apremilast (Otezla(®)) is an orally administered, small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast 30 mg twice daily reduced the severity of moderate to severe plaque psoriasis in the phase 3 ESTEEM trials, as well as improving difficult-to-treat nail, scalp and palmoplantar psoriasis. Most patient-reported outcomes, including pruritus and the total Dermatology Life Quality Index, also improved to a significantly greater extent with apremilast than with placebo, with significant improvements in pruritus and skin discomfort/pain visual analogue scale scores seen as early as week 2 with apremilast...
February 18, 2017: Drugs
https://www.readbyqxmd.com/read/28213107/hypoglycemic-effect-of-the-polyphenols-rich-extract-from-rose-rugosa-thunb-on-high-fat-diet-and-stz-induced-diabetic-rats
#3
Liu Liu, Dan Tang, Haiqing Zhao, Xuelei Xin, Haji Akber Aisa
ETHNOPHARMACOLOGICAL RELEVANCE: Rosa rugosa Thunb is traditional Uygur medicine, it is widely used for regulating blood condition, nourishing liver and gallbladder in Uygur ancient prescription. But the mechanism of Rosa rugosa Thunb on diabetes is still unclear. In here, we studied the hypoglycemic effect and explained one probable pathway of polyphenols rich extract from Rosa rugosa Thunb (RPE) on diabetic rats. MATERIALS AND METHODS: In vitro, the effect of RPE on α-glucosidase inhibition was finished, and the antioxidant activity of RPE was evaluated by ABTS and DPPH assay...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28213002/a-phase-ii-trial-of-dovitinib-in-previously-treated-advanced-pleural-mesothelioma-the-ontario-clinical-oncology-group
#4
Scott A Laurie, Desiree Hao, Natasha B Leighl, John Goffin, Abderrahim Khomani, Ashish Gupta, Christina L Addison, Anita Bane, Jean Seely, Marc L Filion, Gregory R Pond, Mark N Levine
OBJECTIVES: Following failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM. METHODS: This open-label multicentre phase II trial [NCT01769547] enrolled fit, consenting adult patients with advanced MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212845/safety-assessment-of-medium-and-long-chain-triacylglycerols-containing-30-w-w-medium-chain-fatty-acids-in-mice-and-rats
#5
Shengmin Zhou, Yueqiang Wang, Yuanrong Jiang, Liangli Lucy Yu
A novel medium- and long-chain triacylglycerols (MLCT), with 30% (w/w) medium-chain fatty acids (MCFA) was evaluated for its safety as a dietary fat in mice and rats. The subacute oral toxicity study showed that the maximum tolerated dose exceeded 54.33 g/kg body weight (kg bw)/day. In the 90-day feeding study, no dose-related adverse effects were observed in rats administered diets formulated with different levels of MLCT (2.0, 4.0, and 8.0 g/kg bw/day) as compared to the rapeseed oil control diet. Further safety assessment in pregnant rats did not reveal any significant difference relative to the control at a treatment level up to 8...
February 14, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28211608/preclinical-characterisation-of-55p0251-a-novel-compound-that-amplifies-glucose-stimulated-insulin-secretion-and-counteracts-hyperglycaemia-in-rodents
#6
Karin Stadlbauer, Barbara Brunmair, Zsuzsanna Lehner, Immanuel Adorjan, Thomas Scherer, Anton Luger, Leonhardt Bauer, Clemens Fürnsinn
AIMS: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action. MATERIALS AND METHODS: Pharmacokinetic properties of 55P0251 were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets, and comparison to established drugs...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28211545/the-effect-of-gut-microbiome-on-tolerance-to-morphine-mediated-antinociception-in-mice
#7
Minho Kang, Ryan A Mischel, Sukhada Bhave, Essie Komla, Alvin Cho, Charity Huang, William L Dewey, Hamid I Akbarali
There is growing appreciation for the importance of gastrointestinal microbiota in many physiological and pathophysiological processes. While morphine and other narcotics are the most widely prescribed therapy for moderate to severe pain clinically, they have been noted to alter microbial composition and promote bacterial translocation to other tissues. Here we examined the pharmacodynamic properties of chronic morphine in mice following bacterial depletion with oral gavage of an antibiotic cocktail (ABX). ABX significantly reduced gut bacteria and prevented chronic morphine induced increases in gut permeability, colonic mucosal destruction, and colonic IL-1β expression...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211162/efficacy-of-the-oral-mtorc1-inhibitor-everolimus-in-relapsed-or-refractory-indolent-lymphoma
#8
N Nora Bennani, Betsy R LaPlant, Stephen M Ansell, Thomas M Habermann, David J Inwards, Ivana N Micallef, Patrick B Johnston, Luis F Porrata, Joseph P Colgan, Svetomir N Markovic, Grzegorz S Nowakowski, William R Macon, Craig B Reeder, Joseph R Mikhael, Donald W Northfelt, Irene M Ghobrial, Thomas E Witzig
Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas...
February 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28210989/net-clinical-benefit-of-dabigatran-vs-warfarin-in-venous-thromboembolism-analyses-from-re-cover-%C3%A2-re-cover%C3%A2-ii-and-re-medy%C3%A2
#9
Martin Feuring, Sam Schulman, Henry Eriksson, Ajay J Kakkar, Sebastian Schellong, Stefan Hantel, Elke Schueler, Jörg Kreuzer, Samuel Z Goldhaber
The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2...
February 16, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28210869/serum-1-5-anhydroglucitol-levels-slightly-increase-rather-than-decrease-after-a-glucose-load-in-subjects-with-different-glucose-tolerance-status
#10
Hang Su, Xiaojing Ma, Jun Yin, Yufei Wang, Xingxing He, Yuqian Bao, Jian Zhou, Weiping Jia
AIMS: Previous studies showed that serum 1,5-anhydroglucitol (1,5-AG) levels are significantly reduced in patients with diabetes mellitus (DM). However, it remains unclear how 1,5-AG levels acutely change in response to a glucose load. This study explored acute changes in 1,5-AG levels after a glucose load and the related influencing factors in individuals with differing degrees of glucose tolerance. METHODS: A total of 681 participants (353 without DM and 328 with DM) without a prior history of DM were enrolled...
February 16, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28209466/pharmacokinetics-and-safety-of-cavosonstat-n91115-in-healthy-and-cystic-fibrosis-adults-homozygous-for-f508del-cftr
#11
Scott H Donaldson, George M Solomon, Pamela L Zeitlin, Patrick A Flume, Alicia Casey, Karen McCoy, Edith T Zemanick, Arun Mandagere, Janice M Troha, Steven A Shoemaker, James F Chmiel, Jennifer L Taylor-Cousar
BACKGROUND: Cavosonstat (N91115), an orally bioavailable inhibitor of S-nitrosoglutathione reductase, promotes cystic fibrosis transmembrane conductance regulator (CFTR) maturation and plasma membrane stability, with a mechanism of action complementary to CFTR correctors and potentiators. METHODS: A Phase I program evaluated pharmacokinetics, drug-drug interactions and safety of cavosonstat in healthy and cystic fibrosis (CF) subjects homozygous for F508del-CFTR...
February 13, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28208695/the-role-of-inhaled-loxapine-in-the-treatment-of-acute-agitation-in-patients-with-psychiatric-disorders-a-clinical-review
#12
REVIEW
Domenico de Berardis, Michele Fornaro, Laura Orsolini, Felice Iasevoli, Carmine Tomasetti, Andrea de Bartolomeis, Nicola Serroni, Alessandro Valchera, Alessandro Carano, Federica Vellante, Stefano Marini, Monica Piersanti, Giampaolo Perna, Giovanni Martinotti, Massimo Di Giannantonio
Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207876/circulating-c1q-complement-tnf-related-protein-ctrp-1-ctrp9-ctrp12-and-ctrp13-concentrations-in-type-2-diabetes-mellitus-in-vivo-regulation-by-glucose
#13
Bo Bai, Bo Ban, Zunjing Liu, Man Man Zhang, Bee Kang Tan, Jing Chen
OBJECTIVES: The C1q complement/TNF-related protein (CTRP) superfamily, which includes the adipokine adiponectin, has been shown in animal models to have positive metabolic and cardiovascular effects. We sought to investigate circulating CTRP1, CTRP9, CTRP12 and CTRP13 concentrations in persons with type 2 diabetes mellitus (T2DM), with age and BMI matched controls, and to examine the effects of a 2 hour 75g oral glucose tolerance test (OGTT) on serum CTRP1, CTRP9, CTRP12 and CTRP13 levels in persons with T2DM...
2017: PloS One
https://www.readbyqxmd.com/read/28207540/different-dosages-of-mifepristone-versus-enantone-to-treat-uterine-fibroids-a-multicenter-randomized-controlled-trial
#14
Chongdong Liu, Qi Lu, Hong Qu, Li Geng, Meilu Bian, Minli Huang, Huilan Wang, Youzhong Zhang, Zeqing Wen, Shurong Zheng, Zhenyu Zhang
BACKGROUND: To evaluate the efficacy and safety of 10 mg and 25 mg mifepristone per day compared with 3.75 mg enantone in treating uterine fibroids. METHODS: This is a Multicenter randomized controlled trial. A total of 501 subjects with symptomatic uterine fibroids were enrolled and randomized into the group of 10mg, 25mg mifepristone and 3.75 enantone (with 307, 102 and 92 subjects respectively), with 458 subjects completed the treatment. Three months of daily therapy with oral mifepristone (at a dose of either 10 mg or 25 mg) or once-monthly subcutaneous injections of enantone (at a dose of 3...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28206871/swallowing-therapy-and-progressive-resistance-training-in-head-and-neck-cancer-patients-undergoing-radiotherapy-treatment-randomized-control-trial-protocol-and-preliminary-data
#15
Sara F Hajdú, Irene Wessel, Christoffer Johansen, Claus A Kristensen, Zahra T Kadkhoda, Christina C Plaschke, Susanne O Dalton
BACKGROUND: Head and neck cancer (HNC) patients are often challenged by treatment induced dysphagia and trismus. Traditionally, rehabilitation is initiated when loss of function has already occurred. There is increasing evidence that it is of benefit to patients to initiate an early rehabilitation process before and during treatment. HNC patients have a unique set of functional challenges such as pre- and post-treatment dysphagia, pain and weight loss. The aim of the trial is to investigate the effects of swallowing and mouth-opening exercises combined with progressive resistance training (PRT) during radiotherapy...
February 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28206810/safety-of-oral-and-intravenous-mycophenolate-mofetil-in-healthy-cats
#16
Jennifer E Slovak, Nicolas F Villarino
Objectives The aim of this study was to evaluate the safety and clinical effects of intravenous (IV) and oral mycophenolate mofetil (MMF) in healthy cats. Methods A total of 24 healthy adult cats weighing >3.5 kg were either administered IV MMF (over a 2 h infusion) or oral MMF. The dosages used were as follows: 5 mg/kg IV once (n = 2), 10 mg/kg q12h IV for 1 day (n = 1), 20 mg/kg q12h IV for 1 day (n = 6) and 10 mg/kg q12h IV for 3 days (n = 5). Blood was collected from each cat at intervals of up to 12 h from the last dose for analysis purposes...
February 1, 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28206732/clinical-efficacy-and-safety-of-a-new-once-daily-1000-mg-suspension-versus-twice-daily-500-mg-tablets-of-micronized-purified-flavonoid-fraction-in-patients-with-symptomatic-chronic-venous-disorders-a-randomized-controlled-trial
#17
Patrick Carpentier, Debora Karetova, Harunarashid Hanafiah, Elisabeth Enriquez-Vega, Andrej Dzupina, Miso Sabovic, Lourdes Reina Gutierrez, Somboom Subwongcharoen, Hasan Tüzün, Arnaud Maggioli
BACKGROUND: Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000 mg oral suspension of MPFF. METHODS: In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks...
February 15, 2017: International Angiology: a Journal of the International Union of Angiology
https://www.readbyqxmd.com/read/28206704/lipid-lowering-efficacy-and-safety-of-alirocumab-in-patients-with-or-without-diabetes-a-sub-analysis-of-odyssey-combo-ii
#18
Lawrence A Leiter, Jose Luis Zamorano, Maja Bujas-Bobanovic, Michael J Louie, Guillaume Lecorps, Christopher P Cannon, Yehuda Handelsman
AIM: This sub-analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy. MATERIALS AND METHODS: COMBO II was a 104-week, double-blind study (n = 720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL-C ≥70 mg/dL (1...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28205558/plant-based-vaccines-for-oral-delivery-of-type-1-diabetes-related-autoantigens-evaluating-oral-tolerance-mechanisms-and-disease-prevention-in-nod-mice
#19
Amanda L Posgai, Clive H Wasserfall, Kwang-Chul Kwon, Henry Daniell, Desmond A Schatz, Mark A Atkinson
Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3(+) and LAP(+) regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205322/efficacy-and-safety-of-autoinjected-exenatide-once-weekly-suspension-versus-sitagliptin-or-placebo-with-metformin-in-patients-with-type-2-diabetes-the-duration-neo-2-randomized-clinical-study
#20
Kishore M Gadde, Marion L Vetter, Nayyar Iqbal, Elise Hardy, Peter Öhman
AIMS: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo. MATERIALS AND METHODS: In this open-label, multicenter study of patients with type 2 diabetes who had suboptimal glycemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2...
February 16, 2017: Diabetes, Obesity & Metabolism
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