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https://www.readbyqxmd.com/read/28449186/the-risk-of-lower-gastrointestinal-bleeding-in-low-dose-aspirin-users
#1
W-C Chen, K-H Lin, Y-T Huang, T-J Tsai, W-C Sun, S-K Chuah, D-C Wu, P-I Hsu
BACKGROUND: Aspirin increases the risk of gastrointestinal bleeding. AIM: To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users. METHODS: Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers...
April 27, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28448895/incidence-of-diabetic-ketoacidosis-among-patients-with-type-2-diabetes-mellitus-treated-with-sglt2-inhibitors-and-other-antihyperglycemic-agents
#2
Yiting Wang, Mehul Desai, Patrick B Ryan, Frank J DeFalco, Martijn J Schuemie, Paul E Stang, Jesse A Berlin, Zhong Yuan
AIMS: To estimate and compare incidence of diabetes ketoacidosis (DKA) among patients with type 2 diabetes who are newly treated with SGLT2 inhibitors (SGLT2i) versus non-SGLT2i antihyperglycemic agents (AHAs) in actual clinical practice. METHODS: A new-user cohort study design using a large insurance claims database in the US. DKA incidence was compared between new users of SGLT2i and new users of non-SGLT2i AHAs pair-matched on exposure propensity scores (EPS) using Cox regression models...
April 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28448188/effects-of-indomethacin-on-prostanoid-synthesis-and-vasomotor-responsiveness-in-endothelium-denuded-abdominal-and-thoracic-aortas-of-wistar-rats
#3
Ruth M López, Janette E López, Jorge S López, María C Castillo, Gustavo Guevara, José A Morales, Oscar A López, Jair Lozano, Enrique F Castillo
In endothelium-denuded abdominal (but not thoracic) aortas of rats, the nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed contractions evoked by α-adrenergic agonists hypothetically mediated by prostanoids. We aimed to identify these non-endothelial-derived contractile prostanoids released by α-adrenergic receptors activation. Endothelium-denuded abdominal and thoracic aortas of Wistar rats were used for biochemical and functional analyses. Western blot analysis showed that COX-1 and COX-2 protein levels were respectively equivalent in endothelium-denuded abdominal and thoracic aortas...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28446278/-clinical-analysis-for-42-imatinib-resistant-patients-with-chronic-myelogenous-leukemia
#4
Xi Liu, Si-Lin Gan, Jie Ma, Yan-Fang Liu, Xin-Sheng Xie, Zhong-Xing Jiang, Yuan-Dong Cheng, Hui Sun
OBJECTIVE: To analyze the kinase mutation ratio, related factors, effectiveness and safety of the second generation drugs for imatinib-resistant patients with chronic myeloid leukemia(CML). METHODS: COX proportional hazard regression model was used for unvariate and multvariate analysis of various factors affecting the kinase mutation and for evaluating the effectiveness and safety of second generation tyrosine kinase inhibitor(TKI). RESULTS: 13 kinds of mutation were detected in 19 out of 42 cases for 22 times, including 4 times of F359V, 3 times of E255K, 2 time for F359C, F317L, T315I, Y253H, 1 time for D256R, C250R, D276G, F486S, M244V, Y256H and G250E, 3 cases with mixed mutations...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446249/adipose-derived-mesenchymal-stem-cells-modulate-cd14-cd16-expression-on-monocytes-from-sepsis-patients-in-vitro-via-prostaglandin-e2
#5
Guanguan Qiu, Guoping Zheng, Menghua Ge, Lanfang Huang, Haijiang Tong, Ping Chen, Dengming Lai, Yaoqin Hu, Baoli Cheng, Qiang Shu, Jianguo Xu
BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to reduce sepsis-induced inflammation and improve survival in mouse models of sepsis. CD16(+) monocytes are proinflammatory and abundant in inflammatory conditions such as sepsis. The primary objective in this exploratory study was to determine the effects of adipose-derived MSCs (ASCs) on three subsets of monocytes from sepsis patients in vitro and to delineate the underlying mechanism. METHODS: This is a prospective cohort study of patients admitted to the medical intensive care unit (ICU) at an academic medical center...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28440462/imperatorin-efficiently-blocks-tnf-%C3%AE-mediated-activation-of-ros-pi3k-akt-nf-%C3%AE%C2%BAb-pathway
#6
Ke Si Wang, Ying Lv, Zhe Wang, Juan Ma, Chunliu Mi, Xuezheng Li, Guang Hua Xu, Lian Xun Piao, Sheng Zhe Zheng, Xuejun Jin
Inflammation contributes to development and progression in a variety of cancers, including cervical cancer, which is the second leading cause of cancer deaths in women worldwide. In this study, we examined the anti-inflammatory effects of imperatorin, a psoralen-type furanocoumarin from the fruits of Angelica dahurica, in tumor necrosis factor-α (TNF-α)-stimulated HeLa cells by investigating its impact on the production and expression of cytokines and the major signal-transduction pathways. We found this compound significantly inhibited the TNF-α-induced expression of NF-κB target genes, such as COX-2, cyclin  D1, MMP-9, VEGF, IL-6 and Bcl-xL in a concentration-dependent manner...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28438649/pathophysiological-roles-of-canstatin-on-myofibroblasts-after-myocardial-infarction-in-rats
#7
Akira Sugiyama, Muneyoshi Okada, Hideyuki Yamawaki
Myofibroblasts play an important role during remodeling process after myocardial infarction through proliferation, migration, production and degradation of extracellular matrix (ECM) and contraction. Canstatin, a 24kDa polypeptide, is cleaved from α2 chain of type IV collagen, which is a major component of basement membrane around cardiomyocytes. We examined the effects of canstatin on myofibroblasts isolated from the areas of myocardial infarction. Myocardial infarction model was made by ligating left anterior descending artery of Wistar rats...
April 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28438043/comparative-effectiveness-and-safety-analysis-of-dual-antiplatelet-therapies-within-an-integrated-delivery-system
#8
James C Coons, Carlo J Iasella, Tyler Chanas, Nan Wang, Kiersten Williams, Anthony Boyd, John Lyons, Jamie Eckardt, Lindsey Rihtarchik, Alison Merkel, Alexandra Chambers, Lara S Lemon, Randall Smith, Christopher R Ensor
BACKGROUND: Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes. OBJECTIVE: To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients. METHODS: We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI...
April 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28436250/effect-of-treatment-dose-reductions-in-the-setting-of-hand-foot-syndrome-on-survival-outcomes-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-vascular-endothelial-growth-factor-receptor-inhibitors
#9
Erin B Bailey, Joseph Merriman, Benjamin Maughan, Austin Poole, Srinivas K Tantravahi, Archana M Agarwal, Julia A Batten, Shiven B Patel, Sumanta K Pal, David D Stenehjem, Neeraj Agarwal
Purpose Hand-foot syndrome is a common dose limiting toxicity of vascular endothelial growth factor receptor tyrosine kinase inhibitors used for treatment of patients with metastatic renal cell carcinoma. The effect of treatment dose reductions, in the context of hand-foot syndrome, on survival outcomes is reported. Methods This was a retrospective case series of patients receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors from 1 January 2004 to 31 October 2013. The main outcomes were progression-free and overall survival in these patients experiencing hand-foot syndrome and undergoing treatment dose reductions...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28433945/cqmuh-011-a-novel-adamantane-sulfonamide-compound-inhibits-lipopolysaccharide-and-d-galactosamine-induced-fulminant-hepatic-failure-in-mice
#10
Liping Yan, Xiangnan Hu, Qihong Wu, Rong Jiang, Sisi Zhang, Qiao Ling, Hailin Liu, Xuejun Jiang, Jingyuan Wan, Yingju Liu
CQMUH-011, a novel adamantane sulfonamide compound, was shown to suppress macrophage activation and proliferation in our previous study. However, it is unknown whether CQMUH-011 has anti-inflammatory and hepatoprotective properties. In this study, we investigated the potential effects and mechanisms of CQMUH-011 on lipopolysaccharide (LPS)-induced RAW264.7 cell activation in vitro and LPS- and D-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF) in vivo. The results showed that in RAW264.7 cells challenged by LPS, CQMUH-011 inhibited cell proliferation and induced cell cycle arrest and apoptosis...
April 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28433514/cox-2-inhibition-potentiates-mouse-bone-marrow-stem-cell-engraftment-and-differentiation-mediated-wound-repair
#11
Ramasatyaveni Geesala, Neha R Dhoke, Amitava Das
BACKGROUND: Engraftment of transplanted stem cells is often limited by cytokine and noncytokine proinflammatory mediators at the injury site. We examined the role of Cyclooxygenase-2 (Cox-2)-induced cytokine-mediated inflammation on engraftment of transplanted bone marrow stem cells (BMSCs) at the wound site. METHODS: BMSCs isolated from male C57/BL6J mice were transplanted onto excisional splinting wounds in syngenic females in presence or absence of celecoxib, Cox-2 specific inhibitor (50 mg/kg, body weight [b wt]), to evaluate engraftment and wound closure...
April 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28432754/intraclass-differences-in-the-risk-of-hospitalisazion-for-heart-failure-among-type-2-diabetic-patients-initiating-a-dipeptydil-peptidase-4-inhibitor-or-a-sulphonylurea-results-from-the-osmed-health-db-registry
#12
Gian Paolo Fadini, Stefania Saragoni, Pierluigi Russo, Luca Degli Esposti, Saula Vigili de Kreutzenberg, Mario Melazzini, Angelo Avogaro
AIMS: Heart failure (HF) is frequent in type 2 diabetes (T2D) and several glucose-lowering medications may increase HF risk. In the SAVOR-TIMI trial, patients on Saxagliptin experienced a 27% higher risk of hospitalisation for HF (HHF). In a retrospective study on 127,555 patients, we showed that DPP-4i therapy was associated with a lower HHF risk than sulphonylurea (SU) therapy. We herein re-analyzed such data to evaluate intraclass differences among DPP-4i and SU. MATERIALS AND METHODS: We included T2D patients initiating DPP-4i or SU alone or in combination with metformin...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28431181/protective-effect-of-mesenchymal-stem-cells-against-the-development-of-intracranial-aneurysm-rupture-in-mice
#13
Atsushi Kuwabara, Jia Liu, Yoshinobu Kamio, Airan Liu, Michael T Lawton, Jae-Woo Lee, Tomoki Hashimoto
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stem or stromal cells found in multiple tissues. Intravenous MSC injections have been used to treat various diseases with an inflammatory component in animals and humans. Inflammation is emerging as a key component of pathophysiology of intracranial aneurysms. Modulation of inflammation by MSCs may affect sustained inflammatory processes that lead to aneurysmal rupture. OBJECTIVE: To assess the effect of MSCs on the development of aneurysm rupture using a mouse model...
April 19, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28431162/risk-of-serious-bacterial-infection-associated-with-tumour-necrosis-factor-alpha-inhibitors-in-children-with-juvenile-idiopathic-arthritis
#14
Wan-Ju Lee, Todd A Lee, Katie J Suda, Gregory S Calip, Leslie Briars, Glen T Schumock
Objectives.: TNF-α inhibitors (TNFIs) have a black box warning for increased risk of serious infection that was based on evidence from studies of adults. Evidence of the association is lacking for children. We aimed to examine the risk of infection posed by TNFIs compared with DMARDs in children with JIA. Methods.: We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims and Encounters database. Children <16 years old with JIA who initiated monotherapy with TNFIs or DMARDs were identified and followed for occurrence of serious bacterial infection requiring hospitalization...
April 18, 2017: Rheumatology
https://www.readbyqxmd.com/read/28428070/no-production-and-potassium-channels-activation-induced-by-crotalus-durissus-cascavella-underlie-mesenteric-artery-relaxation
#15
S S Santos, R L C Jesus, L O Simões, W P Vasconcelos, I A Medeiros, R C Veras, L L Casais-E-Silva, D F Silva
Animal toxins are natural resources for pharmacological studies. The venom of Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio-prospecting of new anti-hypertensive agents. The aim of this study was to investigate vascular effects of the venom of C.d. cascavella in normotensive rats. Studies were performed using isolated mesenteric artery segments and aortic endothelial cells. The cumulative administration of the venom of C.d. cascavella (0.001-30 μg/mL) on phenylephrine (Phe; 10 μM) pre-contracted rings induced a concentration-dependent vasorelaxation in the presence of vascular endothelium (Emax = 47...
April 18, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28427813/novel-pyrazoles-and-pyrazolo-1-2-a-pyridazines-as-selective-cox-2-inhibitors-ultrasound-assisted-synthesis-biological-evaluation-and-dft-calculations
#16
Nagat Ghareb, Hosam A Elshihawy, Mohamed M Abdel-Daim, Mohamed A Helal
COX-2 is an inducible enzyme mediating inflammatory responses. Selective targeting of COX-2 is useful for developing anti-inflammatory agents devoid of ulcerogenic activity. Herein, we report the design and synthesis of a series of pyrazoles and pyrazolo[1,2-a]pyridazines with selective COX-2 inhibitory activity and in vivo anti-inflammatory effect. Both series were accessed through acid-catalyzed ultrasound-assisted reactions. The most active compounds in this study are two novel molecules, 11 and 16, showing promising selectivity and decent IC50 of 16...
April 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28426106/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#17
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28424593/phospholipase-a2-of-peroxiredoxin-6-plays-a-critical-role-in-cerebral-ischemia-reperfusion-inflammatory-injury
#18
Yu Shanshan, Jiang Beibei, Tan Li, Gao Minna, Lei Shipeng, Peng Li, Zhao Yong
Microglia-mediated inflammation is an important step in the progression of cerebral ischemia/reperfusion injury and the associated production of receptors of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6 (Prdx6) has been demonstrated as the endogenous antioxidant protein for its peroxidase properties. However, the role of the independent phospholipase A2 (iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33) would have a critical effect on inflammatory brain damage...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28423516/the-addition-of-celecoxib-improves-the-antitumor-effect-of-cetuximab-in-colorectal-cancer-role-of-egfr-ras-foxm1-%C3%AE-catenin-signaling-axis
#19
Araceli Valverde, Jon Peñarando, Amanda Cañas, Laura M López-Sánchez, Francisco Conde, Silvia Guil-Luna, Vanessa Hernández, Carlos Villar, Cristina Morales-Estévez, Juan de la Haba-Rodríguez, Enrique Aranda, Antonio Rodríguez-Ariza
Here we showed that the addition of the COX-2 inhibitor celecoxib improved the antitumor efficacy in colorectal cancer (CRC) of the monoclonal anti-EGFR antibody cetuximab. The addition of celecoxib augmented the efficacy of cetuximab to inhibit cell proliferation and to induce apoptosis in CRC cells. Moreover, the combination of celecoxib and cetuximab was more effective than either treatment alone in reducing the tumor volume in a mouse xenograft model. The combined treatment enhanced the inhibition of EGFR signaling and altered the subcellular distribution of β-catenin...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423154/association-of-mental-disorders-and-related-medication-use-with-risk-for-major-osteoporotic-fractures
#20
James M Bolton, Suzanne N Morin, Sumit R Majumdar, Jitender Sareen, Lisa M Lix, Helena Johansson, Anders Odén, Eugene V McCloskey, John A Kanis, William D Leslie
Importance: Osteoporotic fractures are a leading cause of disability, costs, and mortality. FRAX is a tool used to assess fracture risk in the general population. Mental disorders and medications to treat them have been reported to adversely affect bone health, but, to date, they have not been systematically studied in relation to osteoporotic fractures. Objective: To examine the association of mental disorders and psychotropic medication use with osteoporotic fracture risk in routine clinical practice...
April 19, 2017: JAMA Psychiatry
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