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https://www.readbyqxmd.com/read/28079927/developmental-programming-interaction-between-prenatal-bpa-and-postnatal-overfeeding-on-cardiac-tissue-gene-expression-in-female-sheep
#1
L A Koneva, A K Vyas, R C McEachin, M Puttabyatappa, H-S Wang, M A Sartor, V Padmanabhan
Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known...
January 12, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28079606/relationship-between-alternative-resuscitation-strategies-host-response-and-injury-biomarkers-and-outcome-in-septic-shock-analysis-of-the-protocol-based-care-for-early-septic-shock-study
#2
John A Kellum, Francis Pike, Donald M Yealy, David T Huang, Nathan I Shapiro, Derek C Angus
OBJECTIVES: The Protocol-based Care for Early Septic Shock trial found no differences across alternative resuscitation strategies in all-cause mortality. A separate aim was to determine whether differences in resuscitation strategies affected trajectories of biomarkers of key pathways associated with downstream clinical outcomes of sepsis and whether there were differences in survival across treatment arms for patients with different baseline biomarker profiles. DESIGN: Secondary analysis of a large randomized clinical trial...
January 10, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28076309/activation-of-the-tryptophan-serotonin-pathway-is-associated-with-severity-and-predicts-outcomes-in-pneumonia-results-of-a-long-term-cohort-study
#3
Marc A Meier, Manuel Ottiger, Alaadin Vögeli, Christian Steuer, Luca Bernasconi, Robert Thomann, Mirjam Christ-Crain, Christoph Henzen, Claus Hoess, Werner Zimmerli, Andreas Huber, Beat Mueller, Philipp Schuetz
BACKGROUND: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP)...
January 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28070879/a-review-of-pharmacogenetics-of-antimalarials-and-associated-clinical-implications
#4
REVIEW
Hazem Elewa, Kyle John Wilby
Genetic variability in drug-metabolizing enzymes and drug transporters is known to influence the pharmacokinetics of many drugs. Antimalarial drugs are a class of agents known to utilize metabolic and elimination pathways prone to genetic variation. This paper aims to review the genetic variants affecting antimalarial medications and discuss their clinical implications. Data were identified for the genes coding for the cytochrome P450 (CYP) enzymes: CYP2C8, CYP2C19, CYP2A6, CYP2D6, CYP2B6, and the P-glycoprotein drug transporter...
January 9, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28069485/alternative-approaches-for-identifying-acute-systemic-toxicity-moving-from-research-to-regulatory-testing
#5
REVIEW
Jon Hamm, Kristie Sullivan, Amy J Clippinger, Judy Strickland, Shannon Bell, Barun Bhhatarai, Bas Blaauboer, Warren Casey, David Dorman, Anna Forsby, Natàlia Garcia-Reyero, Sean Gehen, Rabea Graepel, Jon Hotchkiss, Anna Lowit, Joanna Matheson, Elissa Reaves, Louis Scarano, Catherine Sprankle, Jay Tunkel, Dan Wilson, Menghang Xia, Hao Zhu, David Allen
Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives...
January 6, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28063342/linking-genomic-responses-of-gonads-with-reproductive-impairment-in-marine-medaka-oryzias-melastigma-exposed-chronically-to-the-chemopreventive-and-antifouling-agent-3-3-diindolylmethane-dim
#6
Lianguo Chen, Doris W T Au, Chenyan Hu, Weipeng Zhang, Bingsheng Zhou, Lin Cai, John P Giesy, Pei-Yuan Qian
3,3'-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28days) aqueous exposure to relatively low doses (0μg/L or 8.5μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway...
December 30, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/28063021/hepatotoxicity-with-vismodegib-an-md-anderson-cancer-center-and-research-on-adverse-drug-events-and-reports-project
#7
Beatrice J Edwards, Dennis W Raisch, Smita S Saraykar, Ming Sun, Josh A Hammel, Hai T Tran, Nathaniel Wehr, Rasha Arabyat, Dennis P West
BACKGROUND: On 30 January 2012, the US FDA approved vismodegib (Erivedge(®), Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. OBJECTIVE: Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. METHODS: FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others...
January 6, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28054800/mother-son-discrepant-reporting-on-parenting-practices-the-contribution-of-temperament-and-depression
#8
Yuri Shishido, Robert D Latzman
Despite low to moderate convergent correlations, assessment of youth typically relies on multiple informants for information across a range of psychosocial domains including parenting practices. Although parent-youth informant discrepancies have been found to predict adverse youth outcomes, few studies have examined contributing factors to the explanation of informant disagreements on parenting practices. The current study represents the first investigation to concurrently examine the role of mother and son's self-reported affective dimensions of temperament and depression as pathways to informant discrepancies on parenting practices...
January 5, 2017: Journal of Family Psychology: JFP
https://www.readbyqxmd.com/read/28054356/impact-of-a-peri-operative-quality-improvement-programme-on-postoperative-pulmonary-complications
#9
J A Moore, D H Conway, N Thomas, D Cummings, D Atkinson
Postoperative pulmonary complications are common, with a reported incidence of 2-40%, and are associated with adverse outcomes that include death, longer hospital stay and reduced long-term survival. Enhanced recovery is now a standard of care for patients undergoing elective major surgery. Despite the high prevalence of pulmonary complications in this population, few elements of enhanced recovery specifically address reducing these complications. In 2013, a prevalence audit confirmed a postoperative pulmonary complication rate of 16/83 (19...
January 4, 2017: Anaesthesia
https://www.readbyqxmd.com/read/28054230/tumor-necrosis-factor-alpha-and-pregnancy-focus-on-biologics-an-updated-and-comprehensive-review
#10
REVIEW
Jaume Alijotas-Reig, Enrique Esteve-Valverde, Raquel Ferrer-Oliveras, Elisa Llurba, Josep Maria Gris
Tumor necrosis factor-α (TNF-α) is a central regulator of inflammation, and TNF-α antagonists may be effective in treating inflammatory disorders in which TNF-α plays a major pathogenic role. TNF-α has also been associated with inflammatory mechanisms related to implantation, placentation, and pregnancy outcome. TNF-α is secreted by immune cells and works by binding to TNFR1 and TNFR2 cell receptors. TNF-α is also related to JAK/STAT pathways, which opens up hypothetical new targets for modifying. The accurate balance between Th1 cytokines, mainly TNF-α, Th17, and Th2, particularly IL-10 is essential to achieve good obstetric outcomes...
January 4, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28045533/computational-model-of-secondary-palate-fusion-and-disruption
#11
M Shane Hutson, Maxwell C K Leung, Nancy Baker, Richard M Spencer, Thomas B Knudsen
Morphogenetic events are driven by cell-generated physical forces and complex cellular dynamics. To improve our capacity to predict developmental effects from chemical-induced cellular alterations, we built a multi-cellular agent-based model in CompuCell3D that recapitulates the cellular networks and collective cell behavior underlying growth and fusion of the mammalian secondary palate. The model incorporated multiple signaling pathways (TGFβ, BMP, FGF, EGF, SHH) in a biological framework to recapitulate morphogenetic events from palatal outgrowth through midline fusion...
January 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28042617/temporary-systemic-inhibition-of-the-wnt-%C3%AE-catenin-pathway-promotes-regenerative-cardiac-repair-following-myocardial-infarct
#12
Dikshya Bastakoty, Sarika Saraswati, Piyush Joshi, James Atkinson, Igor Feoktistov, Jun Liu, Jennifer L Harris, Pampee P Young
AIMS: The WNT/β-catenin pathway is temporarily activated in the heart following myocardial infarction (MI). Despite data from genetic models indicating both positive and negative roles for the WNT pathway depending on the model used, the effect of therapeutic inhibition of WNT pathway on post-injury outcome and the cellular mediators involved are not completely understood. Using a newly available, small molecule, GNF-6231, which averts WNT pathway activation by blocking secretion of all WNT ligands, we sought to investigate whether therapeutic inhibition of the WNT pathway temporarily after infarct can mitigate post injury cardiac dysfunction and fibrosis and the cellular mechanisms responsible for the effects...
November 2016: Cell Stem Cells Regen Med
https://www.readbyqxmd.com/read/28040247/spermatozoa-a-relevant-biological-target-for-genotoxicity-assessment-of-contaminants-in-the-estuarine-bivalve-scrobicularia-plana
#13
Amélie Châtel, Mélanie Bruneau, Clémence Lièvre, Astrid Goupil, Catherine Mouneyrac
Evaluation of DNA quality of gametes is a relevant method to predict potential consequences of pollutants in the next generations, as it allows to define adverse outcome pathways implicated in pollutant-mediated toxicity for risk assessment. In the present study, a comet assay was developed for the spermatozoa of Scrobicularia plana exposed to 10 and 100μg/L of benzo[a]pyrene (B[a]P) for 24h and 5days. The induction of apoptosis and repair mechanisms was assessed by determining caspase-3 activity and polymerase cell nuclear antigen (PCNA) mRNA expression level...
December 28, 2016: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28039570/different-transcriptional-profiling-between-senescent-and-non-senescent-human-coronary-artery-endothelial-cells-hcaecs-by-omeprazole-and-lansoprazole-treatment
#14
Laura Costarelli, Robertina Giacconi, Marco Malavolta, Andrea Basso, Francesco Piacenza, Mauro Provinciali, Marcello G Maggio, Andrea Corsonello, Fabrizia Lattanzio
Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment...
December 30, 2016: Biogerontology
https://www.readbyqxmd.com/read/28032527/bioreactivity-of-stent-material-activation-of-platelets-coagulation-leukocytes-and-endothelial-cell-dysfunction-in-vitro
#15
Veronique Ollivier, Caroline Roques, Nicolas Receveur, Matthias Gratz, Laurent Feldman, Didier Letourneur, Christian Gachet, Pierre H Mangin, Martine Jandrot-Perrus
Outcome of patients with coronary artery disease has been significantly improved by percutaneous coronary interventions with stent implantation. However, despite progress made on devices and antithrombotic treatments, stent thrombosis remains an important issue because of serious adverse consequences. Several mechanisms are assumed to favor stent thrombosis as platelet aggregation, fibrin formation, defective healing and local inflammation. The objective of this study was to evaluate in vitro the thrombogenicity, proinflammatory properties and healing capacities of cobalt-chromium (CoCr), an alloy commonly used for cardiovascular implants...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#16
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T-cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed or refractory acute lymphoblastic leukemia (r/r ALL), has led to innovative methods for directing cytotoxic T-cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T-cells and cancer cells. Another approach infuses ex vivo-engineered T-cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28024145/calorie-restriction-prevents-the-development-of-insulin-resistance-and-impaired-lipid-metabolism-in-gestational-diabetes-offspring
#17
Tao Li, Keyang Chen, Gang Liu, Li-Ping Huang, Long Chen, Qiu-Wei Wang, Chuan-Lai Hu, Li-Juan Hou
BackgroundGestational diabetes mellitus (GDM) has long-lasting influence on offspring, which is associated with increased risks of insulin resistance, obesity and type II diabetes mellitus. Calorie restriction (CR) is one of the most common and available nutritional interventions to prevent obesity and diabetes. We are trying to explore the effect of CR on GDM offspring.MethodsThe streptozotocin was used to stimulate C57BL/6J mice to develop GDM, a number of metabolic characteristics and related protein expression were determined in GDM offspring that were fed ad-libitum or treated with calorie restriction...
December 26, 2016: Pediatric Research
https://www.readbyqxmd.com/read/28018968/atg16l1-governs-placental-infection-risk-and-preterm-birth-in-mice-and-women
#18
Bin Cao, Colin Macones, Indira U Mysorekar
The placenta is a barrier against maternal-fetal transmission of pathogens. Placental infections can cause several adverse pregnancy outcomes, including preterm birth (PTB). Yet, we have limited knowledge regarding the mechanisms the placenta uses to control infections. Here, we show that autophagy, a cellular recycling pathway important for host defense against pathogens, and the autophagy gene Atg16L1 play a key role in placental defense and are negatively associated with PTB in pregnant women. First, we demonstrate that placentas from women who delivered preterm exhibit reduced autophagy activity and are associated with higher infection indicators...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28018759/could-the-use-of-an-enhanced-recovery-protocol-in-laparoscopic-donor-nephrectomy-be-an-incentive-for-live-kidney-donation
#19
Aparna Rege, Harold Leraas, Deepak Vikraman, Kadiyala Ravindra, Todd Brennan, Tim Miller, Julie Thacker, Debra Sudan
INTRODUCTION AND BACKGROUND: Gastrointestinal (GI) recovery after major abdominal surgery can be delayed from an ongoing need for narcotic analgesia thereby prolonging hospitalization. Enhanced recovery after surgery (ERAS) is a multimodal perioperative care pathway designed to facilitate early recovery after major surgery by maintaining preoperative body composition and physiological organ function and modifying the stress response induced by surgical exposure. Enhanced recovery programs (ERPs) in colorectal surgery have decreased the duration of postoperative ileus and the hospital stay while showing equivalent morbidity, mortality, and readmission rates in comparison to the traditional standard of care...
November 22, 2016: Curēus
https://www.readbyqxmd.com/read/28017767/evaluation-of-in-vitro-assays-for-the-assessment-of-the-skin-sensitization-hazard-of-functional-polysiloxanes-and-silanes
#20
Thomas Petry, Axel Bosch, Xavier Coste, Dorothea Eigler, Pierre Germain, Shawn Seidel, Paul A Jean
The skin sensitization potential of chemicals has traditionally been evaluated in vivo according to OECD testing guidelines in guinea pigs or the mouse local lymph node assay. There has lately been a great emphasis on establishing in vitro test methods reflecting the key biological events in the adverse outcome pathway (AOP) for skin sensitization as published by the OECD. Against this background, a group of 8 polysiloxanes and silanes, seven of them aminofunctionalised, for which in vivo data were already available, has been tested in vitro in the direct peptide reactivity assay (DPRA), the KeratinoSens™ and the human cell line activation test (h-CLAT) and in the modified myeloid U937 skin sensitization test (mMUSST) as far as technically feasible...
December 22, 2016: Regulatory Toxicology and Pharmacology: RTP
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