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https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#1
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28088771/do-we-still-need-cross-sectional-studies-in-nephrology-yes-we-do
#2
Giovanni Tripepi, Graziella D'Arrigo, Kitty J Jager, Vianda S Stel, Friedo W Dekker, Carmine Zoccali
Cross-sectional studies represent the second line of evidence (after case reports) in the ladder of evidence aimed at defining disease aetiology. This study design is used to generate hypotheses about the determinants of a given disease but also to investigate the accuracy of diagnostic tests and to assess the burden of a given disease in a population. The intrinsic limitation of cross-sectional studies, when applied to generate aetiological hypotheses, is that both the exposure under investigation and the disease of interest are measured at the same point in time...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088753/mitochondrial-redox-plays-a-critical-role-in-the-paradoxical-effects-of-napdh-oxidase-derived-ros-on-coronary-endothelium
#3
Ehtesham Shafique, Anali Torina, Karla Reichert, Bonnie Colantuono, Nasifa Nur, Khawaja Zeeshan, Vani Ravichandran, Yuhong Liu, Jun Feng, Khawaja Zeeshan, Laura E Benjamin, Kaikobad Irani, Elizabeth O Harrington, Frank W Sellke, Md Ruhul Abid
AIMS: There are conflicting reports on the role of reactive oxygen species (ROS) i.e. beneficial vs. harmful, in vascular endothelium. Here, we aim to examine whether duration of exposure to ROS and/or subcellular ROS levels are responsible for the apparently paradoxical effects of oxidants on endothelium. METHODS AND RESULTS: We have recently generated binary (Tet-ON/OFF) conditional transgenic mice (Tet-Nox2:VE-Cad-tTA) that can induce 1.8 ± 0.42-fold increase in NADPH oxidase (NOX)-derived ROS specifically in vascular endothelium upon withdrawal of tetracycline from the drinking water...
January 14, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28088741/prevalence-and-correlates-of-fentanyl-contaminated-heroin-exposure-among-young-adults-who-use-prescription-opioids-non-medically
#4
Alexandria Macmadu, Jennifer J Carroll, Scott E Hadland, Traci C Green, Brandon D L Marshall
BACKGROUND: The rate of overdose deaths caused by fentanyl-contaminated heroin (FCH) use is increasing rapidly in the United States. We examined risk factors for exposure to FCH and experiences with FCH use among young adult non-medical prescription opioids (NMPO) users. METHODS: We analyzed data from the Rhode Island Young Adult Prescription Drug Study (RAPiDS), which enrolled young adults aged 18 to 29 reporting prior 30day NMPO use between January 2015 and February 2016...
January 6, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28088715/micropollutant-induced-tolerance-of-in-situ-periphyton-establishing-causality-in-wastewater-impacted-streams
#5
Ahmed Tlili, Juliane Hollender, Cornelia Kienle, Renata Behra
The overarching aim of this field study was to examine causal links between in-situ exposure to complex mixtures of micropollutants from wastewater treatment plants and effects on freshwater microbial communities in the receiving streams. To reach this goal, we assessed the toxicity of serial dilutions of micropollutant mixtures, extracted from deployed passive samplers at the discharge sites of four Swiss wastewater treatment plants, to in situ periphyton from upstream and downstream of the effluents. On the one hand, comparison of the sensitivities of upstream and downstream periphyton to the micropollutant mixtures indicated that algal and bacterial communities composing the periphyton displayed higher tolerance towards these micropollutants downstream than upstream...
January 7, 2017: Water Research
https://www.readbyqxmd.com/read/28088686/immune-history-and-influenza-virus-susceptibility
#6
REVIEW
Sarah Cobey, Scott E Hensley
Antibody responses to influenza viruses are critical for protection, but the ways in which repeated viral exposures shape antibody evolution and effectiveness over time remain controversial. Early observations demonstrated that viral exposure history has a profound effect on the specificity and magnitude of antibody responses to a new viral strain, a phenomenon called 'original antigenic sin.' Although 'sin' might suppress some aspects of the immune response, so far there is little indication that hosts with pre-existing immunity are more susceptible to viral infections compared to naïve hosts...
January 12, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28088675/involvement-of-water-channel-aquaporin-5-in-h2s-induced-pulmonary-edema
#7
Chunyang Xu, Lei Jiang, Yuxia Zou, Jingjing Xing, Hao Sun, Baoli Zhu, Hengdong Zhang, Jun Wang, Jinsong Zhang
Acute exposure to hydrogen sulfide (H2S) poses a significant threat to life, and the lung is one of the primary target organs of H2S. However, the mechanisms involved in H2S-induced acute pulmonary edema are poorly understood. This study aims to investigate the effects of H2S on the expression of water channel aquaporin 5 (AQP5) and to elucidate the signaling pathways involved in AQP5 regulation. In an in vivo study, C57BL6 mice were exposed to sub-lethal concentrations of inhaled H2S, and histological injury of the lungs and ultrastructure injury of the epithelial cells were evaluated...
December 30, 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28088658/exposure-to-chronic-early-life-stress-lastingly-alters-the-adipose-tissue-the-leptin-system-and-changes-the-vulnerability-to-western-style-diet-later-in-life-in-mice
#8
K Y Yam, E F G Naninck, M R Abbink, S E la Fleur, L Schipper, J C van den Beukel, A Grefhorst, A Oosting, E M van der Beek, P J Lucassen, A Korosi
Early-life stress (ES) increases the vulnerability to develop psychopathologies and cognitive decline in adulthood. Interestingly, this is often comorbid with metabolic disorders, such as obesity. However, it is unclear whether ES leads to lasting metabolic changes and to what extent this is associated with the ES-induced cognitive impairments. Here, we used an established chronic ES mouse model (from postnatal day (P) 2 to P9) to investigate the short- and long-term effects of ES exposure on parameters of the adipose tissue and the leptin system (i...
December 23, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28088583/environmental-carcinogenesis-and-ph-homeostasis-not-only-a-matter-of-dysregulated-metabolism
#9
REVIEW
Kévin Hardonniere, Laurence Huc, Odile Sergent, Jørn A Holme, Dominique Lagadic-Gossmann
According to the World Health Organization, around 20% of all cancers would be due to environmental factors. Among these factors, several chemicals are indeed well recognized carcinogens. The widespread contaminant benzo[a]pyrene (B[a]P), an often used model carcinogen of the polycyclic aromatic hydrocarbons' family, has been suggested to target most, if not all, cancer hallmarks described by Hanahan and Weinberg. It is classified as a group I carcinogen by the International Agency for Research on Cancer; however, the precise intracellular mechanisms underlying its carcinogenic properties remain yet to be thoroughly defined...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28088544/off-site-impacts-of-wildfires-on-aquatic-systems-biomarker-responses-of-the-mosquitofish-gambusia-holbrooki
#10
Bruno Nunes, Vera Silva, Isabel Campos, Joana Luísa Pereira, Patrícia Pereira, Jan Jacob Keizer, Fernando Gonçalves, Nelson Abrantes
The number of wildfires has markedly increased in Mediterranean Europe, including in Portugal. Wildfires are environmentally concerning, not only due to the loss of biodiversity and forest area, but also as a consequence of environmental contamination by specific compounds including metals and polycyclic aromatic compounds (PAHs). These contaminants, mostly bound to ashes, can reach downstream water bodies, namely through surface runoff, being ultimately dispersed by vast areas and contacting with aquatic biota...
January 11, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28088539/the-dna-damage-response-of-c-elegans-affected-by-gravity-sensing-and-radiosensitivity-during-the-shenzhou-8-spaceflight
#11
Ying Gao, Dan Xu, Lei Zhao, Yeqing Sun
Space radiation and microgravity are recognized as primary and inevitable risk factors for humans traveling in space, but the reports regarding their synergistic effects remain inconclusive and vary across studies due to differences in the environmental conditions and intrinsic biological sensitivity. Thus, we studied the synergistic effects on transcriptional changes in the global genome and DNA damage response (DDR) by using dys-1 mutant and ced-1 mutant of C. elegans, which respectively presented microgravity-insensitivity and radiosensitivity when exposure to spaceflight condition (SF) and space radiation (SR)...
January 7, 2017: Mutation Research
https://www.readbyqxmd.com/read/28088535/neurobiological-consequences-of-juvenile-stress-a-gabaergic-perspective-on-risk-and-resilience
#12
REVIEW
Anne Albrecht, Iris Müller, Ziv Ardi, Gürsel Çalışkan, David Gruber, Sebastian Ivens, Menahem Segal, Joachim Behr, Uwe Heinemann, Oliver Stork, Gal Richter-Levin
ALBRECHT, A., MÜLLER, I., ARDI, Z., ÇALIŞKAN, G., GRUBER, D., IVENS, S., SEGAL, M., BEHR, J., HEINEMANN, U., STORK, O., and RICHTER-LEVIN, G. Neurobiological consequences of juvenile stress: a GABAergic perspective on risk and resilience. NEUROSCI BIOBEHAV REV XXX-XXX, 2016. - Childhood adversity is among the most potent risk factors for developing mood and anxiety disorders later in life. Therefore, understanding how stress during childhood shapes and rewires the brain may optimize preventive and therapeutic strategies for these disorders...
January 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28088514/assessing-the-feasibility-acceptability-and-potential-effectiveness-of-an-integrated-approach-to-smoking-cessation-for-new-and-expectant-fathers-the-dads-in-gear-study-protocol
#13
Joan L Bottorff, John L Oliffe, Gayl Sarbit, Cristina Caperchione, Marianne Clark, Anima Anand, Kym Howay
BACKGROUND: Evidence related to the effects of tobacco exposure in pregnancy and on infant and child health have focused on women's smoking cessation. Less often addressed is men's smoking, which when continued in fatherhood, reduces the chances of female partners' cessation and can negatively impact children's health as well as men's health. Dads in Gear (DIG) is an innovative program designed specifically for new fathers who want to reduce and quit smoking that includes three components: smoking cessation, fathering, and physical activity...
January 11, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28088501/a-review-of-reproductive-and-developmental-toxicity-of-silver-nanoparticles-in-laboratory-animals
#14
REVIEW
Makoto Ema, Hirokazu Okuda, Masashi Gamo, Kazumasa Honda
We summarized significant effects reported in the literature on the reproductive and developmental toxicity of silver nanoparticles (AgNPs) in laboratory animals. AgNPs showed testicular/sperm toxicity in males and ovarian and embryonic toxicity in females. Maternal injection of AgNPs delayed physical development and impaired cognitive behavior in offspring. Ag was accumulated in the testes after administration of AgNPs. AgNPs were identified in the visceral yolk sac after administration during early gestation in mice...
January 11, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28088477/selected-scorpion-toxin-exposures-induce-cytokine-release-in-human-peripheral-blood-mononuclear-cells
#15
Gerardo Corzo, Gerardo Pavel Espino-Solis
A cytokine screening on human peripheral blood mononuclear cells (PBMCs) stimulated with selected scorpion toxins (ScTx's) was performed in order to evaluate their effect on human immune cells. The ScTx's chosen for this report were three typical buthid scorpion venom peptides, one with lethal effects on mammals Centruroides suffussus suffusus toxin II (CssII), another, with lethal effects on insects and crustaceans Centruroides noxius toxin 5 (Cn5), and one more without lethal effects Tityus discrepans toxin (Discrepin)...
January 11, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28088460/ultrasound-mediated-delivery-of-rna-to-colonic-mucosa-of-live-mice
#16
Carl M Schoellhammer, Gregory Y Lauwers, Jeremy A Goettel, Matthias A Oberli, Cody Cleveland, June Y Park, Daniel Minahan, Yiyun Chen, Daniel G Anderson, Ana Jaklenec, Scott B Snapper, Robert Langer, Giovanni Traverso
BACKGROUND & AIMS: It is a challenge to deliver nucleic acids to gastrointestinal (GI) tissues due to their size and need for intracellular delivery. They are also extremely susceptible to degradation by nucleases, which are ubiquitous in the GI tract. We investigated whether ultrasound, which can permeabilize tissue through a phenomenon known as transient cavitation, can be used to deliver RNA to the colonic mucosa of living mice. METHODS: We investigated delivery of fluorescently labeled permeants to colon tissues of Yorkshire pigs ex vivo and mice in vivo...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28088432/detection-of-upper-tract-urothelial-malignancies-by-computed-tomography-urography-in-patients-referred-for-hematuria-at-a-large-tertiary-referral-center
#17
Clayton W Commander, David C Johnson, Mathew C Raynor, Lauren M Burke, Kathryn E Hacker, Bryan Hoag, Julia R Fielding, Richard C Semelka, Ellie R Lee
OBJECTIVE: To evaluate the age-stratified prevalence of upper tract urothelial malignancies diagnosed on computed tomography urography in a large cohort of patients referred for initial evaluation of hematuria. MATERIALS AND METHODS: A total of 1123 consecutive adults without a history of urothelial cancer underwent initial computed tomography urography for gross hematuria (n = 652), microscopic hematuria (n = 457), or unspecified hematuria (n = 14) at a single institution from October 2006 to October 2012...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28088424/comparison-between-conjugated-linoleic-acid-and-essential-fatty-acids-in-preventing-oxidative-stress-in-bovine-mammary-epithelial-cells
#18
L Basiricò, P Morera, D Dipasquale, A Tröscher, U Bernabucci
Some in vitro and in vivo studies have demonstrated protective effects of conjugated linoleic acid (CLA) isomers against oxidative stress and lipid peroxidation. However, only a few and conflicting studies have been conducted showing the antioxidant potential of essential fatty acids. The objectives of the study were to compare the effects of CLA to other essential fatty acids on the thiol redox status of bovine mammary epithelia cells (BME-UV1) and their protective role against oxidative damage on the mammary gland by an in vitro study...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088416/space-allowance-influences-individually-housed-holstein-bull-calf-innate-immune-measures-and-standing-behaviors-after-castration-at-3-weeks-of-age
#19
M S Calvo-Lorenzo, L E Hulbert, M A Ballou, A L Fowler, Y Luo, K C Klasing, F M Mitloehner
Dairy calves in the Southwest regions of the United States are typically raised individually in wooden hutches with 1.23 m(2) of space. The objective of the study was to determine if increased space allowance in wooden hutches influences measures of innate immunity and behaviors of Holstein bull calves pre- and postcastration. Calves were randomly assigned at 4 d of age to conventional (CONV; 1.23 m(2) of space; n = 18), moderate (MOD; 1.85 m(2) space; n = 17), or maximized space allowance (MAX; 3.71 m(2) space; n = 19) in hutches...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088397/antibiotics-in-pregnancy-increase-children-s-risk-of-otitis-media-and-ventilation-tubes
#20
Tine Marie Pedersen, Jakob Stokholm, Jonathan Thorsen, Anna-Rosa Cecilie Mora-Jensen, Hans Bisgaard
OBJECTIVES: To study the association between antibiotic intake in pregnancy and the development of otitis media and placement of ventilation tubes (VTs) in the offspring under the hypothesis that antibiotics in pregnancy may alter the offspring's propensity for disease. STUDY DESIGN: Data from the 700 children in the Copenhagen Prospective Studies on Asthma in Childhood 2010 unselected birth cohort study were used. Information on maternal antibiotic use and other exposures during pregnancy was collected prospectively from interviews and validated in national registries...
January 11, 2017: Journal of Pediatrics
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