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Alessandra Gasior, Giulia Brisighelli, Karen Diefenbach, Victoria Alison Lane, Carlos Reck, Richard J Wood, Marc Levitt
Introduction Functional constipation is a common problem in children. It usually can be managed with laxatives but a small subset of patients develop intolerable cramps and need to be temporarily treated with enemas. The senior author has previously reported: 1) open sigmoid resection as a surgical option, but this did not sufficiently reduce the laxative need, then 2) a transanal approach (with resection of rectosigmoid), but this led to a high rate of soiling due to extensive stretching of the anal canal and loss of the rectal reservoir...
October 25, 2016: European Journal of Pediatric Surgery
Wen-Lei Shi, Ting Zhang, Jiang-Rui Zhou, Yong-Hua Huang, Chun-Lei Jiang
Glucocorticoids (GCs) play a vital role in the regulation of blood pressure by their permissive effects in potentiating vasoactive responses to catecholamines through glucocorticoid receptors. GCs achieve this function by controlling vascular smooth muscle tone. Clinically, low to moderate doses of GCs are generally used in the treatment of septic shock in recent years. GCs are now known to have both genomic and non-genomic effects. While genomic effects of GCs were well studied, few non-genomic effects were reported, much less the non-genomic mechanisms...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bakhta Aouey, Amira Mahjoubi Samet, Hamadi Fetoui, Monique S J Simmonds, Mohamed Bouaziz
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Vitis vinifera is used in traditional medicine for diarrhea, hepatitis and stomachaches. The objective of this study was to investigate the anti-oxidant, anti-inflammatory, analgesic and antipyretic properties of the hydroalcoholic leaf extract of Vitis vinifera (EVV) on experimental models to provide scientific basis for its use. MATERIALS AND METHODS: The EVV was chemically characterized by LC-MS/MS analyses. The in vitro antioxidant activities of the EVV extract were measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and Ferric reducing antioxidant power assay (FRAP)...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Per Erik Karlsson, Jenny Klingberg, Magnuz Engardt, Camilla Andersson, Joakim Langner, Gunilla Pihl Karlsson, Håkan Pleijel
This review summarizes new information on the current status of ground-level ozone in Europe north of the Alps. There has been a re-distribution in the hourly ozone concentrations in northern Europe during 1990-2015. The highest concentrations during summer daytime hours have decreased while the summer night-time and winter day- and night-time concentrations have increased. The yearly maximum 8-h mean concentrations ([O3]8h,max), a metric used to assess ozone impacts on human health, have decreased significantly during 1990-2015 at four out of eight studied sites in Fennoscandia and northern UK...
October 22, 2016: Science of the Total Environment
Anthony M Cadena, Edwin C Klein, Alexander G White, Jaime A Tomko, Chelsea L Chedrick, Douglas S Reed, Laura E Via, Philana Ling Lin, JoAnne L Flynn
Identifying and refining small-animal models of tuberculosis that recapitulate aspects of human Mycobacterium tuberculosis infection can contribute to advancing our understanding of critical facets of the disease. To study the effects of very low-dose infections with 2 strains of M. tuberculosis on disease progression and survival in common marmosets, animals were challenged with strains Erdman and CDC1551 at doses ranging from 1 to 12 cfu. These data revealed that the susceptibility of marmosets to M. tuberculosis infection is influenced by strain virulence and initial dose...
2016: Comparative Medicine
Jeppe H Ekberg, Maria Hauge, Line V Kristensen, Andreas N Madsen, Maja S Engelstoft, Anna-Sofie Husted, Rasmus Sichlau, Kristoffer L Egerod, Pascal Timshel, Timothy J Kowalski, Fiona M Gribble, Frank Reiman, Harald S Hansen, Andrew D Howard, Birgitte Holst, Thue W Schwartz
Triglycerides are among the most efficacious stimulators of incretin secretion; however the relative importance of FFA1 (GPR40), FFA4 (GPR120) and GPR119 which all recognize triglyceride metabolites, i.e. LCFA and 2-MAG respectively, is still unclear. Here, we find all three receptors to be highly expressed and highly enriched in FACS-purified GLP-1 and GIP cells isolated from transgenic reporter mice. In vivo, the triglyceride-induced increase in plasma GIP was significantly reduced in FFA1 deficient mice (to 34% - mean of four experiments each with 8-10 animals), in GPR119 deficient mice (to 24 %) and in FFA1/FFA4 double deficient mice (to 15%) but not in FFA4 deficient mice...
October 25, 2016: Endocrinology
Chi F Hung, Yu-Hua Chow, W Conrad Liles, William A Altemeier, Lynn M Schnapp
: We previously demonstrated that FoxD1-derived cells in the lung are enriched in pericyte-like cells in mouse lung. These cells express the common pericyte markers and are located adjacent to endothelial cells. In this study we demonstrate the feasibility of administering diphtheria toxin (DT) by oropharyngeal aspiration as an approach to ablate FoxD1-derived cells. METHOD: We crossed mice expressing Cre-recombinase under the FoxD1 promoter to Rosa26-loxP-STOP-loxP-iDTR mice and generated a bitransgenic line (FoxD1-Cre;Rs26-iDTR) where FoxD1-derived cells heritably express iDTR and are sensitive to DT...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
Gregory Peter Horne, Thomas Ashley Donoclift, Howard Sims, Robin Orr, Simon M Pimblott
A multi-scale modelling approach has been developed for the extended timescale long-term radiolysis of aqueous systems. The approach uses a combination of stochastic track structure and track chemistry as well as deterministic homogeneous chemistry techniques and involves four key stages; radiation track structure simulation, the subsequent physicochemical processes, nonhomogeneous diffusion-reaction kinetic evolution, and homogeneous bulk chemistry modelling. The first three components model the physical and chemical evolution of an isolated radiation chemical track and provide radiolysis yields, within the extremely low dose isolated track paradigm, as the input parameters for a bulk deterministic chemistry model...
October 25, 2016: Journal of Physical Chemistry. B
Dian Su, Carl K Ng, Mehraban Khosraviani, Shang-Fan Yu, Ely Cosino, Surinder Kaur, Keyang Xu
Affinity capture liquid chromatography-mass spectrometry (LC-MS) intact antibody assay has been widely used for direct drug-to-antibody ratio (DAR) and catabolite characterization of antibody-drug conjugates (ADCs). However, the intact mass spectra of new ADCs, which incorporate new types of linkers and/or payloads other than maytansines and auristatins, are more complex than those examined previously. The current method has showed some limitations in elucidating certain structural modifications. Herein, we report an alternative analytical approach for ADCs, such as THIOMABTM antibody-drug conjugates (TDCs), where the linker-drugs are site-specifically conjugated in the Fab region...
October 25, 2016: Analytical Chemistry
Amanda N Fletcher, Agostino Molteni, Rakesh Ponnapureddy, Chirag Patel, Mark Pluym, Alan M Poisner
BACKGROUND: Fat embolism (FE) and the consequent fat embolism syndrome (FES) occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FES is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system (RAS) plays a significant role in the pathophysiology of FE since drugs interfering with the RAS, captopril and losartan, reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model...
October 25, 2016: Journal of Trauma and Acute Care Surgery
Nanette Santoro, Amanda Allshouse, Genevieve Neal-Perry, Lubna Pal, Rogerio A Lobo, Frederick Naftolin, Dennis M Black, Eliot A Brinton, Matthew J Budoff, Marcelle I Cedars, N Maritza Dowling, Mary Dunn, Carey E Gleason, Howard N Hodis, Barbara Isaac, Maureen Magnani, JoAnn E Manson, Virginia M Miller, Hugh S Taylor, Whitney Wharton, Erin Wolff, Viola Zepeda, S Mitchell Harman
OBJECTIVE: The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years. METHODS: A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275)...
October 24, 2016: Menopause: the Journal of the North American Menopause Society
Heather K Neilson, Megan S Farris, Chelsea R Stone, Marcus M Vaska, Darren R Brenner, Christine M Friedenreich
OBJECTIVE: Physical inactivity increases postmenopausal and possibly premenopausal breast cancer risk, although different biologic mechanisms are proposed. Our primary objective was to estimate breast cancer risk associated with high versus low levels of moderate-vigorous recreational activity, separately for premenopausal and postmenopausal women. METHODS: We conducted a systematic review of literature published to July 2015. Included reports were cohort or case-control studies relating moderate-vigorous recreational physical activity (metabolic equivalent ≥3...
October 24, 2016: Menopause: the Journal of the North American Menopause Society
Christoph Töpper, Cathérine Louise Steinbach, Christoph Dorn, Alexander Kratzer, Sebastian G Wicha, Michael Schleibinger, Uwe Liebchen, Frieder Kees, Bernd Salzberger, Martin G Kees
BACKGROUND: Standard doses of linezolid may not be suitable for all patient groups. ICU patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. PATIENTS AND METHODS: Plasma concentrations of linezolid were determined by HPLC in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7...
October 24, 2016: Therapeutic Drug Monitoring
H Satoh, R Kondo, T Shinoda, S Idaka, K Ishigami, S Shiotani
Recent progress in endoscopic techniques has revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but effective therapy is not available at present. In the present study, we investigated the effects of feeding condition and the amount of dietary fiber (DF) in the diet on the formation of gastrointestinal ulcers induced by NSAIDs in dogs. Several types of diets containing various percentages of DF were given to dogs. Indomethacin (1 or 3 mg/kg, p.o...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Jack H Crawford, Matthew S Hull, Santiago Borasino, Brad L Steenwyk, Kristal M Hock, Kevin Wall, Jeffrey A Alten
BACKGROUND: Cardiopulmonary bypass (CPB) may lead to adrenal insufficiency (AI). Emerging evidence supports association of AI with morbidity after cardiac surgery. AIMS: The aim of this study was to define AI incidence in neonates undergoing complex cardiac surgery with CPB and its association with intraoperative post-CPB outcomes. METHODS: Forty subjects enrolled in a prior randomized control trial who received preoperative methylprednisolone as part of our institutional neonatal bypass protocol were included...
October 25, 2016: Paediatric Anaesthesia
Cheong K C Kwong Chung, Francesca Ronchi, Markus B Geuking
Healthy host-microbial mutualism relies on compartmentalization and proper regulation of systemic and mucosal immune responses. Nevertheless, the systemic immune system is frequently exposed to bouts of bacteraemia, which can trigger systemic antimicrobial immune reactivity including CD4(+) T cells. Low level bacteraemia can occur when immune compartmentalization is compromised, for example in the presence of innate immune deficiency or following use of nonsteroidal anti-inflammatory drugs (NSAID). We generated an Escherichia coli strain expressing a defined T helper neo-epitope to study systemic antigen-specific antimicrobial CD4(+) T cells and their potential involvement in the pathogenicity of inflammatory bowel diseases (IBD)...
October 24, 2016: Immunology
Jin-Hui Ma, Wan-Shou Guo, Zi-Rong Li, Bai-Liang Wang
BACKGROUND: Systemic administration of bisphosphonates has shown promising results in the treatment of osteonecrosis of the femoral head (ONFH). However, few studies have evaluated the efficacy of local zoledronate (ZOL) administration in the treatment of ONFH. The purpose of this study was to investigate whether local administration of bisphosphonate-soaked hydroxyapatite (HA) could improve bone healing in an experimental rabbit model of ONFH. METHODS: This experimental study was conducted between October 2014 and June 2015...
2016: Chinese Medical Journal
Andrzej Wojcik, Ursula Oestreicher, Lleonard Barrios, Anne Vral, Georgia Terzoudi, Elizabeth Ainsbury, Kai Rothkamm, Francois Trompier, Ulrike Kulka
PURPOSE: To set up an operational basis of the Realizing the European Network of Biodosimetry (RENEB) network within which the application of seven established biodosimetric tools (the dicentric assay, the FISH assay, the micronucleus assay, the PCC assay, the gamma-H2AX assay, electron paramagnetic resonance and optically stimulated luminescence) will be compared and standardized among the participating laboratories. METHODOLOGY: Two intercomparisons were organized where blood samples and smartphone components were irradiated, coded and sent out to participating laboratories for dosimetric analysis...
October 25, 2016: International Journal of Radiation Biology
Benoît Silvestre de Ferron, Catherine Vilpoux, Myriam Kervern, Alexandre Robert, Johan Antol, Mickael Naassila, Olivier Pierrefiche
Low to moderate perinatal ethanol exposure (PEE) may have disastrous consequences for the central nervous system resulting notably in permanent cognitive deficits. Learning and memory are mediated in the hippocampus by long-term potentiation (LTP) and long term depression (LTD), two forms of synaptic plasticity. PEE decreases LTP but also abnormally facilitates LTD (Kervern et al. ) through a presently unknown mechanism. We studied in rat hippocampus slice, the involvement of the chloride co-transporters NKCC1 and KCC2, in the role of GABAA inhibitions in facilitated LTD after moderate PEE...
October 25, 2016: Addiction Biology
M Viprey, R Jeannin, V Piriou, P Chevalier, C Michel, G Aulagner, J Berthiller, X Armoiry
WHAT IS KNOWN AND OBJECTIVE: The complex dose regimens of the direct-acting oral anticoagulants (DOAC) make their appropriate prescribing highly challenging. Inappropriate prescribing of the DOAC remains poorly addressed. We studied the patterns of DOAC prescription and estimated the prevalence of drug-related problems (DRPs) associated with their use. METHODS: A cross-sectional study was conducted using data from medical records system of the Lyon teaching hospitals...
October 24, 2016: Journal of Clinical Pharmacy and Therapeutics
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