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https://www.readbyqxmd.com/read/29236237/outcome-of-children-and-adolescents-with-central-nervous-system-tumors-in-phase-i-trials
#1
Fernando Carceller, Francisco Bautista, Irene Jiménez, Raquel Hladun-Álvaro, Cécile Giraud, Luca Bergamaschi, Madhumita Dandapani, Isabelle Aerts, François Doz, Didier Frappaz, Michela Casanova, Bruce Morland, Darren R Hargrave, Gilles Vassal, Andrew D J Pearson, Birgit Geoerger, Lucas Moreno, Lynley V Marshall
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses...
December 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29236229/model-based-therapeutic-drug-monitoring-of-infliximab-using-a-single-serum-trough-concentration
#2
David Ternant, Christophe Passot, Alexandre Aubourg, Philippe Goupille, Céline Desvignes, Laurence Picon, Thierry Lecomte, Denis Mulleman, Gilles Paintaud
BACKGROUND AND OBJECTIVES: The pharmacokinetics of infliximab are highly variable and influence clinical response in chronic inflammatory diseases. The goal of this study was to build a Bayesian model allowing predictions of upcoming infliximab concentrations and dosing regimen adjustment, using only one concentration measurement and information regarding the last infliximab infusion. METHODS: This retrospective study was based on data from 218 patients treated with infliximab in Tours University Hospital who were randomly assigned to learning (two-thirds) or validation (one-third) data subsets...
December 13, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29236219/radioresistant-sf9-insect-cells-readily-undergo-an-intrinsic-mode-of-apoptosis-in-response-to-histone-deacetylase-hdac-inhibition
#3
Jyoti Swaroop Kumar, Shubhankar Suman, Sudhir Chandna
Insect cell lines have been utilized as an important higher eukaryotic model system to decipher stress responses and cell death mechanisms. Lepidopteran Sf9 cells (derived from the ovaries of Spodoptera frugiperda) display nearly 100 times higher resistance to ionizing radiation in contrast to mammalian cells, which is partly contributed by an unusually high HDAC activity. However, their response to HDAC inhibition remains to be evaluated. In the present study, the effects of HDAC inhibitor (NaBt) on Sf9 cellular/nuclear morphology, cell cycle progression, DNA damage/repair, redox status, and mitochondrial perturbations were evaluated...
December 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29236198/sdf-1-induces-tnf-mediated-apoptosis-in-cardiac-myocytes
#4
Andrew A Jarrah, Martina Schwarskopf, Edward R Wang, Thomas LaRocca, Ashwini Dhume, Shihong Zhang, Lahouria Hadri, Roger J Hajjar, Alison D Schecter, Sima T Tarzami
Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation. One such chemokine, Stromal cell-derived factor-1 (SDF-1) also known as CXCL12, and its receptor, CXCR4, are expressed and functional in cardiac myocytes. SDF-1 both stimulates and enhances the cellular signal which attracts potentially beneficial stem cells for tissue repair within the ischemic heart. Paradoxically however, this chemokine is known to act in concert with the inflammatory cytokines of the innate immune response which contributes to cellular injury through the recruitment of inflammatory cells during ischemia...
December 13, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29236165/polyphenol-rich-curry-made-with-mixed-spices-and-vegetables-benefits-glucose-homeostasis-in-chinese-males-polyspice-study-a-dose-response-randomized-controlled-crossover-trial
#5
Sumanto Haldar, Siok Ching Chia, Sze Han Lee, Joseph Lim, Melvin Khee-Shing Leow, Eric Chun Yong Chan, Christiani Jeyakumar Henry
PURPOSE: To investigate acute effects of two doses of a polyphenol-rich curry made with seven different spices and four base vegetables, eaten with white rice, on 24 h glucose response, postprandial insulinemia, triglyceridemia and 24 h urinary total polyphenol excretion (TPE). METHODS: Randomized, controlled, dose-response crossover trial in healthy, Chinese men [n = 20, mean ± standard deviation (SD) age 23.7 ± 2.30 years, BMI 23.0 ± 2.31 kg/m2] who consumed test meals matched for calories, macronutrients and total vegetables content, consisting either Dose 0 Control (D0C) or Dose 1 Curry (D1C) or Dose 2 Curry (D2C) meal...
December 13, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29236155/oxidative-stress-response-induced-by-butachlor-in-zebrafish-embryo-larvae-the-protective-effect-of-vitamin-c
#6
Qingqing Xiang, Bofan Xu, Yilun Ding, Xiaoyi Liu, Ying Zhou, Farooq Ahmad
The widespread contamination and persistence of the herbicide butachlor in the environment resulted in the exposure of non-target organisms. The present study investigated the toxicity effect of butachlor (1-15 µmol/L) and the protective effect of vitamin C (VC) against butachlor-induced toxicity in zebrafish. It was found that butachlor significantly increased the mortality and malformation rates in a dose-dependent manner, which caused elevation in reactive oxygen species (ROS) and malondialdehyde (MDA) after 72 h exposure...
December 13, 2017: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/29235993/raman-micro-spectroscopy-analysis-of-human-lens-epithelial-cells-exposed-to-a-low-dose-range-of-ionizing-radiation
#7
Christian Harry Allen, Achint Kumar, Sami Qutob, Balazs J Nyiri, Vinita Chauhan, Sangeeta Murugkar
Recent findings in populations exposed to ionizing radiation (IR) indicate dose-related lens opacification occurs at much lower doses (< 2Gy) than indicated in radiation protection guidelines. As a result, research efforts are now being directed towards identifying early predictors of lens degeneration resulting in cataractogenesis. In this study, Raman micro-spectroscopy was used to investigate the effects of varying doses of radiation, ranging from 0.01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 hrs post-irradiation...
December 13, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29235746/clinical-problem-solving-a-tobacco-merchant-who-can-t-spit
#8
Sandra Benizri, Nancy Agmon-Levin, Noam D Kitrey, Dan Carter, Elinor Goshen, Yehonathan Sharabi
A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren's syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed...
December 2017: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/29235570/targeting-negative-regulation-of-p53-by-mdm2-and-wip1-as-a-therapeutic-strategy-in-cutaneous-melanoma
#9
Chiao-En Wu, Arman Esfandiari, Yi-Hsuan Ho, Nan Wang, Ahmed Khairallah Mahdi, Erhan Aptullahoglu, Penny Lovat, John Lunec
BACKGROUND: Cutaneous melanoma is the most serious skin malignancy and new therapeutic strategies are needed for advanced melanoma. TP53 mutations are rare in cutaneous melanoma and hence activation of wild-type p53 is a potential therapeutic strategy in cutaneous melanoma. Here, we investigated the WIP1 inhibitor, GSK2830371, and MDM2-p53 binding antagonists (nutlin-3, RG7388 and HDM201) alone and in combination treatment in cutaneous melanoma cell lines and explored the mechanistic basis of these responses in relation to the genotype and induced gene expression profile of the cells...
December 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29235518/the-efficacy-of-intensity-modulated-radiation-therapy-in-treating-thyroid-associated-ophthalmopathy-and-predictive-factors-for-treatment-response
#10
Yong-Jiang Li, Yong Luo, Xiao-Qi Xie, Wei-Min He, Cheng Yi, Ping Li, Feng Wang
The study evaluated clinical efficacy of intensity modulated radiation therapy (IMRT) in treating patients with thyroid-associated ophthalmopathy (TAO) and defined predictive factors that associated with treatment response. A total of 178 TAO patients were treated with retro-orbital IMRT with radiation dose of 20 Gy in 10 fractions. The immediate and long-term treatment response and complications were evaluated. Besides, logistic-regression analysis was conducted to identify possible predictive factors. TAO symptom score significantly fell from the initiation to 6-month post-treatment (P < 0...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235453/potential-impact-of-thermal-effects-during-ultrasonic-neurostimulation-retrospective-numerical-estimation-of-temperature-elevation-in-seven-rodent-setups
#11
Charlotte Constans, Philippe Mateo, Mickael Tanter, Jean-Francois Aubry
In the past decade, a handful but growing number of groups have reported worldwide successful low intensity focused ultrasound induced neurostimulation trials on rodents with effects ranging from movement elicitations to reduction of anesthesia time or reduction of the duration of drug induced seizures. The mechanisms underlying ultrasonic neuromodulation are still not fully understood. Given the low intensities used in most of the studies, a mechanical effect is more likely to be responsible for the neuromodulation effect, but a clear description of the thermal and mechanical effects is necessary to optimize clinical applications...
December 13, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29235439/theoretical-analysis-of-angular-distribution-of-scattering-in-nozzle-components-using-a-response-function-method-for-proton-spot-scanning-therapy
#12
Hideaki Ueda, Michihiro Furusaka, Taeko Matsuura, Shusuke Hirayama, Kikuo Umegaki
In spot-scanning proton therapy, highly precise beam control is required in the treatment nozzle such that the proton beam does not spread out during transportation by restraining the divergence of the beam angle and spot size, simultaneously. In order to evaluate the beam-broadening behaviour induced by passing through the various nozzle components, we have developed a new method to calculate the angular divergence profile of a proton beam in the nozzle. The angular divergence of the proton beam for each nozzle component is calculated by the Monte Carlo simulation code, Geant4, assuming that the initial beam has no divergence...
December 13, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29235347/nano-electromechanical-switch-based-on-a-physical-unclonable-function-for-highly-robust-and-stable-performance-in-harsh-environments
#13
Kyu-Man Hwang, Jun-Young Park, Hagyoul Bae, Seung-Wook Lee, Choong-Ki Kim, Myungsoo Seo, Hwon Im, Do-Hyun Kim, Seong-Yeon Kim, Geon-Beom Lee, Yang-Kyu Choi
A physical unclonable function (PUF) device using a nano-electromechanical (NEM) switch was demonstrated. The most important feature of the NEM-switch-based PUF is its use of stiction. Stiction is one of the chronic problems associated with micro- and nano-electromechanical system (MEMS/NEMS) devices; however, here, it was utilized to intentionally implement a PUF for hardware-based security. The stiction is caused by capillary and van der Waals forces, producing strong adhesion, which can be utilized to design a highly robust and stable PUF...
December 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/29235261/interferon-%C3%AE-2-and-interferon-%C3%AE-induce-the-degranulation-independent-production-of-vegf-a-and-il-1-receptor-antagonist-and-other-mediators-from-human-mast-cells
#14
Sharon A Oldford, Suzanne P Salsman, Liliana Portales-Cervantes, Raidan Alyazidi, Robert Anderson, Ian D Haidl, Jean S Marshall
BACKGROUND: Mast cells are resident immune effector cells, often studied in the context of allergic disease. Found in substantial numbers at sites of potential infection they are increased at sites of angiogenesis and can be pivotal for the sensing and clearance of a variety of pathogens. Interferons (IFNs) are cytokines that are critical for host defence against intracellular pathogens. Increased levels of IFNs are observed during viral infection and in autoimmune diseases. IFNs are also widely used therapeutically and have been examined in the therapy of severe asthma...
December 13, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29235124/silver-nanoparticles-increase-connexin43-mediated-gap-junctional-intercellular-communication-in-hacat-cells-through-activation-of-reactive-oxygen-species-and-mitogen-activated-protein-kinase-signal-pathway
#15
Yu Qin, Limin Han, Di Yang, Hongying Wei, Yue Liu, Junhui Xu, Herman Autrup, Furong Deng, Xinbiao Guo
Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to maintain tissue homeostasis. The aim of this study is to examine if non-coated AgNPs affect GJIC in human keratinocytes (HaCaT cells), and to identify the possible molecular mechanisms responsible for the effects. GJIC, connexin (Cx)43 protein and mRNA expression, and the effect of siRNA-mediated knockdown of Cx43 on GJIC were assessed...
December 13, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29235121/a-simple-and-rapid-hplc-uv-method-for-the-determination-of-retigabine-in-human-plasma
#16
Valentina Franco, Katia Baruffi, Giuliana Gatti, Roberto Marchiselli, Cinzia Fattore, Maria Paola Canevini, Francesca Crema, Emilio Perucca
A simple and rapid high-performance liquid chromatographic method with ultraviolet detection was developed for the quantitative determination of retigabine, known also as ezogabine, in human plasma. The assay uses a simple solid phase extraction for sample preparation and direct injection of the extract into the chromatograph. Flupirtine is used as an internal standard. Chromatographic separation is achieved on a C18 Chromolith column (Chromolith Performance, 100 x 4.6 mm ID), using as mobile phase water/acetonitrile/methanol (72:18:10 vol/vol/vol) mixed with 0...
December 12, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29235095/immune-cells-regulate-vegf-signaling-via-release-of-vegf-and-antagonistic-soluble-vegf-receptor-1
#17
Timm Hoeres, Martin Wilhelm, Manfred Smetak, Elisabeth Holzmann, Gundula Schulze-Tanzil, Josef Birkmann
Vascular endothelial growth factor (VEGF) is an important regulator of physiological and pathological angiogenesis. Beside malignant and stromal cells, local immune cells shape VEGF signaling in the tumor microenvironment. Aminobisphosphonates like zoledronic acid (Zol) are drugs known to inhibit osteoclast activity and bone resorption, but also have immunomodulatory and anti-tumor effects. These properties have previously been linked to the downregulation of VEGF and interference with tumor neo-angiogenesis...
December 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29235025/effects-of-exposure-to-malathion-on-blood-glucose-concentration-a-meta-analysis
#18
Marco Antonio Ramirez-Vargas, Eugenia Flores-Alfaro, Mayrut Uriostegui-Acosta, Patricia Alvarez-Fitz, Isela Parra-Rojas, Ma Elena Moreno-Godinez
Exposure to malathion (an organophosphate pesticide widely used around the world) has been associated with alterations in blood glucose concentration in animal models. However, the results are inconsistent. The aim of this meta-analysis was to evaluate whether malathion exposure can disturb the concentrations of blood glucose in exposed rats. We performed a literature search of online databases including PubMed, EBSCO, and Google Scholar and reviewed original articles that analyzed the relation between malathion exposure and glucose levels in animal models...
December 12, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29234869/a-controlled-trial-of-inhaled-bronchodilators-in-familial-dysautonomia
#19
Bat-El Bar-Aluma, Ori Efrati, Horacio Kaufmann, Jose-Alberto Palma, Lucy Norcliffe-Kaufmann
BACKGROUND: Chronic lung disease is a leading cause of premature death in patients with familial dysautonomia (FD). A significant number of patients have obstructive airway disease, yet it is not known whether this is pharmacologically reversible. METHODS: We conducted a double-blind, placebo-controlled, randomized clinical trial comparing the beta 2 agonist albuterol with the muscarinic blocker ipratropium bromide in patients homozygous for the IKBKAP founder mutation...
December 12, 2017: Lung
https://www.readbyqxmd.com/read/29234833/towards-a-generic-physiologically-based-kinetic-model-to-predict-in-vivo-uterotrophic-responses-in-rats-by-reverse-dosimetry-of-in-vitro-estrogenicity-data
#20
Mengying Zhang, Bennard van Ravenzwaay, Eric Fabian, Ivonne M C M Rietjens, Jochem Louisse
Physiologically based kinetic (PBK) modelling-based reverse dosimetry is a promising tool for the prediction of in vivo developmental toxicity using in vitro concentration-response data. In the present study, the potential of this approach to predict the dose-dependent increase of uterus weight in rats upon exposure to estrogenic chemicals was assessed. In vitro concentration-response data of 17β-estradiol (E2) and bisphenol A (BPA) obtained in the MCF-7/BOS proliferation assay, the U2OS ER-CALUX assay and the yeast estrogen screen (YES) assay, were translated into in vivo dose-response data in rat, using a PBK model with a minimum number of in vitro and in silico determined parameter values...
December 12, 2017: Archives of Toxicology
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