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https://www.readbyqxmd.com/read/29141532/seizures-and-antiepileptic-drugs-from-pathophysiology-to-clinical-practice
#1
Nihan CarCaka, Cigdem Ozkara
Recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy, a common chronic neurological disorder. Recent research that has expanded the knowledge of the cellular and molecular mechanisms that modulate neuronal excitability and network activity in the brain provides the development and discovery of antiepileptic drugs (AEDs). AED therapy starts with the selection of the most appropriate drug for individual patient on the basis of strategic decision of the risk-benefit ratio...
November 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29128300/enteral-versus-parenteral-early-nutrition-in-ventilated-adults-with-shock-a-randomised-controlled-multicentre-open-label-parallel-group-study-nutrirea-2
#2
Jean Reignier, Julie Boisramé-Helms, Laurent Brisard, Jean-Baptiste Lascarrou, Ali Ait Hssain, Nadia Anguel, Laurent Argaud, Karim Asehnoune, Pierre Asfar, Frédéric Bellec, Vlad Botoc, Anne Bretagnol, Hoang-Nam Bui, Emmanuel Canet, Daniel Da Silva, Michael Darmon, Vincent Das, Jérôme Devaquet, Michel Djibre, Frédérique Ganster, Maité Garrouste-Orgeas, Stéphane Gaudry, Olivier Gontier, Claude Guérin, Bertrand Guidet, Christophe Guitton, Jean-Etienne Herbrecht, Jean-Claude Lacherade, Philippe Letocart, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Jean-Paul Mira, Saad Nseir, Gael Piton, Jean-Pierre Quenot, Jack Richecoeur, Jean-Philippe Rigaud, René Robert, Nathalie Rolin, Carole Schwebel, Michel Sirodot, François Tinturier, Didier Thévenin, Bruno Giraudeau, Amélie Le Gouge
BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation...
November 8, 2017: Lancet
https://www.readbyqxmd.com/read/29120249/alcohol-addiction-the-safety-of-available-approved-treatment-options
#3
Mariangela Antonelli, Anna Ferrulli, Luisa Sestito, Gabriele A Vassallo, Claudia Tarli, Carolina Mosoni, Maria M Rando, Antonio Mirijello, Antonio Gasbarrini, Giovanni Addolorato
Alcohol Use Disorder (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a "temporary recommendation for use" in France. Areas covered. The safety of the medications mentioned above on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed...
November 9, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29117615/safety-of-metformin-therapy-in-patients-with-type-2-diabetes-living-on-an-oxygen-deficient-plateau-tibet-china
#4
Xuemei Lv, Qian Ren, Lingli Zhou, Yanyan Geng, Jia Song, A Mina, Basang Puchi, Senlin Yang, Shuyou Meng, Lihui Yang
Background In the general population, the absolute risk of lactic acidosis in patients treated with metformin appears to be low. However, in the Tibetan plateau, an extreme oxygen-deficient environment, there are no data available concerning the safety of metformin. The aim of our study is to assess the safety of metformin in people of the plateau area. Methods We conducted an observational cross-sectional study in Tibet. All the 166 subjects were divided into two groups: T2DM+metformin group and T2DM group...
November 8, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/29115948/evaluation-of-intravenous-regional-anaesthesia-and-four-point-nerve-block-efficacy-in-the-distal-hind-limb-of-dairy-cows
#5
S Yavari, N Khraim, G Szura, A Starke, E Engelke, C Pfarrer, K Hopster, M Schmicke, W Kehler, M Heppelmann, S B R Kästner, J Rehage
BACKGROUND: Intravenous regional anaesthesia (IVRA) and hindfoot four-point nerve block anaesthesia (NBA) are recommended for local anaesthesia (LA) in the distal limb of dairy cows. Two studies were conducted to compare the efficacy, time until onset and stress responses to IVRA and NBA in dairy cows. In the first cross-over designed study, eight healthy unsedated German Holstein cows, restrained in lateral recumbency (LR) on a surgical tipping table, were treated with IVRA and NBA using procaine 2% as a local anaesthetic...
November 7, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29109483/safety-of-nonporous-silica-nanoparticles-in-human-corneal-endothelial-cells
#6
Ja-Yeon Kim, Joo-Hee Park, Martha Kim, Hyejoong Jeong, Jinkee Hong, Roy S Chuck, Choul Yong Park
Nonporous silica nanoparticles (SiNPs) are promising drug carrier platforms for intraocular drug delivery. In this study, we investigated the safety of three different sizes of SiNPs (50, 100, and 150 nm) in a human corneal endothelial cell (HCEC) line, B4G12. The HCECs were exposed to different concentrations (0, 25, 50, and 100 µg/ml) of three sizes of SiNPs for up to 48 h. Cellular viability, autophagy, lactate dehydrogenase (LDH) assay, and mammalian target of rapamycin (mTOR) pathway activation were evaluated...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107441/real-life-experience-with-hydroxyurea-in-sickle-cell-disease-a-multicenter-study-in-a-cohort-of-patients-with-heterogeneous-descent
#7
Paolo Rigano, Lucia De Franceschi, Laura Sainati, Antonio Piga, Frédéric B Piel, Maria Domenica Cappellini, Carmelo Fidone, Nicoletta Masera, Giovanni Palazzi, Barbara Gianesin, Gian Luca Forni
We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: <1year to 29years) at a mean therapeutic dose of 18±4.7mg/kg/day. Hydroxyurea was associated with a significant increase in mean total and fetal hemoglobin and a significant decrease in mean hemoglobin S, white blood and platelet counts, and lactate dehydrogenase levels...
October 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29103687/reproduction-of-respiratory-mycoplasmosis-in-calves-by-exposure-to-an-aerosolised-culture-of-mycoplasma-bovis
#8
Anna Kanci, Nadeeka K Wawegama, Marc S Marenda, Peter D Mansell, Glenn F Browning, Philip F Markham
Mycoplasma bovis is an important pathogen of cattle, causing pneumonia, arthritis and otitis media in young calves, and mastitis in lactating cows, resulting in increased morbidity and, in some instances, mortality. The objective of this study was to evaluate the survival of a M. bovis isolate following nebulisation and to establish whether respiratory disease similar to that seen in the field could be induced in calves by exposing them to an aerosolised culture of M. bovis. A group of eight M. bovis-free calves 14-28days old were exposed to an aerosolised culture of a field isolate of M...
October 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29091796/tbbpa-disposition-and-kinetics-in-pregnant-and-nursing-wistar-han-igs-rats
#9
Gabriel A Knudsen, Samantha M Hall, Alicia C Richards, Linda S Birnbaum
Tetrabromobisphenol-A (TBBPA) is a brominated flame retardant (BFR) commonly used in electronics to meet fire safety standards and has the largest worldwide production of any BFR. TBBPA has been detected in human breast milk and maternal/cord serum, indicating exposure to mothers, fetuses, and breastfeeding newborns although exposure to fetuses and newborns is poorly understood. Pregnant or nursing Wistar Han IGS rats were administered [(14)C]-TBBPA in a single dose (25 mg/kg, 2.5 μCi/kg) and euthanized between 0...
October 28, 2017: Chemosphere
https://www.readbyqxmd.com/read/29076657/safety-profile-of-a-replication-deficient-human-adenovirus-vectored-foot-and-mouth-disease-virus-serotype-a24-subunit-vaccine-in-cattle
#10
J Barrera, D A Brake, B J Kamicker, C Purcell, R Kaptur, T Schieber, K Lechtenberg, T D Miller, D Ettyreddy, D E Brough, B T Butman, M Colby, J G Neilan
The safety of a replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was evaluated in five independent safety studies. The target animal safety studies were designed in compliance with United States (U.S.) regulatory requirements (Title 9, U.S. Code of Federal Regulation [9CFR]) and international standard guidelines (VICH Topic GL-44) for veterinary live vaccines. The first three studies were conducted in a total of 22 vaccinees and demonstrated that the AdtA24 master seed virus (MSV) was safe, did not revert to virulence and was not shed or spread from vaccinees to susceptible cattle or pigs...
October 27, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29070107/-clinical-analysis-of-7-children-with-mature-b-cell-acute-lymphoblastic-leukemia
#11
Jun Wang, Qin Lu, Lu-Lu He, Xiao-Yan Sun, Meng-Jiao Sun, Yong-Jun Fang
OBJECTIVE: To evaluate the efficacy of CCCG-BNHL-2015 protocol in treatment of children with mature B-cell acute lymphoblastic leukemia (mature B-ALL). METHODS: Seven pediatric patients with newly diagnosed mature B-ALL were treated by CCCG-BNHL-2015 protocol (risk group R4) in Children's Hospital of Nanjing Medical University from November 2014 to January 2017. RESULTS: The median age of patients at initial diagnosis was 7.2 years (range 4...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29067001/culture-in-glucose-depleted-medium-supplemented-with-fatty-acid-and-3-3-5-triiodo-l-thyronine-facilitates-purification-and-maturation-of-human-pluripotent-stem-cell-derived-cardiomyocytes
#12
Bin Lin, Xianming Lin, Maxine Stachel, Elisha Wang, Yumei Luo, Joshua Lader, Xiaofang Sun, Mario Delmar, Lei Bu
With recent advances in stem cell technology, it is becoming efficient to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes, which can subsequently be used for myriad purposes, ranging from interrogating mechanisms of cardiovascular disease, developing novel cellular therapeutic approaches, as well as assessing the cardiac safety profile of compounds. However, the relative inability to acquire abundant pure and mature cardiomyocytes still hinders these applications. Recently, it was reported that glucose-depleted culture medium supplemented with lactate can facilitate purification of hPSC-derived cardiomyocytes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29046247/optimal-usage-of-radium-223-in-metastatic-castration-resistant-prostate-cancer
#13
REVIEW
Tai-Lung Cha, Tony Tong-Lin Wu, Nicholas John Vogelzang, Chao-Yuan Huang, Shu-Pin Huang, Chia-Chi Lin, Yen-Chuan Ou, See-Tong Pang, Daniel Heung-Yuan Shen, Wen-Jeng Wu, Wayne Yen-Hwa Chang
Radium-223 is a first-in-class α-emitting radiopharmaceutical that targets bone metastases associated with metastatic castration-resistant prostate cancer (mCRPC). In the pivotal phase III trial ALSYMPCA, radium-223 significantly increased overall survival (OS), compared with placebo (median 14.9 vs 11.3 months; hazard ratio 0.70; 95% CI 0.58-0.83; p < 0.001), in patients with mCRPC and symptomatic bone metastases-with a comparable safety profile. To optimize treatment outcomes, selection of appropriate patients is important...
November 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29036695/identifying-greener-and-safer-plasticizers-a-4-step-approach
#14
Océane Albert, Thomas C Nardelli, Barbara F Hales, Bernard Robaire
The health and economic burden of endocrine disrupting chemicals, such as the plasticizer di(2-ethylhexyl) phthalate (DEHP), is prompting industry to develop alternatives. However, the absence of requirements for manufacturers to ensure the safety of these alternatives has led to the generation of replacements that may have similar or worse effects than the original chemicals. Consequently, there is increasing recognition by scientists, regulators and industry that proactive approaches are needed to develop safe chemical substitutes...
August 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29025961/phosphate-replacement-in-the-critically-ill-potential-implications-for-military-patients
#15
A E Coulden, L J Rickard, N Crooks, N Arora
BACKGROUND: Severe hypophosphataemia in the intensive care unit (ICU) setting has been widely associated with adverse clinical outcomes across multiple organ systems, as well as increased mortality. However, the clinical significance of mild or moderate hypophosphataemia remains uncertain. This can lead to heterogeneous phosphate replacement protocols across different institutions. The aim of this study was to assess the significance of mild and moderate hypophosphataemia on clinical outcomes across several organ systems...
October 12, 2017: Journal of the Royal Army Medical Corps
https://www.readbyqxmd.com/read/29020341/percutaneous-short-term-active-mechanical-support-devices-in-cardiogenic-shock-a-systematic-review-and-collaborative-meta-analysis-of-randomized-trials
#16
Holger Thiele, Alexander Jobs, Dagmar M Ouweneel, Jose P S Henriques, Melchior Seyfarth, Steffen Desch, Ingo Eitel, Janine Pöss, Georg Fuernau, Suzanne de Waha
Aims: Evidence on the impact on clinical outcome of active mechanical circulatory support (MCS) devices in cardiogenic shock (CS) is scarce. This collaborative meta-analysis of randomized trials thus aims to investigate the efficacy and safety of percutanzeous active MCS vs. control in CS. Methods and results: Randomized trials comparing percutaneous active MCS to control in patients with CS were identified through searches of medical literature databases. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated to analyse the primary endpoint of 30-day mortality and device-related complications including bleeding and leg ischaemia...
July 7, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28993014/-r-%C3%AE-lipoyl-gly-l-pro-l-glu-dimethyl-ester-as-dual-acting-agent-for-the-treatment-of-alzheimer-s-disease
#17
Lisa Marinelli, Erika Fornasari, Antonio Di Stefano, Hasan Turkez, Mehmet Enes Arslan, Piera Eusepi, Michele Ciulla, Ivana Cacciatore
In this study, effects of LA-GPE (R-α-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester) and GPE (Gly-L-Pro-L-Glu) on the cytotoxic action of Aβ1-42 were tested with differentiated human neuroblastoma SH-SY5Y cells as cellular Alzheimer model via measurements of mitochondrial viability (MTT assay) and lactate dehydrogenase release (LDH assay). Effects of LA-GPE and GPE on acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels, and neural cell apoptosis and necrosis were also determined...
December 2017: Neuropeptides
https://www.readbyqxmd.com/read/28991513/long-term-outcomes-in-patients-with-braf-v600-mutant-metastatic-melanoma-who-received-dabrafenib-combined-with-trametinib
#18
Georgina V Long, Zeynep Eroglu, Jeffrey Infante, Sapna Patel, Adil Daud, Douglas B Johnson, Rene Gonzalez, Richard Kefford, Omid Hamid, Lynn Schuchter, Jonathan Cebon, William Sharfman, Robert McWilliams, Mario Sznol, Suman Redhu, Eduard Gasal, Bijoyesh Mookerjee, Jeffrey Weber, Keith T Flaherty
Purpose To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1:1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2)...
October 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28987016/sensitivity-of-aspiration-as-a-safety-test-before-injection-of-soft-tissue-fillers
#19
Jani Aj Van Loghem, James J Fouché, Job Thuis
BACKGROUND: Embolism due to accidental intra-arterial injection of a soft tissue filler (STF) can lead to serious complications. Physicians practice aspiration as a safety test before injection to rule out intra-arterial placement of the needle tip. The value of aspiration as a safety test is evaluated in this study, which also considered the rheological properties of different STFs and their needle dimensions. METHODS: Aspiration with eleven different needle sizes and 24 different STFs was performed using Ringer's lactate (RL) colored with blue skin marking ink and secondly an empty saline bag containing anticoagulated blood, both pressurized to 150 mm Hg to mimic arterial blood pressure...
October 7, 2017: Journal of Cosmetic Dermatology
https://www.readbyqxmd.com/read/28986290/assessment-of-hepatic-metabolism-dependent-nephrotoxicity-on-an-organs-on-a-chip-microdevice
#20
Zhongyu Li, Lei Jiang, Yujuan Zhu, Wentao Su, Cong Xu, Tingting Tao, Yang Shi, Jianhua Qin
Drug-induced nephrotoxicity is one of the most frequent adverse events in pharmacotherapy. It has resulted in numerous clinical trial failures and high drug development costs. The predictive capabilities of existing in vitro models are limited by their inability to recapitulate the complex process of drug metabolism at the multi-organ level in vivo. We present a novel integrated liver-kidney chip that allows the evaluation of drug-induced nephrotoxicity following liver metabolism in vitro. The liver-kidney chip consists of two polydimethylsiloxane layers with compartmentalized micro-channels separated by a porous membrane...
October 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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