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https://www.readbyqxmd.com/read/28539002/from-in-vivo-to-in-vitro-the-medical-device-testing-paradigm-shift
#1
Dayna Kerecman Myers, Alan M Goldberg, Albrecht Poth, Michael F Wolf, Joseph Carraway, James McKim, Kelly P Coleman, Richard Hutchinson, Ronald Brown, Harald F Krug, Anthony Bahinski, Thomas Hartung
Amid growing efforts to advance the replacement, reduction, and refinement of the use of animals in research, there is a growing recognition that in vitro testing of medical devices can be more effective, both in terms of cost and time, and also more reliable than in vivo testing. Although the technological landscape has evolved rapidly in support of these concepts, regulatory acceptance of alternative testing methods has not kept pace. Despite the acceptance by regulators of some in vitro tests (cytotoxicity, gene toxicity, and some hemocompatibility assays), many toxicity tests still rely on animals (irritation, sensitization, acute toxicity, reproductive/developmental toxicity), even where other industrial sectors have already abandoned them...
May 25, 2017: ALTEX
https://www.readbyqxmd.com/read/28538848/-chemoprotective-effect-of-the-alkaloid-extract-of-melocactus-bellavistensis-against-colon-cancer-induced-in-rats-using-1-2-dimethylhydrazine
#2
Karla Ríos-León, Cesar Fuertes-Ruiton, Jorge Arroyo, Julio Ruiz
Objectives: To determine the toxicity and chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine (DMH). Materials and methods: The alkaloid extract was obtained from the fleshy part of M. bellavistensis, and an acute toxicity test was then carried out on 30 mice of the Balb C57 strain. To assess its chemoprotective effect, colon cancer was induced in 45 Holtzman rats using DMH according to the following experimental design: one control group received 2 mL/kg sodium polysorbate, and four groups received 20 mg/kg DMH plus 0, 1, 5, or 10 mg/kg M...
January 2017: Revista Peruana de Medicina Experimental y Salud Pública
https://www.readbyqxmd.com/read/28538816/antioxidant-effect-of-quinoline-derivatives-containing-or-not-selenium-relationship-with-antinociceptive-action-quinolines-are-antioxidant-and-antinociceptive
#3
Ethel A Wilhelm, Ana Teresinha Ferreira, Mikaela P Pinz, Angélica S Dos Reis, Ane G Vogt, Andre L Stein, Gilson Zeni, Cristiane Luchese
The present study investigated the antioxidant effect of a new class of quinoline derivatives (a-d) on assays in vitro. Lipid peroxidation, thiol peroxidase-like and free radical scavenging activities were determined to evaluate antioxidant activity of compounds. Thiol oxidase-like and δ-aminolevulinate dehydratase activities were performed as a toxicological parameter. A second objective of this study was to evaluate the in vivo antinociceptive effect of the compound with better antioxidant effect and without toxic effects in a model of nociception induced by formalin in mice...
May 22, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#4
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538697/mammalian-metallothionein-3-new-functional-and-structural-insights
#5
REVIEW
Milan Vašák, Gabriele Meloni
Metallothionein-3 (MT-3), a member of the mammalian metallothionein (MT) family, is mainly expressed in the central nervous system (CNS). MT-3 possesses a unique neuronal growth inhibitory activity, and the levels of this intra- and extracellularly occurring metalloprotein are markedly diminished in the brain of patients affected by a number of metal-linked neurodegenerative disorders, including Alzheimer's disease (AD). In these pathologies, the redox cycling of copper, accompanied by the production of reactive oxygen species (ROS), plays a key role in the neuronal toxicity...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538692/exploring-anti-prion-glyco-based-and-aromatic-scaffolds-a-chemical-strategy-for-the-quality-of-life
#6
REVIEW
María Teresa Blázquez-Sánchez, Ana M de Matos, Amélia P Rauter
Prion diseases are fatal neurodegenerative disorders caused by protein misfolding and aggregation, affecting the brain progressively and consequently the quality of life. Alzheimer's is also a protein misfolding disease, causing dementia in over 40 million people worldwide. There are no therapeutics able to cure these diseases. Cellular prion protein is a high-affinity binding partner of amyloid β (Aβ) oligomers, the most toxic species in Alzheimer's pathology. These findings motivate the development of new chemicals for a better understanding of the events involved...
May 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28538683/metabolic-investigations-of-the-molecular-mechanisms-associated-with-parkinson-s-disease
#7
REVIEW
Robert Powers, Shulei Lei, Annadurai Anandhan, Darrell D Marshall, Bradley Worley, Ronald L Cerny, Eric D Dodds, Yuting Huang, Mihalis I Panayiotidis, Aglaia Pappa, Rodrigo Franco
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies) and the associated loss of dopaminergic cells in the substantia nigra. Mutations in genes such as α-synuclein (SNCA) account for only 10% of PD occurrences. Exposure to environmental toxicants including pesticides and metals (e.g., paraquat (PQ) and manganese (Mn)) is also recognized as an important PD risk factor. Thus, aging, genetic alterations, and environmental factors all contribute to the etiology of PD...
May 24, 2017: Metabolites
https://www.readbyqxmd.com/read/28538674/biosynthesis-of-zno-nanoparticles-by-a-new-pichia-kudriavzevii-yeast-strain-and-evaluation-of-their-antimicrobial-and-antioxidant-activities
#8
Amin Boroumand Moghaddam, Mona Moniri, Susan Azizi, Raha Abdul Rahim, Arbakariya Bin Ariff, Wan Zuhainis Saad, Farideh Namvar, Mohammad Navaderi
The potential ability of a new yeast strain, Pichia kudriavzevii, in the synthesis of zinc oxide nanoparticles (ZnO-NPs) through a green method was explored in this study. The effect of reaction time (12, 24 and 36 h) on the structure of the resulting ZnO nanoparticles was investigated. From the XRD and TEM results, the ZnO-NPs with a hexagonal wurtzite structure and a particle crystal size of ~10-61 nm was formed at different reaction times. Combing XRD, TEM, and PL results, it was revealed that the sample prepared at intermediate duration (24 h) has the most favorable nanosized structure with the lowest defect concentration...
May 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28538654/a-monitoring-system-for-laying-hens-that-uses-a-detection-sensor-based-on-infrared-technology-and-image-pattern-recognition
#9
Mauro Zaninelli, Veronica Redaelli, Fabio Luzi, Valentino Bontempo, Vittorio Dell'Orto, Giovanni Savoini
In Italy, organic egg production farms use free-range housing systems with a big outdoor area and a flock of no more than 500 hens. With additional devices and/or farming procedures, the whole flock could be forced to stay in the outdoor area for a limited time of the day. As a consequence, ozone treatments of housing areas could be performed in order to reduce the levels of atmospheric ammonia and bacterial load without risks, due by its toxicity, both for hens and workers. However, an automatic monitoring system, and a sensor able to detect the presence of animals, would be necessary...
May 24, 2017: Sensors
https://www.readbyqxmd.com/read/28538613/acute-retinal-damage-after-using-a-toxic-perfluoro-octane-for-vitreo-retinal-surgery
#10
J Carlos Pastor, Rosa M Coco, Ivan Fernandez-Bueno, Maria L Alonso-Alonso, Jesús Medina, Aurelio Sanz-Arranz, Fernando Rull, Manuel J Gayoso, Antonio Dueñas, Maria T Garcia-Gutierrez, Lucia Gonzalez-Buendia, Santiago Delgado-Tirado, Emilio Abecia, Miguel Ruiz-Miguel, Miguel A Serrano, Jose M Ruiz-Moreno, Girish K Srivastava
PURPOSE: To describe a series of retinal acute toxicity cases with severe visual loss after intraocular use of a toxic perfluoro-octane (PFO). The clinical presentation is described, and the likely causes are analyzed. New biological methods for testing safety of intraocular medical devices are proposed. METHODS: Information regarding a series of eyes suffering acute severe events after intraocular use of a toxic PFO was analyzed. Four types of spectroscopy, nuclear magnetic resonance, and chromatography were used to identify the potential PFO contaminants...
June 2017: Retina
https://www.readbyqxmd.com/read/28538284/the-advance-study-a-groundbreaking-trial-to-evaluate-a-candidate-universal-antiretroviral-regimen
#11
Willem D F Venter, Polly Clayden, Celicia Serenata
PURPOSE OF REVIEW: Current WHO-recommended first-line therapy in low-income and middle-income countries has been very successful in saving millions of lives but still has toxicity concerns and a low barrier to resistance. RECENT FINDINGS: Two candidate antiretrovirals may substantially transform first-line therapy in low-income and middle-income countries, yielding a safer, more robust and cheaper regimen. Tenofovir alafenamide carries toxicity and cost benefits over tenofovir disoproxil fumarate...
May 19, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28538228/glycemic-control-in-the-treatment-of-psoriasis
#12
Wilfred Ip, Mark G Kirchhof
Psoriasis is a common chronic inflammatory skin disease that manifests as scaly erythematous plaques as a consequence of keratinocyte hyperproliferation and inflammation. It is commonly associated with diabetes, obesity, and the metabolic syndrome. While there are numerous approved treatment options available, they have limitations including availability, toxicities such as immunosuppression, and high cost. There is increasing evidence to suggest that several hypoglycemic agents used in the treatment of type 2 diabetes, including glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, thiazolidinediones and biguanides, exert beneficial effects in psoriasis...
May 25, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28538211/the-oxido-metabolic-driver-atf4-enhances-temozolamide-chemo-resistance-in-human-gliomas
#13
Daishi Chen, Manfred Rauh, Michael Buchfelder, Ilker Y Eyupoglu, Nicolai Savaskan
Malignant gliomas are devastating neoplasia with limited curative treatment options. Temozolomide (TMZ, Temcat®, Temodal® or Temodar®) is a first-line treatment for malignant gliomas but the development of drug resistance remains a major concern. Activating transcription factor 4 (ATF4) is a critical oxido-metabolic regulator in gliomas, and its role in the pathogenesis of TMZ-resistance remains elusive. We investigated the effect of TMZ on human glioma cells under conditions of enhanced ATF4 expression (ATF4OE) and ATF4 knock down (ATF4KD)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28538107/local-anesthetics-systemic-toxicity-association-with-exparel-bupivacaine-liposome-a-pharmacovigilance-evaluation
#14
Nitish Aggarwal
BACKGROUND: Local Anesthetic Systemic Toxicity (LAST) is a rare life threatening complication usually from intra-arterial or intravenous injection leading to systemic absorption of regional anesthesia drug. The objective of this research was to statistically quantify the association between Exparel (bupivacaine liposome) injectable suspension and LAST. METHODS: Adverse Event Reporting System database of FDA, which houses public and industry submitted adverse event case reports, was queried and analyzed to quantify the passive pharmacovigilance signal for Local Anesthetic Systemic Toxicity as associated with use of bupivacaine Liposome...
May 24, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28538103/detoxification-of-fusaric-acid-by-the-soil-microbe-mucor-rouxii
#15
Frankie K Crutcher, Lorraine S Puckhaber, Alois A Bell, Jinggao Liu, Sara E Duke, Robert D Stipanovic, Robert L Nichols
Fusarium oxysporum f. sp. vasinfectum race 4 (VCG0114), which causes root rot and wilt of cotton (Gossypium hirsutum and G. barbadense) has been identified recently for the first time in the western hemisphere in certain fields in the San Joaquin Valley of California. This pathotype produces copious quantities of the plant toxin fusaric acid (5-butyl-2-pyridinecarboxylic acid) compared to other isolates of F. oxysporum f. sp. vasinfectum (Fov) that are indigenous to the U. S. Fusaric acid is toxic to cotton plants and may help the pathogen compete with other microbes in the soil...
May 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28538095/high-resolution-structures-of-the-amyloid-%C3%AE-1-42-dimers-from-the-comparison-of-four-atomistic-force-fields
#16
Viet Hoang Man, Phuong Hoang Nguyen, Philippe Derreumaux
The dimer of the amyloid-beta peptide Aβ of 42 residues is the smallest toxic species in Alzheimer's disease, but its equilibrium structures are unknown. Here we determined the equilibrium ensembles generated by the four atomistic OPLS-AA, CHARMM22*, AMBER99sb-ildn and AMBERsb14 force fields with the TIP3P water model. Based on 144 microsecond replica exchange molecular dynamics simulations (with 750 ns per replica), we find that the four force fields lead to random coil ensembles with calculated cross-collision sections, hydrodynamics properties and small-angle X-ray scattering profiles independent on the force field...
May 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28538093/toxic-byproduct-formation-during-electrochemical-treatment-of-latrine-wastewater
#17
Justin T Jasper, Yang Yang, Michael R Hoffmann
Electrochemical systems are an attractive option for onsite latrine wastewater treatment due to their high efficiency and small footprint. While concerns remain over formation of toxic byproducts during treatment, rigorous studies examining byproduct formation are lacking. Experiments treating authentic latrine wastewater over variable treatment times, current densities, chloride concentrations, and anode materials were conducted to characterize byproducts and identify conditions that minimize their formation...
May 24, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28538013/update-on-the-pathogenesis-and-treatment-of-juvenile-idiopathic-arthritis
#18
Gabriella Giancane, Alessandra Alongi, Angelo Ravelli
PURPOSE OF REVIEW: To provide an overview of recently published studies on pathogenesis and management of juvenile idiopathic arthritis (JIA). RECENT FINDINGS: In the past year, the potential role of network analysis in the understanding of the molecular phenotype of individual JIA subgroups has been highlighted. In addition, potential new targets for pharmacologic interventions have been identified through the elucidation of mechanisms that modulate the function of cells involved in the inflammatory process...
May 22, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28537942/locomotor-and-discriminative-stimulus-effects-of-four-novel-hallucinogens-in-rodents
#19
Michael B Gatch, Sean B Dolan, Michael J Forster
There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe), and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA)...
May 19, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28537935/cardiovascular-toxicity-of-abacavir-a-clinical-controversy-in-need-of-a-pharmacological-explanation
#20
Angeles Alvarez, Samuel Orden, Isabel Andújar, Victor Collado-Diaz, Sara Núñez-Delgado, Maria Jose Galindo, Vicente Estrada, Nadezda Apostolova, Juan V Esplugues
: There is a long-lasting controversy surrounding an association between Abacavir (ABC) and an increased risk of cardiovascular (CV) disease in HIV-positive subjects. While differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation, and have pointed to methodological differences to explain discrepancies...
May 23, 2017: AIDS
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