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https://www.readbyqxmd.com/read/27923110/impact-of-oligonucleotide-structure-chemistry-and-delivery-method-on-in-vitro-cytotoxicity
#1
Maja M Janas, Yongfeng Jiang, Mark K Schlegel, Scott Waldron, Satya Kuchimanchi, Scott A Barros
Single-stranded (ss) 2'-fluoro (2'-F)-modified oligonucleotides (ONs) with a full phosphorothioate (PS) backbone have been reported to be cytotoxic and cause DNA double-strand breaks (DSBs) when transfected into HeLa cells. However, the molecular determinants of these effects have not been fully explored. In this study, we investigated the impact of ON structure, chemistry, delivery method, and cell type on in vitro cytotoxicity and DSBs. We found that ss PS-ONs were more cytotoxic than double-stranded (ds) PS-ONs, irrespective of the 2'-ribose chemistry, inclusive of the 2'-F modification...
December 6, 2016: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/27922821/identification-of-salvia-haenkei-as-gerosuppressant-agent-by-using-an-integrated-senescence-screening-assay
#2
Ivana Matic, Ajinkya Revandkar, Jingjing Chen, Angela Bisio, Stefano Dall'Acqua, Veronica Cocetta, Paola Brun, Giorgio Mancino, Martina Milanese, Maurizio Mattei, Monica Montopoli, Andrea Alimonti
Cellular senescence is a stable cell cycle arrest that is the causative process of aging. The PI3K/AKT/mTOR pathway is implicated in the control of cellular senescence and inhibitors of this pathway have been successfully used for life span prolongation experiments in mammals. PTEN is the major regulator of the PI3K/AKT/mTOR pathway and loss of PTEN promotes a senescence response termed PICS. Here we report a novel-screening assay, for the identification of compounds that block different types of senescence response...
December 1, 2016: Aging
https://www.readbyqxmd.com/read/27922762/nonchemotherapy-drug-induced-agranulocytosis-in-children-detected-by-a-prospective-pharmacovigilance-program
#3
Nicolás Medrano-Casique, Hoi Y Tong, Alberto M Borobia, Antonio J Carcas, Jesús Frías, Elena Ramírez
OBJECTIVES: A prospective evaluation of nonchemotherapy drug-induced agranulocytosis (DIA) cases, which are infrequent in the pediatric population. We characterize agranulocytosis cases and assess lab test differences between drug- and nondrug-induced agranulocytosis. METHODS: Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital we detected pediatric agranulocytosis cases from July 2007 to December 2010. This program estimates the incidence, drug causality, clinical features, outcomes of DIA pediatric cases, and assesses laboratory differences with respect to non-DIA...
December 6, 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27922065/detc-based-bacterial-cellulose-bio-curatives-for-topical-treatment-of-cutaneous-leishmaniasis
#4
Fabiana S Celes, Eliane Trovatti, Ricardo Khouri, Johan Van Weyenbergh, Sidney J L Ribeiro, Valeria M Borges, Hernane S Barud, Camila I de Oliveira
The treatment of leishmaniasis still relies on drugs with potentially serious adverse effects. Herein, we tested a topical formulation of bacterial cellulose (BC) membranes containing Diethyldithiocarbamate (DETC), a superoxide dismutase 1 inhibitor. Leishmania-infected macrophages exposed to BC-DETC resulted in parasite killing, without pronounced toxic effects to host cells. This outcome was associated with lower SOD1 activity and higher production of superoxide and cytokine mediators. Topical application of BC-DETC significantly decreased lesion size, parasite load and the inflammatory response at the infection site, as well as the production of both IFN-γ and TNF...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921245/a-novel-method-for-preventing-surface-film-entrapment-of-water-fleas-and-its-application-for-toxicity-testing-with-heavy-metals
#5
Rongxue Cui, Jin Il Kwak, Youn-Joo An
Some water fleas such as Daphnia galeata and Bosmina longirostris are difficult to culture and use in ecotoxicity testing since they can easily become entrapped at the surface film. Cetyl alcohol was the most prevalent chemical used to prevent the entrapment of water fleas in previous studies. However, cetyl alcohol possesses a number of disadvantages including its toxicity and water insolubility. This study presents a novel method for preventing surface film entrapment of the water flea D. galeata and B. longirostris acute testing...
December 5, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27921244/towards-green-oviposition-deterrents-effectiveness-of-syzygium-lanceolatum-myrtaceae-essential-oil-against-six-mosquito-vectors-and-impact-on-four-aquatic-biological-control-agents
#6
Giovanni Benelli, Mohan Rajeswary, Marimuthu Govindarajan
Essential oils (EOs) from plants may be alternative sources of molecules toxic against mosquito vectors of public health relevance. Most of researches in this field focused on EOs as larvicides or ovicides, while limited efforts focused on the exploitation of EOs as oviposition deterrents. In the present study, the larvicidal and oviposition deterrent activity of Syzygium lanceolatum leaf EO was evaluated against six mosquito species, Anopheles stephensi, An. subpictus, Aedes aegypti, Ae. albopictus, Culex quinquefasciatus, and Cx...
December 5, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27920625/a-retrospective-analysis-of-toxicity-and-efficacy-for-2-hypofractionated-irradiation-schedules-versus-a-conventional-one-for-post-mastectomy-adjuvant-radiotherapy-in-breast-cancer
#7
Vassilis Kouloulias, Eftychia Mosa, Anna Zygogianni, Efrosini Kypraiou, John Georgakopoulos, Kalliopi Platoni, Christos Antypas, George Kyrgias, Maria Tolia, Christos Papadimitriou, Amanda Psyrri, George Patatoukas, Maria Dilvoi, Christina Armpilia, Kyriaki Theodorou, Maria-Aggeliki Kalogeridi, Ivelina Beli, John Kouvaris, Nikolaos Kelekis
INTRODUCTION: The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients. METHODS: 3 irradiation schedules were analyzed: 48.30 Gy in 21 fractions (group A, n = 60), 42.56 Gy in 16 fractions (group B, n = 27) and 50 Gy in 25 fractions (group C, n = 30) of the front chest wall. All groups were also treated with a supraclavicular field, with 39...
October 2016: Breast Care
https://www.readbyqxmd.com/read/27920610/volumetric-image-guided-highly-conformal-radiotherapy-of-the-prostate-bed-toxicity-analysis
#8
Gianluca Ingrosso, Alessandra Carosi, Daniela di Cristino, Elisabetta Ponti, Andrea Lancia, Alessandra Murgia, Claudia Bruni, Pasquale Morelli, Franca Pietrasanta, Riccardo Santoni
AIM: To evaluate toxicity of high conformal image-guided radiotherapy of the prostate bed. BACKGROUND: Radiotherapy of the prostate bed has a pivotal role in the post-operative and salvage settings, but few clinical data are available on the use of daily image guidance in combination with highly conformal techniques, and data on long-term results are lacking. MATERIALS AND METHODS: We analyzed 118 patients irradiated on the prostate bed using conformal plans processed with a micro-multileaf collimator, and daily checking treatment set-up with a cone-beam CT system...
January 2017: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/27920527/pharmacokinetics-and-safety-of-dts-108-a-human-oligopeptide-bound-to-sn-38-with-an-esterase-sensitive-cross-linker-in-patients-with-advanced-malignancies-a-phase-i-study
#9
Romain Coriat, Sandrine J Faivre, Olivier Mir, Chantal Dreyer, Stanislas Ropert, Mohammed Bouattour, Robert Desjardins, François Goldwasser, Eric Raymond
BACKGROUND: DTS-108 is a hydrosoluble prodrug, where the SN-38 moiety is covalently linked to a 20-amino acid vector peptide by a specific esterase-sensitive cross-linker, releasing 7-ethyl-10-hydroxycampthotecin (SN-38) by esterase bond cleavage. METHODS: The pharmacokinetics of DTS-108, adverse events graded according to NCI-CTCv3.1, dose-limiting toxicities at cycle 1, the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of intravenous DTS-108 (1-2 hours) every 2 weeks were evaluated in a first-in-human Phase I study in patients with advanced/metastatic carcinomas, according to an accelerated dose escalation design...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919957/simultaneous-administration-of-statins-and-pioglitazone-limits-tumor-growth-in-a-rat-model-of-malignant-glioma
#10
Jorge Humberto Tapia-Pérez, Robert Preininger, Elmar Kirches, Annegret Reinhold, Jana Butzmann, Sylvia Prilloff, Christian Mawrin, Thomas Schneider
BACKGROUND/AIM: Statins are cholesterol reducers with considerable dose-dependent effect against glioma cells. The apoptotic effect could be increased by combining statins or by adding pioglitazone (PGZ). The last one is an anti-diabetic drug, an agonist of the peroxisome proliferator-activated receptor-gamma (PPARG). We used an animal model to test the effect of such combination in vivo and we investigated the changes on immunological processes. MATERIALS AND METHODS: Thirty-three rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919709/evaluation-of-anti-zika-virus-activities-of-broad-spectrum-antivirals-and-nih-clinical-collection-compounds-using-a-cell-based-high-throughput-screen-assay
#11
Robert S Adcock, Yong-Kyu Chu, Jennifer E Golden, Dong-Hoon Chung
Recent studies have clearly underscored the association between Zika virus (ZIKV) and severe neurological diseases such as microcephaly and Guillain-Barre syndrome. Given the historical complacency surrounding this virus, however, no significant antiviral screenings have been performed to specifically target ZIKV. As a result, there is an urgent need for a validated screening method and strategy that is focused on highlighting potential anti-ZIKV inhibitors that can be further advanced via rigorous validation and optimization...
December 2, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27919644/comparative-investigation-of-methionine-and-novel-formulation-metovitan-protective-effects-in-wistar-rats-with-testicular-and-epididymal-toxicity-induced-by-anti-tuberculosis-drugs-co-administration
#12
Ganna M Shayakhmetova, Larysa B Bondarenko, Alla K Voronina, Valentina M Kovalenko
Despite clear beneficial effects, studies on the efficacy of different formulations of micronutrients and vitamins in the treatment of male infertility are still very limited. The aim of the study was to compare the efficacy of methionine and novel formulation Metovitan based on the combination of methionine, thiamine, nicotinamide, α-tocopherol acetate and zinc salt as remedies for prevention of anti-tuberculosis drugs (ATD) anti-fertility effects in male rats. ATD co-administration resulted in testicular CYP2E1, CYP2C23 and CYP3A2 transcriptional activation...
December 2, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27919536/causes-of-highway-road-dust-toxicity-to-an-estuarine-amphipod-evaluating-the-effects-of-nicotine
#13
Kyoshiro Hiki, Fumiyuki Nakajima, Tomohiro Tobino
Urban road dust can potentially have adverse effects on ecosystems if it is discharged into receiving waters. This study investigated the causes of highway road dust toxicity by performing sediment toxicity identification evaluation (TIE) tests with an estuarine amphipod, Grandidierella japonica. In addition to metals and polycyclic aromatic hydrocarbons, which are traditionally considered to be the major toxicants in road runoff, we focused on dissolved nicotine as a causative toxicant. The sediment TIE results suggested that organic contaminants contributed to the majority of toxicity, and that the contribution of unionized nicotine to the toxicity was the highest among the chemicals considered...
December 2, 2016: Chemosphere
https://www.readbyqxmd.com/read/27919228/antimicrobial-activity-and-safety-evaluation-of-peptides-isolated-from-the-hemoglobin-of-chickens
#14
Fengjiao Hu, Qiaoxing Wu, Shuang Song, Ruiping She, Yue Zhao, Yifei Yang, Meikun Zhang, Fang Du, Majid Hussain Soomro, Ruihan Shi
BACKGROUND: Hemoglobin is a rich source of biological peptides. As a byproduct and even wastewater of poultry-slaughtering facilities, chicken blood is one of the most abundant source of hemoglobin. RESULTS: In this study, the chicken hemoglobin antimicrobial peptides (CHAP) were isolated and the antimicrobial and bactericidal activities were tested by the agarose diffusion assay, minimum inhibitory concentration (MIC) analysis, minimal bactericidal concentration (MBC) analysis, and time-dependent inhibitory and bactericidal assays...
December 5, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27919180/investigation-of-a-mortality-cluster-in-wild-adult-yellow-eyed-penguins-megadyptes-antipodes-at-otago-peninsula-new-zealand
#15
Brett Gartrell, David Agnew, Maurice Alley, Tim Carpenter, Hye Jeong Ha, Laryssa Howe, Stuart Hunter, Kate McInnes, Rex Munday, Roe Wendi, Young Melanie
We investigated an epidemic mortality cluster of yellow-eyed penguins (Megadyptes antipodes) that involved 67 moribund or dead birds found on various beaches of the Otago Peninsula, New Zealand, between January 21 and March 20, 2013. Twenty-four carcases were examined postmortem. Histological lesions of pulmonary, hepatic and splenic erythrophagocytosis and haemosiderosis were found in 23 of 24 birds. Fifteen birds also had haemoglobin-like protein droplets within renal tubular epithelial cells. Despite consistent histological lesions, a cause of death could not be established...
December 6, 2016: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27918990/effects-of-tripolyphosphate-on-cellular-uptake-and-rna-interference-efficiency-of-chitosan-based-nanoparticles-in-raw-264-7-macrophages
#16
Bo Xiao, Panpan Ma, Lijun Ma, Qiubing Chen, Xiaoying Si, Lewins Walter, Didier Merlin
Tumor necrosis factor-α (TNF-α) is a major pro-inflammatory cytokine that is mainly secreted by macrophages during inflammation. Here, we synthesized a series of N-(2-hydroxy)propyl-3-trimethyl ammonium chitosan chlorides (HTCCs), and then used a complex coacervation technique or tripolyphosphate (TPP)-assisted ionotropic gelation strategy to complex the HTCCs with TNF-α siRNA (siTNF) to form nanoparticles (NPs). The resultant NPs had a desirable particle size (210-279nm), a slightly positive zeta potential (14-22mV), and negligible cytotoxicity against Raw 264...
November 26, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/27918965/saponaria-officinalis-l-extract-surface-active-properties-and-impact-on-environmental-bacterial-strains
#17
Wojciech Smułek, Agata Zdarta, Amanda Pacholak, Agnieszka Zgoła-Grześkowiak, Łukasz Marczak, Maciej Jarzębski, Ewa Kaczorek
Plant-derived surfactants are characterised by low toxicity, high biodegradability and environmental compatibility. They therefore have many applications; for instance, they can be used in bioremediation to accelerate biodegradation processes, especially of hydrophobic pollutants. This paper analyses the properties of an extract from Saponaria officinalis L. containing saponins and its impact on bacterial strains isolated from soil, as well as its potential for application in hydrocarbon bioremediation. The tested extract from Saponaria officinalis L...
November 27, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27918946/toxicity-of-ar-curcumene-and-epi-%C3%AE-bisabolol-from-hedychium-larsenii-zingiberaceae-essential-oil-on-malaria-chikungunya-and-japanese-encephalitis-mosquito-vectors
#18
Mashael Marzouq AlShebly, Fatma Saeed AlQahtani, Marimuthu Govindarajan, Kasi Gopinath, Periasamy Vijayan, Giovanni Benelli
Mosquitoes act as vectors of key pathogens and parasites. Plant essential oils have been recognized as important sources of biopesticides, which do not induce resistance and have limited toxic effects on human health and non-target organisms. In this research, we evaluated the larvicidal and oviposition deterrence activity of Hedychium larsenii essential oil (EO) and its major compounds ar-curcumene and epi-β-bisabolol. Both molecules showed high toxicity against early third instars of Anopheles stephensi (LC50=10...
December 2, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27918858/d10-in-the-treatment-of-prehospital-hypoglycemia-a-24-month-observational-cohort-study
#19
H Gene Hern, Matthew Kiefer, Derex Louie, Joseph Barger, Harrison J Alter
INTRODUCTION: Prehospital first responders historically have used an IV bolus of 50 mL of 50% dextrose solution (D50) for the treatment of hypoglycemia in the field. A local Emergency Medical Services (EMS) system recently approved a hypoglycemia treatment protocol of IV 10% dextrose solution (D10) due to occasional shortages and higher cost of D50. We use the experience of this EMS system to report the feasibility, safety, and efficacy of this approach. METHODS: Over the course of 104 weeks, paramedics treated 1,323 hypoglycemic patients with D10 and recorded patient demographics and clinical outcomes...
December 5, 2016: Prehospital Emergency Care
https://www.readbyqxmd.com/read/27918762/alternating-treatment-with-pazopanib-and-everolimus-vs-continuous-pazopanib-to-delay-disease-progression-in-patients-with-metastatic-clear-cell-renal-cell-cancer-the-ropetar-randomized-clinical-trial
#20
Geert A Cirkel, Paul Hamberg, Stefan Sleijfer, Olaf J L Loosveld, M Wouter Dercksen, Maartje Los, Marco B Polee, Franchette van den Berkmortel, Maureen J Aarts, Laurens V Beerepoot, Gerard Groenewegen, Martijn P Lolkema, Metin Tascilar, Johanna E A Portielje, Frank P J Peters, Heinz-Josef Klümpen, Vincent van der Noort, John B A G Haanen, Emile E Voest
Importance: To our knowledge, this is the first randomized clinical trial evaluating an alternating treatment regimen in an attempt to delay disease progression in clear cell renal cell carcinoma. Objective: To test our hypothesis that an 8-week rotating treatment schedule with pazopanib and everolimus delays disease progression, exhibits more favorable toxic effects, and improves quality of life when compared with continuous treatment with pazopanib. Design, Setting, and Participants: This was an open-label, randomized (1:1) study (ROPETAR trial)...
December 1, 2016: JAMA Oncology
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