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https://www.readbyqxmd.com/read/28088659/altered-cerebral-insulin-response-in-transgenic-mice-expressing-the-epsilon-4-allele-of-the-human-apolipoprotein-e-gene
#1
Marie-Thérèse Traversy, Milène Vandal, Cyntia Tremblay, Marine Tournissac, Ariane Giguère-Rancourt, A David Bennett, Frédéric Calon
Apolipoprotein E epsilon-4 (APOEε4 or APOE4), an allelic variation of the APOE gene, not only increases the risk of developing the late-onset form of Alzheimer's disease (AD), but also influences the outcome of treatment. Indeed, data from clinical studies show that the beneficial effect of insulin on cognition is blunted in APOE4 carriers. To investigate how APOE impacts insulin response, we assessed the effects of an acute insulin injection in APOE3- and APOE4-targeted replacement mice that respectively express the human APOE3 or APOE4 isoform instead of the endogenous murine ApoE protein...
November 30, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28088639/docosahexaenoic-acid-loaded-lipid-nanoparticles-with-bactericidal-activity-against-helicobacter-pylori
#2
Catarina Leal Seabra, Cláudia Nunes, Maria Gomez-Lazaro, Marta Correia, José Carlos Machado, Inês C Gonçalves, Celso A Reis, Salette Reis, M Cristina L Martins
Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol ATO5(®), Miglyol-812(®)) and a surfactant (Tween 60(®))...
January 11, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28088634/chitosan-g-poly-n-isopropylacrylamide-copolymers-as-delivery-carriers-for-intracameral-pilocarpine-administration
#3
Jui-Yang Lai, Li-Jyuan Luo
This study reports, for the first time, the development of a chitosan-g-poly(N-isopropylacrylamide) (Chi-PN) biodegradable in situ gelling delivery system for ocular pilocarpine administration through intracameral injection. The number of thermo-responsive polymer segments grafted onto the chitosan via carbodiimide-mediated formation of amide linkages was greatly affected by varying the feeding amount of carboxyl-terminated poly(N-isopropylacrylamide) in the synthesis, thereby determining the phase transition temperature and enzymatic degradability of Chi-PN materials...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28088456/development-of-a-predictive-model-for-the-long-term-stability-assessment-of-drug-in-adhesive-transdermal-films-using-polar-pressure-sensitive-adhesives-as-carrier-matrix
#4
Clémence Chenevas-Paule, Hans-Michael Wolff, Mark Ashton, Martin Schubert, Kalliopi Dodou
Drug crystallization in transdermal drug delivery systems (TDDS) is a critical quality defect. The impact of drug load and hydration on the physical stability of polar (acrylic) drug-in-adhesive (DIA) films was investigated with the objective to identify predictive formulation parameters with respect to drug solubility and long-term stability. Medicated acrylic films were prepared over a range of drug concentrations below and above saturation solubility; and were characterized by FTIR, differential scanning calorimetry (DSC), polarized microscopy and Dynamic Vapor Sorption (DVS) analysis...
January 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28088425/short-communication-staphylococcus-aureus-infection-modulates-expression-of-drug-transporters-and-inflammatory-biomarkers-in-mouse-mammary-gland
#5
A Oskarsson, Y Yagdiran, S Nazemi, J Tallkvist, C H Knight
Mastitis is the most common disease in dairy herds worldwide and is often caused by Staphylococcus aureus. Little is known about the effect of mastitis on transporters in the mammary gland and the effect on transporter-mediated secretion of drugs into milk. We studied gene expressions of ATP-binding cassette and solute carrier transporters in S. aureus-infected mammary glands of mice. On d 7 of lactation, NMRI mice were inoculated with 1,000 cfu of S. aureus in 2 mammary glands and with a saline vehicle in 2 control glands...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28088333/mitochondrial-uncoupling-in-cancer-cells-liabilities-and-opportunities
#6
REVIEW
Gyorgy Baffy
Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088213/glycine-alanine-dipeptide-repeat-protein-contributes-to-toxicity-in-a-zebrafish-model-of-c9orf72-associated-neurodegeneration
#7
Yu Ohki, Andrea Wenninger-Weinzierl, Alexander Hruscha, Kazuhide Asakawa, Koichi Kawakami, Christian Haass, Dieter Edbauer, Bettina Schmid
BACKGROUND: The most frequent genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the expansion of a GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 (C9orf72) locus. The pathological hallmarks observed in C9orf72 repeat expansion carriers are the formation of RNA foci and deposition of dipeptide repeat (DPR) proteins derived from repeat associated non-ATG (RAN) translation. Currently, it is unclear whether formation of RNA foci, DPR translation products, or partial loss of C9orf72 predominantly drive neurotoxicity in vivo...
January 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28088148/lithium-ion-micrometer-diffusion-in-a-garnet-type-cubic-li7la3zr2o12-llzo-studied-using-7-li-nmr-spectroscopy
#8
Kikuko Hayamizu, Shiro Seki, Tomoyuki Haishi
Mobile lithium ions in a cubic garnet Li7La3Zr2O12 (Al-stabilized) were studied using (7)Li NMR spectroscopy for membrane and powder samples, the latter of which was ground from the membrane. Lithium diffusion in a micrometer space was measured using the pulsed-gradient spin-echo (7)Li NMR method between 70 and 130 °C. When the observation time (Δ) was shorter than 20 ms, the echo attenuation showed diffusive diffraction patterns, indicating that the Li(+) diffusing space is not free but restricted. For longer Δ, the values of apparent diffusion constant (Dapparent) became gradually smaller to approach an equilibrated value (close to a tracer diffusion constant)...
January 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28088147/hopping-charge-transport-in-amorphous-semiconductors-with-the-spatially-correlated-exponential-density-of-states
#9
S V Novikov
Hopping charge transport in amorphous semiconductors having spatially correlated exponential density of states has been considered. Average carrier velocity is exactly calculated for the quasi-equilibrium (nondispersive) transport regime. We suggest also a heuristic approach for the consideration of the carrier velocity for the non-equilibrium dispersive regime.
January 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28088077/rhoa-knockdown-by-cationic-amphiphilic-copolymer-sirhoa-polyplexes-enhances-axonal-regeneration-in-rat-spinal-cord-injury-model
#10
So-Jung Gwak, Christian Macks, Da Un Jeong, Mark Kindy, Michael Lynn, Ken Webb, Jeoung Soo Lee
Spinal cord injury (SCI) results in permanent loss of motor and sensory function due to developmentally-related and injured-induced changes in the extrinsic microenvironment and intrinsic neuronal biochemistry that limit plasticity and axonal regeneration. Our long term goal is to develop cationic, amphiphilic copolymers (poly (lactide-co-glycolide)-g-polyethylenimine, PgP) for combinatorial delivery of therapeutic nucleic acids (TNAs) and drugs targeting these different barriers. In this study, we evaluated the ability of PgP to deliver siRNA targeting RhoA, a critical signaling pathway activated by multiple extracellular inhibitors of axonal regeneration...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28088075/development-of-a-hypoxia-triggered-and-hypoxic-radiosensitized-liposome-as-a-doxorubicin-carrier-to-promote-synergetic-chemo-radio-therapy-for-glioma
#11
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28088004/a-catechin-nanoformulation-inhibits-wm266-melanoma-cell-proliferation-migration-and-associated-neo-angiogenesis
#12
Nicoletta di Leo, Matteo Battaglini, Liron Berger, Martina Giannaccini, Luciana Dente, Silke Hampel, Orazio Vittorio, Giuseppe Cirillo, Vittoria Raffa
We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The anticancer potential of the resulting nanohybrid was validated on an aggressive melanoma cell line, in vitro and in zebrafish xenotransplants...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28087982/the-impact-of-ces1-genotypes-on-the-pharmacokinetics-of-methylphenidate-in-healthy-danish-subjects
#13
Claus Stage, Gesche Jürgens, Louise Schow Guski, Ragnar Thomsen, Ditte Bjerre, Laura Ferrero-Miliani, Yassine Kamal Lyauk, Henrik Berg Rasmussen, Kim Dalhoff
AIM: This study investigated the influence of CES1 variations, including the SNP rs71647871 (G143E) and variation in copy number, on the pharmacokinetics of a single oral dose of 10 mg methylphenidate. METHODS: CES1 genotype was obtained from 200 healthy Danish Caucasian volunteers. Based on the genotype, 44 (19 males and 25 females) were invited to participate in an open, prospective trial involving six predefined genotypes: three groups with two, three, and four CES1 copies, respectively; a group of carriers of the CES1 143E allele; a group of individuals homozygous for CES1A1c (CES1VAR); and a group having three CES1 copies, in which the duplication, CES1A2, had increased transcriptional activity...
January 14, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28087720/a-liminal-stage-after-predictive-testing-for-huntington-disease
#14
Marcela Gargiulo, Sophie Tezenas du Montcel, Marie France Jutras, Ariane Herson, Cecile Cazeneuve, Alexandra Durr
BACKGROUND: Following predictive testing for Huntington disease (HD), knowledge of one's carrier status may have consequences on disease onset. Our study aimed to address two questions. First, does knowledge of being a carrier of the pathological HD mutation trigger onset of the disease? Second, does this knowledge influence self-awareness and allow carriers to identify signs and symptoms of disease onset? METHODS: Between 2012 and 2015, 75 HD mutation carriers were examined using the Unified Huntington's Disease Rating Scale (UHDRS) motor score...
January 13, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28087643/tumor-brca1-reversion-mutation-arising-during-neoadjuvant-platinum-based-chemotherapy-in-triple-negative-breast-cancer-is-associated-with-therapy-resistance
#15
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth A Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
BACKGROUND: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy. METHODS: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80)...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087485/stepwise-targeted-drug-delivery-to-liver-cancer-cells-for-enhanced-therapeutic-efficacy-by-galactose-grafted-ultra-ph-sensitive-micelles
#16
Guoqing Yan, Jun Wang, Liefeng Hu, Xin Wang, Guanqing Yang, Shengxiang Fu, Xu Cheng, Panpan Zhang, Rupei Tang
: To promote drug accumulation and cell-killing ability at tumor tissue, we have prepared a stepwise targeted drug delivery system that can remain stealthy and long-circulating in the blood vessels, improve drug retention at extracellular stimuli, enhance cellular uptake through special targeting ligands, and then achieve rapid drug release to improve toxicity to tumor cells at intracellular stimuli. Herein, galactose-grafted, ultra-pH-sensitive drug carriers (POEAd-g-LA-DOX micelles), which could respond to both extracellular and intracellular pH, and combine with galactose-receptors in cell membrane, were constructed by a facile method, therefore achieving: (i) remaining stable at pH 7...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087466/-monkey-see-monkey-do-peers-behaviors-predict-preschoolers-physical-activity-and-dietary-intake-in-childcare-centers
#17
Stéphanie Ward, Mathieu Bélanger, Denise Donovan, Jonathan Boudreau, Hassan Vatanparast, Nazeem Muhajarine, Anne Leis, M Louise Humbert, Natalie Carrier
Preschoolers observe and imitate the behaviors of those who are similar to them. Therefore, peers may be role models for preschoolers' dietary intake and physical activity in childcare centers. This study examined whether peers' behaviors predict change in preschoolers' dietary intake and physical activity in childcare centers over 9months. A total of 238 preschoolers (3 to 5years old) from 23 childcare centers in two Canadian provinces provided data at the beginning (October 2013 and 2014) and the end (June 2014 and 2015) of a 9-month period for this longitudinal study...
January 10, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28087438/dopa-responsive-dystonia-in-chinese-patients-including-a-novel-heterozygous-mutation-in-the-gch1-gene-with-an-intermediate-phenotype-and-one-case-of-prenatal-diagnosis
#18
Wen Zhang, Zhizi Zhou, Xiuzhen Li, Yonglan Huang, Taolin Li, Yunting Lin, Yongxian Shao, Hao Hu, Hongsheng Liu, Li Liu
Dopa-responsive dystonia (DRD) is a rare inherited disorder characterized by childhood-onset dystonia with diurnal fluctuation and dramatic response to levodopa. DRD is caused by the mutations in the genes encoding the enzymes involved in the dopamine and tetrahydrobiopterin (BH4) biosynthesis, including the GTP cyclohydrolase 1 (GCH1) gene and the tyrosine hydroxylase (TH) gene. In order to improve the diagnosis and expand the knowledge of the disease, we collected and analyzed relevant data of clinical diagnosis and molecular mutational analysis in five Chinese patients with DRD...
January 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28087408/effects-of-loading-concentration-blood-and-synovial-fluid-on-antibiotic-release-and-anti-biofilm-activity-of-bone-cement-beads
#19
Devendra Dusane, Scott Diamond, Cory Knecht, Nicholas Farrar, Casey Peters, Robert Howlin, Matthew Swearingen, Jason Calhoun, Roger D Plaut, Tanya Nocera, Jeffrey Granger, Paul Stoodley
Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and lawn biofilm bacteria...
January 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28087407/polymeric-micelles-for-ocular-drug-delivery-from-structural-frameworks-to-recent-preclinical-studies
#20
REVIEW
Abhirup Mandal, Rohit Bisht, Ilva D Rupenthal, Ashim K Mitra
Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials...
January 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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