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https://www.readbyqxmd.com/read/29146240/channelled-tablets-an-innovative-approach-to-accelerating-drug-release-from-3d-printed-tablets
#1
Muzna Sadia, Basel Arafat, Waqar Ahmed, Robert E Forbes, Mohamed A Alhnan
Conventional immediate release dosage forms involve compressing the powder with a disintegrating agent that enables rapid disintegration and dissolution upon oral ingestion. Among 3D printing technologies, the fused deposition modelling (FDM) 3D printing technique has considerable potential for patient-specific dosage form. However, the use of FDM 3D printing in tablet manufacturing requires large portion of polymer, which slows down drug release through erosion and diffusion mechanisms. In this study, we demonstrate for the first time the use of a novel design approach of caplets with perforating channels to accelerate drug release from 3D printed tablets...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29143606/metabolic-pathways-and-genes-identified-by-rna-seq-analysis-of-barley-near-isogenic-lines-differing-by-allelic-state-of-the-black-lemma-and-pericarp-blp-gene
#2
Anastasiya Y Glagoleva, Nikolay A Shmakov, Olesya Y Shoeva, Gennady V Vasiliev, Natalia V Shatskaya, Andreas Börner, Dmitry A Afonnikov, Elena K Khlestkina
BACKGROUND: Some plant species have 'melanin-like' black seed pigmentation. However, the chemical and genetic nature of this 'melanin-like' black pigment have not yet been fully explored due to its complex structure and ability to withstand almost all solvents. Nevertheless, identification of genetic networks participating in trait formation is key to understanding metabolic processes involved in the expression of 'melanin-like' black seed pigmentation. The aim of the current study was to identify differentially expressed genes (DEGs) in barley near-isogenic lines (NILs) differing by allelic state of the Blp (black lemma and pericarp) locus...
November 14, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29143057/accelerating-ion-diffusion-with-unique-three-dimensionally-interconnected-nanopores-for-self-membrane-high-performance-pseudocapacitors
#3
Yuan Gao, Yuanjing Lin, Zehua Peng, Qingfeng Zhou, Zhiyong Fan
Herein, a unique three-dimensionally interconnected nanoporous structure (3-D INPOS) pseudocapacitor electrode, which possesses a large surface area, an efficient electron and ion transport, together with a remarkable structural stability, has been constructed via soft anodization of an aluminum alloy, cost-effective ultrasonic spray pyrolysis (USP)-assisted deposition of fluorine-doped tin oxide (FTO), and controllable electrochemical deposition of nanostructured manganese dioxide (MnO2). Taking the advantage of large surface area, the as-built 3-D INPOS pseudocapacitor electrode exhibits the highest areal capacitance of 540 mF cm(-2) and a volumetric capacitance of 135 F cm(-3), which is 53% higher than that achieved from the conventional 3-D nanopore pseudocapacitor electrode and 17...
November 16, 2017: Nanoscale
https://www.readbyqxmd.com/read/29139142/safety-of-orally-administered-usp-compliant-levothyroxine-sodium-tablets-in-dogs
#4
J E Hare, C M K Morrow, J Caldwell, W E Lloyd
The safety of synthetic levothyroxine sodium tablets (Thyro-Tabs® Canine; LLOYD, Inc.) in dogs was evaluated in a randomized, sham-dose controlled, parallel-group study. Young, healthy, euthyroid Beagle dogs were randomized into four groups (four females and four males per group) and received single daily doses of 0×, 2× (0.044 mg/kg), 6× (0.132 mg/kg), or 10× (0.22 mg/kg) the labeled starting dose of 0.022 mg kg(-1)  day(-1) for 182 days. Every 2 weeks, physical examinations, electrocardiology examinations, and sample collections for thyroid panel, hematology, serum biochemistry, coagulation panel, and urinalysis were performed...
November 15, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29131570/identification-and-characterisation-of-dual-inhibitors-of-the-usp25-28-deubiquitinating-enzyme-subfamily
#5
Jonathan D Wrigley, Gerald Gavory, Iain Simpson, Marian Preston, Helen Plant, Jenna Bradley, Anne U Goeppert, Ewelina Rozycka, Gareth Davies, Jarrod Walsh, Andrea Valentine, Keeva McClelland, Krzysztofa Ewa Odrzywol, Jonathan Renshaw, Joanna Boros, Jonathan Tart, Lindsey Leach, Thorsten Nowak, Richard A Ward, Timothy Harrison, David M Andrews
The Ubiquitin Proteasome System is widely postulated to be a new and important field of drug discovery for the future, with the Ubiquitin Specific Proteases (USP) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the finding that USP28 is required for c-Myc stability suggests that USP28 inhibition may represent a novel approach to target this so far undruggable oncogene. Here we describe the discovery of the first reported inhibitors of USP28, which we demonstrate are able to bind to and inhibit USP28, and whilst displaying a dual activity against the closest homologue USP25, these inhibitors show a high degree of selectivity over other deubiquitinases...
November 13, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29122582/biorelevant-media-slows-the-solution-mediated-phase-transformation-of-amorphous-spironolactone
#6
Mary S Kleppe, Roy J Haskell, Robin H Bogner
Solution-mediated phase transformation (SMPT) can reduce the high drug concentration expected from amorphous formulations, eliminating the improvement in drug absorption one hoped to gain from this high energy drug state. The differences in SMPT of a supersaturating system were compared in biorelevant media (Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF)) and USP compendial medium, Simulated Intestinal Fluid without pancreatin (SIFsp). Amorphous spironolactone underwent SMPT to the same hydrate of spironolactone in all three media which was confirmed by the decrease in dissolution rates assessed in a flow-through dissolution apparatus, as well as by the appearance of crystals on the amorphous solid surface detected by polarized light microscopy...
November 6, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29117514/investigating-cascade-impactor-performance-using-a-modified-3d-printed-induction-port
#7
Kai Berkenfeld, Michael Bernauer, Jason T McConville, Alf Lamprecht
Based on a computer tomographic scan of a human trachea, a modified induction port (mIP), for use with the Next Generation Cascade Impactor, was manufactured using 3D printing technology. Standard United States Pharmacopoeia IP (USPIP) was compared to the mIP and a 3D printed version of the USPIP (USP3DIP) by analyzing different types of commercial salbutamol formulations for inhalation. Increased retention of particles in the mIP was found analyzing a pMDI formulation, leading to a decrease in the FPF from 28...
November 5, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29114360/contributions-to-the-cytogenetics-of-the-neotropical-fish-fauna
#8
Luiz Antônio Carlos Bertollo, Marcelo de Bello Cioffi, Pedro Manoel Galetti Jr, Orlando Moreira Filho
Brazilian fish cytogenetics started as early as the seventies in three pioneering research groups, located at the Universidade Estadual Paulista (UNESP, Botucatu, SP), Universidade Federal de São Carlos (UFSCar, São Carlos, SP) and Universidade de São Paulo (USP, São Paulo, SP). Investigations that have been conducted in these groups led to the discovery of a huge chromosomal and genomic biodiversity among Neotropical fishes. Besides, they also provided the expansion of this research area, with the genesis of several other South American research groups, in view of a number of dissertations and doctoral theses developed over years...
2017: Comparative Cytogenetics
https://www.readbyqxmd.com/read/29111204/the-impacts-of-nineteen-mutations-on-the-enzymatic-activity-of-usp26
#9
Ying-Li Liu, Jie Zheng, Ying-Jun Mi, Jing Zhao, Qing-Bao Tian
OBJECTIVE: The association between mutations in the USP26 gene and male infertility has been studied intensively. However, the biological function of the mutant proteins remains to be elucidated. To confirm the effects of the reported mutations, we analyse the enzyme activity of USP26 between the wild-type and the variants from a molecular perspective. METHODS: Using pGEX-USP26 as a template, site-directed mutagenesis was conducted to generate nineteen USP26 mutant plasmids...
October 27, 2017: Gene
https://www.readbyqxmd.com/read/29111151/experimental-optimization-of-lornoxicam-liposomes-for-sustained-topical-delivery
#10
Joshny Joseph, Vedha Hari B N, Ramya Devi D
The purpose of the present investigation is to formulate liposomes of Lornoxicam for topical delivery using Central Composite Design, to provide a sustained release of the drug and thereby extend its elimination half-life. Liposomes were prepared by thin film hydration method with pH induced vesiculation. The liposomes were assessed for their particle size, charge, morphology and drug entrapment and characterized using TGA-DSC and FTIR analysis, to assess the interaction between the drug and excipients. The in vitro release study was performed using modified USP dissolution apparatus-I using three different dissolution media and the ex vivo release study was performed using goat skin...
October 27, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29100264/microwave-mediated-synthesis-and-analytical-method-development-for-the-estimation-of-novel-1-4-dihydropyridines-in-bulk-by-rp-hplc
#11
Anupreet Kaur, Jaspreet Kaur, Ranju Bansal
The present work describes a rapid and green microwave mediated method for the synthesis and a simple and precise isocratic reverse phase HPLC method for the estimation of the biologically significant dihydropyridines. The conventional synthesis of these dihydropyridines has been previously reported from our lab. The analysis of a standard solution (1 mg/ml) was accomplished on a symmetry (4.6 mm I.D x 250 mm) C-18 column using mobile phase acetonitrile:water:triethylamine (TEA) (70:30:0.1 v/v/v) at a flow rate of 0...
November 3, 2017: Drug Research
https://www.readbyqxmd.com/read/29095656/fabrication-of-eudragit-polymeric-nanoparticles-using-ultrasonic-nebulization-method-for-enhanced-oral-absorption-of-megestrol-acetate
#12
Seo Young Dai, Su-Eon Jin, Daehyun Kim, Don Haeng Lee, Su-Geun Yang
Megestrol acetate (MGA) is used as a progestagen to treat advanced cancers in the breast or uterus and anorexia-cachexia syndrome in cancer patients. Due to its low solubility (BCS class II), MGA bioavailability needs to be enhanced for efficacy and safety. We developed MGA-encapsulated Eudragit(®) L100 (EUD) nanoparticles (MGA-EUD (1:1) and MGA-EUD (2:1)) using an ultrasonic nebulization method. MGA-EUD (1:1) and MGA-EUD (2:1) consisted of MGA and EUD at the mass ratios of 1:1 and 2:1. Their physicochemical properties, i...
November 2, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29091922/characterization-of-the-deubiquitination-activity-and-substrate-specificity-of-the-chicken-ubiquitin-specific-protease-1-usp-associated-factor-1-complex
#13
Hainan Zheng, Mengyun Wang, Chengcheng Zhao, Shanli Wu, Peifeng Yu, Yan Lü, Tiedong Wang, Yongxing Ai
Deubiquitinases (DUBs) are essential regulators of intracellular processes involving ubiquitin (Ub) modification. The human DUB ubiquitin-specific protease 1 (hUSP1) interacts with human USP-associated factor 1 (hUAF1), and helps to regulate processes such as DNA damage repair. Previously, we identified a chicken USP1 homologue (chUSP1) during an investigation into the properties of Marek's disease virus (MDV). However, chUSP1's deubiquitination activity, interaction with chUAF1, and substrate specificity remained unknown...
2017: PloS One
https://www.readbyqxmd.com/read/29077583/phenotypic-characterization-of-corneal-endothelial-dystrophy-in-german-shorthaired-and-wirehaired-pointers-using-in-vivo-advanced-corneal-imaging-and-histopathology
#14
Olivia R Shull, Christopher M Reilly, Lola B Davis, Christopher J Murphy, Sara M Thomasy
PURPOSE: To evaluate corneal morphology using ultrasonic pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), and in vivo confocal microscopy (IVCM) in 2 related canine breeds-German shorthaired pointers (GSHPs) and German wirehaired pointers (GWHPs)-with and without corneal endothelial dystrophy (CED). This condition is characterized by premature endothelial cell degeneration leading to concomitant corneal edema and is similar to Fuchs endothelial corneal dystrophy...
October 25, 2017: Cornea
https://www.readbyqxmd.com/read/29066052/strategy-for-an-abbreviated-in-house-qualification-of-a-commercially-available-rapid-microbiology-method-rmm-for-canadian-regulatory-approval
#15
Jolene Chisholm, Shashank Bhatt, Amélie Chaboureau, Sowmya Viswanathan
BACKGROUND AIMS: Cell therapy products (CTP) typically require full sterility, endotoxin and Mycoplasma testing before product release. Often this is not feasible with fresh cells, and sponsors may rely on rapid microbiological methods (RMM). RMM must be qualified in-house using the sponsor's facilities, equipment, consumables, cells and matrices to meet regulatory approval. Herein, we present a cost-effective strategy to conduct an in-house abbreviated qualification of a commercially available RMM kit to meet Health Canada regulatory requirements...
October 20, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29064679/mutation-of-asn-475-in-the-venezuelan-equine-encephalitis-virus-nsp2-cysteine-protease-leads-to-a-self-inhibited-state
#16
Jaimee R Compton, Matthew J Mickey, Xin Hu, Juan J Marugan, Patricia M Legler
The alphaviral nsP2 cysteine protease of the Venezuelan equine encephalitis virus (VEEV) is a validated antiviral drug target. Clan CN proteases contain a cysteine protease domain that is intimately packed with an S-adenosyl-l-methionine-dependent RNA methyltransferase (SAM MTase) domain. Within a cleft formed at the interface of these two domains, the peptide substrate is thought to bind. The nucleophilic cysteine can be found within a conserved motif, (475)NVCWAK(480), which differs from that of papain ((22)CGSCWAFS(29))...
November 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/29064257/effect-of-coadministered-water-on-the-in-vivo-performance-of-oral-formulations-containing-n-acetylcysteine-an-in-vitro-approach-using-the-dynamic-open-flow-through-test-apparatus
#17
Maximilian Sager, Felix Schneider, Philipp Jedamzik, Markus Wiedmann, Ellen Schremmer, Mirko Koziolek, Werner Weitschies
The drug plasma profile after oral administration of immediate release dosage forms can be affected by the human gastrointestinal physiology, the formulation, and the drug itself. In this work, we investigated the in vivo and in vitro performance of two formulations (granules vs. tablet) containing the highly soluble drug N-Acetylcysteine (BCS class I). Thereby, special attention was paid to the effect of the dosage form and the coadministration of water on drug release. Interestingly, the in vivo results from a pharmacokinetic study with 11 healthy volunteers indicated that the drug plasma concentrations were comparable for the tablet given with water as well as for the granules given with and without water...
November 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29056421/structure-guided-development-of-a-potent-and-selective-non-covalent-active-site-inhibitor-of-usp7
#18
Ilaria Lamberto, Xiaoxi Liu, Hyuk-Soo Seo, Nathan J Schauer, Roxana E Iacob, Wanyi Hu, Deepika Das, Tatiana Mikhailova, Ellen L Weisberg, John R Engen, Kenneth C Anderson, Dharminder Chauhan, Sirano Dhe-Paganon, Sara J Buhrlage
Deubiquitinating enzymes (DUBs) have garnered significant attention as drug targets in the last 5-10 years. The excitement stems in large part from the powerful ability of DUB inhibitors to promote degradation of oncogenic proteins, especially proteins that are challenging to directly target but which are stabilized by DUB family members. Highly optimized and well-characterized DUB inhibitors have thus become highly sought after tools. Most reported DUB inhibitors, however, are polypharmacological agents possessing weak (micromolar) potency toward their primary target, limiting their utility in target validation and mechanism studies...
September 28, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29056420/usp7-specific-inhibitors-target-and-modify-the-enzyme-s-active-site-via-distinct-chemical-mechanisms
#19
Alexandra Pozhidaeva, Gabrielle Valles, Feng Wang, Jian Wu, David E Sterner, Phuong Nguyen, Joseph Weinstock, K G Suresh Kumar, Jean Kanyo, Dennis Wright, Irina Bezsonova
USP7 is a deubiquitinating enzyme that plays a pivotal role in multiple oncogenic pathways and therefore is a desirable target for new anti-cancer therapies. However, the lack of structural information about the USP7-inhibitor interactions has been a critical gap in the development of potent inhibitors. USP7 is unique among USPs in that its active site is catalytically incompetent, and is postulated to rearrange into a productive conformation only upon binding to ubiquitin. Surprisingly, we found that ubiquitin alone does not induce an active conformation in solution...
October 4, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29055735/sucrosomial%C3%A2-iron-absorption-studied-by-in-vitro-and-ex-vivo-models
#20
Angela Fabiano, Elisa Brilli, Stefano Fogli, Denise Beconcini, Sara Carpi, Germano Tarantino, Ylenia Zambito
This paper presents a comparative evaluation of different oral ferric iron formulations for ability to retain Fe(3+) in simulated gastric fluid (SGF), be internalized by cells lining intestinal epithelium, and cross it to reach the bloodstream. In all formulations iron was ferric pyrophosphate, the excipients were different types and fractions of lecithin plus sucrose esters of fatty acids matrix (Sideral® RM; PRT1; PRT2) or lecithin without sucrester (SUN). Dissolution kinetics of formulations in SGF was studied by USP method...
October 18, 2017: European Journal of Pharmaceutical Sciences
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