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Markus Rupp, Jendrik Hardes, Michael J Raschke, Adrian Skwara
Hereditary multiple exostosis (HME) is an autosomal dominant disorder characterized by two or more benign growing, cartilage capped tumors of long bones called osteochondromas. If abnormal growth and clinical symptoms of osteochondromas newly appear in adults, malignant transformation of the usually benign growing tumors should be suspected and diagnostic testing should be initiated. Against the background of hypothesized higher malignant transformation of osteochondromas into chondrosarcoma in individuals with shoulder exostoses, we report a case of bilateral scapulothoracic osteochondromas in a patient suffering from HME...
September 19, 2016: Orthopedic Reviews
Matthew R Wilson, David S Jones, Gavin P Andrews
OBJECTIVES: This research examined the application of hot melt extrusion (HME) in the preparation of matrix formulations containing hydroxypropyl cellulose (HPC) as a base polymer in combination with methyl cellulose (MC) and hydroxypropyl methylcellulose (HPMC). METHODS: The limit to which formulations could control drug release under varying paddle speeds, high alcohol environments and high and low drug loads was investigated on a Caleva 10 ST dissolution tester...
October 17, 2016: Journal of Pharmacy and Pharmacology
Justine Thiry, Fabrice Krier, Shenelka Ratwatte, Jean-Michel Thomassin, Christine Jerome, Brigitte Evrard
The aim of this study was to evaluate hot-melt extrusion (HME) as a continuous process to form cyclodextrin (CD) inclusion complexes in order to increase the solubility and dissolution rate of itraconazole (ITZ), a class II model drug molecule of the Biopharmaceutics Classification System. Different CD derivatives were tested in a 1:1 (CD:ITZ) molar ratio to obtain CD ternary inclusion complexes in the presence of a polymer, namely Soluplus(®) (SOL). The CD used in this series of experiments were β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD) with degrees of substitution of 0...
September 26, 2016: European Journal of Pharmaceutical Sciences
G Verstraete, P Mertens, W Grymonpré, P J Van Bockstal, T De Beer, M N Boone, L Van Hoorebeke, J P Remon, C Vervaet
During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i...
September 26, 2016: International Journal of Pharmaceutics
Julien P Maincent, Laura K Najvar, William R Kirkpatrick, Siyuan Huang, Thomas F Patterson, Nathan P Wiederhold, Jay I Peters, Robert O Williams
Previously, modified release itraconazole in the form of a melt-extruded amorphous solid dispersion based on a pH dependent enteric polymer combined with hydrophilic additives (HME-ITZ), exhibited improved in vitro dissolution properties. These properties agreed with pharmacokinetic results in rats showing high and sustained itraconazole (ITZ) systemic levels. The objective of the present study was to better understand the best choice of rodent model for evaluating the pharmacokinetic and efficacy of this orally administered modified release ITZ dosage form against invasive Aspergillus fumigatus...
October 5, 2016: Drug Development and Industrial Pharmacy
Muzna Sadia, Agata Sośnicka, Basel Arafat, Abdullah Isreb, Waqar Ahmed, Antonios Kelarakis, Mohamed A Alhnan
This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet...
September 15, 2016: International Journal of Pharmaceutics
Jeffrey C Posnick, Jorge Perez, Anish Chavda
PURPOSE: The purpose of this study was to assess for the maintenance of a corrected occlusion and ongoing mandibular growth in a group of patients younger than 26 years with hemimandibular elongation (HME) who underwent bimaxillary orthognathic reconstruction. MATERIALS AND METHODS: We conducted a retrospective cohort study of HME patients operated on by a single surgeon at 1 institution between 1999 and 2013. At a minimum, all patients underwent Le Fort I and bilateral sagittal ramus osteotomies...
August 24, 2016: Journal of Oral and Maxillofacial Surgery
L Lansaat, B J de Kleijn, F J M Hilgers, B F A M van der Laan, M W M van den Brekel
Evaluation of short- and long-term clinical feasibility and exploration of limitations and advantages of a new automatic speaking valve (ASV) for laryngectomized patients with integrated HME, the Provox FreeHands FlexiVoice (FlexiVoice). This ASV not only enables automatic, but also manual closure of the valve. A multicenter, prospective clinical study in 40 laryngectomized patients was conducted. Participants were asked to use the FlexiVoice for 26 weeks. The primary outcome measure was long-term compliance...
September 14, 2016: European Archives of Oto-rhino-laryngology
Diana L Cousminer, Alexandre Arkader, Benjamin F Voight, Maurizio Pacifici, Struan F A Grant
Hereditary multiple exostoses (HME) is a rare childhood-onset skeletal disease linked to mutations in exostosin glycosyltransferase 1 (EXT1) or 2 (EXT2). Patients are heterozygous for either an EXT1 or EXT2 mutation, and it is widely assumed that exostosis formation and associated defects, such as growth retardation and skeletal deformities, require loss-of-heterozygosity or a second hit in affected cells. However, the relevance and phenotypic impact of many presumed pathogenic EXT variants remain uncertain...
November 2016: Bone
Shaokang Wang, Brian S Marks, Curtis R Menyuk
Fast saturable absorbers (FSAs) play a critical role in stabilizing many passively modelocked lasers. The most commonly used averaged model to study these lasers is the Haus modelocking equation (HME) that includes a third-order nonlinear FSA. However, it predicts a narrow region of stability that is inconsistent with experiments. To better replicate the laser physics, averaged laser models that include FSAs with higher-than-third-order nonlinearities have been introduced. Here, we compare three common FSA models to each other and to the HME using the recently-developed boundary tracking algorithms...
September 5, 2016: Optics Express
Fengyuan Yang, Yongchao Su, Jingtao Zhang, James DiNunzio, Anthony Leone, Chengbin Huang, Chad D Brown
The production of amorphous solid dispersions via hot melt extrusion (HME) relies on elevated temperature and prolonged residence time, which can result in potential degradation and decomposition of thermally sensitive components. Herein, the rheological properties of a physical mixture of polymer and an active pharmaceutical ingredient (API) were utilized to guide the selection of appropriate HME processing temperature. In the currently studied copovidone-nifedipine system, a critical temperature, which is substantially lower (∼13 °C) than the melting point of crystalline API, was captured during a temperature ramp examination and regarded as the critical point at which the API could molecularly dissolve into the polymer...
October 3, 2016: Molecular Pharmaceutics
Ikechukwu P Ejidike, Peter A Ajibade
Mononuclear Ru(III) complexes of the type [Ru(LL)Cl2(H2O)] (LL = monobasic tridentate Schiff base anion: (1Z)-N'-(2-{(E)-[1-(2,4-dihydroxyphenyl)ethylidene]amino}ethyl)-N-phenylethanimidamide [DAE], 4-[(1E)-N-{2-[(Z)-(4-hydroxy-3-methoxybenzylidene)amino]ethyl}ethanimidoyl]benzene-1,3-diol [HME], 4-[(1E)-N-{2-[(Z)-(3,4-dimethoxybenzylidene)amino]ethyl}ethanimidoyl]benzene-1,3-diol [MBE], and N-(2-{(E)-[1-(2,4-dihydroxyphenyl)ethylidene]amino}ethyl)benzenecarboximidoyl chloride [DEE]) were synthesized and characterized using the microanalytical, conductivity measurements, electronic spectra, and FTIR spectroscopy...
2016: Bioinorganic Chemistry and Applications
Yayoi Takahashi, Tamotsu Sugai, Wataru Habano, Kazuyuki Ishida, Makoto Eizuka, Koki Otsuka, Akira Sasaki, Takayuki Matsumoto, Takanori Morikawa, Michiaki Unno, Hiromu Suzuki
Differences in the pathogenesis of microsatellite stable (MSS) sporadic colorectal cancers (CRCs) between left-sided CRC (LC) and right-sided CRC (RC) have not been clarified. To identify pathogenesis-related genomic differences between MSS CRCs within the two locations, we performed a comprehensive molecular analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite instability (MSI; high and low/negative) and DNA methylation status (low methylation epigenome; intermediate methylation epigenome [IME] or high methylation epigenome [HME]) were determined using polymerase chain reaction (PCR) microsatellite analysis and PCR-bisulfite pyrosequencing, respectively...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
Tochukwu C Okwuosa, Dominika Stefaniak, Basel Arafat, Abdullah Isreb, Ka-Wai Wan, Mohamed A Alhnan
PURPOSE: The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. METHODS: Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME)...
November 2016: Pharmaceutical Research
Bader B Alsulays, Vijay Kulkarni, Sultan M Alshehri, Bjad K Almutairy, Eman A Ashour, Joseph T Morott, Abdullah S Alshetaili, Jun-Bom Park, Roshan V Tiwari, Michael A Repka
The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol(®) F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug...
August 3, 2016: Drug Development and Industrial Pharmacy
Nicole I Bieberstein, Eva Kozáková, Martina Huranová, Prasoon K Thakur, Zuzana Krchňáková, Michaela Krausová, Fernando Carrillo Oesterreich, David Staněk
In search for the function of local chromatin environment on pre-mRNA processing we established a new tool, which allows for the modification of chromatin using a targeted approach. Using Transcription Activator-Like Effector domains fused to histone modifying enzymes (TALE-HME), we show locally restricted alteration of histone methylation modulates the splicing of target exons. We provide evidence that a local increase in H3K9 di- and trimethylation promotes inclusion of the target alternative exon, while demethylation by JMJD2D leads to exon skipping...
2016: Scientific Reports
A Foreman, R J De Santis, F Sultanov, D J Enepekides, K M Higgins
BACKGROUND: Total laryngectomy (TL) is an appropriate oncologic operation for many patients with laryngeal cancer delivering excellent oncologic outcomes, however it remains beset with significant functional consequences. Following TL, the upper and lower airways are permanently disconnected, which causes unfiltered, cold air with reduced humidity to enter the tracheobronchial tree, resulting in mucus overproduction and an increase in the viscosity of the mucus. In response to this, Heat and moisture exchangers were developed to compensate for the lost functions of the upper respiratory tract and their effect on the patients' respiratory performance in addition to their quality of life...
2016: Journal of Otolaryngology—Head & Neck Surgery
Taslima T Lina, Paige S Dunphy, Tian Luo, Jere W McBride
UNLABELLED: Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP) effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival...
2016: MBio
Hua Wang, Brian Bierie, Andrew G Li, Shailja Pathania, Kimberly Toomire, Stoil D Dimitrov, Ben Liu, Rebecca Gelman, Anita Giobbie-Hurder, Jean Feunteun, Kornelia Polyak, David M Livingston
An abnormal differentiation state is common in BRCA1-deficient mammary epithelial cells, but the underlying mechanism is unclear. Here, we report a convergence between DNA repair and normal, cultured human mammary epithelial (HME) cell differentiation. Surprisingly, depleting BRCA1 or FANCD2 (Fanconi anemia [FA] proteins) or BRG1, a mSWI/SNF subunit, caused HME cells to undergo spontaneous epithelial-to-mesenchymal transition (EMT) and aberrant differentiation. This also occurred when wild-type HMEs were exposed to chemicals that generate DNA interstrand crosslinks (repaired by FA proteins), but not in response to double-strand breaks...
July 21, 2016: Molecular Cell
Esther S Bochmann, Dirk Neumann, Andreas Gryczke, Karl G Wagner
A new predictive micro-scale solubility and process model for amorphous solid dispersions (ASDs) by hot-melt extrusion (HME) is presented. It is based on DSC measurements consisting of an annealing step and a subsequent analysis of the glass transition temperature (Tg). The application of a complex mathematical model (BCKV-equation) to describe the dependency of Tg on the active pharmaceutical ingredient (API)/polymer ratio, enables the prediction of API solubility at ambient conditions (25°C). Furthermore, estimation of the minimal processing temperature for forming ASDs during HME trials could be defined and was additionally confirmed by X-ray powder diffraction data...
October 2016: European Journal of Pharmaceutics and Biopharmaceutics
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