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https://www.readbyqxmd.com/read/28231003/utilization-of-gastrointestinal-simulator-gis-an-in-vivo-predictive-dissolution-methodology-coupled-with-computational-approach-to-forecast-oral-absorption-of-dipyridamole
#1
Kazuki Matsui, Yasuhiro Tsume, Susumu Takeuchi, Amanda Searls, Gordon L Amidon
Weakly basic drugs exhibit a pH-dependent dissolution profile in the gastrointestinal (GI) tract, making it difficult to predict their oral absorption profile. The aim of this study was to investigate the utility of the Gastrointestinal Simulator (GIS), a novel in vivo predictive dissolution (iPD) methodology, in predicting the in vivo behavior of the weakly basic drug, dipyridamole, when coupled with in silico analysis. The GIS is a multi-compartmental dissolution apparatus, which represents physiological gastric emptying in the fasted state...
February 23, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28229454/analysis-of-a-fully-penetrant-spinocerebellar-ataxia-type-8-brazilian-family
#2
V P Cintra, C M Lourenço, M M V Rocha, P J Tomaselli, W Marques
Spinocerebellar ataxia type 8 (SCA8) is a progressive neurological disorder caused by the expanded repeat CTA/CTG of two overlapping genes, ATXN8OS and ATXN8, expressed bidirectionally. Normal alleles have 15-50 repeats, and pathogenic alleles range from 71 to 1300 repeats. The disorder is relatively rare, accounting for about 2%-5% of the autosomal dominant forms of hereditary ataxia worldwide. However, the prevalence of disease-causing ATXN8OS/ATXN8 expansions is higher than the disease because of the reduced penetrance of the expanded allele...
February 22, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28227107/a-comparison-of-the-cluster-span-threshold-and-the-union-of-shortest-paths-as-objective-thresholds-of-eeg-functional-connectivity-networks-from-beta-activity-in-alzheimer-s-disease
#3
Keith Smith, Daniel Abasolo, Javier Escudero, Keith Smith, Daniel Abasolo, Javier Escudero, Javier Escudero, Keith Smith, Daniel Abasolo
The Cluster-Span Threshold (CST) is a recently introduced unbiased threshold for functional connectivity networks. This binarisation technique offers a natural trade-off of sparsity and density of information by balancing the ratio of closed to open triples in the network topology. Here we present findings comparing it with the Union of Shortest Paths (USP), another recently proposed objective method. We analyse standard network metrics of binarised networks for sensitivity to clinical Alzheimer's disease in the Beta band of Electroencephalogram activity...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28224389/development-of-a-discriminative-in-vitro-release-test-for-rivastigmine-transdermal-patches-using-pharmacopeial-apparatuses-usp-5-and-usp-6
#4
Alice Simon, Maria Inês Amaro, Anne Marie Healy, Lucio Mendes Cabral, Valeria Pereira de Sousa
The aim of this study was to develop and validate a discriminating in vitro release test to evaluate rivastigmine transdermal patches. The Exelon® Patch was chosen as a model transdermal product. The studies of in vitro release were designed to determine the impact of the official apparatus chosen (USP apparatus 5 and USP apparatus 6), the rotation speed, and the dissolution medium characteristics on the rivastigmine release profile from transdermal patches. Patches with different drug release profiles were tested in order to evaluate the discriminating power of the in vitro release test developed and validated...
February 21, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28221894/usp-3-united-in-safeguarding-patients-personnel-and-providers
#5
Robin T Zon
No abstract text is available yet for this article.
February 21, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28220152/lack-of-mycothiol-and-ergothioneine-induces-different-protective-mechanisms-in-mycobacterium-smegmatis
#6
Arishma Rajkarnikar Singh, Andrew Strankman, Ruzan Orkusyan, Endang Purwantini, Mamta Rawat
Mycobacterium smegmatis contains the low molecular weight thiols, mycothiol (MSH) and ergothioneine (ESH). Examination of transposon mutants disrupted in mshC and egtA, involved in the biosynthesis of MSH and ESH respectively, demonstrated that both mutants were sensitive to oxidative, alkylating, and metal stress. However, the mshC mutant exhibited significantly more protein carbonylation and lipid peroxidation than wildtype, while the egtA mutant had less protein and lipid damage than wildtype. We further show that Ohr, KatN, and AhpC, involved in protection against oxidative stress, are upregulated in the egtA mutant...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28213251/on-line-monitoring-of-in-vitro-oral-bioaccessibility-tests-as-front-end-to-liquid-chromatography-for-determination-of-chlorogenic-acid-isomers-in-dietary-supplements
#7
Daniel Kremr, David J Cocovi-Solberg, Petra Bajerová, Karel Ventura, Manuel Miró
A novel fully automated in-vitro oral dissolution test assay as a front-end to liquid chromatography has been developed and validated for on-line chemical profiling and monitoring of temporal release profiles of three caffeoylquinic acid (CQA) isomers, namely, 3-CQA,4-CQA and 5-CQA, known as chlorogenic acids, in dietary supplements. Tangential-flow filtration is harnessed as a sample processing approach for on-line handling of CQA containing extracts of hard gelatin capsules and introduction of protein-free samples into the liquid chromatograph...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28210824/ultrasound-palpation-for-fast-in-situ-quantification-of-articular-cartilage-stiffness-thickness-and-relaxation-capacity
#8
M Schöne, R M Schulz, H Tzschätzsch, P Varga, K Raum
Most current cartilage testing devices require the preparation of excised samples and therefore do not allow intra-operative application for diagnostic purposes. The gold standard during open or arthroscopic surgery is still the subjective perception of manual palpation. This work presents a new diagnostic method of ultrasound palpation (USP) to acquire applied stress and strain data during manual palpation of articular cartilage. With the proposed method, we obtain cartilage thickness and stiffness. Moreover, repeated palpations allow the quantification of relaxation effects...
February 16, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28196917/validation-of-milliflex%C3%A2-quantum-for-bioburden-testing-of-pharmaceutical-products
#9
Oliver Gordon, Marcel Goverde, Alexandra Staerk, David Roesti
This article reports the validation strategy used to demonstrate that the Milliflex® Quantum yielded non-inferior results to the traditional bioburden method. It was validated according to USP <1223>, Ph. Eur. 5.1.6 and PDA Technical Report No. 33 and comprised the validation parameters Robustness, Ruggedness, Repeatability, Specificity, Limit of Detection and Quantification, Accuracy, Precision, Linearity, Range and Equivalence in Routine Operation. For the validation, a combination of pharmacopeial ATCC strains as well as a broad selection of in-house isolates was used...
February 14, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/28193468/using-the-fundamentals-of-adsorption-to-understand-peak-distortion-due-to-strong-solvent-effect-in-hydrophilic-interaction-chromatography
#10
Fabrice Gritti, Jyotsna Sehajpal, Jacob Fairchild
The peak distortion observed in hydrophilic interaction chromatography (HILIC) may be caused by the sample diluent to mobile phase mismatch. The United States Pharmacopeia (USP) method for organic impurities in cetirizine HCl tablets calls for such a mismatch, having a higher concentration of strong solvent in the sample diluent than in the mobile phase. A significant peak deformation is reported for cetirizine (a second-generation antihistamine) when it is purified on a Ethylene Bridged Hybrid (BEH) HILIC column (4...
March 17, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28187457/the-b-box-module-of-cyld-is-responsible-for-its-intermolecular-interaction-and-cytoplasmic-localization
#11
Songbo Xie, Miao Chen, Siqi Gao, Tao Zhong, Peng Zhou, Dengwen Li, Jun Zhou, Jinmin Gao, Min Liu
The tumor suppressor protein cylindromatosis (CYLD), as a microtubule-associated deubiquitinase, plays a pivotal role in a wide range of cellular activities, including innate immunity, cell division, and ciliogenesis. Structural characterization reveals a small zinc-binding B-box inserted within the ubiquitin specific protease (USP) domain of CYLD; however, the exact role for this module remains yet to be elucidated. Here we identify a critical role for the B-box in facilitating the intermolecular interaction and subcellular localization of CYLD...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185305/cgmp-production-of-the-radiopharmaceutical-18-f-mk-6240-for-pet-imaging-of-human-neurofibrillary-tangles
#12
Thomas Lee Collier, Daniel L Yokell, Eli Livni, Peter A Rice, Sofie Celen, Kim Serdons, Ramesh Neelamegam, Guy Bormans, Dawn Harris, Abbas Walji, Eric D Hostetler, Idriss Bennacef, Neil Vasdev
Fluorine-18 labelled 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18) F]MK-6240) is a novel potent and selective PET radiopharmaceutical for detecting human neurofibrillary tangles, which are made up of aggregated tau protein. Herein, we report the fully automated two-step radiosynthesis of [(18) F]MK-6240 using a commercially available radiosynthesis module, GE Healthcare Tracerlab(TM) FXFN . Nucleophilic fluorination of the 5-diBoc-6-nitro precursor with potassium cryptand [(18) F]fluoride (K[(18) F]/K222 ) was carried out by conventional heating, followed by acid deprotection and semi-preparative HPLC under isocratic conditions...
February 9, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28179741/innovations-in-medication-preparation-safety-and-wastage-reduction-use-of-a-workflow-management-system-in-a-pediatric-hospital
#13
Stephen Jerome Davis, Josephine Hurtado, Rosemary Nguyen, Tran Huynh, Ivan Lindon, Cedric Hudnall, Sara Bork
Background: USP <797> regulatory requirements have mandated that pharmacies improve aseptic techniques and cleanliness of the medication preparation areas. In addition, the Institute for Safe Medication Practices (ISMP) recommends that technology and automation be used as much as possible for preparing and verifying compounded sterile products. Objective: To determine the benefits associated with the implementation of the workflow management system, such as reducing medication preparation and delivery errors, reducing quantity and frequency of medication errors, avoiding costs, and enhancing the organization's decision to move toward positive patient identification (PPID)...
January 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/28177828/isolation-and-characterization-of-a-novel-pollen-specific-promoter-in-maize%C3%AF-i-zea-mays-l-i-%C3%AF
#14
He Wang, Mingxia Fan, Guohong Wang, Chunyu Zhang, Lei Shi, Zhengyi Wei, Wenjuan Ma, Jing Chang, Senxin Huang, Feng Lin
<i>ZmSTK2_USP</i>, located on the long arm of chromosome 4, belongs to the serine/threonine kinase gene in maize. The sequence analysis of 2,100 bp upstream from the start codon ATG has shown that it contains <i>cis</i>-element motifs and two types of anther/pollen-specific promoter elements (GTGA and AGAAA), suggesting that it is the pollen-specific promoter. To investigate the function of <i>ZmSTK2_USP</i> promoter, the GUS gene fusion system was employed. In pro<i>ZmSTK2_USP-GUS</i> genetically modified plants, GUS activity was detected in mature pollen grains and pollen tubes but not found in other floral and vegetable tissues...
January 4, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28165509/structural-basis-of-the-specificity-of-usp18-toward-isg15
#15
Anja Basters, Paul P Geurink, Annika Röcker, Katharina F Witting, Roya Tadayon, Sandra Hess, Marta S Semrau, Paola Storici, Huib Ovaa, Klaus-Peter Knobeloch, Günter Fritz
Protein modification by ubiquitin and ubiquitin-like modifiers (Ubls) is counteracted by ubiquitin proteases and Ubl proteases, collectively termed DUBs. In contrast to other proteases of the ubiquitin-specific protease (USP) family, USP18 shows no reactivity toward ubiquitin but specifically deconjugates the interferon-induced Ubl ISG15. To identify the molecular determinants of this specificity, we solved the crystal structures of mouse USP18 alone and in complex with mouse ISG15. USP18 was crystallized in an open and a closed conformation, thus revealing high flexibility of the enzyme...
February 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28160502/deubiquitinating-enzyme-usp22-positively-regulates-c-myc-stability-and-tumorigenic-activity-in-mammalian-and-breast-cancer-cells
#16
Dongyeon Kim, Ahyoung Hong, Hye In Park, Woo Hyun Shin, Lang Yoo, Seo Jeong Jeon, Kwang Chul Chung
The proto-oncogene c-Myc has a pivotal function in growth control, differentiation and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28153651/accelerated-in-vitro-release-testing-method-for-naltrexone-loaded-plga-microspheres
#17
Janki V Andhariya, Stephanie Choi, Yan Wang, Yuan Zou, Diane J Burgess, Jie Shen
The objective of the present study was to develop a discriminatory and reproducible accelerated release testing method for naltrexone loaded parenteral polymeric microspheres. The commercially available naltrexone microsphere product (Vivitrol(®)) was used as the testing formulation in the in vitro release method development, and both sample-and-separate and USP apparatus 4 methods were investigated. Following an in vitro drug stability study, frequent media replacement and addition of anti-oxidant in the release medium were used to prevent degradation of naltrexone during release testing at "real-time" (37°C) and "accelerated" (45°C), respectively...
January 30, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28153596/measurement-and-accurate-interpretation-of-the-solubility-of-pharmaceutical-salts
#18
Yan He, Chris Ho, Donglai Yang, Jeane Chen, Edward Orton
Salt formation is one of the primary approaches to improve the developability of ionizable poorly water soluble compounds. Solubility determination of the salt candidates in aqueous media or bio-relevant fluids is a critical step in salt screening. Salt solubility measurements can be complicated due to dynamic changes in both solution and solid phases. Because of the early implementation of salt screening in research, solubility measurements often are performed using minimal amount of material. Some salts have transient high solubility upon dissolution...
January 30, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28146289/in-vitro-evaluation-of-square-and-surgeon-s-knots-in-large-gauge-suture
#19
Alex M Gillen, Amelia S Munsterman, Ramsis Farag, Matthew O D Coleridge, R Reid Hanson
OBJECTIVE: To investigate the strength and size of surgeon's and square knots for starting and ending continuous suture lines using large gauge suture. STUDY DESIGN: In vitro mechanical study. STUDY POPULATION: Knotted suture. METHODS: Surgeon's and square knots were tested using 2 and 3 USP polyglactin 910 and 2 USP polydioxanone under linear tension on a universal testing machine. Failure mode and knot holding capacity (KHC) were recorded, and relative knot security (RKS) was calculated as a percentage of KHC...
February 2017: Veterinary Surgery: VS
https://www.readbyqxmd.com/read/28138820/development-of-extended-release-oral-flexible-tablet-er-oft-formulation-for-pediatric-and-geriatric-compliance-an-age-appropriate-formulation
#20
Prabagaran Chandrasekaran, Ruckmani Kandasamy
Development of age-appropriate formulation suitable for pediatric and geriatric patients involves various challenges. The objective of this research was to develop extended-release oral flexible tablet (ER-OFT) formulation using carbamazepine (CBZ) as model drug for pediatric and geriatric compliance. ER-microparticles of carbamazepine, a BCS class 2, and narrow therapeutic index (NTI) drug, were prepared using ethyl cellulose as matrixing polymer and hypromellose as hydrophilic pore former. Microparticles were prepared using high-shear granulator fitted with an atomizing spray system...
January 30, 2017: AAPS PharmSciTech
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