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Manuela Terrinoni, Stefan L Nordqvist, Susanne Källgård, Jan Holmgren, Michael Lebens
Antibiotic selection for maintenance of expression plasmids is discouraged in production of recombinant proteins for pharmaceutical or other human uses due to the risks of antibiotic residue contamination of the final products and release of DNA encoding antibiotic resistance into the environment. We describe the construction of expression plasmids that are instead maintained by complementation of the lgt gene encoding a (pro)lipoprotein glyceryl transferase essential for biosynthesis of bacterial lipoprotein...
December 8, 2017: Applied and Environmental Microbiology
Uffe Nygaard, Mette Deleuran, Christian Vestergaard
Atopic dermatitis is a chronic inflammatory skin disorder affecting children and adults, with the majority presenting mild to moderate disease severity. The use of topical corticosteroids (TCSs) in combination with emollients has been the mainstay for treating mild to moderate atopic dermatitis since the 1950s, and as a supplement to systemic treatment in severe disease. However, while very effective, TCSs are often accompanied by poor adherence due to corticophobia (fear of using corticosteroids in patients or doctors), unwanted side effects, and in some cases insufficient clinical response...
December 8, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
Edita Voitechovič, Anton Korepanov, Dmitry Kirsanov, Andrey Legin
Quantification of proteins is a key biochemical assay in molecular biology, biotechnology, medicine and pharmacology. Protein quantification protocols can be based on spectrophotometry, enzyme-linked immunosorbent assay, mass spectrometry or quantitative immunoblotting depending on analyte. In case of immobilized protein these methods require suitable sample preparation. Thus, sophisticated analysis becomes even more complex, expensive and time-consuming. Such drawbacks are highly undesirable in industry. In this study we propose a new approach for evaluation of immobilized protein concentration based on application of bio-assisted potentiometric multisensor system...
December 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
Leire Mijangos, Haizea Ziarrusta, Maitane Olivares, Olatz Zuloaga, Monika Möder, Nestor Etxebarria, Ailette Prieto
A new procedure using polyethersulfone (PES) microextraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was developed in this work for the simultaneous determination of 41 multiclass priority and emerging organic pollutants including herbicides, hormones, personal care products, and pharmaceuticals, among others, in seawater, wastewater treatment plant (WWTP) effluents, and estuary samples. The optimization of the analysis included two different chromatographic columns and different variables (polarity, fragmentor voltage, collision energy, and collision cell accelerator) of the mass spectrometer...
December 6, 2017: Analytical and Bioanalytical Chemistry
Elisabet Berggren, Andrew White, Gladys Ouedraogo, Alicia Paini, Andrea-Nicole Richarz, Frederic Y Bois, Thomas Exner, Sofia Leite, Leo A van Grunsven, Andrew Worth, Catherine Mahony
We describe and illustrate a workflow for chemical safety assessment that completely avoids animal testing. The workflow, which was developed within the SEURAT-1 initiative, is designed to be applicable to cosmetic ingredients as well as to other types of chemicals, e.g. active ingredients in plant protection products, biocides or pharmaceuticals. The aim of this work was to develop a workflow to assess chemical safety without relying on any animal testing, but instead constructing a hypothesis based on existing data, in silico modelling, biokinetic considerations and then by targeted non-animal testing...
November 2017: Computational Toxicology
Charles Dalcanale Tesser
Quaternary prevention consists in the identification of persons at risk of excessive medicalization and their protection against new unnecessary interventions, avoiding iatrogenic damages. Here, we argue about the importance of quaternary prevention in specific primary and secondary prevention. The recent great development of preventive medicine, biomedicalization of risks and their treatment as if they were diseases, and the powerful influence of the commercial interests of pharmaceutical industries on the production of medical-sanitary knowledge alter classifications, create diseases and pre-diseases, lower cutoff points, and erase the distinction between prevention and healing...
December 4, 2017: Revista de Saúde Pública
Shivankar Agrawal, Debabrata Acharya, Alok Adholeya, Colin J Barrow, Sunil K Deshmukh
Marine environments are largely unexplored and can be a source of new molecules for the treatment of many diseases such as malaria, cancer, tuberculosis, HIV etc. The Marine environment is one of the untapped bioresource of getting pharmacologically active nonribosomal peptides (NRPs). Bioprospecting of marine microbes have achieved many remarkable milestones in pharmaceutics. Till date, more than 50% of drugs which are in clinical use belong to the nonribosomal peptide or mixed polyketide-nonribosomal peptide families of natural products isolated from marine bacteria, cyanobacteria and fungi...
2017: Frontiers in Pharmacology
Wiem Meddeb, Leila Rezig, Manef Abderrabba, Gérard Lizard, Mondher Mejri
In this study, milk thistle seeds growing in different areas in Tunisia were cold pressed and the extracted oils were examined for their chemical and antioxidant properties. The major fatty acids were linoleic acid (C18:2) (57.0%, 60.0%, and 60.3% for the milk thistle seed oils native to Bizerte, Zaghouan and Sousse, respectively) and oleic acid (C18:1) (15.5%, 21.5%, and 22.4% for the milk thistle seed oils originating from Bizerte, Zaghouan and Sousse, respectively). High performance liquid chromatography (HPLC) analysis showed the richness of the milk thistle seed oils (MTSO) in α-tocopherol...
December 2, 2017: International Journal of Molecular Sciences
Zhichao Lu, Xiaojun Zeng, Gerald B Hammond, Bo Xu
Expanding the use of fluorine in pharmaceuticals, agrochemicals and materials requires a widely applicable and more efficient protocol for the preparation of fluorinated compounds. We have developed a new generation nucleophilic fluorination reagent--KHSO4-13HF, HF 68 wt/wt%--that is not only easily-handled and inexpensive but also capable of hydrofluorinating diverse, highly functionalized alkenes, including natural products. The high efficiency observed in this reaction hinges on the activation of HF using a highly 'acidic' hydrogen bond acceptor...
December 5, 2017: Journal of the American Chemical Society
Abdel Naser Zaid, Nihal Zohud, Bushra E'layan, Tasneem Aburadi, Nidal Jaradat, Iyad Ali, Fatima Hussein, Mashhour Ghanem, Aiman Qaddomi, Yara Abu Zaaror
Background: Orlistat is an irreversible inhibitor of the lipase enzyme that prevents trigylcerides from being digested, thereby inhibiting triglyceride hydrolysis and absorption. The resultant reduced calorie uptake enables a positive effect on weight control. Systemic absorption of the drug is, therefore, not necessary for its mode of action. An alternative in vitro study (pharmacodynamic) has been introduced for this drug, as in vivo bioavailability studies are irrelevant with regard to the achievement of the product's intended purposes...
2017: Drug Design, Development and Therapy
C Hare, T Bonakdar, M Ghadiri, J Strong
Tablets are the most common solid dosage form of pharmaceutical active ingredients due to their ease of use. Their dissolution behaviour depends on the particle size distribution and physicochemical properties of the formulation, and the compression process, which need to be optimised for producing consistently robust tablets, as weaker tablets are often prone to breakage during production, transport and end use. Tablet strength is typically determined by diametric compression and friability tests. The former gives rise to propagation of a crack on a plane along the compression axis, whilst the latter, carried out in a rotating drum, incurs surface damage and produces chips and debris...
November 29, 2017: International Journal of Pharmaceutics
Biancarosa Irene, Belghit Ikram, Bruckner G Christian, Liland S Nina, Waagbø Rune, Amlund Heidi, Heesch Svenja, Lock Erik-Jan
BACKGROUND: In the past few years, much effort has been invested into developing a new blue economy based on harvesting, cultivating and processing marine macroalgae in Norway. Macroalgae have a high potential for a wide range of applications, e.g. as source of pharmaceuticals, production of biofuels or as food and feed. However, data on the chemical composition of macroalgae from Norwegian waters are scant. This study was designed to characterize the chemical composition of 21 algae species...
November 28, 2017: Journal of the Science of Food and Agriculture
Richard S Rogers, Michael Abernathy, Douglas D Richardson, Jason C Rouse, Justin B Sperry, Patrick Swann, Jette Wypych, Christopher Yu, Li Zang, Rohini Deshpande
Today, we are experiencing unprecedented growth and innovation within the pharmaceutical industry. Established protein therapeutic modalities, such as recombinant human proteins, monoclonal antibodies (mAbs), and fusion proteins, are being used to treat previously unmet medical needs. Novel therapies such as bispecific T cell engagers (BiTEs), chimeric antigen T cell receptors (CARTs), siRNA, and gene therapies are paving the path towards increasingly personalized medicine. This advancement of new indications and therapeutic modalities is paralleled by development of new analytical technologies and methods that provide enhanced information content in a more efficient manner...
November 30, 2017: AAPS Journal
Peter Hertzman, Paul Miller, Keith Tolley
With the introduction of new expensive medicines, traditional pricing schemes based on constructs such as price per pill/vial have been challenged. Potential innovative schemes could be either financial-based or performance-based. Within financial-based schemes the use of price discrimination is an emerging option, which we explore in this assessment. Areas covered: In the short term the price per indication approach is likely to become more prevalent for high cost, high benefit new pharmaceuticals, such as those emerging in oncology (e...
November 30, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
Craig Galligan, Christopher Nguyen, John Nelson, Patrick Spooner, Todd Miller, Brian M Davis, Ralf Lenigk, Christopher M Puleo
We present methods to fabricate high-capacity redox electrodes using thick membrane or fiber casting of conjugated polymer solutions. Unlike common solution casting or printing methods used in current organic electronics, the presented techniques enable production of PEDOT:PSS electrodes with high charge capacity and the capability to operate under applied voltages greater than 100 V without electrochemical overoxidation. The electrodes are shown integrated into several electrokinetic components commonly used in automated bioprocess or bioassay workflows, including electrophoretic DNA separation and extraction, cellular electroporation/lysis, and electroosmotic pumping...
November 1, 2017: SLAS Technology
J Javier Hernandez, Michael Pryszlak, Lindsay Smith, Connor Yanchus, Naheed Kurji, Vijay M Shahani, Steven V Molinski
The repositioning or "repurposing" of existing therapies for alternative disease indications is an attractive approach that can save significant investments of time and money during drug development. For cancer indications, the primary goal of repurposed therapies is on efficacy, with less restriction on safety due to the immediate need to treat this patient population. This report provides a high-level overview of how drug developers pursuing repurposed assets have previously navigated funding efforts, regulatory affairs, and intellectual property laws to commercialize these "new" medicines in oncology...
2017: Frontiers in Oncology
Joakim Riikonen, Wujun Xu, Vesa-Pekka Lehto
When poor aqueous solubility of active pharmaceutical ingredients is encountered during a drug formulation process, the toolbox typically utilized contains pharmaceutical salts, co-crystals, solid dispersions, cyclodextrins, lipids, liposomes and nanocrystals etc. Especially in the pharmaceutical industry, the option which confers the greatest benefit with the lowest risk is usually chosen. Several factors affect the final decision, but new technologies should also be considered especially if they can address several issues at the same time...
November 25, 2017: International Journal of Pharmaceutics
Nina Beyer, Justyna K Kulig, Marco W Fraaije, Martin A Hayes, Dick Janssen
The conversion of a series of pharmaceutical compounds was examined with three variants of cytochrome P450BM3 fused to phosphite dehydrogenase to enable cofactor recycling. Conditions for enzyme production were optimized and the purified PTDH-P450BM3 variants were tested against 32 commercial drugs using rapid UPLC-MS analysis. The sets of mutations (R47L/F87V/L188Q and R47L/F87V/L188Q/E267V/G415S) improved conversion for all compounds and a variety of products were detected. Product analysis showed that reaction types included C-hydroxylation, N-oxidation, demethylation, and aromatization...
November 27, 2017: Chembiochem: a European Journal of Chemical Biology
Mehrnaz Rezaei, Hamed Taj Mohammadi, Atiyeh Mahdavi, Mostafa Shourian, Hossein Ghafoori
Tyrosinase (EC is a key copper-containing metalloenzyme widely distributed in nature and plays determinant role in melanin biosynthesis. The enzyme manifests two unusual catalytic properties including oxidase and monooxygenase activities. Its inhibitors may be applied to efficiently treat of hyperpigmentation and widely used in pharmaceutical and cosmetic products, as well as food supplements and insecticides. The present study aims to evaluate the inhibitory effects of some novel azo-hydrazone tautomeric dyes (4a-e) including bioactive thiazolidinone moiety on the activity of the mushroom tyrosinase...
November 24, 2017: International Journal of Biological Macromolecules
John M Woodley
Biocatalysis uses enzymes for chemical synthesis and production, offering selective, safe and sustainable catalysis. While today the majority of applications are in the pharmaceutical sector, new opportunities are arising every day in other industry sectors, where production costs become a more important driver. In the early applications of the technology, it was necessary to design processes to match the properties of the biocatalyst. With the advent of protein engineering, organic chemists started to develop and improve enzymes to suit their needs...
January 13, 2018: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
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