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Drug innovations

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https://www.readbyqxmd.com/read/28329898/-analysis-of-secondary-data-to-determine-the-prevalence%C3%A2-of%C3%A2-cardiovascular-high-risk-patients-with-hypercholesterolemia-and-refractory-course-of-treatment
#1
Franz-Werner Dippel, Klaus G Parhofer, Thomas Müller-Bohn, Steffen Gebhardt, Karel Kostev
Background Hypercholesterolemia plays a causal role in the development of cardiovascular diseases. Patients are affected differently. There is a lack of epidemiological data about the frequence and characteristics of patients in Germany, especially about those who do not respond sufficiently to high intensity statins with or without other lipid modifying therapies. Methods From more than 2.6 million patient records of office based general practitioners, patients with hypercholestrolemia and high cardiovascular risk, who do not reach their individual LDL-C goal despite a best supplied twelve month maximum lipid lowering therapy (MPR ≥ 80 %), were extracted from the database...
March 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28327993/stepwise-distributed-open-innovation-contests-for-software-development-acceleration-of-genome-wide-association-analysis
#2
Andrew Hill, Po-Ru Loh, Ragu B Bharadwaj, Pascal Pons, Jingbo Shang, Eva Guinan, Karim Lakhani, Iain Kilty, Scott A Jelinsky
BACKGROUND: The association of differing genotypes with disease related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low cost genotyping and sequencing has made collecting large scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies are being used to capture numerous new and complex phenotypic descriptors...
February 28, 2017: GigaScience
https://www.readbyqxmd.com/read/28327584/hybrid-core-shell-hycos-nanoparticles-produced-by-complex-coacervation-for-multimodal-applications
#3
D Vecchione, A M Grimaldi, E Forte, Paolo Bevilacqua, P A Netti, E Torino
Multimodal imaging probes can provide diagnostic information combining different imaging modalities. Nanoparticles (NPs) can contain two or more imaging tracers that allow several diagnostic techniques to be used simultaneously. In this work, a complex coacervation process to produce core-shell completely biocompatible polymeric nanoparticles (HyCoS) for multimodal imaging applications is described. Innovations on the traditional coacervation process are found in the control of the reaction temperature, allowing a speeding up of the reaction itself, and the production of a double-crosslinked system to improve the stability of the nanostructures in the presence of a clinically relevant contrast agent for MRI (Gd-DTPA)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326166/trail-delivery-by-msc-derived-extracellular-vesicles-is-an-effective-anticancer-therapy
#4
ZhengQiang Yuan, Krishna K Kolluri, Kate H C Gowers, Sam M Janes
Extracellular vesicles (EVs) are lipid membrane-enclosed nanoparticles released by cells. They mediate intercellular communication by transferring biological molecules and therefore have potential as innovative drug delivery vehicles. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of cancer cells. Unfortunately, the clinical application of recombinant rTRAIL has been hampered by its low bioavailability and resistance of cancer cells. EV-mediated TRAIL delivery may circumvent these problems...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28322303/a-new-electro-optical-approach-for-conductance-measurement-an-assay-for-the-study-of-drugs-acting-on-ligand-gated-ion-channels
#5
A Menegon, S Pitassi, N Mazzocchi, L Redaelli, R Rizzetto, J F Rolland, C Poli, M Imberti, A Lanati, F Grohovaz
Ligand gated ion channels are involved in many pathophysiological processes and represent a relevant, although challenging, target for drug discovery. We propose an innovative electro-optical approach to their analysis able to derive membrane conductance values from the local membrane potential changes imposed by test current pulses and measured by fast voltage-sensitive fluorescent dyes. We exploited the potential of this proprietary method by developing a drug testing system called "ionChannel Optical High-content Microscope" (ionChannelΩ)...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28319074/tregs-hype-or-hope-for-allogeneic-hematopoietic-stem-cell-transplantation
#6
REVIEW
F Lussana, M Di Ianni, A Rambaldi
The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28318148/barriers-to-innovation-in-human-rabies-prophylaxis-and-treatment-a-causal-analysis-of-insights-from-key-opinion-leaders-and-literature
#7
L H M van de Burgwal, A M G Neevel, C A C M Pittens, A D M E Osterhaus, C E Rupprecht, E Claassen
Rabies is an essentially 100% fatal, zoonotic disease, caused by Lyssaviruses. Currently, the disease is vaccine-preventable with pre- and post-exposure prophylaxis (PrEP and PEP). Still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural Asia and Africa, due to the inaccessibility of prophylaxis and non-existence of treatment. Despite these unmet clinical needs, rabies control mainly focuses on the sylvatic reservoir and drug innovation receives relatively little attention compared to other neglected tropical diseases (NTDs)...
March 20, 2017: Zoonoses and Public Health
https://www.readbyqxmd.com/read/28317290/the-effect-of-engagement-in-an-hiv-aids-integrated-health-programme-on-plasma-hiv-1-rna-suppression-among-hiv-positive-people-who-use-illicit-drugs-a-marginal-structural-modelling-analysis
#8
L Ti, H Dong, T Kerr, R B Turje, S Parashar, J E Min, J Montaner, E Wood, M-J Milloy
OBJECTIVES: HIV treatment-as-prevention campaigns emphasize early diagnosis and immediate access to care and antiretroviral therapy for HIV-positive individuals in order to increase levels of plasma HIV RNA viral load (VL) suppression. However, the possible role of harm reduction-based programmes in this objective has not yet been well evaluated. The objective of the study was to examine the relationship between being a client of the Dr. Peter Centre (DPC; an HIV/AIDS-focused adult integrated health programme) and VL suppression among highly active antiretroviral therapy (HAART)-exposed HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada...
March 19, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28315466/innovative-approach-for-identifying-root-causes-of-glass-defects-in-sterile-drug-product-manufacturing
#9
Lukas Eberle, Alexander Svensson, Andreas Graser, Joerg Luemkemann, Hirokazu Sugiyama, Rainer Schmidt, Konrad Hungerbuehler
In sterile drug product manufacturing, scratched and broken glass containers (i.e., vials) cause product losses, glass particles, equipment contamination and additional cleaning efforts. However, mechanical resistance and exposure of vials to mechanical stress are not sufficiently understood, and no systematic approach for reducing glass-related losses is established. Manufacturers may tackle glass-related losses more rationally if (i) frequencies for inflicting disqualifying damages to drug product containers are known for given forces, (ii) actual exposure in industrial filling lines is quantified and (iii) process enhancements are derived based on collected information...
March 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28315430/oncolytic-adenovirus-expressing-relaxin-ydc002-enhances-therapeutic-efficacy-of-gemcitabine-against-pancreatic-cancer
#10
Kyung Hee Jung, Il-Kyu Choi, Hee-Seung Lee, Hong Hua Yan, Mi Kwon Son, Hyo Min Ahn, JinWoo Hong, Chae-Ok Yun, Soon-Sun Hong
Pancreatic cancer is a highly lethal disease for which limited therapeutic options are available. Pancreatic cancer exhibits a pronounced collagen-rich stromal reaction, which induces chemoresistance by inhibiting drug diffusion into the tumor. Complementary treatment with oncolytic virus such as an oncolytic adenovirus expressing relaxin (YDC002) is an innovative treatment option for combating chemoresistant pancreatic cancer. Here, we examined the ability of combined treatment with gemcitabine and YDC002, which degrades extracellular matrix (ECM), to efficiently treat chemoresistant and desmoplastic pancreatic cancer...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28314976/enzyme-replacement-therapy-and-beyond-in-memoriam-roscoe-o-brady-m-d-1923-2016
#11
REVIEW
Markus Ries
Lysosomal storage disorders are strong candidates for the development of specific innovative therapies. The discovery of enzyme deficiencies is an important milestone in understanding the underlying cause of disease. Being able to replace the first missing enzyme in a lysosomal storage required three decades of dedicated research. Successful drug development for lysosomal storage disorders was fostered by the U.S. Orphan Drug Act. Various optimization strategies have the potential to overcome the current limitations of enzyme replacement therapies...
March 17, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28306751/peptidomic-and-transcriptomic-profiling-of-four-distinct-spider-venoms
#12
Vera Oldrati, Dominique Koua, Pierre-Marie Allard, Nicolas Hulo, Miriam Arrell, Wolfgang Nentwig, Frédérique Lisacek, Jean-Luc Wolfender, Lucia Kuhn-Nentwig, Reto Stöcklin
Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples...
2017: PloS One
https://www.readbyqxmd.com/read/28306222/functionalizing-nanoemulsions-with-carboxylates-impact-on-the-biodistribution-and-pharmacokinetics-in-mice
#13
Mohamed F Attia, Sidy M Dieng, Mayeul Collot, Andrey S Klymchenko, Caroline Bouillot, Christophe A Serra, Marc Schmutz, Meriem Er-Rafik, Thierry F Vandamme, Nicolas Anton
Efficiency of drug administration is related to the inhibition of adverse effects, and can be improved by drug targeting through lipid nanocarriers encapsulation. Targeting technology generally goes along with the nanocarrier functionalization that can be surface modification and/or ligand grafting. The great advantage of nanoemulsions is their loading capability and the possibilities to encapsulate several entities in a single droplet, however, the decoration of the lipid droplets with strongly anchored reactive functions is challenging...
March 17, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28304215/use-of-statistical-and-pharmacokinetic-pharmacodynamic-modeling-and-simulation-to-improve-decision-making-a-section-summary-report-of-the-trends-and-innovations-in-clinical-trial-statistics-conference
#14
Holly Kimko, Seth Berry, Michael O'Kelly, Nitin Mehrotra, Matthew Hutmacher, Venkat Sethuraman
The application of modeling and simulation (M&S) methods to improve decision-making was discussed during the Trends & Innovations in Clinical Trial Statistics Conference held in Durham, North Carolina, USA on May 1-4, 2016. Uses of both pharmacometric and statistical M&S were presented during the conference, highlighting the diversity of the methods employed by pharmacometricians and statisticians to address a broad range of quantitative issues in drug development. Five presentations are summarized herein, which cover the development strategy of employing M&S to drive decision-making; European initiatives on best practice in M&S; case studies of pharmacokinetic/pharmacodynamics modeling in regulatory decisions; estimation of exposure-response relationships in the presence of confounding; and the utility of estimating the probability of a correct decision for dose selection when prior information is limited...
February 7, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28303548/long-acting-antiretrovirals-where-are-we-now
#15
REVIEW
Amesika N Nyaku, Sean G Kelly, Babafemi O Taiwo
PURPOSE OF REVIEW: Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. RECENT FINDINGS: Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development...
March 16, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28303465/pharmacotherapy-in-generalized-anxiety-disorder-novel-experimental-medicine-models-and-emerging-drug-targets
#16
REVIEW
David S Baldwin, Ruihua Hou, Robert Gordon, Nathan T M Huneke, Matthew Garner
Many pharmacological and psychological approaches have been found efficacious in patients with generalized anxiety disorder (GAD), but many treatment-seeking patients will not respond and others will relapse despite continuing with interventions that initially had beneficial effects. Other patients will respond but then stop treatment early because of untoward effects such as sexual dysfunction, drowsiness, and weight gain. There is much scope for the development of novel approaches that could have greater overall effectiveness or acceptability than currently available interventions or that have particular effectiveness in specific clinical subgroups...
March 16, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28303218/the-modification-of-natural-products-for-medical-use
#17
REVIEW
Zongru Guo
Drug innovation is characterized by painstaking molecular-level syntheses and modifications as the basic components of research and development. Similarly, natural products are chemically tailored and modified based upon their structural and biological properties. To some extent, the modification of natural products is quite different from de novo structure-based drug discovery. This review describes the general strategies and principles for the modification of natural products to drugs, as illustrated by several successful medicines that originated from natural products...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28302915/sex-differences-in-ischaemic-stroke-potential-cellular-mechanisms
#18
REVIEW
Anjali Chauhan, Hope Moser, Louise D McCullough
Stroke remains a leading cause of mortality and disability worldwide. More women than men have strokes each year, in part because women live longer. Women have poorer functional outcomes, are more likely to need nursing home care and have higher rates of recurrent stroke compared with men. Despite continued advancements in primary prevention, innovative acute therapies and ongoing developments in neurorehabilitation, stroke incidence and mortality continue to increase due to the aging of the U.S. POPULATION: Sex chromosomes (XX compared with XY), sex hormones (oestrogen and androgen), epigenetic regulation and environmental factors all contribute to sex differences...
April 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28300871/glial-scar-modulation-as-therapeutic-tool-in-spinal-cord-injury-in-animal-models
#19
Jéssica Rodrigues Orlandin, Carlos Eduardo Ambrósio, Valéria Maria Lara
PURPOSE: Spinal Cord injury represents, in veterinary medicine, most of the neurological attendances and may result in permanent disability, death or euthanasia. Due to inflammation resulting from trauma, it originates the glial scar, which is a cell interaction complex system. Its function is to preserve the healthy circuits, however, it creates a physical and molecular barrier that prevents cell migration and restricts the neuroregeneration ability. METHODS: This review aims to present innovations in the scene of treatment of spinal cord injury, approaching cell therapy, administration of enzyme, anti-inflammatory, and other active principles capable of modulating the inflammatory response, resulting in glial scar reduction and subsequent functional improvement of animals...
February 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28296612/polar-extremes-in-the-clinical-use-of-stem-cells
#20
George Q Daley
The U.S. biotechnology and pharmaceutical industries arguably lead the world in innovation while operating under stringent regulations set by the Food and Drug Administration (FDA). Although flexible pathways exist to accelerate the development or approval of treatments for serious illnesses or..
March 16, 2017: New England Journal of Medicine
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