WorldWideScience

Sample records for advancing drug innovation

  1. Protein Innovations Advance Drug Treatments, Skin Care

    Science.gov (United States)

    2012-01-01

    Dan Carter carefully layered the sheets of tracing paper on the light box. On each sheet were renderings of the atomic components of an essential human protein, one whose structure had long been a mystery. With each layer Carter laid down, a never-before-seen image became clearer. Carter joined NASA s Marshall Space Flight Center in 1985 and began exploring processes of protein crystal growth in space. By bouncing intense X-rays off the crystals, researchers can determine the electron densities around the thousands of atoms forming the protein molecules, unveiling their atomic structures. Cultivating crystals of sufficient quality on Earth was problematic; the microgravity conditions of space were far more accommodating. At the time, only a few hundred protein structures had been mapped, and the methods were time consuming and tedious. Carter hoped his work would help reveal the structure of human serum albumin, a major protein in the human circulatory system responsible for ferrying numerous small molecules in the blood. More was at stake than scientific curiosity. Albumin has a high affinity for most of the world s pharmaceuticals, Carter explains, and its interaction with drugs can change their safety and efficacy. When a medication enters the bloodstream a cancer chemotherapy drug, for example a majority of it can bind with albumin, leaving only a small percentage active for treatment. How a drug interacts with albumin can influence considerations like the necessary effective dosage, playing a significant role in the design and application of therapeutic measures. In spite of numerous difficulties, including having no access to microgravity following the 1986 Space Shuttle Challenger disaster, the image Carter had hoped to see was finally clarifying. In 1988, his lab had acquired specialized X-ray and detection equipment a tipping point. Carter and his colleagues began to piece together albumin s portrait, the formation of its electron densities coalescing on

  2. [Innovation in Surgery for Advanced Lung Cancer].

    Science.gov (United States)

    Nakano, Tomoyuki; Yasunori, Sohara; Endo, Shunsuke

    2016-07-01

    Thoracoscopic surgery can be one of less invasive surgical interventions for early stage lung cancer. Locally advanced lung cancer, however, cannot avoid aggressive procedures including pneumonectomy and/or extended combined resection of chest wall, aorta, esophagus, etc. for complete resection. Surgical approach even for advanced lung cancer can be less invasive by benefit from new anti-cancer treatment, innovated manipulations of bronchoplasty and angioplasty, and bench surgery( lung autotransplantation technique). We herein reviewed the strategy to minimize invasive interventions for locally advanced lung cancer, introducing 2 successful cases with advanced lung cancer. The 1st patient is a 62-year old man with centrally advanced lung cancer invading to mediastinum. Right upper sleeve lobectomy with one-stoma carinoplasty following induction chemoradiation therapy was successful. The operation time was 241 minutes. The performance status is good with no recurrence for 60 months after surgery. The 2nd is a 79-year old man with advanced lung cancer invading to the distal aortic arch. Left upper segmentectomy following thoracic endovascular aortic repair with stentgraft was successful with no extracorporeal circulation. The operation time was 170 minutes. The performance status is good with no recurrence for 30 months after surgery. The invasiveness of surgical interventions for local advanced lung cancer can be minimized by innovated device and new anti-cancer drugs.

  3. Advances in psoriasis physiopathology and treatments: Up to date of mechanistic insights and perspectives of novel therapies based on innovative skin drug delivery systems (ISDDS).

    Science.gov (United States)

    Sala, M; Elaissari, A; Fessi, H

    2016-10-10

    Psoriasis is a chronic inflammatory disease affecting mainly the skin but which can be complicated by psoriatic arthritis (PsA).This autoimmune skin disorder concerns 2-5% of the world population. To date, the physiopathology of psoriasis is not still completely elucidated but many researches are ongoing which have led for example to the discovery of the Th17/Th22 pathway. The conventional therapeutic approaches (local or systemic route) appeal to various classes of drugs with complex mechanisms of action and non-negligible side effects. Although there is no therapy capable to cure psoriasis, the current goal is to relieve symptoms as longer as possible with a good benefit/risk ratio. That is one of the principal limits of conventional antipsoriatic drugs. New formulations based on nanoencapsulation are a promising opportunity to answer to this limit by offering an optimization of the conventional antipsoriatic drug use (higher activity, lower side effects and frequency of application, etc.). Herein, we tried to put in perspective the mechanistic insights (histological and immunological views) proposed into scientific literature these last years in order to have a better comprehension of psoriasis physiopathology resulting in skin lesions and PsA. The therapeutic armamentarium and the different strategies in the management of psoriasis are discussed in greater details. To finish, the field of encapsulation in nanoparticles is broached in order to put forward recent advances in innovative skin drug delivery systems (ISDDSs) of antipsoriatic active agents for a better efficacy, safety and compliance.

  4. International Conference on Advanced Computing for Innovation

    CERN Document Server

    Angelova, Galia; Agre, Gennady

    2016-01-01

    This volume is a selected collection of papers presented and discussed at the International Conference “Advanced Computing for Innovation (AComIn 2015)”. The Conference was held at 10th -11th of November, 2015 in Sofia, Bulgaria and was aimed at providing a forum for international scientific exchange between Central/Eastern Europe and the rest of the world on several fundamental topics of computational intelligence. The papers report innovative approaches and solutions in hot topics of computational intelligence – advanced computing, language and semantic technologies, signal and image processing, as well as optimization and intelligent control.

  5. Continuous innovation in the drug life cycle

    NARCIS (Netherlands)

    Langedijk, Joris

    2016-01-01

    Patients may benefit from new uses for old drugs. Competent authorities such as the European Medicines Agency evaluate the quality, efficacy and safety of a medicinal product for the use in a well-defined therapeutic indication. Innovations may continue upon the approval, for example through the lic

  6. Advanced materials and processing for drug delivery: the past and the future.

    Science.gov (United States)

    Zhang, Ying; Chan, Hon Fai; Leong, Kam W

    2013-01-01

    Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery.

  7. Defining rewardable innovation in drug therapy.

    Science.gov (United States)

    Aronson, Jeffrey K; Ferner, Robin E; Hughes, Dyfrig A

    2012-03-30

    Implementing mechanisms for rewarding those who introduce innovative medicinal products requires a definition of 'rewardable innovation'. Here, we propose a definition of innovation with respect to medicinal products, accompanied by a ranking of the importance of different types of innovativeness, with the aim of providing a basis for rewarding such innovation.

  8. Developing a paradigm of drug innovation: an evaluation algorithm.

    Science.gov (United States)

    Caprino, Luciano; Russo, Pierluigi

    2006-11-01

    Assessment of drug innovation is a burning issue because it involves so many different perspectives, mainly those of patients, decision- and policy-makers, regulatory authorities and pharmaceutical companies. Moreover, the innovative value of a new medicine is usually an intrinsic property of the compound, but it also depends on the specific context in which the medicine is introduced and the availability of other medicines for treating the same clinical condition. Thus, a model designed to assess drug innovation should be able to capture the intrinsic properties of a compound (which usually emerge during R&D) and/or modification of its innovative value with time. Here we describe the innovation assessment algorithm (IAA), a simulation model for assessing drug innovation. IAA provides a score of drug innovation by assessing information generated during both the pre-marketing and the post-marketing authorization phase.

  9. Jiangsu Innovative New Drug Research Center (BPW CHINA)

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Jiangsu Innovative New Drug Research Center Co., Ltd. (BPW CHINA), established on August 8th, 2002, is the first research institute in China which is keeping pace with other international research institutes in the innovative new drugs development. Its sole investor is Basilea Pharmaceutica Ltd.

  10. Defining "innovativeness" in drug development: a systematic review.

    Science.gov (United States)

    Kesselheim, A S; Wang, B; Avorn, J

    2013-09-01

    Some observers of drug development argue that the pace of pharmaceutical innovation is declining, but others deny that contention. This controversy may be due to different methods of defining and assessing innovation. We conducted a systematic review of the literature to develop a taxonomy of methods for measuring innovation in drug development. The 42 studies fell into four main categories: counts of new drugs approved, assessments of therapeutic value, economic outcomes, and patents issued. The definition determined whether a study found a positive or negative trend in innovative drug development. Of 21 studies that relied on counts, 9 (43%) concluded that the trend for drug discovery was favorable, 11 (52%) concluded that the trend was not favorable, and 1 reached no conclusion. By contrast, of 21 studies that used other measures of innovation, 0 concluded that the trend was favorable, 8 (47%) concluded that the trend was not favorable, and 13 reached no conclusion (P = 0.03).

  11. Open Innovation at NASA: A New Business Model for Advancing Human Health and Performance Innovations

    Science.gov (United States)

    Davis, Jeffrey R.; Richard, Elizabeth E.; Keeton, Kathryn E.

    2014-01-01

    This paper describes a new business model for advancing NASA human health and performance innovations and demonstrates how open innovation shaped its development. A 45 percent research and technology development budget reduction drove formulation of a strategic plan grounded in collaboration. We describe the strategy execution, including adoption and results of open innovation initiatives, the challenges of cultural change, and the development of virtual centers and a knowledge management tool to educate and engage the workforce and promote cultural change.

  12. Something new every day: defining innovation and innovativeness in drug therapy.

    Science.gov (United States)

    Aronson, Jeffrey K

    2008-01-01

    The word "innovation" comes from the Latin noun innovatio, derived from the verb innovare, to introduce [something] new. It can refer either to the act of introducing something new or to the thing itself that is introduced. In terms of commerce, it is defined in the Oxford English Dictionary as "the action of introducing a new product into the market; a product newly brought on to the market," a definition that illustrates both aspects of the word's meaning. "Innovativeness" is the property of being an innovation. Here I identify several different types of innovativeness in drug therapy, including structural, pharmacological or pharmacodynamic, pharmaceutical, and pharmacokinetic innovativeness, and I stress the over-riding importance of clinical innovativeness, which should result in a better benefit to harm balance at an affordable cost.

  13. Advanced Polymeric Materials for High-tech Innovations

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ High technology is advancing our society and modernizing our life and advanced materials play an important role in the technological innovations. My research group has been working on the development of advanced polymeric materials and in this talk I will report our recent work on the creation of new conjugated polymers with novel molecular structures and unique materials properties.1-18 Our work include the design of molecular structures of monomeric building blocks, development of stable, effective and environmentally benign "green” polymerization catalysts, discovery of new polymerization reactions, synthesis of functional macromolecules, fabrication of nanodimensional composites, assembly and control of hierarchical structures, and construction of electrooptical devices. We have revealed the liquid crystallinity, light emission, photoconductivity, optical limiting, nano-hybridization, solvatochromism, optical activity, self-organization, and biological activity of the linear polyacetylenes and hyperbranched polyarylenes. The utilization of the advanced polymers and their interesting materials properties for high-tech innovations will be discussed.

  14. Advanced Polymeric Materials for High-tech Innovations

    Institute of Scientific and Technical Information of China (English)

    TANG; BenZhong

    2001-01-01

    High technology is advancing our society and modernizing our life and advanced materials play an important role in the technological innovations. My research group has been working on the development of advanced polymeric materials and in this talk I will report our recent work on the creation of new conjugated polymers with novel molecular structures and unique materials properties.1-18 Our work include the design of molecular structures of monomeric building blocks, development of stable, effective and environmentally benign "green” polymerization catalysts, discovery of new polymerization reactions, synthesis of functional macromolecules, fabrication of nanodimensional composites, assembly and control of hierarchical structures, and construction of electrooptical devices. We have revealed the liquid crystallinity, light emission, photoconductivity, optical limiting, nano-hybridization, solvatochromism, optical activity, self-organization, and biological activity of the linear polyacetylenes and hyperbranched polyarylenes. The utilization of the advanced polymers and their interesting materials properties for high-tech innovations will be discussed.  ……

  15. Antiviral Information Management System (AIMS): a prototype for operational innovation in drug development.

    Science.gov (United States)

    Jadhav, Pravin R; Neal, Lauren; Florian, Jeff; Chen, Ying; Naeger, Lisa; Robertson, Sarah; Soon, Guoxing; Birnkrant, Debra

    2010-09-01

    This article presents a prototype for an operational innovation in knowledge management (KM). These operational innovations are geared toward managing knowledge efficiently and accessing all available information by embracing advances in bioinformatics and allied fields. The specific components of the proposed KM system are (1) a database to archive hepatitis C virus (HCV) treatment data in a structured format and retrieve information in a query-capable manner and (2) an automated analysis tool to inform trial design elements for HCV drug development. The proposed framework is intended to benefit drug development by increasing efficiency of dose selection and improving the consistency of advice from US Food and Drug Administration (FDA). It is also hoped that the framework will encourage collaboration among FDA, industry, and academic scientists to guide the HCV drug development process using model-based quantitative analysis techniques.

  16. Innovative Tools Advance Revolutionary Weld Technique

    Science.gov (United States)

    2009-01-01

    The iconic, orange external tank of the space shuttle launch system not only contains the fuel used by the shuttle s main engines during liftoff but also comprises the shuttle s backbone, supporting the space shuttle orbiter and solid rocket boosters. Given the tank s structural importance and the extreme forces (7.8 million pounds of thrust load) and temperatures it encounters during launch, the welds used to construct the tank must be highly reliable. Variable polarity plasma arc welding, developed for manufacturing the external tank and later employed for building the International Space Station, was until 1994 the best process for joining the aluminum alloys used during construction. That year, Marshall Space Flight Center engineers began experimenting with a relatively new welding technique called friction stir welding (FSW), developed in 1991 by The Welding Institute, of Cambridge, England. FSW differs from traditional fusion welding in that it is a solid-state welding technique, using frictional heat and motion to join structural components without actually melting any of the material. The weld is created by a shouldered pin tool that is plunged into the seam of the materials to be joined. The tool traverses the line while rotating at high speeds, generating friction that heats and softens but does not melt the metal. (The heat produced approaches about 80 percent of the metal s melting temperature.) The pin tool s rotation crushes and stirs the plasticized metal, extruding it along the seam as the tool moves forward. The material cools and consolidates, resulting in a weld with superior mechanical properties as compared to those weld properties of fusion welds. The innovative FSW technology promises a number of attractive benefits. Because the welded materials are not melted, many of the undesirables associated with fusion welding porosity, cracking, shrinkage, and distortion of the weld are minimized or avoided. The process is more energy efficient, safe

  17. Advances in the diagnosis of drug eruptions.

    Science.gov (United States)

    de la Torre, C; Suh Oh, H J

    2013-11-01

    Drug eruptions affecting the skin or mucosas (toxicoderma) are the most common adverse effects of drugs and represent one of the more common diagnostic challenges for the dermatologist. A better understanding of the pathogenic mechanisms of drug reactions, pharmacogenetics, and pharmacoepidemiology will help us to resolve the main dilemmas and to anticipate and even prevent such reactions. Many drug eruptions are due to T cell-mediated hypersensitivity reactions that can involve activation of different proinflammatory mechanisms, which would explain the varied manifestations. Some aspects defy the classical understanding of antigen processing and presentation. New immunological hypotheses, such as the «p-i concept», have been introduced to complement the hapten theory and, at least in part, help to explain why drug reactions tend to affect the skin and why certain viral infections increase the risk of drug eruptions. In this paper we analyze these pathogenic concepts and the role of HLA genes in the susceptibility to certain severe adverse drug reactions, and also examine other advances in the diagnosis of drug eruptions. We briefly discuss a number of recently described reactions to new drugs.

  18. CURRENT STATUS AND FUTURE INNOVATIONS IN TRANSDERMAL DRUG DELIVERY

    Directory of Open Access Journals (Sweden)

    Shalini Chhabaria et al

    2012-08-01

    Full Text Available Transdermal drug delivery system (TDDS in comparison to conventional system offers sustained drug release as well as decrease the intensity of action and decrease in the side effects associated with conventional therapy. Presently only about 40 products of more than 20 drug molecules are available in market. The barrier property of the stratum corneum is the main obstructer in the release of drug from the transdermal patch. Various approaches to overcome this barrier function of skin have been broadly studied. Innovations in technologies continue to occur at a positive rate, making the technology a productive and exciting area of innovation, research and product development. In this review, various new development in the field of TDDS are included which are intended to be a need base system. In this review, we have summarized various physical and chemical approaches for transdermal flux enhancement as well as the application of electricity, ultrasound, microneedle and chemical enhancers.

  19. Innovation strategies for generic drug companies: moving into supergenerics.

    Science.gov (United States)

    Ross, Malcolm S F

    2010-04-01

    Pharmaceutical companies that market generic products generally are not regarded as innovators, but rather as companies that produce copies of originator products to be launched at patent expiration. However, many generics companies have developed excellent scientific innovative skills in an effort to circumvent the defense patents of originator companies. More patents per product, in terms of both drug substances (process patents and polymorph patents) and formulations, are issued to generics companies than to companies that are traditionally considered to be 'innovators'. This quantity of issued patents highlights the technical knowledge and skill sets that are available in generics companies. In order to adopt a completely innovative model (ie, the development of NCEs), a generics company would require a completely new set of skills in several fields, including a sufficient knowledge base, project and risk management experience, and capability for clinical data evaluation. However, with relatively little investment, generics companies should be able to progress into the so-called 'supergeneric' drug space - an area of innovation that reflects the existing competencies of both innovative and generics companies.

  20. Recent advances in (therapeutic protein) drug development

    Science.gov (United States)

    Lagassé, H.A. Daniel; Alexaki, Aikaterini; Simhadri, Vijaya L.; Katagiri, Nobuko H.; Jankowski, Wojciech; Sauna, Zuben E.; Kimchi-Sarfaty, Chava

    2017-01-01

    Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing) product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016). PMID:28232867

  1. Medical innovation then and now: perspectives of innovators responsible for transformative drugs.

    Science.gov (United States)

    Xu, Shuai; Kesselheim, Aaron S

    2014-01-01

    Effective medical innovation is a common goal of policymakers, physicians, researchers, and patients both in the private and public sectors. With the recent slowdown in approval of new transformative prescription drugs, many have looked back to the "golden years" of the 1980s and 1990s when numerous breakthrough products emerged. We conducted a qualitative study of innovators (n=127) directly involved in creation of groundbreaking drugs during that era to determine what made their work successful and how the process of conducting medical innovation has changed over the past 3 decades. Transcripts were analyzed using standard coding techniques and the constant comparative method of qualitative data analysis to identify the positive features of and challenges posed by the past and present therapeutic innovation environments (70 of the 127 interviewees explicitly addressed these issues). Interviewees emphasized the continued central role played by individuals and the institutions they were a part of in driving innovation. In addition, respondents discussed the importance of collaboration between individuals and institutions to share resources and expertise. Strong underlying basic science was also cited to be a major contributing factor to the success of an innovation. The climate for modern-day medical innovation involves a greater emphasis on patenting in academia, difficulty negotiating the technology transfer process, and funding constraints. Regulatory demands or reimbursement concerns were not commonly cited as factors that influenced transformative innovation. This study suggests that generating future transformative innovation will require a simplification of the current technology transfer process, continued commitment to basic science research, and policy changes that promote meaningful collaboration between individuals from disparate institutions.

  2. Advanced materials and nanotechnology for drug delivery.

    Science.gov (United States)

    Yan, Li; Yang, Yang; Zhang, Wenjun; Chen, Xianfeng

    2014-08-20

    Many biological barriers are of great importance. For example, stratum corneum, the outmost layer of skin, effectively protects people from being invaded by external microorganisms such as bacteria and viruses. Cell membranes help organisms maintain homeostasis by controlling substances to enter and leave cells. However, on the other hand, these biological barriers seriously restrict drug delivery. For instance, stratum corneum has a very dense structure and only allows very small molecules with a molecular weight of below 500 Da to permeate whereas most drug molecules are much larger than that. A wide variety of drugs including genes needs to enter cells for proper functioning but cell membranes are not permeable to them. To overcome these biological barriers, many drug-delivery routes are being actively researched and developed. In this research news, we will focus on two advanced materials and nanotechnology approaches for delivering vaccines through the skin for painless and efficient immunization and transporting drug molecules to cross cell membranes for high-throughput intracellular delivery.

  3. Drugs and diagnostic innovations to improve global health.

    Science.gov (United States)

    Peeling, Rosanna W; Nwaka, Solomon

    2011-09-01

    Infectious diseases remain the major cause of morbidity and mortality in the developing world. Affordable effective drugs and diagnostics are critical for patient management and disease control but the development of new drugs and diagnostics is too slow to keep up with the emergence and spread of infectious diseases around the world. Innovative collaborative research and development involving disease endemic countries and developed countries are urgently needed to accelerate progress along the path from discovery to product adoption. These emerging approaches and the need for increased investment in human and financial resources to support them are discussed.

  4. Important drugs for cough in advanced cancer.

    Science.gov (United States)

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management.

  5. Innovations and Advances in Computer, Information, Systems Sciences, and Engineering

    CERN Document Server

    Sobh, Tarek

    2013-01-01

    Innovations and Advances in Computer, Information, Systems Sciences, and Engineering includes the proceedings of the International Joint Conferences on Computer, Information, and Systems Sciences, and Engineering (CISSE 2011). The contents of this book are a set of rigorously reviewed, world-class manuscripts addressing and detailing state-of-the-art research projects in the areas of  Industrial Electronics, Technology and Automation, Telecommunications and Networking, Systems, Computing Sciences and Software Engineering, Engineering Education, Instructional Technology, Assessment, and E-learning.

  6. Advanced design cultures long-term perspective and continuous innovation

    CERN Document Server

    2015-01-01

    This book describes new thinking and practice in Advanced Design (ADD) – design that is not merely highly developed but anticipates the future by envisioning novel products and processes. The focus is especially on the front end of innovation and the search for solutions in complex pioneering processes using design-related tools and practices. The book opens by describing these tools, the approaches that characterize ADD, and its historical dimension. Specific fields in which ADD has flourished are then examined, exploring the dynamics between research and design. The coverage ranges from transportation, lighting, and electrical appliances through to business networks, technology parks, and the development of ground-breaking materials. AdvanceDesign is the name of the research group at the Politecnico di Milano (Italy’s largest technical university) of which the authors are members. It was chosen to reflect both the “advanced”, tangible dimension of design in terms of modern product development, mater...

  7. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Alka Lohani

    2014-01-01

    Full Text Available Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs.

  8. Advanced DNA assembly technologies in drug discovery.

    Science.gov (United States)

    Tsvetanova, Billyana; Peng, Lansha; Liang, Xiquan; Li, Ke; Hammond, Linda; Peterson, Todd C; Katzen, Federico

    2012-05-01

    Recombinant DNA technologies have had a fundamental impact on drug discovery. The continuous emergence of unique gene assembly techniques resulted in the generation of a variety of therapeutic reagents such as vaccines, cancer treatment molecules and regenerative medicine precursors. With the advent of synthetic biology there is a growing need for precise and concerted assembly of multiple DNA fragments of various sizes, including chromosomes. In this article, we summarize the highlights of the recombinant DNA technology since its inception in the early 1970s, emphasizing on the most recent advances, and underscoring their principles, advantages and shortcomings. Current and prior cloning trends are discussed in the context of sequence requirements and scars left behind. Our opinion is that despite the remarkable progress that has enabled the generation and manipulation of very large DNA sequences, a better understanding of the cell's natural circuits is needed in order to fully exploit the current state-of-the-art gene assembly technologies.

  9. Chemical Hydrogeology: Fifty Years of Advances, Breakthroughs, and Innovation

    Science.gov (United States)

    Brusseau, M. L.

    2015-12-01

    Chemical hydrogeology focuses on the composition, properties, and biogeochemical processes inherent to water in subsurface environments. Multiple avenues of research coalesced in the 1960's to foment the development of chemical hydrogeology as a distinct field. In the intervening 50 years, chemical hydrogeology principles have been applied to innumerable issues and problems, and concomitantly, the field has continually experienced advances, breakthroughs, and innovations in theory, analysis, and application. An overarching theme to chemical hydrogeology in both theory and application is integration--- integration of disciplines (interdisciplinary, multidisciplinary), integration of approaches (theoretical, experimental, analytical), and integration of scales (spatial, temporal). Chemical hydrogeology has never been more relevant and more challenged as today, as we face critical issues related to for example water scarcity and availability of clean water, impacts of energy development, production and storage, and human interactions with ecosystem services. This presentation will illustrate recent advances in chemical hydrogeology, ranging from application of advanced imaging for characterization of pore-scale multiphase systems to integrated physical and biogeochemical assessments of field-scale contaminant transport.

  10. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative co

  11. Industry perspectives on market access of innovative drugs

    Directory of Open Access Journals (Sweden)

    Kim ePauwels

    2016-06-01

    Full Text Available This study presents industry perspectives on the challenges related to market access of innovative drugs in general and oncology drugs in specific. Fifteen interviews were conducted with representatives of pharmaceutical companies and industry associations. Interviewees call for a broader recognition of value within the assessment and appraisal of drugs. According to interviewees, focus on value is jeopardized by the lack of a common value definition across Europe, poor availability and validity of value measures and cost-saving measures such as external reference price setting and cost-effectiveness analysis at the side of the payers. Centralized assessment of relative-effectiveness at European level would provide a common value estimate across member states, independent of financial drivers. Empirical evidence on patient reported outcomes and societal preferences is however essential in the development of a value definition. Furthermore, value-based pricing would imply a dynamic approach where the price is differentiated across indications and across the lifecycle of the drug, especially in fields such as oncology. Financial drivers however also threat the application of value-based pricing at the side of the industry, making value-based profitability a more appropriate term.

  12. International conference on Advances in Intelligent Control and Innovative Computing

    CERN Document Server

    Castillo, Oscar; Huang, Xu; Intelligent Control and Innovative Computing

    2012-01-01

    In the lightning-fast world of intelligent control and cutting-edge computing, it is vitally important to stay abreast of developments that seem to follow each other without pause. This publication features the very latest and some of the very best current research in the field, with 32 revised and extended research articles written by prominent researchers in the field. Culled from contributions to the key 2011 conference Advances in Intelligent Control and Innovative Computing, held in Hong Kong, the articles deal with a wealth of relevant topics, from the most recent work in artificial intelligence and decision-supporting systems, to automated planning, modelling and simulation, signal processing, and industrial applications. Not only does this work communicate the current state of the art in intelligent control and innovative computing, it is also an illuminating guide to up-to-date topics for researchers and graduate students in the field. The quality of the contents is absolutely assured by the high pro...

  13. Improved therapeutic entities derived from known generics as an unexplored source of innovative drug products.

    Science.gov (United States)

    Stegemann, Sven; Klebovich, Imre; Antal, István; Blume, Henning H; Magyar, Kálmán; Németh, György; Paál, Tamás L; Stumptner, Willibald; Thaler, György; Van de Putte, Armand; Shah, Vinod P

    2011-11-20

    With a New Drug Application (NDA) innovative drug therapies are reaching the market in a specific dosage form for one or more clinically proven indications of which after expiration of the patent or the data exclusivity copies are launched using Abbreviated New Drug Applications (ANDA). Advanced therapies that emerged from launched molecules during their product life-cycle have gained considerable attention as clinical practice provides evidence for additional therapeutic values, patient centric delivery systems show improved therapeutic outcomes or emerging technologies offer efficiency gains in manufacturing or access to emerging markets. The USA and European regulatory framework has set reasonable regulations in place for these "Supergenerics" or "hybrid" applications. While these regulations are relatively recent the pharmaceutical industry is just starting to use this route for their product development and life-cycle management. From a clinical perspective the potential for advanced product development have been demonstrated. Yet, there is still a lag of common understanding between the different stakeholders regarding the development, application process and commercial incentive in developing enhanced therapeutic entities based on existing drug products for the market.

  14. The role of big data and advanced analytics in drug discovery, development, and commercialization.

    Science.gov (United States)

    Szlezák, N; Evers, M; Wang, J; Pérez, L

    2014-05-01

    In recent years, few ideas have captured the imagination of health-care practitioners as much as the advent of "big data" and the advanced analytical methods and technologies used to interpret it-it is a trend seen as having the potential to revolutionize biology, medicine, and health care.(1,2,3) As new types of data and tools become available, a unique opportunity is emerging for smarter and more effective discovery, development, and commercialization of innovative biopharmaceutical drugs.

  15. Industry Perspectives on Market Access of Innovative Drugs: The Relevance for Oncology Drugs.

    Science.gov (United States)

    Pauwels, Kim; Huys, Isabelle; Casteels, Minne; Simoens, Steven

    2016-01-01

    Key Points - Representatives of the pharmaceutical industry call for a broader recognition of value within the assessment and appraisal of innovative drugs- Focus on value within the assessment and appraisal of drugs is jeopardized by financial drives as the side of industry and at the side of the payers- A well-considered value-framework, with attention for patient reported outcomes, societal preferences and dynamic approach on the drug life cycle, needs to be incorporated in assessment and appraisal at national and European level in order to coordinate the views of different stakeholders and allow efficient resource allocation This study presents industry perspectives on the challenges related to market access of innovative drugs in general and oncology drugs in specific. Fifteen interviews were conducted with representatives of pharmaceutical companies and industry associations. Interviewees call for a broader recognition of value within the assessment and appraisal of drugs. According to interviewees, focus on value is jeopardized by the lack of a common value definition across Europe, poor availability and validity of value measures and cost-saving measures such as external reference price setting and cost-effectiveness analysis at the side of the payers. Centralized assessment of relative-effectiveness at European level would provide a common value estimate across member states, independent of financial drivers. Empirical evidence on PRO and societal preferences is however essential in the development of a value definition. Furthermore, value-based pricing would imply a dynamic approach where the price is differentiated across indications and across the lifecycle of the drug, especially in fields such as oncology. Financial drivers however also threat the application of value-based pricing at the side of the industry, making value-based profitability a more appropriate term.

  16. Innovation Training within the Australian Advanced Manufacturing Industry

    Science.gov (United States)

    Donovan, Jerome Denis; Maritz, Alex; McLellan, Andrew

    2013-01-01

    Innovation has emerged as a core driver for the future profitability and success of the manufacturing sector, and increasingly both governments and the private sector are examining ways to support the development of innovation capabilities within organisations. In this research, we have evaluated a government-funded innovation training course…

  17. Advanced Analyses of Technology Innovations, Patents, and Intellectual Property

    Directory of Open Access Journals (Sweden)

    Amy J. C. Trappey

    2013-08-01

    Full Text Available A good indicator of the technical competitiveness of a country or an enterprise is the number of high quality international patents it owns. The latest statistics from the World Intellectual Property Organization (WIPO showed that USA, Japan, Germany, China, and South Korea are among the top patent filing countries [1]. WIPO data indicate that these countries and their global companies are directing significant resources toward engineering innovations, design inventions, and technology R&D. The end result will be to capitalize their intellectual assets for competitive advantage. The huge and ever growing data and knowledge content of international patent (cyber- depositories creates great challenges for engineers, researchers, and technology strategists to fully utilize the wealth of knowledge [2]. Most critically, engineers must make correct R&D decisions based on the complex sets of patent information. This special issue features research papers focusing on the advances of representing, modeling, reasoning, analyzing, and synthesizing knowledge related to innovations, intellectual property (IP, patents, and technology adoptions. For industries with short life cycles and technical products (e.g., semiconductor, LED, and consumer electronics, state-of-the-art knowledge engineering approaches for IP and patent analysis are essential for sustaining competitive advantage. We have accepted five articles in this special issue and each has developed methodologies using industrial cases for verification. The papers are highlighted briefly as follows. The article “Applying Hybrid-Quantity Analysis in the Asia Semiconductor Industry,” co-authored by Chin-yuan Fan, Ming-Fong Lai, and Shu-Hao Chang, provides an integrated approach to explore competing technological and strategic-group relationships within the semiconductor industry in the Asia-Pacific region. They use a combination of patents, multidimensional scaling, and K-means clustering to

  18. Recent advances in understanding hepatic drug transport

    Science.gov (United States)

    Stieger, Bruno; Hagenbuch, Bruno

    2016-01-01

    Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy. While many drug transporters are expressed in hepatocytes, and some of them are well characterized, several transporters have only recently been identified as new drug transporters. Novel powerful tools to deorphanize (drug) transporters are being applied and show promising results. Although a large set of tools are available for studying transport in vitro and in isolated cells, tools for studying transport in living organisms, including humans, are evolving now and rely predominantly on imaging techniques, e.g. positron emission tomography. Imaging is an area which, certainly in the near future, will provide important insights into "transporters at work" in vivo. PMID:27781095

  19. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... Innovation Act Title VII--Drug Supply Chain; Standards for Admission of Imported Drugs, Registration of... chain. In addition to providing a general overview of Title VII and FDA's approach to implementing these..., including dramatic increases in drug imports, complex and fragmented global supply chains, and...

  20. Important role of translational science in rare disease innovation, discovery, and drug development.

    Science.gov (United States)

    Pariser, Anne R; Gahl, William A

    2014-08-01

    Rare diseases play a leading role in innovation and the advancement of medical and pharmaceutical science. Most rare diseases are genetic disorders or atypical manifestations of infectious, immunologic, or oncologic diseases; they all provide opportunities to study extremes of human pathology and provide insight into both normal and aberrant physiology. Recently, drug development has become increasingly focused on classifying diseases largely on genetic grounds; this has allowed the identification of molecularly defined targets and the development of targeted therapies. Clinical trials are now focusing on progressively smaller subgroups within both common and rare disease populations, often based on genetic tests or biomarkers. Drug developers, researchers, and regulatory agencies face a variety of challenges throughout the life cycle of drug research and development for rare diseases. These include the small numbers of patients available for study, lack of knowledge of the disease's natural history, incomplete understanding of the basic mechanisms causing the disorder, and variability in disease severity, expression, and course. Traditional approaches to rare disease clinical research have not kept pace with advances in basic science, and increased attention to translational science is needed to address these challenges, especially diagnostic testing, registries, and novel trial designs.

  1. Advanced drug delivery systems: Nanotechnology of health design A review

    Directory of Open Access Journals (Sweden)

    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  2. RECENT ADVANCES IN NOVEL DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    Manivannan Rangasamy

    2010-12-01

    Full Text Available Drug delivered can have significant effect on its efficacy. Some drugs have an optimum concentration range with in which maximum benefit is derived and concentrations above (or below the range can be toxic or produce no therapeutic effect. Various drug delivery and drug targeting systems are currently under development. The main goal for developing such delivery systems is to minimize drug degradation and loss, to prevent harmful side effects and to increase bioavailability. Targeting is the ability to direct the drug loaded system to the site of interest. Among drug carrier one can name soluble polymers, microparticles made of insoluble (or biodegradable natural and synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins, liposomes and micelles. Two major mechanisms can be distinguished for addressing the desired sites for drug release, (a Passive and (b Active targeting. Controlled drug carrier systems such as micellar solutions, vescicles and liquid crystal dispersions, as well as nanoparticle dispersions consisting of small particles of 10 – 400 nm show great promise as drug delivery systems. Hydrogels are three dimensional, hydrophilic, polymer networks capable of imbibing large amounts of water or biological fluids. Buckyballs, a novel delivery system with 60 carbon atoms formed in the shape of hollow ball. They are other type’s namely bucky babies, fuzzy balls, gadofullereness, and giant fullerenes. Nanoparticles can be classified as nano tubes, nano wires, nano cantilever, nanoshells, quantum dots, nano pores. Researchers at north western university using gold particles to develop ultra sensitive detection systems for DNA and protein markers associated with many forms of cancer, including breast and prostrate cancer. Drug loaded erythrocytes is one of the growing and potential systems for delivery of drugs and enzymes.

  3. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum.

    Science.gov (United States)

    Alkilani, Ahlam Zaid; McCrudden, Maelíosa T C; Donnelly, Ryan F

    2015-10-22

    The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

  4. Advanced drug delivery and targeting technologies for the ocular diseases

    OpenAIRE

    Barar, Jaleh; AGHANEJAD, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis...

  5. Recent Advances in Ocular Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Shinobu Fujii

    2011-01-01

    Full Text Available Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient’s and doctor’s convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

  6. A Decade of Data Protection for Innovative Drugs in Canada: Issues, Limitations, and Time for a Reassessment.

    Science.gov (United States)

    Kendall, Megan; Hamill, Declan

    2016-12-01

    Drug regulators in Canada and in other nations require innovative pharmaceutical companies to submit undisclosed clinical or other data as a condition of approving the marketing of new pharmaceutical products-the origination of which involves considerable effort and investment. Data protection regulations were enacted in Canada in 2006, which-to some extent-closed a loophole in intellectual property law that had previously left innovative companies with no effective data protection for their clinical data. Although the regulations were intended to clarify and effectively implement Canada's international treaty obligations in the spirit of innovation, a review of Canada's first decade of effective data protection shows that Health Canada and Canadian courts have interpreted the scope of data protection for innovative drugs in a narrow manner that undermines and is inconsistent with the intent of the regulations. As the 10-year anniversary of data protection in Canada is this year (2016), this article demonstrates the need to advance Canada's data protection regime into one that consistently contributes to the promotion of investment in pharmaceutical research and development, to the mutual advantage of innovators and patients, in a manner conducive to the social and economic welfare of Canadians.

  7. Recent Advances in Drug-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Naoko Inomata

    2012-01-01

    Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

  8. Low-Cost Innovative Hi-Temp Fiber Coating Process for Advanced Ceramic Matrix Composites Project

    Data.gov (United States)

    National Aeronautics and Space Administration — MATECH GSM (MG) proposes 1) to demonstrate a low-cost innovative Hi-Temp Si-doped in-situ BN fiber coating process for advanced ceramic matrix composites in order to...

  9. Advanced drug delivery systems: Nanotechnology of health design A review

    OpenAIRE

    Javad Safari; Zohre Zarnegar

    2014-01-01

    Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements ...

  10. Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

    Science.gov (United States)

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2013-11-01

    Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients.

  11. Advances in text analytics for drug discovery.

    Science.gov (United States)

    Roberts, Phoebe M; Hayes, William S

    2005-05-01

    The automated extraction of biological and chemical information has improved over the past year, with advances in access to content, entity extraction of genes, chemicals, kinetic data and relationships, and algorithms for generating and testing hypotheses. As the systems for reading and understanding scientific literature grow more powerful, so must the infrastructure in which to assemble information. Advances in infrastructure systems are discussed in this review. Research efforts have flourished as a result of text analytics competitions that attract participants from various disciplines, from computer science to bioinformatics.

  12. Advanced Manufacturing Technologies and Green Innovation: The Role of Internal Environmental Collaboration

    Directory of Open Access Journals (Sweden)

    Ting Kong

    2016-10-01

    Full Text Available Green innovation has been deemed a key corporate capability to deal with environmental issues. The usage of advanced manufacturing technologies (AMT provides important resources and knowledge for firms’ green innovation. Drawing on a resources-based approach, this study contributes to the existing literature by examining how the adoption of specific types of AMT (process, design, and planning influences two dimensions of green innovation (green product innovation and green process innovation. In particular, we explore these relationships through internal environmental collaboration. Based on data collected from 198 Chinese manufacturing firms, we found that process, design, and planning AMT can contribute to both green products and process innovation. Moreover, the findings confirm the significant mediating role of internal environmental collaboration in this relationship. Specifically, internal environmental collaboration mediates the relationship between process AMT and green product innovation as well as the relationship between design AMT and two dimensions of green innovation; it also partially mediates the relationship between process AMT and green process innovation as well as the relationship between planning AMT and two dimensions of green innovation. These findings provide novel insights into how manufacturing firms can use various types of AMT to enhance their green innovation.

  13. From generic to biosimilar drugs: why take an innovative pace?

    Directory of Open Access Journals (Sweden)

    Fereshteh Barei

    2012-12-01

    Full Text Available BACKGROUND: The transition of the generic/biotechnology industry to innovation by investing in innovative R&D will enhance business expertise in biopharmaceutical development and manufacturing. The major impact of this evolution is on patient access to treatment and savings for the health care systems. OBJECTIVES: The aim of this paper is to investigate the innovative aspect of biosimilar and biobetter products, manufactured by some big generic companies. We will also try to explore the innovative business strategy, implementing this high risk product differentiation policy. METHODS: This qualitative research is conducted by a series of interviews with CEOs, physicians, and academics in different countries. The qualitative data obtained were analyzed by Nvivo9.2 software. A literature review has also contributed to our key findings. RESULTS: The results show that switching into biosimilars/biobetters is an innovative strategic choice, approved by some big generic pharmaceutical companies. The biosimilar/biobetter products can be considered innovative because of their value added quality. CONCLUSION: Expanding the product portfolio to biosimilars/biobetter can be considered as a long run strategy in the innovative business plans aiming to ensure the market access. Patients and their access to better treatments are major components of these innovative business models.

  14. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    Science.gov (United States)

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-03-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.

  15. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    Science.gov (United States)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  16. Advances in Lymphatic Imaging and Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  17. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    Science.gov (United States)

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  18. To Establish a National Technical Platform of Molecular Nuclear Medicine for Innovative Drug Development

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ The development of innovative drugs is no doubt the "top priority" in the fulfillment of the medical and pharmaceutical research task of our country.Previously, the development of drugs was mainly performed by imitation,and expense for importing drugs amounted to more than US$ 1 billion per year. After joining the WTO, we fully realize the urgency and seriousness of the country's situation in the drug development.

  19. Advanced drug delivery approaches against periodontitis.

    Science.gov (United States)

    Joshi, Deeksha; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis.

  20. Open innovation in early drug discovery: roadmaps and roadblocks.

    Science.gov (United States)

    Reichman, Melvin; Simpson, Peter B

    2016-05-01

    Open innovation in pharmaceutical R&D evolved from a triple helix of convergent paradigm shifts in academic, industrial and government research sectors. The birth of the biotechnology sector catalyzed shifts in location dynamics that led to the first wave of open innovation in pharmaceutical R&D between big pharma and startup companies. The National Institutes of Health (NIH) Roadmap was a crucial inflection point that set the stage for a new wave of open innovation models between pharmaceutical companies and universities that have the potential to transform the pharmaceutical R&D landscape. We highlight the attributes of leading protected open innovation models that foster the sharing of proprietary small molecule collections by lowering the risk of premature escape of intellectual property, particularly structure-activity data.

  1. Advances in tau-based drug discovery

    Science.gov (United States)

    Noble, Wendy; Pooler, Amy M.; Hanger, Diane P.

    2011-01-01

    Introduction Tauopathies, including Alzheimer’s disease (AD) and some frontotemporal dementias, are neurodegenerative diseases characterised by pathological lesions comprised of tau protein. There is currently a significant and urgent unmet need for disease-modifying therapies for these conditions and recently attention has turned to tau as a potential target for intervention. Areas covered Increasing evidence has highlighted pathways associated with tau-mediated neurodegeneration as important targets for drug development. Here, the authors review recently published papers in this area and summarise the genetic and pharmacological approaches that have shown efficacy in reducing tau-associated neurodegeneration. These include the use of agents to prevent abnormal tau processing and increase tau clearance, therapies targeting the immune system, and the manipulation of tau pre-mRNA to modify tau isoform expression. Expert opinion Several small molecule tau-based treatments are currently being assessed in clinical trials, the outcomes of which are eagerly awaited. Current evidence suggests that therapies targeting tau are likely, at least in part, to form the basis of an effective and safe treatment for Alzheimer’s disease and related neurodegenerative disorders in which tau deposition is evident. PMID:22003359

  2. Recent advancement of gelatin nanoparticles in drug and vaccine delivery.

    Science.gov (United States)

    Sahoo, Nityananda; Sahoo, Ranjan Ku; Biswas, Nikhil; Guha, Arijit; Kuotsu, Ketousetuo

    2015-11-01

    Novel drug delivery system using nanoscale materials with a broad spectrum of applications provides a new therapeutic foundation for technological integration and innovation. Nanoparticles are suitable drug carrier for various routes of administration as well as rapid recognition by the immune system. Gelatin, the biological macromolecule is a versatile drug/vaccine delivery carrier in pharmaceutical field due to its biodegradable, biocompatible, non-antigenicity and low cost with easy availability. The surface of gelatin nanoparticles can be modified with site-specific ligands, cationized with amine derivatives or, coated with polyethyl glycols to achieve targeted and sustained release drug delivery. Compared to other colloidal carriers, gelatin nanoparticles are better stable in biological fluids to provide the desired controlled and sustained release of entrapped drug molecules. The current review highlights the different formulation aspects of gelatin nanoparticles which affect the particle characteristics like zeta potential, polydispersity index, entrapment efficacy and drug release properties. It has also given emphasis on the major applications of gelatin nanoparticles in drug and vaccine delivery, gene delivery to target tissues and nutraceutical delivery for improving the poor bioavailabity of bioactive phytonutrients.

  3. An Evaluation of an Innovative Drug Education Program: Follow-Up Results.

    Science.gov (United States)

    Moskowitz, Joel M.; And Others

    This study provides a follow-up assessment of an innovative drug education program for seventh and eighth graders. Students learned Lasswell's framework for understanding human needs and motives, a systematic decision-making procedure, and information about the pharmacological, psychological, and social consequences of licit and illicit drug use.…

  4. Recent advances in the enantioselective synthesis of chiral drugs

    Energy Technology Data Exchange (ETDEWEB)

    Juaristi, E. [Departamento de Quimica. Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico (Mexico)

    1997-09-01

    Because of the importance of drug chirality on biological activity, there has been increasing effort both in academic and industrial research to develop more efficient ways for the enantioselective synthesis of chiral therapeutic agents. This review presents some of the most relevant methods that have recently contributed to the advancement of this area. (Author) 45 refs.

  5. Advances in Nuclear Magnetic Resonance for Drug Discovery

    Science.gov (United States)

    Powers, Robert

    2010-01-01

    Background Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exasperated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project time-lines. Recent advances in nuclear magnetic resonance are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. Objective/Method A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process will be presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein-ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by FAST-NMR. Conclusion NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques, and the expansion of NMR amenable targets. PMID:20333269

  6. Recent advances in multiaxial electrospinning for drug delivery.

    Science.gov (United States)

    Khalf, Abdurizzagh; Madihally, Sundararajan V

    2017-03-01

    Electrospun fibers have seen an insurgence in biomedical applications due to their unique characteristics. Coaxial and triaxial electrospinning techniques have added new impetus via fabrication of multilayered nano and micro-size fibers. These techniques offer the possibility of forming fibers with features such as blending, reinforced core, porous and hollow structure. The unique fabrication process can be used to tailor the mechanical properties, biological properties and release of various factors, which can potentially be useful in various controlled drug delivery applications. Harvesting these advantages, various polymers and their combinations have been explored in a number of drug delivery and tissue regeneration applications. New advances have shown the requirement of drug-polymer compatibility in addition to drug-solvent compatibility. We summarize recent findings using both hydrophilic and hydrophobic (or lipophilic) drugs in hydrophobic or hydrophilic polymers on release behavior. We also describe the fundamental forces involved during the electrospinning process providing insight to the factors to be considered to form fibers. Also, various modeling efforts on the drug release profiles are summarized. In addition new developments in the immune response to the electrospun fibers, and advances in scale-up issues needed for industrial size manufacturing.

  7. Innovation

    Science.gov (United States)

    EPA frames innovation as critical to the protection of human health and the environment through initiatives such as sustainable practices, innovative research, prize competitions, innovation awards, partnerships, and community activities.

  8. Biomarkers and sustainable innovation in cardiovascular drug development: lessons from near and far afield.

    Science.gov (United States)

    Medford, Russell M; Dagi, T Forcht; Rosenson, Robert S; Offermann, Margaret K

    2013-05-01

    Future innovative therapies targeting cardiovascular disease (CVD) have the potential to improve health outcomes and to contain rising healthcare costs. Unsustainable increases in the size, cost and duration of clinical trial programs necessary for regulatory approval, however, threaten the entire innovation enterprise. Rising costs for clinical trials are due in large part to increasing demands for hard cardiovascular clinical endpoints as measures of therapeutic efficacy. The development and validation of predictive and surrogate biomarkers, as laboratory or other objective measures predictive or reflective of clinical endpoints, are an important part of the solution to this challenge. This review will discuss insights applicable to CVD derived from the use of predictive biomarkers in oncologic drug development, the evolving role of high density lipoprotein (HDL) in CVD drug development and the impact biomarkers and surrogates have on the continued investment from multiple societal sources critical for innovative CVD drug discovery and development.

  9. Innovator Organizations in New Drug Development: Assessing the Sustainability of the Biopharmaceutical Industry.

    Science.gov (United States)

    Kinch, Michael S; Moore, Ryan

    2016-06-23

    The way new medicines are discovered and brought to market has fundamentally changed over the last 30 years. Our previous analysis showed that biotechnology companies had contributed significantly to the US Food and Drug Administration approval of new molecular entities up to the mid-1980s, when the trends started to decline. Although intriguing, the focus on biotechnology necessarily precluded the wider question of how the biopharmaceutical industry has been delivering on its goals to develop new drugs. Here, we present a comprehensive analysis of all biopharmaceutical innovators and uncover unexpected findings. The present biopharmaceutical industry grew steadily from 1800 to 1950 and then stagnated for two decades, before a burst of growth attributable to the biotechnology revolution took place; but consolidation has reduced the number of active and independent innovators to a level not experienced since 1945. The trajectories and trends we observe raise fundamental questions about biopharmaceutical innovators and the sustainability of the drug-development enterprise.

  10. Efficacy and safety of innovator versus generic drugs in patients with epilepsy: a systematic review.

    Science.gov (United States)

    Talati, Ripple; Scholle, Jennifer M; Phung, Olivia P; Baker, Erika L; Baker, William L; Ashaye, Ajibade; Kluger, Jeffrey; Coleman, Craig I; White, C Michael

    2012-04-01

    Generic antiepileptic drugs achieve blood concentrations similar to those of innovator drugs in healthy volunteers, but their comparative effectiveness has not been well evaluated. Thus, we assessed the efficacy, tolerability, and safety of innovator versus generic antiepileptic drugs. We searched the MEDLINE database, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science for studies that evaluated innovator and generic antiepileptic drugs in patients with epilepsy and reported data on prespecified outcomes. We extracted data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes. Compared with initiation of innovator antiepileptic drugs, initiation of generic antiepileptic drugs did not significantly alter seizure occurrence (relative risk [RR] 0.87, 95% confidence interval [CI] 0.64-1.18; strength of evidence: low) or frequency (standardized mean difference 0.03, 95% CI -0.08-0.14; strength of evidence: low), withdrawals due to lack of efficacy (RR 1.02, 95% CI 0.41-2.54; strength of evidence: low) or adverse events (RR 0.79, 95% CI 0.28-2.20; strength of evidence: low), pharmacokinetic concentrations (maximum, minimum, or area under the curve [strength of evidence: low]), or a myriad of adverse events (strength of evidence: low or insufficient) in clinical trials. In qualitatively evaluated observational studies, switching between forms of antiepileptic drug (innovator to generic, generic to generic) may increase the risk of hospitalization (strength of evidence: low), hospital stay duration (strength of evidence: low), and a composite end point of medical service utilization (strength of evidence: insufficient) but may not increase outpatient service utilization (strength of evidence: low). Data are limited predominantly to carbamazepine, phenytoin, and valproic acid. Clinical trials are limited by small sample size, short-term nature, and lack of

  11. [Recent Advances in Vaccines and Drugs Against the Ebola Virus].

    Science.gov (United States)

    Zhu, Xiang; Yao, Chenguang; Wei, Yanhong; Kou, Zheng; Hu, Kanghong

    2015-05-01

    The Ebola virus belongs to the Filovirus family, which causes Ebola hemorrhagic fever (mortality, 25%-90%). An outbreak of infection by the Ebola virus is sweeping across West Africa, leading to high mortality and worldwide panic. The Ebola virus has caused a serious threat to public health, so intensive scientific studies have been carried out. Several vaccines (e.g., rVSV-ZEBOV, ChAd3-ZEBOV) have been put into clinical trials and antiviral drugs (e.g., TKM-Ebola, ZMAPP) have been administered in the emergency setting to patients infected by the Ebola virus. Here, recent advances in vaccines and drugs against the Ebola virus are reviewed.

  12. Integrating Social Neuroscience and Social Work: Innovations for Advancing Practice-Based Research

    Science.gov (United States)

    Matto, Holly C.; Strolin-Goltzman, Jessica

    2010-01-01

    Throughout the social work profession, there is ongoing interest in building a social science agenda that can address the complex practice-based questions faced by social work professionals today. Methodological innovations and unique funding opportunities have already significantly advanced research on social work practice. Still, there is…

  13. Innovations in building regulation and control for advancing sustainability in buildings (I)

    NARCIS (Netherlands)

    Meacham, B.; Visscher, H.J.; Meijer, F.M.; Chan, C.; Chan, E.; Laubscher, J.; Neng Kwei Sung, J.; Dodds, B.; Serra, J.; Tenorio, J.A.; Echeverria, J.B.; Sanches-Ostiz, A.

    2014-01-01

    This session brings together policy-makers, government officials, researchers and others to present perspectives on how innovation in building regulation and control, such as performancebased approaches, are currently being used to advance sustainability concepts in buildings, and where and how we m

  14. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum

    Directory of Open Access Journals (Sweden)

    Ahlam Zaid Alkilani

    2015-10-01

    Full Text Available The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

  15. Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic chemical space.

    Science.gov (United States)

    Alvim-Gaston, Maria; Grese, Timothy; Mahoui, Abdelaziz; Palkowitz, Alan D; Pineiro-Nunez, Marta; Watson, Ian

    2014-01-01

    The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial, in-house and virtual compound collections has been interrogated by multiple approaches including biochemical, cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease biology models. In this article we will discuss several computational approaches towards describing novel, biologically active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped molecules that may aid in the search for innovative pharmaceuticals.

  16. Innovation Meets Performance Demands of Advanced Lithium-ion Batteries

    Energy Technology Data Exchange (ETDEWEB)

    2016-06-01

    Advancements in high capacity and low density battery technologies have led to a growing need for battery materials with greater charge capacity and therefore stability. NREL's developments in ALD and molecular layer MLD allow for thin film coatings to battery composite electrodes, which can improve battery lifespan, high charge capacity, and stability. Silicon, one of the best high-energy anode materials for Li-ion batteries, can experience capacity fade from volumetric expansion. Using MLD to examine how surface modification could stabilize silicon anode material in Li-ion batteries, researchers discovered a new reaction precursor that leads to a flexible surface coating that accommodates volumetric expansion of silicon electrodes.

  17. Advances and Challenges of Liposome Assisted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Lisa eSercombe

    2015-12-01

    Full Text Available The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

  18. Drug Discovery and Development of Antimalarial Agents: Recent Advances.

    Science.gov (United States)

    Thota, Sreekanth; Yerra, Rajeshwar

    2016-01-01

    Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries. Most of the malarial infections and deaths are due to Plasmodium falciparum and Plasmodium vivax species. The recent emergence of resistance necessitates the search for new antimalarial drugs, which overcome the resistance and act through new mechanisms. Although much effort has been directed towards the discovery of novel antimalarial drugs. 4-anilino quinolone triazines as potent antimalarial agents, their in silico modelling and bioevaluation as Plasmodium falciparum transketolase and β-hematin inhibitors has been reported. This review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action.

  19. The Politics of Access to Expensive Drugs: INESSS and the Innovative Pharmaceutical Industry

    OpenAIRE

    Hughes, David

    2012-01-01

    The innovative pharmaceutical industry employs thousands of people in Quebec and so has the ability to exert strong political pressure; the public statements of Sanofi-Aventis concerning the provincial reimbursement of certain expensive drugs are an example. “Maintaining a dynamic biopharmaceutical industry” is one of four main axes of the drug policy of Quebec's ministry of health. However, this role of government should not take precedence over the efficient and equitable management of heal...

  20. Brian Barry: innovative contributions to transdermal and topical drug delivery.

    Science.gov (United States)

    Williams, A C

    2013-01-01

    Brian Barry published over 300 research articles across topics ranging from colloid science, vasoconstriction and the importance of thermodynamics in dermal drug delivery to exploring the structure and organisation of the stratum corneum barrier lipids and numerous strategies for improving topical and transdermal drug delivery, including penetration enhancers, supersaturation, coacervation, eutectic formation and the use of varied liposomes. As research in the area blossomed in the early 1980s, Brian wrote the book that became essential reading for both new and established dermal delivery scientists, explaining the background mathematics and principles through to formulation design. Brian also worked with numerous scientists, as collaborators and students, who have themselves taken his rigorous approach to scientific investigation into their own research groups. This paper can only describe a small fraction of the many significant contributions that Brian made to the field during his 40-year academic career.

  1. Lessons from innovation in drug-device combination products.

    Science.gov (United States)

    Couto, Daniela S; Perez-Breva, Luis; Saraiva, Pedro; Cooney, Charles L

    2012-01-01

    Drug-device combination products introduced a new dynamic on medical product development, regulatory approval, and corporate interaction that provide valuable lessons for the development of new generations of combination products. This paper examines the case studies of drug-eluting stents and transdermal patches to facilitate a detailed understanding of the challenges and opportunities introduced by combination products when compared to previous generations of traditional medical or drug delivery devices. Our analysis indicates that the largest barrier to introduce a new kind of combination products is the determination of the regulatory center that is to oversee its approval. The first product of a new class of combination products offers a learning opportunity for the regulator and the sponsor. Once that first product is approved, the leading regulatory center is determined, and the uncertainty about the entire class of combination products is drastically reduced. The sponsor pioneering a new class of combination products assumes a central role in reducing this uncertainty by advising the decision on the primary function of the combination product. Our analysis also suggests that this decision influences the nature (pharmaceutical, biotechnology, or medical devices) of the companies that will lead the introduction of these products into the market, and guide the structure of corporate interaction thereon.

  2. Progress, innovation and regulatory science in drug development: the politics of international standard-setting.

    Science.gov (United States)

    Abraham, John; Reed, Tim

    2002-06-01

    This paper examines international standard-setting in the toxicology of pharmaceuticals during the 1990s, which has involved both the pharmaceutical industry and regulatory agencies in an organization known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The analysis shows that the relationships between innovation, regulatory science and 'progress' may be more complex and controversial than is often assumed. An assessment of the ICH's claims about the implications of 'technical' harmonization of drug-testing standards for the maintenance of drug safety, via toxicological testing, and the delivery of therapeutic progress, via innovation, is presented. By demonstrating that there is not a technoscientific validity for these claims, it is argued that, within the ICH, a discourse of technological innovation and scientific progress has been used by regulatory agencies and prominent parts of the transnational pharmaceutical industry to legitimize the lowering and loosening of toxicological standards for drug testing. The mobilization and acceptance of this discourse are shown to be pivotal to the ICH's transformation of reductions in safety standards, which are apparently against the interests of patients and public health, into supposed therapeutic benefits derived from promises of greater access to more innovative drug products. The evidence suggests that it is highly implausible that these reductions in the standards of regulatory toxicology are consistent with therapeutic progress for patients, and highlights a worrying aspect embedded in the 'technical trajectories' of regulatory science.

  3. Should financial incentives be used to differentially reward 'me-too' and innovative drugs?

    Science.gov (United States)

    Pekarsky, Brita

    2010-01-01

    Strategies to change the existing mix of innovative and 'me-too' drugs are intended to increase societal value of a given investment in R&D by providing an incentive for firms to invest in drugs that are more likely to be clinically innovative. How can financial incentives be used to change this mix? Will a strategy have its intended consequence or will it have the unintended outcome of reducing the rate at which the population burden of disease is reduced? The perspective of this review is a country such as Australia, Canada or the UK that has universal health insurance and a drug reimbursement process that is informed by economic evidence. A review of the literature was performed and the views of both the proponents and the opponents of such strategies and the mechanisms by which they could be implemented were summarized. The debate is based largely on hypothesized responses by firms to changes in incentives rather than empirical evidence. The main point of contention is whether a changed mix of new molecular entities (NMEs) increases or decreases the total amount of clinical innovation launched each year. The argument presented in this article is that, despite the limited empirical evidence, it is possible to improve our assessment of the likely costs and consequences of a proposed strategy by appealing to economic theory and observations about the reimbursement process. First, the empirical evidence supporting the view that changing a mix of drugs will improve clinical innovation is based on the average launched drug, not the marginal innovative drug otherwise not developed, and therefore could be misleading. Second, the dynamic and complex nature of evidence of clinical innovation will reduce the feasibility of using contractually based mechanisms to implement such a strategy. Also, a single country is unlikely to have an impact on R&D decisions, and variation in the per capita economic value of new drugs would make multi-jurisdiction contracts with one firm

  4. 77 FR 70166 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

    Science.gov (United States)

    2012-11-23

    ... HUMAN SERVICES Food and Drug Administration Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a...

  5. Innovation

    DEFF Research Database (Denmark)

    Nielsen, Janni; Yaganeh, Suzanne; Bloch Rasmussen, Leif

    2013-01-01

    This paper contributes to a theoretical discussion of creation of innovation with participants in, or outside, organisations. We address the creation of innovation with a complex theoretical understanding drawing on the Scandinavian and the Participatory Design tradition introducing two approaches...... to the processes of innovation. We ask if innovation can be initiated and enhanced looking at two collaborative approaches; participatory innovation (PIN) and cooperative innovation (COIN). We invite to dialogue and reflections on PIN’s conflict and creative frictions on one side and COIN’s complexity......, complementarity in diversity and the didactic scaffolding of the innovation process on the other side. Our contribution focuses on the methods and practices for facilitation of co-creating activities between different groups leading to cooperation, and innovation in thinking....

  6. Recent advances in tuberculosis: New drugs and treatment regimens.

    Science.gov (United States)

    Sloan, Derek J; Davies, Geraint R; Khoo, Saye H

    2013-06-01

    The current treatment regimen against drug susceptible tuberculosis (DS-TB) was defined by the 1980s. Since then the emergence of the global HIV pandemic and the escalation of drug resistant (DR-) forms of TB have presented new challenges for therapeutic research. Priority goals include shortening DS-TB treatment, improving DR-TB treatment and making combined TB-HIV therapy easier. To help achieve these goals, a range of new drugs and treatment strategies are currently being evaluated. Phase IIb and III clinical trials are ongoing to assess combinations involving the high-dose rifamycins, the 8-methoxyquinolones, a diarylquinoline (bedaquiline) and the nitroimidazoles. Other compounds (e.g. novel oxazolidinones and ethylenediamines) are at earlier stages of clinical development. Overall, there are grounds for optimism that recent advances will contribute towards achievement of new treatment regimens in the foreseeable future. However, long-term investment, political commitment and scientific endeavour are crucial to ensure that progress is sustained and the benefits of recent advances reach those in the greatest need.

  7. Advanced drug delivery and targeting technologies for the ocular diseases

    Science.gov (United States)

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  8. Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

    Science.gov (United States)

    Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

    2016-02-10

    Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery.

  9. Unsteady jet in designing innovative drug delivery system

    Science.gov (United States)

    Wang, Cong; Mazur, Paul; Cosse, Julia; Rider, Stephanie; Gharib, Morteza

    2014-11-01

    Micro-needle injections, a promising pain-free drug delivery method, is constrained by its limited penetration depth. This deficiency can be overcome by implementing fast unsteady jet that can penetrate sub-dermally. The development of a faster liquid jet would increase the penetration depth and delivery volume of micro-needles. In this preliminary work, the nonlinear transient behavior of an elastic tube balloon in providing fast discharge is analyzed. A physical model that combines the Mooney Rivlin Material model and Young-Lapalce's Law was developed and used to investigate the fast discharging dynamic phenomenon. A proof of concept prototype was constructed to demonstrate the feasibility of a simple thumb-sized delivery system to generate liquid jet with desired speed in the range of 5-10 m/s. This work is supported by ZCUBE Corporation.

  10. Molecularly targeted therapy for advanced hepatocellularcarcinoma - a drug development crisis?

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Hepatocellular carcinoma is the fastest growing causeof cancer related death globally. Sorafenib, a multitargetedkinase inhibitor, is the only drug proven toimprove outcomes in patients with advanced diseaseoffering modest survival benefit. Although comprehensivegenomic mapping has improved understanding of thegenetic aberrations in hepatocellular cancer (HCC), thisknowledge has not yet impacted clinical care. The lastfew years have seen the failure of several first and secondline phase Ⅲ clinical trials of novel molecularly targetedtherapies, warranting a change in the way new therapiesare investigated in HCC. Potential reasons for thesefailures include clinical and molecular heterogeneity, trialdesign and a lack of biomarkers. This review discussesthe current crisis in HCC drug development and how weshould learn from recent trial failures to develop a moreeffective personalised treatment paradigm for patientswith HCC.

  11. Advancing drug delivery systems for the treatment of multiple sclerosis.

    Science.gov (United States)

    Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

    2015-12-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

  12. Can open-source drug R&D repower pharmaceutical innovation?

    Science.gov (United States)

    Munos, B

    2010-05-01

    Open-source R&D initiatives are multiplying across biomedical research. Some of them-such as public-private partnerships-have achieved notable success in bringing new drugs to market economically, whereas others reflect the pharmaceutical industry's efforts to retool its R&D model. Is open innovation the answer to the innovation crisis? This Commentary argues that although it may likely be part of the solution, significant cultural, scientific, and regulatory barriers can prevent it from delivering on its promise.

  13. Innovative grinding wheel design for cost-effective machining of advanced ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Licht, R.H.; Kuo, P.; Liu, S.; Murphy, D.; Picone, J.W.; Ramanath, S.

    2000-05-01

    This Final Report covers the Phase II Innovative Grinding Wheel (IGW) program in which Norton Company successfully developed a novel grinding wheel for cost-effective cylindrical grinding of advanced ceramics. In 1995, Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics using small prototype wheels. The Phase II program was initiated to scale-up the new superabrasive wheel specification to larger diameters, 305-mm to 406-mm, required for most production grinding of cylindrical ceramic parts, and to perform in-house and independent validation grinding tests.

  14. Enhancing the value delivered by the statistician throughout drug discovery and development: putting statistical science into regulated pharmaceutical innovation.

    Science.gov (United States)

    Enas, G G; Andersen, J S

    With the dawn of the 21st century, the pharmaceutical industry faces a dramatically different constellation of business and scientific predictors of success than those of just a few years ago. Significant advances in science at the genetic, molecular and cellular levels, combined with progress demonstrated around the globe with drug regulations, have increased business and competitive opportunities. This has occurred in search of better and cheaper medicines that reach patients with unmet medical needs as quickly as possible. Herein lie new opportunities for those who can help business and regulatory leaders make good decisions about drug development and market authorization as quickly and efficiently as possible in the presence of uncertainty. The statistician is uniquely trained and qualified to render such value. We show how the statistician can contribute to the process of drug innovation from the very early stages of drug discovery until patients, payers and regulators are satisfied. Indeed, the very nature of regulated innovation demands that efficient and effective processes are implemented which yield the right information for good decision making. The statistician can take the lead in setting a strategy that directs such processes in the direction of greatest value. This demands skills that enable one to identify important sources of variability and uncertainty and then leverage those skills to make decisions. If such decisions call for more information, then the statistician can render experimental designs which generate the right information needed to make the decision in an efficient, timely manner. To add value to the enterprise, statisticians will have to become more intimately associated with business and regulatory decisions by building on their traditional roles (for example, numerical analyst, tactician) and unique skill sets (for example, analysis, computation, logical thought and work process, precision, accuracy). Business and regulatory savvy

  15. The Latest Innovations in the Drug Pipeline for Multiple Sclerosis.

    Science.gov (United States)

    Radick, Lea; Mehr, Stanton R

    2015-11-01

    Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of fingolimod. Ocrelizumab is a CD20-positive B-cell-targeting monoclonal antibody with a promising new mechanism of action. Ofatumumab is also a CD20 inhibitor. Daclizumab, an interleukin-2 inhibitor, has evidence of good efficacy but is associated with unfavorable side effects. Masitinib is a mast-cell inhibitor that also has shown efficacy in Alzheimer's disease and amyotrophic lateral sclerosis. Phase 3 trials for some of these agents will conclude in the next 12 months, and their manufacturers are expected to apply for US Food and Drug Administration approval soon thereafter. This review article summarizes data for newly approved and late-phase investigational agents for the treatment of patients with MS.

  16. Advances and applications of binding affinity prediction methods in drug discovery.

    Science.gov (United States)

    Parenti, Marco Daniele; Rastelli, Giulio

    2012-01-01

    Nowadays, the improvement of R&D productivity is the primary commitment in pharmaceutical research, both in big pharma and smaller biotech companies. To reduce costs, to speed up the discovery process and to increase the chance of success, advanced methods of rational drug design are very helpful, as demonstrated by several successful applications. Among these, computational methods able to predict the binding affinity of small molecules to specific biological targets are of special interest because they can accelerate the discovery of new hit compounds. Here we provide an overview of the most widely used methods in the field of binding affinity prediction, as well as of our own work in developing BEAR, an innovative methodology specifically devised to overtake some limitations in existing approaches. The BEAR method was successfully validated against different biological targets, and proved its efficacy in retrieving active compounds from virtual screening campaigns. The results obtained so far indicate that BEAR may become a leading tool in the drug discovery pipeline. We primarily discuss advantages and drawbacks of each technique and show relevant examples and applications in drug discovery.

  17. Innovations in existing routes and novel drug delivery systems for local anaesthetics

    Directory of Open Access Journals (Sweden)

    Diwanshu Sharma

    2016-06-01

    Full Text Available New drug delivery systems (NDDS are developed for improvement in efficacy of the drugs, provide maximum benefit to the patient and to minimize the adverse drug reactions. For local anaesthetics (LAs, the development of new effective delivery systems modulate the release rate, extend their anaesthetic effect , and helps to enhance their localisation as desired. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous are under innovation these days. Different methods such as include iontophoresis, electroporation, sonophoresis, and magnetophoresis are being used to enhance local anaesthetic permeation. Adjuvants are added to potentiate drug effects. The use of different delivery systems should help to keep the LA at the target site for longer periods prolonging the anesthetic or analgesic effect with an extended range of agents. [Int J Basic Clin Pharmacol 2016; 5(3.000: 566-572

  18. The Advanced Exploration Systems Water Recovery Project: Innovation on 2 Fronts

    Science.gov (United States)

    Sarguisingh, Miriam M.; Neumeyer, Derek; Shull, Sarah

    2012-01-01

    As NASA looks forward to sending humans farther away from Earth, we will have to develop a transportation architecture that is highly reliable and that can sustain life for long durations without the benefit of Earth s proximity for continuous resupply or even operational guidance. NASA has consistently been challenged with performing great feats of innovation, but particularly in this time of economic stress, we are challenged to go farther with less. The Advanced Exploration Systems (AES) projects were implemented to address both of these needs by not only developing innovative technologies, but by incorporating innovative management styles and processes that foster the needed technical innovation given a small amount of resources. This presentation explains how the AES Water Recovery Project is exhibiting innovation on both fronts; technical and process. The AES Water Recovery Project (WRP) is actively engineering innovative technologies in order to maximize the efficiency of water recovery. The development of reliable, energy-efficient, and low-mass spacecraft systems to provide environmental control and life support (ECLS) is critical to enable long-duration human missions outside of low-Earth orbit. Recycling of life support consumables is necessary to reduce resupply mass and provide for vehicle autonomy. To address this, the WRP is working on a rotary distiller that has shown enhanced performance over the state-of-the-art (SOA). Additionally, the WRP is looking at innovative ways to address issues present in the state-of-the-art (SOA) systems pertaining to toxicity and calcium scale buildup. As an AES project, the WRP has a more streamlined Skunk Works like approach to technology development intended to reduce overhead but achieve a more refined end product. The project has incorporated key partnerships between NASA centers as well as between NASA and industry. A minimal project management style has been implemented such that risks are managed and

  19. Drug delivery system innovation and Health Technology Assessment: Upgrading from Clinical to Technological Assessment.

    Science.gov (United States)

    Panzitta, Michele; Bruno, Giorgio; Giovagnoli, Stefano; Mendicino, Francesca R; Ricci, Maurizio

    2015-11-30

    Health Technology Assessment (HTA) is a multidisciplinary health political instrument that evaluates the consequences, mainly clinical and economical, of a health care technology; the HTA aim is to produce and spread information on scientific and technological innovation for health political decision making process. Drug delivery systems (DDS), such as nanocarriers, are technologically complex but they have pivotal relevance in therapeutic innovation. The HTA process, as commonly applied to conventional drug evaluation, should upgrade to a full pharmaceutical assessment, considering the DDS complexity. This is useful to study more in depth the clinical outcome and to broaden its critical assessment toward pharmaceutical issues affecting the patient and not measured by the current clinical evidence approach. We draw out the expertise necessary to perform the pharmaceutical assessment and we propose a format to evaluate the DDS technological topics such as formulation and mechanism of action, physicochemical characteristics, manufacturing process. We integrated the above-mentioned three points in the Evidence Based Medicine approach, which is data source for any HTA process. In this regard, the introduction of a Pharmaceutics Expert figure in the HTA could be fundamental to grant a more detailed evaluation of medicine product characteristics and performances and to help optimizing DDS features to overcome R&D drawbacks. Some aspects of product development, such as manufacturing processes, should be part of the HTA as innovative manufacturing processes allow new products to reach more effectively patient bedside. HTA so upgraded may encourage resource allocating payers to invest in innovative technologies and providers to focus on innovative material properties and manufacturing processes, thus contributing to bring more medicines in therapy in a sustainable manner.

  20. The effect of comparative effectiveness research on drug development innovation: a 360° value appraisal

    Directory of Open Access Journals (Sweden)

    Doyle JJ

    2011-03-01

    Full Text Available John J DoyleQuintiles, NY, USAAbstract: The drug development process is in dire need of transformation. Even after achieving regulatory approval, pharmaceutical companies are increasingly seeing their products subjected to health technology assessments (HTAs by public and private payers. The cornerstone of HTA value appraisal, and thus reimbursability, is comparative effectiveness research (CER, a ‘real-world’ comparison of a new product with the existing standard of care. Burgeoning demand for CER will fundamentally transform drug development by forcing biopharmaceutical manufacturers to view drug innovation from a holistic, 360° perspective. Specifically, drug and device developers must alter their existing approach to R&D by: adapting experimental research design methods to address multiple stakeholder demands; demonstrating real-world value through a suite of post-market observational research methods; and creating a transparent CER evaluation protocol based on standard principles. In the long-term, CER is forecast to propel innovation by focusing R&D on products that deliver real-world value to multiple customers and market stakeholders.Keywords: comparative effectiveness research, comparative effectiveness balance sheet, health technology assessment, large simple trial, moderator, observational studies, patient randomized clinical trial, registry, ‘real-world’ value

  1. Innovation

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    2012-01-01

    Kravet om innovation og kreativitet er på flere måder en stor og en ny udfordring for voksenuddannelserne. Det udfordrer det didaktiske dilemma, det at vi skal gøres til kompetente og frie mennesker gennem pædagogiske handlinger, som netop pålægger os en ufrihed. – Men hvor denne ufrihed...... innovative, netop er det, vi endnu ikke kender...

  2. Multiple sclerosis: Therapeutic applications of advancing drug delivery systems.

    Science.gov (United States)

    Dolati, Sanam; Babaloo, Zohreh; Jadidi-Niaragh, Farhad; Ayromlou, Hormoz; Sadreddini, Sanam; Yousefi, Mehdi

    2017-02-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, which is accompanying with demyelination, neurodegeneration and sensibility to oxidative stress. In MS, auto-reactive lymphocytes cross the blood-brain barrier (BBB) and reside in the perivenous demyelinating lesions which create various distinct inflammatory demyelinated plaques situated predominantly in the white matter. The current MS-related therapeutic approaches can be classified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs suppress circulating immune cells, inhibit passing the BBB and decrease the inflammatory responses. Recent advances have remarkably delayed disease development and improved the quality of life for numerous patients. In spite of major improvements in therapeutic options, there are some limitations regarding the routes of administration and the necessity for repeated and long-term dosing in which cause to systemic disadvantageous consequences and patient non-compliance. Nanotechnology presents promising approaches to improve autoimmune disease treatment with the capability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we emphasis on nanomedicine-based drug delivery approaches of biological immunomodulatory mediators for the treatment of multiple sclerosis. This comprehensive review details the most successful drugs in MS therapy and also focuses on conceptions and clinical potential of novel nanomedicine attitudes for inducing immunosuppression and immunological tolerance in MS to modulate abnormal and pathologic immune responses.

  3. Methodological advances in drug discovery for Chagas disease

    Science.gov (United States)

    Bustamante, Juan M.; Tarleton, Rick L.

    2011-01-01

    Introduction Chagas disease is the highest impact human infectious disease in Latin America, and the leading worldwide cause of myocarditis. Despite the availability of several compounds that have demonstrated efficacy in limiting the effects of T. cruzi, these compounds are rarely used due to their variable efficacy, substantial side effects and the lack of methodologies for confirming their effectiveness. Furthermore, the development of more efficacious compounds is challenged by limitations of systems for assessing drug efficacy in vitro and in vivo. Areas covered Herein, the authors review the development of Chagas disease drug discovery methodology, focusing on recent developments in high throughput screening, in vivo testing methods and assessments of efficacy in humans. Particularly, this review documents the significant progress that has taken place over the last 5 years that have paved the way for both target-focused and high-throughput screens of compound libraries. Expert opinion The tools for in vitro and in vivo screening of anti-T. cruzi compounds have improved dramatically in the last few years and there are now a number of excellent in vivo testing models available; this somewhat alleviates the bottleneck issue of quickly and definitively demonstrating in vivo efficacy in a relevant host animal system. These advances emphasize the potential for additional progress resulting in new treatments for Chagas disease in the coming years. That being said, national and international agencies must improve the coordination of research and development efforts in addition to cultivating the funding sources for the development of these new treatments. PMID:21712965

  4. Drugs in development for toxoplasmosis: advances, challenges, and current status

    Science.gov (United States)

    Alday, P Holland; Doggett, Joseph Stone

    2017-01-01

    Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. PMID:28182168

  5. Grants4Targets - an innovative approach to translate ideas from basic research into novel drugs.

    Science.gov (United States)

    Lessl, Monika; Schoepe, Stefanie; Sommer, Anette; Schneider, Martin; Asadullah, Khusru

    2011-04-01

    Collaborations between industry and academia are steadily gaining importance. To combine expertises Bayer Healthcare has set up a novel open innovation approach called Grants4Targets. Ideas on novel drug targets can easily be submitted to http://www.grants4targets.com. After a review process, grants are provided to perform focused experiments to further validate the proposed targets. In addition to financial support specific know-how on target validation and drug discovery is provided. Experienced scientists are nominated as project partners and, depending on the project, tools or specific models are provided. Around 280 applications have been received and 41 projects granted. According to our experience, this type of bridging fund combined with joint efforts provides a valuable tool to foster drug discovery collaborations.

  6. Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

    Directory of Open Access Journals (Sweden)

    Wang Q

    2016-12-01

    Full Text Available Qun Wang,1,2,* Jian-Ying Huang,2,* Hua-Qiong Li,3,4 Allan Zi-Jian Zhao,4 Yi Wang,4 Ke-Qin Zhang,2,5 Hong-Tao Sun,1 Yue-Kun Lai,2,5 1College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 2National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 3Institute of Biomaterials and Engineering, Wenzhou Medical University, 4Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, 5Research Center of Cooperative Innovation for Functional Organic/Polymer Material Micro/Nanofabrication, Suzhou, People’s Republic of China *These authors contributed equally to this work Abstract: To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. Keywords: TiO2 nanotubes, electrochemical anodization, modification, stimulated drug delivery, drug-releasing implant

  7. Integrating social neuroscience and social work: innovations for advancing practice-based research.

    Science.gov (United States)

    Matto, Holly C; Strolin-Goltzman, Jessica

    2010-04-01

    Throughout the social work profession, there is ongoing interest in building a social science agenda that can address the complex practice-based questions faced by social work professionals today. Methodological innovations and unique funding opportunities have already significantly advanced research on social work practice. Still, there is enthusiastic discussion of how to ensure that such capacity development helps the profession move forward in ways that make use of the biological sciences and that facilitate social work-specific contributions to the larger interdisciplinary scientific community. This article describes how the social work profession can make use of biomedical knowledge and technological advances from social neuroscience to inform psychosocial treatment development, and it illustrates an application to social work practice by giving an example of a substance abuse treatment development process built on social neuroscientific research.

  8. Advanced stent coating for drug delivery and in vivo biocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yi; Wang, Wuchen; Acharya, Gayathri [University of Missouri at Kansas City, Division of Pharmaceutical Sciences, School of Pharmacy (United States); Shim, Yoon-Bo [Pusan National University, Departments of Chemistry (Korea, Republic of); Choe, Eun Sang [Pusan National University, Departments of Biological Sciences (Korea, Republic of); Lee, Chi H., E-mail: leech@umkc.edu [University of Missouri at Kansas City, Division of Pharmaceutical Sciences, School of Pharmacy (United States)

    2013-10-15

    As an effort to alleviate stent-induced cardiovascular injury including restenosis and thrombosis, advanced drug-eluting stent (ADES) with a bilayer construct composed of a top-coat made of collagen and a base-coat incorporated with N-nitrosomelatonin (NOMela)-loaded PLGA nanoparticles has been developed. NOMela is a hydrophobic prodrug of nitric oxide (NO) that is an endogenous anti-platelet compound. ADES was coated with PLGA nanoparticles via either electrophoretic deposition (EPD) technique or dip-coating technique, and their coating characteristics and efficacies were compared. The drug-loading efficacy and in vitro drug-release profiles from ADES were expressed with various variables including the additives to the collagen layer, the number of layers of the collagen top-coat, the hydrophobicity/hydrophilicity of the loaded drug, the coating technique of nanoparticles, and the concentration of coating emulsions in the EPD method. The morphological status of cross-section and surface of ADES was evaluated by laser scanning confocal microscope and scanning electronic microscope. The real-time release profiles of NO were assessed using the NO-microbiosensor. The anti-platelet activity of ADES was evaluated on the rabbit whole blood using an aggregometer. The intima formation and protein expression in aorta were examined using an in vivo rat model. Both collagen and PLGA used in ADES are biodegradable polymers that fully degrade and consequently produce less inflammation responses. NO released from ADES significantly reduced platelet aggregation in the rabbit blood as compared with those exposed to the control stents. ADES coated with a double layer consisted of collagen and PLGA and containing NOMela was less antigenic at the implanted sites and alleviating intima formation and thrombosis. An external exposure of aorta to NO elicits distinct and specific effects on mitogen-activated protein kinase (MAPK) and Ca{sup 2+}/calmodulin-dependent protein kinase II (Ca

  9. THE INNOVATIVE MEDICINES INITIATIVE: A PUBLIC PRIVATE PARTNERSHIP MODEL TO FOSTER DRUG DISCOVERY

    Directory of Open Access Journals (Sweden)

    Elisabetta Vaudano

    2013-03-01

    Full Text Available The Innovative Medicines Initiative (IMI is a large-scale public–private partnership between the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA. IMI aims to boost the development of new medicines across Europe by implementing new collaborative endeavours between large pharmaceutical companies and other key actors in the health-care ecosystem, i.e., academic institutions, small and medium enterprises, patients, and regulatory authorities. Currently there are more than 40 IMI projects covering the whole value chain of pharmaceutical R&D, but with a strong focus on drug discovery, as an ideal arena where the PPP concept of pre-competitive collaboration can rapidly deliver results. This article review recent achievements of the IMI consortia of relevance to drug discovery, providing proof-of-concept evidence for the efficiency of this new model of collaboration.

  10. The Innovative Medicines Initiative: a Public Private Partnership Model to Foster Drug Discovery

    Directory of Open Access Journals (Sweden)

    Elisabetta Vaudano

    2013-03-01

    Full Text Available The Innovative Medicines Initiative (IMI is a large-scale public–private partnership between the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA. IMI aims to boost the development of new medicines across Europe by implementing new collaborative endeavours between large pharmaceutical companies and other key actors in the health-care ecosystem, i.e., academic institutions, small and medium enterprises, patients, and regulatory authorities. Currently there are more than 40 IMI projects covering the whole value chain of pharmaceutical R&D, but with a strong focus on drug discovery, as an ideal arena where the PPP concept of pre-competitive collaboration can rapidly deliver results. This article review recent achievements of the IMI consortia of relevance to drug discovery, providing proof-of-concept evidence for the efficiency of this new model of collaboration.

  11. INNOVATION

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    2012-01-01

    Kravet om innovation og kreativitet er på flere måder en stor og en ny udfordring for voksenuddannelserne. Det udfordrer det didaktiske dilemma, det at vi skal gøres til kompetente og frie mennesker gennem pædagogiske handlinger, som netop pålægger os en ufrihed. – Men hvor denne ufrihed tidligere...... kunne begrundes med, at skolen eller uddannelsen vidste bedre, så er det ikke længere tilfældet. Skolen skal sørge for, at vi lærer noget – og ikke noget andet. Men det kan ikke længere med bestemthed afgøres, hvad det er vi skal lære i skolen, fordi det nye, det kreative og ikke mindst innovative...

  12. Open innovation for phenotypic drug discovery: The PD2 assay panel.

    Science.gov (United States)

    Lee, Jonathan A; Chu, Shaoyou; Willard, Francis S; Cox, Karen L; Sells Galvin, Rachelle J; Peery, Robert B; Oliver, Sarah E; Oler, Jennifer; Meredith, Tamika D; Heidler, Steven A; Gough, Wendy H; Husain, Saba; Palkowitz, Alan D; Moxham, Christopher M

    2011-07-01

    Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target "agnostic" fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD(2)), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD(2) assay panel. Analysis of PD(2) submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD(2) have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD(2), may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

  13. Innovative analytical methods for Central Nervous System Drug analysis in biological fluids

    OpenAIRE

    Musenga, Alessandro

    2009-01-01

    During recent years a consistent number of central nervous system (CNS) drugs have been approved and introduced on the market for the treatment of many psychiatric and neurological disorders, including psychosis, depression, Parkinson disease and epilepsy. Despite the great advancements obtained in the treatment of CNS diseases/disorders, partial response to therapy or treatment failure are frequent, at least in part due to poor compliance, but also genetic variability in the metabolism of ps...

  14. Biomarkers: refining diagnosis and expediting drug development - reality, aspiration and the role of open innovation.

    Science.gov (United States)

    Salter, H; Holland, R

    2014-09-01

    In the last decade, there have been intensive efforts to invent, qualify and use novel biomarkers as a means to improve success rates in drug discovery and development. The biomarkers field is maturing and this article considers whether these research efforts have brought about the expected benefits. The characteristics of a clinically useful biomarker are described and the impact this area of research has had is evaluated by reviewing a few, key examples of emerging biomarkers. There is evidence that the impact has been genuine and is increasing in both the drug and the diagnostic discovery and development processes. Beneficial impact on patient health outcomes seems relatively limited thus far, with the greatest impact in oncology (again, both in terms of novel drugs and in terms of more refined diagnoses and therefore more individualized treatment). However, the momentum of research would indicate that patient benefits are likely to increase substantially and to broaden across multiple therapeutic areas. Even though this research was originally driven by a desire to improve the drug discovery and development process, and was therefore funded with this aim in mind, it seems likely that the largest impact may actually come from more refined diagnosis. Refined diagnosis will facilitate both better allocation of healthcare resources and the use of treatment regimens which are optimized for the individual patient. This article also briefly reviews emerging technological approaches and how they relate to the challenges inherent in biomarker discovery and validation, and discusses the role of public/private partnerships in innovative biomarker research.

  15. Innovations and advances in computing, informatics, systems sciences, networking and engineering

    CERN Document Server

    Elleithy, Khaled

    2015-01-01

    Innovations and Advances in Computing, Informatics, Systems Sciences, Networking and Engineering  This book includes a set of rigorously reviewed world-class manuscripts addressing and detailing state-of-the-art research projects in the areas of Computer Science, Informatics, and Systems Sciences, and Engineering. It includes selected papers from the conference proceedings of the Eighth and some selected papers of the Ninth International Joint Conferences on Computer, Information, and Systems Sciences, and Engineering (CISSE 2012 & CISSE 2013). Coverage includes topics in: Industrial Electronics, Technology & Automation, Telecommunications and Networking, Systems, Computing Sciences and Software Engineering, Engineering Education, Instructional Technology, Assessment, and E-learning.  ·       Provides the latest in a series of books growing out of the International Joint Conferences on Computer, Information, and Systems Sciences, and Engineering; ·       Includes chapters in the most a...

  16. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    Science.gov (United States)

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.

  17. Harnessing Innovative Technologies to Advance Children’s Mental Health: Behavioral Parent Training As an Example

    Science.gov (United States)

    Jones, Deborah J.; Forehand, Rex; Cuellar, Jessica; Kincaid, Carlye; Parent, Justin; Fenton, Nicole; Goodrum, Nada

    2012-01-01

    Disruptive behaviors of childhood are among the most common reasons for referral of children to mental health professionals. Behavioral parent training (BPT) is the most efficacious intervention for these problem behaviors, yet BPT is substantially underutilized beyond university research and clinic settings. With the aim of addressing this research-to-practice gap, this article highlights the considerable, but largely unrealized, potential for technology to overcome the two most pressing challenges hindering the diffusion of BPT: (1). The dearth of BPT training and supervision opportunities for therapists who work with families of children with disruptive behaviors and; (2). The failure to engage and retain families in BPT services when services are available. To this end, this review presents a theoretical framework to guide technological innovations in BPT and highlights examples of how technology is currently being harnessed to overcome these challenges. This review also discusses recommendations for using technology as a delivery vehicle to further advance the field of BPT and the potential implications of technological innovations in BPT for other areas of children’s mental health are discussed. PMID:23313761

  18. Harnessing innovative technologies to advance children's mental health: behavioral parent training as an example.

    Science.gov (United States)

    Jones, Deborah J; Forehand, Rex; Cuellar, Jessica; Kincaid, Carlye; Parent, Justin; Fenton, Nicole; Goodrum, Nada

    2013-03-01

    Disruptive behaviors of childhood are among the most common reasons for referral of children to mental health professionals. Behavioral parent training (BPT) is the most efficacious intervention for these problem behaviors, yet BPT is substantially underutilized beyond university research and clinic settings. With the aim of addressing this research-to-practice gap, this article highlights the considerable, but largely unrealized, potential for technology to overcome the two most pressing challenges hindering the diffusion of BPT: (1). The dearth of BPT training and supervision opportunities for therapists who work with families of children with disruptive behaviors; and (2). The failure to engage and retain families in BPT services when services are available. To this end, this review presents a theoretical framework to guide technological innovations in BPT and highlights examples of how technology is currently being harnessed to overcome these challenges. This review also discusses recommendations for using technology as a delivery vehicle to further advance the field of BPT and the potential implications of technological innovations in BPT for other areas of children's mental health are discussed.

  19. Advances in drug metabolism and pharmacogenetics research in Australia.

    Science.gov (United States)

    Mackenzie, Peter I; Somogyi, Andrew A; Miners, John O

    2017-02-01

    Metabolism facilitates the elimination, detoxification and excretion in urine or bile (as biotransformation products) of a myriad of structurally diverse drugs and other chemicals. The metabolism of drugs, non-drug xenobiotics and many endogenous compounds is catalyzed by families of drug metabolizing enzymes (DMEs). These include the hemoprotein-containing cytochromes P450, which function predominantly as monooxygenases, and conjugation enzymes that transfer a sugar, sulfate, acetate or glutathione moiety to substrates containing a suitable acceptor functional group. Drug and chemical metabolism, especially the enzymes that catalyse these reactions, has been the research focus of several groups in Australia for over four decades. In this review, we highlight the role of recent and current drug metabolism research in Australia, including elucidation of the structure and function of enzymes from the various DME families, factors that modulate enzyme activity in humans (e.g. drug-drug interactions, gene expression and genetic polymorphism) and the application of in vitro approaches for the prediction of drug metabolism parameters in humans, along with the broader pharmacological/clinical pharmacological and toxicological significance of drug metabolism and DMEs and their relevance to drug discovery and development, and to clinical practice.

  20. A REVIEW ON ADVANCES OF SUSTAINED RELEASE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sujit Bose

    2013-06-01

    Full Text Available Sustained release matrix tablets facilitate prolonged and continuous drug release and improve the bioavailability of drugs while avoiding unwanted side effects. Ofloxacin is a broad spectrum antibacterial agent used for treating wide range of gram positive and gram negative infections. The goal in designing sustained or controlled delivery systems is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, providing uniform drug delivery. Sustained release drug administration means not only prolongation of duration of drug delivery, but the term also implies the predictability and reproducibility of drug release kinetics. The controlled release of drug substances and their effective transport to sites of action can be exploited to maximize the beneficial clinical response and to minimize the incidence of unbeneficial adverse reactions and side effects. Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for sustained release systems, oral route of administration has received most of the attention with respect to research on physiological and drug constraints as well as design and testing of products.

  1. Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications.

    Science.gov (United States)

    Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

    To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future.

  2. Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

    Science.gov (United States)

    Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

    2017-01-01

    To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. PMID:28053530

  3. Ethanol effects on drug release from Verapamil Meltrex, an innovative melt extruded formulation.

    Science.gov (United States)

    Roth, W; Setnik, B; Zietsch, M; Burst, A; Breitenbach, J; Sellers, E; Brennan, D

    2009-02-23

    The potential effect of ethanol to accelerate drug release from sustained release (SR) oral formulations is a general concern. Marketed Verapamil is a calcium channel blocker, mainly used as antihypertensive and anti-anginal drug and available in various dose and dosage forms. One is Verapamil Meltrex, combining an innovative and unique SR formulation and technology that achieves a stable solid dispersion of drug by using melt extrusion technology. The aim of this investigation was to determine the influence of ethanol on the in vitro rate of release of marketed Verapamil (240 mg) Meltrex, in contrast to three compressed marketed Verapamil (240 mg) SR formulations. Dissolution was tested under standardized conditions, with mediums containing ethanol concentrations of 0, 5, 20, and 40%. The dissolution profiles for Verapamil Meltrex showed no differences between 5 and 40% ethanol versus 0% ethanol (P>0.05). The mean dissolution percentage (%) was identical at 1h (19%) in 0% versus 40% ethanol. In contrast, the three comparators showed significant increases in dissolution in 20 and 40% ethanol versus 0% ethanol (Pdose dumping when combined with readily accessible ethanol concentrations.

  4. Exploring open innovation with a patient focus in drug discovery: an evolving paradigm of patient engagement.

    Science.gov (United States)

    Allarakhia, Minna

    2015-06-01

    It is suggested in this article that patient engagement should occur further upstream during the drug discovery stage. 'Lead patients', namely those patients who are proactive with respect to their health, possess knowledge of their disease and resulting symptoms. They are also well informed about the conventional as well as non-conventional treatments for disease management; and so can provide a nuanced perspective to drug design. Understanding how patients view the management of their diseases and how they view the use of conventional versus non-conventional interventions is of imperative importance to researchers. Indeed, this can provide insight into how conventional treatments might be designed from the outset to encourage compliance and positive health outcomes. Consequently, a continuum of lead patient engagement is employed that focuses on drug discovery processes ranging from participative, informative to collaborative engagement. This article looks at a variety of open innovation models that are currently employed across this engagement spectrum. It is no longer sufficient for industry stakeholders to consider conventional therapies as the only mechanisms being sought after by patients. Without patient engagement, the industry risks being re-prioritized in terms of its role in the patient journey towards not only recovery of health, but also sustained health and wellness before disease onset.

  5. Penile prosthesis implant: scientific advances and technological innovations over the last four decades

    Science.gov (United States)

    2017-01-01

    Despite introduction of oral phosphodiesterase type 5 inhibitors and intracavernosal vasoactive agents, penile prosthesis implant remains a relevant and desired option with sales of penile prostheses continue to stay high, as many men became refractory to medical therapy and/or seeking a more effective and permanent therapy. There are two types of penile prosthesis implants: inflatable and non-inflatable types, and the inflatable penile implants can be subdivided into single-, two- and three-piece devices. Non-inflatable penile prosthesis (non-IPP) may be referred to as semi-rigid rod or malleable prosthesis. IPP is considered a superior option to malleable prosthesis as it produces penile rigidity and flaccidity that closely replicates a normal penile erectile function. Since the introduction of IPP by Scott in 1973, surgical landscape for penile prosthesis implantation has changed dramatically. Advances in prosthesis design, device technologies and surgical techniques have made penile prosthesis implant a more natural, durable and reliable device. The following article reviews the scientific advances and technological innovation in modern penile prosthesis implants over the last four decades. PMID:28217449

  6. Advanced Recyclable Media System{reg_sign}. Innovative technology summary report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    The objective of the Large-Scale Demonstration Project (LSDP) is to select and demonstrate potentially beneficial technologies at the Argonne National Laboratory East`s (ANL) Chicago Pile-5 (CP-5) Research Reactor. The purpose of the LSDP is to demonstrate that using innovative and improved deactivation and decommissioning (D and D) technologies from various sources can result in significant benefits, such as decreased cost and increased health and safety, as compared with baseline D and D technologies. This report describes a demonstration of the Advanced Recyclable Media System{reg_sign} technology which was employed by Surface Technology Systems, Inc. to remove coatings from a concrete floor. This demonstration is part of the CP-5 LSDP sponsored by the US Department of Energy (DOE) Office of Science and Technology Deactivation and Decommissioning Focus Area (DDFA). The Advanced Recyclable Media System{reg_sign} (ARMS) technology is an open blast technology which uses a soft recyclable media. The patented ARMS Engineered Blast Media consists of a fiber-reinforced polymer matrix which can be manufactured in various grades of abrasiveness. The fiber media can be remade and/or reused up to 20 times and can clean almost any surface (e.g., metal, wood, concrete, lead) and geometry including corners and the inside of air ducts.

  7. Grand Challenges of Advanced Computing for Energy Innovation Report from the Workshop Held July 31-August 2, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Larzelere, Alex R.; Ashby, Steven F.; Christensen, Dana C.; Crawford, Dona L.; Khaleel, Mohammad A.; John, Grosh; Stults, B. Ray; Lee, Steven L.; Hammond, Steven W.; Grover, Benjamin T.; Neely, Rob; Dudney, Lee Ann; Goldstein, Noah C.; Wells, Jack; Peltz, Jim

    2013-03-06

    On July 31-August 2 of 2012, the U.S. Department of Energy (DOE) held a workshop entitled Grand Challenges of Advanced Computing for Energy Innovation. This workshop built on three earlier workshops that clearly identified the potential for the Department and its national laboratories to enable energy innovation. The specific goal of the workshop was to identify the key challenges that the nation must overcome to apply the full benefit of taxpayer-funded advanced computing technologies to U.S. energy innovation in the ways that the country produces, moves, stores, and uses energy. Perhaps more importantly, the workshop also developed a set of recommendations to help the Department overcome those challenges. These recommendations provide an action plan for what the Department can do in the coming years to improve the nation’s energy future.

  8. SOLID LIPID NANOPARTICLES: AN ADVANCED DRUG DELIVERY SYSTEM

    OpenAIRE

    Raghu Nandan Reddy* and Arshia Shariff

    2013-01-01

    Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, research and clinical medicine, as well as in other varied sciences. Solid lipid nanoparticle (SLN) dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. Solid lipid nanoparticles (SLNs) technology represents a promising new approach to lipophilic drug delivery. Solid lipid nanopa...

  9. Research and development in drug innovation: reflections from the 2013 bioeconomy conference in China, lessons learned and future perspectives.

    Science.gov (United States)

    Liu, Changxiao; Constantinides, Panayiotis P; Li, Yazhuo

    2014-04-01

    The enormous progress biotechnology, bioinformatics and nanotechnology made in recent years provides opportunities and scientific framework for development of biomedicine and constitutes a paradigm shift in pharmaceutical R&D and drug innovation. By analyzing the data and related information at R&D level over the past decades, developmental tendency and R&D patterns were summarized. We found that a growing number of biologics in the pipeline of pharma companies with successful products already in the market though, small molecular entities have primarily dominated drug innovation. Additionally, small/medium size companies will continue to play a key role in the development of small molecule drugs and biologics in a multi-channel integrated process. More importantly, modern and effective R&D strategies in biomedicine development to predict and evaluate efficacy and/or safety of 21st century therapeutics are urgently needed. To face new challenges, developmental strategies were proposed, in terms of molecular targeted medicine, generic drugs, new drug delivery system and protein-based drugs. Under the current circumstances, interdisciplinary cooperation mode and policy related to drug innovation in China were deeply discussed as well.

  10. REVIEW ON ADVANCES IN COLON TARGETED DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sunena Sethi, SL Harikumar* and Nirmala

    2012-09-01

    Full Text Available The colon is the terminal part of the GIT which has gained in recent years as a potential site for delivery of various novel therapeutic drugs, i.e. peptides. However, colon is rich in microflora which can be used to target the drug release in the colon. Colon is a site where both local and systemic drug delivery can take place. Local delivery allows the topical treatment of inflammatory bowel disease. If drug can be targeted directly into the colon, treatment can become more effective and side effects can be minimized. These systemic side effects can be minimized by primary approaches for CDDS (Colon specific drug delivery namely prodrugs, pH and time dependent systems and microbially triggered system which gained limited success and have limitations as compared with recently new CDDS namely pressure controlled colon delivery capsules (PCDCS, CODESTM (Novel colon targeted delivery system osmotic controlled drug delivery system, Pulsincap system, time clock system, chronotropic system. This review is to understand the pharmaceutical approaches to colon targeted drug delivery systems for better therapeutic action without compromising on drug degradation (or its low bioavailability.

  11. Advanced Drug Delivery Systems - a Synthetic and Biological Applied Evaluation

    DEFF Research Database (Denmark)

    Bjerg, Lise Nørkjær

    Specific delivery of drugs to diseased sites in the body is a major topic in the development of drug delivery system today. Especially, the field of cancer treatment needs improved drug delivery systems as the strong dose-limiting side effects of chemotherapy today often present a barrier...... unloading of the encapsulated drug have been tried optimized in a variety of ways. Many propose the use of small molecules, such as vitamins and peptides, for active targeting of the liposomes to overexpressed receptors on the cancerous tissue. Once located close to the diseased site a trigger mechanism...... for releasing the drug from the liposome interior is often needed. Several approaches have been suggested to work as release mechanisms such a pH changes, the presence of enzymes or external applied stimulus as heat or light. Chapter two deals with the synthesis of the functionalized phospholipids, which...

  12. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  13. Seven behaviors to advance teamwork: findings from a study of innovation leadership in a simulation center.

    Science.gov (United States)

    Weberg, Dan; Weberg, Kim

    2014-01-01

    Traditional notions of individual-based leadership behaviors are no longer adequate to achieve innovation in health care organizations. A major contributing factor for limited innovation is that outdated leadership practices, such as leader centricity, linear thinking, and poor readiness for innovation, are being used in health care organizations. Through a qualitative case study analysis of innovation implementation, 7 characteristics of innovation leadership, founded in team behaviors, were uncovered. The characteristics that were uncovered included boundary spanning, risk taking, visioning, leveraging opportunity, adaptation, coordination of information flow, and facilitation. These characteristics describe how leaders throughout the system were able to influence and implement innovation successfully.

  14. 76 FR 23543 - The Jobs and Innovation Accelerator Challenge; a Coordinated Initiative To Advance Regional...

    Science.gov (United States)

    2011-04-27

    ... Economic Development Administration The Jobs and Innovation Accelerator Challenge; a Coordinated Initiative... Commerce. ACTION: Notice. SUMMARY: The Obama Administration announces the Jobs and Innovation Accelerator...-fueled job creation and economic prosperity through public-private partnerships. The...

  15. A Nanodroplet Processor for Advanced Microencapsulated Drug Formulations Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this proposal is to provide a demonstration of a nanodroplet synthesis of multifunctional liposomes for drug delivery based on immiscible...

  16. RECENT ADVANCEMENT OF LIPID DRUG CONJUGATE AS NANOPARTICULATE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Ratna Jyoti Das

    2013-01-01

    Full Text Available Nanotechnology by manipulation of characteristics of materials such as polymers and fabrication of nanostructures is able to provide superior drug delivery systems for better management and treatment of diseases. The nanostructures employed as drug delivery systems have multiple advantages which make them superior to conventional delivery systems. Nanotechnology is one approach to overcome challenges of conventional drug delivery systems based on the development and fabrication of nanostructures. Some challenges associated with the technology as it relates to drug effectiveness, toxicity, stability and pharmacokinetics and drug regulatory control. Nanotechnology is a welcome development that is set to transform drug delivery and drug supply chain management, if optimally developed. Lipid Drug Conjugates (LDCs are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Due to their unique size dependent properties, lipid nanoparticles offer possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could use for drug targeting. Hence lipid drug conjugates hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. Solid lipid nanoparticle technology represents a promising new approach to lipophile drug delivery.

  17. [Evaluation of the safety of innovative drugs against viruses and infectious agents].

    Science.gov (United States)

    Kobayashi, Tetsu; Yusa, Keisuke; Kawasaki, Nana

    2013-01-01

    Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.

  18. Fast Dissolving Oral Film: A Novel and Innovative Drug Delivery system

    Directory of Open Access Journals (Sweden)

    Ankita Keshari

    2014-03-01

    Full Text Available The oral route is more suitable than other route of administration of therapeutic agents due to low cost of therapy and ease of administration and of patient compliance. This is noninvasive method and produce less side effect. There are some oral solid dosage forms like capsules and tablets. In geriatric, pediatric and dysphagia like patients find it difficult to swallow capsules and tablets and cannot take their medicines as prescribed manner. In some condition such as, sudden allergic attack, coughing, motion sickness, fear of choking and an unavailability of water, the swallowing of capsules or tablet or may become difficult. To overcome from these types of problem, the pharmaceutical industries are design and develop the new type of drug delivery system such as fast dissolving drug delivery systems. This innovative Oral fast dissolving film is a new dosage form in which a thin film is prepared by using hydrophilic polymers with suitable excipients. The film dissolved quickly in mouth without taking of water. The oral films are prepared by the solvent casting method or hot melt extrusion.

  19. Recent advances in co-amorphous drug formulations

    DEFF Research Database (Denmark)

    Dengale, Swapnil Jayant; Grohganz, Holger; Rades, Thomas;

    2016-01-01

    Co-amorphous drug delivery systems have recently gained considerable interest in the pharmaceutical field because of their potential to improve oral bioavailability of poorly water-soluble drugs through drug dissolution enhancement as a result of the amorphous nature of the material. A co-amorpho...... findings. In particular, we investigate co-amorphous formulations from the viewpoint of solid dispersions, describe their formation and mechanism of stabilization, study their impact on dissolution and in vivo performance and briefly outline the future potentials.......Co-amorphous drug delivery systems have recently gained considerable interest in the pharmaceutical field because of their potential to improve oral bioavailability of poorly water-soluble drugs through drug dissolution enhancement as a result of the amorphous nature of the material. A co-amorphous...... system is characterized by the use of only low molecular weight components that are mixed into a homogeneous single-phase co-amorphous blend. The use of only low molecular weight co-formers makes this approach very attractive, as the amount of amorphous stabilizer can be significantly reduced compared...

  20. Nanostructured lipid carriers system: recent advances in drug delivery.

    Science.gov (United States)

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  1. Assimilation Patterns in the Use of Advanced Manufacturing Technologies in SMEs: Exploring their Effects on Product Innovation Performance

    Directory of Open Access Journals (Sweden)

    Sylvestre Uwizeyemungu

    2015-10-01

    Full Text Available Manufacturing small and medium-sized enterprises (SMEs are more and more adopting advanced manufacturing technologies (AMT aimed at fostering product innovation process, improving product quality, streamlining the production process, and gaining productivity. In this study, we analyze the relationship between AMT proficiency levels in manufacturing SMEs and product innovation performance. Using data from 616 manufacturing SMEs, and considering a wide range of various AMT (20 different types of AMT grouped into 5 categories, we derived three AMT assimilation patterns through a cluster analysis procedure combining hierarchical and non-hierarchical clustering algorithms. The analysis of the relationship between AMT assimilation patterns and product innovation performance shows a rather unexpected picture: in spite of the existence of clearly distinct patterns of AMT assimilation, we find no significant relationship between any pattern and product innovation performance. Instead, we find the organizational and environmental context of SMEs to be more determinant for product innovation performance than any of the AMT assimilation patterns. From a practical point of view, this study indicates that manufacturing SMEs managers interested in fostering their innovation capabilities through AMT assimilation need to be aware of the contingency effects of their organizational size, age, and sector of activity.

  2. Insoluble drug delivery strategies: review of recent advances and business prospects

    Directory of Open Access Journals (Sweden)

    Sandeep Kalepu

    2015-09-01

    Full Text Available The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects.

  3. Insoluble drug delivery strategies: review of recent advances and business prospects.

    Science.gov (United States)

    Kalepu, Sandeep; Nekkanti, Vijaykumar

    2015-09-01

    The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects.

  4. In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery

    Science.gov (United States)

    Darvesh, Altaf S.; Carroll, Richard T.; Geldenhuys, Werner J.; Gudelsky, Gary A.; Klein, Jochen; Meshul, Charles K.; Van der Schyf, Cornelis J.

    2010-01-01

    Introduction Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo microdialysis technique allows measurement of neurotransmitters such as acetycholine (ACh), the biogenic amines including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), amino acids such as glutamate (Glu) and gamma aminobutyric acid (GABA), as well as the metabolites of the aforementioned neurotransmitters, and neuropeptides in neuronal extracellular fluid in discrete brain regions of laboratory animals such as rodents and non-human primates. Areas covered In this review we present a brief overview of the principles and procedures related to in vivo microdialysis and detail the use of this technique in the pre-clinical measurement of drugs designed to be used in the treatment of chemical addiction, neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and as well as psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. This review offers insight into the tremendous utility and versatility of this technique in pursuing neuropharmacological investigations as well its significant potential in rational drug discovery. Expert opinion In vivo microdialysis is an extremely versatile technique, routinely used in the neuropharmacological investigation of drugs used for the treatment of neurological disorders. This technique has been a boon in the elucidation of the neurochemical profile and mechanism of action of several classes of drugs especially their effects on neurotransmitter systems. The exploitation and development of this technique for drug discovery in the near future will enable investigational new drug candidates to be rapidly moved into the clinical trial stages and to market thus providing new successful therapies for neurological diseases

  5. Advances in drug delivery via electrospun and electrosprayed nanomaterials

    Directory of Open Access Journals (Sweden)

    Zamani M

    2013-08-01

    Full Text Available Maedeh Zamani,1 Molamma P Prabhakaran,2 Seeram Ramakrishna1,21Department of Mechanical Engineering, 2Center for Nanofibers and Nanotechnology, National University of Singapore, SingaporeAbstract: Electrohydrodynamic (EHD techniques refer to procedures that utilize electrostatic forces to fabricate fibers or particles of different shapes with sizes in the nano-range to a few microns through electrically charged fluid jet. Employing different techniques, such as blending, surface modification, and coaxial process, there is a great possibility of incorporating bioactive such molecules as drugs, DNA, and growth factors into the nanostructures fabricated via EHD techniques. By careful selection of materials and processing conditions, desired encapsulation efficiency as well as preserved bioactivity of the therapeutic agents can be achieved. The drug-loaded nanostructures produced can be applied via different routes, such as implantation, injection, and topical or oral administration for a wide range of disease treatment. Taking advantage of the recent developments in EHD techniques like the coaxial process or multilayered structures, individually controlled delivery of multiple drugs is achievable, which is of great demand in cancer therapy and growth-factor delivery. This review summarizes the most recent techniques and postmodification methods to fabricate electrospun nanofibers and electrosprayed particles for drug-delivery applications.Keywords: electrospinning, electrospraying, gene delivery, growth-factor delivery, cancer therapy, wound dressing

  6. SOLID LIPID NANOPARTICLES: AN ADVANCED DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Raghu Nandan Reddy* and Arshia Shariff

    2013-01-01

    Full Text Available Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, research and clinical medicine, as well as in other varied sciences. Solid lipid nanoparticle (SLN dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. Solid lipid nanoparticles (SLNs technology represents a promising new approach to lipophilic drug delivery. Solid lipid nanoparticles are spherical lipid particles ranging in size from 1 to 1000 nm and are dispersed in water or in aqueous surfactant solution. It is identical to an oil-in-water emulsion, but the liquid lipid (oil of the emulsion has been replaced by a solid lipid, i.e., yielding Solid Lipid Nanoparticles. SLN are particles made from solid lipid or lipid blends produced by high pressure homogenization. The biodegradable and bioacceptable nature of SLNs makes them less toxic as compared to polymeric nanoparticles. SLNs can also be used to improve the bioavailability of drugs. In this present review this new approach is discussed in terms of their advantages, disadvantages, methods, characterization, pharmacokinetic studies, in-vivo studies, in-vitro studies, and special features

  7. China's new drug R&D is steadily advancing.

    Science.gov (United States)

    Xu, W F

    2007-08-01

    China appears to consistently lag behind developed countries like the US, Japan, and the nations of Europe in the development of pharmaceuticals, putting China in an embarrassing situation. In fact, China is still dependent on foreign imports for most highly effective cures to major diseases such as cancer, diabetes, hepatitis, and neurodegenerative disease. There is no denying the fact that governmental support, and especially a signifi cant amount of fi nancial support and political assistance to include government restructuring, is needed for the establishment of new drug Research and Development (R&D). Fortunately, China's authorities have recently recognized the importance of new drug development and have committed to implementing strong measures to help establish new drug R&D. This improvement in the government's status is showing immediate and substantial promise in the field of pharmaceuticals. On January 4, 2007, a research group directed by Wang Ming-Wei, Head of the National Center for Drug Screening, Shanghai Institute of Materia Medica (SIMM), made a breakthrough in the development of novel category I anti-diabetes drugs with the support of the Ministry of Science & Technology of China, the National Natural Science Foundation (NSFC) of China, and the Shanghai municipal government. Taking almost four years, the group finally developed a nonpeptide agonist of small molecule glucagon-like peptide 1 receptors with effi cacy in diabetic db/db mice (Proc Natl Acad Sci U S A 2007;104:943-948). As an antidiabetes drug, a peptide hormone traditionally had to be taken as an injection, which greatly limited its clinical application. In contrast, the new compound can be taken orally. This offers hope for the development of a new field of peptidomimetics for orally-available nonpeptide small molecules. Today, the ever-growing prevalence of major diseases worldwide is driving growth in new drug spending, encouraging the marketing of newly developed and effi cacious

  8. Conceptual study on a new generation of the high-innovative advanced porous and composite nanostructural functional materials with nanofibers

    OpenAIRE

    L.A. Dobrzański; M. Pawlyta; A. Hudecki

    2011-01-01

    Purpose: The purpose of the paper is to analyse theoretically the possibilities of the development of a new generation of the high-innovative advanced porous and composite nanostructural functional materials with nanofibers and to study into the material science grounds of synthesis and/or production and formulation of such materials’ structure and properties and to characterise and model their structure and properties depending on the compositional, phase and chemical composition and the app...

  9. Recent advances in combinatorial biosynthesis for drug discovery

    Directory of Open Access Journals (Sweden)

    Sun H

    2015-02-01

    Full Text Available Huihua Sun,1,* Zihe Liu,1,* Huimin Zhao,1,2 Ee Lui Ang1 1Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, Singapore; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA *These authors contributed equally to this work Abstract: Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1 precursor-directed biosynthesis; 2 enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3 pathway-level recombination. Recent examples of combinatorial biosynthesis employing these

  10. Drug Response and Resistance in Advanced NF-1-Associated Cancers

    Science.gov (United States)

    2015-07-01

    drugs induced clinical remissions and markedly prolonged survival. However, all of the mice eventually relapsed and died of AML despite continued...in transduced cells using a 32P release assay from labeled recombinant Ras-GTP (54, 55). We also cloned a C-terminal “self- cleaving” T2A peptide ...cells (Fig. 1a). Utilization of the T2A peptide cleavage site establishes an internal reference that insures that the measured fluorescence is

  11. Drug Response and Resistance in Advanced NF1-Associated Cancers

    Science.gov (United States)

    2014-05-01

    generation” MEK inhibitor with enhanced pharmacokinetic properties (27). Both drugs induced clinical remissions and markedly prolonged survival. However...a 32P release assay from labeled recombinant Ras-GTP (47, 48). We also cloned a C- terminal “self-cleaving” T2A peptide into this vector followed by...of the T2A peptide cleavage site establishes an internal reference that insures that the measured fluorescence is directly proportional to the level

  12. The impact of cardiovascular drug innovation on the longevity of elderly residents of Switzerland, 2003-2012

    Directory of Open Access Journals (Sweden)

    Frank R Lichtenberg

    2015-03-01

    Full Text Available Previous investigators have argued that one of the two most important contributors to improved human survival is the treatment of cardiovascular disease. Among Swiss inhabitants age 65 and over, 90% of the 1994-2010 decline in the overall death rate was due to the decline in the rate of deaths from diseases of the circulatory system. Little if any of the decline in cardiovascular mortality is likely to have been due to changes in behavioral risk factors, especially tobacco use and obesity. This study examines the impact of cardiovascular drug innovation on the longevity of elderly residents of Switzerland using cross-sectional patient-level data on about 22 thousand patients insured by a major health insurer (CSS during the period 2003-2011. We investigate the effect of the vintage (world launch year of the cardiovascular drugs used by an individual in 2003 on his or her longevity (time till death, controlling for several demographic characteristics and indicators of health status. We are able to track a patient’s vital status until 12/31/2011: 8 years after the end of the period in which cardiovascular drug use (and other variables are measured. Our estimates indicate that people who used newer cardiovascular drugs in 2003 had longer time till death than people who used older cardiovascular drugs, controlling for the number of 2003 prescriptions and their distribution by main anatomical group, the number of 2003 doctor visits and their distribution by specialty, whether the person was hospitalized in 2003, sex, and age. Our most conservative estimates imply that cardiovascular drug innovation accounted for almost a quarter of the increase in longevity among elderly residents of Switzerland during 2003-2012, and that it increased their longevity by almost 3 months. Other estimates are about twice as large. All of the estimates are consistent with the hypothesis that newer classes of drugs tend to be therapeutically superior to older classes of

  13. Molecularly targeted therapy for advanced hepatocellularcarcinoma - a drug development crisis?

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    This review summarizes the current status of neoadjuvantradiation approaches in the treatment of pancreatic cancer,including a description of modern radiation techniques,and an overview on the literature regarding neoadjuvantradio- or radiochemotherapeutic strategies both forresectable and irresectable pancreatic cancer. Neoadjuvantchemoradiation for locally-advanced, primarily non- orborderline resectable pancreas cancer results in secondaryresectability in a substantial proportion of patients withconsecutively markedly improved overall prognosisand should be considered as possible alternative inpretreatment multidisciplinary evaluations. In resectablepancreatic cancer, outstanding results in terms ofresponse, local control and overall survival have beenobserved with neoadjuvant radio- or radiochemotherapy inseveral phase Ⅰ/Ⅱ trials, which justify further evaluationof this strategy. Further investigation of neoadjuvantchemoradiation strategies should be performed preferentiallyin randomized trials in order to improvecomparability of the current results with other treatmentmodalities. This should include the evaluation of optimalsequencing with newer and more potent systemicinduction therapy approaches. Advances in patientselection based on new molecular markers might be ofcrucial interest in this context. Finally modern externalbeam radiation techniques (intensity-modulated radiationtherapy, image-guided radiation therapy and stereotacticbody radiation therapy), new radiation qualities (protons,heavy ions) or combinations with alternative boostingtechniques widen the therapeutic window and contributeto the reduction of toxicity.

  14. Vismodegib: The first drug approved for advanced and metastatic basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    A K Dubey

    2013-01-01

    Full Text Available Treatment of basal cell carcinoma (BCC usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA. The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  15. Vismodegib: the first drug approved for advanced and metastatic basal cell carcinoma.

    Science.gov (United States)

    Dubey, A K; Dubey, S; Handu, S S; Qazi, M A

    2013-01-01

    Treatment of basal cell carcinoma (BCC) usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA). The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  16. New active drugs for the treatment of advanced colorectalcancer

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Newer active drugs have been recently added to thepharmacological armamentarium for the treatment ofmetastatic colorectal cancer. Aflibercept, a recombinantfusion protein composed of the extracellular domainsof human vascular endothelial growth factor receptors(VEGFR) 1 and 2 and the Fc portion of human immunoglobulinG1 (IgG1), is an attractive second-line optionin combination with folfiri for patients who have failedfolfox +/- bevacizumab. Ramucirumab, a human IgG1monoclonal antibody that targets VEGFR-2, providedsimilar results in the same setting. Tas-102, an oralfluoropyrimidine, and regorafenib, a multi-tyrosinekinase inhibitor, are both able to control the diseasein a considerable proportion of patients when all otheravailable treatments have failed. These new therapeuticoptions along with the emerging concept that previoustherapies may also be reitroduced or rechallenged afterregorafenib and Tas-102 failure are bringing new hopefor thousands of patients and their families.

  17. Drug-induced liver injury: Advances in mechanistic understanding that will inform risk management.

    Science.gov (United States)

    Mosedale, M; Watkins, P B

    2016-11-09

    Drug-induced liver injury (DILI) is a major public health problem. Intrinsic (dose-dependent) DILI associated with acetaminophen overdose is the number one cause of acute liver failure in the US. However, the most problematic type of DILI impacting drug development is idiosyncratic, occurring only very rarely among treated patients and often only after several weeks or months of treatment with the offending drug. Recent advances in our understanding of the pathogenesis of DILI suggest that three mechanisms may underlie most hepatocyte effects in response to both intrinsic and idiosyncratic DILI drugs: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis. However, in some cases hepatocyte stress promotes an immune response that results in clinically important idiosyncratic DILI. This review discusses recent advances in our understanding of the pathogenesis of both intrinsic and idiosyncratic DILI as well as emerging tools and techniques that will likely improve DILI risk identification and management.

  18. Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.

    Science.gov (United States)

    Herrera-Arozamena, Clara; Martí-Marí, Olaia; Estrada, Martín; de la Fuente Revenga, Mario; Rodríguez-Franco, María Isabel

    2016-09-01

    The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).

  19. Vegetable Oil-Loaded Nanocapsules: Innovative Alternative for Incorporating Drugs for Parenteral Administration.

    Science.gov (United States)

    Venturinil, C G; Bruinsmann, A; Oliveira, C P; Contri, R V; Pohlmann, A R; Guterres, S S

    2016-02-01

    An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.

  20. An Innovative Unmanned System for Advanced Environmental Monitoring: Design and Development

    Science.gov (United States)

    Marsella, Ennio; Giordano, Laura; Evangelista, Lorenza; Iengo, Antonio; di Filippo, Alessandro; Coppola, Aniello

    2015-04-01

    The paper summarizes the design and development of a new technology and tools for real-time coordination and control of unmanned vehicles for advanced environmental monitoring. A new Unmanned System has been developed at Institute for Coastal Marine Environmental - National Research Council (Italy), in the framework of two National Operational Programs (PON): Technological Platform for Geophysical and Environmental Marine Survey-PITAM and Integrated Systems and Technologies for Geophysical and Environmental Monitoring in coastal-marine areas-STIGEAC. In particular, the system includes one Unmanned Aerial Vehicle (UAV) and two Unmanned Marine Vehicles (UMV). Major innovations concern the implementation of a new architecture to control each drone and/or to allow the cooperation between heterogeneous vehicles, the integration of distributed sensing techniques and real-time image processing capabilities. Part of the research in these projects involves, therefore, an architecture, where the ground operator can communicate with the Unmanned Vehicles at various levels of abstraction using pointing devices and video viewing. In detail, a Ground Control Station (GCS) has been design and developed to allow the government in security of the drones within a distance up to twenty kilometers for air explorations and within ten nautical miles for marine activities. The Ground Control Station has the following features: 1. hardware / software system for the definition of the mission profiles; 3. autonomous and semi-autonomous control system by remote control (joystick or other) for the UAV and UMVs; 4. integrated control system with comprehensive visualization capabilities, monitoring and archiving of real-time data acquired from scientific payload; 5. open structure to future additions of systems, sensors and / or additional vehicles. In detail, the UAV architecture is a dual-rotor, with an endurance ranging from 55 to 200 minutes, depending on payload weight (maximum 26 kg) and

  1. Next-Generation Entrepreneurs Ready to Advance Breast Cancer Research Innovations | Poster

    Science.gov (United States)

    By Michele Newton and Thomas Stackhouse, Contributing Writers, and Rosemarie Truman, Guest Writer Editor’s note: In May 2014, the Breast Cancer Start-Up Challenge was named one of six finalists in the HHS Innovates Award Competition. This award celebrates innovations developed by employees of the U.S. Department of Health and Human Services (HHS) to support the mission of HHS. In the final phase of the competition, the public will be invited to help select “The People’s Choice” winner; public voting takes place May 29 through June 6, 2014.

  2. Food and drug administration′s critical path initiative and innovations in drug development paradigm: Challenges, progress, and controversies

    Directory of Open Access Journals (Sweden)

    Rajiv Mahajan

    2010-01-01

    Full Text Available During the last decade, despite increased investment in drug research and development related activity, stagnation in new drug discovery has been documented. Despite a 70% increase in investment in research and development-related activities, a 40% fall in launch of new chemical entities was seen during 1994-2004. A steep rise in the attrition rate of drug development has complicated the matter. Rising cost and increased attrition rates proved major barriers to investment in higher risk drugs or in therapies for uncommon diseases or diseases that predominantly afflict the poor. This prompted Food and Drug Administration (FDA to highlight this problem in a 2004 white paper classified as "Critical Path Initiative" (CPI and to initiate steps to target stagnation and rise in attrition rates. Many new drug development projects have started worldwide taking cue from CPI; adopting microdosing, adaptive designs and taking advantage of newly developed biomarkers under the CPI. This review discusses the various strategies adopted under CPI to decrease attrition rate and stagnation of new drug development, and the challenges and controversies associated with CPI.

  3. Conference Scene: From innovative polymers to advanced nanomedicine: Key challenges, recent progress and future perspectives

    NARCIS (Netherlands)

    Feijen, J.; Hennink, W.E.; Zhong, Z.

    2013-01-01

    Recent developments in polymer-based controlled delivery systems have made a significant clinical impact. The second Symposium on Innovative Polymers for Controlled Delivery (SIPCD) was held in Suzhou, China to address the key challenges and provide up-to-date progress and future perspectives in the

  4. Advanced technology care innovation for older people in Italy: necessity and opportunity to promote health and wellbeing.

    Science.gov (United States)

    Lattanzio, Fabrizia; Abbatecola, Angela M; Bevilacqua, Roberta; Chiatti, Carlos; Corsonello, Andrea; Rossi, Lorena; Bustacchini, Silvia; Bernabei, Roberto

    2014-07-01

    Even though there is a constant and accelerating growth of the aging population worldwide, such a rapid rise is negatively impacting available home and community services not able to encompass the necessities associated with the increased number of older people. In particular, there are increasing demands on e-health care services and smart technologies needed for frail elders with chronic diseases and also for those experiencing active aging. Advanced Technology Care Innovation for older persons encompasses all sectors (assistive technology, robotics, home automation, and home care- and institution-based healthcare monitoring, telemedicine) dedicated to promoting health and wellbeing in all types of living environments. Considering that there is a large concern and demand by older persons to remain in familiar social living surroundings, study projects joined with industries have been currently initiated, especially across Europe to improve health and wellbeing. This article will highlight the latest updates in Europe and, in particular in Italy, regarding scientific projects dedicated to unraveling how diverse needs can be translated into an up-to-date technology innovation for the growing elder population. We will provide information regarding advanced technology designed for those with specific geriatric-correlated conditions in familiar living settings and for individuals aging actively. This is an important action because numerous emerging developments are based on user needs identified by geriatricians, thus, underlining the indispensable role of geriatric medicine toward future guidelines on specific technology.

  5. Why animal studies are still being used in drug development. An innovation system perspective

    NARCIS (Netherlands)

    Kooijman, M.

    2013-01-01

    In Europe alone, 3.6 million animals per year are used for drug development. Animal studies are worldwide the gold standard to evaluate the safety, efficacy and quality of drugs before these drugs are tested in humans. Nevertheless the value of animal studies to predict risks for humans has never be

  6. Evaluation of Mutual Drug-Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method.

    Science.gov (United States)

    Bosilkovska, Marija; Samer, Caroline; Déglon, Julien; Thomas, Aurélien; Walder, Bernhard; Desmeules, Jules; Daali, Youssef

    2016-09-01

    Cytochrome P450 (CYP) activity can be assessed using a 'cocktail' phenotyping approach. Recently, we have developed a cocktail (Geneva cocktail) which combines the use of low-dose probes with a low-invasiveness dried blood spots (DBS) sampling technique and a single analytical method for the phenotyping of six major CYP isoforms. We have previously demonstrated that modulation of CYP activity after pre-treatment with CYP inhibitors/inducer could be reliably predicted using Geneva cocktail. To further validate this cocktail, in this study, we have verified whether probe drugs contained in the latter cause mutual drug-drug interactions. In a randomized, four-way, Latin-square crossover study, 30 healthy volunteers received low-dose caffeine, flurbiprofen, omeprazole, dextromethorphan and midazolam (a previously validated combination with no mutual drug-drug interactions); fexofenadine alone; bupropion alone; or all seven drugs simultaneously (Geneva cocktail). Pharmacokinetic profiles of the probe drugs and their metabolites were determined in DBS samples using both conventional micropipette sampling and new microfluidic device allowing for self-sampling. The 90% confidence intervals for the geometric mean ratios of AUC metabolite/AUC probe for CYP probes administered alone or within Geneva cocktail fell within the 0.8-1.25 bioequivalence range indicating the absence of pharmacokinetic interaction. The same result was observed for the chosen phenotyping indices, that is metabolic ratios at 2 hr (CYP1A2, CYP3A) or 3 hr (CYP2B6, CYP2C9, CYP2C19, CYP2D6) post-cocktail administration. DBS sampling could successfully be performed using a new microfluidic device. In conclusion, Geneva cocktail combined with an innovative DBS sampling device can be used routinely as a test for simultaneous CYP phenotyping.

  7. The industrial research project: “Blu-Archeosys – Innovative Technologies and Advanced Systems as Support in Underwater Archaeology”

    Directory of Open Access Journals (Sweden)

    Salvatore Lorusso

    2003-02-01

    Full Text Available The reasons of the research about new technologies as support in naval and underwater archaeology or, more generally, in waters archaeology are various and described in this work, where the characteristics of the research project “BLU-ARCHEOSYS – Innovative Technologies and Advanced SYStems as Support in Underwater ARCHaeology” are illustrated. This industrial research project faces problems regarding innovative technologies and instruments in waters archaeology and it comprehends synergic steps and joined works among skilled professionals that have the competences to interpret qualitative and/or quantitative data within an artistic – historical and technical – historical study, also with the involvement of various public and private institutions. The BLUARCHEOSYS project has, in fact, the objective to create technologies that have a reply in underwater archaeology and contemporaneously in other sectors. In particular, starting from the methodological way that spans from the discovery in underwater or subaerial environment to the collocation of the objects in museums, the intent is to support the different methodological stages with specific tools and innovative technologies. The education project, presented to the Ministry with the research one, is articulated in the different branches of artistic-historical character, of the management, normative and operative character, and of the technical-diagnostic-material-preservative character. The professionals will have not only theoretical knowledge about standard and consolidated technologies, but they will be also experts about methodologies, in particular the diagnostic ones, that put in field the innovative tools evaluated in the project, with consequent competitive advantage in the working field, more and more demanding specific sector competences.

  8. Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

    Science.gov (United States)

    Patel, Mayur M; Patel, Bhoomika M

    2017-02-01

    CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.

  9. Recent advances in Entamoeba biology: RNA interference, drug discovery, and gut microbiome

    Science.gov (United States)

    Singh, Upinder

    2016-01-01

    In recent years, substantial progress has been made in understanding the molecular and cell biology of the human parasite Entamoeba histolytica, an important pathogen with significant global impact. This review outlines some recent advances in the Entamoeba field in the last five years, focusing on areas that have not recently been discussed in detail: (i) molecular mechanisms regulating parasite gene expression, (ii) new efforts at drug discovery using high-throughput drug screens, and (iii) the effect of gut microbiota on amoebiasis. PMID:27853522

  10. Effects of Combined Chinese Drugs and Chemotherapy in Treating Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    陈衍智; 李占东; 高非; 张莹; 孙红; 李萍萍

    2009-01-01

    Objective:To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer(NSCLC).Methods:Sixty-three patients with stageⅢB andⅣNSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table,with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin(NP) chemotherapy,but to the treatment group the Chinese drugs...

  11. Recent Advances in Drug Design and Drug Discovery for Androgen- Dependent Diseases.

    Science.gov (United States)

    Cabeza, Marisa; Sánchez-Márquez, Araceli; Garrido, Mariana; Silva, Aylín; Bratoeff, Eugene

    2016-01-01

    This article summarizes the importance of different targets such as 5α-reductase, 17β-HSD, CYP17A, androgen receptor and protein kinase A for the treatment of prostate cancer and benign prostatic hyperplasia. It is a well known fact that dihydrotestosterone (DHT) is associated with the development of androgen-dependent afflictions. At the present time, several research groups are attempting to develop new steroidal and non-steroidal molecules with the purpose of inhibiting the synthesis and biological response of DHT. This review also discusses the most recent studies reported in the literature that describe the therapeutic potential of novel compounds, as well as the new drugs, principally inhibitors of 5α-reductase.

  12. Conceptual study on a new generation of the high-innovative advanced porous and composite nanostructural functional materials with nanofibers

    Directory of Open Access Journals (Sweden)

    L.A. Dobrzański

    2011-12-01

    Full Text Available Purpose: The purpose of the paper is to analyse theoretically the possibilities of the development of a new generation of the high-innovative advanced porous and composite nanostructural functional materials with nanofibers and to study into the material science grounds of synthesis and/or production and formulation of such materials’ structure and properties and to characterise and model their structure and properties depending on the compositional, phase and chemical composition and the applied synthesis and/or production and/or processing processes, without the attitude towards any direct practical application or use, but with confirming the highly probable future application areas, using the unexpected effects of formulating such materials’ functional properties.Design/methodology/approach: In general, the study is of priority cognitive importance as theoretical considerations and the author’s initial analyses related to technology foresight concerning this group of issues as well as sporadical results of research provided in the literature, usually in its incipient phase, indicating a great need to intensify scientific research, to develop the new groups of materials with quite unexpected predictable effects, resulting from the use of nanofibers for fabricating super advanced composite and porous materials.Findings: The description of the state of the art for the subject of the study has been limited to the issues initially selected with an analysis with the method of weighted scores.Practical implications: The outcoming materials may have direct influence on the development of electronics and photonics, medicine and pharmacy, environmental protection, automotive industry, space industry, machine industry, textile and clothing industry, cosmetic industry, agriculture and food sector.Originality/value: The value of this paper lies in the fact that it proposes a new generation of the high-innovative advanced porous and composite

  13. Boceprevir in combination with HIV protease inhibitors in patients with advanced fibrosis-altered drug-drug interactions?

    Directory of Open Access Journals (Sweden)

    C Schwarze-Zander

    2012-11-01

    Full Text Available In HIV/HCV co-infected patients improved treatment outcomes have been reported for the HCV protease inhibitors (PIs boceprevir (BOC and telaprevir (TVR, reaching SVR rates of up to 70% in pilot trials. Due to complex drug-drug-interactions triple therapy is substantially limited in HIV/HCV-coinfected individuals. Co-administration of BOC with the commonly available HIV PIs has been reported not only to decrease the level of BOC but also to lead to relevant decreases in the respective HIV PI. Here, we report on two patients who received BOC-containing HCV triple therapy in combination with a HIV PI. Patient 1 was on darunavir 800 mg/ritonavir 100 mg once-daily mono-therapy. Using FibroScan a liver stiffness of 34 kPa suggested liver cirrhosis prior to start of HCV triple therapy. At week 5 of HCV triple therapy darunavir trough concentration was measured in the reference range with 3777 ng/ml (reference trough concentration 2400–4600 ng/ml. HCV-RNA became negative at week 10 and HIV-RNA was below detection limit (<40 copies/ml at all times. Patient 2 was on a simplified FTC qd and fos-amprenavir 700 mg/ritonavir 100 mg bid regimen. Liver disease had also progressed to liver cirrhosis, confirmed in FibroScan, with a liver stiffness of 32 kPa. At week 8 of HCV triple therapy fos-amprenavir trough level was measured in the normal reference range with 1699 ng/ml (reference trough concentration 750–2500 ng/ml. At week 11 HCV-RNA was <12 IU/ml and HIV viral load was below detection limit of <40 copies/ml at all times. Our clinical data suggest that in patients with advanced liver disease possibly drug levels of HIV PIs which are coadministered with BOC may be within the normal range. In order to better understand the true amount of drug interactions between BOC and commonly used HIV PIs in HIV/HCV-coinfected patients with more advanced liver fibrosis, urgently more PK studies are required to make HCV triple therapy accessible for a wider number of

  14. HOW ADVERSE DRUG-REACTIONS CAN PLAY A ROLE IN INNOVATIVE DRUG RESEARCH - SIMILARITIES IN ADVERSE DRUG REACTION PROFILES OF CAPTOPRIL AND PENICILLAMINE

    NARCIS (Netherlands)

    RIKKEN, F; VOS, R

    1995-01-01

    We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offe

  15. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  16. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Mohammed Kawser Hossain

    2016-02-01

    Full Text Available Diabetes mellitus (DM is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  17. Diffusion of innovations in social interaction systems. An agent-based model for the introduction of new drugs in markets.

    Science.gov (United States)

    Pombo-Romero, Julio; Varela, Luis M; Ricoy, Carlos J

    2013-06-01

    The existence of imitative behavior among consumers is a well-known phenomenon in the field of Economics. This behavior is especially common in markets determined by a high degree of innovation, asymmetric information and/or price-inelastic demand, features that exist in the pharmaceutical market. This paper presents evidence of the existence of imitative behavior among primary care physicians in Galicia (Spain) when choosing treatments for their patients. From this and other evidence, we propose a dynamic model for determining the entry of new drugs into the market. To do this, we introduce the structure of the organization of primary health care centers and the presence of groups of doctors who are specially interrelated, as well as the existence of commercial pressure on doctors. For modeling purposes, physicians are treated as spins connected in an exponentially distributed complex network of the Watts-Strogatz type. The proposed model provides an explanation for the differences observed in the patterns of the introduction of technological innovations in different regions. The main cause of these differences is the different structure of relationships among consumers, where the existence of small groups that show a higher degree of coordination over the average is particularly influential. The evidence presented, together with the proposed model, might be useful for the design of optimal strategies for the introduction of new drugs, as well as for planning policies to manage pharmaceutical expenditure.

  18. Recent advances on the use of cyclodextrins in the chiral analysis of drugs by capillary electrophoresis.

    Science.gov (United States)

    Saz, J M; Marina, M L

    2016-10-07

    The most recent advances on the use of cyclodextrins as chiral selectors in capillary electrophoresis for the enantioseparation of drugs are reviewed in this article. The types of cyclodextrins employed and the resolutions achieved are discussed. The use of dual chiral systems, modified capillaries, non-aqueous media or microfluidic devices is also included and the mechanisms for enantioseparation of drugs and the inversion of the enantiomer migration order are studied. The most relevant applications developed to carry out the quantitation of chiral drugs, to assess the enantiomeric purity of pharmaceutical formulations, to study their metabolism or to achieve criminalistic or forensic investigations are described. Articles published in the last six years (period from 2010 to 2015) are considered.

  19. Recent advances in lymphatic targeted drug deliver y system for tumor metastasis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yu Zhang; Wei-Yue Lu

    2014-01-01

    Te lymphatic system has an important defensive role in the human body. hTe metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors;the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the speciifcity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

  20. Current Advances in Antitubercular Drug Discovery: Potent Prototypes and New Targets.

    Science.gov (United States)

    Dos Santos Fernandes, Guilherme Felipe; Jornada, Daniela Hartmann; de Souza, Paula Carolina; Chin, Chung Man; Pavan, Fernando Rogerio; Dos Santos, Jean Leandro

    2015-01-01

    Tuberculosis (TB) is an infectious disease caused by bacterium of the Mycobacterium genus, mainly by Mycobacterium tuberculosis (MTB). The World Health Organization aims to substantially reduce the number of cases in the coming years; however, the increased number of multidrug-resistant (MDR) and extremely drug-resistant (XDR) forms of the bacterium and the lack of treatment for latent tuberculosis are challenges to be overcome. In this review, we have identified the most potent compounds described in the literature during recent years with MIC values < 7 µM, low toxicity and a high selective index. In addition, emerging targets in MTB are presented to provide new perspectives for the discovery of new antitubercular drugs. This review aims to summarize the current advances in and promote insights into antitubercular drug discovery.

  1. Advancing Innovation Through Collaboration: Implementation of the NASA Space Life Sciences Strategy

    Science.gov (United States)

    Davis, Jeffrey R.; Richard, Elizabeth E.

    2010-01-01

    On October 18, 2010, the NASA Human Health and Performance center (NHHPC) was opened to enable collaboration among government, academic and industry members. Membership rapidly grew to 90 members (http://nhhpc.nasa.gov ) and members began identifying collaborative projects as detailed in this article. In addition, a first workshop in open collaboration and innovation was conducted on January 19, 2011 by the NHHPC resulting in additional challenges and projects for further development. This first workshop was a result of the SLSD successes in running open innovation challenges over the past two years. In 2008, the NASA Johnson Space Center, Space Life Sciences Directorate (SLSD) began pilot projects in open innovation (crowd sourcing) to determine if these new internet-based platforms could indeed find solutions to difficult technical problems. From 2008 to 2010, the SLSD issued 34 challenges, 14 externally and 20 internally. The 14 external challenges were conducted through three different vendors: InnoCentive, Yet2.com and TopCoder. The 20 internal challenges were conducted using the InnoCentive platform, customized to NASA use, and promoted as NASA@Work. The results from the 34 challenges involved not only technical solutions that were reported previously at the 61st IAC, but also the formation of new collaborative relationships. For example, the TopCoder pilot was expanded by the NASA Space Operations Mission Directorate to the NASA Tournament Lab in collaboration with Harvard Business School and TopCoder. Building on these initial successes, the NHHPC workshop in January of 2011, and ongoing NHHPC member discussions, several important collaborations have been developed: (1) Space Act Agreement between NASA and GE for collaborative projects (2) NASA and academia for a Visual Impairment / Intracranial Hypertension summit (February 2011) (3) NASA and the DoD through the Defense Venture Catalyst Initiative (DeVenCI) for a technical needs workshop (June 2011) (4

  2. Innovative experimental particle physics through technological advances: Past, present and future

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, Harry W.K.; /Fermilab

    2005-01-01

    This mini-course gives an introduction to the techniques used in experimental particle physics with an emphasis on the impact of technological advances. The basic detector types and particle accelerator facilities will be briefly covered with examples of their use and with comparisons. The mini-course ends with what can be expected in the near future from current technology advances. The mini-course is intended for graduate students and post-docs and as an introduction to experimental techniques for theorists.

  3. Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury

    Science.gov (United States)

    Lin, Christine

    2016-01-01

    Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions. The latest platforms coculture PHHs with stromal cells to achieve hepatic stability and enable crosstalk between the various liver cell types towards capturing complex cellular mechanisms in DILI. The recent introduction of induced pluripotent stem cell-derived human hepatocyte-like cells can potentially allow a better understanding of interindividual differences in idiosyncratic DILI. Liver models are also being coupled to other tissue models via microfluidic perfusion to study the intertissue crosstalk upon drug exposure as in a live organism. Here, we review the major advances being made in the engineering of liver models and readouts as they pertain to DILI investigations. We anticipate that engineered human liver models will reduce drug attrition, animal usage, and cases of DILI in humans. PMID:27725933

  4. Music Therapy Advances in Neuro-disability - Innovations in Research and Practice

    DEFF Research Database (Denmark)

    O'Kelly, Julian; Magee, Wendy L.; Street, Alex;

    2014-01-01

    therapy, music neuroscience and music psychology addressing the needs of those with acquired and degenerative neurological conditions. The diverse and evolving work in this field is reflected in the topics covered, including disorders of consciousness, dementia, stroke, and the use of modern neuro......-imaging methods to measure the effects of music therapy at a cortical level. A discussion of the implications of these converging foci highlights the benefits of the cross-disciplinary dialogue that characterised the conference.......This article provides a summary of the oral papers presented during a two day international conference, which took place on 7th & 8th June 2013, at the Royal Hospital for Neuro-disability (RHN) in London. The summary texts detail innovative research projects and clinical developments across music...

  5. Innovative formulations for controlled drug delivery to the lungs and the technical and toxicological challenges to overcome(.).

    Science.gov (United States)

    Aragao-Santiago, Leticia; Bohr, Adam; Delaval, Mathilde; Dalla-Bona, Alexandra C; Gessler, Tobias; Seeger, Werner; Beck-Broichsitter, Moritz

    2016-01-01

    Inhalation of therapeutic aerosols has a long tradition and is, moreover, regarded as a safe and efficient route of drug administration to the respiratory tract. Especially, the targeting opportunities of this approach are beneficial for the treatment of numerous airway diseases. However, the rapid decay of local drug concentration and the resulting short-term duration of action of conventional medications necessitates several daily inhalations, which is clearly in conflict with a patients' convenience and compliance. Recent progress in pharmaceutical engineering has provided promising drug delivery vehicles (e.g., liposomes, nanoparticles and thermo-responsive preparations) allowing for a sustained release of the encapsulated medication at the target site. Nevertheless, aspects such as generating tailored aerosols from these formulations (including stability during aerosolization) and the choice of biocompatible excipients remain considerable challenges, which need to be addressed in order to optimize inhalation therapy. Therefore, toxicology issues raised by these novel drug delivery vehicles with respect to physicochemical and material properties and biocompatibility are described in this review. This brief overview is intended to serve as a foundation to prompt future advancement in the field of controlled drug delivery to the lungs.

  6. An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose.

    Science.gov (United States)

    Caviglioli, Gabriele; Baldassari, Sara; Cirrincione, Paola; Russo, Eleonora; Parodi, Brunella; Gatti, Paolo; Drava, Giuliana

    2013-12-15

    An innovative matrix, produced by thermal treatment on direct compression (DC) tablets containing polycarbophil (POL) and ethylcellulose (EC), identified as matrix forming polymers, and able to control the release of diltiazem hydrochloride, was developed. At pH 7.2, 72 ± 1.2% (w/w) of drug loaded was released in 25 h, mostly at constant rate. This swellable and unerodible matrix controls drug release by an anomalous transport mechanism. The modifications induced by the thermal treatment are irreversible and can be used to control and characterize the matrix. A 3-component constrained mixture design allowed the investigation of the experimental domain in which the matrix forms and the computation of a mathematical model that can be used to optimize the formulation properties. The release rate can be modulated (0.032-0.064% drug released/min) through the choice of suitable treatment conditions and tablet composition. The maximum amount of diltiazem hydrochloride released by zero-order kinetics, at the lowest release rate, occurs for POL:EC ratio in the range of 1:1-2:3 with 20-30% of diluent. The tablets are able to load up to 50% (w/w) of diltiazem hydrochloride without losing their properties. A stability study performed on a selected formulation containing DTZ showed stability for at least 2.7 years at RT conditions.

  7. Potential for Layered Double Hydroxides-Based, Innovative Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Kai Zhang

    2014-04-01

    Full Text Available Layered Double Hydroxides (LDHs-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications.

  8. Potential for layered double hydroxides-based, innovative drug delivery systems.

    Science.gov (United States)

    Zhang, Kai; Xu, Zhi Ping; Lu, Ji; Tang, Zhi Yong; Zhao, Hui Jun; Good, David A; Wei, Ming Qian

    2014-01-01

    Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications.

  9. From innovative polymers to advanced nanomedicine: key challenges, recent progress and future perspectives: the second Symposium on Innovative Polymers for Controlled Delivery Suzhou, China, 11–14 September 2012 .

    Science.gov (United States)

    Feijen, Jan; Hennink, Wim E; Zhong, Zhiyuan

    2013-02-01

    Recent developments in polymer-based controlled delivery systems have made a significant clinical impact. The second Symposium on Innovative Polymers for Controlled Delivery (SIPCD) was held in Suzhou, China to address the key challenges and provide up-to-date progress and future perspectives in the innovation of polymer-based therapeutics. At SIPCD, a stimulating panel discussion was introduced for the first time on "What is the future of nanomedicine?" This report highlights the most recent research and developments in biomedical polymers and nanomedicine made by 29 invited scientists from around the world, as well as important issues regarding clinical advancements of nanomedicine conferred during the panel discussion.

  10. Advanced Artificial Science. The development of an artificial science and engineering research infrastructure to facilitate innovative computational modeling, analysis, and application to interdisciplinary areas of scientific investigation.

    Energy Technology Data Exchange (ETDEWEB)

    Saffer, Shelley (Sam) I.

    2014-12-01

    This is a final report of the DOE award DE-SC0001132, Advanced Artificial Science. The development of an artificial science and engineering research infrastructure to facilitate innovative computational modeling, analysis, and application to interdisciplinary areas of scientific investigation. This document describes the achievements of the goals, and resulting research made possible by this award.

  11. Transdermal Drug Delivery Mediated by Microneedle Arrays: Innovations and Barriers to Success.

    Science.gov (United States)

    Caffarel-Salvador, Ester; Donnelly, Ryan F

    2016-01-01

    Microneedles (MN) offer a simple, minimally invasive and reduced pain alternative to hypodermic needles for drug delivery, including vaccines. Previous studies investigating the use of MN have highlighted the benefit of this technology to facilitate dermal and transdermal drug delivery. Going forward towards commercialization, it is important to consider the perceptions and acceptability that MN technology will have once available in the market. This review collects the opinions and expectations of different population groups such as children, parents, paediatricians and the general public on various MN systems. In addition, the low pain perception scores, based on a visual analog scale for MN application, should also lead to a greater acceptability of this technology as a means of transdermal drug delivery. This review also highlights the potential challenges associated with the different types of MN together with issues of sterility and biocompatibility which will be important future factors to consider.

  12. Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends.

    Science.gov (United States)

    Zhan, Peng; Pannecouque, Christophe; De Clercq, Erik; Liu, Xinyong

    2016-04-14

    The early effectiveness of combinatorial antiretroviral therapy (cART) in the treatment of HIV infection has been compromised to some extent by rapid development of multidrug-resistant HIV strains, poor bioavailability, and cumulative toxicities, and so there is a need for alternative strategies of antiretroviral drug discovery and additional therapeutic agents with novel action modes or targets. From this perspective, we first review current strategies of antiretroviral drug discovery and optimization, with the aid of selected examples from the recent literature. We highlight the development of phosphate ester-based prodrugs as a means to improve the aqueous solubility of HIV inhibitors, and the introduction of the substrate envelope hypothesis as a new approach for overcoming HIV drug resistance. Finally, we discuss future directions for research, including opportunities for exploitation of novel antiretroviral targets, and the strategy of activation of latent HIV reservoirs as a means to eradicate the virus.

  13. Evaluation of intrathecal drug delivery system for intractable pain in advanced malignancies

    Science.gov (United States)

    Zheng, Shuyue; He, Liangliang; Yang, Xiaohui; Li, Xiuhua; Yang, Zhanmin

    2017-01-01

    Abstract Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients. A prospective cohort study was performed between July 2015 and October 2016. Fifty-three patients undergoing intractable cancer-related pain or intolerable drug-related adverse effects were recruited and received IDDS therapy with a patient-controlled intrathecal analgesia pump. The assessment was conducted during admission, in titration period, and followed up monthly to death by scheduled refill visits. Pain numeric rating scale scores, comprehensive toxicity scores, quality of life scores, systemic opioid use (basal and breakthrough dose), intrathecal morphine use (basal and patient-controlled intrathecal analgesia dose), and complications were recorded to evaluate the curative effect and safety. Between baseline and all subsequent follow-ups, statistically significant decreases in pain numeric rating scale scores and comprehensive toxicity scores were verified. A statistical improvement in quality of life scores was found after starting IDDS therapy. Both basal and breakthrough doses of systemic opioid showed a significant decrease during the follow-up period. And there was a modest escalation in the intrathecal morphine dose throughout the duration of study. No infective, device-related, and catheter-related complications were observed. The findings showed that IDDS therapy allowed for rapid and highly effective pain relief with less toxicity in comparison to conservative medications. Patients with

  14. Complex Spine Pathology Simulator: An Innovative Tool for Advanced Spine Surgery Training.

    Science.gov (United States)

    Gragnaniello, Cristian; Abou-Hamden, Amal; Mortini, Pietro; Colombo, Elena V; Bailo, Michele; Seex, Kevin A; Litvack, Zachary; Caputy, Anthony J; Gagliardi, Filippo

    2016-11-01

    Background Technical advancements in spine surgery have made possible the treatment of increasingly complex pathologies with less morbidity. Time constraints in surgeons' training have made it necessary to develop new training models for spine pathology. Objective To describe the application of a novel compound, Stratathane resin ST-504 derived polymer (SRSDP), that can be injected at different spinal target locations to mimic spinal epidural, subdural extra-axial, and intra-axial pathologies for the use in advanced surgical training. Material and Methods Fresh-frozen thoracolumbar and cervical spine segments of human and sheep cadavers were used to study the model. SRSDP is initially liquid after mixing, allowing it to be injected into target areas where it expands and solidifies, mimicking the entire spectrum of spinal pathologies. Results Different polymer concentrations have been codified to vary adhesiveness, texture, spread capability, deformability, and radiologic visibility. Polymer injection was performed under fluoroscopic guidance through pathology-specific injection sites that avoided compromising the surgical approach for subsequent excision of the artificial lesion. Inflation of a balloon catheter of the desired size was used to displace stiff cadaveric neurovascular structures to mimic pathology-related mass effect. Conclusion The traditional cadaveric training models principally only allow surgeons to practice the surgical approach. The complex spine pathology simulator is a novel educational tool that in a user-friendly, low-cost fashion allows trainees to practice advanced technical skills in the removal of complex spine pathology, potentially shortening some of the aspects of the learning curve of operative skills that may otherwise take many years to acquire.

  15. The Trial of Drug Discovery using the In-Silico Screening Methods Developed by Pharmaceutical Innovation Value Chain

    Science.gov (United States)

    Inoue, Tsuyoshi; Matsumura, Hiroyoshi; Adachi, Hiroaki; Mori, Yusuke; Takano, Kazufumi; Murakami, Satoshi; Fukunishi, Yoshifumi; Nakamura, Haruki; Kinoshita, Takayoshi; Nakanishi, Isao; Okuno, Yasushi; Minakata, Satoshi; Mikami, Yoshiaki; Sakuma, Toshihiro; Kitajima, Masato; Fukuoka, Yoshitada; Takada, Toshikazu; Sakata, Tsuneaki

    We have recently established Pharmaceutical Innovation Value Chain collaborated by The SOSHO project (http://www.so-sho.jp) and The BioGrid Project (http://www.biogrid.jp/) to accelerate new drug development. The in-silico group calculated the matrices on the interaction between the proteins and chemical compounds, and developed the novel in-silico screening methods, Multiple Target Screening (MTS) and Docking score index (DSI), improving the hit rate of screening a lead compound. We have applied these methods for the two target enzymes; human hematopoietic prostaglandin D synthase (H-PGDS) and orotidine 5’-monophosphate decarboxylase from human malaria parasite plasmodium falciparum (PfOMPDC). The optimizing of HQL-79, one of the known inhibitors for human H-PGDS and the screening of lead compounds for both enzymes are in study.

  16. The potential of protein-nanomaterial interaction for advanced drug delivery

    DEFF Research Database (Denmark)

    Peng, Qiang; Mu, Huiling

    2016-01-01

    Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itse...... of such interaction for advanced drug delivery are presented.......Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself...

  17. Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways.

    Science.gov (United States)

    An, Songzhu Michael; Ding, Qiang; Zhang, Jie; Xie, JingYi; Li, LingSong

    2014-06-01

    Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions. In stem cells, a small number of pathways, notably those of TGF-β/BMP, Hedgehog, Notch, and Wnt, are responsible for the regulation of pluripotency and differentiation. During embryonic development, these pathways govern cell fate specifications as well as the formation of tissues and organs. In adulthood, their normal functions are important for tissue homeostasis and regeneration, whereas aberrations result in diseases, such as cancer and degenerative disorders. In complex biological systems, stem cell signaling pathways work in concert as a network and exhibit crosstalk, such as the negative crosstalk between Wnt and Notch. Over the past decade, genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways. Indeed, discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry. Remarkable progress has been made and several promising drug candidates have entered into clinical trials. This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.

  18. AN UPDATED REVIEW ON TECHNICAL ADVANCES TO ENHANCE DISSOLUTION RATE OF HYDROPHOBIC DRUGS

    Directory of Open Access Journals (Sweden)

    Anjan K. Mahapatra

    2012-10-01

    Full Text Available The dissolution behavior of drugs continues to be one of the challenging aspects in formulation development. The advent of combinatorial chemistry and high throughput screening increased the number of hydrophobic compounds significantly. The Biopharmaceutical classification scheme (BCS takes into account three major factors: solubility, intestinal permeability, and dissolution rate and all the three govern the rate and extent of oral absorption and hence bioavailability. Especially for BCS Class II substances the bioavailability of a poorly soluble drug may be enhanced by increasing the solubility and dissolution rate of it in the gastro-intestinal fluids. Drug substances whose highest dose is soluble in less than 250 ml of water over a range of pH from 1.0 to 7.5 are considered as highly soluble. In contrast, the drug compounds with solubility below 1mg mL-1 face significant dissolution or bioavailability problems. With the introduction of advanced technologies it could be possible to overcome the problems. The article provides an overview on the theoretical definitions and technical approaches broadly covering technologies and hydrophilic carriers or excipients used. Further part of the manuscript is committed to the formulation, analytical methods for the characterization of samples, dissolution or release kinetics and model fittings.

  19. Fixing the system, not the women: an innovative approach to faculty advancement.

    Science.gov (United States)

    Morrissey, Claudia S; Schmidt, Mary Lou

    2008-10-01

    Women in academic medicine are approaching parity without power. Although the number of women choosing careers in medicine has grown substantially over the last 35 years, there has not been a commensurate increase in the percentage of women in senior leadership positions. To redress this situation at the University of Illinois College of Medicine (UICM), the Faculty Academic Advancement Committee (FAAC) was established in January 2003. FAAC's long-term goals are to create an institution whose faculty, department leaders, and deans reflect the gender and ethnic profile of the college's student body and to enable excellence in research, teaching, and patient care while promoting work/life balance. Commissioned as a Dean's Committee, FAAC brings together a diverse group of faculty and academic professionals from inside and outside the college to learn, reflect, and act. FAAC has committed to increasing the percentage of tenured women faculty and advancing women into leadership positions by carrying out an ambitious evidence-based institutional transformation effort. FAAC's initiatives-data gathering, constituency building, department transformation, policy reform, and advocacy-have helped to create an enabling environment for change at UICM. This case study outlines the history, conceptual approach, structure, initiatives, and initial outcomes of FAAC's efforts.

  20. WE-D-BRD-01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

    Energy Technology Data Exchange (ETDEWEB)

    Xing, L [Stanford University, Stanford, CA (United States); Wong, J [Johns Hopkins University, Baltimore, MD (United States); Li, R [Stanford University, Palo Alto, CA (United States)

    2014-06-15

    Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF-beam based IMRT and VMAT, respiration-gated VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted. Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications.

  1. Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

    NARCIS (Netherlands)

    Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

    2011-01-01

    The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

  2. A Perspective on Implementing a Quantitative Systems Pharmacology Platform for Drug Discovery and the Advancement of Personalized Medicine

    Science.gov (United States)

    Stern, Andrew M.; Schurdak, Mark E.; Bahar, Ivet; Berg, Jeremy M.; Taylor, D. Lansing

    2016-01-01

    Drug candidates exhibiting well-defined pharmacokinetic and pharmacodynamic profiles that are otherwise safe often fail to demonstrate proof-of-concept in phase II and III trials. Innovation in drug discovery and development has been identified as a critical need for improving the efficiency of drug discovery, especially through collaborations between academia, government agencies, and industry. To address the innovation challenge, we describe a comprehensive, unbiased, integrated, and iterative quantitative systems pharmacology (QSP)–driven drug discovery and development strategy and platform that we have implemented at the University of Pittsburgh Drug Discovery Institute. Intrinsic to QSP is its integrated use of multiscale experimental and computational methods to identify mechanisms of disease progression and to test predicted therapeutic strategies likely to achieve clinical validation for appropriate subpopulations of patients. The QSP platform can address biological heterogeneity and anticipate the evolution of resistance mechanisms, which are major challenges for drug development. The implementation of this platform is dedicated to gaining an understanding of mechanism(s) of disease progression to enable the identification of novel therapeutic strategies as well as repurposing drugs. The QSP platform will help promote the paradigm shift from reactive population-based medicine to proactive personalized medicine by focusing on the patient as the starting and the end point. PMID:26962875

  3. Innovative grinding wheel design for cost-effective machining of advanced ceramics. Phase I, final report

    Energy Technology Data Exchange (ETDEWEB)

    Licht, R.H.; Ramanath, S.; Simpson, M.; Lilley, E.

    1996-02-01

    Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics. This program was a cooperative effort involving three Norton groups representing a superabrasive grinding wheel manufacturer, a diamond film manufacturing division and a ceramic research center. The program was divided into two technical tasks, Task 1, Analysis of Required Grinding Wheel Characteristics, and Task 2, Design and Prototype Development. In Task 1 we performed a parallel path approach with Superabrasive metal-bond development and the higher technical risk, CVD diamond wheel development. For the Superabrasive approach, Task 1 included bond wear and strength tests to engineer bond-wear characteristics. This task culminated in a small-wheel screening test plunge grinding sialon disks. In Task 2, an improved Superabrasive metal-bond specification for low-cost machining of ceramics in external cylindrical grinding mode was identified. The experimental wheel successfully ground three types of advanced ceramics without the need for wheel dressing. The spindle power consumed by this wheel during test grinding of NC-520 sialon is as much as to 30% lower compared to a standard resin bonded wheel with 100 diamond concentration. The wheel wear with this improved metal bond was an order of magnitude lower than the resin-bonded wheel, which would significantly reduce ceramic grinding costs through fewer wheel changes for retruing and replacements. Evaluation of ceramic specimens from both Tasks 1 and 2 tests for all three ceramic materials did not show evidence of unusual grinding damage. The novel CVD-diamond-wheel approach was incorporated in this program as part of Task 1. The important factors affecting the grinding performance of diamond wheels made by CVD coating preforms were determined.

  4. Sudden death related to advanced coronary atherosclerosis in mini-pigs. Influence of some drugs

    Energy Technology Data Exchange (ETDEWEB)

    Jacobsson, L.; Lundholm, L.; Wingren, G. (Department of Pharmacology, Linkoeping University, Linkoeping, Sweden)

    1984-01-01

    Advanced coronary atherosclerosis was produced in 30 mini-pigs by a combination of a hypercholesterolaemic diet and X-irradiation to the precordial region. Within 11-25 weeks after the irradiation, 13 of the 30 animals died a sudden death probably caused by coronary atherosclerosis. The contents of free and ester-bound cholesterol in the right coronary artery were significantly higher in the animals which died spontaneously than in surviving animals. In an untreated group of 12 animals 7 died whereas in a group treated with ..beta..-pyridylcarbinol only 1 out of 5 died. In the coronary arteries, the contents of both free and ester-bound cholesterol were significantly lower in the ..beta..-pyridylcarbinol-treated animals. In a sulfinpyrazontreated group 3 out of 8, and in a metoprolol-treated group 2 out of 5 animals died. None of these drugs reduced the accumulation of cholesterol in the coronary arteries. The rate of sudden death was 26 +- 6% (P<0.05) lower in the combined group of treated animals than in the untreated ones. By regular ECG recordings, signs which could predict the fatal outcome of the experiment were looked for. Although depressed ST segments were present before death in a few animals, this was not a regular phenomenon. It is concluded that advanced coronary atherosclerosis in mini-pigs often leads to sudden death and that this animal model seems suitable for testing the potential therapeutic effects of drugs.

  5. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Science.gov (United States)

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J.; Fogel, Wieslawa A.; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders. PMID:27891070

  6. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Directory of Open Access Journals (Sweden)

    Dubravka Svob Strac

    2016-11-01

    Full Text Available A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions and comorbid psychiatric disorders commonly seen in people with epilepsy. However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine and melatonin in epilepsy. Recent experimental, clinical and genetic evidence, will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of one-molecule-one-target, have turned out to be effective only in a percentage of people with epilepsy. Although no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins present on both neurons and glia cells may represent a new approach in the management of seizures and their generation as well as comorbid neuropsychiatric disorders.

  7. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs.

    Science.gov (United States)

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J; Fogel, Wieslawa A; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of "one-molecule-one-target," have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders.

  8. Crossdisciplinary fundamental research--the seed for scientific advance and technological innovation.

    Science.gov (United States)

    Kroto, Harold

    2011-12-28

    As it was earlier in the 1980's, so it is now, fundamental science research is under threat as decisions are made on science funding by people who do not do fundamental research, seem congenitally incapable of understanding what it is and furthermore in the face of countless examples seem blind to how important it has been to the technologies that govern our modern life and will be to the future technologies that we desperately need to develop to survive. In this article some general observations are made on how the fascination for what happens in space and stars was the key trigger that gave birth to Science itself and a particular case is outlined which indicates that this same fascination is still the catalyst of some fundamental breakthroughs today. This article also outlines an archetypal example of the way major breakthroughs are often made by the synergy that comes from cross-disciplinary research in a way which is totally surprising. In this case it started from a curiosity about the quantum mechanical description of molecular dynamics and involved pioneering advances in synthetic organic chemistry which led to the suprising discovery that some exotic carbon molecules were abundant in space and stars. These results initiated an experiment using a new technology that represented a major breakthrough in cluster science. The upshot was totally unpredictable, the birth of a whole new field of Chemistry as well as a paradigm shift in major areas of Nanoscience and Nanotechnology.

  9. Advancing the Frontiers in Nanocatalysis, Biointerfaces, and Renewable Energy Conversion by Innovations of Surface Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Somorjai, G.A.; Frei, H.; Park, J.Y.

    2009-07-23

    The challenge of chemistry in the 21st century is to achieve 100% selectivity of the desired product molecule in multipath reactions ('green chemistry') and develop renewable energy based processes. Surface chemistry and catalysis play key roles in this enterprise. Development of in situ surface techniques such as high-pressure scanning tunneling microscopy, sum frequency generation (SFG) vibrational spectroscopy, time-resolved Fourier transform infrared methods, and ambient pressure X-ray photoelectron spectroscopy enabled the rapid advancement of three fields: nanocatalysts, biointerfaces, and renewable energy conversion chemistry. In materials nanoscience, synthetic methods have been developed to produce monodisperse metal and oxide nanoparticles (NPs) in the 0.8-10 nm range with controlled shape, oxidation states, and composition; these NPs can be used as selective catalysts since chemical selectivity appears to be dependent on all of these experimental parameters. New spectroscopic and microscopic techniques have been developed that operate under reaction conditions and reveal the dynamic change of molecular structure of catalysts and adsorbed molecules as the reactions proceed with changes in reaction intermediates, catalyst composition, and oxidation states. SFG vibrational spectroscopy detects amino acids, peptides, and proteins adsorbed at hydrophobic and hydrophilic interfaces and monitors the change of surface structure and interactions with coadsorbed water. Exothermic reactions and photons generate hot electrons in metal NPs that may be utilized in chemical energy conversion. The photosplitting of water and carbon dioxide, an important research direction in renewable energy conversion, is discussed.

  10. Fabrication and characterization of anisotropic nanofiber scaffolds for advanced drug delivery systems

    Directory of Open Access Journals (Sweden)

    Jalani G

    2014-05-01

    Full Text Available Ghulam Jalani,* Chan Woo Jung,* Jae Sang Lee, Dong Woo Lim Department of Bionano Engineering, College of Engineering Sciences, Hanyang University, Education Research Industry Cluster at Ansan Campus, Ansan, South Korea*These authors contributed equally to this workAbstract: Stimuli-responsive, polymer-based nanostructures with anisotropic compartments are of great interest as advanced materials because they are capable of switching their shape via environmentally-triggered conformational changes, while maintaining discrete compartments. In this study, a new class of stimuli-responsive, anisotropic nanofiber scaffolds with physically and chemically distinct compartments was prepared via electrohydrodynamic cojetting with side-by-side needle geometry. These nanofibers have a thermally responsive, physically-crosslinked compartment, and a chemically-crosslinked compartment at the nanoscale. The thermally responsive compartment is composed of physically crosslinkable poly(N-isopropylacrylamide poly(NIPAM copolymers, and poly(NIPAM-co-stearyl acrylate poly(NIPAM-co-SA, while the thermally-unresponsive compartment is composed of polyethylene glycol dimethacrylates. The two distinct compartments were physically crosslinked by the hydrophobic interaction of the stearyl chains of poly(NIPAM-co-SA or chemically stabilized via ultraviolet irradiation, and were swollen in physiologically relevant buffers due to their hydrophilic polymer networks. Bicompartmental nanofibers with the physically-crosslinked network of the poly(NIPAM-co-SA compartment showed a thermally-triggered shape change due to thermally-induced aggregation of poly(NIPAM-co-SA. Furthermore, when bovine serum albumin and dexamethasone phosphate were separately loaded into each compartment, the bicompartmental nanofibers with anisotropic actuation exhibited decoupled, controlled release profiles of both drugs in response to a temperature. A new class of multicompartmental nanofibers could be

  11. Nanosuspension Technology For Poorly Soluble Drugs: Recent Researches, Advances and Patents.

    Science.gov (United States)

    Agarwal, Vijay; Bajpai, Meenakshi

    2015-01-01

    Nowadays, in pharmaceutical industries, the attention on nanosized materials is growing gradually due to their wide applications in drug delivery systems. Recently, out of different nanosize systems, nanosuspension system has undergone a lot of interest in such a way to rectify the solubility and bioavailability problem due to their technical simplicity and cost-effectiveness property compared to other colloidal systems. Nanosuspension technology has proven that it can be a superior substitute over alternative approaches, which are available for enhancing the bioavailability of different drugs having low solubility. Since today, nanosuspensions have been greatly evolved for a huge number of drugs and also investigated for their potential applications. The various unique features make the nanosuspension to enable their utilization in numerous dosage forms and given through different routes, including parenteral, oral, topical, peroral, ocular and pulmonary routes. A large number of products grounded in nanosuspension technology are present in the market, and some are on the way. In fact, the number of such types of products is much more in comparison of other nanotechnologies based products. Additionally, the different preparation methods used to prepare the nanosuspensions are also well- established and patented. This article reviews the recent research, advances in formulation and their approaches related to nanosuspensions with emphasis given on different patents related to nanosuspension methods.

  12. The strategic relevance of manufacturing technology: An overall quality concept to promote innovation preventing drug shortage.

    Science.gov (United States)

    Panzitta, Michele; Ponti, Mauro; Bruno, Giorgio; Cois, Giancarlo; D'Arpino, Alessandro; Minghetti, Paola; Mendicino, Francesca Romana; Perioli, Luana; Ricci, Maurizio

    2017-01-10

    Manufacturing is the bridge between research and patient: without product, there is no clinical outcome. Shortage has a variety of causes, in this paper we analyse only causes related to manufacturing technology and we use shortage as a paradigm highliting the relevance of Pharmaceutical Technology. Product and process complexity and capacity issues are the main challenge for the Pharmaceutical Industry Supply chain. Manufacturing Technology should be acknowledged as a R&D step and as a very important matter during University degree in Pharmacy and related disciplines, promoting collaboration between Academia and Industry, measured during HTA step and rewarded in terms of price and reimbursement. The above elements are not yet properly recognised, and manufacturing technology is taken in to consideration only when a shortage is in place. In a previous work, Panzitta et al. proposed to perform a full technology assessment at the Health Technological Assessment stage, evaluating three main technical aspects of a medicine: manufacturing process, physicochemical properties, and formulation characteristics. In this paper, we develop the concept of manufacturing appraisal, providing a technical overview of upcoming challenges, a risk based approach and an economic picture of shortage costs. We develop also an overall quality concept, not limited to GMP factors but broaden to all elements leading to a robust supply and promoting technical innovation.

  13. EPOSAR: an innovative service to provide EPOS community with advanced DInSAR products

    Science.gov (United States)

    Manunta, Michele; De Luca, Claudio; Elefante, Stefano; Lanari, Riccardo; Pepe, Antonio; Zinno, Ivana; Casu, Francesco

    2015-04-01

    The quantitative evaluation of ground deformation is traditionally based on in-situ surveying techniques that, through the intensive use of GPS stations, automatic total stations and levelling benchmarks, can measure up to sub-centimetre displacements. In the last decades, the extensive use of satellite remote sensing data, such as Synthetic Aperture Radar (SAR) images, has represented an important breakthrough in the context of non-invasive ground deformation analyses over large areas, thanks to their large spatial coverage and relatively short revisit time, as well as to their medium-high ground resolution. In such a context, the well-known Differential SAR Interferometry (DInSAR) technique allows us to map and measure deformation phenomena due to both natural and man-made causes with centimetre to millimetre accuracy. The Earth Science community has a wide interest in the use of DInSAR displacement maps both for crisis management and risk mitigation activities, and for surveillance, monitoring and analysis of geophysical phenomena. In areas characterized by high level of hazards the availability of routinely generated advanced DInSAR products would allow a fast analysis of their current status, providing a near real time monitoring. Similarly, an on-demand service would allow the customization of the products by selecting the area of interest, the SAR data to be processed, and other processing parameters to be set by the users to edit/correct/improve the final products. In this work we discuss the Satellite Data Thematic Core Service of EPOS and we present the EPOSAR service. In particular, the EPOSAR service, based on the well-known DInSAR approach referred to as Small Baseline Subset (SBAS), accomplishes a shared and synergic Earth Observation (EO) service aimed at designing, implementing and harmonizing efficient satellite data processing chains capable of ingesting the significantly increased data stream expected from the ESA Sentinel-1 satellites. EPOSAR

  14. An Innovative Cell Microincubator for Drug Discovery Based on 3D Silicon Structures

    Directory of Open Access Journals (Sweden)

    Francesca Aredia

    2016-01-01

    Full Text Available We recently employed three-dimensional (3D silicon microstructures (SMSs consisting in arrays of 3 μm-thick silicon walls separated by 50 μm-deep, 5 μm-wide gaps, as microincubators for monitoring the biomechanical properties of tumor cells. They were here applied to investigate the in vitro behavior of HT1080 human fibrosarcoma cells driven to apoptosis by the chemotherapeutic drug Bleomycin. Our results, obtained by fluorescence microscopy, demonstrated that HT1080 cells exhibited a great ability to colonize the narrow gaps. Remarkably, HT1080 cells grown on 3D-SMS, when treated with the DNA damaging agent Bleomycin under conditions leading to apoptosis, tended to shrink, reducing their volume and mimicking the normal behavior of apoptotic cells, and were prone to leave the gaps. Finally, we performed label-free detection of cells adherent to the vertical silicon wall, inside the gap of 3D-SMS, by exploiting optical low coherence reflectometry using infrared, low power radiation. This kind of approach may become a new tool for increasing automation in the drug discovery area. Our results open new perspectives in view of future applications of the 3D-SMS as the core element of a lab-on-a-chip suitable for screening the effect of new molecules potentially able to kill tumor cells.

  15. New advances in models and strategies for developing anti-obesity drugs

    Science.gov (United States)

    Kim, Gilbert W.; Lin, Jieru E.; Blomain, Erik S.; Waldman, Scott A.

    2014-01-01

    Introduction Obesity is a worldwide pandemic. Obesity-related health and economic costs are staggering. Existing strategies to combat obesity through lifestyle improvements and medical intervention have had limited success. Pharmacotherapy, in combination with lifestyle modification, may play a vital role in reversing the disease burden. However, past and current weight-loss medications have had serious safety risks, notably cardiovascular and psychiatric events. Areas covered We review the strategies for designing new anti-obesity drugs by describing those currently in development. We describe their target, mechanism of action, and developmental or regulatory status. We also discuss the problem of weight regain following weight loss, and its relevance to the long-term success of anti-obesity pharmacotherapy. Expert opinion For weight management drugs to achieve the safety and efficacy required to be impactful, current studies are uncovering and characterizing new targets, including new signaling circuits and hormones regulating appetite and metabolism, and re-evaluating the role of pharmacotherapy in weight management. To avoid the safety failures of many past weight-loss drugs, the models and strategies covered in this article incorporate recent advances in knowledge and technology. We discuss the emergence of cGMP signaling as a potentially transformative target in weight management. Modulating cGMP signaling may represent an ideal goal for an anti-obesity pharmacotherapy, reflecting some of the major themes described in the present review: targeting pathways that are newly realized as relevant for weight management; promoting safety by re-purposing drugs that are safe, proven, and approved for clinical use; and having a synergistic effect on multiple, reinforcing pathways. PMID:23621300

  16. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    Marilisa Molinaro

    2015-01-01

    Full Text Available Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV dysfunction, and heart failure (HF. The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure.

  17. Inhibition of bacterial carbonic anhydrases and zinc proteases: from orphan targets to innovative new antibiotic drugs.

    Science.gov (United States)

    Supuran, C T

    2012-01-01

    Zinc-containing enzymes, such as carbonic anhydrases (CAs) and metalloproteases (MPs) play critical functions in bacteria, being involved in various steps of their life cycle, which are important for survival, colonization, acquisition of nutrients for growth and proliferation, facilitation of dissemination, invasion and pathogenicity. The development of resistance to many classes of clinically used antibiotics emphasizes the need of new antibacterial drug targets to be explored. There is a wealth of data regarding bacterial CAs and zinc MPs present in many pathogenic species, such as Neisseria spp., Helycobacter pylori Escherichia coli, Mycobacterium tuberculosis, Brucella spp., Streptococcus pneumoniae, Salmonella enterica, Haemophilus influenzae, Listeria spp, Vibrio spp., Pseudomonas aeruginosa, Legionella pneumophila, Streptomyces spp., Clostridium spp., Enterococcus spp., etc. Some of these enzymes have been cloned, purified and characterized by crystallographic techniques. However, for the moment, few potent and specific inhibitors for bacterial MPs have been reported except for Clostridium histolyticum collagenase, botulinum and tetanus neurotoxin and anthrax lethal factor, which will be reviewed in this article. Bacteria encode α-,β-, and/or γ-CA families, but up to now only the first two classes have been investigated in some detail in different species. The α-CAs from Neisseria spp. and H. pylori as well as the β-class enzymes from E. coli, H. pylori, M. tuberculosis, Brucella spp., S. pneumoniae, S. enterica and H. influenzae have been cloned and characterized. The catalytic/inhibition mechanisms of these CAs are well understood as X-ray crystal structures are available for some of them, but no adducts of these enzymes with inhibitors have been characterized so far. In vitro and in vivo studies with various classes of inhibitors, such as anions, sulfonamides and sulfamates have been reported. Only for Neisseria spp., H. pylori, B. suis and S

  18. Expecting innovation: psychoactive drug primes and the generation of creative solutions.

    Science.gov (United States)

    Hicks, Joshua A; Pedersen, Sarah L; Pederson, Sarah L; Friedman, Ronald S; McCarthy, Denis M

    2011-08-01

    Many individuals expect that alcohol and drug consumption will enhance creativity. The present studies tested whether substance related primes would influence creative performance for individuals who possessed creativity-related substance expectancies. Participants (n = 566) were briefly exposed to stimuli related to psychoactive substances (alcohol, for Study 1, Sample 1, and Study 2; and marijuana, for Study 1, Sample 2) or neutral stimuli. Participants in Study 1 then completed a creative problem-solving task, while participants in Study 2 completed a divergent thinking task or a task unrelated to creative problem solving. The results of Study 1 revealed that exposure to the experimental stimuli enhanced performance on the creative problem-solving task for those who expected the corresponding substance would trigger creative functioning. In a conceptual replication, Study 2 showed that participants exposed to alcohol cues performed better on a divergent thinking task if they expected alcohol to enhance creativity. It is important to note that this same interaction did not influence performance on measures unrelated to creative problem solving, suggesting that the activation of creativity-related expectancies influenced creative performance, specifically. These findings highlight the importance of assessing expectancies when examining pharmacological effects of alcohol and marijuana. Future directions and implications for substance-related interventions are discussed.

  19. Advancing Clouds Lifecycle Representation in Numerical Models Using Innovative Analysis Methods that Bridge ARM Observations and Models Over a Breadth of Scales

    Energy Technology Data Exchange (ETDEWEB)

    Kollias, Pavlos [McGill Univ., Montreal, QC (Canada

    2016-09-06

    This the final report for the DE-SC0007096 - Advancing Clouds Lifecycle Representation in Numerical Models Using Innovative Analysis Methods that Bridge ARM Observations and Models Over a Breadth of Scales - PI: Pavlos Kollias. The final report outline the main findings of the research conducted using the aforementioned award in the area of cloud research from the cloud scale (10-100 m) to the mesoscale (20-50 km).

  20. Advances in small animal mesentery models for in vivo flow cytometry, dynamic microscopy, and drug screening

    Institute of Scientific and Technical Information of China (English)

    Ekaterina I Galanzha; Vladimir P Zharov; Philips Classic

    2007-01-01

    Using animal mesentery with intravital optical microscopy is a well-established experimental model for studying blood and lymph microcirculation in vivo.Recent advances in cell biology and optical techniques provide the basis for extending this model for new applications, which should generate significantly improved experimental data. This review summarizes the achievements in this specific area, including in vivo label-free blood and lymph photothermal flow cytometry,super-sensitive fluorescence image cytometry, light scattering and speckle flow cytometry, microvessel dynamic microscopy, infrared (IR) angiography, and high-speed imaging of individual cells in fast flow. The capabilities of these techniques, using the rat mesentery model, were demonstrated in various studies; e.g., realtime quantitative detection of circulating and migrating individual blood and cancer cells, studies on vascular dynamics with a focus on lymphatics under normal conditions and under different interventions (e.g. lasers,drugs, nicotine), assessment of lymphatic disturbances from experimental lymphedema, monitoring cell traffic between blood and lymph systems, and highspeed imaging of cell transient deformability in flow.In particular, the obtained results demonstrated that individual cell transportation in living organisms depends on cell type (e.g., normal blood or leukemic cells), the cell's functional state (e.g., live, apoptotic, or necrotic),and the functional status of the organism. Possible future applications, including in vivo early diagnosis and prevention of disease, monitoring immune response and apoptosis, chemo- and radio-sensitivity tests, and drug screening, are also discussed.

  1. Recent advances in drug delivery strategies for improved therapeutic efficacy of gemcitabine.

    Science.gov (United States)

    Dubey, Ravindra Dhar; Saneja, Ankit; Gupta, Prasoon K; Gupta, Prem N

    2016-10-10

    Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdC) is an efficacious anticancer agent acting against a wide range of solid tumors, including pancreatic, non-small cell lung, bladder, breast, ovarian, thyroid and multiple myelomas. However, short plasma half-life due to metabolism by cytidine deaminase necessitates administration of high dose, which limits its medical applicability. Further, due to its hydrophilic nature, it cannot traverse cell membranes by passive diffusion and, therefore, enters via nucleoside transporters that may lead to drug resistance. To circumvent these limitations, macromolecular prodrugs and nanocarrier-based formulations of Gemcitabine are gaining wide recognition. The nanoformulations based approaches by virtue of their controlled release and targeted delivery have proved to improve bioavailability, increase therapeutic efficacy and reduce adverse effects of the drug. Furthermore, the combination of Gemcitabine with other anticancer agents as well as siRNAs using nanocarriers has also been investigated in order to enhance its therapeutic potential. This review deals with challenges and recent advances in the delivery of Gemcitabine with particular emphasis on macromolecular prodrugs and nanomedicines.

  2. Recent advances in the pathogenesis and drug actions in periodic paralyses and related channelophaties

    Directory of Open Access Journals (Sweden)

    Domenico eTricarico

    2011-02-01

    Full Text Available The periodic paralysis(PP are rare autosomal-dominant disorders associated to mutations in the skeletal muscle sodium, calcium and potassium channel genes characterized by muscle fiber depolarization with un-excitability, episodes of weakness with variations in serum potassium concentrations. Recent advances in thyrotoxic-PP(TPP and hypokalemic-PP(hypoPP confirm the involvement of the muscle potassium channels in the pathogenesis of the diseases and their role as target of action for drugs of therapeutic interest. The novelty in the gating pore currents theory help to explain the disease symptoms, and open the possibility to more specifically target the disease. It is now known that the fiber depolarization in the hypoPP is due to an unbalance between the novel identified depolarizing gating pore currents(Igp carried by protons or Na+ ions flowing through aberrant alternative pathways of the mutant subunits and repolarizing inwardly rectifying potassium channel(Kir currents which also includes the ATP-sensitive subtype. Abnormal activation of the Igp or deficiency in the Kir channels predispose to fiber depolarization. One pharmacological strategy is based on blocking the Igp without affecting normal channel gating. It remains safe and effective the proposal of targeting the KATP, Kir channels or BK channels by drugs capable to specifically open at nanomolar concentrations the skeletal muscle subtypes with less side effects.

  3. Innovative drugs to treat depression: did animal models fail to be predictive or did clinical trials fail to detect effects?

    Science.gov (United States)

    Belzung, Catherine

    2014-04-01

    Over recent decades, encouraging preclinical evidence using rodent models pointed to innovative pharmacological targets to treat major depressive disorder. However, subsequent clinical trials have failed to show convincing results. Two explanations for these rather disappointing results can be put forward, either animal models of psychiatric disorders have failed to predict the clinical effectiveness of treatments or clinical trials have failed to detect the effects of these new drugs. A careful analysis of the literature reveals that both statements are true. Indeed, in some cases, clinical efficacy has been predicted on the basis of inappropriate animal models, although the contrary is also true, as some clinical trials have not targeted the appropriate dose or clinical population. On the one hand, refinement of animal models requires using species that have better homological validity, designing models that rely on experimental manipulations inducing pathological features, and trying to model subtypes of depression. On the other hand, clinical research should consider carefully the results from preclinical studies, in order to study these compounds at the correct dose, in the appropriate psychiatric nosological entity or symptomatology, in relevant subpopulations of patients characterized by specific biomarkers. To achieve these goals, translational research has to strengthen the dialogue between basic and clinical science.

  4. A case study of lean drug discovery: from project driven research to innovation studios and process factories.

    Science.gov (United States)

    Ullman, Fredrik; Boutellier, Roman

    2008-06-01

    At the operational level, the number of investigational new drugs or candidates for development per dollar spent in research, and the number of patents per year are highly integrated measures of productivity and, thus, difficult to influence at the individual or lab level. Hence, different metrics are needed to assess and thereby improve productivity in research at the individual and group level. This review centers on a case study, including over 70 interviews, in a research department of a global pharmaceutical company as well as over 40 interviews in contract research organizations (CROs) and 5 in small biotechnology firms. For each lab, its value adding process was plotted according to lean six sigma methods and appropriate metrics were defined. We suggest a strong focus on short feedback loops in research as an indicator for efficiency. Our results reveal two categories of activities: creativity-driven ones and process-driven ones, both discussed with respect to the methodology used. The fundamental differences in nature of these activities require different sets of metrics to assess them. On the basis of these metrics, different organizational forms can be derived to achieve a lean research structure: innovation studios and process factories, respectively.

  5. The new drug innovation system of Americawith enlightenment to our country%美国新药创新体系对我国的启示

    Institute of Scientific and Technical Information of China (English)

    李科举; 宋民宪

    2015-01-01

    By literature review method and contrast research method,through the study of the related legal policies of the United States such as drug research and development,drug registration system,the protection of intellectual property rights,commercializa-tion and so on,to provide references for our country for better encourages drug innovation,should be developed such as market fran-chise,special approval system and other incentives,and revising the related legal policies such as Drug Administration Lawto improve new drug innovation ability and new drug registration level.%借助文献研究方法和对比研究方法,通过对美国新药研发及注册、知识产权保护、成果商业化等相关法律政策的研究,为我国更好的鼓励新药创新,制订诸如市场专营权、特殊审批体系等的激励机制,修订完善《药品管理法》等相关法律政策,提高我国新药创新能力和新药注册水平提供参考。

  6. A review on the advance of experimental assay methods and models in drug screening   %药物筛选模型研究进展

    Institute of Scientific and Technical Information of China (English)

    胡娟娟; 杜冠华

    2001-01-01

    The experimental models for drug screening are very important points in drug discovery. Although the drug screening techniques have been developed, such as high throughput screening (HTS), the screening assay methods (models) still limited drug discovery. In present paper, advanced animal models, cell assays and molecular methodology used for drug discovery were reviewed. The characteristics and requires of the assay methods used for drug discovery in HTS were also discussed.

  7. Regional Innovation Clusters

    Data.gov (United States)

    Small Business Administration — The Regional Innovation Clusters serve a diverse group of sectors and geographies. Three of the initial pilot clusters, termed Advanced Defense Technology clusters,...

  8. 基于"先进合同研究组织"的生物医药产业创新模式探讨%Advanced Contract Research Organization-Based Innovated Pattern of Biopharmaceutical Industry

    Institute of Scientific and Technical Information of China (English)

    蔡雨阳; 李际; 任军; 黄阳滨; 芮明杰

    2009-01-01

    目的:探索我国的生物医药产业创新模式.方法:分析我国生物医药产业的核心--新药研发中存在的研发基地建设薄弱、资金不足、成果转化难三大问题,基于"合同研究组织(CRO)"建立产业创新模式.结果:提出由"多并发CRO"的研发模式、风险投资与专利/新药证书对接的融资形式以及新药证书为导向的研发过程管理组成的产业创新模式,并整合为"先进合同研究组织(CRO+)".结论:该模式是一种开放性集成服务体系,有利于缩短生物医药研发周期,降低研发成本与研发风险,促进我国生物医药产业发展.%OBJECTIVE: To explore the innovation pattern of biopharmaceutical industry in China. METHODS: Three major problems encountered by the research and development (R&D) of new drug, the core of Chinese biopharmaceutical in-dustry, including the weak construction of operation base for R&D of new drug, insufficient fund, difficulty in the transfor-mation of achievements were analyzed. An innovation pattern of biopharmaceutical industry was founded based on the "Contract Research Organization(CRO)" . RESULTS: An innovation industry pattern consisting of multiple-concurrent CRO R&D mode, venture capital and patent/ new drug certificate tie-in financing form and new drug certificate oriented R& D process management has been put forward, which was integrated into an "advanced CRO"(CRO+ ) mode. CONCLUSION: The CRO+ mode is an open and integrative service system which can help shorten the R&D cycle, lower the cost and risk of R&D and promote the development of biopharmaceutical industry in China.

  9. The Development of Magnetic Drug Delivery and Disposition

    OpenAIRE

    Marszall, Michal Piotr

    2012-01-01

    Available from: http://www.intechopen.com/books/the-delivery-of-nanoparticles/the-development-of-magnetic-drug-deliveryand-disposition The process of drug delivery and disposition in the modern scientific aspect is very complex. Advances in many fields are converging to make the commercialisation of advanced drug delivery concepts possible. It integrates many disciplines, including biotechnology, medicine and pharmacology. Innovative devices should protect labile active ingredient...

  10. The potential of protein-nanomaterial interaction for advanced drug delivery.

    Science.gov (United States)

    Peng, Qiang; Mu, Huiling

    2016-03-10

    Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself, would be the real substance the organs and cells firstly encounter. Consequently, the behavior of nanomaterials in vivo is uncontrollable and some undesired effects may occur, like rapid clearance from blood stream; risk of capillary blockage; loss of targeting capacity; and potential toxicity. Therefore, protein-nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized by selected protein corona using endogenous proteins would have greater promise for clinical use. In this review, we aim to provide a comprehensive understanding of protein-nanomaterial interaction. Importantly, a discussion about how to use such interaction is launched and some possible applications of such interaction for advanced drug delivery are presented.

  11. Recent advances in understanding and mitigating adipogenic and metabolic effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Julia M Gohlke

    2012-06-01

    Full Text Available Although offering many benefits for several psychiatric disorders, antipsychotic drugs (APDs as a class have a major liability in their tendency to promote adiposity, obesity, and metabolic dysregulation in an already metabolically vulnerable population. The past decade has witnessed substantial research aimed at investigating the mechanisms of these adverse effects and mitigating them. On July 11 and 12, 2011, with support from 2 NIH institutes, leading experts convened to discuss current research findings and to consider future research strategies. Five areas where significant advances are being made emerged from the conference: (1 methodological issues in the study of APD effects; (2 unique characteristics and needs of pediatric patients; (3 genetic components underlying susceptibility to APD-induced metabolic effects; (4 APD effects on weight gain and adiposity in relation to their acute effects on glucose regulation and diabetes risk; and (5 the utility of behavioral, dietary, and pharmacological interventions in mitigating APD-induced metabolic side effects. This paper summarizes the major conclusions and important supporting data from the meeting.

  12. [Advances of CRBN in Immunomodulatory Drugs for Multiple Myeloma-Review].

    Science.gov (United States)

    An, Ran; Hou, Jian

    2016-12-01

    Multiple myeloma is a plasma cell malignant clone proliferation diseases and has been remained incurable. In the resent years, the widespread application of immunomodulatory drugs (IMiD) have made a great progress in the treatment of multiple myeloma, greatly improved the complete remission rate and prolonged the overall survival of MM patients. According to recent researches, CRBN (cereblon) plays an important role in mediating anti-myeloma effects of IMiD, and its expression correlated with the effect of IMiD treatment and the prognosis of multiple myeloma. The discovery of CRBN not only deepened the understanding the molecular pharmacological mechanisms of IMiD, but also provide new insights into the novel therapeutic targets and therapeutic strategies for myeloma. This review focuses on the research advances of effectiveness and related mechanisms of CRBN and IMiD for MM, the concrete problems discussing in this review are discover of CRBN, therapeutic effect of CRBN and IMiD, mechnism of CRBN in IMiD treatment for MM, and so on.

  13. The Innovative Medicines Initiative's New Drugs for Bad Bugs programme: European public-private partnerships for the development of new strategies to tackle antibiotic resistance.

    Science.gov (United States)

    Kostyanev, T; Bonten, M J M; O'Brien, S; Steel, H; Ross, S; François, B; Tacconelli, E; Winterhalter, M; Stavenger, R A; Karlén, A; Harbarth, S; Hackett, J; Jafri, H S; Vuong, C; MacGowan, A; Witschi, A; Angyalosi, G; Elborn, J S; deWinter, R; Goossens, H

    2016-02-01

    Antibiotic resistance (ABR) is a global public health threat. Despite the emergence of highly resistant organisms and the huge medical need for new drugs, the development of antibacterials has slowed to an unacceptable level worldwide. Numerous government and non-government agencies have called for public-private partnerships and innovative funding mechanisms to address this problem. To respond to this public health crisis, the Innovative Medicines Initiative Joint Undertaking programme has invested more than €660 million, with a goal of matched contributions from the European Commission and the European Federation of Pharmaceutical Industries and Associations, in the development of new antibacterial strategies. The New Drugs for Bad Bugs (ND4BB) programme, an Innovative Medicines Initiative, has the ultimate goal to boost the fight against ABR at every level from basic science and drug discovery, through clinical development to new business models and responsible use of antibiotics. Seven projects have been launched within the ND4BB programme to achieve this goal. Four of them will include clinical trials of new anti-infective compounds, as well as epidemiological studies on an unprecedented scale, which will increase our knowledge of ABR and specific pathogens, and improve the designs of the clinical trials with new investigational drugs. The need for rapid concerted action has driven the funding of seven topics, each of which should add significantly to progress in the fight against ABR. ND4BB unites expertise and provides a platform where the commitment and resources required by all parties are streamlined into a joint public-private partnership initiative of unprecedented scale.

  14. Dynamics of rapid innovation

    OpenAIRE

    Fink, T. M. A.; Reeves, M.; Palma, R.; Farr, R. S.

    2016-01-01

    Innovation is to organizations what evolution is to organisms: it is how organisations adapt to changes in the environment and improve. Yet despite steady advances in our understanding of evolution, what drives innovation remains elusive. There is a tension between a managerial school, which seeks a systematic prescription for innovation, and a visionary school, which ascribes innovation to serendipity and the intuition of great minds. We therefore provide a mathematical foundation for innova...

  15. JUST in time health emergency interventions: an innovative approach to training the citizen for emergency situations using virtual reality techniques and advanced IT tools (the Web-CD).

    Science.gov (United States)

    Manganas, A; Tsiknakis, M; Leisch, E; Karefilaki, L; Monsieurs, K; Bossaert, L L; Giorgini, F

    2004-01-01

    This paper reports the results of the first of the two systems developed by JUST, a collaborative project supported by the European Union under the Information Society Technologies (IST) Programme. The most innovative content of the project has been the design and development of a complementary training course for non-professional health emergency operators, which supports the traditional learning phase, and which purports to improve the retention capability of the trainees. This was achieved with the use of advanced information technology techniques, which provide adequate support and can help to overcome the present weaknesses of the existing training mechanisms.

  16. JUST in time health emergency interventions: an innovative approach to training the citizen for emergency situations using virtual reality techniques and advanced IT tools (the VR Tool).

    Science.gov (United States)

    Manganas, A; Tsiknakis, M; Leisch, E; Ponder, M; Molet, T; Herbelin, B; Magnetat-Thalmann, N; Thalmann, D; Fato, M; Schenone, A

    2004-01-01

    This paper reports the results of the second of the two systems developed by JUST, a collaborative project supported by the European Union under the Information Society Technologies (IST) Programme. The most innovative content of the project has been the design and development of a complementary training course for non-professional health emergency operators, which supports the traditional learning phase, and which purports to improve the retention capability of the trainees. This was achieved with the use of advanced information technology techniques, which provide adequate support and can help to overcome the present weaknesses of the existing training mechanisms.

  17. Organizational Innovation and Redesign in the Information Age: The Drug War, Netwar, and Other Lower-End Conflict.

    Science.gov (United States)

    1998-03-01

    connectivity, and make them more innovative. However, what most of these books promise is a magical recipe for creating an innovative and flexible company...1995. 45 Ibid, 16. 46 Clifford Stohl’s The Cuckoo’s Egg (New York: Simon & Schuster, 1989) chronicles the author’s efforts to catch the "Hannover...environment has forced the security structure, notably military and intelligence forces, to scramble at the last minute to deal with constant

  18. Issues In-Depth: Advancing Understanding of Drug Addiction and Treatment

    Science.gov (United States)

    Miller, Roxanne Greitz

    2009-01-01

    While most school districts utilize a drug abuse resistance curriculum, as science teachers, it is our responsibility to understand the science behind drug addiction in order to most effectively educate our students against drug abuse. In the last two decades, increases in scientific technology have permitted significant discoveries surrounding…

  19. An innovative approach to enhance dermatology competencies for advanced practice nurses: service–learning with a migrant farm worker health clinic.

    Science.gov (United States)

    Downes, Elizabeth A; Connor, Ann; Howett, Maeve

    2014-12-01

    The purpose of this article is to describe a novel service–learning opportunity for graduate nursing students that promotes competency in dermatology. A hybrid service–learning course with online didactic content is described, along with tools for evaluation of dermatology competencies. Student evaluation of the course is discussed, and selected research articles are reviewed. Advanced practice nursing and medical education frequently does not adequately prepare primary care providers to be competent in the assessment and management of dermatologic conditions. Embedding dermatology content in a service–learning program can optimize the provision of care, strengthen competencies in dermatology and inter-professional care, and allow students to gain a deeper understanding of the population with which they work. The innovative service–learning program presented is a model for advanced practice nursing education. Tools for evaluating clinical competency and courses often need validation.

  20. Energy systems. Tome 3: advanced cycles, low environmental impact innovative systems; Systeme energetiques, TOME 3: cycles avances, systemes innovants a faible impact environnemental

    Energy Technology Data Exchange (ETDEWEB)

    Gicquel, R

    2009-07-01

    This third tome about energy systems completes the two previous ones by showing up advanced thermodynamical cycles, in particular having a low environmental impact, and by dealing with two other questions linked with the study of systems with a changing regime operation: - the time management of energy, with the use of thermal and pneumatic storage systems and time simulation (schedule for instance) of systems (solar energy type in particular); - the technological dimensioning and non-nominal regime operation studies. Because this last topic is particularly complex, new functionalities have been implemented mainly by using the external classes mechanism, which allows the user to freely personalize his models. This tome is illustrated with about 50 examples of cycles modelled with Thermoptim software. Content: foreword; 1 - generic external classes; 2 - advanced gas turbine cycles; 3 - evaporation-concentration, mechanical steam compression, desalination, hot gas drying; 4 - cryogenic cycles; 5 - electrochemical converters; 6 - global warming, CO{sub 2} capture and sequestration; 7 - future nuclear reactors (coupled to Hirn and Brayton cycles); 8 - thermodynamic solar cycles; 10 - pneumatic and thermal storage; 11 - calculation of thermodynamic solar facilities; 12 - problem of technological dimensioning and non-nominal regime; 13 - exchangers modeling and parameterizing for the dimensioning and the non-nominal regime; 14 - modeling and parameterizing of volumetric compressors; 15 - modeling and parameterizing of turbo-compressors and turbines; 16 - identification methodology of component parameters; 17 - case studies. (J.S.)

  1. Advances in MRSA drug discovery: where are we and where do we need to be?

    Science.gov (United States)

    Kurosu, Michio; Siricilla, Shajila; Mitachi, Katsuhiko

    2013-01-01

    Introduction Methicillin-resistant Staphylococcus aureus (MRSA) have been on the increase during the past decade, due to the steady growth of the elderly and immunocompromised patients, and the emergence of multi-drug-resistant (MDR) bacterial strains. Although, only a limited number of anti-MRSA drugs are available, a number of different combination antimicrobial drug regimens have been used to treat serious MRSA infections. Thus, addition of several new antistaphylococcal drugs into clinical practice should broaden therapeutic options. Because MRSA is one of the most common and problematic bacteria associated with increasing antimicrobial resistance, continuous efforts on discovery of lead compounds as well as development of alternative therapies and faster diagnostics to ensure effective antistaphylococcal therapy are required. Areas covered This article summarizes the FDA approved drugs to treat MRSA infections, the drugs in clinical trials, and the drug leads for MRSA and related Gram-positive bacterial infections. In addition, the mode of action of antistaphylococcal molecules and resistant mechanisms of some molecules are briefly discussed. Expert opinion The number of pipeline drugs presently undergoing clinical trials is not particularly encouraging. There are limited and rather expensive therapeutic options for the infections by MRSA in the critically ill. This review article provides an update on antistaphylococcal drugs in clinical trials and antibacterial molecules effective against Gram-positive bacteria including MRSA. The structural and biological information of antibacterials summarized here are very useful for designing drug leads to develop into new anti-MRSA drugs. PMID:23829425

  2. Social Capital and Entrepreneurial Behaviour Advancing Innovativeness in Interaction between Small Rural Entrepreneurs and Researchers: A Phenomenographic Study

    Science.gov (United States)

    Iivonen, Sari; Kyro, Paula; Mynttinen, Sinikka; Sarkka-Tirkkonen, Marjo; Kahiluoto, Helena

    2011-01-01

    Innovation processes between entrepreneurs and researchers are activated by interaction. Social capital increases the efficiency of action, for example, information dissemination by minimising redundancy. To learn more about how to build and develop social capital assumes that we understand how entrepreneurs behave and what their expectations of…

  3. Advances in material design for regenerative medicine, drug delivery and targeting/imaging

    Science.gov (United States)

    Many of the major breakthroughs and paradigm shifts in medicine to date have occurred due to innovations and materials and/or application/implementation of materials in clinical medicine. Artificial heart valves, implantable cardiac devices, limb prosthesis, cardiovascular stents, orthopedic implan...

  4. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

    Science.gov (United States)

    Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo

    2014-08-01

    Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

  5. Webinar as the innovative marketing tool: its place and a role in system of advancement of educational services

    Directory of Open Access Journals (Sweden)

    Matuhina Tatiana Vasilevna

    2011-04-01

    Full Text Available Marketing of webinar represents research which is carried out by seminar carrying out in a network the Internet, by means of virtual conference. Webinar as the innovative marketing tool allows the buyer to investigate a product or service, and to the supplier to investigate requirements and interests of the consumers by means of decrease in expenses for marketing since the technology of webinar-marketing is much more economic traditional than means of marketing, advertising, polls, seminars and conferences.

  6. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  7. Application of the Price-Volume Approach in Cases of Innovative Drugs Where Value-Based Pricing is Inadequate: Description of Real Experiences in Italy.

    Science.gov (United States)

    Messori, Andrea

    2016-08-01

    Several cases of expensive drugs designed for large patient populations (e.g. sofosbuvir) have raised a complex question in terms of drug pricing. Even assuming value-based pricing, the treatment with these drugs of all eligible patients would have an immense budgetary impact, which is unsustainable also for the richest countries. This raises the need to reduce the prices of these agents in comparison with those suggested by the value-based approach and to devise new pricing methods that can achieve this goal. The present study discusses in detail the following two methods: (i) The approach based on setting nation-wide budget thresholds for individual innovative agents in which a fixed proportion of the historical pharmaceutical expenditure represents the maximum budget attributable to an innovative treatment; (ii) The approach based on nation-wide price-volume agreements in which drug prices are progressively reduced as more patients receive the treatment. The first approach has been developed in the USA by the Institute for Clinical and Economic Review and has been applied to PCSK9 inhibitors (alirocumab and evolocumab). The second approach has been designed for the Italian market and has found a systematic application to manage the price of ranibizumab, sofosbuvir, and PCSK9 inhibitors. While, in the past, price-volume agreements have been applied only on an empirical basis (i.e. in the absence of any quantitative theoretical rule), more recently some explicit mathematical models have been described. The performance of these models is now being evaluated on the basis of the real-world experiences conducted in some European countries, especially Italy.

  8. 抗艾滋病药物靶向递送系统的研究进展%Anti-AIDS drugs targeting drug delivery systems: research advances

    Institute of Scientific and Technical Information of China (English)

    谢向阳; 韩亮; 陈晨; 廖祥茹

    2011-01-01

    The discovery and utilization of anti-AIDS drugs therapy have not only increased lifespan, but also enhanced the quality of life of HIV infected people.However,limitations of currently available drug regimens and dosage forms often fail to effectively reduce the HIV viral load in the viral reservoirs in vivo.To overcome the drawbacks of present anti-AIDS drugs' dosage forms,engineered nanocarriers including polymeric nanoparticles,liposomes,solid lipid nanoparticles and dendrimers are developed to facilitate these drugs targeting to the HIV viral reservoirs. This article reviews recent advances in the field of targeting drug delivery systems fir the treatment of AIDS.%抗艾滋病药物的发现及使用有效地延长了患者的生命,提高了患者的生活质量,但其治疗针对性不强,不能有效清除体内特定部位的HIV病毒.为此,人们采用多种技术手段.制备各种形式的抗艾滋病药物递送载体.如纳米粒、脂质体、树状大分子等,希望针对不同细胞和解剖学的病原体库进行靶向药物递送.本文对近年来有关抗艾滋病药物靶向制剂研究的进展做一综述.

  9. Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases

    Science.gov (United States)

    Fornaguera, C.; Feiner-Gracia, N.; Calderó, G.; García-Celma, M. J.; Solans, C.

    2015-07-01

    Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases.Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from

  10. The weak-ties in advanced business services as a major force of innovation and diffusion; Las Eak-Ties en los servicios avanzados a empresas como factor relevante de la innovacion y su difusion

    Energy Technology Data Exchange (ETDEWEB)

    Almenar i Llongo, V.; Hernandez Sancho, F.; Solar i Marco, V.

    2012-07-01

    This paper tries to expose the role of weak-ties of advanced business services in both mechanisms which generate innovation as well as allow technological diffusion and transfer of innovations (spillovers). Assuming that the latest information generally flows to agents through weak ties, the Weak-Ties Hypothesis (WTH) is an approach that helps to explain the importance of the relations with the environment in the process of innovation and generation of new knowledge and its implementation and dissemination, evaluating the synergy's resulting from cooperation between agents. (Author) 21 refs.

  11. A Typology of Reverse Innovation

    DEFF Research Database (Denmark)

    von Zedtwitz, Max; Corsi, Simone; Søberg, Peder Veng;

    2015-01-01

    Reverse innovation commonly refers to an innovation initially launched in a developing country and later introduced to an advanced country. Adopting a linear innovation model with the four sequential phases of concept ideation, product development, primary target market introduction, and subsequent...... secondary market introduction, this study expands the espoused definition of reverse innovation beyond its market-introduction focus with reversals in the flow of innovation in the ideation and product development phases. Recognizing that each phase can take place in different geographical locations......, the paper then introduces a typology of global innovation with 16 different types of innovation flows between advanced and emerging countries, 10 of which are reverse innovation flows. The latter are further differentiated into weak and strong reverse innovation, depending on the number of innovation phases...

  12. Advances in anti-drug-resistant tuberculosis drugs%抗耐药结核病的药物研究进展

    Institute of Scientific and Technical Information of China (English)

    李奎; 杜娟

    2012-01-01

    The advances in anti-drug-resistant tuberculosis drugs in recent years are reviewed in this article.It focuses on some promising fields of novel anti-tuberculous agents,among which PNU100480,TMC207,SQ-109,OPC-67683 and SQ641-2AUA are more promising candidates.The headway of combined chemotherapy is exciting.However,the associated obstacles increase.It needs further study to develop new drugs which are simple,effective and low toxic.%此文综述了近年抗耐药结核病的药物研究进展,重点讲述了一些新型抗结核药物研发新领域,其中较有开发前景的抗结核候选药物有PNU100480、TMC207、SQ-109、OPC-67683和SQ641-2AUA.尽管目前联合化疗进展令人鼓舞,但是困难也不断出现,仍需要做更多的工作,以便今后开发出简单、有效与毒性低的药物.

  13. An engineering approach to biomedical sciences: advanced strategies in drug delivery systems production.

    Science.gov (United States)

    Barba, Anna Angela; Dalmoro, Annalisa; d'Amore, Matteo

    2012-09-01

    Development and optimization of novel production techniques for drug delivery systems are fundamental steps in the "from the bench to the bedside" process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drug delivery systems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported.

  14. An Engineering Approach to Biomedical Sciences: Advanced Strategies in Drug Delivery Systems Production

    Science.gov (United States)

    Barba, Anna Angela; Dalmoro, Annalisa; d’Amore, Matteo

    2012-01-01

    Development and optimization of novel production techniques for drug delivery systems are fundamental steps in the “from the bench to the bedside” process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drug delivery systems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported. PMID:23905058

  15. [Research advances in gene polymorphisms in biological pathways of drugs for asthma].

    Science.gov (United States)

    Guo, Dan-Dan; Zheng, Xiang-Rong

    2016-06-01

    The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are β2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

  16. Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers

    NARCIS (Netherlands)

    Chen, Wei; Meng, F.; Cheng, R.; Deng, C.; Feijen, J.; Zhong, Z.

    2014-01-01

    Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention

  17. Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Piyush Mehta

    2016-01-01

    Full Text Available Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases.

  18. Providing the Basis for Innovative Improvements in Advanced LWR Reactor Passive Safety Systems Design: An Educational R&D Project

    Energy Technology Data Exchange (ETDEWEB)

    Brian G. Williams; Jim C. P. Liou; Hiral Kadakia; Bill Phoenix; Richard R. Schultz

    2007-02-27

    This project characterizes typical two-phase stratified flow conditions in advanced water reactor horizontal pipe sections, following activation of passive cooling systems. It provides (1) a means to educate nuclear engineering students regarding the importance of two-phase stratified flow in passive cooling systems to the safety of advanced reactor systems and (2) describes the experimental apparatus and process to measure key parameters essential to consider when designing passive emergency core cooling flow paths that may encounter this flow regime. Based on data collected, the state of analysis capabilities can be determined regarding stratified flow in advanced reactor systems and the best paths forward can be identified to ensure that the nuclear industry can properly characterize two-phase stratified flow in passive emergency core cooling systems.

  19. Recent advances in nanoformulations for co-delivery of curcumin and chemotherapeutic drugs

    Directory of Open Access Journals (Sweden)

    Maryam Hashemi

    2017-01-01

    Full Text Available The application of chemotherapy in cancer treatment has been limited due to cause side effects such as toxicity against normal cells and drug resistance. In recent years, numerous studies have been focused on using natural products with chemotherapeutic drugs to enhance therapeutic efficiency and reduce cytotoxicity. On the other hand, encapsulation of drugs into nanoparticles (NPs can improve solubility of hydrophobic drug; circulation time in blood and the residence at the pathological site by enhance permeation and retention (EPR effect. It has been shown that curcumin (CUR has  wide range of pharmacological activities against many diseases such as cancer. CUR has been demonstrated to be a potent chemosensitizer that can induce additive or synergistic effects with chemotherapeutic drugs against different cancer cell lines.  Recently, various types of nanocarriers have been investigated for CUR.  In this review, different co-formulations containing Cur and chemotherapeutic drugs used in cancer therapy are discussed with emphasis on their pharmaceutical properties.

  20. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues

    Directory of Open Access Journals (Sweden)

    MunJu eKim

    2013-11-01

    Full Text Available Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  1. Successful analysis of anticancer drug sensitivity by CD-DST using pleural fluid and ascites from patients with advanced ovarian cancer: case reports.

    Science.gov (United States)

    Kawaguchi, Makiko; Banno, Kouji; Susumu, Nobuyuki; Yanokura, Megumi; Kuwabara, Yoshiko; Hirao, Nobumaru; Tsukazaki, Katsumi; Nozawa, Shiro

    2005-01-01

    In vitro anticancer drug sensitivity tests have been performed for various types of cancers, and a relationship with clinical response has been observed. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is a new in vitro anticancer drug sensitivity test by Yabushita et al., recently reported to be useful in ovarian cancer. CD-DST allows analysis of a small number of cells, compared to other anticancer drug sensitivity tests. Here, we report a successful analysis of anticancer drug sensitivity by CD-DST using cancerous ascites and pleural fluid samples from 2 patients with advanced ovarian cancer. To our knowledge, this is only the second report of the application of CD-DST in ovarian cancer, and our results suggest that CD-DST could be helpful in the selection of anticancer drugs for neoadjuvant chemotherapy in advanced ovarian cancer.

  2. "Is there nothing more practical than a good theory?": Why innovations and advances in health behavior change will arise if interventions are used to test and refine theory

    Directory of Open Access Journals (Sweden)

    Rothman Alexander J

    2004-07-01

    Full Text Available Abstract Theoretical and practical innovations are needed if we are to advance efforts to persuade and enable people to make healthy changes in their behavior. In this paper, I propose that progress in our understanding of and ability to promote health behavior change depends upon greater interdependence in the research activities undertaken by basic and applied behavioral scientists. In particular, both theorists and interventionists need to treat a theory as a dynamic entity whose form and value rests upon it being rigorously applied, tested and refined in both the laboratory and the field. To this end, greater advantage needs to be taken of the opportunities that interventions afford for theory-testing and, moreover, the data generated by these activities need to stimulate and inform efforts to revise, refine, or reject theoretical principles.

  3. 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems.

    Science.gov (United States)

    Goyanes, Alvaro; Det-Amornrat, Usanee; Wang, Jie; Basit, Abdul W; Gaisford, Simon

    2016-07-28

    Acne is a multifactorial inflammatory skin disease with high prevalence. In this work, the potential of 3D printing to produce flexible personalised-shape anti-acne drug (salicylic acid) loaded devices was demonstrated by two different 3D printing (3DP) technologies: Fused Deposition Modelling (FDM) and stereolithography (SLA). 3D scanning technology was used to obtain a 3D model of a nose adapted to the morphology of an individual. In FDM 3DP, commercially produced Flex EcoPLA™ (FPLA) and polycaprolactone (PCL) filaments were loaded with salicylic acid by hot melt extrusion (HME) (theoretical drug loading - 2% w/w) and used as feedstock material for 3D printing. Drug loading in the FPLA-salicylic acid and PCL-salicylic acid 3D printed patches was 0.4% w/w and 1.2% w/w respectively, indicating significant thermal degradation of drug during HME and 3D printing. Diffusion testing in Franz cells using a synthetic membrane revealed that the drug loaded printed samples released printed as a nose-shape mask by FDM 3DP, but the PCL-salicylic acid filament was not. In the SLA printing process, the drug was dissolved in different mixtures of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) (PEG) that were solidified by the action of a laser beam. SLA printing led to 3D printed devices (nose-shape) with higher resolution and higher drug loading (1.9% w/w) than FDM, with no drug degradation. The results of drug diffusion tests revealed that drug diffusion was faster than with the FDM devices, 229 and 291μg/cm(2) within 3h for the two formulations evaluated. In this study, SLA printing was the more appropriate 3D printing technology to manufacture anti-acne devices with salicylic acid. The combination of 3D scanning and 3D printing has the potential to offer solutions to produce personalised drug loaded devices, adapted in shape and size to individual patients.

  4. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

    Directory of Open Access Journals (Sweden)

    Ali Khan A

    2013-07-01

    Full Text Available Arshad Ali Khan, Jahanzeb Mudassir, Noratiqah Mohtar, Yusrida Darwis School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia Abstract: The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects

  5. Current advances in Phi29 pRNA biology and its application in drug delivery.

    Science.gov (United States)

    Ye, Xin; Hemida, Maged; Zhang, Huifang M; Hanson, Paul; Ye, Qiu; Yang, Decheng

    2012-01-01

    Bacteriophage 29 (Phi29) packaging RNA (pRNA) is one of the key components in the viral DNA-packaging motor. It contains two functional domains facilitating the translocation of DNA into the viral capsid by interacting with other elements in the motor and promoting adenosine triphosphates hydrolysis. Through the connection between interlocking loops in adjacent pRNA monomers, pRNA functions in the form of multimer ring in the motor. Previous studies have addressed the unique structure and conformation of pRNA. However, there are different DNA-packaging models proposed for the viral genome transportation mechanism. The DNA-packaging ability and the unique features of pRNA have been attracting efforts to study its potential applications in nanotechnology. The pRNA has been proved to be a promising tool for delivering nucleic acid-based therapeutic molecules by covalent linkage with ribozymes, small interfering RNAs, aptamers, and artificial microRNAs. The flexibility in constructing dimers, trimers, and hexamers enables the assembly of polyvalent nanoparticles to carry drug molecules for therapeutic purposes, cell ligands for target delivery, image detector for drug entry monitoring, and endosome disrupter for drug release. Besides these fascinating pharmacological advantages, pRNA-based drug delivery has also been demonstrated to prolong the drug half life with minimal induction of immune response and toxicity.

  6. Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

    Science.gov (United States)

    Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

    2016-05-01

    Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma.

  7. Recent advances in the preparation progress of protein/peptide drug loaded PLA/PLGA microspheres.

    Science.gov (United States)

    Xu, Feng-Hua; Zhang, Qiang

    2007-01-01

    Sustained release drug delivery from microparticles is an excellent alternative for daily protein/peptide drug administration protocol. Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are the most commonly used polymer carriers in the development of protein/peptide microspheres. Basically there are three preparation methods for PLA/PLGA microspheres: the solvent extraction/evaporation based multiple emulsion (W/O/W emulsion) method, the phase separation method and the spray drying method. The stability of the protein/pipetide loaded, encapsulation efficiency, and the burst effect of the microspheres are key problems usually met in the preparation of microspheres. In this review the preparation techniques and progress in the development of protein/pipetide microspheres which aimed to stabilize protein/peptide structural integrity, keep the bioactivity of drugs, increase the encapsulation efficiency and improve the release profile were summarized and evaluated.

  8. From silk spinning in insects and spiders to advanced silk fibroin drug delivery systems.

    Science.gov (United States)

    Werner, Vera; Meinel, Lorenz

    2015-11-01

    The natural process of silk spinning covers a fascinating versatility of aggregate states, ranging from colloidal solutions through hydrogels to solid systems. The transition among these states is controlled by a carefully orchestrated process in vivo. Major players within the natural process include the control of spatial pH throughout passage of the silk dope, the composition and type of ions, and fluid flow mechanics within the duct, respectively. The function of these input parameters on the spinning process is reviewed before detailing their impact on the design and manufacture of silk based drug delivery systems (DDS). Examples are reported including the control of hydrogel formation during storage or significant parameters controlling precipitation in the presence of appropriate salts, respectively. The review details the use of silk fibroin (SF) to develop liquid, semiliquid or solid DDS with a focus on the control of SF crystallization, particle formation, and drug-SF interaction for tailored drug load.

  9. Novel opportunities for computational biology and sociology in drug discovery.

    Science.gov (United States)

    Yao, Lixia; Evans, James A; Rzhetsky, Andrey

    2010-04-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development,explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery.These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use.Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies.

  10. Innovation networks

    CERN Document Server

    Ahrweiler, Petra

    2013-01-01

    This paper advances a framework for modeling the component interactions between cognitive and social aspects of scientific creativity and technological innovation. Specifically, it aims to characterize Innovation Networks; those networks that involve the interplay of people, ideas and organizations to create new, technologically feasible, commercially-realizable products, processes and organizational structures. The tri-partite framework captures networks of ideas (Concept Level), people (Individual Level) and social structures (Social-Organizational Level) and the interactions between these levels. At the concept level, new ideas are the nodes that are created and linked, kept open for further investigation or closed if solved by actors at the individual or organizational levels. At the individual level, the nodes are actors linked by shared worldviews (based on shared professional, educational, experiential backgrounds) who are the builders of the concept level. At the social-organizational level, the nodes...

  11. Overview of a test facility designed to guide innovations in the development of advanced thermal insulation materials and systems

    Science.gov (United States)

    Zweig, Jessica L.; Boroski, William N.; Hart, Frank R.

    To aid in the development of advanced thermal insulating materials and systems, Lydall, Inc. Manning Nonwovens Division has acquired acalorimeter. The calorimeter is specially-designed to measure the thermal conductivity of high-efficiency insulating materials and multilayer insulation systems under various operating conditions. A description of the apparatus is included. The calorimeter has the capabilities of measuring thermal conductivity in the temperature range of 10K to 300K and under insulating vacuum levels ranging from 10 -2 torr (1.33 Pa) through 10 -8 torr (1.33×10 -6 Pa). The calorimeter has been calibrated over its operating range and measurements have been made on several insulation systems to quantify thermal performance. Details of the calibration process will be presented. Preliminary measurements results demonstrate that the capabilities of this system will enhance the development of advanced thermal insulation materials and systems.

  12. But does it do any good? Measuring the impact of music therapy on people with advanced dementia: (Innovative practice).

    Science.gov (United States)

    Gold, Karen

    2014-03-01

    This article describes the impact of music therapy upon a group of nine people with advanced dementia in a hospital setting. It demonstrates how the impact of music therapy was measured using the case notes completed by nursing and care staff and how these notes suggested that music therapy had a positive effect on the mood and behaviour on eight of the nine people receiving music therapy.

  13. Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Andersen, Jacob; Kristensen, Anders Skov; Bang-Andersen, Benny;

    2009-01-01

    and amphetamine. Seminal advances in the understanding of the structure and function of this transporter family have recently been accomplished by structural studies of a bacterial transporter, as well as medicinal chemistry and pharmacological studies of mammalian transporters. This feature article focuses...

  14. Recent advances using zebrafish animal models for muscle disease drug discovery

    Science.gov (United States)

    Maves, Lisa

    2015-01-01

    Introduction Animal models have enabled great progress in the discovery and understanding of pharmacological approaches for treating muscle diseases like Duchenne muscular dystrophy. Areas covered With this article, the author provides the reader with a description of the zebrafish animal model, which has been employed to identify and study pharmacological approaches to muscle disease. In particular, the author focuses on how both large-scale chemical screens and targeted drug treatment studies have established zebrafish as an important model for muscle disease drug discovery. Expert opinion There are a number of opportunities arising for the use of zebrafish models for further developing pharmacological approaches to muscle diseases, including studying drug combination therapies and utilizing genome editing to engineer zebrafish muscle disease models. It is the author’s particular belief that the availability of a wide range of zebrafish transgenic strains for labeling immune cell types, combined with live imaging and drug treatment of muscle disease models, should allow for new elegant studies demonstrating how pharmacological approaches might influence inflammation and the immune response in muscle disease. PMID:24931439

  15. [Impact of rapid advancement of international standardization on technical requirements for new drug registration].

    Science.gov (United States)

    Kurokawa, T

    1996-04-01

    Internationalization of new drug research and development is rapidly progressing. When mutual international acceptance of clinical trial data is realized, scientifically superior data will eradicate and replace all not so scientific data. This means that healthy competition would benefit the data of clinical trials. The same is true of anti-tumor drugs. Some Japan originated antitumor drugs were developed in foreign countries prior to domestic clinical development. In future, geographic centralization of clinical trials in areas which can conduct scientifically more consistent trials is expected. There are only a limited number of institutes which can conduct high-quality clinical trials of antitumor drugs, so they want Japan, a potential country, to come to other areas to produce high-quality clinical trial data. The resolution of a number of daily stumbling blocks such as informing the patient that he or she is suffering from cancer is a prerequisite for conducting high-quality clinical trials. But every effort must be made so that it will not be said: "Data produced overseas are better. There is no need for Japan to use its knowledge and effort in the field of clinical development."

  16. Recent advances in carbon nanotubes as delivery systems for anticancer drugs.

    Science.gov (United States)

    Iannazzo, Daniela; Piperno, Anna; Pistone, Alessandro; Grassi, Giovanni; Galvagno, Signorino

    2013-01-01

    Problems associated with the administration of anticancer drugs, such as limited solubility, poor biodistribution,lack of selectivity, and healthy tissue damage, can be overcome by the implementation of drug delivery systems. A wide range of materials, including liposomes, microspheres, polymers and recently, carbon nanotubes (CNTs), have been investigated for delivering anticancer drugs on the purpose of reducing the number of necessary administrations, providing more localized and better use of the active agents, and increasing patient compliance. Carbon nanotubes (CNTs) have attracted particular attention as carriers of biologically relevant molecules due to their unique physical, chemical and physiological properties. The exact relationship between the physical-chemical properties of carbon nanotubes, their cell to-cell interactions, reactivity, and biological/systemic consequences are relevant issues and it is important to know suchinter-relationships beforehand to employ the benefits of these nanomaterials without the hazardous consequences. The purpose of this review is to present highlight of recent developments in the application of carbon nanotubes as cargoes for anti cancer drugs and in the diagnosis of cancer diseases.

  17. General and advanced diagnostic tools to detect Mycobacterium tuberculosis and their drug susceptibility: a review

    NARCIS (Netherlands)

    Gazi, M.A.; Islam, M.R.; Kibria, M.; Mahmud, Z.

    2015-01-01

    The global control of tuberculosis remains a great challenge from the standpoint of diagnosis, detection of drug resistance, and treatment, because treatment can only be initiated when infection is detected, and is guided by the results of antimicrobial susceptibility testing. To a large extent, non

  18. Advancing safe drug use through interprofessional learning (IPL): a pilot study.

    Science.gov (United States)

    Achike, Francis I; Smith, John; Leonard, Stuart; Williams, Janet; Browning, Felicia; Glisson, James

    2014-07-01

    Interprofessional collaborative patient-centered care (IPCPC) improves healthcare quality and cost. Drug-related morbidity drives healthcare costs, thus requiring IPCPC approaches. The lack of educational preparedness for would-be IPCPC practitioners underlies the failure of historic IPCPC attempts, hence today's emphasis on pre-licensure interprofessional education (IPE). A pilot IPE class was conducted on rational drug use (RDU) through rational drug prescribing. Twenty fourth-year nursing students and 88 second-year medical students participated (8-10 medical per 2-3 nursing students) in small group activity in a lecture hall. A case study on rational drug choice and prescription writing processes from medical and nursing perspectives was used. Eighty of 108 (74%) students completed the post-activity questionnaire and were satisfied with the class, with a mean weighted score (mws) of 0.8. The learning outcomes (mws = 1.0) contributed more (P classroom were, respectively, the most- and least-liked aspects of the class. The study revealed students' appetite for IPE, highlights the challenges in developing IPE curricula, and could serve as impetus for schools developing IPE for RDU curricula.

  19. The eTOX data-sharing project to advance in silico drug-induced toxicity prediction.

    Science.gov (United States)

    Cases, Montserrat; Briggs, Katharine; Steger-Hartmann, Thomas; Pognan, François; Marc, Philippe; Kleinöder, Thomas; Schwab, Christof H; Pastor, Manuel; Wichard, Jörg; Sanz, Ferran

    2014-11-14

    The high-quality in vivo preclinical safety data produced by the pharmaceutical industry during drug development, which follows numerous strict guidelines, are mostly not available in the public domain. These safety data are sometimes published as a condensed summary for the few compounds that reach the market, but the majority of studies are never made public and are often difficult to access in an automated way, even sometimes within the owning company itself. It is evident from many academic and industrial examples, that useful data mining and model development requires large and representative data sets and careful curation of the collected data. In 2010, under the auspices of the Innovative Medicines Initiative, the eTOX project started with the objective of extracting and sharing preclinical study data from paper or pdf archives of toxicology departments of the 13 participating pharmaceutical companies and using such data for establishing a detailed, well-curated database, which could then serve as source for read-across approaches (early assessment of the potential toxicity of a drug candidate by comparison of similar structure and/or effects) and training of predictive models. The paper describes the efforts undertaken to allow effective data sharing intellectual property (IP) protection and set up of adequate controlled vocabularies) and to establish the database (currently with over 4000 studies contributed by the pharma companies corresponding to more than 1400 compounds). In addition, the status of predictive models building and some specific features of the eTOX predictive system (eTOXsys) are presented as decision support knowledge-based tools for drug development process at an early stage.

  20. The eTOX Data-Sharing Project to Advance in Silico Drug-Induced Toxicity Prediction

    Directory of Open Access Journals (Sweden)

    Montserrat Cases

    2014-11-01

    Full Text Available The high-quality in vivo preclinical safety data produced by the pharmaceutical industry during drug development, which follows numerous strict guidelines, are mostly not available in the public domain. These safety data are sometimes published as a condensed summary for the few compounds that reach the market, but the majority of studies are never made public and are often difficult to access in an automated way, even sometimes within the owning company itself. It is evident from many academic and industrial examples, that useful data mining and model development requires large and representative data sets and careful curation of the collected data. In 2010, under the auspices of the Innovative Medicines Initiative, the eTOX project started with the objective of extracting and sharing preclinical study data from paper or pdf archives of toxicology departments of the 13 participating pharmaceutical companies and using such data for establishing a detailed, well-curated database, which could then serve as source for read-across approaches (early assessment of the potential toxicity of a drug candidate by comparison of similar structure and/or effects and training of predictive models. The paper describes the efforts undertaken to allow effective data sharing intellectual property (IP protection and set up of adequate controlled vocabularies and to establish the database (currently with over 4000 studies contributed by the pharma companies corresponding to more than 1400 compounds. In addition, the status of predictive models building and some specific features of the eTOX predictive system (eTOXsys are presented as decision support knowledge-based tools for drug development process at an early stage.

  1. 我国医药产业创新药物研发面临的问题及对策探讨%Discussion on Problems of Innovative Drug R&D Faced by Pharmaceutical Industry and Countermeasures in China

    Institute of Scientific and Technical Information of China (English)

    刘昌孝

    2012-01-01

    目的:为推动我国医药产业创新药物研发提供参考.方法:在研究我国创新药物研发现状的基础上,分析创新药物研发所面临的问题.结果与结论:我国创新药物研发面临研发资金投入不足、研发主题错位、知识产权保护不力、机制落后等问题.建议加大研发资金投入、促使企业成为研发主体、完善知识产权保护、优化相关机制.相信随着我国医药产业结构的调整,行业规范日趋合理,市场运行机制日趋完善,一定能够实现从原料药和仿制药大国到创新药大国的跨越.%OBJECTIVE: To provide reference for the promotion of innovative drug R&D in pharmaceutical industry in China. METHODS: Based on the status quo of innovative drug R&D in China, the problems of innovative drug R&D were analyzed. RE-SULTS&CONCLUSION: The problems of innovative drug R&D are inadequate fund, R&D subject misplacement, insufficient intellectual property protection, behindhand mechanism, etc. It is suggested to expand input, promote enterprise to be R&D subject, perfect intellectual property protection, optimize related mechanism. The crossover from raw material drug and global generic-drugs great power to innovative drug great power could be realized by adjusting pharmaceutical industrial structure, standardizing industry norms, perfecting operation mechanism.

  2. Innovation on Energy Power Technology (15)Great Advances in Power System Stabilizing Technology triggered by the Wide-area Outage

    Science.gov (United States)

    Egawa, Masanao

    On July 23, 1987, a very hot day, the largest wide-area power outage occurred in Kanto-Area, Japan. The cause was a voltage collapse on the bulk power network of Tokyo Electric Power Company, due to the abnormal rate of demand rising following resume after lunch break. Aggressive studies on voltage collapse throughout industry and university have led to great advances in power system stability. This essay describes the detail record of the outage, the applied countermeasures, and the inside story when the multiple voltage solutions of power flow on actual power system were found out for the first time.

  3. Innovative Training Experience for Advancing Entry Level, Mid-Skilled and Professional Level URM Participation in the Geosciences Workforce

    Science.gov (United States)

    Okoro, M. H.; Johnson, A.

    2015-12-01

    The representation of URMs in the U.S. Geosciences workforce remains proportionally low compared to their representation in the general population (Bureau of Labor Sta.s.cs, 2014). Employment in this and related industries is projected to grow 32% by 2030 for minority workers (Gillula and Fullenbaum, 2014), corresponding to an additional 48,000 jobs expected to be filled by minorities (National Research Council, 2014). However, there is a shortage of employees with proper training in the hard sciences (Holeywell, 2014; Ganzglass, 2011), as well as craft skills (Hoover and Duncan, 2013), both important for middle skill employment. Industry recognizes the need for developing and retaining a diverse workforce, therefore we hightlight a program to serve as a potential vanguard initative for developing an innovative training experience for URM and underserved middle skilled workers with essential knowledge, experience and skills necessary to meet the demands of the Geosciences industry's growing need for a safe, productive and diverse workforce. Objectives are for participants to achieve the following: understanding of geosciences workforce trends and associated available opportunities; mastery of key environmental, health and safety topics; improvements in decision making skills and preparedness for responding to potential environmental, health and safety related situations; and engagement in one-on-one coaching sessions focused on resume writing, job interviewing and key "soft skills" (including conflict resolution, problem solving and critical observation, representing 3 major skills that entry- level workers typically lack.

  4. Recent advances in protein and Peptide drug delivery: a special emphasis on polymeric nanoparticles.

    Science.gov (United States)

    Patel, Ashaben; Patel, Mitesh; Yang, Xiaoyan; Mitra, Ashim K

    2014-01-01

    Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly em- ployed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patient compliance. Non-invasive drug delivery routes such as nasal, transdermal, pulmonary, and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transder mal, and ocular administrations.

  5. Parent engagement in youth drug prevention in Chinese families: advancement in program development and evaluation.

    Science.gov (United States)

    Tsang, Sandra K M

    2011-01-01

    The escalating youth drug abuse problem in Hong Kong has attracted intense attention from the government, schools, and youth service professionals. Most preventive efforts have focused directly on positive youth development, very often through school programs delivered to secondary school students. There have been limited efforts to engage parents even though it is obvious that the family is actually the primary context of children and youth development. This paper will assert the importance of parental engagement in youth drug-prevention work, discuss some barriers in such parental involvement, present some promising local attempts and their strengths and limitations, and propose that sustained efforts are needed to build up theory-driven and evidence-based resources for Chinese communities on the subject.

  6. Parent Engagement in Youth Drug Prevention in Chinese Families: Advancement in Program Development and Evaluation

    Directory of Open Access Journals (Sweden)

    Sandra K. M. Tsang

    2011-01-01

    Full Text Available The escalating youth drug abuse problem in Hong Kong has attracted intense attention from the government, schools, and youth service professionals. Most preventive efforts have focused directly on positive youth development, very often through school programs delivered to secondary school students. There have been limited efforts to engage parents even though it is obvious that the family is actually the primary context of children and youth development. This paper will assert the importance of parental engagement in youth drug-prevention work, discuss some barriers in such parental involvement, present some promising local attempts and their strengths and limitations, and propose that sustained efforts are needed to build up theory-driven and evidence-based resources for Chinese communities on the subject.

  7. Smart electrospun nanofibers for controlled drug release: recent advances and new perspectives.

    Science.gov (United States)

    Weng, Lin; Xie, Jingwei

    2015-01-01

    In biological systems, chemical molecules or ions often release upon certain conditions, at a specific location, and over a desired period of time. Electrospun nanofibers that undergo alterations in the physicochemical characteristics corresponding to environmental changes have gained considerable interest for various applications. Inspired by biological systems, therapeutic molecules have been integrated with these smart electrospun nanofibers, presenting activation-modulated or feedback-regulated control of drug release. Compared to other materials like smart hydrogels, environment-responsive nanofiber-based drug delivery systems are relatively new but possess incomparable advantages due to their greater permeability, which allows shorter response time and more precise control over the release rate. In this article, we review the mechanisms of various environmental parameters functioning as stimuli to tailor the release rates of smart electrospun nanofibers. We also illustrate several typical examples in specific applications. We conclude this article with a discussion on perspectives and future possibilities in this field.

  8. Recent advances in amphiphilic polymers for simultaneous delivery of hydrophobic and hydrophilic drugs.

    Science.gov (United States)

    Martin, Chloe; Aibani, Noorjahan; Callan, John F; Callan, Bridgeen

    2016-01-01

    Nanomedicine has evolved with the use of biological compounds such as proteins, peptides and DNA. These hydrophilic and often highly charged compounds require a delivery system to allow effective transport and release at the site of action. These new biological therapeutics have not replaced the more traditional smaller molecule, but instead are working synergistically to the benefit of the end user. To that end, drug delivery systems are now required to encapsulate both larger hydrophilic compounds as well as the smaller and generally more hydrophobic compound. This review highlights the emerging role in drug delivery of amphiphilic polymers that by their very nature can associate with compounds of differing physicochemical properties, in particular the role of micelles, polymersomes and nanocapsules.

  9. Advanced surface chemical analysis of continuously manufactured drug loaded composite pellets

    OpenAIRE

    2016-01-01

    The aim of the present study was to develop and characterise polymeric composite pellets by means of continuous melt extrusion techniques. Powder blends of a steroid hormone (SH) as a model drug and either ethyl cellulose (EC N10 and EC P7 grades) or hydroxylpropyl methylcellulose (HPMC AS grade) as polymeric carrier were extruded using a Pharma 11 mm twin screw extruder in a continuous mode of operation to manufacture extruded composite pellets of 1 mm length. Molecular modelling study using...

  10. Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain.

    Science.gov (United States)

    Denora, Nunzio; Trapani, Adriana; Laquintana, Valentino; Lopedota, Angela; Trapani, Giuseppe

    2009-01-01

    This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.

  11. Challenges, applications, and recent advances of protein-ligand docking in structure-based drug design.

    Science.gov (United States)

    Grinter, Sam Z; Zou, Xiaoqin

    2014-07-11

    The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich a database of compounds, so that more compounds that are subsequently experimentally tested are found to be pharmaceutically interesting. In addition, like all virtual screening methods used for drug design, structure-based virtual screening can focus on curated libraries of synthesizable compounds, helping to reduce the expense of subsequent experimental verification. In this review, we introduce the protein-ligand docking methods used for structure-based drug design and other biological applications. We discuss the fundamental challenges facing these methods and some of the current methodological topics of interest. We also discuss the main approaches for applying protein-ligand docking methods. We end with a discussion of the challenging aspects of evaluating or benchmarking the accuracy of docking methods for their improvement, and discuss future directions.

  12. Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment

    Directory of Open Access Journals (Sweden)

    Chendi Ding

    2016-12-01

    Full Text Available Benefiting from the development of nanotechnology, drug delivery systems (DDSs with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs, quantum dots (QDs and carbon nanotubes (CNTs. The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules and extrinsic (temperature, light irradiation, magnetic field and ultrasound ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.

  13. [Advance in thrombopoietic drugs used in treatment of children's immune thrombocytopenia].

    Science.gov (United States)

    Ma, Jing-Yao; Wu, Run-Hui

    2012-12-01

    Immune thrombocytopenia (ITP) is a common acquired hemorrhagic disease. Conventional view considered its pathogenesis as the destruction of platelets induced by platelet associated antibodies, the target of treatment are inhibiting the production of antibodies and blocking the destruction of platelets in reticuloendothelial system, but they are ineffective in part of ITP patients, who transform to chronic/refractory ITP (C/RITP). As to children's C/RITP, the effect of first-line therapy is low, while the second-line therapy isn't effective definitely and has obvious side effects. The safe and effective second-line drugs to prevent disease progressing are urgently required. Recently, a pathogenesis that decrease the platelet production has been confirmed, thrombopoietic drugs, including thrombopoietin (TPO) and its receptor agonist (TRA), are under research and clinical application gradually. Recombinate human TPO (rhTPO) has accomplished Phase III clinical trails in adult C/RITP and tumor children. The Phase III clinical trails of romiplostim and eltrombopag, as the representative of TRA, in adult C/RITP have been performed. There are also two clinical trails of TRA for children's C/RITP, the efficacy and safety have been approved, with the convenience for using. In pediatric population, they have a good clinical application. In this article the research and development of thrombopoietic drugs and their perspective in pediatric clinical use are reviewed.

  14. Challenges, Applications, and Recent Advances of Protein-Ligand Docking in Structure-Based Drug Design

    Directory of Open Access Journals (Sweden)

    Sam Z. Grinter

    2014-07-01

    Full Text Available The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich a database of compounds, so that more compounds that are subsequently experimentally tested are found to be pharmaceutically interesting. In addition, like all virtual screening methods used for drug design, structure-based virtual screening can focus on curated libraries of synthesizable compounds, helping to reduce the expense of subsequent experimental verification. In this review, we introduce the protein-ligand docking methods used for structure-based drug design and other biological applications. We discuss the fundamental challenges facing these methods and some of the current methodological topics of interest. We also discuss the main approaches for applying protein-ligand docking methods. We end with a discussion of the challenging aspects of evaluating or benchmarking the accuracy of docking methods for their improvement, and discuss future directions.

  15. Opening the door to innovation.

    Science.gov (United States)

    Schuurman, Janine; Graus, Yvo F; Labrijn, Aran F; Ruuls, Sigrid; Parren, Paul W H I

    2014-01-01

    Open innovation is the new buzz, with initiatives popping up left and right. Here, we give a personal perspective on a very successful, knowledge-driven innovation initiated in an academia- industry alliance, which culminated in technology platforms that enable the generation of therapeutic antibodies with novel properties. To start, we provide a general background on open innovation in the drug development field.

  16. Creating Innovative Opportunities

    DEFF Research Database (Denmark)

    Ljungberg, Daniel; McKelvey, Maureen; Lassen, Astrid Heidemann

    2012-01-01

    to illustrations of the processes, and the 86 case studies in knowledge intensive entrepreneurship in Europe. These case studies were developed during the European Union research project AEGIS (Advancing Knowledge-Intensive Entrepreneurship and Innovation for Economic Growth and Well-being in Europe). The case...... studies do demonstrate how the individual KIE ventures are dependent upon variables and processes in the surrounding innovation systems. The overall analysis of the cases provides insight into how KIE processes link the KIE venture and the innovation system, thereby highlighting e.g. the importance...... of knowledge networks to create innovative opportunities....

  17. Euler Technology Assessment - SPLITFLOW Code Applications for Stability and Control Analysis on an Advanced Fighter Model Employing Innovative Control Concepts

    Science.gov (United States)

    Jordan, Keith J.

    1998-01-01

    This report documents results from the NASA-Langley sponsored Euler Technology Assessment Study conducted by Lockheed-Martin Tactical Aircraft Systems (LMTAS). The purpose of the study was to evaluate the ability of the SPLITFLOW code using viscous and inviscid flow models to predict aerodynamic stability and control of an advanced fighter model. The inviscid flow model was found to perform well at incidence angles below approximately 15 deg, but not as well at higher angles of attack. The results using a turbulent, viscous flow model matched the trends of the wind tunnel data, but did not show significant improvement over the Euler solutions. Overall, the predictions were found to be useful for stability and control design purposes.

  18. Medical innovation laws: an unnecessary innovation.

    Science.gov (United States)

    Richards, Bernadette

    2016-06-01

    Objective This paper aims to demonstrate that any suggestion that there is a need for specific innovation laws is flawed. Innovation is central to good medical practice and is adequately supported by current law. Methods The paper reviews the nature of medical innovation and outlines recent attempts in the UK to introduce specific laws aimed at 'encouraging' and 'supporting' innovation. The current legal framework is outlined and the role of the law in relation to medical innovation explored. Results The analysis demonstrates the cyclic relationship between medical advancement and the law and concludes that there is no requirement for specific innovation laws. Conclusions The law not only supports innovation and development in medical treatment but encourages it as central to a functioning medical system. There is no need to introduce specific laws aimed at medical innovation; to do so represents an unnecessary legal innovation and serves to complicate matters. What is known about the topic? Over recent months, there has been a great deal of discussion surrounding the law in the context of medical innovation. This was driven by the attempts in the UK to introduce specific laws in the Medical Innovation Bill. The general subject matter - negligence and the expected standard of care in the provision of treatment - is very well understood, but not in cases where the treatment can be described as innovative. The general rhetoric in both the UK and Australia around the Medical Innovation Bill demonstrates a lack of understanding of the position of the law with regards to innovative treatment. What does this paper add? This paper adds clarity to the debate. It presents the law and explains the manner in which the law can operate around innovative treatment. The paper asserts that medical innovation is both supported and encouraged by existing legal principles. What are the implications for practitioners? The paper presents an argument that can guide the policy position

  19. Evaluation of innovative stationary phase ligand chemistries and analytical conditions for the analysis of basic drugs by supercritical fluid chromatography.

    Science.gov (United States)

    Desfontaine, Vincent; Veuthey, Jean-Luc; Guillarme, Davy

    2016-03-18

    Similar to reversed phase liquid chromatography, basic compounds can be highly challenging to analyze by supercritical fluid chromatography (SFC), as they tend to exhibit poor peak shape, especially those with high pKa values. In this study, three new stationary phase ligand chemistries available in sub -2 μm particle sizes, namely 2-picolylamine (2-PIC), 1-aminoanthracene (1-AA) and diethylamine (DEA), were tested in SFC conditions for the analysis of basic drugs. Due to the basic properties of these ligands, it is expected that the repulsive forces may improve peak shape of basic substances, similarly to the widely used 2-ethypyridine (2-EP) phase. However, among the 38 tested basic drugs, less of 10% displayed Gaussian peaks (asymmetry between 0.8 and 1.4) using pure CO2/methanol on these phases. The addition of 10mM ammonium formate as mobile phase additive, drastically improved peak shapes and increased this proportion to 67% on 2-PIC. Introducing the additive in the injection solvent rather than in the organic modifier, gave acceptable results for 2-PIC only, with 31% of Gaussian peaks with an average asymmetry of 1.89 for the 38 selected basic drugs. These columns were also compared to hybrid silica (BEH), DIOL and 2-EP stationary phases, commonly employed in SFC. These phases commonly exhibit alternative retention and selectivity. In the end, the two most interesting ligands used as complementary columns were 2-PIC and BEH, as they provided suitable peak shapes for the basic drugs and almost orthogonal selectivities.

  20. Advances in huntington disease drug discovery: novel approaches to model disease phenotypes.

    Science.gov (United States)

    Bard, Jonathan; Wall, Michael D; Lazari, Ovadia; Arjomand, Jamshid; Munoz-Sanjuan, Ignacio

    2014-02-01

    Huntington disease is a monogenic, autosomal dominant, progressive neurodegenerative disorder caused by a trinucleotide CAG repeat expansion in exon 1 of the huntingtin (HTT) gene; age of onset of clinical symptoms inversely correlates with expanded CAG repeat length. HD leads to extensive degeneration of the basal ganglia, hypothalamic nuclei, and selected cortical areas, and a wide range of molecular mechanisms have been implicated in disease pathology in animal or cellular models expressing mutated HTT (mHTT) proteins, either full-length or amino-terminal fragments. However, HD cellular models that recapitulate the slow progression of the disease have not been available due to the toxicity of overexpressed exogenous mHTT or to limitations with using primary cells for long-term studies. Most investigations of the effects of mHTT relied on cytotoxicity or aggregation end points in heterologous systems or in primary embryonic neuroglial cultures derived from HD mouse models. More innovative approaches are currently under active investigation, including screening using electrophysiological endpoints, as well as the recent use of primary blood mononuclear cells and of human embryonic stem cells derived from a variety of HD research participants. Here we describe how these cellular systems are being used to investigate HD biology as well as to identify mechanisms with therapeutic potential.

  1. Recent Advances Towards The Discovery Of Drug-Like Peptides De Novo

    Science.gov (United States)

    Goldflam, Michael; Ullman, Christopher

    2015-12-01

    Peptides are important natural molecules that possess functions as diverse as antibiotics, toxins, venoms and hormones, for example. However, whilst these peptides have useful properties, there are many targets and pathways that are not addressed through the activities of natural peptidic compounds. In these circumstances, directed evolution techniques, such as phage display, have been developed to sample the diverse chemical and structural repertoire of small peptides for useful means. In this review, we consider recent concepts that relate peptide structure to drug-like attributes and how these are incorporated within display technologies to deliver peptides de novo with valuable pharmaceutical properties.

  2. On Chinese medicine innovation based on drug system of natural pharmacy concept%基于自然药学观药物体系的中药药物创新相关性思考

    Institute of Scientific and Technical Information of China (English)

    石任兵; 王永炎; 吕松涛

    2015-01-01

    Based on the nature medicine concept drug system, the drug innovation and the top de-sign of traditional Chinese medicine ( TCM) was set up,. to improve the level of drug and guid optimum drug for TCM. The method of correlation analysis on basic drug system characteristic was used for guiding drug preparation and quality evaluation. The results show that on the basis of top design and drug innovation model by nature medicine concept drug system thinking, the goal of drug innovation can be achieved through optimum drug preparation, excellent quality control and pharmacokinetic properties characteriza-tion. Therefore, TCM drugs innovation from drug system can carry out on TCM optimum drug more original, more precise and more effective, and can radically improve the quality of TCM.%基于自然药学观药物体系构架中药药物创新思维及其顶层设计,以提高中药药物创新水平,指导中药理想药物创制。在研究中,应用药物体系基本特性表征关联分析方法确定有效物质基础,导向药物制备与质量表征关联评价。研究结果表明:基于自然药学观药物体系所构架的药物创新顶层设计及其系列创新模式,可适用于中药药物优质制备、质量精准控制与药动学特性表征,从而指导药物创新目标的实现。因此,药物体系导向中药药物创新,可更新颖、本原、精准、有效地进行中药理想药物研究,从根本上提升中药药物质量。

  3. 双相心境障碍的药物治疗进展%Recent advances in treatment of drug for bipolar mood disorder drug therapy

    Institute of Scientific and Technical Information of China (English)

    张伟

    2014-01-01

    Bipolar mood disorder ( BPD ) is a common mental disorders , clinically the emotional disorders is about 50% for borderline personality disorder , particularly the onset , recurrent characteristics of BPD, long-term break out repeatedly , cause disease in patients with chronic , personality changes and social function is impaired .To strengthen the drug treatment of bipolar mood disorders is commonly .The drug treatment of the disease, in addition to the required is safe and effective , also need not trigger emotional phase inversion , and can prevent recurrent .In this paper , the recent advances in the treatment of bipolar mood disorder in clinical medicine are reviewed .%双相心境障碍( BPD)是一种常见的精神障碍,临床的情感障碍中约50%是BPD,BPD的发作性、复发性特点尤为明显,长期的反复发作,导致患者疾病慢性化、人格改变和社会功能受损。加强双相心境障碍的药物治疗受到普遍重视。该疾病的药物治疗,除要求安全有效外,还需要不致促发情感转相,并能预防反复发作。本文就近年来临床上双相心境障碍药物治疗进展做一综述。

  4. MEASURING MANUFACTURING INNOVATIVENESS

    DEFF Research Database (Denmark)

    Blichfeldt, Henrik; Knudsen, Mette Præst

    2017-01-01

    Globalization and customization increases the pressure on manufacturing companies, and the ability to provide innovativeness is a potential source of competitive advantage. This paper positions the manufacturing entity in the innovation process, and investigates the relation between innovation vers...... technology and organizational concepts. Based on Danish survey data from the European Manufacturing Survey (EMS-2015) this paper finds that there is a relation between innovative companies, and their level of technology and use of organizational concepts. Technology and organizational concepts act...... as manufacturing levers to support the manufacturing and production system to provide innovativeness. The managerial implication lies in building manufacturing capabilities to support the innovative process, by standardization, optimization and creating stability in combination with automation and advanced...

  5. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment.

    Science.gov (United States)

    Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-12-01

    Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs.

  6. Teaching innovation.

    Science.gov (United States)

    Lachman, Vicki D; Glasgow, Mary Ellen Smith; Donnelly, Gloria F

    2009-01-01

    Innovation in healthcare is essential to solve the "wicked problems" currently facing healthcare. This article focuses on nature of innovation and how it operates, how innovators think and view problems, how the theory and practice of innovation can be taught in novel ways, and how organizational cultures foster or suppress innovation. Examples of teaching strategies and nurse-driven innovation illustrate the theory and practice of innovation.

  7. Preliminary Study Results Of Multiple Drug Resistance In Patients With Advanced Types Of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    S Navruzov

    2010-04-01

    Full Text Available In the department of coloproctology of NORC MH RUz 17 patients with disseminated forms of colorectal cancer was made the study of oncogenes and complex treatment by 2 protocols using FOLFOX-4 regime and FOLFIRI regime. In second protocol there used 2 sessions of endolymphatical polychemotherapy FOLFOX-4 regime against EHF-hyperthermia. All patients were performed additional investigations directed to study the presence of multiple drug resistance in them where definition of р53, bcl-2 oncogene expression. In our observations we followed resistance to FOLFOX-4 scheme in 4 patients, and to FOLFIRI scheme in 2 cases. In our studies hyperexpression of oncoproteine  р53 was correlated with the effect of conducted therapy whereas hyperexpression of oncoproteine bcl-2 showed therapy resistance. 

  8. Irinotecan drug eluting beads used as a treatment of advanced intra hepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Jean Amede Roch

    2008-10-01

    Full Text Available

    This report describes a 74-year-old male with unresectable intrahepatic cholangiocarcinoma (ICC. However surgical procedure is the only curative treatment, it often seems to be ineffective because of the aggressive behaviour of the disease. The role of systemic chemotherapy in the ICC is undefined with a median survival between 6.43 to 12.17 months obtained by using the combination chemotherapy of gemcitabine with cisplatin. In the present case, we performed a targeted treatment using drug eluting beads (DEB with irinotecan (IRI administered as transarterial-chemoembolization (TACE. After one session, the tumour vascularity decreased significantly at the one month evaluation on computed tomography (CT scan of the liver.  This case report suggested that minimally invasive transcatheter DEB embolization could be a promising, safe and effective treatment for selective patients with unresectable ICC.

  9. [Projects to accelerate the practical use of innovative medical devices to collaborate with TWIns, Center for Advanced Biomedical Sciences, Waseda University and School of Engineering, The University of Tokyo].

    Science.gov (United States)

    Niimi, Shingo; Umezu, Mitsuo; Iseki, Hiroshi; Harada, Hiroshi Kasanuki Noboru; Mitsuishi, Mamoru; Kitamori, Takehiko; Tei, Yuichi; Nakaoka, Ryusuke; Haishima, Yuji

    2014-01-01

    Division of Medical Devices has been conducting the projects to accelerate the practical use of innovative medical devices to collaborate with TWIns, Center for Advanced Biomedical Sciences, Waseda University and School of Engineering, The University of Tokyo. The TWIns has been studying to aim at establishment of preclinical evaluation methods by "Engineering Based Medicine", and established Regulatory Science Institute for Medical Devices. School of Engineering, The University of Tokyo has been studying to aim at establishment of assessment methodology for innovative minimally invasive therapeutic devices, materials, and nanobio diagnostic devices. This report reviews the exchanges of personnel, the implement systems and the research progress of these projects.

  10. Cystathionine beta-synthase (CBS contributes to advanced ovarian cancer progression and drug resistance.

    Directory of Open Access Journals (Sweden)

    Sanjib Bhattacharyya

    Full Text Available BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA, in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

  11. STUDY OF COORDINATION OF IMMUNOACTIVE PEPTIDES WITH METAL IONS AS A BASIS FOR THE DEVELOPMENT OF INNOVATIVE DRUGS

    Directory of Open Access Journals (Sweden)

    N. D. Bunyatyan

    2014-01-01

    Full Text Available The results of development of the immunomodulator timotsin based on coordination compounds dipeptide isoleucyl-tryptophan with zinc, including the synthesis of low molecular weight peptides by immunoactive activated esters, determination regarding the immunostimulatory activity of thymosin α1, study of coordination of dipeptide isoleucyltryptophan with zinc, study the immunostimulatory activity of coordination compounds, the results of preclinical and clinical studies of timotsin. pH-metric method and red-ox titration showed that the interaction of zinc and of dipeptide isoleucyl-tryptophan formed in solution following complex forms: [ZnHL] (lgæ = 3,71, Zn(HL2 (lgβ = 0,279, ZnL(HL (lgβ = 6,6, Zn2(HL2 (lgβ = 188, Zn(OH(HL (lgβ = -0,256. It was shown that the immunostimulatory activity of coordination compounds is in 2-8 times greater than the starting dipeptide.The developed immunomodulatory drug timotsin showed high therapeutic efficacy in the treatment of viral hepatitis, malignant tumors of different localization, psoriasis and neurodermatitis. Timotsin is registered in Tajikistan (registration number of medical drug№000085T, Kyrgyzstan (medical drug №7137 and Turkmenistan (registration number 006371.

  12. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.

    Science.gov (United States)

    Axelson, Michael; Liu, Ke; Jiang, Xiaoping; He, Kun; Wang, Jian; Zhao, Hong; Kufrin, Dubravka; Palmby, Todd; Dong, Zedong; Russell, Anne Marie; Miksinski, Sarah; Keegan, Patricia; Pazdur, Richard

    2013-05-01

    The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.

  13. Target delivery and controlled release of the chemopreventive drug sulindac by using an advanced layered double hydroxide nanomatrix formulation system.

    Science.gov (United States)

    Minagawa, Keiji; Berber, Mohamed R; Hafez, Inas H; Mori, Takeshi; Tanaka, Masami

    2012-04-01

    Target delivery and controlled release of the chemopreventive drug sulindac that possesses low water solubility present a great challenge for its pharmaceutical industry. Here, we offered an advanced nanomatrix formulation system of sulindac based on layered double hydroxide materials. The X-ray analysis and infrared spectroscopy confirmed the incorporation of sulindac into the gallery of the layered double hydroxides. The incorporation ratios of sulindac were recorded to be 45, 31 and 20 for coprecipitation, anion-exchange and reconstruction techniques, respectively. The scanning electron microscopy showed a nanomatrix-structure of ~50 nm. The release studies of sulindac-nanomatrix showed a 96% controlled release at the small intestine solution during 3 h(s), indicating an enhancement in the dissolution profile of sulindac after the matrix formation. The layered structure of the matrix supplied sulindac with a well-ordered structure and a relatively hydrophobic microenvironment that controlled the guest hydrolysis and reactivity during the release process. The laminar structure of layered double hydroxides offered a safe preservation for sulindac against photodecarboxylation, and enhanced the drug thermal stability from 190 to 230° C. The ionic electrostatic interaction of sulindac through its acidic group with layered double hydroxides demolished the gastrointestinal ulceration.

  14. Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

    Directory of Open Access Journals (Sweden)

    Ritesh Fule

    2014-01-01

    Full Text Available Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD with immediate release and improved bioavailability was prepared using Soluplus (Sol as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72 and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72 and Cmax higher than those with the commercial capsule (Noxafil. Molecular dynamic (MD simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  15. Hot melt extruded amorphous solid dispersion of posaconazole with improved bioavailability: investigating drug-polymer miscibility with advanced characterisation.

    Science.gov (United States)

    Fule, Ritesh; Amin, Purnima

    2014-01-01

    Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0-72) and C(max) of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0-72) and C(max) higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  16. Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference. October 14-17, 2010, Cascais, Portugal.

    Science.gov (United States)

    Vucic, Domagoj

    2010-12-01

    The Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference, held in Cascais, Portugal, included topics covering new therapeutic developments in the field of cell death and cancer. This conference report highlights selected presentations on inhibiting the inhibitor of apoptosis (IAP) proteins, activating death receptors (DRs), and targeting ubiquitins and the Bcl-2 family. Investigational drugs discussed include LCL-161 (Novartis) and navitoclax (Abbott Laboratories/Genentech).

  17. Remote access directional drilling : an innovative technological advancement in directional drilling based on a collaborative and strategic R and D effort

    Energy Technology Data Exchange (ETDEWEB)

    Buker, M. [Phoenix Income Trust, Toronto, ON (Canada); Gillett, G. [EnCana Oil and Gas Partnership, Bonnyville, AB (Canada)

    2008-07-01

    EnCana and Phoenix Income Trust identified an opportunity to develop a system that could reduce directional personnel in the field because of numerous rigs that were in close proximity to each other and the repetitive nature of well profiles. Directional personnel also had familiarity with drilling programs. This presentation discussed an innovative technological advancement in directional drilling based on a collaborative and strategic research and development effort between EnCana and Phoenix Income Trust called remote access directional drilling (RADD). The RADD system and process were presented in detail. Challenges that were addressed included the development of a system that could provide all the necessary drilling information remotely; establishing effective communication between the command center and rig; and training of Phoenix and EnCana personnel. The presentation also reviewed equipment solutions and re-defining job roles. A total of 265 wells have been drilled with this system at a cost savings of $350,000 and a savings of 12-15 per cent of total directional costs. It was concluded that fewer wellsite trailers are needed when field personnel is reduced, resulting in reduced cost and reduced safety liability. 2 figs.

  18. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

    Directory of Open Access Journals (Sweden)

    Scanlon SA

    2011-12-01

    Full Text Available Samantha A Scanlon1, Joseph A Murray1,21Department of Internal Medicine, 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USAAbstract: Celiac disease (CD is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions.Keywords: immune-mediated enteropathy, gliadin, gluten, epidemiology, CD diagnosis, therapy

  19. Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives

    Science.gov (United States)

    He, Ni-ya; Li, Qing; Wu, Chun-yan; Ren, Zhong; Gao, Ya; Pan, Li-hong; Wang, Mei-mei; Wen, Hong-yan; Jiang, Zhi-sheng; Tang, Zhi-han; Liu, Lu-shan

    2017-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors. PMID:28112180

  20. Non-Oral Drug Delivery Strategies: From Early Diagnosis to Advanced Treatments

    Directory of Open Access Journals (Sweden)

    Claudia Trenkwalder

    2015-08-01

    Full Text Available This educational symposium, sponsored by Britannia Pharmaceuticals Limited, was held during the 1st Congress of the European Academy of Neurology (EAN, which took place from 20th-23rd June 2015 in Berlin, Germany. The symposium reviewed the role of non-oral drug delivery strategies in patients with Parkinson’s disease (PD and how they can overcome problems that occur with the gastrointestinal (GI route of administration in many patients. GI dysfunction is recognised as a common problem in PD and may in fact be a preclinical marker of the disease. It can affect the absorption of oral medication resulting in OFF periods and unreliable control of motor symptoms, which in turn can have a negative impact on quality of life (QoL. Delayed time-to-ON (TTO after an oral levodopa dose and dose failures are known to be significant contributors to total OFF time. Results of the recently completed AM-IMPAKT trial in patients with morning akinesia due to a delay in the onset of oral levodopa effect demonstrate that apomorphine intermittent injection (penject is able to provide rapid and effective resolution of such complications, restoring patients to the ON state quickly and allowing them to get on with their daily activities.

  1. Diminazene aceturate--An antiparasitic drug of antiquity: Advances in pharmacology & therapeutics.

    Science.gov (United States)

    da Silva Oliveira, George Laylson; de Freitas, Rivelilson Mendes

    2015-12-01

    Diminazene aceturate (C14H15N7.2C4H7NO3) is an aromatic diamidine that was developed more than six decades ago and has been marketed until today for the control of trypanosomiasis. In recent years, however, this trypanocidal compound has been extensively studied with respect to its therapeutic potential and has consequently attracted much interest for the development of further research. The objective of this study was to conduct a systematic review on diminazene aceturate regarding its pharmacological properties. In this way, databases were searched for articles (ScienceDirect, Scopus, PubMed, Web of Science and SciFinder) and patents (INPI, USPTO, WIPO, DPMA, SIPO, DERWENT, CIPO and EPO). For the development of this review, 115 articles and 22 patents were selected and analyzed. It was thus possible to highlight several researches that have investigated alternatives in order to improve success in the treatment of animal trypanosomiasis, by using new drugs in associations with diminazene aceturate, as well as looking for new pharmacological applications for this compound, such as leishmanicidal, amebicidal, anti-pneumocystis, anti-rheumatoid arthritis, antihypertensive agent, and mainly as an activator of angiotensin-converting enzyme 2. Another pharmacological property still little studied is the inhibition of acid-sensitive ion channels (ASIC1a, ASIC1b, ASIC2a and ASIC3), which are related to the development of various diseases. Collectively, these studies conducted by several research groups extend the use of diminazene aceturate beyond the antitrypanosomal activity and suggest promising new applications.

  2. Orchestrating innovation

    NARCIS (Netherlands)

    Berkers, F.T.H.M.; Klein Woolthuis, R.J.A.; Boer, J. de

    2015-01-01

    Orchestrating Innovation increases the probability of success, minimizing the probability of failure of technological innovations by creating sustained societal and economic value. Orchestrating innovation propagates to take into account and actively involve all relevant stakeholders of the (future)

  3. Innovation af innovation

    DEFF Research Database (Denmark)

    Harste, Gorm

    2009-01-01

    , at innovation af innovationen forsøges gennemført på en måde, hvor tiden kræves at forholde sig til sin egen tidslighed i form af fremtid, nutid, fortid og ikke mindst i form af samtidighed. I tiden skal vi iagttage, hvordan vi iagttager tiden. Vi dobbelt-koder tiden på samme måde, som forskning forsker i...... organisationssystemerne. De to typer systemer kan noget helt bestemt med fænomenet tid. De kan synkronisere. Analyseres organisationssystemer ser vi, imidlertid at innovation kræver ro. Stærkt innovative systemer er militærsystemet og kunstsystemet, der også inddrages, og hvor vi ser paradokset mellem innovation og...... involution. Tid er med et medium og ikke et lufttomt rum. Tid er end ikke en gasart, men udgør et solidt fluidum, som samfundet bader i og flyder i, konstant i bevægelse. Reformer forudsætter former, og innovation forudsætter involution. Kun sådan muliggøres evolution....

  4. Alternating treatment with didanosine and zidovudine versus either drug alone for the treatment of advanced HIV infection. The Alter Study. Nordic HIV Therapy Group

    DEFF Research Database (Denmark)

    Gerstoft, J; Melander, H; Bruun, J N;

    1997-01-01

    The efficacy and safety of an alternating regime with zidovudine and didanosine versus treatment with either drug alone were investigated in a randomized, open, controlled trial, 552 patients with advanced HIV infection, 47% of whom had received prior treatment with zidovudine, were enrolled...

  5. Innovation Gains More Strengths

    Institute of Scientific and Technical Information of China (English)

    Wang Ting

    2007-01-01

    @@ Innovation ,is a hot word in 2007 for the Chinese textile industry.Encountering the export drawback, RMB appreciation, trade barrier,energy-saving and social compliance, Chinese textile industry find outthat the innovation, along with the advancing of production technology,branding strategy and scientific management,could improve its competitiveness in domestic and overseas markets. The China Textile Innovation Conference, held in Nov.2007, could be defined as an annual general summary, for the textile enterprises in China as well as the whole industry, to acknowledge what they have achieved,and to know what to do in the future.

  6. Human resource management and firm innovativeness in a European context: Advancing our understanding of the relationship (Introduction to the thematic issue)

    NARCIS (Netherlands)

    Ruel, H.J.M.; Bondarouk, T.V.; Florén, H.; Rundquist, J.

    2014-01-01

    This paper introduces the papers included in the thematic issue on Human Resource Management (HRM) and firm innovativeness in a European context. Furthermore it presents the results of a literature review on human resource management and firm innovativeness. The literature shows that the positive re

  7. Innovative didaktik

    DEFF Research Database (Denmark)

    Lund, Birthe

    Innovative didaktik. This deals with innovative didaktik from at methodological point of view in three ways - how to define the concept, how to develop it and how analyse it. Issues analysed: How to create innovative students? How to create innovative learning envoriments? These are core questions...

  8. Mindful innovation

    DEFF Research Database (Denmark)

    Olsen, Poul Bitsch

    2008-01-01

    Mindful innovation is an approach to innovation that pays attention to people's experience in an organization rather than to formal organization or social role.......Mindful innovation is an approach to innovation that pays attention to people's experience in an organization rather than to formal organization or social role....

  9. Orchestrating innovation

    OpenAIRE

    Berkers, F.T.H.M.; Klein Woolthuis, R.J.A.; J. de Boer

    2015-01-01

    Orchestrating Innovation increases the probability of success, minimizing the probability of failure of technological innovations by creating sustained societal and economic value. Orchestrating innovation propagates to take into account and actively involve all relevant stakeholders of the (future) ecosystem in which the innovation will, can or has to be adopted.

  10. Business Process Innovation using the Process Innovation Laboratory

    DEFF Research Database (Denmark)

    Møller, Charles

    process innovation (BPI) in future organizations. There is a significant body of knowledge on various aspect of process innovation, e.g. on conceptual modeling, business processes, supply chains and enterprise systems. Still an overall comprehensive and consistent theoretical framework with guidelines...... for practical applications has not been identified. The aim of this paper is to establish a conceptual framework for business process innovation in the supply chain based on advanced enterprise systems. The main approach to business process innovation in this context is to create a new methodology for exploring...... process models and patterns of applications. The paper thus presents a new concept for business process innovation called the process innovation laboratory a.k.a. the ?-Lab. The ?-Lab is a comprehensive framework for BPI using advanced enterprise systems. The ?-Lab is a collaborative workspace...

  11. 创新药物临床试验不良事件赔付机制调查研究%Investigation and analysis on the innovation drug adverse event relief system

    Institute of Scientific and Technical Information of China (English)

    孙磊; 林晶; 尹鹏; 李月明

    2015-01-01

    目前我国创新药物临床试验中针对出现的不良事件没有可以遵循的相关法律法规,尚未形成统一的赔付标准。本研究选取国家科技重大专项“创新药物临床评价技术平台”课题中标单位为调研对象,探讨建立创新药物临床不良事件赔付机制和实现赔付机制的途径、方式和方法。%Because lack of the law and unified compensation standards about compensation of innovation drug adverse event in China, the sufferers cannot get any compensation from the correlative responsibility party. By choosing the ‘Significant Innovation Drugs Creation’ bid units , this research carry out survey to find out and discuss the optimization approach to establish innovation drug adverse event compensation system.

  12. Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

    Science.gov (United States)

    Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-06-01

    From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

  13. 新常态、高端人力资本与区域创新能力的关系研究——兼论高端人力资本集聚策略%Research on the Relationship between the New Normal, Advanced Human Capital and Regional Innovation Capability--and on the Strategy of Accumulating Advanced Human Capital

    Institute of Scientific and Technical Information of China (English)

    常珊

    2015-01-01

    Under the background of the new normal economy, the ordinary human capital regarded as the main part to drive regional economic innovation has been unable to satisfy the requirements of the new economy, and therefore, it needs to enhance the regional innovation capability relying on the advanced human capital. Firstly, the paper defines the concept of advanced human capital, and then analyzes the influence of advanced human capi-tal on regional innovation from aspects such as the promotion of enterprises innovation capability, the enhancement of universities and research institutes innovation capability, the improvement of the service agencies service capa-bility and so on. Besides, the paper also analyzes the impact of the new normal on advanced human capital from three sides such as the economic growth, the adjusting of economic structure and the innovation driving. Finally, the paper talks about how to gather advanced human capital and strengthen the regional innovation capability in the new normal economy.%经济新常态背景下,作为区域经济创新驱动主体的普通人力资本已经无法满足新经济的要求,因此,需要依靠高端人力资本增强区域创新能力. 本文首先对高端人力资本的概念进行了界定,然后从企业创新能力提升、高校与科研院所创新能力提升、服务机构服务能力提升等方面,分析了高端人力资本对区域创新能力的影响机理. 又从经济增长速度、经济结构调整、创新驱动三个方面分析了新常态经济对高端人力资本产生的影响. 最后讨论了在新常态的背景下,如何集聚高端人力资本,提升区域创新能力.

  14. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

    Science.gov (United States)

    Lam, P L; Gambari, R

    2014-03-28

    This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown.

  15. Laboratory Innovation Towards Quality Program Sustainability.

    Science.gov (United States)

    Abimiku, Alash'le; Timperi, Ralph; Blattner, William

    2016-08-01

    Laboratory innovation significantly affects program sustainability of HIV programs in low and middle income countries (LMICs) far beyond its immediate sphere of impact. Innovation in rapid development of diagnostic technologies, improved quality management systems, strengthened laboratory management, affordable external quality assurance and accreditation schemes, and building local capacity have reduced costs, brought quality improvement to point-of-care testing, increased access to testing services, reduced treatment and prevention costs and opened the door to the real possibility of ending the AIDS epidemic. However, for effectively implemented laboratory innovation to contribute to HIV quality program sustainability, it must be implemented within the overall context of the national strategic plan and HIV treatment programs. The high quality of HIV rapid diagnostic test was a breakthrough that made it possible for more persons to learn their HIV status, receive counseling, and if infected to receive treatment. Likewise, the use of dried blood spots made the shipment of samples easier for the assessment of different variables of HIV infection-molecular diagnosis, CD4+ cell counts, HIV antibodies, drug resistance surveillance, and even antiretroviral drug level measurements. Such advancement is critical for to reaching the UNAIDS target of 90-90-90 and for bringing the AIDS epidemic to an end, especially in LMICs.

  16. Collaborative innovation

    DEFF Research Database (Denmark)

    Torfing, Jacob; Sørensen, Eva; Hartley, Jean

    2013-01-01

    There are growing pressures for the public sector to be more innovative but considerable disagreement about how to achieve it. This article uses institutional and organizational analysis to compare three major public innovation strategies. The article confronts the myth that the market......-driven private sector is more innovative than the public sector by showing that both sectors have a number of drivers of as well as barriers to innovation, some of which are similar, while others are sector specific. The article then systematically analyzes three strategies for innovation: New Public Management...... for enhancing public innovation is contingent rather than absolute. Some contingencies for each strategy are outlined....

  17. Advances in drug research of osteoporosis%骨质疏松症药物研究进展

    Institute of Scientific and Technical Information of China (English)

    周涛龙; 蒋作锋; 余慧文

    2015-01-01

    Osteoporosis is a systemic metabolic bone disease identified by bone mass loss and bone microstructure failure which is easy to fracture. The major symptoms, low back pain and pathological fractures, mainly occur in the elderly, especially in the post-menopausal women. The incidence is up to more than 60%. Some drugs have been shown to reduce the risk of osteoporotic verte-bral and non vertebral fractures. However, in the process of population ageing and modern industrializ, more and more osteoporotic fracture occurred. Osteoporosis treatment needs new drugs and new ideas. The new bone formation enhancers and inhibitors of bone resorption, such as cathepsin K inhibitors, can improved bone formation by maintaining the osteoclast and osteoblast balance. Based on advancement of osteoporosis in the pathophysiology, The appearance of new drugs, will have a great improvement on the prevention and treatment of osteoporotic fractures, helps to reduce the osteoporosis complicated with fracture in the incidence, this paper reviewed this.%骨质疏松症是以骨量降低,骨组织的显微结构破坏为特征,导致骨的脆性增高,易于骨折的一种全身代谢性骨病。在临床上表现为腰背疼和病理性骨折,主要发生在中老年人,尤其是绝经后妇女中,发生率高达60%以上。一些最新提供的药物已证实能够降低骨质疏松症椎体和非椎体骨折的风险。然而,在现代工业化国家的人口老龄化进程中,现在仍然有越来越多的骨折发生,骨质疏松症的治疗需要新的治疗药物和理念。新的骨形成促进剂和骨吸收抑制剂,如组织蛋白酶K抑制剂,通过维持破骨细胞-成骨细胞的平衡,从而维持骨形成。基于对骨质疏松症在病理生理学上更深入的理解,这些新药物的出现,将对防治骨质疏松性骨折有很大的改善,有助于大大降低目前骨质疏松症并发骨折在发生率,该研究就此作一综述。

  18. Strategic and Everyday Innovative Narratives

    DEFF Research Database (Denmark)

    Reff Pedersen, Anne; Brehm Johansen, Mette

    2012-01-01

    in making sense of innovative ideas in everyday practice. An empirical case is offered to demonstrate how two types of innovation narratives emerge: strategic and everyday narratives through involvement of spokespersons and employees. These findings suggest that an advanced understanding of the roles...

  19. 关于中药新药研发创新的几点思考%Considerations on the research and development of new drug innovation from traditional Chinese medicine

    Institute of Scientific and Technical Information of China (English)

    张晓东; 王海南; 张磊

    2011-01-01

    基于对近年来中药新药研发和注册申请状况的回顾分析,从中药新药技术审评和注册管理的视角,阐述了对“中药新药研发创新”议题的若干观点.包括对中药新药研发创新内涵的理解,对中药新药研发创新具体形式的认识,以及对当前中药新药研发创新方面存在问题的剖析等.%The authors expounded their considerations on the issue "research and development of new drug innovation from traditional Chinese medicine (TCM ) ". These considerations are based on the perspective of new drugs evaluation, registration management, and the status of development and registration applications of new drugs from TCM in recent years. The specific forms of new drugs development innovation and the existing problems were also analyzed.

  20. Drug Development for Neurodegenerative Diseases--Second Annual marcus evans Conference. Advances in drug development for NDD and expediting discovery through novel compounds and sound clinical trials.

    Science.gov (United States)

    Morimoto, Bruce

    2010-07-01

    The Second Annual marcus evens Drug Development for Neurodegenerative Diseases Conference, held in Boston, included topics covering new therapeutic developments in the field of neurodegenerative diseases. This conference report highlights selected presentations on biomarkers for neurodegenerative diseases; novel approaches to therapy for neurodegenerative disorders, including targeting PKCepsilon in Alzheimer's disease, small-molecule therapeutics for neurogenesis, neureglins to promote neurorecovery, and updates on several investigational drugs; and progress in neurodegenerative disease research, including measuring microtubule dynamics in Parkinson's disease and drug delivery to the brain. Investigational drugs discussed include NNI-251 (NeuroNascent Inc), neuregulins including glial growth factor 2 (Acorda Therapeutics Inc), AL-108 (Allon Therapeutics Inc) and EVP-0962 (EnVivo Pharmaceuticals Inc).

  1. Research Innovation

    Science.gov (United States)

    EPA provides innovative research activities that help transform the protection of human health and the environment with high-risk, high-reward Pathfinder Innovation Projects, the P3 student competition, and low-cost air monitoring.

  2. Technology Innovation

    Science.gov (United States)

    EPA produces innovative technologies and facilitates their creation in line with the Agency mission to create products such as the stormwater calculator, remote sensing, innovation clusters, and low-cost air sensors.

  3. Responsive Innovation

    DEFF Research Database (Denmark)

    Pedersen, Carsten

    Although the importance of stakeholder networks has been recognized in recent years, a non-teleological model that incorporates their collective sensing into innovation processes has so far not been developed. Hence, this paper argues that traditional linear and sequential innovation models...... are insufficient in hypercompetitive environments. Instead, it is proposed that companies should ground their innovation processes in the collective sensing of frontline-employees and customers that operate around the organizational periphery. This frames the concept of responsive innovation, where key...

  4. Advancement on pharmacogenomics of partial antitumor drugs%部分抗肿瘤药物基因组学研究进展

    Institute of Scientific and Technical Information of China (English)

    华之卉; 侯颖; 宋洪涛

    2009-01-01

    Recently, diverse effects and side effects of antitumor drugs induced by individual difference have received considerable attention. Studies on pharmacogenomics show that genomic polymorphism is closely associated with individual difference and side effects of antitumor drugs. The paper summarizes the advancement on pharmacogenomics of partial antitumor drugs.%近年来,由于个体差异引起抗肿瘤药物疗效和毒副作用的不同受到越来越多的重视.药物基因组学的研究结果表明基因多态性与抗肿瘤药物个体间作用多样性及毒副作用之间的关系密切.本文就部分抗肿瘤药物基因组学的研究进展加以综述.

  5. Innovative Universities.

    Science.gov (United States)

    Barsi, Louis M.; Kaebnick, Gweneth W.

    1989-01-01

    The phenomenon of innovation within the university is examined, noting the possibility of innovation as a key to college vitality. A study was conducted using a group of institutions that demonstrated recent innovative spirit. Members of the American Association of State Colleges and Universities (AASCU), each has been recognized in an annual…

  6. Private versus social incentives for pharmaceutical innovation.

    Science.gov (United States)

    González, Paula; Macho-Stadler, Inés; Pérez-Castrillo, David

    2016-12-01

    We provide a theoretical framework to contribute to the current debate regarding the tendency of pharmaceutical companies to direct their R&D toward marketing products that are "follow-on" drugs of already existing drugs, rather than toward the development of breakthrough drugs. We construct a model with a population of patients who can be treated with drugs that are horizontally and vertically differentiated. In addition to a pioneering drug, a new drug can be marketed as the result of an innovative process. We analyze physician prescription choices and the optimal pricing decision of an innovative firm. We also characterize the incentives of the innovative firm to conduct R&D activities, disentangling the quest for breakthrough drugs from the firm effort to develop follow-on drugs. Our results offer theoretical support for the conventional wisdom that pharmaceutical firms devote too many resources to conducting R&D activities that lead to incremental innovations.

  7. Loading of Drug-Polymer Matrices in Microreservoirs for Oral Drug Delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Keller, Stephan Sylvest; Boisen, Anja

    2016-01-01

    For major advances in microfabricated drug delivery systems (DDS), fabrication methods with high throughput using biocompatible polymers are required. Once these DDS are fabricated, loading of drug poses a significant challenge. Here, hot punching is presented as an innovative method for drug...... loading in microfabricated DDS. The microfabricated DDS are microcontainers fabricated in photoresist SU-8 and biopolymer poly-L-lactic-acid (PLLA). Furosemide (F) drug is embedded in poly-ε-caprolactone (PCL) polymer matrix. This F-PCL drug polymer matrix is loaded in SU-8 and PLLA microcontainers using...... hot punching with >99% yield. Thus, it is illustrated that hot punching allows high-throughput, parallel loading of 3D polymer microcontainers with drug-polymer matrices in a single process step....

  8. Innovation network.

    Science.gov (United States)

    Acemoglu, Daron; Akcigit, Ufuk; Kerr, William R

    2016-10-11

    Technological progress builds upon itself, with the expansion of invention in one domain propelling future work in linked fields. Our analysis uses 1.8 million US patents and their citation properties to map the innovation network and its strength. Past innovation network structures are calculated using citation patterns across technology classes during 1975-1994. The interaction of this preexisting network structure with patent growth in upstream technology fields has strong predictive power on future innovation after 1995. This pattern is consistent with the idea that when there is more past upstream innovation for a particular technology class to build on, then that technology class innovates more.

  9. HIMSS Venture+ Forum and HX360 Provide Industry View of Health Technology Innovation, Startup and Investment Activity; Advancing the New Model of Care.

    Science.gov (United States)

    Burde, Howard A; Scarfo, Richard

    2015-01-01

    Presented by HIMSS, the Venture+ Forum program and pitch competition provides a 360-degree view on health technology investing and today's top innovative companies. It features exciting 3-minute pitch presentations from emerging and growth-stage companies, investor panels and a networking reception. Recent Venture+ Forum winners include TowerView Health, Prima-Temp, ActuaiMeds and M3 Clinician. As an industry catalyst for health IT innovation and business-building resource for growing companies and emerging technology solutions, HIMSS has co-developed with A VIA, a new initiative that addresses how emerging technologies, health system business model changes and investment will transform the delivery of care. HX360 engages senior healthcare leaders, innovation teams, investors and entrepreneurs around the vision of transforming healthcare delivery by leveraging technology, process and structure.

  10. Innovation hubs

    DEFF Research Database (Denmark)

    O´Hara, J.; Hansen, Poul H. Kyvsgård; Turner, N.

    2008-01-01

    "Whilst ‘incremental innovation' is an imperative for the short-to-medium term success of a company, there is also a need for companies to engage in innovation activity that goes beyond the incremental in order to guarantee long-term success. However, such ‘radical innovation' (RI) poses new...... challenges and requires new competencies, some of which may conflict with existing best-practices for incremental innovations. ‘Innovation hubs' are a type of organisational structure dedicated to RI projects that have been used by companies to manage these conflicts by maintaining a certain degree...... of separation from the culture and routines of the mainstream organisation. Unfortunately, it would appear that many attempts to set-up innovation hubs have ended in failure within a few years; not before considerable time, effort and resource has been expended. This paper reports on a study of six innovation...

  11. Ethical issues in surgical innovation.

    Science.gov (United States)

    Miller, Megan E; Siegler, Mark; Angelos, Peter

    2014-07-01

    Innovation is responsible for most advances in the field of surgery. Innovative approaches to solving clinical problems have significantly decreased morbidity and mortality for many surgical procedures, and have led to improved patient outcomes. While innovation is motivated by the surgeon's expectation that the new approach will be beneficial to patients, not all innovations are successful or result in improved patient care. The ethical dilemma of surgical innovation lies in the uncertainty of whether a particular innovation will prove to be a "good thing." This uncertainty creates challenges for surgeons, patients, and the healthcare system. By its very nature, innovation introduces a potential risk to patient safety, a risk that may not be fully known, and it simultaneously fosters an optimism bias. These factors increase the complexity of informed consent and shared decision making for the surgeon and the patient. Innovative procedures and their associated technology raise issues of cost and resource distribution in the contemporary, financially conscious, healthcare environment. Surgeons and institutions must identify and address conflicts of interest created by the development and application of an innovation, always preserving the best interest of the patient above the academic or financial rewards of success. Potential strategies to address the challenges inherent in surgical innovation include collecting and reporting objective outcomes data, enhancing the informed consent process, and adhering to the principles of disclosure and professionalism. As surgeons, we must encourage creativity and innovation while maintaining our ethical awareness and responsibility to patients.

  12. DUAL-MODE PROPULSION SYSTEM ENABLING CUBESAT EXPLORATION OF THE SOLAR SYSTEM NASA Innovative Advanced Concepts (NIAC) Phase I Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Nathan Jerred; Troy Howe; Adarsh Rajguru; Dr. Steven Howe

    2014-06-01

    -based systems. The second scenario allows for the production of electrical power, which is then available for electric-based propulsion. Additionally, once at location the production of electrical power can be dedicated to the payload’s communication system for data transfer. Ultimately, the proposed dual-mode propulsion platform capitalizes on the benefits of two types of propulsion methods – the thrust of thermal propulsion ideal for quick orbital maneuvers and the specific impulse of electric propulsion ideal for efficient inter-planetary travel. Previous versions of this RTR-based concept have been studied for various applications [NETS 1-3]. The current version of this concept is being matured through a NASA Innovative Advanced Concepts (NIAC) Phase I grant, awarded for FY 2014. In this study the RTR concept is being developed to deliver a 6U CubeSat payload to the orbit of the Saturnian moon - Enceladus. Additionally, this study will develop an entire mission architecture for Enceladus targeting a total allowable launch mass of 1,000 kg.

  13. Chronomodulated drug delivery system: A comprehensive review on the recent advances in a new sub-discipline of ′chronopharmaceutics′

    Directory of Open Access Journals (Sweden)

    Bisht Rohit

    2011-01-01

    Full Text Available With the advancement in the field of chronobiology, modern drug delivery approaches have been elevated to a new concept of chronopharmacology, that is, the ability to deliver the therapeutic agent to a patient in a staggered profile. The mammalian circadian pacemaker resides in the paired suprachiasmatic nuclei and influences a multitude of biological processes, including the sleep-wake rhythm. Clock genes are the genes that control the circadian rhythms in physiology and behavior. Twenty-four hours rhythms are demonstrated for the function of physiology and the pathophysiology of diseases. The effectiveness and toxicity of many drugs vary depending on the dosing time. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics, but also the pharmacokinetics of medications. The underlying mechanisms are associated with the 24-hour rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. New technology for delivering medications precisely in a time-modulated fashion, by bedside or ambulatory pumps, is being developed to manage human diseases. From the point of view of pharmaceutics, the application of a biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tablets and capsules, and a special drug delivery system, to synchronize the drug concentrations with the rhythms in the disease activity. Therefore, the present article gives an overview of the dosing time-dependent alterations in the therapeutic outcome and safety of the drug. The underlying mechanisms and usefulness are introduced from the point of view of chronopharmacology and chronotherapy.

  14. Evaluating Innovation and Moral Hazard in Pharmaceuticals

    OpenAIRE

    Paris Cleanthous

    2011-01-01

    This paper formulates an empirical methodology that evaluates pharmaceutical innovation in the American antidepressant market by quantifying patient welfare benefits from innovation. While evaluating pharmaceutical innovation in antidepressants, I uncover and address the moral hazard issue that arises due to the existence of prescription drug insurance coverage. A combination of market-level data, drug and patient characteristics are used to estimate demand for all antidepressants between 198...

  15. Sensitive innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    Present paper discusses sources of innovation as heterogenic and at times intangible processes. Arguing for heterogeneity and intangibility as sources of innovation originates from a theoretical reading in STS and ANT studies (e.g. Callon 1986, Latour 1996, Mol 2002, Pols 2005) and from field work...... in the area of mental health (Dupret Søndergaard 2009, 2010). The concept of sensitive innovation is developed to capture and conceptualise exactly those heterogenic and intangible processes. Sensitive innovation is therefore primarily a way to understand innovative sources that can be......, but are not necessarily, recognized and acknowledged as such in the outer organisational culture or by management. The added value that qualifies these processes to be defined as “innovative” are thus argued for along different lines than in more traditional innovation studies (e.g. studies that build on the classic...

  16. Innovation @ NASA

    Science.gov (United States)

    Roman, Juan A.

    2014-01-01

    This presentation provides an overview of the activities National Aeronautics and Space Administration (NASA) is doing to encourage innovation across the agency. All information provided is available publicly.

  17. Drug Elucidation: Invertebrate Genetics Sheds New Light on the Molecular Targets of CNS Drugs

    Directory of Open Access Journals (Sweden)

    Donard S. Dwyer

    2014-07-01

    Full Text Available Many important drugs approved to treat common human diseases were discovered by serendipity, without a firm understanding of their modes of action. As a result, the side effects and interactions of these medications are often unpredictable, and there is limited guidance for improving the design of next-generation drugs. Here, we review the innovative use of simple model organisms, especially Caenorhabditis elegans, to gain fresh insights into the complex biological effects of approved CNS medications. Whereas drug discovery involves the identification of new drug targets and lead compounds/biologics, and drug development spans preclinical testing to FDA approval, drug elucidation refers to the process of understanding the mechanisms of action of marketed drugs by studying their novel effects in model organisms. Drug elucidation studies have revealed new pathways affected by antipsychotic drugs, e.g., the insulin signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor. Similarly, novel targets of antidepressant drugs and lithium have been identified in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling pathway, respectively. Elucidation of the mode of action of anesthetic agents has shown that anesthesia can involve mitochondrial targets, leak currents and gap junctions. The general approach reviewed in this article has advanced our knowledge about important drugs for CNS disorders and can guide future drug discovery efforts.

  18. 某地药品安全监管信息化建设现状分析及创新策略%Situation and Innovation Strategy of Construction of Drug Safety Administration Information in A City

    Institute of Scientific and Technical Information of China (English)

    罗莉; 陈晓隽; 陈勇

    2016-01-01

    Objective To strengthen and innovate the construction of drug safety administration information in a city. Methods To in-vestigate the construction situation of the drug safety administration in one food and drug administration,and to analyze the current situ-ation and deficiency of the drug safety administration system. Results and Conclusion The countermeasure and suggestion of the con-struction of the drug safety administration were put forward on the basis of big data:to establish the big data thinking,innovative drug regulatory mode;build big data centers,perfect the drug safety administration model divined by information,construct the 3 big basic da-ta bases of pharmaceutical information,pharmaceutical enterprise subject information,pharmaceutical enterprise behavior,and consolidate the basis of information interconnection and intercommunication.%目的:促进药品安全监管信息化建设的加强和创新。方法对某地食品药品监管部门药品安全监管信息化建设情况进行调研,对其药品安全监管信息系统的运行现状及存在的不足进行分析。结果与结论基于大数据思维提出了药品安全监管信息化建设的对策与建议,即建立“大数据思维”,创新药品安全监管模式;构建大数据中心,完善信息驱动下的药品安全监管模式;建设药品信息、医药企业主体信息、医药企业行为三大基础数据库,夯实信息互联互通基础。

  19. Service innovation in China

    DEFF Research Database (Denmark)

    Slepniov, Dmitrij; Jin, Jun

    2014-01-01

    Purpose – The aim of this paper is to advance our understanding of service innovation in China and to identify the major drivers and impediments for manufacturing companies pushing into services in China. Design/methodology/approach – By employing an in-depth longitudinal case of a Chinese company...... the industry by increasing transparency and connectedness between track owners and third-party logistics (3PL) companies. We find that the service concept helped the company to diversify as well as enhanced its growth and competitive advantages in a very competitive environment of the second and third tier...... Chinese cities. Both internal and external factors played a significant role in influencing the development and implementation of service innovation in the case. The paper details and discusses the factors that affect service innovation in China. Research Limitations – The study is exposed...

  20. Advances in simultaneous DSC-FTIR microspectroscopy for rapid solid-state chemical stability studies: some dipeptide drugs as examples.

    Science.gov (United States)

    Lin, Shan-Yang; Wang, Shun-Li

    2012-04-01

    The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations.

  1. 扁平苔藓药物治疗进展%Advances in the drug treatment of lichen planus

    Institute of Scientific and Technical Information of China (English)

    周勐; 简晓清

    2013-01-01

    Lichen planus ( LP ) is a chronic or subacute inflammatory dermatosis of the mucocutaneous surfaces that can present with a variety of clinical manifestations. The pathogenesis of LP is unknown and LP is difficult to cure. A variety of drugs are used to treat LP, in addition to commonly used drugs such as steroid hormones, retinoic acid, immunosuppressant, etc. There are sul-fasalazine, levamisole, biological agents and other drugs. In this paper, the latest research on the LP drug therapy are reviewed, in order to provide drug information and treatment guidance for the correct treatment of LP.%扁平苔藓(lichen planus,LP)是慢性或亚急性炎症性疾病,病因未明,治疗较困难.现在有多种药物用于治疗LP,除类固醇激素、维甲酸类、免疫抑制剂等常用药物外,还有柳氮磺吡啶、左旋咪唑、生物制剂等药物.文中就近年来治疗LP的药物研究进展做一综述,为正确治疗LP提供药物信息和指导.

  2. High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery

    Directory of Open Access Journals (Sweden)

    Cervantes Serena

    2009-06-01

    Full Text Available Abstract Background Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs. Discovering novel compounds to be used as antimalarials is expedited by the use of a high-throughput screen (HTS to detect parasite growth and proliferation. Fluorescent dyes that bind to DNA have replaced expensive traditional radioisotope incorporation for HTS growth assays, but do not give additional information regarding the parasite stage affected by the drug and a better indication of the drug's mode of action. Live cell imaging with RNA dyes, which correlates with cell growth and proliferation, has been limited by the availability of successful commercial dyes. Results After screening a library of newly synthesized stryrl dyes, we discovered three RNA binding dyes that provide morphological details of live parasites. Utilizing an inverted confocal imaging platform, live cell imaging of parasites increases parasite detection, improves the spatial and temporal resolution of the parasite under drug treatments, and can resolve morphological changes in individual cells. Conclusion This simple one-step technique is suitable for automation in a microplate format for novel antimalarial compound HTS. We have developed a new P. falciparum RNA high-content imaging growth inhibition assay that is robust with time and energy efficiency.

  3. Managing Innovation.

    Science.gov (United States)

    Mason, Marilyn Gell

    1991-01-01

    Describes one library's use of technological innovation to provide Associated Press updates over the library's 24-hour dial-up service during the Persian Gulf War. Suggests five rules for innovation: (1) develop a shared vision; (2) foster frequent, formal, and informal communication; (3) empower employees; (4) take limited risks; and (5) use, but…

  4. Informal Innovation

    DEFF Research Database (Denmark)

    Hartmann, Mia Rosa Koss; Hartmann, Rasmus Koss

    Informal innovation, defined as the development and putting-into-use of novel solutions by non-R&D employees without prior formal approval from or subsequent revealing to superiors, has been recurrently observed in organizational research. But even as it is increasingly recognized that R&D is not......Informal innovation, defined as the development and putting-into-use of novel solutions by non-R&D employees without prior formal approval from or subsequent revealing to superiors, has been recurrently observed in organizational research. But even as it is increasingly recognized that R......&D is not the only plausible source of innovation inside organizations, informal innovation has yet to be systematically explored or theorized. We propose a theory of informal innovation based on analyses of prior literature and mixed-method, multi-site studies of innovation at the working level of two extreme......-case organizations. We propose that informal innovation occurs as 1) employees personally experience problems that they believe are not recognized or prioritized by superiors; 2) some employees are able to develop solutions, essentially at no cost; 3) innovators face no benefits from revealing to superiors, but can...

  5. Innovation process

    DEFF Research Database (Denmark)

    Kolodovski, A.

    2006-01-01

    Purpose of this report: This report was prepared for RISO team involved in design of the innovation system Report provides innovation methodology to establish common understanding of the process concepts and related terminology The report does not includeRISO- or Denmark-specific cultural, economic...

  6. MAPPING INNOVATION

    DEFF Research Database (Denmark)

    Thuesen, Christian Langhoff; Koch, Christian

    2011-01-01

    By adopting a theoretical framework from strategic niche management research (SNM) this paper presents an analysis of the innovation system of the Danish Construction industry. Theories within SNM look upon innovation in a sector as a socio-technical phenomenon and identifies three levels of socio......-technical interaction within which sectorial innovation can be explained. The analysis shows a multifaceted landscape of innovation around an existing regime, built in the existing ways of working and developing over generations. The regime is challenged from various niches and the sociotechnical landscape through...... trends as globalization. Three niches (Lean Construction, BIM and System Deliveries) are subject to a detailed analysis showing partly incompatible rationales and various degrees of innovation potential. The paper further discusses how existing policymaking operates in a number of tensions one being...

  7. Accidental Innovation

    DEFF Research Database (Denmark)

    Austin, Robert D.; Devin, Lee; Sullivan, Erin E.

    2012-01-01

    Historical accounts of human achievement suggest that accidents can play an important role in innovation. In this paper, we seek to contribute to an understanding of how digital systems might support valuable unpredictability in innovation processes by examining how innovators who obtain value from...... they incorporate accidents into their deliberate processes and arranged surroundings. By comparing makers working in varied conditions, we identify specific factors (e.g., technologies, characteristics of technologies) that appear to support accidental innovation. We show that makers in certain specified...... conditions not only remain open to accident but also intentionally design their processes and surroundings to invite and exploit valuable accidents. Based on these findings, we offer advice for the design of digital systems to support innovation processes that can access valuable unpredictability....

  8. Participatory Innovation

    DEFF Research Database (Denmark)

    Buur, Jacob; Matthews, Ben

    2008-01-01

    An increasing number of corporations engage with users in co-innovation of products and services. But there are a number of competing perspectives on how best to integrate these understandings into existing corporate innovation development processes. This paper maps out three of the dominant...... approaches, compares them in terms of goals, methods and basic philosophy, and shows how they may beneficially enrich one another. We will present an industrial innovation case that has been instrumental to the development of what we have termed ‘Participatory Innovation’. Based on this we will list...... the challenges such an approach sets to innovation management, and discuss research directions we see as fundamental to the development of the field of user-driven innovation. Udgivelsesdato: September...

  9. Everyday Innovation

    DEFF Research Database (Denmark)

    Lippke, Lena; Wegener, Charlotte

    2014-01-01

    Purpose – The purpose of this paper is to explore how vocational teachers’ everyday practices can constitute innovative learning spaces that help students to experience engagement and commitment towards education and thus increase their possibilities for completing their studies despite notable...... difficulties. Design/methodology/approach – Based on two ethnographic field studies, we analyse vocational teaching situations in which teachers and students engage in daily remaking of the vocational educational training practice. It is argued that these everyday situations can be understood as innovative...... transformation of participation and practice. Findings – The exploration of teachers’ practicing new learning spaces sheds light on innovation potential embedded in everyday educational practices. The paper thus challenges the celebration of radical innovation and argues that innovation emerges from everyday...

  10. Responsible innovation

    CERN Document Server

    De Woot, Philippe

    2015-01-01

    Economic development is rooted in disruption, not in equilibrium. And a powerful engine of economic development is innovation; but is this innovation always for the common good? The dark side of the extraordinary dynamism of innovation lies precisely in its destructive power. If simply left to market forces, it could lead to social chaos and great human suffering. To face the challenges of our time, we must create the proper climate and culture to develop strong entrepreneurial drive. But, more than ever, we must give this entrepreneurial drive its ethical and societal dimensions. Responsible innovation means a more voluntary orientation towards the great problems of the 21st century, e.g. depletion of the planet's resources, rising inequality, and new scientific developments potentially threatening freedom, democracy and human integrity. We need to transform our ceaseless creativity into real progress for humankind. In this respect, the rapid development of social innovation opens the door for new methods an...

  11. Online Innovation

    DEFF Research Database (Denmark)

    Vujovic, Sladjana; Ulhøi, John Parm

    2008-01-01

    ways of communicating, cooperating and coordinating during the innovation and product development process. Moreover, it challenges the traditional business model in that it forces the actors involved to shift the focus from the innovation itself to the identification of new supporting services higher...... implications for existing software manufacturers. The paper therefore includes the case of IBM, a company which has successfully integrated this new and more open way of collaboration into its business model. Findings - The paper concludes that online computer-based innovation fundamentally challenges current......  Purpose - The aim of this paper is to investigate the role of online networking during the innovation process, including its role(s) in communication, cooperation and coordination. The paper neither implicitly assumes that online computer-based networking is a prerequisite for the innovation...

  12. Recent advances regarding the role of ABC subfamily C member 10 (ABCC10) in the efflux of antitumor drugs

    Institute of Scientific and Technical Information of China (English)

    Rishil J. Kathawala; Yi-Jun Wang; Charles R. Ashby Jr; Zhe-Sheng Chen

    2014-01-01

    ABCC10, also known as multidrug-resistant protein 7 (MRP7), is the tenth member of the C subfamily of the ATP-binding cassette (ABC) superfamily. ABCC10 mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs. The ABCC10 transporter is a 171-kDa protein that is localized on the basolateral cell membrane. ABCC10 is a broad-specificity transporter of xenobiotics, including antitumor drugs, such as taxanes, epothilone B, vinca alkaloids, and cytarabine, as wel as modulators of the estrogen pathway, such as tamoxifen. In recent years, ABCC10 inhibitors, including cepharanthine, lapatinib, erlotinib, nilotinib, imatinib, sildenafil, and vardenafil, have been reported to overcome ABCC10-mediated MDR. This review discusses some recent and clinically relevant aspects of the ABCC10 drug efflux transporter from the perspective of current chemotherapy, particularly its inhibition by tyrosine kinase inhibitors and phosphodiesterase type 5 inhibitors.

  13. 阿尔茨海默病药物治疗进展%Advance of drug therapy for Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    赵烨; 徐美华; 董文心

    2011-01-01

    The pathogenesy of Alzheimer's disease (AD) is complex and unclear. The drug therapy for AD currently is principally to improve the symptoms. This review describes the common and new drugs for AD to provide some references for AD drug therapy in clinic.%阿尔茨海默病(AD)发病机制复杂,现有药物大多以缓解病情为主要治疗目的,尚未有能彻底治愈的有效药物.本文综述目前常用的AD治疗药物和具有前景的新型治疗药物,以期能够对AD的药物治疗提供参考.

  14. From innovation to co-innovation? An exploration of African agrifood chains

    NARCIS (Netherlands)

    Bitzer, V.C.; Bijman, J.

    2015-01-01

    Purpose – Building on recent advances in innovation research on developing country agriculture, this paper explores the concept of co-innovation, i.e. innovations that combine technological, organisational and institutional changes and that encompass different actors in and around the value chain. T

  15. A Breath of Fresh Air? Firm Type, Scale, Scope, and Selection Effects in Drug Development

    OpenAIRE

    Ashish Arora; Alfonso Gambardella; Laura Magazzini; Fabio Pammolli

    2009-01-01

    This paper compares the innovation performance of established pharmaceutical firms and biotech companies, controlling for differences in the scale and scope of research. We develop a structural model to analyze more than 3,000 drug research and development projects advanced to preclinical and clinical trials in the United States between 1980 and 1994. Key to our approach is careful attention to the issue of selection. Firms choose which compounds to advance into clinical trials. This choice d...

  16. Indigenous innovation in China

    DEFF Research Database (Denmark)

    Jin, Jun; Slepniov, Dmitrij

    2012-01-01

    In the past two decades, China has earned the reputation of ‘manufacturing power house’ of the world. Chinese companies in their vast numbers have been very successful in exploiting their access to low-cost labour and have established themselves as unbeatable high volume low-cost manufacturing...... a foothold in these markets and to tap into the advanced technologies and concepts originating from this developed context. Another category of Chinese companies includes those who seek to move from routine transactional tasks to more innovation-intensive concepts while remaining in China and relying......, this paper seeks to advance our understanding of indigenous innovation in China and to identify its major drivers and impediments....

  17. Accelerating advanced-materials commercialization

    Science.gov (United States)

    Maine, Elicia; Seegopaul, Purnesh

    2016-05-01

    Long commercialization times, high capital costs and sustained uncertainty deter investment in innovation for advanced materials. With appropriate strategies, technology and market uncertainties can be reduced, and the commercialization of advanced materials accelerated.

  18. 20 Observations on Innovation

    Science.gov (United States)

    2016-08-01

    Configuration Management Division’s Small Caliber Systems Branch at the Army Armament Research, Development and Engineering Center in Rock Island...government than in the private sector; that’s just the way it is. It’s not easy, but it can be done. For those leaders and innovators who work inside the...educating kids, is advancing the goals of the orga­ nization. A school administrator who worries about increas­ ing budgets, reducing classroom sizes and

  19. Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device in patients with mild to moderate obstructive sleep apnoea.

    Science.gov (United States)

    De Corso, E; Bastanza, G; Della Marca, G; Grippaudo, C; Rizzotto, G; Marchese, M R; Fiorita, A; Sergi, B; Meucci, D; Di Nardo, W; Paludetti, G; Scarano, E

    2015-12-01

    Nowadays oral appliance therapy is recognised as an effective therapy for many patients with primary snoring and mild to moderate obstructive sleep apnoea (OSA), as well as those with more severe OSA who cannot tolerate positive airway pressure (PAP) therapies. For this reason, it is important to focus on objective criteria to indicate which subjects may benefit from treatment with a mandibular advancement device (MAD). Various anthropometric and polysomnographic predictors have been described in the literature, whereas there are still controversies about the role of drug-induced sleep endoscopy (DISE) and advancement bimanual manoeuvre as predictor factors of treatment outcome by oral device. Herein, we report our experience in treatment of mild moderate OSA by oral appliance selected by DISE. We performed a single institution, longitudinal prospective evaluation of a consecutive group of mild moderate patients with obstructive sleep apnoea syndrome who underwent DISE. During sleep endoscopy, gentle manoeuvre of mandibular advancement less than 5 mm was performed. In 30 of 65 patients (46.2%) we obtained an unsuccessful improvement of airway patency whereas in 35 of 65 patients (53.8%) the improvement was successful and patients were considered suitable for oral device application. Because 7 of 35 patients were excluded due to conditions interfering with oral appliance therapy, we finally treated 28 patients. After 3 months of treatment, we observed a significant improvement in the Epworth medium index [(7.35 ± 2.8 versus 4.1 ± 2.2 (p DISE for MAD therapy. In the current study, mandibular advancement splint therapy was successfully prescribed on the basis not only of severity of disease, as determined by the subject's initial AHI, but also by DISE findings combined with results of gentle mandibular advancement manoeuvre allowing direct view of the effects of mandibular protrusion on breathing spaces in obstruction sites, and showing good optimisation of

  20. Recent advances in traditional plant drugs and orchids%传统植物药和兰花的最新进展

    Institute of Scientific and Technical Information of China (English)

    KONG Jin-Ming; GOH Ngoh-Khang; CHIA Lian-Sai; CHLA Tet-Fatt

    2003-01-01

    The main objective of this paper is to review recent advances in plant drug research and developments in orchid study, in an attempt to provide useful references for plant drag studies. Plants have been used as medicine for millennia. Out of estimated 250 000 to 350 000 plant species identified so far, about 35 000 are used worldwide for medicinal purposes. It has been confirmed by WHO that herbal medicines serve the health needs of about 80 percent of the world's population; especially for millions of people in the vast rural areas of developing countries.Meanwhile, consumers in developed countries are becoming disillusioned with modem healthcare and are seeking alternatives. The recent resurgence of plant remedies results from several factors: 1) the effectiveness of plant medicines; 2) the side effect of most modem drugs; and 3) the development of science and technology. It has been estimated that in the mid-1990s over 200 companies and research organizations worldwide are screening plant and animal compounds for medicinal properties. Actually, several important drugs used in modern medicine have come from medicinal plant studies, eg, taxol/paclitaxel, vinblastine, vincristine, topotecan, irinotecan, etoposide, teniposide,etc. As for drugs derived from orchids, some novel discoveries, both in phytochemical and pharmacological properties, were reported by some universities. However, studies on plants are very limited. Only about a third of the million or so species of higher plants have been identified and named by scientists. Of those named, only a tiny fraction has been studied. Nowadays the linking of the indigenous knowledge of medicinal plants to modem research activities provides a new approach, which makes the rate of discovery of drugs much more effective than with random collection.

  1. Advances in research on targeting drug delivery system%靶向递释系统的研究进展

    Institute of Scientific and Technical Information of China (English)

    钟延强

    2012-01-01

    靶向递释系统(targeting drug delivery system,TDDS)能够选择性作用于病变部位,控制药物的分布与释放,提高药效和降低毒副作用,已成为癌症等疾病治疗领域的研究热点之一.本文综述J各类TDDS的机制、载体类型、制备技术和体内外靶向性,对近年来靶向递释系统的研究现状、未来产品研发与临床应用的可行性进行了探讨.%Targeting drug delivery system (TDDS) could efficiently and specially deliver antitumor and other medicines to the lesion regions with high potency and low toxicity. It could also change the distribution and releasing rate of encapsulated drugs in vivo. TDDS has emerged as a kind of novel drug delivery system in recent years. Targeting mechanism,carrier types, preparation amd targeting effect in vivo and in vitro of TDDS are reviewed. Current research on TDDS, development of new products and its perspective clinical applications in the future are also discussed in this paper.

  2. Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

    Directory of Open Access Journals (Sweden)

    Smita Raghuvanshi

    2014-01-01

    Full Text Available Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

  3. Innovative and Advanced Coupled Neutron Transport and Thermal Hydraulic Method (Tool) for the Design, Analysis and Optimization of VHTR/NGNP Prismatic Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Rahnema, Farzad; Garimeela, Srinivas; Ougouag, Abderrafi; Zhang, Dingkang

    2013-11-29

    This project will develop a 3D, advanced coarse mesh transport method (COMET-Hex) for steady- state and transient analyses in advanced very high-temperature reactors (VHTRs). The project will lead to a coupled neutronics and thermal hydraulic (T/H) core simulation tool with fuel depletion capability. The computational tool will be developed in hexagonal geometry, based solely on transport theory without (spatial) homogenization in complicated 3D geometries. In addition to the hexagonal geometry extension, collaborators will concurrently develop three additional capabilities to increase the code’s versatility as an advanced and robust core simulator for VHTRs. First, the project team will develop and implement a depletion method within the core simulator. Second, the team will develop an elementary (proof-of-concept) 1D time-dependent transport method for efficient transient analyses. The third capability will be a thermal hydraulic method coupled to the neutronics transport module for VHTRs. Current advancements in reactor core design are pushing VHTRs toward greater core and fuel heterogeneity to pursue higher burn-ups, efficiently transmute used fuel, maximize energy production, and improve plant economics and safety. As a result, an accurate and efficient neutron transport, with capabilities to treat heterogeneous burnable poison effects, is highly desirable for predicting VHTR neutronics performance. This research project’s primary objective is to advance the state of the art for reactor analysis.

  4. Funding pharmaceutical innovation through direct tax credits.

    Science.gov (United States)

    Lybecker, Kristina M; Freeman, Robert A

    2007-07-01

    Rising pharmaceutical prices, increasing demand for more effective innovative drugs and growing public outrage have heightened criticism of the pharmaceutical industry. The public debate has focused on drug prices and access. As a consequence, the patent system is being reexamined as an efficient mechanism for encouraging pharmaceutical innovation and drug development. We propose an alternative to the existing patent system, instead rewarding the innovating firm with direct tax credits in exchange for marginal cost pricing. This concept is based on the fundamental assumption that innovation that benefits society at large may be financed publicly. As an industry which produces a social good characterized by high fixed costs, high information and regulatory costs, and relatively low marginal costs of production, pharmaceuticals are well-suited to such a mechanism. Under this proposal, drug prices fall, consumer surplus increases, access is enhanced, and the incentives to innovate are preserved.

  5. Controlled drug delivery systems towards new frontiers in patient care

    CERN Document Server

    Rossi, Filippo; Masi, Maurizio

    2016-01-01

    This book offers a state-of-the-art overview of controlled drug delivery systems, covering the most important innovative applications. The principles of controlled drug release and the mechanisms involved in controlled release are clearly explained. The various existing polymeric drug delivery systems are reviewed, and new frontiers in material design are examined in detail, covering a wide range of polymer modification techniques. The concluding chapter is a case study focusing on use of a drug-eluting stent. The book is designed to provide the reader with a complete understanding of the mechanisms and design of controlled drug delivery systems, and to this end includes numerous step-by-step tutorials. It illustrates how chemical engineers can advance medical care by designing polymeric delivery systems that achieve either temporal or spatial control of drug delivery and thus ensure more effective therapy that eliminates the potential for both under-and overdosing.

  6. Participatory Innovation

    DEFF Research Database (Denmark)

    Buur, Jacob; Matthews, Ben

    In this paper we discuss the potential for Participatory Design (PD) to make a fundamental contribution to the business-oriented field of user-driven innovation, taking note of where we find PD can best benefit from interaction with this other field. We examine some of the challenges that must...... be addressed if PD is to contribute to innovation processes in companies. We conclude by presenting a research agenda comprising of six promising topics to shape a new discipline of Participatory Innovation....

  7. Responsive Innovation

    DEFF Research Database (Denmark)

    Pedersen, Carsten

    of the firm’s daily operations. Yet, they are rarely asked to provide updated information about critical issues. The present paper seeks to conceptually develop the notion of responsive innovation, by drawing on literary streams concerning collective sensing, strategic issue diagnosis and integra......-tive strategy within a micro foundations perspective. It is posited that companies should root their innovation processes in the collective sensing of frontline-employees and customers that operate around the organizational periphery. This frames the con-cept of responsive innovation, where individuals engaged...

  8. Design & Innovation

    DEFF Research Database (Denmark)

    Boelskifte, Per; Jørgensen, Ulrik

    2005-01-01

    The new design and innovation programme at DTU is challenging some of the standard concepts dominating most engineering educations. The programme, its background, context and basic educational ideas are presented and discussed in this paper. To build competences that match the need for innovative...... and design oriented engineers in industry and society has turned out to challenge a number of the standard – and often taken for granted – concepts in engineering education still dominated world wide by rather strict norms and concepts of learning that do not challenge the students creativity and innovative...

  9. 水飞蓟素纳米传递系统的研究进展%Advances in the nanoparticle drug delivery systems of silymarin

    Institute of Scientific and Technical Information of China (English)

    陈美婉; 谭雯; 王胜鹏; 钟章锋; 王一涛

    2011-01-01

    The recent advances in nanoscience and nanotechnology have greatly facilitated the development of nanoparticle drug delivery system.A nanoparticle drug delivery system of silymarin will improve its poor solubility in water and oil,thus enhancing its bioavailability.A variety of nanoparticle formulations of silymarin such as solid lipid nanoparticles,microemulsion and self-emulsifying drug delivery system,and liposomes have been extensively investigated.This paper reviews the advances of these formulations on their preparation and characterization,absorption and bioavailability,as well as in vivo and in vitro studies,in order to provide an assessment of current research for further pharmaceutical studies of silymarin.%纳米科学和纳米技术在纳米药物传递系统中具有很大的潜力.水飞蓟素纳米药物传递系统的研究和开发将改善其水溶性和脂溶性,并提高生物利用度.固体脂质纳米粒、微乳、自微乳和脂质体等一系列水飞蓟素纳米处方的研究已越来越受到关注.本文综述了水飞蓟素纳米制剂的制备表征,性能评价,吸收、生物利用度等体内外研究,为其制剂的进一步研究提供科学基础.

  10. A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes

    Directory of Open Access Journals (Sweden)

    Li T

    2013-10-01

    Full Text Available Tianshu Li, Shinji TakeokaDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns, Shinjuku-ku, Tokyo, JapanAbstract: Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol% of maleimide-polyethylene glycol (PEG to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG/cholesterol/poly(ethylene glycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG5000-DSPE/maleimide-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03. Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (≥2-fold internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of

  11. 牙周局部缓释给药系统研究进展%Advance in research on periodontal sustained-release local drug delivery systems

    Institute of Scientific and Technical Information of China (English)

    刘庆晓; 杨美燕; 高春生

    2009-01-01

    Periodontal disease is a kind of local inflammatory and destructive diseases,and it is one of the most common human oral diseases. Compared with systemic administration,periodontal sustained-release local drug delivery systems can not only achieve high drug concentration and slow drug release in periodontal pocket,but also minimize side effects and bacterial resistance to drugs caused by systemic administration. Therefore,periodontal sus-tained - release local drug delivery systems have become the focus of the study on periodontal disease therapy at home and abroad. At present,the periodontal sustained-release local drug delivery systems include fiber,film,micro-spheres,gels,stylus and bucco-adhesive tablets. In this article,we reviewed the advance in research on periodontal sustained-release local drug delivery systems.%牙周病是局部炎症破坏性疾病,是人类最常见的口腔疾病之一.与全身给药相比,牙周局部缓释给药系统不仅使药物在牙周袋内达到高浓度,持续杀灭牙周致病菌,而且可以减少全身给药造成的不良反应和细菌耐药性.因此运用局部缓释给药系统治疗牙周病已成为国内外的研究热点,目前已有纤维剂、膜剂、微球、缓释凝胶、棒剂和口腔黏膜粘附片等牙周局部缓释给药系统在临床中使用或已有文献报道.文中主要围绕治疗牙周病的各种局部给药剂型的处方设计原理、关键辅料性质及其制剂优缺点等,详细综述牙周局部缓释给药系统的研究进展.

  12. Advanced in silico approaches for drug discovery: Mining information from multiple biological and chemical data through mtk-QSBER and pt-QSPR strategies.

    Science.gov (United States)

    Speck-Planche, Alejandro; Cordeiro, Maria Natália Dias Soeiro

    2017-01-24

    The last decade has been seeing an increase of public-private partnerships in drug discovery, mostly driven by factors such as the decline in productivity, the high costs, time, and resources needed, along with the requirements of regulatory agencies. In this context, traditional computer-aided drug discovery techniques have been playing an important role, enabling the identification of new molecular entities at early stages. However, recent advances in chemoinformatics and systems pharmacology, alongside with a growing body of high quality, publicly accessible medicinal chemistry data, have led to the emergence of novel in silico approaches. These novel approaches are able to integrate a vast amount of multiple chemical and biological data into a single modeling equation. The present review analyzes two main kinds of such cutting-edge in silico approaches. In a first subsection, we discuss the updates on multitasking models for quantitative structure-biological effect relationships (mtk-QSBER), whose applications have been significantly increasing in the past years. In a second subsection, we provide detailed information regarding a novel approach that combines perturbation theory with quantitative structure-property relationships modeling tools (pt-QSPR). Finally, and most importantly, we show that the joint use of mtk-QSBER and pt-QSPR modeling tools are apt to guide drug discovery through its multiple stages: from in vitro assays to preclinical studies and clinical trials.

  13. Public policy and pharmaceutical innovation.

    Science.gov (United States)

    Grabowski, H G

    1982-09-01

    Historically, new drug introductions have played a central role in medical progress and the availability of cost-effective therapies. Nevertheless, public policy toward pharmaceuticals has been characterized in recent times by increasingly stringent regulatory controls, shorter effective patent terms, and increased encouragement of generic product usage. This has had an adverse effect on the incentives and capabilities of firms to undertake new drug research and development activity. The industry has experienced sharply rising research and development costs, declining annual new drug introductions, and fewer independent sources of drug development. This paper considers the effects of government regulatory policies on the pharmaceutical innovation process from several related perspectives. It also examines the merits of current public policy proposals designed to stimulate drug innovation including patent restoration and various regulatory reform measures.

  14. An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.

    Science.gov (United States)

    Kimishima, Atsushi; Wenthur, Cody J; Zhou, Bin; Janda, Kim D

    2017-01-20

    Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design. Administration of these vaccines resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.

  15. The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

    Science.gov (United States)

    Molzon, J A; Giaquinto, A; Lindstrom, L; Tominaga, T; Ward, M; Doerr, P; Hunt, L; Rago, L

    2011-04-01

    The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

  16. Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report

    Directory of Open Access Journals (Sweden)

    Patricia Miranda Romero

    2015-02-01

    Full Text Available Trastuzumab emtansina (T-DM1 is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC, who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS and the overall survival (OS. It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 €. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at € 70,490,850. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients

  17. Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation report.

    Science.gov (United States)

    Miranda Romero, Patricia; Marín Gil, Roberto

    2015-05-01

    Trastuzumab emtansina (T-DM1) is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC), who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS) and the overall survival (OS). It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 €. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at € 70,490,850. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients.

  18. Two-photon polymerization microfabrication of hydrogels: an advanced 3D printing technology for tissue engineering and drug delivery.

    Science.gov (United States)

    Xing, Jin-Feng; Zheng, Mei-Ling; Duan, Xuan-Ming

    2015-08-07

    3D printing technology has attracted much attention due to its high potential in scientific and industrial applications. As an outstanding 3D printing technology, two-photon polymerization (TPP) microfabrication has been applied in the fields of micro/nanophotonics, micro-electromechanical systems, microfluidics, biomedical implants and microdevices. In particular, TPP microfabrication is very useful in tissue engineering and drug delivery due to its powerful fabrication capability for precise microstructures with high spatial resolution on both the microscopic and the nanometric scale. The design and fabrication of 3D hydrogels widely used in tissue engineering and drug delivery has been an important research area of TPP microfabrication. The resolution is a key parameter for 3D hydrogels to simulate the native 3D environment in which the cells reside and the drug is controlled to release with optimal temporal and spatial distribution in vitro and in vivo. The resolution of 3D hydrogels largely depends on the efficiency of TPP initiators. In this paper, we will review the widely used photoresists, the development of TPP photoinitiators, the strategies for improving the resolution and the microfabrication of 3D hydrogels.

  19. Software Innovation

    DEFF Research Database (Denmark)

    Rose, Jeremy

      Innovation is the forgotten key to modern systems development - the element that defines the enterprising engineer, the thriving software firm and the cutting edge software application.  Traditional forms of technical education pay little attention to creativity - often encouraging overly...... rationalistic ways of thinking which stifle the ability to innovate. Professional software developers are often drowned in commercial drudgery and overwhelmed by work pressure and deadlines. The topic that will both ensure success in the market and revitalize their work lives is never addressed. This book sets...... out the new field of software innovation. It organizes the existing scientific research into eight simple heuristics - guiding principles for organizing a system developer's work-life so that it focuses on innovation....

  20. MAPPING INNOVATION

    DEFF Research Database (Denmark)

    Thuesen, Christian Langhoff; Koch, Christian

    2011-01-01

    By adopting a theoretical framework from strategic niche management research (SNM) this paper presents an analysis of the innovation system of the Danish Construction industry. The analysis shows a multifaceted landscape of innovation around an existing regime, built around existing ways of working...... and developed over generations. The regime is challenged from various niches and the socio-technical landscape through trends as globalization. Three niches (Lean Construction, BIM and System Deliveries) are subject to a detailed analysis showing partly incompatible rationales and various degrees of innovation...... potential. The paper further discusses how existing policymaking operates in a number of tensions one being between government and governance. Based on the concepts from SNM the paper introduces an innovation map in order to support the development of meta-governance policymaking. By mapping some...

  1. Innovation Awards

    Science.gov (United States)

    EPA promotes environmental stewardship by recognizing innovators in schools, communities and businesses in categories such as environmental education, green chemistry, smart growth, green power, and reducing air pollution and climate change impacts.

  2. Reconsidering Innovation

    DEFF Research Database (Denmark)

    Vaaben, Nana Katrine

    2014-01-01

    and debates about change, myths, and othering can help us rethink theoretical approaches to innovation in organizational studies, and the concern is especially to consider the implications that our “innovation myths” can have for public employees and the valuation their work. The argument in the paper......, is by taking the reader along on a journey through a fieldwork that changed my own understanding of innovation, made me look for alternative theories to address cultural understandings of change and continuity in organizational settings, and brought me back to myths of creation, Claude Lévi......Innovation and reforms seem to be on the agenda everywhere, not least in political attempts to reorganize the public sector in ways that are supposed to enable our welfare societies to survive economic turmoil and sinister future prognosis. This paper examines how classical anthropological theories...

  3. Innovation in wind turbine design

    CERN Document Server

    Jamieson, Peter

    2011-01-01

    Innovation in Wind Turbine Design addresses the fundamentals of design, the reasons behind design choices, and describes the methodology for evaluating innovative systems and components. Always referencing a state of the art system for comparison, Jamieson discusses the basics of wind turbine theory and design, as well as how to apply existing engineering knowledge to further advance the technology, enabling the reader to gain a thorough understanding of current technology before assessing where it can go in the future. Innovation in Wind Turbine Design is divided into four mai

  4. Recent advances in vacuum sciences and applications

    Science.gov (United States)

    Mozetič, M.; Ostrikov, K.; Ruzic, D. N.; Curreli, D.; Cvelbar, U.; Vesel, A.; Primc, G.; Leisch, M.; Jousten, K.; Malyshev, O. B.; Hendricks, J. H.; Kövér, L.; Tagliaferro, A.; Conde, O.; Silvestre, A. J.; Giapintzakis, J.; Buljan, M.; Radić, N.; Dražić, G.; Bernstorff, S.; Biederman, H.; Kylián, O.; Hanuš, J.; Miloševič, S.; Galtayries, A.; Dietrich, P.; Unger, W.; Lehocky, M.; Sedlarik, V.; Stana-Kleinschek, K.; Drmota-Petrič, A.; Pireaux, J. J.; Rogers, J. W.; Anderle, M.

    2014-04-01

    Recent advances in vacuum sciences and applications are reviewed. Novel optical interferometer cavity devices enable pressure measurements with ppm accuracy. The innovative dynamic vacuum standard allows for pressure measurements with temporal resolution of 2 ms. Vacuum issues in the construction of huge ultra-high vacuum devices worldwide are reviewed. Recent advances in surface science and thin films include new phenomena observed in electron transport near solid surfaces as well as novel results on the properties of carbon nanomaterials. Precise techniques for surface and thin-film characterization have been applied in the conservation technology of cultural heritage objects and recent advances in the characterization of biointerfaces are presented. The combination of various vacuum and atmospheric-pressure techniques enables an insight into the complex phenomena of protein and other biomolecule conformations on solid surfaces. Studying these phenomena at solid-liquid interfaces is regarded as the main issue in the development of alternative techniques for drug delivery, tissue engineering and thus the development of innovative techniques for curing cancer and cardiovascular diseases. A review on recent advances in plasma medicine is presented as well as novel hypotheses on cell apoptosis upon treatment with gaseous plasma. Finally, recent advances in plasma nanoscience are illustrated with several examples and a roadmap for future activities is presented.

  5. Advance in drug therapy of gout%治疗痛风药物研究进展

    Institute of Scientific and Technical Information of China (English)

    徐娜; 陈海生

    2013-01-01

    With the development of the living standard, the incidence of gout was rising and the trend of patient age with gout getting younger. Developing high-effective and low-adverse anti-gout drugs was a priority of the research agenda. At present, conventional therapies of gout lean on western medicines. These drugs relieved or treated gout with different mechanisms, but all of them had different side-effects. Recently, more and more researchers started to develop traditional Chinese medicine to treat gout and their effectiveness and the side-effects need further clinical verification. The commonly used anti-gout drugs or new drugs under research including their treatment characteristics, potential hazards and their therapeutic principles at different clinical stages were summarized in this article, especially in some anti-hyperuricemia or anti-gout Chinese Medicine, which gave an effective way to develop new anti-gout drugs.%随着人们生活水平的提高,痛风的发病率不断上升并出现低龄化,寻找高效低毒的抗痛风药物成为当务之急.目前,对于痛风的常规治疗仍以西药为主,这些药物以不同的作用机制达到缓解或治疗痛风的目的,但临床发现它们都具有一定的毒副作用.近年来,越来越多的研究者着手于抗痛风天然药物的开发,其疗效与毒副作用尚待进一步的临床验证.本文对目前临床上常用的抗痛风药物及正在研发中的抗痛风药物进行了综述,总结痛风病不同分期的药物治疗特点,阐述各期药物治疗潜在危害和处理方法,归纳抗高尿酸血症或痛风的中药研究,为开发新型抗痛风药物提供有效途径,并对抗痛风新药的研发进行了展望.

  6. Problems and strategy of drug innovation for cerebrovascular diseases%脑血管病创新药物研发的问题与对策

    Institute of Scientific and Technical Information of China (English)

    王拥军

    2011-01-01

    The successful rate of new drug research and development in Chinese pharmaceutical companies is lower and lower.The reasons include the medical need of patients is rapidly growing; the term of new drug patent is short; the growth of traditional pharmaceutical market is slow; new competitors are increasing, and the health budget is cut.The annual direct in-patient medical cost of drugs for cerebrovascular diseases is 20 billion.The drug development for cerebrovascular diseases has many difficulties: ( 1 ) many known drug targets have been well developed, so new targets are needed.(2) approval standards of new drugs around the world become much stricter.(3) the time gap between drug research and clinical evaluation is very long.Therefore, the research and development of new drugs for cerebrovascular diseases will follow the following four trends: ( 1 ) new drug target discovery should base on basic research.(2) the efficacy standard for cerebrovascular diseases will be adjusted.(3) evidence based medicine demands higher level of clinical trial.(4) systems biology has much deeper influence on new cerebrovascular drug discovery and development.%随着我国患者医疗需求的快速增长,新药专利期限缩短、传统市场的增长再下降、新的竞争者越来越多以及健康预算整体压缩等原因致使我国医药企业的新药研产率日益下降.每年脑血管药物占直接住院医疗费用的200亿,其新药研发面临着巨大压力:第一,已知的药物靶点已经被开发很多.第二,各国的药审部门标准越来越严格.第三,从药物研发到临床评价周期长.因此,脑血管病创新药物研发必须顺应4个新的趋势来加快发展该领域的新药研发:第一,新的靶点的发现必须要依赖基础研究.第二,脑血管病的疗效标准在不断调整.第三,循证医学对临床试验要求越来越高.第四,系统生物学对脑血管药物研发的影响越来越大.

  7. Music Therapy Advances in Neuro-disability - Innovations in Research and Practice: Summary Report and Reflections on a Two-Day International Conference

    Directory of Open Access Journals (Sweden)

    Julian Winn O'Kelly

    2014-03-01

    Full Text Available This article provides a summary of the oral papers presented during a two day international conference, which took place on 7th & 8th June 2013, at the Royal Hospital for Neuro-disability (RHN in London. The summary texts detail innovative research projects and clinical developments across music therapy, music neuroscience and music psychology addressing the needs of those with acquired and degenerative neurological conditions. The diverse and evolving work in this field is reflected in the topics covered, including disorders of consciousness, dementia, stroke, and the use of modern neuro-imaging methods to measure the effects of music therapy at a cortical level. A discussion of the implications of these converging foci highlights the benefits of the cross-disciplinary dialogue that characterised the conference.

  8. What is Media Innovation?

    OpenAIRE

    2014-01-01

    In order to understand and explain current developments in the media landscape, using the lens of innovation and innovation theory adds value to media research. This chapter gives a theoretical introduction to the concept of innovation. It argues that media innovations may be related to product innovation, process innovation, position innovation, paradigmatic innovation and social innovation, and that innovation may involve different degrees of novelty. The chapter also highlights key influen...

  9. Recent Advances in Nanoparticle-Based Förster Resonance Energy Transfer for Biosensing, Molecular Imaging and Drug Release Profiling

    Directory of Open Access Journals (Sweden)

    Nai-Tzu Chen

    2012-12-01

    Full Text Available Förster resonance energy transfer (FRET may be regarded as a “smart” technology in the design of fluorescence probes for biological sensing and imaging. Recently, a variety of nanoparticles that include quantum dots, gold nanoparticles, polymer, mesoporous silica nanoparticles and upconversion nanoparticles have been employed to modulate FRET. Researchers have developed a number of “visible” and “activatable” FRET probes sensitive to specific changes in the biological environment that are especially attractive from the biomedical point of view. This article reviews recent progress in bringing these nanoparticle-modulated energy transfer schemes to fruition for applications in biosensing, molecular imaging and drug delivery.

  10. Policy Innovation in Innovation Policy

    DEFF Research Database (Denmark)

    Borras, Susana

    During the past two decades Europe has experienced important changes and transformations in the way in which governments approach the issue of science, technology and innovation, and their relation to economic growth and competitiveness. This has to do with the European Union level as well...... as with national and sub-national governments in Europe, all of them introducing interesting novelties in their innovation policy. These changes refer to different aspects of policy, mainly the content of policy initiatives towards science, technology and innovation; the instruments governments are using...... at the EU level, and mentions similar trends taking place at national and sub-national levels. The questions that guide the contents here are essentially three, namely, what are the main traits of innovation policies in Europe since the 1990s and how have the EU and different national governments approached...

  11. Social innovation as institutional innovation

    OpenAIRE

    Edwards Schachter, Mónica E.; Benneworth, Paul; Amanatidou, Effie; Gulbrandsen, Magnus

    2015-01-01

    Trabajo presentado a la Annual Conference of the EU-SPRI Forum: "Innovation policies for economic and social transitions: Developing strategies for knowledge, practices and organizations" celebrada en Helsinki (Finlandia) del 9 al 12 de junio de 2015.

  12. 新型抗抑郁药物的研究进展%Advances in the development of new antidepressive drugs

    Institute of Scientific and Technical Information of China (English)

    孟秀君; 曲蕾; 马燕; 朱琳; 赵临襄

    2011-01-01

    With an increasing knowledge, neurotrophic hypothesis and cytokine hypothesis, neuroplastici-ty, hippocampus-neurogenesis, HPA axis and immune system are included in the pathogenesis of depression, which might be the antidepressant targets. Several potential therapeutic targets have been identified for the disease, such as glutamic acid receptors, neuropeptide receptors, glucocorticoid receptors, melatonin receptors and cytokine receptors. With the development of understanding the new drug targets of depression, the research on new depressive drugs becomes a new research hotspot. A lot of novel antidepressive compounds have been designed and synthesized ; more than ten of them are currently used in clinic or in advanced clinical trials. The mlatonin receptor agonist agomelatine and the corticotrophin releasing hormone receptor antagonist quetiapine have been approved as new antidepressive drugs. Mifepristone and saredutant, as a glucocorticoid receptor antagonist and a neurokinin 2 receptor antagonist, are in phase III clinical trials. Advances in the development of novel depressive targets and drugs in recent 5 years are discussed in the paper.%近年来对抑郁症发病机制和药物治疗靶标的研究取得了很大进展,围绕神经可塑性、神经发生、下丘脑-垂体-肾上腺( HPA)轴等后续神经系统适应性改变以及免疫系统变化,确定了谷氨酸受体、神经肽受体、糖皮质激素受体、褪黑激素受体和细胞因子受体等抗抑郁药物作用的新靶标.目前,已发现大量具有抗抑郁作用的新化合物,褪黑激素受体激动剂阿戈美拉丁、促肾上腺皮质激素释放激素受体拮抗剂喹硫平已经上市,神经激肽2受体拮抗剂沙瑞度坦、糖皮质激素受体拮抗剂米非司酮正在进行Ⅲ期临床研究,10余个药物进入临床研究阶段.本文对近5年新型抗抑郁药物的研究进展进行简要综述.

  13. Photo-irradiation paradigm: Mapping a remarkable facile technique used for advanced drug, gene and cell delivery.

    Science.gov (United States)

    Shaker, Mohamed A; Younes, Husam M

    2015-11-10

    Undoubtedly, the progression of photo-irradiation technique has provided a smart engineering tool for the state-of-the-art biomaterials that guide the biomedical and therapeutic domains for promoting the modern pharmaceutical industry. Many investigators had exploited such a potential technique to create/ameliorate numerous pharmaceutical carriers. These carriers show promising applications that vary from small drug to therapeutic protein delivery and from gene to living cell encapsulation design. Harmony between the properties of precisely engineered precursors and the formed network structure broadens the investigator's intellect for both brilliant creations and effective applications. As well, controlling photo-curing at the formulation level, through manipulating the absorption of light stimuli, photoinitiator system and photo-responsive precursor, facilitates the exploration of novel distinctive biomaterials. Discussion of utilizing different photo-curing procedures in designing/formulation of different pharmaceutical carriers is the main emphasis of this review. In addition, recent applications of these intelligent techniques in targeted, controlled, and sustained drug delivery with understanding of photo-irradiation concept and mechanism are illustrated.

  14. Development and evaluation of lafutidine solid dispersion via hot melt extrusion: Investigating drug-polymer miscibility with advanced characterisation

    Directory of Open Access Journals (Sweden)

    Ritesh Fule

    2014-04-01

    Full Text Available In current study, immediate release solid dispersion (SD formulation of antiulcer drug lafutidine (LAFT was developed using hot melt extrusion (HME technique. Amphiphilic Soluplus® used as a primary solubilizing agent, with different concentrations of selected surfactants like PEG 400, Lutrol F127 (LF127, Lutrol F68 (LF68 were used to investigate their influence on formulations processing via HME. Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable. On the contrary, traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry (DSC, X-ray diffraction (XRD, scanning electron microscopy (SEM and Raman spectroscopy. Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC. Atomic Force microscopy (AFM studies revealed drug- polymer molecular miscibility and surface interaction at micro level. 1H–COSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus®, with chemical shift drifting and line broadening. MD simulation studies using computational modelling showed intermolecular interaction between molecules. Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems. Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD. The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.

  15. Innovative Clean Coal Technology (ICCT): 500 MW demonstration of advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NO{sub x}) emissions from coal-fired boilers. Technical progress report, First quarter 1992

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-31

    This quarterly report discusses the technical progress of an Innovative Clean Coal Technology (ICCT) demonstration of advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NO{sub x}) emissions from coal-fired boilers. The project is being conducted at Georgia Power Company`s Plant Hammond Unit 4 located near Rome, Georgia. The primary goal of this project is the characterization of the low NO{sub x} combustion equipment through the collection and analysis of long-term emissions data. A target of achieving fifty percent NO{sub x} reduction using combustion modifications has been established for the project. The project provides a stepwise retrofit of an advanced overfire air (AOFA) system followed by low NO{sub x} burners (LNB). During each test phase of the project, diagnostic, performance, long-term, and verification testing will be performed. These tests are used to quantify the NO{sub x} reductions of each technology and evaluate the effects of those reductions on other combustion parameters such as particulate characteristics and boiler efficiency.

  16. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective.

    Science.gov (United States)

    Roeber, Florian; Jex, Aaron R; Gasser, Robin B

    2013-05-27

    Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases.

  17. 减重药物的现状及进展%Anti-obesity Drugs: Status Quo and Recent Advances

    Institute of Scientific and Technical Information of China (English)

    朱惠娟; 金自孟

    2011-01-01

    肥胖症已成为危害全球人类健康的重要问题之一,糖尿病、高血压和心脑血管疾病乃至肿瘤等肥胖相关并发症的发病率和死亡率也显著增加,肥胖症的治疗成为临床医生面临的挑战.减重治疗能够预防甚至逆转肥胖症相关并发症的发生.目前公认的减重治疗仍是以科学合理控制饮食和规律运动的行为治疗,对于行为治疗失败或者已出现肥胖并发症的患者可考虑药物治疗.目前临床常用的减重药物包括胃肠道脂肪酶抑制剂、中枢食欲抑制剂等.新型的降糖药物胰高糖素样肽-1也被发现具有显著减重作用,而更多类型的减重药物也在积极的研发过程中,如选择性5-HT2c激动剂、选择性β3受体激动剂和黑皮质素受体4激动剂等,有望成为减重治疗的药物选择之一.%Obesity has become a major health problem worldwide.The prevalence and morbidity of obesity-related diseases including diabetes, hypertension, cerebro-cardiovascular diseases, and tumors also have remarkably increased.Treatment of obesity poses a challenge for clinicians.Anti-obesity treatment is helpful to improve and even reverse obesity-related complications.Diet control and physical exercises remain the predominant interventions for obese patients.Anti-obesity drugs can be considered in those who respond poorly to behavioral intervention or those who have developed obesity-related complications.The commonly used anti-obesity drugs include gastrointestinal lipase inhibitors and appetite suppressants.Glucagon-like peptide 1 has also been found to be effective in reducing body weight.Some more drugs are under development, which include selective 5-HT2c agonist, β3 receptor agonist, and melanocortin receptor 4 agonist, may also be promising.

  18. The Innovative Medicines Initiative's New Drugs for Bad Bugs programme : European public-private partnerships for the development of new strategies to tackle antibiotic resistance

    NARCIS (Netherlands)

    Kostyanev, T.; Bonten, M. J M; O'Brien, S.; Steel, H.; Ross, S.; François, B.; Tacconelli, E.; Winterhalter, M.; Stavenger, R. A.; Karlén, A.; Harbarth, S.; Hackett, J.; Jafri, H. S.; Vuong, C.; MacGowan, A.; Witschi, A.; Angyalosi, G.; Elborn, J. S.; deWinter, R.; Goossens, H.

    2016-01-01

    Antibiotic resistance (ABR) is a global public health threat. Despite the emergence of highly resistant organisms and the huge medical need for new drugs, the development of antibacterials has slowed to an unacceptable level worldwide. Numerous government and non-government agencies have called for

  19. Innovative studerende

    DEFF Research Database (Denmark)

    Rohde, Lilian; Boelsmand, Jens

    Innovative studerende præsenterer en metode til at designe projekter, som gør en forskel i velfærdssamfundet, det vil sige skaber merværdi i virkelighedens verden. Undervejs trænes studerendes innovative kompetencer til at nytænke ydelser, produkter og processer, som skaber værdi for borgerne i...... samfundet.Metoden er bygget op om modellen FIRE-Designs fire faser: Forstå, Ideudvikle, Realisere og Evaluere. Første del af bogen beskriver modellens faser og forklarer begreber som kreativitet, innovation, entreprenørskab, intraprenørskab og iværksætteri. Anden del giver undervisere og studerende en række...

  20. Reconsidering Innovation

    DEFF Research Database (Denmark)

    Vaaben, Nana Katrine

    2014-01-01

    Innovation og reformer er på dagsordenen allevegne, ikke mindst i politiske forsøg på at reorganisere den offentlige sektor for at få velfærdssamfundet til at kunne overleve økonomisk tumult og dystre fremtidsprognoser. Dette papir undersøger, hvordan klassiske antropologiske teorier og debatter om...... forandring og myter kan hjælpe os med at genoverveje teoretiske forståelser af innovation i organisatoriske studier. I særlig grad sættes der fokus på de implikationer som vores "innovationsmyte" kan have for offentligt ansatte og værdsættelsen af deres arbejde. Analysens argument er, at innovation ikke skal...

  1. Collaborative innovation

    DEFF Research Database (Denmark)

    Timenes Laugen, Bjørge; Lassen, Astrid Heidemann

    2011-01-01

    Industry and academia alike are increasingly becoming aware of the fact that innovation does not take place in isolated cells or functions within the firm. Although the idea of involving internal and external actors in the new product development (NPD) process is not new, the knowledge about...... the benefits and pitfalls is still limited. This paper aims to contribute to refining the concept of open innovation, by investigating how strategic priorities influence the degree of external and internal involvement in the NPD process, moderated by contextual factors. The results indicate that suppliers...... are heavily involved in the NPD process in firms in B2C markets aiming at increasing the innovation volume. For B2B companies the reverse picture emerges. However, when the aim is to increase the radicality of new products, suppliers and customers are heavily involved for firms in B2B markets....

  2. Brugerdreven innovation

    DEFF Research Database (Denmark)

    Helms, Niels Henrik; Larsen, Lasse Juel

    2007-01-01

    På et generelt plan er vores afsæt et opgør med traditionelle modeller for kreativitet og innovation. Artiklen mener, at brugerdreven innovation ikke bare en god idé, men en beskrivelse af, hvordan innovation finder sted. Vores afsæt er interaktionsdesign, hvor vi bygger på den antagelse......, at udviklingen af it-systemer i høj grad handler om, hvordan sådanne systemer medierer praksis lokalt frem for fokus på tekniske detaljer eller traditionel kognitiv HCI-design. Denne praksis ser vi som en mediering mellem omstændigheder og processer, hvor tekniske systemer ikke skal ses som en neutralt...

  3. Innovative clean coal technology: 500 MW demonstration of advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NOx) emissions from coal-fired boilers. Final report, Phases 1 - 3B

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-01-01

    This report presents the results of a U.S. Department of Energy (DOE) Innovative Clean Coal Technology (ICCT) project demonstrating advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NOx) emissions from coal-fired boilers. The project was conducted at Georgia Power Company`s Plant Hammond Unit 4 located near Rome, Georgia. The technologies demonstrated at this site include Foster Wheeler Energy Corporation`s advanced overfire air system and Controlled Flow/Split Flame low NOx burner. The primary objective of the demonstration at Hammond Unit 4 was to determine the long-term effects of commercially available wall-fired low NOx combustion technologies on NOx emissions and boiler performance. Short-term tests of each technology were also performed to provide engineering information about emissions and performance trends. A target of achieving fifty percent NOx reduction using combustion modifications was established for the project. Short-term and long-term baseline testing was conducted in an {open_quotes}as-found{close_quotes} condition from November 1989 through March 1990. Following retrofit of the AOFA system during a four-week outage in spring 1990, the AOFA configuration was tested from August 1990 through March 1991. The FWEC CF/SF low NOx burners were then installed during a seven-week outage starting on March 8, 1991 and continuing to May 5, 1991. Following optimization of the LNBs and ancillary combustion equipment by FWEC personnel, LNB testing commenced during July 1991 and continued until January 1992. Testing in the LNB+AOFA configuration was completed during August 1993. This report provides documentation on the design criteria used in the performance of this project as it pertains to the scope involved with the low NOx burners and advanced overfire systems.

  4. 聚酮合酶与药物筛选的研究进展%Advances in polyketide synthases and drug screening

    Institute of Scientific and Technical Information of China (English)

    陈路劼; 赵薇; 连云阳

    2012-01-01

    由于结构多样化和生物活性多样性,聚酮化合物已经成为新药的重要来源.聚酮合酶(polyketide synthase,PKS)是合成聚酮类物质的酶复合体.本文介绍了聚酮合酶的分类、作用机制及相关药物筛选的研究进展.并对通过宏基因组技术,从自然环境中获得新聚酮化合物的基因筛选方法的研究进展进行了总结.%Polyketide with the diversity in chemical structure and biological activity is one of the most important source of novel drugs. Polyketide synthase catalyses the syntheses of polyketides. In this paper, the type, the mechanism and the research advance of drug screening of polyketide synthases were summarized. In addition, the gene screening method that acquiring new polyketides from natural environment via metagenome library technique was introduced.

  5. Effektiv innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret; Brandi, Ulrik

    2011-01-01

    Er det vækst og udvikling eller åbenhed, videnudvikling, netværk, leg og innovation? Eller er det prisregulering, tilpasning og stærk styring, som skal gøre universiteterne til førende drivkræfter for dansk vækst?......Er det vækst og udvikling eller åbenhed, videnudvikling, netværk, leg og innovation? Eller er det prisregulering, tilpasning og stærk styring, som skal gøre universiteterne til førende drivkræfter for dansk vækst?...

  6. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Li-li ZHANG

    2013-09-01

    Full Text Available Objective To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

  7. Academic Drug Discovery Centres

    DEFF Research Database (Denmark)

    Kirkegaard, Henriette Schultz; Valentin, Finn

    2014-01-01

    Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic and organi......Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...... their performance....

  8. People, Politics, and Innovation: A Process Perspective

    NARCIS (Netherlands)

    L. Alexander (Lameez)

    2014-01-01

    markdownabstract__Abstract__ Innovation is often considered the Holy Grail of competitive advantage and growth in modern organizations. Organizing for innovation can therefore be seen as the cornerstone of organizational success. In this dissertation, I aimed to advance a more complex and dynamic

  9. The Path to Enduring Innovation in Schools

    Science.gov (United States)

    Hall, Catherine J.

    2016-01-01

    It is difficult, if not impossible, for a school proud of its reputation for excellence not to feel the need to claim to have a firm grip on "innovation." Leading in innovation suggests many things that the school is--such as being technologically advanced, current in pedagogy and practice, and generally ahead of the curve. Yet, in…

  10. Innovating Teacher Education in a Complex Era

    Science.gov (United States)

    Tan, Oon Seng

    2015-01-01

    The meteoric increase in technological advancement in the last few decades has dramatically transformed how people live their lives. Innovation is seen to be essential as it ensures sustainable growth in a knowledge-based economy and a competitive global marketplace. Consequently, enabling innovation to occur becomes of prime concern to educators…

  11. Ensuring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction

    Directory of Open Access Journals (Sweden)

    Francoeur RB

    2011-09-01

    Full Text Available Richard B FrancoeurSchool of Social Work, Adelphi University, Garden City, NY, USA; Center for the Psychosocial Study of Health and Illness, Columbia University, New York, NY, USAAbstract: This article proposes and develops novel components of community-oriented programs for creating and affording access to safe medication dispensing centers in existing retail pharmacies and in permanent or travelling pharmacy clinics that are guarded by assigned or off-duty police officers. Pharmacists at these centers would work with police, medical providers, social workers, hospital administrators, and other professionals in: planning and overseeing the safe storage of controlled substance medications in off-site community safe-deposit boxes; strengthening communication and cooperation with the prescribing medical provider; assisting the prescribing medical provider in patient monitoring (checking the state prescription registry, providing pill counts and urine samples; expanding access to lower-cost, and in some cases, abuse-resistant formulations of controlled substance medications; improving transportation access for underserved patients and caregivers to obtain prescriptions; and integrating community agencies and social networks as resources for patient support and monitoring. Novel components of two related community-oriented programs, which may be hosted outside of safe medication dispensing centers, are also suggested and described: (1 developing medication purchasing cooperatives (ie, to help patients, families, and health institutions afford the costs of medications, including tamper- or abuse-resistant/deterrent drug formulations; and (2 expanding the role of inner-city methadone maintenance treatment programs in palliative care (ie, to provide additional patient monitoring from a second treatment team focusing on narcotics addiction, and potentially, to serve as an untapped source of opioid medication for pain that is less subject to abuse

  12. A theoretical and empirical investigation into the willingness-to-pay function for new innovative drugs by Germany's health technology assessment agency (IQWiG).

    Science.gov (United States)

    Gandjour, Afschin

    2013-11-01

    Under the recently enacted pharmaceutical price and reimbursement regulation in Germany, new drugs are subject to a rapid assessment to determine whether there is sufficient evidence of added clinical benefits compared with the existing standard of treatment. If such added benefits are confirmed, manufacturers and representatives of the Statutory Health Insurance (SHI) are expected to negotiate an appropriate reimbursement price. If parties fail to reach an agreement, a final decision on the reimbursement price will be made by an arbitration body. If one of the parties involved wishes so, then the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) will be commissioned with a formal evaluation of costs and benefits of the product in question. IQWiG will make a recommendation for a reimbursement price based on the 'efficiency frontier' in a therapeutic area. The purpose of the assessments is to provide support for decision-making bodies that act on behalf of the SHI insurants. To determine the willingness to pay for new drugs, IQWiG uses the following decision rule: the incremental cost-effectiveness ratio of a new drug compared with the next effective intervention should not be higher than that of the next effective intervention compared with its comparator. The purpose of this paper was to investigate the theoretical and empirical relationship between the willingness to pay for drugs and their health benefits. The analysis shows that across disease areas IQWiG has a curvilinear relationship between willingness to pay and health benefits. Future research may address the validity of the willingness-to-pay function from the viewpoint of the individual SHI insurants.

  13. Counting on natural products for drug design

    Science.gov (United States)

    Rodrigues, Tiago; Reker, Daniel; Schneider, Petra; Schneider, Gisbert

    2016-06-01

    Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.

  14. Reflections on the Innovative Medicines Initiative.

    Science.gov (United States)

    Goldman, Michel

    2011-05-01

    The pharmaceutical industry is developing new collaborative models for drug development. This article discusses the experience so far of the Innovative Medicines Initiative, which is currently the largest public-private partnership that is dedicated to pharmaceutical innovation, highlighting lessons learned for the success of precompetitive consortia.

  15. Advances in drug treatment of acromegaly%肢端肥大症的药物治疗进展

    Institute of Scientific and Technical Information of China (English)

    周良; 张义

    2015-01-01

    肢端肥大症是一种隐袭起病、缓慢进展的内分泌疾病。肢端肥大症主要由生长激素垂体瘤引起,这种垂体瘤长期、过度分泌生长激素导致循环胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)升高,从而导致靶器官受损、增加患者死亡率并且降低生活质量。本文检索5年来的相关文献,回顾肢端肥大症的药物治疗进展。%Acromegaly is mostly caused by a pituitary adenoma secreting growth hormone ( GH ) , which leads to a wide range of endocrine morbidities, with an insidious onset and slow progression.A long-term overproduction of GH results in elevated insulin-like growth factor-1 ( IGF-1 ) level, which in turn, would cause target organ damage and an increased risk for mortality and decreased quality of life.Herein, the literature regarding the progress of drug therapy for acromegaly in recent five years is reviewed.

  16. Open innovation

    DEFF Research Database (Denmark)

    West, Joel; Bogers, Marcel

    2017-01-01

    by small, new, and not-for-profit organizations, as well as the linkage of individual actions and motivations to open innovation. Other opportunities include better measuring the costs, benefits, antecedents, mediators and moderators of the effects of OI on performance, and understanding why and how OI...

  17. Veblen, Bataille and Financial Innovation

    DEFF Research Database (Denmark)

    Gammon, Earl; Wigan, Duncan

    2015-01-01

    This article advances towards the reconceptualization of financial innovation. It examines the calamitous role of financial innovation in the global financial crisis, developing a non-rational theorization of finance within the social economy that factors in the role of affect. Outlining...... the foundations for such an approach, the analysis draws on Thorstein Veblen and Georges Bataille, whose work encompasses psycho-social conceptions of political-economic agency. From the more anthropological lens of Veblen and Bataille's theorizations, it is possible to move beyond instrumentalist accounts...... of financial innovation premised on pecuniary expedients and aspirations of market completion. As we argue, in a broader affective economy, contemporary financial innovation serves invidious ends, providing a means of attaining social distinction, constituting a medium for violent expenditure and bestowing...

  18. Challenges in developing drugs for primary headaches

    DEFF Research Database (Denmark)

    Schytz, Henrik Winther; Hargreaves, Richard; Ashina, Messoud

    2017-01-01

    This review considers the history of drug development in primary headaches and discusses challenges to the discovery of innovative headache therapeutics. Advances in headache genetics have yet to translate to new classes of therapeutics and there are currently no clear predictive human biomarkers......, there have been many near misses and failures in the discovery and development of headache therapeutics. Glutamate receptor antagonism whilst efficacious has central side effects and some approaches such as nitric oxide synthase inhibition, substance P antagonism and cortical spreading depression blockade...

  19. The tuberculosis drug discovery and development pipeline and emerging drug targets.

    Science.gov (United States)

    Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

    2015-01-29

    The recent accelerated approval for use in extensively drug-resistant and multidrug-resistant-tuberculosis (MDR-TB) of two first-in-class TB drugs, bedaquiline and delamanid, has reinvigorated the TB drug discovery and development field. However, although several promising clinical development programs are ongoing to evaluate new TB drugs and regimens, the number of novel series represented is few. The global early-development pipeline is also woefully thin. To have a chance of achieving the goal of better, shorter, safer TB drug regimens with utility against drug-sensitive and drug-resistant disease, a robust and diverse global TB drug discovery pipeline is key, including innovative approaches that make use of recently acquired knowledge on the biology of TB. Fortunately, drug discovery for TB has resurged in recent years, generating compounds with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review summarizes the current TB drug development pipeline and proposes strategies for generating improved hits and leads in the discovery phase that could help achieve this goal.

  20. 急性毒性试验的研究进展%Advance in studies of acute drug toxicity

    Institute of Scientific and Technical Information of China (English)

    王庆利; 王海学; 马磊

    2009-01-01

    ICH及其指导原则M3中对急性毒性试验的科学意义、在药物研发进程中的时间安排、注册要求等进行了大量讨论.近几年,随着制药企业间药物非临床研究资料的共享,以及动物试验3R原则的不断推进,急性毒性试验在药物研发及注册中的作用正发生着深刻的变化.文中结合我国新药研发和指导原则的实际情况,对该试验的研究进展及科学背景进行讨论,为我国的研究和管理要求提供一些参考.%Traditionally, single dose toxicity studies in animals, programmed in early phase of new drug development, are usually required for any pharmaceuticals intended for human use. International conference on harmonization of technical requirements for registration of pharmaceuticals for human use (ICH) and the guideline M3 discussed the scientific background of the study, and recommended the development strategies and requirements for registration. In recent years, with the share of nonclinical safety studies conducted between companies and the consideration of the 3Rs principles, suggestions in refining the single dose toxicity study were presented.

  1. INNOVATION IN THE CONSTRUCTION INDUSTRY

    Directory of Open Access Journals (Sweden)

    David Arditi

    2000-01-01

    Full Text Available In this paper%2C existing innovation models are reviewed. The influence of technology and market-driven schools of thought on the creation and diffusion of innovation is examined. Incremental vs. radical models and autonomous vs. systemic models are considered in the context of the construction industry. The concept of %93technology adoption life cycle%94 is investigated to understand better the acceptance of new technology by key parties. A new model of innovation is proposed. In this model%2C the transformation process of invention into adoption flows through a cyclical mechanism encompassing six phases%3A 1%29 need%2C 2%29 creation%2C 3%29 invention%2C 4%29 innovation%2C 5%29 diffusion%2C and 6%29 adoption. This model clearly shows the interaction of the three most influential domains%3A users%2C changes%2C and the environment. The model also takes into consideration the influence of technology and market-driven forces on the creation and diffusion of innovation. As a consequence of their particular function in the construction activity%2C construction management firms should perform as catalysts in the generation and diffusion of technological advances in the Abstract in Bahasa Indonesia : Innovation%2C+invention%2C+innovation+models%2C+technology+adoption+life+cycle%2C+construction+management.+

  2. Computational Science and Innovation

    CERN Document Server

    Dean, D J

    2010-01-01

    Simulations - utilizing computers to solve complicated science and engineering problems - are a key ingredient of modern science. The U.S. Department of Energy (DOE) is a world leader in the development of high-performance computing (HPC), the development of applied math and algorithms that utilize the full potential of HPC platforms, and the application of computing to science and engineering problems. An interesting general question is whether the DOE can strategically utilize its capability in simulations to advance innovation more broadly. In this article, I will argue that this is certainly possible.

  3. Innovations in bereavement education.

    Science.gov (United States)

    Wright, Patricia Moyle

    2011-08-01

    Advanced practice nursing students provide care for clients and families in numerous settings where they will encounter end-of-life issues. Thus, graduate nursing education should include information on current trends in thanatology, such as the debate over the proposed complicated grief criteria and the paradigmatic shift toward evidence-based grief theory. In this article, an innovative approach to teaching bereavement content to graduate nursing students during a 3-hour class is presented. The assignments were developed specifically for adult learners with clinical experience. Students' responses to the learning activities and recommendations for modifications of the teaching methods are presented.

  4. Rethinking Open Innovation Beyond the Innovation Funnel

    Directory of Open Access Journals (Sweden)

    Wim Vanhaverbeke

    2013-04-01

    Full Text Available In his article, I first argue that open innovation can be applied in situations where companies do not themselves develop new products or services. As a consequence, open innovation becomes relevant for a much larger group of organizations than previously considered. Second, I argue that open-innovation scholars have insufficiently differentiated open-innovation initiatives in terms of their impact on companies’ growth: some open-innovation initiatives lead to incremental innovations in an existing business while, in other cases, open-innovation initiatives are used to establish completely new businesses. Both arguments illustrate the need to integrate open-innovation initiatives into the strategy of the firm.

  5. 支气管哮喘防治药物的进展%The Advances of Clinical Research and Application of Drugs for Prevention and Treatment of Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    杨玉

    2001-01-01

    文章系统地介绍了支气管哮喘防治药物的进展,内容包括β2-激动药、茶碱、抗胆碱药物、糖皮质激素、肥大细胞稳定药、抗组胺药、抗白三烯类药物、新型抗炎药、免疫抑制药及免疫疗法的进展等,可供大家参考。%In This paper, the advances of clinical research and application of the drugs for preventing and treating bronchial asthma were reviewed, with a detailed reference to such drugs as β2-adrenoceptor agonist, theophylline, anticholinergic drugs, glucocorticoids, mast cell membrane stabilizers, antihistamines, leukotriene receptor antogonists, new anti-inflammatory drugs and immunosuppressive drugs as well as immunotherapy.

  6. Innovations in urban agriculture

    NARCIS (Netherlands)

    Schans, van der J.W.; Renting, Henk; Veenhuizen, Van René

    2014-01-01

    This issuehighlights innovations in urban agriculture. Innovation and the various forms of innovations are of particular importance because urban agriculture is adapted to specific urban challenges and opportunities. Innovation is taking place continuously, exploring the multiple fundions of urban a

  7. Methodology and tools of enterprise innovativeness evaluation

    Directory of Open Access Journals (Sweden)

    L.O. Ligonenko

    2015-09-01

    base for the innovativeness internal indicator calculation. It helps to make conclusions more profound and develope appropriate management decisions. The author proposed a comprehensive system of enterprise innovativeness public evaluation. It is based on the current Ukrainian statistical reporting and comprises of two subsystems (determinants: preconditions and results (manifestations of innovativeness. It is proposed to evaluate preconditions of innovativeness in such areas as: intellectual property rights formation; cooperation with educational, scientific, and entrepreneurial sectors; information and personnel readiness for innovations implementation; financial and investment support of innovative enterprise activity; state (regional promotion of enterprise innovativeness. It is proposed to evaluate the results of innovativeness in the context of such directions as innovative enterprise activity; market launch of innovative products; introduction of new technique and advanced technologies; introduction of new information and communication technologies; participation in technological transfers. It is also proposed to summarize analytical indicators into an integral indicator of innovativeness according to the principles of additive weighted average clotting. A specially formed group of experts should assess coefficients of significance of individual valuation indicators. Interpretation of innovative level can be based on quantitative assessment (close to one or according to 5-interval scale of linguistic interpretation of Harrington. This integral indicator of innovation can further be used for dynamic and comparative analysis (comparison with the corresponding indicator of other enterprises or average values in the industry. To determine the reference value one can use the average or maximum value in the aggregate researched. Conclusions and directions for future research. This methodology of innovativeness evaluation may interest different groups of enterprise

  8. INNOVATIVE ANTIHYPERTENSIVE THERAPY IN THE LIGHT OF COMPLETED CLINICAL TRIALS

    Directory of Open Access Journals (Sweden)

    N. A. Nikolaev

    2016-01-01

    Full Text Available The innovative approaches to antihypertensive pharmacotherapy and advantages of modern antihypertensive drugs are discussed on the basis of randomized controlled trial. The recommendations for usage of different class of antihypertensive drugs including their combinations are presented.

  9. INNOVATIVE ANTIHYPERTENSIVE THERAPY IN THE LIGHT OF COMPLETED CLINICAL TRIALS

    Directory of Open Access Journals (Sweden)

    N. A. Nikolaev

    2009-01-01

    Full Text Available The innovative approaches to antihypertensive pharmacotherapy and advantages of modern antihypertensive drugs are discussed on the basis of randomized controlled trial. The recommendations for usage of different class of antihypertensive drugs including their combinations are presented.

  10. Innovative Clean Coal Technology (ICCT): 500 MW demonstration of advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NO{sub x}) emissions from coal-fired boilers. Third quarterly technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-31

    This quarterly report discusses the technical progress of an Innovative Clean Coal Technology (ICCT) demonstration of advanced wall-fired combustion techniques for the reduction of nitrogen oxide (NO{sub x}) emissions from coal-fired boilers. The project provides a stepwise retrofit of an advanced overfire air (AOFA) system followed by low NO{sub x} burners (LNB). During each test phase of the project, diagnostic, performance, long-term, and verification testing will be performed. These tests are used to quantify the NO{sub x} reductions of each technology and evaluate the effects of those reductions on other combustion parameters such as particulate characteristics and boiler efficiency. Baseline, AOFA, LNB, and LNB plus AOFA test segments have been completed. Analysis of the 94 days of LNB long-term data collected show the full-load NO{sub x} emission levels to be approximately 0.65 lb/MBtu with fly ash LOI values of approximately 8 percent. Corresponding values for the AOFA configuration are 0.94 lb/MBtu and approximately 10 percent. For comparison, the long-term full-load, baseline NO{sub x} emission level was approximately 1.24 lb/MBtu at 5.2 percent LOI. Comprehensive testing in the LNB+AOFA configuration indicate that at full-load, NO{sub x} emissions and fly ash LOI are near 0.40 lb/MBtu and 8 percent, respectively. However, it is believed that a substantial portion of the incremental change in NO{sub x} emissions between the LNB and LNB+AOFA configurations is the result of additional burner tuning and other operational adjustments and is not the result of the AOFA system. During this quarter, LNB+AOFA testing was concluded. Testing performed during this quarter included long-term and verification testing in the LNB+AOFA configuration.

  11. 《毒品化学》实践教学模式的改革与创新%Innovation and Reform of Practical Teaching Mode in the Course of Forensic Drug Chemistry

    Institute of Scientific and Technical Information of China (English)

    孟梁

    2015-01-01

    目前我国公安教育普遍面临实践教学体系薄弱的现状,因此在公安技术教育中坚持以实战为导向具有重要的意义。坚持以培养具有实战办案和科技创新能力的应用型禁毒侦查专业人才为目标,优化和改革《毒品化学》教学模式,结合侦查学和刑事科学技术领域的最新研究进展,及时调整课程教学内容,创新课程教学方法,引入新的教学手段和考核方式,建立符合新形势下公安实际工作需要的实践教学模式,从而促进学生的知识积累和应用,提高学生的办案实践能力,以培养出优秀的禁毒民警。%At present, public security education is confronted with the situation of weak practical teaching sys-tem, so it is important that public security education must insist on the practical teaching .Therefore,we should im-prove the teaching mode in the course of Forensic Drug Chemistry , aiming at cultivating professional police candi-dates with practical experiences and innovative skills .Meanwhile , with reorganizing the teaching content , innova-ting the teaching methods and introducing the new evaluation system , we should adjust our practical teaching mode to the changing situation in order to help students to promote their accumulation and application of knowledge , as well as the practical ability .

  12. Disruptive innovations

    OpenAIRE

    Viglia, Giampaolo; Werthner, H.; Buhalis, Dimitrios

    2016-01-01

    The diffusion of disrupting innovations has generated significant market changes, modifying the dominant logic and affecting the strategic positioning of companies. This structural change is affecting market structure, the networks and the services that tourism players are supposed to use (Gretzel et al. 2015). One can also refer to the notion of digital infrastructure, which provides a nice framework that connects the different stakeholders, their relations as well as internal dynamics. At t...

  13. Flotation advances

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, D.

    1998-11-01

    This paper describes recent advances in flotation cell and mechanism design. OutoKumpu have designed larger cells, suitable for the flotation of smaller particles, with differing mechanisms for particles of different types. Froth handling is also closely controlled. Flotation cells from BQR are also described. Flotation columns are also increasingly being adopted, complementing the use of conventional flotation cells. Designs by Wemco, Multotec, VERTI-MIX, Jameson, Suedala, Quinn and Cytec are detailed, giving improvements in fine coal separation coarse particle separation, and other innovations. 8 figs., 2 tabs.

  14. Does Increased Spending on Pharmaceutical Marketing Inhibit Pioneering Innovation?

    Science.gov (United States)

    Arnold, Denis G; Troyer, Jennifer L

    2016-04-01

    The pharmaceutical industry has been criticized for developing and aggressively marketing drugs that do not provide significant health benefits relative to existing drugs but retain the benefits of patent protection. Critics argue that drug marketing increases health care expenditures and provides a disincentive for pioneering drug innovation. However, evidence that marketing expenditures have any relationship to new drug approvals has been anecdotal. We hypothesized that, at publicly traded pharmaceutical firms, increased marketing expenditures will result in a reduced volume of pioneering new drugs in comparison to less innovative new drugs. We also hypothesized that additional research and development spending will result in an increased volume of pioneering new drugs in comparison to less innovative drugs. Results confirm our hypotheses. Specific policy recommendations for altering firms' incentives for the development of pioneering drugs are provided.

  15. Innovative drug delivery nanosystems improve the anti-tumor activity in vitro and in vivo of anti-estrogens in human breast cancer and multiple myeloma.

    Science.gov (United States)

    Maillard, Sébastien; Ameller, Thibault; Gauduchon, Juliette; Gougelet, Angélique; Gouilleux, Fabrice; Legrand, Philippe; Marsaud, Véronique; Fattal, Elias; Sola, Brigitte; Renoir, Jack-Michel

    2005-02-01

    Anticancer drug efficiency is governed by its bioavailability. In order to increase this parameter, we synthesized several injectable and biodegradable systems based on incorporation of anti-estrogens (AEs) in nanoparticles (NPs) and liposomes were synthesized. Both nanospheres (NS) and nanocapsules (NCs, polymers with an oily core in which AEs were solubilized) incorporated high amounts of 4-hydroxy-tamoxifen (4-HT) or RU 58668 (RU). Physico-chemical and biological parameters of these delivery systems, and coupling of polyethylene-glycol chains on the NP surface revealed to enhance the anti-tumoral activity of trapped AEs in a breast cancer MCF-7 cell xenograft model and to induce apoptosis. These features correlated with an augmentation of p21(Waf-1/Cip1) and of p27(Kip1) and a concomitant decrease of cyclin D1 and E in tumor extracts. Liposomes containing various ratios of lipids enhanced the apoptotic activity of RU in several multiple myeloma (MM) cell lines tested by flow cytometry. MM cell lines expressed both estrogen receptor alpha and beta subtypes except Karpas 620. Karpas 620 cells which did not respond to AEs became responsive following ER cDNA transfection. A new MM xenograft model was generated after s.c. injection of RPMI 8226 cells in nude mice. RU-loaded liposomes, administered i.v. in this model, at a dose of 12mgRU/kg/week, induced the arrest of tumor growth contrary to free RU or to empty liposomes. Thus, the drug delivery of anti-estrogens enhances their ability to arrest the growth of tumors which express estrogen receptors and are of particular interest for estrogen-dependent breast cancer treatment. In addition it represents a new potent therapeutic approach for multiple myeloma.

  16. European Innovation Policy Concepts and the Governance of Innovation: Slovenia and the Struggle for Organizational Readiness at the National Level

    Science.gov (United States)

    Gebhardt, Christiane; Stanovnik, Peter

    2016-01-01

    This paper examines the interdependency of European Policy and governance of innovation. The authors elaborate on the policy implementation context of Slovenia, a small and less advanced European member state in a transition process. The literature on innovation policy, governance and existing innovation concepts aiming to accelerate economic…

  17. Development and Testing of the Advanced CHP System Utilizing the Off-Gas from the Innovative Green Coke Calcining Process in Fluidized Bed

    Energy Technology Data Exchange (ETDEWEB)

    Chudnovsky, Yaroslav; Kozlov, Aleksandr

    2013-08-15

    petroleum coke calcination process. - Increase the opportunity of heat (chemical and physical) utilization from process off-gases and solid product. - Develop a design of advanced CHP system utilizing off-gases as an “opportunity fuel” for petroleum coke calcinations and sensible heat of calcined coke. A successful accomplishment of the aforementioned objectives will contribute toward the following U.S. DOE programmatic goals: - Drive a 25% reduction in U. S. industrial energy intensity by 2017 in support of EPAct 2005; - Contribute to an 18% reduction in U.S. carbon intensity by 2012 as established by the Administration’s “National Goal to Reduce Emissions Intensity.” 8

  18. Service Innovations

    DEFF Research Database (Denmark)

    Sørensen, Lene Tolstrup; Nicolajsen, Hanne Westh

    2010-01-01

    This article discusses the challenges in relation to an ongoing project named converged advanced mobile media platform (CAMMP), where all the different stakeholders need to have a saying in the service development for the upcoming rich, mobile broadcasting services....

  19. German innovation initiative for nanotechnology

    Science.gov (United States)

    Rieke, Volker; Bachmann, Gerd

    2004-10-01

    In many areas of nanotechnology, Germany can count on a good knowledge basis due to its diverse activities in nanosciences. This knowledge basis, when paired with the production and sales structures needed for implementation and the internationally renowned German talent for system integration, should consequently lead to success in the marketplace. And this is exactly the field of application for the innovation initiative "Nanotechnologie erobert Märkte" (nanotechnology conquers markets) and for the new BMBF strategy in support of nanotechnology. Until now, aspects of nanotechnology have been advanced within the confines of their respective technical subject areas. However, the primary aim of incorporating them into an overall national strategy is to build on Germany's well-developed and internationally competitive research in science and technology to tap the potential of Germany's important industrial sectors for the application of nanotechnology through joint research projects (leading-edge innovations) that strategically target the value-added chain. This development is to be supported by government education policy to remedy a threatening shortage of skilled professionals. To realize that goal, forward-looking political policymaking must become oriented to a uniform concept of innovation, one that takes into consideration all facets of new technological advances that can contribute to a new culture of innovation in Germany. And that includes education and research policy as well as a climate that encourages and supports innovation in science, business and society.

  20. Global Health Innovation Technology Models

    Directory of Open Access Journals (Sweden)

    Kimberly Harding

    2016-04-01

    Full Text Available Chronic technology and business process disparities between High Income, Low Middle Income and Low Income (HIC, LMIC, LIC research collaborators directly prevent the growth of sustainable Global Health innova‐ tion for infectious and rare diseases. There is a need for an Open Source-Open Science Architecture Framework to bridge this divide. We are proposing such a framework for consideration by the Global Health community, by utiliz‐ ing a hybrid approach of integrating agnostic Open Source technology and healthcare interoperability standards and Total Quality Management principles. We will validate this architecture framework through our programme called Project Orchid. Project Orchid is a conceptual Clinical Intelligence Exchange and Virtual Innovation platform utilizing this approach to support clinical innovation efforts for multi-national collaboration that can be locally sustainable for LIC and LMIC research cohorts. The goal is to enable LIC and LMIC research organizations to acceler‐ ate their clinical trial process maturity in the field of drug discovery, population health innovation initiatives and public domain knowledge networks. When sponsored, this concept will be tested by 12 confirmed clinical research and public health organizations in six countries. The potential impact of this platform is reduced drug discovery and public health innovation lag time and improved clinical trial interventions, due to reliable clinical intelligence and bio-surveillance across all phases of the clinical innovation process.

  1. HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Francesca Esposito

    2012-01-01

    Full Text Available During the retrotranscription process, characteristic of all retroviruses, the viral ssRNA genome is converted into integration-competent dsDNA. This process is accomplished by the virus-coded reverse transcriptase (RT protein, which is a primary target in the current treatments for HIV-1 infection. In particular, in the approved therapeutic regimens two classes of drugs target RT, namely, nucleoside RT inhibitors (NRTIs and nonnucleoside RT inhibitors (NNRTIs. Both classes inhibit the RT-associated polymerase activity: the NRTIs compete with the natural dNTP substrate and act as chain terminators, while the NNRTIs bind to an allosteric pocket and inhibit polymerization noncompetitively. In addition to these two classes, other RT inhibitors (RTIs that target RT by distinct mechanisms have been identified and are currently under development. These include translocation-defective RTIs, delayed chain terminators RTIs, lethal mutagenesis RTIs, dinucleotide tetraphosphates, nucleotide-competing RTIs, pyrophosphate analogs, RT-associated RNase H function inhibitors, and dual activities inhibitors. This paper describes the HIV-1 RT function and molecular structure, illustrates the currently approved RTIs, and focuses on the mechanisms of action of the newer classes of RTIs.

  2. Technological Innovations in Forensic Genetics

    DEFF Research Database (Denmark)

    Wienroth, Matthias; Morling, Niels; Williams, Robin

    2014-01-01

    This paper discusses the nature of four waves of technological innovations in forensic genetics alongside the social, legal and ethical aspect of these innovations. It emphasises the way in which technological advances and their socio-legal frameworks are co-produced, shaping technology...... expectations, social identities, and legal institutions. It also considers how imagined and actual uses of forensic genetic technologies are entangled with assertions about social order, affirmations of common values and civil rights, and promises about security and justice. Our comments seek to encourage...

  3. Disruptive Innovation in Numerical Hydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Waltz, Jacob I. [Los Alamos National Laboratory

    2012-09-06

    We propose the research and development of a high-fidelity hydrodynamic algorithm for tetrahedral meshes that will lead to a disruptive innovation in the numerical modeling of Laboratory problems. Our proposed innovation has the potential to reduce turnaround time by orders of magnitude relative to Advanced Simulation and Computing (ASC) codes; reduce simulation setup costs by millions of dollars per year; and effectively leverage Graphics Processing Unit (GPU) and future Exascale computing hardware. If successful, this work will lead to a dramatic leap forward in the Laboratory's quest for a predictive simulation capability.

  4. Problem framing in new innovation spaces

    DEFF Research Database (Denmark)

    Lema, Rasmus

    2015-01-01

    This paper is concerned with the global distribution of innovation activity. It uses the case of the software industry to show that there is considerable scope for innovation as an incremental extension of routine outsourcing low-cost countries. To show this, the paper develops a new vocabulary...... for the analysis of innovation outsourcing in global value chains. It then draws on qualitative case study research focused on outsourcing from firms in OECD countries to firms in Bangalore, India. Some buyers are willing to farm out ‘advanced’ activities to firms of the new innovation spaces. But such advanced...... innovation activities are rarely outsourced on a standalone basis; instead they are integrated with standard services. Such ‘integrated’ innovation activities are difficult to identify and measure and they are therefore often overlooked. For this reason, much of the existing literature on outsourcing...

  5. Microfluidic cell chips for high-throughput drug screening.

    Science.gov (United States)

    Chi, Chun-Wei; Ahmed, Ah Rezwanuddin; Dereli-Korkut, Zeynep; Wang, Sihong

    2016-05-01

    The current state of screening methods for drug discovery is still riddled with several inefficiencies. Although some widely used high-throughput screening platforms may enhance the drug screening process, their cost and oversimplification of cell-drug interactions pose a translational difficulty. Microfluidic cell-chips resolve many issues found in conventional HTS technology, providing benefits such as reduced sample quantity and integration of 3D cell culture physically more representative of the physiological/pathological microenvironment. In this review, we introduce the advantages of microfluidic devices in drug screening, and outline the critical factors which influence device design, highlighting recent innovations and advances in the field including a summary of commercialization efforts on microfluidic cell chips. Future perspectives of microfluidic cell devices are also provided based on considerations of present technological limitations and translational barriers.

  6. A concise review on smart polymers for controlled drug release.

    Science.gov (United States)

    Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

    2016-06-01

    Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications.

  7. Advancing Concentrating Solar Power Research (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2014-02-01

    Researchers at the National Renewable Energy Laboratory (NREL) provide scientific, engineering, and analytical expertise to help advance innovation in concentrating solar power (CSP). This fact sheet summarizes how NREL is advancing CSP research.

  8. 中石油装备制造业务技术创新发展与展望%Advance and Prospect of Technology Innovation of CNPC’s Equipment Manufacturing Business

    Institute of Scientific and Technical Information of China (English)

    张晗亮; 罗超; 刘兆黎; 秦莲香

    2016-01-01

    石油装备制造是石油行业的重要支撑性产业,先进的技术装备是勘探开发和炼油化工水平提升的前提和保证。面临长期低油价,中石油装备制造业务发展何去何从,是亟待思考的问题。介绍了中石油装备制造业务技术创新成果和存在的不足,通过分析指出:中石油装备制造业务应以满足油气主业发展需要为出发点,以提高自主创新能力为核心,以市场为导向,加强绿色、深层、海洋、非常规等高端替代进口装备研发和现有优势传统主导产品技术升级,加快产品结构调整,加快向服务延伸,打造技术竞争优势。%The petroleum equipment manufacturing is an important supportive industry for the petroleum in⁃dustry. Advanced equipment is the premise and the guarantee of promoting the exploitation and refining level. The development of CNPC equipment manufacturing business has been an urgent issue under the long term low oil price environment. The CNPC equipment manufacturing technology innovation products and the shortcomings have been introduced. Analyses show that, the CNPC equipment manufacturing business should set satisfying the main petro⁃leum business development as target, improving independent innovation as the core, taking the market as the trend guide, so that to enhance research and development of high⁃end equipment for green, deep formation, offshore and unconventional oil and gas reservoir development, improve upgrade of the main conventional products, promote ad⁃justment of products structure and stretching into service, thus establish the technical competitive advantage.

  9. CSR and market changing product innovations: Indian case studies

    OpenAIRE

    Ramani, S.V.; Mukherjee, V.

    2010-01-01

    Do firms need to sacrifice profit while innovating in order to further social objectives, as corporate social responsibility (CSR) would seem to suggest? To answer this question, the paper compiles a classification of innovations according to market impact and CSR potential. Then it details case studies of two market changing (MC) innovations in India: genetically modified cotton of Monsanto and a drugs cocktail for HIV/AIDS of Cipla. It demonstrates that the CSR potential of an MC innovation...

  10. Ensuring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction.

    Science.gov (United States)

    Francoeur, Richard B

    2011-01-01

    This article proposes and develops novel components of community-oriented programs for creating and affording access to safe medication dispensing centers in existing retail pharmacies and in permanent or travelling pharmacy clinics that are guarded by assigned or off-duty police officers. Pharmacists at these centers would work with police, medical providers, social workers, hospital administrators, and other professionals in: planning and overseeing the safe storage of controlled substance medications in off-site community safe-deposit boxes; strengthening communication and cooperation with the prescribing medical provider; assisting the prescribing medical provider in patient monitoring (checking the state prescription registry, providing pill counts and urine samples); expanding access to lower-cost, and in some cases, abuse-resistant formulations of controlled substance medications; improving transportation access for underserved patients and caregivers to obtain prescriptions; and integrating community agencies and social networks as resources for patient support and monitoring. Novel components of two related community-oriented programs, which may be hosted outside of safe medication dispensing centers, are also suggested and described: (1) developing medication purchasing cooperatives (ie, to help patients, families, and health institutions afford the costs of medications, including tamper-or abuse-resistant/deterrent drug formulations); and (2) expanding the role of inner-city methadone maintenance treatment programs in palliative care (ie, to provide additional patient monitoring from a second treatment team focusing on narcotics addiction, and potentially, to serve as an untapped source of opioid medication for pain that is less subject to abuse, misuse, or diversion).

  11. Exploration on Innovative Management Mode of National Drugs in Medical Institution%医疗机构制剂民族药创新管理模式初探

    Institute of Scientific and Technical Information of China (English)

    吕艳; 袁建平

    2016-01-01

    依据当前国家相关法律法规及医药学研究领域的新动态结合民族药研究创新机制,提出医疗机构制剂发展的新模式。探讨当前医疗机构制剂生存与发展的思路,构建三大管理体系,获取政府及第三方机构支持,建立民族药研究平台,打造特色民族药制剂精品。%According to the current national laws and regulations and new developments in the field of pharmaceutical research with national innovation mechanism,proposed the development of new formulations of medical institutions model.To seek the current medical institutions to survive and development,build three management system,access to government and third-party support,the establishment of national drug research platform to create specialty products.

  12. Nanotechnology Innovations

    Science.gov (United States)

    Malroy, Eric

    2010-01-01

    Nanotechnology is rapidly affecting all engineering disciplines as new products and applications are being found and brought to market. This session will present an overview of nanotechnology and let you learn about the advances in the field and how it could impact you. Some of the areas touched upon will be nanomaterials with their multifunctional capabilities, nanotechnology impact on energy systems, nanobiotechnology including nanomedicine, and nanotechnology relevant to space systems with a focus on ECLSS. Also, some important advances related to thermal systems will be presented as well as future predictions on nanotechnology.

  13. Approaching Service Innovation Patterns

    Directory of Open Access Journals (Sweden)

    Andrea NAGY

    2013-06-01

    Full Text Available The present paper aims at analyzing the types of innovation in the field of services. First, the concept of innovation is defined and second, field literature is reviewed from the perspective of service innovation. The main types of innovation are identified based on several attempts at defining innovation, the most notable being Schumpeter’s. Thus, it is possible to approach concepts such as product and process innovation, incremental and radical innovation. Another aim has been to regard service innovation as a standout type of innovation.

  14. Advanced Cathode Electrolyzer (ACE) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a static, cathode-fed, 2000 psi, balanced-pressure Advanced Cathode Electrolyzer (ACE) based on PEM electrolysis technology. It...

  15. Innovation Promises and Evidence Realities.

    Science.gov (United States)

    Maschke, Karen J

    2016-09-01

    Over the past year media outlets and scientific and bioethics journals have reported about several medical and scientific innovations touted as having the potential to fundamentally change not only how diseases and disorders are diagnosed and treated but even how to alter the genomes of future generations. The purported "miracle" blood-testing technology of Theranos and the potential use of the genome editing technology CRISPR-Cas9 to modify human and nonhuman organisms reflect dramatic advances in scientific understanding about the biological mechanisms of humans and other living organisms. Yet evidence about whether these and other innovative biomedical technologies are safe and effective and lead to improved health outcomes for patients young and old is often in dispute. How to assess the safety and effectiveness of innovative biomedical technologies, who should be involved in that effort, and how to define risks and benefits of those technologies are questions at the intersection of values, interests, and politics.

  16. Innovative Clean Coal Technology (ICCT): 180 MW demonstration of advanced tangentially-fired combustion techniques for the reduction of nitrogen oxide (NO[sub x]) emissions from coal-fired boilers

    Energy Technology Data Exchange (ETDEWEB)

    1992-11-25

    This quarterly report discusses the technical progress of a US Department of Energy (DOE) Innovative Clean Coal Technology (ICCT) Project demonstrating advanced tangentially-fired combustion techniques for the reduction of nitrogen oxide (NO[sub x]) emissions from a coal-fired boiler. The project is being conducted at Gulf Power Company's Plant Lansing Smith Unit 2 located near Panama City, Florida. The primary objective of this demonstration is to determine the long-term effects of commercially available tangentially-fired low NO[sub x] combustion technologies on NO[sub x] emissions and boiler performance. A target of achieving fifty percent NO[sub x] reduction using combustion modifications has been established for the project. The stepwise approach that is being used to evaluate the NO[sub x] control technologies requires three plant outages to successively install the test instrumentation and the different levels of the low NO[sub x] concentric firing system (LNCFS). Following each outage, a series of four groups of tests are performed. These are (1) diagnostic, (2) performance, (3) long-term, and (4) verification. These tests are used to quantify the NO[sub x] reductions of each technology and evaluate the effects of those reductions on other combustion parameters such as particulate characteristics and boiler efficiency. This technical progress report presents the LNCFS Level I short-term data collected during this quarter. In addition, a comparison of all the long-term emissions data that have been collected to date is included.

  17. Innovative Clean Coal Technology (ICCT): 180 MW demonstration of advanced tangentially-fired combustion techniques for the reduction of nitrogen oxide (NO{sub x}) emissions from coal-fired boilers. Technical progress report, second quarter 1992

    Energy Technology Data Exchange (ETDEWEB)

    1992-11-25

    This quarterly report discusses the technical progress of a US Department of Energy (DOE) Innovative Clean Coal Technology (ICCT) Project demonstrating advanced tangentially-fired combustion techniques for the reduction of nitrogen oxide (NO{sub x}) emissions from a coal-fired boiler. The project is being conducted at Gulf Power Company`s Plant Lansing Smith Unit 2 located near Panama City, Florida. The primary objective of this demonstration is to determine the long-term effects of commercially available tangentially-fired low NO{sub x} combustion technologies on NO{sub x} emissions and boiler performance. A target of achieving fifty percent NO{sub x} reduction using combustion modifications has been established for the project. The stepwise approach that is being used to evaluate the NO{sub x} control technologies requires three plant outages to successively install the test instrumentation and the different levels of the low NO{sub x} concentric firing system (LNCFS). Following each outage, a series of four groups of tests are performed. These are (1) diagnostic, (2) performance, (3) long-term, and (4) verification. These tests are used to quantify the NO{sub x} reductions of each technology and evaluate the effects of those reductions on other combustion parameters such as particulate characteristics and boiler efficiency. This technical progress report presents the LNCFS Level I short-term data collected during this quarter. In addition, a comparison of all the long-term emissions data that have been collected to date is included.

  18. Evaluation of melanoma antigen gene A3 expression in drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors in advanced nonsmall cell lung cancer treatment

    Directory of Open Access Journals (Sweden)

    Ju Jin

    2015-01-01

    Conclusion: MAGE-A3 expression in EGFR-TKIs target therapy in NSCLC patient suggests that there might be EGFR-TKIs drug resistance, and the higher the level of expression, the shorter the time of acquired drug resistance.

  19. Funding innovation

    CERN Multimedia

    Marina Giampietro

    2012-01-01

    For the first time, six knowledge and technology transfer activities are set to benefit from a dedicated fund made available by the Knowledge Transfer group. This initiative cements CERN’s commitment to sharing its technological knowledge and expertise with society.   GEM detectors for flame detection and early earthquake prediction, radio-frequency absorbers for energy recovery, and exotic radioisotopes for medical applications are among the projects funded by the recently introduced KT Fund. “CERN’s scientific programme generates a considerable amount of intellectual property, a natural driver for innovation,” explains Giovanni Anelli, Head of the Knowledge Transfer Group. “Very often, though, financial support is needed to bring the newly-born technologies a step further and make them ready for transfer to other research institutes or to companies.” This is where the KT fund comes into play. It provides vital support in the early sta...

  20. Innovative Pedagogy

    DEFF Research Database (Denmark)

    and educational changes might challenge or facilitate learning for students and educators. Besides its relevance within the education sector, the content presented here can be applied in non-formal learning environments, such as museums, cultural institutions, as well as other educational settings where emotions......The main purpose of this book is to take a closer look at how students and teachers in educational institutions apply the innovative, the playful and the emotional and creative dimensions of learning. With this contribution, the authors aim at reaching an international audience of educators...... at several levels, including primary and secondary schools, higher and adult education, university colleges, graduate, undergraduate and PhD schools. Driven by the common interest of the authors to reflect on emotions in education, the chapters in this book encompass multiple perspectives: the socio...

  1. Protein chemical synthesis in drug discovery.

    Science.gov (United States)

    Liu, Fa; Mayer, John P

    2015-01-01

    The discovery of novel therapeutics to combat human disease has traditionally been among the most important goals of research chemists. After a century of innovation, state-of-the-art chemical protein synthesis is now capable of efficiently assembling proteins of up to several hundred residues in length from individual amino acids. By virtue of its unique ability to incorporate non-native structural elements, chemical protein synthesis has been seminal in the recent development of several novel drug discovery technologies. In this chapter, we review the key advances in peptide and protein chemistry which have enabled our current synthetic capabilities. We also discuss the synthesis of D-proteins and their applications in mirror image phage-display and racemic protein crystallography, the synthesis of enzymes for structure-based drug discovery, and the direct synthesis of homogenous protein pharmaceuticals.

  2. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  3. Innovative potential, innovative strategy, environment factors, estimation of innovative potential, innovative development

    OpenAIRE

    Chernoivanova, G.

    2011-01-01

    The paper summarizes the elements of the innovation potential and the criteria for its evaluation. It is proposed methodical approach to the formation of innovation strategies with innovative potential.

  4. Innovation in Your Community

    Science.gov (United States)

    EPA has many innovation programs that can help the public bring innovative solutions to their local areas by reducing waste, engaging students to contribute innovative ideas, and helping businesses implement sustainable practices.

  5. Innovative Separations Technologies

    Energy Technology Data Exchange (ETDEWEB)

    J. Tripp; N. Soelberg; R. Wigeland

    2011-05-01

    Reprocessing used nuclear fuel (UNF) is a multi-faceted problem involving chemistry, material properties, and engineering. Technology options are available to meet a variety of processing goals. A decision about which reprocessing method is best depends significantly on the process attributes considered to be a priority. New methods of reprocessing that could provide advantages over the aqueous Plutonium Uranium Reduction Extraction (PUREX) and Uranium Extraction + (UREX+) processes, electrochemical, and other approaches are under investigation in the Fuel Cycle Research and Development (FCR&D) Separations Campaign. In an attempt to develop a revolutionary approach to UNF recycle that may have more favorable characteristics than existing technologies, five innovative separations projects have been initiated. These include: (1) Nitrogen Trifluoride for UNF Processing; (2) Reactive Fluoride Gas (SF6) for UNF Processing; (3) Dry Head-end Nitration Processing; (4) Chlorination Processing of UNF; and (5) Enhanced Oxidation/Chlorination Processing of UNF. This report provides a description of the proposed processes, explores how they fit into the Modified Open Cycle (MOC) and Full Recycle (FR) fuel cycles, and identifies performance differences when compared to 'reference' advanced aqueous and fluoride volatility separations cases. To be able to highlight the key changes to the reference case, general background on advanced aqueous solvent extraction, advanced oxidative processes (e.g., volumetric oxidation, or 'voloxidation,' which is high temperature reaction of oxide UNF with oxygen, or modified using other oxidizing and reducing gases), and fluorination and chlorination processes is provided.

  6. 日本创新药物研发激励政策及对我国的启示——基于依达拉奉研发的实证分析%Research on incentive policies of innovative drugs in Japan and its enlightenment to China-an empirical study on research and development of edaravone

    Institute of Scientific and Technical Information of China (English)

    丁锦希; 孟立立; 罗茜玮

    2011-01-01

    本研究意在为完善我国创新药物研发激励政策提供借鉴并提出建议.通过简要分析日本创新药物研发各项激励政策,并以日本重大创新药物依达拉奉为实证研究对象,采用个案剖析的方法,深入探讨激励政策对创新药物研发的激励机制及实施绩效.结果表明,日本创新政策对该国的创新药物研发起到了极大的促进和激励作用.我国应借鉴日本的成功经验,积极调整和完善相关创新药物研发激励政策.%This study aims at providing specific reference and guidance to improve incentive policies on innovative drugs in our country. Based on a brief analysis of the incentive policies on the innovative drugs in Japan, this study deeply explores the mechanism as well as the performance of the implementation of the incentive policies, utilizing the case analysis method and taking the innovative drug edaravone as an example. The result shows that the series of incentive policies adopted by Japan had greatly promoted its research and development. The successful experience of Japan should be introduced to improve and perfect the research and development of incentive policies on innovative drugs in our country.

  7. Modeling Innovations Advance Wind Energy Industry

    Science.gov (United States)

    2009-01-01

    In 1981, Glenn Research Center scientist Dr. Larry Viterna developed a model that predicted certain elements of wind turbine performance with far greater accuracy than previous methods. The model was met with derision from others in the wind energy industry, but years later, Viterna discovered it had become the most widely used method of its kind, enabling significant wind energy technologies-like the fixed pitch turbines produced by manufacturers like Aerostar Inc. of Westport, Massachusetts-that are providing sustainable, climate friendly energy sources today.

  8. Rocket Engine Innovations Advance Clean Energy

    Science.gov (United States)

    2012-01-01

    During launch countdown, at approximately T-7 seconds, the Space Shuttle Main Engines (SSMEs) roar to life. When the controllers indicate normal operation, the solid rocket boosters ignite and the shuttle blasts off. Initially, the SSMEs throttle down to reduce stress during the period of maximum dynamic pressure, but soon after, they throttle up to propel the orbiter to 17,500 miles per hour. In just under 9 minutes, the three SSMEs burn over 1.6 million pounds of propellant, and temperatures inside the main combustion chamber reach 6,000 F. To cool the engines, liquid hydrogen circulates through miles of tubing at -423 F. From 1981to 2011, the Space Shuttle fleet carried crew and cargo into orbit to perform a myriad of unprecedented tasks. After 30 years and 135 missions, the feat of engineering known as the SSME boasted a 100-percent flight success rate.

  9. Systematic Implementation of Innovation Best Practices:Thota Framework for Innovation

    Institute of Scientific and Technical Information of China (English)

    Hamsa; Thota

    2011-01-01

    The Product Development and Management Association(PDMA)comparative performance assessment studies(CPAS)teach us that the new product development(NPD)and innovation management practices continue to evolve.However,advances in the practice of NPD and innovation did not yield significant increases in new product success rates.However,the PDMA 2003 CPAS reported a significant difference in the success rates for top performing businesses versus the"rest".This paper summarizes innovation practices of top performing businesses from CPAS and compares them with the practices of PDMA Outstanding Corporate Innovator(OCI)Award winning companies.The paper verifies that what the top performers say they do in research surveys is actually what the outstanding corporate innovators do in practice.The paper then raises the question of how underperforming companies can implement key learnings from the best to improve their own innovation performance.The development of Thota framework for innovation as a systematic framework to help underperformers implement the best practices is discussed.As a case study,the implementation of the Thota framework for innovation is illustrated with BMW,an OCI award winning company.The Thota Framework for Innovation is based on three organizing principles and eight actions.Underperforming businesses can improve their innovation performance by internalizing the three organizing principles and rigorously implementing eight actions specified in the Thota framework for innovation.

  10. INTERORGANIZATIONAL INNOVATION DYNAMICS

    OpenAIRE

    Dan SERGHIE

    2013-01-01

    The directions of research on innovation or on the staging of innovative processes progress have evaluated over time from an innovational perspective constraint within an activity pursued by the entrepreneur (regarded as an entity creating possible and numerous innovative combinations) to an innovational perspective (induced in innovative processes and structures) framed and carried wider within the organizational internal environment, as response triggered and driven by market requirements. ...

  11. Innovation Management and Knowledge Economics

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This paper includes three parts: (1) The main characteristics of knowledge economics in new era; (2) Innovation management is an inevitable trend; (3) Corporate culture lead literary excellence. With the advance of science technique and development of productive force , huma nity entered on knowledge economics era.It is a new social economic pattern that occupy and coordinate intellectual resources and causes some essential changes of produce method. Investment pattern, industrial construction, throug...

  12. Services in innovation - Innovation in services

    OpenAIRE

    Hauknes, Johan

    1998-01-01

    There has been a considerable gap between efforts to understand innovation and other change processes, and ongoing structural changes in national economies. The SI4S project has aimed at developing concepts, empirical evidence and proposals for practical action concerning the role of services in European innovation systems. The general objectives were to map, understand and analyse the changing role of services and service innovations as users, carriers, shapers and sources of innovations in ...

  13. The changing environment for technological innovation in health care.

    Science.gov (United States)

    Goodman, C S; Gelijns, A C

    1996-01-01

    A distinguishing feature of American health care is its emphasis on advanced technology. Yet today's changing health care environment is overhauling the engine of technological innovation. The rate and direction of technological innovation are affected by a complex of supply- and demandside factors, including biomedical research, education, patent law, regulation, health care payment, tort law, and more. Some distinguishing features of technological innovation in health care are now at increased risk. Regulatory requirements and rising payment hurdles are especially challenging to small technology companies. Closer management of health care delivery and payment, particularly the standardization that may derive from practice guidelines and clamping down on payment for investigational technologies, curtails opportunities for innovation. Levels and distribution of biomedical research funding in government and industry are changing. Financial constraints are limiting the traditional roles of academic health centers in fostering innovation. Despite notable steps in recent years to lower regulatory barriers and speed approvals, especially for products for life-threatening conditions, the Food and Drug Administration is under great pressure from Congress, industry, and patients to do more. Technology gatekeeping is shifting from hundreds of thousands of physicians acting on behalf of their patients to fewer, yet more powerful, managed care organizations and health care networks. Beyond its direct effects on adoption, payment, and use of technologies, the extraordinary buying leverage of these large providers is cutting technology profit margins and heightening competition among technology companies. It is contributing to unprecedented restructuring of the pharmaceutical and medical device industries, leading to unprecedented alliances with generic product companies, health care providers, utilization review companies, and other agents. These industry changes are already

  14. Designing collaborative policy innovation

    DEFF Research Database (Denmark)

    Agger, Annika; Sørensen, Eva

    2014-01-01

    Recent approaches to enhancing public innovation suffer from two shortcomings: They overemphasize competition as a driver of innovation and overlook the fact that public sector innovation involves policy innovation as well as service innovation. Drawing on governance research and innovation theory......, the chapter investigates the extent to which and how collaboration between politicians and relevant stakeholders can spur the formulation, implementation and diffusion of new innovative policies. A case study of a process of collaborative policy innovation in a Danish municipality shows that collaborative...

  15. Challenging the Innovation Paradigm

    CERN Document Server

    Sveiby, Karl Erik; Segercrantz, Beata

    2012-01-01

    Innovation is almost always seen as a "good thing". Challenging the Innovation Paradigm is a critical analysis of the innovation frenzy and contemporary innovation research. The one-sided focus on desirable effects of innovation misses many opportunities to reduce the undesirable consequences. Authors in this book show how systemic effects outside the innovating firms reduce the net benefits of innovation for individual employees, customers, as well as for society as a whole - also the innovators' own organizations. This book analyzes the dominant discourses that construct and recons

  16. Innovations in national nutrition surveys.

    Science.gov (United States)

    Stephen, Alison M; Mak, Tsz Ning; Fitt, Emily; Nicholson, Sonja; Roberts, Caireen; Sommerville, Jill

    2013-02-01

    The aim of this paper is to describe innovations taking place in national nutrition surveys in the UK and the challenges of undertaking innovations in such settings. National nutrition surveys must be representative of the overall population in characteristics such as socio-economic circumstances, age, sex and region. High response rates are critical. Dietary assessment innovations must therefore be suitable for all types of individuals, from the very young to the very old, for variable literacy and/or technical skills, different ethnic backgrounds and life circumstances, such as multiple carers and frequent travel. At the same time, national surveys need details on foods consumed. Current advances in dietary assessment use either technological innovations or simplified methods; neither lend themselves to national surveys. The National Diet and Nutrition Survey (NDNS) rolling programme, and the Diet and Nutrition Survey of Infants and Young Children (DNSIYC), currently use the 4-d estimated diary, a compromise for detail and respondent burden. Collection of food packaging enables identification of specific products. Providing space for location of eating, others eating, the television being on and eating at a table, adds to eating context information. Disaggregation of mixed dishes enables determination of true intakes of meat and fruit and vegetables. Measurement of nutritional status requires blood sampling and processing in DNSIYC clinics throughout the country and mobile units were used to optimise response. Hence, innovations in national surveys can and are being made but must take into account the paramount concerns of detail and response rate.

  17. Workplace innovation and social innovation : an introduction

    NARCIS (Netherlands)

    Howaldt, Jürgen; Oeij, Peter R.A.; Dhondt, Steven; Fruytier, Ben

    2016-01-01

    This is the introduction to the special issue of World Review of Entrepreneurship, Management and Sustainable Development (WREMSD) dedicated to workplace innovation and social innovation related to work and organisation. As technological and business model innovations alone are not sufficient to enh

  18. Workplace innovation and social innovation: an introduction

    NARCIS (Netherlands)

    Howaldt, J.; Oeij, P.R.A.; Dhondt, S.; Fruytier, B.

    2016-01-01

    This is the introduction to this special issue of World Review of Entrepreneurship, Management and Sustainable Development (WREMSD) dedicated to workplace innovation and social innovation related to work and organisation. As technological and business model innovations alone are not sufficient to en

  19. 78 FR 34346 - Proposed Information Collection; Comment Request; NIST MEP Advanced Manufacturing Jobs and...

    Science.gov (United States)

    2013-06-07

    ... Advanced Manufacturing Jobs and Innovation Accelerator Challenge (AMJIAC) Client Impact Survey AGENCY... information collection. The purpose of the Advanced Manufacturing Jobs and Innovation Accelerator Challenge... to support job creation, encourage economic development, and enhance the competitiveness of...

  20. Supporting FEI through innovation strategy implementation

    DEFF Research Database (Denmark)

    Aagaard, Annabeth

    discovered therapeutic agent with blockbuster potential still faces more than a 90% change of failure during the development phase (Duyck, 2003), and knowing that the fully loaded cost for the development of the agent amount to about one billion dollars (Pacl et al., 2004) underlines that enhancing......, Steven & Burly, 2003, and Vernorn et al., 2008) and that innovation strategies play a central role in optimization of innovation (Clark & Wheelwright, 1995; Cottam et al., 2001; Morgan & Berthon, 2008). Cottam et al. (2001) stress that in order to maximize the benefits of previous innovations innovative......, are increasingly being compelled to provide stronger drug candidates for efficient drug development and quick market launches. This challenges the organization and structures of pharmaceutical FEI emphasizing the need to support and enable the front end activities in a targeted manner. In an industry where a newly...