WorldWideScience

Sample records for biological drug products

  1. 75 FR 33312 - Indexing Structured Product Labeling for Human Prescription Drug and Biological Products; Request...

    Science.gov (United States)

    2010-06-11

    ...] Indexing Structured Product Labeling for Human Prescription Drug and Biological Products; Request for... Biologics Evaluation and Research (CBER) are indexing certain categories of information in product labeling for use as terms to search repositories of approved prescription medical product structured product...

  2. 78 FR 65904 - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products

    Science.gov (United States)

    2013-11-04

    ... Manufacturing of Certain Drug or Biological Products AGENCY: Food and Drug Administration, HHS. ACTION: Proposed.... The Fabrazyme shortage resulted from contamination at the manufacturing [[Page 65910

  3. Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products. Final rule.

    Science.gov (United States)

    2015-07-08

    The Food and Drug Administration (FDA or the Agency) is amending its regulations to implement certain drug shortages provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA). The rule requires all applicants of covered approved drugs or biological products--including certain applicants of blood or blood components for transfusion and all manufacturers of covered drugs marketed without an approved application--to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (or a significant disruption in supply for blood or blood components) of the product in the United States.

  4. Production of biological nanoparticles from Θ- lactalbumin for drug ...

    African Journals Online (AJOL)

    In recent years, the concept of controlled release of encapsulated ingredients at the right place and the right time has become of more interest to the food and pharmaceutical industry. Whey proteins are valuable by-products from the cheese industry. The physicochemical properties of the whey proteins suggest that they ...

  5. 78 FR 12760 - Guidance for Industry on Labeling for Human Prescription Drug and Biological Products...

    Science.gov (United States)

    2013-02-25

    ...--Implementing the Physician Labeling Rule Content and Format Requirements; Availability AGENCY: Food and Drug...--Implementing the PLR Content and Format Requirements.'' This guidance is intended to assist applicants in complying with the content and format requirements of labeling for human prescription drug and biological...

  6. 78 FR 58311 - Complex Issues in Developing Drug and Biological Products for Rare Diseases; Public Workshop...

    Science.gov (United States)

    2013-09-23

    ... public workshop must register online by December 20, 2013. Early registration is recommended because...; however, it does not alter the statutory standards for marketing approval. To gain approval, all drugs must demonstrate substantial evidence of effectiveness, safety, and product quality for the treatment...

  7. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    Science.gov (United States)

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  8. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Science.gov (United States)

    2010-10-01

    ... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug product that meets all of the following conditions: (1) The drug product was approved by the Food and Drug...) Any drug product that is identical, related, or similar, as defined in 21 CFR 310.6, to a drug product...

  9. Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

    Science.gov (United States)

    Li, Zhaoyang; Easton, Rachael

    2018-01-01

    The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

  10. Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

    Science.gov (United States)

    Easton, Rachael

    2018-01-01

    ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

  11. 76 FR 66235 - Bar Code Technologies for Drugs and Biological Products; Retrospective Review Under Executive...

    Science.gov (United States)

    2011-10-26

    ... interactions, overdoses, and patient allergies) and retail pharmacy-based computer systems that use a bar-coded... drugs. The goal of this initiative is to implement a system to further ensure patient safety and to..., and ideas on the need, maturity, and acceptability of alternative identification technologies for the...

  12. 78 FR 67985 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

    Science.gov (United States)

    2013-11-13

    ... add or strengthen a statement about drug abuse, dependence, psychological effect, or overdosage; To... other aspect of labeling protected by patent or exclusivity. FDA has generally taken the position that a... patients with diabetes. Source: Published literature, epidemiologic study.'' iii. The basis for the...

  13. Identification of transformation products of antiviral drugs formed during biological wastewater treatment and their occurrence in the urban water cycle.

    Science.gov (United States)

    Funke, Jan; Prasse, Carsten; Ternes, Thomas A

    2016-07-01

    The fate of five antiviral drugs (abacavir, emtricitabine, ganciclovir, lamivudine and zidovudine) was investigated in biological wastewater treatment. Investigations of degradation kinetics were accompanied by the elucidation of formed transformation products (TPs) using activated sludge lab experiments and subsequent LC-HRMS analysis. Degradation rate constants ranged between 0.46 L d(-1) gSS(-1) (zidovudine) and 55.8 L d(-1) gSS(-1) (abacavir). Despite these differences of the degradation kinetics, the same main biotransformation reaction was observed for all five compounds: oxidation of the terminal hydroxyl-moiety to the corresponding carboxylic acid (formation of carboxy-TPs). In addition, the oxidation of thioether moieties to sulfoxides was observed for emtricitabine and lamivudine. Antiviral drugs were detected in influents of municipal wastewater treatment plants (WWTPs) with concentrations up to 980 ng L(-1) (emtricitabine), while in WWTP effluents mainly the TPs were found with concentration levels up to 1320 ng L(-1) (carboxy-abacavir). Except of zidovudine none of the original antiviral drugs were detected in German rivers and streams, whereas the concentrations of the TPs ranged from 16 ng L(-1) for carboxy-lamivudine up to 750 ng L(-1) for carboxy-acyclovir. These concentrations indicate an appreciable portion from WWTP effluents present in rivers and streams, as well as the high environmental persistence of the carboxy-TPs. As a result three of the carboxylic TPs were detected in finished drinking water. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Biological anti-TNF drugs

    DEFF Research Database (Denmark)

    Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

    2017-01-01

    practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure...... is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review...... provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological...

  15. 77 FR 47397 - Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the...

    Science.gov (United States)

    2012-08-08

    ... decision-making processes. Significant public health and safety issues are brought before these committees... future pediatric product development by focusing on products whose development would benefit the most...

  16. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  17. Synthetic biology for pharmaceutical drug discovery

    Directory of Open Access Journals (Sweden)

    Trosset JY

    2015-12-01

    Full Text Available Jean-Yves Trosset,1 Pablo Carbonell2,3 1Bioinformation Research Laboratory, Sup’Biotech, Villejuif, France; 2Faculty of Life Sciences, SYNBIOCHEM Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK; 3Department of Experimental and Health Sciences (DCEXS, Research Programme on Biomedical Informatics (GRIB, Hospital del Mar Medical Research Institute (IMIM, Universitat Pompeu Fabra (UPF, Barcelona, Spain Abstract: Synthetic biology (SB is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. Keywords: metabolic engineering, plant synthetic biology, natural products, synthetic quorum sensing, drug resistance

  18. Biological hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Benemann, J.R. [Univ. of California, Berkeley, CA (United States)

    1995-11-01

    Biological hydrogen production can be accomplished by either thermochemical (gasification) conversion of woody biomass and agricultural residues or by microbiological processes that yield hydrogen gas from organic wastes or water. Biomass gasification is a well established technology; however, the synthesis gas produced, a mixture of CO and H{sub 2}, requires a shift reaction to convert the CO to H{sub 2}. Microbiological processes can carry out this reaction more efficiently than conventional catalysts, and may be more appropriate for the relatively small-scale of biomass gasification processes. Development of a microbial shift reaction may be a near-term practical application of microbial hydrogen production.

  19. FDA 101: Regulating Biological Products

    Science.gov (United States)

    ... based and cellular biologics, at the forefront of biomedical research today, may make it possible to treat a ... transplantation vaccines The Center for Drug Evaluation and Research ... as targeted therapies in cancer and other diseases cytokines (types of ...

  20. 21 CFR 601.50 - Confidentiality of data and information in an investigational new drug notice for a biological...

    Science.gov (United States)

    2010-04-01

    ... investigational new drug notice for a biological product. 601.50 Section 601.50 Food and Drugs FOOD AND DRUG... biological product. (a) The existence of an IND notice for a biological product will not be disclosed by the... availability for public disclosure of all data and information in an IND file for a biological product shall be...

  1. 21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

    Science.gov (United States)

    2010-04-01

    ... evidence of effectiveness. Conclusions based on animal data but necessary for safe and effective use of the....3 Nursing mothers 8.4 Pediatric use 8.5 Geriatric use 9 Drug Abuse and Dependence 9.1 Controlled substance 9.2 Abuse 9.3 Dependence 10 Overdosage 11 Description 12 Clinical Pharmacology 12.1 Mechanism of...

  2. Photostability and Photostabilization of Drugs and Drug Products

    Directory of Open Access Journals (Sweden)

    Iqbal Ahmad

    2016-01-01

    Full Text Available Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups important for the photoreactivity of drugs, explains photophysical processes, and deals with the kinetics of photochemical reactions. The various modes of photodegradation of drugs with examples of selected compounds are presented. The biological consequences of the effect of light on the drug degradation are described. The photostability testing of drugs and drug products and the requirements under ICH guideline are discussed. Some information on the packaging requirements for the formulated products is provided. The various methods used for the photostabilization of solid and liquid dosage forms are also discussed.

  3. Drug product selection: legal issues.

    Science.gov (United States)

    Christensen, T P; Kirking, D M; Ascione, F J; Welage, L S; Gaither, C A

    2001-01-01

    To review the potential legal liability of the pharmacist in the drug product selection process. Published articles identified through MEDLINE, published law reviews identified through InfoTrac, and appellate court decisions. Search terms used included pharmacist liability, drug product selection, and generic substitution. Additional articles, books, and appellate court decisions were identified from the bibliographies of retrieved articles and citations in appellate court decisions. Pharmacists engaging in drug product selection are civilly liable under three legal theories: negligence, express or implied warranties, and strict product liability. Potential criminal liability includes prosecution for insurance fraud, deceptive business practices, and violation of state drug product selection laws and regulation. Pharmacists increase their liability when engaging in drug product selection, but the increase is small. Still, the law continues to evolve as pharmacists seek expanded roles and responsibilities. When courts give closer examination to pharmacists' expanded role, it is likely that pharmacists' liability will increase.

  4. Biosynthesis of therapeutic natural products using synthetic biology.

    Science.gov (United States)

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 76 FR 59705 - Guidance for Industry on User Fee Waivers, Reductions, and Refunds for Drug and Biological...

    Science.gov (United States)

    2011-09-27

    ...] Guidance for Industry on User Fee Waivers, Reductions, and Refunds for Drug and Biological Products..., Reductions, and Refunds for Drug and Biological Products.'' This guidance provides recommendations to... ``User Fee Waivers, Reductions, and Refunds for Drug and Biological Products.'' This guidance provides...

  6. in OECD countries concerning biological drugs

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... the pharmaceutical sector about biological drugs come under the umbrella of innovation system of each country. ... The cost of biotechnology R and D within public research centres and ... Existence of a suitable system to protect intellectual property ... biotechnology that provide the capital for industry and.

  7. 21 CFR 25.31 - Human drugs and biologics.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Human drugs and biologics. 25.31 Section 25.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.31 Human drugs and biologics. The classes of...

  8. Radical production in biological systems

    International Nuclear Information System (INIS)

    Johnson, J.R.; Akabani, G.

    1994-10-01

    This paper describes our effort to develop a metric for radiation exposure that is more fundamental than adsorbed dose and upon which a metric for exposure to chemicals could be based. This metric is based on the production of radicals by the two agents. Radicals produced by radiation in biological systems commonly assumed to be the same as those produced in water despite the presence of a variety of complex molecules. This may explain why the extensive efforts to describe the relationship between energy deposition (track structure) and molecular damage to DNA, based on the spectrum of radicals produced, have not been successful in explaining simple biological effects such as cell killing. Current models assume that DNA and its basic elements are immersed in water-like media and only model the production and diffusion of water-based radicals and their interaction with DNA structures; these models lack the cross sections associated with each macro-component of DNA and only treat water-based radicals. It has been found that such models are not realistic because DNA is not immersed in pure water. A computer code capable of simulating electron tracks, low-energy electrons, energy deposition in small molecules, and radical production and diffusion in water like media has been developed. This code is still in at a primitive stage and development is continuing. It is being used to study radical production by radiation, and radical diffusion and interactions in simple molecular systems following their production. We are extending the code to radical production by chemicals to complement our PBPK modeling efforts. It therefore has been developed primarily for use with radionuclides that are in biological materials, and not for radiation fields

  9. 42 CFR 409.13 - Drugs and biologicals.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Drugs and biologicals. 409.13 Section 409.13 Public... § 409.13 Drugs and biologicals. (a) Except as specified in paragraph (b) of this section, Medicare pays for drugs and biologicals as inpatient hospital or inpatient CAH services only if— (1) They represent...

  10. Synthetic Biology Guides Biofuel Production

    Directory of Open Access Journals (Sweden)

    Michael R. Connor

    2010-01-01

    Full Text Available The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges.

  11. Production of a biological surfactant

    Directory of Open Access Journals (Sweden)

    N. Gladys Rosero

    2002-01-01

    Full Text Available This paper summarizes the scale up work performed at the Colombian Petroleum Institute on a process to produce at pilot plant level a biosurfactant of the rhamnolipid type. By examination of both the activation conditions of the microorganism and design aspects of the broth, a stable condition was achieved which consistently triggers the production mechanisms and thus it was obtained a significant increment in biosurfactant productivity. The biological surfactant exhibited high efficiency in applications such as hydrocarbon biodegradation in saline environments, corrosion inhibition, and crude oil recovery from storage tank bottom sludges.

  12. Linking neuroethology to the chemical biology of natural products

    DEFF Research Database (Denmark)

    Olivera, Baldomero M.; Raghuraman, Shrinivasan; Schmidt, Eric W.

    2017-01-01

    From a biological perspective, a natural product can be defined as a compound evolved by an organism for chemical interactions with another organism including prey, predator, competitor, pathogen, symbiont or host. Natural products hold tremendous potential as drug leads and have been extensively...... a better understanding of the evolution, biology and biochemistry of natural products will facilitate both neuroscience and the potential for drug leads. The larger goal is to establish a new sub-discipline in the broader field of neuroethology that we refer to as “Chemical Neuroethology”, linking...... the substantial work carried out by chemists on natural products with accelerating advances in neuroethology....

  13. Production of biological nanoparticles from bovine serum albumin ...

    African Journals Online (AJOL)

    Production of biological nanoparticles from bovine serum albumin for drug delivery. ... Bovine serum albumin (BSA) was used for generation of nanoparticles in a drug delivery system. ... The impact of protein concentration and additional rate of organic solvent (i.e. ethanol) upon the particle ... AJOL African Journals Online.

  14. Optimizing clinical drug product performance

    DEFF Research Database (Denmark)

    Dickinson, Paul A.; Kesisoglou, Filippos; Flanagan, Talia

    2016-01-01

    The aim of Biopharmaceutics Risk Assessment Roadmap (BioRAM) and the BioRAM Scoring Grid is to facilitate optimization of clinical performance of drug products. BioRAM strategy relies on therapy-driven drug delivery and follows an integrated systems approach for formulating and addressing critical...... questions and decision-making (J Pharm Sci. 2014,103(11): 3777-97). In BioRAM, risk is defined as not achieving the intended in vivo drug product performance, and success is assessed by time to decision-making and action. Emphasis on time to decision-making and time to action highlights the value of well....... Application of the BioRAM Scoring Grid is illustrated using published literature. Organizational considerations for implementing BioRAM strategy, including the interactions, function, and skillsets of the BioRAM group members, are also reviewed. As a creative and innovative systems approach, we believe...

  15. A new strategy to deliver synthetic protein drugs: self-reproducible biologics using minicircles.

    Science.gov (United States)

    Yi, Hyoju; Kim, Youngkyun; Kim, Juryun; Jung, Hyerin; Rim, Yeri Alice; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

    2014-08-05

    Biologics are the most successful drugs used in anticytokine therapy. However, they remain partially unsuccessful because of the elevated cost of their synthesis and purification. Development of novel biologics has also been hampered by the high cost. Biologics are made of protein components; thus, theoretically, they can be produced in vivo. Here we tried to invent a novel strategy to allow the production of synthetic drugs in vivo by the host itself. The recombinant minicircles encoding etanercept or tocilizumab, which are synthesized currently by pharmaceutical companies, were injected intravenously into animal models. Self-reproduced etanercept and tocilizumab were detected in the serum of mice. Moreover, arthritis subsided in mice that were injected with minicircle vectors carrying biologics. Self-reproducible biologics need neither factory facilities for drug production nor clinical processes, such as frequent drug injection. Although this novel strategy is in its very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics.

  16. Biology of Addiction: Drugs and Alcohol Can Hijack Your Brain

    Science.gov (United States)

    ... Special Issues Subscribe October 2015 Print this issue Biology of Addiction Drugs and Alcohol Can Hijack Your ... scientists are working to learn more about the biology of addiction. They’ve shown that addiction is ...

  17. Electronic Animal Drug Product Listing Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Electronic Animal Drug Product Listing Directory is a directory of all animal drug products that have been listed electronically since June 1, 2009, to comply...

  18. Administration costs of intravenous biologic drugs for rheumatoid arthritis

    OpenAIRE

    Soini, Erkki J; Leussu, Miina; Hallinen, Taru

    2013-01-01

    Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs wit...

  19. 78 FR 60884 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-02

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Immunoregulation, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics...

  20. 77 FR 3780 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-01-25

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. The...

  1. 76 FR 44016 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-07-22

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research...

  2. Toxicological Analysis of Some Drugs of Abuse in Biological Samples

    OpenAIRE

    Anne Marie Ciobanu; Daniela Baconi; Cristian Bălălău; Carolina Negrei; Miriana Stan; Maria Bârcă

    2015-01-01

    Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their consequences are one of the major current problems of European society because of the significant repercussions in individual, family, social and economic level. In this context, toxicological analysis of the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an auto-response, mandatory screening in some treatment programs, identification of a substance ...

  3. 21 CFR 310.4 - Biologics; products subject to license control.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Biologics; products subject to license control... to license control. (a) If a drug has an approved license under section 351 of the Public Health.... (b) To obtain marketing approval for radioactive biological products for human use, as defined in...

  4. The year's new drugs & biologics 2014 - Part II: trends & challenges.

    Science.gov (United States)

    Graul, A I; Serebrov, M; Cruces, E; Tracy, M; Dulsat, C

    2015-02-01

    2014 was a year of continued high activity in the pharma and biotech industry, as evidenced in part I of this annual two-part review article published last month in this journal (1). As of December 23, 2014, a total of 55 new chemical and biological entities had reached their first markets worldwide, together with another 29 important new line extensions. Another 19 products were approved for the first time during the year but not yet launched by December 23. Furthermore, during the now-traditional year-end sprint, several regulatory agencies issued last-minute approvals for other compounds that missed the deadline for inclusion in that article, bringing the total of new approvals for the year to a somewhat higher number. In addition to the successful development, registration and launch of new drugs and biologics, there are various other trends and tendencies that serve as indicators of the overall health and status of the industry. These include the pursuit of novel programs designed by regulators to stimulate the development of drugs for diseases that are currently under-treated; the regular and pragmatic culling by companies of their R&D pipelines; and the decision to unify pipelines, portfolios and sales forces through mergers and acquisitions. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  5. Photostability and Photostabilization of Drugs and Drug Products

    OpenAIRE

    Ahmad, Iqbal; Ahmed, Sofia; Anwar, Zubair; Sheraz, Muhammad Ali; Sikorski, Marek

    2016-01-01

    Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups ...

  6. Systems biology approaches to the study of cardiovascular drugs

    NARCIS (Netherlands)

    Nikolsky, Y.; Kleemann, R.

    2010-01-01

    Atherogenic lipids and chronic inflammation drive the development of cardiovascular disorders such as atherosclerosis. Many cardiovascular drugs target the liver which is involved in the formation of lipid and inflammatory risk factors. With robust systems biology tools and comprehensive

  7. Drug-device combination products: regulatory landscape and market growth.

    Science.gov (United States)

    Bayarri, L

    2015-08-01

    Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  8. 78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-04-05

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function..., Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. FDA intends to...

  9. Synthetic biology advances for pharmaceutical production

    OpenAIRE

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems.

  10. Synthetic biology advances for pharmaceutical production

    Science.gov (United States)

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

  11. Is biological aging accelerated in drug addiction?

    Science.gov (United States)

    Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-02-01

    Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

  12. Novel opportunities for computational biology and sociology in drug discovery☆

    Science.gov (United States)

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

    2013-01-01

    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. PMID:20349528

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

    Science.gov (United States)

    Yao, Lixia

    2009-01-01

    Drug discovery today is impossible without sophisticated modeling and computation. In this review we touch on previous advances in computational biology and by tracing the steps involved in pharmaceutical development, we 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 ties 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. PMID:19674801

  14. Toxicological Analysis of Some Drugs of Abuse in Biological Samples

    Directory of Open Access Journals (Sweden)

    Anne Marie Ciobanu

    2015-10-01

    Full Text Available Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their consequences are one of the major current problems of European society because of the significant repercussions in individual, family, social and economic level. In this context, toxicological analysis of the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an auto-response, mandatory screening in some treatment programs, identification of a substance in the case of an overdose, determining compliance of the treatment. The present paper aims to address the needs of healthcare professionals involved in drugs addiction treatment through systematic presentation of information regarding their toxicological analysis. Basically, it is a tool that help you to select the suitable biological sample and the right collecting time, as well as the proper analysis technique, depending on the purpose of analysis, pharmacokinetic characteristics of the drugs of abuse, available equipment and staff expertise.

  15. Biological production of organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jianping; Paddock, Troy; Carrieri, Damian; Maness, Pin-Ching; Seibert, Michael

    2016-04-12

    Strains of cyanobacteria that produce high levels of alpha ketoglutarate (AKG) and pyruvate are disclosed herein. Methods of culturing these cyanobacteria to produce AKG or pyruvate and recover AKG or pyruvate from the culture are also described herein. Nucleic acid sequences encoding polypeptides that function as ethylene-forming enzymes and their use in the production of ethylene are further disclosed herein. These nucleic acids may be expressed in hosts such as cyanobacteria, which in turn may be cultured to produce ethylene.

  16. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-03-14

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Polysaccharides, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review...

  17. 76 FR 55397 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-09-07

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... Laboratory of Method Development, Division of Viral Products, Office of Vaccines Research and Review, Center...

  18. Lipophilic drug transfer between liposomal and biological membranes

    DEFF Research Database (Denmark)

    Fahr, Alfred; van Hoogevest, Peter; Kuntsche, Judith

    2006-01-01

    This review presents the current knowledge on the interaction of lipophilic, poorly water soluble drugs with liposomal and biological membranes. The center of attention will be on drugs having the potential to dissolve in a lipid membrane without perturbing them too much. The degree of interaction...... is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes. Finally, the consequences of these two factors on the design of lipid-based carriers for oral, as well as parenteral use, for lipophilic drugs and lead selection of oral...... lipophilic drugs is described. Since liposomes serve as model-membranes for natural membranes, the assessment of lipid solubility and transfer kinetics of lipophilic drug using liposome formulations may additionally have predictive value for bioavailability and biodistribution and the pharmacokinetics...

  19. The effect of network biology on drug toxicology

    DEFF Research Database (Denmark)

    Gautier, Laurent; Taboureau, Olivier; Audouze, Karine Marie Laure

    2013-01-01

    Introduction: The high failure rate of drug candidates due to toxicity, during clinical trials, is a critical issue in drug discovery. Network biology has become a promising approach, in this regard, using the increasingly large amount of biological and chemical data available and combining...... it with bioinformatics. With this approach, the assessment of chemical safety can be done across multiple scales of complexity from molecular to cellular and system levels in human health. Network biology can be used at several levels of complexity. Areas covered: This review describes the strengths and limitations...... of network biology. The authors specifically assess this approach across different biological scales when it is applied to toxicity. Expert opinion: There has been much progress made with the amount of data that is generated by various omics technologies. With this large amount of useful data, network...

  20. Natural product synthesis at the interface of chemistry and biology

    Science.gov (United States)

    2014-01-01

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880

  1. 9 CFR 114.6 - Mixing biological products.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mixing biological products. 114.6... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form, shall be mixed thoroughly in a single container. During bottling operations, the product shall be...

  2. Striking balance between expedited review and expecting efficacious anticancer drug and biologics: An ongoing challenge

    Directory of Open Access Journals (Sweden)

    Krishnan Vengadaragava Chary

    2017-01-01

    Full Text Available Objective: The objective of this study is to assess the postmarketing status: Efficacy and safety drugs and biologics related with cancer approved under expedited review. Methods: This observational, analytical study was carried between January and April 2016 by the Department of Pharmacology and Medical Oncology, Saveetha Medical College. Drugs approved under expedited review, fast-track status and its association with anti-cancer effects, postmarketing efficacy and safety, propensity to induce the second tumor was noted. Drug approval status and average time of review process were obtained from the United States-Food and Drug Administration (FDA, Center for Drugs and Biologics Center (Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research. Postmarketing adverse events and safety issues were collected FDA adverse effects reporting system. Further, evidence efficacy and safety of drugs were taken from various meta-analysis, reports on BioMed journals, and Cochrane systematic reviews. Results: In the last 5 years, 166 products were approved by expedited review. Out of 166, 48 (28.9% drugs/biologics are anticancer drugs and drugs used in precancerous conditions. The average time of review varies from19 months to 8.2 months. Out of these 48 molecules, 37 (77% molecules received serious adverse event alert. Positive correlation is seen between average time of review and number of adverse events reported. Seven (14.5% drugs were proven to induce second tumor among receivers. Conclusion: Although expedited review facilitates faster approval of drugs; selection and assessment criteria should be stringent to prevent clinical failure, serious adverse effects of such drugs exposed to many individuals. Focus should be given developing chemosensitizing molecule and evaluation of metronomic regimen which is being more optimistic in current cancer therapeutics.

  3. Design control considerations for biologic-device combination products.

    Science.gov (United States)

    Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

    2017-03-01

    Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting

  4. PCMO L01-Setting Specifications for Biological Investigational Medicinal Products.

    Science.gov (United States)

    Krause, Stephan O

    2015-01-01

    This paper provides overall guidance and best practices for the setting of specifications for clinical biological drug substances and drug products within the framework of ICH guidelines on pharmaceutical development [Q8(R2) and Q11], quality risk management (Q9), and quality systems (Q10). A review is provided of the current regulatory expectations for the specification setting process as part of a control strategy during product development, pointing to existing challenges for the investigational new drug/investigational medicinal product dossier (IND/IMPD) sponsor. A case study illustrates how the investigational medicinal product specification revision process can be managed within a flexible quality system, and how specifications can be set and justified for early and late development stages. This paper provides an overview for the setting of product specifications for investigational medicinal products used in clinical trials. A case study illustrates how product specifications of investigational medicinal products can be justified and managed within a modern product quality system. © PDA, Inc. 2015.

  5. Bone effects of biologic drugs in rheumatoid arthritis.

    Science.gov (United States)

    Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

    2013-01-01

    Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

  6. Development Considerations for Nanocrystal Drug Products.

    Science.gov (United States)

    Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.

  7. Inactive ingredient Search for Approved Drug Products

    Data.gov (United States)

    U.S. Department of Health & Human Services — According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product other than the active ingredient. Only inactive ingredients in the final...

  8. Sex as a biological variable: Drug use and abuse.

    Science.gov (United States)

    Riley, Anthony L; Hempel, Briana J; Clasen, Matthew M

    2018-04-01

    The study of sex as a biological variable is a necessary emphasis across a wide array of endpoints, including basic neuroscience, medicine, mental health, physiology and behavior. The present review summarizes work from clinical and preclinical populations on sex differences in drug use and abuse, ranging from initiation to escalation/dysregulation and from drug cessation/abstinence to relapse. These differences are analyzed in the context of the addiction cycle conceptualization of Koob and his colleagues and address patterns of drug use (binge/intoxication), motivation underlying its use (withdrawal/negative affect) and likelihood and causes of craving and relapse of drug taking (preoccupation/anticipation). Following this overview, an assessment of the basis for the reported sex differences is discussed in the context of the affective (rewarding and aversive) properties of drugs of abuse and how such properties and their balance vary with sex and contribute to drug intake. Finally, the interaction of sex with several experiential (drug history) and subject (age) factors and how these interactions affect reward and aversion are discussed to highlight the importance of understanding such interactions in predicting drug use and abuse. We note that sex as a biological variable remains one of critical evaluation and that such investigations of sex differences in drug use and abuse continue and be expanded to assess all facets of their mediation, including these affective properties, how their balance may be impacted by the multiple conditions under which drugs are taken and how this overall balance affects drug use and addiction vulnerability. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 21 CFR 333.350 - Labeling of acne drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of acne drug products. 333.350 Section... Acne Drug Products § 333.350 Labeling of acne drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “acne...

  10. Electrolytic reduction of nitroheterocyclic drugs leads to biologically important damage in DNA

    International Nuclear Information System (INIS)

    Lafleur, M.V.M.; Pluijmackers-Westmijze, E.J.; Loman, H.

    1985-01-01

    The effects of electrolytic reduction of nitroimidazole drugs on biologically active DNA was studied. The results show that reduction of the drugs in the presence of DNA affects inactivation for both double-stranded (RF) and single-stranded phiX174 DNA. However, stable reduction products did not make a significant contribution to the lethal damage in DNA. This suggests that probably a short-lived intermediate of reduction of nitro-compounds is responsible for damage to DNA. (author)

  11. Examining the production costs of antiretroviral drugs.

    Science.gov (United States)

    Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

    2006-08-22

    To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

  12. 77 FR 42319 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-07-18

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... consideration of the appropriateness of cell lines derived from human tumors for vaccine manufacture. FDA...

  13. 75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-09-28

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Vaccines and Related Biological Products Advisory Committee. General Function... vaccines for a post-exposure prophylaxis indication using the animal rule. On November 17, 2010, the...

  14. 77 FR 63839 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-17

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide...) Virus Monovalent Vaccine manufactured by GlaxoSmithKline. On November 15, 2012, the committee will meet...

  15. 75 FR 2876 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-01-19

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... virus vaccine for the 2010 - 2011 influenza season. FDA intends to make background material available to...

  16. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-01-20

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... the influenza virus vaccine for the 2011-2012 influenza season. The committee will also hear an update...

  17. 78 FR 5465 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-01-25

    ...] Vaccines and Related Biological Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Vaccines and Related Biological Products Advisory Committee. General Function of the Committee: To provide... virus vaccine for the 2013- 2014 influenza season. FDA intends to make background material available to...

  18. Genetics of rheumatoid arthritis conributes to biology and drug discovery

    NARCIS (Netherlands)

    Okada, Yukinori; Wu, Di; Trynka, Gosia; Raj, Towfique; Terao, Chikashi; Ikari, Katsunori; Kochi, Yuta; Ohmura, Koichiro; Suzuki, A.; Yoshida, S.; Graham, R.R.; Manoharan, A.; Ortmann, W.; Bhangale, T.; Denny, J.C.; Carroll, R.J.; Eyler, A.E.; Greenberg, J.D.; Kremer, J.M.; Pappas, D.A.; Jiang, L.; Yin, L.; Ye, L.; Su, D.F.; Yang, J.; Xie, G.; Keystone, E.; Westra, H.J.; Esko, T.; Metspalu, A.; Zhou, X.; Gupta, N.; Mirel, D.; Stahl, Eli A.; Diogo, D.; Cui, J.; Liao, K.; Guo, M.H.; Myouzen, K.; Kawaguchi, T.; Coenen, M.J.; van Riel, P.L.; van de Laar, Mart A.F.J.; Guchelaar, H.J.; Huizinga, T.W.; Dieudé, P.; Mariette, X.; Louis Bridges Jr, S.; Zhernakova, A.; Toes, R.E.; Tak, P.P.; Miceli-Richard, C.; Bang, S.Y.; Lee, H.S.; Martin, J.; Gonzales-Gay, M.A.; Rodriguez-Rodriguez, L.; Rantapää-Dhlqvist, S.; Arlestig, L.; Choi, H.K.; Kamatani, Y.; Galan, P.; Lathrop, M.; Eyre, S.; Bowes, J.; Barton, A.; de Vries, N.; Moreland, L.W.; Criswell, L.A.; Karlson, E.W.; Taniguchi, A.; Yamada, R; Kubo, M.; Bae, S.C.; Worthington, J.; Padyukov, L.; Klareskog, L.; Gregersen, Peter K.; Raychaudhuri, S.; Stranger, B.E.; de Jager, P.L.; Franke, L.; Visscher, P.M.; Brown, M.A.; Yamanaka, H.; Mimori, T.; Takahashi, A.; Xu, H.; Behrens, T.W.; Siminovitch, K.A.; Momohara, S.; Matsuda, F.; Yamamoto, K.; Plenge, Robert M.

    2013-01-01

    A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed

  19. 21 CFR 211.94 - Drug product containers and closures.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drug product containers and closures. 211.94 Section 211.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and use that can cause deterioration or contamination of the drug product. (c) Drug product containers...

  20. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  1. Potential of Continuous Manufacturing for Liposomal Drug Products.

    Science.gov (United States)

    Worsham, Robert D; Thomas, Vaughan; Farid, Suzanne S

    2018-05-21

    Over the last several years, continuous manufacturing of pharmaceuticals has evolved from bulk APIs and solid oral dosages into the more complex realm of biologics. The development of continuous downstream processing techniques has allowed biologics manufacturing to realize the benefits (e.g. improved economics, more consistent quality) that come with continuous processing. If relevant processing techniques and principles are selected, the opportunity arises to develop continuous manufacturing designs for additional pharmaceutical products including liposomal drug formulations. Liposome manufacturing has some inherent aspects that make it favorable for a continuous process. Other aspects such as formulation refinement, materials of construction, and aseptic processing need development, but present an achievable challenge. This paper reviews the current state of continuous manufacturing technology applicable to liposomal drug product manufacturing and an assessment of the challenges and potential of this application. This article is protected by copyright. All rights reserved.

  2. Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

    Science.gov (United States)

    Kiyosawa, Naoki; Manabe, Sunao

    2016-01-01

    Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

  3. 78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

    Science.gov (United States)

    2013-05-31

    ... products. This guidance revises the guidance for industry entitled ``Clinical Development Programs for... Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave... (HFM-40), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville...

  4. Regulatory considerations concerning IND radiopharmaceutical drug products

    International Nuclear Information System (INIS)

    Nissel, M.

    1985-01-01

    The Food and Drug Administration is charged by the Food, Drug, and Cosmetic Act, as presently amended, to assure that any drug introduced into interstate commerce is safe and effective for the purposes for which it is labeled. A radiopharmaceutical is, by definition, a new drug unless there is in effect an approved New Drug Application (NDA) for it. Before the data for the NDA are compiled, investigative studies have to be done. Before such studies can be performed in humans, an exemption from the Act is necessary. This exemption, technically the Claimed Exemption for an Investigational New Drug, is termed the IND. Both the scientific and the administrative requirements for an IND are discussed. For radiopharmaceutical drug products (RDP's), the radiation hazards, as well as the pharmacological ones, must be documented. Should the early studies demonstrate a potential for efficacy in a certain condition or disease state, an investigative protocol for an extended clinical trial is presented. The necessary requirements for Institutional Review Board (IRB) approval and consent forms are discussed. For certain research purposes, uniquely for radioactive drugs, an IND is not required for certain specific studies; the requirements for such a research study, conducted under the auspices of an approved radioactive drug research committee, are outlined

  5. Systems biology solutions for biochemical production challenges

    DEFF Research Database (Denmark)

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus

    2017-01-01

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics...... characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity...... compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains...

  6. Systems biology solutions for biochemical production challenges.

    Science.gov (United States)

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

    2017-06-01

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Hydrogen production from biomass by biological systems

    International Nuclear Information System (INIS)

    Sharifan, H.R.; Qader, S.

    2009-01-01

    Hydrogen gas is seen as a future energy carrier, not involved in 'greenhouse' gas and its released energy in combustion can be converted to electric power. Biological system with low energy can produce hydrogen compared to electrochemical hydrogen production via solar battery-based water splitting which requires the use of solar batteries with high energy requirements. The biological hydrogen production occurs in microalgae and cyanobacteria by photosynthesis. They consume biochemical energy to produce molecular hydrogen. Hydrogen in some algae is an anaerobic production in the absence of light. In cyanobacteria the hydrogen production simultaneously happens with nitrogen fixation, and also catalyzed by nitrogenase as a side reaction. Hydrogen production by photosynthetic bacteria is mediated by nitrogenase activity, although hydrogenases may be active for both hydrogen production and hydrogen uptake under some conditions. Genetic studies on photosynthetic microorganisms have markedly increased in recent times, relatively few genetic engineering studies have focused on altering the characteristics of these microorganisms, particularly with respect to enhancing the hydrogen-producing capabilities of photosynthetic bacteria and cyanobacteria. (author)

  8. Marine natural products: a new wave of drugs?

    Science.gov (United States)

    Montaser, Rana; Luesch, Hendrik

    2011-01-01

    The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future. PMID:21882941

  9. 9 CFR 112.6 - Packaging biological products.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Packaging biological products. 112.6... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.6 Packaging biological products. (a) Each multiple-dose final container of a biological product...

  10. 21 CFR 340.50 - Labeling of stimulant drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of stimulant drug products. 340.50 Section 340.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 340.50...

  11. Drug Products in the Medicaid Drug Rebate Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

  12. Biologic Drugs: A New Target Therapy in COPD?

    Science.gov (United States)

    Yousuf, Ahmed; Brightling, Christopher E

    2018-04-23

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Current diagnostic criteria based on the presence of fixed airflow obstruction and symptoms do not integrate the complex pathological changes occurring within the lung and they do not define different airway inflammatory patterns. The current management of COPD is based on 'one size fits all' approach and does not take the importance of heterogeneity in COPD population into account. The available treatments aim to alleviate symptoms and reduce exacerbation frequency but do not alter the course of the disease. Recent advances in molecular biology have furthered our understanding of inflammatory pathways in pathogenesis of COPD and have led to development of targeted therapies (biologics and small molecules) based on predefined biomarkers. Herein we shall review the trials of biologics in COPD and potential future drug developments in the field.

  13. Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

    Science.gov (United States)

    ... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

  14. Defining Patient Centric Pharmaceutical Drug Product Design.

    Science.gov (United States)

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

  15. Chemical Biology of Microbial Anticancer Natural Products

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Gotfredsen, Charlotte Held

    than 100 years. New natural products (NPs) are continually discovered and with the increase in selective biological assays, previously described compounds often also display novel bioactivities, justifying their presence in novel screening efforts. Screening and discovery of compounds with activity...... towards chronic lymphocytic leukemia (CLL) cells is crucial since CLL is considered as an incurable disease. To discover novel agents that targets CLL cells is complicated. CLL cells rapidly undergo apoptosis in vitro when they are removed from their natural microenvironment, even though they are long...

  16. Urine: Waste product or biologically active tissue?

    Science.gov (United States)

    2018-03-01

    Historically, urine has been viewed primarily as a waste product with little biological role in the overall health of an individual. Increasingly, data suggest that urine plays a role in human health beyond waste excretion. For example, urine might act as an irritant and contribute to symptoms through interaction with-and potential compromise of-the urothelium. To explore the concept that urine may be a vehicle for agents with potential or occult bioactivity and to discuss existing evidence and novel research questions that may yield insight into such a role, the National Institute of Diabetes and Digestive and Kidney Disease invited experts in the fields of comparative evolutionary physiology, basic science, nephrology, urology, pediatrics, metabolomics, and proteomics (among others) to a Urinology Think Tank meeting on February 9, 2015. This report reflects ideas that evolved from this meeting and current literature, including the concept of urine quality, the biological, chemical, and physical characteristics of urine, including the microbiota, cells, exosomes, pH, metabolites, proteins, and specific gravity (among others). Additionally, the manuscript presents speculative, and hopefully testable, ideas about the functional roles of urine constituents in health and disease. Moving forward, there are several questions that need further understanding and pursuit. There were suggestions to consider actively using various animal models and their biological specimens to elaborate on basic mechanistic information regarding human bladder dysfunction. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  17. 42 CFR 409.25 - Drugs, biologicals, supplies, appliances, and equipment.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Drugs, biologicals, supplies, appliances, and... Drugs, biologicals, supplies, appliances, and equipment. (a) Drugs and biologicals. Except as specified... can obtain a continuing supply. (c) Supplies, appliances, and equipment. Except as specified in...

  18. Evaluating the administration costs of biologic drugs: development of a cost algorithm.

    Science.gov (United States)

    Tetteh, Ebenezer K; Morris, Stephen

    2014-12-01

    Biologic drugs, as with all other medical technologies, are subject to a number of regulatory, marketing, reimbursement (financing) and other demand-restricting hurdles applied by healthcare payers. One example is the routine use of cost-effectiveness analyses or health technology assessments to determine which medical technologies offer value-for-money. The manner in which these assessments are conducted suggests that, holding all else equal, the economic value of biologic drugs may be determined by how much is spent on administering these drugs or trade-offs between drug acquisition and administration costs. Yet, on the supply-side, it seems very little attention is given to how manufacturing and formulation choices affect healthcare delivery costs. This paper evaluates variations in the administration costs of biologic drugs, taking care to ensure consistent inclusion of all relevant cost resources. From this, it develops a regression-based algorithm with which manufacturers could possibly predict, during process development, how their manufacturing and formulation choices may impact on the healthcare delivery costs of their products.

  19. Genetics of Psoriasis and Pharmacogenetics of Biological Drugs

    Directory of Open Access Journals (Sweden)

    Rocío Prieto-Pérez

    2013-01-01

    Full Text Available Psoriasis is a chronic inflammatory disease of the skin. The causes of psoriasis are unknown, although family and twin studies have shown genetic factors to play a key role in its development. The many genes associated with psoriasis and the immune response include TNFα, IL23, and IL12. Advances in knowledge of the pathogenesis of psoriasis have enabled the development of new drugs that target cytokines (e.g., etanercept, adalimumab, and infliximab, which target TNFα, and ustekinumab, which targets the p40 subunit of IL23 and IL12. These drugs have improved the safety and efficacy of treatment in comparison with previous therapies. However, not all patients respond equally to treatment, possibly owing to interindividual genetic variability. In this review, we describe the genes associated with psoriasis and the immune response, the biological drugs used to treat chronic severe plaque psoriasis, new drugs in phase II and III trials, and current knowledge on the implications of pharmacogenomics in predicting response to these treatments.

  20. What does systems biology mean for drug development?

    Science.gov (United States)

    Schrattenholz, André; Soskić, Vukić

    2008-01-01

    The complexity and flexibility of cellular architectures is increasingly recognized by impressive progress on the side of molecular analytics, i.e. proteomics, genomics and metabolomics. One of the messages from systems biology is that the number of molecular species in cellular networks is orders of magnitude bigger than anticipated by genomic analysis, in particular by fast posttranslational modifications of proteins. The requirements to manage external signals, integrate spatiotemporal signal transduction inside an organism and at the same time optimizing networks of biochemical and chemical reactions result in chemically extremely fine tuned molecular entities. Chemical side reactions of enzymatic activity, like e.g. random oxidative damage of proteins by free radicals during aging constantly introduce epigenetic alterations of protein targets. These events gradually and on an individual stochastic scale, keep modifying activities of these targets, and their affinities and selectivities towards biological and pharmacological ligands. One further message is that many of the key reactions in living systems are essentially based on interactions of low affinities and even low selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. So, in complex disorders like cancer or neurodegenerative diseases, which are rooted in relatively subtle and multimodal dysfunction of important physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which still dominate the pharmaceutical industry increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade and the treatment of "complex diseases" remains a most pressing medical need. Currently a change of paradigm can be observed with

  1. Systems biology of microbial exopolysaccharides production

    Directory of Open Access Journals (Sweden)

    Ozlem eAtes

    2015-12-01

    Full Text Available Exopolysaccharides (EPS produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture and medicine. EPSs are mainly associated with high-value applications and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore a systems-based approach constitutes an important step towards understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan and dextran.

  2. Systems Biology of Microbial Exopolysaccharides Production.

    Science.gov (United States)

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran.

  3. The yeast stands alone: the future of protein biologic production.

    Science.gov (United States)

    Love, Kerry R; Dalvie, Neil C; Love, J Christopher

    2017-12-22

    Yeasts are promising alternative hosts for the manufacturing of recombinant protein therapeutics because they simply and efficiently meet needs for both platform and small-market drugs. Fast accumulation of biomass and low-cost media reduce the cost-of-goods when using yeast, which in turn can enable agile, small-volume manufacturing facilities. Small, tractable yeast genomes are amenable to rapid process development, facilitating strain and product quality by design. Specifically, Pichia pastoris is becoming a widely accepted yeast for biopharmaceutical manufacturing in much of the world owing to a clean secreted product and the rapidly expanding understanding of its cell biology as a host organism. We advocate for a near term partnership spanning industry and academia to promote open source, timely development of yeast hosts. Copyright © 2017. Published by Elsevier Ltd.

  4. Approved Drug Products with Therapuetic Equivalence Evaluations (Orange Book)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The publication Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book) identifies drug products approved on...

  5. Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

    Science.gov (United States)

    Neumann, Heinz; Neumann-Staubitz, Petra

    2010-06-01

    Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

  6. Drug diffusion and biological responses of arteries using a drug-eluting stent with nonuniform coating

    Directory of Open Access Journals (Sweden)

    Saito N

    2016-03-01

    Full Text Available Noboru Saito, Yuhei Mori, Sayaka Uchiyama Terumo Corporation R&D Center, Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan Abstract: The purpose of this study was to determine the effect of a nonuniform coating, abluminal-gradient coating (AGC, which leaves the abluminal surface of the curves and links parts of the stent free from the drug coating, on the diffusion direction of the drug and the biological responses of the artery to drug-eluting stent (DES by comparing the AGC-sirolimus stent and the conventional full-surface coating (CFC sirolimus stent. The study aimed to verify whether the AGC approach was appropriate for the development of a safer DES, minimizing the risks of stent thrombosis due to delayed endothelialization by the drug and distal embolization due to cracking of the coating layer on the hinge parts of the DES on stent expansion. In the in vitro local drug diffusion study, we used rhodamine B as a model drug, and rhodamine B released from the AGC stent diffused predominantly into the abluminal side of the alginate artery model. Conversely, rhodamine B released from the CFC stent quickly spread to the luminal side of the artery model, where endothelial cell regeneration is required. In the biological responses study, the luminal surface of the iliac artery implanted with the AGC-sirolimus stent in a rabbit iliac artery for 2 weeks was completely covered with endothelial-like cells. On the other hand, the luminal surface of the iliac artery implanted with the CFC-sirolimus stent for 2 weeks only showed partial coverage with endothelial-like cells. While thrombosis was observed in two of the three CFC-sirolimus stents, it was observed in only one of the three AGC-sirolimus stents. Taken together, these findings indicate that the designed nonuniform coating (AGC is an appropriate approach to ensure a safer DES. However, the number of studies is limited and a larger study should be conducted to reach a statistically

  7. Learning from biology: synthetic lipoproteins for drug delivery.

    Science.gov (United States)

    Huang, Huang; Cruz, William; Chen, Juan; Zheng, Gang

    2015-01-01

    Synthetic lipoproteins represent a relevant tool for targeted delivery of biological/chemical agents (chemotherapeutics, siRNAs, photosensitizers, and imaging contrast agents) into various cell types. These nanoparticles offer a number of advantages for drugs delivery over their native counterparts while retaining their natural characteristics and biological functions. Their ultra-small size (lipoprotein receptors, i.e., low-density lipoprotein receptor (LDLR) and Scavenger receptor class B member 1 (SRB1) that are found in a number of pathological conditions (e.g., cancer, atherosclerosis), make them superior delivery strategies when compared with other nanoparticle systems. We review the various approaches that have been developed for the generation of synthetic lipoproteins and their respective applications in vitro and in vivo. More specifically, we summarize the approaches employed to address the limitation on use of reconstituted lipoproteins by means of natural or recombinant apolipoproteins, as well as apolipoprotein mimetic molecules. Finally, we provide an overview of the advantages and disadvantages of these approaches and discuss future perspectives for clinical translation of these nanoparticles. © 2014 Wiley Periodicals, Inc.

  8. Natural Products as Leads in Schistosome Drug Discovery

    Directory of Open Access Journals (Sweden)

    Bruno J. Neves

    2015-01-01

    Full Text Available Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ, the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

  9. Structure-based synthesis from natural products to drug prototypes

    International Nuclear Information System (INIS)

    Hanessian, S.

    2009-01-01

    X-Ray crystallographic data available from complexes of natural and synthetic molecules with the enzyme thrombin has aided to the design and synthesis of truncated and hybrid molecules exhibiting excellent inhibition in vitro. The vital importance of natural products for the well-being of man has been known lor millennia. Their therapeutic benefits to alleviate pain or cure diseases continue to rank natural products among the primary sources of potential drugs. Great advances have been made in the methods of isolation, identification, and structure elucidation of some of the most complex natural products in recent years. The advent of molecular biology and genetic mapping has also aided in our understanding of the intriguing biosynthetic pathways leading to various classes of therapeutically relevant antibiotic, anticancer, and related natural products. Elegant and practical methodology has been developed leading to the total synthesis of virtually every class of medicinally important natural product. In some cases, natural products or their chemically modified congeners have been manufactured by total synthesis on an industrial level which is a testament to the ingenuity of process chemists. In spite of their potent activities HI enzymatic ox receptor-mediated assays, not all natural products are amenable to being developed as marketable drags. In many instances unfavorable pharmacological effects cannot be overcome without drastic structural and functional modifications, which may also result in altered efficacy. Structure modification through truncation, functional group variations, isosteric replacements, and skeletal rigidifications aided by molecular modeling, X ray crystallography of protein targets, or NMR data are valid objectives in the context of small molecule drug discovery starting with bioactive natural products. A large proportion of these pertain to chemotherapeutic agents against cancer

  10. Biological control and sustainable food production

    NARCIS (Netherlands)

    Bale, J.S.; Lenteren, van J.C.; Bigler, F.

    2008-01-01

    The use of biological control for the management of pest insects pre-dates the modern pesticide era. The first major successes in biological control occurred with exotic pests controlled by natural enemy species collected from the country or area of origin of the pest (classical control).

  11. Derivatization reactions in the gas—liquid chromatographic analysis of drugs in biological fluids

    NARCIS (Netherlands)

    Hulshoff, A.; Lingeman, H.

    1984-01-01

    Alkylation, acylation, silylation and other derivatization reactions applied to the gas chromatographic analysis of drugs in biological matrices are reviewed. Reaction conditions are discussed in relation to reaction mechanisms. Detector-oriented labelling of drugs, and derivatization with chiral

  12. In situ biomolecule production by bacteria; a synthetic biology approach to medicine.

    Science.gov (United States)

    Flores Bueso, Yensi; Lehouritis, Panos; Tangney, Mark

    2018-04-10

    The ability to modify existing microbiota at different sites presents enormous potential for local or indirect management of various diseases. Because bacteria can be maintained for lengthy periods in various regions of the body, they represent a platform with enormous potential for targeted production of biomolecules, which offer tremendous promise for therapeutic and diagnostic approaches for various diseases. While biological medicines are currently limited in the clinic to patient administration of exogenously produced biomolecules from engineered cells, in situ production of biomolecules presents enormous scope in medicine and beyond. The slow pace and high expense of traditional research approaches has particularly hampered the development of biological medicines. It may be argued that bacterial-based medicine has been "waiting" for the advent of enabling technology. We propose that this technology is Synthetic Biology, and that the wait is over. Synthetic Biology facilitates a systematic approach to programming living entities and/or their products, using an approach to Research and Development (R&D) that facilitates rapid, cheap, accessible, yet sophisticated product development. Full engagement with the Synthetic Biology approach to R&D can unlock the potential for bacteria as medicines for cancer and other indications. In this review, we describe how by employing Synthetic Biology, designer bugs can be used as drugs, drug-production factories or diagnostic devices, using oncology as an exemplar for the concept of in situ biomolecule production in medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. 9 CFR 101.3 - Biological products and related terms.

    Science.gov (United States)

    2010-01-01

    ... as required by the regulations. (e) Released product. A finished product released for marketing after... total quantity of completed product which has been thoroughly mixed in a single container and identified... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products and related terms...

  14. 75 FR 61497 - Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request...

    Science.gov (United States)

    2010-10-05

    ... Price Competition and Innovation Act of 2009 (BPCI Act) that amends the Public Health Service Act (PHS... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0477] Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request for...

  15. Plant natural products research in tuberculosis drug discovery and ...

    African Journals Online (AJOL)

    Plant natural products research in tuberculosis drug discovery and development: A situation report ... African Journal of Biotechnology ... tuberculosis (XDR-TB), call for the development of new anti-tuberculosis drugs to combat this disease.

  16. Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions.

    Science.gov (United States)

    Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi

    2017-06-01

    Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.

  17. Presence and biological activity of antibiotics used in fuel ethanol and corn co-product production.

    Science.gov (United States)

    Compart, D M Paulus; Carlson, A M; Crawford, G I; Fink, R C; Diez-Gonzalez, F; Dicostanzo, A; Shurson, G C

    2013-05-01

    Antibiotics are used in ethanol production to control bacteria from competing with yeast for nutrients during starch fermentation. However, there is no published scientific information on whether antibiotic residues are present in distillers grains (DG), co-products from ethanol production, or whether they retain their biological activity. Therefore, the objectives of this study were to quantify concentrations of various antibiotic residues in DG and determine whether residues were biologically active. Twenty distillers wet grains and 20 distillers dried grains samples were collected quarterly from 9 states and 43 ethanol plants in the United States. Samples were analyzed for DM, CP, NDF, crude fat, S, P, and pH to describe the nutritional characteristics of the samples evaluated. Samples were also analyzed for the presence of erythromycin, penicillin G, tetracycline, tylosin, and virginiamycin M1, using liquid chromatography and mass spectrometry. Additionally, virginiamycin residues were determined, using a U.S. Food and Drug Administration-approved bioassay method. Samples were extracted and further analyzed for biological activity by exposing the sample extracts to 10(4) to 10(7) CFU/mL concentrations of sentinel bacterial strains Escherichia coli ATCC 8739 and Listeria monocytogenes ATCC 19115. Extracts that inhibited bacterial growth were considered to have biological activity. Physiochemical characteristics varied among samples but were consistent with previous findings. Thirteen percent of all samples contained low (≤1.12 mg/kg) antibiotic concentrations. Only 1 sample extract inhibited growth of Escherichia coli at 10(4) CFU/mL, but this sample contained no detectable concentrations of antibiotic residues. No extracts inhibited Listeria monocytogenes growth. These data indicate that the likelihood of detectable concentrations of antibiotic residues in DG is low; and if detected, they are found in very low concentrations. The inhibition in only 1 DG

  18. 75 FR 73108 - Guidance for Industry on Abbreviated New Drug Applications: Impurities in Drug Products...

    Science.gov (United States)

    2010-11-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0584... Products.'' This guidance updates recommendations regarding degradation products and updates the draft... information on listing of degradation products, setting acceptance criteria, and qualifying degradation...

  19. 9 CFR 114.17 - Rebottling of biological products.

    Science.gov (United States)

    2010-01-01

    ... reports of all tests conducted on the rebottled product shall be submitted to Animal and Plant Health... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...

  20. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

  1. Versatile and on-demand biologics co-production in yeast.

    Science.gov (United States)

    Cao, Jicong; Perez-Pinera, Pablo; Lowenhaupt, Ky; Wu, Ming-Ru; Purcell, Oliver; de la Fuente-Nunez, Cesar; Lu, Timothy K

    2018-01-08

    Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.

  2. Biological Variance in Agricultural Products. Theoretical Considerations

    NARCIS (Netherlands)

    Tijskens, L.M.M.; Konopacki, P.

    2003-01-01

    The food that we eat is uniform neither in shape or appearance nor in internal composition or content. Since technology became increasingly important, the presence of biological variance in our food became more and more of a nuisance. Techniques and procedures (statistical, technical) were

  3. Cholesterol oxidation products and their biological importance

    Czech Academy of Sciences Publication Activity Database

    Kulig, W.; Cwiklik, Lukasz; Jurkiewicz, P.; Rog, T.; Vattulainen, I.

    2016-01-01

    Roč. 199, Sep (2016), s. 144-160 ISSN 0009-3084 R&D Projects: GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388963 Keywords : cholesterol * oxidation * oxysterols * biological membranes * biophysical properties Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.361, year: 2016

  4. Purification of drugs from biological fluids by counter-current chromatography.

    Science.gov (United States)

    Hochlowski, Jill E; Pan, Jeffrey Y; Searle, Philip A; Buck, Wayne R; Spanton, Stephen G

    2009-08-21

    Experiments were performed to demonstrate the potential of counter-current chromatography (CCC) for the isolation of drugs and their metabolites from biological matrices relevant to the metabolism studies of pharmaceutical research. Examples of typical drugs are spiked into biological media ex vivo to provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows for the detection of small molecule drugs within the matrix through selected ion monitoring, and fraction collection can provide material for further structural elucidation by NMR.

  5. Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis

    DEFF Research Database (Denmark)

    Egeberg, A; Ottosen, M B; Gniadecki, R

    2018-01-01

    BACKGROUND: Real-life data on newer biologic and biosimilar agents for moderate-to-severe psoriasis are lacking. OBJECTIVES: To examine safety, efficacy, and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab, and ustekinumab) and compare origina...... the long-term safety of novel biologics for psoriasis. This article is protected by copyright. All rights reserved....

  6. Biological hydrogen production from industrial wastewaters

    Energy Technology Data Exchange (ETDEWEB)

    Peixoto, Guilherme; Pantoja Filho, Jorge Luis Rodrigues; Zaiat, Marcelo [Universidade de Sao Paulo (EESC/USP), Sao Carlos, SP (Brazil). School of Engineering. Dept. Hydraulics and Sanitation], Email: peixoto@sc.usp.br

    2010-07-01

    This research evaluates the potential for producing hydrogen in anaerobic reactors using industrial wastewaters (glycerol from bio diesel production, wastewater from the parboilization of rice, and vinasse from ethanol production). In a complementary experiment the soluble products formed during hydrogen production were evaluated for methane generation. The assays were performed in batch reactors with 2 liters volume, and sucrose was used as a control substrate. The acidogenic inoculum was taken from a packed-bed reactor used to produce hydrogen from a sucrose-based synthetic substrate. The methanogenic inoculum was taken from an upflow anaerobic sludge blanket reactor treating poultry slaughterhouse wastewater. Hydrogen was produced from rice parboilization wastewater (24.27 ml H{sub 2} g{sup -1} COD) vinasse (22.75 ml H{sub 2} g{sup -1} COD) and sucrose (25.60 ml H{sub 2} g{sup -1} COD), while glycerol only showed potential for methane generation. (author)

  7. 9 CFR 114.18 - Reprocessing of biological products.

    Science.gov (United States)

    2010-01-01

    ... for all tests conducted shall be submitted to Animal and Plant Health Inspection Service. The licensee... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE...

  8. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false U.S. Veterinary Biological Product... BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a) Authorization to produce each biological product shall be specified on a U.S. Veterinary Biological Product License, issued by the...

  9. Cholesterol oxidation products and their biological importance

    DEFF Research Database (Denmark)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr

    2016-01-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low...... and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have...

  10. Limited bacterial diversity within a treatment plant receiving antibiotic containing waste from bulk drug production

    NARCIS (Netherlands)

    Marathe, Nachiket P.; Shetty, Sudarshan A.; Shouche, Yogesh S.; Larsson, D.G.J.

    2016-01-01

    Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted

  11. Biocomes: new biological products for sustainable farming and forestry

    NARCIS (Netherlands)

    Teixidó, N.; Cal, de A.L.; Usall, J.; Guijarro, B.; Larena, I.; Torres, R.; Abadias, M.; Köhl, J.

    2016-01-01

    The growing interest in biological control has been reflected during last decades in a big number of scientific publications, books and symposia. However, biocontrol commercial application at a European level is limited and biological control products are not currently available for the control of

  12. Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

    Science.gov (United States)

    Hamilton, Gregory S

    2015-09-01

    Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  13. Systematic synergy modeling: understanding drug synergy from a systems biology perspective.

    Science.gov (United States)

    Chen, Di; Liu, Xi; Yang, Yiping; Yang, Hongjun; Lu, Peng

    2015-09-16

    Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose-response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and "omic"-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug-disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations.

  14. 21 CFR 336.50 - Labeling of antiemetic drug products.

    Science.gov (United States)

    2010-04-01

    ... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... Section 336.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... under 12 years of age. “Do not give this product to children who have a breathing problem such as...

  15. Drug Production in Tertiary Health Institutions – Needs, Constraints ...

    African Journals Online (AJOL)

    The use of questionnaires was employed in the study covering all pharmacists in the pharmaceutical services department, pharmacy technicians and quality control technologist in the drug production unit of the hospital. It was unanimously agreed by the respondents that local drug production was necessary in tertiary ...

  16. Systems Biology in Animal Production and Health

    DEFF Research Database (Denmark)

    for improved animal production and health. The book will contain online resources where additional data and programs can be accessed. Some chapters also come with computer programming codes and example datasets to provide readers hands-on (computer) exercises. This second volume deals with integrated modeling...... and analyses of multi-omics datasets from theoretical and computational approaches and presents their applications in animal production and health as well as veterinary medicine to improve diagnosis, prevention and treatment of animal diseases. This book is suitable for both students and teachers in animal...

  17. Protein Complex Production from the Drug Discovery Standpoint.

    Science.gov (United States)

    Moarefi, Ismail

    2016-01-01

    Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.

  18. Solid Phase Microextraction and Related Techniques for Drugs in Biological Samples

    OpenAIRE

    Moein, Mohammad Mahdi; Said, Rana; Bassyouni, Fatma; Abdel-Rehim, Mohamed

    2014-01-01

    In drug discovery and development, the quantification of drugs in biological samples is an important task for the determination of the physiological performance of the investigated drugs. After sampling, the next step in the analytical process is sample preparation. Because of the low concentration levels of drug in plasma and the variety of the metabolites, the selected extraction technique should be virtually exhaustive. Recent developments of sample handling techniques are directed, from o...

  19. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

    Science.gov (United States)

    Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

    2017-11-01

    Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  20. Biological productivity, terrigenous influence and noncrustal ...

    Indian Academy of Sciences (India)

    1100ka. Our data suggest that during ~ 1100 ka and ~ 400 ka siliceous productivity was lower, ... Manganese, Ba, Cu, Ni, Zn, and Co have around 90% of their supply from noncrustal ...... Pattan J N, Masuzawa T, Divakar Naidu P, Parthiban G.

  1. Approved Animal Drug Products (Green Book)

    Data.gov (United States)

    U.S. Department of Health & Human Services — On November 16, 1988, the President of the United States signed into law the Generic Animal Drug and Patent Restoration Act (GADPTRA). Among its major provisions,...

  2. Biological production of liquid fuels from biomass

    Energy Technology Data Exchange (ETDEWEB)

    None

    1982-01-01

    A scheme for the production of liquid fuels from renewable resources such as poplar wood and lignocellulosic wastes from a refuse hydropulper was investigated. The particular scheme being studied involves the conversion of a cellulosic residue, resulting from a solvent delignified lignocellulosic feed, into either high concentration sugar syrups or into ethyl and/or butyl alcohol. The construction of a pilot apparatus for solvent delignifying 150 g samples of lignocellulosic feeds was completed. Also, an analysis method for characterizing the delignified product has been selected and tested. This is a method recommended in the Forage Fiber Handbook. Delignified samples are now being prepared and tested for their extent of delignification and susceptibility to enzyme hydrolysis. Work is continuing on characterizing the cellulase and cellobiase enzyme systems derived from the YX strain of Thermomonospora.

  3. Biological production of gas from farmyard manure

    Energy Technology Data Exchange (ETDEWEB)

    Scheffer, F; Kemmler, G

    1953-01-08

    Under anaerobic conditions of farmyard-manure storage, the products include organic acids from which methane is formed. The Schmidt-Eggersgluss method is described in which 5 to 7m/sup 3/ of gas is formed per 100 kg of fresh manure, without loss of N, P, K, or Ca from the residual sludge which is of high nutrient content. Large N losses occur if the sludge comes long in contact with atmosphere.

  4. 77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

    Science.gov (United States)

    2012-12-04

    ... PET Drug Products--Questions and Answers.'' This guidance provides questions and answers that address.... 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in... availability of a guidance entitled ``FDA Oversight of PET Drug Products--Questions and Answers.'' In 1997...

  5. The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).

    Science.gov (United States)

    Paskiet, Diane; Jenke, Dennis; Ball, Douglas; Houston, Christopher; Norwood, Daniel L; Markovic, Ingrid

    2013-01-01

    The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a

  6. A Synthetic Biology Project - Developing a single-molecule device for screening drug-target interactions.

    Science.gov (United States)

    Firman, Keith; Evans, Luke; Youell, James

    2012-07-16

    This review describes a European-funded project in the area of Synthetic Biology. The project seeks to demonstrate the application of engineering techniques and methodologies to the design and construction of a biosensor for detecting drug-target interactions at the single-molecule level. Production of the proteins required for the system followed the principle of previously described "bioparts" concepts (a system where a database of biological parts - promoters, genes, terminators, linking tags and cleavage sequences - is used to construct novel gene assemblies) and cassette-type assembly of gene expression systems (the concept of linking different "bioparts" to produce functional "cassettes"), but problems were quickly identified with these approaches. DNA substrates for the device were also constructed using a cassette-system. Finally, micro-engineering was used to build a magnetoresistive Magnetic Tweezer device for detection of single molecule DNA modifying enzymes (motors), while the possibility of constructing a Hall Effect version of this device was explored. The device is currently being used to study helicases from Plasmodium as potential targets for anti-malarial drugs, but we also suggest other potential uses for the device. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Elucidating antimalarial drug targets/mode-of-action by application of system biology technologies

    CSIR Research Space (South Africa)

    Becker, J

    2008-11-01

    Full Text Available targets/mode-of-action by application of systems biology technologies J BECKER, L MTWISHA, B CRAMPTON AND D MANCAMA CSIR Biosciences, PO Box 395, Pretoria, 0001, South Africa Email: JBecker@csir.co.za – www.csir.co.za INTRODUCTION Malaria is one... The objective of this study was to use systems biology tools to unravel the drug target/mode-of-action (MoA) of an antimalarial drug (cyclohexylamine) with a known drug target/MoA, by analysing differential expression profiles of drug treated vs untreated...

  8. BIOLOGICALLY ACTIVE SUBSTANCES OF SPIRIT PRODUCTION WASTE

    Directory of Open Access Journals (Sweden)

    A. S. Kayshev

    2014-01-01

    Full Text Available A content of biologically active compounds (BAC with signified pharmacological activity in distillers grains was proved. It is prospective for applications of these grains as a raw material resource of pharmaceuticals. A composition of BAC distillers grains received from wheat, corn, barley, millet at different spirit enterprises which use hydro fermentative grain processing. Considering polydispersity of distillers grains they were separated on solid and liquid phases preliminary. Physical and chemical characteristics of distillers grains' liquid base were identified. Elementary composition of distillers grains is signified by active accumulation of biogenic elements (phosphorus, potassium, magnesium, calcium, sodium, iron and low content of heavy metals. The solid phase of distillers grains accumulates carbon, hydrogen and nitrogen in high concentration. The liquid phase of distillers grains contains: proteins and amino acids (20-46%, reducing sugars (5,6%-17,5%, galacturonides (0,8-1,4%, ascorbic acid (6,2-11,4 mg%. The solid base of distillers grains contains: galacturonides (3,4-5,3%, fatty oil (8,4-11,1% with predomination of essential fatty acids, proteins and amino acids (2,1-2,5%, flavonoids (0,4-0,9%, tocopherols (3,4-7,7 mg%. A method of complex processing of distillers grains based on application of membrane filtering of liquid phase and liquid extraction by inorganic and organic solvents of solid phase, which allows almost full extraction of the sum of biologically active compounds (BAC from liquid phase (Biobardin BM and solid phase (Biobardin UL. Biobardin BM comprises the following elements: proteins and amino acids (41-69%, reducing sugars (3,5-15,6%, fatty oil (0,2-0,3%, flavonoids (0,2-0,7%, ascorbic acid (17-37 mg%. Biobardin UL includes: oligouronids (16,4-19,5%, proteins and amino acids (11-21%, fatty oil (3,2-4,9% which includes essential acids; flavonoids (0,6-1,5%, tocopherols (6,6-10,2 mg%, carotinoids (0,13-0,21 mg

  9. Harnessing the potential of natural products in drug discovery from a cheminformatics vantage point.

    Science.gov (United States)

    Rodrigues, Tiago

    2017-11-15

    Natural products (NPs) present a privileged source of inspiration for chemical probe and drug design. Despite the biological pre-validation of the underlying molecular architectures and their relevance in drug discovery, the poor accessibility to NPs, complexity of the synthetic routes and scarce knowledge of their macromolecular counterparts in phenotypic screens still hinder their broader exploration. Cheminformatics algorithms now provide a powerful means of circumventing the abovementioned challenges and unlocking the full potential of NPs in a drug discovery context. Herein, I discuss recent advances in the computer-assisted design of NP mimics and how artificial intelligence may accelerate future NP-inspired molecular medicine.

  10. Biological studies of matrix metalloproteinase sensitive drug delivery systems

    DEFF Research Database (Denmark)

    Johansen, Pia Thermann

    due to severe side effects as a result of drug distribution to healthy tissues. To enhance ecacy of treatment and improve life quality of patients, tumor specific drug delivery strategies, such as liposome encapsulated drugs, which accumulate in tumor tissue, has gained increased attention. Several....... The system exploits the increased MMP-2 activity present in tumor tissue as a site-specific trigger of liposomal activation and controlled drug release after accumulation due to the enhanced permeability and retention effect. Enzymatic activity of MMP-2 results in shedding of a novel PEG coating, consisting...... of a negatively charged lipopeptide-PEG conjugates containing a MMP-2 cleavable peptide, which leads to cationic liposomes with enhanced ability to interact with negatively charged cell membranes. Activation of the liposomal formulation developed here resulted in enhanced association of liposomes with cancer...

  11. Stacking-cyclodextrin-microchip electrokinetic chromatographic determination of gabapentinoid drugs in pharmaceutical and biological matrices.

    Science.gov (United States)

    Zeid, Abdallah M; Kaji, Noritada; Nasr, Jenny Jeehan M; Belal, Fathalla F; Baba, Yoshinobu; Walash, Mohamed I

    2017-06-23

    A facile, rapid, and highly sensitive microchip-based electrokinetic chromatographic method was developed for the simultaneous analysis of two gabapentinoid drugs, gabapentin (GPN) and pregabalin (PGN). Both drugs were first reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) via nucleophilic substitution reactions to yield highly fluorescent products with λ ex/em 470/540nm. Analyses of both fluorescently labeled compounds were achieved within 200s in a poly(methyl methacrylate) (PMMA) microchip with a 30mm separation channel. Optimum separation was achieved using a borate buffer (pH 9.0) solution containing methylcellulose and β-cyclodextrin (β-CD) as buffer additives. Methylcellulose acted as a dynamic coating to prevent adsorption of the studied compounds on the inner surfaces of the microchannels, while β-CD acted as a pseudo-stationary phase to improve the separation efficiency between the labeled drugs with high resolution (Rs>7). The fluorescence intensities of the labeled drugs were measured using a light emitting diode-induced fluorescence detector at 540nm after excitation at 470nm. The sensitivity of the method was enhanced 14- and 17-fold for PGN and GPN, respectively by field-amplified stacking relative to traditional pinched injection so that it could quantify 10ngmL -1 for both analytes, with a detection limit lower than 3ngmL -1 . The developed method was efficiently applied to analyze PGN and GPN in their pharmaceutical dosage forms and in biological fluids. The extraction recoveries of the studied drugs from plasma and urine samples were more than 89% with%RSD values lower than 6.2. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. [Biological availability of ophthalmic drugs. 1. Increasing drug permeability in the cornea].

    Science.gov (United States)

    Masteiková, R; Chalupová, Z; Savickiene, N

    2004-03-01

    Most eye diseases are treated by topical administration of ophthalmic preparations. Low ophthalmic bioavailability is due to a number of physiological and physicochemical factors. The main obstacle to the penetration of active ingredients to the eye is the layered character of the cornea. Formulation of ophthalmic preparations enabling easier penetration of this biological barrier thus ranks among the most effective ways of improving bioavailability. Penetrability of the cornea can be increased by the following methods: a) adjustment of the actual acidity in such a way that pH of the preparation makes it possible to produce the optimal portion of non-ionized particles; b) incorporation of absorption enhancers (non-ionic tensides, salts of bile acids, some antimicrobial substances, EDTA, cyclodextrins, etc.) into the composition of the preparation, and c) production of prodrugs or ionic pairs.

  13. Bead-based screening in chemical biology and drug discovery

    DEFF Research Database (Denmark)

    Komnatnyy, Vitaly V.; Nielsen, Thomas Eiland; Qvortrup, Katrine

    2018-01-01

    libraries for early drug discovery. Among the various library forms, the one-bead-one-compound (OBOC) library, where each bead carries many copies of a single compound, holds the greatest potential for the rapid identification of novel hits against emerging drug targets. However, this potential has not yet...... been fully realized due to a number of technical obstacles. In this feature article, we review the progress that has been made towards bead-based library screening and applications to the discovery of bioactive compounds. We identify the key challenges of this approach and highlight key steps needed......High-throughput screening is an important component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds requires assays amanable to miniaturisation and automization. Combinatorial chemistry holds a unique promise to deliver structural diverse...

  14. Biological effects induced by low amounts of nuclear fission products

    International Nuclear Information System (INIS)

    Vasilenko, I.Ya.; Shishkin, V.F.; Khudyakova, N.V.

    1991-01-01

    The review deals with the problem of biological hazard of low radiation doses for animals and human beings taking into the danger of internal and external irradiation by nuclear fission products under conditions of enhancing anthropogenic radiation contamination of biosphere. An attention is paid to the estimation of life span carcinogenesis, genetic and delayed effects. A conclusion is made on a necessity of multiaspect investigation of biological importance of low radiation doses taking into account modifying effects of other environmental factors

  15. Systems biology-embedded target validation: improving efficacy in drug discovery.

    Science.gov (United States)

    Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

    2014-01-01

    The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

  16. Success rates for product development strategies in new drug development.

    Science.gov (United States)

    Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

    2016-04-01

    While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008

  17. 21 CFR 341.72 - Labeling of antihistamine drug products.

    Science.gov (United States)

    2010-04-01

    ..., unless directed by a doctor, if you have a breathing problem such as emphysema or chronic bronchitis, or... Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... product if you are taking sedatives or tranquilizers, without first consulting your doctor. Use caution...

  18. The Role of Biologically Active Ingredients from Natural Drug Treatments for Arrhythmias in Different Mechanisms

    OpenAIRE

    Li, Jie; Hu, Dan; Song, Xiaoli; Han, Tao; Gao, Yonghong; Xing, Yanwei

    2017-01-01

    Arrhythmia is a disease that is caused by abnormal electrical activity in the heart rate or rhythm. It is the major cause of cardiovascular morbidity and mortality. Although several antiarrhythmic drugs have been used in clinic for decades, their application is often limited by their adverse effects. As a result, natural drugs, which have fewer side effects, are now being used to treat arrhythmias. We searched for all articles on the role of biologically active ingredients from natural drug t...

  19. Biological Evidence for Paradoxical Improvement of Psychiatric Disorder Symptoms by Addictive Drugs.

    Science.gov (United States)

    Müller, Christian P; Kornhuber, Johannes

    2017-06-01

    Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience and opens a new dimension for the development of personalized pharmacotherapy of drug addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Systems Biology and the Development of Vaccines and Drugs for ...

    African Journals Online (AJOL)

    transcriptome at an unprecedented resolution. The close correlation between gene transcription and function, allow the inference of biological processes from the assessed transcriptome profile. Among the sophisticated analytical problems in microarray technology at the front and back ends respectively, are the selection of ...

  1. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  2. Generic Drugs: Questions and Answers

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

  3. MILK KEFIR: COMPOSITION, MICROBIAL CULTURES, BIOLOGICAL ACTIVITIES AND RELATED PRODUCTS

    Directory of Open Access Journals (Sweden)

    Maria Rosa Prado

    2015-10-01

    Full Text Available In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance.

  4. Milk kefir: composition, microbial cultures, biological activities, and related products.

    Science.gov (United States)

    Prado, Maria R; Blandón, Lina Marcela; Vandenberghe, Luciana P S; Rodrigues, Cristine; Castro, Guillermo R; Thomaz-Soccol, Vanete; Soccol, Carlos R

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir's exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir's microflora and the importance of kefiran as a beneficial health substance.

  5. Ionizing radiation for sterilization of medical products and biological tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S K; Raghevendrarao, M K [Bhabha Atomic Research Centre, Bombay (India). Library and Technical Information Section

    1975-10-01

    The article reviews the deliberations of the International Symposium on Ionizing Radiation for Sterilization of Medical Products and Biological Tissues which was held during 9-13 December 1974 under the auspices of the IAEA at the Bhabha Atomic Research Centre, Bombay. 42 papers were presented in the following broad subject areas: (1) Microbiological Control aspects of radiation sterilization, (2) Dosimetry aspects of radiation sterilization practices, (3) Effects of sterilizing radiation dose on the constituents of medical products, (4) Application of radiation sterilization of medical products of biological origin, (5) Technological aspects of radiation sterilization facilities, (6) Radiation sterilization of pharmaceutical substances, (7) Reports on current status of radiation sterilization of medical products in IAEA member states and (8) Working group discussion on the revision of the IAEA recommended code of practice for radiation sterilization of medical products.

  6. Yeast synthetic biology toolbox and applications for biofuel production.

    Science.gov (United States)

    Tsai, Ching-Sung; Kwak, Suryang; Turner, Timothy L; Jin, Yong-Su

    2015-02-01

    Yeasts are efficient biofuel producers with numerous advantages outcompeting bacterial counterparts. While most synthetic biology tools have been developed and customized for bacteria especially for Escherichia coli, yeast synthetic biological tools have been exploited for improving yeast to produce fuels and chemicals from renewable biomass. Here we review the current status of synthetic biological tools and their applications for biofuel production, focusing on the model strain Saccharomyces cerevisiae We describe assembly techniques that have been developed for constructing genes, pathways, and genomes in yeast. Moreover, we discuss synthetic parts for allowing precise control of gene expression at both transcriptional and translational levels. Applications of these synthetic biological approaches have led to identification of effective gene targets that are responsible for desirable traits, such as cellulosic sugar utilization, advanced biofuel production, and enhanced tolerance against toxic products for biofuel production from renewable biomass. Although an array of synthetic biology tools and devices are available, we observed some gaps existing in tool development to achieve industrial utilization. Looking forward, future tool development should focus on industrial cultivation conditions utilizing industrial strains. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  7. Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

    Directory of Open Access Journals (Sweden)

    Kenji Yamamoto

    2013-01-01

    Full Text Available Silicon quantum dots (Si-QDs have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si. Alminoprofen is a non-steroid anti-inflammatory drug (NSAID used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development.

  8. Toward a generic approach for : Stress testing of drug substances and drug products

    NARCIS (Netherlands)

    Klick, Silke; Muijselaar, Pim G.; Waterval, Joop; Eichinger, Thomas; Korn, Christian; Gerding, Thijs K.; Debets, Alexander J.; Sänger-Van De Griend, Cari; Van Den Beld, Cas; Somsen, Govert W.; De Jong, Gerhardus J.

    The Impurity Profiling Group has developed a generic approach for conducting stress testing on drug substances and drug products. The proposed strategy is evaluated and verified with historical data and new experiments. Results demonstrate that the proposed approach is reasonable and generates

  9. Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind

    Directory of Open Access Journals (Sweden)

    Maria Pantelidou

    2017-02-01

    Full Text Available Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes. A number of mechanisms are presented. Structure-activity studies are also discussed. Vitamin E, as well as two synthetic novel compounds, seem to reduce both oxidative and biological stress and, consequently, influence drug response and metabolism.

  10. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Science.gov (United States)

    2010-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products...). Dexfenfluramine hydrochloride: All drug products containing dexfenfluramine hydrochloride. Diamthazole... dihydrostreptomycin sulfate. Dipyrone: All drug products containing dipyrone. Encainide hydrochloride: All drug...

  11. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

    Directory of Open Access Journals (Sweden)

    Nicholas Ekow Thomford

    2018-05-01

    Full Text Available The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of “active compound” has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of ‘organ-on chip’ and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug

  12. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery.

    Science.gov (United States)

    Thomford, Nicholas Ekow; Senthebane, Dimakatso Alice; Rowe, Arielle; Munro, Daniella; Seele, Palesa; Maroyi, Alfred; Dzobo, Kevin

    2018-05-25

    The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review

  13. Synthetic and systems biology for microbial production of commodity chemicals.

    Science.gov (United States)

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J; Keasling, Jay D; Martín, Héctor García

    2016-01-01

    The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.

  14. Biological hydrogen production by moderately thermophilic anaerobic bacteria

    International Nuclear Information System (INIS)

    HP Goorissen; AJM Stams

    2006-01-01

    This study focuses on the biological production of hydrogen at moderate temperatures (65-75 C) by anaerobic bacteria. A survey was made to select the best (moderate) thermophiles for hydrogen production from cellulolytic biomass. From this survey we selected Caldicellulosiruptor saccharolyticus (a gram-positive bacterium) and Thermotoga elfii (a gram-negative bacterium) as potential candidates for biological hydrogen production on mixtures of C 5 -C 6 sugars. Xylose and glucose were used as model substrates to describe growth and hydrogen production from hydrolyzed biomass. Mixed substrate utilization in batch cultures revealed differences in the sequence of substrate consumption and in catabolites repression of the two microorganisms. The regulatory mechanisms of catabolites repression in these microorganisms are not known yet. (authors)

  15. Importance of systems biology in engineering microbes for biofuel production

    Energy Technology Data Exchange (ETDEWEB)

    Mukhopadhyay, Aindrila; Redding, Alyssa M.; Rutherford, Becky J.; Keasling, Jay D.

    2009-12-02

    Microorganisms have been rich sources for natural products, some of which have found use as fuels, commodity chemicals, specialty chemicals, polymers, and drugs, to name a few. The recent interest in production of transportation fuels from renewable resources has catalyzed numerous research endeavors that focus on developing microbial systems for production of such natural products. Eliminating bottlenecks in microbial metabolic pathways and alleviating the stresses due to production of these chemicals are crucial in the generation of robust and efficient production hosts. The use of systems-level studies makes it possible to comprehensively understand the impact of pathway engineering within the context of the entire host metabolism, to diagnose stresses due to product synthesis, and provides the rationale to cost-effectively engineer optimal industrial microorganisms.

  16. 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. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Continuous downstream processing for high value biological products: A Review.

    Science.gov (United States)

    Zydney, Andrew L

    2016-03-01

    There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. © 2015 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    Bjerg, Lise Nørkjær

    function as the targeting moiety on the surface of the liposomes. Several examples of synthetic procedures known from the literature are presented. The chapter is completed with a study covering the conjugation efficiencies of a variety of chemical functionalities. Large differences are revealed between...... to guide the uptake, in addition to an enzymatically cleavable peptide sequence, whose cleavage would result in removal of the polymer layer as well as uncovering cationic charges on the liposomal surface. These systems were shown to have superior drug efficacy in vitro....

  19. Using Nonexperts for Annotating Pharmacokinetic Drug-Drug Interaction Mentions in Product Labeling: A Feasibility Study.

    Science.gov (United States)

    Hochheiser, Harry; Ning, Yifan; Hernandez, Andres; Horn, John R; Jacobson, Rebecca; Boyce, Richard D

    2016-04-11

    Because vital details of potential pharmacokinetic drug-drug interactions are often described in free-text structured product labels, manual curation is a necessary but expensive step in the development of electronic drug-drug interaction information resources. The use of nonexperts to annotate potential drug-drug interaction (PDDI) mentions in drug product label annotation may be a means of lessening the burden of manual curation. Our goal was to explore the practicality of using nonexpert participants to annotate drug-drug interaction descriptions from structured product labels. By presenting annotation tasks to both pharmacy experts and relatively naïve participants, we hoped to demonstrate the feasibility of using nonexpert annotators for drug-drug information annotation. We were also interested in exploring whether and to what extent natural language processing (NLP) preannotation helped improve task completion time, accuracy, and subjective satisfaction. Two experts and 4 nonexperts were asked to annotate 208 structured product label sections under 4 conditions completed sequentially: (1) no NLP assistance, (2) preannotation of drug mentions, (3) preannotation of drug mentions and PDDIs, and (4) a repeat of the no-annotation condition. Results were evaluated within the 2 groups and relative to an existing gold standard. Participants were asked to provide reports on the time required to complete tasks and their perceptions of task difficulty. One of the experts and 3 of the nonexperts completed all tasks. Annotation results from the nonexpert group were relatively strong in every scenario and better than the performance of the NLP pipeline. The expert and 2 of the nonexperts were able to complete most tasks in less than 3 hours. Usability perceptions were generally positive (3.67 for expert, mean of 3.33 for nonexperts). The results suggest that nonexpert annotation might be a feasible option for comprehensive labeling of annotated PDDIs across a broader

  20. Nano-sized crystalline drug production by milling technology.

    Science.gov (United States)

    Moribe, Kunikazu; Ueda, Keisuke; Limwikrant, Waree; Higashi, Kenjirou; Yamamoto, Keiji

    2013-01-01

    Nano-formulation of poorly water-soluble drugs has been developed to enhance drug dissolution. In this review, we introduce nano-milling technology described in recently published papers. Factors affecting the size of drug crystals are compared based on the preparation methods and drug and excipient types. A top-down approach using the comminution process is a method conventionally used to prepare crystalline drug nanoparticles. Wet milling using media is well studied and several wet-milled drug formulations are now on the market. Several trials on drug nanosuspension preparation using different apparatuses, materials, and conditions have been reported. Wet milling using a high-pressure homogenizer is another alternative to preparing production-scale drug nanosuspensions. Dry milling is a simple method of preparing a solid-state drug nano-formulation. The effect of size on the dissolution of a drug from nanoparticles is an area of fundamental research, but it is sometimes incorrectly evaluated. Here, we discuss evaluation procedures and the associated problems. Lastly, the importance of quality control, process optimization, and physicochemical characterization are briefly discussed.

  1. Influence of vitamins on cytostatic drugs: radiation-chemical and radiation-biological investigations in vitro

    International Nuclear Information System (INIS)

    Heinrich, E.

    2002-03-01

    Many environmental burdens (air pollution, formation of ozone etc.), humans nowadays are exposed to, in connection with unhealthy way of living promote the formation of free radicals e.g. OH and peroxylradicals in the organism. Those show an enormous cell-damaging effect, and can weaken the immune system or cause cancer diseases. The number of humans suffering from different forms of cancer is rising world-wide. Therefore it is necessary to find new and better therapy forms for this illness. The organism has its own protective system, which is able to capture free radicals and make them innocuous to a large extent. Apart from various enzyme systems the antioxidizing vitamins C (ascorbic acid), E (α-tocopherol) and β-carotin play an important role in this process. Now it was of interest whether vitamin B1 (thiamine) also possesses the ability to work as a radiation protector or to influence the effect of different cytostatic drugs. In the context of this thesis the radiation-chemical and radiation-biological behaviour of vitamin B1 was examined under different conditions (in presence and absence of oxygen as well as in media saturated with N 2 O). HPLC analysis were performed to establish radiolysis products. Furthermore the synergistic effect of vitamin B1 on cytostatic drugs (sanazole, mitomycin C) was studied alone or in combination with other vitamins (C, E and β-carotin) by using two different E. coli bacteria strains as a model for living systems. (author)

  2. Technical suitability mapping of feedstocks for biological hydrogen production

    NARCIS (Netherlands)

    Panagiotopoulos, I.A.; Karaoglanoglou, L.S.; Koullas, D.P.; Bakker, R.R.; Claassen, P.A.M.; Koukios, E.G.

    2015-01-01

    The objective of this work was to map and compare the technical suitability of different raw materials for biological hydrogen production. Our model was based on hydrogen yield potential, sugar mobilization efficiency, fermentability and coproduct yield and value. The suitability of the studied

  3. Posttranslational Modification Biology of Glutamate Receptors and Drug Addiction

    Directory of Open Access Journals (Sweden)

    Li-Min eMao

    2011-03-01

    Full Text Available Posttranslational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues on their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling and protein-protein interactions, subcellular redistribution (trafficking, endocytosis, synaptic delivery and clustering, and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamines. Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.

  4. Insects: an underrepresented resource for the discovery of biologically active natural products

    Directory of Open Access Journals (Sweden)

    Lauren Seabrooks

    2017-07-01

    Full Text Available Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.

  5. 21 CFR 310.509 - Parenteral drug products in plastic containers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

  6. The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

    Science.gov (United States)

    Barreira, Sofia Carvalho; Fonseca, João Eurico

    2016-08-01

    The bone and the immune system have a very tight interaction. Systemic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), induce bone loss, leading to a twofold increase in osteoporosis and an increase of fragility fracture risk of 1.35-2.13 times. This review focuses on the effects of conventional and biological disease modifying antirheumatic drugs (DMARDs) on bone biology, in the context of systemic inflammation, with a focus on RA. Published evidence supports a decrease in osteoclastic activity induced by DMARDs, which leads to positive effects on bone mineral density (BMD). It is unknown if this effect could be translated into fracture risk reduction. The combination with antiosteoclastic drugs can have an additional benefit.

  7. A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

    Science.gov (United States)

    Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

    2011-08-01

    Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

  8. Molecular biological studies on the human radioresistance and drug resistance

    International Nuclear Information System (INIS)

    Kim, Chang Min; Hong, Weon Seon

    1992-04-01

    We irradiated the MKN45 and PC14 cell lines with 500 rads and also established the adriamycin-resistant and cis-platinum resistant cell line. The genomic DNA and total RNA were extracted and subjected to the Southern and Northern analysis using various probes including heat shock protein 70, MDR1, fos, TGFb etc. The mRNA transcript was increased 1 hour after the irradiation and sustained during the 48 hours and returned to the level of pre-irradiation. No significant change was observed with the drug resistant cell lines at the level of gene dosage. We suggest that the marked increase of the hsp70 transcript is very important finding and is believed to be a good candidate for the modulation of the cellular response to irradiation and the radioresistance. (Author)

  9. Illicit drugs in alternative biological specimens: a case report.

    Science.gov (United States)

    Margalho, Cláudia; Franco, João; Corte-Real, Francisco; Vieira, Duarte Nuno

    2011-04-01

    Postmortem tissues (e.g. liver, kidney) have been long used in forensic applications especially in those cases where blood is unavailable. The aim of this paper is to demonstrate the importance of the information provided to the forensic toxicologist at the time of carrying out the toxicological analysis, especially in cases where the samples commonly used in forensic toxicology are unavailable. This work describes the toxicological findings in a violent death resulting from a man who was hit by a train. Vitreous humor, liver and kidney were sent for toxicological analysis, once it was not possible to obtain blood and urine. The validated procedures used in the routine casework of Forensic Toxicology Laboratory of the Centre Branch of the National Institute of Legal Medicine, were applied in the analysis of liver, kidney and vitreous humor, using gas chromatography-mass spectrometry after solid-phase extraction and gas chromatography-flame ionization detector for the analysis of drugs of abuse and ethanol, respectively. Morphine, codeine, cocaine, benzoylecgonine and ecgonine methyl ester were found in the liver and in the kidney and no ethanol was found in the vitreous humor. The method validation included the study of specificity, selectivity, limits of detection, recovery and carryover. Although blood and urine are the most common and preferred matrices used for toxicological studies involving drugs of abuse, sometimes the choice of specimen is determined by the case under investigation. The forensic pathologist must be aware that relevant information must be provided so that the toxicological analysis can be conducted in accordance with case history, particularly when the only samples available for analysis are these "unconventional" specimens, since the interpretation of the obtained results is more difficult. Copyright © 2011 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  10. PERSPECTIVES FOR DEVELOPMENT OF THE BIOLOGIC PLUM PRODUCTION IN BULGARIA

    Directory of Open Access Journals (Sweden)

    Ivanka Vitanova

    2014-03-01

    Full Text Available The Bulgarian plum cultivars Gabrovska, Nevena, Strinava, Guliaeva and Balvanska slava, breeding in the Plum Experimental Station in the town of Dryanovo and the introduced cultivars Stanley, Chachanska lepotitsa, Opal, Malvazinka, Hramova renkloda, Tuleu timpuriu, Althan’s Gage, Pacific, Mirabell de Nancy, Anna Schpet and Jojo, what are high productive and are tolerant to sharka and other important economic plum diseases are suitable for the biologic plum production. The organic fertilization is a basic element of the technology for the biologic plum production. The fertilization with manure and the green manure with a winter green peas and with a peas-rye mix increased the humus content, influenced positive action on the supplying of the plum plants with the main nutrient macro elements, increased the yield and to be able apply successfully in the plum orchards and at not irrigation conditions.

  11. "Product on Stopper" in a Lyophilized Drug Product: Cosmetic Defect or a Product Quality Concern?

    Science.gov (United States)

    Mehta, Shyam B; Roy, Shouvik; Yang, Han-Chang Cathy

    2018-06-01

    During manufacturing of a lyophilized drug product, operator errors in product handling during loading of product filled vials onto the lyophilizer can lead to a seemingly cosmetic defect which can impact certain critical quality attributes of finished product. In this study, filling of a formulated monoclonal antibody in vials was performed using a peristaltic pump filling unit, and subsequently, the product was lyophilized. After lyophilization, upon visual inspection, around 40% of vials had cosmetic defect with residual product around stopper of the vial and were categorized as "product on stopper" vials, whereas remaining 60% vials with no cosmetic defect were called "acceptable vials." Both groups of vials from 1 single batch were tested for critical quality attributes including protein concentration (ultraviolet absorbance at 280), residual moisture (Karl Fischer), sterility (membrane filtration), and container closure integrity (CCI) (blue dye ingress). Analysis of protein quality attributes such as aggregation, protein concentration, residual moisture showed no significant difference between vials with "product on stopper" and "acceptable vials." However, CCI of the "product on stopper" vials was compromised due to the presence of product around stopper of the vial. The results from this case study demonstrate the following 2 important findings: (1) that a seemingly cosmetic defect may impact product quality, compromising the integrity of the product and (2) that CCI test method can be used as an orthogonal method to sterility testing to evaluate sterility assurance of the product. The corrective action proposed to mitigate this defect is use of a larger sized vial that can potentially minimize this defect that arises because of product handling errors. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Cell culture media impact on drug product solution stability.

    Science.gov (United States)

    Purdie, Jennifer L; Kowle, Ronald L; Langland, Amie L; Patel, Chetan N; Ouyang, Anli; Olson, Donald J

    2016-07-08

    To enable subcutaneous administration of monoclonal antibodies, drug product solutions are often needed at high concentrations. A significant risk associated with high drug product concentrations is an increase in aggregate level over the shelf-life dating period. While much work has been done to understand the impact of drug product formulation on aggregation, there is limited understanding of the link between cell culture process conditions and soluble aggregate growth in drug product. During cell culture process development, soluble aggregates are often measured at harvest using cell-free material purified by Protein A chromatography. In the work reported here, cell culture media components were evaluated with respect to their impact on aggregate levels in high concentration solution drug product during accelerated stability studies. Two components, cysteine and ferric ammonium citrate, were found to impact aggregate growth rates in our current media (version 1) leading to the development of new chemically defined media and concentrated feed formulations. The new version of media and associated concentrated feeds (version 2) were evaluated across four cell lines producing recombinant IgG4 monoclonal antibodies and a bispecific antibody. In all four cell lines, the version 2 media reduced aggregate growth over the course of a 12 week accelerated stability study compared with the version 1 media, although the degree to which aggregate growth decreased was cell line dependent. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:998-1008, 2016. © 2016 American Institute of Chemical Engineers.

  13. 75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

    Science.gov (United States)

    2010-05-05

    ... [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Application; Buquinolate; Coumaphos AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations by...

  14. Back to the Roots: Prediction of Biologically Active Natural Products from Ayurveda Traditional Medicine

    DEFF Research Database (Denmark)

    Polur, Honey; Joshi, Tejal; Workman, Christopher

    2011-01-01

    Ayurveda, the traditional Indian medicine is one of the most ancient, yet living medicinal traditions. In the present work, we developed an in silico library of natural products from Ayurveda medicine, coupled with structural information, plant origin and traditional therapeutic use. Following this....... We hereby present a number of examples where the traditional medicinal use of the plant matches with the medicinal use of the drug that is structurally similar to a plant component. With this approach, we have brought to light a number of obscure compounds of natural origin (e.g. kanugin......, we compared their structures with those of drugs from DrugBank and we constructed a structural similarity network. Information on the traditional therapeutic use of the plants was integrated in the network in order to provide further evidence for the predicted biologically active natural compounds...

  15. Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

    Science.gov (United States)

    Altmann, Karl-Heinz

    2017-10-25

    The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.

  16. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product states...

  17. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

  18. The preparation of albumin as a biological drug from human plasma by fiber filtration

    Directory of Open Access Journals (Sweden)

    Mousavi Hosseini K

    2011-08-01

    Full Text Available "nBackground: In recent years, consumption of whole-blood for the treatment of patients has decreased but use of biological plasma-derived medicines such as albumin, immunoglobulin and coagulation factors have increased instead. Paying attention to albumin molecular structure is important for its isolation from human plasma. Albumin is a single-chain protein consisting of about 585 amino acids and a molecular weight of 66500 Daltons. Albumin is a stable molecule and it is spherical in shape. There are different methods for human albumin preparation. Considering the large consumption of this biological drug in clinical settings, methods with fewer steps in production line are of big advantage in saving time and manufacturing more products."n "nMethods: In this project, we prepared human albumin using hollow fiber cartridges in order to omit the rework on fraction V+VI. Human albumin is usually produced by the application of cold ethanol method, where albumin is obtained from fraction V by doing a rework on fraction V+VI to separate fraction V."n "nResults: In the current work, human albumin was prepared from fraction V+VI by the help of hollow fiber cartridges. With a concentration of 20%, the obtained albumin had 96.5% of monomer and 3.5% of polymer and polymer aggregate."n "nConclusion: Comparing the obtained human albumin with a number of commercial human albumin samples by the use of SDS-page, the results were satisfactory regarding the 3.5 percent polymer and aggregate rate for the prepared albumin.

  19. Analysis of antiepileptic drugs in biological fluids by means of electrokinetic chromatography.

    Science.gov (United States)

    Pucci, Vincenzo; Raggi, Maria Augusta

    2005-02-01

    An overview of the electrokinetic chromatographic methods for the analysis of antiepileptic drug levels in biological samples is presented. In particular, micellar electrokinetic capillary chromatography is a very suitable method for the determination of these drugs, because it allows a rapid, selective, and accurate analysis. In addition to the electrokinetic chromatographic studies on the determination of antiepileptic drugs, some information regarding sample pretreatment will also be reported: this is a critical step when the analysis of biological fluids is concerned. The electrokinetic chromatographic methods for the determination of recent antiepileptic drugs (e.g., lamotrigine, levetiracetam) and classical anticonvulsants (e.g., carbamazepine, phenytoin, ethosuximide, valproic acid) will be discussed in depth, and their pharmacological profiles will be briefly described as well.

  20. FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects.

    Science.gov (United States)

    Lagorce, David; Sperandio, Olivier; Galons, Hervé; Miteva, Maria A; Villoutreix, Bruno O

    2008-09-24

    Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses) and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making. This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python) based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries. We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after) experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules) that can be easily tuned.

  1. Package selection for moisture protection for solid, oral drug products.

    Science.gov (United States)

    Waterman, Kenneth C; MacDonald, Bruce C

    2010-11-01

    This review describes how best to select the appropriate packaging options for solid, oral drug products based on both chemical and physical stability, with respect to moisture protection. This process combines an accounting for the initial moisture content of dosage form components, moisture transfer into (out of) packaging based on a moisture vapor transfer rate (MVTR), and equilibration between drug products and desiccants based on their moisture sorption isotherms to provide an estimate of the instantaneous relative humidity (RH) within the packaging. This time-based RH is calculationally combined with a moisture-sensitive Arrhenius equation (determined using the accelerated stability assessment program, ASAP) to predict the drug product's chemical stability over time as a function of storage conditions and packaging options. While physical stability of dosage forms with respect to moisture has been less well documented, a process is recommended based on the threshold RH at which changes (e.g., dosage form dissolution, tablet hardness, drug form) become problematic. The overall process described allows packaging to be determined for a drug product scientifically, with the effect of any changes to storage conditions or packaging to be explicitly accounted for. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  2. 21 CFR 344.52 - Labeling of ear drying aid drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of ear drying aid drug products. 344.52 Section 344.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains...

  3. Biological risks associated with consumption of reptile products

    DEFF Research Database (Denmark)

    Magnino, S.; Colin, P.; Dei-Cas, E.

    2009-01-01

    recently increased in some areas of the world. Biological risks associated with the consumption of products from both farmed and wild reptile meat and eggs include infections caused by bacteria (Salmonella spp., Vibrio spp.). parasites (Spirometra, Trichinella, Gnathostoma, pentastomids), as well...... to increase the occurrence of biological hazards in reptile meat. Application of GHP, GMP and HACCP procedures, respectively at farm and slaughterhouse level, is crucial for controlling the hazards.......The consumption of a wide variety of species of reptiles caught from the wild has been an important source of protein for humans world-wide for millennia. Terrapins. snakes, lizards, crocodiles and iguanas are now farmed and the consumption and trade of their meat and other edible products have...

  4. National experience in radiosterelization or radiodescontamination of biological products

    International Nuclear Information System (INIS)

    Padron, E.; Romay, Z.; Otero, I.; Chavez, A.; Prieto, E.; Sainz, D.; Rodriguez, R.; Diaz, D.

    1997-01-01

    The ionizing radiations are especially important when other chemical and physical methods can't be used, or they don't give the result required, for which the employment of advanced technologies for the sterilization is found in ascent at world level. To such effect, the International Atomic Energy Agency has, sponsored a coordinated program for the radiosterilization of medical and biological products in Latin America, in which Cuba participates. (author) [es

  5. Implementation of Plasma Fractionation in Biological Medicines Production

    OpenAIRE

    Mousavi Hosseini, Kamran; Ghasemzadeh, Mehran

    2016-01-01

    Context The major motivation for the preparation of the plasma derived biological medicine was the treatment of casualties from the Second World War. Due to the high expenses for preparation of plasma derived products, achievement of self-sufficiency in human plasma biotechnological industry is an important goal for developing countries. Evidence Acquisition The complexity of the blood plasma was first revealed by the Nobel Prize laureate, Arne Tiselius and Theodor Svedberg, which resulted in...

  6. State of the art of biological hydrogen production processes

    International Nuclear Information System (INIS)

    Loubette, N.; Junker, M.

    2006-01-01

    Our report gives an overview of hydrogen production processes with bacteria or algae. 4 main processes are described: water biophotolysis, photo- fermentation biological CO conversion and dark fermentation. Chemical phenomena which lead to hydrogen generation are exp/aired. Performances, limits and outlook are given for each process. Main projects, programs and key players involved in this field of research have been listed. This paper resumes few results of this report. (authors)

  7. State of the art of biological hydrogen production processes

    International Nuclear Information System (INIS)

    Nicolas Loubette; Michel Junker

    2006-01-01

    Our report gives an overview of hydrogen production processes with bacteria or algae. 4 main processes are described: water bio-photolysis, photo-fermentation biological CO conversion and dark fermentation. Chemical phenomena which lead to hydrogen generation are explained. Performances, limits and outlook are given for each process. Main projects, programs and key players involved in this field of research have been listed. This paper resumes few results of this report. (authors)

  8. Production of biological nanoparticles from α- lactalbumin for drug ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-12-15

    Dec 15, 2009 ... Available online at http://www.academicjournals.org/AJB ... to characterize the two step desolvation process of α-lactalbumin for preparation of its nanoparticles. Following the .... tage of the emulsion methods for particle preparation is the need for .... To the best of our knowledge, the current paper is.

  9. Formate Formation and Formate Conversion in Biological Fuels Production

    Directory of Open Access Journals (Sweden)

    Bryan R. Crable

    2011-01-01

    Full Text Available Biomethanation is a mature technology for fuel production. Fourth generation biofuels research will focus on sequestering CO2 and providing carbon-neutral or carbon-negative strategies to cope with dwindling fossil fuel supplies and environmental impact. Formate is an important intermediate in the methanogenic breakdown of complex organic material and serves as an important precursor for biological fuels production in the form of methane, hydrogen, and potentially methanol. Formate is produced by either CoA-dependent cleavage of pyruvate or enzymatic reduction of CO2 in an NADH- or ferredoxin-dependent manner. Formate is consumed through oxidation to CO2 and H2 or can be further reduced via the Wood-Ljungdahl pathway for carbon fixation or industrially for the production of methanol. Here, we review the enzymes involved in the interconversion of formate and discuss potential applications for biofuels production.

  10. Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.

    Science.gov (United States)

    Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio

    2014-07-01

    Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.

  11. Photochemical versus biological production of methyl iodide during Meteor 55

    Science.gov (United States)

    Richter, U.; Wallace, D.

    2003-04-01

    The flux of methyl iodide from sea to air represents the largest flux of iodine from the ocean to the atmosphere. Surface water concentrations and hence fluxes are particularly high in tropical regions. This flux may be responsible for the enrichment of iodine in the marine aerosol and may contribute to important processes in the marine boundary layer, including particle formation. Methyl iodide is commonly referred to as a biogenic gas, with both macroalgae and phytoplankton identified as important sources. On the other hand experimental and field data have shown the importance of photochemical production that is not necessarily associated directly with biological activity. During the Meteor cruise 55 along 11°N in the tropical Atlantic Ocean, a series of experiments were conducted to examine the biological vs. photochemical production of methyl iodide. A total of eight separate experiments were conducted. Production of CH3I in quartz glass flasks during 24 hour incubations (dark and natural sunlight) was measured under three experimental treatments: untreated seawater, filtered seawater (0.1 um pore size filter to exclude most phytoplankton and bacteria), and seawater that was poisoned with mercuric chloride. There were two clear findings from these experiments: (1) methyl iodide production was significantly higher in all the incubations that were exposed to the light than in the dark incubations; (2) there was no significant difference between CH3I production under the three experimental treatments. These results argue very strongly for the primary importance of photochemical production of CH3I as opposed to biogenic production at least for the tropical open ocean surface waters. Further experiments are required to investigate the reactants involved, their sources, the wavelength and depth dependence of production, etc. as well as (possibly related) sink processes.

  12. 21 CFR 250.250 - Hexachlorophene, as a component of drug and cosmetic products.

    Science.gov (United States)

    2010-04-01

    ... cosmetic products. 250.250 Section 250.250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Requirements for Drugs and Cosmetics § 250.250 Hexachlorophene, as a component of drug and cosmetic products... cosmetic products has expanded widely in recent years. It is used in such products because of its...

  13. 41 CFR 101-42.1102-5 - Drugs, biologicals, and reagents other than controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Drugs, biologicals, and reagents other than controlled substances. 101-42.1102-5 Section 101-42.1102-5 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS...

  14. Drug screening in biological fluids - The need for a systematic approach

    NARCIS (Netherlands)

    de Zeeuw, R.A

    1997-01-01

    In this paper the key steps towards drug screening in biological fluids are considered: (i) sample work up-isolation-concentration: (ii) differentiation-detection; (iii) identification. For (i) solid-phase extraction has very good potential; for (ii) thin-layer chromatography, gas chromatography and

  15. Evolution of approaches to viral safety issues for biological products.

    Science.gov (United States)

    Lubiniecki, Anthony S

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has

  16. Identification of antimycotic drugs transformation products upon UV exposure

    International Nuclear Information System (INIS)

    Casado, Jorge; Rodríguez, Isaac; Ramil, María; Cela, Rafael

    2015-01-01

    Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs

  17. Identification of antimycotic drugs transformation products upon UV exposure

    Energy Technology Data Exchange (ETDEWEB)

    Casado, Jorge; Rodríguez, Isaac, E-mail: isaac.rodriguez@usc.es; Ramil, María; Cela, Rafael

    2015-05-30

    Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs.

  18. Prudent Use of Veterinary Drugs: Impact on Safe Animal Products ...

    African Journals Online (AJOL)

    Like any other therapeutic compounds, veterinary drugs are used to alleviate diseases in animals as either therapeutic or prophylactic compounds for specific disease entities. They can also be used as production aids in food producing animals to increase market sale of these animals whereby the producers save on the ...

  19. 21 CFR 350.50 - Labeling of antiperspirant drug products.

    Science.gov (United States)

    2010-04-01

    ...: ‘dampness,’ ‘perspiration,’ ‘sweat,’ ‘sweating,’ or ‘wetness’] due to stress”. (3) For products that... this chapter for definition of bullet. (ii) The warning required by § 369.21 of this chapter for drugs...

  20. Determination of drugs in biological fluids by direct injection of samples for liquid-chromatographic analysis.

    Science.gov (United States)

    Mullett, Wayne M

    2007-03-10

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time-consuming, tedious, and frequently overlooked. However, direct on-line injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. The objective of this review is to present an overview of the existing literature with emphasis on advances in automated sample preparation methods for liquid-chromatographic methods. More specifically, this review concentrates on the use of direct injection techniques, such as restricted-access materials, turbulent-flow chromatography and other automated on-line solid-phase extraction (SPE) procedures. It also includes short overviews of emerging automated extraction-phase technologies, such as molecularly imprinted polymers, in-tube solid-phase micro-extraction, and micro-extraction in a packed syringe for a more selective extraction of analytes from complex samples, providing further improvements in the analysis of biological materials. Lastly, the outlook for these methods and potential new applications for these technologies are briefly discussed.

  1. Biological treatment of chicken feather waste for improved biogas production

    Institute of Scientific and Technical Information of China (English)

    Gergely Forgács; Saeid Alinezhad; Amir Mirabdollah; Elisabeth Feuk-Lagerstedt; Ilona Sárvári Horwáth

    2011-01-01

    A two-stage system was developed which combines the biological degradation of keratin-rich waste with the production of biogas.Chicken feather waste was treated biologically with a recombinant Bacillus megaterium strain showing keratinase activity prior to biogas production.Chopped,autoclaved chicken feathers (4%,W/V) were completely degraded,resulting in a yellowish fermentation broth with a level of 0.51 mg/mL soluble proteins after 8 days of cultivation of the recombinant strain.During the subsequent anaerobic batch digestion experiments,methane production of 0.35 Nm3/kg dry feathers (i.e.,0.4 Nm3/kg volatile solids of feathers),corresponding to 80% of the theoretical value on proteins,was achieved from the feather hydrolyzates,independently of the prehydrolysis time period of 1,2 or 8 days.Cultivation with a native keratinase producing strain,Bacillus licheniformis resulted in only 0.25 mg/mL soluble proteins in the feather hydrolyzate,which then was digested achieving a maximum accumulated methane production of 0.31 Nm3/kg dry feathers.Feather hydrolyzates treated with the wild type B.megaterium produced 0.21 Nm3 CH4/kg dry feathers as maximum yield.

  2. Production of drug nanosuspensions: effect of drug physical properties on nanosizing efficiency.

    Science.gov (United States)

    Liu, Tao; Müller, Rainer H; Möschwitzer, Jan P

    2018-02-01

    Drug nanosuspension is one of the established methods to improve the bioavailability of poorly soluble drugs. Drug physical properties aspect (morphology, solid state, starting size et al) is a critical parameter determining the production efficiency. Some drug modification approaches such as spray-drying were proved to improve the millability of drug powders. However, the mechanism behind those improved performances is unclear. This study is to systematically investigate the influence of those physical properties. Five different APIs (active pharmaceutical ingredients) with different millabilities, i.e. resveratrol, hesperetin, glibenclamide, rutin, and quercetin, were processed by standard high pressure homogenization (HPH), wet bead milling (WBM), and a combinative method of spray-drying and HPH. Smaller starting sizes of certain APIs could accelerate the particle size reduction velocity during both HPH and WBM processes. Spherical particles were observed for almost all spray-dried powders (except spray-dried hesperetin) after spray-drying. The crystallinity of some spray-dried samples such as rutin and glibenclamide became much lower than their corresponding unmodified powders. Almost all spray-dried drug powders after HPH processes could lead to smaller nanocrystal particle size than unmodified APIs. The modified microstructure instead of solid state after spray-drying explained the potential reason for improved nanosizing efficiency. In addition, the contribution of starting size on the production efficiency was also critical according to both HPH and WBM results.

  3. Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

    Science.gov (United States)

    Laing, R O; McGoldrick, K M

    2000-12-01

    Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

  4. Sustained climate warming drives declining marine biological productivity

    Science.gov (United States)

    Moore, J. Keith; Fu, Weiwei; Primeau, Francois; Britten, Gregory L.; Lindsay, Keith; Long, Matthew; Doney, Scott C.; Mahowald, Natalie; Hoffman, Forrest; Randerson, James T.

    2018-03-01

    Climate change projections to the year 2100 may miss physical-biogeochemical feedbacks that emerge later from the cumulative effects of climate warming. In a coupled climate simulation to the year 2300, the westerly winds strengthen and shift poleward, surface waters warm, and sea ice disappears, leading to intense nutrient trapping in the Southern Ocean. The trapping drives a global-scale nutrient redistribution, with net transfer to the deep ocean. Ensuing surface nutrient reductions north of 30°S drive steady declines in primary production and carbon export (decreases of 24 and 41%, respectively, by 2300). Potential fishery yields, constrained by lower–trophic-level productivity, decrease by more than 20% globally and by nearly 60% in the North Atlantic. Continued high levels of greenhouse gas emissions could suppress marine biological productivity for a millennium.

  5. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2016-11-01

    Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  6. Semi-supervised drug-protein interaction prediction from heterogeneous biological spaces.

    Science.gov (United States)

    Xia, Zheng; Wu, Ling-Yun; Zhou, Xiaobo; Wong, Stephen T C

    2010-09-13

    Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data. Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG. We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs.

  7. FDA's requirements for radiation dosimetry of radiopharmaceutical drug products

    International Nuclear Information System (INIS)

    Abel, N.M.

    1986-01-01

    The primary concern of the Office of Drug Research and Review of the Food and Drug Administration in the field of radiation dosimetry is to ensure that radiopharmaceutical drug products are safe when used as investigational drugs (INDs) and are both safe and effective when a new drug application (NDA) is approved. In order to accomplish this, the sponsor of either an IND or applicant in the case of NDA must provide information that clearly describes the radiation dose that a patient will receive from the administration of the drug. The submitted numerical estimates of the radiation dose should be based on an absorbed fraction method of radiation dose calculation, such as the system set forth by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine or the system set forth by the International Commission on Radiological Protection (ICRP). This presentation will describe in detail the data that a sponsor of an IND needs to submit to satisfy the regulatory requirements. Examples will be given of common mistakes and omissions by sponsors in their presentation of data

  8. Cumulative exposure to phthalates from phthalate-containing drug products

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Broe, Anne; Pottegård, Anton

    2018-01-01

    European regulatory limit of exposure ranging between 380-1710 mg/year throughout the study period. Lithium-products constituted the majority of dibutyl phthalate exposure. Diethyl phthalate exposure, mainly caused by erythromycin, theophylline and diclofenac products, did not exceed the EMA regulatory...... to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held...

  9. FAF-Drugs2: Free ADME/tox filtering tool to assist drug discovery and chemical biology projects

    Directory of Open Access Journals (Sweden)

    Miteva Maria A

    2008-09-01

    Full Text Available Abstract Background Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making. Results This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries. Conclusion We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules that can be easily tuned.

  10. Molecular biology in studies of oceanic primary production

    International Nuclear Information System (INIS)

    LaRoche, J.; Falkowski, P.G.; Geider, R.

    1992-01-01

    Remote sensing and the use of moored in situ instrumentation has greatly improved our ability to measure phytoplankton chlorophyll and photosynthesis on global scales with high temporal resolution. However, the interpretation of these measurements and their significance with respect to the biogeochemical cycling of carbon relies on their relationship with physiological and biochemical processes in phytoplankton. For example, the use of satellite images of surface chlorophyll to estimate primary production is often based on the functional relationship between photosynthesis and irradiance. A variety of environmental factors such as light, temperature, nutrient availability affect the photosynthesis/irradiance (P vs I) relationship in phytoplankton. We present three examples showing how molecular biology can be used to provide basic insight into the factors controlling primary productivity at three different levels of complexity: 1. Studies of light intensity regulation in unicellular alga show how molecular biology can help understand the processing of environmental cues leading to the regulation of photosynthetic gene expression. 2. Probing of the photosynthetic apparatus using molecular techniques can be used to test existing mechanistic models derived from the interpretation of physiological and biophysical measurements. 3. Exploratory work on the expression of specific proteins during nutrient-limited growth of phytoplankton may lead to the identification and production of molecular probes for field studies

  11. 21 CFR 20.2 - Production of records by Food and Drug Administration employees.

    Science.gov (United States)

    2010-04-01

    ... upon an officer or employee of the Food and Drug Administration commanding the production of any record... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Production of records by Food and Drug Administration employees. 20.2 Section 20.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  12. A primer of drug safety surveillance: an industry perspective. Part II: Product labeling and product knowledge.

    Science.gov (United States)

    Allan, M C

    1992-01-01

    To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered

  13. MALDI-MS drug analysis in biological samples: opportunities and challenges.

    Science.gov (United States)

    Steuer, Andrea E; Poetzsch, Michael; Kraemer, Thomas

    2016-09-01

    Drug analysis represents a large field in different disciplines. Plasma is commonly considered to be the biosample of choice for that purpose. However, concentrations often do not represent the levels present within deeper compartments and therefore cannot sufficiently explain efficacy or toxicology of drugs. MALDI-MS in drug analysis is of great interest for high-throughput quantification and particularly spatially resolved tissue imaging. The current perspective article will deal with challenges and opportunities of MALDI-MS drug analysis in different biological samples. A particular focus will be on hair samples. Recent applications were included, reviewed for their instrumental setup and sample preparation and pros and cons as well as future perspectives are critically discussed.

  14. Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?

    Science.gov (United States)

    Gopalakrishnan, Ranganath; Frolov, Andrey I; Knerr, Laurent; Drury, William J; Valeur, Eric

    2016-11-10

    Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.

  15. Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers.

    Science.gov (United States)

    de Oliveira, Carolina C; Abud, Ana Paula R; de Oliveira, Simone M; Guimarães, Fernando de S F; de Andrade, Lucas F; Di Bernardi, Raffaello P; Coletto, Ediely L de O; Kuczera, Diogo; Da Lozzo, Eneida J; Gonçalves, Jenifer P; Trindade, Edvaldo da S; Buchi, Dorly de F

    2011-10-26

    In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.

  16. Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

    Directory of Open Access Journals (Sweden)

    de Oliveira Carolina C

    2011-10-01

    Full Text Available Abstract Background In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. Methods We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. Results None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS, nitric oxide (NO production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Conclusions Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.

  17. Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach.

    Science.gov (United States)

    Peng, Huiming; Peng, Tao; Wen, Jianguo; Engler, David A; Matsunami, Risë K; Su, Jing; Zhang, Le; Chang, Chung-Che Jeff; Zhou, Xiaobo

    2014-07-01

    p38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown. To explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography-mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph. New mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFкB pathway. ERK pathway regulating cell growth is synergistically regulated by p38δ isoform, whereas nuclear factor kappa B (NFкB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38δ isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFκB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Biological hydrogen production from biomass by thermophilic bacteria

    International Nuclear Information System (INIS)

    Claassen, P.A.M.; Mars, A.E.; Budde, M.A.W.; Lai, M.; de Vrije, T.; van Niel, E.W.J.

    2006-01-01

    To meet the reduction of the emission of CO 2 imposed by the Kyoto protocol, hydrogen should be produced from renewable primary energy. Besides the indirect production of hydrogen by electrolysis using electricity from renewable resources, such as sunlight, wind and hydropower, hydrogen can be directly produced from biomass. At present, there are two strategies for the production of hydrogen from biomass: the thermochemical technology, such as gasification, and the biotechnological approach using micro-organisms. Biological hydrogen production delivers clean hydrogen with an environmental-friendly technology and is very suitable for the conversion of wet biomass in small-scale applications, thus having a high chance of becoming an economically feasible technology. Many micro-organisms are able to produce hydrogen from mono- and disaccharides, starch and (hemi)cellulose under anaerobic conditions. The anaerobic production of hydrogen is a common phenomenon, occurring during the process of anaerobic digestion. Here, hydrogen producing micro-organisms are in syn-trophy with methanogenic bacteria which consume the hydrogen as soon as it is produced. In this way, hydrogen production remains obscure and methane is the end-product. By uncoupling hydrogen production from methane production, hydrogen becomes available for recovery and exploitation. This study describes the use of extreme thermophilic bacteria, selected because of a higher hydrogen production efficiency as compared to mesophilic bacteria, for the production of hydrogen from renewable resources. As feedstock energy crops like Miscanthus and Sorghum bicolor and waste streams like domestic organic waste, paper sludge and potato steam peels were used. The feedstock was pretreated and/or enzymatically hydrolyzed prior to fermentation to make a fermentable substrate. Hydrogen production by Caldicellulosiruptor saccharolyticus, Thermotoga elfii and T. neapolitana on all substrates was observed. Nutrient

  19. 21 CFR 347.50 - Labeling of skin protectant drug products.

    Science.gov (United States)

    2010-04-01

    ... omitted. (f) Products containing only cocoa butter, petrolatum, or white petrolatum identified in § 347.10... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of skin protectant drug products. 347.50... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347...

  20. Yeast synthetic biology for the production of recombinant therapeutic proteins.

    Science.gov (United States)

    Kim, Hyunah; Yoo, Su Jin; Kang, Hyun Ah

    2015-02-01

    The production of recombinant therapeutic proteins is one of the fast-growing areas of molecular medicine and currently plays an important role in treatment of several diseases. Yeasts are unicellular eukaryotic microbial host cells that offer unique advantages in producing biopharmaceutical proteins. Yeasts are capable of robust growth on simple media, readily accommodate genetic modifications, and incorporate typical eukaryotic post-translational modifications. Saccharomyces cerevisiae is a traditional baker's yeast that has been used as a major host for the production of biopharmaceuticals; however, several nonconventional yeast species including Hansenula polymorpha, Pichia pastoris, and Yarrowia lipolytica have gained increasing attention as alternative hosts for the industrial production of recombinant proteins. In this review, we address the established and emerging genetic tools and host strains suitable for recombinant protein production in various yeast expression systems, particularly focusing on current efforts toward synthetic biology approaches in developing yeast cell factories for the production of therapeutic recombinant proteins. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  1. PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

    Science.gov (United States)

    Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

    2015-04-01

    PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

  2. The Role of Biologically Active Ingredients from Natural Drug Treatments for Arrhythmias in Different Mechanisms.

    Science.gov (United States)

    Li, Jie; Hu, Dan; Song, Xiaoli; Han, Tao; Gao, Yonghong; Xing, Yanwei

    2017-01-01

    Arrhythmia is a disease that is caused by abnormal electrical activity in the heart rate or rhythm. It is the major cause of cardiovascular morbidity and mortality. Although several antiarrhythmic drugs have been used in clinic for decades, their application is often limited by their adverse effects. As a result, natural drugs, which have fewer side effects, are now being used to treat arrhythmias. We searched for all articles on the role of biologically active ingredients from natural drug treatments for arrhythmias in different mechanisms in PubMed. This study reviews 19 natural drug therapies, with 18 active ingredient therapies, such as alkaloids, flavonoids, saponins, quinones, and terpenes, and two kinds of traditional Chinese medicine compound (Wenxin-Keli and Shensongyangxin), all of which have been studied and reported as having antiarrhythmic effects. The primary focus is the proposed antiarrhythmic mechanism of each natural drug agent. Conclusion . We stress persistent vigilance on the part of the provider in discussing the use of natural drug agents to provide a solid theoretical foundation for further research on antiarrhythmia drugs.

  3. Natural products as a resource for biologically active compounds

    International Nuclear Information System (INIS)

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod) 3 is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous 13 C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the 1 H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants

  4. Indicators of club management practices and biological measurements of patrons' drug and alcohol use.

    Science.gov (United States)

    Byrnes, Hilary F; Miller, Brenda A; Johnson, Mark B; Voas, Robert B

    2014-12-01

    Electronic music and dance events in nightclubs attract patrons with heavy alcohol/drug use. Public health concerns are raised from risks related to these behaviors. Practices associated with increased risk in these club settings need to be identified. The relationship between club management practices and biological measures of patrons' alcohol/drug use is examined. Observational data from 25 events across six urban clubs were integrated with survey data (N = 738 patrons, 42.8% female) from patrons exiting these events, 2010-2012. Five indicators of club management practices were examined using mixed model regressions: club security, bar crowding, safety signs, serving intoxicated patrons, and isolation. Analyses revealed that serving intoxicated patrons and safety signs were related to substance use. Specifically, serving intoxicated patrons was related to heavy alcohol and drug use at exit, while safety signs were marginally related to less exit drug use. CONCLUSIONS/IMPORTANCE: Findings indicate observable measures in nightclubs provide important indicators for alcohol/drug use, suggesting practices to target. Study strengths include the use of biological measures of substance use on a relatively large scale. Limitations and future directions are discussed.

  5. Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells and Tissues Following Combat Associated Trauma

    Science.gov (United States)

    2013-09-01

    death pathways such as apoptosis subsequent to acute trauma as soon as possible, ideally by self- administration of a drug or a biologic that can be... Drugs to Ocular Tissues Including Retina and Cornea . Mol Ther, 2007;16(1):107- 14. 3. Read SP, Cashman SM, and Kumar-Singh R: POD...1 AD_________________ Award Number: W81XWH-12-1-0374 TITLE: Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells

  6. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  7. Recent advances on biological production of difructose dianhydride III.

    Science.gov (United States)

    Zhu, Yingying; Yu, Shuhuai; Zhang, Wenli; Zhang, Tao; Guang, Cuie; Mu, Wanmeng

    2018-04-01

    Difructose dianhydride III (DFA III) is a cyclic difructose containing two reciprocal glycosidic linkages. It is easily generated with a small amount by sucrose caramelization and thus occurs in a wide range of food-stuffs during food processing. DFA III has half sweetness but only 1/15 energy of sucrose, showing potential industrial application as low-calorie sucrose substitute. In addition, it displays many benefits including prebiotic effect, low cariogenicity property, and hypocholesterolemic effect, and improves absorption of minerals, flavonoids, and immunoglobulin G. DFA III is biologically produced from inulin by inulin fructotransferase (IFTase, EC 4.2.2.18). Plenty of DFA III-producing enzymes have been identified. The crystal structure of inulin fructotransferase has been determined, and its molecular modification has been performed to improve the catalytic activity and structural stability. Large-scale production of DFA III has been studied by various IFTases, especially using an ultrafiltration membrane bioreactor. In this article, the recent findings on physiological effects of DFA III are briefly summarized; the research progresses on identification, expression, and molecular modification of IFTase and large-scale biological production of DFA III by IFTase are reviewed in detail.

  8. Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

    Directory of Open Access Journals (Sweden)

    Jack Xie

    2010-08-01

    Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

  9. Applying insights from biofilm biology to drug development - can a new approach be developed?

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Ciofu, Oana; Molin, Søren

    2013-01-01

    Most of the research on bacterial pathogenesis has focused on acute infections, but much less is known about the pathogenesis of infections caused by bacteria that grow as aggregates in biofilms. These infections tend to be chronic as they resist innate and adaptive immune defence mechanisms...... and pathology, and discuss how a deep insight into the physical and biological characteristics of biofilms can inform therapeutic strategies and molecular targets for the development of anti-biofilm drugs....

  10. MODERN TECHNOLOGICAL SOLUTIONS USED IN THE PRODUCTION OF BAKERY PRODUCTS WITH HIGH BIOLOGICAL VALUE

    OpenAIRE

    Marta Brodowska; Dominika Guzek; Agnieszka Wierzbicka

    2014-01-01

    Biological value of the food products is a result of the presence of bioactive substances and the proportions of the components. Technological development allows to optimize and accelerate the processes of bread production and increase value of food. Bakery industry used whole grains and pseudocereals as additional source of active compounds, biotechnological techniques as using appropriate yeast strain and encapsulation, which provide protection of substance and their controlled release in p...

  11. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  12. Crop production in salt affected soils: A biological approach

    Energy Technology Data Exchange (ETDEWEB)

    Malik, K A [National Inst. for Biotechnology and Genetic Engineering (NIBGE), Faisalabad (Pakistan)

    1995-01-01

    Plant are susceptible to various stresses, affecting growth productivity. Among the abiotic stresses, soil salinity is most significant and prevalent in both developed and developing countries. As a result, good productive lands are being desertified at a very high pace. To combat this problem various approaches involving soil management and drainage are underway but with little success. It seems that a durable solution of the salinity and water-logging problems may take a long time and we may have to learn to live with salinity and to find other ways to utilize the affected lands fruitfully. A possible approach could be to tailor plants to suit the deleterious environment. The saline-sodic soils have excess of sodium, are impermeable, have little or no organic matter and are biologically almost dead. Introduction of a salt tolerant crop will provide a green cover and will improve the environment for biological activity, increase organic matter and will improve the soil fertility. The plant growth will result in higher carbon dioxide levels, and would thus create acidic conditions in the soil which would dissolve the insoluble calcium carbonate and will help exchange sodium with calcium ions on the soil complex. The biomass produced could be used directly as fodder or by the use of biotechnological and other procedures it could be converted into other value added products. However, in order to tailor plants to suit these deleterious environments, acquisition of better understanding of the biochemical and genetic aspects of salt tolerance at the cellular/molecular level is essential. For this purpose model systems have been carefully selected to carry out fundamental basic research that elucidates and identifies the major factors that confer salt tolerance in a living system. With the development of modern biotechnological methods it is now possible to introduce any foreign genetic material known to confer salt tolerance into crop plants. (Abstract Truncated)

  13. BIOMASS PRODUCTION AND FORMULATION OF Bacillus subtilis FOR BIOLOGICAL CONTROL

    Directory of Open Access Journals (Sweden)

    Amran Muis

    2016-10-01

    Full Text Available Bacillus subtilis is a widespread bacterium found in soil, water, and air. It controls the growth of certain harmful bacteria and fungi, presumably by competing for nutrients, growth sites on plants, and by directly colonizing and attaching to fungal pathogens. When applied to seeds, it colonizes the developing root system of the plants and continues to live on the root system and provides protection throughout the growing season. The study on biomass production and formulation of B. subtilis for biological control was conducted in the laboratory of Department of Plant Pathology, College of Agriculture, University of the Philippines Los Baños (UPLB-CA, College, Laguna from May to July 2005. The objective of the study was to determine the optimum pH and a good carbon source for biomass production of B. subtilis and to develop a seed treatment formulation of B. subtilis as biological control agent. Results showed that the optimum pH for growth of B. subtilis was pH 6 (1.85 x 109 cfu/ml. In laboratory tests for biomass production using cassava flour, corn flour, rice flour, and brown sugar as carbon sources, it grew best in brown sugar plus yeast extract medium (6.8 x 108 cfu ml-1 in sterile distilled water and 7.8 x 108 cfu ml-1 in coconut water. In test for bacterial biomass carriers, talc proved to be the best in terms of number of bacteria recovered from the seeds (3.98 x 105 cfu seed-1.

  14. Suitability of Gray Water for Hydroponic Crop Production Following Biological and Physical Chemical and Biological Subsystems

    Science.gov (United States)

    Bubenheim, David L.; Harper, Lynn D.; Wignarajah, Kanapathipillai; Greene, Catherine

    1994-01-01

    The water present in waste streams from a human habitat must be recycled in Controlled Ecological Life Support Systems (CELSS) to limit resupply needs and attain self-sufficiency. Plants play an important role in providing food, regenerating air, and producing purified water via transpiration. However, we have shown that the surfactants present in hygiene waste water have acute toxic effects on plant growth (Bubenheim et al. 1994; Greene et al., 1994). These phytotoxic affects can be mitigated by allowing the microbial population on the root surface to degrade the surfactant, however, a significant suppression (several days) in crop performance is experienced prior to reaching sub-toxic surfactant levels and plant recovery. An effective alternative is to stabilize the microbial population responsible for degradation of the surfactant on an aerobic bioreactor and process the waste water prior to utilization in the hydroponic solution (Wisniewski and Bubenheim, 1993). A sensitive bioassay indicates that the surfactant phytotoxicity is suppressed by more than 90% within 5 hours of introduction of the gray water to the bioreactor; processing for more than 12 hours degrades more than 99% of the phytotoxin. Vapor Compression Distillation (VCD) is a physical / chemical method for water purification which employees sequential distillation steps to separate water from solids and to volatilize contaminants. The solids from the waste water are concentrated in a brine and the pure product water (70 - 90% of the total waste water volume depending on operating conditions) retains non of the phytotoxic effects. Results of the bioassay were used to guide evaluations of the suitability of recovered gray water following biological and VCD processing for hydroponic lettuce production in controlled environments. Lettuce crops were grown for 28 days with 100% of the input water supplied with recovered water from the biological processor or VCD. When compared with the growth of plants

  15. Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014).

    Science.gov (United States)

    Gnanasakthy, Ari; DeMuro, Carla; Clark, Marci; Haydysch, Emily; Ma, Esprit; Bonthapally, Vijayveer

    2016-06-01

    To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging. © 2016 by American Society of Clinical Oncology.

  16. Novel approaches to develop community-built biological network models for potential drug discovery.

    Science.gov (United States)

    Talikka, Marja; Bukharov, Natalia; Hayes, William S; Hofmann-Apitius, Martin; Alexopoulos, Leonidas; Peitsch, Manuel C; Hoeng, Julia

    2017-08-01

    Hundreds of thousands of data points are now routinely generated in clinical trials by molecular profiling and NGS technologies. A true translation of this data into knowledge is not possible without analysis and interpretation in a well-defined biology context. Currently, there are many public and commercial pathway tools and network models that can facilitate such analysis. At the same time, insights and knowledge that can be gained is highly dependent on the underlying biological content of these resources. Crowdsourcing can be employed to guarantee the accuracy and transparency of the biological content underlining the tools used to interpret rich molecular data. Areas covered: In this review, the authors describe crowdsourcing in drug discovery. The focal point is the efforts that have successfully used the crowdsourcing approach to verify and augment pathway tools and biological network models. Technologies that enable the building of biological networks with the community are also described. Expert opinion: A crowd of experts can be leveraged for the entire development process of biological network models, from ontologies to the evaluation of their mechanistic completeness. The ultimate goal is to facilitate biomarker discovery and personalized medicine by mechanistically explaining patients' differences with respect to disease prevention, diagnosis, and therapy outcome.

  17. Analytical detection and biological assay of antileukemic drug using gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Selvaraj, V. [Department of Chemical Engineering, Alagappa College of Technology, Anna University, Chennai 600025 (India)]. E-mail: rajselva_77@yahoo.co.in; Alagar, M. [Department of Chemical Engineering, Alagappa College of Technology, Anna University, Chennai 600025 (India)]. E-mail: mkalagar@yahoo.com; Hamerton, I. [Chemistry Division, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)

    2006-11-12

    Gold nanoparticles are reported and evaluated as probes for the detection of anticancer drug 6-mercaptopurine (6-MP). The nature of binding between 6-MP and the gold nanoparticles via complexation is investigated using ultraviolet-visible spectrum, cyclic voltammetry, transmission electron microscopy, fluorescence and Fourier transform infrared (FT-IR) spectroscopy. The bound antileukemic drug is fluorescent and the quenching property of gold nanoparticles could be exploited for biological investigations. The 6-MP-colloidal gold complex is observed to have appreciable antibacterial and antifungal activity against Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Aspergillus fumigatus, and Aspergillus niger. The experimental studies suggest that gold nanoparticles have the potential to be used as effective carriers for anticancer drugs.

  18. Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

    Science.gov (United States)

    Simm, Jaak; Klambauer, Günter; Arany, Adam; Steijaert, Marvin; Wegner, Jörg Kurt; Gustin, Emmanuel; Chupakhin, Vladimir; Chong, Yolanda T; Vialard, Jorge; Buijnsters, Peter; Velter, Ingrid; Vapirev, Alexander; Singh, Shantanu; Carpenter, Anne E; Wuyts, Roel; Hochreiter, Sepp; Moreau, Yves; Ceulemans, Hugo

    2018-05-17

    In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

    Science.gov (United States)

    Madrid, Peter B.; Chopra, Sidharth; Manger, Ian D.; Gilfillan, Lynne; Keepers, Tiffany R.; Shurtleff, Amy C.; Green, Carol E.; Iyer, Lalitha V.; Dilks, Holli Hutcheson; Davey, Robert A.; Kolokoltsov, Andrey A.; Carrion, Ricardo; Patterson, Jean L.; Bavari, Sina; Panchal, Rekha G.; Warren, Travis K.; Wells, Jay B.; Moos, Walter H.; Burke, RaeLyn L.; Tanga, Mary J.

    2013-01-01

    Background The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. Methodology/Principal Findings A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. Conclusions/Significance The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses. PMID:23577127

  20. A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.

    Directory of Open Access Journals (Sweden)

    Peter B Madrid

    Full Text Available BACKGROUND: The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. METHODOLOGY/PRINCIPAL FINDINGS: A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. CONCLUSIONS/SIGNIFICANCE: The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses.

  1. Interdisciplinary researches for potential developments of drugs and natural products

    Directory of Open Access Journals (Sweden)

    Arunrat Chaveerach

    2017-04-01

    Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.

  2. Interdisciplinary researches for potential developments of drugs and natural products

    Institute of Scientific and Technical Information of China (English)

    Arunrat Chaveerach; Runglawan Sudmoon; Tawatchai Tanee

    2017-01-01

    Developments of drugs or natural products from plants are possibly made,simple to use and lower cost than modern drugs.The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas,such as foods,traditional medicine,fragrances and seasonings.Then those data will be associated with scientific researches,namely plant collection and identification,phytochemical screening by gas chromatography-mass spectrometry,pharmacological study/review for their functions,and finally safety and efficiency tests in human.For safety testing,in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed.When active chemicals and functions containing plants were chosen with safety and efficacy for human uses,then,the potential medicinal natural products will be produced.Based on these procedures,the producing cost will be cheaper and the products can be evaluated for their clinical properties.Thus,the best and lowest-priced medicines and natural products can be distributed worldwide.

  3. 78 FR 75570 - Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products Administered...

    Science.gov (United States)

    2013-12-12

    ... Guidance for Industry (GFI) 209, ``The Judicious Use of Medically Important Antimicrobial Drugs in Food... of certain antimicrobial new animal drug products who are interested in revising conditions of use... Medically Important Antimicrobial Drugs in Food-Producing Animals,'' and to set timelines for stakeholders...

  4. 75 FR 65565 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Science.gov (United States)

    2010-10-26

    ... 558 [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole Hydrochloride; Nitromide and Sulfanitran AGENCY...) is amending the animal drug regulations by removing those portions that reflect approval of eight new...

  5. Production and biological activities of yellow pigments from Monascus fungi.

    Science.gov (United States)

    Chen, Gong; Wu, Zhenqiang

    2016-08-01

    Monascus yellow pigments (MYPs), are azaphilone compounds and one of the three main components of total Monascus pigments (MPs). Thirty-five hydrophilic or hydrophobic MYPs have been identified, with the majority being hydrophobic. Apart from screening special Monascus strains, some advanced approaches, such as extractive and high-cell-density fermentations, have been applied for developing or producing new MYPs, especially extracellular hydrophilic MYPs. The outstanding performance of MYPs in terms of resistance to photodegradation, as well as tolerance for temperature and pH, give natural MYPs reasonable prospects, compared with the orange and red MPs, for practical use in the present and future. Meanwhile, MYPs have shown promising potential for applications in the food and pharmaceutical industries based on their described bioactivities. This review briefly summarizes the reports to date on chemical structures, biological activities, biosynthetic pathways, production technologies, and physicochemical performances of MYPs. The existing problems for MYPs are discussed and research prospects proposed.

  6. MODERN TECHNOLOGICAL SOLUTIONS USED IN THE PRODUCTION OF BAKERY PRODUCTS WITH HIGH BIOLOGICAL VALUE

    Directory of Open Access Journals (Sweden)

    Marta Brodowska

    2014-06-01

    Full Text Available Biological value of the food products is a result of the presence of bioactive substances and the proportions of the components. Technological development allows to optimize and accelerate the processes of bread production and increase value of food. Bakery industry used whole grains and pseudocereals as additional source of active compounds, biotechnological techniques as using appropriate yeast strain and encapsulation, which provide protection of substance and their controlled release in production of functional bread. The adding to bread fruits, vegetables and condiments may increase content of vitamin, minerals, dietary fiber and other bioactive compounds.

  7. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  8. 77 FR 71006 - Sodium Nitrite Injection and Sodium Thiosulfate Injection Drug Products Labeled for the Treatment...

    Science.gov (United States)

    2012-11-28

    ... poisoning and unapproved injectable drug products containing sodium thiosulfate labeled for the treatment of... for the treatment of cyanide poisoning are new drugs that require approved new drug applications (NDAs... Injection and Sodium Thiosulfate Injection drug product, labeled for treatment of acute cyanide poisoning...

  9. Scientific workflows as productivity tools for drug discovery.

    Science.gov (United States)

    Shon, John; Ohkawa, Hitomi; Hammer, Juergen

    2008-05-01

    Large pharmaceutical companies annually invest tens to hundreds of millions of US dollars in research informatics to support their early drug discovery processes. Traditionally, most of these investments are designed to increase the efficiency of drug discovery. The introduction of do-it-yourself scientific workflow platforms has enabled research informatics organizations to shift their efforts toward scientific innovation, ultimately resulting in a possible increase in return on their investments. Unlike the handling of most scientific data and application integration approaches, researchers apply scientific workflows to in silico experimentation and exploration, leading to scientific discoveries that lie beyond automation and integration. This review highlights some key requirements for scientific workflow environments in the pharmaceutical industry that are necessary for increasing research productivity. Examples of the application of scientific workflows in research and a summary of recent platform advances are also provided.

  10. Biological drugs for the treatment of psoriasis in a public health system

    Directory of Open Access Journals (Sweden)

    Luciane Cruz Lopes

    2014-08-01

    Full Text Available OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil. METHODS This is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions. RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab were analyzed. Patients obtained these medications as a result of injunctions (59.5% or without having ever demanded biological medication from any health institution (86.2%, i.e., public or private health services. They used the prerogative of free legal aid (72.6%, even though they were represented by private lawyers (91.1% and treated in private facilities (69.5%. Most of the patients used a biological medication for more than 13 months (66.0%, and some patients were undergoing treatment with this medication when interviewed (44.9%. Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%, adverse drug reactions (20.5%, lack of efficacy, or because the doctor discontinued this medication (13.8%. None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests for treatment control purposes. CONCLUSIONS The plaintiffs resorted to legal action to get access to biological

  11. Biological drugs for the treatment of psoriasis in a public health system

    Science.gov (United States)

    Lopes, Luciane Cruz; Silveira, Miriam Sanches do Nascimento; de Camargo, Iara Alves; Barberato, Silvio; Del Fiol, Fernando de Sá; Osorio-de-Castro, Claudia Garcia Serpa

    2014-01-01

    OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil. METHODS This is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions. RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab) were analyzed. Patients obtained these medications as a result of injunctions (59.5%) or without having ever demanded biological medication from any health institution (86.2%), i.e., public or private health services. They used the prerogative of free legal aid (72.6%), even though they were represented by private lawyers (91.1%) and treated in private facilities (69.5%). Most of the patients used a biological medication for more than 13 months (66.0%), and some patients were undergoing treatment with this medication when interviewed (44.9%). Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%), adverse drug reactions (20.5%), lack of efficacy, or because the doctor discontinued this medication (13.8%). None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests) for treatment control purposes. CONCLUSIONS The plaintiffs resorted to legal action to get access to biological medications

  12. Production of drug-loaded polymeric nanoparticles by electrospraying technology.

    Science.gov (United States)

    Sosnik, Alejandro

    2014-09-01

    The pharmaceutical industry struggles with high attrition. The outbreak of pharmaceutical micro/nanotechnology has been fundamental to overcome several (bio)pharmaceutic drawbacks of drugs such as poor aqueous solubility, physicochemical instability, short half life, inappropriate biodistribution and toxicity. The spatiotemporal release of drugs directly in the site of action and the restriction of the systemic exposure by means of nanotechnology has notoriously improved drug safety ratios. At the same time, the development of production methods that are cost-effective, scalable and reproducible under industrial settings becomes crucial to ensure the clinical translation of any development. The electrospraying process, also known as electrohydrodynamic atomization (EHDA), is a single-stage technique of liquid atomization by means of electrical forces that enables the generation of micro/nanoparticles with especially narrow size distribution. EHDA is based on the ability of an electric field to deform the interface of a liquid drop and break it into smaller mono-disperse droplets. The main advantageous features over conventional methods are the possibility to produce particles without the use of surfactants, at ambient temperature and pressure and with maximum encapsulation efficiency due to the absence of an external medium that allows the migration and/or dissolution of water-soluble cargos. In addition, the mild conditions are optimal for the encapsulation of thermo-sensitive cargos. The present article overviews the applications of this technology for the production of nano-drug delivery systems and discusses its key role to support the transfer of a broad spectrum of nanomedicines to the market.

  13. Biological evaluation of nanosilver incorporated cellulose pulp for hygiene products

    Energy Technology Data Exchange (ETDEWEB)

    Kavitha Sankar, P.C.; Ramakrishnan, Reshmi; Rosemary, M.J., E-mail: rosemarymj@lifecarehll.com

    2016-04-01

    Cellulose pulp has a visible market share in personal hygiene products such as sanitary napkins and baby diapers. However it offers good surface for growth of microorganisms. Huge amount of research is going on in developing hygiene products that do not initiate microbial growth. The objective of the present work is to produce antibacterial cellulose pulp by depositing silver nanopowder on the cellulose fiber. The silver nanoparticles used were of less than 100 nm in size and were characterised using transmission electron microscopy and X-ray powder diffraction studies. Antibacterial activity of the functionalized cellulose pulp was proved by JIS L 1902 method. The in-vitro cytotoxicity, in-vivo vaginal irritation and intracutaneous reactivity studies were done with silver nanopowder incorporated cellulose pulp for introducing a new value added product to the market. Cytotoxicity evaluation suggested that the silver nanoparticle incorporated cellulose pulp is non-cytotoxic. No irritation and skin sensitization were identified in animals tested with specific extracts prepared from the test material in the in-vivo experiments. The results indicated that the silver nanopowder incorporated cellulose pulp meets the requirements of the standard practices recommended for evaluating the biological reactivity and has good biocompatibility, hence can be classified as a safe hygiene product. - Highlights: • Different amounts of silver nanoparticles (0.2 g–0.4 g/napkin) were added to cellulose pulp. • The silver nanoparticle incorporated cellulose pulp was proved to be antibacterial by JIS L 1902 method. • The minimum concentration of silver required for antibacterial activity with no cytotoxicity has been found out. • In-vivo vaginal irritation and intracutaneous reactivity studies confirmed the biocompatibility of the material.

  14. Biological evaluation of nanosilver incorporated cellulose pulp for hygiene products

    International Nuclear Information System (INIS)

    Kavitha Sankar, P.C.; Ramakrishnan, Reshmi; Rosemary, M.J.

    2016-01-01

    Cellulose pulp has a visible market share in personal hygiene products such as sanitary napkins and baby diapers. However it offers good surface for growth of microorganisms. Huge amount of research is going on in developing hygiene products that do not initiate microbial growth. The objective of the present work is to produce antibacterial cellulose pulp by depositing silver nanopowder on the cellulose fiber. The silver nanoparticles used were of less than 100 nm in size and were characterised using transmission electron microscopy and X-ray powder diffraction studies. Antibacterial activity of the functionalized cellulose pulp was proved by JIS L 1902 method. The in-vitro cytotoxicity, in-vivo vaginal irritation and intracutaneous reactivity studies were done with silver nanopowder incorporated cellulose pulp for introducing a new value added product to the market. Cytotoxicity evaluation suggested that the silver nanoparticle incorporated cellulose pulp is non-cytotoxic. No irritation and skin sensitization were identified in animals tested with specific extracts prepared from the test material in the in-vivo experiments. The results indicated that the silver nanopowder incorporated cellulose pulp meets the requirements of the standard practices recommended for evaluating the biological reactivity and has good biocompatibility, hence can be classified as a safe hygiene product. - Highlights: • Different amounts of silver nanoparticles (0.2 g–0.4 g/napkin) were added to cellulose pulp. • The silver nanoparticle incorporated cellulose pulp was proved to be antibacterial by JIS L 1902 method. • The minimum concentration of silver required for antibacterial activity with no cytotoxicity has been found out. • In-vivo vaginal irritation and intracutaneous reactivity studies confirmed the biocompatibility of the material.

  15. 76 FR 60504 - Guidance for Industry on Time and Extent Applications for Nonprescription Drug Products...

    Science.gov (United States)

    2011-09-29

    ... monograph need not obtain FDA approval before marketing if their drug product meets the conditions in part... introduce into the United States an OTC drug product that had been marketed solely in a foreign country...

  16. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

    Science.gov (United States)

    Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

    2013-01-01

    Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

  17. Hormones in international meat production: biological, sociological and consumer issues.

    Science.gov (United States)

    Galbraith, Hugh

    2002-12-01

    Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds ('hormones') to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17beta and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17beta as a carcinogen in certain tissues. Now subject to a 'permanent' EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate

  18. Total Synthesis of Natural Products of Microbial Origins(Recent Topics of the Agricultunal Biological Science in Tohoku University)

    OpenAIRE

    Hiromasa, KIYOTA; Shigefumi, KUWAHARA; Laboratory of Applied Bioorganic Chemistry, Division of Bioscience & Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University; Laboratory of Applied Bioorganic Chemistry, Division of Bioscience & Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University

    2008-01-01

    Microorganisms are an important rich source of secondary metabolites, which could be useful leads to valuable agrochemicals and/or medicinal drugs. This mini-review describes our recent achievements on the total synthesis of biologically active natural products of microbial origins: pteridic acids A and B (strong plant growth promoters), epoxyquinols A and B (anti-angiogenic compounds), communiols A-F, G, and H, and macrotetrolide α (antibiotics), pyricuol and tabtoxinine-β-lactam (phytotoxin...

  19. Synthetic and bioengineered products in nuclear medicine and drug delivery

    International Nuclear Information System (INIS)

    Frier, M.

    1997-01-01

    Full text. The supply of radio pharmaceuticals based on pooled human blood products, for example human serum albumin (H S A) and fibrinogen, has previously met with some problems due to the possibility of donor infection A common feature of all biologicals of animal or human origin is the potential risk of viral contamination from the source material. Recombinant DNA technology provides an alternative source of biological materials that have applications throughout medicine. Micro capsules prepared from recombinant human serum albumin (r H S A) are currently under development as ultrasound contrast agents. Similar products would serve as an alternative source of material to serum albumin pooled from human donors and would offer great potential in the production of radio pharmaceuticals. There is a growing interest in the use of macromolecular carriers for therapeutic agents. When labelled with and appropriate gamma-emitter, their biodistribution can be be followed by scintigraphy. The biodistribution of a synthetic branched polypeptide, based on a poly-L-lysine backbone (average molecular mass 45 kDa) is described. The polymer was conjugated to diethylene triamine penta-acetic acid and labelled by chelation with Indium-111. Mice were injected i.v. with labelled material and imaged with a gamma camera with a pin hole collimator. Images showed the majority of tracer remaining in the blood poll, but about 35% appeared in the urinary bladder within 1.5 h

  20. Biological risks associated with consumption of reptile products.

    Science.gov (United States)

    Magnino, Simone; Colin, Pierre; Dei-Cas, Eduardo; Madsen, Mogens; McLauchlin, Jim; Nöckler, Karsten; Maradona, Miguel Prieto; Tsigarida, Eirini; Vanopdenbosch, Emmanuel; Van Peteghem, Carlos

    2009-09-15

    The consumption of a wide variety of species of reptiles caught from the wild has been an important source of protein for humans world-wide for millennia. Terrapins, snakes, lizards, crocodiles and iguanas are now farmed and the consumption and trade of their meat and other edible products have recently increased in some areas of the world. Biological risks associated with the consumption of products from both farmed and wild reptile meat and eggs include infections caused by bacteria (Salmonella spp., Vibrio spp.), parasites (Spirometra, Trichinella, Gnathostoma, pentastomids), as well as intoxications by biotoxins. For crocodiles, Salmonella spp. constitute a significant public health risk due to the high intestinal carrier rate which is reflected in an equally high contamination rate in their fresh and frozen meat. There is a lack of information about the presence of Salmonella spp. in meat from other edible reptilians, though captive reptiles used as pets (lizards or turtles) are frequently carriers of these bacteria in Europe. Parasitic protozoa in reptiles represent a negligible risk for public health compared to parasitic metazoans, of which trichinellosis, pentastomiasis, gnathostomiasis and sparganosis can be acquired through consumption of contaminated crocodile, monitor lizard, turtle and snake meat, respectively. Other reptiles, although found to harbour the above parasites, have not been implicated with their transmission to humans. Freezing treatment inactivates Spirometra and Trichinella in crocodile meat, while the effectiveness of freezing of other reptilian meat is unknown. Biotoxins that accumulate in the flesh of sea turtles may cause chelonitoxism, a type of food poisoning with a high mortality rate in humans. Infections by fungi, including yeasts, and viruses widely occur in reptiles but have not been linked to a human health risk through the contamination of their meat. Currently there are no indications that natural transmissible spongiform

  1. 78 FR 19492 - Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product...

    Science.gov (United States)

    2013-04-01

    ..., or Office of Communication, Outreach, and Development (HFM-40), Center for Biologics Evaluation and... biological product. This draft guidance describes the Agency's current thinking on how it intends to... review of biosimilar biological products. Because these meetings often will represent critical points in...

  2. Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

    Directory of Open Access Journals (Sweden)

    Matthew J Robertson

    Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

  3. In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control

    Directory of Open Access Journals (Sweden)

    J. N. Vieira

    Full Text Available Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animal’s endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC. MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

  4. Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

    Science.gov (United States)

    Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

    2010-01-01

    Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of "complex

  5. Sustainable production of biologically active molecules of marine based origin.

    Science.gov (United States)

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Impurities in Drug Products and Active Pharmaceutical Ingredients.

    Science.gov (United States)

    Kątny, M; Frankowski, M

    2017-05-04

    Analytical methods should be selective and fast. In modern times, scientists strive to meet the criteria of green chemistry, so they choose analytical procedures that are as short as possible and use the least toxic solvents. It is quite obvious that the products intended for human consumption should be characterized as completely as possible. The safety of a drug is dependent mainly on the impurities that it contains. High pressure liquid chromatography and ultra-high pressure liquid chromatography have been proposed as the main techniques for forced degradation and impurity profiling. The aim of this article was to characterize the relevant classification of drug impurities and to review the methods of impurities determination for atorvastatin (ATV) and duloxetine (DLX) (both in active pharmaceutical ingredients and in different dosage forms). These drugs have an impact on two systems of the human body: cardiac and nervous. Simple characteristics of ATV and DLX, their properties and specificity of action on the human body, are also included in this review. The analyzed pharmaceuticals-ATV (brand name Lipiron) and DLX (brand name Cymbalta)-were selected for this study based on annual rankings prepared by Information Medical Statistics.

  7. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  8. Facilitating a More Efficient Commercial Review Process for Pediatric Drugs and Biologics

    Directory of Open Access Journals (Sweden)

    Ryan D. Rykhus

    2017-12-01

    Full Text Available Over the past two decades, the biopharmaceutical industry has seen unprecedented expansion and innovation in concert with significant technological advancements. While the industry has experienced marked growth, the regulatory system in the United States still operates at a capacity much lower than the influx of new drug and biologic candidates. As a result, it has become standard for months or even years of waiting for commercial approval by the U.S. Food and Drug Administration. These regulatory delays have generated a system that stifles growth and innovation due to the exorbitant costs associated with awaiting approval from the nation’s sole regulatory agency. The recent re-emergence of diseases that impact pediatric demographics represents one particularly acute reason for developing a regulatory system that facilitates a more efficient commercial review process. Herein, we present a range of initiatives that could represent early steps toward alleviating the delays in approving life-saving therapeutics.

  9. Study on the Chinese traditional drugs' sterilization and disinfestation by radiation and their biological effects

    International Nuclear Information System (INIS)

    Ma Shouxiang; Yang Ruikun; Liu Desheng

    1987-01-01

    The study of the sterilization and disinfestation by 60 Co γ-radiation and their biological effects on tuber of elevated gastrodia, Chinese angelica and Dangshen have been carried out. The experimental results show that optimal dose was 2 x 10 5 - 4 x 10 5 rad to kill insect in the three Chinese traditional drugs. The results also show that the content of the chemical composition of irradiated group is similar to control group under 6 x 10 5 rad. The thin-layer chromatography colour-maculae are almost the same. They have the same Rf exponent

  10. Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Kirsi Ketola

    Full Text Available Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram

  11. Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

    International Nuclear Information System (INIS)

    Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

    2010-01-01

    Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125 I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

  12. Production of biologically active recombinant human factor H in Physcomitrella.

    Science.gov (United States)

    Büttner-Mainik, Annette; Parsons, Juliana; Jérôme, Hanna; Hartmann, Andrea; Lamer, Stephanie; Schaaf, Andreas; Schlosser, Andreas; Zipfel, Peter F; Reski, Ralf; Decker, Eva L

    2011-04-01

    The human complement regulatory serum protein factor H (FH) is a promising future biopharmaceutical. Defects in the gene encoding FH are associated with human diseases like severe kidney and retinal disorders in the form of atypical haemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis II (MPGN II) or age-related macular degeneration (AMD). There is a current need to apply intact full-length FH for the therapy of patients with congenital or acquired defects of this protein. Application of purified or recombinant FH (rFH) to these patients is an important and promising approach for the treatment of these diseases. However, neither protein purified from plasma of healthy individuals nor recombinant protein is currently available on the market. Here, we report the first stable expression of the full-length human FH cDNA and the subsequent production of this glycoprotein in a plant system. The moss Physcomitrella patens perfectly suits the requirements for the production of complex biopharmaceuticals as this eukaryotic system not only offers an outstanding genetical accessibility, but moreover, proteins can be produced safely in scalable photobioreactors without the need for animal-derived medium compounds. Transgenic moss lines were created, which express the human FH cDNA and target the recombinant protein to the culture supernatant via a moss-derived secretion signal. Correct processing of the signal peptide and integrity of the moss-produced rFH were verified via peptide mapping by mass spectrometry. Ultimately, we show that the rFH displays complement regulatory activity comparable to FH purified from plasma. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  13. 75 FR 8968 - Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0090] Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability... familiar and less familiar approaches. As more experience is obtained with the less familiar designs...

  14. Liquid chromatography coupled with tandem mass spectrometry for the quantitative analysis of anticancer drugs in biological matrices

    NARCIS (Netherlands)

    Stokvis, Ellen

    2004-01-01

    In this thesis, the development and validation of liquid chromatography tandem mass spectrometric (LC-MS/MS) methods for the quantitative bioanalysis of anticancer drugs are described. The monitoring of these drugs in biological fluids and tissues is important during both pre-clinical and clinical

  15. Integrated anaerobic/aerobic biological treatment for intensive swine production.

    Science.gov (United States)

    Bortone, Giuseppe

    2009-11-01

    Manure processing could help farmers to effectively manage nitrogen (N) surplus load. Many pig farms have to treat wastewater. Piggery wastewater treatment is a complex challenge, due to the high COD and N concentrations and low C/N ratio. Anaerobic digestion (AD) could be a convenient pre-treatment, particularly from the energetic view point and farm income, but this causes further reduction of C/N ratio and makes denitrification difficult. N removal can only be obtained integrating anaerobic/aerobic treatment by taking into account the best use of electron donors. Experiences gained in Italy during development of integrated biological treatment approaches for swine manure, from bench to full scale, are reported in this paper. Solid/liquid separation as pre-treatment of raw manure is an efficient strategy to facilitate liquid fraction treatment without significantly lowering C/N ratio. In Italy, two full scale SBRs showed excellent efficiency and reliability. Current renewable energy policy and incentives makes economically attractive the application of AD to the separated solid fraction using high solid anaerobic digester (HSAD) technology. Economic evaluation showed that energy production can reduce costs up to 60%, making sustainable the overall treatment.

  16. Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patients

    Directory of Open Access Journals (Sweden)

    Paolo Faccendini

    2017-09-01

    Full Text Available Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patientsObjectives:The aim of this analysis was to provide an estimate of drug utilization indicators (dose escalation and dose tapering related to biologic drugs in the chronic treatment of adult patients with Immune-Mediated Inflammatory Diseases (IMIDs.Methods:We conducted an observational retrospective cohort analysis using the Policlinico di Tor Vergata (PTV database. We considered all biologic drugs dispensed by the PTV hospital pharmacy between January 2010 and December 2015:abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab (originator and biosimilar, tocilizumab, and ustekinumab were included. Drug dose escalation and dose tapering were calculated and compared with their Defined Daily Dose (DDD.Results:A total of 1803 patients with IMID and biologic drug prescription were analyzed (male: 51.2%. The majority of patients were in the class 36-50 years (n = 612. The median follow-up was 33.8 months (IQR 14.43-56.20. Dermatology was the ward with the largest number of patients (n = 882; 48.9%, followed by rheumatology (n = 619; 34.3% and gastroenterology (n = 302; 16.8%. Dose escalation was observed in 406 patients (22.5%. Infliximab biosimilar (n = 51 was the biological drug with the highest dose escalation rate (86.3%, followed by infliximab originator (n = 28; 60.3% and ustekinumab (37.8%. Etanercept was the biological drug with the lowest dose escalation rate (7.4%, followed by golimumab (12.2% and adalimumab (13.8%. In 677 patients (37.5% a dose tapering was observed. Etanercept showed the highest rate of patients with dose tapering (41.6%, followed by adalimumab (33.6%.Conclusions:The results of this analysis show that dose modification is quite common in PTV clinical practice. Considering the strong focus on the pharmaceutical expenditure and the need of cost containment

  17. Drug Development Process

    Science.gov (United States)

    ... Preclinical Research Preclinical Research Drugs undergo laboratory and animal testing to answer basic questions about safety. More Information ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  18. The secondary metabolite bioinformatics portal: Computational tools to facilitate synthetic biology of secondary metabolite production

    Directory of Open Access Journals (Sweden)

    Tilmann Weber

    2016-06-01

    Full Text Available Natural products are among the most important sources of lead molecules for drug discovery. With the development of affordable whole-genome sequencing technologies and other ‘omics tools, the field of natural products research is currently undergoing a shift in paradigms. While, for decades, mainly analytical and chemical methods gave access to this group of compounds, nowadays genomics-based methods offer complementary approaches to find, identify and characterize such molecules. This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work. In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http://www.secondarymetabolites.org is introduced to provide a one-stop catalog and links to these bioinformatics resources. In addition, an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field.

  19. 21 CFR 212.110 - How must I maintain records of my production of PET drugs?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... those not stored at the inspected establishment, must be legible, stored to prevent deterioration or...

  20. 78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

    Science.gov (United States)

    2013-04-18

    ... mitigation strategy (REMS) http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor... Blueprint for Prescriber Education for Extended- Release and Long-Acting Opioid Analgesics'' ( http://www...

  1. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2014-05-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  2. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2015-08-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  3. Biological evaluation of recombinant human erythropoietin in pharmaceutical products

    Directory of Open Access Journals (Sweden)

    Ramos A.S.

    2003-01-01

    Full Text Available The potencies of mammalian cell-derived recombinant human erythropoietin pharmaceutical preparations, from a total of five manufacturers, were assessed by in vivo bioassay using standardized protocols. Eight-week-old normocythemic mice received a single subcutaneous injection followed by blood sampling 96 h later or multiple daily injections with blood sampling 24 h after the last injection. Reticulocyte counting by microscopic examination was employed as the end-point using the brilliant cresyl blue or selective hemolysis methods, together with automated flow cytometry. Different injection schedules were investigated and dose-response curves for the European Pharmacopoeia Biological Reference Preparation of erythropoietin were compared. Manual and automated methods of reticulocyte counting were correlated with respect to assay validity and precision. Using 8 mice per treatment group, intra-assay precision determined for all of the assays in the study showed coefficients of variation of 12.1-28.4% for the brilliant cresyl blue method, 14.1-30.8% for the selective hemolysis method and 8.5-19.7% for the flow cytometry method. Applying the single injection protocol, a combination of at least two independent assays was required to achieve the precision potency and confidence limits indicated by the manufacturers, while the multiple daily injection protocol yielded the same acceptable results within a single assay. Although the latter protocol using flow cytometry for reticulocyte counting gave more precise and reproducible results (intra-assay coefficients of variation: 5.9-14.2%, the well-characterized manual methods provide equally valid alternatives for the quality control of recombinant human erythropoietin therapeutic products.

  4. Biological hydrogen production by dark fermentation: challenges and prospects towards scaled-up production.

    Science.gov (United States)

    RenNanqi; GuoWanqian; LiuBingfeng; CaoGuangli; DingJie

    2011-06-01

    Among different technologies of hydrogen production, bio-hydrogen production exhibits perhaps the greatest potential to replace fossil fuels. Based on recent research on dark fermentative hydrogen production, this article reviews the following aspects towards scaled-up application of this technology: bioreactor development and parameter optimization, process modeling and simulation, exploitation of cheaper raw materials and combining dark-fermentation with photo-fermentation. Bioreactors are necessary for dark-fermentation hydrogen production, so the design of reactor type and optimization of parameters are essential. Process modeling and simulation can help engineers design and optimize large-scale systems and operations. Use of cheaper raw materials will surely accelerate the pace of scaled-up production of biological hydrogen. And finally, combining dark-fermentation with photo-fermentation holds considerable promise, and has successfully achieved maximum overall hydrogen yield from a single substrate. Future development of bio-hydrogen production will also be discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Development of biological platform for the autotrophic production of biofuels

    Science.gov (United States)

    Khan, Nymul

    The research described herein is aimed at developing an advanced biofuel platform that has the potential to surpass the natural rate of solar energy capture and CO2 fixation. The underlying concept is to use the electricity from a renewable source, such as wind or solar, to capture CO 2 via a biological agent, such as a microbe, into liquid fuels that can be used for the transportation sector. In addition to being renewable, the higher rate of energy capture by photovoltaic cells than natural photosynthesis is expected to facilitate higher rate of liquid fuel production than traditional biofuel processes. The envisioned platform is part of ARPA-E's (Advanced Research Projects Agency - Energy) Electrofuels initiative which aims at supplementing the country's petroleum based fuel production with renewable liquid fuels that can integrate easily with the existing refining and distribution infrastructure (http://arpae. energy.gov/ProgramsProjects/Electrofuels.aspx). The Electrofuels initiative aimed to develop liquid biofuels that avoid the issues encountered in the current generation of biofuels: (1) the reliance of biomass-derived technologies on the inefficient process of photosynthesis, (2) the relatively energy- and resource-intensive nature of agronomic processes, and (3) the occupation of large areas of arable land for feedstock production. The process proceeds by the capture of solar energy into electrical energy via photovoltaic cells, using the generated electricity to split water into molecular hydrogen (H2) and oxygen (O2), and feeding these gases, along with carbon dioxide (CO2) emitted from point sources such as a biomass or coal-fired power plant, to a microbial bioprocessing platform. The proposed microbial bioprocessing platform leverages a chemolithoautotrophic microorganism (Rhodobacter capsulatus or Ralstonia eutropha) naturally able to utilize these gases as growth substrates, and genetically modified to produce a triterpene hydrocarbon fuel

  6. The potential of plants as a system for the development and production of human biologics [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Qiang Chen

    2016-05-01

    Full Text Available The growing promise of plant-made biologics is highlighted by the success story of ZMapp™ as a potentially life-saving drug during the Ebola outbreak of 2014-2016. Current plant expression platforms offer features beyond the traditional advantages of low cost, high scalability, increased safety, and eukaryotic protein modification. Novel transient expression vectors have been developed that allow the production of vaccines and therapeutics at unprecedented speed to control potential pandemics or bioterrorism attacks. Plant-host engineering provides a method for producing proteins with unique and uniform mammalian post-translational modifications, providing opportunities to develop biologics with increased efficacy relative to their mammalian cell-produced counterparts. Recent demonstrations that plant-made proteins can function as biocontrol agents of foodborne pathogens further exemplify the potential utility of plant-based protein production. However, resolving the technical and regulatory challenges of commercial-scale production, garnering acceptance from large pharmaceutical companies, and obtaining U.S. Food and Drug Administration approval for several major classes of biologics are essential steps to fulfilling the untapped potential of this technology.

  7. An Intercompany Perspective on Biopharmaceutical Drug Product Robustness Studies.

    Science.gov (United States)

    Morar-Mitrica, Sorina; Adams, Monica L; Crotts, George; Wurth, Christine; Ihnat, Peter M; Tabish, Tanvir; Antochshuk, Valentyn; DiLuzio, Willow; Dix, Daniel B; Fernandez, Jason E; Gupta, Kapil; Fleming, Michael S; He, Bing; Kranz, James K; Liu, Dingjiang; Narasimhan, Chakravarthy; Routhier, Eric; Taylor, Katherine D; Truong, Nobel; Stokes, Elaine S E

    2018-02-01

    The Biophorum Development Group (BPDG) is an industry-wide consortium enabling networking and sharing of best practices for the development of biopharmaceuticals. To gain a better understanding of current industry approaches for establishing biopharmaceutical drug product (DP) robustness, the BPDG-Formulation Point Share group conducted an intercompany collaboration exercise, which included a bench-marking survey and extensive group discussions around the scope, design, and execution of robustness studies. The results of this industry collaboration revealed several key common themes: (1) overall DP robustness is defined by both the formulation and the manufacturing process robustness; (2) robustness integrates the principles of quality by design (QbD); (3) DP robustness is an important factor in setting critical quality attribute control strategies and commercial specifications; (4) most companies employ robustness studies, along with prior knowledge, risk assessments, and statistics, to develop the DP design space; (5) studies are tailored to commercial development needs and the practices of each company. Three case studies further illustrate how a robustness study design for a biopharmaceutical DP balances experimental complexity, statistical power, scientific understanding, and risk assessment to provide the desired product and process knowledge. The BPDG-Formulation Point Share discusses identified industry challenges with regard to biopharmaceutical DP robustness and presents some recommendations for best practices. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Hydrological structure and biological productivity of the tropical Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Muraleedharan, U.D.; Muraleedharan, P.M.

    Hydrological structure analyses of regions in the tropical Atlantic Ocean have consistently revealed the existence of a typical tropical structure characterized by a nitrate-depleted mixed layer above the thermocline. The important biological...

  9. 75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

    Science.gov (United States)

    2010-09-29

    ... Health Organization's Council for International Organizations of Medical Sciences (CIOMS), and which have...'' definition and reaction use of alternative terminology (2) 312.32(a) Serious adverse event or Changed... alternative terminology (6) Incorporated the definition from former Sec. 312.32(a) of ``disability'' within...

  10. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Science.gov (United States)

    2010-07-01

    ... period beginning on the date the authority to prepare an experimental biological product under the Virus... diligence; (iii) One-half the number of days remaining in the period defined by paragraph (c)(1) of this... experimental biological product under the Virus-Serum-Toxin Act was submitted before November 16, 1988, by— (A...

  11. Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity

    OpenAIRE

    Turner, David P.

    2015-01-01

    Low income, poor diet, obesity and a lack of exercise are inter-related lifestyle factors that can profoundly alter our biological make-up to increase cancer risk, growth and development. We recently reported a potential mechanistic link between carbohydrate derived metabolites and cancer which may provide a biological consequence of lifestyle that can directly impact tumor biology. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism. F...

  12. 21 CFR 335.50 - Labeling of antidiarrheal drug products.

    Science.gov (United States)

    2010-04-01

    ... problem”. (iii) “Ask a doctor or pharmacist before use if you are taking any drug for [bullet... Section 335.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... identified in § 335.10. (i) “Do not use if you have [bullet] bloody or black stool”. (ii) “Ask a doctor...

  13. Structural Biology Meets Drug Resistance: An Overview on Multidrug Resistance Transporters

    DEFF Research Database (Denmark)

    Shaheen, Aqsa; Iqbal, Mazhar; Mirza, Osman

    2017-01-01

    . Research on the underlying causes of multidrug resistance in cancerous cells and later on in infectious bacteria revealed the involvement of integral membrane transporters, capable of recognizing a broad range of structurally different molecules as substrates and exporting them from the cell using cellular...... superfamilies, viz., ATP-binding cassette superfamily, major facilitator superfamily and resistance nodulation division superfamily are presented. Further, the future role of structural biology in improving our understanding of drug-transporter interactions and in designing novel inhibitors against MDR pump...... century, mankind has become aware and confronted with the emergence of antibiotic-resistant pathogens. In parallel to the failure of antibiotic therapy against infectious pathogens, there had been continuous reports of cancerous cells not responding to chemotherapy with increase in the duration of therapy...

  14. Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design.

    Science.gov (United States)

    Neshich, Izabella Agostinho Pena; Nishimura, Leticia; de Moraes, Fabio Rogerio; Salim, Jose Augusto; Villalta-Romero, Fabian; Borro, Luiz; Yano, Inacio Henrique; Mazoni, Ivan; Tasic, Ljubica; Jardine, Jose Gilberto; Neshich, Goran

    2015-01-01

    The term "agrochemicals" is used in its generic form to represent a spectrum of pesticides, such as insecticides, fungicides or bactericides. They contain active components designed for optimized pest management and control, therefore allowing for economically sound and labor efficient agricultural production. A "drug" on the other side is a term that is used for compounds designed for controlling human diseases. Although drugs are subjected to much more severe testing and regulation procedures before reaching the market, they might contain exactly the same active ingredient as certain agrochemicals, what is the case described in present work, showing how a small chemical compound might be used to control pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates citrus plantations, as well as for control of, for example, meningitis in humans. It is also clear that so far the production of new agrochemicals is not benefiting as much from the in silico new chemical compound identification/discovery as pharmaceutical production. Rational drug design crucially depends on detailed knowledge of structural information about the receptor (target protein) and the ligand (drug/agrochemical). The interaction between the two molecules is the subject of analysis that aims to understand relationship between structure and function, mainly deciphering some fundamental elements of the nanoenvironment where the interaction occurs. In this work we will emphasize the role of understanding nanoenvironmental factors that guide recognition and interaction of target protein and its function modifier, an agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for two selected and specific cases we have approached in order to offer a technological solution for some very important problems that needs special attention in agriculture: elimination of pathogenicity of a bacterium which is attacking citrus plants and formulation of a new fungicide. Finally

  15. Perturbation biology nominates upstream–downstream drug combinations in RAF inhibitor resistant melanoma cells

    Science.gov (United States)

    Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

    2015-01-01

    Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs. DOI: http://dx.doi.org/10.7554/eLife.04640.001 PMID:26284497

  16. Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.

    Science.gov (United States)

    Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

    2015-08-18

    Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs.

  17. The double radio-isotope derivative techniques for the assay of drugs in biological material

    International Nuclear Information System (INIS)

    Riess, W.

    1977-01-01

    The neuroleptic drug opipramol and its deshydroxyethyl metabolite can be determined simultaneously in the same biological sample. Known amounts of 14 C-labelled opipramol and 14 C-labelled metabolite are added to the sample to serve as internal standards. After suitable extraction, both compounds are acetylated by 3 H-labelled acetic anhydride. Together with μg-amounts of carrier compounds, the O-acetyl derivative of opipramol and the N-acetyl derivative of the metabolite are purified and separated by two-dimensional thin-layer chromatography. Each of the derivatives is isolated and counted for 14 C- and 3 H-activity. The 14 C-activities recovered serve to determine the overall yield of the opipramol and metabolite, and to convert the measured 3 H-activity to 100% theoretical yield. From analyses of standard samples, the specific 3 H-activities of the acetyl derivatives were calculated and these values were used to convert the measured 3 H-activites from biological samples to concentrations of original opipramol and metabolite. For both compounds the standard deviations of blank samples were +- 1 ng/ml. For concentrations up to 100 ng/ml the standard deviation was +- 3 ng/ml

  18. Inductively coupled plasma mass spectrometry in the analysis of biological samples and pharmaceutical drugs

    Science.gov (United States)

    Ossipov, K.; Seregina, I. F.; Bolshov, M. A.

    2016-04-01

    Inductively coupled plasma mass spectrometry (ICP-MS) is widely used in the analysis of biological samples (whole blood, serum, blood plasma, urine, tissues, etc.) and pharmaceutical drugs. The shortcomings of this method related to spectral and non-spectral interferences are manifested in full measure in determination of the target analytes in these complex samples strongly differing in composition. The spectral interferences are caused by similarity of masses of the target component and sample matrix components. Non-spectral interferences are related to the influence of sample matrix components on the physicochemical processes taking place during formation and transportation of liquid sample aerosols into the plasma, on the value and spatial distribution of plasma temperature and on the transmission of the ion beam from the interface to mass spectrometer detector. The review is devoted to analysis of different mechanisms of appearance of non-spectral interferences and to ways for their minimization or elimination. Special attention is paid to the techniques of biological sample preparation, which largely determine the mechanisms of the influence of sample composition on the results of element determination. The ways of lowering non-spectral interferences by instrumental parameter tuning and application of internal standards are considered. The bibliography includes 189 references.

  19. Site-selective protein-modification chemistry for basic biology and drug development.

    Science.gov (United States)

    Krall, Nikolaus; da Cruz, Filipa P; Boutureira, Omar; Bernardes, Gonçalo J L

    2016-02-01

    Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.

  20. Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup

    2016-01-01

    Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches...... for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

  1. Synthetic biology for microbial production of lipid-based biofuels.

    Science.gov (United States)

    d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

    2015-12-01

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing. Published by Elsevier Ltd.

  2. Synthetic biology for microbial production of lipid-based biofuels

    Energy Technology Data Exchange (ETDEWEB)

    d' Espaux, L; Mendez-Perez, D; Li, R; Keasling, JD

    2015-10-23

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here in this paper we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. Lastly, we further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing.

  3. The production and sales of anti-tuberculosis drugs in China.

    Science.gov (United States)

    Huang, Yang-Mu; Zhao, Qi-Peng; Ren, Qiao-Meng; Peng, Dan-Lu; Guo, Yan

    2016-10-04

    Tuberculosis (TB) is a major infectious disease globally. Adequate and proper use of anti-TB drugs is essential for TB control. This study aims to study China's production capacity and sales situation of anti-TB drugs, and to further discuss the potential for China to contribute to global TB control. The production data of anti-TB drugs in China from 2011 to 2013 and the sales data from 2010 to 2014 were extracted from Ministry of Industry and Information Technology database of China and IMS Health database, respectively. The number of drugs was standardized to the molecular level of the key components before calculating. All data were described and analyzed by Microsoft Excel. First-line drugs were the majority in both sales (89.5 %) and production (92.3 %) of anti-TB drugs in China. The production of rifampicin held the majority share in active pharmaceutical ingredients (APIs) and finished products, whilst ethambutol and pyrazinamide were the top two sales in finished products. Fixed-dose combinations only held small percentages in total production and sales weight, though a slight increase was observed. The production and sales of streptomycin showed a tendency of decrease after 2012. The trends and proportion of different anti-TB drugs were similar in production and sales, however, the production weight was much larger than that of sales, especially for rifampicin and isoniazid. First-line drugs were the predominant medicine produced and used in China. While the low production and sales of the second-line TB drugs and FDCs rose concerns for the treatment of multiple drug resistant TB. The redundant production amount, as well as the prompt influence of national policy on drug production and sales, indicated the potential for China to better contribute to global TB control.

  4. Liquid chromatographic determination of CPZEN-45, a novel anti-tubercular drug, in biological samples.

    Science.gov (United States)

    Hanif, S N M; Hickey, A J; Garcia-Contreras, L

    2014-01-01

    CPZEN-45 is a new drug candidate being considered for the treatment of tuberculosis (TB). The aim of this study was to develop and validate a reverse-phase high-performance liquid chromatographic (HPLC) method suitable to determine CPZEN-45 concentrations in biological samples. CPZEN-45 was extracted from biological fluids and tissues (plasma, lung and spleen from guinea pig) by sequential extraction with acetonitrile and quantified by a Waters HPLC Alliance System coupled with a ZORBAX Bonus-RP column, guard column and UV detection at 263nm. The mobile phase was 20:80 acetonitrile:ultrapure-water with 0.05% TFA. The CPZEN-45 peak was eluted at 5.1min with no interference from the inherent peaks of plasma, bronchoalveolar lavage (BAL), lung or spleen tissues. Recovery of CPZEN-45 from biological samples was >96% of the spiked amount. The limit of detection was 0.05μg/ml and the limit of quantitation was 0.29μg/ml which was more than 5 and 21 times lower than the reported minimal inhibitory concentration of CPZEN-45 (MIC=1.56μg/ml for Mycobacterium tuberculosis and 6.25μg/ml for MDR-TB, respectively). Thus, HPLC method was deemed reliable, sensitive, reproducible and accurate for the determination of CPZEN-45 concentrations in plasma, BAL, lung and spleen tissues. Therefore, this method was used in subsequent studies in the guinea pig model to determine the disposition of CPZEN-45 after administration of solutions by the IV and SC routes. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is.

    Science.gov (United States)

    Benson, Neil

    2015-08-01

    Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Biological production of alcohols from coal through indirect liquefaction

    Energy Technology Data Exchange (ETDEWEB)

    Barik, S; Prieto, S; Harrison, S B; Clausen, E C; Gaddy, J L

    1988-08-01

    The purpose of this project is to demonstrate the feasibility of producing liquid fuels from the components of synthesis gas through biological indirect liquefaction. The results of pure culture and natural source screening studies aimed at finding organisms capable of carrying out the conversions are presented and discussed. 17 refs., 2 figs., 8 tabs.

  7. Advances in reproductive biology and seed production systems of ...

    African Journals Online (AJOL)

    Eucalyptus globulus is the main eucalypt species grown in Australian plantations. The focus on seedling deployment systems, coupled with exploitation of large, open-pollinated base populations for breeding purposes over the last two decades, has required a detailed understanding of the reproductive biology of this ...

  8. Influence of radiation on the content of biologically active substances in herbal raw materials. Pharmacological activity of herbal drugs after microbiological decontamination by irradiation

    International Nuclear Information System (INIS)

    Migdal, W.; Owczarczyk, H.B.

    2005-01-01

    Several thousand tons of medical herbs are produced annually by pharmaceutical industry in Poland. This product should be of highest quality and microbial purity. Recently chemical methods of decontamination are recognized as less safe, thus irradiation technique was chosen to replace them in use. In the Institute of Nuclear Chemistry and Technology research work on microbiological decontamination of herbal raw materials and herbal drugs by irradiation has been carried out since 1996. It was shown that using ionizing radiation (a dose 10 kGy) can obtain satisfactory results of microbiological decontamination of these products. The content of biologically substances such a essential oils, flavonoids, glycosides, anthocyans, antra-compounds, poliphenoloacids, triterpene saponins, oleanosides and plants mucus did not change significantly after irradiation. Pharmacological activity of herbal drugs has been found satisfactory after microbiological decontamination by irradiation. (author)

  9. Model Analytical Development for Physical, Chemical, and Biological Characterization of Momordica charantia Vegetable Drug

    Science.gov (United States)

    Guimarães, Geovani Pereira; Santos, Ravely Lucena; Júnior, Fernando José de Lima Ramos; da Silva, Karla Monik Alves; de Souza, Fabio Santos

    2016-01-01

    Momordica charantia is a species cultivated throughout the world and widely used in folk medicine, and its medicinal benefits are well documented, especially its pharmacological properties, including antimicrobial activities. Analytical methods have been used to aid in the characterization of compounds derived from plant drug extracts and their products. This paper developed a methodological model to evaluate the integrity of the vegetable drug M. charantia in different particle sizes, using different analytical methods. M. charantia was collected in the semiarid region of Paraíba, Brazil. The herbal medicine raw material derived from the leaves and fruits in different particle sizes was analyzed using thermoanalytical techniques as thermogravimetry (TG) and differential thermal analysis (DTA), pyrolysis coupled to gas chromatography/mass spectrometry (PYR-GC/MS), and nuclear magnetic resonance (1H NMR), in addition to the determination of antimicrobial activity. The different particle surface area among the samples was differentiated by the techniques. DTA and TG were used for assessing thermal and kinetic parameters and PYR-GC/MS was used for degradation products chromatographic identification through the pyrograms. The infusions obtained from the fruit and leaves of Momordica charantia presented antimicrobial activity. PMID:27579215

  10. Radiation biological technology for preservation of agricultural products

    International Nuclear Information System (INIS)

    Kudryasheva, A.

    1988-01-01

    A study is reported on the food irradiation procedures experimented in the Moskow Institute for National Economy. The effect of gamma radiation on the quality, mass loss and storage life of fruits and vegetables is investigated. The combined effect of several biological and environmental factors on the microorganisms affecting foodstuffs are discussed. The influence of dose rate is illustrated quantitatively for different species of fruits and vegetables. 3 tabs., 6 refs

  11. Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

    Science.gov (United States)

    Zha, Weibin

    2018-04-01

    The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

  12. Biological processes for the production of aryl sulfates

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention generally relates to the field of biotechnology as it applies to the production of aryl sulfates using polypeptides or recombinant cells comprising said polypeptides. More particularly, the present invention pertains to polypeptides having aryl sulfotransferase activity......, recombinant host cells expressing same and processes for the production of aryl sulfates employing these polypeptides or recombinant host cells....

  13. Strategies for Optimizing Algal Biology for Enhanced Biomass Production

    Energy Technology Data Exchange (ETDEWEB)

    Barry, Amanda N.; Starkenburg, Shawn R.; Sayre, Richard T., E-mail: rsayre@newmexicoconsortium.org [Los Alamos National Laboratory, New Mexico Consortium, Los Alamos, NM (United States)

    2015-02-02

    One of the most environmentally sustainable ways to produce high-energy density (oils) feed stocks for the production of liquid transportation fuels is from biomass. Photosynthetic carbon capture combined with biomass combustion (point source) and subsequent carbon capture and sequestration has also been proposed in the intergovernmental panel on climate change report as one of the most effective and economical strategies to remediate atmospheric greenhouse gases. To maximize photosynthetic carbon capture efficiency and energy-return-on-investment, we must develop biomass production systems that achieve the greatest yields with the lowest inputs. Numerous studies have demonstrated that microalgae have among the greatest potentials for biomass production. This is in part due to the fact that all alga cells are photoautotrophic, they have active carbon concentrating mechanisms to increase photosynthetic productivity, and all the biomass is harvestable unlike plants. All photosynthetic organisms, however, convert only a fraction of the solar energy they capture into chemical energy (reduced carbon or biomass). To increase aerial carbon capture rates and biomass productivity, it will be necessary to identify the most robust algal strains and increase their biomass production efficiency often by genetic manipulation. We review recent large-scale efforts to identify the best biomass producing strains and metabolic engineering strategies to improve aerial productivity. These strategies include optimization of photosynthetic light-harvesting antenna size to increase energy capture and conversion efficiency and the potential development of advanced molecular breeding techniques. To date, these strategies have resulted in up to twofold increases in biomass productivity.

  14. Strategies for Optimizing Algal Biology for Enhanced Biomass Production

    International Nuclear Information System (INIS)

    Barry, Amanda N.; Starkenburg, Shawn R.; Sayre, Richard T.

    2015-01-01

    One of the most environmentally sustainable ways to produce high-energy density (oils) feed stocks for the production of liquid transportation fuels is from biomass. Photosynthetic carbon capture combined with biomass combustion (point source) and subsequent carbon capture and sequestration has also been proposed in the intergovernmental panel on climate change report as one of the most effective and economical strategies to remediate atmospheric greenhouse gases. To maximize photosynthetic carbon capture efficiency and energy-return-on-investment, we must develop biomass production systems that achieve the greatest yields with the lowest inputs. Numerous studies have demonstrated that microalgae have among the greatest potentials for biomass production. This is in part due to the fact that all alga cells are photoautotrophic, they have active carbon concentrating mechanisms to increase photosynthetic productivity, and all the biomass is harvestable unlike plants. All photosynthetic organisms, however, convert only a fraction of the solar energy they capture into chemical energy (reduced carbon or biomass). To increase aerial carbon capture rates and biomass productivity, it will be necessary to identify the most robust algal strains and increase their biomass production efficiency often by genetic manipulation. We review recent large-scale efforts to identify the best biomass producing strains and metabolic engineering strategies to improve aerial productivity. These strategies include optimization of photosynthetic light-harvesting antenna size to increase energy capture and conversion efficiency and the potential development of advanced molecular breeding techniques. To date, these strategies have resulted in up to twofold increases in biomass productivity.

  15. Biology Needs a Modern Assessment System for Professional Productivity

    Science.gov (United States)

    McDade, Lucinda A.; Maddison, David R.; Guralnick, Robert; Piwowar, Heather A.; Jameson, Mary Liz; Helgen, Kristofer M.; Herendeen, Patrick S.; Hill, Andrew; Vis, Morgan L.

    2011-01-01

    Stimulated in large part by the advent of the Internet, research productivity in many academic disciplines has changed dramatically over the last two decades. However, the assessment system that governs professional success has not kept pace, creating a mismatch between modes of scholarly productivity and academic assessment criteria. In this…

  16. Multi drug resistance and β-lactamase production by Klebsiella ...

    African Journals Online (AJOL)

    SERVER

    2007-08-06

    Aug 6, 2007 ... *Corresponding author. E-mail: gnsimha123@rediffmail.com. (Rice, 1999). plasmid that can be easily spread from one organisms to another (Sirot, 1995) these enzymes are capable of inactivating a variety of β-lactam drugs (Rice,. 1999). The ESBL producing organisms often show multi- drug resistant as ...

  17. 21 CFR 341.74 - Labeling of antitussive drug products.

    Science.gov (United States)

    2010-04-01

    ... directed by a doctor, if you have a breathing problem such as emphysema or chronic bronchitis, or if you... Section 341.74 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES..., consult a doctor.” (2) For oral and topical antitussives labeled for adults or for adults and children...

  18. Application of Combination High-Throughput Phenotypic Screening and Target Identification Methods for the Discovery of Natural Product-Based Combination Drugs.

    Science.gov (United States)

    Isgut, Monica; Rao, Mukkavilli; Yang, Chunhua; Subrahmanyam, Vangala; Rida, Padmashree C G; Aneja, Ritu

    2018-03-01

    Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple targets and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural products in drug discovery. Natural products consist of a multitude of constituents that can act on a variety of targets in the body to induce pharmacodynamic responses that may together culminate in an additive or synergistic therapeutic effect. Although natural products cannot be patented, they can be used as starting points in the discovery of potent combination therapeutics. The optimal mix of bioactive ingredients in natural products can be determined via phenotypic screening. The targets and molecular mechanisms of action of these active ingredients can then be determined using chemical proteomics, and by implementing a reverse pharmacokinetics approach. This review article provides evidence supporting the potential benefits of natural product-based combination drugs, and summarizes drug discovery methods that can be applied to this class of drugs. © 2017 Wiley Periodicals, Inc.

  19. Synoptic events force biological productivity in Patagonian fjord ecosystems

    Science.gov (United States)

    Daneri, Giovanni

    2016-04-01

    The annual cycle of primary productivity of the Patagonian fjords has, to date, been described as a two phase system consisting of a short non productive winter phase (during June and July) and a productive phase extending from late winter (August) to autumn (May). Low levels of primary production, phytoplankton biomass and high concentrations of surface nutrients have been described as characterizing winter conditions while pulsed productivity events typifies the productivity pattern during the extended productive season. Pulsed productivity events characterize coastal waters where inorganic nutrients in surface layers are replenished following periods of intensive utilization by autotrophs. Freshwater input in Patagonian fjords in southern Chile (41-55°S) results in one of the largest estuarine regions worldwide. Here strong haline water column stratification prevents nutrient mixing to the surface layers thus potentially shutting off algal production. Our working hypothesis considered that in order to reconcile the observed pulsed productivity pattern, periodic breaking (associated to surface nutrient replenishment) and re-establishment of estuarine conditions (associated to water column stratification) would be required. Up to now however our understanding of the physical processes that control water column conditions in the Patagonian fjord area has been extremely limited. Here we present evidence linking the passage of synoptic low pressure fronts to pulsed productivity events in the Patagonian fjord area. These front controls and influence local processes of interaction between the fjord and the atmosphere generating a rapid water column response. In the specific case of the Puyuhuapi fjord we have been able to show that such synoptic fronts induce surface flow reversal and water column mixing. Phytoplankton blooming occurs after the passage of the synoptic front once calmer conditions prevail and estuarine conditions are re established. The occurrence of

  20. Statin Drugs Markedly Inhibit Testosterone Production by Rat Leydig Cells In Vitro: Implications for Men

    Science.gov (United States)

    Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase. During drug development it was shown that statins inhibit production of cholesterol in the testis. We evaluated testosterone production in vitro, using highly purified rat ...

  1. 21 CFR 349.65 - Labeling of ophthalmic emollient drug products.

    Science.gov (United States)

    2010-04-01

    ... product contains the established name of the drug(s), if any, and identifies the product as a “lubricant... the eye or to exposure to wind or sun.” (3) “For use as a protectant against further irritation or to...

  2. 21 CFR 349.60 - Labeling of ophthalmic demulcent drug products.

    Science.gov (United States)

    2010-04-01

    ... product contains the established name of the drug(s), if any, and identifies the product as a “lubricant... exposure to wind or sun.” (3) “For use as a protectant against further irritation or to relieve dryness of...

  3. Biological production of hydroxylated aromatics : Optimization strategies for Pseudomonas putida S12

    NARCIS (Netherlands)

    Verhoef, A.

    2010-01-01

    To replace environmentally unfriendly petrochemical production processes, the demand for bio-based production of organic chemicals is increasing. This thesis focuses on the biological production of hydroxylated aromatics from renewable substrates by engineered P. putida S12 including several cases

  4. Recombinant biologic products versus nutraceuticals from plants - a regulatory choice?

    Science.gov (United States)

    Drake, Pascal M W; Szeto, Tim H; Paul, Mathew J; Teh, Audrey Y-H; Ma, Julian K-C

    2017-01-01

    Biotechnology has transformed the potential for plants to be a manufacturing source of pharmaceutical compounds. Now, with transgenic and transient expression techniques, virtually any biologic, including vaccines and therapeutics, could be manufactured in plants. However, uncertainty over the regulatory path for such new pharmaceuticals has been a deterrent. Consideration has been given to using alternative regulatory paths, including those for nutraceuticals or cosmetic agents. This review will consider these possibilities, and discuss the difficulties in establishing regulatory guidelines for new pharmaceutical manufacturing technologies. © 2016 The British Pharmacological Society.

  5. New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management.

    Science.gov (United States)

    Carrascosa, J M; Del-Alcazar, E

    2018-04-01

    Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.

  6. Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress.

    Science.gov (United States)

    Bhattacharyya, Sudip; Sinha, Krishnendu; Sil, Parames C

    2014-01-01

    Cytochrome monooxygenases P450 enzymes (CYPs) are terminal oxidases, belonging to the multi-gene family of heme-thiolate enzymes and located in multiple sites of ER, cytosol and mitochondria. CYPs act as catalysts in drugs metabolism. This review highlights the mitochondrial and microsomal CYPs metabolic functions, CYPs mediated ROS generation and its feedback, bioactivation of drugs and related hypersensitivity, metabolic disposition as well as the therapeutic approaches. CYPs mediated drugs bioactivation may trigger oxidative stress and cause pathophysiology. Almost all drugs show some adverse reactions at high doses or accidental overdoses. Drugs lead to hypersensitivity reactions while metabolic predisposition to drug hypersensitivity exaggerates it. Mostly different intermediate bioactive products of CYPs mediated drug metabolism is the principal issue in this respect. On the other hand, CYPs are the main source of ROS. Their generation and feedback are of major concern of this review. Besides drug metabolism, CYPs also contribute significantly to carcinogen metabolism. Ultimately other enzymes in drug metabolism and antioxidant therapy are indispensible. Importance of this field: In a global sense, understanding of exact mechanism can facilitate pharmaceutical industries' challenge of developing drugs without toxicity. Ultimate message: This review would accentuate the recent advances in molecular mechanism of CYPs mediated drug metabolism and complex cross-talks between various restorative novel strategies evolved by CYPs to sustain the redox balance and limit the source of oxidative stress.

  7. Chemical and biological effects of radiation sterilization of medical products

    International Nuclear Information System (INIS)

    Gupta, B.L.

    1975-01-01

    Radiation is extensively used for the sterilization of plastic materials, pharmaceuticals and biological tissue grafts. The pharmaceuticals may be solid, liquid, or suspension in a liquid or a solution. Cobalt-60 gamma radiation, generally used for sterilization, primarily interacts with these materials through the Compton process. The resulting damage may be direct or indirect. In aqueous systems the primary species produced compete for interaction among themselves and the dissolved solutes. The nature, the G-values and the reactions of the primary species very much depend on the pH of the solution. The important chemical changes in plastic materials are gas liberation, change in concentration of double bonds, cross-linking, degradation and oxidation. These chemical changes lead to some physical changes like crystallinity, specific conductivity and permeability. The reactions in biological systems are very complex and are influenced by the presence or absence of water and oxygen. Water produces indirect damage and the radiation effect is generally more in the presence of oxygen. Most microorganisms are relatively radioresistant. Various tissues of an animal differ in their response to radiation. Catgut is not stable to irradiation. Lyophilized human serum is stable to irradiation whereas, when irradiated in aqueous solutions, several changes are observed. Generally, pharmaceuticals are considerably more stable in the dry solid state to ionizing radiations than in aqueous solutions or in any other form of molecular aggregation. (author)

  8. Determination of drugs in biological fluids by high-performance liquid chromatography with on-line sample processing.

    Science.gov (United States)

    Oertel, R; Richter, K; Gramatté, T; Kirch, W

    1998-02-27

    An automated two column HPLC system with the new packing material LiChrospher RP-18 ADS (alkyl-diol-silica) was tested for the determination of several drugs and metabolites (talinolol, celiprolol, metoprolol, oxprenolol, triamterene, trimethoprim, tiracizine, articaine, detajmium, ajmaline, lamotrigine) in various biological fluids (serum, urine, intestinal aspirates, supernatants of cell cultures and supernatants after protein denaturation). The method allows the direct injection of biological fluids into a reversed-phase HPLC system and on-line clean-up and sample enrichment by a column-switching technique. Precision, accuracy and sensitivity were similar to conventional assays as described in the literature. With this new method it was possible to measure drug concentrations in various biological fluids without changing the sample preparation procedure. In some cases an additional sample preparation like protein denaturation or solid-phase extraction was advantageous to enhance the sensitivity of the method and the life-time of the ADS column.

  9. 76 FR 7743 - Professional Labeling for Laxative Drug Products for Over-the-Counter Human Use; Proposed...

    Science.gov (United States)

    2011-02-11

    ... enzyme inhibitor; a prescription drug for hypertension. Acute phosphate nephropathy means a type of... abbreviation for angiotension receptor blocker, a prescription drug for hypertension. Biologic plausibility...] unstable angina [cir] preexisting electrolyte disturbances (such as dehydration, or those secondary to the...

  10. Synthesis and Biological Investigation of Antioxidant Pyrrolomorpholine Spiroketal Natural Products

    Science.gov (United States)

    Verano, Alyssa Leigh

    The pyrrolomorpholine spiroketal natural product family is comprised of epimeric furanose and pyranose isomers. These compounds were isolated from diverse plant species, all of which are used as traditional Chinese medicines for the treatment of a variety of diseases. Notably, the spiroketal natural products acortatarins A and B exhibit antioxidant activity in a diabetic renal cell model, significantly attenuating hyperglycemia-induced production of reactive oxygen species (ROS), a hallmark of diabetic nephropathy. The xylapyrrosides, additional members of the family, also inhibit t-butyl hydroperoxide-induced cytotoxicity in rat vascular smooth muscle cells. Accordingly, these natural products have therapeutic potential for the treatment of oxidative stress-related pathologies, and synthetic access would provide an exciting opportunity to investigate bioactivity and mechanism of action. Herein, we report the stereoselective synthesis of acortatarins A and B, furanose members of the pyrrolomorpholine spiroketal family. Our synthetic route was expanded to synthesize the pyranose congeners, thus completing entire D-enantiomeric family of natural products. Efficient access towards these scaffolds enabled systematic analogue synthesis, investigation of mechanism-of-action, and the discovery of novel antioxidants.

  11. Biological Methanol Production by a Type II Methanotroph Methylocystis bryophila.

    Science.gov (United States)

    Patel, Sanjay K S; Mardina, Primata; Kim, Sang-Yong; Lee, Jung-Kul; Kim, In-Won

    2016-04-28

    Methane (CH₄) is the most abundant component in natural gas. To reduce its harmful environmental effect as a greenhouse gas, CH₄ can be utilized as a low-cost feed for the synthesis of methanol by methanotrophs. In this study, several methanotrophs were examined for their ability to produce methanol from CH₄; including Methylocella silvestris, Methylocystis bryophila, Methyloferula stellata, and Methylomonas methanica. Among these methanotrophs, M. bryophila exhibited the highest methanol production. The optimum process parameters aided in significant enhancement of methanol production up to 4.63 mM. Maximum methanol production was observed at pH 6.8, 30°C, 175 rpm, 100 mM phosphate buffer, 50 mM MgCl₂ as a methanol dehydrogenase inhibitor, 50% CH₄ concentration, 24 h of incubation, and 9 mg of dry cell mass ml(-1) inoculum load, respectively. Optimization of the process parameters, screening of methanol dehydrogenase inhibitors, and supplementation with formate resulted in significant improvements in methanol production using M. bryophila. This report suggests, for the first time, the potential of using M. bryophila for industrial methanol production from CH₄.

  12. Synthesis, Structural Characterization and Biological Screening of Various Sulfa Drugs Derived from 2-Anisidine

    International Nuclear Information System (INIS)

    Abbasi, M.A.; Rehman, A.U.; Muhmood, T.; Khan, K.M.

    2013-01-01

    In the present study, a series of N-alkyl substituted sulfa drugs (sulfonamides) has been synthesized. The reaction of 2-anisidine (1) with 4-methylbenzenesulfonyl chloride (2) yielded N-(2-methoxyphenyl)-4-methylbenzenesulfonamide (3), which on bromination with bromine in the presence of glacial acetic acid gave N-(4,5-dibromo-2-methoxyphenyl) 4-methylbenzenesulfonamide (6). These two products 3 and 6 on further treatment with different alkyl halides in the presence of lithium hydride yielded fourteen new N-substituted sulfonamides. These compounds were characterized by their EI-MS and 1H-NMR spectra and screened against acetylcholinesterase, butyrlcholinesterase and chymotrypsin enzymes. The results revealed that N-propyl-N-(2-methoxyphenyl)-4-methylbenzenesulfonamide (5c), N-(4,5-dibromo-2-methoxy-phenyl)-4-methylbenzenesulfonamide (6) and N-methyl-N-(4,5-dibromo-2-methoxyphenyl) 4-methylbenzenesulfonamide (7e) exhibited good inhibitory potential against acetylcholinesterase, butyrlcholinesterase and chymotrypsin respectively. (author)

  13. Some aspects of biological production and fishery resources of the EEZ of India

    Digital Repository Service at National Institute of Oceanography (India)

    Bhargava, R.M.S.

    Region and season-wise biological production in the Exclusive Economic Zone (EEZ) of India has been computed from the data of more than twenty years available at the Indian National Oceanographic Data Centre of the National Institute of Oceanography...

  14. [Therapeutic Concepts for Treatment of Patients with Non-infectious Uveitis Biologic Disease Modifying Antirheumatic Drugs].

    Science.gov (United States)

    Walscheid, Karoline; Pleyer, Uwe; Heiligenhaus, Arnd

    2018-04-12

    Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities. Currently, the TNF-α-inhibitor Adalimumab is the only in-label therapeutic option, whereas, all other bDMARDs need to be given as an off-label therapy. bDMARDs are indicated in diseases refractory to conventional synthetic DMARD therapy and/or systemic steroids, or in patients in whom treatment with those is not possible due to side effects. Therapeutic mechanisms currently employed are cytokine-specific (interferons, inhibition of TNF-α or of interleukin [IL]-1-, IL-6- or IL-17-signalling), inhibit T cell costimulation (CTLA-4 fusion protein), or act via depletion of B cells (anti-CD20). All bDMARDs need to be administered parenterally, and therapy is initiated by the treating internal specialist only after interdisciplinary coordination of all treating subspecialties and after exclusion of contraindications. Regular clinical and laboratory monitoring is mandatory for all patients while under bDMARD therapy. Georg Thieme Verlag KG Stuttgart · New York.

  15. Synthesis of [13C6]-labelled phenethylamine derivatives for drug quantification in biological samples.

    Science.gov (United States)

    Karlsen, Morten; Liu, HuiLing; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bård Helge

    2014-05-15

    The availability of high-quality (13)C-labelled internal standards will improve accurate quantification of narcotics and drugs in biological samples. Thus, the synthesis of 10 [(13)C6]-labelled phenethylamine derivatives, namely amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-N-ethylamphetamine, 4-methoxyamphetamine, 4-methoxymethamphetamine, 3,5-dimethoxyphenethylamine 4-bromo-2,5-dimethoxyphenethylamine and 2,5-dimethoxy-4-iodophenethylamine, have been undertaken. [(13)C6]-Phenol proved to be an excellent starting material for making (13)C-labelled narcotic substances in the phenethylamine class, and a developed Stille-type coupling enabled an efficient synthesis of the 3,4-methylenedioxy and 4-methoxy derivatives. The pros and cons of alternative routes and transformations are also discussed. The [(13)C6]-labelled compounds are intended for use as internal standards in forensic analysis, health sciences and metabolomics studies by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

    Science.gov (United States)

    Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

    2013-05-14

    Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

  17. Development of parenteral formulations and evaluation of the biological activity of the trypanocide drug benznidazole.

    Science.gov (United States)

    Lamas, María C; Villaggi, Luciano; Nocito, Isabel; Bassani, Georgina; Leonardi, Darío; Pascutti, Fernanda; Serra, Esteban; Salomón, Claudio J

    2006-01-13

    Chagas disease, caused by Trypanosoma cruzi, is a major public health problem in Latin America. According to the World Health Organization, around 20 million people are infected and another 40 million are at risk of acquiring the disease. One of the drugs most frequently used for the treatment of Chagas disease is benznidazole (BZL). It is practically insoluble in water (0.4 mg/ml), which precludes the preparation of liquid dosage forms, in particular, parenteral formulations. Thus, the aim of this work was to investigate the solubilization of BZL at two pH values using various cosolvents such as ethyl alcohol, propylene glycol, polyethylene glycol 400, benzyl alcohol, diethylene glycol monoethyl ether (Transcutol) and surfactants such as polysorbates (Tween) 40 and 80, and sodium dioctyl sulfosuccinate (AOT). Solvent systems based on PEG 400, with the addition ethyl alcohol and/or potassium biphthalate buffer solution, increased the BZL solubility up to 10 mg/ml. These alcoholic vehicles showed no toxicity against parasite when assayed at 1%. Physical and chemical stability studies showed that the formulations were stable for at least 1.5 years. In agreement with the biological activity results, the selected formulations are suitable for further clinical studies. Moreover, increasing the aqueous solubility of BZL reduced the problems in vitro testing techniques and bioassays leading to more reliable results and/or reproducibility.

  18. High biological productivity in the central Arabian Sea during the summer monsoon driven by Ekman pumping and lateral advection

    Digital Repository Service at National Institute of Oceanography (India)

    PrasannaKumar, S.; Madhupratap, M.; DileepKumar, M.; Muraleedharan, P.M.; DeSouza, S.N.; Gauns, M.; Sarma, V.V.S.S.

    Open oceans are generally oligotrophic and support less biological production. Results from the central Arabian Sea show that it may be an exception to this. We provide the observational evidence of fairly high biological production (up to 1700 mg C...

  19. Toxicological methods for tracing drug abuse: chromatographic, spectroscopic and biological characterisation of ecstasy derivatives.

    Science.gov (United States)

    Belhadj-Tahar, Hafid; Payoux, Pierre; Tafani, Mathieu; Coulais, Yvon; Calet, Serge; Bousseksou, Azzedine

    2010-03-01

    Analysis often reveals variability in the composition of ecstasy pills from pure 3,4-methylenedioxymethamphetamine (MDMA) to mixtures of MDMA derivatives, amphetamine, and other unidentified substances. For a comprehensive toxicological analysis one needs to know all steps to MDMA synthesis which may originate impurities. The aim of this study was to synthesise and determine the chemical-physical and in vitro biological properties of a series of MDMA derivatives.3,4-methylendioxyphenyl-2-nitropropene (MDNP) was obtained by condensation of piperonal with an excess of nitroethane in the presence of ammonium acetate. MDNP was then reduced to methylenedioxyamphetamine (MDA) by LiAlH3. All compounds were analysed using HPLC and spectroscopic technique [Raman, nuclear magnetic resonance (NMR), or infrared (IR)] at all the steps of synthesis. In addition, we assessed the biological potentials of these compounds by measuring in vitro their (i) blood cell/whole blood partition coefficient, (ii) binding to plasmatic proteins (Fbp), and (iii) membrane adsorption. Chemical structure was determined with antibody fluorescence polarisation immunoassay (FPIA). This study showed the presence of solid impurities, particularly of a neurotoxic compound of Al3+ in the final products. FPIA identified the aminoethane group close to the substituted benzene ring, but did not detect the two major precursors of MDMA: MDNP and piperonal. Raman spectroscopy is an attractive alternative technique to characterise ecstasy pills and it can identify stereoisomeric forms such as cis-MDNP and trans-MDNP, which exhibit signals at 1650 cm-1 and 1300 cm-1, respectively.

  20. Biological pretreatment and ethanol production from olive cake

    DEFF Research Database (Denmark)

    Jurado, Esperanza; Gavala, Hariklia N.; Baroi, George Nabin

    2010-01-01

    Olive oil is one of the major Mediterranean products, whose nutritional and economic importance is well-known. However the extraction of olive oil yields a highly contaminating residue that causes serious environmental concerns in the olive oil producing countries. The olive cake (OC) coming out...... of the three-phase olive oil production process could be used as low price feedstock for lignocellulosic ethanol production due to its high concentration in carbohydrates. However, the binding of the carbohydrates with lignin may significantly hinder the necessary enzymatic hydrolysis of the polymeric sugars...... before ethanol fermentation. Treatment with three white rot fungi, Phaneroachaete chrysosporium, Ceriporiopsis subvermispora and Ceriolopsis polyzona has been applied on olive cake in order to investigate the potential for performing delignification and thus enhancing the efficiency of the subsequent...

  1. Systems-Level Synthetic Biology for Advanced Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    Ruffing, Anne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jensen, Travis J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Strickland, Lucas Marshall [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Meserole, Stephen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tallant, David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    Cyanobacteria have been shown to be capable of producing a variety of advanced biofuels; however, product yields remain well below those necessary for large scale production. New genetic tools and high throughput metabolic engineering techniques are needed to optimize cyanobacterial metabolisms for enhanced biofuel production. Towards this goal, this project advances the development of a multiple promoter replacement technique for systems-level optimization of gene expression in a model cyanobacterial host: Synechococcus sp. PCC 7002. To realize this multiple-target approach, key capabilities were developed, including a high throughput detection method for advanced biofuels, enhanced transformation efficiency, and genetic tools for Synechococcus sp. PCC 7002. Moreover, several additional obstacles were identified for realization of this multiple promoter replacement technique. The techniques and tools developed in this project will help to enable future efforts in the advancement of cyanobacterial biofuels.

  2. Improved biological processes for the production of aryl sulfates

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention generally relates to the field of biotechnology as it applies to the production of aryl sulfates using recombinant host cells. More particularly, the present invention pertains to recombinant host cells comprising (e.g., expressing) a polypeptide having aryl sulfotransferase...... activity, wherein said recombinant host cells have been modified to have an increased uptake of sulfate compared to identical host cells that does not carry said modification. Further provided are processes for the production of aryl sulfates, such as zosteric acid, employing such recombinant host cells....

  3. Just say "I don't": lack of concordance between teen report and biological measures of drug use.

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Ager, Joel; Sokol, Robert J

    2010-11-01

    Prevalence estimates of illicit drug use by teens are typically generated from confidential or anonymous self-report. While data comparing teen self-report with biological measures are limited, adult studies identify varying degrees of under-reporting. Hair analyses for cocaine, opiates and marijuana were compared to confidential teen self- and parent-reported teen drug use in a longitudinal cohort of >400 high-risk urban teens and parents. Both teens and parents substantially underreported recent teen cocaine and opiate use. However, compared with parents, teens were more likely to deny biomarker-verified cocaine use. Teen specimens (hair) were 52 times more likely to identify cocaine use compared with self-report. Parent hair analyses for cocaine and opiate use were 6.5 times and 5.5 times, respectively, more likely to indicate drug use than were parental self-report. The lack of concordance between self-report and bioassay occurred despite participant's knowledge that a "certificate of confidentiality" protected both teen and adult participants, and that the biological specimens would be tested for drugs. These findings confirm prior reports of adult under-reporting of their own drug use while extending our understanding of teen's self-admitted drug use. The lack of concordance between teen self- or parent-reported teen drug use and biomarkers confirm our concerns that both teen- and parent-reported teen drug use is limited, at least for youth in high-risk urban settings. Methods of ascertainment other than self- or parent-report must be considered when health care providers, researchers and public health agencies attempt to estimate teen drug-use prevalence.

  4. Just Say “I Don’t”: Lack of Concordance Between Teen Report and Biological Measures of Drug Use

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Ager, Joel; Sokol, Robert J.

    2012-01-01

    BACKGROUND Prevalence estimates of illicit drug use by teens are typically generated from confidential or anonymous self-report. While data comparing teen self-report with biological measures are limited, adult studies identify varying degrees of under-reporting. METHODS Hair analyses for cocaine, opiates and marijuana were compared to confidential teen self- and parent-reported teen drug use in a longitudinal cohort of >400 high-risk urban teens and parents. RESULTS Both teens and parents substantially underreported recent teen cocaine and opiate use. However, compared with parents, teens were more likely to deny biomarker-verified cocaine use. Teen specimens (hair) were 52 times more likely to identify cocaine use compared with self-report. Parent hair analyses for cocaine and opiate use were 6.5 times and 5.5 times, respectively, more likely to indicate drug use than were parental self-report. The lack of concordance between self-report and bioassay occurred despite participant’s knowledge that a “certificate of confidentiality” protected both teen and adult participants, and that the biological specimens would be tested for drugs. CONCLUSIONS These findings confirm prior reports of adult under-reporting of their own drug use while extending our understanding of teen’s self-admitted drug use. The lack of concordance between teen self- or parent-reported teen drug use and biomarkers confirm our concerns that both teen- and parent-reported teen drug use is limited, at least for youth in high-risk urban settings. Methods of ascertainment other than self- or parent-report must be considered when health care providers, researchers and public health agencies attempt to estimate teen drug-use prevalence. PMID:20974792

  5. Product-line extensions and pricing strategies of brand-name drugs facing patent expiration.

    Science.gov (United States)

    Hong, Song Hee; Shepherd, Marvin D; Scoones, David; Wan, Thomas T H

    2005-01-01

    This study proposed an alternative to brand loyalty as the explanation for the continued price rigidity of patent-expired brand-name prescription drugs despite the increase in market entry of generic drugs facilitated by the 1984 Drug Price Competition and Patent Term Restoration Act. Study hypotheses were to test (1) whether market entries of new-product extensions are associated with market success of original brand-name drugs before generic drug entry, and (2) whether original brand-name drugs exhibit price rigidity to generic entry only when they are extended. The design is a retrospective follow-up study for the prescription drug brands that lost their patents between 1987 and 1992. The drug brands were limited to nonantibiotic, orally administered drugs containing only 1 active pharmaceutical ingredient. Information on patent expiration, entry of a product extension, and market success were determined from the U.S. Food and Drug Administration.s Orange Book, First DataBank, and American Druggist, respectively. Market success was defined as whether an original drug brand was listed in the top 100 prescriptions most frequently dispensed before facing generic entry. Product-line extension was defined as the appearance of another product that a company introduces within the same market after its existing product. Drug prices were average wholesale prices from the Drug Topics Red Book. The relationship between product-line extension and market success was examined using a logistic regression analysis. The price rigidity to entry was tested using a panel regression analysis. A total of 27 drug brands lost their patents between 1987 and 1992. Drug brands that achieved market success were 16 times more likely to be extended than were those that did not (OR=16, 95% confidence interval, 2.12-120.65). The price rigidity to entry existed in drug brands with extensions (beta=2.65%, P new product-line extension introduced for an original brand helps the original price be

  6. Bovine mammary stem cells: Cell biology meets production agriculture

    Science.gov (United States)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  7. 9 CFR 113.3 - Sampling of biological products.

    Science.gov (United States)

    2010-01-01

    ... into the United States as prescribed in this section. Additional samples may be purchased in the open market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the... operation. Bulk containers of completed product may be sampled when authorized by the Administrator. (iii...

  8. Improvements in Fermentative Biological Hydrogen Production Through Metabolic Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Hallenbeck, P. C.; Ghosh, D.; Sabourin-Provost, G.

    2009-07-01

    Dramatically rising oil prices and increasing awareness of the dire environmental consequences of fossil fuel use, including startling effects of climate change, are refocusing attention world-wide on the search for alternative fuels. Hydrogen is poised to become an important future energy carrier. Renewable hydrogen production is pivotal in making it a truly sustainable replacement for fossil fuels. (Author)

  9. Improvements in Fermentative Biological Hydrogen Production Through Metabolic Engineering

    International Nuclear Information System (INIS)

    Hallenbeck, P. C.; Ghosh, D.; Sabourin-Provost, G.

    2009-01-01

    Dramatically rising oil prices and increasing awareness of the dire environmental consequences of fossil fuel use, including startling effects of climate change, are refocusing attention world-wide on the search for alternative fuels. Hydrogen is poised to become an important future energy carrier. Renewable hydrogen production is pivotal in making it a truly sustainable replacement for fossil fuels. (Author)

  10. Persistence, switch rates, drug consumption and costs of biological treatment of rheumatoid arthritis: an observational study in Italy.

    Science.gov (United States)

    Degli Esposti, Luca; Favalli, Ennio Giulio; Sangiorgi, Diego; Di Turi, Roberta; Farina, Giuseppina; Gambera, Marco; Ravasio, Roberto

    2017-01-01

    The aim of this analysis was to provide an estimate of drug utilization indicators (persistence, switch rate and drug consumption) on biologics and the corresponding costs (drugs, admissions and specialist care) incurred by the Italian National Health Service in the management of adult patients with rheumatoid arthritis (RA). We conducted an observational retrospective cohort analysis using the administrative databases of three local health units. We considered all patients aged ≥18 years with a diagnosis of RA and at least one biologic drug prescription between January 2010 and December 2012 (recruitment period). Persistence was defined as maintenance over the last 3 months of the follow-up period of the same biological therapy administered at the index date. A switch was defined as the presence of a biological therapy other than that administered at the index date during the last 3 months of the follow-up period. Hospital admissions (with a diagnosis of RA or other RA-related diagnoses), specialist outpatient services, instrumental diagnostics and pharmaceutical consumption were assessed. The drug utilization analysis took into account only biologics with at least 90 patients on treatment at baseline (adalimumab n=144, etanercept n=236 and infliximab n=94). In each year, etanercept showed better persistence with initial treatment than adalimumab or infliximab. Etanercept was characterized by the lowest number of patients increasing the initial drug consumption (2.6%) and by the highest number of patients reducing the initial drug consumption (10.5%). The mean cost of treatment for a patient persisting with the initial treatment was €12,388 (€14,182 for adalimumab, €12,103 for etanercept and €11,002 for infliximab). The treatment costs for patients switching from initial treatment during the first year of follow-up were higher than for patients who did not switch (€12,710 vs. €11,332). Persistence, switch rate and drug consumption seem to directly

  11. In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin.

    Science.gov (United States)

    Ntie-Kang, Fidele; Lifongo, Lydia L; Mbah, James A; Owono Owono, Luc C; Megnassan, Eugene; Mbaze, Luc Meva'a; Judson, Philip N; Sippl, Wolfgang; Efange, Simon M N

    2013-01-01

    Drug metabolism and pharmacokinetics (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. The use of computer modelling to predict the DMPK and toxicity properties of a natural product library derived from medicinal plants from Central Africa (named ConMedNP). Material from some of the plant sources are currently employed in African Traditional Medicine. Computer-based methods are slowly gaining ground in this area and are often used as preliminary criteria for the elimination of compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of discovery of a drug. In the present study, we present an in silico assessment of the DMPK and toxicity profile of a natural product library containing ~3,200 compounds, derived from 379 species of medicinal plants from 10 countries in the Congo Basin forests and savannas, which have been published in the literature. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination and toxicity (ADMET) of the compounds. This survey demonstrated that about 45% of the compounds within the ConMedNP compound library are compliant, having properties which fall within the range of ADME properties of 95% of currently known drugs, while about 69% of the compounds have ≤ 2 violations. Moreover, about 73% of the compounds within the corresponding "drug-like" subset showed compliance. In addition to the verified levels of "drug-likeness", diversity and the wide range of measured biological activities, the compounds from medicinal plants in Central Africa show interesting DMPK profiles and hence could represent an important starting point for hit/lead discovery.

  12. Assessing the drug-likeness of lamellarins, a marine-derived natural product class with diverse oncological activities.

    Science.gov (United States)

    Chittchang, Montakarn; Gleeson, M Paul; Ploypradith, Poonsakdi; Ruchirawat, Somsak

    2010-06-01

    Natural products currently represent an underutilized source of leads for the pharmaceutical industry, especially when one considers that almost 50% of all drugs were either derived from such sources or are very closely related. Lamellarins are a class of natural products with diverse biological activities and have entered into preclinical development for the treatment of multidrug-resistant tumors. Although these compounds demonstrated good cell penetration, as observed by their low microM activity in whole cell models, they have not been extensively profiled from a physicochemical point of view, and this is the goal of this study. For this study, we have determined the experimental logP values of a set of 25 lamellarins, given it is the single most important parameter in determining multiple ADMET parameters. We also discuss the relationship between this natural product class, natural product derivatives in development and on the market, oral marketed drugs, as well as drug molecules in development, using a range of physicochemical parameters in conjunction with principal components analysis (PCA). The impact of this systematic analysis on our ongoing medicinal chemistry strategy is also discussed. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  13. Regeneration of nutrients and biological productivity in Antarctic waters

    Digital Repository Service at National Institute of Oceanography (India)

    Verlecar, X.N.; Somasundar, K.; Qasim, S.Z.

    0 30r-. -::.12°..:E~30:_·--Y..':.-_~~ HEARD Is. • .. " 08 x IN 0 I A N o C fAN rJ ~MAURIT!US x ';ol"!> 0" ill IS (:] l 158 010 148 9& CROZET 130 .. , 15. KERGUELEN X.. Is,.'b 120 ANTARCTICA a BOUVET Is. 0' 20 50 Verlencar et al.: Production... and from 0.4 to 3.33 mg C m- 3 h- 1 respectively (Table 1). In the eupho tic column daily production ranged from 0.3 to 1.03 g C m- 2 d- 1 and chlorophyll a from 21.1 to 85.5 mg m- 2 (Table 2). Microscopic examination of 500 ml of sedimented water samples...

  14. Time-ordered product expansions for computational stochastic system biology

    International Nuclear Information System (INIS)

    Mjolsness, Eric

    2013-01-01

    The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie’s stochastic simulation algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems. (paper)

  15. Production of biological reagents for radioimmunoassay second antibody

    International Nuclear Information System (INIS)

    Borghi, V.C.; Silva, S.R. da; Bellini, M.H.; Lin, L.H.

    1992-02-01

    The experimental production of second antibody to be used in hormonal assays, in which the first antibody is raised in rabbits, is described. Four sheep were immunized with the rabbit immunoglobulin prepared at IPEN-CNEN laboratory. Their antisera were evaluated by the human thyrotropin radioimmunoassay employing materials provided by the National Hormone and Pituitary Program (USA), in comparison with a reference antiserum of known quality, produced in goat by the Radioassay Systems Laboratories - RSL (USA). From the fourth booster injection the animals developed antiserum with titer similar to that exhibited by the commercial product, even presenting higher values. These antisera are now being examinated for the optimal conditions of precipitation before be packed for future use and distribution. (author)

  16. Applied systems biology - vanillin production in Saccharomyces cerevisiae

    OpenAIRE

    Strucko, Tomas; Eriksen, Jens Christian; Nielsen, J.; Mortensen, Uffe Hasbro

    2012-01-01

    Vanillin is the most important aroma compound based on market value, and natural vanillin is extracted from the cured seed pods of the Vanilla orchid. Most of the world’s vanillin, however, is obtained by chemical synthesis from petrochemicals or wood pulp lignins. As an alternative, de novo biosynthesis of vanillin in baker’s yeast Saccharomyces cerevisiae was recently demonstrated by successfully introducing the metabolic pathway for vanillin production in yeast. Nevertheless, the amount of...

  17. Biological therapeutics

    National Research Council Canada - National Science Library

    Greenstein, Ben; Brook, Daniel A

    2011-01-01

    This introductory textbook covers all the main categories of biological medicines, including vaccines, hormonal preparations, drugs for rheumatoid arthritis and other connective tissue diseases, drugs...

  18. Direct detection of illicit drugs from biological fluids by desorption/ionization mass spectrometry with nanoporous silicon microparticles.

    Science.gov (United States)

    Guinan, T M; Kirkbride, P; Della Vedova, C B; Kershaw, S G; Kobus, H; Voelcker, N H

    2015-12-07

    Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is a high throughput analytical technique capable of detecting low molecular weight analytes, including illicit drugs, and with potential applications in forensic toxicology as well as athlete and workplace testing, particularly for biological fluids (oral fluids, urine and blood). However, successful detection of illicit drugs using SALDI-MS often requires extraction steps to reduce the inherent complexity of biological fluids. Here, we demonstrate an all-in-one extraction and analytical system consisting of hydrophobically functionalized porous silicon microparticles (pSi-MPs) for affinity SALDI-MS of prescription and illicit drugs. This novel approach allows for the analysis of drugs from multiple biological fluids without sample preparation protocols. The effect of pSi-MP size, pore diameter, pore depth and functionalization on analytical performance is investigated. pSi-MPs were optimized for the rapid and high sensitivity detection of methadone, cocaine and 3,4-methylenedioxymethamphetamine (MDMA). This optimized system allowed extraction and detection of methadone from spiked saliva and clinical urine samples. Furthermore, by detecting oxycodone in additional clinical saliva and plasma samples, we were able to demonstrate the versatility of the pSi-MP SALDI-MS technique.

  19. Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.

    Science.gov (United States)

    Nickerson, M L; Witte, N; Im, K M; Turan, S; Owens, C; Misner, K; Tsang, S X; Cai, Z; Wu, S; Dean, M; Costello, J C; Theodorescu, D

    2017-01-05

    The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study

  20. Tailored approaches in drug development and diagnostics : from molecular design to biological model systems

    NARCIS (Netherlands)

    Sahlgren, C.M.; Meinander, A.; Zhang, H.; Cheng, F.; Preis, Maren; Xu, C.; Salminen, T.A.; Toivola, D.M.; Abankwa, D.; Rosling, A.; Karaman, D.Ş.; Salo-Ahen, O.M.H.; Österbacka, R.; Eriksson, J.E.; Willför, S.; Petre, I.; Peltonen, J.; Leino, R.; Johnson, M.; Rosenholm, J.; Sandler, N.

    2017-01-01

    Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic

  1. Biological methane production under putative Enceladus-like conditions.

    Science.gov (United States)

    Taubner, Ruth-Sophie; Pappenreiter, Patricia; Zwicker, Jennifer; Smrzka, Daniel; Pruckner, Christian; Kolar, Philipp; Bernacchi, Sébastien; Seifert, Arne H; Krajete, Alexander; Bach, Wolfgang; Peckmann, Jörn; Paulik, Christian; Firneis, Maria G; Schleper, Christa; Rittmann, Simon K-M R

    2018-02-27

    The detection of silica-rich dust particles, as an indication for ongoing hydrothermal activity, and the presence of water and organic molecules in the plume of Enceladus, have made Saturn's icy moon a hot spot in the search for potential extraterrestrial life. Methanogenic archaea are among the organisms that could potentially thrive under the predicted conditions on Enceladus, considering that both molecular hydrogen (H 2 ) and methane (CH 4 ) have been detected in the plume. Here we show that a methanogenic archaeon, Methanothermococcus okinawensis, can produce CH 4 under physicochemical conditions extrapolated for Enceladus. Up to 72% carbon dioxide to CH 4 conversion is reached at 50 bar in the presence of potential inhibitors. Furthermore, kinetic and thermodynamic computations of low-temperature serpentinization indicate that there may be sufficient H 2 gas production to serve as a substrate for CH 4 production on Enceladus. We conclude that some of the CH 4 detected in the plume of Enceladus might, in principle, be produced by methanogens.

  2. Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

    Science.gov (United States)

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2018-02-01

    The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

  3. Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Taroumian, Sara; Knowles, Susan L; Lisse, Jeffrey R; Yanes, James; Ampel, Neil M; Vaz, Austin; Galgiani, John N; Hoover, Susan E

    2012-12-01

    Coccidioidomycosis (valley fever) is an endemic fungal infection of the American Southwest, an area with a large population of patients with rheumatic diseases. There are currently no guidelines for management of patients who develop coccidioidomycosis while under treatment with biologic response modifiers (BRMs) or disease-modifying antirheumatic drugs (DMARDs). We conducted a retrospective study of how both concurrent diseases were managed and the patient outcomes at 2 centers in Tucson, Arizona. A retrospective chart review identified patients who developed coccidioidomycosis during treatment with DMARDs or BRMs. Patients were seen at least once in a university-affiliated or Veterans Affairs outpatient rheumatology clinic in Tucson, Arizona, between 2007 and 2009. Forty-four patients were identified. Rheumatologic treatment included a BRM alone (n = 11), a DMARD alone (n = 8), or combination therapy (n = 25). Manifestations of coccidioidomycosis included pulmonary infection (n = 29), disseminated disease (n = 9), and asymptomatic positive coccidioidal serologies (n = 6). After the diagnosis of coccidioidomycosis, 26 patients had BRMs and DMARDs stopped, 8 patients had BRMs stopped but DMARD therapy continued, and 10 patients had no change in their immunosuppressive therapy. Forty-one patients had antifungal therapy initiated for 1 month or longer. Followup data were available for 38 patients. BRM and/or DMARD therapy was continued or resumed in 33 patients, only 16 of whom continued concurrent antifungal therapy. None of the patients have had subsequent dissemination or complications of coccidioidomycosis. Re-treating rheumatic disease patients with a BRM and/or a DMARD after coccidioidomycosis appears to be safe in some patients. We propose a management strategy based on coccidioidomycosis disease activity. Copyright © 2012 by the American College of Rheumatology.

  4. Development of biological functional material and product from Nelumbo nucifera

    International Nuclear Information System (INIS)

    Jeong, Il Yun; Park, Yong Dae; Jin, Chang Hyun; Choi, Dae Seong

    2008-01-01

    The solvent extracts of Nelumbo nucifera G. were investigated for the activities of antioxidant, whitening, anti-wrinkle and antimicrobial effects to apply as a functional ingredient for cosmetic products. The electron donating ability of irradiated NN-L extract was above 85% at the concentration of 50ppm. The superoxide dismutase(SOD)-like activity of irradiated NN-L extract was about 76% at 1,000ppm concentration. The xanthine oxidase inhibitory effect of irradiated NN-L extract was about 15% at 1,000ppm. The tyrosinase inhibitory effect of irradiated NN-L extract was about 18% at 1,000ppm. Anti-wrinkle effect, the elastase inhibition activity of irradiated NN-L extract was about 45% at 1,000ppm concentration. All these findings suggested that Nelumbo nucifera G. has a great potential as a cosmeceutical ingredient

  5. Development of biological functional material and product from Nelumbo nucifera

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Il Yun; Park, Yong Dae; Jin, Chang Hyun; Choi, Dae Seong

    2008-01-15

    The solvent extracts of Nelumbo nucifera G. were investigated for the activities of antioxidant, whitening, anti-wrinkle and antimicrobial effects to apply as a functional ingredient for cosmetic products. The electron donating ability of irradiated NN-L extract was above 85% at the concentration of 50ppm. The superoxide dismutase(SOD)-like activity of irradiated NN-L extract was about 76% at 1,000ppm concentration. The xanthine oxidase inhibitory effect of irradiated NN-L extract was about 15% at 1,000ppm. The tyrosinase inhibitory effect of irradiated NN-L extract was about 18% at 1,000ppm. Anti-wrinkle effect, the elastase inhibition activity of irradiated NN-L extract was about 45% at 1,000ppm concentration. All these findings suggested that Nelumbo nucifera G. has a great potential as a cosmeceutical ingredient.

  6. A novel biological hydrogen production system. Impact of organic loading

    Energy Technology Data Exchange (ETDEWEB)

    Hafez, Hisham; Nakhla, George; El Naggar, Hesham [Western Ontario Univ. (Canada)

    2010-07-01

    The patent-pending system comprises a novel biohydrogen reactor with a gravity settler for decoupling of SRT from HRT. Two biohydrogenators were operated for 220 days at 37 C, hydraulic retention time 8 h and solids retention time ranged from 1.4 to 2 days under four different glucose concentrations of 2, 8, 16, 32, 48 and 64 g/L, corresponding to organic loading rates of 6.5-206 kg COD/m{sup 3}-d, and started up using anaerobically-digested sludge from the St. Marys wastewater treatment plant (St.Mary, Ontario, Canada) as the seed. The system steadily produced hydrogen with no methane. A maximum hydrogen yield of 3.1 mol H{sub 2} /mol glucose was achieved in the system for all the organic loading rates with an average of 2.8mol H{sub 2} /mol glucose. Acetate and butyrate were the main effluent liquid products at concentrations ranging from 640-7400 mg/L and 400-4600 mg/l, respectively, with no lactate detection. Microbial community analysis using denaturing gradient gel electrophoresis (DGGE) confirmed the absence of lactate producing bacteria Lactobacillus fermentum and other non-hydrogen producing species, and the predominance of various Clostridium species. Biomass concentrations in the biohydrogenators were steady, during the runs, varying form 1500 mg/L at the OLR of 6.5 kg COD/m{sup 3}-d to 14000 mg/L at the 104 kg COD/m{sup 3}-d, thus emphasizing the potential of this novel system for sustained stable hydrogen production and prevention of biomass washout. (orig.)

  7. 21 CFR 328.50 - Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol. 328.50 Section 328.50 Food and Drugs FOOD AND DRUG... PRODUCTS INTENDED FOR ORAL INGESTION THAT CONTAIN ALCOHOL Labeling § 328.50 Principal display panel of all...

  8. 21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What controls and acceptance criteria must I have... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Finished Drug Product Controls and Acceptance § 212.70 What controls and acceptance criteria must I have for my finished PET drug products? (a) Specifications...

  9. 21 CFR 310.528 - Drug products containing active ingredients offered over-the-counter (OTC) for use as an...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing active ingredients offered over-the-counter (OTC) for use as an aphrodisiac. 310.528 Section 310.528 Food and Drugs FOOD AND... drug product. Anise, cantharides, don qual, estrogens, fennel, ginseng, golden seal, gotu kola, Korean...

  10. Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

    Directory of Open Access Journals (Sweden)

    Rukiye Yavaşer

    2016-08-01

    Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

  11. 21 CFR 310.530 - Topically applied hormone-containing drug products for over-the-counter (OTC) human use.

    Science.gov (United States)

    2010-04-01

    ... labeling or in the ingredient statement is an implied drug claim. The claim implied by the use of this term... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Topically applied hormone-containing drug products for over-the-counter (OTC) human use. 310.530 Section 310.530 Food and Drugs FOOD AND DRUG...

  12. 21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Packaging and Labeling § 212.80 What are the...

  13. Nutrient availability limits biological production in Arctic sea ice melt ponds

    DEFF Research Database (Denmark)

    Sørensen, Heidi Louise; Thamdrup, Bo; Jeppesen, Erik

    2017-01-01

    nutrient limitation in melt ponds. We also document that the addition of nutrients, although at relative high concentrations, can stimulate biological productivity at several trophic levels. Given the projected increase in first-year ice, increased melt pond coverage during the Arctic spring and potential......Every spring and summer melt ponds form at the surface of polar sea ice and become habitats where biological production may take place. Previous studies report a large variability in the productivity, but the causes are unknown. We investigated if nutrients limit the productivity in these first...... additional nutrient supply from, e.g. terrestrial sources imply that biological activity of melt ponds may become increasingly important for the sympagic carbon cycling in the future Arctic....

  14. [Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

    Science.gov (United States)

    Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

    2009-01-01

    With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

  15. Variations in composition of farmyard manure in biologic gas production

    Energy Technology Data Exchange (ETDEWEB)

    Scheffer, F; Welte, E; Kemmler, G

    1953-01-01

    The advantages of the ''Bihugas'' method, Schmidt-Eggersgluss system, are discussed. The losses of organic matter and of C are about 33 percent for a gas output of 270 l/kg of organic matter, but 55 percent of the C of the decomposition products is utilized as mixed gas (about 60 percent as methane). The gas output amounts to 3-7 m/sup 3/ per 100 kg fresh manure. The maximum heating value of the mixed gas is 5700 kcal. The loss of N is only 1 percent of the total N; no P, K, and Ca are lost. No formation of humus was observed. The average composition of fermented manure was dry matter 10.56 organic matter 6.9, C 3.47, N 0.36, ammonia N in percentage of total N 38, K/sub 2/O/sub 7/ 0.27, CaO 0.18, and P/sub 2/O/sub 5/ 0.13 percent. The process, compared with the conventional handling of manure, decreases losses in N from 18.5 percent to 1 percent, and those in C from 38 percent to 7.3 percent.

  16. 78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

    Science.gov (United States)

    2013-06-25

    ... marketing for reasons other than safety or effectiveness. FDA will not begin procedures to withdraw approval... Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug...-610 were not withdrawn from sale for reasons of safety or effectiveness. This determination means that...

  17. Evaluation of In-Use Stability of Anticoagulant Drug Products: Warfarin Sodium.

    Science.gov (United States)

    Nguyenpho, Agnes; Ciavarella, Anthony B; Siddiqui, Akhtar; Rahman, Ziyaur; Akhtar, Sohail; Hunt, Robert; Korang-Yeboah, Maxwell; Khan, Mansoor A

    2015-12-01

    The objective of the study was to evaluate the stability of warfarin products during use by patients or caregivers. For evaluation, three commercial products manufactured by different processes were selected and placed at 30°C/75%RH to simulate in use condition. Samples were withdrawn up to 12 weeks and analyzed for the physicochemical changes. Scanning electron microscopy demonstrated increasing holes and craters in the tablets over the timeframe. Near-infrared chemical imaging and powder X-ray powder diffraction corroborated the change arising from conversion of crystalline to amorphous forms of the drug. Hardness and disintegration time of the tablets were found to increase progressively. With increasing time, moisture contents of the products were found to increase and consequent decrease in isopropyl alcohol content of the product. Dissolution of the tablets in media at pH 4.5 demonstrated discrimination between crystalline and amorphous drug products. Overall, percent drug dissolved in each product at 30 min was found to decrease with increasing exposure time. Dissolution of drug decreased from 54% to 38% and 82% to 54% for the two products while the third product maintained consistently high level of dissolution. These results suggest that the drug product quality attributes can change during use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  18. Use of drugs and antibiotics in poultry production in Ghana | Turkson ...

    African Journals Online (AJOL)

    This study was designed to assess the extent of drug and antibiotic use in small and large commercial poultry producers in Ghana, and the extent of the knowledge, perceptions and practice of drug withdrawal period in poultry production. In all, 483 poultry farmers in Greater Accra, Ashanti and Central regions were ...

  19. 21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

    Science.gov (United States)

    2010-04-01

    ... for more than 2 weeks, consult your doctor. Insomnia may be a symptom of serious underlying medical illness.” (3) “Do not take this product, unless directed by a doctor, if you have a breathing problem such....50 Section 338.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  20. 75 FR 48352 - Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn...

    Science.gov (United States)

    2010-08-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0391] Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn From Sale for... Applicant NDA 17-463 MOTRIN (ibuprofen) Tablets, 300 milligrams (mg), McNeil Consumer Healthcare, 7050 Camp...

  1. Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Laura R. Jarboe

    2010-01-01

    Full Text Available Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors.

  2. Mixing monoclonal antibody formulations using bottom-mounted mixers: impact of mechanism and design on drug product quality.

    Science.gov (United States)

    Gikanga, Benson; Chen, Yufei; Stauch, Oliver B; Maa, Yuh-Fun

    2015-01-01

    Using bottom-mounted mixers, particularly those that are magnetically driven, is becoming increasingly common during the mixing process in pharmaceutical and biotechnology manufacturing because of their associated low risk of contamination, ease of use, and ability to accommodate low minimum mixing volumes. Despite these benefits, the impact of bottom-mounted mixers on biologic drug product is not yet fully understood and is scarcely reported. This study evaluated four bottom-mounted mixers to assess their impact on monoclonal antibody formulations. Changes in product quality (size variants, particles, and turbidity) and impact on process performance (sterile filtration) were evaluated after mixing. The results suggested that mixers that are designed to function with no contact between the impeller and the drive unit are the most favorable and gentle to monoclonal antibody molecules. Designs with contact or a narrow clearance tended to shear and grind the protein and resulted in high particle count in the liquid, which would subsequently foul a filter membrane during sterile filtration using a 0.22 μm pore size filter. Despite particle formation, increases in turbidity of the protein solution and protein aggregation/fragmentation were not detected. Further particle analysis indicated particles in the range of 0.2-2 μm are responsible for filter fouling. A small-scale screening model was developed using two types of magnetic stir bars mimicking the presence or absence of contact between the impeller and drive unit in the bottom-mounted mixers. The model is capable of differentiating the sensitivity of monoclonal antibody formulations to bottom-mounted mixers with a small sample size. This study fills an important gap in understanding a critical bioprocess unit operation. Mixing is an important unit operation in drug product manufacturing for compounding (dilution, pooling, homogenization, etc.). The current trend in adopting disposable bottom-mounted mixers has

  3. Common biology of craving across legal and illegal drugs - a quantitative meta-analysis of cue-reactivity brain response.

    Science.gov (United States)

    Kühn, Simone; Gallinat, Jürgen

    2011-04-01

    The present quantitative meta-analysis set out to test whether cue-reactivity responses in humans differ across drugs of abuse and whether these responses constitute the biological basis of drug craving as a core psychopathology of addiction. By means of activation likelihood estimation, we investigated the concurrence of brain regions activated by cue-induced craving paradigms across studies on nicotine, alcohol and cocaine addicts. Furthermore, we analysed the concurrence of brain regions positively correlated with self-reported craving in nicotine and alcohol studies. We found direct overlap between nicotine, alcohol and cocaine cue reactivity in the ventral striatum. In addition, regions of close proximity were observed in the anterior cingulate cortex (ACC; nicotine and cocaine) and amygdala (alcohol, nicotine and cocaine). Brain regions of concurrence in drug cue-reactivity paradigms that overlapped with brain regions of concurrence in self-reported craving correlations were found in the ACC, ventral striatum and right pallidum (for alcohol). This first quantitative meta-analysis on drug cue reactivity identifies brain regions underlying nicotine, alcohol and cocaine dependency, i.e. the ventral striatum. The ACC, right pallidum and ventral striatum were related to drug cue reactivity as well as self-reported craving, suggesting that this set of brain regions constitutes the core circuit of drug craving in nicotine and alcohol addiction. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  4. G‐LoSA: An efficient computational tool for local structure‐centric biological studies and drug design

    Science.gov (United States)

    2016-01-01

    Abstract Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G‐LoSA. G‐LoSA aligns protein local structures in a sequence order independent way and provides a GA‐score, a chemical feature‐based and size‐independent structure similarity score. Our benchmark validation shows the robust performance of G‐LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure‐centric comparative biology studies. In particular, G‐LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G‐LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer‐aided drug design. We hope that G‐LoSA can be a useful computational method for exploring interesting biological problems through large‐scale comparison of protein local structures and facilitating drug discovery research and development. G‐LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. PMID:26813336

  5. G-LoSA: An efficient computational tool for local structure-centric biological studies and drug design.

    Science.gov (United States)

    Lee, Hui Sun; Im, Wonpil

    2016-04-01

    Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G-LoSA. G-LoSA aligns protein local structures in a sequence order independent way and provides a GA-score, a chemical feature-based and size-independent structure similarity score. Our benchmark validation shows the robust performance of G-LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure-centric comparative biology studies. In particular, G-LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G-LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer-aided drug design. We hope that G-LoSA can be a useful computational method for exploring interesting biological problems through large-scale comparison of protein local structures and facilitating drug discovery research and development. G-LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. © 2016 The Protein Society.

  6. 77 FR 12311 - Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability

    Science.gov (United States)

    2012-02-29

    ...] Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability AGENCY: Food and... the availability of a guidance for industry entitled ``Size of Beads in Drug Products Labeled for... Evaluation and Research's (CDER's) current thinking on appropriate size ranges for beads in drug products...

  7. 76 FR 3144 - Draft Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability

    Science.gov (United States)

    2011-01-19

    ...] Draft Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``Size of Beads in Drug Products... Evaluation and Research's (CDER's) current thinking on appropriate size ranges for beads in drug products...

  8. Enhanced biological production off Chennai triggered by October 1999 super cyclone (Orissa)

    Digital Repository Service at National Institute of Oceanography (India)

    Madhu, N.V.; Maheswaran, P.A.; Jyothibabu, R.; Sunil, V.; Revichandran, C.; Balasubramanian, T.; Gopalakrishnan, T.C.; Nair, K.K.C.

    COMMUNICATIONS CURRENT SCIENCE, VOL. 82, NO. 12, 25 JUNE 2002 *For correspondence. (e - mail: madhu@niokochi.org) Enhanced biological production off Chennai triggered by October 1999 super cyclone (Orissa) N. V. Madhu*, P. A. Maheswaran, R... in the world?s oceans typically have duration of only a few days, but the physical and biological effects due to this perturbation can last up to several weeks 1 ? 4 . The integrated effect from these storm events has the potential to account for a...

  9. 75 FR 48179 - Comprehensive List of Guidance Documents at the Food and Drug Administration

    Science.gov (United States)

    2010-08-09

    ... Products (PDF - 57KB) 11/1994 Preparation of Investigational New Drug Products (Human and Animal) (PDF... Form FDA 356h ``Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use'' 5/10... Description Information for Human Plasma-Derived Biological Products, Animal Plasma or Serum-Derived Products...

  10. Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight.

    Science.gov (United States)

    Román Ivorra, José Andrés; Ivorra, José; Monte-Boquet, Emilio; Canal, Cristina; Oyagüez, Itziar; Gómez-Barrera, Manuel

    2016-01-01

    The objective was to assess the influence of patients' weight in the cost of rheumatoid arthritis treatment with biologic drugs used in first line after non-adequate response to methotrexate. Pharmaceutical and administration costs were calculated in two scenarios: non-optimization and optimization of intravenous (IV) vials. The retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service was used to obtain posology and weight data. The study time horizon was two years. Costs were expressed in 2013 euros. For an average 69kg-weighted patient the lowest cost corresponded to abatacept subcutaneous (SC ABA) (€21,028.09) in the scenario without IV vials optimization and infliximab (IFX) (€20,779.29) with optimization. Considering patients' weight in the scenario without IV vials optimization infliximab (IFX) was the least expensive drug in patients ranged 45-49kg, IV ABA in 50-59kg and SC ABA in patients over 60kg. With IV vials optimization IFX was the least expensive drug in patients under 69kg and SC ABA over 70kg. Assuming comparable effectiveness of biological drugs, patient's weight is a variable to consider, potentials savings could reach €20,000 in two years. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. The year's new drugs & biologics, 2017, part II - News that shaped the industry in 2017.

    Science.gov (United States)

    Graul, A I; Dulsat, C; Pina, P; Tracy, M; D'Souza, P

    2018-02-01

    This eagle's-eye overview of the drug industry in 2017 provides insight into some of last year's top stories, including the growing opioid crisis affecting the U.S. and other developed countries and the 2017-2018 influenza epidemic, with a spotlight on the need for a universal flu vaccine. As in previous years, we also review orphan drug development, new agency-supported programs such as PRIME and RMAT, pipeline attrition and drug pricing, as well as pharma/biotech mergers and acquisitions of note. Finally, we take a glimpse into the crystal ball to anticipate the new drugs that will be approved in 2018. Copyright 2018 Clarivate Analytics.

  12. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

    Directory of Open Access Journals (Sweden)

    Jane P. F. Bai

    2017-03-01

    Full Text Available Developing drugs to treat the toxic effects of lethal toxin (LT and edema toxin (ET produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.

  13. Persistence, switch rates, drug consumption and costs of biological treatment of rheumatoid arthritis: an observational study in Italy

    Directory of Open Access Journals (Sweden)

    Degli Esposti L

    2016-12-01

    Full Text Available Luca Degli Esposti,1 Ennio Giulio Favalli,2 Diego Sangiorgi,1 Roberta Di Turi,3 Giuseppina Farina,4 Marco Gambera,5 Roberto Ravasio,6 1CliCon S.r.l. – Health, Economics & Outcomes Research, Ravenna, 2Department of Rheumatology, Istituto Ortopedico Gaetano Pini, Milan, 3Local Pharmaceutical and Supplementary Assistance Unit, Roma Local Health Authority D, Rome, 4Internal Management Control Unit – Pharmaceutical Spending Control Sector, Caserta Local Health Authority, Caserta, 5Local Pharmaceutical Service, Bergamo Local Health Authority, Bergamo, 6Health Publishing & Services Srl, Milan, Italy Objectives: The aim of this analysis was to provide an estimate of drug utilization indicators (persistence, switch rate and drug consumption on biologics and the corresponding costs (drugs, admissions and specialist care incurred by the Italian National Health Service in the management of adult patients with rheumatoid arthritis (RA.Methods: We conducted an observational retrospective cohort analysis using the administrative databases of three local health units. We considered all patients aged ≥18 years with a diagnosis of RA and at least one biologic drug prescription between January 2010 and December 2012 (recruitment period. Persistence was defined as maintenance over the last 3 months of the follow-up period of the same biological therapy administered at the index date. A switch was defined as the presence of a biological therapy other than that administered at the index date during the last 3 months of the follow-up period. Hospital admissions (with a diagnosis of RA or other RA-related diagnoses, specialist outpatient services, instrumental diagnostics and pharmaceutical consumption were assessed.Results: The drug utilization analysis took into account only biologics with at least 90 patients on treatment at baseline (adalimumab n=144, etanercept n=236 and infliximab n=94. In each year, etanercept showed better persistence with initial

  14. The synergistic use of computation, chemistry and biology to discover novel peptide-based drugs: the time is right.

    Science.gov (United States)

    Audie, J; Boyd, C

    2010-01-01

    The case for peptide-based drugs is compelling. Due to their chemical, physical and conformational diversity, and relatively unproblematic toxicity and immunogenicity, peptides represent excellent starting material for drug discovery. Nature has solved many physiological and pharmacological problems through the use of peptides, polypeptides and proteins. If nature could solve such a diversity of challenging biological problems through the use of peptides, it seems reasonable to infer that human ingenuity will prove even more successful. And this, indeed, appears to be the case, as a number of scientific and methodological advances are making peptides and peptide-based compounds ever more promising pharmacological agents. Chief among these advances are powerful chemical and biological screening technologies for lead identification and optimization, methods for enhancing peptide in vivo stability, bioavailability and cell-permeability, and new delivery technologies. Other advances include the development and experimental validation of robust computational methods for peptide lead identification and optimization. Finally, scientific analysis, biology and chemistry indicate the prospect of designing relatively small peptides to therapeutically modulate so-called 'undruggable' protein-protein interactions. Taken together a clear picture is emerging: through the synergistic use of the scientific imagination and the computational, chemical and biological methods that are currently available, effective peptide therapeutics for novel targets can be designed that surpass even the proven peptidic designs of nature.

  15. Biological waste by-production costs in forest management and possibilities for their reduction

    Directory of Open Access Journals (Sweden)

    Jiří Kadlec

    2004-01-01

    Full Text Available Biological wastes in forestry were observed from view of their by-production in silvicultural and logging operations. There were identified points where biological waste was produced in this paper, waste costs ratio for silvicultural and logging operations and were made suggestions for reduction of these costs. Biological waste costs give 34.4% of total costs of silvicultural operations and 30% of total costs of logging operations. Natural regeneration and minor forest produce operations are opportunities for reduction of these costs.

  16. Analysis of Investigational Drugs in Biological Fluids - Method Development and Analysis of Pre-Clinical Samples

    National Research Council Canada - National Science Library

    Lin, Emil

    2001-01-01

    ... (and metabolites and artesunate). Work on routine analyses of biological specimens during this period was performed for studies that required determination of concentrations of artelinic acid, choroquine...

  17. Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR®/ABASAGLAR®) approved in the European Union.

    Science.gov (United States)

    Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

    2017-08-01

    Basaglar ® /Abasaglar ® (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus ® (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Colchicine in Pericardial Disease: from the Underlying Biology and Clinical Benefits to the Drug-Drug Interactions in Cardiovascular Medicine.

    Science.gov (United States)

    Schenone, Aldo L; Menon, Venu

    2018-06-14

    This is an in-depth review on the mechanism of action, clinical utility, and drug-drug interactions of colchicine in the management of pericardial disease. Recent evidence about therapeutic targets on pericarditis has demonstrated that NALP3 inflammasome blockade is the cornerstone in the clinical benefits of colchicine. Such benefits extend from acute and recurrent pericarditis to transient constriction and post-pericardiotomy syndrome. Despite the increased utilization of colchicine in cardiovascular medicine, safety concerns remains unsolved regarding the long-term use of colchicine in the cardiac patient. Moreover, recent evidence has demonstrated that numerous cardiovascular medications, ranging from antihypertensive medication to antiarrhythmics, are known to interact with the CYP3A4 and/or P-gp system increasing the toxicity potential of colchicine. The use of adjunctive colchicine in the management of inflammatory pericardial diseases is standard of care in current practice. It is advised that a careful medication reconciliation with emphasis on pharmacokinetic is completed before prescribing colchicine in order to avoid harmful interaction by finding an alternative regimen or adjusting colchicine dosing.

  19. Potential for widespread application of biological control of stored-product pests

    DEFF Research Database (Denmark)

    Hansen, Lise Stengaard

    2007-01-01

    Biological control of stored product pests has substantial potential in Europe". This is essentially the conclusion of the activities of a European working group funded by the COST system, an intergovernmental networking system. Working group 4 of COST action 842 (2000-2005) focussed on biologica...... for these situations will contribute to ensuring that stored food products are protected from insect and mite pests using techniques that are safe for consumers, workers and the environment.......Biological control of stored product pests has substantial potential in Europe". This is essentially the conclusion of the activities of a European working group funded by the COST system, an intergovernmental networking system. Working group 4 of COST action 842 (2000-2005) focussed on biological...

  20. Recent progress in synthetic biology for microbial production of C3-C10 alcohols

    Directory of Open Access Journals (Sweden)

    Edna N. Lamsen

    2012-06-01

    Full Text Available The growing need to address current energy and environmental problems has sparked an interest in developing improved biological methods to produce liquid fuels from renewable sources. While microbial ethanol production is well established, higher chain alcohols possess chemical properties that are more similar to gasoline. Unfortunately, these alcohols (except 1-butanol are not produced efficiently in natural microorganisms, and thus economical production in industrial volumes remains a challenge. Synthetic biology, however, offers additional tools to engineer synthetic pathways in user-friendly hosts to help increase titers and productivity of these advanced biofuels. This review concentrates on recent developments in synthetic biology to produce higher-chain alcohols as viable renewable replacements for traditional fuel.

  1. Overview of Skin Whitening Agents: Drugs and Cosmetic Products

    Directory of Open Access Journals (Sweden)

    Céline Couteau

    2016-07-01

    Full Text Available Depigmentation and skin lightening products, which have been in use for ages in Asian countries where skin whiteness is a major esthetic criterion, are now also highly valued by Western populations, who expose themselves excessively to the sun and develop skin spots as a consequence. After discussing the various possible mechanisms of depigmentation, the different molecules that can be used as well as the status of the products containing them will now be presented. Hydroquinone and derivatives thereof, retinoids, alpha- and beta-hydroxy acids, ascorbic acid, divalent ion chelators, kojic acid, azelaic acid, as well as diverse herbal extracts are described in terms of their efficacy and safety. Since a genuine effect (without toxic effects is difficult to obtain, prevention by using sunscreen products is always preferable.

  2. Zebrafish as a visual and dynamic model to study the transport of nanosized drug delivery systems across the biological barriers.

    Science.gov (United States)

    Li, Ye; Miao, Xiaoqing; Chen, Tongkai; Yi, Xiang; Wang, Ruibing; Zhao, Haitao; Lee, Simon Ming-Yuen; Wang, Xueqing; Zheng, Ying

    2017-08-01

    With the wide application of nanotechnology to drug delivery systems, a simple, dynamic and visual in vivo model for high-throughput screening of novel formulations with fluorescence markers across biological barriers is desperately needed. In vitro cell culture models have been widely used, although they are far from a complimentary in vivo system. Mammalian animal models are common predictive models to study transport, but they are costly and time consuming. Zebrafish (Danio rerio), a small vertebrate model, have the potential to be developed as an "intermediate" model for quick evaluations. Based on our previously established coumarin 6 nanocrystals (C6-NCs), which have two different sizes, the present study investigates the transportation of C6-NCs across four biological barriers, including the chorion, blood brain barrier (BBB), blood retinal barrier (BRB) and gastrointestinal (GI) barrier, using zebrafish embryos and larvae as in vivo models. The biodistribution and elimination of C6 from different organs were quantified in adult zebrafish. The results showed that compared to 200nm C6-NCs, 70nm C6-NCs showed better permeability across these biological barriers. A FRET study suggested that intact C6-NCs together with the free dissolved form of C6 were absorbed into the larval zebrafish. More C6 was accumulated in different organs after incubation with small sized NCs via lipid raft-mediated endocytosis in adult zebrafish, which is consistent with the findings from in vitro cell monolayers and the zebrafish larvae model. C6-NCs could be gradually eliminated in each organ over time. This study demonstrated the successful application of zebrafish as a simple and dynamic model to simultaneously assess the transport of nanosized drug delivery systems across several biological barriers and biodistribution in different organs, especially in the brain, which could be used for central nervous system (CNS) drug and delivery system screening. Copyright © 2017 Elsevier B

  3. 21 CFR 352.52 - Labeling of sunscreen drug products.

    Science.gov (United States)

    2010-04-01

    ... sunburn [bullet] higher SPF gives more sunburn protection”. 1 See § 201.66(b)(4) of this chapter. (ii) For... “minimum”) “protection against” (select one of the following: “sunburn” or “sunburn and tanning”)], or “[bullet] for skin that sunburns minimally”. (ii) For products that provide an SPF of 12 to under 30...

  4. 21 CFR 357.150 - Labeling of anthelmintic drug products.

    Science.gov (United States)

    2010-04-01

    ... “pinworm treatment.” (b) Indication. The labeling of the product states, under the heading “Indication,” the following: “For the treatment of pinworms.” Other truthful and nonmisleading statements... repeat treatment unless directed by a doctor. When one individual in a household has pinworms, the entire...

  5. 21 CFR 349.78 - Labeling of eyewash drug products.

    Science.gov (United States)

    2010-04-01

    ...,” “air pollutants (smog or pollen),” or “chlorinated water”). (2) “For” (select one of the following...),” or “chlorinated water”). (c) Warnings. In addition to the warnings in § 349.50, the labeling of the... products intended for use with an eyecup. Rinse cup with clean water immediately before each use. Avoid...

  6. Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase

    Directory of Open Access Journals (Sweden)

    Dragic Vukomanovic

    2017-01-01

    Full Text Available Carbon monoxide (CO formed endogenously is considered to be cytoprotective, and the vast majority of CO formation is attributed to the degradation of heme by heme oxygenases-1 and -2 (HO-1, HO-2. Previously, we observed that brain microsomes containing HO-2 produced many-fold more CO in the presence of menadione and its congeners; herein we explored these observations further. We determined the effects of various drugs on CO production of rat brain microsomes and recombinant human cytochrome P450 reductase (CPR; CO was measured by gas chromatography with reductive detection. Brain microsomes of Sprague-Dawley rats or recombinant human cytochrome P450 reductase (CPR were incubated with NADPH and various drugs in closed vials in phosphate buffer at pH 7.4 and 37°C. After 15 minutes, the reaction was stopped by cooling in dry ice, and the headspace gas was analyzed for CO production using gas chromatography with reductive (mercuric oxide detection. We observed drug-enhanced CO production in the presence of both microsomes and recombinant CPR alone; the presence of HO was not required. A range of structurally diverse drugs were capable of amplifying this CO formation; these molecules had structures consistent with redox cycling capability. The addition of catalase to a reaction mixture, that contained activating drugs, inhibited the production of CO. Drug-enhanced CO formation can be catalyzed by CPR. The mechanism of CPR activation was not through classical drug-receptor mediation. Redox cycling may be involved in the drug-induced amplification of CO production by CPR through the production of reactive oxygen species.

  7. Biological basis of sex differences in drug abuse: preclinical and clinical studies.

    Science.gov (United States)

    Lynch, Wendy J; Roth, Megan E; Carroll, Marilyn E

    2002-11-01

    The recent focus on drug abuse in women has brought attention to numerous differences between women and men. In this review, we discuss both preclinical and clinical findings of sex differences in drug abuse as well as mechanisms that may underlie these differences. Recent evidence suggests that the progression to dependence and abuse may differ between women and men; thus, different prevention and treatment strategies may be required. Similar sex differences in drug sensitivity and self-administration have been reported in laboratory animal studies. Females appear to be more vulnerable than males to the reinforcing effects of psychostimulants, opiates, and nicotine during many phases of the addiction process (e.g. acquisition, maintenance, dysregulation-escalation, relapse). Male and female animals differ in their behavioral, neurological, and pharmacological responses to drugs. Although the role of sex in the mechanisms of drug action remains unclear, preclinical and clinical studies indicate that ovarian hormones, particularly estrogen, play a role in producing sex differences in drug abuse. Future research is necessary to provide information on how to design more effective drug abuse treatment programs and resources that are sex specific.

  8. A field survey of chemicals and biological products used in shrimp farming

    International Nuclear Information System (INIS)

    Graeslund, S.; Holmstroem, K.; Wahlstroem, A.

    2003-01-01

    This study documented the use of chemicals and biological products in marine and brackish water shrimp farming in Thailand, the world's top producer of farmed shrimp. Interviews were conducted with 76 shrimp farmers in three major shrimp producing regions, the eastern Gulf coast, the southern Gulf coast and the Andaman coast area. Farmers in the study used on average 13 different chemicals and biological products. The most commonly used products were soil and water treatment products, pesticides and disinfectants. Farmers in the southern Gulf coast area used a larger number of products than farmers in the other two areas. In the study, the use of more than 290 different chemicals and biological products was documented. Many of the pesticides, disinfectants and antibiotics used by the farmers could have negative effects on the cultured shrimps, cause a risk for food safety, occupational health, and/or have negative effects on adjacent ecosystems. Manufacturers and retailers of the products often neglected to provide farmers with necessary information regarding active ingredient and relevant instructions for safe and efficient use

  9. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    Science.gov (United States)

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  10. Genome Analysis of the First Extensively Drug-Resistant (XDR Mycobacterium tuberculosis in Malaysia Provides Insights into the Genetic Basis of Its Biology and Drug Resistance.

    Directory of Open Access Journals (Sweden)

    Chee Sian Kuan

    Full Text Available The outbreak of extensively drug-resistant tuberculosis (XDR-TB has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia.

  11. [Alternative biological materials to detect prenatal exposure to drugs of abuse in the third trimester of pregnancy].

    Science.gov (United States)

    García-Serra, J; Ramis, J; Simó, S; Joya, X; Pichini, S; Vall, O; García-Algar, O

    2012-11-01

    Detection of prenatal drug abuse exposure is essential to ensure an appropriate monitoring of affected children. A maternal questionnaire is not an efficient screening tool. The usefulness of maternal hair and meconium as biological materials to assess this exposure has been described in last few years. The aim of this study was to compare both these alternative biological materials for prenatal drug exposure detection in the third trimester of pregnancy, in order to assess its use as a screening tool. Between January and March 2010, samples of maternal hair and meconium from 107 mother-infant dyads were collected in Can Misses Hospital, Ibiza. The presence of opiates, cocaine, cannabis, and amphetamines, was determined in both materials, using standard chromatographic techniques. Maternal hair analysis showed a 15.9% positivity for drugs of abuse (17 cases): 11 cannabis, 7 cocaine, 1 cannabis and ecstasy, and 1 cannabis and cocaine. Only one mother reported cannabis consumption and another one, cocaine. Of the 7 cocaine positive cases in hair, 6 were confirmed in meconium analysis, while of 11 cannabis positive cases, only 3 were confirmed in meconium. Two different consumer profiles were defined: cocaine consumers and cannabis consumers (with only 2 cases of multiple drug use). The highest level of cocaine ever published was detected (1.582ng/g) in one case. This study reveals a high prevalence of drug abuse in this cohort during pregnancy. Improved screening methods may optimize prevention and monitoring of exposed infants. Maternal hair seems to be more sensitive than meconium to detect prenatal exposure to cannabis during the third trimester, so it might become a good screening tool. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  12. New approaches to estimation of peat deposits for production of biologically active compounds

    Science.gov (United States)

    Stepchenko, L. M.; Yurchenko, V. I.; Krasnik, V. G.; Syedykh, N. J.

    2009-04-01

    It is known, that biologically active preparations from peat increase animals productivity as well as resistance against stress-factors and have adaptogeneous, antioxidant, immunomodulative properties. Optymal choice of peat deposits for the production of biologically active preparations supposes the detailed comparative analysis of peat properties from different deposits. For this the cadastre of peat of Ukraine is developed in the humic substances laboratory named after prof. Khristeva L.A. (Dnipropetrovsk Agrarian University, Ukraine). It based on the research of its physical and chemical properties, toxicity and biological activity, and called Biocadastre. The Biocadastre is based on the set of parameters, including the descriptions of physical and chemical properties (active acidity, degree of decomposition, botanical composition etc.), toxicity estimation (by parabyotyc, infusorial, inhibitor and other tests), biological activity indexes (growth-promoting, antioxidative, adaptogeneous, immunomodulative antistress and other actions). The blocks of Biocadastre indexes are differentiated, taking into account their use for creation the preparations for vegetable, animals and microorganisms. The Biocadastre will allow to choose the peat deposits, most suitable for the production of different biologically active preparations, both wide directed and narrow spectrum of action, depending on application fields (medicine, agriculture, veterinary medicine, microbiological industry, balneology, cosmetology).

  13. A consilience model to describe N2O production during biological N removal

    DEFF Research Database (Denmark)

    Domingo Felez, Carlos; Smets, Barth F.

    2016-01-01

    Nitrous oxide (N2O), a potent greenhouse gas, is produced during biological nitrogen conversion in wastewater treatment operations. Complex mechanisms underlie N2O production by autotrophic and heterotrophic organisms, which continue to be unravelled. Mathematical models that describe nitric oxide...... (NO) and N2O dynamics have been proposed. Here, a first comprehensive model that considers all relevant NO and N2O production and consumption mechanisms is proposed. The model describes autotrophic NO production by ammonia oxidizing bacteria associated with ammonia oxidation and with nitrite reduction......, followed by NO reduction to N2O. It also considers NO and N2O as intermediates in heterotrophic denitrification in a 4-step model. Three biological NO and N2O production pathways are accounted for, improving the capabilities of existing models while not increasing their complexity. Abiotic contributions...

  14. Biological activities of Agave by-products and their possible applications in food and pharmaceuticals.

    Science.gov (United States)

    López-Romero, Julio Cesar; Ayala-Zavala, Jesús Fernando; González-Aguilar, Gustavo Adolfo; Peña-Ramos, Etna Aida; González-Ríos, Humberto

    2018-05-01

    Agave leaves are considered a by-product of alcoholic beverage production (tequila, mezcal and bacanora) because they are discarded during the production process, despite accounting for approximately 50% of the total plant weight. These by-products constitute a potential source of Agave extracts rich in bioactive compounds, such as saponins, phenolic compounds and terpenes, and possess different biological effects, as demonstrated by in vitro and in vivo tests (e.g. antimicrobial, antifungal, antioxidant, anti-inflammatory, antihypertensive, immunomodulatory, antiparasitic and anticancer activity). Despite their positive results in biological assays, Agave extracts have not been widely evaluated in food systems and pharmaceutical areas, and these fields represent a potential route to improve the usage of Agave plants as food additives and agents for treating medical diseases. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  15. 21 CFR 211.110 - Sampling and testing of in-process materials and drug products.

    Science.gov (United States)

    2010-04-01

    ... PHARMACEUTICALS Production and Process Controls § 211.110 Sampling and testing of in-process materials and drug... capsule weight variation; (2) Disintegration time; (3) Adequacy of mixing to assure uniformity and... production process, e.g., at commencement or completion of significant phases or after storage for long...

  16. The Use of Alternative Raw Material in Production of Pastry Products as a Progressive Direction in Creating the Products of High Biological Value

    Directory of Open Access Journals (Sweden)

    Janа Bachinska

    2017-02-01

    Full Text Available This paper examines the impact of the use of alternative vegetable raw materials in the manufacture of pastry products with high biological value; it presents the results of evaluation of commodity of the developed products and compares them with the main samples presented in Kharkiv trade network. The feasibility of using a mixture of fiber and pumpkin seeds in the technology of pastry production to extend the range of confectionery products of high biological value and products with reduced calories has been proved. Adding the mixture of fiber and pumpkin seeds to biscuits and cakes positively affected the chemical composition of the ready-made product, saturating it with useful and necessary to human body mineral elements, vitamins, dietary fiber.

  17. Photoreactivity of biologically active compounds. VIII. Photosensitized polymerization of lens proteins by antimalarial drugs in vitro.

    Science.gov (United States)

    Kristensen, S; Wang, R H; Tønnesen, H H; Dillon, J; Roberts, J E

    1995-02-01

    The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds cause dermal and ocular toxic reactions that may be light induced. The in vitro photopolymerization of calf lens proteins in the presence of antimalarial drugs was studied as part of a screening of the photochemical properties and phototoxic capabilities of these compounds. The pseudo-first-order rate constant for the reaction was calculated, and related to the amount of light absorbed by the compounds in order to determine the relative photosensitizing effect of each drug. The reaction mechanisms were evaluated by adding a variety of quenchers to the reaction medium during irradiation. Based on the results obtained in this study and previous knowledge about the pharmacokinetic behavior of these compounds, several of the drugs investigated have to be considered as potential photosensitizers in the human lens, the retina and the skin.

  18. Application of synthetic biology for production of chemicals in yeast Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Borodina, Irina; Li, Mingji

    2015-01-01

    Synthetic biology and metabolic engineering enable generation of novel cell factories that efficiently convert renewable feedstocks into biofuels, bulk, and fine chemicals, thus creating the basis for biosustainable economy independent on fossil resources. While over a hundred proof...... biology has the potential to bring down this cost by improving our ability to predictably engineer biological systems. This review highlights synthetic biology applications for design, assembly, and optimization of non-native biochemical pathways in baker's yeast Saccharomyces cerevisiae. We describe......-of-concept chemicals have been made in yeast, only a very small fraction of those has reached commercial-scale production so far. The limiting factor is the high research cost associated with the development of a robust cell factory that can produce the desired chemical at high titer, rate, and yield. Synthetic...

  19. Special forest products: integrating social, economic, and biological considerations into ecosystem management.

    Science.gov (United States)

    R. Molina; N. Vance; J.F. Weigand; D. Pilz; M.P. Amaranthus

    1997-01-01

    Throughout history, forests have provided a wealth of beneficial and essential products ranging from foods and medicines to building materials. Ancient pharmacopoeias list myriad forest plants and fungi for treating various ailments. Many of these ancient remedies have evolved and continue to evolve into the important drugs of modern medicine. Use of diverse forest...

  20. SYNBIOCHEM Synthetic Biology Research Centre, Manchester – A UK foundry for fine and speciality chemicals production

    Directory of Open Access Journals (Sweden)

    Le Feuvre RA

    2016-12-01

    Full Text Available The UK Synthetic Biology Research Centre, SYNBIOCHEM, hosted by the Manchester Institute of Biotechnology at the University of Manchester is delivering innovative technology platforms to facilitate the predictable engineering of microbial bio-factories for fine and speciality chemicals production. We provide an overview of our foundry activities that are being applied to grand challenge projects to deliver innovation in bio-based chemicals production for industrial biotechnology.

  1. BICLUSTERING METHODS FOR RE-ORDERING DATA MATRICES IN SYSTEMS BIOLOGY, DRUG DISCOVERY AND TOXICOLOGY

    Directory of Open Access Journals (Sweden)

    Christodoulos A. Floudas

    2010-12-01

    Full Text Available Biclustering has emerged as an important problem in the analysis of gene expression data since genes may only jointly respond over a subset of conditions. Many of the methods for biclustering, and clustering algorithms in general, utilize simplified models or heuristic strategies for identifying the ``best'' grouping of elements according to some metric and cluster definition and thus result in suboptimal clusters. In the first part of the presentation, we present a rigorous approach to biclustering, OREO, which is based on the Optimal RE-Ordering of the rows and columns of a data matrix so as to globally minimize the dissimilarity metric [1,2]. The physical permutations of the rows and columns of the data matrix can be modeled as either a network flow problem or a traveling salesman problem. The performance of OREO is tested on several important data matrices arising in systems biology to validate the ability of the proposed method and compare it to existing biclustering and clustering methods. In the second part of the talk, we will focus on novel methods for clustering of data matrices that are very sparse [3]. These types of data matrices arise in drug discovery where the x- and y-axis of a data matrix can correspond to different functional groups for two distinct substituent sites on a molecular scaffold. Each possible x and y pair corresponds to a single molecule which can be synthesized and tested for a certain property, such as percent inhibition of a protein function. For even moderate size matrices, synthesizing and testing a small fraction of the molecules is labor intensive and not economically feasible. Thus, it is of paramount importance to have a reliable method for guiding the synthesis process to select molecules that have a high probability of success. In the second part of the presentation, we introduce a new strategy to enable efficient substituent reordering and descriptor-free property estimation. Our approach casts

  2. Effectiveness of biologic and non-biologic antirheumatic drugs on anaemia markers in 153,788 patients with rheumatoid arthritis: New evidence from real-world data.

    Science.gov (United States)

    Paul, Sanjoy Ketan; Montvida, Olga; Best, Jennie H; Gale, Sara; Pethoe-Schramm, Attila; Sarsour, Khaled

    2018-02-01

    To evaluate the impact of treatment with disease-modifying antirheumatic drugs (DMARDs), including IL-6 receptor inhibitor tocilizumab (TCZ), on anaemia markers in patients with rheumatoid arthritis. Using the Centricity Electronic Medical Records from USA, patients with rheumatoid arthritis diagnosed between January 2000 and April 2016, who initiated TCZ (n = 3732); tofacitinib (TOFA, n = 3126); other biologic DMARD (obDMARD, n = 55,964); or other non-biologic DMARD (onbDMARD, n = 91,236) were identified. Changes in haemoglobin (Hb) and haematocrit (Hct) over 2 years of treatment initiation were evaluated, adjusting and balancing for confounders. Mean (95% CI) adjusted increase in Hb and Hct levels at 24 months in TCZ group were 0.23g/dL (0.14, 0.42) and 0.96% (0.41, 1.52) respectively. Among patients with anaemia in the TCZ group, Hb and Hct increased significantly by 0.72g/dL and 2.06%, respectively. Patients in the TCZ group were 86% (95% CI of OR: 1.43, 2.00) more likely to increase Hb ≥ 1g/dL compared to the other groups combined. No clinically significant changes in Hb were observed in the other groups. The obDMARD group demonstrated lower Hct increase than TCZ group, while no significant changes were observed in the remaining groups. Compared to those who initiated TCZ therapy after 1 year of diagnosis of rheumatoid arthritis, those who initiated earlier were 95% (OR = 1.95; 95% CI: 1.19, 3.21; p < 0.001) more likely to increase Hb within 6 months. This real-world study suggests significant increase in Hb and Hct levels after TCZ therapy in anaemic and non-anaemic patients with rheumatoid arthritis, compared with other biologic and non-biologic DMARDs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Designing structural features of novel benznidazole-loaded cationic nanoparticles for inducing slow drug release and improvement of biological efficacy.

    Science.gov (United States)

    Dos Santos-Silva, Alaine M; de Caland, Lilia B; de S L Oliveira, Ana Luíza C; de Araújo-Júnior, Raimundo F; Fernandes-Pedrosa, Matheus F; Cornélio, Alianda Maira; da Silva-Júnior, Arnóbio A

    2017-09-01

    Several polymers have been investigated for producing cationic nanocarriers due to their ability to cross biological barriers. Polycations such as copolymers of polymethylmethacrylate are highlighted due to their biocompatibility and low toxicity. The purpose of this study was to produce small and narrow-sized cationic nanoparticles able to overcome cell membranes and improve the biological activity of benznidazole (BNZ) in normal and cancer cells. The effect of composition and procedure parameters of the used emulsification-solvent evaporation method were controlled for this purpose. The experimental approach included particle size, polydispersity index, zeta potential, atomic force microscopy (AFM), attenuated total reflectance Fourier transforms infrared spectroscopy (ATR- FTIR), drug loading efficiency, and physical stability assays. Spherical and stable (over six weeks) sub 150nm cationic nanoparticles were optimized, with the encapsulation efficiency >80%. The used drug/copolymer ratio modulated the slow drug release, which was adjusted by the parabolic diffusion mathematical model. In addition, the ability of the cationic nanoparticles improve the BNZ uptake in the normal kidney cells (HEK 293) and the human colorectal cancer cells (HT 29) demonstrate that this novel BNZ-loaded cationic has great potential as a chemotherapeutic application of benznidazole. Copyright © 2017. Published by Elsevier B.V.

  4. Biological sludge solubilisation for reduction of excess sludge production in wastewater treatment process.

    Science.gov (United States)

    Yamaguchi, T; Yao, Y; Kihara, Y

    2006-01-01

    A novel sludge disintegration system (JFE-SD system) was developed for the reduction of excess sludge production in wastewater treatment plants. Chemical and biological treatments were applied to disintegrate excess sludge. At the first step, to enhance biological disintegration, the sludge was pretreated with alkali. At the second step, the sludge was disintegrated by biological treatment. Many kinds of sludge degrading microorganisms integrated the sludge. The efficiency of the new sludge disintegration system was confirmed in a full-scale experiment. The JFE-SD system reduced excess sludge production by approximately 50% during the experimental period. The quality of effluent was kept at quite a good level. Economic analysis revealed that this system could significantly decrease the excess sludge treatment cost.

  5. Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence.

    Science.gov (United States)

    Collamati, Agnese; Martone, Anna Maria; Poscia, Andrea; Brandi, Vincenzo; Celi, Michela; Marzetti, Emanuele; Cherubini, Antonio; Landi, Francesco

    2016-02-01

    The use of medication with anticholinergic properties is widespread among older subjects. Many drugs of common use such as antispasmodics, bronchodilators, antiarrhythmics, antihistamines, anti-hypertensive drugs, antiparkinson agents, skeletal muscle relaxants, and psychotropic drugs have been demonstrated to have an anticholinergic activity. The most frequent adverse effects are dry mouth, nausea, vomiting, constipation, abdominal pain, urinary retention, blurred vision, tachycardia and neurologic impairment such as confusion, agitation and coma. A growing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment in the elderly population. However, the morbidity and management issues associated with unwanted anticholinergic activity are underestimated and frequently overlooked. Moreover, their possible relation with specific negative outcome in the elderly population is still not firmly established. The aim of the present review was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older persons. We searched PubMed and Cochrane combining the search terms "anticholinergic", "delirium", "cognitive impairment", "falls", "mortality" and "discontinuation". Medicines with anticholinergic properties may increase the risks of functional and cognitive decline, morbidity, institutionalization and mortality in older people. However, such evidences are still not conclusive probably due to possible confounding factors. In particular, more studies are needed to investigate the effects of discontinuation of drug with anticholinergic properties. Overall, minimizing anticholinergic burden should always be encouraged in clinical practice to improve short-term memory, confusion and delirium, quality of life and daily functioning.

  6. Clinical utility of therapeutic drug monitoring in biological disease modifying anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative review.

    Science.gov (United States)

    Van Herwaarden, Noortje; Van Den Bemt, Bart J F; Wientjes, Maike H M; Kramers, Cornelis; Den Broeder, Alfons A

    2017-08-01

    Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient. Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity. Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.

  7. Probes & Drugs portal: an interactive, open data resource for chemical biology

    Czech Academy of Sciences Publication Activity Database

    Škuta, Ctibor; Popr, M.; Muller, Tomáš; Jindřich, Jindřich; Kahle, Michal; Sedlák, David; Svozil, Daniel; Bartůněk, Petr

    2017-01-01

    Roč. 14, č. 8 (2017), s. 758-759 ISSN 1548-7091 R&D Projects: GA MŠk LO1220 Institutional support: RVO:68378050 Keywords : bioactive compound, ,, * chemical probe * chemical biology * portal Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 25.062, year: 2016

  8. Manufacturing of curd products of increased biological value for the elderly from dried components.

    Science.gov (United States)

    Zabodalova, Ludmila A; Belozerova, Maria S; Evstigneeva, Tatiana N

    2018-01-01

    In recent years, the number of elderly people has increased, and the diseases that arise in old age are associated, amongst other factors, with malnutrition. In the elderly, the need for primary nutrients and energy changes, so the development of food products intended for this particular group of people is becom- ing increasingly important. The purpose of this research is to work out the composition of and technology for producing low-fat curd products from raw milk and vegetable components. The developed products can be used for their gerodietetic properties, because nutritional and energy needs in the elderly were taken into account when designing the product. The curd product was manufactured from skimmed dried milk (SDM), soy isolate protein (SIP) and spelt grain. Optimal conditions for the recombination of SIP were determined. The influence of mass fraction of SIP on the properties of the clot and the end product was studied. The degree of dispersion of the grain component was determined, from the organoleptic evaluation of samples of the mixture, and the optimum method of addition was chosen. The method of adding cooked spelt into the clot after pressing was chosen. Harrington’s generalized desirability function was used for the calculation of the optimum mass frac- tion of the grain component in the end product. The formulation and technology for a curd product based on dry ingredients were determined. The amino acid composition and content of essential components in the developed product were determined, and the biological and nutritional value were calculated. The use of dry ingredients for the production of a curd product makes it possible to manufac- ture the product in the absence of raw milk. The formulation of the product is designed taking into account the needs of the body in old age. The incorporation of spelt increases the biological value of the curd product to 81.5%.

  9. Synthetic biology approaches for the production of plant metabolites in unicellular organisms.

    Science.gov (United States)

    Moses, Tessa; Mehrshahi, Payam; Smith, Alison G; Goossens, Alain

    2017-07-10

    Synthetic biology is the repurposing of biological systems for novel objectives and applications. Through the co-ordinated and balanced expression of genes, both native and those introduced from other organisms, resources within an industrial chassis can be siphoned for the commercial production of high-value commodities. This developing interdisciplinary field has the potential to revolutionize natural product discovery from higher plants, by providing a diverse array of tools, technologies, and strategies for exploring the large chemically complex space of plant natural products using unicellular organisms. In this review, we emphasize the key features that influence the generation of biorefineries and highlight technologies and strategic solutions that can be used to overcome engineering pitfalls with rational design. Also presented is a succinct guide to assist the selection of unicellular chassis most suited for the engineering and subsequent production of the desired natural product, in order to meet the global demand for plant natural products in a safe and sustainable manner. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Biological productivity and potential resources of the exclusive economic zone (EEZ) of India

    Digital Repository Service at National Institute of Oceanography (India)

    Goswami, S.C.

    An assessment of the biological production and the potential fishery resources has been made based on the data collected over a period of 15 years (1976-1991). The entire Exclusive Economic Zone (EEZ), measuring 2.02 million km sup(2) was divided...

  11. 9 CFR 113.53 - Requirements for ingredients of animal origin used for production of biologics.

    Science.gov (United States)

    2010-01-01

    ... biological product shall be tested as prescribed in this section by the licensee or a laboratory acceptable to VS. Results of all tests shall be recorded by the testing laboratory and made a part of the... diluent sufficient to fill a centrifuge angle head. After centrifuging for 1 hour at 80,000×g, the pellet...

  12. Biological control of Alternaria radicina in seed production of carrots with Ulocladium atrum

    NARCIS (Netherlands)

    Köhl, J.; Langerak, C.J.; Meekes, E.T.M.; Molhoek, W.M.L.

    2004-01-01

    Black rot of carrots is caused by seed-borne Alternaria radicina. Biological control of seed infestation by treatments applied to plants in flower during seed production with the fungal antagonist Ulocladium atrum was investigated in laboratory and field experiments resulting in a reduction of seed

  13. Dilute-acid pretreatment of barley straw for biological hydrogen production using Caldicellulosiruptor saccharolyticus

    NARCIS (Netherlands)

    Panagiotopoulos, I.A.; Bakker, R.R.C.; Vrije, de G.J.; Claassen, P.A.M.; Koukios, E.G.

    2012-01-01

    The main objective of this study was to use the fermentability test to investigate the feasibility of applying various dilute acids in the pretreatment of barley straw for biological hydrogen production. At a fixed acid loading of 1% (w/w dry matter) 28-32% of barley straw was converted to soluble

  14. 76 FR 79203 - Prospective Grant of Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines

    Science.gov (United States)

    2011-12-21

    ... Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines AGENCY: National Institutes....7. The invention relates to compositions and methods of use as Veterinary Influenza Vaccines... to humans. This technology describes DNA vaccines against influenza serotypes H5N1, H1N1, H3N2, and...

  15. Microwave-ultrasound combined reactor suitable for atmospheric sample preparation procedure of biological and chemical products

    NARCIS (Netherlands)

    Lagha, A.; Chemat, S.; Bartels, P.V.; Chemat, F.

    1999-01-01

    A compact apparatus in which a specific position can be irradiated by microwaves (MW) and ultrasound (US) simultaneously has been developed. The MW-US reactor has been designed for atmospheric pressure digestion and dissolution of biological and chemical products. The reactor can treat a range of

  16. Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances.

    Science.gov (United States)

    Bäckberg, Matilda; Jönsson, Karl-Henrik; Beck, Olof; Helander, Anders

    2018-02-01

    The web-based open sale of unregulated new psychoactive substances (NPS) has shown a steady increase in recent years. Analysis of drug products sold as NPS is useful to confirm the true chemical contents, for comparison with the substances detected in corresponding body fluids, but also to study drug trends. This work describes the examination of 251 drug products that were randomly submitted for analysis in 173 cases of suspected NPS-related intoxications in the Swedish STRIDA project in 2010-2015. Of the products, 39% were powders/crystals, 32% tablets/capsules, 16% herbal materials, 8% liquids, 1% blotters, and 4% others. The analysis involved tandem mass spectrometry and nuclear magnetic resonance spectroscopy. In 88 products (35%), classic psychoactive substances, prescription pharmaceuticals, dietary supplements, or doping agents were found; however, in none of these cases had an NPS-related intoxication been indicated from product markings or patient self-reports. Another 12 products tested negative for psychoactive substances. The remaining 151 products contained 86 different NPS (30% contained ≥2 substances). In 104 drug products, a specific NPS ingredient was indicated based on labelling (69%) or patient self-report; in 92 cases this was also analytically confirmed to be correct. Overall, the NPS products submitted for analysis in the STRIDA project showed a high degree of consistency between suspected and actual content (88%). The results of related urine and/or blood analysis further demonstrated that the patients commonly (89%) tested positive for the indicated NPS, but also revealed that polysubstance intoxication was common (83%), indicating use of additional drug products. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Sample preparation composite and replicate strategy for assay of solid oral drug products.

    Science.gov (United States)

    Harrington, Brent; Nickerson, Beverly; Guo, Michele Xuemei; Barber, Marc; Giamalva, David; Lee, Carlos; Scrivens, Garry

    2014-12-16

    In pharmaceutical analysis, the results of drug product assay testing are used to make decisions regarding the quality, efficacy, and stability of the drug product. In order to make sound risk-based decisions concerning drug product potency, an understanding of the uncertainty of the reportable assay value is required. Utilizing the most restrictive criteria in current regulatory documentation, a maximum variability attributed to method repeatability is defined for a drug product potency assay. A sampling strategy that reduces the repeatability component of the assay variability below this predefined maximum is demonstrated. The sampling strategy consists of determining the number of dosage units (k) to be prepared in a composite sample of which there may be a number of equivalent replicate (r) sample preparations. The variability, as measured by the standard error (SE), of a potency assay consists of several sources such as sample preparation and dosage unit variability. A sampling scheme that increases the number of sample preparations (r) and/or number of dosage units (k) per sample preparation will reduce the assay variability and thus decrease the uncertainty around decisions made concerning the potency of the drug product. A maximum allowable repeatability component of the standard error (SE) for the potency assay is derived using material in current regulatory documents. A table of solutions for the number of dosage units per sample preparation (r) and number of replicate sample preparations (k) is presented for any ratio of sample preparation and dosage unit variability.

  18. 78 FR 72840 - Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A and 503B...

    Science.gov (United States)

    2013-12-04

    ... reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product'' (section 503A... because it included restrictions on the advertising or promotion of the compounding of any particular drug... effect on the safety or effectiveness of that drug product. In addition, the DQSA adds a new section 503B...

  19. 21 CFR 358.750 - Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis.

    Science.gov (United States)

    2010-04-01

    ... dandruff, seborrheic dermatitis, or psoriasis. 358.750 Section 358.750 Food and Drugs FOOD AND DRUG... Dermatitis, and Psoriasis § 358.750 Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (a) Statement of identity. The labeling of the product contains the established...

  20. 21 CFR 310.548 - Drug products containing colloidal silver ingredients or silver salts offered over-the-counter...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing colloidal silver... Drug products containing colloidal silver ingredients or silver salts offered over-the-counter (OTC) for the treatment and/or prevention of disease. (a) Colloidal silver ingredients and silver salts have...

  1. Microvesicle formulations used in topical drugs and cosmetics affect product efficiency, performance and allergenicity

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Ejner Andersen, Klaus

    2010-01-01

    transdermal delivery more efficient for a number of drugs. Vesicular systems may also allow a more precise drug delivery to the site of action (ie, the hair follicles) and thereby minimize the applied drug concentration, reducing potential side effects. On the other hand, this may increase the risk of other......Attempts to improve the formulations of topical products are continuing processes (ie, to increase cosmetic performance, enhance effects, and protect ingredients from degradation). The development of micro- and nanovesicular systems has led to the marketing of topical drugs and cosmetics that use...... these technologies. Several articles have reported improved clinical efficacy by the encapsulation of pharmaceuticals in vesicular systems, and the numbers of publications and patents are rising. Some vesicular systems may deliver the drug deeper in the skin as compared to conventional vehicles, or even make...

  2. Stability of Reconstituted Telavancin Drug Product in Frozen Intravenous Bags.

    Science.gov (United States)

    Gu, Zhengtian; Wong, Anissa; Raquinio, Elvira; Nguyen, Alice

    2015-07-01

    Intravenous (IV) infusions of telavancin for injection are generally administered in-hospital, but in some circumstances they may be administered in an outpatient environment. In that setting, antibiotics may be premixed and frozen. This study determined the chemical stability of nonpreserved telavancin in various commonly used reconstitution diluents stored in IV bags (polyvinyl chloride [PVC] and PVC-free) at -20°C (-4°F) without light. Telavancin (750 mg/vial) was reconstituted with 5% dextrose injection USP (D5W) or 0.9% sodium chloride injection USP (NS) to obtain drug solutions at approximately 15 mg/mL. Infusion solutions of telavancin at diluted concentrations of 0.6 mg/mL and 8.0 mg/mL covering the range utilized in clinical practice were prepared in both PVC and PVC-free IV bags using D5W or NS solutions. The infusion solutions were stored under frozen conditions (-20°C ± 5°C [-4°F ± 41°F]) and the chemical stability was evaluated for up to 32 days. Telavancin concentration, purity, and degradant levels were determined using a stability-indicating high-performance liquid chromatography (HPLC) method. Telavancin IV infusion solutions in D5W or NS at 0.6 mg/mL and 8 mg/mL and stored at -20°C (-4°F) met the chemical stability criteria when tested on days 0, 7, 14, and 32. The assayed telavancin concentration at each time point was within 97% to 103% of the initial mean assay value. The total degradants quantified by the HPLC stability-indicating method did not show any significant change over the 32-day study period. Telavancin IV infusion solutions (in D5W or NS) in both PVC and PVC-free IV bags were stable for at least 32 days when stored at -20°C (-4°F) without light. These results provide prolonged frozen stability data further to that previously established for 7 days under refrigerated conditions (2°C-8°C [36°F -46°F]), and for 12 hours at room temperature when diluted into IV bags containing D5W, NS, or lactated Ringer's solution.

  3. Knowledge of Adverse Drug Reaction Reporting and the Pharmacovigilance of Biological Medicines: A Survey of Healthcare Professionals in Ireland.

    Science.gov (United States)

    O'Callaghan, J; Griffin, B T; Morris, J M; Bermingham, Margaret

    2018-06-01

    In Europe, changes to pharmacovigilance legislation, which include additional monitoring of medicines, aim to optimise adverse drug reaction (ADR) reporting systems. The legislation also makes provisions related to the traceability of biological medicines. The objective of this study was to assess (i) knowledge and general experience of ADR reporting, (ii) knowledge, behaviours, and attitudes related to the pharmacovigilance of biologicals, and (iii) awareness of additional monitoring among healthcare professionals (HCPs) in Ireland. Hospital doctors (n = 88), general practitioners (GPs) (n = 197), nurses (n = 104) and pharmacists (n = 309) completed an online questionnaire. There were differences in mean knowledge scores relating to ADR reporting and the pharmacovigilance of biologicals among the HCP groups. The majority of HCPs who use biological medicines in their practice generally record biologicals by brand name but practice behaviours relating to batch number recording differed between some professions. HCPs consider batch number recording to be valuable but also regard it as being more difficult than brand name recording. Most respondents were aware of the concept of additional monitoring but awareness rates differed between some groups. Among those who knew about additional monitoring, there was higher awareness of the inverted black triangle symbol among pharmacists (> 86.4%) compared with hospital doctors (35.1%), GPs (35.6%), and nurses (14.9%). Hospital pharmacists had more experience and knowledge of ADR reporting than other practising HCPs. This study highlights the important role hospital pharmacists play in post-marketing surveillance. There is a need to increase pharmacovigilance awareness of biological medicines and improve systems to support their batch traceability.

  4. Biological Mesh Implants for Abdominal Hernia Repair: US Food and Drug Administration Approval Process and Systematic Review of Its Efficacy.

    Science.gov (United States)

    Huerta, Sergio; Varshney, Anubodh; Patel, Prachi M; Mayo, Helen G; Livingston, Edward H

    2016-04-01

    Expensive biological mesh materials are increasingly used to reinforce abdominal wall hernia repairs. The clinical and cost benefit of these materials are unknown. To review the published evidence on the use of biological mesh materials and to examine the US Food and Drug Administration (FDA) approval history for these devices. Search of multiple electronic databases (Ovid, MEDLINE, EMBASE, Cochrane Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Cochrane National Health Service Economic Evaluation Database) to identify articles published between 1948 and June 30, 2015, on the use of biological mesh materials used to reinforce abdominal wall hernia repair. Keywords searched included surgical mesh, abdominal hernia, recurrence, infection, fistula, bioprosthesis, biocompatible materials, absorbable implants, dermis, and collagen. The FDA online database for 510(k) clearances was reviewed for all commercially available biological mesh materials. The median national price for mesh materials was established by a benchmarking query through several Integrated Delivery Network and Group Purchasing Organization tools. Of 274 screened articles, 20 met the search criteria. Most were case series that reported results of convenience samples of patients at single institutions with a variety of clinical problems. Only 3 of the 20 were comparative studies. There were no randomized clinical trials. In total, outcomes for 1033 patients were described. Studies varied widely in follow-up time, operative technique, meshes used, and patient selection criteria. Reported outcomes and clinical outcomes, such as fistula formation and infection, were inconsistently reported across studies. Conflicts of interest were not reported in 16 of the 20 studies. Recurrence rates ranged from 0% to 80%. All biological mesh devices were approved by the FDA based on substantial equivalence to a group of nonbiological predicate

  5. Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity.

    Science.gov (United States)

    Turner, David P

    2015-05-15

    Low income, poor diet, obesity, and a lack of exercise are interrelated lifestyle factors that can profoundly alter our biologic make up to increase cancer risk, growth, and development. We recently reported a potential mechanistic link between carbohydrate-derived metabolites and cancer, which may provide a biologic consequence of lifestyle that can directly affect tumor biology. Advanced glycation end-products (AGE) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race-specific, tumor-dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype, with a particular emphasis on their biologic links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biologic role of AGEs in promoting cancer, opportunities exist for collaborations affecting basic, translational, epidemiologic, and cancer prevention initiatives. ©2015 American Association for Cancer Research.

  6. [Drug vectorization or how to modulate tissular and cellular distribution of biologically active compounds].

    Science.gov (United States)

    Couvreur, P

    2001-07-01

    Drug vectorization has undergone considerable development over the last few years. This review focuses on the intravenous route of administration. Colloid formulations allow a modulation of drug tissue distribution. Using liposomes and nanoparticles with unmodified surfaces, drugs can be targeted to macrophages of the reticulum endothelium system. When the liposomes or nanoparticles are covered with hydrophilic or flexible polymers, the vascular phase can be favored in order, for example, to facilitate selective extravasation at a tumor site. Therapeutic applications of these systems are presented. The development of "intelligent" vectors capable of modulating intracellular distribution of an active compounds is an equally interesting approach, for example pH-sensitive liposomes or nanoparticles decorated with folic acid capable of targeting intracellular cytoplasm.

  7. Fabrication of luminescent hydroxyapatite nanorods through surface-initiated RAFT polymerization: Characterization, biological imaging and drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Heng, Chunning [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an, 710069 (China); Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Zheng, Xiaoyan [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an, 710069 (China); Liu, Meiying; Xu, Dazhuang; Huang, Hongye; Deng, Fengjie [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Hui, Junfeng, E-mail: huijunfeng@126.com [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an, 710069 (China); Zhang, Xiaoyong, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: weiyen@tsinghua.edu.cn [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing, 100084 (China)

    2016-11-15

    Highlights: • Hydrophobic hydroxyapatite nanorods were obtained from hydrothermal synthesis. • Surface initiated RAFT polymerization was adopted to surface modification of hydroxyapatite nanorods. • These modified hydroxyapatite nanorods showed high water dispersibility and biocompatibility. • These modified hydroxyapatite nanorods can be used for controlled drug delivery. - Abstract: Hydroxyapatite nanomaterials as an important class of nanomaterials, have been widely applied for different biomedical applications for their excellent biocompatibility, biodegradation potential and low cost. In this work, hydroxyapatite nanorods with uniform size and morphology were prepared through hydrothermal synthesis. The surfaces of these hydroxyapatite nanorods are covered with hydrophobic oleic acid, making them poor dispersibility in aqueous solution and difficult for biomedical applications. To overcome this issue, a simple surface initiated polymerization strategy has been developed via combination of the surface ligand exchange and reversible addition fragmentation chain transfer (RAFT) polymerization. Hydroxyapatite nanorods were first modified with Riboflavin-5-phosphate sodium (RPSSD) via ligand exchange reaction between the phosphate group of RPSSD and oleic acid. Then hydroxyl group of nHAp-RPSSD was used to immobilize chain transfer agent, which was used as the initiator for surface-initiated RAFT polymerization. The nHAp-RPSSD-poly(IA-PEGMA) nanocomposites were characterized by means of {sup 1}H nuclear magnetic resonance, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal gravimetric analysis in detailed. The biocompatibility, biological imaging and drug delivery of nHAp-RPSSD-poly(IA-PEGMA) were also investigated. Results showed that nHAp-RPSSD-poly(IA-PEGMA) exhibited excellent water dispersibility, desirable optical properties, good biocompatibility and high drug loading capability, making them promising candidates for

  8. Fabrication of luminescent hydroxyapatite nanorods through surface-initiated RAFT polymerization: Characterization, biological imaging and drug delivery applications

    International Nuclear Information System (INIS)

    Heng, Chunning; Zheng, Xiaoyan; Liu, Meiying; Xu, Dazhuang; Huang, Hongye; Deng, Fengjie; Hui, Junfeng; Zhang, Xiaoyong; Wei, Yen

    2016-01-01

    Highlights: • Hydrophobic hydroxyapatite nanorods were obtained from hydrothermal synthesis. • Surface initiated RAFT polymerization was adopted to surface modification of hydroxyapatite nanorods. • These modified hydroxyapatite nanorods showed high water dispersibility and biocompatibility. • These modified hydroxyapatite nanorods can be used for controlled drug delivery. - Abstract: Hydroxyapatite nanomaterials as an important class of nanomaterials, have been widely applied for different biomedical applications for their excellent biocompatibility, biodegradation potential and low cost. In this work, hydroxyapatite nanorods with uniform size and morphology were prepared through hydrothermal synthesis. The surfaces of these hydroxyapatite nanorods are covered with hydrophobic oleic acid, making them poor dispersibility in aqueous solution and difficult for biomedical applications. To overcome this issue, a simple surface initiated polymerization strategy has been developed via combination of the surface ligand exchange and reversible addition fragmentation chain transfer (RAFT) polymerization. Hydroxyapatite nanorods were first modified with Riboflavin-5-phosphate sodium (RPSSD) via ligand exchange reaction between the phosphate group of RPSSD and oleic acid. Then hydroxyl group of nHAp-RPSSD was used to immobilize chain transfer agent, which was used as the initiator for surface-initiated RAFT polymerization. The nHAp-RPSSD-poly(IA-PEGMA) nanocomposites were characterized by means of "1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal gravimetric analysis in detailed. The biocompatibility, biological imaging and drug delivery of nHAp-RPSSD-poly(IA-PEGMA) were also investigated. Results showed that nHAp-RPSSD-poly(IA-PEGMA) exhibited excellent water dispersibility, desirable optical properties, good biocompatibility and high drug loading capability, making them promising candidates for biological

  9. Building New Bridges between In Vitro and In Vivo in Early Drug Discovery: Where Molecular Modeling Meets Systems Biology.

    Science.gov (United States)

    Pearlstein, Robert A; McKay, Daniel J J; Hornak, Viktor; Dickson, Callum; Golosov, Andrei; Harrison, Tyler; Velez-Vega, Camilo; Duca, José

    2017-01-01

    Cellular drug targets exist within networked function-generating systems whose constituent molecular species undergo dynamic interdependent non-equilibrium state transitions in response to specific perturbations (i.e.. inputs). Cellular phenotypic behaviors are manifested through the integrated behaviors of such networks. However, in vitro data are frequently measured and/or interpreted with empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs-Haldane) relevant to isolated target populations. We propose that cells act as analog computers, "solving" sets of coupled "molecular differential equations" (i.e. represented by populations of interacting species)via "integration" of the dynamic state probability distributions among those populations. Disconnects between biochemical and functional/phenotypic assays (cellular/in vivo) may arise with targetcontaining systems that operate far from equilibrium, and/or when coupled contributions (including target-cognate partner binding and drug pharmacokinetics) are neglected in the analysis of biochemical results. The transformation of drug discovery from a trial-and-error endeavor to one based on reliable design criteria depends on improved understanding of the dynamic mechanisms powering cellular function/dysfunction at the systems level. Here, we address the general mechanisms of molecular and cellular function and pharmacological modulation thereof. We outline a first principles theory on the mechanisms by which free energy is stored and transduced into biological function, and by which biological function is modulated by drug-target binding. We propose that cellular function depends on dynamic counter-balanced molecular systems necessitated by the exponential behavior of molecular state transitions under non-equilibrium conditions, including positive versus negative mass action kinetics and solute-induced perturbations to the hydrogen bonds of solvating water versus kT. Copyright© Bentham

  10. Ethnic hair care products may increase false positives in hair drug testing.

    Science.gov (United States)

    Kidwell, David A; Smith, Frederick P; Shepherd, Arica R

    2015-12-01

    The question of why different races appear more susceptible to hair contamination by external drugs remains controversial. This research studied susceptibility of head hair to external cocaine and methamphetamine when hair products have been applied. Three different chemical classes of ethnic hair products were applied to Caucasian, Asian, and African hair. Some products increased the methamphetamine and cocaine concentrations in all hair types. A unique finding of this research is that certain ethnic hair products can replace moisture as a diffusion medium, thereby increasing the susceptibility to contamination over 100-fold compared to petroleum-based products. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Apple biological and physiological disorders in the orchard and in postharvest according to production system

    Directory of Open Access Journals (Sweden)

    Carlos Roberto Martins

    2013-03-01

    Full Text Available The study aimed to evaluate the incidence of biological and physiological disorders in the field and postharvested apples cvs. Gala, Fuji and Catarina grown in four production systems: conventional, organic transition, integrated and organic. Apples were evaluated for damages related to biological and physiological disorders in the orchard and after harvest. The greatest damages were attributed to pests, especially Anastrepha fraterculus in the organic system and Grapholita molesta in the organic transition. Apples produced in organic orchards had higher damage levels caused by postharvest physiological disorders than those grown in other production systems. For apples becoming from organic orchards most of the damage was due to lenticels breakdown and degeneration ('Gala', and bitter pit ('Fuji' and 'Catarina'. The incidence of postharvest rot was not influenced by apple production system.

  12. Combinative Particle Size Reduction Technologies for the Production of Drug Nanocrystals

    Directory of Open Access Journals (Sweden)

    Jaime Salazar

    2014-01-01

    Full Text Available Nanosizing is a suitable method to enhance the dissolution rate and therefore the bioavailability of poorly soluble drugs. The success of the particle size reduction processes depends on critical factors such as the employed technology, equipment, and drug physicochemical properties. High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. This review article discusses the development of combinative methods, such as the NANOEDGE, H 96, H 69, H 42, and CT technologies. These processes were developed to improve the particle size reduction effectiveness of the standard techniques. These novel technologies can combine bottom-up and/or top-down techniques in a two-step process. The combinative processes lead in general to improved particle size reduction effectiveness. Faster production of drug nanocrystals and smaller final mean particle sizes are among the main advantages. The combinative particle size reduction technologies are very useful formulation tools, and they will continue acquiring importance for the production of drug nanocrystals.

  13. Transit and lifespan in neutrophil production: implications for drug intervention.

    Science.gov (United States)

    Câmara De Souza, Daniel; Craig, Morgan; Cassidy, Tyler; Li, Jun; Nekka, Fahima; Bélair, Jacques; Humphries, Antony R

    2018-02-01

    A comparison of the transit compartment ordinary differential equation modelling approach to distributed and discrete delay differential equation models is studied by focusing on Quartino's extension to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after chemotherapy, and on a QSP delay differential equation model of granulopoiesis. An extension to the Quartino model is provided by considering a general number of transit compartments and introducing an extra parameter that allows for the decoupling of the maturation time from the production rate of cells. An overview of the well established linear chain technique, used to reformulate transit compartment models with constant transit rates as distributed delay differential equations (DDEs), is then given. A state-dependent time rescaling of the Quartino model is performed to apply the linear chain technique and rewrite the Quartino model as a distributed DDE, yielding a discrete DDE model in a certain parameter limit. Next, stability and bifurcation analyses are undertaken in an effort to situate such studies in a mathematical pharmacology context. We show that both the original Friberg and the Quartino extension models incorrectly define the mean maturation time, essentially treating the proliferative pool as an additional maturation compartment. This misspecification can have far reaching consequences on the development of future models of myelosuppression in PK/PD.

  14. Plants’ Natural Products as Alternative Promising Anti-Candida Drugs

    Science.gov (United States)

    Soliman, Sameh; Alnajdy, Dina; El-Keblawy, Ali A.; Mosa, Kareem A.; Khoder, Ghalia; Noreddin, Ayman M.

    2017-01-01

    Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID:28989245

  15. Sample preparation composite and replicate strategy case studies for assay of solid oral drug products.

    Science.gov (United States)

    Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei

    2017-11-30

    Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) [5], a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Waste water biological purification plants of dairy products industry and energy management

    Science.gov (United States)

    Stepanov, Sergey; Solkina, Olga; Stepanov, Alexander; Zhukova, Maria

    2017-10-01

    The paper presents results of engineering and economical comparison of waste water biological purification plants of dairy products industry. Three methods of purification are compared: traditional biological purification with the use of secondary clarifiers and afterpurification through granular-bed filters, biomembrane technology and physical-and-chemical treatment together with biomembrane technology for new construction conditions. The improvement of the biological purification technology using nitro-denitrification and membrane un-mixing of sludge mixture is a promising trend in this area. In these calculations, an energy management which is widely applied abroad was used. The descriptions of the three methods are illustrated with structural schemes. Costs of equipment and production areas are taken from manufacturers’ data. The research is aimed at an engineering and economical comparison of new constructions of waste water purification of dairy products industry. The experiment demonstrates advantages of biomembrane technology in waste water purification. This technology offers prospects of 122 million rubles cost saving during 25 years of operation when compared with of the technology of preparatory reagent flotation and of 13.7 million rubles cost saving compared to the option of traditional biological purification.

  17. Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study

    Science.gov (United States)

    Sarpatwari, Ameet; Dejene, Sara; Khan, Nazleen F; Lii, Joyce; Rogers, James R; Dutcher, Sarah K; Raofi, Saeid; Bohn, Justin; Connolly, John; Fischer, Michael A; Kesselheim, Aaron S; Gagne, Joshua J

    2018-01-01

    Abstract Objectives To compare rates of switchbacks to branded drug products for patients switched from branded to authorized generic drug products, which have the same active ingredients, appearance, and excipients as the branded product, with patients switched from branded to generic drug products, which have the same active ingredients as the branded product but may differ in appearance and excipients. Design Observational cohort study. Setting Private (a large commercial health plan) and public (Medicaid) insurance programs in the US. Participants Beneficiaries of a large US commercial health insurer between 2004 and 2013 (primary cohort) and Medicaid beneficiaries between 2000 and 2010 (replication cohort). Main outcome measures Patients taking branded products for one of the study drugs (alendronate tablets, amlodipine tablets, amlodipine-benazepril capsules, calcitonin salmon nasal spray, escitalopram tablets, glipizide extended release tablets, quinapril tablets, and sertraline tablets) were identified when they switched to an authorized generic or a generic drug product after the date of market entry of generic drug products. These patients were followed for switchbacks to the branded drug product in the year after their switch to an authorized generic or a generic drug product. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals after adjusting for demographics, including age, sex, and calendar year. Inverse variance meta-analysis was used to pool adjusted hazard ratios across all drug products. Results A total of 94 909 patients switched from branded to authorized generic drug products and 116 017 patients switched from branded to generic drug products and contributed to the switchback analysis. Unadjusted incidence rates of switchback varied across drug products, ranging from a low of 3.8 per 100 person years (for alendronate tablets) to a high of 17.8 per 100 person years (for amlodipine

  18. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Charles-Schoeman, Christina; Burmester, Gerd; Nash, Peter; Zerbini, Cristiano A F; Soma, Koshika; Kwok, Kenneth; Hendrikx, Thijs; Bananis, Eustratios; Fleischmann, Roy

    2016-07-01

    Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR). Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed. 2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs). Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. (NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385). Published by the BMJ Publishing Group Limited

  19. Concurrent Use of Conventional Drugs with Chinese Herbal Products in Taiwan: A Population-based Study

    Directory of Open Access Journals (Sweden)

    Ming-Chen Chen

    2013-10-01

    Full Text Available The increased use of Chinese herbal products (CHPs worldwide has raised the concern of herb–drug interactions. The aim of this study was to determine the prevalence and utilization patterns of concurrent use of conventional drugs and CHPs in Taiwan. The usage and frequency of services in the co-prescription of a CHP and a conventional drug were evaluated. Subjects were recruited from a simple random sample of 1,000,000 subjects from over 22 million beneficiaries of the National Health Insurance in 2007. The logistic regression method was employed to estimate the odds ratios (ORs for the co-prescription of a CHP and a conventional drug (CH+D and a conventional drug alone (D-alone. The prevalence of the CH+D was 14.1%. Females, regular salary earners, and elderly (65 years and above were more likely to consume a CHP and a conventional drug concurrently. Painkillers, especially acetaminophen, and anti-cough medicines were the top two conventional drugs that were most frequently co-prescribed with a CHP. Anti-cough medication is the most common conventional drug co-prescribed with CHP, after painkillers. We recommend that safety issues be investigated in future research and integrating both healthcare technologies may be beneficial for the overall health and quality of life of patients.

  20. Electrospun Fibers as a Dressing Material for Drug and Biological Agent Delivery in Wound Healing Applications

    Science.gov (United States)

    Gizaw, Mulugeta; Thompson, Jeffrey; Faglie, Addison; Lee, Shih-Yu; Neuenschwander, Pierre; Chou, Shih-Feng

    2018-01-01

    Wound healing is a complex tissue regeneration process that promotes the growth of new tissue to provide the body with the necessary barrier from the outside environment. In the class of non-healing wounds, diabetic wounds, and ulcers, dressing materials that are available clinically (e.g., gels and creams) have demonstrated only a slow improvement with current available technologies. Among all available current technologies, electrospun fibers exhibit several characteristics that may provide novel replacement dressing materials for the above-mentioned wounds. Therefore, in this review, we focus on recent achievements in electrospun drug-eluting fibers for wound healing applications. In particular, we review drug release, including small molecule drugs, proteins and peptides, and gene vectors from electrospun fibers with respect to wound healing. Furthermore, we provide an overview on multifunctional dressing materials based on electrospun fibers, including those that are capable of achieving wound debridement and wound healing simultaneously as well as multi-drugs loading/types suitable for various stages of the healing process. Our review provides important and sufficient information to inform the field in development of fiber-based dressing materials for clinical treatment of non-healing wounds. PMID:29382065

  1. Random Forest Segregation of Drug Responses May define Regions of Biological Significance

    Directory of Open Access Journals (Sweden)

    Qasim eBukhari

    2016-03-01

    Full Text Available The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF method to detect differences in the pharmacological MRI (phMRI response in rats to treatment with an analgesic drug (buprenorphine as compared to control (saline. Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD and high dose (HD, and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow an unsupervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

  2. Micro-electromembrane extraction across free liquid membranes. Extractions of basic drugs from undiluted biological samples

    Czech Academy of Sciences Publication Activity Database

    Kubáň, Pavel; Boček, Petr

    2014-01-01

    Roč. 1337, Apr (2014), s. 32-39 ISSN 0021-9673 R&D Projects: GA ČR(CZ) GA13-05762S Institutional support: RVO:68081715 Keywords : micro-electromembrane extraction * free liquid membranes * biological samples Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.169, year: 2014

  3. Limited Bacterial Diversity within a Treatment Plant Receiving Antibiotic-Containing Waste from Bulk Drug Production

    Science.gov (United States)

    Shouche, Yogesh S.; Larsson, D. G. Joakim

    2016-01-01

    Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted by the use of activated sludge (AS) technology, where microbes that are able to thrive on the chemicals within the wastewater are reintroduced at an earlier stage of the process to further enhance degradation of incoming chemicals. The microbial community structure within such a treatment plant is, however, largely unclear. In this study, Illumina-based 16S rRNA amplicon sequencing was applied to investigate the bacterial communities of different stages from an Indian treatment plant operated by Patancheru Environment Technology Limited (PETL) in Hyderabad, India. The plant receives waste water with high levels of fluoroquinolones and applies AS technology. A total of 1,019,400 sequences from samples of different stages of the treatment process were analyzed. In total 202, 303, 732, 652, 947 and 864 operational taxonomic units (OTUs) were obtained at 3% distance cutoff in the equilibrator, aeration tanks 1 and 2, settling tank, secondary sludge and old sludge samples from PETL, respectively. Proteobacteria was the most dominant phyla in all samples with Gammaproteobacteria and Betaproteobacteria being the dominant classes. Alcaligenaceae and Pseudomonadaceae, bacterial families from PETL previously reported to be highly multidrug resistant, were the dominant families in aeration tank samples. Despite regular addition of human sewage (approximately 20%) to uphold microbial activity, the bacterial diversity within aeration tanks from PETL was considerably lower than corresponding samples from seven, regular municipal waste water treatment plants. The strong selection pressure from antibiotics present may be one important factor in structuring the microbial community in PETL

  4. Limited Bacterial Diversity within a Treatment Plant Receiving Antibiotic-Containing Waste from Bulk Drug Production.

    Science.gov (United States)

    Marathe, Nachiket P; Shetty, Sudarshan A; Shouche, Yogesh S; Larsson, D G Joakim

    2016-01-01

    Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted by the use of activated sludge (AS) technology, where microbes that are able to thrive on the chemicals within the wastewater are reintroduced at an earlier stage of the process to further enhance degradation of incoming chemicals. The microbial community structure within such a treatment plant is, however, largely unclear. In this study, Illumina-based 16S rRNA amplicon sequencing was applied to investigate the bacterial communities of different stages from an Indian treatment plant operated by Patancheru Environment Technology Limited (PETL) in Hyderabad, India. The plant receives waste water with high levels of fluoroquinolones and applies AS technology. A total of 1,019,400 sequences from samples of different stages of the treatment process were analyzed. In total 202, 303, 732, 652, 947 and 864 operational taxonomic units (OTUs) were obtained at 3% distance cutoff in the equilibrator, aeration tanks 1 and 2, settling tank, secondary sludge and old sludge samples from PETL, respectively. Proteobacteria was the most dominant phyla in all samples with Gammaproteobacteria and Betaproteobacteria being the dominant classes. Alcaligenaceae and Pseudomonadaceae, bacterial families from PETL previously reported to be highly multidrug resistant, were the dominant families in aeration tank samples. Despite regular addition of human sewage (approximately 20%) to uphold microbial activity, the bacterial diversity within aeration tanks from PETL was considerably lower than corresponding samples from seven, regular municipal waste water treatment plants. The strong selection pressure from antibiotics present may be one important factor in structuring the microbial community in PETL

  5. Limited Bacterial Diversity within a Treatment Plant Receiving Antibiotic-Containing Waste from Bulk Drug Production.

    Directory of Open Access Journals (Sweden)

    Nachiket P Marathe

    Full Text Available Biological treatment of waste water from bulk drug production, contaminated with high levels of fluoroquinolone antibiotics, can lead to massive enrichment of antibiotic resistant bacteria, resistance genes and associated mobile elements, as previously shown. Such strong selection may be boosted by the use of activated sludge (AS technology, where microbes that are able to thrive on the chemicals within the wastewater are reintroduced at an earlier stage of the process to further enhance degradation of incoming chemicals. The microbial community structure within such a treatment plant is, however, largely unclear. In this study, Illumina-based 16S rRNA amplicon sequencing was applied to investigate the bacterial communities of different stages from an Indian treatment plant operated by Patancheru Environment Technology Limited (PETL in Hyderabad, India. The plant receives waste water with high levels of fluoroquinolones and applies AS technology. A total of 1,019,400 sequences from samples of different stages of the treatment process were analyzed. In total 202, 303, 732, 652, 947 and 864 operational taxonomic units (OTUs were obtained at 3% distance cutoff in the equilibrator, aeration tanks 1 and 2, settling tank, secondary sludge and old sludge samples from PETL, respectively. Proteobacteria was the most dominant phyla in all samples with Gammaproteobacteria and Betaproteobacteria being the dominant classes. Alcaligenaceae and Pseudomonadaceae, bacterial families from PETL previously reported to be highly multidrug resistant, were the dominant families in aeration tank samples. Despite regular addition of human sewage (approximately 20% to uphold microbial activity, the bacterial diversity within aeration tanks from PETL was considerably lower than corresponding samples from seven, regular municipal waste water treatment plants. The strong selection pressure from antibiotics present may be one important factor in structuring the microbial

  6. Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels

    Energy Technology Data Exchange (ETDEWEB)

    Kuk Lee, Sung; Chou, Howard; Ham, Timothy S.; Soon Lee, Taek; Keasling, Jay D.

    2009-12-02

    The ability to generate microorganisms that can produce biofuels similar to petroleum-based transportation fuels would allow the use of existing engines and infrastructure and would save an enormous amount of capital required for replacing the current infrastructure to accommodate biofuels that have properties significantly different from petroleum-based fuels. Several groups have demonstrated the feasibility of manipulating microbes to produce molecules similar to petroleum-derived products, albeit at relatively low productivity (e.g. maximum butanol production is around 20 g/L). For cost-effective production of biofuels, the fuel-producing hosts and pathways must be engineered and optimized. Advances in metabolic engineering and synthetic biology will provide new tools for metabolic engineers to better understand how to rewire the cell in order to create the desired phenotypes for the production of economically viable biofuels.

  7. Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

    Science.gov (United States)

    Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

    2013-12-23

    Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

  8. A chemical-biological evaluation of rhodium(I) N-heterocyclic carbene complexes as prospective anticancer drugs.

    Science.gov (United States)

    Oehninger, Luciano; Küster, Laura Nadine; Schmidt, Claudia; Muñoz-Castro, Alvaro; Prokop, Aram; Ott, Ingo

    2013-12-23

    Rhodium(I) complexes bearing N-heterocyclic carbene (NHC) ligands have been widely used in catalytic chemistry, but there are very few reports of biological properties of these organometallics. A series of Rh(I)-NHC derivatives with 1,5-cyclooctadiene and CO as secondary ligands were synthesized, characterized, and biologically investigated as prospective antitumor drug candidates. Pronounced antiproliferative effects were noted for all complexes, along with moderate inhibitory activity of thioredoxin reductase (TrxR) and efficient binding to biomolecules (DNA, albumin). Biodistribution studies showed that the presence of albumin lowered the cellular uptake and confirmed the transport of rhodium into the nuclei. Changes in the mitochondrial membrane potential (MMP) were observed as well as DNA fragmentation in wild-type and daunorubicin- or vincristine-resistant Nalm-6 leukemia cells. Overall, these studies indicated that Rh(I)-NHC fragments could be used as partial structures of new antitumor agents, in particular in those drugs designed to address resistant malignant tissues. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Very-large-scale production of antibodies in plants: The biologization of manufacturing.

    Science.gov (United States)

    Buyel, J F; Twyman, R M; Fischer, R

    2017-07-01

    Gene technology has facilitated the biologization of manufacturing, i.e. the use and production of complex biological molecules and systems at an industrial scale. Monoclonal antibodies (mAbs) are currently the major class of biopharmaceutical products, but they are typically used to treat specific diseases which individually have comparably low incidences. The therapeutic potential of mAbs could also be used for more prevalent diseases, but this would require a massive increase in production capacity that could not be met by traditional fermenter systems. Here we outline the potential of plants to be used for the very-large-scale (VLS) production of biopharmaceutical proteins such as mAbs. We discuss the potential market sizes and their corresponding production capacities. We then consider available process technologies and scale-down models and how these can be used to develop VLS processes. Finally, we discuss which adaptations will likely be required for VLS production, lessons learned from existing cell culture-based processes and the food industry, and practical requirements for the implementation of a VLS process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Biological Production of 3-Hydroxypropionic Acid: An Update on the Current Status

    Directory of Open Access Journals (Sweden)

    Leonidas Matsakas

    2018-02-01

    Full Text Available The production of high added-value chemicals from renewable resources is a necessity in our attempts to switch to a more sustainable society. 3-Hydroxypropionic acid (3HP is a promising molecule that can be used for the production of an important array of high added-value chemicals, such as 1,3-propanediol, acrylic acid, acrylamide, and bioplastics. Biological production of 3HP has been studied extensively, mainly from glycerol and glucose, which are both renewable resources. To enable conversion of these carbon sources to 3HP, extensive work has been performed to identify appropriate biochemical pathways and the enzymes that are involved in them. Novel enzymes have also been identified and expressed in host microorganisms to improve the production yields of 3HP. Various process configurations have also been proposed, resulting in improved conversion yields. The intense research efforts have resulted in the production of as much as 83.8 g/L 3HP from renewable carbon resources, and a system whereby 3-hydroxypropionitrile was converted to 3HP through whole-cell catalysis which resulted in 184.7 g/L 3HP. Although there are still challenges and difficulties that need to be addressed, the research results from the past four years have been an important step towards biological production of 3HP at the industrial level.

  11. Biofuel production in Escherichia coli. The role of metabolic engineering and synthetic biology

    Energy Technology Data Exchange (ETDEWEB)

    Clomburg, James M. [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Gonzalez, Ramon [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Rice Univ., Houston, TX (United States). Dept. of Bioengineering

    2010-03-15

    The microbial production of biofuels is a promising avenue for the development of viable processes for the generation of fuels from sustainable resources. In order to become cost and energy effective, these processes must utilize organisms that can be optimized to efficiently produce candidate fuels from a variety of feedstocks. Escherichia coli has become a promising host organism for the microbial production of biofuels in part due to the ease at which this organism can be manipulated. Advancements in metabolic engineering and synthetic biology have led to the ability to efficiently engineer E. coli as a biocatalyst for the production of a wide variety of potential biofuels from several biomass constituents. This review focuses on recent efforts devoted to engineering E. coli for the production of biofuels, with emphasis on the key aspects of both the utilization of a variety of substrates as well as the synthesis of several promising biofuels. Strategies for the efficient utilization of carbohydrates, carbohydrate mixtures, and noncarbohydrate carbon sources will be discussed along with engineering efforts for the exploitation of both fermentative and nonfermentative pathways for the production of candidate biofuels such as alcohols and higher carbon biofuels derived from fatty acid and isoprenoid pathways. Continued advancements in metabolic engineering and synthetic biology will help improve not only the titers, yields, and productivities of biofuels discussed herein, but also increase the potential range of compounds that can be produced. (orig.)

  12. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

    Science.gov (United States)

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2016-07-01

    We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

  13. 21 CFR 201.26 - Exceptions or alternatives to labeling requirements for human drug products held by the Strategic...

    Science.gov (United States)

    2010-04-01

    ... requirements for human drug products held by the Strategic National Stockpile. 201.26 Section 201.26 Food and... drug products held by the Strategic National Stockpile. (a) The appropriate FDA Center Director may... safety, effectiveness, or availability of such product that is or will be included in the Strategic...

  14. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

    Directory of Open Access Journals (Sweden)

    J. Sedef Göçmen

    2012-12-01

    Full Text Available Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four different preparations containing Glyceryl trinitrate (Perlinganit®, Dexmedetomidine (Precedex®, Esmolol (Brevibloc®, and Propofol (Propofol® on slime production of 24Staphylococcus epidermidis strains isolated from blood cultures of patients, and reference strain were investigated. Slimeproduction was determined using ‘the quantitative microdilution plaque test’ described by Christensen.Results: Under controlled medium, eight strains formed slimes, and in the media containing esmolol, glyceryl trinitrate,dexmedetomidine, and propofol slimes were positive for five, 21, 15, and 18 strains, respectively. The rate of slime productionin glyceryl trinitrate, dexmedetomidine, and propofol containing media were higher than that of the controls.Conclusions: In the light of the results of this study, it is concluded that the drugs and/or additives increase the rate ofslime production. The effects of the preparations administered through catheters on slime production should be investigated,and these effects should be kept in mind during their use. J Microbiol Infect Dis 2012; 2(4: 150-154Key words: Slime Production, Coagulase Negative Staphyloccoci, Parenteral drugs

  15. Juvenile Animal Testing: Assessing Need and Use in the Drug Product Label.

    Science.gov (United States)

    Baldrick, Paul

    2018-01-01

    Juvenile animal testing has become an established part of drug development to support safe clinical use in the human pediatric population and for eventual drug product label use. A review of European Paediatric Investigation Plan decisions showed that from 2007 to mid-2017, 229 drugs had juvenile animal work requested, almost exclusively incorporating general toxicology study designs, in rat (57.5%), dog (8%), mouse (4.5%), monkey (4%), pig (2%), sheep (1%), rabbit (1%), hamster (0.5%), and species not specified (21.5%). A range of therapeutic areas were found, but the most common areas were infectious diseases (15%), endocrinology (13.5%), oncology (13%), neurology (11%), and cardiovascular diseases (10%). Examination of major clinical indications within these therapeutic areas showed some level of consistency in the species of choice for testing and the pediatric age that required support. Examination of juvenile animal study findings presented in product labels raises questions around how useful the data are to allow prescribing the drug to a child. It is hopeful that the new ICH S11 guideline "Nonclinical Safety Testing in Support of Development of Pediatric Medicines" currently in preparation will aid drug developers in clarifying the need for juvenile animal studies as well as in promoting a move away from toxicology studies with a conventional design. This would permit more focused testing to examine identified areas of toxicity or safety concerns and clarify the presentation/interpretation of juvenile animal study findings for proper risk assessment by a drug prescriber.

  16. Electrochemical Analysis of Antichemotherapeutic Drug Zanosar in Pharmaceutical and Biological Samples by Differential Pulse Polarography

    OpenAIRE

    Reddy, Chennupalle Nageswara; ReddyPrasad, Puthalapattu; Sreedhar, NeelamYughandhar

    2013-01-01

    The electrochemical reduction of zanosar was investigated systematically by direct current polarography, cyclic voltammetry, and differential pulse polarography (DPP). A simple DPP technique was proposed for the direct quantitative determination of anticancer drug zanosar in pharmaceutical formulation and spiked human urine samples for the first time. The reduction potential was −0.28 V versus Ag/AgCl with a hanging mercury drop electrode in Britton-Robinson buffer as supporting electrolyte. ...

  17. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  18. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Science.gov (United States)

    2010-04-01

    ... requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and... requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA Center... Strategic National Stockpile. (b)(1)(i) A Strategic National Stockpile official or any entity that...

  19. Radioiodination and Biological Evaluation of some Drugs for Inflammatory Foci Imaging

    International Nuclear Information System (INIS)

    El Refaie, M.S.A.

    2011-01-01

    A radiopharmaceutical is defined as a chemical or pharmaceutical preparation labeled with a radionuclide in tracer or therapeutic concentration, used as a diagnostic or therapeutic agent. A radiopharmaceutical agent is usually administrated into a vein. Depending on which type of scan is being performed, the imaging will be done either immediately, a few hours later, or even several days after the injection. Imaging time varies, generally ranging from 20 to 45 minutes.In this thesis, we are more interested in the drugs that can be used for the treatment of all kinds of inflammation whether septic or aseptic. The inflammation by itself can be a controllable disease, but as the inflammation, specially the chronic type, can be the reason and the beginning of many more serious diseases as autoimmune disease, pulmonary disease, cardiovascular disease, neurological disease and cancer, the study and the early diagnosis of the inflammation can prevent many future problems for the patient. The study of the inflammation has been discussed before by labeling drugs with Iodine-125 for the imaging of inflammatory foci like etodolac, meloxicam, piroxicam and other drugs.

  20. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

    International Nuclear Information System (INIS)

    Cowan-Jacob, Sandra W.; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W.

    2006-01-01

    A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery